726 research outputs found

    ADAM10 is essential for Notch2-dependent marginal zone B cell development and CD23 cleavage in vivo

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    The proteolytic activity of a disintegrin and metalloproteinase 10 (ADAM10) regulates cell-fate decisions in Drosophila and mouse embryos. However, in utero lethality of ADAM10−/− mice has prevented examination of ADAM10 cleavage events in lymphocytes. To investigate their role in B cell development, we generated B cell–specific ADAM10 knockout mice. Intriguingly, deletion of ADAM10 prevented development of the entire marginal zone B cell (MZB) lineage. Additionally, cleavage of the low affinity IgE receptor, CD23, was profoundly impaired, but subsequent experiments demonstrated that ADAM10 regulates CD23 cleavage and MZB development by independent mechanisms. Development of MZBs is dependent on Notch2 signaling, which requires proteolysis of the Notch2 receptor by a previously unidentified proteinase. Further experiments revealed that Notch2 signaling is severely impaired in ADAM10-null B cells. Thus, ADAM10 critically regulates MZB development by initiating Notch2 signaling. This study identifies ADAM10 as the in vivo CD23 sheddase and an important regulator of B cell development. Moreover, it has important implications for the treatment of numerous CD23- and Notch-mediated pathologies, ranging from allergy to cancer

    Electrical transport between epitaxial manganites and carbon nanotubes

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    The possibility of performing spintronics at the molecular level may be realized in devices that combine fully spin polarized oxides such as manganites with carbon nanotubes. However, it is not clear whether electrical transport between such different material systems is viable. Here we show that the room temperature conductance of manganite-nanotube-manganite devices is only half the value recorded in similar palladium-nanotube-palladium devices. Interestingly, the former shows a pseudogap in the conductivity below the relatively high temperature of 200 K. Our results suggest the possibility of new spintronics heterostructures that exploit fully spin polarized sources and drains

    Focal Bone Marrow Lesions: A Complication of Ultrasound Diathermy

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    Ultrasound diathermy is widely used for the treatment of musculoskeletal disorders and other soft tissue injuries. Its use as a therapeutic modality is believed to be safe, with very few reported complications. Here, we report two patients who developed focal bone marrow abnormalities after receiving ultrasound diathermy. Both patients’ magnetic resonance (MR) evaluations revealed linear subchondral bone lesions of the superolateral humeral head similar to those in osteonecrosis. The patients’ symptoms subsequently improved, and available follow-up MR evaluation revealed near complete resolution of bone lesions. These findings suggest that ultrasound diathermy, and its interaction with bone tissue through thermal mechanisms, can cause focal bone marrow abnormalities. Furthermore, the bone marrow abnormalities seem to be transient, resolving upon cessation of ultrasound diathermy, therefore osteonecrosis should be differentiated from this temporal lesion

    Collider Signatures of Neutrino Masses and Mixing from R-parity Violation

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    R-parity violation in the supersymmetric standard model can be the source of neutrino masses and mixing. We analyze the neutrino mass matrix coming from either bilinear or trilinear R-parity violation and its collider signatures, assuming that the atmospheric and solar neutrino data are explained by three active neutrino oscillations. Taking the gauge mediated supersymmetry breaking mechanism, we show that the lightest neutralino decays well inside the detector and the model could be tested by observing its branching ratios in the future colliders. In the bilinear model where only the small solar neutrino mixing angle can be accommodated, the relation, 10310^3 BR(νe±τ\nu e^\pm \tau^\mp) \sim BR(νμ±τ\nu \mu^\pm \tau^\mp) \approx BR(ντ±τ\nu \tau^\pm \tau^\mp), serves as a robust test of the model. The large mixing angle solution can be realized in the trilinear model which predicts BR(νe±τ\nu e^\pm \tau^\mp) \sim BR(νμ±τ\nu \mu^\pm \tau^\mp) \sim BR(ντ±τ\nu \tau^\pm \tau^\mp). In either case, the relation, BR(ejje jj) \ll BR(μjj\mu jj) \sim BR(τjj\tau jj), should hold to be consistent with the atmospheric neutrino and CHOOZ experiments.Comment: 24pages, Late

    Changes of fat-mass and obesity-associated protein expression in the hippocampus in animal models of high-fat diet-induced obesity and D-galactose-induced aging

