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81.
82.
Catalina Vich Matthew Clapp Jonathan E. Rubin Timothy Verstynen 《PLoS computational biology》2022,18(6)
In situations featuring uncertainty about action-reward contingencies, mammals can flexibly adopt strategies for decision-making that are tuned in response to environmental changes. Although the cortico-basal ganglia thalamic (CBGT) network has been identified as contributing to the decision-making process, it features a complex synaptic architecture, comprised of multiple feed-forward, reciprocal, and feedback pathways, that complicate efforts to elucidate the roles of specific CBGT populations in the process by which evidence is accumulated and influences behavior. In this paper we apply a strategic sampling approach, based on Latin hypercube sampling, to explore how variations in CBGT network properties, including subpopulation firing rates and synaptic weights, map to variability of parameters in a normative drift diffusion model (DDM), representing algorithmic aspects of information processing during decision-making. Through the application of canonical correlation analysis, we find that this relationship can be characterized in terms of three low-dimensional control ensembles within the CBGT network that impact specific qualities of the emergent decision policy: responsiveness (a measure of how quickly evidence evaluation gets underway, associated with overall activity in corticothalamic and direct pathways), pliancy (a measure of the standard of evidence needed to commit to a decision, associated largely with overall activity in components of the indirect pathway of the basal ganglia), and choice (a measure of commitment toward one available option, associated with differences in direct and indirect pathways across action channels). These analyses provide mechanistic predictions about the roles of specific CBGT network elements in tuning the way that information is accumulated and translated into decision-related behavior. 相似文献
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84.
Mark A. Feger Jonathan Isaacs Satya Mallu Dorne Yager Mary Shall Gaurangkumar Patel Omar Protzuk Akhil S. Bokkisam 《Journal of brachial plexus and peripheral nerve injury》2022,17(1):e12
Background Muscle recovery following peripheral nerve repair is sup-optimal. Follistatin (FST), a potent muscle stimulant, enhances muscle size and satellite cell counts following reinnervation when administered as recombinant FST DNA via viral vectors. Local administration of recombinant FST protein, if effective, would be more clinically translatable but has yet to be investigated following muscle reinnervation. Objective The aim of this study is to assess the effect of direct delivery of recombinant FST protein on muscle recovery following muscle reinnervation. Materials and Methods In total, 72 Sprague-Dawley rats underwent temporary (3 or 6 months) denervation or sham denervation. After reinnervation, rats received FST protein (isoform FS-288) or sham treatment via a subcutaneous osmotic pump delivery system. Outcome measures included muscle force, muscle histomorphology, and FST protein quantification. Results Follistatin treatment resulted in smaller muscles after 3 months denervation ( p = 0.019) and reduced force after 3 months sham denervation ( p < 0.001). Conversely, after 6 months of denervation, FST treatment trended toward increased force output ( p = 0.066). Follistatin increased satellite cell counts after denervation ( p < 0.001) but reduced satellite cell counts after sham denervation ( p = 0.037). Conclusion Follistatin had mixed effects on muscle weight and force. Direct FST protein delivery enhanced satellite cell counts following reinnervation. The positive effect on the satellite cell population is intriguing and warrants further investigation. 相似文献
85.
Jonathan A. Williams Carmen Huesa Mikael J. Turunen James A. Oo Oskars Radzins Wilf Gardner James F.C. Windmill Hanna Isaksson K. Elizabeth Tanner John S. Riddell Sylvie Coupaud 《Journal of musculoskeletal & neuronal interactions》2022,22(2):212
Objective:Characterise the spatiotemporal trabecular and cortical bone responses to complete spinal cord injury (SCI) in young rats.Methods:8-week-old male Wistar rats received T9-transection SCI and were euthanised 2-, 6-, 10- or 16-weeks post-surgery. Outcome measures were assessed using micro-computed tomography, mechanical testing, serum markers and Fourier-transform infrared spectroscopy.Results:The trabecular and cortical bone responses to SCI are site-specific. Metaphyseal trabecular BV/TV was 59% lower, characterised by fewer and thinner trabeculae at 2-weeks post-SCI, while epiphyseal BV/TV was 23% lower with maintained connectivity. At later-time points, metaphyseal BV/TV remained unchanged, while epiphyseal BV/TV increased. The total area of metaphyseal and mid-diaphyseal cortical bone were lower from 2-weeks and between 6- and 10-weeks post-SCI, respectively. This suggested that SCI-induced bone changes observed in the rat model were not solely attributable to bone loss, but also to suppressed bone growth. No tissue mineral density differences were observed at any time-point, suggesting that decreased whole-bone mechanical properties were primarily the result of changes to the spatial distribution of bone.Conclusion:Young SCI rat trabecular bone changes resemble those observed clinically in adult and paediatric SCI, while cortical bone changes resemble paediatric SCI only. 相似文献
86.
Kathy Darragh Gabriela Montejo‐Kovacevich Krzysztof M. Kozak Colin R. Morrison Clarisse M. E. Figueiredo Jonathan S. Ready Camilo Salazar Mauricio Linares Kelsey J. R. P. Byers Richard M. Merrill W. Owen McMillan Stefan Schulz Chris D. Jiggins 《Ecology and evolution》2020,10(9):3895-3918
In many animals, mate choice is important for the maintenance of reproductive isolation between species. Traits important for mate choice and behavioral isolation are predicted to be under strong stabilizing selection within species; however, such traits can also exhibit variation at the population level driven by neutral and adaptive evolutionary processes. Here, we describe patterns of divergence among androconial and genital chemical profiles at inter‐ and intraspecific levels in mimetic Heliconius butterflies. Most variation in chemical bouquets was found between species, but there were also quantitative differences at the population level. We found a strong correlation between interspecific chemical and genetic divergence, but this correlation varied in intraspecific comparisons. We identified “indicator” compounds characteristic of particular species that included compounds already known to elicit a behavioral response, suggesting an approach for identification of candidate compounds for future behavioral studies in novel systems. Overall, the strong signal of species identity suggests a role for these compounds in species recognition, but with additional potentially neutral variation at the population level. 相似文献
87.
