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Viruses Jan 2020Human immunodeficiency virus (HIV) is a chronic infection that destroys the immune system in infected individuals. Although antiretroviral therapy is effective at... (Review)
Review
Human immunodeficiency virus (HIV) is a chronic infection that destroys the immune system in infected individuals. Although antiretroviral therapy is effective at preventing infection of new cells, it is not curative. The inability to clear infection is due to the presence of a rare, but long-lasting latent cellular reservoir. These cells harboring silent integrated proviral genomes have the potential to become activated at any moment, making therapy necessary for life. Latently-infected cells can also proliferate and expand the viral reservoir through several methods including homeostatic proliferation and differentiation. The chromosomal location of HIV proviruses within cells influences the survival and proliferative potential of host cells. Proliferating, latently-infected cells can harbor proviruses that are both replication-competent and defective. Replication-competent proviral genomes contribute to viral rebound in an infected individual. The majority of available techniques can only assess the integration site or the proviral genome, but not both, preventing reliable evaluation of HIV reservoirs.
Topics: CD4-Positive T-Lymphocytes; Cell Proliferation; HIV Infections; HIV-1; Hematopoietic Stem Cells; Host Microbial Interactions; Humans; Proviruses; Viral Load; Virus Latency; Virus Replication
PubMed: 31973022
DOI: 10.3390/v12020127 -
Glia Mar 2022Microglia proliferate during brain development and brain lesions, but how this is coordinated at the transcriptional level is not well understood. Here, we investigated...
Microglia proliferate during brain development and brain lesions, but how this is coordinated at the transcriptional level is not well understood. Here, we investigated fundamental aspects of the transcriptional process associated with proliferation of mouse microglia during postnatal development and in adults in a model of induced microglial depletion-repopulation. While each proliferative subset displayed globally a distinct signature of gene expression, they also co-expressed a subgroup of 1370 genes at higher levels than quiescent microglia. Expression of these may be coordinated by one of two mechanisms of regulation with distinct properties. A first mechanism augments expression of genes already expressed in quiescent microglia and is subject to regulation by Klf/Sp, Nfy, and Ets transcription factors. Alternatively, a second mechanism enables de novo transcription of cell cycle genes and requires additional regulatory input from Lin54 and E2f transcription factors. Of note, transcriptional upregulation of E2f1 and E2f2 family members may represent a critical regulatory checkpoint to enable microglia to achieve efficient cell cycling. Furthermore, analysis of the activity profile of the repertoire of promoter-distal genomic regulatory elements suggests a relatively restricted role for these elements in coordinating cell cycle gene expression in microglia. Overall, proliferating microglia integrates regulation of cell cycle gene expression with their broader, context-dependent, transcriptional landscape.
Topics: Animals; Cell Proliferation; Gene Expression Regulation; Mice; Microglia; Promoter Regions, Genetic; Transcription Factors
PubMed: 34862814
DOI: 10.1002/glia.24124 -
Soft Matter Feb 2023We extend the continuum theory of active nematic fluids to study cell flows and tissue dynamics inside multicellular spheroids, spherical, self-assembled aggregates of...
We extend the continuum theory of active nematic fluids to study cell flows and tissue dynamics inside multicellular spheroids, spherical, self-assembled aggregates of cells that are widely used as model systems to study tumour dynamics. Cells near the surface of spheroids have better access to nutrients and therefore proliferate more rapidly than those in the resource-depleted core. Using both analytical arguments and three-dimensional simulations, we find that the proliferation gradients result in flows and in gradients of activity both of which can align the orientation axis of cells inside the aggregates. Depending on environmental conditions and the intrinsic tissue properties, we identify three distinct alignment regimes: spheroids in which all the cells align either radially or tangentially to the surface throughout the aggregate and spheroids with angular cell orientation close to the surface and radial alignment in the core. The continuum description of tissue dynamics inside spheroids not only allows us to infer dynamic cell parameters from experimentally measured cell alignment profiles, but more generally motivates novel mechanisms for controlling the alignment of cells within aggregates which has been shown to influence the mechanical properties and invasive capabilities of tumors.
Topics: Humans; Spheroids, Cellular; Neoplasms
PubMed: 36625444
DOI: 10.1039/d2sm01239a -
Biotechnology & Genetic Engineering... Apr 2023To investigate the image computer analysis of abnormally proliferating transformed cells of gastric mucosa and its clinical significance. The pathological pictures of...
