Dissertations / Theses: 'Cell compartment'

1

Fallen, Paul Raymond. "Reconstitution of the T-cell compartment post-allogeneic haematopoietic cell transplantation." Thesis, University College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.268750.

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Alderson, Kory L. "Deleterious changes to the T cell compartment following immunotherapy." abstract and full text PDF (UNR users only), 2009. http://0-gateway.proquest.com.innopac.library.unr.edu/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3355571.

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3

Tshering, Sherpa Rinzhin. "Sensory Primary Cilium is a Distinct Signaling Compartment." Chapman University Digital Commons, 2019. https://digitalcommons.chapman.edu/pharmaceutical_sciences_dissertations/1.

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The primary cilium is a solitary cellular organelle that protrudes from the apical cell membrane. Findings on cilia-dependent mechanosenstation have shown that the primary cilium acts as a transducer of fluid-shear stress into intracellular signaling. Over recent years, studies in primary cilia have intensified after determining a causal relationship between dysfunctional primary cilia and cystic diseases. Along with its mechanosensory function, the primary cilium houses a variety of receptors, ion channels and transporter proteins. Studies in cilia biology have shown that primary cilia are coordinators of signaling pathways such as Hedgehog (Hh), Wnt, and platelet-derived growth factor (PDGF) pathways during development and tissue homeostasis. The primary cilium has been established as a mechano, chemo- and osmosensing unit that transmits extracellular cues to the cell, which supports the importance of the primary cilium. As an important organelle involved in sensory functions and signal transductions, we encompass methodology for measuring cilia signaling along with a study of pH sensing function and cAMP signaling dynamics in the cilium. Defects in the structure of cilia or protein complexes located in the primary cilia cause a variety of diseases. With increasing the knowledge of ciliary biology, we can strategize approaches to repair defective cilia. Here we try to contribute to understanding the complex dynamic pathways of the cilia and point to potential pathways in regulating ciliary structure and function.

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Buffa, Laura. "Cell Biology of the ICA69 protein family in Neurosecretory cells." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2007. http://nbn-resolving.de/urn:nbn:de:swb:14-1174057636463-96361.

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In type 1 diabetes (T1D), an autoimmune disease, autoantibodies are preferentially directed against proteins associated with Golgi and post-Golgi secretory vesicles, including insulin secretory granules and synaptic-like microvesicles. Thus, the study of beta-cell autoantigens with yet unknown function may provide novel insight into the secretory machinery of beta-cells and led to the discovery of novel pathways. Islet cell autoantigen of 69 kDa (ICA69) is a T1D autoantigen. It is a cytosolic protein of still unknown function. An impairment in neurotransmitter release upon mutation of its homologue in C. elegans suggests, however, an involvement of ICA69 in neurosecretion. Interestingly, ICA69 contains a BAR domain, present in several proteins involved in intracellular transport. The BAR domain functions as a dimerization motif, provides a general binding interface for different types of GTPases, and is a membrane binding/bending module. Its presence in ICA69 is a further hint supporting the putative involvement of ICA69 in intracellular membrane trafficking. The first part of this thesis was concerned with the characterization of ICA69, and the elucidation of its role in membrane traffic in pancreatic beta-cells. ICA69 was shown to be enriched in the perinuclear region, where also markers of the Golgi region are found. ICA69 was shown to interact with several membrane lipids, preferentially with PI(4)P, enriched on the Golgi complex. During the course of this thesis a combination of biochemical and imaging techniques were applied to investigate the interaction between ICA69 and Rab2, a small GTPase associated with the intermediate compartment and involved in the trafficking between the ER and the Golgi complex. ICA69 was shown to co-immunoprecipitate with Rab2 from INS-1 cells extracts. GST-pull down assays demonstrated that this interaction is GTP-dependent. Furthermore, confocal microscopy indicated that ICA69 and Rab2 extensively colocalize in particulate structures throughout the cytoplasm. Immunocytochemistry and subcellular fractionation experiments suggested that Rab2 recruits ICA69 to membranes. Functional studies indicated that ICA69 over-expression in INS-1 cells has effects that resemble, and in some cases amplify those observed upon Rab2 over-expression. Specifically, it impairs the trafficking between ER and Golgi, measured through the appearance and the conversion of the pro-form of ICA512 in the mature form of the protein. Moreover, it correlates with a redistribution of the beta-COP subunit of the coatomer, participating in the early secretory pathway, between membrane-bound compartments and the cytosol and it reduces stimulated insulin secretion. The data reported in this thesis conclusively point to ICA69 as a novel Rab2 effector, and may therefore contribute to the elucidation the yet poorly understood mechanism of action of Rab2 in the secretory pathway. The second part of the thesis was devoted to the study of an ICA69 paralogue gene, called ICA69-RP. Similarly to ICA69, ICA69-RP mRNA was shown to be primarily present in tissues such as brain and pancreatic islets, showing the expression pattern of a gene preferentially expressed in neuroendocrine cells. Unlike ICA69, however, and similar to other genes associated with the secretory machinery of beta-cells, ICA69-RP appeared to be glucose regulated, as shown by a 1.55 fold increase in mRNA levels upon stimulation of the cells with 25 mM glucose for two hours.Glucose stimulation of beta-cells prompts the activation of post-transcripional mechanisms which quickly up-regulate the expression of secretory granule genes and consequently renew granule stores. The increased expression of ICA69-RP upon glucose stimulation of cells may be part of this process. Unfortunately, all attempts to elucidate the intracellular localization of endogenous ICA69-RP failed, and it was not possible to obtain significant insights about its localization by over-expressing a fusion protein between ICA69-RP and GFP. Unlike other paralogues containing the BAR domain, such as amphiphysin 1 and 2 or Rvs167p and Rvs161p, ICA69 and ICA69-RP were shown not to form heterodimers. Furthermore, ICA69-RP did not show any interaction with Rab2 or Rab1, involved in the anterograde transport between ER and Golgi. Thus, its physiological role remains to be investigated.

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Dujardin, Hélène. "Ontogeny and homeostasis of the peripheral regulatory CD4T cell compartment." Paris 6, 2006. http://www.theses.fr/2006PA066109.

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Onions, Louise. "Immunological monitoring of the B-cell compartment in renal transplant recipients." Thesis, Queen Mary, University of London, 2014. http://qmro.qmul.ac.uk/xmlui/handle/123456789/8969.

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B cells contribute to chronic allograft deterioration, negatively impacting graft survival, and curtailing the lifespan of a resource already in short supply. Given this, identifying alloreactive B cells could generate an important target in the battle against rejection. This study described an IgG-detecting ELISPOT used to determine if the risk of developing antibody-mediated rejection (AMR) could be predicted pretransplantation by in vitro analysis of allospecific B cells. This method failed to discriminate accurately B-cell responses to donor antigen. An alternative approach used was to detect peripheral HLA-specific B cells. Circulating HLA–A*0201 and – DQB1*0301 B cells were identified at higher frequency in sensitised patients, and this correlated with the level of serum alloantibody. Expression of HLA-DQB1*0301 B cells were at a higher frequency than HLA-A*0201 B cells in those with serum de novo donor-specific antibody (dnDSA). Next, levels of B-cell activating factor (BAFF) were investigated. Excess BAFF has been related to rejection and the development of DSA. Here elevated serum BAFF, low BAFF-receptor and DSA were all associated with deteriorating graft function. In addition intrarenal CD19+ cells, BAFF and BAFFreceptor identified with acute AMR. In contrast to a pathogenic role of B cells, a small population may be protective. The presence of regulatory B cells, defined by IL-10 production were higher in those with stable graft function, and identified with naïve B cells rather than memory B cells when compared to those with deteriorating grafts. The CD19+CD24highCD38high subset was also elevated in stable patients, and the ability to supress T-cell activation and secretion of the Th1 cell pro-inflammatory cytokine, IFN-γ was altered as a function of allograft stability. These data demonstrated characteristics within the B-cell compartment associated with stable graft function. The ability to monitor these cells may have clinical implications for predicating the risk of rejection, to dictate immunosuppressive therapy and promote allograft survival.

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Carr, Jonathon M. "Heterogeneity within the stem cell compartment : impact on fate determination of human pluripotent stem cells." Thesis, University of Sheffield, 2018. http://etheses.whiterose.ac.uk/20386/.

