Selenoprotein R (SelR) is a mammalian selenocysteine-containing protein with no known function. Here we report that cysteine homologs of SelR are present in all organisms except certain parasites and hyperthermophiles, and this pattern of occurrence closely matches that of only one protein, peptide methionine sulfoxide reductase (MsrA). Moreover, in several genomes, SelR and MsrA genes are fused or clustered, and their expression patterns suggest a role of both proteins in protection against oxidative stress. Consistent with these computational screens, growth of Saccharomyces cerevisiae SelR and MsrA mutant strains was inhibited, and the strain lacking both genes could not grow, in the presence of H2O2 and methionine sulfoxide. We found that the cysteine mutant of mouse SelR, as well as the Drosophila SelR homolog, contained zinc and reduced methionine-R-sulfoxide, but not methionine-S-sulfoxide, in in vitro assays, a function that is both distinct and complementary to the stereo-specific activity of MsrA. These findings identify a function of the conserved SelR enzyme family, define a pathway of methionine sulfoxide reduction, reveal a case of convergent evolution of similar function in structurally distinct enzymes, and suggest a previously uncharacterized redox regulatory role of selenium in mammals.
Sheldon and colleagues have recently focused research attention on the concept of self-concordance, in which people feel that they pursue their goals because the goals fit with their underlying interests and values rather than because others say they should pursue them. Self-concordant individuals typically evidence higher subjective well-being (SWB). But is this also true in non-Western cultures, which emphasize people's duty to conform to societal expectations and group-centered norms? To address this question, this study assessed goal self-concordance and SWB in four different cultures. U.S., Chinese, and South Korean samples evidenced equal levels of self-concordance, whereas a Taiwanese sample evidenced somewhat less selfconcordance. More importantly, self-concordance predicted SWB within every culture. It appears that "owning one's actions"-that is, feeling that one's goals are consistent with the self-may be important for most if not all humans.
Programmed cell death 4 (Pdcd4) is a tumor suppressor that inhibits neoplastic transformation and tumor invasion. Tissue microarray analysis showed that Pdcd4 expression is downregulated in colon adenocarcinoma and carcinoma relative to adjacent normal tissues. To address the issue of whether reduced Pdcd4 expression is sufficient to promote tumor progression, we knocked down Pdcd4 expression in colon tumor HT29 cells using pdcd4 short hairpin RNA (shRNA). Pdcd4 knockdown results in a fibroblast-like transition, while the control cells (expressing LacZ shRNA) remain as clumped similar to the parental cells. In addition, expression of pdcd4 shRNA in HT29 cells promotes invasion. In an effort to characterize the molecular mechanism underlying these observations, we discovered that knockdown of Pdcd4 results in reduction of E-cadherin expression, and accumulation of active b-catenin in the nucleus. The active b-catenin binds with T-cell factor 4 (Tcf4) and activates b-catenin/ Tcf-dependent transcription. Furthermore, Pdcd4 knockdown dramatically increases AP-1-dependent transcription. Thus, the mechanism by which reduced Pdcd4 expression promotes invasion appears to involve the activation of b-catenin/Tcf and AP-1-dependent transcription.
The purpose of this study was to investigate the hemodynamic effect of variations in the angulations of the left coronary artery, based on simulated and realistic coronary artery models. Twelve models consisting of four realistic and eight simulated coronary artery geometries were generated with the inclusion of left main stem, left anterior descending and left circumflex branches. The simulated models included various coronary artery angulations, namely, 15°, 30°, 45°, 60°, 75°, 90°, 105° and 120°. The realistic coronary angulations were based on selected patient's data with angles ranging from narrow angles of 58° and 73° to wide angles of 110° and 120°. Computational fluid dynamics analysis was performed to simulate realistic physiological conditions that reflect the in vivo cardiac hemodynamics. The wall shear stress, wall shear stress gradient, velocity flow patterns and wall pressure were measured in simulated and realistic models during the cardiac cycle. Our results showed that a disturbed flow pattern was observed in models with wider angulations, and wall pressure was found to reduce when the flow changed from the left main stem to the bifurcated regions, based on simulated and realistic models. A low wall shear stress gradient was demonstrated at left bifurcations with wide angles. There is a direct correlation between coronary angulations and subsequent hemodynamic changes, based on realistic and simulated models. Further studies based on patients with different severities of coronary artery disease are required to verify our results.
