1,250 research outputs found

    Rhythmic interaction between Period1 mRNA and HnRNP Q leads to circadian time-dependent translation

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    The mouse PERIOD1 (mPER1) protein, along with other clock proteins, plays a crucial role in the maintenance of circadian rhythms. mPER1 also provides an important link between the circadian system and the cell cycle system. Here we show that the circadian expression of mPER1 is regulated by rhythmic translational control of mPer1 mRNA together with transcriptional modulation. This time-dependent translation was controlled by an internal ribosomal entry site (IRES) element in the 5' untranslated region (5'-UTR) of mPer1 mRNA along with the trans-acting factor mouse heterogeneous nuclear ribonucleoprotein Q (mhnRNP Q). Knockdown of mhnRNP Q caused a decrease in mPER1 levels and a slight delay in mPER1 expression without changing mRNA levels. The rate of IRES-mediated translation exhibits phase-dependent characteristics through rhythmic interactions between mPer1 mRNA and mhnRNP Q. Here, we demonstrate 5'-UTR-mediated rhythmic mPer1 translation and provide evidence for posttranscriptional regulation of the circadian rhythmicity of core clock genes.X112932sciescopu

    Obesity-induced DNA hypermethylation of the adiponectin gene mediates insulin resistance

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    Adiponectin plays a key role in the regulation of the whole-body energy homeostasis by modulating glucose and lipid metabolism. Although obesity-induced reduction of adiponectin expression is primarily ascribed to a transcriptional regulation failure, the underlying mechanisms are largely undefined. Here we show that DNA hypermethylation of a particular region of the adiponectin promoter suppresses adiponectin expression through epigenetic control and, in turn, exacerbates metabolic diseases in obesity. Obesity-induced, pro-inflammatory cytokines promote DNMT1 expression and its enzymatic activity. Activated DNMT1 selectively methylates and stimulates compact chromatin structure in the adiponectin promoter, impeding adiponectin expression. Suppressing DNMT1 activity with a DNMT inhibitor resulted in the amelioration of obesity-induced glucose intolerance and insulin resistance in an adiponectin-dependent manner. These findings suggest a critical role of adiponectin gene epigenetic control by DNMT1 in governing energy homeostasis, implying that modulating DNMT1 activity represents a new strategy for the treatment of obesity-related diseases.published_or_final_versio

    Hypertrophy of the feet and ankles presenting in primary hypertrophic osteoarthropathy or pachydermoperiostosis: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>Pachydermoperiostosis or primary hypertrophic osteoathropathy is a rare genetic disease with autosomal transmission. This disorder, which affects both bones and skin, is characterized by the association of dermatologic changes (pachydermia or thickening of the skin) and rheumatologic manifestations (periostosis and finger clubbing). Here, we report a new observation of pachydermoperiostosis.</p> <p>Case presentation</p> <p>A 20-year-old North African Tunisian Caucasian man presented with hypertrophic osteoarthropathy. On a clinical examination, we found morphologic abnormalities of his face and extremities associated with skin changes. The laboratory findings were normal. A work-up disclosed no organic etiology. The final diagnosis consisted of pachydermoperiostosis syndrome.</p> <p>Conclusion</p> <p>Pachydermoperiostosis is a rare entity that should be differentiated from secondary hypertrophic osteoarthropathy and chronic rheumatic diseases.</p

    Inter-calibration of a proposed new primary reference standard AA-ETH Zn for zinc isotopic analysis

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    We have prepared a large volume of pure, concentrated and homogenous zinc standard solution. This new standard solution is intended to be used as a primary reference standard for the zinc isotope community, and to serve as a replacement for the nearly exhausted current reference standard, the so-called JMC-Lyon Zn. The isotopic composition of this new zinc standard (AA-ETH Zn) has been determined through an inter-laboratory calibration exercise, calibrated against the existing JMC-Lyon standard, as well as the certified Zn reference standard IRMM-3702. The data show that the new standard is isotopically indistinguishable from the IRMM-3702 zinc standard, with a weighted δ66/64Zn value of 0.28 ± 0.02‰ relative to JMC-Lyon. We suggest that this new standard be assigned a δ66/64Zn value of +0.28‰ for reporting of future Zn isotope data, with the rationale that all existing published Zn isotope data are presented relative to the JMC-Lyon standard. Therefore our proposed presentation allows for a direct comparison with all previously published data, and that are directly traceable to a certified reference standard, IRMM-3702 Zn. This standard will be made freely available to all interested labs through contact with the corresponding author

