38 research outputs found

    Stability of the hard-sphere icosahedral quasilattice

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    The stability of the hard-sphere icosahedral quasilattice is analyzed using the differential formulation of the generalized effective liquid approximation. We find that the icosahedral quasilattice is metastable with respect to the hard-sphere crystal structures. Our results agree with recent findings by McCarley and Ashcroft [Phys. Rev. B {\bf 49}, 15600 (1994)] carried out using the modified weighted density approximation.Comment: 15 pages, 2 figures available from authors upon request, (revtex), submitted to Phys. Rev.

    Phytochemicals as antibiotic alternatives to promote growth and enhance host health

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    There are heightened concerns globally on emerging drug-resistant superbugs and the lack of new antibiotics for treating human and animal diseases. For the agricultural industry, there is an urgent need to develop strategies to replace antibiotics for food-producing animals, especially poultry and livestock. The 2nd International Symposium on Alternatives to Antibiotics was held at the World Organization for Animal Health in Paris, France, December 12-15, 2016 to discuss recent scientific developments on strategic antibiotic-free management plans, to evaluate regional differences in policies regarding the reduction of antibiotics in animal agriculture and to develop antibiotic alternatives to combat the global increase in antibiotic resistance. More than 270 participants from academia, government research institutions, regulatory agencies, and private animal industries from >25 different countries came together to discuss recent research and promising novel technologies that could provide alternatives to antibiotics for use in animal health and production; assess challenges associated with their commercialization; and devise actionable strategies to facilitate the development of alternatives to antibiotic growth promoters (AGPs) without hampering animal production. The 3-day meeting consisted of four scientific sessions including vaccines, microbial products, phytochemicals, immune-related products, and innovative drugs, chemicals and enzymes, followed by the last session on regulation and funding. Each session was followed by an expert panel discussion that included industry representatives and session speakers. The session on phytochemicals included talks describing recent research achievements, with examples of successful agricultural use of various phytochemicals as antibiotic alternatives and their mode of action in major agricultural animals (poultry, swine and ruminants). Scientists from industry and academia and government research institutes shared their experience in developing and applying potential antibiotic-alternative phytochemicals commercially to reduce AGPs and to develop a sustainable animal production system in the absence of antibiotics.Fil: Lillehoj, Hyun. United States Department of Agriculture. Agricultural Research Service; ArgentinaFil: Liu, Yanhong. University of California; Estados UnidosFil: Calsamiglia, Sergio. Universitat Autònoma de Barcelona; EspañaFil: Fernandez Miyakawa, Mariano Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología; ArgentinaFil: Chi, Fang. Amlan International; Estados UnidosFil: Cravens, Ron L.. Amlan International; Estados UnidosFil: Oh, Sungtaek. United States Department of Agriculture. Agricultural Research Service; ArgentinaFil: Gay, Cyril G.. United States Department of Agriculture. Agricultural Research Service; Argentin

    Understanding the Sequence-Dependence of DNA Groove Dimensions: Implications for DNA Interactions

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    BACKGROUND: The B-DNA major and minor groove dimensions are crucial for DNA-protein interactions. It has long been thought that the groove dimensions depend on the DNA sequence, however this relationship has remained elusive. Here, our aim is to elucidate how the DNA sequence intrinsically shapes the grooves. METHODOLOGY/PRINCIPAL FINDINGS: The present study is based on the analysis of datasets of free and protein-bound DNA crystal structures, and from a compilation of NMR (31)P chemical shifts measured on free DNA in solution on a broad range of representative sequences. The (31)P chemical shifts can be interpreted in terms of the BI↔BII backbone conformations and dynamics. The grooves width and depth of free and protein-bound DNA are found to be clearly related to the BI/BII backbone conformational states. The DNA propensity to undergo BI↔BII backbone transitions is highly sequence-dependent and can be quantified at the dinucleotide level. This dual relationship, between DNA sequence and backbone behavior on one hand, and backbone behavior and groove dimensions on the other hand, allows to decipher the link between DNA sequence and groove dimensions. It also firmly establishes that proteins take advantage of the intrinsic DNA groove properties. CONCLUSIONS/SIGNIFICANCE: The study provides a general framework explaining how the DNA sequence shapes the groove dimensions in free and protein-bound DNA, with far-reaching implications for DNA-protein indirect readout in both specific and non specific interactions

    Disruption of integrin-dependent adhesion and survival of endothelial cells by recombinant adenovirus expressing isolated beta integrin cytoplasmic domains

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    We explored the possibility of using a genetic approach to inhibit integrin-mediated endothelial cell adhesion and survival. We constructed recombinant adenoviruses (Ads) expressing chimeric proteins consisting of the cytoplasmic and transmembrane domains of integrin beta1 (CH1), beta3 (CH3) or the beta1 transmembrane domain alone (CH2) connected to the extracellular domain of L3T4 placed under the control of the CMV promoter (AdCMV) or the endothelial cell specific Tie-1 promoter (AdTie). All constructs were expressed in a dose- and time-dependent manner with over 90% of cells expressing the constructs within 24 h (AdCMVs) or 72 h (AdTies) after infection. Confluent monolayers of HUVEC infected with AdCMVCH1 or AdCMVCH3 detached from the substrate in a time- and dose-dependent manner with over 95% of the cells being detached 2 days (AdCMVs) or 3 to 4 days (AdTies) after infection. Cell detachment was preceded by the disruption of focal adhesions and reorganization of the actin cytoskeleton and was associated with a reduced ligand-binding activity of beta1, while cell surface density of beta1 integrins remained unchanged. Detached cells failed to re-adhere to different matrix proteins, without, however, any specificity toward beta1 or beta3 integrin-mediated adhesion. Upon detachment, HUVEC rapidly died by apoptosis. These results demonstrate that dominant negative inhibition of integrin function is an effective approach to disrupt endothelial cell adhesion and survival in vitro

    Continuous Erythropoietin Receptor Activator (CERA) administered at extended administration intervals corrects anaemia in patients with chronic kidney disease on dialysis: a randomised, multicentre, multiple-dose, phase II study

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    This dose-finding, open-label study examined the potential of subcutaneous Continuous Erythropoietin Receptor Activator (C.E.R.A.) to correct anaemia at extended administration intervals in 61 erythropoiesis-stimulating agent-naive patients with chronic kidney disease (CKD) on dialysis. After a 4-week run-in, patients were randomised to C.E.R.A. 0.15, 0.30 and 0.45 mu g/kg/week. Within these dose groups, patients were further randomised to once weekly, once every 2 weeks or once every 3 weeks treatment. Mean changes in haemoglobin (Hb) increased with increasing C.E.R.A. dose during a period of 6 weeks where no dose adjustments were permitted. The effect was independent of administration schedule. Erythropoietic responses were sustained until the end of the study (12 weeks) in all groups. In total, 90% of patients in the 0.30 mu g/kg/week group and 79% in the 0.45 mu g/kg/week group responded to treatment (Hb increase >= 1.0 g/dl), compared with 72% in the 0.15 mu g/kg/week group. Faster median response time was associated with increasing dose (51, 38 and 31 days, respectively) and response was unrelated to administration frequency. C.E.R.A. was generally well tolerated. Our results suggest that 0.60 mu g/kg twice monthly would be a suitable starting dose of C.E.R.A. for the initiation of anaemia correction in patients with CKD on dialysis. Phase III studies will confirm the feasibility of using C.E.R.A. at extended administration intervals in patients with CKD and anaemia
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