Structural insights into Legionella RidL-Vps29 retromer subunit interaction reveal displacement of the regulator TBC1D5

Legionella pneumophila can cause Legionnaires’ disease and replicates intracellularly in a distinct Legionella-containing vacuole (LCV). LCV formation is a complex process that involves a plethora of type IV-secreted effector proteins. The effector RidL binds the Vps29 retromer subunit, blocks retrograde vesicle trafficking, and promotes intracellular bacterial replication. Here, we reveal that the 29-kDa N-terminal domain of RidL (RidL2–281) adopts a “foot-like” fold comprising a protruding β-hairpin at its “heel”. The deletion of the β-hairpin, the exchange to Glu of Ile170 in the β-hairpin, or Leu152 in Vps29 abolishes the interaction in eukaryotic cells and in vitro. RidL2–281 or RidL displace the Rab7 GTPase-activating protein (GAP) TBC1D5 from the retromer and LCVs, respectively, and TBC1D5 promotes the intracellular growth of L. pneumophila. Thus, the hydrophobic β-hairpin of RidL is critical for binding of the L. pneumophila effector to the Vps29 retromer subunit and displacement of the regulator TBC1D5

Star Formation in the Gulf of Mexico

We present an optical/infrared study of the dense molecular cloud, L935, dubbed "The Gulf of Mexico", which separates the North America and the Pelican nebulae, and we demonstrate that this area is a very active star forming region. A wide-field imaging study with interference filters has revealed 35 new Herbig-Haro objects in the Gulf of Mexico. A grism survey has identified 41 Halpha emission-line stars, 30 of them new. A small cluster of partly embedded pre-main sequence stars is located around the known LkHalpha 185-189 group of stars, which includes the recently erupting FUor HBC 722.Comment: Submitted to A&A, 14 pages, 18 figure

High-Resolution Spectroscopy of FUors

High-resolution spectroscopy was obtained of the FUors FU Ori and V1057 Cyg between 1995 and 2002 with SOFIN at NOT and with HIRES at Keck I. During those years FU Ori remained about 1 mag. (in B) below its 1938-39 maximum brightness, but V1057 Cyg (B ~ 10.5 at peak in 1970-71) faded from about 13.5 to 14.9 and then recovered slightly. Their photospheric spectra resemble a rotating G0 Ib supergiant, with v_eq sin i = 70 km/s for FU Ori and 55 km/s for V1057 Cyg. As V1057 Cyg faded, P Cyg structure in Halpha and the IR CaII lines strengthened and a complex shortward-displaced shell spectrum increased in strength, disappeared in 1999, and reappeared in 2001. Night-to-night changes in the wind structure of FU Ori show evidence of sporadic infall. The strength of P Cyg absorption varied cyclically with a period of 14.8 days, with phase stability maintained over 3 seasons, and is believed to be the rotation period. The structure of the photospheric lines also varies cyclically, but with a period of 3.54 days. A similar variation may be present in V1057 Cyg. As V1057 Cyg has faded, the emission lines of a pre-existing low-excitation chromosphere have emerged, so we believe the `line doubling' in V1057 Cyg is produced by these central emission cores in the absorption lines, not by orbital motion in an inclined Keplerian disk. No dependence of v_eq sin i on wavelength or excitation potential was detected in either star, again contrary to expectation for a self-luminous accretion disk. Nor are critical lines in the near infrared accounted for by synthetic disk spectra. A rapidly rotating star near the edge of stability (Larson 1980), can better explain these observations. FUor eruptions may not be a property of ordinary TTS, but may be confined to a special subspecies of rapid rotators having powerful quasi-permanent winds.Comment: 41 pages (including 32 figures and 9 tables); ApJ, in press; author affiliation, figs. 3 and 9 correcte

Ectopic expression of GmNHX3 and GmNHX1, encoding two Glycine max Na+/H+ vacuolar antiporters, improves water deficit tolerance in Arabidopsis thaliana

The importance of Na+/H+ antiporters in salt tolerance in plants has been demonstrated in many studies, but much less is known about their protective role during drought stress. To study their possible contribution to water deficit tolerance, two closely related soybean Na+/H+ antiporters belonging to the intracellular NHX exchanger protein family, GmNHX3 and GmNHX1, were evaluated in transgenic Arabidopsis thaliana. A. thaliana plants ectopically expressing GmNHX3 or GmNHX1 displayed a more drought-tolerant phenotype compared to wild-type plants, which was accompanied by an increase in relative water content and chlorophyll content during stress conditions. Both GmHNX1 and GmHNX3 transgenic lines accumulated higher amounts of Na+ and K+ cations, showed increased antioxidant enzyme activities and less membrane damage due to lipid peroxidation under water deficit, as compared to non-transformed plants. Furthermore, plants expressing GmNHX3 showed an increased sensitivity to abscisic acid as deduced from stomatal closure and seed germination inhibition studies. Finally, a significant up-regulation of abiotic stress-related genes was observed in both transgenic lines compared to wild-type plants in response to abscisic acid and mannitol treatments. These results demonstrate that GmNHX3 and GmNHX1 antiporters confer protection during drought stress in A. thaliana and hence are potential genetic targets to improve drought tolerance in soybean and other crops

