Level structures on the Weierstrass family of cubics

Let W -> A^2 be the universal Weierstrass family of cubic curves over C. For each N >= 2, we construct surfaces parametrizing the three standard kinds of level N structures on the smooth fibers of W. We then complete these surfaces to finite covers of A^2. Since W -> A^2 is the versal deformation space of a cusp singularity, these surfaces convey information about the level structure on any family of curves of genus g degenerating to a cuspidal curve. Our goal in this note is to determine for which values of N these surfaces are smooth over (0,0). From a topological perspective, the results determine the homeomorphism type of certain branched covers of S^3 with monodromy in SL_2(Z/N).Comment: LaTeX, 12 pages; added section giving a topological interpretation of the result

Polarization restricts hepatitis C virus entry into HepG2 hepatoma cells

The primary reservoir for hepatitis C virus (HCV) replication is believed to be hepatocytes, which are highly polarized with tight junctions (TJ) separating their basolateral and apical domains. HepG2 cells develop polarity over time, resulting in the formation and remodeling of bile canalicular (BC) structures. HepG2 cells expressing CD81 provide a model system to study the effects of hepatic polarity on HCV infection. We found an inverse association between HepG2-CD81 polarization and HCV pseudoparticle entry. As HepG2 cells polarize, discrete pools of claudin-1 (CLDN1) at the TJ and basal/lateral membranes develop, consistent with the pattern of receptor staining observed in liver tissue. The TJ and nonjunctional pools of CLDN1 show an altered association with CD81 and localization in response to the PKA antagonist Rp-8-Br-cyclic AMPs (cAMPs). Rp-8-Br-cAMPs reduced CLDN1 expression at the basal membrane and inhibited HCV infection, supporting a model where the nonjunctional pools of CLDN1 have a role in HCV entry. Treatment of HepG2 cells with proinflammatory cytokines, tumor necrosis factor alpha and gamma interferon, perturbed TJ integrity but had minimal effect(s) on cellular polarity and HCV infection, suggesting that TJ integrity does not limit HCV entry into polarized HepG2 cells. In contrast, activation of PKC with phorbol ester reduced TJ integrity, ablated HepG2 polarity, and stimulated HCV entry. Overall, these data show that complex hepatocyte-like polarity alters CLDN1 localization and limits HCV entry, suggesting that agents which disrupt hepatocyte polarity may promote HCV infection and transmission within the liver

Cep70 and Cep131 contribute to ciliogenesis in zebrafish embryos.

BACKGROUND: The centrosome is the cell's microtubule organising centre, an organelle with important roles in cell division, migration and polarity. However, cells can divide and flies can, for a large part of development, develop without them. Many centrosome proteins have been identified but the roles of most are still poorly understood. The centrioles of the centrosome are similar to the basal bodies of cilia, hair-like extensions of many cells that have important roles in cell signalling and development. In a number of human diseases, such Bardet-Biedl syndrome, centrosome/cilium proteins are mutated, leading to polycystic kidney disease, situs inversus, and neurological problems, amongst other symptoms. RESULTS: We describe zebrafish (Danio rerio) embryos depleted for two uncharacterised, centrosome proteins, Cep70 and Cep131. The phenotype of these embryos resembles that of zebrafish mutants for intraflagellar transport proteins (IFTs), with kidney and ear development affected and left-right asymmetry randomised. These organs and processes are those affected in Bardet-Biedl syndrome and other similar diseases. Like these diseases, the root cause of the phenotype lies, in fact, in dysfunctional cilia, which are shortened but not eliminated in several tissues in the morphants. Centrosomes and basal bodies, on the other hand, are present. Both Cep70 and Cep131 possess a putative HDAC (histone deacetylase) interacting domain. However, we could not detect in yeast two-hybrid assays any interaction with the deacetylase that controls cilium length, HDAC6, or any of the IFTs that we tested. CONCLUSION: Cep70 and Cep131 contribute to ciliogenesis in many tissues in the zebrafish embryo: cilia are made in cep70 and cep131 morphant zebrafish embryos but are shortened. We propose that the role of these centrosomal/basal body proteins is in making the cilium and that they are involved in determination of the length of the axoneme.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Neuromuscular adaptations to different set configurations during a periodized power training block in elite junior Judokas

