Control of mechanical pain hypersensitivity in mice through ligand-targeted photoablation of TrkB-positive sensory neurons

Mechanical allodynia is a major symptom of neuropathic pain whereby innocuous touch evokes severe pain. Here we identify a population of peripheral sensory neurons expressing TrkB that are both necessary and sufficient for producing pain from light touch after nerve injury in mice. Mice in which TrkB-Cre-expressing neurons are ablated are less sensitive to the lightest touch under basal conditions, and fail to develop mechanical allodynia in a model of neuropathic pain. Moreover, selective optogenetic activation of these neurons after nerve injury evokes marked nociceptive behavior. Using a phototherapeutic approach based upon BDNF, the ligand for TrkB, we perform molecule-guided laser ablation of these neurons and achieve long-term retraction of TrkB-positive neurons from the skin and pronounced reversal of mechanical allodynia across multiple types of neuropathic pain. Thus we identify the peripheral neurons which transmit pain from light touch and uncover a novel pharmacological strategy for its treatment

Influence of Low-Level Stimulus Features, Task Dependent Factors, and Spatial Biases on Overt Visual Attention

Visual attention is thought to be driven by the interplay between low-level visual features and task dependent information content of local image regions, as well as by spatial viewing biases. Though dependent on experimental paradigms and model assumptions, this idea has given rise to varying claims that either bottom-up or top-down mechanisms dominate visual attention. To contribute toward a resolution of this discussion, here we quantify the influence of these factors and their relative importance in a set of classification tasks. Our stimuli consist of individual image patches (bubbles). For each bubble we derive three measures: a measure of salience based on low-level stimulus features, a measure of salience based on the task dependent information content derived from our subjects' classification responses and a measure of salience based on spatial viewing biases. Furthermore, we measure the empirical salience of each bubble based on our subjects' measured eye gazes thus characterizing the overt visual attention each bubble receives. A multivariate linear model relates the three salience measures to overt visual attention. It reveals that all three salience measures contribute significantly. The effect of spatial viewing biases is highest and rather constant in different tasks. The contribution of task dependent information is a close runner-up. Specifically, in a standardized task of judging facial expressions it scores highly. The contribution of low-level features is, on average, somewhat lower. However, in a prototypical search task, without an available template, it makes a strong contribution on par with the two other measures. Finally, the contributions of the three factors are only slightly redundant, and the semi-partial correlation coefficients are only slightly lower than the coefficients for full correlations. These data provide evidence that all three measures make significant and independent contributions and that none can be neglected in a model of human overt visual attention

Identification and prevalence of coral diseases on three Western Indian Ocean coral reefs

Coral diseases have caused a substantial decline in the biodiversity and abundance of reef-building corals. To date, more than 30 distinct diseases of scleractinian corals have been reported, which cause progressive tissue loss and/or affect coral growth, reproductive capacity, recruitment, species diversity and the abundance of reef-associated organisms. While coral disease research has increased over the last 4 decades, very little is known about coral diseases in the Western Indian Ocean. Surveys conducted at multiple sites in Reunion, South Africa and Mayotte between August 2010 and June 2012 revealed the presence of 6 main coral diseases: black band disease (BBD), white syndrome (WS), pink line syndrome (PLS), growth anomalies (GA), skeleton eroding band (SEB) and Porites white patch syndrome (PWPS). Overall, disease prevalence was higher in Reunion (7.5 +/- 2.2%; mean +/- SE) compared to South Africa (3.9 +/- 0.8%) and Mayotte (2.7 +/- 0.3%). Across locations, Acropora and Porites were the genera most susceptible to disease. Spatial variability was detected in both Reunion and South Africa, with BBD and WS more prevalent on shallow than deep reefs. There was also evidence of seasonality in 2 diseases: the prevalence of BBD and WS was higher in summer than winter. This was the first study to investigate the ecology of coral diseases, providing both qualitative and quantitative data, on Western Indian Ocean reefs, and surveys should be expanded to confirm these patterns