Development of PSP1: A Biostimulant Based on the Elicitor AsES for Disease Management in Monocot and Dicot Crops

In this work we present a novel biostimulant for sustainable crop disease management named PSP1. PSP1 is based on the plant defense-elicitor AsES, an extracellular protease produced by the strawberry fungal pathogen Acremonium strictum. Fungal fermentation conditions and downstream processing were determined to maximize extracellular protein production, product stability and a high plant defense-eliciting activity, as monitored by anthracnose resistance in supernatant-treated strawberry plants subsequently infected with a viral strain of Colletotrichum acutatum. Fermentation batches were shown to reduce anthracnose development by 30 to 60% as compared to infected non-treated plants. Product formulation was shown to be stable for 6 months when stored at temperatures up to 45°C and toxicological tests showed that PSP1 was harmless to beneficial organisms and non-toxic to mammalian species at concentrations 50 times higher than those used in plant experiments. Furthermore, disease protection studies using dilutions of PSP1 indicated that there is a minimum threshold protease activity needed to induce pathogen defense in strawberry and that this induction effect is dose-independent. A significant characteristic of PSP1 is its broad-range protection against different diseases in various crop species. In soybean, PSP1 reduced the symptomatology by 70% of Corynespora cassiicola, etiological agent of the target spot. This protection effect was similar to the commercial inducer BION 500 WG based on BTH, and both products were shown to induce an oxidative burst and up-regulated PR1-gene expression in soybean. Furthermore, a double PSP1-treatment on greenhouse-grown sugarcane plants provided protection against bacterial red stripe disease caused by Acidovorax avenae and a double foliar application of PSP1 on field-grown wheat plants significantly increased resistance against Fusarium graminearum, causal agent of head blight disease, manifested mainly in an increased seed germination rate. In summary, these disease protection studies demonstrated an effective control against both bacterial and fungal pathogens in both monocot and dicot crop species, which together with its low production cost, effectiveness at low concentrations, long shelf-life, tolerance to high temperatures, harmlessness to non-target organisms and simple handling and application, make PSP1 a very promising candidate for effective and sustainable disease management in many crop species.Fil: Chalfoun, Nadia Regina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Instituto de Tecnología Agroindustrial del Noroeste Argentino; Argentina. Estación Experimental Agroindustrial Obispo Colombres; ArgentinaFil: Sandra B. Durman. Bayer S.A., Argentina – Crop Science LATAM 2, Crop Science Research, Buenos Aires; ArgentinaFil: Budeguer, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Instituto de Tecnología Agroindustrial del Noroeste Argentino; Argentina. Estación Experimental Agroindustrial Obispo Colombres; ArgentinaFil: Caro, María del Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Romina P. Bertani. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Instituto de Tecnología Agroindustrial del Noroeste Argentino; Argentina. Estación Experimental Agroindustrial Obispo Colombres; ArgentinaFil: Pia d.l.A. di-Peto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Instituto de Tecnología Agroindustrial del Noroeste Argentino;; Argentina. Estación Experimental Agroindustrial Obispo Colombres; ArgentinaFil: Sebastian A. Stenglein. Laboratorio de Biología Funcional y Biotecnología, Universidad Nacional del Centro de la Provincia de Buenos Aires-Comisión de Investigaciones Científicas de la Provincia de Buenos Aires and Instituto de Investigaciones en Biodiversidad y Biotecnología – Consejo Nacional de Investigaciones Científicas y Técnicas, Azul; ArgentinaFil: Filippone, María Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Instituto de Tecnología Agroindustrial del Noroeste Argentino; Argentina. Estación Experimental Agroindustrial Obispo Colombres; ArgentinaFil: Enrique R. Moretti. Annuit S.a; ArgentinaFil: Juan C. Díaz Ricci. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Bjorn Welin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Instituto de Tecnología Agroindustrial del Noroeste Argentino; Argentina. Estación Experimental Agroindustrial Obispo Colombres; ArgentinaFil: Castagnaro, Atilio Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Instituto de Tecnología Agroindustrial del Noroeste Argentino; Argentina. Estación Experimental Agroindustrial Obispo Colombres; Argentin

Comparative economic evaluation of data from the ACRIN national CT colonography trial with three cancer intervention and surveillance modeling network microsimulations