Laura Dumas C. Michael Dickens Nathan Anderson Jonathan Davis Beth Bennett Richard A. Radcliffe James M. Sikela 《Mammalian genome》2014,25(5-6):235-243
It has been well documented that genetic factors can influence predisposition to develop alcoholism. While the underlying genomic changes may be of several types, two of the most common and disease associated are copy number variations (CNVs) and sequence alterations of protein coding regions. The goal of this study was to identify CNVs and single-nucleotide polymorphisms that occur in gene coding regions that may play a role in influencing the risk of an individual developing alcoholism. Toward this end, two mouse strains were used that have been selectively bred based on their differential sensitivity to alcohol: the Inbred long sleep (ILS) and Inbred short sleep (ISS) mouse strains. Differences in initial response to alcohol have been linked to risk for alcoholism, and the ILS/ISS strains are used to investigate the genetics of initial sensitivity to alcohol. Array comparative genomic hybridization (arrayCGH) and exome sequencing were conducted to identify CNVs and gene coding sequence differences, respectively, between ILS and ISS mice. Mouse arrayCGH was performed using catalog Agilent 1 × 244 k mouse arrays. Subsequently, exome sequencing was carried out using an Illumina HiSeq 2000 instrument. ArrayCGH detected 74 CNVs that were strain-specific (38 ILS/36 ISS), including several ISS-specific deletions that contained genes implicated in brain function and neurotransmitter release. Among several interesting coding variations detected by exome sequencing was the gain of a premature stop codon in the alpha-amylase 2B (AMY2B) gene specifically in the ILS strain. In total, exome sequencing detected 2,597 and 1,768 strain-specific exonic gene variants in the ILS and ISS mice, respectively. This study represents the most comprehensive and detailed genomic comparison of ILS and ISS mouse strains to date. The two complementary genome-wide approaches identified strain-specific CNVs and gene coding sequence variations that should provide strong candidates to contribute to the alcohol-related phenotypic differences associated with these strains. 相似文献
88.
siRNA-directed inhibition of HIV-1 infection 总被引:133,自引:0,他引:133
Novina CD Murray MF Dykxhoorn DM Beresford PJ Riess J Lee SK Collman RG Lieberman J Shankar P Sharp PA 《Nature medicine》2002,8(7):681-686
RNA interference silences gene expression through short interfering 21 23-mer double-strand RNA segments that guide mRNA degradation in a sequence-specific fashion. Here we report that siRNAs inhibit virus production by targeting the mRNAs for either the HIV-1 cellular receptor CD4, the viral structural Gag protein or green fluorescence protein substituted for the Nef regulatory protein. siRNAs effectively inhibit pre- and/or post-integration infection events in the HIV-1 life cycle. Thus, siRNAs may have potential for therapeutic intervention in HIV-1 and other viral infections. 相似文献
89.
Shared patterns of species turnover between seaweeds and seed plants break down at increasing distances from the sea 下载免费PDF全文
Carlos F. D. Gurgel Thomas Wernberg Mads S. Thomsen Bayden D. Russell Paul Adam Jonathan M. Waters Sean D. Connell 《Ecology and evolution》2014,4(1):27-34
We tested for correlations in the degree of spatial similarity between algal and terrestrial plants communities along 5500 km of temperate Australian coastline and whether the strength of correlation weakens with increasing distance from the coast. We identified strong correlations between macroalgal and terrestrial plant communities within the first 100 km from shore, where the strength of these marine–terrestrial correlations indeed weakens with increasing distance inland. As such, our results suggest that marine‐driven community homogenization processes decompose with increasing distance from the shore toward inland. We speculate that the proximity to the marine environment produces lower levels of community turnover on land, and this effect decreases progressively farther inland. Our analysis suggests underlying ecological and evolutionary processes that give rise to continental‐scale biogeographic influence from sea to land. 相似文献
90.
Estimating temporal trends in spatially structured populations has a critical role to play in understanding regional changes in biological populations and developing management strategies. Designing effective monitoring programmes to estimate these trends requires important decisions to be made about how to allocate sampling effort among spatial replicates (i.e. number of sites) and temporal replicates (i.e. how often to survey) to minimise uncertainty in trend estimates. In particular, the optimal mix of spatial and temporal replicates is likely to depend upon the spatial and temporal correlations in population dynamics. Although there has been considerable interest in the ecological literature on understanding spatial and temporal correlations in species’ population dynamics, little attention has been paid to its consequences for monitoring design. We address this issue using model‐based survey design to identify the optimal allocation of sampling effort among spatial and temporal replicates for estimating population trends under different levels of spatial and temporal correlation. Based on linear trends, we show that how we should allocate sampling effort among spatial and temporal replicates depends crucially on the spatial and temporal correlations in population dynamics, environmental variation, observation error and the spatial variation in temporal trends. When spatial correlation is low and temporal correlation is high, the best option is likely to be to sample many sites infrequently, particularly when observation error and/or spatial variation in temporal trends are high. When spatial correlation is high and temporal correlation is low, the best option is likely to be to sample few sites frequently, particularly when observation error and/or spatial variation in temporal trends are low. When abundances are spatially independent, it is always preferable to maximise spatial replication. This provides important insights into how spatio‐temporal monitoring programmes should be designed to estimate temporal trends in spatially structured populations. 相似文献