Whole-brain functional hypoconnectivity as an endophenotype of autism in adolescents.

Endophenotypes are heritable and quantifiable markers that may assist in the identification of the complex genetic underpinnings of psychiatric conditions. Here we examined global hypoconnectivity as an endophenotype of autism spectrum conditions (ASCs). We studied well-matched groups of adolescent males with autism, genetically-related siblings of individuals with autism, and typically-developing control participants. We parcellated the brain into 258 regions and used complex-network analysis to detect a robust hypoconnectivity endophenotype in our participant group. We observed that whole-brain functional connectivity was highest in controls, intermediate in siblings, and lowest in ASC, in task and rest conditions. We identified additional, local endophenotype effects in specific networks including the visual processing and default mode networks. Our analyses are the first to show that whole-brain functional hypoconnectivity is an endophenotype of autism in adolescence, and may thus underlie the heritable similarities seen in adolescents with ASC and their relatives.The authors wish to thank the participants and their families for their participation and the autism support organisations who assisted with recruitment. We thank colleagues at the Brain Mapping Unit for methodological discussions and thank Meng-Chuan Lai, Amber Ruigrok and Richard Bethlehem for the same. Data collection was funded by a Clinical Scientist Fellowship from the UK Medical Research Council (MRC) (G0701919) to MDS. LRC was supported by the Gates Cambridge Scholarship Trust. The study was conducted in associated with the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for Cambridgeshire, and Peterborough National Health Service (NHS) Foundation Trust. The present analysis was funded by a NARSAD Young Investigator award (to MR) and by the Isaac Newton Trust (to MR); RJFY is additionally supported by a Rubicon Fellowship from the Netherlands Organisation for Scientific Research. The Brain Mapping Unit (MR, RLM, RJFY, JS and ETB) is part of the Behavioural & Clinical Neuroscience Institute, which is funded by the MRC and the Wellcome Trust. High performance computing facilities were supported by the NIHR Cambridge Biomedical Research Centre.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.nicl.2015.07.01

Spatio-temporal variability of droughts in Bolivia: 1955-2012

In this study, the spatio-temporal variability and trends of droughts across Bolivia between 1955 and 2012 were investigated using two climate drought indices: the Standardized Precipitation Index (SPI), which is based on precipitation data, and the Standardized Precipitation Evapotranspiration Index (SPEI), which is based on the difference between the precipitation and the reference evapotranspiration (ETo). We found that the average drought conditions across the country showed a temporal behaviour mainly characterized by decadal variations. The spatial pattern of drought evolution showed marked differences between the Amazonian region and the Bolivian Altiplano. Both regions showed different drought periods, a lower frequency of drought variability in the Amazon region and trends towards drier conditions in the Altiplano, mainly due to a higher atmospheric water demand as a consequence of increased ETo. We also showed that inclusion of ETo, obtained from maximum and minimum temperature records, increased the spatial heterogeneity of the drought evolution in relation to the evolution observed when only precipitation droughts were considered. The SPEI, the calculation of which includes precipitation and ETo, indicated intensification in drought severity in the last years analysed relative to the pattern found when precipitation droughts alone were considered, and also indicated an increase in the magnitude and duration of drought events. The potential for increasing drought conditions under various climate change scenarios is discussed. © 2015 Royal Meteorological Society.This work has been supported by research projects I-COOP H2O 2013CD0006: ‘Test multisectorial y actividades demostrativa sobre el potencial desarrollo de sistemas de monitorización de sequías en tiempo real en la región del oeste de Sudamérica’ financed by the Spanish National Research Council (CSIC), CGL2011-27574-CO2-02 financed by the Spanish Commission of Science and Technology and FEDER, ‘Demonstration and validation of innovative methodology for regional climate change adaptation in the Mediterranean area (LIFE MEDACC)’ financed by the LIFE programme of the European Commission, C.A.-M. received a postdoctoral fellowship # JCI-2011-10263. A.S.-L. is supported by the ‘Secretaria per a Universitats i Recerca del Departament d'Economia i Coneixement, de la Generalitat de Catalunya i del programa Cofund de les Accions Marie Curie del 7è Programa marc d'R + D de la Unió Europea’ (2011 BP-B 00078) and the postdoctoral fellowship # JCI-2012-12508.Peer Reviewe

