74 research outputs found

    Repressor element-1 silencing transcription factor/neuronal restrictive silencer factor (REST/NRSF) can regulate HSV-1 immediate-early transcription via histone modification

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    <p>Abstract</p> <p>Background</p> <p>During primary infection of its human host, Herpes Simplex Virus Type-1 (HSV-1) establishes latency in neurons where the viral genome is maintained in a circular form associated with nucleosomes in a chromatin configration. During latency, most viral genes are silenced, although the molecular mechanisms responsible for this are unclear. We hypothesized that neuronal factors repress HSV-1 gene expression during latency. A search of the HSV-1 DNA sequence for potential regulatory elements identified a Repressor Element-1/Neuronal Restrictive Silencer Element (RE-1/NRSE) located between HSV-1 genes ICP22 and ICP4. We predicted that the Repressor Element Silencing Transcription Factor/Neuronal Restrictive Silencer Factor (REST/NRSF) regulates expression of ICP22 and ICP4.</p> <p>Results</p> <p>Transient cotransfection indicated that REST/NRSF inhibited the activity of both promoters. In contrast, cotransfection of a mutant form of REST/NRSF encoding only the DNA-binding domain of the protein resulted in less inhibition. Stably transformed cell lines containing episomal reporter plasmids with a chromatin structure showed that REST/NRSF specifically inhibited the ICP4 promoter, but not the ICP22 promoter. REST/NRSF inhibition of the ICP4 promoter was reversed by histone deacetylase (HDAC) inhibitor Trichostatin A (TSA). Additionally, chromatin immuno-precipitation (ChIP) assays indicated that the corepressor CoREST was recruited to the proximity of ICP4 promoter and that acetylation of histone H4 was reduced in the presence of REST/NRSF.</p> <p>Conclusion</p> <p>Since the ICP4 protein is a key transactivator of HSV-1 lytic cycle genes, these results suggest that REST/NRSF may have an important role in the establishment and/or maintenance of HSV-1 gene silencing during latency by targeting ICP4 expression.</p

    Enhanced superfluid density on twin boundaries in Ba(Fe1-xCox)2As2

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    Superconducting quantum interference device (SQUID) microscopy shows stripes of increased diamagnetic susceptibility in underdoped, but not overdoped, single crystals of Ba(Fe1-xCox)2As2. These stripes of increased diamagnetic susceptibility are consistent with enhanced superfluid density on twin boundaries. Individual vortices avoid pinning on or crossing the stripes, and prefer to travel parallel to them. These results indicate a relationship between superfluid density, local strain, and frustrated magnetism, and demonstrate two mechanisms for enhancing critical currents.Comment: 16 pages, 4 figure

    General Report - Session 6

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    This general report provides a summary of 40 accepted papers submitted to sessions 6a on ground improvement methods and session 6b on geoenvironmental engineering. The papers are contributed by the researchers and professionals from the United States and 15 other countries and they cover a wide range of topics based on laboratory experiments, field design, construction and monitoring, and mathematical modeling. A brief summary of each paper is provided under organized sections and the reader is referred to consult the full paper for details. Finally, the topics for discussion are listed

    Local measurement of the penetration depth in the pnictide superconductor Ba(Fe0.95_{0.95}Co0.05_{0.05})2_2As2_2

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    We use magnetic force microscopy (MFM) and scanning SQUID susceptometry to measure the local superfluid density ρs\rho_{s} in Ba(Fe0.95_{0.95}Co0.05_{0.05})2_2As2_2 single crystals from 0.4 K to the critical temperature Tc=18.5T_c=18.5 K. We observe that the penetration depth λ\lambda varies about ten times more slowly with temperature than previously published, with a dependence that can be well described by a clean two-band fully gapped model. We demonstrate that MFM can measure the important and hard-to-determine absolute value of λ\lambda, as well as obtain its temperature dependence and spatial homogeneity. We find ρs\rho_{s} to be uniform despite the highly disordered vortex pinning

    Effect of thermization of dahi on post fermentation acidification during refrigerated storage

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    Post fermentation acidification is defined as the development of acidity past the desired level of fermentation or acid development. Effect of thermization at 65oC for different periods (30 sec, 60 sec, 2 min and 5 min) on post fermentation acidification of dahi samples prepared using Lacticaseibacillus rhamnosus 18 or Lacticaseibacillus casei 01 upon refrigerated storage was assessed in this study. Significant changes (p< 0.01) were observed between the two starter cultures in terms of their post acidification potential with L. rhamnosus 18 dahi showing lower pH, higher titratable acidity and lactobacilli count than L. casei 01 during refrigerated storage. On assessing the impact of heat treatment on post acidification, significant decrease (p< 0.05) in pH, increase (p< 0.01) in titratable acidity and lactobacilli count of the heat treated and control samples were observed throughout the storage. Based on this study, it can be inferred that heat treatment at 65oC for even upto 5 min is not having any significant inhibitory effect on post fermentation acidification characteristics of the lactobacilli cultures tested

    Tests for Genetic Interactions in Type 1 Diabetes: Linkage and Stratification Analyses of 4,422 Affected Sib-Pairs

