Topological organization of whole-brain white matter in HIV infection

Infection with human immunodeficiency virus (HIV) is associated with neuroimaging alterations. However, little is known about the topological organization of whole-brain networks and the corresponding association with cognition. As such, we examined structural whole-brain white matter connectivity patterns and cognitive performance in 29 HIV+ young adults (mean age = 25.9) with limited or no HIV treatment history. HIV+ participants and demographically similar HIV− controls (n = 16) residing in South Africa underwent magnetic resonance imaging (MRI) and neuropsychological testing. Structural network models were constructed using diffusion MRI-based multifiber tractography and T(1)-weighted MRI-based regional gray matter segmentation. Global network measures included whole-brain structural integration, connection strength, and structural segregation. Cognition was measured using a neuropsychological global deficit score (GDS) as well as individual cognitive domains. Results revealed that HIV+ participants exhibited significant disruptions to whole-brain networks, characterized by weaker structural integration (characteristic path length and efficiency), connection strength, and structural segregation (clustering coefficient) than HIV− controls (p < 0.05). GDSs and performance on learning/recall tasks were negatively correlated with the clustering coefficient (p < 0.05) in HIV+ participants. Results from this study indicate disruption to brain network integrity in treatment-limited HIV+ young adults with corresponding abnormalities in cognitive performance

Application of a Novel Quantitative Tractography Based Analysis of Diffusion Tensor Imaging to Examine Fiber Bundle Length in Human Cerebral White Matter

This paper reviews basic methods and recent applications of length-based fiber bundle analysis of cerebral white matter using diffusion magnetic resonance imaging (dMRI). Diffusion weighted imaging (DWI) is a dMRI technique that uses the random motion of water to probe tissue microstructure in the brain. Diffusion tensor imaging (DTI) is an extension of DWI that measures the magnitude and direction of water diffusion in cerebral white matter, using either voxel-based scalar metrics or tractography-based analyses. More recently, quantitative tractography based on diffusion tensor imaging (qtDTI) technology has been developed to help quantify aggregate structural anatomical properties of white matter fiber bundles, including both scalar metrics of bundle diffusion and more complex morphometric properties, such as fiber bundle length (FBL). Unlike traditional scalar diffusion metrics, FBL reflects the direction and curvature of white matter pathways coursing through the brain and is sensitive to changes within the entire tractography model. In this paper, we discuss applications of this approach to date that have provided new insights into brain organization and function. We also discuss opportunities for improving the methodology through more complex anatomical models and potential areas of new application for qtDTI

Endogenous Gonadal Hormone Exposure and Bone Sarcoma Risk

Although experimental and clinical evidence suggest that endogenous sex hormones influence bone sarcoma genesis, the hypothesis has not been adequately tested in an appropriate animal model. We conducted a historical cohort study of Rottweiler dogs because they frequently undergo elective gonadectomy and spontaneously develop appendicular bone sarcomas, which mimic the biological behavior of the osteosarcomas that affect children and adolescents. Data were collected by questionnaire from owners of 683 Rottweiler dogs living in North America. To determine whether there was an association between endogenous sex hormones and risk of bone sarcoma, relative risk (RR) of incidence rates and hazard ratios for bone sarcoma were calculated for dogs subdivided on the basis of lifetime gonadal hormone exposure. Bone sarcoma was diagnosed in 12.6% of dogs in this cohort during 71,004 dog-months follow-up. Risk for bone sarcoma was significantly influenced by age at gonadectomy. Male and female dogs that underwent gonadectomy before 1 year of age had an approximate one in four lifetime risk for bone sarcoma and were significantly more likely to develop bone sarcoma than dogs that were sexually intact [RR ±95% CI = 3.8 (1.5–9.2) for males; RR ±95% CI = 3.1 (1.1–8.3) for females]. χ2 test for trend showed a highly significant inverse dose-response relationship between duration of lifetime gonadal exposure and incidence rate of bone sarcoma (P = 0.008 for males, P = 0.006 for females). This association was independent of adult height or body weight. We conclude that the subset of Rottweiler dogs that undergo early gonadectomy represent a unique, highly accessible target population to further study the gene:environment interactions that determine bone sarcoma risk and to test whether interventions can inhibit the spontaneous development of bone sarcoma

A Code of Conduct for Marine Carbon Dioxide Removal Research

Given the clear need to inform societal decision-making on the role marine Carbon Dioxide Removal (mCDR) can play in solving the climate crisis, it is imperative that researchers begin to answer questions about its effectiveness and impacts. Yet overly hasty deployment of new ocean-based climate interventions risks harm to communities and ecosystems and could jeopardize public perception of the field as a whole. In addition, the harms, risks and benefits of mCDR efforts are unlikely to be evenly distributed. Unabated, climate change could have a devastating impact on global ecosystems and human populations, and the impacts of mCDR should be contemplated in this context. This Code of Conduct exclusively applies to mCDR research and does not attempt to put any affiliated risk in the context of the risk of delaying climate action. Its purpose is to ensure that the impacts of mCDR research activities themselves are adequately understood and accounted for as they progress. It provides a roadmap of processes, procedures, and activities that project leads should follow to ensure that decisions regarding whether, when, where, and how to conduct mCDR research are informed by relevant ethical, scientific, economic, environmental, and regulatory considerations

A thin layer angiogenesis assay: a modified basement matrix assay for assessment of endothelial cell differentiation

