740 research outputs found
Conductivity and quasinormal modes in holographic theories
We show that in field theories with a holographic dual the retarded Green's
function of a conserved current can be represented as a convergent sum over the
quasinormal modes. We find that the zero-frequency conductivity is related to
the sum over quasinormal modes and their high-frequency asymptotics via a sum
rule. We derive the asymptotics of the quasinormal mode frequencies and their
residues using the phase-integral (WKB) approach and provide analytic insight
into the existing numerical observations concerning the asymptotic behavior of
the spectral densities.Comment: 24 pages, 3 figure
Rhetoric of stability and change:The organizational identity work of institutional leadership
This article highlights a dynamic and productive duality in the expression of organizational identity claims between demonstrating coherence with the past and responsiveness in the present. Informed by renewed interest in the concept of institutional leadership, which is precisely concerned with the management of this temporal duality, we argue that its reconciliation depends on active discursive intervention. Drawing from archive data of executive speeches at Procter & Gamble (P&G), we suggest that through dissociation, the rhetorical device to distinguish the claim of an accurate or essential interpretation of core and distinctive values from a peripheral or apparent understanding, leaders actively construct fresh potentialities for organizational change. We thereby develop new insights into the dynamic processes of organizational identity maintenance, revealing its capacity to be regenerative and a herald to the new.</p
An Improved PSO Algorithm for Generating Protective SNP Barcodes in Breast Cancer
BACKGROUND: Possible single nucleotide polymorphism (SNP) interactions in breast cancer are usually not investigated in genome-wide association studies. Previously, we proposed a particle swarm optimization (PSO) method to compute these kinds of SNP interactions. However, this PSO does not guarantee to find the best result in every implement, especially when high-dimensional data is investigated for SNP-SNP interactions. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we propose IPSO algorithm to improve the reliability of PSO for the identification of the best protective SNP barcodes (SNP combinations and genotypes with maximum difference between cases and controls) associated with breast cancer. SNP barcodes containing different numbers of SNPs were computed. The top five SNP barcode results are retained for computing the next SNP barcode with a one-SNP-increase for each processing step. Based on the simulated data for 23 SNPs of six steroid hormone metabolisms and signalling-related genes, the performance of our proposed IPSO algorithm is evaluated. Among 23 SNPs, 13 SNPs displayed significant odds ratio (OR) values (1.268 to 0.848; p<0.05) for breast cancer. Based on IPSO algorithm, the jointed effect in terms of SNP barcodes with two to seven SNPs show significantly decreasing OR values (0.84 to 0.57; p<0.05 to 0.001). Using PSO algorithm, two to four SNPs show significantly decreasing OR values (0.84 to 0.77; p<0.05 to 0.001). Based on the results of 20 simulations, medians of the maximum differences for each SNP barcode generated by IPSO are higher than by PSO. The interquartile ranges of the boxplot, as well as the upper and lower hinges for each n-SNP barcode (n = 3∼10) are more narrow in IPSO than in PSO, suggesting that IPSO is highly reliable for SNP barcode identification. CONCLUSIONS/SIGNIFICANCE: Overall, the proposed IPSO algorithm is robust to provide exact identification of the best protective SNP barcodes for breast cancer
Murine Gammaherpesvirus-68 Inhibits Antigen Presentation by Dendritic Cells
Dendritic cells (DCs) play a central role in initiating adaptive immunity. Murine gammaherpesvirus-68 (MHV-68), like many persistent viruses, infects DCs during normal host colonization. It therefore provides a means to understanding what host and viral genes contribute to this aspect of pathogenesis. The infected DC phenotype is likely to depend on whether viral gene expression is lytic or latent and whether antigen presentation is maintained. For MHV-68, neither parameter has been well defined. Here we show that MHV-68 infects immature but not mature bone marrow-derived DCs. Infection was predominantly latent and these DCs showed no obvious defect in antigen presentation. Lytically infected DCs were very different. These down-regulated CD86 and MHC class I expression and presented a viral epitope poorly to CD8+ T cells. Antigen presentation improved markedly when the MHV-68 K3 gene was disrupted, indicating that K3 fulfils an important function in infected DCs. MHV-68 infects only a small fraction of the DCs present in lymphoid tissue, so K3 expression is unlikely to compromise significantly global CD8+ T cell priming. Instead it probably helps to maintain lytic gene expression in DCs once CD8+ T cell priming has occurred
Ryanodine receptors are part of the myospryn complex in cardiac muscle
