55 research outputs found

    Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

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    The Observed Correlations for the Strange Multibaryon States in Systems with Λ\Lambda-Hyperon from pa Collision at Momentum of 10 Gev/cc

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    he observed well-known resonances Σ0\Sigma^0 Σ+\Sigma^{*+}(1385) and K±K^{*\pm}(892) from PDG are good tests of this method. Exotic strange multibaryon states have been observed in the effective mass spectra of: Λπ±\Lambda \pi^{\pm},Λγ\Lambda \gamma, Λp\Lambda p, Λpp\Lambda p p subsystems. The mean value of mass for Σ(1385)\Sigma^{*-}(1385) resonance is shifted till mass of 1370 MeV/c2c^2 and width is two times larger than the same value from PDG. Such kind of behavior for width and invariant mass of Σ(1385)\Sigma^{*-}(1385) resonance is interpreted as extensive contribution from stopped ΞΛπ\Xi^-\to\Lambda\pi^- and medium effect with invariant mass. The mean value of mass for Σ+(1385)\Sigma^{*+}(1385) from secondary interactions is also shifted till mass of 1370 MeV/c2c^2. The width of Σ0\Sigma^0 is \approx 2 times larger than the experimental error. There are enhancement production for all observed hyperons.Comment: 4 pages, 6 figures, XXIst Rencontres de Blois "Windows on the Universe " Blois, France June 21st - June 26th, 200

    PTEN regulates AMPA receptor-mediated cell viability in iPS-derived motor neurons

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    Excitatory transmission in the brain is commonly mediated by the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. In amyotrophic lateral sclerosis (ALS), AMPA receptors allow cytotoxic levels of calcium into neurons, contributing to motor neuron injury. We have previously shown that oculomotor neurons resistant to the disease process in ALS show reduced AMPA-mediated inward calcium currents compared with vulnerable spinal motor neurons. We have also shown that PTEN (phosphatase and tensin homolog deleted on chromosome 10) knockdown via siRNA promotes motor neuron survival in models of spinal muscular atrophy (SMA) and ALS. It has been reported that inhibition of PTEN attenuates the death of hippocampal neurons post injury by decreasing the effective translocation of the GluR2 subunit into the membrane. In addition, leptin can regulate AMPA receptor trafficking via PTEN inhibition. Thus, we speculate that manipulation of AMPA receptors by PTEN may represent a potential therapeutic strategy for neuroprotective intervention in ALS and other neurodegenerative disorders. To this end, the first step is to establish a fibroblast–iPS–motor neuron in vitro cell model to study AMPA receptor manipulation. Here we report that iPS-derived motor neurons from human fibroblasts express AMPA receptors. PTEN depletion decreases AMPA receptor expression and AMPA-mediated whole-cell currents, resulting in inhibition of AMPA-induced neuronal death in primary cultured and iPS-derived motor neurons. Taken together, our results imply that PTEN depletion may protect motor neurons by inhibition of excitatory transmission that represents a therapeutic strategy of potential benefit for the amelioration of excitotoxicity in ALS and other neurodegenerative disorders

    Alpha-Blockers as colorectal cancer chemopreventive: findings from a case-control study, human cell cultures, and in vivo preclinical testing

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    A retrospective case-controlled analysis was performed to identify drug candidates in the current use that may prevent colorectal cancer, outside of aspirin. A total of 37,510 patients aged ≥20 years were assessed to identify subjects who had been diagnosed with colorectal cancer by colonoscopy without a previous diagnosis of colorectal cancer, inflammatory bowel disease (IBD), or gastrointestinal symptoms; 1,560 patients were identified who were diagnosed with colorectal cancer by colonoscopy. The patients with colorectal cancer were matched with 1,560 age, gender, family history of colorectal cancer and comorbidity-matched control patients who were not diagnosed with colorectal cancer at colonoscopy. The medication histories were compared between the two groups. Next, candidate drugs that were more frequently used by the control patients were selected and their effects on human colorectal cancer cell lines in vitro and an inflammation-induced mouse model of colorectal cancer were tested. Putative colorectal cancer preventative agents were identified, including aspirin, vitamin D, vitamin B, vitamin C, vitamin E, xanthine oxidase inhibitor, alpha-blockers, angiotensin receptor blocker, nateglinide, probiotics, thienopyridine, folic acid, nitrovasodilators, bisphosphonates, calcium channel blockers, steroids, and statins (P < 0.05). Alpha-blockers and xanthine oxidase inhibitors were selected for further study because these agents have not been analyzed previously as factors that may affect colorectal cancer outcomes. In vitro doxazosin (alpha-blocker), but not febuxostat (xanthine oxidase inhibitor), suppressed the proliferation of human colorectal cancer cells. Doxazosin also decreased tumorigenesis in an AOM/DSS mouse colorectal cancer model. Alpha-blockers may prevent colorectal cancer.Nobumi Suzuki, Ryota Niikura, Sozaburo Ihara, Yohko Hikiba, Hiroto Kinoshita, Naoko Higashishima ... et al
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