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1

Abedon, Stephen T. "Phage Therapy: Eco-Physiological Pharmacology." Scientifica 2014 (2014): 1–29. http://dx.doi.org/10.1155/2014/581639.

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Bacterial virus use as antibacterial agents, in the guise of what is commonly known as phage therapy, is an inherently physiological, ecological, and also pharmacological process. Physiologically we can consider metabolic properties of phage infections of bacteria and variation in those properties as a function of preexisting bacterial states. In addition, there are patient responses to pathogenesis, patient responses to phage infections of pathogens, and also patient responses to phage virions alone. Ecologically, we can consider phage propagation, densities, distribution (within bodies), impact on body-associated microbiota (as ecological communities), and modification of the functioning of body “ecosystems” more generally. These ecological and physiological components in many ways represent different perspectives on otherwise equivalent phenomena. Comparable to drugs, one also can view phages during phage therapy in pharmacological terms. The relatively unique status of phages within the context of phage therapy as essentially replicating antimicrobials can therefore result in a confluence of perspectives, many of which can be useful towards gaining a better mechanistic appreciation of phage therapy, as I consider here. Pharmacology more generally may be viewed as a discipline that lies at an interface between organism-associated phenomena, as considered by physiology, and environmental interactions as considered by ecology.
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Jauhari, Mujahid Shiroth Rasyid, and Hanif Achmad Rasyid Jauhari. "PHENOMENA OF WORK FROM HOME POLICY IN DEALING WITH THE COVID-19 PANDEMIC." Journal of Public Administration 1, no. 2 (October 30, 2022): 43–52. http://dx.doi.org/10.61317/jc.v1i2.16.

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This scientific paper discusses the phenomenon of public policy, namely the policy of working from home (Work From Home) due to the co-19 pandemic. The author's purpose in choosing this title is because the Covid-19 pandemic is not only about health problems or prolonged transmission of the virus which results in death, but also about service, physiological, communication, psychological problems, and the tendency to overuse gadgets. This policy that has been regulated by the government by working from home (Work From Home) is in order to reduce cases of contracting the Covid-19 virus and can reduce the death rate which continues to grow, other policies regulated by the government also require every citizen to take vaccinations. Of course the work from home policy has advantages and disadvantages in several aspects of life and work. This scientific work seeks to provide an analysis of the Work From Home phenomenon during the Covid-19 pandemic. The Covid-19 pandemic has brought major changes to all levels of society in various aspects, including the socio-cultural aspects. The Covid-19 pandemic forced restrictions on social activities between individuals, giving rise to habits that were different from their previous lives. In other words, this pandemic has given rise to a new societal culture to respond to existing policies of limiting social activities. The results of the author's analysis, the Covid-19 pandemic is still happening today.
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Voisset, Cécile, Anne Op de Beeck, Pauline Horellou, Marlène Dreux, Thierry Gustot, Gilles Duverlie, François-Loic Cosset, Ngoc Vu-Dac, and Jean Dubuisson. "High-density lipoproteins reduce the neutralizing effect of hepatitis C virus (HCV)-infected patient antibodies by promoting HCV entry." Journal of General Virology 87, no. 9 (September 1, 2006): 2577–81. http://dx.doi.org/10.1099/vir.0.81932-0.

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The neutralizing activity of anti-hepatitis C virus (HCV) antibodies is attenuated by a factor present in human sera, which has been proposed to be high-density lipoproteins (HDLs). HDLs have also been shown to facilitate the entry of HCV pseudoparticles (HCVpp) into target cells. Here, the aim of the study was to determine whether HDL-mediated facilitation of HCVpp and infectious HCV (HCVcc) entry and attenuation of neutralization are two related phenomena. The data indicated that HDLs attenuate neutralization at a constant rate. In addition, as for HDL-mediated facilitation of HCVpp entry, attenuation of neutralization depended on the expression of the scavenger receptor BI (SR-BI) and its selective lipid-uptake function. Finally, kinetic experiments showed that HDL-mediated facilitation of HCVpp entry is more rapid than virus neutralization. Altogether, these observations indicate that HCV is exploiting the physiological activity of SR-BI for promoting its entry into target cells, which consequently also protects the virus against neutralizing antibodies.
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Sultana, Sonia, and Tawhida Jahan. "Physiological Effects of Pandemic COVID-19 On Children With Autism Spectrum Disorder In Bangladesh." Social Science Review 38, no. 1 (January 28, 2022): 203–16. http://dx.doi.org/10.3329/ssr.v38i1.56531.

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Novel Coronavirus (Covid-19) pandemic is considered as the most challenging and life-threatening condition in today’s world. It has been evident that children with autism spectrum disorder (ASD) face double challenge during the pandemic situation due to disrupted routine and unavailability of therapy resulting in some new adopted physiological symptoms that increases the risk of getting infected with corona virus. So, this study aims to find out the nature and causes of the physiological effects of Covid 19 pandemic on children with autism and at the same time suggest taking the proper action regarding these physiological phenomena reducing the of rate of vulnerability. The participants of this study are the parents and the therapists of the children (age range: 5-15 years) with ASD who have been chosen purposefully from Dhaka and Chattogram divisions, Bangladesh. Data has been collected from the participants with the questionnaire and focus group discussion tools through online platform zoom cloud. Results demonstrates that most of the children have an increase in body weight, reduced energy burning, and sleep disturbances since lockdown started that further worsen their hyperactivity suggesting the necessity of acting for the awareness of parents group and thus prevention of covid-19 among children with ASD. Social Science Review, Vol. 38(1), June 2021 Page 203-216
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5

Stoltz, Kyle, Tatyana Golovkina, and Vera Tarakanova. "Non-classical major histocompatibility factor H2-O counteracts gammaherpesvirus manipulation of the germinal center response." Journal of Immunology 208, no. 1_Supplement (May 1, 2022): 126.35. http://dx.doi.org/10.4049/jimmunol.208.supp.126.35.

