Metatranscriptomic analysis of larvae guts from field-collected and laboratory-reared Spodoptera frugiperda from the South American subtropical region

This is the first study to report a high-throughput approach integrating gene expression data from Spodoptera frugiperda guts and their associated metatranscriptomes. Our datasets provide information on the potential effects of environmental conditions on the expression profile of S. frugiperda larval guts, their associated metatranscriptome, and putative interactions between them.Fil: Mccarthy, Cristina Beryl. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Universidad Nacional del Noroeste de la Provincia de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cabrera, Natalia Alina. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; ArgentinaFil: Virla, Eduardo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Planta Piloto de Procesos Industriales Microbiologicos; Argentin

Inside the gut: Revelations of metatranscriptomic and transcriptomic analyses of Spodoptera frugiperda larvae from an organic maize plantation at 2283 meters above sea level (Tafí del Valle, Tucumán)

Spodoptera frugiperda is a noctuid moth that devastates various crops, including corn, and is found in most of the American continent. Transgenic crops that produce insecticidal proteins from Bacillus thuringiensis are currently the most successful biotechnological pest management application, but S. frugiperda has developed field-evolved resistance. In this regard, insect gut microbiota conform a complex community that establishes symbiotic relationships with its host, contributing to its viability. For this reason, metatranscriptomic and transcriptomic analyses of insect guts in their natural environment are invaluable to better comprehend their biology and to identify genes as targets for pest control. We previously captured S. frugiperda specimens from different environments, altitudes and food sources in the province of Tucumán (Argentina). For all samples, total RNA extracted from fifth instar larval guts was submitted to a one-step reverse transcription and PCR sequence independent amplification procedure, and then pyrosequenced. In this study we analysed one of these samples, namely, larvae that were captured in an organic maize field in Tafí del Valle (26°55´40.75´´S, 65°45´19.90´´W; Tucumán province) at 2283 meters above sea level. Sequence reads were trimmed and assembled. Homology searches were performed against various NCBI databases. Taxonomic and functional contents were analysed with MEGAN. The metatranscriptome, in which we identified sequences from archaea, bacteria, fungi, nematodes and plants, revealed potential biocontrol candidates for this pest, and others related with host metabolism and digestion. Furthermore, the host transcriptome showed that most transcripts were associated with the digestive tract structure and development, among others. Some of these genes could be possible targets for pest control via RNA interference (RNAi). In summary, this study has shown the potential effects of this particular food source (i.e., organic maize) and of the environmental conditions (altitude, among others), on the expression profile of S. frugiperda larval guts, their associated metatranscriptome, and putative interactions between them. Future studies will test the potential biocontrol candidates that we identified.Fil: Rozadilla, Gastón. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cabrera, Natalia Alina. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; ArgentinaFil: Virla, Eduardo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Planta Piloto de Procesos Industriales Microbiológicos; ArgentinaFil: Mccarthy, Cristina Beryl. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; ArgentinaX Congreso Argentino de EntomologíaMendozaArgentinaSociedad Argentina de EntomologíaUniversidad Nacional de Cuyo. Facultad de Ciencias AgrariasUniversidad Nacional de Cuyo. Instituto Argentino de Investigaciones de las Zonas ÁridasInstituto Nacional de Tecnología Agropecuari

Safety, Tolerability, Pharmacokinetics, and Antimalarial Activity of the Novel Plasmodium Phosphatidylinositol 4-Kinase Inhibitor MMV390048 in Healthy Volunteers.

