Supersymmetric Extension of GCA in 2d

We derive the infinite dimensional Supersymmetric Galilean Conformal Algebra (SGCA) in the case of two spacetime dimensions by performing group contraction on 2d superconformal algebra. We also obtain the representations of the generators in terms of superspace coordinates. Here we find realisations of the SGCA by considering scaling limits of certain 2d SCFTs which are non-unitary and have their left and right central charges become large in magnitude and opposite in sign. We focus on the Neveu-Schwarz sector of the parent SCFTs and develop, in parallel to the GCA studies recently in (arXiv:0912.1090), the representation theory based on SGCA primaries, Ward identities for their correlation functions and their descendants which are null states.Comment: La TeX file, 32 pages; v2: typos corrected, journal versio

GCA in 2d

We make a detailed study of the infinite dimensional Galilean Conformal Algebra (GCA) in the case of two spacetime dimensions. Classically, this algebra is precisely obtained from a contraction of the generators of the relativistic conformal symmetry in 2d. Here we find quantum mechanical realisations of the (centrally extended) GCA by considering scaling limits of certain 2d CFTs. These parent CFTs are non-unitary and have their left and right central charges become large in magnitude and opposite in sign. We therefore develop, in parallel to the usual machinery for 2d CFT, many of the tools for the analysis of the quantum mechanical GCA. These include the representation theory based on GCA primaries, Ward identities for their correlation functions and a nonrelativistic Kac table. In particular, the null vectors of the GCA lead to differential equations for the four point function. The solution to these equations in the simplest case is explicitly obtained and checked to be consistent with various requirements.Comment: 45 pages; v2: 47 pages. Restructured introduction, minor corrections, added references. Journal versio

Constraints on energetic particles in the Fleischmann-Pons experiment

In recent Fleischmann–Pons experiments carried out by different groups, a thermal signal is seen indicative of excess energy production of a magnitude much greater than can be accounted for by chemistry. Correlated with the excess heat appears to be 4He, with the associated energy near 24 MeV per helium atom. In nuclear reactions, the energy produced is expressed through the kinetic energy of the products; hence, it would be natural to assume that some of the reaction energy ends up as kinetic energy of the 4He nucleus. Depending on the energy that the helium nucleus is born with, it will result in radiation (such as neutrons or x-rays) that can be seen outside of the cell. We have computed estimates of the expected neutron and x-ray emission as a function of helium energy and compared the results with upper limits taken from experiments. Experimental results with upper limits of neutron emission between 0.008 and 0.8 n/J are found to correspond to upper limits in alpha energy between 6.2 and 20.2 keV

Modulation of enhancer looping and differential gene targeting by Epstein-Barr virus transcription factors directs cellular reprogramming

Epstein-Barr virus (EBV) epigenetically reprogrammes B-lymphocytes to drive immortalization and facilitate viral persistence. Host-cell transcription is perturbed principally through the actions of EBV EBNA 2, 3A, 3B and 3C, with cellular genes deregulated by specific combinations of these EBNAs through unknown mechanisms. Comparing human genome binding by these viral transcription factors, we discovered that 25% of binding sites were shared by EBNA 2 and the EBNA 3s and were located predominantly in enhancers. Moreover, 80% of potential EBNA 3A, 3B or 3C target genes were also targeted by EBNA 2, implicating extensive interplay between EBNA 2 and 3 proteins in cellular reprogramming. Investigating shared enhancer sites neighbouring two new targets (WEE1 and CTBP2) we discovered that EBNA 3 proteins repress transcription by modulating enhancer-promoter loop formation to establish repressive chromatin hubs or prevent assembly of active hubs. Re-ChIP analysis revealed that EBNA 2 and 3 proteins do not bind simultaneously at shared sites but compete for binding thereby modulating enhancer-promoter interactions. At an EBNA 3-only intergenic enhancer site between ADAM28 and ADAMDEC1 EBNA 3C was also able to independently direct epigenetic repression of both genes through enhancer-promoter looping. Significantly, studying shared or unique EBNA 3 binding sites at WEE1, CTBP2, ITGAL (LFA-1 alpha chain), BCL2L11 (Bim) and the ADAMs, we also discovered that different sets of EBNA 3 proteins bind regulatory elements in a gene and cell-type specific manner. Binding profiles correlated with the effects of individual EBNA 3 proteins on the expression of these genes, providing a molecular basis for the targeting of different sets of cellular genes by the EBNA 3s. Our results therefore highlight the influence of the genomic and cellular context in determining the specificity of gene deregulation by EBV and provide a paradigm for host-cell reprogramming through modulation of enhancer-promoter interactions by viral transcription factors