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Abstract Gammaherpesviruses, such as Epstein Barr virus, infect 95% of adults and form lifelong infection primarily through manipulation of B cells. During primary infection, gammaherpesviruses establish latent infections within B cells and drive robust, polyclonal germinal center (GC) responses, which atypically include B cells specific to both viral and self antigens. Consequently, this humoral response results in production of both autoantibodies, and interestingly, antibodies reactive to antigens of non-human species. While this non-physiological production of antibodies suggests viral manipulation of immune tolerance, the underlying mechanisms driving these phenomena are poorly understood. Utilizing murine gammaherpesvirus 68 (MHV68), a rodent pathogen highly similar to EBV which serves as an animal model of EBV infection, we have discovered that the host factor H2-O (HLA-DO in humans) attenuates MHV68 latency establishment and the MHV68 driven GC response. H2-O acts as an inhibitor of H2-M (HLA-DM), the protein which regulates peptide exchange and thus the repertoire of peptides associated with the MHC-II peptide binding groove. We found that mice deficient in H2-O displayed increased MHV68 latent reservoirs, increased GC response, and a selective increase in dsDNA specific IgG, with no change in virus specific IgG at the peak of latent viral infection. These results show a novel role of H2-O in attenuating the non-physiological, self-directed B cell response driven by MHV68. Furthermore, these studies are the first to demonstrate that fine tuning of MHC-II antigen presentation is sufficient to alter the self-directed B cell differentiation usurped by a ubiquitous viral pathogen during establishment of life-long infection.
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Morikawa, Yuko, Toshiyuki Goto, Daisuke Yasuoka, Fumitaka Momose, and Tetsuro Matano. "Defect of Human Immunodeficiency Virus Type 2 Gag Assembly in Saccharomyces cerevisiae." Journal of Virology 81, no. 18 (July 3, 2007): 9911–21. http://dx.doi.org/10.1128/jvi.00027-07.

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ABSTRACT We have previously shown that the expression of human immunodeficiency virus type 1 (HIV-1) Gag protein in Saccharomyces cerevisiae spheroplasts produces Gag virus-like particles (VLPs) at the plasma membrane, indicating that yeast has all the host factors necessary for HIV-1 Gag assembly. Here we expand the study by using diverse primate lentiviral Gags and show that yeast does not support the production of HIV-2 or simian immunodeficiency virus SIVmac Gag VLPs but allows the production of SIVagm and SIVmnd Gag VLPs. Particle budding was observed at the surfaces of cells expressing SIVagm and SIVmnd Gags, but cells expressing HIV-2 and SIVmac Gags showed only membrane-ruffling structures, although they were accompanied with electron-dense submembrane layers, suggesting arrest at an early stage of particle budding. Comparison of HIV-1 and HIV-2 Gag expression revealed broadly equivalent levels of intracellular Gag expression and Gag N-terminal myristoylation in yeast. Both Gags showed the same membrane-binding ability and were incorporated into lipid raft fractions at a physiological concentration of salt. HIV-2 Gag, however, failed to form a high-order multimer and easily dissociated from the membrane, phenomena which were not observed in higher eukaryotic cells. A series of chimeric Gags between HIV-1 and HIV-2 and Gag mutants with amino acid substitutions revealed that a defined region in helix 2 of HIV-2 MA (located on the membrane-binding surface of MA) affects higher-order Gag assembly and particle production in yeast. Together, these data suggest that yeast may lack a host factor(s) for HIV-2 and SIVmac Gag assembly.
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Desai, Nisarg, Pawel Fedurek, Katie Slocombe, Adam Clark Arcadi, Lisa O'Bryan, Charlotte Uhlenbroek, and Michael Wilson. "Acoustic properties of chimpanzee pant-hoots reflect male mate quality." Journal of the Acoustical Society of America 153, no. 3_supplement (March 1, 2023): A186. http://dx.doi.org/10.1121/10.0018605.

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Sexual selection theory predicts that acoustic structure may provide cues of individual traits correlated with mate quality. Chimpanzee pant-hoots are complex, conspicuous calls that may be products of sexual selection. Insofar as pant-hoots are difficult to produce, requiring individuals to approach their physiological limits of sound production, they may serve as honest signals of physical condition. The highest pitch elements in pant-hoots appear the most difficult elements to produce, as they sometimes exhibit distortions in acoustic structure known as non-linear phenomena (NLP). Producing high pitch vocalizations with fewer NLPs may, thus, signal superior physical condition. We examined whether the proportion of NLPs, the pitch, and noise in these elements of the pant-hoots contain cues of mate quality including age, rank, and a measure of health (infection with the simian immunodeficiency virus, SIVcpz), and if they predict male mating success. Consistent with predictions from sexual selection, we found that (i) the proportion of NLPs was associated with age in a non-linear fashion—specifically, subadult and old males exhibited higher proportions of NLPs compared to males in their prime mating age; (ii) a lower proportion of NLPs predicted higher mating success; and (iii) SIVcpz positive individuals exhibited more noise in their pant-hoots.
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8

Fang, Shaozhong, Mi Lin, Muhammad Moaaz Ali, Yiping Zheng, Xiaoyan Yi, Shaojuan Wang, Faxing Chen, and Zhimin Lin. "LhANS-rr1, LhDFR, and LhMYB114 Regulate Anthocyanin Biosynthesis in Flower Buds of Lilium ‘Siberia’." Genes 14, no. 3 (February 23, 2023): 559. http://dx.doi.org/10.3390/genes14030559.

