A Combined Satellite-Derived Drought Indicator to Support Humanitarian Aid Organizations

Governments, aid organizations and researchers are struggling with the complexity of detecting and monitoring drought events, which leads to weaknesses regarding the translation of early warnings into action. Embedded in an advanced decision-support framework for Doctors without Borders (Médecins sans Frontières), this study focuses on identifying the added-value of combining different satellite-derived datasets for drought monitoring and forecasting in Ethiopia. The core of the study is the improvement of an existing drought index via methodical adaptations and the integration of various satellite-derived datasets. The resulting Enhanced Combined Drought Index (ECDI) links four input datasets (rainfall, soil moisture, land surface temperature and vegetation status). The respective weight of each input dataset is calculated for every grid point at a spatial resolution of 0.25 degrees (roughly 28 kilometers). In the case of data gaps in one input dataset, the weights are automatically redistributed to other available variables. Ranking the years 1992 to 2014 according to the ECDI-based warning levels allows for the identification of all large-scale drought events in Ethiopia. Our results also indicate a good match between the ECDI-based drought warning levels and reported drought impacts for both the start and the end of the season

Food security monitoring via mobile data collection and remote sensing: results from the Central African Republic

The Central African Republic is one of the world's most vulnerable countries, suffering from chronic poverty, violent conflicts and weak disaster resilience. In collaboration with Doctors without Borders/Midecins Sans Frontieres (MSF), this study presents a novel approach to collect information about socio-economic vulnerabilities related to malnutrition, access to resources and coping capacities. The first technical test was carried out in the North of the country (sub-prefecture Kabo) in May 2015. All activities were aimed at the investigation of technical feasibility, not at operational data collection, which requires a random sampling strategy. At the core of the study is an open-source Android application named SATIDA COLLECT that facilitates rapid and simple data collection. All assessments were carried out by local MSF staff after they had been trained for one day. Once a mobile network is available, all assessments can easily be uploaded to a database for further processing and trend analysis via MSF in-house software. On one hand, regularly updated food security assessments can complement traditional large-scale surveys, whose completion can take up to eight months. Ideally, this leads to a gain in time for disaster logistics. On the other hand, recording the location of every assessment via the smart phones. GPS receiver helps to analyze and display the coupling between drought risk and impacts over many years. Although the current situation in the Central African Republic is mostly related to violent conflict it is necessary to consider information about drought risk, because climatic shocks can further disrupt the already vulnerable system. SATIDA COLLECT can easily be adapted to local conditions or other applications, such as the evaluation of vaccination campaigns. Most importantly, it facilitates the standardized collection of information without pen and paper, as well as straightforward sharing of collected data with the MSF headquarters or other aid organizations

Addressing Grand Challenges in Earth Observation Science: The Earth Observation Data Centre for Water Resources Monitoring

Earth observation is entering a new era where the increasing availability of free and open global satellite data sets combined with the computing power offered by modern information technologies opens up the possibility to process high-resolution data sets at global scale and short repeat intervals in a fully automatic fashion. This will not only boost the availability of higher level earth observation data in purely quantitative terms, but can also be expected to trigger a step change in the quality and usability of earth observation data. However, the technical, scientific, and organisational challenges that need to be overcome to arrive at this point are significant. First of all, Petabyte-scale data centres are needed for storing and processing complete satellite data records. Second, innovative processing chains that allow fully automatic processing of the satellite data from the raw sensor records to higher-level geophysical products need to be developed. Last but not least, new models of cooperation between public and private actors need to be found in order to live up to the first two challenges. This paper offers a discussion of how the Earth Observation Data Centre for Water Resources Monitoring (EODC) – a catalyser for an open and international cooperation of public and private organisations – will address these three grand challenges with the aim to foster the use of earth observation for monitoring of global water resources

The Lsm2-8 complex determines nuclear localization of the spliceosomal U6 snRNA

Lsm proteins are ubiquitous, multifunctional proteins that are involved in the processing and/or turnover of many, if not all, RNAs in eukaryotes. They generally interact only transiently with their substrate RNAs, in keeping with their likely roles as RNA chaperones. The spliceosomal U6 snRNA is an exception, being stably associated with the Lsm2-8 complex. The U6 snRNA is generally considered to be intrinsically nuclear but the mechanism of its nuclear retention has not been demonstrated, although La protein has been implicated. We show here that the complete Lsm2-8 complex is required for nuclear accumulation of U6 snRNA in yeast. Therefore, just as Sm proteins effect nuclear localization of the other spliceosomal snRNPs, the Lsm proteins mediate U6 snRNP localization except that nuclear retention is the likely mechanism for the U6 snRNP. La protein, which binds only transiently to the nascent U6 transcript, has a smaller, apparently indirect, effect on U6 localization that is compatible with its proposed role as a chaperone in facilitating U6 snRNP assembly

Altered Composition of Liver Proteasome Assemblies Contributes to Enhanced Proteasome Activity in the Exceptionally Long-Lived Naked Mole-Rat