To investigate the image computer analysis of abnormally proliferating transformed cells of gastric mucosa and its clinical significance. The pathological pictures of gastric adenomatous polyp cells, abnormally proliferating altered cells, and tubular adenocarcinoma cells in the stomach mucosa were assessed by image computer method on a total of 96 gastroscopic biopsy and ESD resection specimens. The data of cytoplasmic area, nuclear area, nuclear-cytoplasmic ratio, nuclear factor and N-heterotypic index of gastric adenomatous polyps, abnormal proliferative transformation and gastric intramucosal tubular adenocarcinoma were collected, and the mean, standard deviation and variance were calculated respectively. Standard Error, Maximum, Minimum Parameters and Statistical Structure. There were substantial discrepancies between gastric mucosal gastric adenomatous polyp cells and gastric mucosal abnormally proliferating transformed cells, according to the five data in the abnormal cells in the stomach mucosal proliferation area ( < 0.01); There was no significant difference between cells ( > 0.05). Computer analysis of cell images can provide quantitative values for the pathological diagnosis of gastric adenomatous polyp cells, abnormally proliferating transformed cells and tubular adenocarcinoma cells in the gastric mucosa, especially the degree of atypical proliferation. The monitoring of abnormally proliferated and transformed cells in gastric mucosa is of great significance for clinicians to accurately treat and track cell transformation, and to control the occurrence and development of gastric adenocarcinoma.
PubMed: 37067362
DOI: 10.1080/02648725.2023.2197382 -
Veterinary Immunology and... May 2020CellTrace Violet™ is a commonly used fluorescent dye used with flow cytometry to identify cell proliferation. Activated equine lymphocytes were examined using flow...
CellTrace Violet™ is a commonly used fluorescent dye used with flow cytometry to identify cell proliferation. Activated equine lymphocytes were examined using flow cytometry, microscopy and tritiated thymidine proliferation assays. CellTrace Violet™ was incorporated into the equine lymphocytes effectively. Equine lymphocytes proliferated when activated with pokeweed mitogen, but did not proliferate when previously stained with CellTrace Violet™. Serial dilutions of CellTrace Violet™ did not eliminate the inhibition of activated lymphocytes. Equine lymphocyte viability was greater than 90 % for both stained and unstained cells. Based on these data, CellTrace Violet™ is not recommended for the assessment of lymphocyte proliferation in equine cells. The mechanism of inhibition of equine lymphocyte proliferation by CellTrace Violet™ is unknown.
Topics: Animals; Cell Proliferation; Cell Survival; Concanavalin A; Flow Cytometry; Fluorescent Dyes; Horses; Lymphocyte Activation; Lymphocytes; Pokeweed Mitogens
PubMed: 32229340
DOI: 10.1016/j.vetimm.2020.110037 -
Journal of Theoretical Biology Feb 2022In this paper we introduce random proliferation models on graphs. We consider two types of particles: type-1/mutant/invader/red particles proliferates on a population of...
In this paper we introduce random proliferation models on graphs. We consider two types of particles: type-1/mutant/invader/red particles proliferates on a population of type-2/wild-type/resident/blue particles. Unlike the well-known Moran model on graphs -as introduced in Lieberman et al. (2005)-, type-1 particles can occupy in a single iteration several neighbouring sites previously occupied by type-2 particles. Two variants are considered, depending on the random distribution involving the proliferation mechanism: Bernoulli and binomial proliferation. By comparison with fixation probability of type-1 particles in the Moran process, critical parameters are introduced. Properties of proliferation are studied and some particular cases are analytically solved. Finally, by updating the parameters that drive the processes through a density-dependent mechanism, it is possible to capture additional relevant features as fluctuating waves of type-1 particles over long periods of time. In fact, the models can be adapted to tackle more general, complex and realistic situations.
Topics: Biological Evolution; Cell Proliferation; Probability
PubMed: 34717934
DOI: 10.1016/j.jtbi.2021.110942 -
Gastroenterology Research Oct 2019Gastrointestinal (GI) hormones are essential to many physiologic functions in our body. They have many GI and extra-GI functions. Some of the functions of these... (Review)
Review
Gastrointestinal (GI) hormones are essential to many physiologic functions in our body. They have many GI and extra-GI functions. Some of the functions of these hormones, which have GI and extra-GI sources, are still unknown. Specific GI hormones can affect the brain to control food intake, while others can proliferate normal and neoplastic tissue when their receptors are expressed in certain neoplasms. GI hormones also have many diagnostic and therapeutic roles. Physiologic and pathophysiologic aspects as well as the diagnostic and therapeutic values of GI hormones are elaborated in this review.