Purpose: To estimate the cost-effectiveness of computed tomographic (CT) colonography for colorectal cancer (CRC) screening in average-risk asymptomatic subjects in the United States aged 50 years. Materials and Methods: Enrollees in the American College of Radiology Imaging Network National CT Colonography Trial provided informed consent, and approval was obtained from the institutional review board at each site. CT colonography performance estimates from the trial were incorporated into three Cancer Intervention and Surveillance Modeling Network CRC microsimulations. Simulated survival and lifetime costs for screening 50-year-old subjects in the United States with CT colonography every 5 or 10 years were compared with those for guideline-concordant screening with colonoscopy, flexible sigmoidoscopy plus either sensitive unrehydrated fecal occult blood testing (FOBT) or fecal immunochemical testing (FIT), and no screening. Perfect and reduced screening adherence scenarios were considered. Incremental cost-effectiveness and net health benefits were estimated from the U.S. health care sector perspective, assuming a 3% discount rate. Results: CT colonography at 5- and 10-year screening intervals was more costly and less effective than FOBT plus flexible sigmoidoscopy in all three models in both 100% and 50% adherence scenarios. Colonoscopy also was more costly and less effective than FOBT plus flexible sigmoidoscopy, except in the CRC-SPIN model assuming 100% adherence (incremental cost-effectiveness ratio: $26 300 per life-year gained). CT colonography at 5- and 10-year screening intervals and colonoscopy were net beneficial compared with no screening in all model scenarios. The 5-year screening interval was net beneficial over the 10-year interval except in the MISCAN model when assuming 100$50 000 per life-year gained. Conclusion: All three models predict CT colonography to be more costly and less effective than non-CT colonographic screening but net beneficial compared with no screening given model assumptions

The prognosis for individuals on disability retirement An 18-year mortality follow-up study of 6887 men and women sampled from the general population

BACKGROUND: Several studies have shown a markedly higher mortality rate among disability pensioners than among non-retired. Since most disability pensions are granted because of non-fatal diseases the reason for the increased mortality therefore remains largely unknown. The aim of this study was to evaluate potential explanatory factors. METHODS: Data from five longitudinal cohort studies in Sweden, including 6,887 men and women less than 65 years old at baseline were linked to disability pension data, hospital admission data, and mortality data from 1971 until 2001. Mortality odds ratios were analyzed with Poisson regression and Cox's proportional hazards regression models. RESULTS: 1,683 (24.4%) subjects had a disability pension at baseline or received one during follow up. 525 (7.6%) subjects died during follow up. The subjects on disability pension had a higher mortality rate than the non-retired, the hazards ratio (HR) being 2.78 (95%CI 2.08–3.71) among women and 3.43 (95%CI 2.61–4.51) among men. HR was highest among individuals granted a disability pension at young ages (HR >7), and declined parallel to age at which the disability pension was granted. The higher mortality rate among the retired subjects was not explained by disability pension cause or underlying disease or differences in age, marital status, educational level, smoking habits or drug abuse. There was no significant association between reason for disability pension and cause of death. CONCLUSION: Subjects with a disability pension had increased mortality rates as compared with non-retired subjects, only modestly affected by adjustments for psycho-socio-economic factors, underlying disease, etcetera. It is unlikely that these factors were the causes of the unfavorable outcome. Other factors must be at work

Hyperinsulinaemia as long-term predictor of death and ischaemic heart disease in nondiabetic men: The Malmö Preventive Project.

Objectives. Prospective studies have indicated that hyperinsulinaemia/insulin resistance is a risk factor for ischaemic heart disease (IHD), the risk decreasing with time of follow-up. Few studies have so far investigated the role of hyperinsulinaemia in the prediction of long-term total mortality. Setting. Section of Preventive Medicine, Department of Medicine, University Hospital, Malmö, Sweden. Subjects. A total of 6074 nondiabetic, middle-aged, healthy Swedish males. Screening examination. We determined IHD risk factors including blood glucose and plasma insulin before and 2 h after an oral glucose tolerance test (OGTT). Total follow-up time was 19 years. Hyperinsulinaemia was defined as values above the 10th decentile of fasting or 2 h insulin concentration. Main outcome measures. Total mortality and cardiac event (CE) rate for IHD. Results. Unadjusted relative risks (RRs) for both death and CE were J-shaped with the highest relative risk (RR: 1.4-1.6) in the hyperinsulinaemic group compared with all other men. The RRs for death and CE were significant for fasting insulin but became nonsignificant after adjustment for other risk factors and also with a longer follow-up. The risk of death in hyperinsulinaemic men, defined on the basis of 2-h insulin level, increased with time of follow-up and was still significantly increased after 19 years [RR: 1.32 (95% CI: 1.05-1.65], even after adjustment for other risk factors. Conclusions. Fasting hyperinsulinaemia was a predictor of total mortality and IHD in nondiabetic men, although not more significantly after adjustment for other risk factors and with lengthening of follow-up time. The 2-h postglucose hyperinsulinaemia appeared to be a stronger and independent predictor of mortality over long-term follow-up. These findings support the view that insulin resistance with associated cluster of risk factors predicts increased long-term risk of mortality and IHD