The domestication of animals led to a major shift in human subsistence patterns, from a hunter-gatherer to a sedentary agricultural lifestyle, which ultimately resulted in the development of complex ...societies. Over the past 15,000 years, the phenotype and genotype of multiple animal species, such as dogs, pigs, sheep, goats, cattle and horses, have been substantially altered during their adaptation to the human niche. Recent methodological innovations, such as improved ancient DNA extraction methods and next-generation sequencing, have enabled the sequencing of whole ancient genomes. These genomes have helped reconstruct the process by which animals entered into domestic relationships with humans and were subjected to novel selection pressures. Here, we discuss and update key concepts in animal domestication in light of recent contributions from ancient genomics.
Schistosomiasis Chemotherapy Thétiot-Laurent, Sophie A.-L.; Boissier, Jérôme; Robert, Anne ...
Angewandte Chemie,
July 29, 2013, Letnik:
52, Številka:
31
Journal Article
Recenzirano
After malaria, schistosomiasis (or bilharzia) is the second most prevalent disease in Africa, and is occurring in over 70 countries in tropical and subtropical regions. It is estimated that 600 ...million people are at risk of infection, 200 million people are infected, and at least 200 000 deaths per year are associated with the disease. All schistosome species are transmitted through contact with fresh water that is infested with free‐swimming forms of the parasite, which is known as cercariae and produced by snails. When located in the blood vessels of the host, larval and adult schistosomes digest red cells to acquire amino acids for growth and development. Vaccine candidates have been unsuccessful up to now. Against such devastating parasitic disease, the antischistosomal arsenal is currently limited to a single drug, praziquantel, which has been used for more than 35 years. Because the question of the reduction of the activity of praziquantel was raised recently, it is thus urgent to create new and safe antischistosomal drugs that should be combined with praziquantel to develop efficient bitherapies.
Bilharziasis (schistosomiasis) is the second most prevalent parasitic disease in Africa after malaria. The therapeutic arsenal against this disease is currently limited to a single drug, praziquantel, which has been used for 35 years. It is thus urgent to develop new antischistosomal drugs for efficient bi‐ or tri‐therapies in combination with praziquantel.
We demonstrate that a deep neural network can be trained to virtually refocus a two-dimensional fluorescence image onto user-defined three-dimensional (3D) surfaces within the sample. Using this ...method, termed Deep-Z, we imaged the neuronal activity of a Caenorhabditis elegans worm in 3D using a time sequence of fluorescence images acquired at a single focal plane, digitally increasing the depth-of-field by 20-fold without any axial scanning, additional hardware or a trade-off of imaging resolution and speed. Furthermore, we demonstrate that this approach can correct for sample drift, tilt and other aberrations, all digitally performed after the acquisition of a single fluorescence image. This framework also cross-connects different imaging modalities to each other, enabling 3D refocusing of a single wide-field fluorescence image to match confocal microscopy images acquired at different sample planes. Deep-Z has the potential to improve volumetric imaging speed while reducing challenges relating to sample drift, aberration and defocusing that are associated with standard 3D fluorescence microscopy.
Abstract
The long-acting antiretroviral cabotegravir and rilpivirine combination has just received FDA, EMA and Health Canada approval. This novel drug delivery approach is about to revolutionize the ...therapy of people living with HIV, decreasing the 365 daily pill burden to only six intramuscular injections per year. In addition, islatravir, a first-in-class nucleoside reverse transcriptase translocation inhibitor, is intended to be formulated as an implant with a dosing interval of 1 year or more. At present, long-acting antiretroviral therapies (LA-ARTs) are given at fixed standard doses, irrespectively of the patient’s weight and BMI, and without consideration for host genetic and non-genetic factors likely influencing their systemic disposition. Despite a few remaining challenges related to administration (e.g. pain, dedicated medical procedure), the development and implementation of LA-ARTs can overcome long-term adherence issues by improving patients’ privacy and reducing social stigma associated with the daily oral intake of anti-HIV treatments. Yet, the current ‘one-size-fits-all’ approach does not account for the recognized significant inter-individual variability in LA-ART pharmacokinetics. Therapeutic drug monitoring (TDM), an important tool for precision medicine, may provide physicians with valuable information on actual drug exposure in patients, contributing to improve their management in real life. The present review aims to update the current state of knowledge on these novel promising LA-ARTs and discusses their implications, particularly from a clinical pharmacokinetics perspective, for the future management and prevention of HIV infection, issues of ongoing importance in the absence of curative treatment or an effective vaccine.
