Thrifty phenotype versus cold adaptation: trade-offs in upper limb proportions of Himalayan populations of Nepal.

The multi-stress environment of high altitude has been associated with growth deficits in humans, particularly in zeugopod elements (forearm and lower leg). This is consistent with the thrifty phenotype hypothesis, which has been observed in Andeans, but has yet to be tested in other high-altitude populations. In Himalayan populations, other factors, such as cold stress, may shape limb proportions. The current study investigated whether relative upper limb proportions of Himalayan adults (n = 254) differ between highland and lowland populations, and whether cold adaptation or a thrifty phenotype mechanism may be acting here. Height, weight, humerus length, ulna length, hand length and hand width were measured using standard methods. Relative to height, total upper limb and ulna lengths were significantly shorter in highlanders compared with lowlanders in both sexes, while hand and humerus length were not. Hand width did not significantly differ between populations. These results support the thrifty phenotype hypothesis, as hand and humerus proportions are conserved at the expense of the ulna. The reduction in relative ulna length could be attributed to cold adaptation, but the lack of difference between populations in both hand length and width indicates that cold adaptation is not shaping hand proportions in this case.National Geographic Society; British Association for Biological Anthropology and Osteoarchaeology; Sigma Xi Scientific Research Society; Trinity Hall, University of Cambridge; and Department of Archaeology, University of Cambridge

Methodological perspectives on the application of compound-specific stable isotope fingerprinting for sediment source apportionment

Compound-specific stable isotope (CSSI) fingerprinting of sediment sources is a recently introduced tool to overcome some limitations of conventional approaches for sediment source apportionment. The technique uses the C-13 CSSI signature of plant-derived fatty acids (delta C-13-fatty acids) associated with soil minerals as a tracer. This paper provides methodological perspectives to advance the use of CSSI fingerprinting in combination with stable isotope mixing models (SIMMs) to apportion the relative contributions of different sediment sources (i.e. land uses) to sediments. CSSI fingerprinting allows quantitative estimation of the relative contribution of sediment sources within a catchment at a spatio-temporal resolution, taking into account the following approaches. First, application of CSSI fingerprinting techniques to complex catchments presents particular challenges and calls for well-designed sampling strategies and data handling. Hereby, it is essential to balance the effort required for representative sample collection and analyses against the need to accurately quantify the variability within the system. Second, robustness of the CSSI approach depends on the specificity and conservativeness of the delta C-13-FA fingerprint. Therefore, saturated long-chain (> 20 carbon atoms) FAs, which are biosynthesised exclusively by higher plants and are more stable than the more commonly used short-chain FAs, should be used. Third, given that FA concentrations can vary largely between sources, concentration-dependent SIMMs that are also able to incorporate delta C-13-FA variability should be standard operation procedures to correctly assess the contribution of sediment sources via SIMMs. This paper reflects on the use of delta C-13-FAs in erosion studies and provides recommendations for its application. We strongly advise the use of saturated long-chain (> 20 carbon atoms) FAs as tracers and concentration-dependent Bayesian SIMMs. We anticipate progress in CSSI sediment fingerprinting from two current developments: (i) development of hierarchical Bayesian SIMMs to better address catchment complexity and (ii) incorporation of dual isotope approaches (delta C-13- and delta H-2-FA) to improve estimates of sediment sources

Systematic Dissection and Trajectory-Scanning Mutagenesis of the Molecular Interface That Ensures Specificity of Two-Component Signaling Pathways

Two-component signal transduction systems enable bacteria to sense and respond to a wide range of environmental stimuli. Sensor histidine kinases transmit signals to their cognate response regulators via phosphorylation. The faithful transmission of information through two-component pathways and the avoidance of unwanted cross-talk require exquisite specificity of histidine kinase-response regulator interactions to ensure that cells mount the appropriate response to external signals. To identify putative specificity-determining residues, we have analyzed amino acid coevolution in two-component proteins and identified a set of residues that can be used to rationally rewire a model signaling pathway, EnvZ-OmpR. To explore how a relatively small set of residues can dictate partner selectivity, we combined alanine-scanning mutagenesis with an approach we call trajectory-scanning mutagenesis, in which all mutational intermediates between the specificity residues of EnvZ and another kinase, RstB, were systematically examined for phosphotransfer specificity. The same approach was used for the response regulators OmpR and RstA. Collectively, the results begin to reveal the molecular mechanism by which a small set of amino acids enables an individual kinase to discriminate amongst a large set of highly-related response regulators and vice versa. Our results also suggest that the mutational trajectories taken by two-component signaling proteins following gene or pathway duplication may be constrained and subject to differential selective pressures. Only some trajectories allow both the maintenance of phosphotransfer and the avoidance of unwanted cross-talk

Cervical epithelial damage promotes Ureaplasma parvum ascending infection, intrauterine inflammation and preterm birth induction in mice

Around 40% of preterm births are attributed to ascending intrauterine infection, and Ureaplasma parvum (UP) is commonly isolated in these cases. Here we present a mouse model of ascending UP infection that resembles human disease, using vaginal inoculation combined with mild cervical injury induced by a common spermicide (Nonoxynol-9, as a surrogate for any mechanism of cervical epithelial damage). We measure bacterial load in a non-invasive manner using a luciferase-expressing UP strain, and post-mortem by qPCR and bacterial titration. Cervical exposure to Nonoxynol-9, 24 h pre-inoculation, facilitates intrauterine UP infection, upregulates pro-inflammatory cytokines, and increases preterm birth rates from 13 to 28%. Our results highlight the crucial role of the cervical epithelium as a barrier against ascending infection. In addition, we expect the mouse model will facilitate further research on the potential links between UP infection and preterm birth

