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By randomly sampling non-overlapping sets of core genes, we show that F1 scores and error rates are stable and have little variance between replicates. Although these small core gene models have lower accuracies and higher error rates than models built from the corresponding assembled genomes, the results suggest that sufficient variation exists in the core non-AMR genes of a species for predicting AMR phenotypes.The lack of effective vaccines for many endemic diseases often forces policymakers to rely on non-immunizing control measures, such as vector control, to reduce the massive burden of these diseases. Controls can have well-known counterintuitive effects on endemic infections, including the honeymoon effect, in which partially effective controls cause not only a greater initial reduction in infection than expected, but also large outbreaks during control resulting from accumulation of susceptibles. Unfortunately, many control measures cannot be maintained indefinitely, and the results of cessation are poorly understood. Here, we examine the results of stopped or failed non-immunizing control measures in endemic settings. By using a mathematical model to compare the cumulative number of cases expected with and without control, we show that deployment of control can lead to a larger total number of infections, counting from the time that control started, than without any control-the divorce effect. This result is directly related to the population-level loss of immunity resulting from non-immunizing controls and is seen in a variety of models when non-immunizing controls are used against an infection that confers immunity. Finally, we examine three control plans for minimizing the magnitude of the divorce effect in seasonal infections and show that they are incapable of eliminating the divorce effect. While we do not suggest stopping control programs that rely on non-immunizing controls, our results strongly argue that the accumulation of susceptibility should be considered before deploying such controls against endemic infections when indefinite use of the control is unlikely. We highlight that our results are particularly germane to endemic mosquito-borne infections, such as dengue virus, both for routine management involving vector control and for field trials of novel control approaches, and in the context of non-pharmaceutical interventions aimed at COVID-19.While interacting with objects during every-day activities, e.g. when sliding a glass on a counter top, people obtain constant feedback whether they are acting in accordance with physical laws. However, classical research on intuitive physics has revealed that people's judgements systematically deviate from predictions of Newtonian physics. Recent research has explained at least some of these deviations not as consequence of misconceptions about physics but instead as the consequence of the probabilistic interaction between inevitable perceptual uncertainties and prior beliefs. How intuitive physical reasoning relates to visuomotor actions is much less known. Here, we present an experiment in which participants had to slide pucks under the influence of naturalistic friction in a simulated virtual environment. The puck was controlled by the duration of a button press, which needed to be scaled linearly with the puck's mass and with the square-root of initial distance to reach a target. Over four phases of the h Newtonian physics and weighed potential outcomes with a cost functions based on their knowledge about their own variability.3D macromolecular structural data is growing ever more complex and plentiful in the wake of substantive advances in experimental and computational structure determination methods including macromolecular crystallography, cryo-electron microscopy, and integrative methods. Efficient means of working with 3D macromolecular structural data for archiving, analyses, and visualization are central to facilitating interoperability and reusability in compliance with the FAIR Principles. We address two challenges posed by growth in data size and complexity. #link# First, data size is reduced by bespoke compression techniques. link2 Second, complexity is managed through improved software tooling and fully leveraging available data dictionary schemas. To this end, we introduce BinaryCIF, a serialization of Crystallographic Information File (CIF) format files that maintains full compatibility to related data schemas, such as PDBx/mmCIF, while reducing file sizes by more than a factor of two versus gzip compressed CIF files. Moreover, for the largest structures, BinaryCIF provides even better compression-factor ten and four versus CIF files and gzipped CIF files, respectively. Herein, we describe CIFTools, a set of libraries in Java and TypeScript for generic and typed handling of CIF and BinaryCIF files. Together, BinaryCIF and CIFTools enable lightweight, efficient, and extensible handling of 3D macromolecular structural data.Anthrax is an important but neglected zoonosis in southern Africa and elsewhere which occurs naturally in herbivorous wildlife and livestock. Fatal outbreaks in animals are spaced by potentially extended periods of non-activity during which the bacterium is maintained in soil. The ecology of the pathogen in the multi-host system and the environment is still not fully understood. This study investigated the patterns of anthrax in Zimbabwe in order to better understand the occurrence of disease in susceptible wildlife and livestock and hence its control. The study used available data in governmental reports between 1995 and 2018 and structured interviewer-administered questionnaires of local communities in three porous wildlife-livestock-human interface sites where livestock/wildlife interactions were documented from previous researches. Two non-interface sites were also included for comparison based on known previous anthrax outbreaks. Respondents from non-interface sites had significantly higher odds (χ2 = 23ase containment measures to minimize its impact on livestock, wildlife and humans.Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae). In lepromatous leprosy (LL), skin macrophages, harboring extensive bacterial multiplication, gain a distinctive foamy appearance due to increased intracellular lipid load. To determine the mechanism by which M. leprae modifies the lipid homeostasis in host cells, an in vitro M. leprae infection system, using human macrophage precursor THP-1 cells and M. leprae prepared from the footpads of nude mice, was employed. RNA extracted from skin smear samples of patients was used to investigate host gene expressions before and after multidrug therapy (MDT). We found that a cluster of peroxisome proliferator-activated receptor (PPAR) target genes associated with adipocyte differentiation were strongly induced in M. leprae-infected THP-1 cells, with increased intracellular lipid accumulation. PPAR-δ and PPAR-γ expressions were induced by M. leprae infection in a bacterial load-dependent manner, and their proteins underwent nuclear translocalization after infection, indicating activation of PPAR signaling in host cells. Either PPAR-δ or PPAR-γ antagonist abolished the effect of M. leprae to modify host gene expressions and inhibited intracellular lipid accumulation in host cells. M. leprae-specific gene expressions were detected in the skin smear samples both before and after MDT, whereas PPAR target gene expressions were dramatically diminished after MDT. These results suggest that M. leprae infection activates host PPAR signaling to induce an array of adipocyte differentiation-associated genes, leading to accumulation of intracellular lipids to accommodate M. leprae parasitization. Certain PPAR target genes in skin lesions may serve as biomarkers for monitoring treatment efficacy.The timescales of adaptation to novel dynamics are well explained by a dual-rate model with slow and fast states. This model can predict interference, savings and spontaneous recovery, but cannot account for adaptation to multiple tasks, as each new task drives unlearning of the previously learned task. Nevertheless, in the presence of appropriate contextual cues, humans are able to adapt simultaneously to opposing dynamics. Consequently learn more was expanded, suggesting that dual-adaptation occurs through a single fast process and multiple slow processes. However, such a model does not predict spontaneous recovery within dual-adaptation. Here we assess the existence of multiple fast processes by examining the presence of spontaneous recovery in two experimental variations of an adaptation-de-adaptation-error-clamp paradigm within dual-task adaptation in humans. In both experiments, evidence for spontaneous recovery towards the initially learned dynamics (A) was found in the error-clamp phase, invalidating the one-fast-two-slow dual-rate model. link3 However, as adaptation is not only constrained to two timescales, we fit twelve multi-rate models to the experimental data. BIC model comparison again supported the existence of two fast processes, but extended the timescales to include a third rate the ultraslow process. Even within our single day experiment, we found little evidence for decay of the learned memory over several hundred error-clamp trials. Overall, we show that dual-adaptation can be best explained by a two-fast-triple-rate model over the timescales of adaptation studied here. Longer term learning may require even slower timescales, explaining why we never forget how to ride a bicycle.The amygdala, a subcortical structure known for social and emotional processing, consists of multiple subnuclei with unique functions and connectivity patterns. Tracer studies in adult macaques have shown that the basolateral subnuclei differentially connect to parts of visual cortex, with stronger connections to anterior regions and weaker connections to posterior regions; infant macaques show robust connectivity even with posterior visual regions. Do these developmental differences also exist in the human amygdala, and are there specific functional regions that undergo the most pronounced developmental changes in their connections with the amygdala? To address these questions, we explored the functional connectivity (from resting-state fMRI data) of the basolateral amygdala to occipitotemporal cortex in human neonates scanned within one week of life and compared the connectivity patterns to those observed in young adults. Specifically, we calculated amygdala connectivity to anterior-posterior gradients of the anatomically-defined occipitotemporal cortex, and also to putative occipitotemporal functional parcels, including primary and high-level visual and auditory cortices (V1, A1, face, scene, object, body, high-level auditory regions). Results showed a decreasing gradient of functional connectivity to the occipitotemporal cortex in adults-similar to the gradient seen in macaque tracer studies-but no such gradient was observed in neonates. Further, adults had stronger connections to high-level functional regions associated with face, body, and object processing, and weaker connections to primary sensory regions (i.e., A1, V1), whereas neonates showed the same amount of connectivity to primary and high-level sensory regions. Overall, these results show that functional connectivity between the amygdala and occipitotemporal cortex is not yet differentiated in neonates, suggesting a role of maturation and experience in shaping these connections later in life.
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