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The bulb formation of Lilium is affected by many physiological and biochemical phenomena, including flower bud differentiation, starch and sucrose accumulation, photoperiod, carbon fixation, plant hormone transduction, etc. The transcriptome analysis of flower buds of Lilium hybrid ‘Siberia’ at different maturity stages showed that floral bud formation is associated with the accumulation of anthocyanins. The results of HPLC-MS showed that cyanidin is the major anthocyanin found in Lilium ‘Siberia’. Transcriptome KEGG enrichment analysis and qRT-PCR validation showed that two genes related to flavonoid biosynthesis (LhANS-rr1 and LhDFR) were significantly up-regulated. The functional analysis of differential genes revealed that LhMYB114 was directly related to anthocyanin accumulation among 19 MYB transcription factors. Furthermore, the qRT-PCR results suggested that their expression patterns were very similar at different developmental stages of the lily bulbs. Virus-induced gene silencing (VIGS) revealed that down-regulation of LhANS-rr1, LhDFR, and LhMYB114 could directly lead to a decrease in anthocyanin accumulation, turning the purple phenotype into a white color. Moreover, this is the first report to reveal that LhMYB114 can regulate anthocyanin accumulation at the mature stage of lily bulbs. The accumulation of anthocyanins is an important sign of lily maturity. Therefore, these findings have laid a solid theoretical foundation for further discussion on lily bulb development in the future.
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9

Bogdanova, Simona, Tanya Shivacheva, Tsvetoslav Georgiev, and Petar Petrov. "Pain in COVID-19 and features of pathogenetic molecular mechanisms." Rheumatology (Bulgaria) 30, no. 4 (March 6, 2023): 28–33. http://dx.doi.org/10.35465/30.4.2022.pp28-33.

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Although it has been almost three years since the World Health Organization (WHO) declared a pandemic, COVID-19 is still an unsolved problem, thereby attracting great scientific interest. The disease has a heterogeneous clinical picture with multiple manifestations from different organs and systems. Currently, COVID-19 is perceived as a polysyndromic inflammatory disease involving not only the respiratory system, but also the musculoskeletal system, the cardiovascular system, the skin, the excretory and the nervous system, and is accompanied by a number of hematological, gastrohepatoenterological and endocrine disorders. Various pain phenomena also appear in the clinical presentation of the disease, often as a single manifestation or in combination with symptoms from different organs and systems. The pathogenesis of pain is complex and there is still no consensus on the exact driving mechanisms. Several different signaling pathways play an important role in the generation of pain impulses and perception. They are different for different types of pain. At this stage, the role of angiotensin-converting enzyme 2 (ACE), the renin-angiotensin system (RAC), angiotensin 2 receptors (AT2R), direct neuronal invasion of the virus, the involvement of pro-inflammatory cytokines, hypoxia, the involvement of macrophages, is discussed. as well as the role of overactivity of the immune system, causing the so-called "cytokine storm". Pain is the result of complex biochemical processes influenced to varying degrees by biological, physiological and social factors. Our knowledge at this stage remains scarce and is the subject of many studies on the key pathogenic mechanisms. Therefore, the purpose of this review is to describe the known mechanisms for the occurrence and persistence of pain in patients with COVID-19, as well as to classify the pain phenomena and present its most common localizations. The diagnosis and treatment of COVID-19 and associated pain should be carried out by a multidisciplinary team of specialists, given the heterogeneous clinical presentation of the disease.
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10

Petković, Marijana, and Radmila Metlaš. "Cross -Reactivity of the V3-Specific Antibodies with the Human C1q." Zeitschrift für Naturforschung C 56, no. 11-12 (December 1, 2001): 1135–43. http://dx.doi.org/10.1515/znc-2001-11-1235.

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Abstract It has been previously shown that the sequence similarity between a portion of the enve­lope glycoprotein 120 (gp120) from the human immunodeficiency virus type-1 (HIV-1) and several types of human collagen and collagen-like molecules exists. That observation led to the suggestion that the antibodies against the third hypervariable region (V3) of HIV-1 gpl20 (V3-specific antibodies) might have a role in the autoimmune phenomena observed in HIV-infected persons. In this study we have examined the cross-reactivity of the V3-specific anti­ bodies purified from sera of HIV-infected individuals, sera obtained from the rheumatoid arthritis and systemic lupus erythematosus patients, as well as from the sera of healthy volun­ teers with the separate chains of a subcomponent of the first component of the human com­ plement system, C1q. Our results show that the V3-specific antibodies are present in the sera of the HIV-infected individuals, patients suffering of the systemic autoimmune diseases as well as in the sera of healthy volunteers. Whereas these antibodies appeared in the HIV+-sera after antigen challenge, those present in the H IV --sera probably represent the antibod­ ies that are cross-reactive with the antigen. V3-reactive antibodies can be purified by affinity chromatography and they were highly specific for the V3-peptide. Additionally, they showed cross-reactivity with the separate chains of the human C1q as well as with the chicken colla­ gen type VI. Possible physiological implications are discussed.
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11

Savchenko, Serhii E., Olena O. Dyadyk, Kyrylo V. Chaika, Ludmila M. Onyshchyk, Ludmila I. Vorobey, Roman V. Zhykharskyi, and Volodymyr P. Bondaruk. "Pathomorphological characteristics and immunohistochemical features of placentae from hiv-positive pregnant women with fetal growth retardation." Wiadomości Lekarskie 73, no. 2 (2020): 215–19. http://dx.doi.org/10.36740/wlek202002101.

