1,000 research outputs found
THE IMPORTANCE OF LOOP REGION RESIDUES 40-46 IN HUMAN DIHYDROFOLATE-REDUCTASE AS REVEALED BY SITE-DIRECTED MUTAGENESIS
Study on GMZ bentonite-sand mixture by undrained triaxial tests
© 2016 The Authors. It is particularly necessary to study the deformation, strength and the changes of pore water pressure of bentonite-based buffer/backfill materials under the undrained condition. A series of isotropic compression tests and triaxial shear tests under undrained conditions were conducted on the compacted saturated/unsaturated GMZ bentonite-sand mixtures with dry mass ratio of bentonite/sand of 30:70. During the tests, the images of the sample were collected by photographic equipment and subsequently were cropped, binarized and centroids marked by image processing technique. Based on identification of the variation of the position of marked centroids, the deformation of the sample can be determined automatically in real-time. Finally, the hydro-mechanical behaviour of saturated and unsaturated bentonite-sand mixtures under the undrained condition can be obtained. From results of triaxial shear tests on unsaturated samples under constant water content, inflated volumetric deformation transforms to contractive volumetric deformation due to the increase of the confining pressure and lateral expansion deformation are observed due to the increase in the shearing stress. Moreover, the net mean stress affects the initial stiffness, undrained shear strength and deformation of the sample during the undrained shear tests
ROLE OF LYSINE-54 IN DETERMINING COFACTOR SPECIFICITY AND BINDING IN HUMAN DIHYDROFOLATE-REDUCTASE
Microtubules gate tau condensation to spatially regulate microtubule functions.
Tau is an abundant microtubule-associated protein in neurons. Tau aggregation into insoluble fibrils is a hallmark of Alzheimer's disease and other types of dementia1, yet the physiological state of tau molecules within cells remains unclear. Using single-molecule imaging, we directly observe that the microtubule lattice regulates reversible tau self-association, leading to localized, dynamic condensation of tau molecules on the microtubule surface. Tau condensates form selectively permissible barriers, spatially regulating the activity of microtubule-severing enzymes and the movement of molecular motors through their boundaries. We propose that reversible self-association of tau molecules, gated by the microtubule lattice, is an important mechanism of the biological functions of tau, and that oligomerization of tau is a common property shared between the physiological and disease-associated forms of the molecule
Homoclinic solutions for a second-order p-Laplacian functional differential system with local condition
High density lipoproteins improve insulin sensitivity in high-fat diet-fed mice by suppressing hepatic inflammation
Obesity-induced liver inflammation can drive insulin resistance. HDL has anti-inflammatory properties, so we hypothesized that low levels of HDL would perpetuate inflammatory responses in the liver and that HDL treatment would suppress liver inflammation and insulin resistance. The aim of this study was to investigate the effects of lipid-free apoAI on hepatic inflammation and insulin resistance in mice. We also investigated apoAI as a component of reconstituted HDLs (rHDLs) in hepatocytes to confirm results we observed in vivo. To test our hypothesis, C57BL/6 mice were fed a high-fat diet (HFD) for 16 weeks and administered either saline or lipid-free apoAI. Injections of lipid-free apoAI twice a week for 2 or 4 weeks with lipid-free apoAI resulted in: i) improved insulin sensitivity associated with decreased systemic and hepatic inflammation; ii) suppression of hepatic mRNA expression for key transcriptional regulators of lipogenic gene expression; and iii) suppression of nuclear factor κB (NF-κB) activation. Human hepatoma HuH-7 cells exposed to rHDLs showed suppressed TNFα-induced NF-κB activation, correlating with decreased NF-κB target gene expression. We conclude that apoAI suppresses liver inflammation in HFD mice and improves insulin resistance via a mechanism that involves a downregulation of NF-κB activation. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc
A Genome-Wide Association Study Identifies Genetic Variants Associated with Mathematics Ability
published_or_final_versio
Cross-Platform Comparison of Microarray-Based Multiple-Class Prediction
High-throughput microarray technology has been widely applied in biological and medical decision-making research during the past decade. However, the diversity of platforms has made it a challenge to re-use and/or integrate datasets generated in different experiments or labs for constructing array-based diagnostic models. Using large toxicogenomics datasets generated using both Affymetrix and Agilent microarray platforms, we carried out a benchmark evaluation of cross-platform consistency in multiple-class prediction using three widely-used machine learning algorithms. After an initial assessment of model performance on different platforms, we evaluated whether predictive signature features selected in one platform could be directly used to train a model in the other platform and whether predictive models trained using data from one platform could predict datasets profiled using the other platform with comparable performance. Our results established that it is possible to successfully apply multiple-class prediction models across different commercial microarray platforms, offering a number of important benefits such as accelerating the possible translation of biomarkers identified with microarrays to clinically-validated assays. However, this investigation focuses on a technical platform comparison and is actually only the beginning of exploring cross-platform consistency. Further studies are needed to confirm the feasibility of microarray-based cross-platform prediction, especially using independent datasets
Observation of CR Anisotropy with ARGO-YBJ
The measurement of the anisotropies of cosmic ray arrival direction provides
important informations on the propagation mechanisms and on the identification
of their sources. In this paper we report the observation of anisotropy regions
at different angular scales. In particular, the observation of a possible
anisotropy on scales between 10 and 30
suggests the presence of unknown features of the magnetic fields the charged
cosmic rays propagate through, as well as potential contributions of nearby
sources to the total flux of cosmic rays. Evidence of new weaker few-degree
excesses throughout the sky region R.A. is
reported for the first time.Comment: Talk given at 12th TAUP Conference 2011, 5-9 September 2011, Munich,
German
Rhabdastrellic Acid-A Induced Autophagy-Associated Cell Death through Blocking Akt Pathway in Human Cancer Cells
BACKGROUND: Autophagy is an evolutionarily conserved protein degradation pathway. A defect in autophagy may contribute to tumorigenesis. Autophagy inducers could have a potential function in tumor prevention and treatment. METHODOLOGY/PRINCIPAL FINDINGS: Our results showed that Rhabdastrellic acid-A, an isomalabaricane triterpenoid isolated from the sponge Rhabdastrella globostellata, inhibited proliferation of human cancer cell lines Hep3B and A549 and induced caspase-independent cell death in both the cell lines. Further investigation showed that Rhabdastrellic acid-A induced autophagy of cancer cells determined by YFP-LC3 punctation and increased LC3-II. The pretreatment with autophagy inhibitor 3-MA inhibited Rhabdastrellic acid-A-induced cell death. Knockdown of autophagy-related gene Atg5 inhibited Rhabdastrellic acid-A-induced cell death in A549 cells. Also, phospho-Akt and its downstream targets significantly decreased after treatment with Rhabdastrellic acid-A in both cancer cell lines. Transfection of constitutive active Akt plasmid abrogated autophagy and cell death induced by Rhabdastrellic acid-A. CONCLUSIONS/SIGNIFICANCE: These results suggest that Rhabdastrellic acid-A could induce autophagy-associated cell death through blocking Akt pathway in cancer cells. It also provides the evidence that Rhabdastrellic acid-A deserves further investigation as a potential anticancer or cancer preventive agent
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