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101.
102.
Mu-En Liu Chu-Chung Huang Albert C. Yang Pei-Chi Tu Heng-Liang Yeh Chen-Jee Hong Jin-Fan Chen Ying-Jay Liou Ching-Po Lin Shih-Jen Tsai 《PloS one》2013,8(2)
The anti-apoptotic protein B-cell CLL/lymphoma 2 (Bcl-2) gene is a major regulator of neural plasticity and cellular resilience. Recently, the Bcl-2 rs956572 single nucleotide polymorphism was proposed to be a functional allelic variant that modulates cellular vulnerability to apoptosis. Our cross-sectional study investigated the genetic effect of this Bcl-2 polymorphism on age-related decreases in gray matter (GM) volume across the adult lifespan. Our sample comprised 330 healthy volunteers (191 male, 139 female) with a mean age of 56.2±22.0 years (range: 21–92). Magnetic resonance imaging and genotyping of the Bcl-2 rs956572 were performed for each participant. The differences in regional GM volumes between G homozygotes and A-allele carriers were tested using optimized voxel-based morphometry. The association between the Bcl-2 rs956572 polymorphism and age was a predictor of regional GM volumes in the right cerebellum, bilateral lingual gyrus, right middle temporal gyrus, and right parahippocampal gyrus. We found that the volume of these five regions decreased with increasing age (all P<.001). Moreover, the downward slope was steeper among the Bcl-2 rs956572 A-allele carriers than in the G-homozygous participants. Our data provide convergent evidence for the genetic effect of the Bcl-2 functional allelic variant in brain aging. The rs956572 G-allele, which is associated with significantly higher Bcl-2 protein expression and diminished cellular sensitivity to stress-induced apoptosis, conferred a protective effect against age-related changes in brain GM volume, particularly in the cerebellum. 相似文献
103.
Chih-Ming Hung Rong-Chien Lin Jui-Hua Chu Chia-Fen Yeh Chiou-Ju Yao Shou-Hsien Li 《PloS one》2013,8(2)
The information from ancient DNA (aDNA) provides an unparalleled opportunity to infer phylogenetic relationships and population history of extinct species and to investigate genetic evolution directly. However, the degraded and fragmented nature of aDNA has posed technical challenges for studies based on conventional PCR amplification. In this study, we present an approach based on next generation sequencing to efficiently sequence the complete mitochondrial genome (mitogenome) of two extinct passenger pigeons (Ectopistes migratorius) using de novo assembly of massive short (90 bp), paired-end or single-end reads. Although varying levels of human contamination and low levels of postmortem nucleotide lesion were observed, they did not impact sequencing accuracy. Our results demonstrated that the de novo assembly of shotgun sequence reads could be a potent approach to sequence mitogenomes, and offered an efficient way to infer evolutionary history of extinct species. 相似文献
104.
Kai-Lee Wang Shih-Min Hsia Jiun-Yih Yeh Shao-Chi Cheng Paulus S. Wang Shyi-Wu Wang 《PloS one》2013,8(6)
Endocrine sensitivity, assessed by the expression of estrogen receptor (ER), has long been the predict factor to guide therapeutic decisions. Tamoxifen has been the most successful hormonal treatment in endocrine-sensitive breast cancer. However, in estrogen-insensitive cancer tamoxifen showed less effectiveness than in estrogen-sensitive cancer. It is interesting to develop new drugs against both hormone-sensitive and insensitive tumor. In this present study we examined anticancer effects of evodiamine extracted from the Chinese herb, Evodiae fructus, in estrogen-dependent and –independent human breast cancer cells, MCF-7 and MDA-MB-231 cells, respectively. Evodiamine inhibited the proliferation of MCF-7 and MDA-MB-231 cells in a concentration-dependent manner with concentration of 1×10−6 and 1×10−5 M. Evodiamine also induced apoptosis via up-regulation of caspase 7 activation, PARP cleavage (Bik and Bax expression). The expression of ER α and β in protein and mRNA levels was down-regulated by evodiamine according to data from immunoblotting and RT-PCR analysis. Overall, our results indicate that evodiamine mediates degradation of ER and induces caspase-dependent pathway leading to inhibit proliferation of breast cancer cell lines. It suggests that evodiamine may in part mediate through ER-inhibitory pathway to inhibit breast cancer cell proliferation. 相似文献
105.