We consider modeling and forecasting large realized covariance matrices by penalized vector autoregressive models. We consider Lasso-type estimators to reduce the dimensionality and provide strong ...theoretical guarantees on the forecast capability of our procedure. We show that we can forecast realized covariance matrices almost as precisely as if we had known the true driving dynamics of these in advance. We next investigate the sources of these driving dynamics as well as the performance of the proposed models for forecasting the realized covariance matrices of the 30 Dow Jones stocks. We find that the dynamics are not stable as the data are aggregated from the daily to lower frequencies. Furthermore, we are able beat our benchmark by a wide margin. Finally, we investigate the economic value of our forecasts in a portfolio selection exercise and find that in certain cases an investor is willing to pay a considerable amount in order get access to our forecasts.
Value-driven attentional capture Anderson, Brian A.; Laurent, Patryk A.; Yantis, Steven
Proceedings of the National Academy of Sciences - PNAS,
06/2011, Letnik:
108, Številka:
25
Journal Article
Recenzirano
Odprti dostop
Attention selects which aspects of sensory input are brought to awareness. To promote survival and well-being, attention prioritizes stimuli both voluntarily, according to context-specific goals ...(e.g., searching for car keys), and involuntarily, through attentional capture driven by physical salience (e.g., looking toward a sudden noise). Valuable stimuli strongly modulate voluntary attention allocation, but there is little evidence that high-value but contextually irrelevant stimuli capture attention as a consequence of reward learning. Here we show that visual search for a salient target is slowed by the presence of an inconspicuous, task-irrelevant item that was previously associated with monetary reward during a brief training session. Thus, arbitrary and otherwise neutral stimuli imbued with value via associative learning capture attention powerfully and persistently during extinction, independently of goals and salience. Vulnerability to such value-driven attentional capture covaries across individuals with working memory capacity and trait impulsivity. This unique form of attentional capture may provide a useful model for investigating failures of cognitive control in clinical syndromes in which value assigned to stimuli conflicts with behavioral goals (e.g., addiction, obesity).
Abstract
WikiPathways (https://www.wikipathways.org) is a biological pathway database known for its collaborative nature and open science approaches. With the core idea of the scientific community ...developing and curating biological knowledge in pathway models, WikiPathways lowers all barriers for accessing and using its content. Increasingly more content creators, initiatives, projects and tools have started using WikiPathways. Central in this growth and increased use of WikiPathways are the various communities that focus on particular subsets of molecular pathways such as for rare diseases and lipid metabolism. Knowledge from published pathway figures helps prioritize pathway development, using optical character and named entity recognition. We show the growth of WikiPathways over the last three years, highlight the new communities and collaborations of pathway authors and curators, and describe various technologies to connect to external resources and initiatives. The road toward a sustainable, community-driven pathway database goes through integration with other resources such as Wikidata and allowing more use, curation and redistribution of WikiPathways content.
Graphical Abstract
Graphical Abstract
WikiPathways enables research communities to collaborate on molecular pathway curation to create reusable, machine-readable pathway models. The pathway collections are freely available and integrated with many analysis tools and resources.
Inbreeding has long been recognized as a primary cause of fitness reduction in both wild and domesticated populations. Consanguineous matings cause inheritance of haplotypes that are identical by ...descent (IBD) and result in homozygous stretches along the genome of the offspring. Size and position of regions of homozygosity (ROHs) are expected to correlate with genomic features such as GC content and recombination rate, but also direction of selection. Thus, ROHs should be non-randomly distributed across the genome. Therefore, demographic history may not fully predict the effects of inbreeding. The porcine genome has a relatively heterogeneous distribution of recombination rate, making Sus scrofa an excellent model to study the influence of both recombination landscape and demography on genomic variation. This study utilizes next-generation sequencing data for the analysis of genomic ROH patterns, using a comparative sliding window approach. We present an in-depth study of genomic variation based on three different parameters: nucleotide diversity outside ROHs, the number of ROHs in the genome, and the average ROH size. We identified an abundance of ROHs in all genomes of multiple pigs from commercial breeds and wild populations from Eurasia. Size and number of ROHs are in agreement with known demography of the populations, with population bottlenecks highly increasing ROH occurrence. Nucleotide diversity outside ROHs is high in populations derived from a large ancient population, regardless of current population size. In addition, we show an unequal genomic ROH distribution, with strong correlations of ROH size and abundance with recombination rate and GC content. Global gene content does not correlate with ROH frequency, but some ROH hotspots do contain positive selected genes in commercial lines and wild populations. This study highlights the importance of the influence of demography and recombination on homozygosity in the genome to understand the effects of inbreeding.
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