Chest computed tomography (CT) is frequently used in diagnosing coronavirus disease 2019 for detecting abnormal changes in the lungs and monitoring disease progression during the treatment process. Furthermore, CT imaging appearances are correlated with patients presenting with different clinical scenarios, such as early versus advanced stages, asymptomatic versus symptomatic patients, and severe versus nonsevere situations. However, its role as a screening and diagnostic tool in COVID-19 remains to be clarified. This article provides a systematic review and meta-analysis of the current literature on chest CT imaging findings with the aim of highlighting the contribution and judicious use of CT in the diagnosis of COVID-19. A search of PubMed/Medline, Web of Science, ScienceDirect, Google Scholar and Scopus was performed to identify studies reporting chest imaging findings in COVID-19. Chest imaging abnormalities associated with COVID-19 were extracted from the eligible studies and diagnostic value of CT in detecting these abnormal changes was compared between studies consisting of both COVID-19 and non-COVID-19 patients. A random-effects model was used to perform meta-analysis for calculation of pooled mean values and 95% confidence intervals (95% CI) of abnormal imaging findings. Fifty-five studies met the selection criteria and were included in the analysis. Pulmonary lesions more often involved bilateral lungs (78%, 95% CI: 45-100%) and were more likely to have a peripheral (65.35%, 95% CI: 25.93-100%) and peripheral plus central distribution (31.12%, 95% CI: 1.96-74.07%), but less likely to have a central distribution (3.57%, 95% CI: 0.99-9.80%). Ground glass opacities (GGO) (58.05%, 95% CI: 16.67-100%), consolidation (44.18%, 95% CI: 1.61-71.46%) and GGO plus consolidation (52.99%, 95% CI: 19.05-76.79%) were the most common findings reported in 94.5% (52/55) of the studies, followed by air bronchogram (42.50%, 95% CI: 7.78-80.39%), linear opacities (41.29%, 95% CI: 7.44-65.06%), crazypaving pattern (23.57%, 95% CI: 3.13-91.67%) and interlobular septal thickening (22.91%, 95% CI: 0.90-80.49%). CT has low specificity in differentiating pneumonia-related lung changes due to significant overlap between COVID-19 and non-COVID-19 patients with no significant differences in most of the imaging findings between these two groups (P>0.05). Furthermore, normal CT (13.31%, 95% CI: 0.74-38.36%) was reported in 26 (47.3%) studies. Despite widespread use of CT in the diagnosis of COVID-19 patients based on the current literature, CT findings are not pathognomonic as it lacks specificity in differentiating imaging appearances caused by different types of pneumonia. Further, there is a relatively high percentage of normal CT scans. Use of CT as a first-line diagnostic or screening tool in COVID-19 is not recommended.
Coronary CT angiography has been increasingly used in the diagnosis of coronary artery disease owing to rapid technological developments, which are reflected in the improved spatial and temporal resolution of the images. High diagnostic accuracy has been achieved with multislice CT scanners (64 slice and higher), and in selected patients coronary CT angiography is regarded as a reliable alternative to invasive coronary angiography. With high-quality coronary CT imaging increasingly being performed, patients can benefit from an imaging modality that provides a rapid and accurate diagnosis while avoiding an invasive procedure. Despite the tremendous contributions of coronary CT angiography to cardiac imaging, study results reported in the literature should be interpreted with caution as there are some limitations existing within the study design or related to patient risk factors. In addition, some attention must be given to the potential health risks associated with the ionising radiation received during cardiac CT examinations. Radiation dose associated with coronary CT angiography has raised serious concerns in the literature, as the risk of developing malignancy is not negligible. Various dose-saving strategies have been implemented, with some of the strategies resulting in significant dose reduction. The aim of this review is to present an overview of the role of coronary CT angiography on cardiac imaging, with focus on coronary artery disease in terms of the diagnostic and prognostic value of coronary CT angiography. Various approaches for dose reduction commonly recommended in the literature are discussed. Limitations of coronary CT angiography are identified. Finally, future directions and challenges with the use of coronary CT angiography are highlighted.
Computation of FFRQCA is a novel method that allows the assessment of the functional significance of intermediate stenosis. It may emerge as a safe, efficient, and cost-reducing tool for evaluation of coronary stenosis severity during diagnostic angiography.
Voltage-gated calcium channels (VGCCs) comprise five subtypes: The L-type; R-type; N-type; P/Q-type; and T-type, which are encoded by α1 subunit genes. Calcium ion channels also have confirmed roles in cellular functions, including mitogenesis, proliferation, differentiation, apoptosis and metastasis. An association between VGCCs, a reduction in proliferation and an increase in apoptosis in prostate cancer cells has also been reported. Therefore, in the present study, the online clinical database Oncomine was used to identify the alterations in the mRNA expression level of VGCCs in 19 cancer subtypes. Overall, VGCC family genes exhibited under-expression in numerous types of cancer, including brain, breast, kidney and lung cancers. Notably, the majority of VGCC family members (CACNA1C, CACNA1D, CACNA1A, CACNA1B, CACNA1E, CACNA1H and CACNA1I) exhibited low expression in brain tumors, with mRNA expression levels in the top 1–9% of downregulated gene rankings. A total of 5 VGCC family members (CACNA1A, CACNA1B, CACNA1E, CACNA1G and CACNA1I) were under-expressed in breast cancer, with a gene ranking in the top 1–10% of the low-expressed genes compared with normal tissue. In kidney and lung cancers, CACNA1S, CACNA1C, CACNA1D, CACNA1A and CACNA1H exhibited low expression, with gene rankings in the top 1–8% of downregulated genes. In conclusion, the present findings may contribute to the development of new cancer treatment approaches by identifying target genes involved in specific types of cancer.
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