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The aim: To study the pathomorphological characteristics and immunohistochemical features of placentae from human immunodeficiency virus-positive (HIV-positive) pregnant women with FGR. Materials and methods: The study material was 32 placentae, including 12 placentae from HIV-positive pregnant women with FGR (study group), 10 placentae from HIVpositivepregnant women without FGR (comparison group) and 10 placentae from HIV-negative women with physiological pregnancy (control group). An immunohistochemical study was performed using monoclonal antibodies (MCA) against CD31+ and vascular endothelial growth factor (VEGF). Results: Pathomorphologic changes of the placentae from HIV-positive pregnant women with FGR were characterized by edema in the umbilical cord tissue, partial dissection of the vascular wall fibers, dysmucoidosis; intracellular edema and hemorrhage in the fetal membrane tissues. In the placentae tissue it was found marked manifestations of degenerative changes in the form of the areas of fibrinoid necrosis, pronounced manifestations of dysmucoidosis, vacuolation of the villi stroma, an increase in the number of avascular villi and immature villi of small caliber with the phenomena of syncytiotrophoblast focal hyperplasia. An immunohistochemical study with MCA against CD31+ revealed the expression (optical density) of the vascular endothelial cells up to 2 points, and the expression level up to 3 points in the isolated areas with the appearance of the expression on the villi surface and in their thickness. During immunohistochemical studies with VEGF the expression level and its optical density increased up to 2-3 points, in some areas the expression of deposits were detected on the villi surface, in their thickness and in the intervillous space. Conclusions: The comparative pathomorphological and immunohistochemical study of the placentae demonstrated more significant changes in the group of HIV-positive pregnant women with FGR. In the placentae of HIV-positive pregnant women with FGR immunohistochemical examinations revealed a high level of CD31+ and VEGF expression.
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12

Epand, Richard M. "Relationship of phospholipid hexagonal phases to biological phenomena." Biochemistry and Cell Biology 68, no. 1 (January 1, 1990): 17–23. http://dx.doi.org/10.1139/o90-003.

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Phospholipid bilayers can undergo morphological rearrangements to other phases. The formation of one of these nonbilayer phases, the hexagonal phase, is preceded by an increase in the hydrophobicity of the bilayer surface and a destabilization of the bilayer structure. Certain membrane additives promote, while others inhibit, the formation of the hexagonal phase. Many of the molecular features that determine this phase preference are understood. Some of the properties of membranes are modulated by agents that affect the relative stability of the bilayer and hexagonal phases. Addition of bilayer stabilizers to a membrane decreases its fusogenic behaviour. One such bilayer stabilizer is cholesterol sulfate, which may function physiologically to inhibit the fusion of sperm cells. Several antiviral agents are also found to be bilayer stabilizers and some have been shown to inhibit membrane fusion phenomena. Another biological property that is modulated in a predictable manner by agents which affect the bilayer–hexagonal phase equilibrium is insulin-promoted glucose uptake in adipocytes. Bilayer stabilizers inhibit this process showing that the effects of insulin can be modulated by the bulk biophysical properties of the membrane. The activity of a number of membrane-bound enzymes is also lowered by bilayer stabilizers. Neutral and zwitterionic bilayer stabilizers are inhibitors of protein kinase C. Thus, the alteration of the bilayer–hexagonal phase transition by drugs may provide a useful parameter for predicting their effects on biological membranes.Key words: hexagonal phase, phosphatidylethanolamine, membrane fusion, virus, insulin, protein kinase C.
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13

Grabowski, Jeffrey M., Olof R. Nilsson, Elizabeth R. Fischer, Dan Long, Danielle K. Offerdahl, Yoonseong Park, Dana P. Scott, and Marshall E. Bloom. "Dissecting Flavivirus Biology in Salivary Gland Cultures from Fed and Unfed Ixodes scapularis (Black-Legged Tick)." mBio 10, no. 1 (January 29, 2019): e02628-18. http://dx.doi.org/10.1128/mbio.02628-18.

