Homeostatic Properties and Phenotypic Maturation of Murine CD4+ Pre-Thymic Emigrants in the Thymus

After a tightly regulated developmental program in the thymus, “mature” single positive (SP) thymocytes leave the thymus and enter the periphery. These newly arrived recent thymic emigrants (RTEs) are phenotypically and functionally immature, and will complete a dynamic maturation in the peripheral lymphoid organs before being licensed to be resident naïve T cells. To study the early events occurring in the RTE maturation process, we identified the phenotype of CD4⁺ pre-RTEs, a population of CD4⁺ SP thymocytes that have acquired the thymus egress capability. Compared to peripheral naïve T cells, CD4⁺ pre-RTEs displayed superior survival capability in lymphoreplete mice and faster proliferation under lymphopenic condition. The differences in Bcl2/Bim expression and/or heightened IL-7 signaling pathway may account for the pre-RTEs’ better responsiveness to homeostatic signals. Qa2, the expression of which indicates the phenotypic maturation of SPs and RTEs, was found to be upregulated in CD4⁺ pre-RTEs in thymic perivascular space. Migratory dendritic cells that surround this region contribute to Qa2 expression in pre-RTEs. The dendritic cell-driven Qa2 induction of CD4⁺ pre-RTEs is independent of MHC class II and Aire molecules.     

Association between MMP1 -1607 1G>2G Polymorphism and Head and Neck Cancer Risk: A Meta-Analysis

Background

MMP1 is an important member of the MMP endopeptidase family that plays a critical role in the development of head and neck cancer (HNC). Several studies have investigated the association between the MMP1 -1607 1G>2G polymorphism and risk of HNC, but their results have been inconsistent. Here, we conducted a meta-analysis to further explore the role of the MMP1 -1607 1G>2G polymorphism in HNC development.

Methods

We identified all eligible studies in the electronic databases of PubMed, ISI Web of Knowledge, MEDLINE, Embase, and Google Scholar (from January 2000 to June 2012). A meta-analysis was performed to evaluate the association between the MMP1 -1607 1G>2G polymorphism and risk of HNC by calculating odds ratios (OR) and 95% confidence interval (CIs).

Results

Twelve studies were included in this meta-analysis. In overall comparison, significant associations were found using the recessive and allelic contrast models (OR, 1.38; 95% CI, 1.07–1.79 and OR, 1.27; 95% CI, 1.05–1.53, respectively), but no association was detected using the dominant model. In the stratified analyses by several variables, significant associations were observed using the recessive, dominant, and allelic contrast models in the Asian population (OR, 1.64; 95% CI, 1.29–2.08; OR, 1.39; 95% CI, 1.06–1.82; and OR, 1.41; 95% CI, 1.21–1.65, respectively), European population (OR, 0.58; 95% CI, 0.40–0.84; OR, 0.64; 95% CI, 0.44–0.92; and OR, 0.68; 95% CI, 0.54–0.85, respectively), and population-based subgroup (OR, 1.24; 95% CI,1.05–1.47; OR,1.48; 95% CI,1.04–2.12; and OR, 1.22; 95% CI, 1.07–1.38, respectively). Furthermore, significant associations were detected in oral cavity cancer and nasopharyngeal cancer under the recessive model.

Conclusion

Our results suggest that the MMP1 -1607 1G>2G polymorphism is associated with risk of HNC and that it plays different roles in Asian and European populations. Further studies with large sample size are needed to validate our findings.     

Diabetes Mellitus and Risk of Bladder Cancer: A Meta-Analysis of Cohort Studies

Objective

Diabetes is associated with increased risk of cancer at several sites, but its association with risk of bladder cancer is still controversial. We examined this association by conducting a systematic review and meta-analysis of cohort studies.

Methods

Studies were identified by searching PubMed, EMBASE, Scopus, Web of Science, Cochrane register, and Chinese National Knowledge Infrastructure (CNKI) databases through April 29, 2012. Summary relative risks (SRRs) with their corresponding 95% confidence intervals (CIs) were calculated using a random-effects model.

