Identification of a Natural Source of Resistance to Watermelon Chlorotic Stunt Virus in an Indigenous Accession of Cucumis Melo Var. Agrestis

Watermelon chlorotic stunt virus (WCSV) is among the most important viral diseases of the family Cucurbitaceae. It is a bipartite begomovirus (DNA-A and DNA-B genome components) that belongs to the family Geminividae (Walkely et al., 1990). It causes severe crop losses, particularly in watermelon and melon (Lecoq et al.,1994). In Sudan, WCSV causes high reduction in yield and quality of watermelon, melon, snake cucumber and squashes. Leaves of infected plants are crinkled, stunted and develop striking chlorotic mottle. The whole plant looked stunted and chlorotic and may be devoid of marketable fruits (Walkely et al., 1990). Resistance to major diseases is very common among indigenous Sudanese melons, Tibish and agrestis (C. melo var. agrestis), compared to other melon types (Mohamed, 2000).    Experiments were conducted at the University of Gezira Research Farm in April (1996-1997) to identify a natural source of resistance to watermelon chlorotic stunt virus in Cucumis melo L. The screened material included: 101 accessions of C. melo var. cantalupensis and C. melo var flexuousus collected in Sudan; nine accessions belong to the indigenous Humaid type (C. melo var. agrestis) and eleven introduced lines such as P1 313970, P1 131375, Pl 255478, Vedrantais, Nantais Oblong, MR-I, Isoblon, Virgos, Margot and Zumo. The inoculation pressure of the virus in the field was increased by growing plants of the susceptible watermelon cultivar "Sugar Baby", obtained from Peto Seed Company, about one month before conducting the screening experiments

Genetics and Stability of Resistance to Watermelon Chlorotic Stunt Virus in Melon (Cucumis Melo L).

Experiments were carried out under field conditions at the University Gezira Research Farm, Sudan and the agroinoculation and green houses conditions in France (le Centre National de la Recherche Scientifique (CNRS*) and le Institut National de la Recherche Agronomique (INRA**) to study the inheritance and stability of resistance to watermelon chlorotic stunt virus (WCSV) in melon (C. melo L.).   The techniques of autoradiography, using the ratioactive WCSV P32, probe was used to detect WCSV in plant tissue and the phospho-imager machine was used to obtain quantified results of DNA particles within the examined plant tissue. The results indicated the presence of one dominant gene and another recessive independent gene controlling WCSV resistance in the resistant lines P1414723, P1124112 and HSD2445- 005. Multi-locational trials on resistant lines under natural field conditions revealed that the resistance to WCSV in melon is uniform and stable. Results of studying the movement of the virus within the plant tissues indicated that the blockage in the plant indigenous trafficking system was one of the mechanisms that are involved in plant resistance to WCSV in the lines P1414723, P1282448, P1124440, Pl 124112, 90625 and HSD 2445-005

Scale without Conformal Invariance at Three Loops

We carry out a three-loop computation that establishes the existence of scale without conformal invariance in dimensional regularization with the MS scheme in d=4-epsilon spacetime dimensions. We also comment on the effects of scheme changes in theories with many couplings, as well as in theories that live on non-conformal scale-invariant renormalization group trajectories. Stability properties of such trajectories are analyzed, revealing both attractive and repulsive directions in a specific example. We explain how our results are in accord with those of Jack & Osborn on a c-theorem in d=4 (and d=4-epsilon) dimensions. Finally, we point out that limit cycles with turning points are unlike limit cycles with continuous scale invariance.Comment: 21 pages, 3 figures, Erratum adde

Knowledge, Perception, Attitudes and Behavior on Influenza Immunization and the Determinants of Vaccination

