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Transducin (beta)-like 1X related protein 1 (TBL1XR1/TBLR1) is an integral subunit of the NCoR (nuclear receptor corepressor) and SMRT (silencing mediator of retinoic acid and thyroid hormone receptors) repressor complexes. It is ...
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Transducin (beta)-like 1X related protein 1 (TBL1XR1/TBLR1) is an integral subunit of the NCoR (nuclear receptor corepressor) and SMRT (silencing mediator of retinoic acid and thyroid hormone receptors) repressor complexes. It is an evolutionally conserved protein that shares high similarity across all species. TBL1XR1 is essential for transcriptional repression mediated by unliganded nuclear receptors (NRs) and othe regulated transcription factors (TFs). However, it can also act as a transcription activator through the recruitment of the ubiquitin-conjugating/19S proteasome complex that mediates the exchange of corepressors for coactivators. TBL1XR1 is required for the activation of multiple intracellular signaling pathways. TBL1XR1 germline mutations and recurrent mutations are linked to intellectual disability. Upregulation of TBL1XR1 is observed in a variety of solid tumors, which is associated with advanced tumor stage, metastasis and poor prognosis. A variety of genomic alterations, such as translocation, deletion and mutation have been identified in many types of neoplasms. Loss of TBL1XR1 in B-lymphoblastic leukemia disrupts glucocorticoid receptor recruitment to chromatin and results in glucocorticoid resistance. However, the mechanisms of other types of genomic changes in tumorogenesis are still not clear. A pre-clinical study has shown that the disruption of the interaction between TBL1X and β-catenin using a small molecule can inhibit the growth of AML stem and blast cells both in vitro and in vivo. These findings shed light on the therapeutic potentials of targeting TBL1XR1 related proteins in cancer treatment.
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Transducin (β)-like 1 X-linked receptor 1(TBL1XR1) has been reported to be overexpressed in various human cancers, as well as contributing to carcinogenesis and progression. This synthetic analysis was performed to assess whether...
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Transducin (β)-like 1 X-linked receptor 1(TBL1XR1) has been reported to be overexpressed in various human cancers, as well as contributing to carcinogenesis and progression. This synthetic analysis was performed to assess whether TBL1XR1 protein could act as a potential prognostic molecular marker for human cancers. Several online databases (PubMed, Web of Science, Embase together with Wanfang and China National Knowledge Internet database) were retrieved to identify TBL1XR1-related publications. A total of ten studies with 1837 cancer patients were included in this meta-analysis. Hazard ratios (HR) with 95% confidence intervals (CI) were applied to assess the association between TBL1XR1 expression and cancer prognosis. Odds ratios (OR) were calculated to determine the relationship between TBL1XR1 expression and clinicopathological characteristics. The overall results revealed that the overexpression of TBL1XR1 was correlated with poorer overall survival (OS) (HR: 1.77, 95% CI: 1.49–2.06, p < 0.001) and worse disease-free survival (DFS) (HR: 1.51, 95% CI: 1.19–1.84, p < 0.001) in human solid cancers. Statistical significance for OS was also found in subgroup analysis stratified by the cancer type, analysis method and follow-up time. Furthermore, elevated TBL1XR1 was associated with unfavorable clinicopathological characteristics including tumor size, depth of invasion, lymph node metastasis and TNM stage. Our meta-analysis suggested that TBL1XR1 might be served as a novel and promising biomarker to predict prognosis and clinicopathologic characteristic for cancer patients.
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We introduced two variants of team based learning (TBL) strategies in pathology course to seek their efficacy in a problem based learning (PBL) curriculum. The TBL strategy was adopted in two different sessions. One during regular...
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We introduced two variants of team based learning (TBL) strategies in pathology course to seek their efficacy in a problem based learning (PBL) curriculum. The TBL strategy was adopted in two different sessions. One during regular resource session (RS-TBL) and other during a weekly review session (RVS-TBL) of the PBL curriculum. The study involved 104 second year students during their 8 weeks of cardiovascular-respiratory units and 3 weeks of hematology units. RS-TBL was adopted for cardiovascular-respiratory unit and RVS-TBL for hematology unit. The first 8 weeks of the course were implemented as RS-TBL and the last 3 weeks as RVS-TBL. The results showed that the group performance was markedly improved than individual performance in both RS-TBL and RVS-TBL (p < 0.001). Comparison between the RS-TBL and RVS-TBL revealed that individual student and group performance was better in the RVS-BL (p < 0.001). The result of the student attitudinal survey indicated an 88% agreement that TBL enhanced their understanding of pathology concepts and critical analysis. Most of the participants (85%) found RVS-TBL to be more useful. Post-TBL, end of semester examination results proved beneficial for the students in risk. The study demonstrated that RVS-TBL may be preferably adopted to enhance the philosophy of TBL in a PBL curriculum.
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Pierpont syndrome is a rare and sporadic syndrome, including developmental delay, facial characteristics, and abnormal extremities. Recently, a recurrent de novo TBL1XR1 variant (c.1337A > G; p.Tyr446Cys) has been identified in ei...
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Pierpont syndrome is a rare and sporadic syndrome, including developmental delay, facial characteristics, and abnormal extremities. Recently, a recurrent de novo TBL1XR1 variant (c.1337A > G; p.Tyr446Cys) has been identified in eight patients by whole-exome sequencing. A dominant-negative effect of this mutation is strongly suspected, since patients with TBL1XR1 deletion and other variants predicting loss of function do not share the same phenotype. We report two patients with typical Pierpont-like syndrome features. Exome sequencing allowed identifying a de novo heterozygous missense TBL1XR1 variant in both patients, different from those already reported: p.Cys325Tyr and p.Tyr446His. The localization of these mutations and clinical features of Pierpont-like syndrome suggest that their functional consequences are comparable with the recurrent mutation previously described, and provided additional data to understand molecular mechanisms of TBL1XR1 anomalies.
