1,694 research outputs found

    Induction of miR-155 after Brain Injury Promotes Type 1 Interferon and has a Neuroprotective Effect.

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    Traumatic brain injury (TBI) produces profound and lasting neuroinflammation that has both beneficial and detrimental effects. Recent evidence has implicated microRNAs (miRNAs) in the regulation of inflammation both in the periphery and the CNS. We examined the expression of inflammation associated miRNAs in the context of TBI using a mouse controlled cortical impact (CCI) model and found increased levels of miR-21, miR-223 and miR-155 in the hippocampus after CCI. The expression of miR-155 was elevated 9-fold after CCI, an increase confirmed by in situ hybridization (ISH). Interestingly, expression of miR-155 was largely found in neuronal nuclei as evidenced by co-localization with DAPI in MAP2 positive neurons. In miR-155 knock out (KO) mice expression of type I interferons IFNα and IFNβ, as well as IFN regulatory factor 1 and IFN-induced chemokine CXCL10 was decreased after TBI relative to wild type (WT) mice. Unexpectedly, miR-155 KO mice had increased levels of microglial marker Iba1 and increased neuronal degeneration as measured by fluoro-jade C (FJC) staining, suggesting a neuroprotective role for miR-155 in the context of TBI. This work demonstrates a role for miR-155 in regulation of the IFN response and neurodegeneration in the aftermath of TBI. While the presence of neuronal nuclear miRNAs has been described previously, their importance in disease states is relatively unknown. Here, we show evidence of dynamic regulation and pathological function of a nuclear miRNA in TBI

    Real-time augmented reality filters expressive of user sentiment

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    Body language and facial expressions are an important component of human communication. Some messaging applications include features to send emoji, animated GIFs, etc. to express emotion. However, such content does not include the user’s image. This disclosure describes techniques that enable users to choose augmented reality effects that are added to a user’s image and that help users express an emotion

    Traumatic brain injury increases levels of miR-21 in extracellular vesicles: implications for neuroinflammation

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    Traumatic brain injury (TBI) is an important health concern and effective treatment strategies remain elusive. Understanding the complex multicellular response to TBI may provide new avenues for intervention. In the context of TBI, cell–cell communication is critical. One relatively unexplored form of cell–cell communication in TBI is extracellular vesicles (EVs). These membrane‐bound vesicles can carry many different types of cargo between cells. Recently, miRNA in EVs have been shown to mediate neuroinflammation and neuronal injury. To explore the role of EV‐associated miRNA in TBI, we isolated EVs from the brain of injured mice and controls, purified RNA from brain EVs, and performed miRNA sequencing. We found that the expression of miR‐212 decreased, while miR‐21, miR‐146, miR‐7a, and miR‐7b were significantly increased with injury, with miR‐21 showing the largest change between conditions. The expression of miR‐21 in the brain was primarily localized to neurons near the lesion site. Interestingly, adjacent to these miR‐21‐expressing neurons were activated microglia. The concurrent increase in miR‐21 in EVs with the elevation of miR‐21 in neurons, suggests that miR‐21 is secreted from neurons as potential EV cargo. Thus, this study reveals a new potential mechanism of cell–cell communication not previously described in TBI

    High-resolution temporal profiling of transcripts during Arabidopsis leaf senescence reveals a distinct chronology of processes and regulation

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    Leaf senescence is an essential developmental process that impacts dramatically on crop yields and involves altered regulation of thousands of genes and many metabolic and signaling pathways, resulting in major changes in the leaf. The regulation of senescence is complex, and although senescence regulatory genes have been characterized, there is little information on how these function in the global control of the process. We used microarray analysis to obtain a highresolution time-course profile of gene expression during development of a single leaf over a 3-week period to senescence. A complex experimental design approach and a combination of methods were used to extract high-quality replicated data and to identify differentially expressed genes. The multiple time points enable the use of highly informative clustering to reveal distinct time points at which signaling and metabolic pathways change. Analysis of motif enrichment, as well as comparison of transcription factor (TF) families showing altered expression over the time course, identify clear groups of TFs active at different stages of leaf development and senescence. These data enable connection of metabolic processes, signaling pathways, and specific TF activity, which will underpin the development of network models to elucidate the process of senescence

