56 research outputs found

    The molecular basis of color vision in colorful fish: Four Long Wave-Sensitive (LWS) opsins in guppies (Poecilia reticulata) are defined by amino acid substitutions at key functional sites

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    <p>Abstract</p> <p>Background</p> <p>Comparisons of functionally important changes at the molecular level in model systems have identified key adaptations driving isolation and speciation. In cichlids, for example, long wavelength-sensitive (LWS) opsins appear to play a role in mate choice and male color variation within and among species. To test the hypothesis that the evolution of elaborate coloration in male guppies (<it>Poecilia reticulata</it>) is also associated with opsin gene diversity, we sequenced long wavelength-sensitive (LWS) opsin genes in six species of the family Poeciliidae.</p> <p>Results</p> <p>Sequences of four LWS opsin genes were amplified from the guppy genome and from mRNA isolated from adult guppy eyes. Variation in expression was quantified using qPCR. Three of the four genes encode opsins predicted to be most sensitive to different wavelengths of light because they vary at key amino acid positions. This family of LWS opsin genes was produced by a diversity of duplication events. One, an intronless gene, was produced prior to the divergence of families Fundulidae and Poeciliidae. Between-gene PCR and DNA sequencing show that two of the guppy LWS opsins are linked in an inverted orientation. This inverted tandem duplication event occurred near the base of the poeciliid tree in the common ancestor of <it>Poecilia </it>and <it>Xiphophorus</it>. The fourth sequence has been uncovered only in the genus <it>Poecilia</it>. In the guppies surveyed here, this sequence is a hybrid, with the 5' end most similar to one of the tandem duplicates and the 3' end identical to the other.</p> <p>Conclusion</p> <p>Enhanced wavelength discrimination, a possible consequence of opsin gene duplication and divergence, might have been an evolutionary prerequisite for color-based sexual selection and have led to the extraordinary coloration now observed in male guppies and in many other poeciliids.</p

    An inhibitory pull-push circuit in frontal cortex.

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    Push-pull is a canonical computation of excitatory cortical circuits. By contrast, we identify a pull-push inhibitory circuit in frontal cortex that originates in vasoactive intestinal polypeptide (VIP)-expressing interneurons. During arousal, VIP cells rapidly and directly inhibit pyramidal neurons; VIP cells also indirectly excite these pyramidal neurons via parallel disinhibition. Thus, arousal exerts a feedback pull-push influence on excitatory neurons-an inversion of the canonical push-pull of feedforward input

    Active Trachoma among Children in Mali: Clustering and Environmental Risk Factors

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    Active trachoma is not uniformly distributed in endemic areas, and local environmental factors influencing its prevalence are not yet adequately understood. Determining whether clustering is a consistent phenomenon may help predict likely modes of transmission and help to determine the appropriate level at which to target control interventions. In this work, we estimated the magnitude of clustering at different levels and investigated the influence of socio-economic factors and environmental features on active trachoma prevalence among children in Mali (1996–1997 nationwide survey). Clustering revealed significant results at the child, caretaker, household, and village levels. Moreover, beyond some well-established individual risk factors (age between 3 and 5, dirty face, and flies on the face), we found that temperature, sunshine fraction, and presence of rainy days were negatively associated with active trachoma prevalence. This study clearly indicates the importance of directing control efforts both at children with active trachoma as well as those with close contact, and at communities. These results support facial cleanliness and environmental improvements as population-health initiatives to combat blinding trachoma

    Nonrandom Distribution of Vector Ticks (Dermacentor variabilis) Infected by Francisella tularensis