Jih-Kai Yeh Yuan-Chuan Hsiao Cian-Ruei Jian Chao-Hung Wang Ming-Shien Wen Chi-Tai Kuo Feng-Chun Tsai Victor Chien-Chia Wu Tien-Hsing Chen 《PloS one》2016,11(1)
Aims
The prognostic values of left ventricular ejection fraction (LVEF) during heart failure (HF) with acute decompensation or after optimal treatment have not been extensively studied. We hypothesized that posttreatment LVEF has superior predictive value for long-term prognosis than LVEF at admission does.Methods and Results
In Protocol 1, 428 acute decompensated HF (ADHF) patients with LVEF ≤35% in a tertiary medical center were enrolled and followed for a mean period of 34.7 ± 10.8 months. The primary and secondary end points were all-cause mortality and HF readmission, respectively. In total, 86 deaths and 240 HF readmissions were recorded. The predictive values of baseline LVEF at admission and LVEF 6 months posttreatment were analyzed and compared. The posttreatment LVEFs were predictive for future events (P = 0.01 for all-cause mortality, P < 0.001 for HF readmission), but the baseline LVEFs were not. In Protocol 2, the outcomes of patients with improved LVEF (change of LVEF: ≥+10%), unchanged LVEF (change of LVEF: –10% to +10%), and reduced LVEF (change of LVEF: ≤–10%) were analyzed and compared. Improved LVEF occurred in 171 patients and was associated with a superior long-term prognosis among all groups (P = 0.02 for all-cause mortality, P < 0.001 for HF readmission). In Protocol 3, independent predictors of improved LVEF were analyzed, and baseline LV end-diastolic dimension (LVEDD) was identified as a powerful predictor in ADHF patients (P < 0.001).Conclusions
In patients with ADHF, posttreatment LVEF but not baseline LVEF had prognostic power. Improved LVEF was associated with superior long-term prognosis, and baseline LVEDD identified patients who were more likely to have improved LVEF. Therefore, baseline LVEF should not be considered a relevant prognosis factor in clinical practice for patients with ADHF. 相似文献106.
Visual crowding—the inability to see an object when it is surrounded by flankers in the periphery—does not block semantic activation: unrecognizable words due to visual crowding still generated robust semantic priming in subsequent lexical decision tasks. Based on the previous finding, the current study further explored whether unrecognizable crowded words can be temporally integrated into a phrase. By showing one word at a time, we presented Chinese four-word idioms with either a congruent or incongruent ending word in order to examine whether the three preceding crowded words can be temporally integrated to form a semantic context so as to affect the processing of the ending word. Results from both behavioral (Experiment 1) and Event-Related Potential (Experiment 2 and 3) measures showed congruency effect in only the non-crowded condition, which does not support the existence of unconscious multi-word integration. Aside from four-word idioms, we also found that two-word (modifier + adjective combination) integration—the simplest kind of temporal semantic integration—did not occur in visual crowding (Experiment 4). Our findings suggest that integration of temporally separated words might require conscious awareness, at least under the timing conditions tested in the current study. 相似文献
107.
Kim J. Brolin Ribacke Alex J. van Duinen Helena Nordenstedt Jonas H?ijer Ragnhild Molnes Torunn Wigum Froseth AP Koroma Elisabeth Darj H?kon Angel Bolkan AnnaMia Ekstr?m 《PloS one》2016,11(2)
Background
As Sierra Leone celebrates the end of the Ebola Virus Disease (EVD) outbreak, we can begin to fully grasp its impact on already weak health systems. The EVD outbreak in West Africa forced many hospitals to close down or reduce their activity, either to prevent nosocomial transmission or because of staff shortages. The aim of this study is to assess the potential impact of EVD on nationwide access to obstetric care in Sierra Leone.Methods and Findings
Community health officers collected weekly data between January 2014—May 2015 on in-hospital deliveries and caesarean sections (C-sections) from all open facilities (public, private for-profit and private non-profit sectors) offering emergency obstetrics in Sierra Leone. This was compared to official data of EVD cases per district. Logistic and Poisson regression analyses were used to compute risk and rate estimates. Nationwide, the number of in-hospital deliveries and C-sections decreased by over 20% during the EVD outbreak. The decline occurred early on in the EVD outbreak and was mainly attributable to the closing of private not-for-profit hospitals rather than government facilities. Due to difficulties in collecting data in the midst of an epidemic, limitations of this study include some missing data points.Conclusions
Both the number of in-hospital deliveries and C-sections substantially declined shortly after the onset of the EVD outbreak. Since access to emergency obstetric care, like C-sections, is associated with decreased maternal mortality, many women are likely to have died due to the reduced access to appropriate care during childbirth. Future research on indirect health effects of health system breakdown should ideally be nationwide and continue also into the recovery phase. It is also important to understand the mechanisms behind the deterioration so that important health services can be reestablished. 相似文献108.
Strategies for successful primary treatment of HER2-positive breast cancer include use of the HER2 inhibitors trastuzumab or lapatinib in combination with standard chemotherapy. While successful, many patients develop resistance to these HER2 inhibitors indicating an unmet need. Consequently, current research efforts are geared toward understanding mechanisms of resistance and the signaling modalities that regulate these mechanisms. We have undertaken a study to examine whether signaling molecules downstream of epidermal growth factor receptor, which often act as compensatory signaling outlets to circumvent HER2 inhibition, can be co-targeted to overcome resistance. We identified JNK signaling as a potential area of intervention and now show that inhibiting JNK using the pan-JNK inhibitor, SP600125, is effective in the HER2-positive, resistant JIMT-1 xenograft mammary tumor model. We also investigate potential combination strategies to bolster the effects of JNK inhibition and find that co-targeting of JNK and the protein kinase HUNK can prohibit tumor growth of resistant HER2-positive mammary tumors in vivo. 相似文献
109.
110.
Wei-En Yang Chuan-Chen Ho Shun-Fa Yang Shu-Hui Lin Kun-Tu Yeh Chiao-Wen Lin Mu-Kuan Chen 《PloS one》2016,11(3)