Towards ontology-driven navigation of the lipid bibliosphere

10.1186/1471-2105-9-S1-S5BMC Bioinformatics9SUPPL. 1BBMI

Peak Width of Skeletonized Mean Diffusivity as a Marker of Diffuse Cerebrovascular Damage.

The peak width of skeletonized mean diffusivity (PSMD) has been proposed as a fully automated imaging marker of relevance to cerebral small vessel disease (SVD). We assessed PSMD in relation to conventional SVD markers, global measures of neurodegeneration, and cognition. 145 participants underwent 3T brain MRI and cognitive assessment. 112 were patients with mild cognitive impairment, Alzheimer's disease, progressive supranuclear palsy, dementia with Lewy bodies, or frontotemporal dementia. PSMD, SVD burden [white matter hyperintensities (WMH), enlarged perivascular spaces (EPVS), microbleeds, lacunes], average mean diffusivity (MD), gray matter (GM), white matter (WM), and total intracranial volume were quantified. Robust linear regression was conducted to examine associations between variables. Dominance analysis assessed the relative importance of markers in predicting various outcomes. Regional analyses examined spatial overlap between PSMD and WMH. PSMD was associated with global and regional SVD measures, especially WMH and microbleeds. Dominance analysis demonstrated that among SVD markers, WMH was the strongest predictor of PSMD. Furthermore, PSMD was more closely associated to WMH than with GM and WM volumes. PSMD was associated with WMH across all regions, and correlations were not significantly stronger in corresponding regions (e.g., frontal PSMD and frontal WMH) compared to non-corresponding regions. PSMD outperformed all four conventional SVD markers and MD in predicting cognition, but was comparable to GM and WM volumes. PSMD was robustly associated with established SVD markers. This new measure appears to be a marker of diffuse brain injury, largely due to vascular pathology, and may be a useful and convenient metric of overall cerebrovascular burden

A Nonlinear Force-Free Magnetic Field Approximation Suitable for Fast Forward-Fitting to Coronal Loops. I. Theory

We derive an analytical approximation of nonlinear force-free magnetic field solutions (NLFFF) that can efficiently be used for fast forward-fitting to solar magnetic data, constrained either by observed line-of-sight magnetograms and stereoscopically triangulated coronal loops, or by 3D vector-magnetograph data. The derived NLFFF solutions provide the magnetic field components $B_x({\bf x})$, $B_y({\bf x})$, $B_z({\bf x})$, the force-free parameter $\alpha({\bf x})$, the electric current density ${\bf j}({\bf x})$, and are accurate to second-order (of the nonlinear force-free $\alpha$-parameter). The explicit expressions of a force-free field can easily be applied to modeling or forward-fitting of many coronal phenomena.Comment: Solar Physics (in press), 26 pages, 11 figure

A Nonlinear Force-Free Magnetic Field Approximation Suitable for Fast Forward-Fitting to Coronal Loops. II. Numeric Code and Tests

Based on a second-order approximation of nonlinear force-free magnetic field solutions in terms of uniformly twisted field lines derived in Paper I, we develop here a numeric code that is capable to forward-fit such analytical solutions to arbitrary magnetogram (or vector magnetograph) data combined with (stereoscopically triangulated) coronal loop 3D coordinates. We test the code here by forward-fitting to six potential field and six nonpotential field cases simulated with our analytical model, as well as by forward-fitting to an exactly force-free solution of the Low and Lou (1990) model. The forward-fitting tests demonstrate: (i) a satisfactory convergence behavior (with typical misalignment angles of $\mu \approx 1^\circ-10^\circ$), (ii) relatively fast computation times (from seconds to a few minutes), and (iii) the high fidelity of retrieved force-free $\alpha$-parameters ($\alpha_{\rm fit}/\alpha_{\rm model} \approx 0.9-1.0$ for simulations and $\alpha_{\rm fit}/\alpha_{\rm model} \approx 0.7\pm0.3$ for the Low and Lou model). The salient feature of this numeric code is the relatively fast computation of a quasi-forcefree magnetic field, which closely matches the geometry of coronal loops in active regions, and complements the existing {\sl nonlinear force-free field (NLFFF)} codes based on photospheric magnetograms without coronal constraints.Comment: Solar PHysics, (in press), 25 pages, 11 figure

