177 research outputs found

    Structure-Activity Determinants in Antifungal Plant Defensins MsDef1 and MtDef4 with Different Modes of Action against Fusarium graminearum

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    Plant defensins are small cysteine-rich antimicrobial proteins. Their three-dimensional structures are similar in that they consist of an α-helix and three anti-parallel β-strands stabilized by four disulfide bonds. Plant defensins MsDef1 and MtDef4 are potent inhibitors of the growth of several filamentous fungi including Fusarium graminearum. However, they differ markedly in their antifungal properties as well as modes of antifungal action. MsDef1 induces prolific hyperbranching of fungal hyphae, whereas MtDef4 does not. Both defensins contain a highly conserved γ-core motif (GXCX3–9C), a hallmark signature present in the disulfide-stabilized antimicrobial peptides, composed of β2 and β3 strands and the interposed loop. The γ-core motifs of these two defensins differ significantly in their primary amino acid sequences and in their net charge. In this study, we have found that the major determinants of the antifungal activity and morphogenicity of these defensins reside in their γ-core motifs. The MsDef1-γ4 variant in which the γ-core motif of MsDef1 was replaced by that of MtDef4 was almost as potent as MtDef4 and also failed to induce hyperbranching of fungal hyphae. Importantly, the γ-core motif of MtDef4 alone was capable of inhibiting fungal growth, but that of MsDef1 was not. The analysis of synthetic γ-core variants of MtDef4 indicated that the cationic and hydrophobic amino acids were important for antifungal activity. Both MsDef1 and MtDef4 induced plasma membrane permeabilization; however, kinetic studies revealed that MtDef4 was more efficient in permeabilizing fungal plasma membrane than MsDef1. Furthermore, the in vitro antifungal activity of MsDef1, MsDef1-γ4, MtDef4 and peptides derived from the γ-core motif of each defensin was not solely dependent on their ability to permeabilize the fungal plasma membrane. The data reported here indicate that the γ-core motif defines the unique antifungal properties of each defensin and may facilitate de novo design of more potent antifungal peptides

    Correlation of umbilical cord blood haematopoietic stem and progenitor cell levels with birth weight: implications for a prenatal influence on cancer risk

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    We examined the relation with birth weight and umbilical cord blood concentrations of haematopoietic stem and progenitor populations in 288 singleton infants. Across the whole range of birth weight, there was a positive relation between birth weight and CD34+CD38− cells, with each 500 g increase in birth weight being associated with a 15.5% higher (95% confidence interval: 1.6–31.3%) cell concentration. CD34+ and CD34+c-kit+ cells had J-shaped relations and CFU-GM cells had a U-shaped relation with birth weight. Among newborns with ⩾3000 g birth weights, concentrations of these cells increased with birth weight, while those below 3000 g had higher stem cell concentrations than the reference category of 3000–3499 g. Adjustment for cord blood plasma insulin-like growth factor-1 levels weakened the stem and progenitor cell–birth weight associations. The positive associations between birth weight and stem cell measurements for term newborns with a normal-to-high birth weight support the stem cell burden hypothesis of cancer risk

    Cantor Digitalis: chironomic parametric synthesis of singing

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    Cantor Digitalis is a performative singing synthesizer that is composed of two main parts: a chironomic control interface and a parametric voice synthesizer. The control interface is based on a pen/touch graphic tablet equipped with a template representing vocalic and melodic spaces. Hand and pen positions, pen pressure, and a graphical user interface are assigned to specific vocal controls. This interface allows for real-time accurate control over high-level singing synthesis parameters. The sound generation system is based on a parametric synthesizer that features a spectral voice source model, a vocal tract model consisting of parallel filters for vocalic formants and cascaded with anti-resonance for the spectral effect of hypo-pharynx cavities, and rules for parameter settings and source/filter dependencies between fundamental frequency, vocal effort, and formants. Because Cantor Digitalis is a parametric system, every aspect of voice quality can be controlled (e.g., vocal tract size, aperiodicities in the voice source, vowels, and so forth). It offers several presets for different voice types. Cantor Digitalis has been played on stage in several public concerts, and it has also been proven to be useful as a tool for voice pedagogy. The aim of this article is to provide a comprehensive technical overview of Cantor Digitalis

    Who Needs Microtubules? Myogenic Reorganization of MTOC, Golgi Complex and ER Exit Sites Persists Despite Lack of Normal Microtubule Tracks

