Journal articles on the topic 'Front polaire'

Cells polarize to a single front and rear to achieve rapid actin-based motility, but the mechanisms preventing the formation of multiple fronts are unclear. We developed embryonic zebrafish keratocytes as a model system for investigating establishment of a single axis. We observed that, although keratocytes from 2 d postfertilization (dpf) embryos resembled canonical fan-shaped keratocytes, keratocytes from 4 dpf embryos often formed multiple protrusions despite unchanged membrane tension. Using genomic, genetic, and pharmacological approaches, we determined that the multiple-protrusion phenotype was primarily due to increased myosin light chain kinase (MLCK) expression. MLCK activity influences cell polarity by increasing myosin accumulation in lamellipodia, which locally decreases protrusion lifetime, limiting lamellipodial size and allowing for multiple protrusions to coexist within the context of membrane tension limiting protrusion globally. In contrast, Rho kinase (ROCK) regulates myosin accumulation at the cell rear and does not determine protrusion size. These results suggest a novel MLCK-specific mechanism for controlling cell polarity via regulation of myosin activity in protrusions.

AbstractThis article adopts a political approach to examine the reasons why Edward Heath's government wanted to upgrade Polaris and the reasons why they did so by way of a programme called Super Antelope, to improve the front-ends of the missiles against Soviet Anti-Ballistic Missile defence, as opposed to the alternatives on offer. It argues that the political contexts within which Heath took the decision have been insufficiently understood, and shows that the acceptance of the ‘Moscow criterion’ – the understanding that Britain had to have the capability to destroy Moscow – by central government represented continuity in Britain's cold war stance.

Chemoattractants such as formyl-Met-Leu-Phe (fMLP) induce neutrophils to polarize by triggering divergent pathways that promote formation of a protrusive front and contracting back and sides. RhoA, a Rho GTPase, stimulates assembly of actomyosin contractile complexes at the sides and back. We show here, in differentiated HL60 cells, that PDZRhoGEF (PRG), a guanine nucleotide exchange factor (GEF) for RhoA, mediates RhoA-dependent responses and determines their spatial distribution. As with RNAi knock-down of PRG, a GEF-deleted PRG mutant blocks fMLP-dependent RhoA activation and causes neutrophils to exhibit multiple fronts and long tails. Similarly, inhibition of RhoA, a Rho-dependent protein kinase (ROCK), or myosin II produces the same morphologies. PRG inhibition reduces or mislocalizes monophosphorylated myosin light chains in fMLP-stimulated cells, and myosin II ATPase inhibition reciprocally disrupts normal localization of PRG. We propose a cooperative reinforcing mechanism at the back of cells, in which PRG, RhoA, ROCK, myosin II, and actomyosin spatially cooperate to consolidate attractant-induced contractility and ensure robust cell polarity.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive non-Hodgkin lymphoma in the US. For nearly 2 decades, standard front-line treatment has consisted of chemoimmunotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Numerous trials have unsuccessfully attempted to achieve better outcomes in these patients. Recently, the results of the phase III POLARIX trial were published. This study randomized newly diagnosed DLBCL patients to receive polatuzumab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (pola-R-CHP) or standard-of-care R-CHOP. The POLARIX trial demonstrated 2-year progression-free survival of 76.7% for pola-R-CHP compared with 70.2% for R-CHOP with comparable safety profiles between the two arms. Based on these results, a new standard of care may be emerging in patients with DLBCL. This article provides a practical approach to managing a newly diagnosed patient with DLBCL.

To migrate efficiently, neutrophils must polarize their cytoskeletal regulators along a single axis of motion. This polarization process is thought to be mediated through local positive feedback that amplifies leading edge signals and global negative feedback that enables sites of positive feedback to compete for dominance. Though this two-component model efficiently establishes cell polarity, it has potential limitations, including a tendency to “lock” onto a particular direction, limiting the ability of cells to reorient. We use spatially defined optogenetic control of a leading edge organizer (PI3K) to probe how neutrophil-like HL-60 cells balance “decisiveness” needed to polarize in a single direction with the flexibility needed to respond to new cues. Underlying this balancing act is a local Rac inhibition process that destabilizes the leading edge to promote exploration. We show that this local inhibition enables cells to process input signal dynamics, linking front stability and orientation to local temporal increases in input signals.

RhoGTPases organize the actin cytoskeleton to generate diverse polarities, from front–back polarity in migrating cells to dendritic spine morphology in neurons. For example, RhoA through its effector kinase, RhoA kinase (ROCK), activates myosin II to form actomyosin filament bundles and large adhesions that locally inhibit and thereby polarize Rac1-driven actin polymerization to the protrusions of migratory fibroblasts and the head of dendritic spines. We have found that the two ROCK isoforms, ROCK1 and ROCK2, differentially regulate distinct molecular pathways downstream of RhoA, and their coordinated activities drive polarity in both cell migration and synapse formation. In particular, ROCK1 forms the stable actomyosin filament bundles that initiate front–back and dendritic spine polarity. In contrast, ROCK2 regulates contractile force and Rac1 activity at the leading edge of migratory cells and the spine head of neurons; it also specifically regulates cofilin-mediated actin remodeling that underlies the maturation of adhesions and the postsynaptic density of dendritic spines.

Receptor-bound urokinase-type plasminogen activator (uPA) remains associated to the surface of human monocytes for many hours. Monocytes induced to migrate in a chemotactic gradient of f-Met-Leu-Phe rapidly polarize their uPA receptors to the leading front of the cells. Receptor-bound enzyme can be inhibited by plasminogen activator inhibitor 2 (PAI-2), with a kinetics comparable to that determined for the free enzyme, and uPA/PAI-2 complexes can bind to the uPA receptor. In contrast to the active enzyme, the uPA/PAI-2 complex is rapidly cleared from the monocyte cell surface; this involves an initial cleavage of the complex at the cell surface, followed by endocytosis and degradation. These results indicate that the uPA receptor can function both to focus plasmin-mediated extracellular matrix degradation in front of migrating cells, and to target uPA/PAI-2 enzyme/inhibitor complexes for degradation; they suggest that this receptor is a key determinant in the control of uPA-catalyzed extracellular proteolysis.

Myoblast migration is crucial for myogenesis and muscular tissue homeostasis. However, its spatiotemporal control remains elusive. Here, we explored the involvement of plasma membrane cholesterol and sphingolipids in this process. In resting C2C12 mouse myoblasts, those lipids clustered in sphingomyelin/cholesterol/GM1 ganglioside (SM/chol/GM1)- and cholesterol (chol)-enriched domains, which presented a lower stiffness than the bulk membrane. Upon migration, cholesterol and sphingomyelin polarized at the front, forming cholesterol (chol)- and sphingomyelin/cholesterol (SM/chol)-enriched domains, while GM1-enriched domains polarized at the rear. A comparison of domain proportion suggested that SM/chol- and GM1-enriched domains originated from the SM/chol/GM1-coenriched domains found at resting state. Modulation of domain proportion (through cholesterol depletion, combined or not with actin polymerization inhibition, or sphingolipid synthesis inhibition) revealed that the higher the chol- and SM/chol-enriched domains, the higher the myoblast migration. At the front, chol- and SM/chol-enriched domains were found in proximity with F-actin fibers and the lateral mobility of sphingomyelin in domains was specifically restricted in a cholesterol- and cytoskeleton-dependent manner while domain abrogation impaired F-actin and focal adhesion polarization. Altogether, we showed the polarization of cholesterol and sphingomyelin and their clustering in chol- and SM/chol-enriched domains with differential properties and roles, providing a mechanism for the spatial and functional control of myoblast migration.

Chemoattractants like f-Met-Leu-Phe (fMLP) induce neutrophils to polarize by triggering divergent signals that promote the formation of protrusive filamentous actin (F-actin; frontness) and RhoA-dependent actomyosin contraction (backness). Frontness locally inhibits backness and vice versa. In neutrophil-like HL60 cells, blocking phosphatidylinositol-3,4,5-tris-phosphate (PIP3) accumulation with selective inhibitors of PIP3 synthesis completely prevents fMLP from activating a PIP3-dependent kinase and Cdc42 but not from stimulating F-actin accumulation. PIP3-deficient cells show reduced fMLP-dependent Rac activity and unstable pseudopods, which is consistent with the established role of PIP3 as a mediator of positive feedback pathways that augment Rac activation at the front. Surprisingly, such cells also show reduced RhoA activation and RhoA-dependent contraction at the trailing edge, leading to the formation of multiple lateral pseudopods. Cdc42 mediates PIP3's positive effect on RhoA activity. Thus, PIP3 and Cdc42 maintain stable polarity with a single front and a single back not only by strengthening pseudopods but also, at longer range, by promoting RhoA-dependent actomyosin contraction at the trailing edge.

Chemotaxis is a process by which cells polarize and move up a chemical gradient through the spatiotemporal regulation of actin assembly and actomyosin contractility, which ultimately control front protrusions and back retractions. We previously demonstrated that in neutrophils, mammalian target of rapamycin complex 2 (mTORC2) is required for chemoattractant-mediated activation of adenylyl cyclase 9 (AC9), which converts ATP into cAMP and regulates back contraction through MyoII phosphorylation. Here we study the mechanism by which mTORC2 regulates neutrophil chemotaxis and AC9 activity. We show that inhibition of protein kinase CβII (PKCβII) by CPG53353 or short hairpin RNA knockdown severely inhibits chemoattractant-induced cAMP synthesis and chemotaxis in neutrophils. Remarkably, PKCβII-inhibited cells exhibit specific and severe tail retraction defects. In response to chemoattractant stimulation, phosphorylated PKCβII, but not PKCα, is transiently translocated to the plasma membrane, where it phosphorylates and activates AC9. mTORC2-mediated PKCβII phosphorylation on its turn motif, but not its hydrophobic motif, is required for membrane translocation of PKCβII. Inhibition of mTORC2 activity by Rictor knockdown not only dramatically decreases PKCβII activity, but it also strongly inhibits membrane translocation of PKCβII. Together our findings show that PKCβII is specifically required for mTORC2-dependent AC9 activation and back retraction during neutrophil chemotaxis.

Abstract The Lupin mine, located in the central Slave province just east of the western boundary of Nunavut Territory, is a world-class example of a Neoarchean-aged banded iron formation (BIF)-hosted lode-gold deposit. At the minesite the gold-mineralized Lupin BIF, separating stratigraphically underlying psammitic wacke and overlying argillaceous turbidite sequences, delineates the Lupin dome, a hammerhead-shaped F2/F3 interference fold structure occurring at the greenschist to amphibolite facies metamorphic transition within the thermal aureole of the Contwoyto batholith. Detailed paragenetic relationships indicate that peak thermal metamorphism coincided with the switch from regional D2 compression to rapid D3 unroofing of the Neoarchean orogenic infrastructure. Gold initially precipitated with pyrrhotite, replacing amphibolitic BIF at the apex of the Lupin deformation zone, separating the east and west lobes of the Contwoyto batholith. Over the course of associated prograde/retrograde metasomatic overprints, gold was further remobilized during garnet and loellingite/arsenopyrite growth in chlorite-altered selvages of late-forming ladder quartz veins. A metamorphic model of ore genesis, with gold being scavenged and transported by metamorphic fluid that was shed and structurally trapped at the amphibolite recrystallization front, is favored over the previously proposed syngenetic and exogenic models of gold concentration that have tended to polarize genetic interpretations to date.

TPS7571 Background: Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) remains the standard of care in pts with previously untreated diffuse large B-cell lymphoma (DLBCL) but outcomes remain poor in pts with high-risk disease. Pola is an antibody–drug conjugate targeting CD79b; it delivers the antimitotic agent monomethyl auristatin E. Addition of pola to bendamustine and R in pts with transplant-ineligible DLBCL resulted in improved OS (Sehn et al, 2018). In front-line treatment of DLBCL, pola is being evaluated as a replacement for vincristine within the R-CHOP regimen. In a phase Ib/II study in pts with higher risk DLBCL, pola + R-CHP demonstrated promising efficacy and a safety profile similar to that observed in the R-CHOP arm of the GOYA study (Tilly et al, 2017; Vitolo et al, 2017). The phase 3 POLARIX study investigates pola + R-CHP in untreated DLBCL. Methods: POLARIX is an ongoing, international, randomized, double-blind, active-placebo-controlled, phase 3 study in pts with previously untreated DLBCL. Pts aged 18–80 years with CD20-positive DLBCL (including DLBCL not otherwise specified, GCB, and ABC subtypes), ECOG performance status 0–2, and IPI score 2–5, are stratified by IPI score (2 vs 3–5), bulky disease and geographical region and randomized (1:1). Pts receive 6 cycles of either: pola 1.8 mg/kg on Day 1 plus R-CHP (standard dosing schedule) plus vincristine placebo; or pola placebo plus R-CHOP (standard dosing schedule). R monotherapy is administered in cycles 7 and 8 (both arms). PET-CT and CT scans are obtained at screening, after 4 cycles (planned interim assessment), and 6–8 weeks after end of study treatment. Follow-up will continue for 5 years after treatment. Primary endpoint: investigator-assessed progression-free survival (PFS; Lugano classification). Secondary endpoints: independent review committee-assessed PET-CT complete response rate at end of treatment, event-free survival, 2-year PFS rate, and OS. Enrolment began Nov 2017. This trial is currently recruiting, and plans to enrol 875 patients in 24 countries. Clinical trial information: NCT03274492.

ABSTRACT There is growing amount of very high resolution polarized scattered light images of circumstellar discs. Nascent giant planets are surrounded by their own circumplanetary discs that may scatter and polarize both the planetary and stellar light. Here, we investigate whether we could detect circumplanetary discs with the same technique and what can we learn from such detections. Here, we created scattered light mock observations at 1.245 microns (J band) for instruments like SPHERE and GPI, for various planetary masses (0.3, 1.0, 5.0, and 10.0 $\rm {\mathrm{ M}_{Jup}}$), disc inclinations (90, 60, 30, and 0 deg), and planet position angles (0, 45, and 90 deg). We found that the detection of a circumplanetary disc at 50 au from the star is significantly favoured if the planet is massive (${\ge} 5 \,\rm {\mathrm{ M}_{Jup}}$) and the system is nearly face-on (≤30°). In these cases, the accretion shock front on the surface of the circumplanetary discs is strong and bright enough to help the visibility of this subdisc. Its detection is hindered by the neighbouring circumstellar disc that also provides a strong polarized flux. However, the comparison between the PI and the Qϕ maps is a viable tool to pinpoint the presence of the circumplanetary disc within the circumstellar disc, as the two discs are behaving differently on those images.

The contractile actin cortex is a thin layer of filamentous actin, myosin motors, and regulatory proteins beneath the plasma membrane crucial to cytokinesis, morphogenesis, and cell migration. However, the factors regulating actin assembly in this compartment are not well understood. Using the Dictyostelium model system, we show that the three Diaphanous-related formins (DRFs) ForA, ForE, and ForH are regulated by the RhoA-like GTPase RacE and synergize in the assembly of filaments in the actin cortex. Single or double formin-null mutants displayed only moderate defects in cortex function whereas the concurrent elimination of all three formins or of RacE caused massive defects in cortical rigidity and architecture as assessed by aspiration assays and electron microscopy. Consistently, the triple formin and RacE mutants encompassed large peripheral patches devoid of cortical F-actin and exhibited severe defects in cytokinesis and multicellular development. Unexpectedly, many forA−/E−/H− and racE− mutants protruded efficiently, formed multiple exaggerated fronts, and migrated with morphologies reminiscent of rapidly moving fish keratocytes. In 2D-confinement, however, these mutants failed to properly polarize and recruit myosin II to the cell rear essential for migration. Cells arrested in these conditions displayed dramatically amplified flow of cortical actin filaments, as revealed by total internal reflection fluorescence (TIRF) imaging and iterative particle image velocimetry (PIV). Consistently, individual and combined, CRISPR/Cas9-mediated disruption of genes encoding mDia1 and -3 formins in B16-F1 mouse melanoma cells revealed enhanced frequency of cells displaying multiple fronts, again accompanied by defects in cell polarization and migration. These results suggest evolutionarily conserved functions for formin-mediated actin assembly in actin cortex mechanics.

ABSTRACT: War tends to polarise national and global conflicts as encapsulated by the phrase, 'you are either with us or against us'. There is further danger of knee jerk reactions at such times, including the present, towards unconditionally funding long-term military security hardware and dedicating scarce resources that are badly needed for more benevolent projects, including equitable redistribution of resources, not to mention the challenge to move away from fossil fuels in our climate crisis. These tensions are evident on recognising European dependence on Russian oil and gas, which unfortunately is helping to fund the ongoing Ukrainian war. This paper will explore how a sample of more contemporary wars and national conflicts have been dramatised on film since the pandemic. Focusing specifically on three contrasting approaches to the tragedy of war and its effects on citizens and soldiers: from an insider's personal response to the massacre in the Balkans during the 1990s in Quo Vadis, Aida? (2020), to the reworked conventional World War One classic All Quiet on the Western Front (2022), before finally coming full circle with the big budget Hollywood celebration of aerial war heroics in the sequel Top Gun: Maverick (2022). Sample textual and contextual analysis will be used to explore how such war narratives have become repurposed, both from an insider soldier's perspective and also through a rejuvenated cinematic war framework, as contemporary audiences strive to cope with ever-increasing crises and conflicts facing the planet, having recently endured a global pandemic.

Persistent directional movement of neutrophils in shallow chemotactic gradients raises the possibility that cells can increase their sensitivity to the chemotactic signal at the front, relative to the back. Redistribution of chemoattractant receptors to the anterior pole of a polarized neutrophil could impose asymmetric sensitivity by increasing the relative strength of detected signals at the cell’s leading edge. Previous experiments have produced contradictory observations with respect to receptor location in moving neutrophils. To visualize a chemoattractant receptor directly during chemotaxis, we expressed a green fluorescent protein (GFP)-tagged receptor for a complement component, C5a, in a leukemia cell line, PLB-985. Differentiated PLB-985 cells, like neutrophils, adhere, spread, and polarize in response to a uniform concentration of chemoattractant, and orient and crawl toward a micropipette containing chemoattractant. Recorded in living cells, fluorescence of the tagged receptor, C5aR–GFP, shows no apparent increase anywhere on the plasma membrane of polarized and moving cells, even at the leading edge. During chemotaxis, however, some cells do exhibit increased amounts of highly folded plasma membrane at the leading edge, as detected by a fluorescent probe for membrane lipids; this is accompanied by an apparent increase of C5aR–GFP fluorescence, which is directly proportional to the accumulation of plasma membrane. Thus neutrophils do not actively concentrate chemoattractant receptors at the leading edge during chemotaxis, although asymmetrical distribution of membrane may enrich receptor number, relative to adjacent cytoplasmic volume, at the anterior pole of some polarized cells. This enrichment could help to maintain persistent migration in a shallow gradient of chemoattractant.

