Visualization of metabolic interaction networks in microbial communities using VisANT 5.0

The complexity of metabolic networks in microbial communities poses an unresolved visualization and interpretation challenge. We address this challenge in the newly expanded version of a software tool for the analysis of biological networks, VisANT 5.0. We focus in particular on facilitating the visual exploration of metabolic interaction between microbes in a community, e.g. as predicted by COMETS (Computation of Microbial Ecosystems in Time and Space), a dynamic stoichiometric modeling framework. Using VisANT's unique metagraph implementation, we show how one can use VisANT 5.0 to explore different time-dependent ecosystem-level metabolic networks. In particular, we analyze the metabolic interaction network between two bacteria previously shown to display an obligate cross-feeding interdependency. In addition, we illustrate how a putative minimal gut microbiome community could be represented in our framework, making it possible to highlight interactions across multiple coexisting species. We envisage that the "symbiotic layout" of VisANT can be employed as a general tool for the analysis of metabolism in complex microbial communities as well as heterogeneous human tissues.This work was supported by the National Institutes of Health, R01GM103502-05 to CD, ZH and DS. Partial support was also provided by grants from the Office of Science (BER), U.S. Department of Energy (DE-SC0004962), the Joslin Diabetes Center (Pilot & Feasibility grant P30 DK036836), the Army Research Office under MURI award W911NF-12-1-0390, National Institutes of Health (1RC2GM092602-01, R01GM089978 and 5R01DE024468), NSF (1457695), and Defense Advanced Research Projects Agency Biological Technologies Office (BTO), Program: Biological Robustness In Complex Settings (BRICS), Purchase Request No. HR0011515303, Program Code: TRS-0 Issued by DARPA/CMO under Contract No. HR0011-15-C-0091. Funding for open access charge: National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. (R01GM103502-05 - National Institutes of Health; 1RC2GM092602-01 - National Institutes of Health; R01GM089978 - National Institutes of Health; 5R01DE024468 - National Institutes of Health; DE-SC0004962 - Office of Science (BER), U.S. Department of Energy; P30 DK036836 - Joslin Diabetes Center; W911NF-12-1-0390 - Army Research Office under MURI; 1457695 - NSF; HR0011515303 - Defense Advanced Research Projects Agency Biological Technologies Office (BTO), Program: Biological Robustness In Complex Settings (BRICS); HR0011-15-C-0091 - DARPA/CMO; National Institutes of Health)Published versio

Perivascular adipose tissue as a relevant fat depot for cardiovascular risk in obesity

Obesity is associated with increased risk of premature death, morbidity, and mortality from several cardiovascular diseases (CVDs), including stroke, coronary heart disease (CHD), myocardial infarction, and congestive heart failure. However, this is not a straightforward relationship. Although several studies have substantiated that obesity confers an independent and additive risk of all-cause and cardiovascular death, there is significant variability in these associations, with some lean individuals developing diseases and others remaining healthy despite severe obesity, the so-called metabolically healthy obese. Part of this variability has been attributed to the heterogeneity in both the distribution of body fat and the intrinsic properties of adipose tissue depots, including developmental origin, adipogenic and proliferative capacity, glucose and lipid metabolism, hormonal control, thermogenic ability, and vascularization. In obesity, these depot-specific differences translate into specific fat distribution patterns, which are closely associated with differential cardiometabolic risks. The adventitial fat layer, also known as perivascular adipose tissue (PVAT), is of major importance. Similar to the visceral adipose tissue, PVAT has a pathophysiological role in CVDs. PVAT influences vascular homeostasis by releasing numerous vasoactive factors, cytokines, and adipokines, which can readily target the underlying smooth muscle cell layers, regulating the vascular tone, distribution of blood flow, as well as angiogenesis, inflammatory processes, and redox status. In this review, we summarize the current knowledge and discuss the role of PVAT within the scope of adipose tissue as a major contributing factor to obesity-associated cardiovascular risk. Relevant clinical studies documenting the relationship between PVAT dysfunction and CVD with a focus on potential mechanisms by which PVAT contributes to obesity-related CVDs are pointed out

Active Tension Network model suggests an exotic mechanical state realized in epithelial tissues.

Mechanical interactions play a crucial role in epithelial morphogenesis, yet understanding the complex mechanisms through which stress and deformation affect cell behavior remains an open problem. Here we formulate and analyze the Active Tension Network (ATN) model, which assumes that the mechanical balance of cells within a tissue is dominated by cortical tension and introduces tension-dependent active remodeling of the cortex. We find that ATNs exhibit unusual mechanical properties. Specifically, an ATN behaves as a fluid at short times, but at long times supports external tension like a solid. Furthermore, an ATN has an extensively degenerate equilibrium mechanical state associated with a discrete conformal - "isogonal" - deformation of cells. The ATN model predicts a constraint on equilibrium cell geometries, which we demonstrate to approximately hold in certain epithelial tissues. We further show that isogonal modes are observed in the fruit y embryo, accounting for the striking variability of apical areas of ventral cells and helping understand the early phase of gastrulation. Living matter realizes new and exotic mechanical states, the study of which helps to understand biological phenomena

