83 research outputs found

    Context-specific grasp movement representation in the macaque anterior intraparietal area

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    To perform grasping movements, the hand is shaped according to the form of the target object and the intended manipulation, which in turn depends on the context of the action. The anterior intraparietal cortex (AIP) is strongly involved in the sensorimotor transformation of grasping movements, but the extent to which it encodes context-specific information for hand grasping is unclear. To explore this issue, we recorded 571 single-units in AIP of two macaques during a delayed grasping task, in which animals were instructed by an external context cue (LED) to perform power or precision grips on a handle that was presented in various orientations. While 55% of the recorded neurons encoded the object orientation from the cue epoch on, the number of cells encoding the grip type increased from 25% during the cue epoch to 58% during movement execution. Furthermore, a classification of cells according to the time of their tuning onset revealed differences in the function and anatomical location of early- versus late-tuned cells. In a cue separation task, when the object was presented first, neurons representing power or precision grips were activated simultaneously until the actual grip type was instructed. In contrast, when the grasp type instruction was presented before the object, type information was only weakly represented in AIP, but was strongly encoded after the grasp target was revealed. We conclude that AIP encodes context specific hand grasping movements to perceived objects, but in the absence of a grasp target, the encoding of context information is weak

    Increased Immunogenicity of a DNA-Launched Venezuelan Equine Encephalitis Virus-Based Replicon DNA Vaccine

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    A novel genetic vaccine that is based on a Venezuelan equine encephalitis virus (VEE) replicon launched from plasmid DNA is described. The plasmid encodes a VEE replicon under the transcriptional control of the cytomegalovirus immediate-early promoter (VEE DNA). The VEE DNA consistently expressed 3- to 15-fold more green fluorescent protein in vitro than did a conventional DNA vaccine. Furthermore, transfection with the DNA-launched VEE replicon induced apoptosis and type I interferon production. Inoculation of mice with VEE DNA encoding human immunodeficiency virus type 1 gp160 significantly increased humoral responses by several orders of magnitude compared to an equal dose of a conventional DNA vaccine. These increases were also observed at 10- and 100-fold-lower doses of the VEE DNA. Cellular immune responses measured by gamma interferon and interleukin 2 enzyme-linked immunospot assay were significantly higher in mice immunized with the VEE DNA at decreased doses. The immune responses induced by the VEE DNA-encoded antigen, however, were independent of an intact type I interferon signaling pathway. Moreover, the DNA-launched VEE replicon induced an efficient prime to a VEE replicon particle (VRP) boost, increasing humoral and cellular immunity by at least 1 order of magnitude compared to VEE DNA only. Importantly, immunization with VEE DNA, as opposed to VRP, did not induce any anti-VRP neutralizing antibodies. Increased potency of DNA vaccines and reduced vector immunity may ultimately have an impact on the design of vaccination strategies in humans

    Mapping the planet’s critical natural assets

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    Sustaining the organisms, ecosystems and processes that underpin human wellbeing is necessary to achieve sustainable development. Here we define critical natural assets as the natural and semi-natural ecosystems that provide 90% of the total current magnitude of 14 types of nature’s contributions to people (NCP), and we map the global locations of these critical natural assets at 2 km resolution. Critical natural assets for maintaining local-scale NCP (12 of the 14 NCP) account for 30% of total global land area and 24% of national territorial waters, while 44% of land area is required to also maintain two global-scale NCP (carbon storage and moisture recycling). These areas overlap substantially with cultural diversity (areas containing 96% of global languages) and biodiversity (covering area requirements for 73% of birds and 66% of mammals). At least 87% of the world’s population live in the areas benefitting from critical natural assets for local-scale NCP, while only 16% live on the lands containing these assets. Many of the NCP mapped here are left out of international agreements focused on conserving species or mitigating climate change, yet this analysis shows that explicitly prioritizing critical natural assets and the NCP they provide could simultaneously advance development, climate and conservation goals.We thank all the participants of two working groups hosted by Conservation International and the Natural Capital Project for their insights and intellectual contributions. For further advice or assistance, we thank A. Adams, K. Brandon, K. Brauman, A. Cramer, G. Daily, J. Fisher, R. Gould, L. Mandle, J. Montgomery, A. Rodewald, D. Rossiter, E. Selig, A. Vogl and T. M. Wright. The two working groups that provided the foundation for this analysis were funded by support from the Marcus and Marianne Wallenberg Foundation to the Natural Capital Project (R.C.-K. and R.P.S.) and the Betty and Gordon Moore to Conservation International (R.A.N. and P.M.C.)

    Anthropogenic emission is the main contributor to the rise of atmospheric methane during 1993–2017

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    Atmospheric methane (CH4) concentrations have shown a puzzling resumption in growth since 2007 following a period of stabilization from 2000 to 2006. Multiple hypotheses have been proposed to explain the temporal variations in CH4 growth, and attribute the rise of atmospheric CH4 either to increases in emissions from fossil fuel activities, agriculture and natural wetlands, or to a decrease in the atmospheric chemical sink. Here, we use a comprehensive ensemble of CH4 source estimates and isotopic δ13C-CH4 source signature data to show that the resumption of CH4 growth is most likely due to increased anthropogenic emissions. Our emission scenarios that have the fewest biases with respect to isotopic composition suggest that the agriculture, landfill and waste sectors were responsible for 53 ± 13% of the renewed growth over the period 2007-2017 compared to 2000-2006; industrial fossil fuel sources explained an additional 34 ± 24%, and wetland sources contributed the least at 13 ± 9%. The hypothesis that a large increase in emissions from natural wetlands drove the decrease in atmospheric δ13C-CH4 values cannot be reconciled with current process-based wetland CH4 models. This finding suggests the need for increased wetland measurements to better understand the contemporary and future role of wetlands in the rise of atmospheric methane and climate feedback. Our findings highlight the predominant role of anthropogenic activities in driving the growth of atmospheric CH4 concentrations

