1,374 research outputs found

    Product culturalization

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    Histone Hypervariants H2A.Z.1 and H2A.Z.2 Play Independent and Context-Specific Roles in Neuronal Activity-Induced Transcription of Arc/Arg3.1 and Other Immediate Early Genes.

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    The histone variant H2A.Z is an essential and conserved regulator of eukaryotic gene transcription. However, the exact role of this histone in the transcriptional process remains perplexing. In vertebrates, H2A.Z has two hypervariants, H2A.Z.1 and H2A.Z.2, that have almost identical sequences except for three amino acid residues. Due to such similarity, functional specificity of these hypervariants in neurobiological processes, if any, remain largely unknown. In this study with dissociated rat cortical neurons, we asked if H2A.Z hypervariants have distinct functions in regulating basal and activity-induced gene transcription. Hypervariant-specific RNAi and microarray analyses revealed that H2A.Z.1 and H2A.Z.2 regulate basal expression of largely nonoverlapping gene sets, including genes that code for several synaptic proteins. In response to neuronal activity, rapid transcription of our model gene Arc is impaired by depletion of H2A.Z.2, but not H2A.Z.1. This impairment is partially rescued by codepletion of the H2A.Z chaperone, ANP32E. In contrast, under a different context (after 48 h of tetrodotoxin, TTX), rapid transcription of Arc is impaired by depletion of either hypervariant. Such context-dependent roles of H2A.Z hypervariants, as revealed by our multiplexed gene expression assays, are also evident with several other immediate early genes, where regulatory roles of these hypervariants vary from gene to gene under different conditions. Together, our data suggest that H2A.Z hypervariants have context-specific roles that complement each other to mediate activity-induced neuronal gene transcription

    The impacts of air pollution on human and natural capital in China: A look from a provincial perspective

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    Abstract Air quality has a significant impact on human health and natural systems worldwide. China, as one of the largest developing countries, faces very much serious air pollution and requires much attention. While the influences of air pollution on human or nature have been extensively investigated, few scholars considered the two effects of air pollution on human health and nature simultaneously based on the same framework. Indeed, human and nature coexist in the same biosphere on which they depend for their development and the impacts of air pollution on human health and nature occur at the same time with different and synergic effects. Only by considering both impacts we can develop a more comprehensive understanding of air pollution impacts, in particular including SO2, NO2, CO, PM10 and PM2.5. Impacts can be looked at from the point of view of damage provided and damage repair (health recovery, replacement cost). Therefore, considering the different pollutants and sectors, the influences of air pollution on human health and nature are accounted for in this study by applying the Emergy Accounting and Life Cycle Assessment Eco-indicator 99 methods under a unified framework in 31 provinces of China taken as case study. While LCA provides an accurate assessment of the direct consequences of pollution on human and natural capital (human health and biodiversity losses), the Emergy Accounting approach quantifies the biosphere work associated to repair or replace such losses over time. Furthermore, the spatial agglomeration characteristics of emissions, human and natural capital losses analyzed by means of Moran's I index. Results show that: (1) Concerning human capital losses, the amount of emissions of PM10 and PM2.5 only account for 10% of total impacts, compared to SO2, NO2, and CO emissions, but in some provinces cause more than 70% of human capital losses. And more than 80% of PM2.5 and PM10 that cause human capital losses come from the industrial and civil sectors. (2) As far as natural capital losses are concerned, compared with SO2, the losses caused by NO2 account for 80% in most provinces. And the power, industrial and transportation sectors are the three major sources of NO2 causing natural capital losses. (3) The spatial agglomeration characteristics, such as high-high cluster, high-low cluster, low-low cluster and low–high cluster, are different for air pollution emissions, human and natural capital losses. A comprehensive and detailed understanding of the impacts of air pollution is crucial for policy makers to take informed decisions

    Long-term depression-associated signaling is required for an in vitro model of NMDA receptor-dependent synapse pruning

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    AbstractActivity-dependent pruning of synaptic contacts plays a critical role in shaping neuronal circuitry in response to the environment during postnatal brain development. Although there is compelling evidence that shrinkage of dendritic spines coincides with synaptic long-term depression (LTD), and that LTD is accompanied by synapse loss, whether NMDA receptor (NMDAR)-dependent LTD is a required step in the progression toward synapse pruning is still unknown. Using repeated applications of NMDA to induce LTD in dissociated rat neuronal cultures, we found that synapse density, as measured by colocalization of fluorescent markers for pre- and postsynaptic structures, was decreased irrespective of the presynaptic marker used, post-treatment recovery time, and the dendritic location of synapses. Consistent with previous studies, we found that synapse loss could occur without apparent net spine loss or cell death. Furthermore, synapse loss was unlikely to require direct contact with microglia, as the number of these cells was minimal in our culture preparations. Supporting a model by which NMDAR-LTD is required for synapse loss, the effect of NMDA on fluorescence colocalization was prevented by phosphatase and caspase inhibitors. In addition, gene transcription and protein translation also appeared to be required for loss of putative synapses. These data support the idea that NMDAR-dependent LTD is a required step in synapse pruning and contribute to our understanding of the basic mechanisms of this developmental process

