Articles: signal-transducing-adaptor-proteins.
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Schizophrenia is a severe psychiatric disease characterized by a high heritability and a complex genetic architecture. Recent reports based on exome sequencing analyses have highlighted a significant increase of potentially deleterious de novo mutations in different genes in individuals with schizophrenia. ⋯ This supports the notion that de novo mutations in these four genes are extremely rare in schizophrenia and further highlights the high degree of genetic heterogeneity of this disease.
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The Journal of pathology · Jan 2013
Comparative StudyMLH1-silenced and non-silenced subgroups of hypermutated colorectal carcinomas have distinct mutational landscapes.
Approximately 15% of colorectal carcinomas (CRCs) exhibit a hypermutated genotype accompanied by high levels of microsatellite instability (MSI-H) and defects in DNA mismatch repair. These tumours, unlike the majority of colorectal carcinomas, are often diploid, exhibit frequent epigenetic silencing of the MLH1 DNA mismatch repair gene, and have a better clinical prognosis. As an adjunct study to The Cancer Genome Atlas consortium that recently analysed 224 colorectal cancers by whole exome sequencing, we compared the 35 CRCs (15.6%) with a hypermutated genotype to those with a non-hypermutated genotype. ⋯ Analysis of mRNA and microRNA expression signatures revealed that hypermutated CRCs with MLH1 silencing had greatly reduced levels of WNT signalling and increased BRAF signalling relative to non-hypermutated CRCs. Our findings suggest that hypermutated CRCs include one subgroup with fundamentally different pathways to malignancy than the majority of CRCs. Examination of MLH1 expression status and frequencies of APC, KRAS, and BRAF mutation in CRC may provide a useful diagnostic tool that could supplement the standard microsatellite instability assays and influence therapeutic decisions.
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Asian Pac. J. Cancer Prev. · Jan 2013
Comparative StudySperm-associated antigen 9 is a promising marker for early diagnosis of endometrial cancer.
Sperm-associated antigen 9 (SPAG9) has been recently proposed as a novel biomarker for early diagnosis of several human tumors, including ovarian, cervical and breast cancers. Its clinical value remains to be clarified for endometrial cancer (EC). In this study, we investigated the utility of serum SPAG9 levels in diagnosis of EC and its association with important clinicopathological parameters. ⋯ Testing for SPAG9 may be useful for early detection of EC in asymptomatic high-risk women. Its role in post-treatment follow-up and early detection of recurrence should be assessed in future trials.
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Journal of virology · Jan 2013
TRIM protein-mediated regulation of inflammatory and innate immune signaling and its association with antiretroviral activity.
Members of the tripartite interaction motif (TRIM) family of E3 ligases are emerging as critical regulators of innate immunity. To identify new regulators, we carried out a screen of 43 human TRIM proteins for the ability to activate NF-κB, AP-1, and interferon, hallmarks of many innate immune signaling pathways. We identified 16 TRIM proteins that induced NF-κB and/or AP-1. ⋯ In contrast, human immunodeficiency virus type 1 (HIV-1) gene expression was increased by TRIM proteins that induce NF-κB. HIV-1 resistance to inflammatory TRIM proteins mapped to the NF-κB sites in the HIV-1 long terminal repeat (LTR) U3 and could be transferred to MLV. Thus, our work identifies new TRIM proteins involved in innate immune signaling and reinforces the striking ability of HIV-1 to exploit innate immune signaling for the purpose of viral replication.
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Septic shock remains an important issue for critical care physicians. Despite significant advances in the knowledge of its pathophysiology, new effective therapeutic approaches have yet to emerge. ⋯ In a recent study, Katharina Mederle and colleagues explored the impact of angiotensin 1 receptor-associated protein 1 (Arap1) deficiency on vascular hyporesponsiveness in an experimental model of septic shock. The authors demonstrate that experimental septic shock downregulates Arap1 expression, which in turn contributes to vascular hyporesponsiveness to angiotensin II.