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Tetley, Robert John. "Linking actomyosin patterning with cell behaviours at compartment boundaries in Drosophila embryos." Thesis, University of Cambridge, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708429.

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9

Deng, Yuping. "Studies of intraorganelle dynamics : the lysosome, the pre-lysosomal compartment, and the golgi apparatus /." Diss., This resource online, 1991. http://scholar.lib.vt.edu/theses/available/etd-07282008-134815/.

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Young, Madeleine. "The effects of aberrant Wnt signalling on the murine intestinal stem cell compartment." Thesis, Cardiff University, 2013. http://orca.cf.ac.uk/53683/.

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Colorectal cancer is the 2nd most common cause of death by cancer in the UK, but it is treatable if diagnosed early. In order to increase the likelihood of early diagnosis, more must be understood about the early stages of colorectal tumourigenesis. It is known that intestinal stem cells (ISCs) are the cells of origin of colorectal tumourigenesis, and that an expansion of undifferentiated cell types, akin to ISCs, is one of the earliest events in mouse models of tumourigenesis. This indicates the importance of the relationship between the ISC compartment and tumourigenesis. In order to understand how changes in the ISC compartment may be contributing to tumourigenesis, the ability to accurately quantify this compartment is essential. Currently, analysis of the ISC compartment relies on the analysis of gene expression levels of ISC markers. However, there is a great deal of controversy surrounding the majority of these markers and there is no evidence that alterations in expression levels of these markers results in a functional change in the ISC compartment. Here I present a novel method for assessing the ISC compartment based on a functional capacity of ISCs; the ability to form intestinal organoids in culture. This new method uses organoid formation efficiency as a readout of changes in the ISC compartment, and can be used in conjunction with traditional methods of ISC marker expression to understand the relationship between expression of ISC markers and ISC functionality. I have used this method to further analyse the intestinal phenotype of a range of mouse models of colorectal cancer based on gene deletion of Apc, Cited1, Apc2, Pten and Pml. These experiments have shown that organoid formation efficiency can be a useful method for assessing the ISC compartment, although changes within this compartment may not be accurately predictive of tumourigenesis.

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Sakamaki, Taro. "Hoxb5 defines the heterogeneity of self-renewal capacity in the hematopoietic stem cell compartment." Doctoral thesis, Kyoto University, 2021. http://hdl.handle.net/2433/263564.

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Stroikin, Yuri. "Ageing-associated changes of lysosomal compartment : implications on cellular functions." Doctoral thesis, Linköping : Univ, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-8012.

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13

Luyt, Natasha Alethea. "Interaction of multiple yeast species during fermentation." Thesis, Stellenbosch : Stellenbosch University, 2015. http://hdl.handle.net/10019.1/97013.

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Thesis (MSc)--Stellenbosch University, 2015.
ENGLISH ABSTRACT: The use of non-Saccharomyces yeasts together with the yeast S. cerevisiae in multistarter wine fermentations has emerged as a useful tool to modulate wine aroma and/or to decrease the concentration of undesirable compounds. However, upon inoculation, these yeast species do not co-exist passively, but interact in various ways. While competition for nutrients and the excretion of killer toxins in an antagonistic relationship are obvious and well established types of interactions, some studies have suggested the existence of other forms of cellular or molecular interactions. One of these includes physical cell-cell contact and to our knowledge, only one previous study has confirmed its existence in wine yeasts. Yeast interactions are also influenced by other factors, such as ethanol concentration, however some studies have highlighted the role that dissolved oxygen plays on the survival of non-Saccharomyces yeasts and their ability to compete for space with S. cerevisiae and little research has focused on this. This study aimed to investigate the occurrence of a physical cell-cell and/or metabolic interaction between S. cerevisiae and L. thermotolerans in mixed culture fermentations of synthetic grape must. For this purpose, fermentations in a Double Compartment Bioreactor (DCB) which separates yeast population through the use of a membrane were compared to mixed fermentations in the absence of the membrane, using the same reactor. Furthermore, the impact of oxygen supply on yeast behaviour was also assessed. Following mixed culture fermentations in a DCB, it was observed that the presence of S. cerevisiae led to a significant decline in viability in L. thermotolerans. This decline was significantly less prominent in mixed cultures where the cells were in indirect contact. Together, the data provided evidence for both cell-cell and metabolic interactions whereby S. cerevisiae had a strong negative influence on the growth of L. thermotolerans. However, it was also observed that L. thermotolerans had some negative impact on the growth of S. cerevisiae, leading to a reduction in biomass (when in indirect contact) and a reduced maximum CFU/mL compared to pure cultures. The data also suggest that direct physical contact may increase the production of glycerol and propanol, but this needs further investigation. By decreasing the frequency at which oxygen pulses were provided, a reduction in biomass and increase in fermentation duration was observed for all fermentations. However, this effect was somewhat reduced in mixed cultures. Here, no impact on fermentation duration was observed and the decrease in biomass was less compared to pure cultures. The impact of these oxygen pulses was also greater on L. thermotolerans. In the latter yeast’s pure culture a slight increase in glycerol was observed when less oxygen was provided and in general there appeared to be no impact on acetic acid production. Furthermore, there was little or no impact on volatile production, however, more repeats might reveal different results and therefore more research is needed to confirm these results. To our knowledge, this is the first study of its kind to confirm a physical cell-cell interaction between the yeast pair S. cerevisiae and L. thermotolerans.
AFRIKAANSE OPSOMMING: Die gebruik van nie-Saccharomyces gis saam met die gis S. cerevisiae in multi-inokuleringskulture het die afgelope paar jaar as n goeie hulpmiddel na vore gekom om wyn aroma te moduleer en/of om die konsentrasie van ongewensde verbindings te verminder. Sodra inokulasie plaasgevind het, het hierdie gis die potensiaal om op verskeie maniere teenoor mekaar te reageer. Kompetisie vir nutriente en die afskeiding van toksiese verbindings in n antagonistiese verhouding is alreeds goed beskryf in die literatuur. Somige studies het, alhoewel, die bestaan van ander vorme van sellulêre of molekulêre interaksies voorgestel. Een van hierdie sluit in n fisiese sell-sell interaksie en so ver as wat ons kennis strek, het nog net een studie van tevore so ‘n interaksie bevestig tussen wyn giste. Gis interaksies word ook beïnvloed deur ander faktore, soos byvoorbeeld etanol konsentrasie. Terwyl sommige studies die rol wat opgelosde suurstof speel in die oorlewing van nie-Saccharomyces gis en hulle vermoë om te kompeteer vir spasie met S. cerevisiae alreeds beklemtoon, het min navorsing al hierop gefokus. Hierdie studie het gestreef om die voorkoms van n fisiese sell-sell en/of metaboliese interaksie tussen S. cerevisie en L. thermotolerans in gemengde kultuur fermentasies van sintetiese druiwe sap te ondersoek. Vir hierdie doeleinde was fermentasies uitgevoer met behulp van ‘n Dubbel Kompartement Bioreaktor (DKB) wat gis populasies skei deur middel van ‘n membraan en hierdie was vergelyk met gemengde kultuur fermentasies sonder die membraan in dieselfde reaktor sisteem. Verder was die impak van suurstof toevoer op gis gedrag ook geassesseer. Na afloop van gemengde kultuur fermentasies in ‘n DKB, was daar waargeneem dat die teenwoordigheid van S. cerevisiae gelei het tot ‘n betekenisvolle afname in lewensvatbaarheid in L. thermotolerans. Hierdie afname was aansienlik minder in gemengde kulture waar die gis in indirekte kontak was. Saam verskaf hierdie data bewyse vir n sell-sell asook metaboliese interaksie waardeur S. cerevisiae ‘n sterk, negatiewe invloed op die groei van L. thermotolerans gehad het. Daar was egter ook waargeneem dat L. thermotolerans tot ‘n mindere mate ‘n negatiewe impak op die groei van S. cerevisiae gehad het en dat dit gelei het tot ‘n verlaging in biomassa (toe die gis in indirekte kontak was) en ‘n verlaagde maksimum CFU/mL in vergelyking met suiwer kulture. Die data dui ook aan dat fisiese kontak kon gelei het tot ‘n verhoging in gliserol en propanol produksie, maar hierdie kort verdere ondersoek. Deur die frekwensie te verminder waardeur suurstof pulse aan die fermentasies verskaf was, was ‘n verlaging in biomassa produksie en ‘n verlenging in fermentasie tydperk waargeneem. Hierdie tendense was waargeneem in almal, behalwe die gemengde kultuur fermentasies. Die effek van suurstof puls verlaging was minder op hierdie fermentasies aangesien daar geen impak op fermentasie tydperk was nie en die verlaging in biomassa minder was. Die impak van hierdie suurstof pulse was ook groter op L. thermotolerans. ‘n Klein toename in gliserol produksie was waargeneem in laasgenoemde gis se suiwer kultuur toe minder suurstof beskikbaar was en oor die algemeen was asynsuur onveranderd. Verder was daar ‘n klein of geen impak op vlugtige verbindings nie, alhoewel, meer herhalings mag verskillende resultate lewer en daarom is meer navorsing nodig om hierde resultate te bevestig. So ver as wat ons kennis strek is hierdie die eerste studie van sy soort om ‘n fisiese sell-sell interaksie tussen die gispaar S. cerevisiae en L. thermotolerans te bevestig.