BACKGROUND: We sought to determine the knowledge of, perception, attitudes, and behaviors toward influenza virus and immunization, and the determinants of vaccination among students, patients, and Healthcare Workers (HCWs) at the American University of Beirut and its affiliated Medical Center. METHODS: We conducted a cross-sectional study between October 2016 and January 2017 utilizing a self-administered questionnaire that was provided to 247 randomly selected adult participants. Data collected included socio-demographic characteristics, prior vaccination against influenza, knowledge, perception, attitudes, and behaviors toward influenza and influenza immunization. A multivariable regression model was used to evaluate for independent associations between the different variables and regular or yearly vaccination as a primary outcome. RESULTS: The overall survey response rate was 77%. A substantial proportion of respondents (47.4%) had never received the influenza vaccine. Only 10.2% of students, 19.1% of patients, and 35.6% of HCWs reported regular or yearly influenza vaccine uptake. HCWs had the lowest knowledge score about influenza and its vaccine despite high self-reported levels of knowledge. Barriers to vaccinations included lack of information (31%), fear of adverse effects (29%), and a perception of not being at risk (23%). Several factors were independently associated with regular or yearly vaccination uptake including having children (adjusted OR = 3.8; 95% CI 1.2-12.5), a "very good" self-reported level of knowledge (OR = 16.3; 95% CI 1.4-194.2) and being afraid of the consequences of influenza (OR = 0.2; 95% CI 0.1-0.6). CONCLUSION: Adherence rates with regular or yearly vaccination against influenza remain low across all study groups. We were able to identify predictors as well as barriers to vaccination. Future awareness and vaccination campaigns should specifically aim at correcting misconceptions about vaccination, particularly among HCWs, along with addressing the barriers to vaccination. Predictors of vaccination should be integrated in the design of future campaigns

The tomato phosphatidylinositol-phospholipase C2 (SlPLC2) is required for defense gene induction by the fungal elicitor xylanase

The tomato [Solanum lycopersicum (Sl)] phosphatidylinositol-phospholipase C (PI-PLC) gene family is composed of six members, named SlPLC1 to SlPLC6, differentially regulated upon pathogen attack. We have previously shown that the fungal elicitor xylanase rapidly induces nitric oxide (NO), which is required for PI-PLCs activity and downstream defense responses in tomato cell suspensions. Here, we show that all six SlPLC genes are expressed in tomato cell suspensions. Treatment of the cells with xylanase induces an early increase in SlPLC5 transcript levels, followed by a raise of the amount of SlPLC2 transcripts. The production of NO is required to augment SlPLC5 transcript levels in xylanase-treated tomato cells. Xylanase also induces SlPLC2 and SlPLC5 transcript levels in planta. We knocked-down the expression of SlPLC2 and SlPLC5 by virus-induced gene silencing. We found that SlPLC2 is required for xylanase-induced expression of the defense-related genes PR1 and HSR203J.Fil: Gonorazky, Ana Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigaciones Biológicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaFil: Ramírez, Leonor. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigaciones Biológicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaFil: Abd El Haliem, Ahmed. Wageningen University; Países BajosFil: Vossen, Jack H.. Wageningen University; Países BajosFil: Lamattina, Lorenzo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigaciones Biológicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaFil: Ten Have, Arjen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigaciones Biológicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaFil: Joosten, Matthieu H. A. J.. Wageningen University; Países BajosFil: Laxalt, Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigaciones Biológicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; Argentin

Infrared Multiphoton Dissociation Enables Top-Down Characterization of Membrane Protein Complexes and G Protein-Coupled Receptors

Membrane proteins are challenging to analyze by native mass spectrometry (MS) as their hydrophobic nature typically requires stabilization in detergent micelles that are removed prior to analysis via collisional activation. There is however a practical limit to the amount of energy which can be applied, which often precludes subsequent characterization by top-down MS. To overcome this barrier, we have applied a modified Orbitrap Eclipse Tribrid mass spectrometer coupled to an infrared laser within a high-pressure linear ion trap. We show how tuning the intensity and time of incident photons enables liberation of membrane proteins from detergent micelles. Specifically, we relate the ease of micelle removal to the infrared absorption of detergents in both condensed and gas phases. Top-down MS via infrared multiphoton dissociation (IRMPD), results in good sequence coverage enabling unambiguous identification of membrane proteins and their complexes. By contrasting and comparing the fragmentation patterns of the ammonia channel with two class A GPCRs, we identify successive cleavage of adjacent amino acids within transmembrane domains. Using gas-phase molecular dynamics simulations, we show that areas prone to fragmentation maintain aspects of protein structure at increasing temperatures. Altogether, we propose a rationale to explain why and where in the protein fragment ions are generated