Physician attitude toward depression care interventions: Implications for implementation of quality improvement initiatives

<p>Abstract</p> <p>Background</p> <p>Few individuals with depression treated in the primary care setting receive care consistent with clinical treatment guidelines. Interventions based on the chronic care model (CCM) have been promoted to address barriers and improve the quality of care. A current understanding of barriers to depression care and an awareness of whether physicians believe interventions effectively address those barriers is needed to enhance the success of future implementation.</p> <p>Methods</p> <p>We conducted semi-structured interviews with 23 primary care physicians across the US regarding their experience treating patients with depression, barriers to care, and commonly promoted CCM-based interventions. Themes were identified from interview transcripts using a grounded theory approach.</p> <p>Results</p> <p>Six barriers emerged from the interviews: difficulty diagnosing depression, patient resistance, fragmented mental health system, insurance coverage, lack of expertise, and competing demands and other responsibilities as a primary care provider. A number of interventions were seen as helpful in addressing these barriers – including care managers, mental health integration, and education – while others received mixed reviews. Mental health consultation models received the least endorsement. Two systems-related barriers, the fragmented mental health system and insurance coverage limitations, appeared incompletely addressed by the interventions.</p> <p>Conclusion</p> <p>CCM-based interventions, which include care managers, mental health integration, and patient education, are most likely to be implemented successfully because they effectively address several important barriers to care and are endorsed by physicians. Practices considering the adoption of interventions that received less support should educate physicians about the benefit of the interventions and attend to physician concerns prior to implementation. A focus on interventions that address systems-related barriers is needed to overcome all barriers to care.</p

VAMP7 modulates ciliary biogenesis in kidney cells

Epithelial cells elaborate specialized domains that have distinct protein and lipid compositions, including the apical and basolateral surfaces and primary cilia. Maintaining the identity of these domains is required for proper cell function, and requires the efficient and selective SNARE-mediated fusion of vesicles containing newly synthesized and recycling proteins with the proper target membrane. Multiple pathways exist to deliver newly synthesized proteins to the apical surface of kidney cells, and the post-Golgi SNAREs, or VAMPs, involved in these distinct pathways have not been identified. VAMP7 has been implicated in apical protein delivery in other cell types, and we hypothesized that this SNARE would have differential effects on the trafficking of apical proteins known to take distinct routes to the apical surface in kidney cells. VAMP7 expressed in polarized Madin Darby canine kidney cells colocalized primarily with LAMP2-positive compartments, and siRNA-mediated knockdown modulated lysosome size, consistent with the known function of VAMP7 in lysosomal delivery. Surprisingly, VAMP7 knockdown had no effect on apical delivery of numerous cargoes tested, but did decrease the length and frequency of primary cilia. Additionally, VAMP7 knockdown disrupted cystogenesis in cells grown in a three-dimensional basement membrane matrix. The effects of VAMP7 depletion on ciliogenesis and cystogenesis are not directly linked to the disruption of lysosomal function, as cilia lengths and cyst morphology were unaffected in an MDCK lysosomal storage disorder model. Together, our data suggest that VAMP7 plays an essential role in ciliogenesis and lumen formation. To our knowledge, this is the first study implicating an R-SNARE in ciliogenesis and cystogenesis. © 2014 Szalinski et al

Low-Level Laser Therapy Activates NF-kB via Generation of Reactive Oxygen Species in Mouse Embryonic Fibroblasts