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Lawrence, Ruth Ann. "The role of the apoplast as an osmotic compartment in Suaeda maritima L. Dum. and Beta vulgaris L." Thesis, Bangor University, 1999. https://research.bangor.ac.uk/portal/en/theses/the-role-of-the-apoplast-as-an-osmotic-compartment-in-suaeda-maritima-l-dum-and-beta-vulgaris-l(0ece75b9-6f54-4a47-85da-39707c5e2d49).html.

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The plant cell wall is a living and dynamic compartment of the plant cell. Its many diverse functions range from cell expansion and differentiation to defence and signalling. Furthermore, there is currently a growing body of evidence which suggests that the cell wall/apoplast also plays an important role in cell water relations. The aim of this study was to highlight the importance of apoplastic solutes in plant cell water relations, particularly in turgor regulation. The water relations parameters of two members of the family Chenopodiaceae, Suaeda maritima L. Dum. and Beta vulgaris L., were studied at single cell resolution using the cell pressure probe, single cell sampling and analysis techniques, and the xylem pressure probe. These species share a common peculiarity, in that certain cell types, namely the leaf epidermal cells in Suaeda maritima and the taproot storage parenchyma cells in Beta vulgaris, maintain cell turgor pressure (Pau) at a level which is dramatically lower than the respective cell osmotic pressures (III�). This phenomenon is attributed to the properties of the cell wall/apoplast. The hydrostatic component of the apoplast (P, uau) accounts for only a small fraction of the difference between P. u and H.,, in these species. In light of this the discrepancy between P. u and H can only be due to the presence of osmotically active solutes in the adjacent apoplast Suaeda maritima leaf epidermal cells accumulate NaCl in response to an increase in external NaCl concentration. This accumulation of solutes leads to an increase in leaf epidermal osmotic pressure, which exactly mirrors the increase in the osmotic pressure of the external medium (ITI). Leaf epidermal turgor pressure (P, -. u), however, is maintained at a constant level over a range of external salinities. In the short term the leaf epidermal cells are shielded from abrupt changes in flea by the properties of the root system, and a root reflection coefficient which is close to 0. In the longer term, as NaCl accumulates in the protoplast, Pcen is apparently maintained by the parallel adjustment of solutes in the protoplast and apoplast. Page III Changes in Suaeda maritima leaf epidermal turgor pressure (P. u), induced by modulating the solute content of the apoplast (11. u) in excised leaves, initiated a mechanism which regulated P., u back to in vivo levels within 40 minutes. Turgor regulation was not accompanied by equivalent changes in cell osmotic pressure (H n), suggesting that osmotic adjustment leading to turgor regulation is apoplastic rather than protoplastic in nature. This apoplastic osmotic adjustment mechanism was dependent on the permeant nature of the apoplastic solutes and on the volume of the apoplast. A comparable upward turgor regulation mechanism was observed in excised Beta vulgaris taproot tissue, within 40 - 80 minutes. The presence of apoplastic KK apparently facilitated the turgor regulation mechanism in this case. Proton efflux studies on Beta vulgaris taproot tissue revealed that the driving force behind this osmotic adjustment mechanism is likely to be turgor/external osmotic pressure (P,. u/H, ) dependent modulation of plasma membrane proton ATPase activity. It was concluded that the apoplast should be regarded as a true osmotic compartment in higher plants.

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15

Koch, Sven D. [Verfasser]. "Differentiation and aging of the human T cell compartment : Is there an infectious component? / Sven D. Koch." München : Verlag Dr. Hut, 2010. http://d-nb.info/1221161237/34.

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Korfi, Koorosh. "Epigenetic programming defines stem cell identity and entry into the proliferative compartment in chronic myeloid leukaemia (CML)." Thesis, University of Glasgow, 2012. http://theses.gla.ac.uk/3929/.

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Chronic myeloid leukaemia (CML) is a haematological malignancy that is identified by the presence of a fusion oncogene, BCR-ABL1, which is a constitutive tyrosine kinase. The discovery of tyrosine kinase inhibitors (TKIs) over that past decade has resulted in significantly improved survival rates and disease management in CML patients. However, a subpopulation of BCR-ABL1+ cells in the niche are found which exhibit stem cell-like features, such as self-renewal and quiescence. These CML stem cells (LSCs) are shown to be insensitive to TKI treatment and are capable of deriving the disease during the relapse. Consequently, the elimination of LSCs is a primary goal of current research. Therefore, the aim of this thesis was to obtain a global view of the cellular processes that maintain stem cell identity in CD34+ CD38- LSCs as well as identify those processes which initiate the transition to proliferative CD34+ CD38+ CML progenitor cells (LPCs). A combined approach was exploited to investigate genome-wide gene expression profiles and histone modification signatures of normal HSCs and committed progenitors (HPCs), and their LSC and LPC counterparts. Despite having increased activity in pathways involved in cell division and proliferation, expression levels of the pathways involved in stem cell identity were not significantly different in LSCs to those found in HSCs. These pathways included Wnt, TGF-β signalling, and several novel neurotransmitter signalling pathways. By examining genome-wide histone modification patterns using ChIP-sequencing it was shown that the stem cell identities of HSCs and LSCs are programmed at the epigenetic level. All of the pathways which confer stem cell identity to both HSCs and LSCs are significantly enriched for bivalent gene promoters having both the H3K4me3 and H3K27me3 marks. These similarities were most evident in neurotransmitter signalling and it was demonstrated that these pathways are capable of promoting LSC maintenance in vitro. Intriguingly, although the stem cell entry into the proliferative state occurs through the repression of many of the same stem cell identity pathways in both HSCs and LSCs, it was shown that epigenetic reprogramming in CML mediates this repression via a different mechanism than in normal HSCs. Furthermore, abnormalities in levels of several chromatin enzymes were identified that are likely to be responsible for the epigenetic reprogramming of CML cells. The work presented in this thesis defines the chromatin landscape of a cancer stem cell for the first time and provides new therapeutic targets for the eradication of TKI resistant CML stem cells.

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Jacob, Eshtan Sarah. "Heterogeneity of the human embryonic stem cell compartment and its impact on the generation of otic progenitors." Thesis, University of Sheffield, 2014. http://etheses.whiterose.ac.uk/7613/.

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Sales, Josephine Laura. "The role of Notch signalling in the regulation and maintenance of the satellite cell compartment of adult skeletal muscle." Thesis, Imperial College London, 2007. http://hdl.handle.net/10044/1/7941.

