Bleeding disorders in the tribe: result of consanguineous in breeding

<p>Abstract</p> <p>Objective</p> <p>To determine the frequency and clinical features of bleeding disorders in the tribe as a result of consanguineous marriages.</p> <p>Design</p> <p>Cross Sectional Study</p> <p>Introduction</p> <p>Countries in which consanguinity is a normal practice, these rare autosomal recessive disorders run in close families and tribes. Here we describe a family, living in village Ali Murad Chandio, District Badin, labeled as haemophilia.</p> <p>Patients & Methods</p> <p>Our team visited the village & developed the pedigree of the whole extended family, up to seven generations. Performa was filled by incorporating patients, family history of bleeding, signs & symptoms, and bleeding from any site. From them 144 individuals were screened with CBC, bleeding time, platelet aggregation studies & RiCoF. While for PT, APTT, VWF assay and Factor VIII assay, samples were kept frozen at -70 degrees C until tested.</p> <p>Results</p> <p>The family tree of the seven generations comprises of 533 individuals, 63 subjects died over a period of 20 years and 470 were alive. Out of all those 144 subjects were selected on the basis of the bleeding history. Among them 98(68.1%) were diagnosed to have a bleeding disorder; 44.9% patients were male and 55.1% patients were female. Median age of all the patients was 20.81, range (4 months- 80 yrs). The results of bleeding have shown that majority had gum bleeding, epistaxis and menorrhagia. Most common bleeding disorder was Von Willebrand disease and Platelet functional disorders.</p> <p>Conclusion</p> <p>Consanguineous marriages keep all the beneficial and adversely affecting recessive genes within the family; in homozygous states. These genes express themselves and result in life threatening diseases. Awareness, education & genetic counseling will be needed to prevent the spread of such common occurrence of these bleeding disorders in the community.</p

Back from a Predicted Climatic Extinction of an Island Endemic: A Future for the Corsican Nuthatch

The Corsican Nuthatch (Sitta whiteheadi) is red-listed as vulnerable to extinction by the IUCN because of its endemism, reduced population size, and recent decline. A further cause is the fragmentation and loss of its spatially-restricted favourite habitat, the Corsican pine (Pinus nigra laricio) forest. In this study, we aimed at estimating the potential impact of climate change on the distribution of the Corsican Nuthatch using species distribution models. Because this species has a strong trophic association with the Corsican and Maritime pines (P. nigra laricio and P. pinaster), we first modelled the current and future potential distribution of both pine species in order to use them as habitat variables when modelling the nuthatch distribution. However, the Corsican pine has suffered large distribution losses in the past centuries due to the development of anthropogenic activities, and is now restricted to mountainous woodland. As a consequence, its realized niche is likely significantly smaller than its fundamental niche, so that a projection of the current distribution under future climatic conditions would produce misleading results. To obtain a predicted pine distribution at closest to the geographic projection of the fundamental niche, we used available information on the current pine distribution associated to information on the persistence of isolated natural pine coppices. While common thresholds (maximizing the sum of sensitivity and specificity) predicted a potential large loss of the Corsican Nuthatch distribution by 2100, the use of more appropriate thresholds aiming at getting closer to the fundamental distribution of the Corsican pine predicted that 98% of the current presence points should remain potentially suitable for the nuthatch and its range could be 10% larger in the future. The habitat of the endemic Corsican Nuthatch is therefore more likely threatened by an increasing frequency and intensity of wildfires or anthropogenic activities than by climate change

Galaxy And Mass Assembly (GAMA): end of survey report and data release 2

The Galaxy And Mass Assembly (GAMA) survey is one of the largest contemporary spectroscopic surveys of low-redshift galaxies. Covering an area of ~286 deg^2 (split among five survey regions) down to a limiting magnitude of r < 19.8 mag, we have collected spectra and reliable redshifts for 238,000 objects using the AAOmega spectrograph on the Anglo-Australian Telescope. In addition, we have assembled imaging data from a number of independent surveys in order to generate photometry spanning the wavelength range 1 nm - 1 m. Here we report on the recently completed spectroscopic survey and present a series of diagnostics to assess its final state and the quality of the redshift data. We also describe a number of survey aspects and procedures, or updates thereof, including changes to the input catalogue, redshifting and re-redshifting, and the derivation of ultraviolet, optical and near-infrared photometry. Finally, we present the second public release of GAMA data. In this release we provide input catalogue and targeting information, spectra, redshifts, ultraviolet, optical and near-infrared photometry, single-component S\'ersic fits, stellar masses, H$\alpha$-derived star formation rates, environment information, and group properties for all galaxies with r < 19.0 mag in two of our survey regions, and for all galaxies with r < 19.4 mag in a third region (72,225 objects in total). The database serving these data is available at http://www.gama-survey.org/