The R-CHOP immunochemotherapy protocol has been the first-line (1L) standard of care (SOC) for diffuse large B-cell lymphoma (DLBCL) patients for decades and is curative in approximately two-thirds of patients. Numerous randomized phase III trials, most of them in an “R-CHOP ± X” design, failed to further improve outcomes. This was mainly due to increased toxicity, the large proportion of patients not in need of more than R-CHOP, and the extensive molecular heterogeneity of the disease, raising the bar for “one-size-fits-all” concepts. Recently, an R-CHP regimen extended by the anti-CD79b antibody–drug conjugate (ADC) Polatuzumab Vedotin proved superior to R-CHOP in terms of progression-free survival (PFS) in the POLARIX phase III trial. Moreover, a number of targeted agents, especially the Bruton’s tyrosine kinase (BTK) inhibitor Ibrutinib, seem to have activity in certain patient subsets in 1L and are currently being tested in front-line regimens. Chimeric antigen receptor (CAR) T-cells, achieving remarkable results in ≥3L scenarios, are being exploited in earlier lines of therapy, while T-cell-engaging bispecific antibodies emerge as conceptual competitors of CAR T-cells. Hence, we present here the findings and lessons learnt from phase III 1L trials and piloting phase II studies in relapsed/refractory (R/R) and 1L settings, and survey chemotherapy-free regimens with respect to their efficacy and future potential in 1L. Novel agents and their mode of action will be discussed in light of the molecular landscape of DLBCL and personalized 1L perspectives for the challenging patient population not cured by the SOC.

Abstract Background Inflammatory bowel diseases (IBD) are chronic inflammatory diseases characterized by abdominal pain, bloody diarrhea, fatigue, weight loss, and diminished quality of life. The morbidity associated with IBD is a result of loss of tolerance towards the gastrointestinal commensal microbiota. The high incidence of IBD in Western societies is inversely correlated with the low incidence of intestinal helminth parasite infections, potentially due to the ability of the helminth parasite to induce tolerance by inducing tolerogenic dendritic cells (tolDC) polarization. Although macromolecules from helminth such as proteins and polysaccharides have been shown to polarize tolDCs, to characterize a novel pathway, in this study we focused on small molecules such as metabolites in the helminth secretome. We hypothesized that helminth-derived metabolites (HDMs) polarize DCs towards a tolerogenic phenotype, which alleviates colitis. Aims To evaluate and characterize the tolerogenic response induced by HDMs in DCs, and its ability to alleviate colitis. Methods Heligmosomoides polygyrus worms were culture for 24 h and HDMs were isolated from conditioned media by chromatography. Bone marrow dendritic cells (BMDCs) were differentiated with GM-CSF for 8 days and then incubated with HDM for 4 h before LPS stimulation for 20 h. Cytokine secretion was measured by ELISA. The transcriptome of DCs treated with HDMs was assessed by RNAseq. Colitis was induced by giving 3% DSS in drinking water for 5 days followed by 3 days of tap water. The anti-colitic effect of HDMs was assessed by daily treatment with HDM or DCs treated with HDM in the 3 days of tap water. Results Pre-treatment with HDM decreased LPS-induced TNF and increased IL-10 release by BMDCs, compared to control BMDCs. Colitic mice treated with HDM presented lower disease activity scores, less colon shortening, decreased weight loss, and healthier histopathology compared to vehicle-treated colitic mice. Importantly, there was an increased frequency of CD11c+ CD103+ DCs in the colon of HDM-treated mice, suggesting that HDM alleviates colitis by increasing the abundance of tolDCs in the colon. Adoptive transfer of HDM-treated DCs also reduced the severity of colitis compared with vehicle-treated mice or mice that received naïve DCs. These results indicate that HDM induced tolerogenic DCs, which in turn ameliorates DSS colitis. RNAseq showed that HDM upregulated 183 and downregulated 76 genes. These differentially expressed genes may indicate a novel mechanism by which helminths induce a tolerogenic profile in DCs. Conclusions HDMs induce tolerogenic DCs and alleviate DSS-induced colitis. Funding Agencies NSERC and FRQNT

During chemotaxis large eosinophils from newts exhibit a gradient of [Ca2+]i from rear to front. The direction of the gradient changes on relocation of the chemoattractant source, suggesting that the Ca2+ signal may trigger the cytoskeletal reorganization required for cell reorientation during chemotaxis. The initial stimulatory effect of chemoattractant on [Ca2+]i and the opposite orientations of the intracellular Ca2+ gradient and the external stimulus gradient suggest that more than one chemoattractant-sensitive messenger pathway may be responsible for the generation of spatially graded Ca2+ signals. To identify these messengers, Ca2+ changes were measured in single live cells stimulated with spatially uniform chemoattractant. On stimulation spatially averaged [Ca2+]i increased rapidly from < or = 100 nM to > or = 400 nM and was accompanied by formation of lamellipods. Subsequently cells flattened, polarized and crawled, and [Ca2+]i fluctuated around a mean value of approximately 200 nM. The initial Ca2+ spike was insensitive acutely to removal of extracellular Ca2+ but was abolished by treatments expected to deplete internal Ca2+ stores and by blocking receptors for inositol-trisphosphate, indicating that it is produced by discharge of internal stores, at least some of which are sensitive to InsP3. Activators of protein kinase C (PKC) (diacyl glycerol and phorbol ester) induced flattening and lamellipod activity and suppressed the Ca2+ spike, while cells injected with PKC inhibitors (an inhibitory peptide and low concentrations of heparin-like compounds) produced an enhanced Ca2+ spike on stimulation. Although cell flattening and lamellipod activity were induced by chemoattractant when the normal Ca2+ response was blocked, cells failed to polarize and crawl, indicating that Ca2+ homeostasis is required for these processes. We conclude that InsP3 acting on Ca2+ stores and DAG acting via PKC regulate chemoattractant-induced changes in [Ca2+]i, which in turn control polarization and locomotion. We propose that differences in the spatial distributions of InsP3 and DAG resulting from their respective hydrophilic and lipophilic properties may change Ca2+ distribution in response to stimulus reorientation, enabling the cell to follow the stimulus.

NATO Defense Education Enhancement Program defines Information Warfare as an operation run to get cognitive assets over the opponents, by controlling one’s own information space while disrupting the opponents’ one. Not new as a process, continuous technological progress has endowed this phenomenon with speed and instruments to fight cyber and cognitive battles, to attack perceptions, trust, polarise and disrupt societies at large. The all present and undergoing kinetic conflict between Russia and Ukraine doubled by an even stronger cognitive and information war since February 2022 has highlighted even more the need to better understand individuals’ behaviour and characteristics when faced with unconventional attacks, irrespective of a passive or active feedback. By identifying and analysing specific public categories, one can establish which are contextual variables that trigger a social reaction, to be able to then design a set of protective or defensive measures. For a full understanding of the way Information Warfare impacts people’s thinking and decision-making process, to see how a resilience plan can be designed, one should investigate not only the information war instruments but also their effects over people at large. Not knowing the voice of the hostile authors, it Is still important to understand the domestic audience and their reaction to it, so that protective actions be taken for resilience and protection, through education. The domestic public’s identity and its dominant characteristics are brought into attention to understand which is the relation between these and the way Information Warfare can be countered through education, with examples from the Russian’s hostile activity. Values, national identity, stereotypes and generalist psychological profiles will be looked at in this paper, to be put in relation to behaviours, attitude change and resistance in front of types of messages, campaigns and types of media-embedded grey zone threats. The present paper is part of a larger PhD research program that focuses on consolidating a society’s security culture through better institutional strategic communication, therefore all the findings will be used to this end.

Zonal tundra vegetation occupies slightly sloped watershed surfaces, weakly convex tops and gentle slopes of moraine hills and ridges with moderate snow cover and loamy soils (plakors). Environmental conditions of such sites are most relevant to macroclimate (Aleksandrova, 1971; Matveyeva, 1998). For the East European sector of the Arctic this vegetation was described in 30–70 years of last century by the Soviet geobotanists V. D. Aleksandrova (1956), ­ V. N. Andreyev (1932), I. D. Bogdanovskaya-Giye­nef (1938), A. A. Dedov (2006), A. E. Katenin (1972), Z. N. Smirnova (1938), who, following the dominant approach, attributed the described associations mainly to the moss vegetation type. In the Asian sector of the Arctic (Yamal and Taymyr peninsulas, Arctic Yakutia, Wrangel Isl.) and in Alaska some associations of zonal communities with Carex bigelowii s. str., C. bigelowii subsp. arctisibi­rica and C. lugens have been described according to Braun-Blanquet approach: Carici arctisibiricae–Hylocomietum alaskani Matveyeva 1994, Dryado integrifoliae–Caricetum bigelowii Walker et al. 1994, Salici polaris–Hylocomietum alaskani Matveyeva 1998, Carici lugentis–Hylocomietum alaskani Sekretareva 1998 ex Kholod 2007, Salici polaris–Sanionietum uncinatae Kholod 2007, Tephrosero atropurpureae–Vaccinietum vitis-idaeae Telyatnikov et Pristyazhnyuk 2012, Festuco brachyphyllae–Hylocomietum alaskani Lashchinskiy ex Telyatnikov et al. 2014. Our study area in the East European tundras (730 km of south–north and 550 km of west–east directions) covers 3 tundra subzones (arctic, typical and southern) and two floristic subprovinces (Kanin-Pechora and Ural-Novaya Zemlya) (Fig. 1). 7 associations (one with 5 subassociations) based upon 101 authors’ relevés as well 95 ones by geobotanists-predecessors were described or validated on plakors and habitats close to these. Zonal communities are comprised by thick multi-species moss layer formed by mesophylous bryophytes (Aulacomnium turgidum, Hylocomium splendens, Ptilidium ciliare, Racomitrium lanuginosum and Tomentypnum nitens), the presence of Carex bigelowii subsp. arctisibirica, Deschampsia borealis or D. glauca in the herb layer, the high abundance of dwarf-shrubs, the presence, but not always, of Dryas octopetala and shrubby willows. Their plant cover is closed or discontinuous with frost-boils (3-component module of patch of bare ground – rim – trough or 2-component one of flat surface – patches of bare ground — see Fig. 2, 3). Zonal syntaxa are the richest in species number, compare to all others because the placor habitats are moderate in such important environmental characters as moisture and nutrition of soil and snow depth. That’s why they contain, with the same constancy and sometimes abundance, some character species of alliances and classes of intrazonal vegetation: Kobresio-Dryadion Nordh. 1943 (dryad fell-fields on well drained snowless or poor snowy habitats with slightly carbonated loamy-gravelly soils at outcrops of bedrock) and Carici rupestris–Kobresietea bellardii Ohba 1974, Loiseleurio-Arctostaphylion Kalliola ex Nordhagen 1943 (dwarf-shrub and dwarf-shrub-lichen (often with Betula nana) communities on sandy soils) and Loiseleurio procumbentis–Vaccinietea Eggler ex Schubert 1960, Rubo chamaemori–Dicranion elongati Lavrinenko et Lavrinenko 2015 (dwarf-shrub-cloudberry-moss (Dicranum elongatum, Polytrichum strictum)-lichen communities of oligotrophic palsa and polygon peatlands) and Oxycocco-Sphagnetea Br.-Bl. et Tx. ex Westhoff et al. 1946. The basic syntaxon, whose communities occupy the placor habitats in the arctic tundra subzone (southern­ variant) is Salici polaris–Polytrichetum juniperini Aleksandrova 1956, described on the Southern Island of Novaya Zemlya (Table 1). Similar syntaxa in the typical tundra subzone are Carici arctisibiricae–Hylocomietum splendentis Andreyev 1932 nom. mut. propos. hoc loco (Table 5, Fig. 14–17) and Dryado octopetalae–Hylocomietum splendentis Andreyev 1932 nom. mut. propos. hoc loco salicetosum nummulariae (Bogdanov­skaya-Giyenef 1938) subass. nov. (stat. nov.), nom. corr. hoc loco, described by us and earlier by I. D. Bogdanov­skaya-Giyenef (1938) and Z. N. Smirnova (1938) on the Kolguyev Isl. (Table 2, Fig. 3, 5, 6); D. o.–H. s. caricetosum redowskianae subass. nov. hoc loco and D. o.–H. s. caricetosum arctisibiricae (Koroleva et Kulyugina in Chytrý et al. 2015) subass. nov. (stat. nov.) hoc loco (Table 4, Fig. 4, 9–13) — in the most eastern part of the studied area (Vaygach Isl., Yugorskiy Peninsula and Pay-Khoy Range); D. o.–H. s. typicum subass. nov. hoc loco (Tab­le 3), described by us with use the V. N. Andreyev (1932) relevés on Vangureymusyur Upland (Bolshezemelskaya tundra). In the southern tundra subzone the basic zonal association is Calamagrostio lapponicae–Hylocomietum splenden­tis ass. nov. hoc loco (Table 6, Fig. 20–22). Even small deviations from placor habitat conditions are reflected in the community species composition. In such habitats the following syntaxa are described: Deschampsio borealis–Limprichtietum revolventis Aleksandrova 1956 nom. mut. propos. hoc loco and Flavocet­rario nivalis–Dryadetum octopetalae Aleksandrova 1956 nom. mut. propos. hoc loco on gentle slopes and loamy soils, not in moderate soil moisture, but in wet or, on the contrary, well-drained ecotopes on the Novaya Zemlya (Table 1); Dryado octopetalae–Hylocomietum splendentis caricetosum capillaris subass. nov. hoc loco — on the deluvial tails, in the mid and lower parts of the gentle slopes in Bolshezemelskaya and Malozemelskaya tundras (Table 4, Fig. 2, 7, 8); Oxytropido sordidae–Hylocomietum splendentis ass. nov. hoc loco — in the Pakhancheskaya Bay area (the northern part of the Bolshezemelskaya tundra) on strongly sloping well drained slopes (Table 6, Fig. 18, 19). We attributed these syntaxa to zonal vegetation due to the presence of such taxa of its differential combination as shrub Salix glauca, dwarf-shrub Salix polaris, herbs Bistorta major, Carex bigelowii subsp. arctisibirica, Deschampsia borealis, D. glauca, Eriophorum brachyantherum, Juncus biglumis, Luzula arcuata, Pedicularis lapponica, Petasites frigidus, Poa arctica, Saxifraga hieracifolia, S. hirculus, Stellaria peduncularis, Valeriana capitata, mosses Aulacomnium turgidum, Hylocomium splendens, Ptilidium ciliare, Racomitrium lanuginosum, Tomentypnum nitens and lichens Lobaria linita, Nephroma expallidum, Protopannaria pezizoides, Psoroma hypnorum. This combination of taxa differentiates (by the presence, constancy, abundance) the zonal communities in studied area from vegetation of other classes (Carici rupestris–Kobresietea bellardii, Loiseleurio procumbentis–Vaccinietea, Oxycocco-Sphagnetea) (Table 7). The borders of many species area distribution are held in the East European tundras, so the variation of the community species composition along the latitudinal and longitude gradients is quite natural. Thus, in zonal communities Ledum palustre subsp. decumbens and Salix phylicifolia occur and Betula nana as well as hypoarctic dwarf-shrubs Arctous alpina, Empetrum hermaphroditum, Vaccinium uliginosum subsp. microphyllum­ and V. vitis-idaea subsp. minus are most active only in the southern tundra subzone; Salix polaris (its activity increases to the north) and, in some syntaxa, Dryas octopetala are common in the subzones of typical and arctic tundras. In zonal conditions shrubs Salix glauca, Betula nana (prostrate) and all hypoarctic dwarf-shrubs occur in the typical tundra subzone on the mainland and on Kolguyev Isl., while in the northern part of this subzone on Vaygach Isl. they are already absent, ­except the Vaccinium spp. (with low constancy). In the arctic tundra subzone there are no shrubs and hypoarctic dwarf-shrubs on plakors, while Salix polaris is abundant. We believe that these floristic differences of zonal communities can be considered as markers of their subzonal affiliation. A similar shift in species distribution on the latitudinal gradient is established (Matveyeva, 1998) for the zonal biotopes on Taymyr Peninsula. Some species (Arctagrostis latifolia, Cerastium regelii subsp. caespitosum, Saxifraga oppositifolia, Silene acaulis) have high constancy in zonal communities within the Ural-Novaya Zemlya subprovince, as opposed to the Kanin-Pechora one. Herbs Oxyria digyna, Papaver polare, Parrya nudicaulis, Pedicularis sudetica subsp. arctoeuropaea, Saxifraga cernua and S. cespitosa occur with high constancy only in zonal communities on Novaya Zemlya that brings them closer to syntaxa described in the arctic and typical tundra subzones on Taymyr Peninsula (Matveyeva, 1994, 1998). Already in 1994, N. V. Matveyeva stated the need to describe a new class for zonal vegetation. The name Carici arctisibiricae–Hylocomietea alaskani cl. prov. has been reserved for this class in Yalta’s conference on the classification of Russian vegetation (Lavrinenko et al., 2016), Prague’s “Circumpolar Arctic Vegetation Archive and Classification Workshop” (presentation by N. V. Matveyeva) and “Arctic Science Summit Week 2017” (Lavrinenko et al., 2017). We do not attribute the newly described syntaxa to alliance Dryado octopetalae–Caricion arctisibiricae Koroleva et Kulyugina in Chytrý et al. 2015, which was described at the base of 15 relevés by geobotanists-predecessors (V. N. Andreyev, A. A. Dedov) and as well the 11 ones by E. E. Kulyugina for zonal habitats in the East European tundras (Koroleva, Kulyugina, 2015). At least, it is necessary to revise this alliance, since the name of ass. Pediculari oederi–Dryadetum octopetalae (Andreev 1932) Koroleva et Kulyugina 2015 are not legitimate (nomen superfluum), ass. Salici reticulatae–Dryadetum octopetalae Koroleva et Kulyugina 2015 need to be revised and the rank of the third one (Dryado octopetalae–Caricetum arctisibiricae Koroleva et Kulyugina in Chytrý et al. 2015 was lowered by us (in this paper) to subass. Dryado octopetalae–Hylocomietum splendentis caricetosum arctisibiricae; the definitions of both vegetation and habitats are not quite appropriate to the nature reality; diagnostic species were selected randomly. The current position of this alliance within the Carici rupestris–Kobresietea bellardii is debatable, because this makes vague the syntaxonomical content and expands the syntaxonomical boundaries of class whose communities occur in the intrazonal habitats (fell-fields and dwarf-scrub graminoid stands on base-rich substrates). New higher units of zonal vegetation with sedges Carex bigelowii subsp. arctisibirica, C. bige­lowii s. str. and C. lugens, and, most likely, with cotton grass Eriophorum vaginatum, need to be described in the near future, since the data for this are available from various sectors of the Arctic.

