Proteasome inhibition alleviates prolonged moderate compression-induced muscle pathology

Author name used in this publication: Bee T TengAuthor name used in this publication: Eric W Tam2010-2011 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Brain Tumor Segmentation from Multi-Spectral MR Image Data Using Random Forest Classifier

The development of brain tumor segmentation techniques based on multi-spectral MR image data has relevant impact on the clinical practice via better diagnosis, radiotherapy planning and follow-up studies. This task is also very challenging due to the great variety of tumor appearances, the presence of several noise effects, and the differences in scanner sensitivity. This paper proposes an automatic procedure trained to distinguish gliomas from normal brain tissues in multi-spectral MRI data. The procedure is based on a random forest (RF) classifier, which uses 80 computed features beside the four observed ones, including morphological ones, gradients, and Gabor wavelet features. The intermediary segmentation outcome provided by the RF is fed to a twofold post-processing, which regularizes the shape of detected tumors and enhances the segmentation accuracy. The performance of the procedure was evaluated using the 274 records of the BraTS 2015 train data set. The achieved overall Dice scores between 85-86% represent highly accurate segmentation

The degradation of p53 and its major E3 ligase Mdm2 is differentially dependent on the proteasomal ubiquitin receptor S5a.

p53 and its major E3 ligase Mdm2 are both ubiquitinated and targeted to the proteasome for degradation. Despite the importance of this in regulating the p53 pathway, little is known about the mechanisms of proteasomal recognition of ubiquitinated p53 and Mdm2. In this study, we show that knockdown of the proteasomal ubiquitin receptor S5a/PSMD4/Rpn10 inhibits p53 protein degradation and results in the accumulation of ubiquitinated p53. Overexpression of a dominant-negative deletion of S5a lacking its ubiquitin-interacting motifs (UIM)s, but which can be incorporated into the proteasome, also causes the stabilization of p53. Furthermore, small-interferring RNA (siRNA) rescue experiments confirm that the UIMs of S5a are required for the maintenance of low p53 levels. These observations indicate that S5a participates in the recognition of ubiquitinated p53 by the proteasome. In contrast, targeting S5a has no effect on the rate of degradation of Mdm2, indicating that proteasomal recognition of Mdm2 can be mediated by an S5a-independent pathway. S5a knockdown results in an increase in the transcriptional activity of p53. The selective stabilization of p53 and not Mdm2 provides a mechanism for p53 activation. Depletion of S5a causes a p53-dependent decrease in cell proliferation, demonstrating that p53 can have a dominant role in the response to targeting S5a. This study provides evidence for alternative pathways of proteasomal recognition of p53 and Mdm2. Differences in recognition by the proteasome could provide a means to modulate the relative stability of p53 and Mdm2 in response to cellular signals. In addition, they could be exploited for p53-activating therapies. This work shows that the degradation of proteins by the proteasome can be selectively dependent on S5a in human cells, and that this selectivity can extend to an E3 ubiquitin ligase and its substrate

Groundwater Nitrogen Pollution and Assessment of Its Health Risks: A Case Study of a Typical Village in Rural-Urban Continuum, China

Protecting groundwater from nitrogen contamination is an important public-health concern and a major national environmental issue in China. In this study, we monitored water quality in 29 wells from 2009 to 2010 in a village in Shanghai city, whick belong to typical rural-urban continuum in China. The total N and NO3-N exhibited seasonal changes, and there were large fluctuations in NH4-N in residential areas, but without significant seasonal patterns. NO2-N in the water was not stable, but was present at high levels. Total N and NO3-N were significantly lower in residential areas than in agricultural areas. The groundwater quality in most wells belonged to Class III and IV in the Chinese water standard, which defines water that is unsuitable for human consumption. Our health risk assessments showed that NO3-N posed the greatest carcinogenic risk, with risk values ranging from 19×10−6 to 80×10−6, which accounted for more than 90% of the total risk in the study area

