Backbone and side-chain 1H, 13C and 15N assignments of the ubiquitin-associated domain of human X-linked inhibitor of apoptosis protein

X-linked inhibitor of apoptosis protein (XIAP), a leading member of the family of inhibitor of apoptosis (IAP) proteins, is considered as the most potent and versatile inhibitor of caspases and apoptosis. It has been reported that XIAP is frequently overexpressed in cancer and its expression level is implicated in contributing to tumorigenesis, disease progression, chemoresistance and poor patient-survival. Therefore, XIAP is one of the leading targets in drug development for cancer therapy. Recently, based on bioinformatics study, a previously unrecognized but evolutionarily conserved ubiquitin-associated (UBA) domain in IAPs was identified. The UBA domain is found to be essential for the oncogenic potential of IAP, to maintain endothelial cell survival and to protect cells from TNF-α-induced apoptosis. Moreover, the UBA domain is required for XIAP to activate NF-κB. In the present study, we report the near complete resonance assignments of the UBA domain-containing region of human XIAP protein. Secondary structure prediction based on chemical shift index (CSI) analysis reveals that the protein is predominately α-helical, which is consistent with the structures of known UBA proteins

A rigorous analytical model for shrinkage cracking of reinforced concrete

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Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 × 10(-8), in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms

Risk-adjusted cesarean section rates for the assessment of physician performance in Taiwan: a population-based study

BACKGROUND: Over the past decade, about one-third of all births nationwide in Taiwan were delivered by cesarean section (CS). Previous studies in the US and Europe have documented the need for risk adjustment for fairer comparisons among providers. In this study, we set out to determine the impact that adjustment for patient-specific risk factors has on CS among different physicians in Taiwan. METHODS: There were 172,511 live births which occurred in either hospitals or obstetrics/gynecology clinics between 1 January and 31 December 2003, and for whom birth certificate data could be linked with National Health Insurance (NHI) claims data, available as the sample for this study. Physicians were divided into four equivalent groups based upon the quartile distribution of their crude (actual) CS rates. Stepwise logistic regressions were conducted to develop a predictive model and to determine the expected (risk-adjusted) CS rate and 95% confidence interval (CI) for each physician. The actual rates were then compared with the expected CS rates to see the proportion of physicians whose actual rates were below, within, or above the predicted CI in each quartile. RESULTS: The proportion of physicians whose CS rates were above the predicted CI increased as the quartile moved to the higher level. However, more than half of the physicians whose actual rates were higher than the predicted CI were not in the highest quartile. Conversely, there were some physicians (40 of 258 physicians) in the highest quartile who were actually providing obstetric care that was appropriate to the risk. When a stricter standard was applied to the assessment of physician performance by excluding physicians in quartile 4 for predicting CS rates, as many as 60% of physicians were found to have higher CS rates than the predicted CI, and indeed, the CS rates of no physicians in either quartile 3 or quartile 4 were below the predicted CI. CONCLUSION: Overall, our study found that the comparison of unadjusted CS rates might not provide a valid reflection of the quality of obstetric care delivered by physicians, and may ultimately lead to biased judgments by purchasers. Our study has also shown that when we changed the standard of quality assessment, the evaluation results also changed

Guidelines for histopathological specimen examination and diagnostic reporting of primary bone tumours

This review is intended to provide histopathologists with guidelines for clinical assessment, specimen handling and diagnostic reporting of benign and malignant primary bone tumours. Information from radiology, surgical, oncology and other clinical colleagues involved in the diagnosis and treatment of primary bone tumours should be properly assessed before undertaking a structured approach to specimen handling and histological reporting. This ensures that the information needed for planning appropriate treatment of these complex tumours is provided. Consistency in diagnostic evaluation with respect to both terminology and report content facilitates liaison at multidisciplinary bone tumour meetings and collaboration between cancer units and networks, as well as providing a common database for audit of the clinical, radiological and pathological aspects of bone tumours

Twist and snai1 expression in pharyngeal squamous cell carcinoma stroma is related to cancer progression

<p>Abstract</p> <p>Background</p> <p>Epithelial-mesenchymal transition (EMT) is a crucial process in tumorigenesis since tumor cells attain fibroblast-like features enabling them to invade to surrounding tissue. Two transcription factors, <it>TWIST </it>and <it>SNAI1</it>, are fundamental in regulating EMT.</p> <p>Methods</p> <p>Immunohistochemistry was used to study the expression of TWIST and SNAI1 in 109 pharyngeal squamous cell carcinomas.</p> <p>Results</p> <p>Tumors with intense stromal staining of TWIST relapsed more frequently (p = 0.04). Tumors with both positive TWIST and SNAI1 immunoreactivity in the stroma were at least Stage II (p = 0.05) and located more often in hypopharynx (p = 0.035). Tumors with negative immunostaining of TWIST and SNAI1 in the stromal compartment were smaller (T1-2) (p = 0.008), less advanced (SI-II) (p = 0.031) and located more often in the oropharynx (p = 0.007). Patients with negative SNAI1 and TWIST immunostaining in tumor stroma had a better 5-year disease-specific and overall survival (p = 0.037 and p = 0.014 respectively).</p> <p>Conclusion</p> <p>TWIST and SNAI1 expression in stromal cells is associated with clinical and histopathological characteristics that indicate progressive disease. Negative expression of these EMT-promoting transcription factors predicts a better outcome.</p

MicroRNA-sequence profiling reveals novel osmoregulatory microRNA expression patterns in catadromous eel anguilla marmorata

MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs that regulate gene expression by post-transcriptional repression of mRNAs. Recently, several miRNAs have been confirmed to execute directly or indirectly osmoregulatory functions in fish via translational control. In order to clarify whether miRNAs play relevant roles in the osmoregulation of Anguilla marmorata, three sRNA libraries of A. marmorata during adjusting to three various salinities were sequenced by Illumina sRNA deep sequencing methods. Totally 11,339,168, 11,958,406 and 12,568,964 clear reads were obtained from 3 different libraries, respectively. Meanwhile, 34 conserved miRNAs and 613 novel miRNAs were identified using the sequence data. MiR-10b-5p, miR-181a, miR-26a-5p, miR-30d and miR-99a-5p were dominantly expressed in eels at three salinities. Totally 29 mature miRNAs were significantly up-regulated, while 72 mature miRNAs were significantly down-regulated in brackish water (10‰ salinity) compared with fresh water (0‰ salinity); 24 mature miRNAs were significantly up-regulated, while 54 mature miRNAs were significantly down-regulated in sea water (25‰ salinity) compared with fresh water. Similarly, 24 mature miRNAs were significantly up-regulated, while 45 mature miRNAs were significantly down-regulated in sea water compared with brackish water. The expression patterns of 12 dominantly expressed miRNAs were analyzed at different time points when the eels transferred from fresh water to brackish water or to sea water. These miRNAs showed differential expression patterns in eels at distinct salinities. Interestingly, miR-122, miR-140-3p and miR-10b-5p demonstrated osmoregulatory effects in certain salinities. In addition, the identification and characterization of differentially expressed miRNAs at different salinities can clarify the osmoregulatory roles of miRNAs, which will shed lights for future studies on osmoregulation in fish

PAX6 Haplotypes Are Associated with High Myopia in Han Chinese

Author name used in this publication: Maurice K. H. Yap2010-2011 > Academic research: refereed > Publication in refereed journalpublished_fina