How do species barriers decay? Concordance and local introgression in mosaic hybrid zones of mussels.

The Mytilus complex of marine mussel species forms a mosaic of hybrid zones, found across temperate regions of the globe. This allows us to study 'replicated' instances of secondary contact between closely related species. Previous work on this complex has shown that local introgression is both widespread and highly heterogeneous, and has identified SNPs that are outliers of differentiation between lineages. Here, we developed an ancestry-informative panel of such SNPs. We then compared their frequencies in newly sampled populations, including samples from within the hybrid zones, and parental populations at different distances from the contact. Results show that close to the hybrid zones, some outlier loci are near to fixation for the heterospecific allele, suggesting enhanced local introgression, or the local sweep of a shared ancestral allele. Conversely, genomic cline analyses, treating local parental populations as the reference, reveal a globally high concordance among loci, albeit with a few signals of asymmetric introgression. Enhanced local introgression at specific loci is consistent with the early transfer of adaptive variants after contact, possibly including asymmetric bi-stable variants (Dobzhansky-Muller incompatibilities), or haplotypes loaded with fewer deleterious mutations. Having escaped one barrier, however, these variants can be trapped or delayed at the next barrier, confining the introgression locally. These results shed light on the decay of species barriers during phases of contact.ANR, France; Russian Science Foundatio

The evolution of radiological measurements and the association with clinician and patient reported outcome following distal radius fractures in non-osteoporotic patients:what is clinically relevant?

Introduction: Following distal radius fractures in young non-osteoporotic patients, clinical relevancy of outcome has been scarcely reported. Outcome can be put in perspective by using measurement errors of radiological measurements and Minimal Important Change when reporting on clinician and patient reported outcome. Aim of this study was to assess the clinical relevance of radiological measurements, clinician and patient reported outcomes following distal radius fractures in young non-osteoporotic patients.Methods: Retrospective cohort study. Non-osteoporotic patients following a distal radius fracture were selected. Radiographs of both wrists were obtained at baseline, 6 weeks and at follow-up. Active range of motion and grip strength measurements were obtained at the follow-up visit and 4 questionnaires were answered to assess pain, upper extremity functioning, and health status.Results: Seventy-three patients (32 women, 41 men) with a mean age of 33.5 (SD 9.2) years at the time of injury were included. Median follow up was 62 months (IQR 53.0-84.5). Several radiological measurements evolved statistically significantly over time, however none exceeded measurement errors. Flexion/extension difference of injured compared to uninjured wrist (mean difference 11.2°, t = -7.5, df = 72, p < 0.001), exceeded Minimal Important Change, while grip strength differences did not. When comparing patients with DRFs to healthy controls, only the differences on Patient Reported Wrist Evaluation subscales "pain", "function" and total scores exceeded minimal important change (8, 10 and 13 points, respectively). Multivariable regression analysis revealed statistically significant relationships between residual step-off and respectively diminished flexion/extension (B = -36.8, 95% CI -62; -11.1, p  =  0.006), diminished radial/ulnar deviation (B = -17.9, 95% CI -32.0; -3.9, p  =  0.013) and worse ShortForm-36 "mental component score" (B = -15.4, 95% CI -26.6; -4.2, p < 0.001).Conclusion: Radiological measurements following distal radius fractures seem to evolve over time, but differences were small and were probably not clinically relevant. Range of motion, in particular flexion/extension, was impaired to such extend that it was noticeable for a patient, whereas grip strength was not impaired. The Patient Reported Wrist Evaluation was clinically relevantly diminished. Residual articular incongruency seems to influence range of motion.Implications for rehabilitationReporting Minimal Important Change regarding clinician and patient reported outcome following distal radius fractures is of more clinical value than reporting on statistical significance.Following distal radius fractures, the changes in radiological measurements do not seem to reflect a clinical relevant change.Range of motion, in particular flexion/extension, should be measured following distal radius fractures, as this might be impaired in a clinically relevant way.Measuring grip strength is of less importance following distal radius fractures, because grip strength does not seem to be affected.Residual articular incongruency seems to influence range of motion and therefore should be reduced to a minimum when treating non-osteoporotic patients

Rationalizing the Optimization of Detergents for Membrane Protein Purification

Membrane protein purification by means of detergents is key to isolating membrane-bound therapeutic targets. The role of the detergent structure in this process, however, is not well understood. Detergents are optimized empirically, leading to failed preparations, and thereby raising costs. Here we evaluate the utility of the hydrophilic-lipophilic balance (HLB) concept, which was introduced by Griffin in 1949, for guiding the optimization of the hydrophobic tail in first-generation, dendritic oligoglycerol detergents ([G1] OGDs). Our findings deliver qualitative HLB guidelines for rationalizing the optimization of detergents. Moreover, [G1] OGDs exhibit strongly delipidating properties, regardless of the structure of the hydrophobic tail, which delivers a methodological enabling step for investigating binding strengths of endogenous lipids and their role for membrane protein oligomerization. Our findings will facilitate the analysis of challenging drug targets in the future

Coding Efficiency of Fly Motion Processing Is Set by Firing Rate, Not Firing Precision

To comprehend the principles underlying sensory information processing, it is important to understand how the nervous system deals with various sources of perturbation. Here, we analyze how the representation of motion information in the fly's nervous system changes with temperature and luminance. Although these two environmental variables have a considerable impact on the fly's nervous system, they do not impede the fly to behave suitably over a wide range of conditions. We recorded responses from a motion-sensitive neuron, the H1-cell, to a time-varying stimulus at many different combinations of temperature and luminance. We found that the mean firing rate, but not firing precision, changes with temperature, while both were affected by mean luminance. Because we also found that information rate and coding efficiency are mainly set by the mean firing rate, our results suggest that, in the face of environmental perturbations, the coding efficiency is improved by an increase in the mean firing rate, rather than by an increased firing precision

