Faithful segregation of replicated chromosomes is essential for maintenance of genetic stability and seems to be monitored by several mitotic checkpoints. Various components of these checkpoints have been identified in mammals, but their physiological relevance is largely unknown. Here we show that mutant mice with low levels of the spindle assembly checkpoint protein BubR1 develop progressive aneuploidy along with a variety of progeroid features, including short lifespan, cachectic dwarfism, lordokyphosis, cataracts, loss of subcutaneous fat and impaired wound healing. Graded reduction of BubR1 expression in mouse embryonic fibroblasts causes increased aneuploidy and senescence. Male and female mutant mice have defects in meiotic chromosome segregation and are infertile. Natural aging of wild-type mice is marked by decreased expression of BubR1 in multiple tissues, including testis and ovary. These results suggest a role for BubR1 in regulating aging and infertility.
T he dendritic cell (DC) plays a central role in orchestrating cellular immune responses to self and foreign antigens. A process of ''maturation'' that occurs after the acquisition of antigen results in up-regulation of MHC͞peptide and costimulatory ligands on the surface of DCs and in the secretion of immunomodulatory cytokines. In the mature state the DC is primed to activate T cells in an antigen-specific fashion. DC maturation is not, however, a consequence of antigen acquisition per se. Exposure to substances within the tissue microenvironment regulate DC maturational events. Among the factors that induce DC maturation are components of pathogenic microorganisms, products secreted by parenchymal cells and macrophages, and contact with activated T cells (1-6). Whether the preservation of DCs in an immature state results from the absence of maturational stimuli or is also actively maintained is not known.We
Survival of critically unwell patients has improved in the last decade due to advances in critical care medicine. Some of these survivors develop cognitive, psychiatric and /or physical disability after treatment in intensive care unit (ICU), which is now recognized as post intensive care syndrome (PICS). Given the limited awareness about PICS in the medical faculty this aspect is often overlooked which may lead to reduced quality of life and cause a lot of suffering of these patients and their families. Efforts should be directed towards preventing PICS by minimizing sedation and early mobilization during ICU.All critical care survivors should be evaluated for PICS and those having signs and symptoms of it should be managed by a multidisciplinary team which includes critical care physician, neuro-psychiatrist, physiotherapist and respiratory therapist,with the use of pharmacological and non-apharmacological interventions. This can be achieved through an organizational change and improvement, knowing the high rate of incidence of PICS and its adverse effects on the survivor's life and daily activities and its effect on the survivor's family.
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