Towards structured sharing of raw and derived neuroimaging data across existing resources

Data sharing efforts increasingly contribute to the acceleration of scientific discovery. Neuroimaging data is accumulating in distributed domain-specific databases and there is currently no integrated access mechanism nor an accepted format for the critically important meta-data that is necessary for making use of the combined, available neuroimaging data. In this manuscript, we present work from the Derived Data Working Group, an open-access group sponsored by the Biomedical Informatics Research Network (BIRN) and the International Neuroimaging Coordinating Facility (INCF) focused on practical tools for distributed access to neuroimaging data. The working group develops models and tools facilitating the structured interchange of neuroimaging meta-data and is making progress towards a unified set of tools for such data and meta-data exchange. We report on the key components required for integrated access to raw and derived neuroimaging data as well as associated meta-data and provenance across neuroimaging resources. The components include (1) a structured terminology that provides semantic context to data, (2) a formal data model for neuroimaging with robust tracking of data provenance, (3) a web service-based application programming interface (API) that provides a consistent mechanism to access and query the data model, and (4) a provenance library that can be used for the extraction of provenance data by image analysts and imaging software developers. We believe that the framework and set of tools outlined in this manuscript have great potential for solving many of the issues the neuroimaging community faces when sharing raw and derived neuroimaging data across the various existing database systems for the purpose of accelerating scientific discovery

Controlled rotation mechanism of DNA strand exchange by the Hin serine recombinase.

DNA strand exchange by serine recombinases has been proposed to occur by a large-scale rotation of halves of the recombinase tetramer. Here we provide the first direct physical evidence for the subunit rotation mechanism for the Hin serine invertase. Single-DNA looping assays using an activated mutant (Hin-H107Y) reveal specific synapses between two hix sites. Two-DNA "braiding" experiments, where separate DNA molecules carrying a single hix are interwound, show that Hin-H107Y cleaves both hix sites and mediates multi-step rotational relaxation of the interwinding. The variable numbers of rotations in the DNA braid experiments are in accord with data from bulk experiments that follow DNA topological changes accompanying recombination by the hyperactive enzyme. The relatively slow Hin rotation rates, combined with pauses, indicate considerable rotary friction between synapsed subunit pairs. A rotational pausing mechanism intrinsic to serine recombinases is likely to be crucial for DNA ligation and for preventing deleterious DNA rearrangements

Presence and rehabilitation: toward second-generation virtual reality applications in neuropsychology

Virtual Reality (VR) offers a blend of attractive attributes for rehabilitation. The most exploited is its ability to create a 3D simulation of reality that can be explored by patients under the supervision of a therapist. In fact, VR can be defined as an advanced communication interface based on interactive 3D visualization, able to collect and integrate different inputs and data sets in a single real-like experience. However, "treatment is not just fixing what is broken; it is nurturing what is best" (Seligman & Csikszentmihalyi). For rehabilitators, this statement supports the growing interest in the influence of positive psychological state on objective health care outcomes. This paper introduces a bio-cultural theory of presence linking the state of optimal experience defined as "flow" to a virtual reality experience. This suggests the possibility of using VR for a new breed of rehabilitative applications focused on a strategy defined as transformation of flow. In this view, VR can be used to trigger a broad empowerment process within the flow experience induced by a high sense of presence. The link between its experiential and simulative capabilities may transform VR into the ultimate rehabilitative device. Nevertheless, further research is required to explore more in depth the link between cognitive processes, motor activities, presence and flow

Composite Dark Matter and LHC Interplay

The actual realization of the electroweak symmetry breaking in the context of a natural extension of the Standard Model (SM) and the nature of Dark Matter (DM) are two of the most compelling questions in high-energy particle physics. Composite Higgs models may provide a unified picture in which both the Higgs boson and the DM particle arise as pseudo Nambu-Goldstone bosons of a spontaneously broken global symmetry at a scale $f\sim$ TeV. In this paper we analyze a general class of these models based on the coset SO(6)/SO(5). Assuming the existence of light and weakly coupled spin-1 and spin-1/2 resonances which mix linearly with the elementary SM particles, we are able to compute the effective potential of the theory by means of some generalized Weinberg sum rules. The properties of the Higgs boson, DM, top quark and the above resonances are thus calculable and tightly connected. We perform a wide phenomenological analysis, considering both collider physics at the LHC and astrophysical observables. We find that these models are tightly constrained by present experimental data, which are able to completely exclude the most natural setup with $f\simeq 800$ GeV. Upon increasing the value of $f$, an allowed region appears. In particular for $f\simeq 1.1$ TeV we find a concrete realization that predicts $m_{DM}\simeq 200$ GeV for the DM mass. This DM candidate lies close to the present sensitivity of direct detection experiments and will be ruled out - or discovered - in the near future.Comment: 36 pages + 2 appendices, 9 figure