Plasma fatty acid levels may regulate the Zn2+-dependent activities of histidine-rich glycoprotein

Histidine-rich glycoprotein (HRG) is a plasma adaptor protein involved in the formation of protein complexes that regulate a number of biological processes in the blood, most notably coagulation and the immune system. Elevated levels of HRG are clinically linked to thrombotic disorders such as blood vessel occlusion. A large body of evidence suggests that Zn²⁺ ions stimulate HRG-complex formation; however, under normal conditions the vast majority of Zn²⁺ in the blood is bound to human serum albumin (HSA). We have previously demonstrated that high levels of fatty acid act as an allosteric switch which disrupts the major Zn²⁺-binding site on HSA. Transient or sustained elevation of plasma fatty acid levels may therefore increase the proportion of plasma Zn²⁺ associated with HRG. We speculate that this mechanism may potentiate an increased risk of thrombosis in individuals with elevated fatty acid levels such as those associated with cancer, obesity and diabetes.     

Positive Selection on Loci Associated with Drug and Alcohol Dependence

Much of the evolution of human behavior remains a mystery, including how certain disadvantageous behaviors are so prevalent. Nicotine addiction is one such phenotype. Several loci have been implicated in nicotine related phenotypes including the nicotinic receptor gene clusters (CHRNs) on chromosomes 8 and 15. Here we use 1000 Genomes sequence data from 3 populations (Africans, Asians and Europeans) to examine whether natural selection has occurred at these loci. We used Tajima’s D and the integrated haplotype score (iHS) to test for evidence of natural selection. Our results provide evidence for strong selection in the nicotinic receptor gene cluster on chromosome 8, previously found to be significantly associated with both nicotine and cocaine dependence, as well as evidence selection acting on the region containing the CHRNA5 nicotinic receptor gene on chromosome 15, that is genome wide significant for risk for nicotine dependence. To examine the possibility that this selection is related to memory and learning, we utilized genetic data from the Collaborative Studies on the Genetics of Alcoholism (COGA) to test variants within these regions with three tests of memory and learning, the Wechsler Adult Intelligence Scale (WAIS) Block Design, WAIS Digit Symbol and WAIS Information tests. Of the 17 SNPs genotyped in COGA in this region, we find one significantly associated with WAIS digit symbol test results. This test captures aspects of reaction time and memory, suggesting that a phenotype relating to memory and learning may have been the driving force behind selection at these loci. This study could begin to explain why these seemingly deleterious SNPs are present at their current frequencies.     

Hands-Free Image Capture,Data Tagging and Transfer Using Google Glass: A Pilot Study for Improved Wound Care Management

Chronic wounds, including pressure ulcers, compromise the health of 6.5 million Americans and pose an annual estimated burden of $25 billion to the U.S. health care system. When treating chronic wounds, clinicians must use meticulous documentation to determine wound severity and to monitor healing progress over time. Yet, current wound documentation practices using digital photography are often cumbersome and labor intensive. The process of transferring photos into Electronic Medical Records (EMRs) requires many steps and can take several days. Newer smartphone and tablet-based solutions, such as Epic Haiku, have reduced EMR upload time. However, issues still exist involving patient positioning, image-capture technique, and patient identification. In this paper, we present the development and assessment of the SnapCap System for chronic wound photography. Through leveraging the sensor capabilities of Google Glass, SnapCap enables hands-free digital image capture, and the tagging and transfer of images to a patient’s EMR. In a pilot study with wound care nurses at Stanford Hospital (n=16), we (i) examined feature preferences for hands-free digital image capture and documentation, and (ii) compared SnapCap to the state of the art in digital wound care photography, the Epic Haiku application. We used the Wilcoxon Signed-ranks test to evaluate differences in mean ranks between preference options. Preferred hands-free navigation features include barcode scanning for patient identification, Z(15) = -3.873, p < 0.001, r = 0.71, and double-blinking to take photographs, Z(13) = -3.606, p < 0.001, r = 0.71. In the comparison between SnapCap and Epic Haiku, the SnapCap System was preferred for sterile image-capture technique, Z(16) = -3.873, p < 0.001, r = 0.68. Responses were divided with respect to image quality and overall ease of use. The study’s results have contributed to the future implementation of new features aimed at enhancing mobile hands-free digital photography for chronic wound care.     

