Weight gain and metabolic disturbances in people living with HIV who start antiretroviral therapy with, or switch to, bictegravir/emtricitabine/tenofovir alafenamide after 48 weeks of treatment: A real-world prospective study.

BACKGROUND: People living with HIV (PLWH) starting or switching to an integrase strand transfer inhibitor-based regimen are more likely to experience weight gain than other classes of antiretroviral regimens. The aim of this study was to evaluate the weight gain and metabolic disturbances in PLWH who start antiretroviral therapy (ART) with bictegravir/emtricitabine/tenofovir alafenamide and in individuals who switch from another ART to BIC/FTC/TAF after 48 weeks. METHODS: A prospective longitudinal study was conducted in an HIV clinic in Mexico. Weight and metabolic parameters were measured at baseline, 24 and 48 weeks. A paired t test and Wilcoxon signed-rank test were applied to evaluate weight and metabolic changes. RESULTS: 160 participants completed measurements, median age was 29 (IQR 26-32) and 30 (IQR 27-34) years old for the treatment-naïve and switch group respectively. In the treatment-naïve group, mean weight change was 3.8 kg (±5.8) (p < .001) and BMI increased 1.3 kg/m2 (±2) (p < .001) at 48 weeks. Incidence of BMI >25 kg/m2 was 28% (95%CI; 18%-40%) and BMI >30 kg/m2 was 7% (95%CI; 2%-16%) at 48 weeks in treatment-naïve individuals. In the switch group, mean weight gain and BMI change at 48 weeks was 2.8 kg (±5.9) and 0.9 kg/m2 (±2.0) respectively (p < .001). Incidence of BMI >25 kg/m2 was 17% (95%CI; 8%-32%) and BMI >30 kg/m2 12.8% (95%CI; 5%-26%) at 48 weeks respectively. CONCLUSIONS: Weight gain should be considered when men PLWH are treated with BIC/FTC/TAF regimen. They should be informed about this possible adverse event and strategies of intervention.

Virtual Reality Exposure Simulation for Student Veteran Social Anxiety and PTSD: A Case Study.

Exposure based exercises are a common element of many gold standard treatments for anxiety disorders and post-traumatic stress disorder and virtual reality simulations have been evaluated as a platform for providing clients with opportunities for repeated exposure during treatment. Although research on virtual reality exposure therapy (VRET) indicates effectiveness and high levels of user satisfaction, VRETs require a participant to complete exposure exercises in-offices with specialized equipment. The current exploratory case method study evaluates the experience and outcomes of one student veteran with social anxiety disorder and PTSD completing twelve sessions of VRET exposure using a mobile phone simulation of a virtual grocery store. The participant reported decreases in psychological symptoms, improvements in neurological connectivity, and better sleep quality upon completing the trial. Results suggest that VRET using a mobile application is feasible and warrants further research to evaluate effectiveness more fully. Implications include the use of a mobile based virtual reality simulation for intervening in social anxiety for student veterans.

Expression Atlas update: from tissues to single cells.

Expression Atlas is EMBL-EBI's resource for gene and protein expression. It sources and compiles data on the abundance and localisation of RNA and proteins in various biological systems and contexts and provides open access to this data for the research community. With the increased availability of single cell RNA-Seq datasets in the public archives, we have now extended Expression Atlas with a new added-value service to display gene expression in single cells. Single Cell Expression Atlas was launched in 2018 and currently includes 123 single cell RNA-Seq studies from 12 species. The website can be searched by genes within or across species to reveal experiments, tissues and cell types where this gene is expressed or under which conditions it is a marker gene. Within each study, cells can be visualized using a pre-calculated t-SNE plot and can be coloured by different features or by cell clusters based on gene expression. Within each experiment, there are links to downloadable files, such as RNA quantification matrices, clustering results, reports on protocols and associated metadata, such as assigned cell types.

ArrayExpress update - from bulk to single-cell expression data.

