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Replicative Capacity (replicative + capacity)
Selected AbstractsIdentification and characterization of nucleoplasmin 3 as a histone-binding protein in embryonic stem cellsDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 5 2008Natsuki Motoi Embryonic stem (ES) cells are thought to have unique chromatin structures responsible for their capacity for self-renewal and pluripotency. To examine this possibility, we sought nuclear proteins in mouse ES cells that specifically bind to histones using a pull-down assay with synthetic peptides of histone H3 and H4 tail domain as baits. Nuclear proteins preferentially bound to the latter. We identified 45 proteins associated with the histone H4 tail and grouped them into four categories: 10 chromatin remodeling proteins, five histone chaperones, two histone modification-related proteins, and 28 other proteins. mRNA expression levels of 20 proteins selected from these 45 proteins were compared between undifferentiated and retinoic acid (RA)-induced differentiated ES cells. All of the genes were similarly expressed in both states of ES cells, except nucleoplasmin 3 (NPM3) that was expressed at a higher level in the undifferentiated cells. NPM3 proteins were localized in the nucleoli and nuclei of the cells and expression was decreased during RA-induced differentiation. When transfected with NPM3 gene, ES cells significantly increased their proliferation compared with control cells. The present study strongly suggests that NPM3 is a chromatin remodeling protein responsible for the unique chromatin structure and replicative capacity of ES cells. [source] BTG2 antagonizes Pin1 in response to mitogens and telomere disruption during replicative senescenceAGING CELL, Issue 5 2010Keith Wheaton Summary Cellular senescence limits the replicative capacity of normal cells and acts as an intrinsic barrier that protects against the development of cancer. Telomere shortening,induced replicative senescence is dependent on the ATM-p53-p21 pathway but additional genes likely contribute to senescence. Here, we show that the p53-responsive gene BTG2 plays an essential role in replicative senescence. Similar to p53 and p21 depletion, BTG2 depletion in human fibroblasts leads to an extension of cellular lifespan, and ectopic BTG2 induces senescence independently of p53. The anti-proliferative function of BTG2 during senescence involves its stabilization in response to telomere dysfunction followed by serum-dependent binding and relocalization of the cell cycle regulator prolyl isomerase Pin1. Pin1 inhibition leads to senescence in late-passage cells, and ectopic Pin1 expression rescues cells from BTG2-induced senescence. The neutralization of Pin1 by BTG2 provides a critical mechanism to maintain senescent arrest in the presence of mitogenic signals in normal primary fibroblasts. [source] Favorable outcome of ex-vivo purging of monocytes after the reintroduction of treatment after interruption in patients infected with multidrug resistant HIV-1,JOURNAL OF MEDICAL VIROLOGY, Issue 11 2007Hamid Hasson Abstract In multidrug resistant patients treatment interruptions allow the selection of archived wild-type drug-susceptible viruses that compete for the less fit drug-resistant strains. However, the selection of viruses with increased replicative capacity is often followed by a loss of CD4+ T cells. In addition, drug resistant variants later re-emerge limiting the overall clinical benefit of treatment interruption. Blood monocytes are a key component of the HIV reservoir and can be partially removed by a system for purging of myeloid cells (MYP). This study tested the safety and efficacy of MYP on multidrug resistant patients who underwent treatment interruption. Twelve patients were randomized to receive or not six cycles of MYP during treatment interruption. An optimized antiretroviral regimen was reintroduced after the reappearance of a drug susceptible genotype. Following therapy reintroduction, a long lasting increase in CD4+ T cell counts was observed only in the treatment interruption,+,MYP patients but not in the control patients. Five/six treatment interruption,+,MYP patients never experienced virological rebound during a median follow up period of 98 weeks. In contrast, 4/6 patients who did not receive MYP never reached complete viral suppression and had a virological rebound after a median of 16.5 weeks after treatment reintroduction. The difference between the two groups in the time to virological rebound was statistically significant (P,=,0.021). A consistent decrease of HIV DNA load in CD14+ purified cells was observed only in treatment interruption,+,MYP patients. These data suggest that MYP can improve the immunological and virological response to treatment interruption. J. Med. Virol. 