Efficient infection of cells in culture by type O foot-and-mouth disease virus requires binding to cell surface heparan sulfate.

Foot-and-mouth disease virus (FMDV) enters cells by attaching to cellular receptor molecules of the integrin family, one of which has been identified as the RGD-binding integrin alpha(v)beta3. Here we report that, in addition to an integrin binding site, type O strains of FMDV share with natural ligands of alpha(v)beta3 (i.e., vitronectin and fibronectin) a specific affinity for heparin and that binding to the cellular form of this sulfated glycan, heparan sulfate, is required for efficient infection of cells in culture. Binding of the virus to paraformaldehyde-fixed cells was powerfully inhibited by agents such as heparin, that compete with heparan sulfate or by agents that compete for heparan sulfate (platelet factor 4) or that inactivate it (heparinase). Neither chondroitin sulfate, a structurally related component of the extracellular matrix, nor dextran sulfate appreciably inhibited binding. The functional importance of heparan sulfate binding was demonstrated by the facts that (i) infection of live cells by FMDV could also be blocked specifically by heparin, albeit at a much higher concentration of inhibitor; (ii) pretreatment of cells with heparinase reduced the number of plaques formed compared with that for untreated cells; and (iii) mutant cell lines deficient in heparan sulfate expression were unable to support plaque formation by FMDV, even though they remained equally susceptible to another picornavirus, bovine enterovirus. The results show that entry of type O FMDV into cells is a complex process and suggest that the initial contact with the cell surface is made through heparan sulfate.     

The hypolimnetic protozoan plankton of a eutrophic lake

The seasonal distribution of benthic species in the water column above and below the thermocline in a small eutrophic lake is described. During summer stratification populations of Spirostomum spp, Loxodes spp., Plagiopyla and Deltopylum become established in the plankton on or below the oxycline/thermocline. At shallow sites no migration occurred and populations of the migratory species in the benthos were sparse, with the exception of Plagiopyla which occurred in high densities in the sediment. Two distinct planktonic populations are established during stratification: an epilimnetic community of obligate planktonic ciliates and a hypolimnetic community of benthic migrants.     

Pre-culturing islets with mesenchymal stromal cells using a direct contact configuration is beneficial for transplantation outcome in diabetic mice

Background aimsWe recently showed that co-transplantation of mesenchymal stromal cells (MSCs) improves islet function and revascularization in vivo. Pre-transplant islet culture is associated with the loss of islet cells. MSCs may enhance islet cell survival or function by direct cell contact mechanisms and soluble mediators. We investigated the capacity of MSCs to improve islet cell survival or β-cell function in vitro using direct and indirect contact islet-MSC configurations. We also investigated whether pre-culturing islets with MSCs improves islet transplantation outcome.MethodsThe effect of pre-culturing islets with MSCs on islet function in vitro was investigated by measuring glucose-stimulated insulin secretion. The endothelial cell density of fresh islets and islets cultured with or without MSCs was determined by immunohistochemistry. The efficacy of transplanted islets was tested in vivo using a syngeneic streptozotocin-diabetic minimal islet mass model. Graft function was investigated by monitoring blood glucose concentrations.ResultsIndirect islet-MSC co-culture configurations did not improve islet function in vitro. Pre-culturing islets using a direct contact MSC monolayer configuration improved glucose-stimulated insulin secretion in vitro, which correlated with superior islet graft function in vivo. MSC pre-culture had no effect on islet endothelial cell number in vitro or in vivo.ConclusionsPre-culturing islets with MSCs using a direct contact configuration maintains functional β-cell mass in vitro and the capacity of cultured islets to reverse hyperglycemia in diabetic mice.     

Body Shape Preferences: Associations with Rater Body Shape and Sociosexuality

There is accumulating evidence of condition-dependent mate choice in many species, that is, individual preferences varying in strength according to the condition of the chooser. In humans, for example, people with more attractive faces/bodies, and who are higher in sociosexuality, exhibit stronger preferences for attractive traits in opposite-sex faces/bodies. However, previous studies have tended to use only relatively simple, isolated measures of rater attractiveness. Here we use 3D body scanning technology to examine associations between strength of rater preferences for attractive traits in opposite-sex bodies, and raters’ body shape, self-perceived attractiveness, and sociosexuality. For 118 raters and 80 stimuli models, we used a 3D scanner to extract body measurements associated with attractiveness (male waist-chest ratio [WCR], female waist-hip ratio [WHR], and volume-height index [VHI] in both sexes) and also measured rater self-perceived attractiveness and sociosexuality. As expected, WHR and VHI were important predictors of female body attractiveness, while WCR and VHI were important predictors of male body attractiveness. Results indicated that male rater sociosexuality scores were positively associated with strength of preference for attractive (low) VHI and attractive (low) WHR in female bodies. Moreover, male rater self-perceived attractiveness was positively associated with strength of preference for low VHI in female bodies. The only evidence of condition-dependent preferences in females was a positive association between attractive VHI in female raters and preferences for attractive (low) WCR in male bodies. No other significant associations were observed in either sex between aspects of rater body shape and strength of preferences for attractive opposite-sex body traits. These results suggest that among male raters, rater self-perceived attractiveness and sociosexuality are important predictors of preference strength for attractive opposite-sex body shapes, and that rater body traits –with the exception of VHI in female raters– may not be good predictors of these preferences in either sex.     