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ABSTRACT The Ixodes scapularis tick transmits a number of pathogens, including tick-borne flaviviruses (TBFVs). In the United States, confirmed human infections with the Powassan virus (POWV) TBFV have a fatality rate of ∼10% and are increasing in incidence. Tick salivary glands (SGs) serve as an organ barrier to TBFV transmission, and little is known regarding the location of TBFV infection in SGs from fed ticks. Previous studies showed I. scapularis vanin (VNN) involved with TBFV infection of I. scapularis ISE6 embryonic cells, suggesting a potential role for this gene. The overall goal of this study was to use SG cultures to compare data on TBFV biology in SGs from fully engorged, replete (fed) ticks and from unfed ticks. TBFV multiplication was higher in SGs from fed ticks than in those from unfed ticks. Virus-like particles were observed only in granular acini of SGs from unfed ticks. The location of TBFV infection of SGs from fed ticks was observed in cells lining lobular ducts and trachea but not observed in acini. Transcript knockdown of VNN decreased POWV multiplication in infected SG cultures from both fed and unfed ticks. This work was the first to identify localization of TBFV multiplication in SG cultures from a fed tick and a tick transcript important for POWV multiplication in the tick SG, an organ critical for TBFV transmission. This research exemplifies the use of SG cultures in deciphering TBFV biology in the tick and as a translational tool for screening and identifying potential tick genes as potential countermeasure targets. IMPORTANCE Tick-borne flaviviruses (TBFVs) are responsible for more than 15,000 human disease cases each year, and Powassan virus lineage 2 (POWV-L2) deer tick virus has been a reemerging threat in North America over the past 20 years. Rapid transmission of TBFVs in particular emphasizes the importance of preventing tick bites, the difficulty in developing countermeasures to prevent transmission, and the importance of understanding TBFV infection in tick salivary glands (SGs). Tick blood feeding is responsible for phenomenal physiological changes and is associated with changes in TBFV multiplication within the tick and in SGs. Using SG cultures from Ixodes scapularis female ticks, the primary aims of this study were to identify cellular localization of virus-like particles in acini of infected SGs from fed and unfed ticks, localization of TBFV infection in infected SGs from fed ticks, and a tick transcript (with associated metabolic function) involved in POWV-L2 infection in SG cultures.
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14

Van den Brom, Luco J. "Vormt moderne antropologie een probleem voor het Christelijk geloof?" HTS Teologiese Studies / Theological Studies 69, no. 1 (January 14, 2013). http://dx.doi.org/10.4102/hts.v69i1.1924.

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Does modern anthropology pose a problem to the Christian faith? Contemporary scientific anthropology proposes a naturalistic conception of human personhood because of humankind’s place somewhere in the larger evolutionary process of life. Some authors use the theory of biological evolution to explain phenomena in other areas as well, and due to its success suggest it has universal application in cultural and religious studies too, as if it were a theory of everything. Darwin’s idea of a common origin of all life undermined a supposed superiority of humankind. It signalled the end of an Aristotelian metaphysical notion of classification and constituted a real blow for classical individualistic anthropology. Dawkins explains religion in terms of empirical immanent biological processes in the human brain. He views religious ideas as ‘memes’ that act like an infectious virus in mental processes. His hypothesis seems to be a relapse into the old Aristotelian pattern. Michael Persinger interprets religion as an internal physiological state of an individual brain and reduces the language of mental concepts to physiological states of a material brain. Persinger’s, and also Dennett’s, materialistic view presupposes a God’s Eye Point of View as an Archimedian perspective outside the world. If a God exists, the neurologists Newberg and d’Aquili argue that he needs a point of contact within our brain: the God spot. Sociobiologists Edward Wilson and David Wilson consider religion a form of group adaptation, because cooperating individuals show the primary benefits of cooperation and altruistic behaviour, just as social insects. Religion is an evolutionary support of altruistic instincts and creates a social infrastructure to benefit a cooperative society. However, social insects merely act on their instincts whereas human beings can act intentionally even against their primary instincts, because of motives for altruist practices inspired, for example, by the narratives and concepts of a Christian tradition. The communion of saints does not take place merely because of a social instinct, but because of the shared motive of the community as a whole, that is, the body of Christ, which acts altruistically irrespective of persons, including outsiders!
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Herrera-Velarde, Salvador, José Ramón Villanueva-Valencia, Paola Mendoza-Espinosa, and Ramón Castañeda-Priego. "Stability and structural evolution of double-stranded DNA molecules under high pressures: A molecular dynamics study." Frontiers in Physics 11 (February 6, 2023). http://dx.doi.org/10.3389/fphy.2023.1076787.

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Conformational changes and stability of interacting double-stranded DNA chains under high hydrostatic pressure in biological systems are striking topics of importance to study several biomolecular phenomena. For example, to unravel the physiological conditions at which life might occur and to ensure the right functionality of the biochemical processes into the cell under extreme thermodynamic conditions. Furthermore, such processes could shed light on the physicochemical properties of the DNA under high confinement and how, through different mechanisms, a virus releases its genome in order to infect a cell and, therefore, to promote the process of viral replication. To achieve a few steps toward this direction, we propose an all-atomistic molecular dynamics approach in the NPT isothermal-isobaric ensemble to account for how the interplay of DNA—DNA interaction, hydrogen bonding, and the hydrostatic pressure modifies both the DNA conformational degrees of freedom and the spatial organization of the DNA chains in the available volume. We consider two interacting double-stranded DNA chains immersed in an explicit aqueous solution, i.e., water and ions. Our preliminary results highlight the role of hydrogen bonding and electrostatic interactions between DNA strands to avoid denaturation and, therefore, to provide mechanical stability for the DNA molecules. However, the structural evolution, whose kinetics depends on the relaxation of the stresses induced by the pressure, indicates that almost in all pressure conditions, the equilibrium configuration corresponds to an alignment of the two double-stranded DNA molecules along their main axis of symmetry; the rearrangement between the two approaching DNA dodecamers does not always correspond to complementary base pairs and becomes a function of the thermodynamic conditions.
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Korukonda, Anuradha, Alexia Marriott, and David Weinshenker. "Consequences of Pathogenic Tau Expression in Mouse Locus Coeruleus." Alzheimer's & Dementia 19, S13 (December 2023). http://dx.doi.org/10.1002/alz.079429.