ArrayExpress (https://www.ebi.ac.uk/arrayexpress) is an archive of functional genomics data from a variety of technologies assaying functional modalities of a genome, such as gene expression or promoter occupancy. The number of experiments based on sequencing technologies, in particular RNA-seq experiments, has been increasing over the last few years and submissions of sequencing data have overtaken microarray experiments in the last 12 months. Additionally, there is a significant increase in experiments investigating single cells, rather than bulk samples, known as single-cell RNA-seq. To accommodate these trends, we have substantially changed our submission tool Annotare which, along with raw and processed data, collects all metadata necessary to interpret these experiments. Selected datasets are re-processed and loaded into our sister resource, the value-added Expression Atlas (and its component Single Cell Expression Atlas), which not only enables users to interpret the data easily but also serves as a test for data quality. With an increasing number of studies that combine different assay modalities (multi-omics experiments), a new more general archival resource the BioStudies Database has been developed, which will eventually supersede ArrayExpress. Data submissions will continue unchanged; all existing ArrayExpress data will be incorporated into BioStudies and the existing accession numbers and application programming interfaces will be maintained.

Gramene 2018: unifying comparative genomics and pathway resources for plant research.

Gramene (http://www.gramene.org) is a knowledgebase for comparative functional analysis in major crops and model plant species. The current release, #54, includes over 1.7 million genes from 44 reference genomes, most of which were organized into 62,367 gene families through orthologous and paralogous gene classification, whole-genome alignments, and synteny. Additional gene annotations include ontology-based protein structure and function; genetic, epigenetic, and phenotypic diversity; and pathway associations. Gramene's Plant Reactome provides a knowledgebase of cellular-level plant pathway networks. Specifically, it uses curated rice reference pathways to derive pathway projections for an additional 66 species based on gene orthology, and facilitates display of gene expression, gene-gene interactions, and user-defined omics data in the context of these pathways. As a community portal, Gramene integrates best-of-class software and infrastructure components including the Ensembl genome browser, Reactome pathway browser, and Expression Atlas widgets, and undergoes periodic data and software upgrades. Via powerful, intuitive search interfaces, users can easily query across various portals and interactively analyze search results by clicking on diverse features such as genomic context, highly augmented gene trees, gene expression anatomograms, associated pathways, and external informatics resources. All data in Gramene are accessible through both visual and programmatic interfaces.

Expression Atlas: gene and protein expression across multiple studies and organisms.

Expression Atlas (http://www.ebi.ac.uk/gxa) is an added value database that provides information about gene and protein expression in different species and contexts, such as tissue, developmental stage, disease or cell type. The available public and controlled access data sets from different sources are curated and re-analysed using standardized, open source pipelines and made available for queries, download and visualization. As of August 2017, Expression Atlas holds data from 3,126 studies across 33 different species, including 731 from plants. Data from large-scale RNA sequencing studies including Blueprint, PCAWG, ENCODE, GTEx and HipSci can be visualized next to each other. In Expression Atlas, users can query genes or gene-sets of interest and explore their expression across or within species, tissues, developmental stages in a constitutive or differential context, representing the effects of diseases, conditions or experimental interventions. All processed data matrices are available for direct download in tab-delimited format or as R-data. In addition to the web interface, data sets can now be searched and downloaded through the Expression Atlas R package. Novel features and visualizations include the on-the-fly analysis of gene set overlaps and the option to view gene co-expression in experiments investigating constitutive gene expression across tissues or other conditions.

The RNASeq-er API-a gateway to systematically updated analysis of public RNA-seq data.

MOTIVATION: The exponential growth of publicly available RNA-sequencing (RNA-Seq) data poses an increasing challenge to researchers wishing to discover, analyse and store such data, particularly those based in institutions with limited computational resources. EMBL-EBI is in an ideal position to address these challenges and to allow the scientific community easy access to not just raw, but also processed RNA-Seq data. We present a Web service to access the results of a systematically and continually updated standardized alignment as well as gene and exon expression quantification of all public bulk (and in the near future also single-cell) RNA-Seq runs in 264 species in European Nucleotide Archive, using Representational State Transfer. RESULTS: The RNASeq-er API (Application Programming Interface) enables ontology-powered search for and retrieval of CRAM, bigwig and bedGraph files, gene and exon expression quantification matrices (Fragments Per Kilobase Of Exon Per Million Fragments Mapped, Transcripts Per Million, raw counts) as well as sample attributes annotated with ontology terms. To date over 270 00 RNA-Seq runs in nearly 10 000 studies (1PB of raw FASTQ data) in 264 species in ENA have been processed and made available via the API. AVAILABILITY AND IMPLEMENTATION: The RNASeq-er API can be accessed at http://www.ebi.ac.uk/fg/rnaseq/api . The commands used to analyse the data are available in supplementary materials and at https://github.com/nunofonseca/irap/wiki/iRAP-single-library . CONTACT: rnaseq@ebi.ac.uk ; rpetry@ebi.ac.uk. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Expression Atlas update--an integrated database of gene and protein expression in humans, animals and plants.

