91 research outputs found

    Heat transfer and flow regimes in quasi-static magnetoconvection with a vertical magnetic field

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    Numerical simulations of quasi-static magnetoconvection with a vertical magnetic field are carried out up to a Chandrasekhar number of Q = 108 over a broad range of Rayleigh numbers Ra. Three magnetoconvection regimes are identified: two of the regimes are magnetically constrained in the sense that a leading-order balance exists between the Lorentz and buoyancy forces, whereas the third regime is characterized by unbalanced dynamics that is similar to non-magnetic convection. Each regime is distinguished by flow morphology, momentum and heat equation balances, and heat transport behaviour. One of the magnetically constrained regimes appears to represent an ‘ultimate’ magnetoconvection regime in the dual limit of asymptotically large buoyancy forcing and magnetic field strength; this regime is characterized by an interconnected network of anisotropic, spatially localized fluid columns aligned with the direction of the imposed magnetic field that remain quasi-laminar despite having large flow speeds. As for non-magnetic convection, heat transport is controlled primarily by the thermal boundary layer. Empirically, the scaling of the heat transport and flow speeds with Ra appear to be independent of the thermal Prandtl number within the magnetically constrained, high-Q regimes

    Smc5/6 coordinates formation and resolution of joint molecules with chromosome morphology to ensure meiotic divisions

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    During meiosis, Structural Maintenance of Chromosome (SMC) complexes underpin two fundamental features of meiosis: homologous recombination and chromosome segregation. While meiotic functions of the cohesin and condensin complexes have been delineated, the role of the third SMC complex, Smc5/6, remains enigmatic. Here we identify specific, essential meiotic functions for the Smc5/6 complex in homologous recombination and the regulation of cohesin. We show that Smc5/6 is enriched at centromeres and cohesin-association sites where it regulates sister-chromatid cohesion and the timely removal of cohesin from chromosomal arms, respectively. Smc5/6 also localizes to recombination hotspots, where it promotes normal formation and resolution of a subset of joint-molecule intermediates. In this regard, Smc5/6 functions independently of the major crossover pathway defined by the MutLγ complex. Furthermore, we show that Smc5/6 is required for stable chromosomal localization of the XPF-family endonuclease, Mus81-Mms4Eme1. Our data suggest that the Smc5/6 complex is required for specific recombination and chromosomal processes throughout meiosis and that in its absence, attempts at cell division with unresolved joint molecules and residual cohesin lead to severe recombination-induced meiotic catastroph

    Convection-driven kinematic dynamos at low Rossby and magnetic Prandtl numbers: Single mode solutions

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    The onset of dynamo action is investigated within the context of a newly developed low Rossby, low magnetic Prandtl number, convection-driven dynamo model. This multiscale model represents an asymptotically exact form of an α2 mean field dynamo model in which the small-scale convection is represented explicitly by finite amplitude, single mode solutions. Both steady and oscillatory convection are considered for a variety of horizontal planforms. The kinetic helicity is observed to be a monotonically increasing function of the Rayleigh number. As a result, very small magnetic Prandtl number dynamos can be found for sufficiently large Rayleigh numbers. All dynamos are found to be oscillatory with an oscillation frequency that increases as the strength of the convection is increased and the magnetic Prandtl number is reduced. Kinematic dynamo action is strongly controlled by the profile of the helicity; single mode solutions which exhibit boundary layer behavior in the helicity show a decrease in the efficiency of dynamo action due to the enhancement of magnetic diffusion in the boundary layer regions. For a given value of the Rayleigh number, lower magnetic Prandtl number dynamos are excited for the case of oscillatory convection in comparison to steady convection. With regard to planetary dynamos, these results suggest that the low magnetic Prandtl number dynamos typical of liquid metals are more easily driven by thermal convection than by compositional convection

    Medication adherence among diabetic and hypertensive patients in Al-Qassim region of Saudi Arabia

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    Non-adherence to medication is often an unrecognized risk factor that contributes to failure of the therapeutic plan. The purpose of the study was to identify factors related to high, medium and low medication adherence among adult Saudi patients with hypertension and diabetes mellitus. This study is designed as a descriptive cross sectional survey and was conducted in three tertiary care hospitals of Al-Qassim province of Saudi Arabia. The data was collected using the 8-item Morisky Medication Adherence Scale (MMAS-8) and analyzed by SPSS. Three levels of adherence were considered based on the following scores: 0 to <6 (low); 6 to <8 (medium); 8 (high). Of the 396 patients interviewed, 52% reported low adherence to prescribed medication. Multinomial logistic regression analysis was conducted. Gender, age, literacy level, duration of illness and type of chronic disease were negatively associated with medication adherence. The study shows very high proportion of low and medium adherence on long term medication, which may be responsible for the failure of achieving therapeutic outcome. Further investigation is required to evaluate the applicability of MMAS-8 as a tool of measuring medication adherence among Saudi patients with chronic diseases. Adherence enhancing strategies should also be evaluated in separate patients group