79:1640,1649, 2007. © 2007 Wiley-Liss, Inc. [source] Occult hepatitis B virus infection: a covert operationJOURNAL OF VIRAL HEPATITIS, Issue 1 2010F. B. Hollinger Summary., Detection of occult hepatitis B requires assays of the highest sensitivity and specificity with a lower limit of detection of less than 10 IU/mL for hepatitis B virus (HBV) DNA and <0.1 ng/mL for hepatitis B surface antigen (HBsAg). This covert condition is relatively common in patients with chronic hepatitis C virus (HCV) that seems to exert some influence on the replicative capacity and latency of HBV. Detection of virus-specific nucleic acid does not always translate into infectivity, and the occurrence of primer-generated HBV DNA that is of partial genomic length in immunocompetent individuals who have significant levels of hepatitis B surface antibody (anti-HBs) may not be biologically relevant. Acute flares of alanine aminotransferase (ALT) that occur during the early phase of therapy for HCV or ALT levels that remain elevated at the end of therapy in biochemical nonresponders should prompt an assessment for occult hepatitis B. Similarly, the plasma from patients with chronic hepatitis C that is hepatitis B core antibody (anti-HBc) positive (±anti-HBs at levels of <100 mIU/mL) should be examined for HBV DNA with the most sensitive assay available. If a liver biopsy is available, immunostaining for hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) should be contemplated and a portion of the sample tested for HBV DNA. This is another reason for optimal collection of a specimen (e.g. two passes with a 16-guage needle under ultrasound guidance). Transmission of HBV to immunosuppressed orthotopic liver transplant recipients by donors with occult hepatitis B (OHB) will continue to occupy the interests of the transplant hepatologist. As patients with OHB may have detectable HBV DNA in serum, peripheral blood mononuclear cells (PBMC) and/or liver that can be reactivated following immunosuppression or intensive cytotoxic chemotherapy, the patient needs to be either monitored or treated depending on the pretreatment serological results such as an isolated anti-HBc reaction or a detectable HBV DNA. [source] The impact of media composition and petite mutation on the longevity of a polyploid brewing yeast strainLETTERS IN APPLIED MICROBIOLOGY, Issue 1 2000C.D. Powell Ageing in Saccharomyces cerevisiae is a finite phenomenon, determined by replicative, rather than chronological lifespan. Yeast physiological condition is known to influence industrial fermentation performance, however, until recently cellular senescence has not been considered as a brewing yeast stress factor. A polyploid lager yeast (BB11) and a brewery isolate, exhibiting petite mutation were analysed for longevity. It was observed that mitochondrial deficiency induced a reduction in lifespan. In addition, replicative capacity was perceived to be dependent on environmental conditions. [source] Ageing mechanisms: the role of telomere lossCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 7 2001P. Boukamp The ends of the chromosomes are capped by specialized structures, the telomeres. These are comprised of tracts of hexanucleotid sequences and, in combination with specific proteins, protect the chromosome against degradation, fusion events and as being recognized as 'damaged' DNA; thus, they guarantee chromosomal integrity. Due to deficiencies during DNA replication, the telomeres continuously loose part of their sequences and it has been proposed that this loss is the liming factor for the replicative capacity of a cell, i.e. telomeric loss is the counting mechanism - the internal clock of ageing. In order to proliferate indefinitely, the cells must prevent telomere erosion and this is mostly achieved by upregulation or de novo expression of the ribonucleoprotein complex telomerase. This enzyme, which has a reverse-transcriptase activity, is able to add telomeric sequences to the outer most ends off the telomeres and thereby stabilize or even elongate the telomeres. As telomerase is expressed in about 90% of all tumours while expression is absent in many somatic tissues, it is not surprising that the causal role of telomere erosion is presently the most favoured hypothesis of cellular ageing. [source] | |||||||||||||