Browsing by Issue Date, starting with "2015-07-01"
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- Bioinformatic Analysis of Chlamydia trachomatis Polymorphic Membrane Proteins PmpE, PmpF, PmpG and PmpH as Potential Vaccine AntigensPublication . Nunes, Alexandra; Gomes, João Paulo; Karunakaran, Karuna P; Brunham, Robert C.Chlamydia trachomatis is the most important infectious cause of infertility in women with important implications in public health and for which a vaccine is urgently needed. Recent immunoproteomic vaccine studies found that four polymorphic membrane proteins (PmpE, PmpF, PmpG and PmpH) are immunodominant, recognized by various MHC class II haplotypes and protective in mouse models. In the present study, we aimed to evaluate genetic and protein features of Pmps (focusing on the N-terminal 600 amino acids where MHC class II epitopes were mapped) in order to understand antigen variation that may emerge following vaccine induced immune selection. We used several bioinformatics platforms to study: i) Pmps' phylogeny and genetic polymorphism; ii) the location and distribution of protein features (GGA(I, L)/FxxN motifs and cysteine residues) that may impact pathogen-host interactions and protein conformation; and iii) the existence of phase variation mechanisms that may impact Pmps' expression. We used a well-characterized collection of 53 fully-sequenced strains that represent the C. trachomatis serovars associated with the three disease groups: ocular (N=8), epithelial-genital (N=25) and lymphogranuloma venereum (LGV) (N=20). We observed that PmpF and PmpE are highly polymorphic between LGV and epithelial-genital strains, and also within populations of the latter. We also found heterogeneous representation among strains for GGA(I, L)/FxxN motifs and cysteine residues, suggesting possible alterations in adhesion properties, tissue specificity and immunogenicity. PmpG and, to a lesser extent, PmpH revealed low polymorphism and high conservation of protein features among the genital strains (including the LGV group). Uniquely among the four Pmps, pmpG has regulatory sequences suggestive of phase variation. In aggregate, the results suggest that PmpG may be the lead vaccine candidate because of sequence conservation but may need to be paired with another protective antigen (like PmpH) in order to prevent immune selection of phase variants.
- Characterization of a rare analphoid supernumerary marker chromosome in mosaicPublication . Marques, B.; Alves, C.; Ferreira, C.; Correia, H.; Brito, F.; Pedro, S.; Amorim, M.Analphoid supernumerary marker chromosomes (SMCs) are a rare subclass of SMCs C-band-negative and devoid of alpha-satellite DNA. These marker chromosomes cannot be identified unambiguously by conventional banding techniques alone being necessary to apply molecular cytogenetic methods in favour of a detailed characterization. In this work we report an analphoid SMC involving the terminal long arm of chromosome 7, in 9 years-old boy with several dysmorphic features and severe development delay. Cytogenetic analysis revealed a mosaic karyotype with the presence of an extra SMC, de novo, in 20 % of lymphocytes and 73 % of fibroblast cells. FISH analysis with alpha-satellite probes for all chromosomes, whole chromosome painting probe for chromosome 7, and D7S427 and TelVysion 7q probes, allowed establishing the origin of the SMC as an analphoidmarker resulting of an invdup rearrangement of 7q36-qter region. Affimetrix CytoScan HD microarray analysis, redefined the SMC to arr[hg19] 7q35(143696249-159119707)×2~3, which correspond to a gain of 15.42 Mb and encloses 67 OMIM genes, 16 of which are associated to disease. This result, combined with detailed clinical description, will provide an important means for better genotype-phenotype correlation and a more suitable genetic counselling to the patient and his parents, despite the additional difficulty resulting from being a mosaic (expression varies in different tissues). Analphoid SMCs derived from chromosome 7 are very rare, with only three cases reported so far. With this case we hope contribute to a better understanding of this type of chromosome rearrangements which are difficult for genetic counselling.
- Beach sand and the potential for infectious disease transmission: observations and recommendationsPublication . Solo-Gabriele, Helena M.; Harwood, Valerie J.; Kay, David; Fujioka, Roger S.; Sadowsky, Michael J.; Whitman, Richard L.; Wither, Andrew; Caniça, Manuela; Carvalho da Fonseca, Rita; Duarte, Aida; Edge, Thomas A.; Gargaté, Maria J.; Gunde-Cimerman, Nina; Hagen, Ferry; McLellan, Sandra L.; Nogueira da Silva, Alexandra; Novak Babič, Monika; Prada, Susana; Rodrigues, Raquel; Romão, Daniela; Sabino, Raquel; Samson, Robert A.; Segal, Esther; Staley, Christopher; Taylor, Huw D.; Veríssimo, Cristina; Viegas, Carla; Barroso, Helena; Brandão, JoãoRecent studies suggest that sand can serve as a vehicle for exposure of humans to pathogens at beach sites, resulting in increased health risks. Sampling for microorganisms in sand should therefore be considered for inclusion in regulatory programmes aimed at protecting recreational beach users from infectious disease. Here, we review the literature on pathogen levels in beach sand, and their potential for affecting human health. In an effort to provide specific recommendations for sand sampling programmes, we outline published guidelines for beach monitoring programs, which are currently focused exclusively on measuring microbial levels in water. We also provide background on spatial distribution and temporal characteristics of microbes in sand, as these factors influence sampling programs. First steps toward establishing a sand sampling program include identifying appropriate beach sites and use of initial sanitary assessments to refine site selection. A tiered approach is recommended for monitoring. This approach would include the analysis of samples from many sites for faecal indicator organisms and other conventional analytes, while testing for specific pathogens and unconventional indicators is reserved for high-risk sites. Given the diversity of microbes found in sand, studies are urgently needed to identify the most significant aetiological agent of disease and to relate microbial measurements in sand to human health risk.
- Small Deletion of 143 Kb Encompassing Exon 2 of the AUTS2: Rise of a NewMicrodeletion Syndrome?Publication . Serafim, Silvia; Marques, Barbara; Filomena, Brito; Pedro, Sónia; Ferreira, Cristina; Ventura, Catarina; Gaspar, Isabel; Correia, HildebertoChromosome microarray analysis is a powerful diagnostic tool and is being used as a first-line approach to detect chromosome imbalances associated with intellectual disability, dysmorphic features and congenital anomalies. This test enables the identification of new copy number variants (CNVs) and their association with new microdeletion/microduplication syndromes in patients previously without diagnosis. Here we report the case of a 17 year-old female with severe intellectual disability, absence of speech, microcephaly and congenital abnormalities with a previous normal karyotype performed at a younger age. Affymetrix CytoScan HD chromosome microarray analysis was performed detecting a 143 Kb deletion at the 7q11.22 breakpoint, encompassing exon 2 of AUTS2 gene: arr[hg19] 7q11.22(69238957- 69381975)×1. The AUTS2 gene has been recently implicated in neurodevelopment and is a candidate gene for numerous neurological disorders. Common clinical features described in patients with deletions in AUTS2 gene include intellectual disability, speech delay and microcephaly, among others. Thus, the CNV identified in our patient explains the phenotype observed. We compare our patient with other similar reported cases, adding additional value to the phenotypegenotype correlation of deletions in this region. The growing collection of new cases with similar phenotypes, and the observation of this deletion occurring frequently de novo, indicates this CNV as a possible new single gene microdeletion syndrome.