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AbstractBackgroundDuring the early stages of Alzheimer’s disease (AD), patients often suffer from prodromal symptoms such as anxiety, impulsivity, depression, agitation, and sleep disturbances prior to the onset of cognitive impairment. Incidentally, the brainstem noradrenergic locus coeruleus (LC) is the first structure to develop hyperphosphorylated ‘pretangle’ tau pathology in the human brain. Furthermore, norepinephrine (NE) influences several physiological processes such as sleep/wake cycle, arousal, stress, mood, and attention which have been implicated in the prodromal behavioral abnormalities. While clinical studies show significant correlations between LC dysfunction and neuropsychiatric symptoms, a causal relationship between early tau accumulation in the LC and the manifestations of prodromal behaviors remains to be resolved. To explore this, we developed a translationally‐relevant tau mouse model that recapitulates the ‘LC first’ phenomena commonly observed in humans.MethodAdult male and female tyrosine hydroxylase (TH)‐Cre mice aged 4 months underwent intra‐LC infusions with a Cre‐dependent adeno‐associated virus (AAV) expressing mCherry, wild‐type (WT) human tau or P301S mutant human tau (n = 3/group). 3 months post‐infusion, mice underwent a panel of behavioral tests to assess sleep latency, locomotor activity, compulsivity, stress‐induced anxiety‐like behavior, association memory deficits, impulsivity, and attentional impairments. Following behavioral tests, brain sections comprising the LC, hippocampus and prefrontal cortex (PFC) were immunostained with TH to assess for LC integrity, AT8 to detect pretangle tau, NE transporter (NET) to evaluate NE fiber intensity in projection regions, and GFAP and IBA1 to identify neuroinflammatory markers. Immunoreactivity (IR) will be calculated as a measure of fluorescence via ImageJ.ResultIt has been proposed that tau accumulation in the LC may provoke mild to moderate damage in LC neurons, triggering compensatory mechanisms such as LC hyperactivity. It is hypothesized that at 3 months, LC‐specific tau pathology will result in hyperarousal, compulsivity, anxiety‐like behavior, and impulsivity. In tandem, human tau‐expressing mice are expected to display increased TH, reflecting LC hyperactivity, neuroinflammatory markers and reductions in NE fibers in LC‐projecting regions. These findings will be presented in July 2023.ConclusionThis research will elucidate the role of LC in governing prodromal symptoms. Further studies will be needed to assess molecular mechanisms underlying tau‐mediated LC dysfunction in early AD.
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McDuffie, Dennis, David Barr, Ashutosh Agarwal, and Emmanuel Thomas. "Physiologically relevant microsystems to study viral infection in the human liver." Frontiers in Microbiology 13 (September 28, 2022). http://dx.doi.org/10.3389/fmicb.2022.999366.

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Viral hepatitis is a leading cause of liver disease and mortality. Infection can occur acutely or chronically, but the mechanisms that govern the clearance of virus or lack thereof are poorly understood and merit further investigation. Though cures for viral hepatitis have been developed, they are expensive, not readily accessible in vulnerable populations and some patients may remain at an increased risk of developing hepatocellular carcinoma (HCC) even after viral clearance. To sustain infection in vitro, hepatocytes must be fully mature and remain in a differentiated state. However, primary hepatocytes rapidly dedifferentiate in conventional 2D in vitro platforms. Physiologically relevant or physiomimetic microsystems, are increasingly popular alternatives to traditional two-dimensional (2D) monocultures for in vitro studies. Physiomimetic systems reconstruct and incorporate elements of the native cellular microenvironment to improve biologic functionality in vitro. Multiple elements contribute to these models including ancillary tissue architecture, cell co-cultures, matrix proteins, chemical gradients and mechanical forces that contribute to increased viability, longevity and physiologic function for the tissue of interest. These microsystems are used in a wide variety of applications to study biological phenomena. Here, we explore the use of physiomimetic microsystems as tools for studying viral hepatitis infection in the liver and how the design of these platforms is tailored for enhanced investigation of the viral lifecycle when compared to conventional 2D cell culture models. Although liver-based physiomimetic microsystems are typically applied in the context of drug studies, the platforms developed for drug discovery purposes offer a solid foundation to support studies on viral hepatitis. Physiomimetic platforms may help prolong hepatocyte functionality in order to sustain chronic viral hepatitis infection in vitro for studying virus-host interactions for prolonged periods.
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18

Johnson, Laurie. "Sick Puppies and Other Unbecoming Things." M/C Journal 4, no. 3 (June 1, 2001). http://dx.doi.org/10.5204/mcj.1908.

