Strains and stresses in sub-dermal tissues of the buttocks are greater in paraplegics than in healthy during sitting

A pressure-related deep tissue injury (DTI) is a severe pressure ulcer, which initiates in muscle tissue overlying a bony prominence (e.g. the ischial tuberosities, IT) and progresses outwards through fat and skin, unnoticed by the paralyzed patient. We recently showed that internal strains and stresses in muscle and fat of individuals at anatomical sites susceptible to DTI can be evaluated by integrating Open-MRI scans with subject-specific finite element (FE) analyzes (Linder-Ganz et al., Journal of Biomechanics, 2007); however, sub-dermal soft tissue strains/stresses from paraplegics are still missing in literature. We hypothesize that the pathoanatomy of the buttocks in paraplegia increases the internal soft tissue loads under the IT, making these patients inherently susceptible to DTI. We hence compared the strain and stress peaks in the gluteus muscle and fat tissues under the IT of six healthy and six paraplegic patients, using the coupled MRI-FE method. Peak principal compression, principal tension, von Mises and shear strains in the gluteus were 1.2-, 3.1-, 1.4- and 1.4-fold higher in paraplegics than in healthy, respectively (p<0.02). Likewise, peak principal compression, principal tension, von Mises and shear stresses in the gluteus were 1.9-, 2.5-, 2.1- and 1.7-fold higher for the paraplegics (p<0.05). Peak gluteal compression and shear stresses decreased by as much as 70% when the paraplegic patients moved from a sitting to a lying posture, indicating on the effectiveness of recommending such patients to lie down after prolonged periods of sitting. This is the first attempt to compare internal soft tissue loads between paraplegic and healthy subjects, using an objective standardized bioengineering method of analysis. The findings support our hypothesis that internal tissue loads are significantly higher in paraplegics, and that postural changes significantly affect these loads. The method of analysis is useful for quantifying the effectiveness of various interventions to alleviate sub-dermal tissue loads at sites susceptible to pressure ulcers and DTI, including cushions, mattresses, recommendations for posture and postural changes, etc.     

Analysis of polypeptide movement in the SecY channel during SecA-mediated protein translocation

In bacteria most secretory proteins are transported across the plasma membrane by the interplay of the ATPase SecA with the translocation channel formed by the SecY complex; SecA uses cycles of ATP hydrolysis to "push" consecutive segments of a polypeptide substrate through the channel. Here we have addressed the mechanism of this process by following the fate of stalled translocation intermediates. These were generated by using a polypeptide substrate containing a bulky disulfide-bonded loop, thus preventing the final residues from passing through the channel. Protease protection experiments showed that the intermediates were stable in the presence of ATP and could complete translocation once the block was removed. The translocation intermediate was also stable when SecA associated with ATPgammaS, a poorly hydrolyzable ATP analog, or ADP plus AlF(4), which mimics the transition state during ATP hydrolysis. In contrast, when SecA was in its ADP-bound state, the translocating polypeptide moved back into the cytosol, as indicated by the disappearance of the protected fragment. Backsliding was not significantly altered by deletion of the plug domain, a short helix in the center of the SecY channel, but it was slowed down when changes were introduced into the pore ring, the constriction of the hourglass-shaped channel. In all cases, backsliding was significantly slower than forward translocation. Together, these data suggest that SecA binds the polypeptide chain in its ATP state and releases it in the ADP state. The channel itself does not bind the polypeptide chain but provides "friction" that minimizes backsliding when ADP-bound SecA resets to "grab" the next segment of the substrate.     

The multiple phenylpropene synthases in both Clarkia breweri and Petunia hybrida represent two distinct protein lineages

Many plants synthesize the volatile phenylpropene compounds eugenol and isoeugenol to serve in defense against herbivores and pathogens and to attract pollinators. Clarkia breweri flowers emit a mixture of eugenol and isoeugenol, while Petunia hybrida flowers emit mostly isoeugenol with small amounts of eugenol. We recently reported the identification of a petunia enzyme, isoeugenol synthase 1 (PhIGS1) that catalyzes the formation of isoeugenol, and an Ocimum basilicum (basil) enzyme, eugenol synthase 1 (ObEGS1), that produces eugenol. ObEGS1 and PhIGS1 both utilize coniferyl acetate, are 52% sequence identical, and belong to a family of NADPH-dependent reductases involved in secondary metabolism. Here we show that C. breweri flowers have two closely related proteins (96% identity), CbIGS1 and CbEGS1, that are similar to ObEGS1 (58% and 59% identity, respectively) and catalyze the formation of isoeugenol and eugenol, respectively. In vitro mutagenesis experiments demonstrate that substitution of only a single residue can substantially affect the product specificity of these enzymes. A third C. breweri enzyme identified, CbEGS2, also catalyzes the formation of eugenol from coniferyl acetate and is only 46% identical to CbIGS1 and CbEGS1 but more similar (>70%) to other types of reductases. We also found that petunia flowers contain an enzyme, PhEGS1, that is highly similar to CbEGS2 (82% identity) and that converts coniferyl acetate to eugenol. Our results indicate that plant enzymes with EGS and IGS activities have arisen multiple times and in different protein lineages.     