Moxibustion for cancer care: a systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Moxibustion is a traditional Chinese method that uses the heat generated by burning herbal preparations containing <it>Artemisia vulgaris </it>to stimulate acupuncture points. Considering moxibustion is closely related to acupuncture, it seems pertinent to evaluate the effectiveness of moxibustion as a treatment of symptoms of cancer. The objective of this review was to systematically assess the effectiveness of moxibustion for supportive cancer care.</p> <p>Methods</p> <p>We searched the literature using 11 databases from their inceptions to February 2010, without language restrictions. We included randomised clinical trials (RCTs) in which moxibustion was employed as an adjuvant treatment for conventional medicine in patients with any type of cancer. The selection of studies, data extraction, and validations were performed independently by two reviewers.</p> <p>Results</p> <p>Five RCTs compared the effects of moxibustion with conventional therapy. Four RCTs failed to show favourable effects of moxibustion for response rate compared with chemotherapy (n = 229, RR, 1.04, 95% CI 0.94 to 1.15, P = 0.43). Two RCTs assessed the occurrence of side effects of chemotherapy and showed favourable effects of moxibustion. A meta-analysis showed significant less frequency of nausea and vomiting from chemotherapy for moxibustion group (n = 80, RR, 0.38, 95% CIs 0.22 to 0.65, P = 0.0005, heterogeneity: χ²= 0.18, P = 0.67, I²= 0%).</p> <p>Conclusion</p> <p>The evidence is limited to suggest moxibustion is an effective supportive cancer care in nausea and vomiting. However, all studies have a high risk of bias so effectively there is not enough evidence to draw any conclusion. Further research is required to investigate whether there are specific benefits of moxibustion for supportive cancer care.</p

Nicotinic acetylcholine receptor subunit variants are associated with blood pressure; findings in the Old Order Amish and replication in the Framingham Heart Study

<p>Abstract</p> <p>Background</p> <p>Systemic blood pressure, influenced by both genetic and environmental factors, is regulated via sympathetic nerve activity. We assessed the role of genetic variation in three subunits of the neuromuscular nicotinic acetylcholine receptor positioned on chromosome 2q, a region showing replicated evidence of linkage to blood pressure.</p> <p>Methods</p> <p>We sequenced <it>CHRNA1</it>, <it>CHRND </it>and <it>CHRNG </it>in 24 Amish subjects from the Amish Family Diabetes Study (AFDS) and identified 20 variants. We then performed association analysis of non-redundant variants (n = 12) in the complete AFDS cohort of 1,189 individuals, and followed by genotyping blood pressure-associated variants (n = 5) in a replication sample of 1,759 individuals from the Framingham Heart Study (FHS).</p> <p>Results</p> <p>The minor allele of a synonymous coding SNP, rs2099489 in <it>CHRNG</it>, was associated with higher systolic blood pressure in both the Amish (p = 0.0009) and FHS populations (p = 0.009) (minor allele frequency = 0.20 in both populations).</p> <p>Conclusion</p> <p><it>CHRNG </it>is currently thought to be expressed only during fetal development. These findings support the Barker hypothesis, that fetal genotype and intra-uterine environment influence susceptibility to chronic diseases later in life. Additional studies of this variant in other populations, as well as the effect of this variant on acetylcholine receptor expression and function, are needed to further elucidate its potential role in the regulation of blood pressure. This study suggests for the first time in humans, a possible role for genetic variation in the neuromuscular nicotinic acetylcholine receptor, particularly the gamma subunit, in systolic blood pressure regulation.</p

Generation of Reactive Oxygen Species by Polyenylpyrroles Derivatives Causes DNA Damage Leading to G2/M Arrest and Apoptosis in Human Oral Squamous Cell Carcinoma Cells

10.1371/journal.pone.0067603PLoS ONE86-POLN

Association between Alcohol Consumption and Cancers in the Chinese Population—A Systematic Review and Meta-Analysis