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Lovecraft applies the term "Outsider" to this thing or entity, the Thing, which arrives and passes at the edge, which is linear yet multiple, "teeming, seething, swelling, foaming, spreading like an infectious disease, this nameless horror." Gilles Deleuze and Félix Guattari, A Thousand Plateaus (1987, 245) In the opening sequence to John Carpenter's The Thing (Universal Pictures, 1982), a lone husky flees a Norwegian gunman across the Antarctic tundra. The dog is resuced by an American scientific team and the gunman is killed, leaving no explanation for the hunt. Later, when the dog is caged along with the American husky pack, it mutates violently, attacking the other dogs and members of the expedition. It becomes apparent that what the Americans have taken into their isolated community is an alien lifeform capable of adopting the form of creatures it kills, and the team have no way of knowing who has been replicated/replaced already. Given that Carpenter unashamedly borrows images and dialogue from Howard Hawks in so many of his other films, it is ironic that this film should self-consciously avoid borrowing from Hawks's The Thing From Another World (RKO, 1951 [Dir: Christian Nyby]), of which it is ostensibly a remake. Hawks's Arctic Cold War story is replaced by an Antarctic horror tale-the two films are literally poles apart. The obvious key to this difference is that Rob Bottin's special effects wizardry enables Carpenter (through Bill Lancaster's screenplay) to adhere more closely to the plot of John W. Campbell's 1938 novella ("Who Goes There?") about a shape-shifting menace generating paranoia among inhabitants of a small community. Hawks's film (screenplay by Charles Lederer) also hinges on a sense of paranoia, but its source is unequivocal: Hawks's alien is little more than a blood-sucking vegetable from space. Paranoia in Carpenter's film has something to do with the fear of being killed, but is also as much a matter of not knowing what form the enemy is taking at any point in time. Of course, the special effects do not contribute to this uncertainty-the paranoia is at its most intense when things appear to be normal. Yet this intensity is fed in the first instance by knowing the excesses of which "the thing" is capable when forced to reveal itself. The irony of this remake not being made in the image of its original is compounded by the fact that Carpenter's film was panned by critics and failed badly at the box office on its release in 1982-by contrast, the 1951 version is widely considered to be a classic, credited with starting the alien SF film boom of the 1950s. More recently, Carpenter's film has acquired something of a cult status. Indeed, a 1999 poll by British Total Film magazine rated The Thing as the eleventh scariest film of all time. Yet clearly the "gore factor" which gives to such a film its cult status was a contributing factor in its initial failure, although I think it is necessary to be sure of what we mean when we say this. The timing of the release of The Thing is generally thought to have been a major factor, based on the assumption that a filmgoing public still enamoured with Spielberg's E.T. was always going to be unreceptive to Carpenter's shapeshifting horror. What may be even more pertinent was that Carpenter's horror was released onto the big screen about the time that this same filmgoing public was coming to terms with a new "horror": the advent of AIDS. I recently read a commentary on the resurgence of interest in The Thing, in which the author claims that Carpenter's film functioned in 1982 as a cold war metaphor after the manner of the 1951 original, and that it is the potential AIDS resonances in the film-in as much as "the only way to detect alien infection is a 'blood test'"-which strike a chord with newer audiences. To my way of thinking, Bryant Frazer's review for Deep Focus provides a more appropriate assessment of the immediate context for The Thing when he categorises it "as part of a movement in genre film that dealt with biological horror" along with films like Ridley Scott's Alien and David Cronenberg's Scanners and Videodrome. As Frazer observes, these films provide "unsettling visions of anxiety over the physical nature of our bodies, and of the possibility that our essential natures may be changed by alien entities, by pollutants and disease". Yet Carpenter's film sits uneasily alongside other biohorror films, perhaps because it is such an extreme product of this movement. Scott's virtually indestructible xenomorph literally burst (through John Hurt's chest) onto cinema screens to terrorise audiences by its capacity to turn human beings into expendable commodities (mere links on the food chain or hosts along the creature's parasitic life cycle). Yet this alien's capacity for the spectacular kill is dwarfed by Carpenter's outrageous shapeshifter, sprouting tentacles, serpentine heads, razor-sharp teeth, and other amorphous extensions from what would seem to be normal bodies. Mainstream cinema audiences may have loved Spielberg's tubby, telecommunicating extraterrestrial enough to shun Carpenter's killer, but it may be that even fans of Scott's space monster might have failed to share in the spirit of Carpenter's knowing wink at excess-recall the response of Windows (Thomas Waites) when a severed head sprouts legs and scuttles away: "You've got to be fucking kidding." The irony is that, in spite of its obvious excesses, Carpenter's alien is still closer to home than Scott's: the latter occupies the human body by infestation, the former by infection. Frazer makes explicit the particular resonance of this difference in the biohorror film: "The Thing can be read as a parable of the self-destructive 'witch-hunt' mentality, or of the ravages that an insidious killer like AIDS (just blossoming as The Thing was being shot) can wreak on the survivors, as well as those infected." The point to be made here is that the excesses of Carpenter's film may not, in and of themselves, be sufficient to explain its capacity to unnerve its potential audience at the time of its release. In 1982, the syndrome formerly identified as GRID (Gay-Related Immune Deficiency) was renamed AIDS (Acquired Immune Deficiency Syndrome) as it was discovered that the agent, "possibly a virus that could be spread through blood," could affect people other than just gay men: the first recipient by blood transfusion was identified in the United States as were the first affected infants (Avert: AIDS History). Perhaps unwittingly, Carpenter's film mirrors the spread of discourses about the AIDS syndrome, as much as its monster mirrors the virus itself. The fact that the protagonists in the film are all men living in isolation provides a none too subtle reference to the gay male community to which it was initially thought that GRID could be solely attributed. In the