    Predicting olfactory receptor neuron responses from odorant structure

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    Background Olfactory receptors work at the interface between the chemical world of volatile molecules and the perception of scent in the brain. Their main purpose is to translate chemical space into information that can be processed by neural circuits. Assuming that these receptors have evolved to cope with this task, the analysis of their coding strategy promises to yield valuable insight in how to encode chemical information in an efficient way. Results We mimicked olfactory coding by modeling responses of primary olfactory neurons to small molecules using a large set of physicochemical molecular descriptors and artificial neural networks. We then tested these models by recording in vivo receptor neuron responses to a new set of odorants and successfully predicted the responses of five out of seven receptor neurons. Correlation coefficients ranged from 0.66 to 0.85, demonstrating the applicability of our approach for the analysis of olfactory receptor activation data. The molecular descriptors that are best-suited for response prediction vary for different receptor neurons, implying that each receptor neuron detects a different aspect of chemical space. Finally, we demonstrate that receptor responses themselves can be used as descriptors in a predictive model of neuron activation. Conclusions The chemical meaning of molecular descriptors helps understand structure-response relationships for olfactory receptors and their 'receptive fields'. Moreover, it is possible to predict receptor neuron activation from chemical structure using machine-learning techniques, although this is still complicated by a lack of training data

    Caffeine taste signaling in drosophila larvae

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    The Drosophila larva has a simple peripheral nervous system with a comparably small number of sensory neurons located externally at the head or internally along the pharynx to assess its chemical environment. It is assumed that larval taste coding occurs mainly via external organs (the dorsal, terminal, and ventral organ). However, the contribution of the internal pharyngeal sensory organs has not been explored. Here we find that larvae require a single pharyngeal gustatory receptor neuron pair called D1, which is located in the dorsal pharyngeal sensilla, in order to avoid caffeine and to associate an odor with caffeine punishment. In contrast, caffeine-driven reduction in feeding in non-choice situations does not require D1. Hence, this work provides data on taste coding via different receptor neurons, depending on the behavioral context. Furthermore, we show that the larval pharyngeal system is involved in bitter tasting. Using ectopic expressions, we show that the caffeine receptor in neuron D1 requires the function of at least four receptor genes: the putative co-receptors Gr33a, Gr66a, the putative caffeine-specific receptor Gr93a, and yet unknown additional molecular component(s). This suggests that larval taste perception is more complex than previously assumed already at the sensory level. Taste information from different sensory organs located outside at the head or inside along the pharynx of the larva is assembled to trigger taste guided behaviors

    Meiotic Recombination Intermediates Are Resolved with Minimal Crossover Formation during Return-to-Growth, an Analogue of the Mitotic Cell Cycle

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    Accurate segregation of homologous chromosomes of different parental origin (homologs) during the first division of meiosis (meiosis I) requires inter-homolog crossovers (COs). These are produced at the end of meiosis I prophase, when recombination intermediates that contain Holliday junctions (joint molecules, JMs) are resolved, predominantly as COs. JM resolution during the mitotic cell cycle is less well understood, mainly due to low levels of inter-homolog JMs. To compare JM resolution during meiosis and the mitotic cell cycle, we used a unique feature of Saccharomyces cerevisiae, return to growth (RTG), where cells undergoing meiosis can be returned to the mitotic cell cycle by a nutritional shift. By performing RTG with ndt80 mutants, which arrest in meiosis I prophase with high levels of interhomolog JMs, we could readily monitor JM resolution during the first cell division of RTG genetically and, for the first time, at the molecular level. In contrast to meiosis, where most JMs resolve as COs, most JMs were resolved during the first 1.5–2 hr after RTG without producing COs. Subsequent resolution of the remaining JMs produced COs, and this CO production required the Mus81/Mms4 structure-selective endonuclease. RTG in sgs1-ΔC795 mutants, which lack the helicase and Holliday junction-binding domains of this BLM homolog, led to a substantial delay in JM resolution; and subsequent JM resolution produced both COs and NCOs. Based on these findings, we suggest that most JMs are resolved during the mitotic cell cycle by dissolution, an Sgs1 helicase-dependent process that produces only NCOs. JMs that escape dissolution are mostly resolved by Mus81/Mms4-dependent cleavage that produces both COs and NCOs in a relatively unbiased manner. Thus, in contrast to meiosis, where JM resolution is heavily biased towards COs, JM resolution during RTG minimizes CO formation, thus maintaining genome integrity and minimizing loss of heterozygosity