The syntaxonomical study of Wrangel Island carried out in accordance to Braun-Blanquet approach is proposed. As a result 29 associations, 1 type of com­munity, 18 subassociations, 8 variants and 5 facies are distinguished. A series of associations belong to 13 allian­ces, 12 orders and 9 classes which were des­cribed earlier (some of them are provisional). The procedure of classification have showed some metho­dical difficulties. One of them is the revealing of be­longing syntaxa to any class, a lot of which were described in more south regions. As a result much of diagnostic species of these classes are absent in arctic regions. So far as many species of Arctic characterized by wide distribution they cannot be used as character species. The concept of vicariant syntaxa is used: 5 associations are considered as vicariants of syntaxa already distinguished. At present there are not any higher syntaxa (class) for correct description for zonal (plakor) vegetation, erect shrubs and zoogenic vege­tation in arctic tundra subzone. The syntaxa of Carici rupestris—Kobresietea bellardii and Thlaspietearotun­difolii predominate in island. There are north limits of areas of some syntaxa such as ass. Sphagno—Eriopho­retum vaginati vic. Polytrichastrum alpinum, Bra­chy­thecio salebrosi—Salicetum glaucae, Parryo nudicau­lis—Salicetum lanatae, Equisetetum borealis vic. Polemonium acutiflorum on Wrangel Island. Zonal associations are characterized by lowest number of character species (2—4). The reason of this pheno­mena is the average meaning of ecological parameters in plakors. As a consequence many species of different ecological groups can growth together. There are fr om 9 to 17 character species in some intrazonal associa­tions: Carici membranaceae—Dryadetum integri­foliae, Castillejo elegantis—Caricetum rupestris, Salici calli­carpaeaе—Dryadetum chamissonis, Arte­misio borea­lis—Chamaenerietum latifolii. Following associations of plakor are characterized by the highest species richness: Parryo nudicaulis—Dryadetum punctatae (255 taxa) and Artemisio ti­lesii—Deschampsietum borealis (250). Besides these the ass. Salici polaris—Caricetum podocarpae which is formed in snowbed sites have 251 taxa. A lot of species have middle (III) or low (II, I) constancy. The higher number of species in syntaxa compared to community is due to rare species. The coverage of majority of species varies from <1 % to 5 %, not more than 10 species — from 6 % to 12 %. Only 3 species form an stable coverage more than 25 %: Carexlugens, Dryaspunctata, D. inte­grifolia. Two types of community are characterized by the homogeneous cover: ass. Meesio triquetris—Caricetum stantis vic. Warnstorfia sarmentosa and ass. Salici polaris—Caricetum podocarpae. The tundra turf is heterogeneous in zonal (plakor) communities. It consists of different fragments of mosses, lichens and vascular plants. Frost boils (patches) are most common elements of horizontal structure. The turf around patches forms continuous net. Non closed (open) communities are predominate at all slopes, tops and mountain terraces. Cushions formed by herbs Artemi­siaborealis subsp. richardsoniana, A. glo­merata, Oxytropisgorodkovii, Potentillasubvahliana are usual in such sites. There are 2 layers in com­munities: an upper one (10—30 cm) wh ere herbs are predominate and dwarf shrubs-lichen-moss (less than 10 cm). The height of shrub Salixlanata subsp. richard­sonii layer at the center of island is 45—60 cm.

Abstract Carcinoma dissemination can occur when heterogeneous tumor and tumor stromal cells clusters migrate together via collective migration. Cells at the front lead and direct collective migration, yet how these leader cells form and interact with the microenvironment to direct migration are not fully appreciated. From live videos of primary mouse and human breast tumor organoids in a 3D microfluidic system that mimics the native breast tumor microenvironment, we developed 3D computational models. These hypothesize that for leader cells to polarize to the leading edge and lead directed collective migration they need to generate high protrusive forces and overcome extracellular matrix (ECM) resistance. From scRNAseq of migrating primary tumor organoids, we identify significant K14+ “leader” cell heterogeneity that differs depending upon the environmental signal. We isolate a unique Cadherin-3 (Cdh3) positive leader cell subpopulation that is necessary and sufficient to lead collective migration. Cdh3 controls leader cell protrusion dynamics through controlling the local production of Laminin-332 which is required for integrin/focal adhesion function. Loss of Cdh3 expression in mouse and human primary breast tumor organoids and invasive breast tumor cell lines significantly impairs directed collective migration. In the absence of leader cell Cdh-Cdh3 intercellular adhesions there is reduced cellular β-catenin levels and Laminin 332 production. In syngeneic, orthotopic transplant mouse models, Cdh3 depletion in tumor cells resulted in decreased laminin 332 production at the invasive edge of primary tumors and decreased lung metastasis. Chromatin Immunoprecipitation experiments revealed that in contacted cells β-catenin and TCF4 are present on Lam α3, β3, and γ2 promoter regions. Laminin 332 production by leader cells was required for optimal Integrin/FA function and cellular protrusion stability. These results indicated that in leader cells local Cdh3-Cdh3/β-catenin regulated Laminin 332 production controls protrusion dynamics and overcomes resistance to ECM to lead directed collective tumor migration. Our findings highlight how a unique subset of leader cells in breast tumors interact with the microenvironment to direct collective migration. Citation Format: Yanyang Cao, Priscilla Y. Hwang, Maria Clarke, Jose Almeida, Amit Pathak, Gregory D. Longmore. A Cdh3 - Lam332 signaling axis by a unique subset of leader cells controls breast tumor organoid protrusion dynamics and directed collective migration [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2423.

Abstract Background Parasitic helminths are known to modulate host immune responses. This is thought to be mediated by their secretome. We are interested in the excretory/secretory products and mechanisms for modulating immune dysfunction in autoinflammatory diseases. Aims This research studies the mechanisms of immune modulation by parasitic helminths in the context of IBD. We aim to describe immunomodulatory helminth-derived metabolites (ESM). Methods Helminth-conditioned media was used to isolate ESM, which were further purified using column chromatography. Bone marrow (BM) derived macrophages (BMDM) from C57BL6 mice, were treated with ESP fractions from Trichuris suis, Ascaris suum, Heligmosomoides polygyrus bakeri or Dirofilaria immitis, stimulated with LPS, and secreted cytokine levels measured. Moreover, BM was cultured with or without ESM throughout differentiation to BMDM. Colitic mice (3% DSS, 5 days) were treated with A. suum ESM or PBS once daily IP. Colon lengths and TNFα mRNA were measured, and histological preparations were scored to assess pathology. Bioactive D. immitis ESM were fractionated using preparatory HPLC and assayed for bioactivity. Active fractions were analysed using MS/MS and fragmentation patterns and molecular weights were obtained. The active fractions are currently being studied by NMR to deduce a structure of an active metabolite. Results BMDM treated with crude ESM decreased TNFα secretion and increased IL-10. BMDM precursors which were treated with A. suum ESM throughout differentiation had reduced proliferation in a dose dependent manner. These BMDM showed remodeling of BMDM metabolic pathways. Intracellular ROS production was inversely proportional to Alamar blue oxidation. We found that ESM from A. suum improved DSS-colitis. Specifically, mice with DSS-induced colitis given IP ESM had longer colons, lower histolopathology score, and lower TNFα mRNA expression in gut tissue. HPLC-fractionated D. immitis ESM used to treat BMDM yielded varying suppression of TNFα with LPS stimulation. MS/MS of TNFα suppressive fractions contained masses with fragmentation patterns which were detected in fractions of several of the above-mentioned parasite species. Preliminary NMR studies will determine if this represents a conserved structure. Conclusions Helminth-derived components can immunologically polarize a response in vitro, as well as favour recovery in DSS colitis. Through multiple purification steps, a nearly pure fraction is found to have bioactivity, suggesting a single, bioactive molecule that is conserved across several parasitic helminths. These data are important in understanding the host-parasite interaction modulated by ESM, as well as provide therapeutic potential in IBD. Funding Agencies NSERC, FRQNT

The results of the study of vegetation of the extreme northern point of the Novaya Zemlya archipe­lago, the vicinity of Cape Zhelaniya, which belongs to the southern variant of the polar desert zone, are represented. On the basis of 150 relevés, 20 syntaxa of the floristic classification of the several ranks (6 associations, 1 community type, 4 subassociations, 9 variants) were identified. Zonal vegetation belongs to the ass. Saxifrago oppositifoliae–Cerastietum regelii ass nov. hoc loco (Table 1, nomenclature type (holotypus hoc loco) — relevé 12; field number 68, Novaya Zemlya archipe­lago, Severnyy Island, Cape Zhelaniya area, 5.8 km to south-west of Pospelov Bay, loamy terrace plateau, 76°53ʹ31ʺ N, 68°20ʹ55ʺ E, August 26, author — S. S. Kholod; Table 8, syntaxon 1) within the class Drabo corymbosae–Papaveretea dahliani Daniёls, Elvebakk et Matveyeva in Daniёls et al. 2016 (Daniёls et al., 2016). Within the ass. Saxifrago oppositifoliae–Cerastietum regelii 2 subassociations and 2 variants are described. Subass. S. o.–C. r. typicum subass. nov. hoc loco (Table 1, relevés 1–14, nomenclature type (holotypus hoc loco) of the subassociation — relevé 12, Fig. 2). Subass. S. o.–C. r. cetrarielletosum delisei subass. nov. hoc loco (Table 1, relevé 15–36, nomenclature type (holotypus hoc loco) — relevé 20, field number 79, Novaya Zemlya archipelago, Severnyy Island, Cape Zhelaniya vicinity, the coastal part of Natalia Bay, the mouth of the river Grishina Shara, gentle slope to the seashore, loamy-gravelly, 76°50ʹ26ʺ N, 68°44ʹ55ʺ E, August 29, 2015, author — S. S. Kholod) with 2 variants: S. o.–C. r. c. d. typica (Table 1, relevés 15–31; Fig. 3) and S. o.–C. r. c. d. inops (Table 1, relevés 32–36; Fig. 4). The vegetation of wet sites is presented in 2 syntaxa. Ass. Deschampsio borealis–Bryetum pseudotriquetri ass. nov. hoc loco (Table 2, nomenclature type (holotypus hoc loco) — relevé 9, field number 160, Novaya Zemlya archipelago, Severnyy Island, Cape Zhelaniya vicinity, near Cape Serebrennikov, wet, sea side strip, 76°57ʹ31ʺ N, 68°19ʹ44ʺ E, September 16, 2015, author — S. S. Kholod; Table 8, syntaxon 2), in the drainage gullies. Ass. Deschampsio borealis–Bryetum pseudotriquetri is divided into 2 variants: D. b.–B. p. typica (Table 2, relevés 1–10; Fig. 5) and D. b.–B. p. inops (Table 2, relevés 11–15; Fig. 6). Ass. Campyliostellati–Orthothecie­tum chrysei ass. nov. hoc loco (Table 3, nomenclature type (holotypus hoc loco) — relevé 2, field number 57, Novaya Zemlya archipelago, Severnyy Island, Cape Zhelaniya vicinity, 4.2.km to the south of Cape Loshkin, 76°57ʹ03ʺ N, 68°07ʹ49ʺ E, August 24, 2015, author — S. S. Kholod; Table 8, syntaxon 3) on loamy areas with periodic stagnation of water. Ass. Campyliostellati–Orthothecietum chrysei includes 3 variants: C. s.–O. c. typica (Table 3, relevés 1–13; Fig. 7), C. s.–O. c. Racomitrium lanuginosum (Table 3, relevés 14–26; Fig. 8), C. s.–O. c. Allocetraria madreporiformis (Table 3, relevés 27–30; Fig. 9). The vegetation of nival sites is reflected in two syntaxa. Ass. Stellario edwardsii–Ditrichetum flexicaulis ass. nov. hoc loco (Table 4, nomenclature type (holotypus hoc loco) — relevé 8, field number 1, Novaya Zemlya archipelago, Severnyy Island, Cape Zhelaniya vicinity, 2.5 km to the south of Cape Elizabeth, on the front of a small terrace edge on the sea side plain, small rock, 76º56ʹ39″ N, 68º17ʹ53″ E, August 15, 2015, author — S. S. Kholod; Table 8, syntaxon 4; Fig. 10). Ass. Dicranoweisio crispulae–Cetrarielletum delisei Matveyeva 2006 subass. cerastietosum regelii subass. nov. hoc loco (Table 5, nomenclature type (holotypus hoc loco) — relevé 6, field number 41, Novaya Zemlya archipelago, Severnyy Island, Cape Zhelaniya vicinity, 6.3 km to the south of Cape Elizabeth, the fine-stony slope of the terrace on the coastal plain, 76°54ʹ52ʺ N, 68°10ʹ02ʺ E, August 22, 2015, ­author — S. S. Kholod; Table 8, syntaxon 5). There are 2 variants in subass. Dicranoweisio crispulae–Cetrarielletum delisei cerastietosum regelii: D. c.–C. d. c. r. typica (Table 5, relevés 1–19, Fig. 11), D. c.–C. d. c. r. inops (Table 5, relevés 20–27, Fig. 12). Vegetation of dry moderately and low snow-covered sites is presented by the 2 syntaxa. Ass. Pseudephebo pubescentis–Bryocauletum divergentis Kholod 2007 subass. saxifragetosum cespitosae subass nov. hoc loco (Table 6, nomenclature type (holotypus hoc loco) — relevé 15, field number 152, Novaya Zemlya archipelago, Severnyy Island, Cape Zhelaniya vicinity, 1.0 km to the south-east of Cape Serebrennikov, rocky ridge on the coastal plain, 76°56ʹ 50″N, 68°25ʹ45ʹʹ E, September 15, 2015, author — S. S. Kholod; Table 8, syntaxon 6; Fig. 13). Community type Papaver polare–Saxifraga oppositifolia (Table 7; Table 8, syntaxon 7, Fig. 14) which combines extremely sparse cover of vascular plants, mosses and lichens. The associations Dicranoweisio crispulae–Cetrarielletum delisei and Pseudephebo pubescentis–Bryocauletum divergentis can be considered as regional, which include subassociations described elsewhere in relation to where the typical syntaxa have been described. The zonal association of the Novaya Zemlya — Saxifrago oppositifoliae–Cerastietum regelii, has a number of common diagnostic species combinations to the ass. Deschampsio borealis–Aulacomnietum turgidi (Table 8, syntaxon 8) of the Se­vernaya Zemlya (Draba micropetala, Papaverpolare, Phippsiaalgida, Saxifragacernua and others) may be put in Papaverion dahliani Daniёls, Elvebakk et Matveyeva in Daniёls et al., 2016. Similarly, two associations of wet sites from these two archipelagos can be placed in one union: the Deschampsio borealis–Bryetum pseudotriquetri of the Novaya Zemlya and Stellario edwardsii–Bryetum cryophili Matveyeva 2006 (Table 8, syntaxon 10) of the Severnaya Zemlya. These associations bring together several common species: Phippsiaalgida, Bryumcryophilum, Warnstorfiasarmentosa. Probably, associations reflecting the vegetation of nival sites — Dicranoweisio crispulae–Cetrarielletum delisei Matveyeva 2006 with two subassotiations: typicum (Table 8, syntaxon 13) and cerastietosum regelii (together — regional association), Stellario edwardsii–Ditrichetum flexicaulis of Novaya Zemlya and Ranunculo sabinei–Phippsietum algidae Matveyeva 2006 (Table 8, syntaxon 12) of Severnaya Zemlya — can be attributed to one union. These syntaxa bring together a number of common species included in the diagnostic groups: Papaverpolare, Phippsiaalgida, Niphotrichumericoides, Polytrichastrum alpinum s. str., Cetrarielladelisei and others. In all groups of characteristic species, only 3 — are exclusive — Deschampsiaborealis, Calliergongiganteum, Cinclidiumsubrotundum, inherent to ass. Deschampsio borealis–Bryetum pseudotriquetri, and 16 — are selective. Species richness in syntaxa varies from 62 to 126. The highest number of species is recorded in the ass. Campylio stellati–Orthothecietum chrysei, the lowest — in the extremely sparse cover of the com. type Papaver polare–Saxifraga oppositifolia. The number of taxa in communities varies from 4 to 37. The proportion of the species number with high constancy (IV, V) in all syntaxa is extremely small and varies from 6.5 % in com. type Papaver polare–Saxifraga oppositifolia up to 14.3 % in the ass. Stellario edwardsii–Ditrichetum flexicaulis. Only few species have a high coverage. In general, these are mosses: Scorpidiumrevolvens (up to 40 %), S. cossonii, Ditrichumflexicaule, Racomitriumlanuginosum, Niphotrichumericoides, which in some cases form carpets with of 15–20 % cover. The same cover value is inherent for some species of lichens — Brodoaintestiniformis and Melaneliahepatizon. The high cover values among vascular plants are noted only for Deschampsiaborealis (to 65 %). There are 2 main types of plant-cover structure: regular-cyclic and sporadic-spotty. As part of the first variant are separated: connected and broken-reticulated. Many plants have the form of cushion: up to 8–9 cm in a height and to 10–12 cm in a diameter. There is a single layer which has (an average height of 10 cm) in vertical structure.

