Extended homozygosity is not usually due to cytogenetic abnormality

<p>Abstract</p> <p>Background</p> <p>Previous studies have reported frequent stretches of homozygosity in human subjects but have failed to clarify whether these are due to cytogenetic abnormalities or to autozygosity.</p> <p>Methods</p> <p>Trios which had been typed for closely spaced SNPs spanning the genome were studied. Stretches of extended homozygosity were identified in the child members, as were occasions on which the child had been genotyped as not inheriting one parental allele. The number of times such transmission errors occurred within regions of extended homozygosity was compared with the chance expectation.</p> <p>Results</p> <p>Transmission errors occurred more rarely in regions of extended homozygosity than would be expected by chance.</p> <p>Discussion</p> <p>Regions of extended homozygosity are not generally due to cytogenetic abnormalities such as uniparental isodisomy. They reflect the Mendelian inheritance of haplotypes from a common ancestor. This may have implications for mapping disease genes.</p

Expression of HLA-G in inflammatory bowel disease provides a potential way to distinguish between ulcerative colitis and Crohn's disease.

In addition to being involved in nutrient uptake, the epithelial mucosa constitute the first line of defense against microbial pathogens. A direct consequence of this physiological function is a very complex network of immunological interactions that lead to a strong control of the mucosal immune balance. The dysfunction of immunological tolerance is likely to be a cause of inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD). HLA-G is a non-classical major histocompatibility complex (HLA) class I molecule, which is highly expressed by human cytotrophoblast cells. These cells play a role in immune tolerance by protecting trophoblasts from being killed by uterine NK cells. Because of the deregulation of immune system activity in IBD, as well as the immunoregulatory role of HLA-G, we have analyzed the expression of HLA-G in intestinal biopsies of patients with UC and CD. Our study shows that the differential expression of HLA-G provides a potential way to distinguish between UC and CD. Although the reason for this differential expression is unclear, it might involve a different mechanism of immune regulation. In addition, we demonstrate that in the lamina propria of the colon of patients with UC, IL-10 is strongly expressed. In conclusion, the presence of HLA-G on the surface of intestinal epithelial cell in patients with UC lends support to the notion that this molecule may serve as a regulator of mucosal immune responses to antigens of undefined origin. Thus, this different pattern of HLA-G expression may help to differentiate between the immunopathogenesis of CD and UC

Comportamento à flexão de vigas eco-eficientes de ultra elevada durabilidade

Atualmente, o ecossistema mundial tem vindo a ser confrontado com problemas de grande importância, a elevada poluição do meio ambiente e a limitação dos recursos energéticos. Estes problemas têm contribuído para que a sustentabilidade da construção seja uma prioridade cada vez maior no presente e no futuro. A manutenção e a reabilitação do património construído surge como uma das medidas mais eficazes para prevenir ou reduzir o consumo de energia no setor da construção. No caso da construção nova, a tendência é para verificar-se um aumento da utilização de elementos estruturais pré-fabricados com partes betonadas em obra, obtendose uma maior rapidez de execução associada a um maior controlo de qualidade. O betão de ultra elevada durabilidade, reforçado com fibras metálicas, é considerado um material inovador desenvolvido nas últimas décadas, apresentando um conjunto de caraterísticas especiais, como a durabilidade, a facilidade de aplicação, as elevadas resistências mecânicas, tornando-o num produto particularmente atraente para a reabilitação e reforço de estruturas de betão. No entanto, este betão não deve ser produzido em grandes quantidades devido ao elevado consumo de cimento e adições, resultando em elevados custos económicos e ambientais. Considerando estas desvantagens é proposto que o betão de ultra elevada durabilidade seja usado apenas na camada de recobrimento, formando-se assim uma superskin que protege o elemento estrutural dos ambientes mais agressivos, isto é, aumenta a durabilidade das estruturas de betão sem que, no entanto, seja criado um impacte ambiental muito significativo (a quantidade de CO2 libertada para a atmosfera é menor devido ao menor consumo de cimento e adições). A presente dissertação pretende explorar o conceito de superskin do ponto de vista do comportamento estrutural, nomeadamente, estudar o comportamento de vigas sujeitas a esforços de flexão, compostas por uma camada exterior de betão de ultra elevada durabilidade, associado a um núcleo com betão eco-eficiente, com baixa dosagem de cimento, de modo a obter uma solução mais durável e ao mesmo tempo, ecologicamente mais eficiente. Foram realizadas oito vigas com diferentes taxas de armadura: quatro vigas produzidas apenas com betão com baixa dosagem de cimento (usadas como vigas de referência) e quatro vigas produzidas com um betão de ultra elevada durabilidade na camada de recobrimento e com um betão com baixa dosagem de cimento no núcleo. As diferentes taxas de armadura longitudinal permitem avaliar a influência da superskin em vigas com roturas dúcteis e frágeis. Com base nos dados recolhidos durante os ensaios experimentais estudou-se: (i) relação cargadeslocamento; (ii) os valores teóricos e experimentais do momento resistente; (iii) a evolução da curvatura nas secções críticas; (iv) a evolução da rigidez à flexão com a carga aplicada; (v) a ductilidade; e (vi) a fendilhação e o tipo de rotura. Da análise de resultados foi possível verificar que o recobrimento em betão de ultra elevada durabilidade é uma solução com aspetos muito positivos, nomeadamente, aumenta a resistência à flexão das vigas