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    Abstract Fat-mass and obesity-associated protein (Fto) is highly expressed in the brain including, the hippocampus, and its expression is significantly decreased in the brain of Alzheimers disease patients. In the present study, we measured Fto immunoreactivity and protein levels in the hippocampus of obese and aged mice, which were induced by high-fat diet for 12 weeks and D-galactose treatment for 10 weeks, respectively. The obesity and aging phenotypes were assessed by physiological parameters and Morris water maze test, respectively. High fat diet fed mice showed significant increases in body weight and blood glucose levels compared to that in the control or D-galactose-induced aged mice. In addition, treatment with D-galactose significantly decreased the spatial memory. Fto immunoreactivity in the control group was mainly detected in the pyramidal cells of the CA1 and CA3 regions and in the granule cells of the dentate gyrus. In the hippocampus of high-fat diet-fed mice, Fto immunoreactive structures were similarly found in the hippocampus compared to that in the control group, but Fto immunoreactivity in high-fat diet-fed mice was also found in the stratum oriens and radiatum of the CA1 and CA3 regions and the polymorphic layer of the dentate gyrus. In the hippocampus of D-galactose-induced aged mice, fewer Fto immunoreactive structures were detected in the granule cell layer of the dentate gyrus compared to the control group. Fto mRNA and protein levels based on quantitative real-time polymerase chain reaction and western blot assays were slightly increased in the hippocampus of high-fat diet-fed mice compared to that in control mice. In addition, Fto mRNA and protein levels were significantly decreased in the aged hippocampus compared to that in the control group. Fto protein levels are susceptible to the aging process, but not in the hippocampus of high-fat diet-induced obesity. The reduction of Fto in aged mice may be associated with reduced memory impairment in mice

    Multiplex reverse transcription-PCR for rapid differential detection of porcine epidemic diarrhea virus, transmissible gastroenteritis virus, and porcine group A rotavirus

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    A novel multiplex reverse transcription polymerase chain reaction (multiplex RT-PCR) that can detect porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), and porcine group A rotavirus (GAR) was developed. The 3 viruses (PEDV, TGEV, and porcine GAR) are major agents in viral enteric diseases of piglets. As the clinical signs of these diseases are similar, including watery diarrhea, differential detection is required for etiologic diagnosis. A mixture of 3 pairs of published primers was used for amplification of viral nucleic acids, yielding 3 different amplicons with sizes of 859 bp, 651 bp, and 309 bp for TGEV, PEDV, and porcine GAR, respectively. A total of 157 specimens (78 fecal and 79 intestinal samples) from piglets with acute gastroenteritis were collected in Korea between January 2004 and May 2005. They were tested for the presence of 3 viruses by multiplex RT-PCR. Coinfections with PEDV and porcine GAR were identified in 16 farms (43.2%). PEDV, porcine GAR, and TGEV infection were 26.3%, 13.2%, and 2.7% respectively. The relative sensitivity and specificity of multiplex RT-PCR were evaluated, with results suggesting that this assay is equal in quality to conventional single-agent RT-PCR assays (sensitivity:100%, 92.9%, 100% for TGEV, PEDV, GARs; specificity: 100% for all 3 viruses). This multiplex RT-PCR is a simple assay and may be a potentially useful for rapid, sensitive, and cost-effective etiological diagnostic tool for acute viral gastroenteritis in piglets.This work was supported by Korea Research Foundation Grants (KRF-2002-070-C00069) and the Brain Korea 21 Project of the Ministry of Education & Human Resources Development, Republic of Korea

    Rifaximin Exerts Beneficial Effects Independent of its Ability to Alter Microbiota Composition

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    Rifaximin has clinical benefits in minimal hepatic encephalopathy (MHE) but the mechanism of action is unclear. The antibiotic-dependent and -independent effects of rifaximin need to be elucidated in the setting of MHE-associated microbiota. To assess the action of rifaximin on intestinal barrier, inflammatory milieu and ammonia generation independent of microbiota using rifaximin

    Synthesis and characterization of CuO nanowires by a simple wet chemical method

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    We report a successful synthesis of copper oxide nanowires with an average diameter of 90 nm and lengths of several micrometers by using a simple and inexpensive wet chemical method. The CuO nanowires prepared via this method are advantageous for industrial applications which require mass production and low thermal budget technique. It is found that the concentration and the quantity of precursors are the critical factors for obtaining the desired one-dimensional morphology. Field emission scanning electron microscopy images indicate the influence of thioglycerol on the dispersity of the prepared CuO nanowires possibly due to the stabilization effect of the surface caused by the organic molecule thioglycerol. The Fourier transform infrared spectrum analysis, energy dispersive X-ray analysis, X-ray diffraction analysis, and X-ray photoemission spectrum analysis confirm clearly the formation of a pure phase high-quality CuO with monoclinic crystal structure
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