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The regenerative potential ofadult skeletal muscle is primarily attributed to satellite cells. Normally quiescent, satellite cells are activated 'on demand' to proliferate and differentiate, facilitating growth or repair. Maintenance of the regenerative capacity requires satellite cell replenishment. It has been shown in vitro that activated satellite cells can adopt divergent fates, with most undergoing terminal differentiation, whilst a minority return to quiescence, mediating self-renewal. This occurs in cell clusters, suggesting that cell-cell signalling may direct fate decisions. Notch signalling relies on cell-cell interaction to specify alternate fates in several systems and has been previously implicated in myogenesis. The aim of this project was to investigate the role of Notch signalling in satellite cell regulation and maintenance. Studies were carried out using C2Cl2 cultures as a model of satellite cell specification.When induced to differentiate, most C2C12 myoblasts contribute to differentiated myotubes, but some are retained as undifferentiated reserve cells with a quiescent, satellite cell-like phenotype. This thesis shows that Notch signalling maintains proliferation in myoblasts and inhibits myogenic differentiation in reserve cells via distinct ligand/receptor interactions. Specifically, interaction between Notchl and Jaggedl appears to maintain proliferation, whereas interaction of Notch3 with Delta-like 4 on nascent myotubes specifies a reserve cell phenotype. Evidence consistent with this model was obtained using satellite cells activated on the surface of isolated myofibres and satellite cell-derived primary cultures. Together, the results show that Notch signalling is involved in satellite cell regulation and suggest a mechanism that may specify alternate fates to facilitate stem cell self-renewal.

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Chaudhry, Qasim Ali. "Numerical Approximation of Reaction and Diffusion Systems in Complex Cell Geometry." Licentiate thesis, KTH, Numerisk analys, NA, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-12099.

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The mathematical modelling of the reaction and diffusion mechanism of lipophilic toxic compounds in the mammalian cell is a challenging task because of its considerable complexity and variation in the architecture of the cell. The heterogeneity of the cell regarding the enzyme distribution participating in the bio-transformation, makes the modelling even more difficult. In order to reduce the complexity of the model, and to make it less computationally expensive and numerically treatable, Homogenization techniques have been used. The resulting complex system of Partial Differential Equations (PDEs), generated from the model in 2-dimensional axi-symmetric setting is implemented in Comsol Multiphysics. The numerical results obtained from the model show a nice agreement with the in vitro cell experimental results. The model can be extended to more complex reaction systems and also to 3-dimensional space. For the reduction of complexity and computational cost, we have implemented a model of mixed PDEs and Ordinary Differential Equations (ODEs). We call this model as Non-Standard Compartment Model. Then the model is further reduced to a system of ODEs only, which is a Standard Compartment Model. The numerical results of the PDE Model have been qualitatively verified by using the Compartment Modeling approach. The quantitative analysis of the results of the Compartment Model shows that it cannot fully capture the features of metabolic system considered in general. Hence we need a more sophisticated model using PDEs for our homogenized cell model.
Computational Modelling of the Mammalian Cell and Membrane Protein Enzymology

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Chaudry, Qasim Ali. "Numerical Approximation of Reaction and Diffusion Systems in Complex Cell Geometry." Licentiate thesis, KTH, Numerical Analysis, NA, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-12099.

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The mathematical modelling of the reaction and diffusion mechanism of lipophilic toxic compounds in the mammalian cell is a challenging task because of its considerable complexity and variation in the architecture of the cell. The heterogeneity of the cell regarding the enzyme distribution participating in the bio-transformation, makes the modelling even more difficult. In order to reduce the complexity of the model, and to make it less computationally expensive and numerically treatable, Homogenization techniques have been used. The resulting complex system of Partial Differential Equations (PDEs), generated from the model in 2-dimensional axi-symmetric setting is implemented in Comsol Multiphysics. The numerical results obtained from the model show a nice agreement with the in vitro cell experimental results. The model can be extended to more complex reaction systems and also to 3-dimensional space. For the reduction of complexity and computational cost, we have implemented a model of mixed PDEs and Ordinary Differential Equations (ODEs). We call this model as Non-Standard Compartment Model. Then the model is further reduced to a system of ODEs only, which is a Standard Compartment Model. The numerical results of the PDE Model have been qualitatively verified by using the Compartment Modeling approach. The quantitative analysis of the results of the Compartment Model shows that it cannot fully capture the features of metabolic system considered in general. Hence we need a more sophisticated model using PDEs for our homogenized cell model.

Computational Modelling of the Mammalian Cell and Membrane Protein Enzymology

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Trautsch, Irina Karoline [Verfasser], Wolfram-Hubertus [Akademischer Betreuer] Zimmermann, Wolfram-Hubertus [Gutachter] Zimmermann, and Henning [Gutachter] Urlaub. "A cell-type and compartment specific analysis of glutathione and hydrogen peroxide / Irina Karoline Trautsch ; Gutachter: Wolfram-Hubertus Zimmermann, Henning Urlaub ; Betreuer: Wolfram-Hubertus Zimmermann." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2019. http://d-nb.info/1189904640/34.

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Perchermeier, Sophie [Verfasser], da Costa Clarissa [Akademischer Betreuer] Prazeres, Silvia [Gutachter] Lobmaier, da Costa Clarissa [Gutachter] Prazeres, and Percy A. [Gutachter] Knolle. "Chronic Schistosoma mansoni Infection during Pregnancy: Effects on Offspring’s T Cell Differentiation Capacity, Epigenetics and Memory T Cell Compartment / Sophie Perchermeier ; Gutachter: Silvia Lobmaier, Clarissa Prazeres da Costa, Percy A. Knolle ; Betreuer: Clarissa Prazeres da Costa." München : Universitätsbibliothek der TU München, 2021. http://d-nb.info/1230061045/34.

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Olughu, Williams C. "The systematic consideration of the large-scale fed-batch fermentation inhomogeneities using a genetically modified C. glutamicum strain as a model organism." Thesis, Loughborough University, 2018. https://dspace.lboro.ac.uk/2134/34284.

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The loss of efficiency and performance of bioprocesses on scale-up is well known, but not fully understood. This work addresses this problem, by studying the effect of some fermentation gradients (pH, glucose and oxygen) at a larger scale in a bench-scale two compartment reactor (PFR + STR) using the cadaverine-producing recombinant bacterium, Corynebacterium glutamicum DM1945 Δact3 Ptuf-ldcC_OPT. The initial scale down strategy increased the magnitude of these gradients by only increasing the mean cell residence time in the plug flow reactor (τ_PFR). The cell growth and product related rate constants were compared as the τ_PFR was increased; differences were significant in some cases, but only up to 2 min residence time. For example, losses in cadaverine productivity when compared to the control fed-batch fermentation on average for the τ_PFR of 1 min, 2 min and 5 min were 25 %, 42 % and 46 % respectively. This indicated that the increasing the τ_PFR alone does not necessarily increase the magnitude of fermentation gradients. The new scale-down strategy developed here, increased the magnitude of fermentation gradients by not only increasing the τ_PFR, but also considering the mean frequency at which the bacterial cells entered the PFR section (f_m). The f_m was kept constant by reducing the broth volume in the STR. Hence, the bacterial cells also spent shorter times in the well mixed STR, as the τ_PFR was increased (hypothesised as giving the bacterial cells less time to recover the non-ideal PFR section of the SDR). On adoption of this strategy cadaverine productivity decreases for the τ_PFR of 1 min, 2 min and 5 min were 25 %, 32 % and 53 % respectively. Thus, highlighting that loss in performance is most likely to occur as the magnitude of heterogeneity within the fermentation environment increases. However, Corynebacterium glutamicum DM1945 Δact3 Ptuf-ldcC_OPT did show some resilience in its biomass productivity. It was only marginally affected in the harshest of conditions simulated here.

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Gokay, Kerimi Erden. "Morphology and biogenesis of endosomal compartments in epithelial cells." Diss., The University of Arizona, 2000. http://hdl.handle.net/10150/279796.

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Epithelial tissues which line the body cavities and tubules typically face two environments that are biochemically and physically different from each other. Consequently, these cells possess two structurally and functionally distinct plasma membrane domains; an apical domain facing the lumenal or the free surface and a basolateral domain facing the basement membrane and the intercellular space. Furthermore, via processes such as domain selective absorption, secretion and transcytosis, epithelial cells not only maintain these trans-epithelial differences but also actively contribute to their generation. Therefore, maintenance of high fidelity in polarized protein sorting and membrane trafficking aee of cardinal importance in all epithelia for their proper function. Although the central role membrane trafficking plays in generation and maintenance of epithelial cell polarity is clear, nature of the endosomal compartment(s) involved and the molecular determinants employed in this process remains ill-defined. In this study, using a unique apical endosomal marker, endotubin, and a model polarized epithelial cell line, Madin-Darby canine kidney (MDCK), we characterize the endotubin-positive endosomes as a subset of apical early endosomes which can be reached with an endocytic marker only when it is internalized apically. Furthermore, we show that endotubin-positive endosomes do not contain basolaterally recycling transferrin or the small GTPase Rab 11 and therefore they are distinct from the previously described apical recycling endosomes (ARE) in MDCK cells. In addition, using a panel of endotubin mutants we characterize two cytoplasmic sorting signals, a hydrophobic cluster and a casein kinase II phosphorylation site, as the molecular determinants required for polarized sorting and endosomal targeting of this molecule. Also, using a panel of domain exchange chimeras we show that endotubin cytoplasmic domain is sufficient to mediate apical sorting and early endosomal targeting of an unrelated protein in MDCK cells. Nevertheless, overexpression of these chimeras but not a mutant form defective in endosomal targeting results in missorting of the construct to the basolateral domain. These results indicate that, the endotubin-positive apical endosomes possess a saturable sorting machinery capable of recognizing the cytoplasmic sorting determinants here we characterize.