    Insulin Sensitivity Is Retained in Mice with Endothelial Loss of Carcinoembryonic Antigen Cell Adhesion Molecule 1

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    CEACAM1 regulates endothelial barrier integrity. Because insulin signaling in extrahepatic target tissues is regulated by insulin transport through the endothelium, we aimed at investigating the metabolic role of endothelial CEACAM1. To this end, we generated endothelial cell-specific Ceacam1 null mice (VECadCre+Cc1(fl/fl)) and carried out their metabolic phenotyping and mechanistic analysis by comparison to littermate controls. Hyperinsulinemic-euglycemic clamp analysis showed intact insulin sensitivity in VECadCre+Cc1(fl/fl) mice. This was associated with the absence of visceral obesity and lipolysis and normal levels of circulating non-esterified fatty acids, leptin, and adiponectin. Whereas the loss of endothelial Ceacam1 did not affect insulin-stimulated receptor phosphorylation, it reduced IRS-1/Akt/eNOS activation to lower nitric oxide production resulting from limited SHP2 sequestration. It also reduced Shc sequestration to activate NF-kappaB and increase the transcription of matrix metalloproteases, ultimately inducing plasma IL-6 and TNFalpha levels. Loss of endothelial Ceacam1 also induced the expression of the anti-inflammatory CEACAM1-4L variant in M2 macrophages in white adipose tissue. Together, this could cause endothelial barrier dysfunction and facilitate insulin transport, sustaining normal glucose homeostasis and retaining fat accumulation in adipocytes. The data assign a significant role for endothelial cell CEACAM1 in maintaining insulin sensitivity in peripheral extrahepatic target tissues

    The Liverpool Heart And bRain Project (L-HARP): Protocol for an Observational Cohort Study of Cardiovascular Risk and Outcomes Following Stroke.

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    Further research is needed to refine risk prediction models for adverse cardiovascular outcomes following stroke in contemporary clinical practice, such as incident atrial fibrillation (AF), recurrent stroke, and cognitive impairment and dementia. The aims of this study are to prospectively investigate cardiovascular outcomes and risk factors for incident cardiovascular disease in a post-stroke cohort, and to externally validate, refine and expand current risk prediction models for cardiovascular and cardiovascular-related outcomes. The study sample size was based on the development of post-stroke risk prediction models for AF and was calculated as 1222 participants. The study design is a multicentre, prospective, observational cohort study. Participants will be adult patients admitted for ischaemic stroke confirmed by stroke physician or transient ischaemic attack (TIA) confirmed by MRI. Routinely collected data will be used in addition to the completion of simple validated questionnaires by the participants. Follow-up will be undertaken 12-months from the date of admission to hospital, in addition to linkage to routinely collected follow-up hospitalisation and mortality data. The primary outcomes are cardiovascular outcomes (including incident AF, stroke, TIA and myocardial infarction) at 12-month follow-up, all-cause mortality and mortality from cardiovascular causes, and incident cognitive impairment and dementia. Secondary outcomes include changes in function, depression, anxiety, fatigue and quality of life. The study has received approval from the Health Research Authority Research Ethics Committee (21/WA/0209), and is registered on https://www.clinicaltrials.gov/ (Identifier NCT05132465). Recruitment for the study began in October 2021 with completion of recruitment at all participating centres anticipated by October 2022

    Stomatal development: focusing on the grasses

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    The development and patterning of stomata in the plant epidermis has emerged as an ideal system for studying fundamental plant developmental processes. Over the past twenty years most studies of stomata have used the model dicotyledonous plant Arabidopsis thaliana. However, cultivated monocotyledonous grass (or Gramineae) varieties provide the majority of human nutrition, and future research into grass stomata could be of critical importance for improving food security. Recent studies using Brachypodium distachyon, Hordeum vulgare (barley) and Oryza sativa (rice) have led to the identification of the core transcriptional regulators essential for stomatal initiation and progression in grasses, and begun to unravel the role of secretory signaling peptides in controlling stomatal developmental. This review revisits how stomatal developmental unfolds in grasses, and identifies key ontogenetic steps for which knowledge of the underpinning molecular mechanisms remains outstanding
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