Abstract Background Parasitic helminths Trichuris suis and Ascaris suum are known to modulate host immune responses. This is thought to be mediated by the secretome, or excreted factors released by these parasites. We are interested in the excretory/secretory products (ESP, TsESP and AsESP) and mechanisms responsible for modulating immune disfunciton in autoinflammatory diseases. Aims This research studies the mechanisms of immune modulation by parasitic helminths in the context of IBD. We aim to describe the cellular response in vitro, as well as the systemic response in vivo, to better characterize the scope of immune modulation in ESP treatment. Methods ESPs were collected from T. suis or A. suum-conditioned media and proteins and metabolites were isolated. Bone marrow (BM) derived macrophages (BMDM) from C57BL6 mice, were treated with ESP fractions, stimulated with LPS, and secreted cytokines levels measured. Alternatively, undifferentiated BM was incubated with or without metabolites throughout the process of differentiation. Using a DSS-colitis model, mice were given 3% DSS or water, then treated with ESP or PBS once daily by IP injection. Colon lengths and TNFα mRNA levels were measured and histological preparations were scored to assess pathology. ESP with bioactivity were selected for further HPLC analysis. Fractions were collected and assayed for bioactivity. Results BMDM treated with T. suis or A. suum crude ESP decreased secretion of TNFα and increased IL-10. BMDM precursors incubated with A. suum metabolites during differentiation had fewer BMDM-like cells. Cytokine analysis showed decreased TNFα secretion. Experiments with Alamar suggested that metabolites remmodelled the BMDM metabolic pathways. These effects are being explored further. We found that metabolites released by A. suum improved DSS-colitis. Specifically, mice with DSS-induced colitis given IP metabolites had reduced colon shortening compared to PBS controls, a lower histologic damage score, as well as lower levels TNFα mRNA expression in gut epithelial cells. HPLC showed multiple peaks from crudes analyzed at 210 nm and 280 nm. HPLC fractions used to treat BMDM yielded varying secretion of TNFα. Bioactive fractions from HPLC coincide with the UV/Vis peaks, further suggesting they could be isolated and studied for immunomodulation. Conclusions These data suggested that ESP contains immunomodulators that may provide lead therapeutic compounds for patients with IBD. Helminth-derived components can immunologically polarize a response in vitro, as well as alter disease recovery in DSS colitis. HPLC fractionation and biological testing suggest that a bioactive molecule can be obtained. Further analysis must be done to determine structure using mass spectrometry and NMR analysis. Funding Agencies Natural Sciences and Engineering Research Council of Canada (NSERC) and Fonds de recherche nature et technologies Québec (FRQNT)

Acute myeloid leukemia (AML) is characterized by clonal proliferation of neoplastic myeloid precursor cells resulting in impaired hematopoiesis. Despite initial responses to intensive induction therapy, relapses are frequent and most patients die in less than 5 years (National Cancer Institute 2015). Nucleoside analogues represent an important category of anti-leukemic cytotoxic drugs. Cytarabine (Ara-C) is the most active drug against AML; azacitidine and decitabine are active treatments of myelodysplastic syndrome (MDS) and AML. Sapacitabine is a novel, orally bioavailable nucleoside analogue with a unique ability to induce single-strand DNA breaks after incorporation into DNA, leading eventually to production of double-strand DNA breaks and/or G2 cell cycle arrest. In phase 1 and 2 clinical trials, sapacitabine has induced complete remission (CR), CR with incomplete platelet count recovery (CRp), partial remission (PR), and major hematological improvement (HI) in patients with AML and MDS. A subset of these responding patients were previously treated with other nucleoside analogues, suggesting that the anti-leukemic activity of sapacitabine is not limited by resistance to other nucleoside analogues (Kantarjian H et al, JCO, 2010, ASH, 2013). Two clinical studies have demonstrated the synergistic activity of venetoclax in combination with hypomethylating agents or low-dose ara-C in newly diagnosed AML, leading to its recent approval by the FDA for the front-line treatment of this disease. The synergy between venetoclax and cytotoxic therapy in AML models is mediated by combined targeting of the anti-apoptotic BCL2 and MCL1 mechanisms (Teh T-C et al, Leukemia, 2018). Cytotoxic drugs induce apoptosis through genotoxic damage, TP53 activation and increased expression of pro-apoptotic NOXA and PUMA (Villunger A et al, Science, 2003) - features that have also been demonstrated for sapacitabine (Green S et al. Br J Cancer 2010). Although most cytotoxic agents do not directly affect MCL1 levels, increased levels of the pro-apoptotic NOXA and PUMA proteins can inactivate MCL1 to synergize with venetoclax to induce apoptosis. The combination of CNDAC (2'-C-cyano-2'-deoxy-1-β-D-arabino-pentafuranosylcytosine), the active metabolite of sapacitabine, and BCL2 inhibitor ABT737 was studied in AML cell line MV-411. A synergistic increase in apoptosis induction was observed when CNDAC and ABT737 were combined (Frame S. et al, 14th EHA, 2009, Abs 0761). The above findings support the conduct of a clinical study (NCT01211457) evaluating a combination of sapacitabine with venetoclax in patients with relapsed/refractory AML and MDS. This is an entirely oral treatment regimen. The primary objective is to evaluate the safety and efficacy of two dosing schedules of sapacitabine given concomitantly with venetoclax: twice daily for 5 consecutive days or twice daily for 3 consecutive days per week for 2 weeks. One treatment cycle is 4 weeks. Dose will be escalated in increments of 50 mg twice daily. RP2D is the highest dose level at which ≤2 of 6 patients experience a dose-limiting toxicity during the first 2 treatment cycles. Eligible patients are ≥18 years with previously treated AML or MDS and ≥10% blasts in bone marrow or peripheral blood; adequate bone marrow, renal and liver functions are required. Treatment will continue until progression of disease, unacceptable toxicity or changes in patient condition that renders patients ineligible for further treatment. Laboratory tests and bone marrow aspirate/biopsy will be performed to assess responses according to standard criteria. Disclosures Kadia: Bioline RX: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Research Funding; Celgene: Research Funding; Jazz: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding. Borthakur:Agensys: Research Funding; BMS: Research Funding; Oncoceutics, Inc.: Research Funding; PTC Therapeutics: Consultancy; Eli Lilly and Co.: Research Funding; Janssen: Research Funding; Merck: Research Funding; Polaris: Research Funding; Strategia Therapeutics: Research Funding; Tetralogic Pharmaceuticals: Research Funding; Eisai: Research Funding; Xbiotech USA: Research Funding; Novartis: Research Funding; Oncoceutics: Research Funding; BioLine Rx: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Arvinas: Research Funding; AbbVie: Research Funding; Incyte: Research Funding; AstraZeneca: Research Funding; Bayer Healthcare AG: Research Funding; Argenx: Membership on an entity's Board of Directors or advisory committees; FTC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Cantargia AB: Research Funding; GSK: Research Funding; Cyclacel: Research Funding; BioTheryX: Membership on an entity's Board of Directors or advisory committees; NKarta: Consultancy. Jabbour:Pfizer: Consultancy, Research Funding; Cyclacel LTD: Research Funding; AbbVie: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Adaptive: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding. Konopleva:Kisoji: Consultancy, Honoraria; Ascentage: Research Funding; Genentech: Honoraria, Research Funding; F. Hoffman La-Roche: Consultancy, Honoraria, Research Funding; Agios: Research Funding; Astra Zeneca: Research Funding; Ablynx: Research Funding; Reata Pharmaceuticals: Equity Ownership, Patents & Royalties; Eli Lilly: Research Funding; Forty-Seven: Consultancy, Honoraria; Stemline Therapeutics: Consultancy, Honoraria, Research Funding; Calithera: Research Funding; Amgen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Cellectis: Research Funding. Ravandi:Macrogenix: Consultancy, Research Funding; Selvita: Research Funding; Menarini Ricerche: Research Funding; Xencor: Consultancy, Research Funding; Cyclacel LTD: Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. DiNardo:celgene: Consultancy, Honoraria; medimmune: Honoraria; agios: Consultancy, Honoraria; jazz: Honoraria; syros: Honoraria; daiichi sankyo: Honoraria; abbvie: Consultancy, Honoraria; notable labs: Membership on an entity's Board of Directors or advisory committees. Zheleva:Cyclacel Ltd: Employment, Equity Ownership, Patents & Royalties. Blake:Cyclacel Ltd: Employment, Equity Ownership, Patents & Royalties. Chiao:Cyclacel Ltd: Employment, Equity Ownership, Patents & Royalties.

Introduction Since the advent of tyrosine kinase inhibitors (TKIs) in 2001, the treatment goals in the management of chronic myeloid leukemia (CML) have evolved according to international recommendations. The 2009 European LeukemiaNet (ELN) proposed a category of "suboptimal response". The 2013 recommendations introduced a "warning response" category that saw some "suboptimals" in 2009 becoming failures in 2013. The clinical implications of this intermediate category and the difference in categorizations has not been fully explored. As new recommendations are being prepared, we seek to compare the outcomes of patients with suboptimal/warning using 2009 and 2013 guidelines. Methodology We analyzed 730 patients treated with front-line TKIs in various clinical trials and identified patients who meet the criteria for suboptimal response at 3, 6 and 12 months according to the 2009 ELN guidelines and/or warning criteria according to 2013 ELN criteria. We computed descriptive statistics for patients at each of the above criteria at the 3 time points. Kaplan-Meier product limit method, was used to estimate the median for overall survival (OS), event-free survival (EFS), failure-free survival (FFS) and transformation-free survival (TFS). Results Of the 730 CML patients evaluated, using the 2009 ELN guidelines, 2%, 3% and 5% of the patients met the 3, 6 and 12 months definition of suboptimal response, respectively. Analysis of baseline characteristics show a median age of 44.1, 42.1 and 44.4 years, respectively for the three time lines with a predominantly male and white population. Using the 2013 guidelines 4%, 10% and 17% of the patients met the 3, 6 and 12 months definition of warning, respectively. Patients were again predominantly male and white with a median age at diagnosis of 41.5, 44.1 and 47 years respectively. With regard to achieving complete cytogenetic response (CCyR), a higher percentage of patients achieved CCyR using the 2013 guidelines (55.2%, 80.8% and 98%, for warning cohorts at 3, 6 and 12 months, respectively) compared to using the 2009 guidelines (35.3%, 56.5% and 81.1%, respectively). Similarly, for best molecular response, a higher percentage of patients achieved MR4.5 using the 2013 guidelines (10.7%, 20.8% and 44.2%, for warning cohorts at 3, 6 and 12 months, respectively) compared to using the 2009 guidelines (13.3%, 4.5% and 24.2%, for suboptimal cohorts respectively). With respect to survival outcomes, patients classified as warning per the 2013 guidelines had better outcomes than those with suboptimal response using the 2009 guidelines. For example, for EFS, median survival was longer for the 2013 warning cohort compared to the 2009 suboptimal cohort (29 months vs. 18 months, by 3 months assessment). For FFS, the median survival was longer for the 2013 warning cohort compared to the 2009 suboptimal cohort (68 months vs. 11 months, by 6 months assessment). Using the 2013 guidelines median survival could not be reached for most of the survival outcomes. Conclusion Our assessment reveal that survival outcomes were better for the warning cohort using the ELN 2013 recommendations compared to the suboptimal cohort of the 2009 recommendations. This represents a stage migration by moving the subset of patients with the worse outcome away from this intermediate category and into the failure. An important, still unanswered question, is the optimal management of patients in this intermediate category or of those that migrate from one category to the next based on a change in definitions. Disclosures Kantarjian: Ariad: Research Funding; Amgen: Honoraria, Research Funding; Immunogen: Research Funding; AbbVie: Honoraria, Research Funding; Agios: Honoraria, Research Funding; Astex: Research Funding; Cyclacel: Research Funding; Pfizer: Honoraria, Research Funding; Actinium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz Pharma: Research Funding; BMS: Research Funding; Daiichi-Sankyo: Research Funding; Takeda: Honoraria; Novartis: Research Funding. Borthakur:Eli Lilly and Co.: Research Funding; NKarta: Consultancy; PTC Therapeutics: Consultancy; Cyclacel: Research Funding; Eisai: Research Funding; Janssen: Research Funding; Agensys: Research Funding; Oncoceutics: Research Funding; Tetralogic Pharmaceuticals: Research Funding; Bayer Healthcare AG: Research Funding; BMS: Research Funding; AbbVie: Research Funding; Merck: Research Funding; GSK: Research Funding; Incyte: Research Funding; Arvinas: Research Funding; BioTheryX: Membership on an entity's Board of Directors or advisory committees; Xbiotech USA: Research Funding; Novartis: Research Funding; AstraZeneca: Research Funding; Argenx: Membership on an entity's Board of Directors or advisory committees; Polaris: Research Funding; Cantargia AB: Research Funding; BioLine Rx: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; FTC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Oncoceutics, Inc.: Research Funding; Strategia Therapeutics: Research Funding. Verstovsek:Blueprint Medicines Corp: Research Funding; Celgene: Consultancy, Research Funding; Gilead: Research Funding; Promedior: Research Funding; CTI BioPharma Corp: Research Funding; Genetech: Research Funding; Sierra Oncology: Research Funding; Pharma Essentia: Research Funding; Roche: Research Funding; NS Pharma: Research Funding; Incyte: Research Funding; Astrazeneca: Research Funding; Ital Pharma: Research Funding; Protaganist Therapeutics: Research Funding; Constellation: Consultancy; Pragmatist: Consultancy; Novartis: Consultancy, Research Funding. Kadia:BMS: Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bioline RX: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Research Funding. Pemmaraju:abbvie: Consultancy, Honoraria, Research Funding; samus: Research Funding; celgene: Consultancy, Honoraria; cellectis: Research Funding; Stemline Therapeutics: Consultancy, Honoraria, Research Funding; novartis: Consultancy, Research Funding; plexxikon: Research Funding; Daiichi-Sankyo: Research Funding; sagerstrong: Research Funding; affymetrix: Research Funding; mustangbio: Consultancy, Research Funding; incyte: Consultancy, Research Funding. Garcia-Manero:Amphivena: Consultancy, Research Funding; Helsinn: Research Funding; Novartis: Research Funding; AbbVie: Research Funding; Celgene: Consultancy, Research Funding; Astex: Consultancy, Research Funding; Onconova: Research Funding; H3 Biomedicine: Research Funding; Merck: Research Funding. Konopleva:Agios: Research Funding; Ablynx: Research Funding; Astra Zeneca: Research Funding; Kisoji: Consultancy, Honoraria; Reata Pharmaceuticals: Equity Ownership, Patents & Royalties; Ascentage: Research Funding; F. Hoffman La-Roche: Consultancy, Honoraria, Research Funding; Genentech: Honoraria, Research Funding; Cellectis: Research Funding; Amgen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Eli Lilly: Research Funding; Forty-Seven: Consultancy, Honoraria; Stemline Therapeutics: Consultancy, Honoraria, Research Funding; Calithera: Research Funding. DiNardo:notable labs: Membership on an entity's Board of Directors or advisory committees; jazz: Honoraria; medimmune: Honoraria; syros: Honoraria; daiichi sankyo: Honoraria; abbvie: Consultancy, Honoraria; celgene: Consultancy, Honoraria; agios: Consultancy, Honoraria. Sasaki:Otsuka: Honoraria; Pfizer: Consultancy. Jabbour:Takeda: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Adaptive: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Cyclacel LTD: Research Funding. Cortes:Immunogen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; Sun Pharma: Research Funding; Biopath Holdings: Consultancy, Honoraria; BiolineRx: Consultancy; Pfizer: Consultancy, Honoraria, Research Funding; Astellas Pharma: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Merus: Consultancy, Honoraria, Research Funding; Forma Therapeutics: Consultancy, Honoraria, Research Funding.

AbstractCell migration regulates diverse (patho)physiological processes, including cancer metastasis. According to the Osmotic Engine Model, polarization of NHE1 at the leading edge of confined cells facilitates water uptake, cell protrusion and motility. The physiological relevance of the Osmotic Engine Model and the identity of molecules mediating cell rear shrinkage remain elusive. Here, we demonstrate that NHE1 and SWELL1 preferentially polarize at the cell leading and trailing edges, respectively, mediate cell volume regulation, cell dissemination from spheroids and confined migration. SWELL1 polarization confers migration direction and efficiency, as predicted mathematically and determined experimentally via optogenetic spatiotemporal regulation. Optogenetic RhoA activation at the cell front triggers SWELL1 re-distribution and migration direction reversal in SWELL1-expressing, but not SWELL1-knockdown, cells. Efficient cell reversal also requires Cdc42, which controls NHE1 repolarization. Dual NHE1/SWELL1 knockdown inhibits breast cancer cell extravasation and metastasis in vivo, thereby illustrating the physiological significance of the Osmotic Engine Model.

Cell migration is essential for many biological and pathological processes. Establishing cell polarity with a trailing edge and forming a single lamellipodium at the leading edge of the cell is crucial for efficient directional cell migration and is a hallmark of mesenchymal cell motility. Lamellipodia formation is regulated by spatial-temporal activation of the small GTPases Rac and Cdc42 at the front edge, and RhoA at the rear end. At a molecular level, partitioning-defective (Par) protein complex comprising Par3, Par6, and atypical Protein Kinase (aPKC isoforms ζ and λ/ι) regulates front-rear axis polarization. At the front edge, integrin clustering activates Cdc42, prompting the formation of Par3/Par6/aPKC complexes to modulate MTOC positioning and microtubule stabilization. Consequently, the Par3/Par6/aPKC complex recruits Rac1-GEF Tiam to activate Rac1, leading to lamellipodium formation. At the rear end, RhoA-ROCK phosphorylates Par3 disrupting its interaction with Tiam and inactivating Rac1. RhoA activity at the rear end allows the formation of focal adhesions and stress fibers necessary to generate the traction forces that allow cell movement. Nox1-based NADPH oxidase is necessary for PDGF-induced migration in vitro and in vivo for many cell types, including fibroblasts and smooth muscle cells. Here, we report that Nox1-deficient cells failed to acquire a normal front-to-rear polarity, polarize MTOC, and form a single lamellipodium. Instead, these cells form multiple protrusions that accumulate Par3 and active Tiam. The exogenous addition of H2O2 rescues this phenotype and is associated with the hyperactivation of Par3, Tiam, and Rac1. Mechanistically, Nox1 deficiency induces the inactivation of PP2A phosphatase, leading to increased activation of aPKC. These results were validated in Nox1y/- primary mouse aortic smooth muscle cells (MASMCs), which also showed PP2A inactivation after PDGF-BB stimulation consistent with exacerbated activation of aPKC. Moreover, we evaluated the physiological relevance of this signaling pathway using a femoral artery wire injury model to generate neointimal hyperplasia. Nox1y/- mice showed increased staining for the inactive form of PP2A and increased signal for active aPKC, suggesting that PP2A and aPKC activities might contribute to reducing neointima formation observed in the arteries of Nox1y/- mice.

Although our impression of the media’s role in a democracy and democratising societies is fairly stable, the situation is fundamentally different under unstable and ever shifting conditions of political crisis. To explore dynamics in the latter scenario we analyse the coverage of Zimbabwe’s 2018 elections by the country’s daily newspapers. This allows us to examine the newspapers’ active role in shaping the conditions of crisis through their interpretation and evaluation of issues and events during the period under study. We use frame and rhetoric analytical tools to analyse front-page stories and editorials, which enables us to explore the dimensions of news media’s agency during the context of crisis and assess the nature and direction of such agency using normative theories of the media in a democracy. We argue that a political crisis can easily polarise news media and subsequently induce them into assuming an active partisan posture in their reportage of political issues and events by using rhetorical discursive strategies not only to persuade the audience to accept their standpoint, but subsequently, to influence their political action in the future, with consequential implications for their functional performance of received normative roles.