MMV390048 is a novel antimalarial compound that inhibits Plasmodium phosphatidylinositol-4-kinase. The safety, tolerability, pharmacokinetic profile, and antimalarial activity of MMV390048 were determined in healthy volunteers in three separate studies. A first-in-human, double-blind, randomized, placebo-controlled, single-ascending-dose study was performed. Additionally, a volunteer infection study investigated the antimalarial activity of MMV390048 using the Plasmodium falciparum induced blood-stage malaria (IBSM) model. Due to the high pharmacokinetic variability with the powder-in-bottle formulation used in both of these studies, a third study was undertaken to select a tablet formulation of MMV390048 to take forward into future studies. MMV390048 was generally well tolerated when administered as a single oral dose up to 120 mg, with rapid absorption and a long elimination half-life. Twelve adverse events were considered to be potentially related to MMV390048 in the first-in-human study but with no obvious correlation between these and MMV390048 dose or exposure. Although antimalarial activity was evident in the IBSM study, rapid recrudescence occurred in most subjects after treatment with 20 mg MMV390048, a dose expected to be subtherapeutic. Reformulation of MMV390048 into two tablet formulations (tartaric acid and Syloid) resulted in significantly reduced intersubject pharmacokinetic variability. Overall, the results of this study suggest that MMV390048 is well tolerated in humans, and the pharmacokinetic properties of the compound indicate that it has the potential to be used for antimalarial prophylaxis or inclusion in a single-dose cure. MMV390048 is currently being tested in a phase 2a study in Ethiopian adults with acute, uncomplicated falciparum or vivax malaria monoinfection. (The three clinical trials described here were each registered with ClinicalTrials.gov as follows: first-in-human study, registration no. NCT02230579; IBSM study, registration no. NCT02281344; and formulation optimization study, registration no. NCT02554799.)

Abundance gradient slopes versus mass in spheroids: predictions by monolithic models

We investigate whether it is possible to explain the wide range of observed gradients in early type galaxies in the framework of monolithic models. To do so, we extend the set of hydrodynamical simulations by Pipino et al. (2008a) by including low-mass ellipticals and spiral (true) bulges. These models satisfy the mass-metallicity and the mass-[alpha/Fe] relations. The typical metallicity gradients predicted by our models have a slope of -0.3 dex per decade variation in radius, consistent with the mean values of several observational samples. However, we also find a few quite massive galaxies in which this slope is -0.5 dex per decade, in agreement with some recent data. In particular, we find a mild dependence from the mass tracers when we transform the stellar abundance gradients into radial variations of the Mg_2 line-strength index, but not in the Mg_b. We conclude that, rather than a mass- slope relation, is more appropriate to speak of an increase in the scatter of the gradient slope with the galactic mass. We can explain such a behaviour with different efficiencies of star formation in the framework of the revised monolithic formation scenario, hence the scatter in the observed gradients should not be used as an evidence of the need of mergers. Indeed, model galaxies that exhibit the steepest gradient slopes are preferentially those with the highest star formation efficiency at that given mass.Comment: Accepted for publication by MNRAS, the paper contains 7 figures and 2 table

The general population cohort in rural south-western Uganda: a platform for communicable and non-communicable disease studies.

The General Population Cohort (GPC) was set up in 1989 to examine trends in HIV prevalence and incidence, and their determinants in rural south-western Uganda. Recently, the research questions have included the epidemiology and genetics of communicable and non-communicable diseases (NCDs) to address the limited data on the burden and risk factors for NCDs in sub-Saharan Africa. The cohort comprises all residents (52% aged ≥13years, men and women in equal proportions) within one-half of a rural sub-county, residing in scattered houses, and largely farmers of three major ethnic groups. Data collected through annual surveys include; mapping for spatial analysis and participant location; census for individual socio-demographic and household socioeconomic status assessment; and a medical survey for health, lifestyle and biophysical and blood measurements to ascertain disease outcomes and risk factors for selected participants. This cohort offers a rich platform to investigate the interplay between communicable diseases and NCDs. There is robust infrastructure for data management, sample processing and storage, and diverse expertise in epidemiology, social and basic sciences. For any data access enquiries you may contact the director, MRC/UVRI, Uganda Research Unit on AIDS by email to [email protected] or the corresponding author

Negotiated reorienting: a grounded theory of nurses’ end-of-life decision-making in the intensive care unit

Background Intensive care units (ICUs) focus on treatment for those who are critically ill and interventions to prolong life. Ethical issues arise when decisions have to be made regarding the withdrawal and withholding of life-sustaining treatment and the shift to comfort and palliative care. These issues are particularly challenging for nurses when there are varying degrees of uncertainty regarding prognosis. Little is known about nurses’ end-of-life (EoL) decision-making practice across cultures. Objectives To understand nurses’ EoL decision-making practices in ICUs in different cultural contexts. Design We collected and analysed qualitative data using Grounded Theory. Settings Interviews were conducted with experienced ICU nurses in university or hospital premises in five countries: Brazil, England, Germany, Ireland and Palestine. Participants Semi-structured interviews were conducted with 51 nurses (10 in Brazil, 9 in