Xylella fastidiosa gene expression analysis by DNA microarrays

Xylella fastidiosa genome sequencing has generated valuable data by identifying genes acting either on metabolic pathways or in associated pathogenicity and virulence. Based on available information on these genes, new strategies for studying their expression patterns, such as microarray technology, were employed. A total of 2,600 primer pairs were synthesized and then used to generate fragments using the PCR technique. The arrays were hybridized against cDNAs labeled during reverse transcription reactions and which were obtained from bacteria grown under two different conditions (liquid XDM2 and liquid BCYE). All data were statistically analyzed to verify which genes were differentially expressed. In addition to exploring conditions for X. fastidiosa genome-wide transcriptome analysis, the present work observed the differential expression of several classes of genes (energy, protein, amino acid and nucleotide metabolism, transport, degradation of substances, toxins and hypothetical proteins, among others). The understanding of expressed genes in these two different media will be useful in comprehending the metabolic characteristics of X. fastidiosa, and in evaluating how important certain genes are for the functioning and survival of these bacteria in plants

Medicinal plant knowledge of the Bench ethnic group of Ethiopia: an ethnobotanical investigation

<p>Abstract</p> <p>Background</p> <p>Plants have traditionally been used as a source of medicine in Ethiopia since early times for the control of various ailments afflicting humans and their domestic animals. However, little work has been made in the past to properly document and promote the knowledge. Today medicinal plants and the associated knowledge in the country are threatened due to deforestation, environmental degradation and acculturation. Urgent ethnobotanical studies and subsequent conservation measures are, therefore, required to salvage these resources from further loss. The purpose of the present study was to record and analyse traditional medicinal plant knowledge of the Bench ethnic group in Southwest Ethiopia.</p> <p>Methods</p> <p>Semi-structured interviews were conducted with Bench informants selected during transect walks made to houses as well as those identified as knowledgeable by local administrators and elders to gather data regarding local names of medicinal plants used, parts harvested, ailments treated, remedy preparation methods, administration routes, dosage and side effects. The same method was also employed to gather information on marketability, habitat and abundance of the reported medicinal plants. Purposive sampling method was used in the selection of study sites within the study district. Fidelity Level (FL) value was calculated for each claimed medicinal plant to estimate its healing potential.</p> <p>Results</p> <p>The study revealed 35 Bench medicinal plants: 32 used against human ailments and three to treat both human and livestock ailments. The majority of Bench medicinal plants were herbs and leaf was the most frequently used part in the preparation of remedies. Significantly higher average number of medicinal plants was claimed by men, older people and illiterate ones as compared to women, younger people and literate ones, respectively. The majority of the medicinal plants used in the study area were uncultivated ones.</p> <p>Conclusion</p> <p>The study revealed acculturation as the major threat to the continuation of the traditional medical practice in the study area. Awareness should, therefore, be created among the Bench community, especially the young ones, by concerned organizations and individuals regarding the usefulness of the practice.</p

Serum Uric Acid and Adiposity: Deciphering Causality Using a Bidirectional Mendelian Randomization Approach

Background: Although the relationship between serum uric acid (SUA) and adiposity is well established, the direction of the causality is still unclear in the presence of conflicting evidences. We used a bidirectional Mendelian randomization approach to explore the nature and direction of causality between SUA and adiposity in a population-based study of Caucasians aged 35 to 75 years. Methods and Findings: We used, as instrumental variables, rs6855911 within the SUA gene SLC2A9 in one direction, and combinations of SNPs within the adiposity genes FTO, MC4R and TMEM18 in the other direction. Adiposity markers included weight, body mass index, waist circumference and fat mass. We applied a two-stage least squares regression: a regression of SUA/adiposity markers on our instruments in the first stage and a regression of the response of interest on the fitted values from the first stage regression in the second stage. SUA explained by the SLC2A9 instrument was not associated to fat mass (regression coefficient [95 % confidence interval]: 0.05 [20.10, 0.19] for fat mass) contrasting with the ordinary least square estimate (0.37 [0.34, 0.40]). By contrast, fat mass explained by genetic variants of the FTO, MC4R and TMEM18 genes was positively and significantly associated to SUA (0.31 [0.01, 0.62]), similar to the ordinary least square estimate (0.27 [0.25, 0.29]). Results were similar for the other adiposity markers. Conclusions: Using a bidirectional Mendelian randomization approach in adult Caucasians, our findings suggest tha

Neuroanatomical Variability of Religiosity

We hypothesized that religiosity, a set of traits variably expressed in the population, is modulated by neuroanatomical variability. We tested this idea by determining whether aspects of religiosity were predicted by variability in regional cortical volume. We performed structural magnetic resonance imaging of the brain in 40 healthy adult participants who reported different degrees and patterns of religiosity on a survey. We identified four Principal Components of religiosity by Factor Analysis of the survey items and associated them with regional cortical volumes measured by voxel-based morphometry. Experiencing an intimate relationship with God and engaging in religious behavior was associated with increased volume of R middle temporal cortex, BA 21. Experiencing fear of God was associated with decreased volume of L precuneus and L orbitofrontal cortex BA 11. A cluster of traits related with pragmatism and doubting God's existence was associated with increased volume of the R precuneus. Variability in religiosity of upbringing was not associated with variability in cortical volume of any region. Therefore, key aspects of religiosity are associated with cortical volume differences. This conclusion complements our prior functional neuroimaging findings in elucidating the proximate causes of religion in the brain