An aerobic, Gram-stain-positive and non-spore-forming strain, designated C1-1T, was isolated from a fellfield soil sample collected from frost-sorted polygons on Jane Col, Signy Island, Maritime Antarctic. Cells with a size of 0.65–0.9×1.2–1.7 µm have a flagellar motile apparatus and exhibit a rod–coccus growth cycle. Optimal growth conditions were observed at 15–20 °C, pH 7.0 and NaCl concentration up to 0.5 % (w/v) in the medium. The 16S rRNA gene sequence of C1-1T showed the highest pairwise similarity of 98.77 % to Arthrobacter glacialis NBRC 113092T. Phylogenetic trees based on the 16S rRNA and whole-genome sequences revealed that strain C1-1T belongs to the genus Arthrobacter and is most closely related to members of the ‘ Arthrobacter psychrolactophilus group’. The G+C content of genomic DNA was 58.95 mol%. The original and orthologous average nucleotide identities between strain C1-1T and A. glacialis NBRC 113092T were 77.15 % and 77.38 %, respectively. The digital DNA–DNA relatedness values between strain C1-1T and A. glacialis NBRC 113092T was 21.6 %. The polar lipid profile was composed mainly of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol and an unidentified glycolipid. The predominant cellular fatty acids were anteiso-C15 : 0 (75 %) and anteiso-C17 : 0 (15.2 %). Menaquinone MK-9(H2) (86.4 %) was the major respiratory quinone in strain C1-1T. The peptidoglycan type was determined as A3α (l-Lys–l-Ala3; A11.6). Based on all described phylogenetic, physiological and chemotaxonomic characteristics, we propose that strain C1-1T (=DSM 112353T=CCM 9148T) is the type strain of a novel species Arthrobacter polaris sp. nov.

War tends to polarise national and global conflicts as encapsulated by the phrase, ‘you are either with us or against us’. There is further danger of knee jerk reactions at such times, including the present, towards unconditionally funding long-term military security hardware and dedicating scarce resources that are badly needed for more benevolent projects, including equitable redistribution of resources, not to mention the challenge to move away from fossil fuels in our climate crisis. These tensions are evident on recognising European dependence on Russian oil and gas, which unfortunately is helping to fund the ongoing Ukrainian war. This paper will explore how a sample of more contemporary wars and national conflicts have been dramatised on film since the pandemic. Focusing specifically on three contrasting approaches to the tragedy of war and its effects on citizens and soldiers: from an insider’s personal response to the massacre in the Balkans during the 1990s in Quo Vadis, Aida? (2020), to the reworked conventional World War One classic All Quiet on the Western Front (2022), before finally coming full circle with the big budget Hollywood celebration of aerial war heroics in the sequel Top Gun: Maverick (2022). Sample textual and contextual analysis will be used to explore how such war narratives have become repurposed, both from an insider soldier’s perspective and also through a rejuvenated cinematic war framework, as contemporary audiences strive to cope with ever-increasing crises and conflicts facing the planet, having recently endured a global pandemic.

Cell chirality is crucial for the chiral morphogenesis of biological tissues, yet its underlying mechanism remains unclear. Cell organelle polarization along multiple axes in a cell body, namely, apical–basal, front–rear, and left–right, is known to direct cell behavior such as orientation, rotation, and migration. Among these axes, the left–right bias holds significant sway in determining the chiral directionality of these behaviors. Normally, mouse myoblast (C2C12) cells exhibit a strong counterclockwise chirality on a ring-shaped micropattern, whereas they display a clockwise dominant chirality under Latrunculin A treatment. To investigate the relationship between multicellular chirality and organelle positioning in single cells, we studied the left–right positioning of cell organelles under distinct cell chirality in single cells via micropatterning technique, fluorescent microscopy, and imaging analysis. We found that on a “T”-shaped micropattern, a C2C12 cell adopts a triangular shape, with its nucleus–centrosome axis pointing toward the top-right direction of the “T.” Several other organelles, including the Golgi apparatus, lysosomes, actin filaments, and microtubules, showed a preference to polarize on one side of the axis, indicating the universality of the left–right asymmetrical organelle positioning. Interestingly, upon reversing cell chirality with Latrunculin A, the organelles correspondingly reversed their left–right positioning bias, as suggested by the consistently biased metabolism and contractile properties at the leading edge. This left–right asymmetry in organelle positioning may help predict cell migration direction and serve as a potential marker for identifying cell chirality in biological models.

Gunther Kress and Theo van Leeuwen argue that in “contemporary Western visualization central composition is relatively uncommon” (Reading Images 203). In fact, “most compositions polarise elements as Given and New and/or Ideal and Real” (Reading Images 203). This is the regular situation on the front pages of Australia’s national and capital city dailies; but not on May 28. Rather than the favoured front page structures of left (Given) and right (New) and/or top (Ideal) and bottom (Real), on this morning the layouts in the newspapers centralised the Schapelle Corby judgment. While this is not unprecedented, it is the type of coverage usually kept for major issues such as 9/11 or the Bali Bombing. Even the recent release of Douglas Wood, which was arguably as, if not more, important for the Australian public in terms of the issues it raised about Australia’s involvement in the war in Iraq, did not receive the same type of treatment. Although further study needs to be undertaken, I believe this centralising of issues, that is the running of one story only, on front pages is a growing trend, particularly among the tabloids. The effect of this centralising layout structure is to reduce the news choice for the reader on front pages that they would normally approach with an attitude of scanning and selecting. While this approach could still be taken across the whole paper, the front-page choices are minimised. This essay will examine the coverage of the Corby verdict in the tabloids The Daily Telegraph, the Herald Sun, The Advertiser, The Mercury, and The West Australian, because it is here that the greatest impact of centralisation on the encoded reading paths can be found. Although the broadsheets The Australian, The Sydney Morning Herald, The Age, The Courier-Mail, and The Canberra Times also centralised the issue, there is not room here to cover them in detail. May 28 was the peak of the media frenzy in the Corby coverage, or at least one of the peaks. As the story is ongoing—turning into something of a soap opera in its call to readers and television news viewers to tune in and see the latest bizarre development, such as the chief lawyer admitting he’s a crook—it could peak again, particularly if on appeal a heavier sentence is handed down. On May 28, the focus moved from Corby’s guilt or innocence to the horror of the twenty-year sentence. In each category—broadsheet and tabloid—the layouts were remarkably similar. At a glance, three of the tabloids are so similar that side-by-side on a newsstand they could have been mistaken for the same. Apart from the fact that Corby’s beauty gave her cultural salience, it is not clear why the Australian media was so taken with her story in the first instance when there are and have been many Australians on drug charges in Asia. My interest here is not so much why or how she became news—that’s an issue for another time—but that once she had captured the attention of the Australian print media, how did they visually treat the material and what are the implications of that treatment. I will argue that the treatment elevated her story, giving it the same weight as the war on terror coverage since 9/11. One of the first elements that draws the eye on any newspaper page is the photograph. Tim Harrower suggests photographs “give a page motion and emotion” (28), arguing however that it is the headline “that leaps out, that grabs you” (37). In reality, it is most likely a combination of both that draws a reader’s attention. Both encode the importance of a story with a dominating photograph or a large headline signalling a story’s significance. The varying size of headlines and photographs and their placement signal the page designer’s order of importance. Six of the ten major Australian newspapers chose the same photograph for their front pages on May 28: a picture of Corby with her head held in her left hand and a look of despair on her face. Four of them—The Daily Telegraph, The Mercury, The Advertiser, and the Herald Sun—used the full photograph, while it was heavily cropped into a horizontal picture on the front pages of The West Australian and The Age. The Australian’s choice was similar but the photograph was taken from a slightly different angle. Only one of these newspapers, The West Australian, acknowledged that Corby did not just hang her head in her hand in despair but rather was slapping her head and sobbing as the verdict was read. The television footage gives a different impression of this moment than the still photograph run in the newspapers. The Sydney Morning Herald and The Courier-Mail, in contrast, chose a photograph of Corby struggling with the courtroom police. The Sydney Morning Herald more closely cropped their version so that the emphasis is on Corby. More of the struggle is depicted in The Courier-Mail. The only newspaper making a substantially different choice was The Canberra Times. In this publication, the central vertical photograph was a close up of Corby with tears in her eyes. Her mien is more composed than in the photographs on the other front pages. The source for the photographs, with the exception of The Australian’s choice from Associated Press, was Reuters. Given that the event was in Indonesia and in a crowded courtroom, the array of photographs may have been limited. Of interest was the use of the photograph. The Daily Telegraph, The Mercury, and the Herald Sun ran it full-page, like a poster shot, with the mastheads and headlines over the top. In contrast, The Advertiser maintained a white background for their masthead with the photograph underneath enclosed in a heavy frame and the headlines imposed on top. The other newspapers ran the photograph to the edge of the page without an added frame. The Advertiser, The Mercury, and the Herald Sun chose to forgo their normal front-page teasers. This restricted the scan and select for the reader. Normally readers would have at least two stories, sometimes three, as well as two to three teasers or pointers (usually across the top of the page under the masthead) to scan and select their reading matter. On May 28, however, Corby was centralised with a similar reading path encoded for each of these newspapers. The photograph is the most salient element and the eye moves from this to the main headline at the bottom of the page. As the masthead is known and familiar, unless the reader is selecting the newspaper from a newsstand rather than picking it up from their front yard, it is likely they would only subconsciously register it. These layouts, with a reading path from photograph to headlines down the page, are closer to linear in design, than the normal non-linear format and more interactive front pages. Therefore, the coding is for reading “left to right and from top to bottom, line by line” (Kress and van Leeuwen 218). Newspapers are not normally read in a linear way, but “selectively and partially . . . Their composition sets up particular hierarchies of the movement of the hypothetical reader within and across their different elements. Such reading paths begin with the most salient element, from there move to the next most salient element and so on.” (218) There is also sameness in the headlines and their implications. The Mercury, the most unadorned of the layouts, has “20 Years” in block capitals with a subhead and pointer reading “Corby’s Nightmare Sentence, pages 2-6”. The implication is clear, Corby’s sentence is 20 years in jail and it is pronounced a “nightmare”. The Herald Sun also chose “20 Years” with a subheading of “Shock and tears over jail sentence”. Consolidating this notion of “shock and tears” were three smaller photographs across the bottom of the page depicting crying and sobbing women. No male sympathy was depicted, thus tapping into and reinforcing Australian cultural stereotypes that it is the Australian women rather than the men who cry. The Advertiser’s main headline declared “20 Years in Hell”. Beside this was a smaller underlined headline and pointer “Guilty Corby, sent to jail, Australians react in anger Pages 8-15”. There are slight distinctions in these three pages but essentially the encoded reading path and message is the same. That is not to say that some people may read the pages in a different order. As Kress and van Leeuwen argue “newspaper pages can be read in more than one way” (“Front Page” 205), however, the choice on these pages is limited. The Daily Telegraph uses headlines with different emphasis and includes text from the main story imposed over the photograph. Pointers square-off the pages at the bottom. A kicker head at the top of the page, below the masthead, and set against a photograph of Abu Bakir Bashir, declares: “This terrorist planned the murder of 88 Australians and got two years. Yesterday Schapelle Corby got 20”. This comparison does not appear on the already examined pages. Towards the bottom of the page, the main headline set over two lines reads “Nation’s Fury”. To the right of the “Nation” is a smaller headline, which says “20 years in hell and prosecutor’s still demand life”. The story begins beside the second line “Fury”. The message on this page is more strident than the others and was analysed by the ABC TV show Media Watch on May 30. Media Watch declared the “spin on the verdict” used by The Daily Telegraph as “truly a disgrace”. The criticism was made because Bashir was not convicted in court of masterminding the bombing therefore the word “planned” is problematic and misleading. As the Media Watch report points out, the three Indonesians convicted of masterminding the bombing are on death row and will face the firing squad. The final tabloid, The West Australian, presented a similar message to The Daily Telegraph with a headline of “Bomb plotter: 2½ years / Dope smuggler: 20 years”. The visual impact of this page, however, is not as striking as the other pages. The visual designs of The Advertiser, The Daily Telegraph, The Mercury, and the Herald Sun make it immediately clear that the Corby verdict is the central issue in the news and that all other stories are so marginal they are off the page. In contrast, The West Australian ran its normal teasers just below the masthead, offering four choices for the reader as well as weather and home delivery details at the bottom. The heavily cropped central photograph of Corby leaves in only her wrist and central facial features; it is not even immediately apparent that the photograph is of Corby. The story runs in an L-shape around it. Although Corby is central, the reading path is not as clear. The reader’s eye will most likely be drawn from photograph to caption and to headline or headline, photograph, caption. Whatever the path, the story text is always read last, that is, if the reader chooses this story at all (Kress and van Leeuwen, “Front Pages” 205). The story opens by announcing that Corby’s lawyers want the Australian authorities to “launch an investigation” into the case and Foreign Affairs Minister Alexander Downer has offered the help of two Australian QCs in preparing an appeal. This introduction does not support the headline. The comparison with Bashir comes in paragraph three. While Corby still has salience, the inclusion of teasers on the front of The West Australian brings back the choice for the reader, albeit in a small way. Kress and van Leeuwen argue that newspapers “are the first point of ‘address’ for the readers” presenting “the most significant events and issues of the day for the paper and its readers” (“Front Page” 229). In the Corby coverage on May 28, the newspapers presented the court verdict as the most important of all stories on offer and her image became the most salient element, the “nucleus” of the front pages. All newspapers make choices for their readers in their capacity as gatekeepers (see David Manning White and Glen Bleske), but not, I would argue, to the extent that it appeared in the Corby case. A centralising approach to news can be understood with stories such as 9/11 or the Bali Bombing but does one woman’s plight over drug charges in Bali truly deserve such coverage? As a single event maybe not, but the Corby verdict again raised the issue of Australia’s uneasiness about the laws and culture of its Asian neighbours, feelings amplified in the wake of the Bali Bombing. The rhetoric used in the front pages of The Daily Telegraph and The West Australian clearly state this when they compare Corby’s sentence to Bashir’s. They demonstrate a paranoia about the treatment of “our girl” in a foreign judicial system which appears to deal more leniently with terrorists. Thus, one girl’s story is transformed into part of a much larger issue, a fact reinforced through the visual treatment of the material. There remain some questions. What does it say about the newspaper’s attitude to their readers when they centralise issues so strongly that reader choice is removed? Is this part of the “dumbing down” of the Australian media, where news organisations move towards more clearly dictating views to their reading public? Is it attributable to media ownership, after all four of these tabloids belong to News Corporation? These questions and others about the trend towards the centralising of issues are for a bigger study. For now, we watch to see how much longer Corby remains in the nucleus of the news and for further indication of a growing trend towards centralising issues. References Bleske, Glen K. “Mrs Gates Takes Over: An Updated Version of a 1949 Case Study.” Social Meanings of News. Ed. Dan Berkowitz. Thousand Oaks: Sage Publications, 1997. Harrower, Tim. The Newspaper Designer’s Handbook. Boston: McGraw-Hill, 1998. Kress, Gunther, and Theo van Leeuwen. Reading Images: The Grammar of Visual Design. London and New York: Routledge, 1996. Kress, Gunther, and Theo van Leeuwen. “Front Page: (The Critical) Analysis of Newspaper Layout.” Approaches to Media Discourse. Ed. Allan Bell and Peter Garrett. Oxford: Blackwell Publishers, 2003. Media Watch. May 30, 2005. http://www.abc.net.au/mediawatch/transcripts/s1380398.htm>. Sellers, Leslie. The Simple Subs Book. Oxford: Permagon Press, 1968. White, David Manning. “The ‘Gate Keeper’: A Case Study in the Selection of News.” Social Meanings of News. Ed. Dan Berkowitz. Thousand Oaks: Sage Publications, 1997. Citation reference for this article MLA Style Delaney, Elizabeth. "Scanning the Front Pages: The Schapelle Corby Judgment." M/C Journal 8.4 (2005). echo date('d M. Y'); ?> <http://journal.media-culture.org.au/0508/08-delaney.php>. APA Style Delaney, E. (Aug. 2005) "Scanning the Front Pages: The Schapelle Corby Judgment," M/C Journal, 8(4). Retrieved echo date('d M. Y'); ?> from <http://journal.media-culture.org.au/0508/08-delaney.php>.

The identification and characterization of circulating tumor cells (CTCs) are important for gaining insights into the biology of metastatic cancers, monitoring disease progression, and medical management of the disease. The limiting factor in the enrichment of purified CTC populations is their sparse availability, heterogeneity, and altered phenotypes relative to the primary tumor. Intensive research both at the technical and molecular fronts led to the development of assays that ease CTC detection and identification from peripheral blood. Most CTC detection methods based on single-cell RNA sequencing (scRNA-seq) use a mix of size selection, marker-based white blood cells (WBC) depletion, and antibodies targeting tumor-associated antigens. However, the majority of these methods either miss atypical CTCs or suffer from WBC contamination. We present unCTC, an R package for unbiased identification and characterization of CTCs from single-cell transcriptomic data. unCTC features many standard and novel computational and statistical modules for various analyses. These include a novel method of scRNA-seq clustering, named Deep Dictionary Learning usingk-means clustering cost (DDLK), expression-based copy number variation (CNV) inference, and combinatorial, marker-based verification of the malignant phenotypes. DDLK enables robust segregation of CTCs and WBCs in the pathway space, as opposed to the gene expression space. We validated the utility of unCTC on scRNA-seq profiles of breast CTCs from six patients, captured and profiled using an integrated ClearCell FX and Polaris workflow that works by the principles of size-based separation of CTCs and marker-based WBC depletion.

Abstract Background Patients with resectable and borderline resectable pancreatic ductal adenocarcinoma increasingly receive neoadjuvant therapy prior to surgery. However, the effect of neoadjuvant therapy on the immune microenvironment remains largely unknown. We analyzed the immune microenvironment in pancreatic cancer tumor tissue samples from patients treated with neoadjuvant therapy compared to patients after upfront surgery to gain knowledge about the immunological environment after therapy. Methods Multispectral imaging was performed on tissue from resected specimens from patients with PDAC who underwent upfront surgery (n = 10), neoadjuvant FOLFIRINOX (n = 10) or gemcitabine + radiotherapy (gem-RT) (n = 9) followed by surgery. The samples were selected by a dedicated pancreas pathologist from both the central part and the invasive front of the tumor (by the resected vein or venous surface) and subsequently analyzed using the Vectra Polaris. Results Patients receiving neoadjuvant FOLFIRINOX display a more pro-inflammatory immune profile, with less regulatory T cells and more CD8 T cells in the tumor tissue compared to patients receiving neoadjuvant gem-RTgem-RT or undergoing upfront surgery. Furthermore, CD163+ macrophages were decreased, and a higher CD163− macrophages versus CD163+ macrophages ratio was found in patients with neoadjuvant FOLFIRINOX. In all treatment groups, percentage of FoxP3+ B cells was significantly higher in tumor tissue compared to adjacent tissue. Furthermore, an increase in regulatory T cells in the tumor tissue was found in patients undergoing upfront surgery or receiving neoadjuvant gem-RT. In the gem-RT group, less CD8 T cells and a higher CD163+ macrophages to CD8 ratio were noted in the tumor tissue, suggesting a more immune suppressive profile in the tumor tissue. Conclusion Patients receiving neoadjuvant FOLFIRINOX display a more pro-inflammatory immune profile compared to patients receiving neoadjuvant gem-RT or undergoing upfront surgery. Furthermore, in all treatment groups, a more immune suppressive microenvironment was found in the tumor tissue compared to the adjacent non-tumorous tissue.