Null allele, allelic dropouts or rare sex detection in clonal organisms : simulations and application to real data sets of pathogenic microbes

Background: Pathogens and their vectors are organisms whose ecology is often only accessible through population genetics tools based on spatio-temporal variability of molecular markers. However, molecular tools may present technical difficulties due to the masking of some alleles (allelic dropouts and/or null alleles), which tends to bias the estimation of heterozygosity and thus the inferences concerning the breeding system of the organism under study. This is especially critical in clonal organisms in which deviation from panmixia, as measured by Wright's F-IS, can, in principle, be used to infer both the extent of clonality and structure in a given population. In particular, null alleles and allelic dropouts are locus specific and likely produce high variance of Wright's F-IS across loci, as rare sex is expected to do. In this paper we propose a tool enabling to discriminate between consequences of these technical problems and those of rare sex. Methods: We have performed various simulations of clonal and partially clonal populations. We introduce allelic dropouts and null alleles in clonal data sets and compare the results with those that exhibit increasing rates of sexual recombination. We use the narrow relationship that links Wright's F-IS to genetic diversity in purely clonal populations as assessment criterion, since this relationship disappears faster with sexual recombination than with amplification problems of certain alleles. Results: We show that the relevance of our criterion for detecting poorly amplified alleles depends partly on the population structure, the level of homoplasy and/or mutation rate. However, the interpretation of data becomes difficult when the number of poorly amplified alleles is above 50%. The application of this method to reinterpret published data sets of pathogenic clonal microbes (yeast and trypanosomes) confirms its usefulness and allows refining previous estimates concerning important pathogenic agents. Conclusion: Our criterion of superimposing between the FIS expected under clonality and the observed F-IS, is effective when amplification difficulties occur in low to moderate frequencies (20-30%)

Emergence of rice yellow mottle virus in eastern Uganda : recent and singular interplay between strains in East Africa and in Madagascar

Epidemics of rice yellow mottle virus (RYMV) have developed recently in eastern Uganda, close to Lake Victoria in East Africa. Unexpectedly, all isolates from the affected area belonged to a single strain (named S4ug), a strain that is different from the S4lv strain that has been prevalent in the Lake Victoria basin for the past five decades. Interestingly, the S4ug strain is most closely related at the genomic level (except ORF1) to the strain present in Madagascar (S4mg), 2000 km away. The minor parent of the S4mg recombinant strain could not be detected. Molecular clock dating analysis indicated that the singular sequence of events - that associated the emergence of a new strain (S4ug), a modular recombination between closely related strains (S4mg and S4ug) and a long distance transmission (S4mg) - occurred recently, within the past few decades. This finding is at variance with the process of gradual strain dispersal and diversification over two centuries throughout Africa that was previously established

Population genetics of Trypanosoma brucei gambiense in sleeping sickness patients with treatment failures in the focus of Mbuji-Mayi, Democratic Republic of the Congo

Human African trypanosomiasis (HAT) in the Democratic Republic of the Congo (DRC) is caused by the protozoan Trypanosoma brucei gambiense. Until recently, all patients in the second or neurological stage of the disease were treated with melarsoprol. At the end of the past and the beginning of the present century, alarmingly high relapse rates in patients treated with melarsoprol were reported in isolated HAT foci. In the Mbuji-Mayi focus of DRC, a particular mutation that confers cross resistance for pentamidine and melarsoprol was recently found for all strains studied. Nevertheless, treatment successfully cured a significant proportion of patients. To check for the existence of other possible genetic factors of the parasites, we genotyped trypanosomes isolated from patients before and after treatment (relapsing patients) with eight microsatellite markers. We found no evidence of any genetic correlation between parasite genotype and treatment outcome and we concluded that relapse or cure probably depend more on patients' factors such as disease progression, nutritional or immunological status or co-infections with other pathogens. The existence of a melarsoprol and pentamidine resistance associated mutation at such high rates highlights an increasing problem, even for other drugs, especially those using the same transporters as melarsoprol and pentamidine