Expression Atlas (http://www.ebi.ac.uk/gxa) provides information about gene and protein expression in animal and plant samples of different cell types, organism parts, developmental stages, diseases and other conditions. It consists of selected microarray and RNA-sequencing studies from ArrayExpress, which have been manually curated, annotated with ontology terms, checked for high quality and processed using standardised analysis methods. Since the last update, Atlas has grown seven-fold (1572 studies as of August 2015), and incorporates baseline expression profiles of tissues from Human Protein Atlas, GTEx and FANTOM5, and of cancer cell lines from ENCODE, CCLE and Genentech projects. Plant studies constitute a quarter of Atlas data. For genes of interest, the user can view baseline expression in tissues, and differential expression for biologically meaningful pairwise comparisons-estimated using consistent methodology across all of Atlas. Our first proteomics study in human tissues is now displayed alongside transcriptomics data in the same tissues. Novel analyses and visualisations include: 'enrichment' in each differential comparison of GO terms, Reactome, Plant Reactome pathways and InterPro domains; hierarchical clustering (by baseline expression) of most variable genes and experimental conditions; and, for a given gene-condition, distribution of baseline expression across biological replicates.

Gramene 2016: comparative plant genomics and pathway resources.

Gramene (http://www.gramene.org) is an online resource for comparative functional genomics in crops and model plant species. Its two main frameworks are genomes (collaboration with Ensembl Plants) and pathways (The Plant Reactome and archival BioCyc databases). Since our last NAR update, the database website adopted a new Drupal management platform. The genomes section features 39 fully assembled reference genomes that are integrated using ontology-based annotation and comparative analyses, and accessed through both visual and programmatic interfaces. Additional community data, such as genetic variation, expression and methylation, are also mapped for a subset of genomes. The Plant Reactome pathway portal (http://plantreactome.gramene.org) provides a reference resource for analyzing plant metabolic and regulatory pathways. In addition to ∼ 200 curated rice reference pathways, the portal hosts gene homology-based pathway projections for 33 plant species. Both the genome and pathway browsers interface with the EMBL-EBI's Expression Atlas to enable the projection of baseline and differential expression data from curated expression studies in plants. Gramene's archive website (http://archive.gramene.org) continues to provide previously reported resources on comparative maps, markers and QTL. To further aid our users, we have also introduced a live monthly educational webinar series and a Gramene YouTube channel carrying video tutorials.

Gramene Database: Navigating Plant Comparative Genomics Resources.

Gramene (http://www.gramene.org) is an online, open source, curated resource for plant comparative genomics and pathway analysis designed to support researchers working in plant genomics, breeding, evolutionary biology, system biology, and metabolic engineering. It exploits phylogenetic relationships to enrich the annotation of genomic data and provides tools to perform powerful comparative analyses across a wide spectrum of plant species. It consists of an integrated portal for querying, visualizing and analyzing data for 44 plant reference genomes, genetic variation data sets for 12 species, expression data for 16 species, curated rice pathways and orthology-based pathway projections for 66 plant species including various crops. Here we briefly describe the functions and uses of the Gramene database.

Characterization of gibberellin 20-oxidases in the citrus hybrid Carrizo citrange.

CcGA20ox1 is a gene encoding a GA 20-oxidase, a gibberellin (GA) biosynthetic enzyme, previously isolated from the citrus hybrid Carrizo citrange (Citrus sinensis (L.) Osbeck x Poncirus trifoliata (L.) Raf.). Southern blot analysis of genomic DNA of Carrizo citrange with CcGA20ox1 suggested the presence in the hybrid of another gene encoding another GA 20-oxidase. A cDNA clone from this new gene (CcGA20ox2) was isolated using RNA from the other parent C. sinensis. CcGA20ox2 encoded a protein of 372 amino acids that showed 67.1% identity with CcGA20ox1, and its expression product catalyzed the in vitro conversion of GA12 to GA9, confirming that it corresponds to another active GA20ox. Amplification of genomic DNA and isolation of genomic clones of CcGA20ox1 and CcGA20ox2 revealed that the parental sources of these genes in the hybrid were P. trifoliata and C. sinensis, respectively. The sequences of CcGA20ox1 and CcGA20ox2 showed that both genes contained two introns, which are also conserved in GA20ox genes of other species like Arabidopsis thaliana L., Pisum sativum L. and Solanum lycopersicum L. Determination of transcript levels in the Carrizo citrange hybrid by quantitative real-time polymerase chain reaction showed that CcGA20ox1 was expressed mainly in internodes, leaves and seeds, and CcGA20ox2 in flower buds and flowers at anthesis, with the genes having similar transcript levels in young developing fruits.