Neuropsychological Changes in a Prospectively Followed Cohort of Intravenous Drug Users with and without HIV

We followed a cohort of 223 intravenous drug users (99 HIV and 124 HIV+) for up to 3.5 years, examining change in performance over time as a function of HIV status, disease severity, and neurological signs and symptoms. Analyses were performed by applying generalized estimating equations (GEE) to regression analyses with repeated measures, and controlled for age, education, and length of substance use. None of the subjects had AIDS at baseline. There were 147 men (85 HIV+ and 62 HIV) and 76 women (39 HIV+ and 37 HIV). Memory performance was worse in the HIV+ than HIV− women. In the men, performance on the memory, executive, language, and attention factors improved significantly overtime, but this improvement was attenuated in the HIV men for the attention and orientation factors. In the HIV+ women. AIDS was associated with worsening performance on attention tests. The presence or onset of clinically significant neurological findings was associated with poorer language and motor speed performance. In the HIV+ men, memory performance was worse when the CD4 count fell below 200: it declined over time in men with AIDS but not in those without. A learning effect for language was attenuated in men who developed AIDS. The presence or development of a clinically significant neurological sign was associated with poorer memory, executive, language, attention, and motor speed performance. Our findings parallel those that we previously reported in a prospectively followed cohort of gay men. In combination, our studies of gay men and IDU cohorts suggest that (a) HIV can affect cognition early, even when the patient is medically asymptomatic; (b) cognitive difficulties worsen as the severity of HIV infection increases; and (c) the advent of clinically significant neurologic signs is associated with progression to more severe cognitive deficits. Our data suggest that the neurological and neuropsychological changes are both manifestations of the central effect of HIV on the CNS

Holographic Renormalization of Foliation Preserving Gravity and Trace Anomaly

From the holographic renormalizationg group viewpoint, while the scale transformation plays a primary role in the duality by providing the extra dimension, the special conformal transformation seems to only play a secondary role. We, however, claim that the space-time diffeomorphism is crucially related to the latter. For its demonstration, we study the holographic renormalization group flow of a foliation preserving diffeomophic theory of gravity (a.k.a. space-time flipped Horava gravity). We find that the dual field theory, if any, is only scale invariant but not conformal invariant. In particular, we show that the holographic trace anomaly in four-dimension predicts the Ricci scalar squared term that would be incompatible with the Wess-Zumino consistency condition if it were conformal. This illustrates how the foliation preserving diffeomophic theory of gravity could be inconsistent with a theorem of the dual unitary quantum field theory.Comment: 18 pages, v2: reference added, v3: comments on more recent literature added in response to referee's reques

Selective inhibition of the K⁺ efflux sensitive NLRP3 pathway by Cl^- channel modulation.

From Europe PMC via Jisc Publications RouterHistory: ppub 2020-10-01, epub 2020-10-12Publication status: PublishedFunder: Medical Research Council; Grant(s): MR/N029992/1, MC_PC_17172, MR/T016515/1Funder: Alzheimer's Society; Grant(s): AS-PhD-16-002, 10Funder: Alzheimers Research UK; Grant(s): ARUK-2015DDI-OXThe NLRP3 inflammasome regulates production of the pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18, and contributes to inflammation exacerbating disease. Fenamate non-steroidal anti-inflammatory drugs (NSAIDs) were recently described as NLRP3 inflammasome inhibitors via chloride channel inhibition. Fenamate NSAIDs inhibit cyclooxygenase (COX) enzymes, limiting their potential as therapeutics for NLRP3-associated diseases due to established side effects. The aim here was to develop properties of the fenamates that inhibit NLRP3, and at the same time to reduce COX inhibition. We synthesised a library of analogues, with feedback from in silico COX docking potential, and IL-1β release inhibitory activity. Through iterative screening and rational chemical design, we established a collection of chloride channel inhibiting active lead molecules with potent activity at the canonical NLRP3 inflammasome and no activity at COX enzymes, but only in response to stimuli that activated NLRP3 by a K+ efflux-dependent mechanism. This study identifies a model for the isolation and removal of unwanted off-target effects, with the enhancement of desired activity, and establishes a new chemical motif for the further development of NLRP3 inflammasome inhibitors