Validation of a Cost-Efficient Multi-Purpose SNP Panel for Disease Based Research

BACKGROUND: Here we present convergent methodologies using theoretical calculations, empirical assessment on in-house and publicly available datasets as well as in silico simulations, that validate a panel of SNPs for a variety of necessary tasks in human genetics disease research before resources are committed to larger-scale genotyping studies on those samples. While large-scale well-funded human genetic studies routinely have up to a million SNP genotypes, samples in a human genetics laboratory that are not yet part of such studies may be productively utilized in pilot projects or as part of targeted follow-up work though such smaller scale applications require at least some genome-wide genotype data for quality control purposes such as DNA "barcoding" to detect swaps or contamination issues, determining familial relationships between samples and correcting biases due to population effects such as population stratification in pilot studies. PRINCIPAL FINDINGS: Empirical performance in classification of relative types for any two given DNA samples (e.g., full siblings, parental, etc) indicated that for outbred populations the panel performs sufficiently to classify relationship in extended families and therefore also for smaller structures such as trios and for twin zygosity testing. Additionally, familial relationships do not significantly diminish the (mean match) probability of sharing SNP genotypes in pedigrees, further indicating the uniqueness of the "barcode." Simulation using these SNPs for an African American case-control disease association study demonstrated that population stratification, even in complex admixed samples, can be adequately corrected under a range of disease models using the SNP panel. CONCLUSION: The panel has been validated for use in a variety of human disease genetics research tasks including sample barcoding, relationship verification, population substructure detection and statistical correction. Given the ease of genotyping our specific assay contained herein, this panel represents a useful and economical panel for human geneticists

A 14-year experience with kidney transplantation.

Between November, 1962 and August, 1975, 668 kidney transplants were done in 556 consecutive patients at Denver, Colorado. The Denver experience has been divided into 7 periods of time, according to the conditions of care during each period. The results in related transplantation have changed little during the decade beginning in 1966. The results in unrelated transplantation have not materially changed since 1968. The long-term patient survival after related transplantation has been better than after cadaver transplantation. The results of transplantation in 57 children ages 3 to 18 years have been slightly better than the results of adult transplantation. The outcome of kidney transplantation and the feasibility of improving this therapy with present techniques are limited by our inability to accurately match each patient with the immunologically best donor and by our inability to precisely control the immune system of the recipient. Rejection is still the main reason for graft loss, and sepsis remains the main cause of patient mortality. More specific and less toxic means of achieving graft acceptance are needed before a higher level of patient service can be realized. However, even with the tools now available, thousands of recipients throughout the world have been returned to useful lives

Genetic variants in FGFR2 and FGFR4 genes and skin cancer risk in the Nurses' Health Study

<p>Abstract</p> <p>Background</p> <p>The human fibroblast growth factor (FGF) and its receptor (FGFR) play an important role in tumorigenesis. Deregulation of the <it>FGFR2 </it>gene has been identified in a number of cancer sites. Overexpression of the <it>FGFR4 </it>protein has been linked to cutaneous melanoma progression. Previous studies reported associations between genetic variants in the <it>FGFR2 </it>and <it>FGFR4 </it>genes and development of various cancers.</p> <p>Methods</p> <p>We evaluated the associations of four genetic variants in the <it>FGFR2 </it>gene highly related to breast cancer risk and the three common tag-SNPs in the <it>FGFR4 </it>gene with skin cancer risk in a nested case-control study of Caucasians within the Nurses' Health Study (NHS) among 218 melanoma cases, 285 squamous cell carcinoma (SCC) cases, 300 basal cell carcinoma (BCC) cases, and 870 controls.</p> <p>Results</p> <p>We found no evidence for associations between these seven genetic variants and the risks of melanoma and nonmelanocytic skin cancer.</p> <p>Conclusion</p> <p>Given the power of this study, we did not detect any contribution of genetic variants in the <it>FGFR2 </it>or <it>FGFR4 </it>genes to inherited predisposition to skin cancer among Caucasian women.</p