Contrasting geographic patterns of genetic variation for molecular markers vs. phenotypic traits in the energy grass Miscanthus sinensis

Species and hybrids of Miscanthus are a promising energy crop, but their outcrossing mating systems and perennial life cycles are serious challenges for breeding programs. One approach to accelerating the domestication of Miscanthus is to harness the tremendous genetic variation that is present within this genus using phenotypic data from extensive field trials, high‐density genotyping and sequencing technologies, and rapidly developing statistical methods of relating phenotype to genotype. The success of this approach, however, hinges on detailed knowledge about the population genetic structure of the germplasm used in the breeding program. We therefore used data for 120 single‐nucleotide polymorphism and 52 simple sequence repeat markers to depict patterns of putatively neutral population structure among 244 Miscanthus genotypes grown in a field trial near Aberystwyth (UK) and delineate a population of 145 M . sinensis genotypes that will be used for association mapping and genomic selection. Comparative multivariate analyses of molecular marker and phenotypic data for 17 traits related to phenology, morphology/biomass, and cell wall composition revealed significant geographic patterns in this population. A longitudinal cline accounted for a substantial proportion of molecular marker variation (R² = 0.60, P = 3.4 × 10^?15). In contrast, genetic variation for phenotypic traits tended to follow latitudinal and altitudinal gradients, with several traits appearing to have been affected by divergent selection (i.e., Q_ST >> F_ST). These contrasting geographic trends are unusual relative to other plants and provide opportunities for powerful studies of phenotype–genotype associations and the evolutionary history of M. sinensis.     

A Systematic Review of the Screening Accuracy of the HIV Dementia Scale and International HIV Dementia Scale

Background

The HIV Dementia Scale (HDS) and International HIV Dementia Scale (IHDS) are brief tools that have been developed to screen for and aid diagnosis of HIV-associated dementia (HAD). They are increasingly being used in clinical practice for minor neurocognitive disorder (MND) as well as HAD, despite uncertainty about their accuracy.

Methods and Findings

A systematic review of the accuracy of the HDS and IHDS was conducted. Studies were assessed on Standards for Reporting Diagnostic Accuracy criteria. Pooled sensitivity, specificity, likelihood ratios (LR) and diagnostic odds ratios (DOR) were calculated for each scale as a test for HAD or MND. We retrieved 15 studies of the HDS, 10 of the IHDS, and 1 of both scales. Thirteen studies of the HDS were conducted in North America, and 7 of the IHDS studies were conducted in sub-Saharan Africa. Estimates of accuracy were highly heterogeneous between studies for the HDS but less so for the IHDS. Pooled DOR for the HDS was 7.52 (95% confidence interval 3.75–15.11), sensitivity and specificity for HAD were estimated at 68.1% and 77.9%, and sensitivity and specificity for MND were estimated at 42.0% and 91.2%. Pooled DOR for the IHDS was 3.49 (2.12–5.73), sensitivity and specificity for HAD were 74.3% and 54.7%, and sensitivity and specificity for MND were 64.3% and 66.0%.

Conclusion

Both scales were low in accuracy. The literature is limited by the lack of a gold standard, and variation in estimates of accuracy is likely to be due to differences in reference standard. There is a lack of studies comparing both scales, and they have been studied in different populations, but the IHDS may be less specific than the HDS. These rapid tests are not recommended for diagnostic use, and further research is required to inform their use in asymptomatic screening.     

Do mitochondria make nitric oxide? no?

Several papers have claimed that mitochondria contain nitric oxide synthase (NOS) and make nitric oxide (NO*) in amounts sufficient to affect mitochondrial respiration. However, we found that the addition of L-arginine or the NOS inhibitor L-NMMA to intact rat liver mitochondria did not have any effect on the respiratory rate in both State 3 and State 4. We did not detect mitochondrial NO* production by the oxymyoglobin oxidation assay, or electrochemically using an NO* electrode. An apparent NO* production detected by the Griess assay was identified as an artifact. NO* generated by eNOS added to the mitochondria could easily be detected, although succinate-supplemented mitochondria appeared to consume NO*. Our data show that NO* production by normal rat liver mitochondria cannot be detected in our laboratory, even though the levels of production claimed in the literature should easily have been measured by the techniques used. The implications for the putative mitochondrial NOS are discussed.