    A cryopreservation method to recover laboratory- and field-derived bacterial communities from mosquito larval habitats

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    Mosquitoes develop in a wide range of aquatic habitats containing highly diverse and variable bacterial communities that shape both larval and adult traits, including the capacity of adult females of some mosquito species to transmit disease-causing organisms to humans. However, while most mosquito studies control for host genotype and environmental conditions, the impact of microbiota variation on phenotypic outcomes of mosquitoes is often unaccounted for. The inability to conduct reproducible intra- and inter-laboratory studies of mosquito-microbiota interactions has also greatly limited our ability to identify microbial targets for mosquito-borne disease control. Here, we developed an approach to isolate and cryopreserve bacterial communities derived from lab and field-based larval rearing environments of the yellow fever mosquito Aedes aegypti–a primary vector of dengue, Zika, and chikungunya viruses. We then validated the use of our approach to generate experimental microcosms colonized by standardized lab- and field-derived bacterial communities. Our results overall reveal minimal effects of cryopreservation on the recovery of both lab- and field-derived bacteria when directly compared with isolation from non-cryopreserved fresh material. Our results also reveal improved reproducibility of bacterial communities in replicate microcosms generated using cryopreserved stocks over fresh material. Communities in replicate microcosms further captured the majority of total bacterial diversity present in both lab- and field-based larval environments, although the relative richness of recovered taxa as compared to non-recovered taxa was substantially lower in microcosms containing field-derived bacteria. Altogether, these results provide a critical next step toward the standardization of mosquito studies to include larval rearing environments colonized by defined microbial communities. They also lay the foundation for long-term studies of mosquito-microbe interactions and the identification and manipulation of taxa with potential to reduce mosquito vectorial capacity

    Large-Scale Automatic Audiobook Creation

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    An audiobook can dramatically improve a work of literature's accessibility and improve reader engagement. However, audiobooks can take hundreds of hours of human effort to create, edit, and publish. In this work, we present a system that can automatically generate high-quality audiobooks from online e-books. In particular, we leverage recent advances in neural text-to-speech to create and release thousands of human-quality, open-license audiobooks from the Project Gutenberg e-book collection. Our method can identify the proper subset of e-book content to read for a wide collection of diversely structured books and can operate on hundreds of books in parallel. Our system allows users to customize an audiobook's speaking speed and style, emotional intonation, and can even match a desired voice using a small amount of sample audio. This work contributed over five thousand open-license audiobooks and an interactive demo that allows users to quickly create their own customized audiobooks. To listen to the audiobook collection visit \url{https://aka.ms/audiobook}

    Precise Temporal Action Localization by Evolving Temporal Proposals

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    Locating actions in long untrimmed videos has been a challenging problem in video content analysis. The performances of existing action localization approaches remain unsatisfactory in precisely determining the beginning and the end of an action. Imitating the human perception procedure with observations and refinements, we propose a novel three-phase action localization framework. Our framework is embedded with an Actionness Network to generate initial proposals through frame-wise similarity grouping, and then a Refinement Network to conduct boundary adjustment on these proposals. Finally, the refined proposals are sent to a Localization Network for further fine-grained location regression. The whole process can be deemed as multi-stage refinement using a novel non-local pyramid feature under various temporal granularities. We evaluate our framework on THUMOS14 benchmark and obtain a significant improvement over the state-of-the-arts approaches. Specifically, the performance gain is remarkable under precise localization with high IoU thresholds. Our proposed framework achieves mAP@IoU=0.5 of 34.2%

    Caffeine-induced synaptic potentiation in hippocampal CA2 neurons

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    Caffeine enhances cognition, but even high non-physiological doses have modest effects on synapses. A 1 adenosine receptors (A 1 Rs) are antagonized by caffeine and are most highly enriched in hippocampal CA2, which has not been studied in this context. We found that physiological doses of caffeine in vivo or A 1 R antagonists in vitro induced robust, long-lasting potentiation of synaptic transmission in rat CA2 without affecting other regions of the hippocampus
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