Activation of Type 1 Cannabinoid Receptor (CB1R) promotes neurogenesis in murine subventricular zone cell cultures

The endocannabinoid system has been implicated in the modulation of adult neurogenesis. Here, we describe the effect of type 1 cannabinoid receptor (CB1R) activation on self-renewal, proliferation and neuronal differentiation in mouse neonatal subventricular zone (SVZ) stem/progenitor cell cultures. Expression of CB1R was detected in SVZ-derived immature cells (Nestin-positive), neurons and astrocytes. Stimulation of the CB1R by (R)-(+)-Methanandamide (R-m-AEA) increased self-renewal of SVZ cells, as assessed by counting the number of secondary neurospheres and the number of Sox2+/+ cell pairs, an effect blocked by Notch pathway inhibition. Moreover, R-m-AEA treatment for 48 h, increased proliferation as assessed by BrdU incorporation assay, an effect mediated by activation of MAPK-ERK and AKT pathways. Surprisingly, stimulation of CB1R by R-m-AEA also promoted neuronal differentiation (without affecting glial differentiation), at 7 days, as shown by counting the number of NeuN-positive neurons in the cultures. Moreover, by monitoring intracellular calcium concentrations ([Ca2+](i)) in single cells following KCl and histamine stimuli, a method that allows the functional evaluation of neuronal differentiation, we observed an increase in neuronal-like cells. This proneurogenic effect was blocked when SVZ cells were co-incubated with R-m-AEA and the CB1R antagonist AM 251, for 7 days, thus indicating that this effect involves CB1R activation. In accordance with an effect on neuronal differentiation and maturation, R-m-AEA also increased neurite growth, as evaluated by quantifying and measuring the number of MAP2-positive processes. Taken together, these results demonstrate that CB1R activation induces proliferation, self-renewal and neuronal differentiation from mouse neonatal SVZ cell cultures.Fundacao para a Ciencia e a Tecnologia - Portugal [POCTI/SAU-NEU/68465/2006, PTDC/SAU-NEU/104415/2008, PTDC/SAU-NEU/101783/2008, POCTI/SAU-NEU/110838/2009]; Fundacao Calouste Gulbenkian [96542]; Fundacao para a Ciencia e Tecnologiainfo:eu-repo/semantics/publishedVersio

The Genome of Deep-Sea Vent Chemolithoautotroph Thiomicrospira crunogena XCL-2

Presented here is the complete genome sequence of Thiomicrospira crunogena XCL-2, representative of ubiquitous chemolithoautotrophic sulfur-oxidizing bacteria isolated from deep-sea hydrothermal vents. This gammaproteobacterium has a single chromosome (2,427,734 base pairs), and its genome illustrates many of the adaptations that have enabled it to thrive at vents globally. It has 14 methyl-accepting chemotaxis protein genes, including four that may assist in positioning it in the redoxcline. A relative abundance of coding sequences (CDSs) encoding regulatory proteins likely control the expression of genes encoding carboxysomes, multiple dissolved inorganic nitrogen and phosphate transporters, as well as a phosphonate operon, which provide this species with a variety of options for acquiring these substrates from the environment. Thiom. crunogena XCL-2 is unusual among obligate sulfur-oxidizing bacteria in relying on the Sox system for the oxidation of reduced sulfur compounds. The genome has characteristics consistent with an obligately chemolithoautotrophic lifestyle, including few transporters predicted to have organic allocrits, and Calvin-Benson-Bassham cycle CDSs scattered throughout the genome

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Forensic DNA databases in European countries: is size linked to performance?

