CT694 and pgp3 as Serological Tools for Monitoring Trachoma Programs.

Defining endpoints for trachoma programs can be a challenge as clinical signs of infection may persist in the absence of detectable bacteria. Antibody-based tests may provide an alternative testing strategy for surveillance during terminal phases of the program. Antibody-based assays, in particular ELISAs, have been shown to be useful to document C. trachomatis genital infections, but have not been explored extensively for ocular C. trachomatis infections. An antibody-based multiplex assay was used to test two C. trachomatis antigens, pgp3 and CT694, for detection of trachoma antibodies in bloodspots from Tanzanian children (n = 160) collected after multiple rounds of mass azithromycin treatment. Using samples from C. trachomatis-positive (by PCR) children from Tanzania (n = 11) and control sera from a non-endemic group of U.S. children (n = 122), IgG responses to both pgp3 and CT694 were determined to be 91% sensitive and 98% specific. Antibody responses of Tanzanian children were analyzed with regard to clinical trachoma, PCR positivity, and age. In general, children with more intense ocular pathology (TF/TI = 2 or most severe) had a higher median antibody response to pgp3 (p = 0.0041) and CT694 (p = 0.0282) than those with normal exams (TF/TI = 0). However, 44% of children with no ocular pathology tested positive for antibody, suggesting prior infection. The median titer of antibody responses for children less than three years of age was significantly lower than those of older children. (p<0.0001 for both antigens). The antibody-based multiplex assay is a sensitive and specific additional tool for evaluating trachoma transmission. The assay can also be expanded to include antigens representing different diseases, allowing for a robust assay for monitoring across NTD programs

Genome-wide profiling of humoral immunity and pathogen genes under selection identifies immune evasion tactics of Chlamydia trachomatis during ocular infection

The frequency and duration of Chlamydia trachomatis (Ct) ocular infections decrease with age, suggesting development of partial immunity. However, there is a lack of clear correlates of immunity to Ct infection in humans. We screened sera from a cohort of Gambian children followed for six-months against a Ct-proteome microarray. At genome sequence level, we detected signatures of selection from a population of ocular Ct isolates from Guinea-Bissau. Together these approaches allowed us to highlight the focus of humoral responses and hypothesise new modes of pathogen immune evasion. Children who were susceptible to frequent and/or prolonged Ct infection had a less focussed antibody response, including preferential recognition of forty-two antigens. There was evidence of positive and purifying selection across the genome, but little balancing selection. In contrast, most antigens that were associated with susceptibility were under neutral selection. These data suggest an evasion strategy in which Ct presents a large panel of irrelevant antigens to the immune system to block or misdirect protective responses. Development of a focused immune response, possibly induced through vaccination, may be an effective strategy to promote protection to Ct infection

An integrated ChIP-seq analysis platform with customizable workflows

<p>Abstract</p> <p>Background</p> <p>Chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq), enables unbiased and genome-wide mapping of protein-DNA interactions and epigenetic marks. The first step in ChIP-seq data analysis involves the identification of peaks (i.e., genomic locations with high density of mapped sequence reads). The next step consists of interpreting the biological meaning of the peaks through their association with known genes, pathways, regulatory elements, and integration with other experiments. Although several programs have been published for the analysis of ChIP-seq data, they often focus on the peak detection step and are usually not well suited for thorough, integrative analysis of the detected peaks.</p> <p>Results</p> <p>To address the peak interpretation challenge, we have developed ChIPseeqer, an integrative, comprehensive, fast and user-friendly computational framework for in-depth analysis of ChIP-seq datasets. The novelty of our approach is the capability to combine several computational tools in order to create easily customized workflows that can be adapted to the user's needs and objectives. In this paper, we describe the main components of the ChIPseeqer framework, and also demonstrate the utility and diversity of the analyses offered, by analyzing a published ChIP-seq dataset.</p> <p>Conclusions</p> <p>ChIPseeqer facilitates ChIP-seq data analysis by offering a flexible and powerful set of computational tools that can be used in combination with one another. The framework is freely available as a user-friendly GUI application, but all programs are also executable from the command line, thus providing flexibility and automatability for advanced users.</p

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Sex-biased space-use response to urbanization in an endemic urban adapter

Urbanization impacts on the composition and distribution of wildlife. The tawny frogmouth (Podargus strigoides) is an endemic, nocturnal bird species widespread throughout Australia with recent research highlighting high densities within urban environments. The aim of this study was to investigate homerange size and land-use in response to a gradient of urbanization by determining (a) the key land-use types influencing home-range size and location in the urban landscape (b) whether urbanization impacts on home-range size; and (c) whether the response to urbanization is gender specific. Twelve birds, seven male and five female were radio-tracked within a study zone located in Melbourne, Australia. We used minimum convex polygons (MCP) 95% and 50% fixed-kernel isopleths to calculate home-range size and areas of core use within each home-range. In both the landscape and core areas of their home-range, birds positioned their home-range in areas with more trees, avoiding impervious surfaces and utilizing grassed areas. Male mean kernel home-range was 17.65 &plusmn; 4.35 ha and female 6.55 &plusmn; 1.40 ha. Male home-ranges contained higher levels of impervious surfaces than females. Modelling demonstrated that as urbanization intensified the home-range size of males increased whereas female home-ranges remained static in size. This research identifies land-use selection and highlights the possibility that spatial behaviour in the species is sex-biased in response to a gradient of urbanization. &copy; 2014 Elsevier B.V

APENDICITE CRÔNICA E APENDICITE RECORRENTE: ARTIGO DE REVISÃO E APRESENTAÇÃO DE CASUÍSTICA CHRONIC AND RECURRENT APPENDICITIS: REVIEW ARTICLE AND CASES REPORT

A apendicite crônica e a apendicite recorrente são condições patológicas que diferem da apendicite aguda, a afecção mais comum do apêndice vermiforme. O propósito desse artigo é decifrar com critério os aspectos clínicos, o diagnóstico e a histopatologia da apendicite crônica e da apendicite recorrente. Os dados da literatura e as experiências clínica e cirúrgica dos autores, demonstradas por 10 pacientes com idade média entre 40 e 45 anos, com distribuição similar quanto ao sexo, sendo 6 pacientes com apendicite recorrente e 4 com apendicite crônica, permitem concluir que a apendicite crônica e a recorrente já não devem ser mais uma controvérsia ou dúvida, mas um fato inequívoco de importâncias clínica e acadêmica. Portanto, seus conceitos merecem difusão na literatura científica e nas escolas médicas.<br>Chronic and recurrent appendicitis are pathologic conditions that differ from acute appendicitis, the most common affection of the vermiform appendix. The purpose of the present study was to describe in detail the clinical features, diagnosis and pathology of those conditions