Alcohol consumption is increasing worldwide and is associated with numerous cancers. This systematic review examined the role of alcohol in the incidence of cancer in the Chinese population.Medline/PubMed, EMBASE, CNKI and VIP were searched to identify relevant studies. Cohort and case-control studies on the effect of alcohol use on cancers in Chinese were included. Study quality was evaluated using the Newcastle-Ottawa Scale. Data were independently abstracted by two reviewers. Odds ratios (OR) or relative risks (RR) were pooled using RevMan 5.0. Heterogeneity was evaluated using the Q test and I-squared statistic. P<.01 was considered statistically significant.Pooled results from cohort studies indicated that alcohol consumption was not associated with gastric cancer, esophageal cancers (EC) or lung cancer. Meta-analysis of case-control studies showed that alcohol consumption was a significant risk factor for five cancers; the pooled ORs were 1.79 (99% CI, 1.47–2.17) EC, 1.40 (99% CI, 1.19–1.64) gastric cancer, 1.56 (99% CI, 1.16–2.09) hepatocellular carcinoma, 1.21 (99% CI, 1.00–1.46) nasopharyngeal cancer and 1.71 (99% CI, 1.20–2.44) oral cancer. Pooled ORs of the case-control studies showed that alcohol consumption was protective for female breast cancer and gallbladder cancer: OR 0.76 (99% CI, 0.60–0.97) and 0.70 (99% CI, 0.49–1.00) respectively. There was no significant correlation between alcohol consumption and lung cancer, colorectal cancer, pancreatic cancer, cancer of the ampulla of Vater, prostate cancer or extrahepatic cholangiocarcinoma. Combined results of case-control and cohort studies showed that alcohol consumption was associated with 1.78- and 1.40-fold higher risks of EC and gastric cancer but was not significantly associated with lung cancer.Health programs focused on limiting alcohol intake may be important for cancer control in China. Further studies are needed to examine the interaction between alcohol consumption and other risk factors for cancers in Chinese and other populations

Genetic Structure of the Tree Peony (Paeonia rockii) and the Qinling Mountains as a Geographic Barrier Driving the Fragmentation of a Large Population

Tree peonies are great ornamental plants associated with a rich ethnobotanical history in Chinese culture and have recently been used as an evolutionary model. The Qinling Mountains represent a significant geographic barrier in Asia, dividing mainland China into northern (temperate) and southern (semi-tropical) regions; however, their flora has not been well analyzed. In this study, the genetic differentiation and genetic structure of Paeonia rockii and the role of the Qinling Mountains as a barrier that has driven intraspecific fragmentation were evaluated using 14 microsatellite markers.Twenty wild populations were sampled from the distributional range of P. rockii. Significant population differentiation was suggested (F(ST) value of 0.302). Moderate genetic diversity at the population level (H(S) of 0.516) and high population diversity at the species level (H(T) of 0.749) were detected. Significant excess homozygosity (F(IS) of 0.076) and recent population bottlenecks were detected in three populations. Bayesian clusters, population genetic trees and principal coordinate analysis all classified the P. rockii populations into three genetic groups and one admixed Wenxian population. An isolation-by-distance model for P. rockii was suggested by Mantel tests (r = 0.6074, P<0.001) and supported by AMOVA (P<0.001), revealing a significant molecular variance among the groups (11.32%) and their populations (21.22%). These data support the five geographic boundaries surrounding the Qinling Mountains and adjacent areas that were detected with Monmonier's maximum-difference algorithm.Our data suggest that the current genetic structure of P. rockii has resulted from the fragmentation of a formerly continuously distributed large population following the restriction of gene flow between populations of this species by the Qinling Mountains. This study provides a fundamental genetic profile for the conservation and responsible exploitation of the extant germplasm of this species and for improving the genetic basis for breeding its cultivars