The longest-lived rodent, the naked mole-rat (Bathyergidae; Heterocephalus glaber), maintains robust health for at least 75% of its 32 year lifespan, suggesting that the decline in genomic integrity or protein homeostasis routinely observed during aging, is either attenuated or delayed in this extraordinarily long-lived species. The ubiquitin proteasome system (UPS) plays an integral role in protein homeostasis by degrading oxidatively-damaged and misfolded proteins. In this study, we examined proteasome activity in naked mole-rats and mice in whole liver lysates as well as three subcellular fractions to probe the mechanisms behind the apparently enhanced effectiveness of UPS. We found that when compared with mouse samples, naked mole-rats had significantly higher chymotrypsin-like (ChT-L) activity and a two-fold increase in trypsin-like (T-L) in both whole lysates as well as cytosolic fractions. Native gel electrophoresis of the whole tissue lysates showed that the 20S proteasome was more active in the longer-lived species and that 26S proteasome was both more active and more populous. Western blot analyses revealed that both 19S subunits and immunoproteasome catalytic subunits are present in greater amounts in the naked mole-rat suggesting that the observed higher specific activity may be due to the greater proportion of immunoproteasomes in livers of healthy young adults. It thus appears that proteasomes in this species are primed for the efficient removal of stress-damaged proteins. Further characterization of the naked mole-rat proteasome and its regulation could lead to important insights on how the cells in these animals handle increased stress and protein damage to maintain a longer health in their tissues and ultimately a longer life

Systematic Identification of Novel, Essential Host Genes Affecting Bromovirus RNA Replication

Positive-strand RNA virus replication involves viral proteins and cellular proteins at nearly every replication step. Brome mosaic virus (BMV) is a well-established model for dissecting virus-host interactions and is one of very few viruses whose RNA replication, gene expression and encapsidation have been reproduced in the yeast Saccharomyces cerevisiae. Previously, our laboratory identified ∼100 non-essential host genes whose loss inhibited or enhanced BMV replication at least 3-fold. However, our isolation of additional BMV-modulating host genes by classical genetics and other results underscore that genes essential for cell growth also contribute to BMV RNA replication at a frequency that may be greater than that of non-essential genes. To systematically identify novel, essential host genes affecting BMV RNA replication, we tested a collection of ∼900 yeast strains, each with a single essential gene promoter replaced by a doxycycline-repressible promoter, allowing repression of gene expression by adding doxycycline to the growth medium. Using this strain array of ∼81% of essential yeast genes, we identified 24 essential host genes whose depleted expression reproducibly inhibited or enhanced BMV RNA replication. Relevant host genes are involved in ribosome biosynthesis, cell cycle regulation and protein homeostasis, among other cellular processes. BMV 2aPol levels were significantly increased in strains depleted for a heat shock protein (HSF1) or proteasome components (PRE1 and RPT6), suggesting these genes may affect BMV RNA replication by directly or indirectly modulating 2aPol localization, post-translational modification or interacting partners. Investigating the diverse functions of these newly identified essential host genes should advance our understanding of BMV-host interactions and normal cellular pathways, and suggest new modes of virus control

Trials

BACKGROUND: The aim of this open-label, randomized controlled trial conducted in four African countries (Madagascar, Niger, Central African Republic, and Senegal) is to compare three strategies of renutrition for moderate acute malnutrition (MAM) in children based on modulation of the gut microbiota with enriched flours alone, enriched flours with prebiotics or enriched flours coupled with antibiotic treatment. METHODS: To be included, children aged between 6 months and 2 years are preselected based on mid-upper-arm circumference (MUAC) and are included based on a weight-for-height Z-score (WHZ) between - 3 and - 2 standard deviations (SD). As per current protocols, children receive renutrition treatment for 12 weeks and are assessed weekly to determine improvement. The primary endpoint is recovery, defined by a WHZ >/= - 1.5 SD after 12 weeks of treatment. Data collected include clinical and socioeconomic characteristics, side effects, compliance and tolerance to interventions. Metagenomic analysis of gut microbiota is conducted at inclusion, 3 months, and 6 months. The cognitive development of children is evaluated in Senegal using only the Developmental Milestones Checklist II (DMC II) questionnaire at inclusion and at 3, 6, and 9 months. The data will be correlated with renutrition efficacy and metagenomic data. DISCUSSION: This study will provide new insights for the treatment of MAM, as well as original data on the modulation of gut microbiota during the renutrition process to support (or not) the microbiota hypothesis of malnutrition. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03474276 Last update 28 May 2018

The Role of Proteasome Beta Subunits in Gastrin-Mediated Transcription of Plasminogen Activator Inhibitor-2 and Regenerating Protein1

The hormone gastrin physiologically regulates gastric acid secretion and also contributes to maintaining gastric epithelial architecture by regulating expression of genes such as plasminogen activator inhibitor 2 (PAI-2) and regenerating protein 1(Reg1). Here we examine the role of proteasome subunit PSMB1 in the transcriptional regulation of PAI-2 and Reg1 by gastrin, and its subcellular distribution during gastrin stimulation. We used the gastric cancer cell line AGS, permanently transfected with the CCK2 receptor (AGS-GR) to study gastrin stimulated expression of PAI-2 and Reg1 reporter constructs when PSMB1 was knocked down by siRNA. Binding of PSMB1 to the PAI-2 and Reg1 promoters was assessed by chromatin immunoprecipitation (ChIP) assay. Subcellular distribution of PSMB1 was determined by immunocytochemistry and Western Blot. Gastrin robustly increased expression of PAI-2 and Reg1 in AGS-GR cells, but when PSMB1 was knocked down the responses were dramatically reduced. In ChIP assays, following immunoprecipitation of chromatin with a PSMB1 antibody there was a substantial enrichment of DNA from the gastrin responsive regions of the PAI-2 and Reg1 promoters compared with chromatin precipitated with control IgG. In AGS-GR cells stimulated with gastrin there was a significant increase in the ratio of nuclear:cytoplasmic PSMB1 over the same timescale as recruitment of PSMB1 to the PAI-2 and Reg1 promoters seen in ChIP assays. We conclude that PSMB1 is part of the transcriptional machinery required for gastrin stimulated expression of PAI-2 and Reg1, and that its change in subcellular distribution in response to gastrin is consistent with this role