Refolding by High Pressure of a Toxin Containing Seven Disulfide Bonds: Bothropstoxin-1 from Bothrops jararacussu

Aggregation is a serious obstacle for recovery of biologically active heterologous proteins from inclusion bodies (IBs) produced by recombinant bacteria. E. coli transformed with a vector containing the cDNA for Bothropstoxin-1 (BthTx-1) expressed the recombinant product as IBs. In order to obtain the native toxin, insoluble and aggregated protein was refolded using high hydrostatic pressure (HHP). IBs were dissolved and refolded (2 kbar, 16 h), and the effects of protein concentration, as well as changes in ratio and concentration of oxido-shuffling reagents, guanidine hydrochloride (GdnHCl), and pH in the refolding buffer, were assayed. A 32% yield (7.6 mg per liter of bacterial culture) in refolding of the native BthTx-1 was obtained using optimal conditions of the refolding buffer (Tris–HCl buffer, pH 7.5, containing 3 mM of a 2:3 ratio of GSH/GSSG, and 1 M GdnHCl). Scanning electron microscopy (SEM) showed that that disaggregation of part of IBs particles occurred upon compression and that the morphology of the remaining IBs, spherical particles, was not substantially altered. Dose-dependent cytotoxic activity of high-pressure refolded BthTx-1 was shown in C2C12 muscle cells

Quinoa Phenotyping Methodologies: An International Consensus

Quinoa is a crop originating in the Andes but grown more widely and with the genetic potential for significant further expansion. Due to the phenotypic plasticity of quinoa, varieties need to be assessed across years and multiple locations. To improve comparability among field trials across the globe and to facilitate collaborations, components of the trials need to be kept consistent, including the type and methods of data collected. Here, an internationally open-access framework for phenotyping a wide range of quinoa features is proposed to facilitate the systematic agronomic, physiological and genetic characterization of quinoa for crop adaptation and improvement. Mature plant phenotyping is a central aspect of this paper, including detailed descriptions and the provision of phenotyping cards to facilitate consistency in data collection. High-throughput methods for multi-temporal phenotyping based on remote sensing technologies are described. Tools for higher throughput post-harvest phenotyping of seeds are presented. A guideline for approaching quinoa field trials including the collection of environmental data and designing layouts with statistical robustness is suggested. To move towards developing resources for quinoa in line with major cereal crops, a database was created. The Quinoa Germinate Platform will serve as a central repository of data for quinoa researchers globally

Targeted anti-vascular therapies for ovarian cancer: current evidence

Ovarian cancer presents at advanced stage in around 75% of women, and despite improvements in treatments such as chemotherapy, the 5-year survival from the disease in women diagnosed between 1996 and 1999 in England and Wales was only 36%. Over 80% of patients with advanced ovarian cancer will relapse and despite a good chance of remission from further chemotherapy, they will usually die from their disease. Sequential treatment strategies are employed to maximise quality and length of life but patients eventually become resistant to cytotoxic agents. The expansion in understanding of the molecular biology that characterises cancer cells has led to the rapid development of new agents to target important pathways but the heterogeneity of ovarian cancer biology means that there is no predominant defect. This review attempts to discuss progress to date in tackling a more general target applicable to ovary cancer-angiogenesis

Mutations in DCC cause isolated agenesis of the corpus callosum with incomplete penetrance

Brain malformations involving the corpus callosum are common in children with developmental disabilities. We identified DCC mutations in four families and five sporadic individuals with isolated agenesis of the corpus callosum (ACC) without intellectual disability. DCC mutations result in variable dominant phenotypes with decreased penetrance, including mirror movements and ACC associated with a favorable developmental prognosis. Possible phenotypic modifiers include the type and location of mutation and the sex of the individual

Enteric methane mitigation strategies for ruminant livestock systems in the Latin America and Caribbean region: a meta-analysis.

