269 research outputs found
Endoplasmic reticulum unfolded protein response, aging and exercise: an update
9 p.The endoplasmic reticulum (ER) is a dynamic and multifunctional organelle responsible
for protein biosynthesis, folding, assembly and modifications. Loss of protein folding
regulation, which leads to unfolded or misfolded proteins accumulation inside the ER
lumen, drives ER stress (ERS) and unfolded protein response (UPR) activation. During
aging, there is a decline in the ability of the cell to handle protein folding, accumulation
and aggregation, and the function of UPR is compromised. There is a progressive
failure of the chaperoning systems and a decline in many of its components, so that
the UPR activation cannot rescue the ERS. Physical activity has been proposed as
a powerful tool against aged-related diseases, which are linked to ERS. Interventional
studies have demonstrated that regular exercise is able to decrease oxidative stress
and inflammation and reverse mitochondrial and ER dysfunctions. Exercise-induced
metabolic stress could activate the UPR since muscle contraction is directly involved
in its activation, mediating exercise-induced adaptation responses. In fact, regular
moderate-intensity exercise-induced ERS acts as a protective mechanism against
current and future stressors. However, biological responses vary according to exercise
intensity and therefore induce different degrees of ERS and UPR activation. This article
reviews the effects of aging and exercise on ERS and UPR, also analyzing possible
changes induced by different types of exercise in elderly subjects.S
Steroid-refractory ulcerative colitis treated with corticosteroids, metronidazole and vancomycin: a case report
BACKGROUND: Increasing evidence elucidating the pathogenic mechanisms of ulcerative colitis (UC) has accumulated and the disease is widely assumed to be the consequence of genetic susceptibility and an abnormal immune response to commensal bacteria. However evidence regarding an infectious etiology in UC remains elusive. CASE PRESENTATION: We report a provocative case of UC with profound rheumatologic involvement directly preceded by Clostridium difficile infection and accompanying fever, vomiting, bloody diarrhea, and arthritis. Colonic biopsy revealed a histopathology suggestive of UC. Antibiotic treatment eliminated detectable levels of enteric pathogens but did not abate symptoms. Resolution of symptoms was procurable with oral prednisone, but tapering of corticosteroids was only achievable in combination therapy with vancomycin and metronidazole. CONCLUSIONS: An infectious pathogen may have both precipitated and exacerbated autoimmune disease attributes in UC, symptoms of which could be resolved only with a combination of corticosteroids, vancomycin and metronidazole. This may warrant the need for more perceptive scrutiny of C. difficile and the like in patients with UC
RhoGTPase Regulators Orchestrate Distinct Stages of Synaptic Development
Small RhoGTPases regulate changes in post-synaptic spine morphology and density that support learning and memory. They are also major targets of synaptic disorders, including Autism. Here we sought to determine whether upstream RhoGTPase regulators, including GEFs, GAPs, and GDIs, sculpt specific stages of synaptic development. The majority of examined molecules uniquely regulate either early spine precursor formation or later matura- tion. Specifically, an activator of actin polymerization, the Rac1 GEF ĂÂČ-PIX, drives spine pre- cursor formation, whereas both FRABIN, a Cdc42 GEF, and OLIGOPHRENIN-1, a RhoA GAP, regulate spine precursor elongation. However, in later development, a novel Rac1 GAP, ARHGAP23, and RhoGDIs inactivate actomyosin dynamics to stabilize mature synap- ses. Our observations demonstrate that specific combinations of RhoGTPase regulatory pro- teins temporally balance RhoGTPase activity during post-synaptic spine development
The Kuramoto model in complex networks
181 pages, 48 figures. In Press, Accepted Manuscript, Physics Reports 2015 Acknowledgments We are indebted with B. Sonnenschein, E. R. dos Santos, P. Schultz, C. Grabow, M. Ha and C. Choi for insightful and helpful discussions. T.P. acknowledges FAPESP (No. 2012/22160-7 and No. 2015/02486-3) and IRTG 1740. P.J. thanks founding from the China Scholarship Council (CSC). F.A.R. acknowledges CNPq (Grant No. 305940/2010-4) and FAPESP (Grants No. 2011/50761-2 and No. 2013/26416-9) for financial support. J.K. would like to acknowledge IRTG 1740 (DFG and FAPESP).Peer reviewedPreprin
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