IntroductionFor many, north is an abstract point on a compass, an arrow that tells you which way to hold up a map. Though scientifically defined according to the magnetic north pole, and/or the earth’s axis of rotation, these facts are not necessarily discernible to the average person. Perhaps for this reason, the Oxford English Dictionary begins with reference to the far more mundane and accessible sun and features of the human body, in defining north as; “in the direction of the part of the horizon on the left-hand side of a person facing the rising sun” (OED Online). Indeed, many of the words for ‘north’ around the world are etymologically linked to the left hand side (for example Cornish clēth ‘north, left’). We shall see later that even in English, many speakers conceptualise ‘north’ in an egocentric way. Other languages define ‘north’ in opposition to an orthogonal east-west axis defined by the sun’s rising and setting points (see, e.g., the extensive survey of Brown).Etymology aside, however, studies such as Brown’s presume a set of four cardinal directions which are available as primordial ontological categories which may (or may not) be labelled by the languages of the world. If we accept this premise, the fact that a word is translated as ‘north’ is sufficient to understand the direction it describes. There is good reason to reject this premise, however. We present data from three languages among which there is considerable variance in how the words translated as ‘north’ are typically used and understood. These languages are Kuuk Thaayorre (an Australian Aboriginal language spoken on Cape York Peninsula), Marshallese (an Oceanic language spoken in the Republic of the Marshall Islands), and Dhivehi (an Indo-Aryan language spoken in the Maldives). Lastly, we consider the results of an experiment that show Australian English speakers tend to interpret the word north according to the orientation of their own bodies and the objects they manipulate, rather than as a cardinal direction as such.‘North’ in Kuuk ThaayorreKuuk Thaayorre is a Pama-Nyungan language spoken on the west coast of Australia’s Cape York Peninsula in the community of Pormpuraaw. The Kuuk Thaayorre words equivalent to north, south, east and west (hereafter, ‘directionals’) are both complex and frequently used. They are complex in the sense that they combine with prefixes and suffixes to form dozens of words which indicate not only the direction involved, but also the degree of distance, whether there is motion from, towards, to a fixed point, or within a bounded area in that location, proximity to the local river, and more. The ubiquity of these words is illustrated by the fact that the most common greeting formula involves one person asking nhunt wanthan pal yan? ‘where are you going’ and the other responding, for example, ngay yuurriparrop yan ‘I’m going a long way southwards towards the river’, or ngay iilungkarruw yan ‘I’m coming from the northwest’. Directional terms are strewn liberally throughout Kuuk Thaayorre speech. They are employed in the description of both large-scale and small-scale spaces, whether giving directions to a far-off town, asking another person to ‘move a little to the north’, or identifying the person ‘to the east’ of another in a photograph. Likewise, directional gestures are highly frequent, sometimes augmenting the information given in the speech stream, sometimes used in the absence of spoken directions, and other times redundantly duplicating the information given by a directional word.The forms and meanings of directional words are described in detail in Gaby (Gaby 344–52). At the core of this system are six directional roots referring to the north and south banks of the nearby Edward River as well as two intersecting axes. One of these axes is equivalent to the east—west axis familiar to English speakers, and is defined by the apparent diurnal trajectory of the sun. (At a latitude of 14 degrees 54 minutes south, the Kuuk Thaayorre homeland sees little variation in the location of sunrise and sunset through the year.) While the poles of the second axis are translated by the English terms north and south, from a Western perspective this axis is skewed such that Kuuk Thaayorre -ungkarr ‘~north’ lies approximately 35 degrees west of magnetic north. Rather than being defined by magnetic or polar north, this axis aligns with the local coastline. This is true even when the terms are used at inland locations where there is no visual access to the water or parallel sand ridges. How Kuuk Thaayorre speakers apply this system to environments further removed from this particular stretch of coast—especially in the presence of a differently-oriented coast—remains a topic for future research.‘North’ in MarshalleseMarshallese is the language of the people of the Marshall Islands, an expansive archipelago consisting of 22 inhabited atolls and three inhabited non-atoll islands located in the Northern Pacific. The Marshallese have a long history as master navigators, a skill necessary to keep strong links between far-flung and disparate islands (Lewis; Genz).Figure 1: The location of the Marshall IslandsAs with other Pacific languages (e.g. Palmer; Ross; François), Marshallese deploys a complex system of geocentric references. Cardinal directions are historically derived from the Pacific trade winds, reflecting the importance of these winds for navigation and wayfinding. The etymologies of the Marshallese directions are shown in Table 1 below. The terms given in this table are in the Ralik dialect, spoken in the western Marshall Islands. The terms used in the Ratak (eastern) dialect are related, but slightly different in form. See Schlossberg for more detailed discussion. Etymologies originally sourced from Bender et al. and Ross.Table 1: Marshallese cardinal direction words with etymological source semantics EastWestNorthSouthNoun formrearrilik iōn̄ rōkEtymology‘calm shore (of islet)’‘rough shore (of islet)’‘windy season’; ‘season of northerly winds’‘dry season’; ‘season of southerly winds’Verb modifier formtatonin̄a rōn̄aEtymology‘up(wind)’‘down(wind)’‘windy season’; ‘season of northerly winds’‘dry season’; ‘season of southerly winds’As with many other Oceanic languages, Marshallese has three domains of spatial language use: the local domain, the inshore-maritime domain and the navigational domain. Cardinal directions are the sole strategy employed in the navigational domain, which occurs when sailing on the open ocean. In the inshore-maritime domain, which applies when sailing on the ocean or lagoon in sight of land, a land-sea axis is used (The question of whether, in fact, these directions form axes as such is considered further below). Similarly, when walking around an island, a calm side-rough side (of island) axis is employed. In both situations, either the cardinal north-south axis or east-west axis is used to form a secondary cross-axis to the topography-based axis. The cardinal axis parallel to the calm-rough or land-sea axis is rarely used. When the island is not oriented perfectly perpendicular to one of the cardinal axes, the cardinal axes rotate such that they are perpendicular to the primary axis. This can result in the orientation of iōn̄ ‘north’ being quite skewed away from ‘true’ north. An example of how the cardinal and topographic axes prototypically work is exemplified in Figure 2, which shows Jabor, an islet in Jaluit Atoll in the south-west Marshalls.Figure 2: The geocentric directional system of Jabor, Jaluit AtollWhile cartographic cardinal directions comprise two perpendicular axes, this is not the case for many Marshallese. The clearest evidence for this is the directional system of Kili Island, a small non-atoll island approximately 50km west of Jaluit Atoll. The directional system of Kili is similar to that of Jabor, with one notable exception; the iōn̄-rōk ‘north-south’ and rear-rilik ‘east-west’ axes are not perpendicular but rather parallel (Figure 3) The rear-rilik axis takes precedence and the iōn̄-rōk axis is rarely used, showing the primacy of the east-west axis on Kili. This is a clear indication that the Western abstraction of crossed cardinal axes is not in play in the Marshall Islands; the iōn̄-rōk and rear-rilik axes can function completely independently of one another.Figure 3: Geocentric system of spatial reference on KiliSpringdale is a small city in north-west of the landlocked state of Arkansas. It hosts the largest number of expatriate Marshallese in the United States. Of 26 participants in an object placement task, four respondents were able to correctly identify the four cardinal points (Schlossberg). Aside from some who said they simply did not know others gave a variety of answers, including that iōn̄, rōk, rilik and rear only exist in the Marshall Islands. Others imagined a canonical orientation derived from their home atoll and transposed this onto their current environment; one person who was facing the front door in their house in Springdale reported that they imagined they were in their house in the Marshall Islands, where when oriented towards the door, they were facing iōn̄ ‘north’, thus deriving an orientation with respect to a Marshallese cardinal direction. Aside from the four participants who identified the directions correctly, a further six participants responded in a consistent—if incorrect—way, i.e. although the directions were not correctly identified, the responses were consistent with the conceptualisation of crossed cardinal axes, merely that the locations identified were rotated from their true referents. This leaves 16 of the 26 participants (62%) who did not display evidence of having a conceptual system of two crossed cardinal axes.If one were to point in a direction and say ‘this is north’, most Westerners would easily be able to identify ‘south’ by pointing in the opposite direction. This is not the case with Marshallese speakers, many of whom are unable to do the same if given a Marshallese cardinal direction and asked to name its opposite (cf. Schlossberg). This demonstrates that for many Marshallese, each of these cardinal terms do not form axes at all, but rather are four unique locally-anchored points.‘North’ in DhivehiDhivehi is spoken in the Maldives, an archipelago to the southwest of India and Sri Lanka in the Indian Ocean (see Figure 4). Maldivians have a long history of sailing on the open waters, in order to fish and to trade. Traditionally, much of the adult male population would spend long periods of time on such voyages, riding the trade winds and navigating by the stars. For Maldivians, uturu ‘north’ is a direction of safety—the long axis of the Maldivian archipelago runs north to south, and so by sailing north, one has the best possible chance of reaching another island or (eventually) the mainlands of India or Sri Lanka.Figure 4: Location of the MaldivesIt is perhaps unsurprising, then, that many Maldivians are well attuned to the direction denoted by uturu ‘north’, as well as to the other cardinal directions. In an object placement task performed by 41 participants in Laamu Atoll, 32 participants (78%) correctly placed a plastic block ‘to the north’ (uturaṣ̊) of another block when instructed to do so (Lum). The prompts dekonaṣ̊ ‘to the south’ and huḷangaṣ̊ ‘to the west’ yielded similarly high rates of correct responses, though as many as 37 participants (90%) responded correctly to the prompt iraṣ̊ ‘to the east’—this is perhaps because the term for ‘east’ also means ‘sun’ and is strongly associated with the sunrise, whereas the terms for the other cardinal directions are comparatively opaque. However, the path of the sun is not the only environmental cue that shapes the use of Dhivehi cardinal directions. As in Kuuk Thaayorre and Marshallese, cardinal directions in Dhivehi are often ‘calibrated’ according to the orientation of local coastlines. In Fonadhoo, for example, which is oriented northeast to southwest, the system of cardinal directions is rotated about 45 degrees clockwise: uturu ‘north’ points to what is actually northeast and dekona/dekunu ‘south’ to what is actually southwest (i.e., along the length of the island), while iru/iramati ‘east’ and huḷangu ‘west’ are perpendicular to shore (see Figure 5). However, despite this rotated system being in use, residents of Fonadhoo often comment that these are not the ‘real’ cardinal directions, which are determined by the path of the sun.Figure 5: Directions in Fonadhoo, Laamu Atoll, MaldivesIn addition to the four cardinal directions, Dhivehi possesses four intercardinal directions, which are compound terms: iru-uturu ‘northeast’, iru-dekunu ‘southeast’, huḷangu-uturu ‘northwest’, and huḷangu-dekunu ‘southwest’. Yet even a system of eight compass points is not sufficient for describing directions over long distances, especially on the open sea where there are no landmarks to refer to. A system of 32 ‘sidereal’ compass directions (see Figure 6), based on the rising and setting points of stars in the night sky, is available for such purposes—for example, simāgu īran̊ ‘Arcturus rising’ points ENE or 67.5°, while simāgu astamān̊ ‘Arcturus setting’ points WNW or 292.5°. (These Dhivehi names for the sidereal directions are borrowings from Arabic, and were probably introduced by Arab seafarers in the medieval period, see Lum 174-79). Eight sidereal directions coincide with the basic (inter)cardinal directions of the solar compass described earlier. For example, gahā ‘Polaris’ in the sidereal compass corresponds exactly with uturu ‘north’ in the solar compass. Thus Dhivehi has both a sidereal ‘north’ and a solar ‘north’, though the latter is sometimes rotated according to local topography. However, the system of sidereal compass directions has largely fallen out of use, and is known only to older and some middle-aged men. This appears to be due to the diversification of the Maldivian economy in recent decades along with the modernisation of Maldivian fishing vessels, including the introduction of GPS technology. Nonetheless, fishermen and fishing communities use solar compass directions much more frequently than other groups in the Maldives (Lum; Palmer et al.), and some of the oldest men still use sidereal compass directions occasionally.Figure 6: Dhivehi sidereal compass with directions in Thaana script (used with kind permission of Abdulla Rasheed and Abdulla Zuhury)‘North’ in EnglishThe traditional definition of north in terms of Magnetic North or Geographic North is well known to native English speakers and may appear relatively straightforward. In practice, however, the use and interpretation of north is more variable. English speakers generally draw on cardinal directions only in restricted circumstances, i.e. in large-scale geographical or navigational contexts rather than, for example, small-scale configurations of manipulable objects (Majid et al. 108). Consequently, most English speakers do not need to maintain a mental compass to keep track of North at all times. So, if English speakers are generally unaware of where North is, how do they perform when required to use it?A group of 36 Australian English speakers participated in an experimental task where they were presented with a stimulus object (in this case, a 10cm wide cube) while facing S72ºE (Poulton). They were then handed another cube and asked to place it next to the stimulus cube in a particular direction (e.g. ‘put this cube to the north of that cube’). Participants completed a total of 48 trials, including each of the four cardinal directions as target, as well as expressions such as behind, in front of and to the left of. As shown in Figure 7, participants’ responses were categorised in one of three ways: correct, near-correct, or incorrect.Figure 7: Possible responses to prompt of north: A = correct, B = near-correct (aligned with the side of stimulus object closest to north), C = incorrect.Every participant placed their cube in alignment with the axes of the stimulus object (i.e. responses B and C in Figure 7). Orientation to Magnetic/Geographic North was thus insufficient to override the local cues of the task at hand. The 9% of participants showed some awareness of the location of Magnetic/Geographic North, however, by making the near-correct response type B. No participants who behaved in such a way expressed certainty in their responses, however. Most commonly, they calculated the rough direction concerned by triangulating with local landmarks such as nearby roads, or the location of Melbourne’s CBD (as verbally expressed both during the task and during an informal interview afterwards).The remaining 91% of participants’ responses were entirely incorrect. Of these, 13.2% involved similar thought processes as the near-correct responses, but did not result in the identification of the closest side of the stimulus to the instructed direction. However, 77.8% of the total participants interpreted north as the far side of the stimulus. While such responses were classified incorrect on the basis of Magnetic or Geographic North, they were consistent with one another and correct with respect to an alternative definition of English north in terms of the participant’s own body. One of the participants alludes to this alternative definition, asking “Do you mean my North or physical North?”. We refer to this alternative definition as Relative North. Relative North is not bound to any given point on the Earth or a derivation of the sun’s position; instead, it is entirely bound to the perceiver’s own orientation. This equates the north direction with forward and the other cardinals’ points are derived from this reference point (see Figure 8). Map-reading practices likely support the development of the secondary, Relative sense of North.Figure 8: Relative North and the Relative directions derived from itConclusionWe have compared the words closest in meaning to the English word north in four entirely unrelated languages. In the Australian Aboriginal language Kuuk Thaayorre, the ‘north’ direction aligns with the local coast, pointing in a direction 35 degrees west of Magnetic North. In Marshallese, the compass direction corresponding to ‘north’ is different for each island, being defined in opposition to an axis running between the ocean and lagoon sides of that island. The Dhivehi ‘north’ direction may be defined either in opposition to the (sun-based) east-west axis, calibrated to the configuration of the local island, as in Marshallese, or defined in terms of Polaris, the Pole star. In all these cases, though, the system of directions is anchored by properties of the external environment. English speakers, by contrast, are shown to—at least some of the time—define north with reference to their own embodied perspective, as the direction extending outwards from the front of their bodies. These findings demonstrate that, far from being universal, ‘north’ is a culture-specific category. As such, great care must be taken when translating or drawing equivalencies between these concepts across languages.ReferencesBender, Byron W., et al. “Proto-Micronesian Reconstructions: I.” Oceanic Linguistics 42.1 (2003): 1–110.Brown, Cecil H. “Where Do Cardinal Direction Terms Come From?” Anthropological Linguistics 25.2 (1983): 121–161. François, Alexandre. “Reconstructing the Geocentric System of Proto-Oceanic.” Oceanic Linguistics 43.1 (2004): 1–31. Gaby, Alice R. A Grammar of Kuuk Thaayorre. Vol. 74. Berlin: De Gruyter Mouton, 2017.Genz, Joseph. “Complementarity of Cognitive and Experiential Ways of Knowing the Ocean in Marshallese Navigation.” Ethos 42.3 (2014): 332–351.Lewis, David Henry. We, the Navigators: The Ancient Art of Landfinding in the Pacific. 2nd ed. Honolulu: University of Hawai'i Press, 1994. Lum, Jonathon. "Frames of Spatial Reference in Dhivehi Language and Cognition." PhD Thesis. Melbourne: Monash University, 2018. Majid, Asifa, et al. “Can Language Restructure Cognition? The Case for Space.” Trends in Cognitive Sciences 8.3 (2004): 108–114.OED Online. “North, Adv., Adj., and N.” Oxford English Dictionary. Oxford: Oxford University Press. <http://www.oed.com.ezproxy.lib.monash.edu.au/view/Entry/128325>.Palmer, Bill. “Absolute Spatial Reference and the Grammaticalisation of Perceptually Salient Phenomena.” Representing Space in Oceania: Culture in Language and Mind. Canberra: Pacific Linguistics, 2002. 107–133. ———, et al. "“Sociotopography: The Interplay of Language, Culture, and Environment.” Linguistic Typology 21.3 (2017). DOI:10.1515/lingty-2017-0011.Poulton, Thomas. “Exploring Space: Frame-of-Reference Selection in English.” Honours Thesis. Melbourne: Monash University, 2016.Ross, Malcolm D. “Talking about Space: Terms of Location and Direction.” The Lexicon of Proto-Oceanic: The Culture and Environment of Ancestral Oceanic Society: The Physical Environment. Eds. Malcolm D. Ross, Andrew Pawley, and Meredith Osmond. Vol. 2. Canberra: Pacific Linguistics, 2003. 229–294. Schlossberg, Jonathan. Atolls, Islands and Endless Suburbia: Spatial Reference in Marshallese. PhD thesis. Newcastle: University of Newcastle, in preparation.