Gene expression analysis in citrus reveals the role of gibberellins on photosynthesis and stress.

The effect of gibberellins (GA) on internode transcriptome was investigated in transgenic Carrizo citrange (Citrus sinensis x Poncirus trifoliata) plants overexpressing endogenous CcGA20ox1 (encoding a GA biosynthetic gene), and in non-transformed explants treated with GA(3), using a citrus cDNA microarray. Substantial modulation of gene expression was found in sense CcGA20ox plants. Extensive up-regulation of genes involved in photosynthesis and carbon utilization, and down-regulation of those involved in protein synthesis and ribosome biogenesis were shown for the first time in plants with higher GA content. Importantly, increase of net photosynthesis in attached leaves was also demonstrated. Expression of other genes belonging to functional groups not reported previously to be regulated by GA (mainly abiotic and biotic stresses, and cuticle biosynthesis), and genes involved in cell division and cell wall architecture were also differentially expressed. Culture of citrus explants for 24 h in GA(3) solution produced much lower changes in the transcriptome compared with CcGA20ox plants (1.6% versus 16%, respectively, of total genes in the microarray), suggesting that most of the changes observed in CcGA20ox plants were a consequence of a long-standing GA effect. Interestingly, genes related to abiotic and biotic stresses were similarly modulated in transgenics and GA(3)-treated explants.

Engineering of gibberellin levels in citrus by sense and antisense overexpression of a GA 20-oxidase gene modifies plant architecture.

Carrizo citrange (Citrus sinensisxPoncirus trifoliata) is a citrus hybrid widely used as a rootstock, whose genetic manipulation to improve different growth characteristics is of high agronomic interest. In this work, transgenic Carrizo citrange plants have been produced overexpressing sense and antisense CcGA20ox1 (a key enzyme of GA biosynthesis) under control of the 35S promoter to modify plant architecture. As expected, taller (sense) and shorter (antisense) phenotypes correlated with higher and lower levels, respectively, of active GA1 in growing shoots. In contrast, other phenotypic characteristics seemed to be specific to citrus, or different from those described for similar transgenics in other species. For instance, thorns, typical organs of citrus at juvenile stages, were much longer in sense and shorter in antisense plants, and xylem tissue was reduced in leaf and internode of sense plants. Antisense plants presented a bushy phenotype, suggesting a possible effect of GAs on auxin biosynthesis and/or transport. The main foliole of sense plants was longer, although total leaf area was reduced. Leaf thickness was smaller in sense and larger in antisense plants due to changes in the spongy parenchyma. Internode cell length was not altered in transgenic plants, indicating that, in citrus, GAs regulate cell division rather than cell elongation. Interestingly, the phenotypes described were not apparent when transgenic plants were grafted on non-transgenic rootstock. This suggests that roots contribute to the GA economy of aerial parts in citrus and opens the possibility of using the antisense plants as dwarfing rootstocks.

Neonatal prefrontal cortex lesion using CO2 laser technique.

Prefrontal cortex (PFC) is a large area of the brain and its neonatal lesion with ibotenic or kainic acid is used to study the early abnormalities in neurodevelopment that lead to behavioral changes linked to schizophrenia. However, these exitotoxic drugs produce a large and asymmetric damage in the PFC. We produced the bilateral lesions of the dorsal part of the PFC of neonatal Sprague-Dawley rats (postnatal day 7, P7) at the anteroposterior +2.5 mm and mediolateral +/-0.4 coordinates by the new laser technique that employ the confined radiation of the CO(2) laser in the pulsed mode. The laser was used because its coherent radiation can be focused in a very small spot and as small as of several tens of micrometers in diameters. The CO(2) laser radiation is strongly absorbed by water that is present in any soft tissue. Thereafter, the configuration of the heated zone and, consequently, that of the lesion does not depend on the morphological non-homogeneity of particular structures. We obtained the symmetric, conical in shape and small-size bilateral lesions of the PFC. The size of the lesion depended on the beam spot-size and could be as small as several dozens of micrometers in diameter. Our data suggests that the laser technique will be used for the anatomical-functional studies of the PFC in the brain.