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Previous microbiome and metabolome analyses exploring non-communicable diseases have paid scant attention to major confounders of study outcomes, such as common, pre-morbid and co-morbid conditions, or polypharmacy. Here, in the context of ischemic heart disease (IHD), we used a study design that recapitulates disease initiation, escalation and response to treatment over time, mirroring a longitudinal study that would otherwise be difficult to perform given the protracted nature of IHD pathogenesis. We recruited 1,241 middle-aged Europeans, including healthy individuals, individuals with dysmetabolic morbidities (obesity and type 2 diabetes) but lacking overt IHD diagnosis and individuals with IHD at three distinct clinical stages—acute coronary syndrome, chronic IHD and IHD with heart failure—and characterized their phenome, gut metagenome and serum and urine metabolome. We found that about 75% of microbiome and metabolome features that distinguish individuals with IHD from healthy individuals after adjustment for effects of medication and lifestyle are present in individuals exhibiting dysmetabolism, suggesting that major alterations of the gut microbiome and metabolome might begin long before clinical onset of IHD. We further categorized microbiome and metabolome signatures related to prodromal dysmetabolism, specific to IHD in general or to each of its three subtypes or related to escalation or de-escalation of IHD. Discriminant analysis based on specific IHD microbiome and metabolome features could better differentiate individuals with IHD from healthy individuals or metabolically matched individuals as compared to the conventional risk markers, pointing to a pathophysiological relevance of these features.

sample sizes and a high resolution of clinical phenotypes and medication are required, while accounting for variables known to affect the gut microbiome. Finally, drug effects are often dose-dependent, yet dosage is rarely considered in microbiome studies.To overcome these limitations, we propose a general framework for separating disease from treatment associations in multi-omics cross-sectional studies and apply it to gut metagenomic, host clinical and metabolomic measurements of 2,173 European residents from the multicentre MetaCardis cohort. The MetaCardis cohort includes patients with metabolic syndrome, severe and morbid obesity, T2D, acute and chronic coronary artery disease and heart failure, and healthy control individuals. Considering cardiometabolic disease (CMD) and herein frequently prescribed medications, we investigated drug-hostmicrobiome associations for eight major indications (antidiabetic,

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OryGenesDB (http://orygenesdb.cirad.fr/index.html) is a database developed for rice reverse genetics. OryGenesDB contains FSTs (flanking sequence tags) of various mutagens and functional genomics data, collected from both international insertion collections and the literature. The current release of OryGenesDB contains 171 000 FSTs, and annotations divided among 10 specific categories, totaling 78 annotation layers. Several additional tools have been added to the main interface; these tools enable the user to retrieve FSTs and design probes to analyze insertion lines. The major innovation of OryGenesDB 2008, besides updating the data and tools, is a new tool, Orylink, which was developed to speed up rice functional genomics by taking advantage of the resources developed in two related databases, Oryza Tag Line and GreenPhylDB. Orylink was designed to field complex queries across these three databases and store both the queries and their results in an intuitive manner. Orylink offers a simple and powerful virtual workbench for functional genomics. Alternatively, the Web services developed for Orylink can be used independently of its Web interface, increasing the interoperability between these different bioinformatics applications.

To perform goal-oriented hand movement, humans combine multiple sensory signals (e.g., vision and proprioception) that can be encoded in various reference frames (body centered and/or exo-centered). In a previous study (Tagliabue M, McIntyre J. 8: e68438, 2013), we showed that, when aligning a hand to a remembered target orientation, the brain encodes both target and response in visual space when the target is sensed by one hand and the response is performed by the other, even though both are sensed only through proprioception. Here we ask whether such visual encoding is due) to the necessity of transferring sensory information across the brain hemispheres, or ) to the necessity, due to the arms' anatomical mirror symmetry, of transforming the joint signals of one limb into the reference frame of the other. To answer this question, we asked subjects to perform purely proprioceptive tasks in different conditions: Intra, the same arm sensing the target and performing the movement; Inter/Parallel, one arm sensing the target and the other reproducing its orientation; and Inter/Mirror, one arm sensing the target and the other mirroring its orientation. Performance was very similar between Intra and Inter/Mirror (conditions not requiring joint-signal transformations), while both differed from Inter/Parallel. Manipulation of the visual scene in a virtual reality paradigm showed visual encoding of proprioceptive information only in the latter condition. These results suggest that the visual encoding of purely proprioceptive tasks is not due to interhemispheric transfer of the proprioceptive information per se, but to the necessity of transforming joint signals between mirror-symmetric limbs. Why does the brain encode goal-oriented, intermanual tasks in a visual space, even in the absence of visual feedback about the target and the hand? We show that the visual encoding is not due to the transfer of proprioceptive signals between brain hemispheres per se, but to the need, due to the mirror symmetry of the two limbs, of transforming joint angle signals of one arm in different joint signals of the other.

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