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Garenne, David. "Etude d'un système de transition basé sur des acides gras dans les processus d’encapsulation de biomolécules : vers un nouveau modèle de cellule minimale." Thesis, Bordeaux, 2016. http://www.theses.fr/2016BORD0365/document.

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La compartimentation est un aspect fondamental dans la compréhension de l’apparition de la vie sur terre mais aussi dans l’élaboration de cellules minimales. Les coacervats sont capables de séquestrer de grandes quantités de molécules par diffusion depuis le milieu extérieur mais ne permettent pas d’encapsuler ces molécules à cause de l’absence de barrière physique entre le milieu intérieur et extérieur. Les vésicules quant à elles, ne permettent pas de séquestrer de grandes quantités de molécules à cause de la bicouche membranaire qui empêche la diffusion des molécules depuis le milieu extérieur. Nous avons développé une nouvelle méthode pour encapsuler des biomolécules basées sur une transition de coacervats à vésicules. Notre système basé sur des acides gras saturés à longues chaînes, peut former des coacervats pour séquestrer des biomolécules puis des vésicules en diminuant le pH pour encapsuler les molécules préalablement séquestrées. Les résultats montrent des taux d’encapsulation supérieurs à ceux obtenus par les méthodes d’encapsulation basées sur l’hydratation de films lipidiques. L’encapsulation d’enzymes ainsi que des substrats de la réaction dans les vésicules ont permis de montrer l’accomplissement de réactions enzymatiques dans ces compartiments de manière beaucoup plus rapide qu’en milieu dilué permettant de générer un bioréacteur efficace. La synthèse de protéines ainsi que l’accomplissement de voies métaboliques n’ont pas été clairement mises en évidence dans les vésicules et constituent un élément décisif dans l’élaboration d’un nouveau modèle de cellule minimale
Compartmentalization is of importance for our understanding of the emergence of life on earth but also for the development and design of minimal cells. Coacervation phenomenon allows spontaneous sequestration by molecular diffusion from aqueous medium but do not allow encapsulation of molecule inside. On the contrary, vesicular systems do not allow spontaneous encapsulation of molecules inside. Here we introduce a model built from saturated long chain fatty acids. This system can form both membranous vesicles and membrane free coacervated droplets that result from clouding by decreasing ph. We have shown that a large amount of proteins is encapsulated into vesicles after pre-crowding into coacervated. Encapsulation of enzyme in vesicles allow to increase the reaction rate compared to the reaction rate in diluted medium. Synthesis of proteins by cell-free system and metabolic reactions with proteins of mollicutes have not clearly been shown but they represent an essential element in the development of a minimal cell

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Fitchette, Anne-Catherine. "Immunolocalisation de la xylosylation et le la fucosylation des glycannes complexes dans l'appareil de Golgi des cellules de sycomore (Acer pseudoplatanus L. )." Rouen, 1993. http://www.theses.fr/1993ROUES003.

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Les glycanes complexes portés par les glycoprotéines végétales diffèrent de ceux rencontrés chez les mammifères par l'absence d'acide sialique et par la présence d'un résidu fucose α1,3 lié au GlcNAc de la partie réductrice de l'unité chitobiose et d'un xylose lié en β1,2 au β-mannose. La séquence des évènements de maturation des glycanes n'est pas aussi bien connue dans la cellule végétale que pour la cellule animale. Dans cette étude, nous nous sommes principalement intéressés aux xylosyl- et fucosyl-transférases spécifiques aux plantes et intervenant dans la glycosylation tardive. Nous avons préparé des anticorps dirigés contre les glycanes végétaux contenant des résidus xylose ou fucose. Par immunodétection à l'aide de ces anticorps, nous avons visualisé la distribution subcellulaire des glycoprotéines portant ces glycanes complexes dans les cellules de sycomore. De plus, cette approche immunocytochimique a permis une localisation indirecte des xylosyl- et fucosyl-transférases en détectant les glycanes produits par ces enzymes dans les empilements golgiens des cellules de sycomore. Nos résultats indiquent que les glycanes complexes N-liés aux glycoprotéines vacuolaires ou pariétales sont xylosylés principalement dans le Golgi médian, alors que leur fucosylation est un évènement tardif intervenant dans le Golgi trans

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D'Sa, S. P. "Immune reconstitution of B cell and T cell compartments following reduced intensity allogeneic stem cell transplantation for myeloma." Thesis, University College London (University of London), 2007. http://discovery.ucl.ac.uk/1444713/.

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Immune reconstitution following conventional allogeneic transplantation is a major determinant of survival. A detailed investigation of T and B cell immune reconstitution and clinical outcome in 19 patients with myeloma undergoing reduced intensity stem cell transplantation using in vivo T cell-depletion with alemtuzumab was undertaken. The rate of recovery of lymphocyte numbers and function following transplant was studied using immunophenotyping with 3-colour flow cytometry and intracellular cytokine staining. In addition, T and B cell spectratyping were used to study the repertoire of immune recovery. The patients in this study experienced delayed T cell recovery and T cell receptor spectratype analysis showed a reduced repertoire diversity, which improved rapidly following the administration of DLI and subsequent conversion to full donor T cell chimerism. Post transplant recovery of B cells was also significantly delayed. Spectratype analysis of IgH CDR3 repertoire revealed a gradual normalisation in spectratype complexity by 6- 12 months post transplant. There was a high incidence of viral infection, particularly CMV reactivation but the regimen related mortality was low, perhaps due to the very low incidence of severe acute graft-versus-host disease (GVHD). A total of 10 patients experienced GVHD. Of these patients, 8 eventually demonstrated a disease response alongside clinical evidence of GVHD, demonstrating that the graft-versus-myeloma effect is frequently obtained at the expense of GVHD. Over 80% of all patients have relapsed at a median of 9 months following transplant, suggesting that the initially low rate of GVHD has been achieved at the expense of the desired graft-versus-myeloma effect.

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Santambrogio, Sara. "Neural stem cell compartments in a mouse model of globoid cell leukodystrophy : Implication for therapeutic strategies." Thesis, Open University, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.536058.

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Thomi, Laura [Verfasser]. "Functional nanocarriers as compartments for artificial cells / Laura Thomi." Mainz : Universitätsbibliothek Mainz, 2018. http://d-nb.info/1152104888/34.

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Chavez, Garcia Edison. "Phosphoinositides regulation and function in the ciliary compartment of Neural stem cells and Ependymal cells." Doctoral thesis, Universite Libre de Bruxelles, 2014. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/221625.

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This thesis describes the work that I have carried out in the Laboratory of Neurophysiolgy at the Université Libre de Bruxelles, under the supervision of Prof. Serge Schiffmann, in collaboration with Prof. Stéphane Schurmans of Université of Liège.The work is divided in two distinct but related projects and the results section is thus divided into two main chapters. The results described are presented in the form of two manuscripts, the first chapter is named “Ciliary phosphoinositides regulation by INPP5E controls Shh signaling by allowing trafficking of Gpr161 in neural stem cells primary cilium”.The second is named “Regulation of phosphoinositides ciliary levels controls trafficking and ciliogenesis in ependymal cells”.Since both manuscripts are comprehensive regarding the results, and methods, these are inserted as such into the thesis.An expanded introduction to the field, placing the results into context, precedes these two chapters. An extended discussion section follows each chapter; it presents some elements of discussion not included in the manuscripts, the implications of the results and the scope for further research.
Doctorat en Sciences biomédicales et pharmaceutiques
info:eu-repo/semantics/nonPublished

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Ripoll, Camille. "Modèles compartimentaux de cellules végétales : influence de la croissance sur les flux." Rouen, 1986. http://www.theses.fr/1986ROUES010.

