134 research outputs found
ParMap, an algorithm for the identification of small genomic insertions and deletions in nextgen sequencing data
<p>Abstract</p> <p>Background</p> <p>Next-generation sequencing produces high-throughput data, albeit with greater error and shorter reads than traditional Sanger sequencing methods. This complicates the detection of genomic variations, especially, small insertions and deletions.</p> <p>Findings</p> <p>Here we describe ParMap, a statistical algorithm for the identification of complex genetic variants, such as small insertion and deletions, using partially mapped reads in nextgen sequencing data.</p> <p>Conclusions</p> <p>We report ParMap's successful application to the mutation analysis of chromosome X exome-captured leukemia DNA samples.</p
Electronic Origin of High Temperature Superconductivity in Single-Layer FeSe Superconductor
The latest discovery of high temperature superconductivity signature in
single-layer FeSe is significant because it is possible to break the
superconducting critical temperature ceiling (maximum Tc~55 K) that has been
stagnant since the discovery of Fe-based superconductivity in 2008. It also
blows the superconductivity community by surprise because such a high Tc is
unexpected in FeSe system with the bulk FeSe exhibiting a Tc at only 8 K at
ambient pressure which can be enhanced to 38 K under high pressure. The Tc is
still unusually high even considering the newly-discovered intercalated FeSe
system A_xFe_{2-y}Se_2 (A=K, Cs, Rb and Tl) with a Tc at 32 K at ambient
pressure and possible Tc near 48 K under high pressure. Particularly
interesting is that such a high temperature superconductivity occurs in a
single-layer FeSe system that is considered as a key building block of the
Fe-based superconductors. Understanding the origin of high temperature
superconductivity in such a strictly two-dimensional FeSe system is crucial to
understanding the superconductivity mechanism in Fe-based superconductors in
particular, and providing key insights on how to achieve high temperature
superconductivity in general. Here we report distinct electronic structure
associated with the single-layer FeSe superconductor. Its Fermi surface
topology is different from other Fe-based superconductors; it consists only of
electron pockets near the zone corner without indication of any Fermi surface
around the zone center. Our observation of large and nearly isotropic
superconducting gap in this strictly two-dimensional system rules out existence
of node in the superconducting gap. These results have provided an unambiguous
case that such a unique electronic structure is favorable for realizing high
temperature superconductivity
Mechanisms explaining transitions between tonic and phasic firing in neuronal populations as predicted by a low dimensional firing rate model
Several firing patterns experimentally observed in neural populations have
been successfully correlated to animal behavior. Population bursting, hereby
regarded as a period of high firing rate followed by a period of quiescence, is
typically observed in groups of neurons during behavior. Biophysical
membrane-potential models of single cell bursting involve at least three
equations. Extending such models to study the collective behavior of neural
populations involves thousands of equations and can be very expensive
computationally. For this reason, low dimensional population models that
capture biophysical aspects of networks are needed.
\noindent The present paper uses a firing-rate model to study mechanisms that
trigger and stop transitions between tonic and phasic population firing. These
mechanisms are captured through a two-dimensional system, which can potentially
be extended to include interactions between different areas of the nervous
system with a small number of equations. The typical behavior of midbrain
dopaminergic neurons in the rodent is used as an example to illustrate and
interpret our results.
\noindent The model presented here can be used as a building block to study
interactions between networks of neurons. This theoretical approach may help
contextualize and understand the factors involved in regulating burst firing in
populations and how it may modulate distinct aspects of behavior.Comment: 25 pages (including references and appendices); 12 figures uploaded
as separate file
PPARgamma activity in subcutaneous abdominal fat tissue and fat mass gain during short-term overfeeding
Objective: As the peroxisome proliferator-activated receptor (PPAR) plays a central role in fat mass regulation, we investigated whether initial subcutaneous PPAR activity is related to fat mass generation during overfeeding. Subjects: Fourteen healthy female subjects (age 254 years, BMI 22.12.3 kg/m2). Design and measurements: Subjects were overfed with a diet supplying 50% more energy than baseline energy requirements for 14 days. Fasting blood samples were analyzed for leptin, insulin and glucose. Fasting subcutaneous abdominal fat biopsies were obtained for analysis of PPAR1, PPAR2, aP2 and UCP2 mRNAs. Results: Initial PPAR1 and 2, aP2 and UCP2 mRNAs were not related to fat gain (P>0.12). However, PPAR1, PPAR2 and aP2 mRNA changes were positively related to changes in plasma leptin (