Although the impacts of traditional sets (TS) versus cluster (CL) sets resistance training have been broadly explored among recreationally trained populations, no studies have previously compared these set configurations among elite Judokas. Twenty-two elite male and female Judokas (age = 17.5 ± 1.2 years) performed identical periodized 4-week hypertrophy and strength blocks (8 weeks in total). Following this, for the final 4-week power training block, the cohort was separated into either TS (n = 11) or CL (n = 11) set structures. CL were prescribed by including 45-second intra-set rest every two repetitions. One-repetition maximum (1RM) and peak barbell velocities of the back squat and bench press, and countermovement (CMJ) jump height were assessed before and following each 4-week mesocycle. Significant strength and power improvements were observed after the 4-week hypertrophy training block (1RM bench press = Δ 3.82 kg, ES [95 % CI] = 1.34 [0.76, 1.93], p \u3c 0.001; 1RM squat = Δ 4.71 kg, ES = 0.52 [0.07, 0.96], p = 0.024; CMJ height = Δ 0.54 cm, ES = 0.62 [0.16, 1.07], p = 0.008) and after the 4-week maximal strength training block (1RM bench press = Δ 1.5 kg, ES = 0.68 [0.21, 1.41], p = 0.004; 1RM squat = Δ 5.47 kg, ES = 0.61 [0.15, 1.06], p = 0.010; CMJ height = Δ 0.45 cm, ES = 0.71 [0.23, 1.17], p = 0.003). However, no time × group differences were observed between the TS and CL groups following the 4-week power training block. Though traditional periodized resistance training improved neuromuscular qualities of elite junior Judokas, no between-group neuromuscular differences using either TS or CL suggests that both methods may be used as part of periodized training programs

CD81 and claudin 1 coreceptor association: role in hepatitis C virus entry.

Hepatitis C virus (HCV) is an enveloped positive-stranded RNA hepatotropic virus. HCV pseudoparticles infect liver-derived cells, supporting a model in which liver-specific molecules define HCV internalization. Three host cell molecules have been reported to be important entry factors or receptors for HCV internalization: scavenger receptor BI, the tetraspanin CD81, and the tight junction protein claudin-1 (CLDN1). None of the receptors are uniquely expressed within the liver, leading us to hypothesize that their organization within hepatocytes may explain receptor activity. Since CD81 and CLDN1 act as coreceptors during late stages in the entry process, we investigated their association in a variety of cell lines and human liver tissue. Imaging techniques that take advantage of fluorescence resonance energy transfer (FRET) to study protein-protein interactions have been developed. Aequorea coerulescens green fluorescent protein- and Discosoma sp. red-monomer fluorescent protein-tagged forms of CD81 and CLDN1 colocalized, and FRET occurred between the tagged coreceptors at comparable frequencies in permissive and nonpermissive cells, consistent with the formation of coreceptor complexes. FRET occurred between antibodies specific for CD81 and CLDN1 bound to human liver tissue, suggesting the presence of coreceptor complexes in liver tissue. HCV infection and treatment of Huh-7.5 cells with recombinant HCV E1-E2 glycoproteins and anti-CD81 monoclonal antibody modulated homotypic (CD81-CD81) and heterotypic (CD81-CLDN1) coreceptor protein association(s) at specific cellular locations, suggesting distinct roles in the viral entry process

Astrophysical Supercomputing with GPUs: Critical Decisions for Early Adopters

General purpose computing on graphics processing units (GPGPU) is dramatically changing the landscape of high performance computing in astronomy. In this paper, we identify and investigate several key decision areas, with a goal of simplyfing the early adoption of GPGPU in astronomy. We consider the merits of OpenCL as an open standard in order to reduce risks associated with coding in a native, vendor-specific programming environment, and present a GPU programming philosophy based on using brute force solutions. We assert that effective use of new GPU-based supercomputing facilities will require a change in approach from astronomers. This will likely include improved programming training, an increased need for software development best-practice through the use of profiling and related optimisation tools, and a greater reliance on third-party code libraries. As with any new technology, those willing to take the risks, and make the investment of time and effort to become early adopters of GPGPU in astronomy, stand to reap great benefits.Comment: 13 pages, 5 figures, accepted for publication in PAS

Cross-Product Extensions of the Gene Ontology

The Gene Ontology is being normalized and extended to include computable logical definitions. These definitions are partitioned into mutually exclusive cross-product sets, many of which reference other OBO Foundry ontologies. The results can be used to reason over the ontology, and to make cross-ontology queries