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On propose un modèle approché d'efflux qui se réduit au modèle classique quand le taux de croissance est nul. Les relations exactes de calcul des paramètres cellulaires dans le modèle classique sont également établies. On montre que l'utilisation habituelle de relations approchées est source d'erreurs numériques qui peuvent dans certains cas, être supérieures aux incertitudes expérimentales. Les flux unidirectionnels sont calculés dans le domaine de validité des relations linéaires flux-forces. Ces résultats permettent d'interpréter avec succès nombre de mesures expérimentales de l'influx initial en fonction de la concentration extérieure

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Kasderidis, Stathis P. "A compartmental model neuron, its networks and application to time series." Thesis, King's College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.313657.

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Wiking, Mikaela. "Spatial proteome profiling of the compartments of the human cell using an antibody-based approach." Licentiate thesis, KTH, Proteomik och nanobioteknologi, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-206817.

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The human cell is complex, with countless processes ongoing in parallel in specialized compartments, the organelles. Cells can be studied in vitro by using immortalized cell lines that represent cells in vivo to a varying degree. Gene expression varies between cell types and an average cell line expresses around 10,000-12,000 genes, as measured with RNA sequencing. These genes encode the cell’s proteome; the full set of proteins that perform functions in the cell. In paper I we show that RNA sequencing is a necessary tool for studying the proteome of the human cell. By studying the proteome, and proteins’ localization in the cell, information can be assembled on how the cell functions. Image-based methods allow for detailed spatial resolution of protein localization as well as enable the study of temporal events. Visualization of a protein can be accomplished by using either a cell line that is transfected to express the protein with a fluorescent tag, or by targeting the protein with an affinity reagent such as an antibody. In paper II we present subcellular data for a majority of the human proteins, showing that there is a high degree of complexity in regard to where proteins localize in the cell. Cellular energy is generated in the mitochondria, an important organelle that is also active in many other different functions. Today approximately only a third of the estimated mitochondrial proteome has been validated experimentally, indicating that there is much more to understand with regard to the functions of the mitochondria. In paper III we explore the mitochondrial proteome, based on the results of paper II. We also present a method for sublocalizing proteins to subcompartments that can be performed in a high-throughput manner. To conclude, this thesis shows that transcriptomics is a useful tool for proteome-wide subcellular localization, and presents high-resolution spatial distribution data for the human cell with a deeper analysis of the mitochondrial proteome.

QC 20170512

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Ordemann, Rainer, Duohui Jing, Ana-Violeta Fonseca, Nael Alakel, Fernando A. Fierro, Katrin Muller, Martin Bornhauser, Gerhard Ehninger, and Denis Corbeil. "Hematopoietic stem cells in co-culture with mesenchymal stromal cells - modeling the niche compartments in vitro." Ferrata Storti Foundation, 2010. https://tud.qucosa.de/id/qucosa%3A28891.

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Background Hematopoietic stem cells located in the bone marrow interact with a specific microenvironment referred to as the stem cell niche. Data derived from ex vivo co-culture systems using mesenchymal stromal cells as a feeder cell layer suggest that cell-to-cell contact has a significant impact on the expansion, migratory potential and ‘stemness’ of hematopoietic stem cells. Here we investigated in detail the spatial relationship between hematopoietic stem cells and mesenchymal stromal cells during ex vivo expansion. Design and Methods In the co-culture system, we defined three distinct localizations of hematopoietic stem cells relative to the mesenchymal stromal cell layer: (i) those in supernatant (non-adherent cells); (ii) those adhering to the surface of mesenchymal stromal cells (phase-bright cells) and (iii) those beneath the mesenchymal stromal cells (phase-dim cells). Cell cycle, proliferation, cell division and immunophenotype of these three cell fractions were evaluated from day 1 to 7. Results Phase-bright cells contained the highest proportion of cycling progenitors during co-culture. In contrast, phase-dim cells divided much more slowly and retained a more immature phenotype compared to the other cell fractions. The phase-dim compartment was soon enriched for CD34+/CD38− cells. Migration beneath the mesenchymal stromal cell layer could be hampered by inhibiting integrin β1 or CXCR4. Conclusions Our data suggest that the mesenchymal stromal cell surface is the predominant site of proliferation of hematopoietic stem cells, whereas the compartment beneath the mesenchymal stromal cell layer seems to mimic the stem cell niche for more immature cells. The SDF-1/CXCR4 interaction and integrin-mediated cell adhesion play important roles in the distribution of hematopoietic stem cells in the co-culture system.

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Ordemann, Rainer, Duohui Jing, Ana-Violeta Fonseca, Nael Alakel, Fernando A. Fierro, Katrin Muller, Martin Bornhauser, Gerhard Ehninger, and Denis Corbeil. "Hematopoietic stem cells in co-culture with mesenchymal stromal cells - modeling the niche compartments in vitro." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-177403.

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Background Hematopoietic stem cells located in the bone marrow interact with a specific microenvironment referred to as the stem cell niche. Data derived from ex vivo co-culture systems using mesenchymal stromal cells as a feeder cell layer suggest that cell-to-cell contact has a significant impact on the expansion, migratory potential and ‘stemness’ of hematopoietic stem cells. Here we investigated in detail the spatial relationship between hematopoietic stem cells and mesenchymal stromal cells during ex vivo expansion. Design and Methods In the co-culture system, we defined three distinct localizations of hematopoietic stem cells relative to the mesenchymal stromal cell layer: (i) those in supernatant (non-adherent cells); (ii) those adhering to the surface of mesenchymal stromal cells (phase-bright cells) and (iii) those beneath the mesenchymal stromal cells (phase-dim cells). Cell cycle, proliferation, cell division and immunophenotype of these three cell fractions were evaluated from day 1 to 7. Results Phase-bright cells contained the highest proportion of cycling progenitors during co-culture. In contrast, phase-dim cells divided much more slowly and retained a more immature phenotype compared to the other cell fractions. The phase-dim compartment was soon enriched for CD34+/CD38− cells. Migration beneath the mesenchymal stromal cell layer could be hampered by inhibiting integrin β1 or CXCR4. Conclusions Our data suggest that the mesenchymal stromal cell surface is the predominant site of proliferation of hematopoietic stem cells, whereas the compartment beneath the mesenchymal stromal cell layer seems to mimic the stem cell niche for more immature cells. The SDF-1/CXCR4 interaction and integrin-mediated cell adhesion play important roles in the distribution of hematopoietic stem cells in the co-culture system.

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Yu, Hyun Jae. "HIV Traffics Through a Specialized, Surface-accessible Intracellular Compartment During Trans-infection of T Cells by Mature Dendritic Cells." Case Western Reserve University School of Graduate Studies / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=case1266871870.

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Labidi, Brahim. "Etude de la transcription dans des noyaux contenant un seul chromosome." Grenoble 2 : ANRT, 1987. http://catalogue.bnf.fr/ark:/12148/cb37606769q.

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Grattone, Marisa Lidia. "Étude du rôle des récepteurs du complément de type 1 (CR1/CD35) et de type 2 (CR2/CD21) dans l'internalisation et la localisation intracellulaire des ligands." Grenoble 1, 1998. http://www.theses.fr/1998GRE10075.