Background Despite over forty years of investigation on low-level light therapy (LLLT), the fundamental mechanisms underlying photobiomodulation at a cellular level remain unclear. Methodology/Principal Findings In this study, we isolated murine embryonic fibroblasts (MEF) from transgenic NF-kB luciferase reporter mice and studied their response to 810 nm laser radiation. Significant activation of NF-kB was observed at fluences higher than 0.003 J/cm2 and was confirmed by Western blot analysis. NF-kB was activated earlier (1 hour) by LLLT compared to conventional lipopolysaccharide treatment. We also observed that LLLT induced intracellular reactive oxygen species (ROS) production similar to mitochondrial inhibitors, such as antimycin A, rotenone and paraquat. Furthermore, we observed similar NF-kB activation with these mitochondrial inhibitors. These results, together with inhibition of laser induced NF-kB activation by antioxidants, suggests that ROS play an important role in the laser induced NF-kB signaling pathways. However, LLLT, unlike mitochondrial inhibitors, induced increased cellular ATP levels, which indicates that LLLT also upregulates mitochondrial respiration. Conclusion We conclude that LLLT not only enhances mitochondrial respiration, but also activates the redox-sensitive NFkB signaling via generation of ROS. Expression of anti-apoptosis and pro-survival genes responsive to NFkB could explain many clinical effects of LLLT.National Institutes of Health (U.S.) (grant R01AI050875)Center for Integration of Medicine and Innovative Technology (DAMD17-02-2-0006)United States. Dept. of Defense (CDMRP Program in TBI, W81XWH-09-1-0514)United States. Air Force Office of Scientific Research (FA9950-04-1-0079

An Enriched European Eel Transcriptome Sheds Light upon Host-Pathogen Interactions with Vibrio vulnificus

Infectious diseases are one of the principal bottlenecks for the European eel recovery. The aim of this study was to develop a new molecular tool to be used in host-pathogen interaction experiments in the eel. To this end, we first stimulated adult eels with different pathogen-associated molecular patterns (PAMPs), extracted RNA from the immune-related tissues and sequenced the transcriptome. We obtained more than 2 x 10(6) reads that were assembled and annotated into 45,067 new descriptions with a notable representation of novel transcripts related with pathogen recognition, signal transduction and the immune response. Then, we designed a DNA-microarray that was used to analyze the early immune response against Vibrio vulnificus, a septicemic pathogen that uses the gills as the portal of entry into the blood, as well as the role of the main toxin of this species (RtxA13) on this early interaction. The gill transcriptomic profiles obtained after bath infecting eels with the wild type strain or with a mutant deficient in rtxA13 were analyzed and compared. Results demonstrate that eels react rapidly and locally against the pathogen and that this immune-response is rtxA13-dependent as transcripts related with cell destruction were highly up-regulated only in the gills from eels infected with the wild-type strain. Furthermore, significant differences in the immune response against the wild type and the mutant strain also suggest that host survival after V. vulnificus infection could depend on an efficient local phagocytic activity. Finally, we also found evidence of the presence of an interbranchial lymphoid tissue in European eel gills although further experiments will be necessary to identify such tissue

MicroRNA-sequence profiling reveals novel osmoregulatory microRNA expression patterns in catadromous eel anguilla marmorata

MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs that regulate gene expression by post-transcriptional repression of mRNAs. Recently, several miRNAs have been confirmed to execute directly or indirectly osmoregulatory functions in fish via translational control. In order to clarify whether miRNAs play relevant roles in the osmoregulation of Anguilla marmorata, three sRNA libraries of A. marmorata during adjusting to three various salinities were sequenced by Illumina sRNA deep sequencing methods. Totally 11,339,168, 11,958,406 and 12,568,964 clear reads were obtained from 3 different libraries, respectively. Meanwhile, 34 conserved miRNAs and 613 novel miRNAs were identified using the sequence data. MiR-10b-5p, miR-181a, miR-26a-5p, miR-30d and miR-99a-5p were dominantly expressed in eels at three salinities. Totally 29 mature miRNAs were significantly up-regulated, while 72 mature miRNAs were significantly down-regulated in brackish water (10‰ salinity) compared with fresh water (0‰ salinity); 24 mature miRNAs were significantly up-regulated, while 54 mature miRNAs were significantly down-regulated in sea water (25‰ salinity) compared with fresh water. Similarly, 24 mature miRNAs were significantly up-regulated, while 45 mature miRNAs were significantly down-regulated in sea water compared with brackish water. The expression patterns of 12 dominantly expressed miRNAs were analyzed at different time points when the eels transferred from fresh water to brackish water or to sea water. These miRNAs showed differential expression patterns in eels at distinct salinities. Interestingly, miR-122, miR-140-3p and miR-10b-5p demonstrated osmoregulatory effects in certain salinities. In addition, the identification and characterization of differentially expressed miRNAs at different salinities can clarify the osmoregulatory roles of miRNAs, which will shed lights for future studies on osmoregulation in fish