    Electrically driven single electron spin resonance in a slanting Zeeman field

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    The rapidly rising fields of spintronics and quantum information science have led to a strong interest in developing the ability to coherently manipulate electron spins. Electron spin resonance (ESR) is a powerful technique to manipulate spins that is commonly achieved by applying an oscillating magnetic field. However, the technique has proven very challenging when addressing individual spins. In contrast, by mixing the spin and charge degrees of freedom in a controlled way through engineered non-uniform magnetic fields, electron spin can be manipulated electrically without the need of high-frequency magnetic fields. Here we realize electrically-driven addressable spin rotations on two individual electrons by integrating a micron-size ferromagnet to a double quantum dot device. We find that the electrical control and spin selectivity is enabled by the micro-magnet's stray magnetic field which can be tailored to multi-dots architecture. Our results demonstrate the feasibility of manipulating electron spins electrically in a scalable way.Comment: 25 pages, 6 figure

    Border Crossing to Inject Drugs in Mexico Among Injection Drug Users in San Diego, California

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    We examined correlates of ever injecting drugs in Mexico among residents of San Diego, California. From 2007 to 2010, injecting drug users (IDUs) in San Diego underwent an interviewer-administered survey. Logistic regression identified correlates of injection drug use in Mexico. Of 302 IDUs, 38% were Hispanic, 72% male and median age was 37; 27% ever injected in Mexico; 43% reported distributive syringe sharing there. Factors independently associated with ever injecting drugs in Mexico included being younger at first injection, injecting heroin, distributive syringe sharing at least half of the time, and transporting drugs over the last 6 months. One-quarter of IDUs reported ever injecting drugs in Mexico, among whom syringe sharing was common, suggesting possible mixing between IDUs in the Mexico-US border region. Prospective studies should monitor trends in cross-border drug use in light of recent Mexican drug policy reforms partially decriminalizing drug possession

    Predicting multiplex subcellular localization of proteins using protein-protein interaction network: a comparative study

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    <p>Abstract</p> <p>Background</p> <p>Proteins that interact in vivo tend to reside within the same or "adjacent" subcellular compartments. This observation provides opportunities to reveal protein subcellular localization in the context of the protein-protein interaction (PPI) network. However, so far, only a few efforts based on heuristic rules have been made in this regard.</p> <p>Results</p> <p>We systematically and quantitatively validate the hypothesis that proteins physically interacting with each other probably share at least one common subcellular localization. With the result, for the first time, four graph-based semi-supervised learning algorithms, Majority, <it>χ</it><sup>2</sup>-score, GenMultiCut and FunFlow originally proposed for protein function prediction, are introduced to assign "multiplex localization" to proteins. We analyze these approaches by performing a large-scale cross validation on a <it>Saccharomyces cerevisiae </it>proteome compiled from BioGRID and comparing their predictions for 22 protein subcellular localizations. Furthermore, we build an ensemble classifier to associate 529 unlabeled and 137 ambiguously-annotated proteins with subcellular localizations, most of which have been verified in the previous experimental studies.</p> <p>Conclusions</p> <p>Physical interaction of proteins has actually provided an essential clue for their co-localization. Compared to the local approaches, the global algorithms consistently achieve a superior performance.</p

    Coherent coupling between radio frequency, optical, and acoustic waves in piezo-optomechanical circuits

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    The interaction of optical and mechanical modes in nanoscale optomechanical systems has been widely studied for applications ranging from sensing to quantum information science. Here, we develop a platform for cavity optomechanical circuits in which localized and interacting 1550 nm photons and 2.4 GHz phonons are combined with photonic and phononic waveguides. Working in GaAs facilitates manipulation of the localized mechanical mode either with a radio frequency field through the piezo-electric effect, or optically through the strong photoelastic effect. We use this to demonstrate a novel acoustic wave interference effect, analogous to coherent population trapping in atomic systems, in which the coherent mechanical motion induced by the electrical drive can be completely cancelled out by the optically-driven motion. The ability to manipulate cavity optomechanical systems with equal facility through either photonic or phononic channels enables new device and system architectures for signal transduction between the optical, electrical, and mechanical domains
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