The Eighth Data Release of the Sloan Digital Sky Survey: First Data from SDSS-III

The Sloan Digital Sky Survey (SDSS) started a new phase in August 2008, with new instrumentation and new surveys focused on Galactic structure and chemical evolution, measurements of the baryon oscillation feature in the clustering of galaxies and the quasar Ly alpha forest, and a radial velocity search for planets around ~8000 stars. This paper describes the first data release of SDSS-III (and the eighth counting from the beginning of the SDSS). The release includes five-band imaging of roughly 5200 deg^2 in the Southern Galactic Cap, bringing the total footprint of the SDSS imaging to 14,555 deg^2, or over a third of the Celestial Sphere. All the imaging data have been reprocessed with an improved sky-subtraction algorithm and a final, self-consistent photometric recalibration and flat-field determination. This release also includes all data from the second phase of the Sloan Extension for Galactic Understanding and Evolution (SEGUE-2), consisting of spectroscopy of approximately 118,000 stars at both high and low Galactic latitudes. All the more than half a million stellar spectra obtained with the SDSS spectrograph have been reprocessed through an improved stellar parameters pipeline, which has better determination of metallicity for high metallicity stars.Comment: Astrophysical Journal Supplements, in press (minor updates from submitted version

Endoplasmic Reticulum Stress signalling - from basic mechanisms to clinical applications

The endoplasmic reticulum (ER) is a membranous intracellular organelle and the first compartment of the secretory pathway. As such, the ER contributes to the production and folding of approximately one-third of cellular proteins, and is thus inextricably linked to the maintenance of cellular homeostasis and the fine balance between health and disease. Specific ER stress signalling pathways, collectively known as the unfolded protein response (UPR), are required for maintaining ER homeostasis. The UPR is triggered when ER protein folding capacity is overwhelmed by cellular demand and the UPR initially aims to restore ER homeostasis and normal cellular functions. However, if this fails, then the UPR triggers cell death. In this review, we provide a UPR signalling-centric view of ER functions, from the ER's discovery to the latest advancements in the understanding of ER and UPR biology. Our review provides a synthesis of intracellular ER signalling revolving around proteostasis and the UPR, its impact on other organelles and cellular behaviour, its multifaceted and dynamic response to stress and its role in physiology, before finally exploring the potential exploitation of this knowledge to tackle unresolved biological questions and address unmet biomedical needs. Thus, we provide an integrated and global view of existing literature on ER signalling pathways and their use for therapeutic purposes

Saharan dust and association between particulate matter and case-specific mortality: a case-crossover analysis in Madrid (Spain)

<p>Abstract</p> <p>Background</p> <p>Saharan dust intrusions are a common phenomenon in the Madrid atmosphere, leading induce exceedances of the 50 μg/m³- EU 24 h standard for PM₁₀.</p> <p>Methods</p> <p>We investigated the effects of exposure to PM₁₀between January 2003 and December 2005 in Madrid (Spain) on daily case-specific mortality; changes of effects between Saharan and non-Saharan dust days were assessed using a time-stratified case-crossover design.</p> <p>Results</p> <p>Saharan dust affected 20% of days in the city of Madrid. Mean concentration of PM₁₀was higher during dust days (47.7 μg/m³) than non-dust days (31.4 μg/m³). The rise of mortality per 10 μg/m³PM₁₀concentration were always largely for Saharan dust-days. When stratifying by season risks of PM₁₀, at lag 1, during Saharan dust days were stronger for respiratory causes during cold season (IR% = 3.34% (95% CI: 0.36, 6.41) versus 2.87% (95% CI: 1.30, 4.47)) while for circulatory causes effects were stronger during warm season (IR% = 4.19% (95% CI: 1.34, 7.13) versus 2.65% (95% CI: 0.12, 5.23)). No effects were found for cerebrovascular causes.</p> <p>Conclusions</p> <p>We found evidence of strongest effects of particulate matter during Saharan dust days, providing a suggestion of effect modification, even though interaction terms were not statistically significant. Further investigation is needed to understand the mechanism by which Saharan dust increases mortality.</p