    Gap-filling eddy covariance methane fluxes:Comparison of machine learning model predictions and uncertainties at FLUXNET-CH4 wetlands

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    Time series of wetland methane fluxes measured by eddy covariance require gap-filling to estimate daily, seasonal, and annual emissions. Gap-filling methane fluxes is challenging because of high variability and complex responses to multiple drivers. To date, there is no widely established gap-filling standard for wetland methane fluxes, with regards both to the best model algorithms and predictors. This study synthesizes results of different gap-filling methods systematically applied at 17 wetland sites spanning boreal to tropical regions and including all major wetland classes and two rice paddies. Procedures are proposed for: 1) creating realistic artificial gap scenarios, 2) training and evaluating gap-filling models without overstating performance, and 3) predicting half-hourly methane fluxes and annual emissions with realistic uncertainty estimates. Performance is compared between a conventional method (marginal distribution sampling) and four machine learning algorithms. The conventional method achieved similar median performance as the machine learning models but was worse than the best machine learning models and relatively insensitive to predictor choices. Of the machine learning models, decision tree algorithms performed the best in cross-validation experiments, even with a baseline predictor set, and artificial neural networks showed comparable performance when using all predictors. Soil temperature was frequently the most important predictor whilst water table depth was important at sites with substantial water table fluctuations, highlighting the value of data on wetland soil conditions. Raw gap-filling uncertainties from the machine learning models were underestimated and we propose a method to calibrate uncertainties to observations. The python code for model development, evaluation, and uncertainty estimation is publicly available. This study outlines a modular and robust machine learning workflow and makes recommendations for, and evaluates an improved baseline of, methane gap-filling models that can be implemented in multi-site syntheses or standardized products from regional and global flux networks (e.g., FLUXNET)

    Viral Protein Fragmentation May Broaden T-Cell Responses to HIV Vaccines

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    High mutation rates of human immunodeficiency virus (HIV) allows escape from T cell recognition preventing development of effective T cell vaccines. Vaccines that induce diverse T cell immune responses would help overcome this problem. Using SIV gag as a model vaccine, we investigated two approaches to increase the breadth of the CD8 T cell response. Namely, fusion of vaccine genes to ubiquitin to target the proteasome and increase levels of MHC class I peptide complexes and gene fragmentation to overcome competition between epitopes for presentation and recognition.three vaccines were compared: full-length unmodified SIV-mac239 gag, full-length gag fused at the N-terminus to ubiquitin and 7 gag fragments of equal size spanning the whole of gag with ubiquitin-fused to the N-terminus of each fragment. Genes were cloned into a replication defective adenovirus vector and immunogenicity assessed in an in vitro human priming system. The breadth of the CD8 T cell response, defined by the number of distinct epitopes, was assessed by IFN-γ-ELISPOT and memory phenotype and cytokine production evaluated by flow cytometry. We observed an increase of two- to six-fold in the number of epitopes recognised in the ubiquitin-fused fragments compared to the ubiquitin-fused full-length gag. In contrast, although proteasomal targeting was achieved, there was a marked reduction in the number of epitopes recognised in the ubiquitin-fused full-length gag compared to the full-length unmodified gene, but there were no differences in the number of epitope responses induced by non-ubiquitinated full-length gag and the ubiquitin-fused mini genes. Fragmentation and ubiquitination did not affect T cell memory differentiation and polyfunctionality, though most responses were directed against the Ad5 vector.Fragmentation but not fusion with ubiquitin increases the breadth of the CD8 T vaccine response against SIV-mac239 gag. Thus gene fragmentation of HIV vaccines may maximise responses

    Aquatic Foods to Nourish Nations

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    Despite contributing to healthy diets for billions of people, aquatic foods are often undervalued as a nutritional solution because their diversity is often reduced to the protein and energy value of a single food type (‘seafood’ or ‘fish’)1,2,3,4. Here we create a cohesive model that unites terrestrial foods with nearly 3,000 taxa of aquatic foods to understand the future impact of aquatic foods on human nutrition. We project two plausible futures to 2030: a baseline scenario with moderate growth in aquatic animal-source food (AASF) production, and a high-production scenario with a 15-million-tonne increased supply of AASFs over the business-as-usual scenario in 2030, driven largely by investment and innovation in aquaculture production. By comparing changes in AASF consumption between the scenarios, we elucidate geographic and demographic vulnerabilities and estimate health impacts from diet-related causes. Globally, we find that a high-production scenario will decrease AASF prices by 26% and increase their consumption, thereby reducing the consumption of red and processed meats that can lead to diet-related non-communicable diseases5,6 while also preventing approximately 166 million cases of inadequate micronutrient intake. This finding provides a broad evidentiary basis for policy makers and development stakeholders to capitalize on the potential of aquatic foods to reduce food and nutrition insecurity and tackle malnutrition in all its forms.Additional co-authors: Pierre Charlebois, Manuel Barange, Stefania Vannuccini, Ling Cao, Kristin M. Kleisner, Eric B. Rimm, Goodarz Danaei, Camille DeSisto, Heather Kelahan, Kathryn J. Fiorella, Edward H. Allison, Jessica Fanzo & Shakuntala H. Thilste
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