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    A wave of structural reorganization involving centrosomes, microtubules, Golgi complex and ER exit sites takes place early during skeletal muscle differentiation and completely remodels the secretory pathway. The mechanism of these changes and their functional implications are still poorly understood, in large part because all changes occur seemingly simultaneously. In an effort to uncouple the reorganizations, we have used taxol, nocodazole, and the specific GSK3-β inhibitor DW12, to disrupt the dynamic microtubule network of differentiating cultures of the mouse skeletal muscle cell line C2. Despite strong effects on microtubules, cell shape and cell fusion, none of the treatments prevented early differentiation. Redistribution of centrosomal proteins, conditional on differentiation, was in fact increased by taxol and nocodazole and normal in DW12. Redistributions of Golgi complex and ER exit sites were incomplete but remained tightly linked under all circumstances, and conditional on centrosomal reorganization. We were therefore able to uncouple microtubule reorganization from the other events and to determine that centrosomal proteins lead the reorganization hierarchy. In addition, we have gained new insight into structural and functional aspects of the reorganization of microtubule nucleation during myogenesis

    International Study Group Progress Report On Linear Collider Development

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    Adolescent Brain Development and the Risk for Alcohol and Other Drug Problems

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    Dynamic changes in neurochemistry, fiber architecture, and tissue composition occur in the adolescent brain. The course of these maturational processes is being charted with greater specificity, owing to advances in neuroimaging and indicate grey matter volume reductions and protracted development of white matter in regions known to support complex cognition and behavior. Though fronto-subcortical circuitry development is notable during adolescence, asynchronous maturation of prefrontal and limbic systems may render youth more vulnerable to risky behaviors such as substance use. Indeed, binge-pattern alcohol consumption and comorbid marijuana use are common among adolescents, and are associated with neural consequences. This review summarizes the unique characteristics of adolescent brain development, particularly aspects that predispose individuals to reward seeking and risky choices during this phase of life, and discusses the influence of substance use on neuromaturation. Together, findings in this arena underscore the importance of refined research and programming efforts in adolescent health and interventional needs

    Predictors of smoking lapse in a human laboratory paradigm

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    During a smoking quit attempt, a single smoking lapse is highly predictive of future relapse. While several risk factors for a smoking lapse have been identified during clinical trials, a laboratory model of lapse was until recently unavailable and, therefore, it is unclear whether these characteristics also convey risk for lapse in a laboratory environment.The primary study goal was to examine whether real-world risk factors of lapse are also predictive of smoking behavior in a laboratory model of smoking lapse.After overnight abstinence, 77 smokers completed the McKee smoking lapse task, in which they were presented with the choice of smoking or delaying in exchange for monetary reinforcement. Primary outcome measures were the latency to initiate smoking behavior and the number of cigarettes smoked during the lapse. Several baseline measures of smoking behavior, mood, and individual traits were examined as predictive factors.Craving to relieve the discomfort of withdrawal, withdrawal severity, and tension level were negatively predictive of latency to smoke. In contrast, average number of cigarettes smoked per day, withdrawal severity, level of nicotine dependence, craving for the positive effects of smoking, and craving to relieve the discomfort of withdrawal were positively predictive of number of cigarettes smoked.The results suggest that real-world risk factors for smoking lapse are also predictive of smoking behavior in a laboratory model of lapse. Future studies using the McKee lapse task should account for between subject differences in the unique factors that independently predict each outcome measure

    Composite Sentence as One of the Ways of Expressing Time Relations

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    У статті здійснено спробу виокремити складні речення, які вживаються для вираження часової семантики, і виявлено такі речення вказаного семантичного типу: складнопідрядне речення з підрядним часу, складно-підрядне означальне та псевдопідрядне речення із часовою семантикою, складносурядне речення, зокрема доповнене часовими прислівниками. Проаналізовано семантичні компоненти вказаних речень, а саме: здатність виражати такі категоріальні значення, як таксис, аспектуальність і темпоральність; схарактеризовано основні складові частини складних речень вказаного типу, які здатні модифікувати їх семантику; здійснено спробу кла-сифікації вказаних конституентів складних речень; проведено паралелі в структурі та функціонуванні різних типів складних речень із семантикою часу. The article presents an attempt to distinguish composite sentences, which are used to represent temporal semantics, following types of sentences with mentioned semantics were found out: complex sentence with subordinate clause of time, complex sentence with relativ clause and pseudo-subordinate clause with time semantics, compound sentences. Including compound sentence with time adverbs; semantic components of the mentioned sentences were analyzed and namely the capability to express following categorical meanings: taxis, ascpectuality, temporality; the basic constituents of the mentioned composite sentences were characterized, which are capable to modify their semantics; structure and functioning of different types of composite sentences with time semantics were compared
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