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We report on a 6-year-old child with a de novo 1.6Mb deletion in the 3q26.31q26.32 region identified by SNP array, involving only one relevant gene: TBL1XR1. The girl shows non-specific, mild to moderate intellectual deficiency bu...
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We report on a 6-year-old child with a de novo 1.6Mb deletion in the 3q26.31q26.32 region identified by SNP array, involving only one relevant gene: TBL1XR1. The girl shows non-specific, mild to moderate intellectual deficiency but no autistic behavior. Point mutations in TBL1XR1 have recently been implicated in three patients with intellectual disability (ID) and autistic features. Our report supports that haploinsufficiency for TBL1XR1 could be implicated in non-ASD autosomal dominant ID.
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TBL1XR1 gene is associated with multiple developmental disorders presenting several neurological aspects. The relative protein is involved in regulation of important cellular pathways and master regulators of transcriptional outpu...
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TBL1XR1 gene is associated with multiple developmental disorders presenting several neurological aspects. The relative protein is involved in regulation of important cellular pathways and master regulators of transcriptional output including nuclear receptor repressors, Wnt signaling, and MECP2 protein. However, TBL1XR1 mutations (including complete loss of its functions) have not been experimentally studied in neurological context, leaving a lack of knowledge in the mechanisms at the basis of the diseases. We show that Tbl1xr1 knock-out mice exhibit behavioral and neuronal abnormalities. Either the absence of TBL1XR1, or its point mutations interfering with stability/regulation of NCOR complex, induced decreased proliferation and increased differentiation in neural progenitors. We suggest that this developmental unbalance is due to the failure in the regulation of the MAPK cascade. Together, our results broaden the molecular and functional aftermath of TBL1XR1 deficiency associated with human disorders.
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Transducin (beta)-like 1 X-linked receptor 1 (TBL1XR1) is an evolutionarily conserved protein related to spermatozoa. To clarify its role and mechanism of action in spermatozoa, qRT-PCR was used to analyse the expression of TBL1XR...
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Transducin (beta)-like 1 X-linked receptor 1 (TBL1XR1) is an evolutionarily conserved protein related to spermatozoa. To clarify its role and mechanism of action in spermatozoa, qRT-PCR was used to analyse the expression of TBL1XR1 in human spermatozoa and mouse testes. The mice were established as an animal model by injecting the mice testes with small interfering RNA against TBL1XR1 or control siRNA. Our results indicated that deficiency of TBL1XR1 in mice reduced the motility of spermatozoa and disrupted the histone-to-protamine transition. We also found the decreased expression of TBL1XR1 in the spermatozoa of human patients with asthenozoospermia (AZ) compared with that in the spermatozoa of healthy males. Moreover, we carried out chromatin immunoprecipitation analyses and found that genes downstream of TBL1XR1 were related to sperm motility. Thus, TBL1XR1 might be related to sperm motility and might function through its downstream genes. Our data highlight the role of TBL1XR1 involved in spermatozoa and provide new molecular insights into the intricate systems required for male fertility.
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Background: Liver metastasis is the leading cause of lethal colorectal cancer (CRC). For patients with early stage CRC, metachronous liver metastasis is the primary risk for poor prognosis. Accordingly, identification of prospecti...
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Background: Liver metastasis is the leading cause of lethal colorectal cancer (CRC). For patients with early stage CRC, metachronous liver metastasis is the primary risk for poor prognosis. Accordingly, identification of prospective biomarkers for metachronous liver metastasis would be invaluable in evaluating patients' clinical outcomes and developing personal treatment therapy.
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This paper investigates the numerical accuracy of implicit Large Eddy Simulations (iLES) in relation to compressible turbulent boundary layers (TBL). iLES are conducted in conjunction with Monotonic Upstream-Centred Scheme for Con...
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This paper investigates the numerical accuracy of implicit Large Eddy Simulations (iLES) in relation to compressible turbulent boundary layers (TBL). iLES are conducted in conjunction with Monotonic Upstream-Centred Scheme for Conservation Laws (MUSCL) and Weighted Essentially Non-Oscillatory (WENO), ranging from 2nd to 9th-order. The accuracy effects are presented from a physical perspective showing skewness, flatness and anisotropy calculations, among others. The order of the scheme directly affects the physical representation of the TBL, especially the degree of asymmetry and anisotropy in the sub-layers of the TBL. The study concludes that high-order iLES can provide an accurate and detailed description of TBL directly comparable to available DNS and experimental results. (C) 2017 Elsevier Ltd. All rights reserved.
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The influence of stiffeners on plate vibration and noise radiation induced by turbulent boundary layers is investigated by wind tunnel measurements. Plates with and without stiffeners are tested under the flow speed of 60 m/s, 71 ...
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The influence of stiffeners on plate vibration and noise radiation induced by turbulent boundary layers is investigated by wind tunnel measurements. Plates with and without stiffeners are tested under the flow speed of 60 m/s, 71 m/s and 86 m/s, respectively. The stiffeners are set either perpendicular or parallel to the direction of the free stream. Measured vibration and noise levels are compared with theoretical calculations, where wall pressure cross-spectra are described by the Corcos model. For the plates tested, it is evident that stiffeners perpendicular to the direction of the free stream could increase noise radiation, but have almost no influence on vibration level of plates.
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