714 research outputs found

    Studies on chemical evolution using carbon suboxide

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    It was learned that when carbon suboxide polymers react with hydroxylamine in modified sea water the amino acids glycine and lysine are produced and that they react with urea to produce nucleic acid-like substances. These results lead to the supposition that it is possible that carbon suboxide polymers may have accumulated in the primeval sea some three or more billion years ago and were transformed into the procursors of living molecules

    Bifurcations in a convection problem with temperature-dependent viscosity

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    A convection problem with temperature-dependent viscosity in an infinite layer is presented. As described, this problem has important applications in mantle convection. The existence of a stationary bifurcation is proved together with a condition to obtain the critical parameters at which the bifurcation takes place. For a general dependence of viscosity with temperature a numerical strategy for the calculation of the critical bifurcation curves and the most unstable modes has been developed. For a exponential dependence of viscosity on temperature the numerical calculations have been done. Comparisons with the classical Rayleigh-B\'enard problem with constant viscosity indicate that the critical threshold decreases as the exponential rate parameter increases.Comment: 16 pages, 5 figure

    Monte Carlo simulation of ice models

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    We propose a number of Monte Carlo algorithms for the simulation of ice models and compare their efficiency. One of them, a cluster algorithm for the equivalent three colour model, appears to have a dynamic exponent close to zero, making it particularly useful for simulations of critical ice models. We have performed extensive simulations using our algorithms to determine a number of critical exponents for the square ice and F models.Comment: 32 pages including 15 postscript figures, typeset in LaTeX2e using the Elsevier macro package elsart.cl

    Expanding the Repertoire of Optogenetically Targeted Cells with an Enhanced Gene Expression System

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    Optogenetics has been enthusiastically pursued in recent neuroscience research, and the causal relationship between neural activity and behavior is becoming ever more accessible. Here, we established knockin-mediated enhanced gene expression by improved tetracycline-controlled gene induction (KENGE-tet) and succeeded in generating transgenic mice expressing a highly light-sensitive channelrhodopsin-2 mutant at levels sufficient to drive the activities of multiple cell types. This method requires two lines of mice: one that controls the pattern of expression and another that determines the protein to be produced. The generation of new lines of either type readily expands the repertoire to choose from. In addition to neurons, we were able to manipulate the activity of nonexcitable glial cells in vivo. This shows that our system is applicable not only to neuroscience but also to any biomedical study that requires understanding of how the activity of a selected population of cells propagates through the intricate organic systems

    Poly(ADP-ribose) polymerase family member 14 (PARP14) is a novel effector of the JNK2-dependent pro-survival signal in multiple myeloma

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    Copyright @ 2013 Macmillan Publishers Limited. This is the author's accepted manuscript. The final published article is available from the link below.Regulation of cell survival is a key part of the pathogenesis of multiple myeloma (MM). Jun N-terminal kinase (JNK) signaling has been implicated in MM pathogenesis, but its function is unclear. To elucidate the role of JNK in MM, we evaluated the specific functions of the two major JNK proteins, JNK1 and JNK2. We show here that JNK2 is constitutively activated in a panel of MM cell lines and primary tumors. Using loss-of-function studies, we demonstrate that JNK2 is required for the survival of myeloma cells and constitutively suppresses JNK1-mediated apoptosis by affecting expression of poly(ADP-ribose) polymerase (PARP)14, a key regulator of B-cell survival. Strikingly, we found that PARP14 is highly expressed in myeloma plasma cells and associated with disease progression and poor survival. Overexpression of PARP14 completely rescued myeloma cells from apoptosis induced by JNK2 knockdown, indicating that PARP14 is critically involved in JNK2-dependent survival. Mechanistically, PARP14 was found to promote the survival of myeloma cells by binding and inhibiting JNK1. Moreover, inhibition of PARP14 enhances the sensitization of MM cells to anti-myeloma agents. Our findings reveal a novel regulatory pathway in myeloma cells through which JNK2 signals cell survival via PARP14, and identify PARP14 as a potential therapeutic target in myeloma.Kay Kendall Leukemia Fund, NIH, Cancer Research UK, Italian Association for Cancer Research and the Foundation for Liver Research

