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Algae are photosynthetic organisms that drive aquatic ecosystems, e.g. fuelling food webs or forming harmful blooms. The discovery of viruses that infect eukaryotic algae has raised many questions about their influence on aquatic primary production and their role in algal ecology and evolution. Although the full extent of algal virus diversity is still being discovered, this review summarizes current knowledge of this topic. Where possible, formal taxonomic classifications are referenced from the International Committee on Taxonomy of Viruses (ICTV); since the pace of virus discovery has far surpassed the rate of formal classification, however, numerous unclassified viruses are discussed along with their classified relatives. In total, we recognized 61 distinct algal virus taxa with highly variable morphologies that include dsDNA, ssDNA, dsRNA, and ssRNA genomes ranging from approximately 4.4 to 560 kb, with virion sizes from approximately 20 to 210nm in diameter. These viruses infect a broad range of algae and, although there are a few exceptions, they are generally lytic and highly species or strain specific. Dedicated research efforts have led to the appreciation of algal viruses as diverse, dynamic, and ecologically important members of the biosphere, and future investigations will continue to reveal the full extent of their diversity and impact.Understanding the sequence of events leading to cancer relies in large part upon identifying the tumour cell of origin. Glioblastoma is the most malignant brain cancer but the early stages of disease progression remain elusive. Neural lineages have been implicated as cells of origin, as have glia. Interestingly, high levels of the neural stem cell regulator TLX correlate with poor patient prognosis. Here we show that high levels of the Drosophila TLX homologue, Tailless, initiate tumourigenesis by reverting intermediate neural progenitors to a stem cell state. Strikingly, we could block tumour formation completely by re-expressing Asense (homologue of human ASCL1), which we show is a direct target of Tailless. Our results predict that expression of TLX and ASCL1 should be mutually exclusive in glioblastoma, which was verified in single-cell RNA-seq of human glioblastoma samples. Counteracting high TLX is a potential therapeutic strategy for suppressing tumours originating from intermediate progenitor cells. © 2020, Hakes and Brand.The rates of opioid overdose in the United States quadrupled between 1999 and 2017, reaching a staggering 130 deaths per day. This health epidemic demands innovative solutions that require uncovering the key brain areas and cell types mediating the cause of overdose- opioid-induced respiratory depression. Here, we identify two primary changes to murine breathing after administering opioids. These changes implicate the brainstem's breathing circuitry which we confirm by locally eliminating the µ-Opioid receptor. We find the critical brain site is the preBötzinger Complex, where the breathing rhythm originates, and use genetic tools to reveal that just 70-140 neurons in this region are responsible for its sensitivity to opioids. Future characterization of these neurons may lead to novel therapies that prevent respiratory depression while sparing analgesia. plain-language-summary Opioids such as morphine or fentanyl are powerful substances used to relieve pain in medical settings. However, taken in too high a dosponsible for breathing becoming depressed under the influence of opioids. The region with the most critical impact also happens to be where the breathing rhythms originate. There, a small group of 50 to 140 neurons were used by opioids to depress breathing. Crucially, these cells were not necessary for the drugs’ ability to relieve pain. Overall, the work by Bachmutsky et al. highlights a group of neurons whose role in creating breathing rhythms deserves further attention. It also opens the possibility that targeting these neurons would help to create safer painkillers. © 2020, Bachmutsky et al.Perturbation of neuronal activity is key to understanding the brain's functional properties, however, intervention studies typically perturb neurons in a nonspecific manner. Recent optogenetics techniques have enabled patterned perturbations, in which specific patterns of activity can be invoked in identified target neurons to reveal more specific cortical function. Here, we argue that patterned perturbation of neurons is in fact necessary to reveal the specific dynamics of inhibitory stabilization, emerging in cortical networks with strong excitatory and inhibitory functional subnetworks, as recently reported in mouse visual cortex. We propose a specific perturbative signature of these networks and investigate how this can be measured under different experimental conditions. Functionally, rapid spontaneous transitions between selective ensembles of neurons emerge in such networks, consistent with experimental results. Our study outlines the dynamical and functional properties of feature-specific inhibitory-stabilized networks, and suggests experimental protocols that can be used to detect them in the intact cortex. © 2020, Sadeh & Clopath.Mutations in genes encoding synaptic proteins cause many neurodevelopmental disorders, with the majority affecting postsynaptic apparatuses and much fewer in presynaptic proteins. Syntaxin-binding protein 1 (STXBP1, also known as MUNC18-1) is an essential component of the presynaptic neurotransmitter release machinery. De novo heterozygous pathogenic variants in STXBP1 are among the most frequent causes of neurodevelopmental disorders including intellectual disabilities and epilepsies. These disorders, collectively referred to as STXBP1 encephalopathy, encompass a broad spectrum of neurologic and psychiatric features, but the pathogenesis remains elusive. Here we modeled STXBP1 encephalopathy