IL-10 Blocks the Development of Resistance to Re-Infection with Schistosoma mansoni

Despite effective chemotherapy to treat schistosome infections, re-infection rates are extremely high. Resistance to reinfection can develop, however it typically takes several years following numerous rounds of treatment and re-infection, and often develops in only a small cohort of individuals. Using a well-established and highly permissive mouse model, we investigated whether immunoregulatory mechanisms influence the development of resistance. Following Praziquantel (PZQ) treatment of S. mansoni infected mice we observed a significant and mixed anti-worm response, characterized by Th1, Th2 and Th17 responses. Despite the elevated anti-worm response in PBMC's, liver, spleen and mesenteric lymph nodes, this did not confer any protection from a secondary challenge infection. Because a significant increase in IL-10-producing CD4+CD44+CD25+GITR+ lymphocytes was observed, we hypothesised that IL-10 was obstructing the development of resistance. Blockade of IL-10 combined with PZQ treatment afforded a greater than 50% reduction in parasite establishment during reinfection, compared to PZQ treatment alone, indicating that IL-10 obstructs the development of acquired resistance. Markedly enhanced Th1, Th2 and Th17 responses, worm-specific IgG1, IgG2b and IgE and circulating eosinophils characterized the protection. This study demonstrates that blocking IL-10 signalling during PZQ treatment can facilitate the development of protective immunity and provide a highly effective strategy to protect against reinfection with S. mansoni

Chronic Helminth Infections Protect Against Allergic Diseases by Active Regulatory Processes

Developed countries are suffering from an epidemic rise in immunologic disorders, such as allergy-related diseases and certain autoimmunities. Several studies have demonstrated a negative association between helminth infections and inflammatory diseases (eg, allergy), providing a strong case for the involvement of helminth infections in this respect. However, some studies point in the opposite direction. The discrepancy may be explained by differences in frequency, dose, time, and type of helminth. In this review, new studies are discussed that may support the concept that chronic helminth infections in particular—but not acute infections—are associated with the expression of regulatory networks necessary for downmodulating allergic immune responses to harmless antigens. Furthermore, different components of regulatory networks are highlighted, such as the role of regulatory T and B cells, modulation of dendritic cells, early innate signals from structural cells (eg, epithelial cells), and their individual contributions to protection against allergic diseases. It is of great interest to define and characterize specific helminth molecules that have profound immunomodulatory capacities as targets for therapeutic application in the treatment or prophylaxis of allergic manifestations

Regulating STING in health and disease.

The presence of cytosolic double-stranded DNA molecules can trigger multiple innate immune signalling pathways which converge on the activation of an ER-resident innate immune adaptor named "STimulator of INterferon Genes (STING)". STING has been found to mediate type I interferon response downstream of cyclic dinucleotides and a number of DNA and RNA inducing signalling pathway. In addition to its physiological function, a rapidly increasing body of literature highlights the role for STING in human disease where variants of the STING proteins, as well as dysregulated STING signalling, have been implicated in a number of inflammatory diseases. This review will summarise the recent structural and functional findings of STING, and discuss how STING research has promoted the development of novel therapeutic approaches and experimental tools to improve treatment of tumour and autoimmune diseases

The elegans of spindle assembly

The Caenorhabditis elegans one-cell embryo is a powerful system in which to study microtubule organization because this large cell assembles both meiotic and mitotic spindles within the same cytoplasm over the course of 1 h in a stereotypical manner. The fertilized oocyte assembles two consecutive acentrosomal meiotic spindles that function to reduce the replicated maternal diploid set of chromosomes to a single-copy haploid set. The resulting maternal DNA then unites with the paternal DNA to form a zygotic diploid complement, around which a centrosome-based mitotic spindle forms. The early C. elegans embryo is amenable to live-cell imaging and electron tomography, permitting a detailed structural comparison of the meiotic and mitotic modes of spindle assembly