    Molecular phylogeny of the rotifers with two Indonesian Brachionus lineages

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    The rotifer Brachionus plicatilis is an ecologically and commercially important species, and has been studied in various fields such as population dynamics, ecotoxicology and aging. However, recent studies have revealed that the B. plicatilis lineages involve an unknown number of cryptic species, and the group has been regarded as the Brachionus complex. One cause of this complicated taxonomy is the lack of surveys in the tropical zone, which is characterized by enormous species-richness. Accordingly, in this study we collected two Brachionus rotifers from the Sumatra and Sulawesi Islands, Indonesia, and determined their partial nucleotide sequences of mitochondrial DNA cytochrome c oxidase subunit I gene. Subsequently, we constructed molecular phylogenetic trees with fourteen species/lineages from four genera including the two Indonesian rotifers. The two Indonesian Brachionus rotifers were respectively found to be phylogenetically close to B. ibericus and B. rotundiformis. On the other hand, Japanese B. plicatilis was suggested to be phylogenetically closer to B. Manjavacas, which is proposed to be a new species, than to Spanish B. plicatilis. These results imply that the current taxonomy of the Brachionus is problematic, and a major revision is necessary to establish a reliable taxonomy of this group

    Sphingosine 1-phosphate modulates antigen capture by murine langerhans cells via the S1P2 receptor subtype

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    Dendritic cells (DCs) play a pivotal role in the development of cutaneous contact hypersensitivity (CHS) and atopic dermatitis as they capture and process antigen and present it to T lymphocytes in the lymphoid organs. Recently, it has been indicated that a topical application of the sphingolipid sphingosine 1-phosphate (S1P) prevents the inflammatory response in CHS, but the molecular mechanism is not fully elucidated. Here we indicate that treatment of mice with S1P is connected with an impaired antigen uptake by Langerhans cells (LCs), the initial step of CHS. Most of the known actions of S1P are mediated by a family of five specific G protein-coupled receptors. Our results indicate that S1P inhibits macropinocytosis of the murine LC line XS52 via S1P2 receptor stimulation followed by a reduced phosphatidylinositol 3-kinase (PI3K) activity. As down-regulation of S1P2 not only diminished S1P-mediated action but also enhanced the basal activity of LCs on antigen capture, an autocrine action of S1P has been assumed. Actually, S1P is continuously produced by LCs and secreted via the ATP binding cassette transporter ABCC1 to the extracellular environment. Consequently, inhibition of ABCC1, which decreased extracellular S1P levels, markedly increased the antigen uptake by LCs. Moreover, stimulation of sphingosine kinase activity, the crucial enzyme for S1P formation, is connected not only with enhanced S1P levels but also with diminished antigen capture. These results indicate that S1P is essential in LC homeostasis and influences skin immunity. This is of importance as previous reports suggested an alteration of S1P levels in atopic skin lesions

    Community-acquired Klebsiella pneumoniae meningitis in an alcoholic patient with an infected pancreatic pseudocyst; a case report and review of literature

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    We report a case of a 49-year-old male with a history of chronic alcoholism and evidence of a pancreatic pseudocyst on CT scanning. He presented with a 3-days history of fever, loss of appetite and upper abdominal pain. Blood cultures grew Klebsiella pneumoniae and he improved clinically with a seven-day course of intravenous co-amoxiclav and metronidazole. Two weeks later he was readmitted to hospital with impaired consciousness and septic shock, and died three days later in intensive care. Post mortem examination revealed bacterial meningitis and an infected pancreatic pseudocyst. Klebsiella pneumoniae was isolated from the pancreas and meninges

    Acute Kawasaki Disease: Not Just for Kids

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    Kawasaki Disease is a small-to-medium-vessel vasculitis that preferentially affects children. Kawasaki Disease can occur in adults, but the presentation may differ from that observed in children. Typical findings in both adults and children include fever, conjunctivitis, pharyngitis, and skin erythema progressing to a desquamating rash on the palms and soles. Adults more frequently present with cervical adenopathy (93% of adults vs. 15% of children), hepatitis (65% vs. 10%), and arthralgia (61% vs. 24–38%). In contrast, adults are less frequently affected by meningitis (10% vs. 34%), thrombocytosis (55% vs. 100%), and coronary artery aneurysms (5% vs. 18–25%). We report a case of acute Kawasaki Disease in a 24-year-old man who presented with rash, fever, and arthritis. He was successfully treated with high-dose aspirin and intravenous immunoglobulin (IVIG). Our case highlights the importance of considering Kawasaki Disease in adults presenting with symptoms commonly encountered in a general medical practice
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