Investigating environmental variation and landscape characteristics of an urban–rural gradient using woodland carabid assemblages

Aim To investigate environmental variation and associated assemblage changes of carabid beetles along an urban–rural gradient. Location ‘Quercus–Acer’ (oak–sycamore) woodlands in the city of Birmingham, UK. Methods We collected carabid data using pitfall traps on 12 sites in the city. The traps were run from April–September in 2000, and we collected environmental data on 24 individual variables associated with the individual sites and their landscape context. Changes in carabid assemblages were analysed using repeat measures anova and the environment–species relationships with a Redundancy Analyses (RDA) and Generalized Linear Modelling (GLM). Results We found that: (1) species richness and diversity were lower in the urban and suburban zone and higher in the rural zone; (2) Berger Parker dominance index was higher in the urban and suburban zones; (3) the number of woodland and woodland associated species was significantly higher at the rural end of the gradient; (4) the number of short‐winged (brachypterous) species was highest in the rural zone and decreased towards the urban woodlands, whereas the long‐winged species were more abundant in suburban woodlands; (5) the median weight length (WML) of the assemblage declined along the gradient from the rural to the urban zone, as did the number of large species; and (6) five of the 24 environmental variables showed a significant relationship with variation in the carabid assemblage. At site level the carabid assemblages were related to the level of site disturbance and soil penetrability, whereas site size and amount of woodland and urban land within 5 km of the site were important at a larger landscape scale. Main conclusions The results suggest that urbanization has a deleterious impact on carabid assemblages, causing a reduction in species richness from the rural fringe to the centre of the city. Changes in assemblage structure were related to woodland fragmentation, which led to variations in woodland size, woodland location and site disturbance due to trampling. Large, flightless and specialist woodland species are more susceptible to changes associated with urbanization, presumably due to their longer life spans, lower reproductive rates, more specialized niches and more limited dispersal potential.     

Modeling <Emphasis Type="Italic">Neisseria meningitidis</Emphasis> metabolism: from genome to metabolic fluxes

Background  

Neisseria meningitidis is a human pathogen that can infect diverse sites within the human host. The major diseases caused by N. meningitidis are responsible for death and disability, especially in young infants. In general, most of the recent work on N. meningitidis focuses on potential antigens and their functions, immunogenicity, and pathogenicity mechanisms. Very little work has been carried out on Neisseria primary metabolism over the past 25 years.     

When and how did the terrestrial mid-Permian mass extinction occur? Evidence from the tetrapod record of the Karoo Basin,South Africa

A mid-Permian (Guadalupian epoch) extinction event at approximately 260 Ma has been mooted for two decades. This is based primarily on invertebrate biostratigraphy of Guadalupian–Lopingian marine carbonate platforms in southern China, which are temporally constrained by correlation to the associated Emeishan Large Igneous Province (LIP). Despite attempts to identify a similar biodiversity crisis in the terrestrial realm, the low resolution of mid-Permian tetrapod biostratigraphy and a lack of robust geochronological constraints have until now hampered both the correlation and quantification of terrestrial extinctions. Here we present an extensive compilation of tetrapod-stratigraphic data analysed by the constrained optimization (CONOP) algorithm that reveals a significant extinction event among tetrapods within the lower Beaufort Group of the Karoo Basin, South Africa, in the latest Capitanian. Our fossil dataset reveals a 74–80% loss of generic richness between the upper Tapinocephalus Assemblage Zone (AZ) and the mid-Pristerognathus AZ that is temporally constrained by a U–Pb zircon date (CA-TIMS method) of 260.259 ± 0.081 Ma from a tuff near the top of the Tapinocephalus AZ. This strengthens the biochronology of the Permian Beaufort Group and supports the existence of a mid-Permian mass extinction event on land near the end of the Guadalupian. Our results permit a temporal association between the extinction of dinocephalian therapsids and the LIP volcanism at Emeishan, as well as the marine end-Guadalupian extinctions.     