From (pi, 0) magnetic order to superconductivity with (pi, pi) magnetic resonance in Fe1.02(Te1-xSex)
The iron chalcogenide Fe1+y(Te1-xSex) is structurally the simplest of the
Fe-based superconductors. Although the Fermi surface is similar to iron
pnictides, the parent compound Fe1+yTe exhibits antiferromagnetic order with
in-plane magnetic wave-vector (pi, 0). This contrasts the pnictide parent
compounds where the magnetic order has an in-plane magnetic wave-vector (pi,
pi) that connects hole and electron parts of the Fermi surface. Despite these
differences, both the pnictide and chalcogenide Fe-superconductors exhibit
superconducting spin resonances around (pi, pi), suggesting a common symmetry
for their superconducting order parameter. A central question in this
burgeoning field is therefore how (pi, pi) superconductivity can emerge from a
(pi, 0) magnetic instability. Here, we report that the magnetic soft mode
evolving from the (pi, 0)-type magnetic long-range order is associated with
weak charge carrier localization. Bulk superconductivity occurs only as the
magnetic mode at (pi, pi) becomes dominant upon doping. Our results suggest a
common magnetic origin for superconductivity in iron chalcogenide and pnictide
superconductors.Comment: 17 pages, 4 figure
Granulocytes mediates the Fas-L-associated apoptosis during lung metastasis of melanoma that determines the metastatic behaviour
The survival of tumour cells in a new tissue environment is crucial for tumour metastasis. Factors contributing to the death of tumour cells during metastasis are not completely understood. In murine melanoma model, activation of Fas (CD95, APO-1) signal in tumour cells reduces their lung metastasis potential, which may be associated with an induction of apoptosis in tumours. To elucidate the cellular mechanism, we used a Fas-ligand (Fas-L) specific ribozyme (Fas-Lribozyme) to suppress the expression of Fas-L but not Fas or TNF-α in B16F10 melanoma cells. The Fas-Lribozyme-carrying cells grew slightly faster in vitro with better viability than controls. Suppression of Fas-L in B16F10 melanoma cells by Fas-Lribozyme enhanced lung metastasis of the cells in C57BL/6 mice, and that was correlated with reductions in both apoptotic tumour cells and granulocytic infiltration. Mice depleted of granulocytes, but not CD4+ and CD8+ cells, showed a greatly elevated susceptibility to lung metastasis. Moreover, apoptosis in tumour cells was significantly reduced in granulocyte-depleted mice during the course of tumour formation. Taken together, our findings indicate that Fas-L-associated apoptosis in tumour cells determines the metastasis behaviour of melanoma in the lung and this apoptosis is primarily mediated by the cytotoxicity of recruited granulocytes
Disruption of TBP-2 ameliorates insulin sensitivity and secretion without affecting obesity
Type 2 diabetes mellitus (T2DM) is characterized by defects in both insulin sensitivity and glucose-stimulated insulin secretion (GSIS) and is often accompanied by obesity. In this study, we show that disruption of thioredoxin binding protein-2 (TBP-2, also called Txnip) in obese mice (ob/ob) dramatically improves hyperglycaemia and glucose intolerance, without affecting obesity or adipocytokine concentrations. TBP-2-deficient ob/ob mice exhibited enhanced insulin sensitivity with activated insulin receptor substrate-1/Akt signalling in skeletal muscle and GSIS in islets compared with ob/ob mice. The elevation of uncoupling protein-2 (UCP-2) expression in ob/ob islets was downregulated by TBP-2 deficiency. TBP-2 overexpression suppressed glucose-induced adenosine triphosphate production, Ca2+ influx and GSIS. In β-cells, TBP-2 enhanced the expression level and transcriptional activity of UCP-2 by recruitment of peroxisome proliferator-activated receptor-γ co-activator-1α to the UCP-2 promoter. Thus, TBP-2 is a key regulatory molecule of both insulin sensitivity and GSIS in diabetes, raising the possibility that inhibition of TBP-2 may be a novel therapeutic approach for T2DM
Activation of the AMP-Activated Protein Kinase by Eicosapentaenoic Acid (EPA, 20:5 n-3) Improves Endothelial Function In Vivo
The aim of the present study was to test the hypothesis that the cardiovascular-protective effects of eicosapentaenoic acid (EPA) may be due, in part, to its ability to stimulate the AMP-activated protein kinase (AMPK)-induced endothelial nitric oxide synthase (eNOS) activation. The role of AMPK in EPA-induced eNOS phosphorylation was investigated in bovine aortic endothelial cells (BAEC), in mice deficient of either AMPKα1 or AMPKα2, in eNOS knockout (KO) mice, or in Apo-E/AMPKα1 dual KO mice. EPA-treatment of BAEC increased both AMPK-Thr172 phosphorylation and AMPK activity, which was accompanied by increased eNOS phosphorylation, NO release, and upregulation of mitochondrial uncoupling protein-2 (UCP-2). Pharmacologic or genetic inhibition of AMPK abolished EPA-enhanced NO release and eNOS phosphorylation in HUVEC. This effect of EPA was absent in the aortas isolated from either eNOS KO mice or AMPKα1 KO mice fed a high-fat, high-cholesterol (HFHC) diet. EPA via upregulation of UCP-2 activates AMPKα1 resulting in increased eNOS phosphorylation and consequent improvement of endothelial function in vivo
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