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Le systeme du complement a un role critique dans le developpement de la reponse immune specifique : la deficience acquise ou genetique de la proteine c3 affecte la production des anticorps contre des antigenes (ag) t-dependant. Cette proteine se lie covalemment aux ag lors de l'activation du systeme du complement et est progressivement proteolysee donnant des differents fragments : ic3b, c3dg, c3d qui restent lies a l'ag. Cr1 et cr2 sont deux recepteurs exprimes sur les lymphocytes b, t et les cellules dendritiques folliculaires. Cr1 fixe le fragment c3b et ic3b tandis que cr2 lie ic3b, c3dg et c3d. L'importance de cr1 et cr2 est soulignee par le fait que la production des ac specifiques des ag t-dependant peut etre inhibee par le blocage fonctionnel de ces recepteurs. Il semblerait que c'est au niveau des lymphocytes b que leur expression est essentielle, pour le controle de la reponse immune. Le role respectif de ces recepteurs dans l'internalisation est difficile a determiner du fait qu'ils sont toujours exprimes ensemble sur les lymphocytes b. Pour mieux definir leur role nous avons developpe un modele d'etude base sur la transfection des fibroblastes murins permettant l'expression de cr1, cr2 ou cr1 plus cr2. Nous avons etudie la capacite de ces recepteurs a fixer leurs ligands et a les internaliser. Nous montrons que cr1 et cr2 cooperent dans l'endocytose de c3b, c3b-c3b ou ic3b mais non dans l'endocytose de c3de ou j3d3, un anticorps specifiques de cr1. Pour expliquer cette cooperation, deux hypotheses ont ete emises : 1) apres fixation a cr1, le ligand pourrait etre endocyte ou proteolyse en ic3b ou c3dg, capte par cr2 et endocyte ; 2) un pontage de cr1 et cr2 induit par le ligand declencherait d'une maniere plus efficace les phenomenes d'internalisation, tels que la formation des puits a clathrine. Cette hypothese est particulierement favorisee par notre modele. Par ailleurs, nous avons etudie le role de cr1 dans la localisation intracellulaire des ag lies a c3b. Nous montrons que cet ag localise dans la peripherie cellulaire, en contraste avec l'ag libre qui se distribue dans toute la cellule. Cela pourrait impliquer un transit intracellulaire de l'ag different pouvant affecter sa proteolyse et/ou sa presentation aux lymphocytes t.

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Patel, Pinakeen Shankarbhai Pascual Virginia Banchereau Jacques. "Gene expression profiling to understand the alterations in the monocyte compartment of pediatric systemic lupus erythematosus." Waco, Tex. : Baylor University, 2008. http://hdl.handle.net/2104/5190.

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Sherwood, Mark William. "CaÂ²âº,pH and trypsinogen activation in a novel endocytic compartment of pancreatic acinar cells." Thesis, University of Liverpool, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.437513.

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Fritsch, Fredin Maria. "Dynamic changes in T cell compartments and new approaches in evaluating DSS induced and Galfai2 deficient colitis /." Göteborg : Dept. of Microbiology and Immunology, Institute of Biomedicine, The Sahlgrenska Academy, Göteborg University, 2007. http://hdl.handle.net/2077/7471.

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Chervyachkova, Elizaveta [Verfasser], and G. Elisabeth [Akademischer Betreuer] Pollerberg. "Light-controlled self-assembly and self-sorting of cell-like compartments / Elizaveta Chervyachkova ; Betreuer: G. Elisabeth Pollerberg." Heidelberg : Universitätsbibliothek Heidelberg, 2018. http://d-nb.info/1177149621/34.

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Elani, Yuval. "Development of microfluidic technologies for the construction of Multi-Compartment Vesicles (MCVs) and their applications as artificial cells." Thesis, Imperial College London, 2014. http://hdl.handle.net/10044/1/44522.

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In recent years there has been an increasing interest in using lipid vesicles and related membrane structures as (i) artificial cells that mimic biological processes and (ii) bio-inspired micro-machines that serve functional purposes. To date, vesicles have largely been single-compartment structures with homogenous interiors, which has impeded the fulfilment of these goals. This thesis details the development of technologies to address this. We develop droplet-based methods to controllably generate multi-compartment vesicles (MCVs) for the first time. The potential of these novel structures as artificial cells capable of hosting a range of biological and bio-mimetic processes is explored. Most notably, we introduce spatial segregation of function, thus mimicking eukaryotic organelles, and incorporate an artificial enzymatic signalling cascade to transmit chemical signals between distinct vesicle regions. We also construct microfluidic devices to generate related structures known as multisomes. Microfluidic technologies enable the size of these constructs to be scaled-down (approaching characteristic cellular sizes), and the production throughput to be scaled-up (hundreds of multisomes produced a minute). We demonstrate their use as programmable modular microdroplet 'factories' for in situ chemical synthesis in physiological environments, with potential relevance for therapeutic applications. The above technologies provide a platform for further developments in bottom-up synthetic biology and in microreactor technologies, and will pave the way for the fulfilment of some of the ambitious goals of these fields.

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Ali, Rizwan. "Live Cell Imaging of Intracellular Uptake of Contaminant Molecules (B[a]P) and its Effects on Different Cellular Compartments." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2012. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-91967.

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Exposure of hepatoma cell lines to the polycyclic aromatic hydrocarbon benzo[a]pyrene (B[a]P) is serving as a model for a systems biological study concerning the response of cells to contaminant molecules. Several aspects of the cellular distribution of the aryl hydrocarbon receptor (AhR) and its ligand B[a]P have been addressed by different live cell imaging techniques: The intracellular distribution of the B[a]P/AhR complex is visualized by means of confocal laser scaning microscopy (cLSM) and the intracellular transport rates of the complex is investigated by fluorescence recovery after photobleaching (FRAP) technique. Furthermore, cLSM image stacks of living cells are generated for the modeling of three dimensional (3-D) cell geometries. In order to prevent photochemical damage of the living cells induced by UV excitation of B[a]P, visualization is done by B[a]P’s auto fluorescence using near infrared two-photon-excitation. Murine Hepatoma 1c1c7 cells are exposed to graded concentrations of B[a]P (50 nM to 20 μM) for different incubation time periods (15 minutes to 48 hours). The highest amounts of B[a]P were found in lipid droplets and lysosomes, where the B[a]P molecules are collected and form large aggregates. We were able to work with concentrations down to 50 nM corresponding to that used for genomic and proteomic investigations. Also, for the first time imaging of B[a]P metabolites inside lipid droplets is presented in this work. The data and the model developed in this study will provide new insights into the systematic regulation of the B[a]P, the AhR as well as the receptor-ligand-complex pathway and the study will also serve as a prototype for elucidating other stress response pathways in the future.

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Unzai, Tomo. "Quantitative Analyses of the Projection of Individual Neurons from the Midline Thalamic Nuclei to the Striosome and Matrix Compartments of the Rat Striatum." Kyoto University, 2018. http://hdl.handle.net/2433/230977.

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Doose, Jens Peter. "Modeling of high-frequency coding for single cortical cells and precisely manipulating action-potential timing in vivo." Doctoral thesis, Humboldt-Universität zu Berlin, 2018. http://dx.doi.org/10.18452/19314.

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Diese Arbeit beschäftigt sich sowohl mit der experimentell motivierten Fragestellung nach der Kontrolle der Einzelzellaktivität kortikaler Neurone sowie mit der theoretischen Beschreibung der neuronalen Dynamik und ihrer Transfereigenschaften anhand einfacher Neuronenmodelle. Hierfür werden in-vivo Daten, die mit Hilfe der juxtazellulären Stimulation mit weißem bandpass limitiertem Gaußschem Rauschen erhoben wurden, verwendet. Mit Parameterfits einfacher Neuronenmodelle werden die experimentell ermittelten Pulszugstatistiken sowie die präzisen Zeitpunkte der einzelnen Aktionspotentiale quantitativ reproduziert. Diese Untersuchungen zeigen, dass mit dynamischen Rauschstimuli in juxtazellulärer Stimulation verlässlich und reproduzierbar Pulszüge in einzelnen kortikalen Neuronen hervorgerufen werden können. Weiterhin offenbart die Analyse der Daten die Eigenschaft der untersuchten Neurone frequenzunabhängig, bishin zu Vielfachen der Feuerrate des Neurons, Information über Signalkomponenten zu transferieren. Diese Eigenschaft steht im Widerspruch zum Verhalten der einfachsten (und populärsten) integrate-and-fire Modelle, die die Zelle ohne Auflösung ihrer räumlichen Struktur näherungsweise beschreiben. Die Erweiterung solcher Ein-Kompartiment Modelle auf ein Zwei-Kompartiment Modell und die damit eingeführte Unterscheidung zwischen Soma und Dendrit ermöglicht es, für einzelne Neuronen sämtliche experimentell erhobenen Statistiken, einschließlich des Hochfrequenz- Transfers, quantitativ zu reproduzieren. Zusätzlich zu den obigen Untersuchungen wird eine Methode vorgestellt, um, anhand von Input-Output Statistiken konkreter Neurone, Gaußsche Stimuli zu berechnen, die in der jeweiligen Zelle einen vorgeschriebenen Pulszug hervorrufen. In Experimenten und Simulationen wird gezeigt, dass diese vorgeschriebenen Pulszüge mit einer Verlässlichkeit erzeugt werden können, die in etwa der intrinsischen Verlässlichkeit des untersuchten Neurons entspricht.
This work elaborates on the question to which extent experimental control about the activity of single cortical neurons can be achieved and deals with the theoretical description of the neuronal dynamics. To this end, in-vivo data that have been recorded from juxtacellular experiments in cortical neurons are used. By means of parameter optimization, simple neuron models are fitted in order to quantitatively reproduce the measured spike train statistics and specific action potential timings. The analysis reveals that dynamic noise-stimuli can be used in juxtacellular stimulation to reliably generate reproducible spike trains in single cortical neurons. The analysis also reveals that the cells show a marked broadband coding of information, up to frequencies that are multiples of the firing rate of the respective neuron. This is in contrast to what is known for the simplest (and most popular) integrate-and-fire models, for which the cellular dynamics are described by a single space-independent variable. The extension of these one-compartment models to two-compartment models introduces a spatially distinction between soma and dendrite and we could show that for particular neurons it is sufficient to quantitatively reproduce all experimentally measured spike-train and input-output statistics, including the highfrequency information-transfer. Therefore, the effect of the spatial structure can be an important (structural) mechanism that can have influence on the neuronal dynamics. Additionally to the above considerations, by means of input-output statistics of particular neurons, we propose a method to compute Gaussian stimuli that are supposed to evoke prescribed spike trains in the respective neuron. Using experiments and simulations, we show that the prescribed spike trains can be evoked with a reliability that is comparable to the intrinsic reliability of the neuron under investigation.

