The BIODESERT survey: assessing the impacts of grazing on the structure and functioning of global drylands

Grazing by domestic livestock is both the main land use across drylands worldwide and a major desertification and global change driver. The ecological consequences of this key human activity have been studied for decades, and there is a wealth of information on its impacts on biodiversity and ecosystem processes. However, most field assessments of the ecological impacts of grazing on drylands conducted to date have been carried out at local or regional scales and have focused on single ecosystem attributes (e.g., plant productivity) or particular taxa (mainly aboveground, e.g., plants). Here we introduce the BIODESERT survey, the first systematic field survey devoted to evaluating the joint impacts of grazing by domestic livestock and climate on the structure and functioning of dryland ecosystems worldwide. This collaborative global survey was carried out between 2016 and 2019 and has involved the collection of field data and plant, biocrust, and soil samples from a total of 326 45 m × 45 m plots from 98 sites located in 25 countries from 6 continents. Here we describe the major characteristics and the field protocols used in this survey. We also introduce the organizational aspects followed, as these can be helpful to everyone wishing to establish a global collaborative network of researchers. The BIODESERT survey provides baseline data to assess the current status of dryland rangelands worldwide and the impacts of grazing on these key ecosystems, and it constitutes a good example of the power of collaborative research networks to study the ecology of our planet using much-needed field data.This research has been supported by the European Research Council (ERC grant agreement no. 647038 – BIODESERT) and the Conselleria de Innovación, Universidades, Ciencia y Sociedad Digital, Generalitat Valenciana (grant no. CIDEGENT/2018/041). Nicolas Gross was supported by CAP 20-25 (16-IDEX-0001) and the AgreenSkills+ fellowship program which has received funding from the EU's Seventh Framework Programme under grant agreement no. 996 FP7-609398 (AgreenSkills+ contract). Hugo Saiz is supported by a María Zambrano fellowship funded by the Ministry of Universities and European Union Next Generation plan

Clinical Characteristics of Patients with Severe Asthma by Different Elevated Biomarkers Classifications : patients from Spain in the ISAR Registry

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Baseline disease burden in severe asthma patients treated with biologics, and eligible but not treated : Spanish patients in the ISAR Registry

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Assay strategies for the discovery and validation of therapeutics targeting <i>Brugia pahangi</i> Hsp90

The chemotherapy of lymphatic filariasis relies upon drugs such as diethylcarbamazine and ivermectin that largely target the microfilarial stages of the parasite, necessitating continued treatment over the long reproductive life span of the adult worm. The identification of compounds that target adult worms has been a long-term goal of WHO. Here we describe a fluorescence polarization assay for the identification of compounds that target Hsp90 in adult filarial worms. The assay was originally developed to identify inhibitors of Hsp90 in tumor cells, and relies upon the ability of small molecules to inhibit the binding of fluorescently labelled geldanamycin to Hsp90. We demonstrate that the assay works well with soluble extracts of Brugia, while extracts of the free-living nematode C. elegans fail to bind the probe, in agreement with data from other experiments. The assay was validated using known inhibitors of Hsp90 that compete with geldanamycin for binding to Hsp90, including members of the synthetic purine-scaffold series of compounds. The efficacy of some of these compounds against adult worms was confirmed in vitro. Moreover, the assay is sufficiently sensitive to differentiate between binding of purine-scaffold compounds to human and Brugia Hsp90. The assay is suitable for high-throughput screening and provides the first example of a format with the potential to identify novel inhibitors of Hsp90 in filarial worms and in other parasitic species where Hsp90 may be a target

Molecular profiling of signet ring cell colorectal cancer provides a strong rationale for genomic targeted and immune checkpoint inhibitor therapies

We would like to thank all patients whose samples were used in this study. We are also thankful to the Northern Ireland Biobank and Grampian Biorepository for providing us with tissue blocks and patient data; and Dr HG Coleman (Queen’s University Belfast) for her advice on statistical analyses. This work has been carried out with financial support from Cancer Research UK (grant: C11512/A18067), Experimental Cancer Medicine Centre Network (grant: C36697/A15590 from Cancer Research UK and the NI Health and Social Care Research and Development Division), the Sean Crummey Memorial Fund and the Tom Simms Memorial Fund. The Northern Ireland Biobank is funded by HSC Research and Development Division of the Public Health Agency in Northern Ireland and Cancer Research UK through the Belfast CRUK Centre and the Northern Ireland Experimental Cancer Medicine Centre; additional support was received from Friends of the Cancer Centre. The Northern Ireland Molecular Pathology Laboratory which is responsible for creating resources for the Northern Ireland Biobank has received funding from Cancer Research UK, Friends of the Cancer Centre and Sean Crummey Foundation.Peer reviewedPublisher PD