The political and financial investments in the implementation of forensic DNA databases and the ethical issues related to their use and expansion justify inquiries into their performance and general utility. The main function of a forensic DNA database is to produce matches between individuals and crime scene stains, which requires a constant input of individual profiles and crime scene stains. This is conditioned, among other factors, by the legislation, namely the criteria for inclusion of profiles and the periods of time and conditions for their retention and/or deletion. This article aims to provide an overview of the different legislative models for DNA databasing in Europe and ponder if wider inclusion criteria – and, consequently, database size – translates into more matches between profiles of crime scene stains and included individuals (performance ratio). The legislation governing forensic DNA databases in 22 countries in the European Union was analysed in order to propose a typology of two major groups of legislative criteria for inclusion/retention of profiles that can be classified as having either expansive effects or restrictive effects. We argue that expansive criteria for inclusion and retention of profiles do not necessarily translate into significant gains in output performance.MES -Ministry of Education and Science(SFRH/BPD/34143/2006)info:eu-repo/semantics/publishedVersio

Functional analysis of genes involved in the biosynthesis of isoprene in Bacillus subtilis

In comparison to other bacteria Bacillus subtilis emits the volatile compound isoprene in high concentrations. Isoprene is the smallest representative of the natural product group of terpenoids. A search in the genome of B. subtilis resulted in a set of genes with yet unknown function, but putatively involved in the methylerythritol phosphate (MEP) pathway to isoprene. Further identification of these genes would give the possibility to engineer B. subtilis as a host cell for the production of terpenoids like the valuable plant-produced drugs artemisinin and paclitaxel. Conditional knock-out strains of putative genes were analyzed for the amount of isoprene emitted. Differences in isoprene emission were used to identify the function of the enzymes and of the corresponding selected genes in the MEP pathway. We give proof on a biochemical level that several of these selected genes from this species are involved in isoprene biosynthesis. This opens the possibilities to investigate the physiological function of isoprene emission and to increase the endogenous flux to the terpenoid precursors, isopentenyl diphosphate and dimethylallyl diphosphate, for the heterologous production of more complex terpenoids in B. subtilis

Marine mammal hotspots across the circumpolar Arctic

Aim: Identify hotspots and areas of high species richness for Arctic marine mammals. Location: Circumpolar Arctic. Methods: A total of 2115 biologging devices were deployed on marine mammals from 13 species in the Arctic from 2005 to 2019. Getis-Ord Gi* hotspots were calculated based on the number of individuals in grid cells for each species and for phyloge-netic groups (nine pinnipeds, three cetaceans, all species) and areas with high spe-cies richness were identified for summer (Jun-Nov), winter (Dec-May) and the entire year. Seasonal habitat differences among species’ hotspots were investigated using Principal Component Analysis. Results: Hotspots and areas with high species richness occurred within the Arctic continental-shelf seas and within the marginal ice zone, particularly in the “Arctic gateways” of the north Atlantic and Pacific oceans. Summer hotspots were generally found further north than winter hotspots, but there were exceptions to this pattern, including bowhead whales in the Greenland-Barents Seas and species with coastal distributions in Svalbard, Norway and East Greenland. Areas with high species rich-ness generally overlapped high-density hotspots. Large regional and seasonal dif-ferences in habitat features of hotspots were found among species but also within species from different regions. Gap analysis (discrepancy between hotspots and IUCN ranges) identified species and regions where more research is required. Main conclusions: This study identified important areas (and habitat types) for Arctic marine mammals using available biotelemetry data. The results herein serve as a benchmark to measure future distributional shifts. Expanded monitoring and teleme-try studies are needed on Arctic species to understand the impacts of climate change and concomitant ecosystem changes (synergistic effects of multiple stressors). While efforts should be made to fill knowledge gaps, including regional gaps and more com-plete sex and age coverage, hotspots identified herein can inform management ef-forts to mitigate the impacts of human activities and ecological changes, including creation of protected areas

Sushi in the United States, 1945-1970

Sushi first achieved widespread popularity in the United States in the mid-1960s. Many accounts of sushi’s US establishment foreground the role of a small number of key actors, yet underplay the role of a complex web of large-scale factors that provided the context in which sushi was able to flourish. This article critically reviews existing literature, arguing that sushi’s US popularity arose from contingent, long-term, and gradual processes. It examines US newspaper accounts of sushi during 1945–1970, which suggest the discursive context for US acceptance of sushi was considerably more propitious than generally acknowledged. Using California as a case study, the analysis also explains conducive social and material factors, and directs attention to the interplay of supply- and demand-side forces in the favorable positioning of this “new” food. The article argues that the US establishment of sushi can be understood as part of broader public acceptance of Japanese cuisine