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    The island of Martha's Vineyard, Massachusetts, is the site of a sustained outbreak of tularemia due to Francisella tularensis tularensis. Dog ticks, Dermacentor variabilis, appear to be critical in the perpetuation of the agent there. Tularemia has long been characterized as an agent of natural focality, stably persisting in characteristic sites of transmission, but this suggestion has never been rigorously tested. Accordingly, we sought to identify a natural focus of transmission of the agent of tularemia by mapping the distribution of PCR-positive ticks. From 2004 to 2007, questing D. variabilis were collected from 85 individual waypoints along a 1.5 km transect in a field site on Martha's Vineyard. The positions of PCR-positive ticks were then mapped using ArcGIS. Cluster analysis identified an area approximately 290 meters in diameter, 9 waypoints, that was significantly more likely to yield PCR-positive ticks (relative risk 3.3, P = 0.001) than the rest of the field site. Genotyping of F. tularensis using variable number tandem repeat (VNTR) analysis on PCR-positive ticks yielded 13 different haplotypes, the vast majority of which was one dominant haplotype. Positive ticks collected in the cluster were 3.4 times (relative risk = 3.4, P<0.0001) more likely to have an uncommon haplotype than those collected elsewhere from the transect. We conclude that we have identified a microfocus where the agent of tularemia stably perpetuates and that this area is where genetic diversity is generated

    Trachoma Prevalence and Associated Risk Factors in The Gambia and Tanzania: Baseline Results of a Cluster Randomised Controlled Trial

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    Trachoma is caused by Chlamydia trachomatis and is the leading infectious cause of blindness. The World Health Organization's (WHO) control strategy includes antibiotic treatment of all community members, facial cleanliness, and environmental improvements. By determining how prevalent trachoma is, decisions can be made whether control activities need to be put in place. Knowing what factors make people more at risk of having trachoma can help target trachoma control efforts to those most at risk. We looked at the prevalence of active trachoma and C. trachomatis infection in the eyes of children aged 0–5 years in The Gambia and Tanzania. We also measured risk factors associated with having active trachoma or infection. The prevalence of both active trachoma and infection was lower in The Gambia (6.7% and 0.8%, respectively) than in Tanzania (32.3% and 21.9%, respectively). Risk factors for active trachoma were similar in the two countries. For infection, the risk factors in Tanzania were similar to those for TF, whereas in The Gambia, only ocular discharge was associated with infection. These results show that although the prevalence of active trachoma and infection is very different between the two countries, the risk factors for active trachoma are similar but those for infection are different

    Alum Adjuvant Enhances Protection against Respiratory Syncytial Virus but Exacerbates Pulmonary Inflammation by Modulating Multiple Innate and Adaptive Immune Cells

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    Respiratory syncytial virus (RSV) is well-known for inducing vaccine-enhanced respiratory disease after vaccination of young children with formalin-inactivated RSV (FI-RSV) in alum formulation. Here, we investigated alum adjuvant effects on protection and disease after FIRSV immunization with or without alum in comparison with live RSV reinfections. Despite viral clearance, live RSV reinfections caused weight loss and substantial pulmonary inflammation probably due to high levels of RSV specific IFN-γ+IL4-, IFN-γ-TNF-α+, IFN-γ+ TNF-α- effector CD4 and CD8 T cells. Alum adjuvant significantly improved protection as evidenced by effective viral clearance compared to unadjuvanted FI-RSV. However, in contrast to unadjuvanted FI-RSV, alum-adjuvanted FI-RSV (FI-RSV-A) induced severe vaccine- enhanced RSV disease including weight loss, eosinophilia, and lung histopathology. Alum adjuvant in the FI-RSV-A was found to be mainly responsible for inducing high levels of RSV-specific IFN-γ-IL4+, IFN-γ-TNF-α+ CD4+ T cells, and proinflammatory cytokines IL-6 and IL-4 as well as B220+ plasmacytoid and CD4+ dendritic cells, and inhibiting the induction of IFN-γ+CD8 T cells. This study suggests that alum adjuvant in FI-RSV vaccines increases immunogenicity and viral clearance but also induces atypical T helper CD4+ T cells and multiple inflammatory dendritic cell subsets responsible for vaccine-enhanced severe RSV disease

    Neglected Tropical Diseases in Sub-Saharan Africa: Review of Their Prevalence, Distribution, and Disease Burden