    Alpha-Toxin Induces Programmed Cell Death of Human T cells, B cells, and Monocytes during USA300 Infection

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    This investigation examines the influence of alpha-toxin (Hla) during USA300 infection of human leukocytes. Survival of an USA300 isogenic deletion mutant of hla (USA300Δhla) in human blood was comparable to the parental wild-type strain and polymorphonuclear leukocyte (PMN) plasma membrane permeability caused by USA300 did not require Hla. Flow cytometry analysis of peripheral blood mononuclear cells (PBMCs) following infection by USA300, USA300Δhla, and USA300Δhla transformed with a plasmid over-expressing Hla (USA300Δhla Comp) demonstrated this toxin plays a significant role inducing plasma membrane permeability of CD14+, CD3+, and CD19+ PBMCs. Rapid plasma membrane permeability independent of Hla was observed for PMNs, CD14+ and CD19+ PBMCs following intoxication with USA300 supernatant while the majority of CD3+ PBMC plasma membrane permeability induced by USA300 required Hla. Addition of recombinant Hla to USA300Δhla supernatant rescued CD3+ and CD19+ PBMC plasma membrane permeability generated by USA300 supernatant. An observed delay in plasma membrane permeability caused by Hla in conjunction with Annexin V binding and ApoBrdU Tunel assays examining PBMCs intoxicated with recombinant Hla or infected with USA300, USA300Δhla, USA300Δhla Comp, and USA300ΔsaeR/S suggest Hla induces programmed cell death of monocytes, B cells, and T cells that results in plasma membrane permeability. Together these findings underscore the importance of Hla during S. aureus infection of human tissue and specifically demonstrate Hla activity during USA300 infection triggers programmed cell death of human monocytes, T cells and B cells that leads to plasma membrane permeability

    Management of intra-abdominal infections : recommendations by the WSES 2016 consensus conference

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    This paper reports on the consensus conference on the management of intra-abdominal infections (IAIs) which was held on July 23, 2016, in Dublin, Ireland, as a part of the annual World Society of Emergency Surgery (WSES) meeting. This document covers all aspects of the management of IAIs. The Grading of Recommendations Assessment, Development and Evaluation recommendation is used, and this document represents the executive summary of the consensus conference findings.Peer reviewe

    Parallels between Pathogens and Gluten Peptides in Celiac Sprue

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    Pathogens are exogenous agents capable of causing disease in susceptible organisms. In celiac sprue, a disease triggered by partially hydrolyzed gluten peptides in the small intestine, the offending immunotoxins cannot replicate, but otherwise have many hallmarks of classical pathogens. First, dietary gluten and its peptide metabolites are ubiquitous components of the modern diet, yet only a small, genetically susceptible fraction of the human population contracts celiac sprue. Second, immunotoxic gluten peptides have certain unusual structural features that allow them to survive the harsh proteolytic conditions of the gastrointestinal tract and thereby interact extensively with the mucosal lining of the small intestine. Third, they invade across epithelial barriers intact to access the underlying gut-associated lymphoid tissue. Fourth, they possess recognition sequences for selective modification by an endogenous enzyme, transglutaminase 2, allowing for in situ activation to a more immunotoxic form via host subversion. Fifth, they precipitate a T cell–mediated immune reaction comprising both innate and adaptive responses that causes chronic inflammation of the small intestine. Sixth, complete elimination of immunotoxic gluten peptides from the celiac diet results in remission, whereas reintroduction of gluten in the diet causes relapse. Therefore, in analogy with antibiotics, orally administered proteases that reduce the host's exposure to the immunotoxin by accelerating gluten peptide destruction have considerable therapeutic potential. Last but not least, notwithstanding the power of in vitro methods to reconstitute the essence of the immune response to gluten in a celiac patient, animal models for the disease, while elusive, are likely to yield fundamentally new systems-level insights
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