Automated Assay of Telomere Length Measurement and Informatics for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort

The Kaiser Permanente Research Program on Genes, Environment, and Health (RPGEH) Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort includes DNA specimens extracted from saliva samples of 110,266 individuals. Because of its relationship to aging, telomere length measurement was considered an important biomarker to develop on these subjects. To assay relative telomere length (TL) on this large cohort over a short time period, we created a novel high throughput robotic system for TL analysis and informatics. Samples were run in triplicate, along with control samples, in a randomized design. As part of quality control, we determined the within-sample variability and employed thresholds for the elimination of outlying measurements. Of 106,902 samples assayed, 105,539 (98.7%) passed all quality control (QC) measures. As expected, TL in general showed a decline with age and a sex difference. While telomeres showed a negative correlation with age up to 75 years, in those older than 75 years, age positively correlated with longer telomeres, indicative of an association of longer telomeres with more years of survival in those older than 75. Furthermore, while females in general had longer telomeres than males, this difference was significant only for those older than age 50. An additional novel finding was that the variance of TL between individuals increased with age. This study establishes reliable assay and analysis methodologies for measurement of TL in large, population-based human studies. The GERA cohort represents the largest currently available such resource, linked to comprehensive electronic health and genotype data for analysis.     

A Highlights from MBoC Selection: Characterization of VAMP isoforms in 3T3-L1 adipocytes: implications for GLUT4 trafficking

The fusion of GLUT4-containing vesicles with the plasma membrane of adipocytes is a key facet of insulin action. This process is mediated by the formation of functional soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE) complexes between the plasma membrane t-SNARE complex and the vesicle v-SNARE or VAMP. The t-SNARE complex consists of Syntaxin4 and SNAP23, and whereas many studies identify VAMP2 as the v-SNARE, others suggest that either VAMP3 or VAMP8 may also fulfil this role. Here we characterized the levels of expression, distribution, and association of all the VAMPs expressed in 3T3-L1 adipocytes to provide the first systematic analysis of all members of this protein family for any cell type. Despite our finding that all VAMP isoforms form SDS-resistant SNARE complexes with Syntaxin4/SNAP23 in vitro, a combination of levels of expression (which vary by >30-fold), subcellular distribution, and coimmunoprecipitation analyses lead us to propose that VAMP2 is the major v-SNARE involved in GLUT4 trafficking to the surface of 3T3-L1 adipocytes.     

Simulation of human atherosclerotic femoral plaque tissue: the influence of plaque material model on numerical results

Background

Due to the limited number of experimental studies that mechanically characterise human atherosclerotic plaque tissue from the femoral arteries, a recent trend has emerged in current literature whereby one set of material data based on aortic plaque tissue is employed to numerically represent diseased femoral artery tissue. This study aims to generate novel vessel-appropriate material models for femoral plaque tissue and assess the influence of using material models based on experimental data generated from aortic plaque testing to represent diseased femoral arterial tissue.

Methods

Novel material models based on experimental data generated from testing of atherosclerotic femoral artery tissue are developed and a computational analysis of the revascularisation of a quarter model idealised diseased femoral artery from a 90% diameter stenosis to a 10% diameter stenosis is performed using these novel material models. The simulation is also performed using material models based on experimental data obtained from aortic plaque testing in order to examine the effect of employing vessel appropriate material models versus those currently employed in literature to represent femoral plaque tissue.

Results

Simulations that employ material models based on atherosclerotic aortic tissue exhibit much higher maximum principal stresses within the plaque than simulations that employ material models based on atherosclerotic femoral tissue. Specifically, employing a material model based on calcified aortic tissue, instead of one based on heavily calcified femoral tissue, to represent diseased femoral arterial vessels results in a 487 fold increase in maximum principal stress within the plaque at a depth of 0.8 mm from the lumen.

Conclusions

Large differences are induced on numerical results as a consequence of employing material models based on aortic plaque, in place of material models based on femoral plaque, to represent a diseased femoral vessel. Due to these large discrepancies, future studies should seek to employ vessel-appropriate material models to simulate the response of diseased femoral tissue in order to obtain the most accurate numerical results.