Structural Variants Drive Context-Dependent Oncogene Activation in Cancer

Higher-order chromatin structure is important for the regulation of genes by distal regulatory sequences. Structural variants (SVs) that alter three-dimensional (3D) genome organization can lead to enhancer-promoter rewiring and human disease, particularly in the context of cancer3. However, only a small minority of SVs are associated with altered gene expression4,5, and it remains unclear why certain SVs lead to changes in distal gene expression and others do not. To address these questions, we used a combination of genomic profiling and genome engineering to identify sites of recurrent changes in 3D genome structure in cancer and determine the effects of specific rearrangements on oncogene activation. By analysing Hi-C data from 92 cancer cell lines and patient samples, we identified loci affected by recurrent alterations to 3D genome structure, including oncogenes such as MYC, TERT and CCND1. By using CRISPR-Cas9 genome engineering to generate de novo SVs, we show that oncogene activity can be predicted by using \u27activity-by-contact\u27 models that consider partner region chromatin contacts and enhancer activity. However, activity-by-contact models are only predictive of specific subsets of genes in the genome, suggesting that different classes of genes engage in distinct modes of regulation by distal regulatory elements. These results indicate that SVs that alter 3D genome organization are widespread in cancer genomes and begin to illustrate predictive rules for the consequences of SVs on oncogene activation

Functional rarity and evenness are key facets of biodiversity to boost multifunctionality

The functional traits of organisms within multispecies assemblages regulate biodiversity effects on ecosystem functioning. Yet how traits should assemble to boost multiple ecosystem functions simultaneously (multifunctionality) remains poorly explored. In a multibiome litter experiment covering most of the global variation in leaf trait spectra, we showed that three dimensions of functional diversity (dispersion, rarity, and evenness) explained up to 66% of variations in multifunctionality, although the dominant species and their traits remained an important predictor. While high dispersion impeded multifunctionality, increasing the evenness among functionally dissimilar species was a key dimension to promote higher multifunctionality and to reduce the abundance of plant pathogens. Because too-dissimilar species could have negative effects on ecosystems, our results highlight the need for not only diverse but also functionally even assemblages to promote multifunctionality. The effect of functionally rare species strongly shifted from positive to negative depending on their trait differences with the dominant species. Simultaneously managing the dispersion, evenness, and rarity in multispecies assemblages could be used to design assemblages aimed at maximizing multifunctionality independently of the biome, the identity of dominant species, or the range of trait values considered. Functional evenness and rarity offer promise to improve the management of terrestrial ecosystems and to limit plant disease risks.This work was funded by the British Ecological Society (SR17\1297 grant, PI: P.G.-P.) and by the European Research Council (ERC Grant Agreement #647038, BIODESERT, PI: F.T.M.). Y.L.B.-P. was supported by a Marie Sklodowska-Curie Actions Individual Fellowship within the European Program Horizon 2020 (DRYFUN Project #656035). H.S. was supported by a Juan de la Cierva-Formación grant from the Spanish Ministry of Economy and Competitiveness (FJCI-2015-26782). F.T.M. and S.A. were supported from the Generalitat Valenciana (CIDEGENT/2018/041). M.D. was supported by a Formación del Profesorado Universitario (FPU) fellowship from the Spanish Ministry of Education, Culture and Sports (FPU-15/00392). S.A. was supported by the Spanish MINECO for financial support via the DIGGING_DEEPER project through the 2015 to 2016 BiodivERsA3/FACCE‐JPI joint call for research proposals. B.K.S. research on biodiversity-ecosystem functions was supported by the Australian Research Council (DP170104634 and DP190103714). P.G.-P. was supported by a Ramón y Cajal grant from the Spanish Ministry of Science and Innovation (RYC2018-024766-I). R.M. was supported by MINECO (Grants CGL2014-56567-R and CGL2017-83855-R)

Biomarkers expression, treatment and disease burden in a cohort of Italian patients affected by severe asthma : a sub analysis of the ISAR EVEREST study

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