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47

Park, Joonho. "Spatial development of the cytoplasmic compartments for single cell C₄ photosynthesis, and mechanisms of tolerance to salinity in Bienertia sinuspersici." Online access for everyone, 2008. http://www.dissertations.wsu.edu/Dissertations/Spring2008/j_park_041608.pdf.

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Breen, Kevin Thomas. "Describing the roles of myeloid cells in the compartmental degeneration of retinal ganglion cells in the neurodegenerative disease glaucoma." Thesis, The University of Utah, 2016. http://pqdtopen.proquest.com/#viewpdf?dispub=10036287.

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The role that myeloid innate immune cells play in neurodegeneration has long fascinated researchers because of the apparent changes of these cells found in all neurodegenerative diseases. However, it has become clear that the different parts or compartments of a neuron that traverse different anatomical environments degenerate at different times. Since there are myeloid cells around all of these neuronal compartments, answering the question of how myeloid cells impact the process of compartmentalized neurodegeneration is challenging. Further complicating this question is the fact that these cells can rapidly change their morphology and function in a process termed activation. In these activated states, myeloid cells have the capacity to regulate many aspects of neuronal damage and repair. Lastly, these myeloid cells are derived from different lineages that may play different roles in neurodegeneration.

Many authors have manipulated myeloid cells by loss of the receptor (CX3CR1) for the chemokine fractalkine and arrived at contrasting and context-dependent results even within models of the same neurodegenerative disease. Few studies have examined loss of fractalkine signaling in multiple compartments and even fewer have collected these data for each animal. Therefore, it remains unknown how loss of fractalkine signaling affects compartmentalized neurodegeneration.

Since the chronic mouse model of glaucoma, the DBA/2J, grants easy access to different degenerating retinal ganglion cell (RGC) compartments, it is an ideal system to determine how myeloid cells affect neuronal compartmentalized degeneration. The DBA/2J also features changes to myeloid cells, including microglial activation as early as 3 months and macrophage infiltration at 10 months. We generated DBA/2J mice lacking CX3CR1, and determined that this differentially affected RGC compartmentalized degeneration by increasing numbers of RGCs with a marker of disrupted axonal transport while not affecting RGC transcriptional dysregulation or optic nerve degeneration. Loss of CX3CR1 did not increase microglial activation overall but increased macrophage infiltration. However, numbers of infiltrating macrophage did not correlate with RGC pathology. We found that early microglial activation was composed of resident microglia and that high levels correlated strongly with later optic nerve degeneration. All together, these data implicate the resident microglia in disease progression in neurodegeneration.

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Barthelson, Roger, Georgina Lambert, Cheryl Vanier, Ronald Lynch, and David Galbraith. "Comparison of the contributions of the nuclear and cytoplasmic compartments to global gene expression in human cells." BioMed Central, 2007. http://hdl.handle.net/10150/610400.

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BACKGROUND:In the most general sense, studies involving global analysis of gene expression aim to provide a comprehensive catalog of the components involved in the production of recognizable cellular phenotypes. These studies are often limited by the available technologies. One technology, based on microarrays, categorizes gene expression in terms of the abundance of RNA transcripts, and typically employs RNA prepared from whole cells, where cytoplasmic RNA predominates.RESULTS:Using microarrays comprising oligonucleotide probes that represent either protein-coding transcripts or microRNAs (miRNA), we have studied global transcript accumulation patterns for the HepG2 (human hepatoma) cell line. Through subdividing the total pool of RNA transcripts into samples from nuclei, the cytoplasm, and whole cells, we determined the degree of correlation of these patterns across these different subcellular locations. The transcript and miRNA abundance patterns for the three RNA fractions were largely similar, but with some exceptions: nuclear RNA samples were enriched with respect to the cytoplasm in transcripts encoding proteins associated with specific nuclear functions, such as the cell cycle, mitosis, and transcription. The cytoplasmic RNA fraction also was enriched, when compared to the nucleus, in transcripts for proteins related to specific nuclear functions, including the cell cycle, DNA replication, and DNA repair. Some transcripts related to the ubiquitin cycle, and transcripts for various membrane proteins were sorted into either the nuclear or cytoplasmic fractions.CONCLUSION:Enrichment or compartmentalization of cell cycle and ubiquitin cycle transcripts within the nucleus may be related to the regulation of their expression, by preventing their translation to proteins. In this way, these cellular functions may be tightly controlled by regulating the release of mRNA from the nucleus and thereby the expression of key rate limiting steps in these pathways. Many miRNA precursors were also enriched in the nuclear samples, with significantly fewer being enriched in the cytoplasm. Studies of mRNA localization will help to clarify the roles RNA processing and transport play in the regulation of cellular function.

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Nilson, James E. "Compartmental distribution of two cation chloride cotransporter types along starburst amacrine cell dendrites underlies the directional properties of these dendrites." Thesis, Boston University, 2005. https://hdl.handle.net/2144/37167.

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Thesis (Ph.D.)--Boston University
PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.
A fundamental aspect of vision is the ability to detect motion and to define its direction. In the retina, directionally selective ganglion cells respond to stimulus motion in a 'preferred' direction but respond little to stimulus motion in the opposite or 'null' direction. However despite nearly forty years of investigation, the precise cellular locus and underlying mechanisms of direction selective encoding have remained largely elusive. Recently, starburst amacrine cells, that are presynaptic to directionally selective ganglion cells, have been shown to provide direction specific inhibitory output to these ganglion cells. Therefore defining the biophysical properties specific to starburst amacrine cell dendrites will provide significant insight into the ability of visual systems to encode the direction of objects moving through an animal's visual field. Using a combination of intracellular filling of starburst amacrine cells and immunohistochemical localization of biophysically relevant molecules, we have examined how individual dendrites compute such motion. In order to define the relative degree and pattern of colocalization of these markers on filled dendrites we developed a new set of image acquisition and data analysis procedures that have allowed us to define the biophysical signature intrinsic to different portions of starburst amacrine cell dendrites. We have found that sodium-potassium-chloride cotransporter (NKCC2) and potassium-chloride cotransporter (KCC2) are expressed and differentially distributed on the proximal and distal dendritic compartments of starburst amacrine cells, respectively. The functional relevance of the anatomical distribution pattern of these cation-chloride-cotransporter types has been confirmed by others using physiological techniques. In summary, our studies provide a fundamental mechanism through which starburst amacrine cells define motion direction and transmit this information to directionally selective ganglions cells. In addition, our illumination of the basic concept of segregation of functional components to different dendritic compartments will likely prove to be an important theme of neuronal function throughout the nervous system.
2031-01-01

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