film, as in society, the potential for the menace to spread beyond this immediate community is identified with the knowledge that it spreads through blood, a knowledge that translates into moral panic. When Copper (Richard A. Dysart) discovers through a computer simulation-closely resembling a simulation called "life," which I remember playing in the 1980s-that "the thing" could consume the human race within days, he determines to stop the spread, and when Copper dies, Blair (Wilfrid Grimley) responds even more violently by trying to cut the team off from its external contacts and supplies. Thus, what the film reflects back to its audience is a recognition that the spread of panic associated with AIDS is every bit as insidious as the spread of the virus associated with the same syndrome. This panic operates by isolating and targeting the victims as though they are the infection themselves, potential killers. Initially, this could be done at group levels-for example, the gay male community at first, then drug users, and so on-yet it ultimately proceeds by reducing the limits of the abject, until all that is left is to isolate the individual in each instance. To have been infected is in itself enough to be identified as having the characteristics of any number of the social evils associated with the spread of the virus, but it is nevertheless enough also to be characterised as a threat of infection to the rest of the human race. In this sense, the victim becomes the virus. The reader may now sense the relevance of the reference to Deleuze and Guattari with which I framed this essay at the outset. The epigraph is taken from "1730: Becoming-Intense, Becoming-Animal, Becoming-Imperceptible . . ." (A Thousand Plateaus, 1987, 232-309), an essay that remains the duo's most sustained elaboration of the processes of "becoming." Borrowing the concept for my purposes here, it can be said that The Thing represents in spectacular form the process of victim becoming virus via mechanisms of social isolation: alienation is literalised in the becoming-alien of members of an already isolated community. Central to an understanding of becoming as a process is the relationship between single and multiple phenomena; "between the pack and the loner; between mass contagion and preferential alliance; between pure multiplicity and the exceptional individual" (244). In The Thing, we may recall, the first inclination we have that something is amiss is that a lone husky (nominally a pack animal) is fleeing a crazed gunman. Deleuze and Guattari enable the concept of the pack to fade into the process of contagion. When the isolated animal is restored to a pack existence, contagion is immediately literalised in the film: it first seems to act as though it is sick, and then we are introduced to the spectacle of this shapeshifter in extremis, spreading itself out into the pack, and then into the community. From this early point in the film, we can no longer be in any doubt that becoming-alien through the mechanism of contagion has nothing to do with the coming into reality of a higher order of being, or of the realisation of potential states, etcetera. Commenting on becoming, Catherine Malabou points out that the Deleuzo-Guattarian understanding is a removal of the concept from "the Hegelian definition of an intermediate state between being and nothingness," as it is "not a hesitation between the abyssal vertigo of absence of form and the security of a particular incarnation" ("Who's Afraid," 1996, 125). For it is precisely at the moment that the animal is ushered towards its apparent destiny at the border of the pack that it lashes out against the security of the pack existence. Instead, The Thing offers a representation of the imposition of the molecular onto the incarnate. For this reason, I consider the film to be a neat container for what remains one of Deleuze and Guattari's more elusive concepts. It demonstrates that "becoming" includes processes at every level from the microbial to the communal, leading us to conclude that the spread of the contagion is inseparable from the panic that consumes the community: they are precisely one and the same process of becoming-alien. For a film to visually represent this relation, of course, what must be rendered visible are the intensities that characterise all becomings, hence the visual excesses to which it goes. It is to these intensities, more so than just the "gore factor" alone, that I think audiences react when they view The Thing, cognisant of the spectre of AIDS. The shapeshifter's metamorphoses are not merely excessive, they are intense, which is to say that they are tenuous (and yet tenable) threads in the process of becoming-alien, which we have seen cuts across the molecular and the communal to unite the social with the physiological. Clifford M. Skoog observes that Deleuze's use of biological terminology with reference to social phenomena and their effects is not strictly referential, nor is it metaphorical: "His work in any case powerfully evokes the kinds of processes we observe in life at its cellular and molecular levels, and is especially provocative concerning the extent to which we might look at language and social life as incorporating a 're-incarnation' of life's most elemental processes" (Thinking's Legacy and the Evolution of Experience, 1998). Carpenter's film, I suggest, evokes much the same connection between discursive and social realities and the elemental stuff of which we are made, all of which is fleeting. In reflecting back to us the social context for the "witch-hunt" mentality, or by literalising the process by which the victim becomes the contagion in the eyes of the witch-hunters, The Thing also provides a stark reminder of the physical limits by which we are bound. Held in the grip of contagion, as our bodies succumb at the cellular level to infection, do we somehow cease to be ourselves? Yet the question is not one of physical essences, as our "selves" are defined as much in the social extensions of the body, in the eye of the beholder, as it were, a Deleuzian point brought home to the audience with intensity by The Thing. Becoming, in this sense, is an unbecoming thing, for it is the very opposite of belonging. It turns away from well-being, from being well, or perhaps from being per se. Do we therefore turn away from becoming? Or, as the resurgence in interest in The Thing in the last few years might prompt us to ask, have we begun at last to look back at the unbecoming things from which we have averted our gaze for so long. References Deleuze, Gilles & Félix Guattari. A Thousand Plateaus: Capitalism and Schizophrenia. Trans. Brian Massumi. Minneapolis: University of Minnesota Press (1987). Malabou, Catherine. "Who's Afraid of Hegelian Wolves?" Deleuze: A Critical Reader. Ed. Paul Patton. Oxford: Blackwell Publishers (1996): 114-38.
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