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    The neglected tropical diseases (NTDs) are the most common conditions affecting the poorest 500 million people living in sub-Saharan Africa (SSA), and together produce a burden of disease that may be equivalent to up to one-half of SSA's malaria disease burden and more than double that caused by tuberculosis. Approximately 85% of the NTD disease burden results from helminth infections. Hookworm infection occurs in almost half of SSA's poorest people, including 40–50 million school-aged children and 7 million pregnant women in whom it is a leading cause of anemia. Schistosomiasis is the second most prevalent NTD after hookworm (192 million cases), accounting for 93% of the world's number of cases and possibly associated with increased horizontal transmission of HIV/AIDS. Lymphatic filariasis (46–51 million cases) and onchocerciasis (37 million cases) are also widespread in SSA, each disease representing a significant cause of disability and reduction in the region's agricultural productivity. There is a dearth of information on Africa's non-helminth NTDs. The protozoan infections, human African trypanosomiasis and visceral leishmaniasis, affect almost 100,000 people, primarily in areas of conflict in SSA where they cause high mortality, and where trachoma is the most prevalent bacterial NTD (30 million cases). However, there are little or no data on some very important protozoan infections, e.g., amebiasis and toxoplasmosis; bacterial infections, e.g., typhoid fever and non-typhoidal salmonellosis, the tick-borne bacterial zoonoses, and non-tuberculosis mycobaterial infections; and arboviral infections. Thus, the overall burden of Africa's NTDs may be severely underestimated. A full assessment is an important step for disease control priorities, particularly in Nigeria and the Democratic Republic of Congo, where the greatest number of NTDs may occur

    Mapping of schistosomiasis and soil-transmitted helminths in Namibia: The first large-scale protocol to formally include rapid diagnostic tests

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    Background: Namibia is now ready to begin mass drug administration of praziquantel and albendazole against schistosomiasis and soil-transmitted helminths, respectively. Although historical data identifies areas of transmission of these neglected tropical diseases (NTDs), there is a need to update epidemiological data. For this reason, Namibia adopted a new protocol for mapping of schistosomiasis and geohelminths, formally integrating rapid diagnostic tests (RDTs) for infections and morbidity. In this article, we explain the protocol in detail, and introduce the concept of 'mapping resolution', as well as present results and treatment recommendations for northern Namibia.Methods/Findings/Interpretation: This new protocol allowed a large sample to be surveyed (N = 17 896 children from 299 schools) at relatively low cost (7 USD per person mapped) and very quickly (28 working days). All children were analysed by RDTs, but only a sub-sample was also diagnosed by light microscopy. Overall prevalence of schistosomiasis in the surveyed areas was 9.0%, highly associated with poorer access to potable water (OR = 1.5, P<0.001) and defective (OR = 1.2, P<0.001) or absent sanitation infrastructure (OR = 2.0, P<0.001). Overall prevalence of geohelminths, more particularly hookworm infection, was 12.2%, highly associated with presence of faecal occult blood (OR = 1.9, P<0.001). Prevalence maps were produced and hot spots identified to better guide the national programme in drug administration, as well as targeted improvements in water, sanitation and hygiene. The RDTs employed (circulating cathodic antigen and microhaematuria for Schistosoma mansoni and S. haematobium, respectively) performed well, with sensitivities above 80% and specificities above 95%.Conclusion/Significance: This protocol is cost-effective and sensitive to budget limitations and the potential economic and logistical strains placed on the national Ministries of Health. Here we present a high resolution map of disease prevalence levels, and treatment regimens are recommended.Peer reviewedEntomology and Plant Patholog

    Epidemiology and control of trachoma: systematic review.

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    Trachoma is the commonest infectious cause of blindness. Recurrent episodes of infection with serovars A-C of Chlamydia trachomatis cause conjunctival inflammation in children who go on to develop scarring and blindness as adults. It was estimated that in 2002 at least 1.3 million people were blind from trachoma, and currently 40 million people are thought to have active disease and 8.2 million to have trichiasis. The disease is largely found in poor, rural communities in developing countries, particularly in sub-Saharan Africa. The WHO promotes trachoma control through a multifaceted approach involving surgery, mass antibiotic distribution, encouraging facial cleanliness and environmental improvements. This has been associated with significant reductions in the prevalence of active disease over the past 20 years, but there remain a large number of people with trichiasis who are at risk of blindness
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