IntroductionTasmania hangs from the map of Australia like a drop in freefall from the substance of the mainland. Often the whole state is mislaid from Australian maps and logos (Reddit). Tasmania has, at least since federation, been considered peripheral—a region seen as isolated, a ‘problem’ economically, politically, and culturally. However, Tasmania not only cleaves to the ‘north island’ of Australia but is also subject to the gravitational pull of an even greater land mass—Antarctica. In this article, we upturn the political conventions of map-making that place both Antarctica and Tasmania in obscure positions at the base of the globe. We show how a changing global climate re-frames Antarctica and the Southern Ocean as key drivers of worldwide environmental shifts. The liquid and solid water between Tasmania and Antarctica is revealed not as a homogenous barrier, but as a dynamic and relational medium linking the Tasmanian archipelago with Antarctica. When Antarctica becomes the focus, the script is flipped: Tasmania is no longer on the edge, but core to a network of gateways into the southern land. The state’s capital of Hobart can from this perspective be understood as an “Antarctic city”, central to the geopolitics, economy, and culture of the frozen continent (Salazar et al.). Viewed from the south, we argue, Tasmania is not a problem, but an opportunity for a form of ecological, cultural, economic, and political sustainability that opens up the southern continent to science, discovery, and imagination.A Centre at the End of the Earth? Tasmania as ParadoxThe islands of Tasmania owe their existence to climate change: a period of warming at the end of the last ice age melted the vast sheets of ice covering the polar regions, causing sea levels to rise by more than one hundred metres (Tasmanian Climate Change Office 8). Eleven thousand years ago, Aboriginal people would have witnessed the rise of what is now called Bass Strait, turning what had been a peninsula into an archipelago, with the large island of Tasmania at its heart. The heterogeneous practices and narratives of Tasmanian regional identity have been shaped by the geography of these islands, and their connection to the Southern Ocean and Antarctica. Regions, understood as “centres of collective consciousness and sociospatial identities” (Paasi 241) are constantly reproduced and reimagined through place-based social practices and communications over time. As we will show, diverse and contradictory narratives of Tasmanian regionality often co-exist, interacting in complex and sometimes complementary ways. Ecocritical literary scholar C.A. Cranston considers duality to be embedded in the textual construction of Tasmania, writing “it was hell, it was heaven, it was penal, it was paradise” (29). Tasmania is multiply polarised: it is both isolated and connected; close and far away; rich in resources and poor in capital; the socially conservative birthplace of radical green politics (Hay 60). The weather, as if sensing the fine balance of these paradoxes, blows hot and cold at a moment’s notice.Tasmania has wielded extraordinary political influence at times in its history—notably during the settlement of Melbourne in 1835 (Boyce), and during protests against damming the Franklin River in the early 1980s (Mercer). However, twentieth-century historical and political narratives of Tasmania portray the Bass Strait as a barrier, isolating Tasmanians from the mainland (Harwood 61). Sir Bede Callaghan, who headed one of a long line of federal government inquiries into “the Tasmanian problem” (Harwood 106), was clear that Tasmania was a victim of its own geography:the major disability facing the people of Tasmania (although some residents may consider it an advantage) is that Tasmania is an island. Separation from the mainland adversely affects the economy of the State and the general welfare of the people in many ways. (Callaghan 3)This perspective may stem from the fact that Tasmania has maintained the lowest Gross Domestic Product per capita of all states since federation (Bureau of Infrastructure Transport and Regional Economics 9). Socially, economically, and culturally, Tasmania consistently ranks among the worst regions of Australia. Statistical comparisons with other parts of Australia reveal the population’s high unemployment, low wages, poor educational outcomes, and bad health (West 31). The state’s remoteness and isolation from the mainland states and its reliance on federal income have contributed to the whole of Tasmania, including Hobart, being classified as ‘regional’ by the Australian government, in an attempt to promote immigration and economic growth (Department of Infrastructure and Regional Development 1). Tasmania is indeed both regional and remote. However, in this article we argue that, while regionality may be cast as a disadvantage, the island’s remote location is also an asset, particularly when viewed from a far southern perspective (Image 1).Image 1: Antarctica (Orthographic Projection). Image Credit: Wikimedia Commons, Modified Shading of Tasmania and Addition of Captions by H. Nielsen.Connecting Oceans/Collapsing DistanceTasmania and Antarctica have been closely linked in the past—the future archipelago formed a land bridge between Antarctica and northern land masses until the opening of the Tasman Seaway some 32 million years ago (Barker et al.). The far south was tangible to the Indigenous people of the island in the weather blowing in from the Southern Ocean, while the southern lights, or “nuyina”, formed a visible connection (Australia’s new icebreaker vessel is named RSV Nuyina in recognition of these links). In the contemporary Australian imagination, Tasmania tends to be defined by its marine boundaries, the sea around the islands represented as flat, empty space against which to highlight the topography of its landscape and the isolation of its position (Davies et al.). A more relational geographic perspective illuminates the “power of cross-currents and connections” (Stratford et al. 273) across these seascapes. The sea country of Tasmania is multiple and heterogeneous: the rough, shallow waters of the island-scattered Bass Strait flow into the Tasman Sea, where the continental shelf descends toward an abyssal plain studded with volcanic seamounts. To the south, the Southern Ocean provides nutrient-rich upwellings that attract fish and cetacean populations. Tasmania’s coast is a dynamic, liminal space, moving and changing in response to the global currents that are driven by the shifting, calving and melting ice shelves and sheets in Antarctica.Oceans have long been a medium of connection between Tasmania and Antarctica. In the early colonial period, when the seas were the major thoroughfares of the world and inland travel was treacherous and slow, Tasmania’s connection with the Southern Ocean made it a valuable hub for exploration and exploitation of the south. Between 1642 and 1900, early European explorers were followed by British penal colonists, convicts, sealers, and whalers (Kriwoken and Williamson 93). Tasmania was well known to polar explorers, with expeditions led by Jules Dumont d’Urville, James Clark Ross, Roald Amundsen, and Douglas Mawson all transiting through the port of Hobart. Now that the city is no longer a whaling hub, growing populations of cetaceans continue to migrate past the islands on their annual journeys from the tropics, across the Sub-Antarctic Front and Antarctic circumpolar current, and into the south polar region, while southern species such as leopard seals are occasionally seen around Tasmania (Tasmania Parks and Wildlife). Although the water surrounding Tasmania and Antarctica is at times homogenised as a ‘barrier’, rendering these places isolated, the bodies of water that surround both are in fact permeable, and regularly crossed by both humans and marine species. The waters are diverse in their physical characteristics, underlying topography, sea life, and relationships, and serve to connect many different ocean regions, ecosystems, and weather patterns.Views from the Far SouthWhen considered in terms of its relative proximity to Antarctic, rather than its distance from Australia’s political and economic centres, Tasmania’s identity undergoes a significant shift. A sign at Cockle Creek, in the state’s far south, reminds visitors that they are closer to Antarctica than to Cairns, invoking a discourse of connectedness that collapses the standard ten-day ship voyage to Australia’s closest Antarctic station into a unit comparable with the routinely scheduled 5.5 hour flight to North Queensland. Hobart is the logistical hub for the Australian Antarctic Division and the French Institut Polaire Francais (IPEV), and has hosted Antarctic vessels belonging to the USA, South Korea, and Japan in recent years. From a far southern perspective, Hobart is not a regional Australian capital but a global polar hub. This alters the city’s geographic imaginary not only in a latitudinal sense—from “top down” to “bottom up”—but also a longitudinal one. Via its southward connection to Antarctica, Hobart is also connected east and west to four other recognized gateways: Cape Town in South Africa, Christchurch in New Zealand; Punta Arenas in Chile; and Ushuaia in Argentina (Image 2). The latter cities are considered small by international standards, but play an outsized role in relation to Antarctica.Image 2: H. Nielsen with a Sign Announcing Distances between Antarctic ‘Gateway’ Cities and Antarctica, Ushuaia, Argentina, 2018. Image Credit: Nicki D'Souza.These five cities form what might be called—to adapt geographer Klaus Dodds’ term—a ‘Southern Rim’ around the South Polar region (Dodds Geopolitics). They exist in ambiguous relationship to each other. Although the five cities signed a Statement of Intent in 2009 committing them to collaboration, they continue to compete vigorously for northern hemisphere traffic and the brand identity of the most prominent global gateway. A state government brochure spruiks Hobart, for example, as the “perfect Antarctic Gateway” emphasising its uniqueness and “natural advantages” in this regard (Tasmanian Government, 2016). In practice, the cities are automatically differentiated by their geographic position with respect to Antarctica. Although the ‘ice continent’ is often conceived as one entity, it too has regions, in both scientific and geographical senses (Terauds and Lee; Antonello). Hobart provides access to parts of East Antarctica, where the Australian, French, Japanese, and Chinese programs (among others) have bases; Cape Town is a useful access point for Europeans going to Dronning Maud Land; Christchurch is closest to the Ross Sea region, site of the largest US base; and Punta Arenas and Ushuaia neighbour the Antarctic Peninsula, home to numerous bases as well as a thriving tourist industry.The Antarctic sector is important to the Tasmanian economy, contributing $186 million (AUD) in 2017/18 (Wells; Gutwein; Tasmanian Polar Network). Unsurprisingly, Tasmania’s gateway brand has been actively promoted, with the 2016 Australian Antarctic Strategy and 20 Year Action Plan foregrounding the need to “Build Tasmania’s status as the premier East Antarctic Gateway for science and operations” and the state government releasing a “Tasmanian Antarctic Gateway Strategy” in 2017. The Chinese Antarctic program has been a particular focus: a Memorandum of Understanding focussed on Australia and China’s Antarctic relations includes a “commitment to utilise Australia, including Tasmania, as an Antarctic ‘gateway’.” (Australian Antarctic Division). These efforts towards a closer relationship with China have more recently come under attack as part of a questioning of China’s interests in the region (without, it should be noted, a concomitant questioning of Australia’s own considerable interests) (Baker 9). In these exchanges, a global power and a state of Australia generally classed as regional and peripheral are brought into direct contact via the even more remote Antarctic region. This connection was particularly visible when Chinese President Xi Jinping travelled to Hobart in 2014, in a visit described as both “strategic” and “incongruous” (Burden). There can be differences in how this relationship is narrated to domestic and international audiences, with issues of sovereignty and international cooperation variously foregrounded, laying the ground for what Dodds terms “awkward Antarctic nationalism” (1).Territory and ConnectionsThe awkwardness comes to a head in Tasmania, where domestic and international views of connections with the far south collide. Australia claims sovereignty over almost 6 million km2 of the Antarctic continent—a claim that in area is “roughly the size of mainland Australia minus Queensland” (Bergin). This geopolitical context elevates the importance of a regional part of Australia: the claims to Antarctic territory (which are recognised only by four other claimant nations) are performed not only in Antarctic localities, where they are made visible “with paraphernalia such as maps, flags, and plaques” (Salazar 55), but also in Tasmania, particularly in Hobart and surrounds. A replica of Mawson’s Huts in central Hobart makes Australia’s historic territorial interests in Antarctica visible an urban setting, foregrounding the figure of Douglas Mawson, the well-known Australian scientist and explorer who led the expeditions that proclaimed Australia’s sovereignty in the region of the continent roughly to its south (Leane et al.). Tasmania is caught in a balancing act, as it fosters international Antarctic connections (such hosting vessels from other national programs), while also playing a key role in administering what is domestically referred to as the Australian Antarctic Territory. The rhetoric of protection can offer common ground: island studies scholar Godfrey Baldacchino notes that as island narratives have moved “away from the perspective of the ‘explorer-discoverer-colonist’” they have been replaced by “the perspective of the ‘custodian-steward-environmentalist’” (49), but reminds readers that a colonising disposition still lurks beneath the surface. It must be remembered that terms such as “stewardship” and “leadership” can undertake sovereignty labour (Dodds “Awkward”), and that Tasmania’s Antarctic connections can be mobilised for a range of purposes. When Environment Minister Greg Hunt proclaimed at a press conference that: “Hobart is the gateway to the Antarctic for the future” (26 Apr. 2016), the remark had meaning within discourses of both sovereignty and economics. Tasmania’s capital was leveraged as a way to position Australia as a leader in the Antarctic arena.From ‘Gateway’ to ‘Antarctic City’While discussion of Antarctic ‘Gateway’ Cities often focuses on the economic and logistical benefit of their Antarctic connections, Hobart’s “gateway” identity, like those of its counterparts, stretches well beyond this, encompassing geological, climatic, historical, political, cultural and scientific links. Even the southerly wind, according to cartoonist Jon Kudelka, “has penguins in it” (Image 3). Hobart residents feel a high level of connection to Antarctica. In 2018, a survey of 300 randomly selected residents of Greater Hobart was conducted under the umbrella of the “Antarctic Cities” Australian Research Council Linkage Project led by Assoc. Prof. Juan Francisco Salazar (and involving all three present authors). Fourteen percent of respondents reported having been involved in an economic activity related to Antarctica, and 36% had attended a cultural event about Antarctica. Connections between the southern continent and Hobart were recognised as important: 71.9% agreed that “people in my city can influence the cultural meanings that shape our relationship to Antarctica”, while 90% agreed or strongly agreed that Hobart should play a significant role as a custodian of Antarctica’s future, and 88.4% agreed or strongly agreed that: “How we treat Antarctica is a test of our approach to ecological sustainability.” Image 3: “The Southerly” Demonstrates How Weather Connects Hobart and Antarctica. Image Credit: Jon Kudelka, Reproduced with Permission.Hobart, like the other gateways, activates these connections in its conscious place-branding. The city is particularly strong as a centre of Antarctic research: signs at the cruise-ship terminal on the waterfront claim that “There are more Antarctic scientists based in Hobart […] than at any other one place on earth, making Hobart a globally significant contributor to our understanding of Antarctica and the Southern Ocean.” Researchers are based at the Institute for Marine and Antarctic Studies (IMAS), the Commonwealth Scientific and Industrial Research Organisation (CSIRO), and the Australian Antarctic Division (AAD), with several working between institutions. Many Antarctic researchers located elsewhere in the world also have a connection with the place through affiliations and collaborations, leading journalist Jo Chandler to assert that “the breadth and depth of Hobart’s knowledge of ice, water, and the life forms they nurture […] is arguably unrivalled anywhere in the world” (86).Hobart also plays a significant role in Antarctica’s governance, as the site of the secretariats for the Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR) and the Agreement on the Conservation of Albatrosses and Petrels (ACAP), and as host of the Antarctic Consultative Treaty Meetings on more than one occasion (1986, 2012). The cultural domain is active, with Tasmanian Museum and Art Gallery (TMAG) featuring a permanent exhibit, “Islands to Ice”, emphasising the ocean as connecting the two places; the Mawson’s Huts Replica Museum aiming (among other things) to “highlight Hobart as the gateway to the Antarctic continent for the Asia Pacific region”; and a biennial Australian Antarctic Festival drawing over twenty thousand visitors, about a sixth of them from interstate or overseas (Hingley). Antarctic links are evident in the city’s natural and built environment: the dolerite columns of Mt Wellington, the statue of the Tasmanian Antarctic explorer Louis Bernacchi on the waterfront, and the wharfs that regularly accommodate icebreakers such as the Aurora Australis and the Astrolabe. Antarctica is figured as a southern neighbour; as historian Tom Griffiths puts it, Tasmanians “grow up with Antarctica breathing down their necks” (5). As an Antarctic City, Hobart mediates access to Antarctica both physically and in the cultural imaginary.Perhaps in recognition of the diverse ways in which a region or a city might be connected to Antarctica, researchers have recently been suggesting critical approaches to the ‘gateway’ label. C. Michael Hall points to a fuzziness in the way the term is applied, noting that it has drifted from its initial definition (drawn from economic geography) as denoting an access and supply point to a hinterland that produces a certain level of economic benefits. While Hall looks to keep the term robustly defined to avoid empty “local boosterism” (272–73), Gabriela Roldan aims to move the concept “beyond its function as an entry and exit door”, arguing that, among other things, the local community should be actively engaged in the Antarctic region (57). Leane, examining the representation of Hobart as a gateway in historical travel texts, concurs that “ingress and egress” are insufficient descriptors of Tasmania’s relationship with Antarctica, suggesting that at least discursively the island is positioned as “part of an Antarctic rim, itself sharing qualities of the polar region” (45). The ARC Linkage Project described above, supported by the Hobart City Council, the State Government and the University of Tasmania, as well as other national and international partners, aims to foster the idea of the Hobart and its counterparts as ‘Antarctic cities’ whose citizens act as custodians for the South Polar region, with a genuine concern for and investment in its future.Near and Far: Local Perspectives A changing climate may once again herald a shift in the identity of the Tasmanian islands. Recognition of the central role of Antarctica in regulating the global climate has generated scientific and political re-evaluation of the region. Antarctica is not only the planet’s largest heat sink but is the engine of global water currents and wind patterns that drive weather patterns and biodiversity across the world (Convey et al. 543). For example, Tas van Ommen’s research into Antarctic glaciology shows the tangible connection between increased snowfall in coastal East Antarctica and patterns of drought southwest Western Australia (van Ommen and Morgan). Hobart has become a global centre of marine and Antarctic science, bringing investment and development to the city. As the global climate heats up, Tasmania—thanks to its low latitude and southerly weather patterns—is one of the few regions in Australia likely to remain temperate. This is already leading to migration from the mainland that is impacting house prices and rental availability (Johnston; Landers 1). The region’s future is therefore closely entangled with its proximity to the far south. Salazar writes that “we cannot continue to think of Antarctica as the end of the Earth” (67). Shifting Antarctica into focus also brings Tasmania in from the margins. As an Antarctic city, Hobart assumes a privileged positioned on the global stage. This allows the city to present itself as central to international research efforts—in contrast to domestic views of the place as a small regional capital. The city inhabits dual identities; it is both on the periphery of Australian concerns and at the centre of Antarctic activity. Tasmania, then, is not in freefall, but rather at the forefront of a push to recognise Antarctica as entangled with its neighbours to the north.AcknowledgementsThis work was supported by the Australian Research Council under LP160100210.ReferencesAntonello, Alessandro. “Finding Place in Antarctica.” Antarctica and the Humanities. Eds. Peder Roberts, Lize-Marie van der Watt, and Adrian Howkins. London: Palgrave Macmillan, 2016. 