BACKGROUND: Basement matrices such as Matrigel™ and Geltrex™ are used in a variety of cell culture assays of anchorage-dependent differentiation including endothelial cell tube formation assays. The volumes of matrix recommended for these assays (approximately 150 μl/cm(2)) are costly, limit working distances for microscopy, and require cell detachment for subsequent molecular analysis. Here we describe the development and validation of a thin-layer angiogenesis (TLA) assay for assessing the angiogenic potential of endothelial cells that overcomes these limitations. RESULTS: Geltrex™ basement matrix at 5 μl/cm(2) in 24-well (10 μl) or 96-well (2 μl) plates supports endothelial cell differentiation into tube-like structures in a comparable manner to the standard larger volumes of matrix. Since working distances are reduced, high-resolution single cell microscopy, including DIC and confocal imaging, can be used readily. Using MitoTracker dye we now demonstrate, for the first time, live mitochondrial dynamics and visualise the 3-dimensional network of mitochondria present in differentiated endothelial cells. Using a standard commercial total RNA extraction kit (Qiagen) we also show direct RNA extraction and RT-qPCR from differentiated endothelial cells without the need to initially detach cells from their supporting matrix. CONCLUSIONS: We present here a new thin-layer assay (TLA) for measuring the anchorage-dependent differentiation of endothelial cells into tube-like structures which retains all the characteristics of the traditional approach but with the added benefit of a greatly lowered cost and better compatibility with other techniques, including RT-qPCR and high-resolution microscopy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12860-014-0041-5) contains supplementary material, which is available to authorized users

Liquid Sucrose Consumption Promotes Obesity and Impairs Glucose Tolerance Without Altering Circulating Insulin Levels

© 2018 The Obesity Society Objective: Multiple factors contribute to the rising rates of obesity and to difficulties in weight reduction that exist in the worldwide population. Caloric intake via sugar-sweetened beverages may be influential. This study tested the hypothesis that liquid sucrose intake promotes obesity by increasing serum insulin levels and tissue lipid accumulation. Methods: C57BL/6J mice were given 30% sucrose in liquid form. Changes in weight gain, body composition, energy expenditure (EE), and tissue lipid content were measured. Results: Mice drinking sucrose gained more total body mass (TBM), had greater fat mass, and displayed impaired glucose tolerance relative to control mice. These metabolic changes occurred without alterations in circulating insulin levels and despite increases in whole body EE. Lipid accrued in liver, but not skeletal muscle, of sucrose-consuming mice. Oxygen consumption (VO2) correlated with fat-free mass and moderately with TBM, but not with fat mass. ANCOVA for treatment effects on EE, with TBM, VO2, lean body mass, and fat-free mass taken as potential covariates for EE, revealed VO2 as the most significant correlation. Conclusions: Weight gain induced by intake of liquid sucrose in mice is associated with lipid accrual in liver, but not skeletal muscle, and occurs without an increase in circulating insulin

Vortex Pinning and the Non-Hermitian Mott Transition

The boson Hubbard model has been extensively studied as a model of the zero temperature superfluid/insulator transition in Helium-4 on periodic substrates. It can also serve as a model for vortex lines in superconductors with a magnetic field parallel to a periodic array of columnar pins, due to a formal analogy between the vortex lines and the statistical mechanics of quantum bosons. When the magnetic field has a component perpendicular to the pins, this analogy yields a non-Hermitian boson Hubbard model. At integer filling, we find that for small transverse fields, the insulating phase is preserved, and the transverse field is exponentially screened away from the boundaries of the superconductor. At larger transverse fields, a ``superfluid'' phase of tilted, entangled vortices appears. The universality class of the transition is found to be that of vortex lines entering the Meissner phase at H_{c1}, with the additional feature that the direction of the tilted vortices at the transition bears a non-trivial relationship to the direction of the applied magnetic field. The properties of the Mott Insulator and flux liquid phases with tilt are also discussed.Comment: 20 pages, 12 figures included in text; to appear in Physical Review

Fear of the unknown: a pre-departure qualitative study of Turkish international students

This paper presents findings from eleven in-depth interviews with Turkish undergraduate students, who were, by the time of data collection, about to spend a semester at a European university under the Erasmus exchange scheme. The students all agreed to be interviewed about their feelings about studying in a foreign culture, and were found to be anxious prior to departure about the quality of accommodation in the new destination, their language ability and the opportunity to form friendships. Fears were expressed about possible misconceptions over Turkey as a Muslim and a developing country. Suggestions are made for HEI interventions to allay student travellers’ concerns

Leptospira interrogans Endostatin-Like Outer Membrane Proteins Bind Host Fibronectin, Laminin and Regulators of Complement

The pathogenic spirochete Leptospira interrogans disseminates throughout its hosts via the bloodstream, then invades and colonizes a variety of host tissues. Infectious leptospires are resistant to killing by their hosts' alternative pathway of complement-mediated killing, and interact with various host extracellular matrix (ECM) components. The LenA outer surface protein (formerly called LfhA and Lsa24) was previously shown to bind the host ECM component laminin and the complement regulators factor H and factor H-related protein-1. We now demonstrate that infectious L. interrogans contain five additional paralogs of lenA, which we designated lenB, lenC, lenD, lenE and lenF. All six genes encode domains predicted to bear structural and functional similarities with mammalian endostatins. Sequence analyses of genes from seven infectious L. interrogans serovars indicated development of sequence diversity through recombination and intragenic duplication. LenB was found to bind human factor H, and all of the newly-described Len proteins bound laminin. In addition, LenB, LenC, LenD, LenE and LenF all exhibited affinities for fibronectin, a distinct host extracellular matrix protein. These characteristics suggest that Len proteins together facilitate invasion and colonization of host tissues, and protect against host immune responses during mammalian infection