High-speed, miniaturized fluorescence microscopy in freely moving mice

A central goal in biomedicine is to explain organismic behavior in terms of causal cellular processes. However, concurrent observation of mammalian behavior and underlying cellular dynamics has been a longstanding challenge. We describe a miniaturized (1.1 g mass) epifluorescence microscope for cellular-level brain imaging in freely moving mice, and its application to imaging microcirculation and neuronal Ca(2+) dynamics.     

Biological indicators in marine and coastal waters: a statistical and modelling analysis of the MARS campaign

We perform a statistical analysis of ecological data collected in the MARS project from marine environments of the Red and Mediterranean Seas in Israel, and the North Sea in Germany. In the study of fish parasite data, we examine the basic premise that the complex host lifecycles of heteroxenous (h) parasites make them more sensitive to pollution than monoxenous (m) parasites which have only one host. Unlike results from analyses of earlier survey data, we find that the pooled h/m index for a community is not a clear indicator of environmental stress as originally hypothesized. This is due to the relatively large seasonal variability at the sampling sites over the course of the 3-year survey. Other possible indicators for water pollution gradients are checked, including species richness, diversity and prevalence of parasite populations. A theoretical model of host-parasite population dynamics that makes the presence of ecological thresholds transparent is offered to help explain the abrupt transitions prominent in the distributions of parasites at different sites under different pollution loadings. Heavy metal and chlorinated hydrocarbon data collected from fish tissue samples and molluscs of the three seas are assessed as bioindicators for pollution monitoring. The xenobiotic loads and indices of defence system activity and tissue damage are shown to have great potential as monitoring bioindicators.     

Is Health Aid Reaching the Poor? Analysis of Household Data from Aid Recipient Countries

Objective

To determine the extent to which the narrowing of child mortality across wealth gradients has been related to foreign aid to the health sector in low- and middle-income countries.

Methods

Mortality and wealth data on 989,901 under-5 children from 957,674 households in 49 aid recipient countries in Africa, Asia, South America, and the Caribbean between 1993 and 2012 were used in the analysis. Declines in under-5 mortality in the four poorest wealth quantiles were compared to the decline among the wealthiest at varying levels of health aid per capita using fixed effects multivariable regression models and controlling for maternal education, urbanization, and domestic spending on health among recipient countries.

Results

Each additional dollar in total health aid per capita was associated with 5.7 fewer deaths per 10,000 child-years among children in the poorest relative to the wealthiest households (p<0.001). This was also true when measured in percent declines (1.90% faster decline in under-5 mortality among the poorest compared with the wealthiest with each dollar in total health aid, p = 0.008). The association was stronger when using health aid specifically for malaria than total health aid, 12.60% faster decline among the poorest compared with the wealthiest with each dollar in malaria aid, p = 0.001.

Conclusions

Foreign aid to the health sector is preferentially related to reductions in under-5 mortality among the poorest compared with the wealthiest. Health aid addressing malaria, which imposes a disproportionate burden among the poor, may explain the observed effect.     

INTERACTIONS BETWEEN ENVIRONMENTAL STRESS AND MALE MATING SUCCESS MAY ENHANCE EVOLUTIONARY DIVERGENCE OF STRESS-RESISTANT DROSOPHILA POPULATIONS

Adaptation of natural and laboratory-selected populations of Drosophila to desiccation stress results in enhanced water conservation abilities, and thus increased stress resistance. In this study, we tested whether laboratory selection for desiccation resistance is also reflected in increased mating success of adapted D. melanogaster males under desiccating conditions. Adapted flies perform better under stressful conditions, and as expected males from desiccation-selected populations exhibited significantly higher relative mating success in comparison with controls after 5–6 h of desiccation. However, we show evidence for a trade-off between survival under stressful conditions and mating success in nonstressful and even mildly stressful environments (2.5–3 h of desiccation), where males from selected populations were involved in only ∼40% of observed copulations. This suggests that mutations favored by natural selection, associated with survival when resources are limited, may only be favored by sexual selection above a minimal "threshold" stress level. At milder stress levels increased resistance comes at a cost of lower relative mating success, and thus reduced fitness. This interaction between stress and relative male mating success of adapted and nonadapted males could interrupt gene flow, thus facilitating divergence of resistant populations from the ancestral population.