The Cardiomyopathy–associated gene 5 (Cmya5) encodes myospryn, a large tripartite motif (TRIM)-related protein found predominantly in cardiac and skeletal muscle. Cmya5 is an expression biomarker for a number of diseases affecting striated muscle and may also be a schizophrenia risk gene. To further understand the function of myospryn in striated muscle, we searched for additional myospryn paralogs. Here we identify a novel muscle-expressed TRIM-related protein minispryn, encoded by Fsd2, that has extensive sequence similarity with the C-terminus of myospryn. Cmya5 and Fsd2 appear to have originated by a chromosomal duplication and are found within evolutionarily-conserved gene clusters on different chromosomes. Using immunoaffinity purification and mass spectrometry we show that minispryn co-purifies with myospryn and the major cardiac ryanodine receptor (RyR2) from heart. Accordingly, myospryn, minispryn and RyR2 co-localise at the junctional sarcoplasmic reticulum of isolated cardiomyocytes. Myospryn redistributes RyR2 into clusters when co-expressed in heterologous cells whereas minispryn lacks this activity. Together these data suggest a novel role for the myospryn complex in the assembly of ryanodine receptor clusters in striated muscle
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Increased brain expression of GPNMB is associated with genome wide significant risk for Parkinson's disease on chromosome 7p15.3
Genome wide association studies (GWAS) for Parkinson's disease (PD) have previously revealed a significant association with a locus on chromosome 7p15.3, initially designated as the glycoprotein non-metastatic melanoma protein B (GPNMB) locus. In this study, the functional consequences of this association on expression were explored in depth by integrating different expression quantitative trait locus (eQTL) datasets (Braineac, CAGEseq, GTEx, and Phenotype-Genotype Integrator (PheGenI)). Top risk SNP rs199347 eQTLs demonstrated increased expressions of GPNMB, KLHL7, and NUPL2 with the major allele (AA) in brain, with most significant eQTLs in cortical regions, followed by putamen. In addition, decreased expression of the antisense RNA KLHL7-AS1 was observed in GTEx. Furthermore, rs199347 is an eQTL with long non-coding RNA (AC005082.12) in human tissues other than brain. Interestingly, transcript-specific eQTLs in immune-related tissues (spleen and lymphoblastoid cells) for NUPL2 and KLHL7-AS1 were observed, which suggests a complex functional role of this eQTL in specific tissues, cell types at specific time points. Significantly increased expression of GPNMB linked to rs199347 was consistent across all datasets, and taken in combination with the risk SNP being located within the GPNMB gene, these results suggest that increased expression of GPNMB is the causative link explaining the association of this locus with PD. However, other transcript eQTLs and subsequent functional roles cannot be excluded. This highlights the importance of further investigations to understand the functional interactions between the coding genes, antisense, and non-coding RNA species considering the tissue and cell-type specificity to understand the underlying biological mechanisms in PD
Effective Rheology of Bubbles Moving in a Capillary Tube
We calculate the average volumetric flux versus pressure drop of bubbles
moving in a single capillary tube with varying diameter, finding a square-root
relation from mapping the flow equations onto that of a driven overdamped
pendulum. The calculation is based on a derivation of the equation of motion of
a bubble train from considering the capillary forces and the entropy production
associated with the viscous flow. We also calculate the configurational
probability of the positions of the bubbles.Comment: 4 pages, 1 figur
CSF from Parkinson disease Patients Differentially Affects Cultured Microglia and Astrocytes
<p>Abstract</p> <p>Background</p> <p>Excessive and abnormal accumulation of alpha-synuclein (α-synuclein) is a factor contributing to pathogenic cell death in Parkinson's disease. The purpose of this study, based on earlier observations of Parkinson's disease cerebrospinal fluid (PD-CSF) initiated cell death, was to determine the effects of CSF from PD patients on the functionally different microglia and astrocyte glial cell lines. Microglia cells from human glioblastoma and astrocytes from fetal brain tissue were cultured, grown to confluence, treated with fixed concentrations of PD-CSF, non-PD disease control CSF, or control no-CSF medium, then photographed and fluorescently probed for α-synuclein content by deconvolution fluorescence microscopy. Outcome measures included manually counted cell growth patterns from day 1-8; α-synuclein density and distribution by antibody tagged 3D model stacked deconvoluted fluorescent imaging.</p> <p>Results</p> <p>After PD-CSF treatment, microglia growth was reduced extensively, and a non-confluent pattern with morphological changes developed, that was not evident in disease control CSF and no-CSF treated cultures. Astrocyte growth rates were similarly reduced by exposure to PD-CSF, but morphological changes were not consistently noted. PD-CSF treated microglia showed a significant increase in α-synuclein content by day 4 compared to other treatments (p ≤ 0.02). In microglia only, α-synuclein aggregated and redistributed to peri-nuclear locations.</p> <p>Conclusions</p> <p>Cultured microglia and astrocytes are differentially affected by PD-CSF exposure compared to non-PD-CSF controls. PD-CSF dramatically impacts microglia cell growth, morphology, and α-synuclein deposition compared to astrocytes, supporting the hypothesis of cell specific susceptibility to PD-CSF toxicity.</p
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