Dynamic updating of hippocampal object representations reflects new conceptual knowledge

Concepts organize the relationship among individual stimuli or events by highlighting shared features. Often, new goals require updating conceptual knowledge to reflect relationships based on different goal-relevant features. Here, our aim is to determine how hippocampal (HPC) object representations are organized and updated to reflect changing conceptual knowledge. Participants learned two classification tasks in which successful learning required attention to different stimulus features, thus providing a means to index how representations of individual stimuli are reorganized according to changing task goals. We used a computational learning model to capture how people attended to goal-relevant features and organized object representations based on those features during learning. Using representational similarity analyses of functional magnetic resonance imaging data, we demonstrate that neural representations in left anterior HPC correspond with model predictions of concept organization. Moreover, we show that during early learning, when concept updating is most consequential, HPC is functionally coupled with prefrontal regions. Based on these findings, we propose that when task goals change, object representations in HPC can be organized in new ways, resulting in updated concepts that highlight the features most critical to the new goal

Medial prefrontal cortex compresses concept representations through learning

Prefrontal cortex (PFC) is thought to support the ability to focus on goal-relevant information by filtering out irrelevant information, a process akin to dimensionality reduction. Here, we find direct evidence of goal-directed data compression within medial PFC during learning, such that the degree of neural compression predicts an individual's ability to selectively attend to concept-specific information. These findings suggest a domaingeneral mechanism of learning through compression in mPFC

Building concepts one episode at a time: The hippocampus and concept formation

Concepts organize our experiences and allow for meaningful inferences in novel situations. Acquiring new concepts requires extracting regularities across multiple learning experiences, a process formalized in mathematical models of learning. These models posit a computational framework that has increasingly aligned with the expanding repertoire of functions associated with the hippocampus. Here, we propose the Episodes-to-Concepts (EpCon) theoretical model of hippocampal function in concept learning and review evidence for the hippocampal computations that support concept formation including memory integration, attentional biasing, and memory-based prediction error. We focus on recent studies that have directly assessed the hippocampal role in concept learning with an innovative approach that combines computational modeling and sophisticated neuroimaging measures. Collectively, this work suggests that the hippocampus does much more than encode individual episodes; rather, it adaptively transforms initially-encoded episodic memories into organized conceptual knowledge that drives novel behavior

Allosteric communication in class A β-lactamases occurs via cooperative coupling of loop dynamics

Understanding allostery in enzymes and tools to identify it, offer promising alternative strategies to inhibitor development. Through a combination of equilibrium and nonequilibrium molecular dynamics simulations, we identify allosteric effects and communication pathways in two prototypical class A β-lactamases, TEM-1 and KPC-2, which are important determinants of antibiotic resistance. The nonequilibrium simulations reveal pathways of communication operating over distances of 30 Å or more. Propagation of the signal occurs through cooperative coupling of loop dynamics. Notably, 50% or more of clinically relevant amino acid substitutions map onto the identified signal transduction pathways. This suggests that clinically important variation may affect, or be driven by, differences in allosteric behavior, providing a mechanism by which amino acid substitutions may affect the relationship between spectrum of activity, catalytic turnover and potential allosteric behavior in this clinically important enzyme family. Simulations of the type presented here will help in identifying and analyzing such differences

BioTorrents: A File Sharing Service for Scientific Data

The transfer of scientific data has emerged as a significant challenge, as datasets continue to grow in size and demand for open access sharing increases. Current methods for file transfer do not scale well for large files and can cause long transfer times. In this study we present BioTorrents, a website that allows open access sharing of scientific data and uses the popular BitTorrent peer-to-peer file sharing technology. BioTorrents allows files to be transferred rapidly due to the sharing of bandwidth across multiple institutions and provides more reliable file transfers due to the built-in error checking of the file sharing technology. BioTorrents contains multiple features, including keyword searching, category browsing, RSS feeds, torrent comments, and a discussion forum. BioTorrents is available at http://www.biotorrents.net

Logistics of community smallpox control through contact tracing and ring vaccination: a stochastic network model

BACKGROUND: Previous smallpox ring vaccination models based on contact tracing over a network suggest that ring vaccination would be effective, but have not explicitly included response logistics and limited numbers of vaccinators. METHODS: We developed a continuous-time stochastic simulation of smallpox transmission, including network structure, post-exposure vaccination, vaccination of contacts of contacts, limited response capacity, heterogeneity in symptoms and infectiousness, vaccination prior to the discontinuation of routine vaccination, more rapid diagnosis due to public awareness, surveillance of asymptomatic contacts, and isolation of cases. RESULTS: We found that even in cases of very rapidly spreading smallpox, ring vaccination (when coupled with surveillance) is sufficient in most cases to eliminate smallpox quickly, assuming that 95% of household contacts are traced, 80% of workplace or social contacts are traced, and no casual contacts are traced, and that in most cases the ability to trace 1–5 individuals per day per index case is sufficient. If smallpox is assumed to be transmitted very quickly to contacts, it may at times escape containment by ring vaccination, but could be controlled in these circumstances by mass vaccination. CONCLUSIONS: Small introductions of smallpox are likely to be easily contained by ring vaccination, provided contact tracing is feasible. Uncertainties in the nature of bioterrorist smallpox (infectiousness, vaccine efficacy) support continued planning for ring vaccination as well as mass vaccination. If initiated, ring vaccination should be conducted without delays in vaccination, should include contacts of contacts (whenever there is sufficient capacity) and should be accompanied by increased public awareness and surveillance

A standard numbering scheme for class C β-lactamases

Unlike classes A and B, a standardized amino acid numbering scheme has not been proposed for the class C (AmpC) β-lactamases, which complicates communication in the field. Here, we propose a scheme developed through a collaborative approach that considers both sequence and structure, preserves traditional numbering of catalytically important residues (Ser64, Lys67, Tyr150, and Lys315), is adaptable to new variants or enzymes yet to be discovered, and includes a variation for genetic and epidemiological applications

Extracting key information from historical data to quantify the transmission dynamics of smallpox

<p>Abstract</p> <p>Background</p> <p>Quantification of the transmission dynamics of smallpox is crucial for optimizing intervention strategies in the event of a bioterrorist attack. This article reviews basic methods and findings in mathematical and statistical studies of smallpox which estimate key transmission parameters from historical data.</p> <p>Main findings</p> <p>First, critically important aspects in extracting key information from historical data are briefly summarized. We mention different sources of heterogeneity and potential pitfalls in utilizing historical records. Second, we discuss how smallpox spreads in the absence of interventions and how the optimal timing of quarantine and isolation measures can be determined. Case studies demonstrate the following. (1) The upper confidence limit of the 99th percentile of the incubation period is 22.2 days, suggesting that quarantine should last 23 days. (2) The highest frequency (61.8%) of secondary transmissions occurs 3–5 days after onset of fever so that infected individuals should be isolated before the appearance of rash. (3) The U-shaped age-specific case fatality implies a vulnerability of infants and elderly among non-immune individuals. Estimates of the transmission potential are subsequently reviewed, followed by an assessment of vaccination effects and of the expected effectiveness of interventions.</p> <p>Conclusion</p> <p>Current debates on bio-terrorism preparedness indicate that public health decision making must account for the complex interplay and balance between vaccination strategies and other public health measures (e.g. case isolation and contact tracing) taking into account the frequency of adverse events to vaccination. In this review, we summarize what has already been clarified and point out needs to analyze previous smallpox outbreaks systematically.</p