181–204.Australian Government. 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1909–22: Turkey exterminated over 1.5 million of its ethnically Armenian, and hundreds of thousands of its ethnically Greek and Assyrian, citizens. Most died in 1915. This period of decimation in now widely called the Armenian Genocide (Balakian 179-80).1910: Siamanto first published his poem, The Dance: “The corpses were piled as trees, / and from the springs, from the streams and the road, / the blood was a stubborn murmur.” When springs run red, when the dead are stacked tree-high, when “everything that could happen has already happened,” then time is nothing: “there is no future [and] the language of civilised humanity is not our language” (Nichanian 142).2007: In my novel The Edge of the World a ceramic bowl, luminous blue, recurs as motif. Imagine you are tiny: the bowl is broken but you don’t remember breaking it. You’re awash with tears. You sit on the floor, gather shards but, no matter how you try, you can’t fix it. Imagine, now, that the bowl is the sky, huge and upturned above your head. You have always known, through every wash of your blood, that life is shockingly precarious. Silence—between heartbeats, between the words your parents speak—tells you: something inside you is terribly wrong; home is not home but there is no other home; you “can never be fully grounded in a community which does not share or empathise with the experience of persecution” (Wajnryb 130). This is the stubborn murmur of your body.Because time is nothing, this essay is fragmented, non-linear. Its main characters: my mother, grandmother (Hovsanna), grandfather (Benyamin), some of my mother’s older siblings (Krikor, Maree, Hovsep, Arusiak), and Mustafa Kemal Ataturk (Ottoman military officer, Young Turk leader, first president of Turkey). 1915–2013: Turkey invests much energy in genocide denial, minimisation and deflection of responsibility. 24 April 2012: Barack Obama refers to the Medz Yeghern (Great Calamity). The use of this term is decried as appeasement, privileging political alliance with Turkey over human rights. 2003: Between Genocide and Catastrophe, letters between Armenian-American theorist David Kazanjian and Armenian-French theorist Marc Nichanian, contest the naming of the “event” (126). Nichanian says those who call it the Genocide are:repeating every day, everywhere, in all places, the original denial of the Catastrophe. But this is part of the catastrophic structure of the survivor. By using the word “Genocide”, we survivors are only repeating […] the denial of the loss. We probably cannot help it. We are doing what the executioner wanted us to do […] we claim all over the world that we have been “genocided;” we relentlessly need to prove our own death. We are still in the claws of the executioner. We still belong to the logic of the executioner. (127)1992: In Revolution and Genocide, historian Robert Melson identifies the Armenian Genocide as “total” because it was public policy intended to exterminate a large fraction of Armenian society, “including the families of its members, and the destruction of its social and cultural identity in most or all aspects” (26).1986: Boyajian and Grigorian assert that the Genocide “is still operative” because, without full acknowledgement, “the ghosts won’t go away” (qtd. in Hovannisian 183). They rise up from earth, silence, water, dreams: Armenian literature, Armenian homes haunted by them. 2013: My heart pounds: Medz Yeghern, Aksor (Exile), Anashmaneli (Indefinable), Darakrutiun (Deportation), Chart (Massacre), Brnagaght (Forced migration), Aghed (Catastrophe), Genocide. I am awash. Time is nothing.1909–15: Mustafa Kemal Ataturk was both a serving Ottoman officer and a leader of the revolutionary Young Turks. He led Ottoman troops in the repulsion of the Allied invasion before dawn on 25 April at Gallipoli and other sites. Many troops died in a series of battles that eventually saw the Ottomans triumph. Out of this was born one of Australia’s founding myths: Australian and New Zealand Army Corps (ANZACs), courageous in the face of certain defeat. They are commemorated yearly on 25 April, ANZAC Day. To question this myth is to risk being labelled traitor.1919–23: Ataturk began a nationalist revolution against the occupying Allies, the nascent neighbouring Republic of Armenia, and others. The Allies withdrew two years later. Ataturk was installed as unofficial leader, becoming President in 1923. 1920–1922: The last waves of the Genocide. 2007: Robert Manne published A Turkish Tale: Gallipoli and the Armenian Genocide, calling for a recontextualisation of the cultural view of the Gallipoli landings in light of the concurrence of the Armenian Genocide, which had taken place just over the rise, had been witnessed by many military personnel and widely reported by international media at the time. Armenian networks across Australia were abuzz. There were media discussions. I listened, stared out of my office window at the horizon, imagined Armenian communities in Sydney and Melbourne. Did they feel like me—like they were holding their breath?Then it all went quiet. Manne wrote: “It is a wonderful thing when, at the end of warfare, hatred dies. But I struggle to understand why Gallipoli and the Armenian Genocide continue to exist for Australians in parallel moral universes.” 1992: I bought an old house to make a home for me and my two small children. The rooms were large, the ceilings high, and behind it was a jacaranda with a sturdy tree house built high up in its fork. One of my mother’s Armenian friends kindly offered to help with repairs. He and my mother would spend Saturdays with us, working, looking after the kids. Mum would stay the night; her friend would go home. But one night he took a sleeping bag up the ladder to the tree house, saying it reminded him of growing up in Lebanon. The following morning he was subdued; I suspect there were not as many mosquitoes in Lebanon as we had in our garden. But at dinner the previous night he had been in high spirits. The conversation had turned, as always, to politics. He and my mother had argued about Turkey and Russia, Britain’s role in the development of the Middle East conflict, the USA’s roughshod foreign policy and its effect on the world—and, of course, the Armenian Genocide, and the killingof Turkish governmental representatives by Armenians, in Australia and across the world, during the 1980s. He had intimated he knew the attackers and had materially supported them. But surely it was the beer talking. Later, when I asked my mother, she looked at me with round eyes and shrugged, uncharacteristically silent. 2002: Greek-American diva Diamanda Galas performed Dexifiones: Will and Testament at the Perth Concert Hall, her operatic work for “the forgotten victims of the Armenian and Anatolian Greek Genocide” (Galas).Her voice is so powerful it alters me.1925: My grandmother, Hovsanna, and my grandfather, Benyamin, had twice been separated in the Genocide (1915 and 1922) and twice reunited. But in early 1925, she had buried him, once a prosperous businessman, in a swamp. Armenians were not permitted burial in cemeteries. Once they had lived together in a big house with their dozen children; now there were only three with her. Maree, half-mad and 18 years old, and quiet Hovsep, aged seven,walked. Then five-year-old aunt, Arusiak—small, hungry, tired—had been carried by Hovsanna for months. They were walking from Cilicia to Jerusalem and its Armenian Quarter. Someone had said they had seen Krikor, her eldest son, there. Hovsanna was pregnant for the last time. Together the four reached Aleppo in Syria, found a Christian orphanage for girls, and Hovsanna, her pregnancy near its end, could carry Arusiak no further. She left her, promising to return. Hovsanna’s pains began in Beirut’s busy streets. She found privacy in the only place she could, under a house, crawled in. Whenever my mother spoke of her birth she described it like this: I was born under a stranger’s house like a dog.1975: My friend and I travelled to Albany by bus. After six hours we were looking down York Street, between Mount Clarence and Mount Melville, and beyond to Princess Royal Harbour, sapphire blue, and against which the town’s prosperous life—its shopfronts, hotels, cars, tourists, historic buildings—played out. It took away my breath: the deep harbour, whaling history, fishing boats. Rain and sun and scudding cloud; cliffs and swells; rocky points and the white curves of bays. It was from Albany that young Western Australian men, volunteers for World War I, embarked on ships for the Middle East, Gallipoli, sailing out of Princess Royal Harbour.1985: The Australian Government announced that Turkey had agreed to have the site of the 1915 Gallipoli landings renamed Anzac Cove. Commentators and politicians acknowledged it as historic praised Turkey for her generosity, expressed satisfaction that, 70 years on, former foes were able to embrace the shared human experience of war. We were justifiably proud of ourselves.2005: Turkey made her own requests. The entrance to Albany’s Princess Royal Harbour was renamed Ataturk Channel. A large bronze statue of Ataturk was erected on the headland overlooking the Harbour entrance. 24 April 1915: In the town of Hasan Beyli, in Cilicia, southwest Turkey, my great grandfather, a successful and respected businessman in his 50s, was asleep in his bed beside his wife. He had been born in that house, as had his father, grandfather, and all his children. His brother, my great uncle, had bought the house next door as a young man, brought his bride home to it, lived there ever since; between the two households there had been one child after another. All the cousins grew up together. My great grandfather and great uncle had gone to work that morning, despite their wives’ concerns, but had returned home early. The women had been relieved to see them. They made coffee, talked. Everyone had heard the rumours. Enemy ships were massing off the coast. 1978: The second time in Albany was my honeymoon. We had driven into the Goldfields then headed south. Such distance, such beautiful strangeness: red earth, red rocks; scant forests of low trees, thin arms outstretched; the dry, pale, flat land of Norseman. Shimmering heat. Then the big, wild coast.On our second morning—a cool, overcast day—we took our handline to a jetty. The ocean was mercury; a line of cormorants settled and bobbed. Suddenly fish bit; we reeled them in. I leaned over the jetty’s side, looked down into the deep. The water was clear and undisturbed save the twirling of a pike that looked like it had reversed gravity and was shooting straight up to me. Its scales flashed silver as itbroke the surface.1982: How could I concentrate on splicing a film with this story in my head? Besides the desk, the only other furniture in the editing suite was a whiteboard. I took a marker and divided the board into three columns for the three generations: my grandparents, Hovsanna and Benyamin; my mother; someone like me. There was a lot in the first column, some in the second, nothing in the third. I stared at the blankness of my then-young life.A teacher came in to check my editing. I tried to explain what I had been doing. “I think,” he said, stony-faced, “that should be your third film, not your first.”When he had gone I stared at the reels of film, the white board blankness, the wall. It took 25 years to find the form, the words to say it: a novel not a film, prose not pictures.2007: Ten minutes before the launch of The Edge of the World, the venue was empty. I made myself busy, told myself: what do you expect? Your research has shown, over and over, this is a story about which few know or very much care, an inconvenient, unfashionable story; it is perfectly in keeping that no-one will come. When I stepped onto the rostrum to speak, there were so many people that they crowded the doorway, spilled onto the pavement. “I want to thank my mother,” I said, “who, pretending to do her homework, listened instead to the story her mother told other Armenian survivor-women, kept that story for 50 years, and then passed it on to me.” 2013: There is a section of The Edge of the World I needed to find because it had really happened and, when it happened, I knew, there in my living room, that Boyajian and Grigorian (183) were right about the Armenian Genocide being “still operative.” But I knew even more than that: I knew that the Diaspora triggered by genocide is both rescue and weapon, the new life in this host nation both sanctuary and betrayal. I picked up a copy, paced, flicked, followed my nose, found it:On 25 April, the day after Genocide memorial-day, I am watching television. The Prime Minister stands at the ANZAC memorial in western Turkey and delivers a poetic and moving speech. My eyes fill with tears, and I moan a little and cover them. In his speech he talks about the heroism of the Turkish soldiers in their defence of their homeland, about the extent of their losses – sixty thousand men. I glance at my son. He raises his eyebrows at me. I lose count of how many times Kemal Ataturk is mentioned as the Father of Modern Turkey. I think of my grandmother and grandfather, and all my baby aunts and uncles […] I curl over like a mollusc; the ache in my chest draws me in. I feel small and very tired; I feel like I need to wash.Is it true that if we repeat something often enough and loud enough it becomes the truth? The Prime Minister quotes Kemal Ataturk: the ANZACS who died and are buried on that western coast are deemed ‘sons of Turkey’. My son turns my grandfather’s, my mother’s, my eyes to me and says, It is amazing they can be so friendly after we attacked them.I draw up my knees to my chest, lay my head and arms down. My limbs feel weak and useless. My throat hurts. I look at my Australian son with his Armenian face (325-6).24 April 1915 cont: There had been trouble all my great grandfather’s life: pogrom here, massacre there. But this land was accustomed to colonisers: the Mongols, the Persians, latterly the Ottomans. They invade, conquer, rise, fall; Armenians stay. This had been Armenian homeland for thousands of years.No-one masses ships off a coast unless planning an invasion. So be it. These Europeans could not be worse than the Ottomans. That night, were my great grandfather and great uncle awoken by the pounding at each door, or by the horses and gendarmes’ boots? They were seized, each family herded at gunpoint into its garden, and made to watch. Hanging is slow. There could be no mistakes. The gendarmes used the stoutest branches, stayed until they were sure the men weredead. This happened to hundreds of prominent Armenian men all over Turkey that night.Before dawn, the Allies made landfall.Each year those lost in the Genocide are remembered on 24 April, the day before ANZAC Day.1969: I asked my mother if she had any brothers and sisters. She froze, her hands in the sink. I stared at her, then slipped from the room.1915: The Ottoman government decreed: all Armenians were to surrender their documents and report to authorities. Able-bodied men were taken away, my grandfather among them. Women and children, the elderly and disabled, were told to prepare to walk to a safe camp where they would stay for the duration of the war. They would be accompanied by armed soldiers for their protection. They were permitted to take with them what they could carry (Bryce 1916).It began immediately, pretty young women and children first. There are so many ways to kill. Months later, a few dazed, starved survivors stumbled into the Syrian desert, were driven into lakes, or herded into churches and set alight.Most husbands and fathers were never seen again. 2003: I arrived early at my son’s school, parked in the shade, opened The Silence: How Tragedy Shapes Talk, and began to read. Soon I was annotating furiously. Ruth Wajnryb writes of “growing up among innocent peers in an innocent landscape” and also that the notion of “freedom of speech” in Australia “seems often, to derive from that innocent landscape where reside people who have no personal scars or who have little relevant historical knowledge” (141).1984: I travelled to Vancouver, Canada, and knocked on Arusiak’s door. Afraid she would not agree to meet me, I hadn’t told her I was coming. She was welcoming and gracious. This was my first experience of extended family and I felt loved in a new and important way, a way I had read about, had observed in my friends, had longed for. One afternoon she said, “You know our mother left me in an orphanage…When I saw her again, it was too late. I didn’t know who they were, what a family was. I felt nothing.” “Yes, I know,” I replied, my heart full and hurting. The next morning, over breakfast, she quietly asked me to leave. 1926: When my mother was a baby, her 18 year-old sister, Maree, tried to drown her in the sea. My mother clearly recalled Maree’s face had been disfigured by a sword. Hovsanna, would ask my mother to forgive Maree’s constant abuse and bad behaviour, saying, “She is only half a person.”1930: Someone gave Hovsanna the money to travel to Aleppo and reclaim Arusiak, by then 10 years old. My mother was intrigued by the appearance of this sister but Arusiak was watchful and withdrawn. When she finally did speak to my then five-year-old mother, she hissed: “Why did she leave me behind and keep you?”Soon after Arusiak appeared, Maree, “only half a person,” disappeared. My mother was happy about that.1935: At 15, Arusiak found a live-in job and left. My mother was 10 years old; her brother Hovsep, who cared for her before and after school every day while their mother worked, and always had, was seventeen. She adored him. He had just finished high school and was going to study medicine. One day he fell ill. He died within a week.1980: My mother told me she never saw her mother laugh or, once Hovsep died, in anything other than black. Two or three times before Hovsep died, she saw her smile a little, and twice she heard her singing when she thought she was alone: “A very sad song,” my mother would say, “that made me cry.”1942: At seventeen, my mother had been working as a live-in nanny for three years. Every week on her only half-day off she had caught the bus home. But now Hovsanna was in hospital, so my mother had been visiting her there. One day her employer told her she must go to the hospital immediately. She ran. Hovsanna was lying alone and very still. Something wasn’t right. My mother searched the hospital corridors but found no-one. She picked up a phone. When someone answered she told them to send help. Then she ran all the way home, grabbed Arusiak’s photograph and ran all the way back. She laid it on her mother’s chest, said, “It’s all right, Mama, Arusiak’s here.”1976: My mother said she didn’t like my boyfriend; I was not to go out with him. She said she never disobeyed her own mother because she really loved her mother. I went out with my boyfriend. When I came home, my belongings were on the front porch. The door was bolted. I was seventeen.2003: I read Wajnryb who identifies violent eruptions of anger and frozen silences as some of the behaviours consistent in families with a genocidal history (126). 1970: My father had been dead over a year. My brothers and I were, all under 12, made too much noise. My mother picked up the phone: she can’t stand us, she screamed; she will call an orphanage to take us away. We begged.I fled to my room. I couldn’t sit down. I couldn’t keep still. I paced, pressed my face into a corner; shook and cried, knowing (because she had always told us so) that she didn’t make idle threats, knowing that this was what I had sometimes glimpsed on her face when she looked at us.2012: The Internet reveals images of Ataturk’s bronze statue overlooking Princess Royal Harbour. Of course, it’s outsized, imposing. The inscription on its plinth reads: "Peace at Home/ Peace in the World." He wears a suit, looks like a scholar, is moving towards us, a scroll in his hand. The look in his eyes is all intensity. Something distant has arrested him – a receding or re-emerging vision. Perhaps a murmur that builds, subsides, builds again. (Medz Yeghern, Aksor, Aghed, Genocide). And what is written on that scroll?2013: My partner suggested we go to Albany, escape Perth’s brutal summer. I tried to explain why it’s impossible. There is no memorial in Albany, or anywhere else in Western Australia, to the 1.5 million victims of the Armenian Genocide. ReferencesAkcam, Taner. “The Politics of Genocide.” Online Video Clip. YouTube. YouTube, 11 Dec. 2011. 6 Mar. 2013 ‹http://www.youtube.com/watchv=OxAJaaw81eU&noredirect=1genocide›.Balakian, Peter. The Burning Tigress: The Armenian Genocide. London: William Heinemann, 2004.BBC. “Kemal Ataturk (1881–1938).” BBC History. 2013. 6 Mar. 2013 ‹http://www.bbc.co.uk/history/historic_figures/ataturk_kemal.shtml›.Boyajian, Levon, and Haigaz Grigorian. “Psychological Sequelae of the Armenian Genocide.”The Armenian Genocide in Perspective. Ed. Richard Hovannisian. New Brunswick: Transaction, 1987. 177–85.Bryce, Viscount. The Treatment of the Armenians in the Ottoman Empire. London: Hodder and Stoughton, 1916.Galas, Diamanda. Program Notes. Dexifiones: Will and Testament. Perth Concert Hall, Perth, Australia. 2001.———.“Dexifiones: Will and Testament FULL Live Lisboa 2001 Part 1.” Online Video Clip. YouTube, 5 Nov. 2011. Web. 6 Mar. 2013 ‹http://www.youtube.com/watch?v=mvVnYbxWArM›.Kazanjian, David, and Marc Nichanian. “Between Genocide and Catastrophe.” Loss. Eds. David Eng and David Kazanjian. 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