530 research outputs found

    Successful Treatment of Protein-Losing Gastroenteropathy with Steroid Pulse and Immunosuppressive Therapies in a Patient with Sjögren Syndrome

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    We report the case of a 59-year-old female who developed facial edema together with hypoproteinemia. On the basis of 99mTc-human serum albumin scintigraphy and a1-antitrypsin clearance, she was diagnosed with protein-losing gastroenteropathy. Furthermore, she was diagnosed with Sjögren syndrome on the basis of eye and oral dryness, positive result with anti-SSA antibody, and salivary gland biopsy. Her symptoms improved with the use of immunosuppressive agents following steroid pulse therapy. Therefore, steroid pulse therapy and immunosuppressive agents should be considered as possible effective treatment strategies for protein-losing gastroenteropathy associated with autoimmune diseases

    Ten Misconceptions from the History of Analysis and Their Debunking

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    The widespread idea that infinitesimals were "eliminated" by the "great triumvirate" of Cantor, Dedekind, and Weierstrass is refuted by an uninterrupted chain of work on infinitesimal-enriched number systems. The elimination claim is an oversimplification created by triumvirate followers, who tend to view the history of analysis as a pre-ordained march toward the radiant future of Weierstrassian epsilontics. In the present text, we document distortions of the history of analysis stemming from the triumvirate ideology of ontological minimalism, which identified the continuum with a single number system. Such anachronistic distortions characterize the received interpretation of Stevin, Leibniz, d'Alembert, Cauchy, and others.Comment: 46 pages, 4 figures; Foundations of Science (2012). arXiv admin note: text overlap with arXiv:1108.2885 and arXiv:1110.545

    Arsen Lüpen’in sergüzeştinden: duvardaki akisler

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    Maurice Leblanc'ın İleri'de yayımlanan Arsen Lüpen’in Sergüzeştinden: Duvardaki Akisler adlı romanının ilk ve son tefrikalar

    Microscale arrays for the profiling of start and stop signals coordinating human-neutrophil swarming.

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    Neutrophil swarms protect healthy tissues by sealing off sites of infection. In the absence of swarming, microbial invasion of surrounding tissues can result in severe infections. Recent observations in animal models have shown that swarming requires rapid neutrophil responses and well-choreographed neutrophil migration patterns. However, in animal models physical access to the molecular signals coordinating neutrophil activities during swarming is limited. Here, we report the development and validation of large microscale arrays of zymosan-particle clusters for the study of human neutrophils during swarming ex vivo. We characterized the synchronized swarming of human neutrophils under the guidance of neutrophil-released chemokines, and measured the mediators released at different phases of human-neutrophil swarming against targets simulating infections. We found that the network of mediators coordinating human-neutrophil swarming includes start and stop signals, proteolytic enzymes and enzyme inhibitors, as well as modulators of activation of other immune and non-immune cells. We also show that the swarming behavior of neutrophils from patients following major trauma is deficient and gives rise to smaller swarms than those of neutrophils from healthy individuals

    The Histone H3K79 Methyltransferase Dot1L Is Essential for Mammalian Development and Heterochromatin Structure

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    Dot1 is an evolutionarily conserved histone methyltransferase specific for lysine 79 of histone H3 (H3K79). In Saccharomyces cerevisiae, Dot1-mediated H3K79 methylation is associated with telomere silencing, meiotic checkpoint control, and DNA damage response. The biological function of H3K79 methylation in mammals, however, remains poorly understood. Using gene targeting, we generated mice deficient for Dot1L, the murine Dot1 homologue. Dot1L-deficient embryos show multiple developmental abnormalities, including growth impairment, angiogenesis defects in the yolk sac, and cardiac dilation, and die between 9.5 and 10.5 days post coitum. To gain insights into the cellular function of Dot1L, we derived embryonic stem (ES) cells from Dot1L mutant blastocysts. Dot1L-deficient ES cells show global loss of H3K79 methylation as well as reduced levels of heterochromatic marks (H3K9 di-methylation and H4K20 tri-methylation) at centromeres and telomeres. These changes are accompanied by aneuploidy, telomere elongation, and proliferation defects. Taken together, these results indicate that Dot1L and H3K79 methylation play important roles in heterochromatin formation and in embryonic development

    Mitotic Arrest in Teratoma Susceptible Fetal Male Germ Cells

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    Formation of germ cell derived teratomas occurs in mice of the 129/SvJ strain, but not in C57Bl/6 inbred or CD1 outbred mice. Despite this, there have been few comparative studies aimed at determining the similarities and differences between teratoma susceptible and non-susceptible mouse strains. This study examines the entry of fetal germ cells into the male pathway and mitotic arrest in 129T2/SvJ mice. We find that although the entry of fetal germ cells into mitotic arrest is similar between 129T2/SvJ, C57Bl/6 and CD1 mice, there were significant differences in the size and germ cell content of the testis cords in these strains. In 129T2/SvJ mice germ cell mitotic arrest involves upregulation of p27KIP1, p15INK4B, activation of RB, the expression of male germ cell differentiation markers NANOS2, DNMT3L and MILI and repression of the pluripotency network. The germ-line markers DPPA2 and DPPA4 show reciprocal repression and upregulation, respectively, while FGFR3 is substantially enriched in the nucleus of differentiating male germ cells. Further understanding of fetal male germ cell differentiation promises to provide insight into disorders of the testis and germ cell lineage, such as testis tumour formation and infertility

    CARM1 Mediates Modulation of Sox2

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    Sox2 is a key component of the transcription factor network that maintains the pluripotent state of embryonic stem cells (ESCs). Sox2 is regulated by multiple post-translational modifications, including ubiquitination, sumoylation, acetylation and phosphorylation. Here we report that Sox2 is in association with and methylated by coactivator-associated arginine methyltransferase 1 (CARM1), a protein arginine methyltransferase that plays a pivotal role in ESCs. We found that CARM1 facilitates Sox2-mediated transactivation and directly methylates Sox2 at arginine 113. This methylation event enhances Sox2 self-association. Furthermore, the physiological retention of Sox2 on chromatin restricts the Sox2 methylation level. Our study reveals the direct regulation of Sox2 by CARM1 that sheds lights on how arginine methylation signals are integrated into the pluripotent transcription factor network

    Open Data from the Third Observing Run of LIGO, Virgo, KAGRA, and GEO

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    The global network of gravitational-wave observatories now includes five detectors, namely LIGO Hanford, LIGO Livingston, Virgo, KAGRA, and GEO 600. These detectors collected data during their third observing run, O3, composed of three phases: O3a starting in 2019 April and lasting six months, O3b starting in 2019 November and lasting five months, and O3GK starting in 2020 April and lasting two weeks. In this paper we describe these data and various other science products that can be freely accessed through the Gravitational Wave Open Science Center at https://gwosc.org. The main data set, consisting of the gravitational-wave strain time series that contains the astrophysical signals, is released together with supporting data useful for their analysis and documentation, tutorials, as well as analysis software packages
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