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    OBJECTIVE - Interactions between genetic and environmental factors lead to immune dysregulation causing type 1 diabetes and other autoimmune disorders. Recently, many common genetic variants have been associated with type 1 diabetes risk, but each has modest individual effects. Familial clustering of type 1 diabetes has not been explained fully and could arise from many factors, including undetected genetic variation and gene interactions. RESEARCH DESIGN AND METHODS - To address this issue, the Type 1 Diabetes Genetics Consortium recruited 3,892 families, including 4,422 affected sib-pairs. After genotyping 6,090 markers, linkage analyses of these families were performed, using a novel method and taking into account factors such as genotype at known susceptibility loci. RESULTS - Evidence for linkage was robust at the HLA and INS loci, with logarithm of odds (LOD) scores of 398.6 and 5.5, respectively. There was suggestive support for five other loci. Stratification by other risk factors (including HLA and age at diagnosis) identified one convincing region on chromosome 6q14 showing linkage in male subjects (corrected LOD = 4.49; replication P = 0.0002), a locus on chromosome 19q in HLA identical siblings (replication P = 0.006), and four other suggestive loci. CONCLUSIONS - This is the largest linkage study reported for any disease. Our data indicate there are no major type 1 diabetes subtypes definable by linkage analyses; susceptibility is caused by actions of HLA and an apparently random selection from a large number of modest-effect loci; and apart from HLA and INS, there is no important susceptibility factor discoverable by linkage methods

    The Role of the Iron Transporter ABCB7 in Refractory Anemia with Ring Sideroblasts

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    Refractory Anemia with Ring Sideroblasts (RARS) is an acquired myelodysplastic syndrome (MDS) characterized by an excess iron accumulation in the mitochondria of erythroblasts. The pathogenesis of RARS and the cause of this unusual pattern of iron deposition remain unknown. We considered that the inherited X-linked sideroblastic anemia with ataxia (XLSA/A) might be informative for the acquired disorder, RARS. XLSA/A is caused by partial inactivating mutations of the ABCB7 ATP-binding cassette transporter gene, which functions to enable transport of iron from the mitochondria to the cytoplasm. Furthermore, ABCB7 gene silencing in HeLa cells causes an accumulation of iron in the mitochondria. We have studied the role of ABCB7 in RARS by DNA sequencing, methylation studies, and gene expression studies in primary CD34+ cells and in cultured erythroblasts. The DNA sequence of the ABCB7 gene is normal in patients with RARS. We have investigated ABCB7 gene expression levels in the CD34+ cells of 122 MDS cases, comprising 35 patients with refractory anemia (RA), 33 patients with RARS and 54 patients with RA with excess blasts (RAEB), and in the CD34+ cells of 16 healthy controls. We found that the expression levels of ABCB7 are significantly lower in the RARS group. RARS is thus characterized by lower levels of ABCB7 gene expression in comparison to other MDS subtypes. Moreover, we find a strong relationship between increasing percentage of bone marrow ring sideroblasts and decreasing ABCB7 gene expression levels. Erythroblast cell cultures confirm the low levels of ABCB7 gene expression levels in RARS. These data provide an important link between inherited and acquired forms of sideroblastic anemia and indicate that ABCB7 is a strong candidate gene for RARS

    Seasonal Arctic sea ice forecasting with probabilistic deep learning.

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    Anthropogenic warming has led to an unprecedented year-round reduction in Arctic sea ice extent. This has far-reaching consequences for indigenous and local communities, polar ecosystems, and global climate, motivating the need for accurate seasonal sea ice forecasts. While physics-based dynamical models can successfully forecast sea ice concentration several weeks ahead, they struggle to outperform simple statistical benchmarks at longer lead times. We present a probabilistic, deep learning sea ice forecasting system, IceNet. The system has been trained on climate simulations and observational data to forecast the next 6 months of monthly-averaged sea ice concentration maps. We show that IceNet advances the range of accurate sea ice forecasts, outperforming a state-of-the-art dynamical model in seasonal forecasts of summer sea ice, particularly for extreme sea ice events. This step-change in sea ice forecasting ability brings us closer to conservation tools that mitigate risks associated with rapid sea ice loss

    Initial Sequence and Comparative Analysis of the Cat Genome

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    The genome sequence (1.9-fold coverage) of an inbred Abyssinian domestic cat was assembled, mapped, and annotated with a comparative approach that involved cross-reference to annotated genome assemblies of six mammals (human, chimpanzee, mouse, rat, dog, and cow). The results resolved chromosomal positions for 663,480 contigs, 20,285 putative feline gene orthologs, and 133,499 conserved sequence blocks (CSBs). Additional annotated features include repetitive elements, endogenous retroviral sequences, nuclear mitochondrial (numt) sequences, micro-RNAs, and evolutionary breakpoints that suggest historic balancing of translocation and inversion incidences in distinct mammalian lineages. Large numbers of single nucleotide polymorphisms (SNPs), deletion insertion polymorphisms (DIPs), and short tandem repeats (STRs), suitable for linkage or association studies were characterized in the context of long stretches of chromosome homozygosity. In spite of the light coverage capturing ∼65% of euchromatin sequence from the cat genome, these comparative insights shed new light on the tempo and mode of gene/genome evolution in mammals, promise several research applications for the cat, and also illustrate that a comparative approach using more deeply covered mammals provides an informative, preliminary annotation of a light (1.9-fold) coverage mammal genome sequence
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