In vivo neuroinflammation and cerebral small vessel disease in mild cognitive impairment and Alzheimer’s disease

Introduction: Associations between cerebral small vessel disease (SVD) and inflammation have been largely examined using peripheral blood markers of inflammation, with few studies measuring inflammation within the brain. We investigated the cross-sectional relationship between SVD and in vivo neuroinflammation using [11C]PK11195 positron emission tomography (PET) imaging. Methods: Forty-two participants were recruited (according to NIA-AA guidelines, 14 healthy controls, 14 mild Alzheimer’s disease, 14 amyloid-positive mild cognitive impairment). Neuroinflammation was assessed using [11C]PK11195 PET imaging, a marker of microglial activation. To quantify SVD, we assessed white matter hyperintensities (WMH), enlarged perivascular spaces, cerebral microbleeds and lacunes. Composite scores were calculated for global SVD burden, and SVD subtypes of hypertensive arteriopathy and cerebral amyloid angiopathy (CAA). General linear models examined associations between SVD and [11C]PK11195, adjusting for sex, age, education, cognition, scan interval, and corrected for multiple comparisons via false discovery rate (FDR). Dominance analysis directly compared the relative importance of hypertensive arteriopathy and CAA scores as predictors of [11C]PK11195. Results: Global [11C]PK11195 binding was associated with SVD markers, particularly in regions typical of hypertensive arteriopathy: deep microbleeds (β=0.63, F(1,35)=35.24, p<0.001), deep WMH (β=0.59, t=4.91, p<0.001). In dominance analysis, hypertensive arteriopathy score outperformed CAA in predicting [11C]PK11195 binding globally and in 28 out of 37 regions of interest, especially the medial temporal lobe (β=0.66–0.76, t=3.90–5.58, FDR-corrected p (pFDR)=<0.001–0.002) and orbitofrontal cortex (β=0.51–0.57, t=3.53–4.30, pFDR=0.001–0.004). Conclusion: Microglial activation is associated with SVD, particularly with the hypertensive arteriopathy subtype of SVD. Although further research is needed to determine causality, our study suggests that targeting neuroinflammation might represent a novel therapeutic strategy for SVD

The effects of home-based HIV counseling and testing on HIV/AIDS stigma among individuals and community leaders in western Kenya: Evidence from a cluster-randomized trial 1,2

HIV counseling and testing services play an important role in HIV treatment and prevention efforts in developing countries. Community-wide testing campaigns to detect HIV earlier may additionally impact community knowledge and beliefs about HIV. We conducted a cluster-randomized evaluation of a home-based HIV testing campaign in western Kenya and evaluated the effects of the campaign on community leaders’ and members’ stigma toward people living with HIV/AIDS. We find that this type of large-scale HIV testing can be implemented successfully in the presence of stigma, perhaps due to its “whole community” approach. The home-based HIV testing intervention resulted in community leaders reporting lower levels of stigma. However, stigma among community members reacted in mixed ways, and there is little evidence that the program affected beliefs about HIV prevalence and prevention

Skin-impedance in Fabry Disease: A prospective, controlled, non-randomized clinical study

<p>Abstract</p> <p>Background</p> <p>We previously demonstrated improved sweating after enzyme replacement therapy (ERT) in Fabry disease using the thermo-regularity sweat and quantitative sudomotor axon reflex tests. Skin-impedance, a measure skin-moisture (sweating), has been used in the clinical evaluation of burns and pressure ulcers using the portable dynamic dermal impedance monitor (DDIM) system.</p> <p>Methods</p> <p>We compared skin impedance measurements in hemizygous patients with Fabry disease (22 post 3-years of bi-weekly ERT and 5 ERT naive) and 22 healthy controls. Force compensated skin-moisture values were used for statistical analysis. Outcome measures included 1) moisture reading of the 100^threpetitive reading, 2) rate of change, 3) average of 60–110^threading and 4) overall average of all readings.</p> <p>Results</p> <p>All outcome measures showed a significant difference in skin-moisture between Fabry patients and control subjects (p < 0.0001). There was no difference between Fabry patients on ERT and patients naïve to ERT. Increased skin-impedance values for the four skin-impedance outcome measures were found in a small number of dermatome test-sites two days post-enzyme infusions.</p> <p>Conclusion</p> <p>The instrument portability, ease of its use, a relatively short time required for the assessment, and the fact that DDIM system was able to detect the difference in skin-moisture renders the instrument a useful clinical tool.</p

Caveolin-1 protects B6129 mice against Helicobacter pylori gastritis.