PubMed: 31636773
DOI: 10.14740/gr1219 -
The EMBO Journal May 2017Biochemistry textbooks and cell culture experiments seem to be telling us two different things about the significance of external glutamine supply for mammalian cell... (Review)
Review
Biochemistry textbooks and cell culture experiments seem to be telling us two different things about the significance of external glutamine supply for mammalian cell growth and proliferation. Despite the fact that glutamine is a nonessential amino acid that can be synthesized by cells from glucose-derived carbons and amino acid-derived ammonia, most mammalian cells in tissue culture cannot proliferate or even survive in an environment that does not contain millimolar levels of glutamine. Not only are the levels of glutamine in standard tissue culture media at least ten-fold higher than other amino acids, but glutamine is also the most abundant amino acid in the human bloodstream, where it is assiduously maintained at approximately 0.5 mM through a combination of dietary uptake, synthesis, and muscle protein catabolism. The complex metabolic logic of the proliferating cancer cells' appetite for glutamine-which goes far beyond satisfying their protein synthesis requirements-has only recently come into focus. In this review, we examine the diversity of biosynthetic and regulatory uses of glutamine and their role in proliferation, stress resistance, and cellular identity, as well as discuss the mechanisms that cells utilize in order to adapt to glutamine limitation.
Topics: Animals; Cell Proliferation; Glutamine; Humans; Neoplasms
PubMed: 28420743
DOI: 10.15252/embj.201696151 -
Journal of Developmental Biology May 2022Turner syndrome (TS) is a chromosomal disorder that is caused by a missing or structurally abnormal second sex chromosome. Subjects with TS are at an increased risk of... (Review)
Review
Turner syndrome (TS) is a chromosomal disorder that is caused by a missing or structurally abnormal second sex chromosome. Subjects with TS are at an increased risk of developing intrauterine growth retardation, low birth weight, short stature, congenital heart diseases, infertility, obesity, dyslipidemia, hypertension, insulin resistance, type 2 diabetes mellitus, metabolic syndrome, and cardiovascular diseases (stroke and myocardial infarction). The underlying pathogenetic mechanism of TS is unknown. The assumption that X chromosome-linked gene haploinsufficiency is associated with the TS phenotype is questioned since such genes have not been identified. Thus, other pathogenic mechanisms have been suggested to explain this phenotype. Morphogenesis encompasses a series of events that includes cell division, the production of migratory precursors and their progeny, differentiation, programmed cell death, and integration into organs and systems. The precise control of the growth and differentiation of cells is essential for normal development. The cell cycle frequency and the number of proliferating cells are essential in cell growth. 45,X cells have a failure to proliferate at a normal rate, leading to a decreased cell number in a given tissue during organogenesis. A convergence of data indicates an association between a prolonged cell cycle and the phenotypical features in Turner syndrome. This review aims to examine old and new findings concerning the relationship between a prolonged cell cycle and TS phenotype. These studies reveal a diversity of phenotypic features in TS that could be explained by reduced cell proliferation. The implications of this hypothesis for our understanding of the TS phenotype and its pathogenesis are discussed. It is not surprising that 45,X monosomy leads to cellular growth pathway dysregulation with profound deleterious effects on both embryonic and later stages of development. The prolonged cell cycle could represent the beginning of the pathogenesis of TS, leading to a series of phenotypic consequences in embryonic/fetal, neonatal, pediatric, adolescence, and adulthood life.
PubMed: 35645292
DOI: 10.3390/jdb10020016 -
Neuro-oncology Advances 2022The actin-binding protein filamin A (FLNA) regulates oncogenic signal transduction important for tumor growth, but the role of FLNA in the progression of neuroblastoma...
BACKGROUND
The actin-binding protein filamin A (FLNA) regulates oncogenic signal transduction important for tumor growth, but the role of FLNA in the progression of neuroblastoma (NB) has not been explored.
METHODS
We analyzed mRNA expression in the R2 NB-database and FLNA protein expression in human NB tumors. We then silenced expression in human SKNBE2 and IMR32 NB cells by lentiviral vector encoding shRNA and assayed the cells for proliferation, migration, colony, spheroid formation, and apoptosis. SKNBE2 xenografts expressing or lacking FLNA in BALB/c nude mice were analyzed by both routine histopathology and immunohistochemistry.
RESULTS
We observed shorter patient survival with higher expression of mRNA than patients with lower mRNA expression, and high-risk NB tumors expressed higher FLNA levels. Overexpression of FLNA increased proliferation of SH-SY5 NB cells. NB cell lines transfected with siRNA proliferated and migrated less, expressed lower levels of phosphorylated AKT and ERK1/2, formed smaller colonies and spheroids, as well as increased apoptosis. After inoculation of SKNBE2 cells infected with lentivirus expressing shRNA , size of NB tumors and number of proliferating cells were decreased. Furthermore, we identified STAT3 as an interacting partner of FLNA. Silencing mRNA reduced levels of NF-κB, STAT3 and MYCN, and increased levels of p53 and cleaved caspase 3.
CONCLUSION
Inhibition of FLNA impaired NB cell signaling and function and reduced NB tumor size , suggesting that drugs targeting either FLNA or its interaction with STAT3 may be useful in the treatment of NB.
PubMed: 35441138
DOI: 10.1093/noajnl/vdac028