A comprehensive evaluation of colonic mucosal isolates of Sutterella wadsworthensis from inflammatory bowel disease

Peer reviewedPublisher PD

Patient-centred tuberculosis treatment delivery under programmatic conditions in Tanzania: a cohort study

<p>Abstract</p> <p>Background</p> <p>Directly observed therapy (DOT) remains the cornerstone of the global tuberculosis (TB) control strategy. Tanzania, one of the 22 high-burden countries regarding TB, changed the first-line treatment regimen to contain rifampicin-containing fixed-dose combination for the full 6 months of treatment. As daily health facility-based DOT for this long period is not feasible for the patient, nor for the health system, Tanzania introduced patient centred treatment (PCT). PCT allows patients to choose for daily DOT at a health facility or at their home by a supporter of choice. The introduction of fixed dose combinations in the intensive and continuation phase made PCT feasible by eliminating the risk of selective drug taking by patients and reducing the number of tablets to be taken. The approach was tested in three districts with the objective to assess the effect of this strategy on TB treatment outcomes</p> <p>Methods</p> <p>Cohort analysis comparing patients treated under the PCT strategy (registered April-September 2006) with patients treated under health-facility-based DOT (registered April-September 2005). The primary outcome was the cure rate. Differences were assessed by calculating the risk ratios. Associations between characteristics of the supporters and treatment outcomes in the group of patients opting for home-based DOT were assessed through logistic regression.</p> <p>Results</p> <p>In the PCT cohort there were 1208 patients and 1417 were included in the historic cohort. There was no significant difference in cure rates between the cohorts (risk ratio [RR]: 1.06; 95% confidence interval [CI]: 0.96-1.16). In the PCT cohort, significantly more patients had successful treatment (cure or treatment completed; RR: 1.10; 95%CI: 1.01-1.15). There were no characteristics of supporters that were associated with treatment outcome.</p> <p>Conclusion</p> <p>The PCT approach showed similar cure rates and better treatment success rates compared to daily health-facility DOT. The results indicate that there are no specific prerequisites for the supporter chosen by the patient. The programmatic setting of the study lends strong support for scaling-up of TB treatment observation outside the health facility.</p

Kinetoplastid Phylogenomics Reveals the Evolutionary Innovations Associated with the Origins of Parasitism

The evolution of parasitism is a recurrent event in the history of life and a core problem in evolutionary biology. Trypanosomatids are important parasites and include the human pathogens Trypanosoma brucei, Trypanosoma cruzi, and Leishmania spp., which in humans cause African trypanosomiasis, Chagas disease, and leishmaniasis, respectively. Genome comparison between trypanosomatids reveals that these parasites have evolved specialized cell-surface protein families, overlaid on a well-conserved cell template. Understanding how these features evolved and which ones are specifically associated with parasitism requires comparison with related non-parasites. We have produced genome sequences for Bodo saltans, the closest known non-parasitic relative of trypanosomatids, and a second bodonid, Trypanoplasma borreli. Here we show how genomic reduction and innovation contributed to the character of trypanosomatid genomes. We show that gene loss has “streamlined” trypanosomatid genomes, particularly with respect to macromolecular degradation and ion transport, but consistent with a widespread loss of functional redundancy, while adaptive radiations of gene families involved in membrane function provide the principal innovations in trypanosomatid evolution. Gene gain and loss continued during trypanosomatid diversification, resulting in the asymmetric assortment of ancestral characters such as peptidases between Trypanosoma and Leishmania, genomic differences that were subsequently amplified by lineage-specific innovations after divergence. Finally, we show how species-specific, cell-surface gene families (DGF-1 and PSA) with no apparent structural similarity are independent derivations of a common ancestral form, which we call “bodonin.” This new evidence defines the parasitic innovations of trypanosomatid genomes, revealing how a free-living phagotroph became adapted to exploiting hostile host environments

A case of isolation by distance and short-term temporal stability of population structure in brown trout (Salmo trutta) within the River Dart, southwest England

This is an open access article that is freely available in ORE or from the publisher's web site. Please cite the published version.© 2009 The Authors. Journal compilation © 2009 Blackwell Publishing LtdSalmonid fishes exhibit high levels of population differentiation. In particular, the brown trout (Salmo trutta L.) demonstrates complex within river drainage genetic structure. Increasingly, these patterns can be related to the underlying evolutionary models, of which three scenarios (member-vagrant hypothesis, metapopulation model and panmixia) facilitate testable predictions for investigations into population structure. We analysed 1225 trout collected from the River Dart, a 75 km long river located in southwest England. Specimens were collected from 22 sample sites across three consecutive summers (2001–2003) and genetic variation was examined at nine microsatellite loci. A hierarchical analysis of molecular variance revealed that negligible genetic variation was attributed among temporal samples. The highest levels of differentiation occurred among samples isolated above barriers to fish movement, and once these samples were removed, a significant effect of isolation-by-distance was observed. These results suggest that, at least in the short-term, ecological events are more important in shaping the population structure of Dart trout than stochastic extinction events, and certainly do not contradict the expectations of a member-vagrant hypothesis. Furthermore, individual-level spatial autocorrelation analyses support previous recommendations for the preservation of a number of spawning sites spaced throughout the tributary system to conserve the high levels of genetic variation identified in salmonid species