Latin America and Caribbean (LAC) is a developing region characterized for its importance for global food security, producing 23 and 11% of the global beef and milk production, respectively. The region?s ruminant livestock sector however, is under scrutiny on environmental grounds due to its large contribution to enteric methane (CH4) emissions and influence on global climate change. Thus, the identification of effective CH4 mitigation strategies which do not compromise animal performance is urgently needed, especially in context of the Sustainable Development Goals (SDG) defined in the Paris Agreement of the United Nations. Therefore, the objectives of the current study were to: 1) collate a database of individual sheep, beef and dairy cattle records from enteric CH4 emission studies conducted in the LAC region, and 2) perform a meta-analysis to identify feasible enteric CH4 mitigation strategies, which do not compromise animal performance. After outlier?s removal, 2745 animal records (65% of the original data) from 103 studies were retained (from 2011 to 2021) in the LAC database. Potential mitigation strategies were classified into three main categories (i.e., animal breeding, dietary, and rumen manipulation) and up to three subcategories, totaling 34 evaluated strategies. A random effects model weighted by inverse variance was used (Comprehensive Meta-Analysis V3.3.070). Six strategies decreased at least one enteric CH4 metric and simultaneously increased milk yield (MY; dairy cattle) or average daily gain (ADG; beef cattle and sheep). The breed composition F1 Holstein × Gyr decreased CH4 emission per MY (CH4IMilk) while increasing MY by 99%. Adequate strategies of grazing management under continuous and rotational stocking decreased CH4 emission per ADG (CH4IGain) by 22 and 35%, while increasing ADG by 22 and 71%, respectively. Increased dietary protein concentration, and increased concentrate level through cottonseed meal inclusion, decreased CH4IMilk and CH4IGain by 10 and 20% and increased MY and ADG by 12 and 31%, respectively. Lastly, increased feeding level decreased CH4IGain by 37%, while increasing ADG by 171%. The identified effective mitigation strategies can be adopted by livestock producers according to their specific needs and aid LAC countries in achieving SDG as defined in the Paris Agreement

Recent temperature variability and change in the Altiplano of Bolivia and Peru

This work analysed the changes in air temperature in 25 meteorological stations in the Altiplano and the surrounding Andean slopes of Bolivia and Peru, and their relationship with El Niño-Southern Oscillation (SO) and the Pacific Decadal Oscillation (PDO). The analysis focused on annual, warm season (DJF) and cold season (JJA) maximum and minimum temperatures. All analyses were undertaken during 1965-2012, but some analyses were also from 1945 and 1955 when data were available. Principal component analysis was applied to the annual and seasonal series to identify spatial differences of changes in maximum and minimum air temperature. There was an overall increase of temperatures since the mid-20th century. The most intense and spatially coherent warming was observed for annual and warm season maximum temperature, with warming rates from 0.15 to 0.25 °C decade-1. Changes in the cold season maximum temperature were more heterogeneous, and statistically significant trends were mostly in the Bolivian Altiplano. Minimum temperatures increased, but there was higher spatial variability and lower rates of warming. Maximum temperature was negatively correlated with the Southern Oscillation index (SO) in the warm season, and positively correlated with the SO in the cold season; there were less statistically significant correlations with the PDO, that exhibited inverse sign than those for SO. The strongest correlations were in the region near Lake Titicaca. The negative correlation of minimum temperatures with SO and the positive correlation of minimum temperatures with PDO were lower than the observed for maximum temperature. The changes in temperature and correlations with SO and PDO were highly dependent on the selected period, with stronger trends in the last 30-40 years. This suggests reinforcement of warming rates that cannot be only explained by SO and PDO variability