Computational models in plant-pathogen interactions: the case of Phytophthora infestans

<p>Abstract</p> <p>Background</p> <p><it>Phytophthora infestans </it>is a devastating oomycete pathogen of potato production worldwide. This review explores the use of computational models for studying the molecular interactions between <it>P. infestans </it>and one of its hosts, <it>Solanum tuberosum</it>.</p> <p>Modeling and conclusion</p> <p>Deterministic logistics models have been widely used to study pathogenicity mechanisms since the early 1950s, and have focused on processes at higher biological resolution levels. In recent years, owing to the availability of high throughput biological data and computational resources, interest in stochastic modeling of plant-pathogen interactions has grown. Stochastic models better reflect the behavior of biological systems. Most modern approaches to plant pathology modeling require molecular kinetics information. Unfortunately, this information is not available for many plant pathogens, including <it>P. infestans</it>. Boolean formalism has compensated for the lack of kinetics; this is especially the case where comparative genomics, protein-protein interactions and differential gene expression are the most common data resources.</p

Locus for severity implicates CNS resilience in progression of multiple sclerosis

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that results in significant neurodegeneration in the majority of those affected and is a common cause of chronic neurological disability in young adults(1,2). Here, to provide insight into the potential mechanisms involved in progression, we conducted a genome-wide association study of the age-related MS severity score in 12,584 cases and replicated our findings in a further 9,805 cases. We identified a significant association with rs10191329 in the DYSF-ZNF638 locus, the risk allele of which is associated with a shortening in the median time to requiring a walking aid of a median of 3.7 years in homozygous carriers and with increased brainstem and cortical pathology in brain tissue. We also identified suggestive association with rs149097173 in the DNM3-PIGC locus and significant heritability enrichment in CNS tissues. Mendelian randomization analyses suggested a potential protective role for higher educational attainment. In contrast to immune-driven susceptibility(3), these findings suggest a key role for CNS resilience and potentially neurocognitive reserve in determining outcome in MS

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

One hundred years of EEG for brain and behaviour research

On the centenary of the first human EEG recording, more than 500 experts reflect on the impact that this discovery has had on our understanding of the brain and behaviour. We document their priorities and call for collective action focusing on validity, democratization and responsibility to realize the potential of EEG in science and society over the next 100 years

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Nutritional status of cattie : in rangelands of Mendoza (Argentina)

El trabajo se propuso determinar el estado nutricional de los bovinos durante su ciclo productivo, mediante la valoración de su orina, tomada como medida complementaria de la condición corporal de los animales y, también para pronosticar el riesgo de cetosis. La determinación de parámetros urinarios se realizó en hembras A. Angus efectuando cinco muestreos de orina, concordantes con estados fisiológicos y fases fenológicas vegetativas de las distintas pasturas naturales. Cada muestreo abarcó el 25 % del rodeo. Las muestras, extraídas principalmente por micción espontánea, fueron analizadas con tiras reactivas Multistix (Bayer). La condición corporal (escala de 1 a 5) se observó en cinco áreas del cuerpo. En junio-agosto, cuando las gramíneas están secas y el 50 % de la dieta está integrada por arbustos, no se encontraron alteraciones importantes en el urianálisis de las hembras en el tercio medio de su preñez. A mediados de septiembre, al comenzar el rebrote de las gramíneas y coincidentemente con el último tercio de la preñez se detectaron sustancias cetónicas en orina en aprox. el 40 % de los animales, sin riesgo de cetosis. En el 70 % de ellos, la condición corporal fue igual o mayor a 2,75. En enero y marzo, los meses de mayor crecimiento de las gramíneas, las hembras se encontraban en lactación. Como consecuencia del estado de hipermotilidad intestinal disminuyó la densidad urinaria, debido a la eliminación del exceso de agua, lo que originó probable deficiencia mineral relativa. El urianálisis, conjuntamente con la observación clínica y la valoración de la condición corporal, constituyó un método práctico, barato, de fácil ejecución e interpretación para determinar deficiencias en la dieta de los bovinos. Los resultados corroboran que los recursos forrajeros nativos de la llanura mendocina pueden satisfacer los requerimientos nutritivos de la vaca de cría siempre que se programe adecuadamente la época de parición.The purpose of this work was to determine the nutritional status of cattle during its production cycle by means of the urine analysis, used as a complementary measure of the body condition of the animals, and to prognosticate the risk of ketosis appearance. The determination of the urine parameters was carried out on Angus cows. Five collections of urine samples were made in accordance with different cattle physiologic status and phenological vegetative phases of native species. Each collection comprised the 25 % of the cattle herd. The urine samples were mainly obtained by spontaneous urination and were analized through Multistix (Bayer) reactive narrow stripes. The body condition (1 to 5 range) was determined by observations on five areas of the animal. In June-August, when grasses were dry and the cows diet included 50 % browse, no great alterations in the urine parameters of the dry cow mid pregnancy were found. In the middle of September, when grasses begun lo sprout and the cows were in the last third of pregnancy, ketone bodies were detected in some 40 % of the herd but without risk of ketosis appearance because of 70 % of the cows had body condition equal or higher than 2.75. When Ihe greatest growth of the grasses occurred (January and March), and coincident with the cow lactation period, and as a consequence of the intestinal hypermotility of the cows, decreasing of the urine density was detected, derived from the necessity of the cow to eliminate the water excess. This originated a probable relative mineral deficiency. The urine analysis, used jointly with data from clinical observations and body condition, constitutes a practic, cheap and easy to perform and to interpret method for determining deficiencies nati in cattle diets. The use of this method supports that the native range species of the plain of Mendoza can satisfy the cow nutrient requirements provided that the calving date is correctly planned.Fil: Van den Bosch, Silvia B.. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Departamento de Producción AgropecuariaFil: Guevara, Juan C. . Instituto Argentino de Investigaciones de las Zonas Áridas Fil: Tacchini, Fabio M. . Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Departamento de Producción Agropecuari