Caveolin-1 (Cav1) is a scaffold protein and pathogen receptor in the mucosa of the gastrointestinal tract. Chronic infection of gastric epithelial cells by Helicobacter pylori (H. pylori) is a major risk factor for human gastric cancer (GC) where Cav1 is frequently down-regulated. However, the function of Cav1 in H. pylori infection and pathogenesis of GC remained unknown. We show here that Cav1-deficient mice, infected for 11 months with the CagA-delivery deficient H. pylori strain SS1, developed more severe gastritis and tissue damage, including loss of parietal cells and foveolar hyperplasia, and displayed lower colonisation of the gastric mucosa than wild-type B6129 littermates. Cav1-null mice showed enhanced infiltration of macrophages and B-cells and secretion of chemokines (RANTES) but had reduced levels of CD25+ regulatory T-cells. Cav1-deficient human GC cells (AGS), infected with the CagA-delivery proficient H. pylori strain G27, were more sensitive to CagA-related cytoskeletal stress morphologies ("humming bird") compared to AGS cells stably transfected with Cav1 (AGS/Cav1). Infection of AGS/Cav1 cells triggered the recruitment of p120 RhoGTPase-activating protein/deleted in liver cancer-1 (p120RhoGAP/DLC1) to Cav1 and counteracted CagA-induced cytoskeletal rearrangements. In human GC cell lines (MKN45, N87) and mouse stomach tissue, H. pylori down-regulated endogenous expression of Cav1 independently of CagA. Mechanistically, H. pylori activated sterol-responsive element-binding protein-1 (SREBP1) to repress transcription of the human Cav1 gene from sterol-responsive elements (SREs) in the proximal Cav1 promoter. These data suggested a protective role of Cav1 against H. pylori-induced inflammation and tissue damage. We propose that H. pylori exploits down-regulation of Cav1 to subvert the host's immune response and to promote signalling of its virulence factors in host cells

Elevated atmospheric [CO2] can dramatically increase wheat yields in semi-arid environments and buffer against heat waves

Wheat production will be impacted by increasing concentration of atmospheric CO2 [CO2], which is expected to rise from about 400 μmol mol−1 in 2015 to 550 μmol mol−1 by 2050. Changes to plant physiology and crop responses from elevated [CO2] (e[CO2]) are well documented for some environments, but field-level responses in dryland Mediterranean environments with terminal drought and heat waves are scarce. The Australian Grains Free Air CO2 Enrichment facility was established to compare wheat (Triticum aestivum) growth and yield under ambient (~370 μmol−1 in 2007) and e[CO2] (550 μmol−1) in semi-arid environments. Experiments were undertaken at two dryland sites (Horsham and Walpeup) across three years with two cultivars, two sowing times and two irrigation treatments. Mean yield stimulation due to e[CO2] was 24% at Horsham and 53% at Walpeup, with some treatment responses greater than 70%, depending on environment. Under supplemental irrigation, e[CO2] stimulated yields at Horsham by 37% compared to 13% under rainfed conditions, showing that water limited growth and yield response to e[CO2]. Heat wave effects were ameliorated under e[CO2] as shown by reductions of 31% and 54% in screenings and 10% and 12% larger kernels (Horsham and Walpeup). Greatest yield stimulations occurred in the e[CO2] late sowing and heat stressed treatments, when supplied with more water. There were no clear differences in cultivar response due to e[CO2]. Multiple regression showed that yield response to e[CO2] depended on temperatures and water availability before and after anthesis. Thus, timing of temperature and water and the crop's ability to translocate carbohydrates to the grain postanthesis were all important in determining the e[CO2] response. The large responses to e[CO2] under dryland conditions have not been previously reported and underscore the need for field level research to provide mechanistic understanding for adapting crops to a changing climate