in mice and found that Stxbp1 haploinsufficiency caused cognitive, psychiatric, and motor dysfunctions, as well as cortical hyperexcitability and seizures. Furthermore, Stxbp1 haploinsufficiency reduced cortical inhibitory neurotransmission via distinct mechanisms from parvalbumin-expressing and somatostatin-expressing interneurons. These results demonstrate that Stxbp1 haploinsufficient mice recapitulate cardinal features of STXBP1 encephalopathy and indicate that GABAergic synaptic dysfunction is likely a crucial contributor to disease pathogenesis. © 2020, Chen et al.As the general population ages, more people are affected by eye diseases, such as retinopathies. It is therefore critical to improve imaging of eye disease mouse models. Here, we demonstrate that 1) rapid, quantitative 3D and 4D (time lapse) imaging of cellular and subcellular processes in the mouse eye is feasible, with and without tissue clearing, using light-sheet fluorescent microscopy (LSFM); 2) flat-mounting retinas for confocal microscopy significantly distorts tissue morphology, confirmed by quantitative correlative LSFM-Confocal imaging of vessels; 3) LSFM readily reveals new features of even well-studied eye disease mouse models, such as the oxygen-induced retinopathy (OIR) model, including a previously unappreciated 'knotted' morphology to pathological vascular tufts, abnormal cell motility and altered filopodia dynamics when live-imaged. We conclude that quantitative 3D/4D LSFM imaging and analysis has the potential to advance our understanding of the eye, in particular pathological, neuro-vascular, degenerative processes. © 2020, Prahst et al.Information processing in cortical neuronal networks relies on properly balanced excitatory and inhibitory neurotransmission. A ubiquitous motif for maintaining this balance is the somatostatin interneuron (SOM-IN) feedback microcircuit. Here, we investigated the modulation of this microcircuit by presynaptic GABAB receptors (GABABRs) in the rodent hippocampus. Whole-cell recordings from SOM-INs revealed that both excitatory and inhibitory synaptic inputs are strongly inhibited by GABABRs, while optogenetic activation of the interneurons shows that their inhibitory output is also strongly suppressed. Electron microscopic analysis of immunogold-labelled freeze-fracture replicas confirms that GABABRs are highly expressed presynaptically at both input and output synapses of SOM-INs. Activation of GABABRs selectively suppresses the recruitment of SOM-INs during gamma oscillations induced in vitro. selleck chemicals llc Thus, axonal GABABRs are positioned to efficiently control the input and output synapses of SOM-INs and can functionally uncouple them from local network with implications for rhythmogenesis and the balance of entorhinal versus intrahippocampal afferents. © 2020, Booker et al.in English, French Title Séroprévalence de l’infection par Toxoplasma gondii des moutons dans la province de Mongolie intérieure, Chine. Abstract Toxoplasma gondii est un parasite zoonotique important qui peut infecter presque tous les animaux à sang chaud, y compris les humains, et son infection peut entraîner de nombreux effets néfastes sur la production animale. L’élevage de Mongolie intérieure est développé, mais les données sur l’infection des moutons par T. gondii manquent. Dans cette étude, nous avons déterminé la séroprévalence et les facteurs de risque associés à la séroprévalence de T. gondii en utilisant un test immuno-enzymatique indirect (ELISA). Un total de 1853 échantillons de sérum ont été prélevés dans vingt-neuf comtés de la Ligue Xilin Gol (n = 624), Hohhot City (n = 225), Ordos City (n = 158), Wulanchabu City (n = 144), Bayan Nur City (n = 114) et la ville de Hulunbeir (n = 588). La séroprévalence globale de T. gondii était de 15,43 %. L’analyse des facteurs de risque a montré que le taux d’infection était plus élevé chez les ovins ≥ 12 mois (21,85 %) que chez les ovins less then 12 mois (10,20 %) (p  less then  0,01). Les moutons mâles (18,76 %) avaient une séroprévalence plus élevée que les femelles (12,80 %) (p  less then  0,01). Les moutons nourris à l’étable (23,13 %) avaient une séroprévalence plus élevée que ceux au pâturage (10,94 %) (p  less then  0,01). La séroprévalence était significativement différente entre les différents districts (p  less then  0,01). L’étude a montré que les moutons étaient exposés à T. gondii en Mongolie intérieure et a fourni une référence de données pour la santé publique et la lutte contre les maladies.The eHealth Centre of Excellence, a Waterloo, Ontario-based organization that advances and promotes digital health initiatives in clinical care, developed and assessed an innovative evaluation procurement framework. The purpose of the framework was to assess and support long-term vendor-organization procurement partnerships to develop, improve and expand electronic referral (eReferral) solutions. link2 The framework focused on six criteria the quality of the eReferral solution, its implementation, the service provided, the extent of training and knowledge transfer, the quality of the vendor's team and the vendor's project experience. link3 These domains were further defined by components and key performance indicators unique to the eReferral solution to accommodate the stakeholders' specified needs as well as change management challenges to create value for users and organizations in long-term relationships. The evaluation used both qualitative and quantitative methodologies. The framework used data from three sources (1) the System Coordinated Access program and vendor team experience surveys that focused on the six criteria mentioned earlier; (2) key stakeholder interviews that focused on system quality, user satisfaction and perception of net benefits; and (3) a vendor scorecard that focused on deliverables and efficiencies.

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