Results

A total of fifteen cohort studies were included in this meta-analysis. Analysis of all studies showed that diabetes was associated with a borderline statistically significant increased risk of bladder cancer (RR 1.11, 95% CI 1.00–1.23; p<0.001 for heterogeneity; I² = 84%). When restricting the analysis to studies that had adjusted for cigarette smoking (n = 6) or more than three confounders (n = 7), the RRs were 1.32 (95% CI 1.18–1.49) and 1.20 (95% CI 1.02–1.42), respectively. There was no significant publication bias (p = 0.62 for Egger’s regression asymmetry test).

Conclusions

Our findings support that diabetes was associated with an increased risk of bladder cancer. More future studies are warranted to get a better understanding of the association and to provide convincing evidence for clinical practice in bladder cancer prevention.     

A Bayesian Meta-Analysis on Prevalence of Hepatitis B Virus Infection among Chinese Volunteer Blood Donors

Background

Although transfusion-transmitted infection of hepatitis B virus (HBV) threatens the blood safety of China, the nationwide circumstance of HBV infection among blood donors is still unclear.

Objectives

To comprehensively estimate the prevalence of HBsAg positive and HBV occult infection (OBI) among Chinese volunteer blood donors through bayesian meta-analysis.

Methods

We performed an electronic search in Pub-Med, Web of Knowledge, Medline, Wanfang Data and CNKI, complemented by a hand search of relevant reference lists. Two authors independently extracted data from the eligible studies. Then two bayesian random-effect meta-analyses were performed, followed by bayesian meta-regressions.

Results

5957412 and 571227 donors were identified in HBsAg group and OBI group, respectively. The pooled prevalence of HBsAg group and OBI group among donors is 1.085% (95% credible interval [CI] 0.859%∼1.398%) and 0.094% (95% CI 0.0578%∼0.1655%). For HBsAg group, subgroup analysis shows the more developed area has a lower prevalence than the less developed area; meta-regression indicates there is a significant decreasing trend in HBsAg positive prevalence with sampling year (beta = −0.1202, 95% −0.2081∼−0.0312).

Conclusion

Blood safety against HBV infection in China is suffering serious threats and the government should take effective measures to improve this situation.     

New Structural Insights into Phosphorylation-free Mechanism for Full Cyclin-dependent Kinase (CDK)-Cyclin Activity and Substrate Recognition

Pho85 is a versatile cyclin-dependent kinase (CDK) found in budding yeast that regulates a myriad of eukaryotic cellular functions in concert with 10 cyclins (called Pcls). Unlike cell cycle CDKs that require phosphorylation of a serine/threonine residue by a CDK-activating kinase (CAK) for full activation, Pho85 requires no phosphorylation despite the presence of an equivalent residue. The Pho85-Pcl10 complex is a key regulator of glycogen metabolism by phosphorylating the substrate Gsy2, the predominant, nutritionally regulated form of glycogen synthase. Here we report the crystal structures of Pho85-Pcl10 and its complex with the ATP analog, ATPγS. The structure solidified the mechanism for bypassing CDK phosphorylation to achieve full catalytic activity. An aspartate residue, invariant in all Pcls, acts as a surrogate for the phosphoryl adduct of the phosphorylated, fully activated CDK2, the prototypic cell cycle CDK, complexed with cyclin A. Unlike the canonical recognition motif, SPX(K/R), of phosphorylation sites of substrates of several cell cycle CDKs, the motif in the Gys2 substrate of Pho85-Pcl10 is SPXX. CDK5, an important signal transducer in neural development and the closest known functional homolog of Pho85, does not require phosphorylation either, and we found that in its crystal structure complexed with p25 cyclin a water/hydroxide molecule remarkably plays a similar role to the phosphoryl or aspartate group. Comparison between Pho85-Pcl10, phosphorylated CDK2-cyclin A, and CDK5-p25 complexes reveals the convergent structural characteristics necessary for full kinase activity and the variations in the substrate recognition mechanism.     

Nicorandil in Patients with Acute Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis

Background

Nicorandil, as an adjunctive therapy with primary percutaneous coronary intervention (PCI), had controversial benefits in cardioprotection in patients with acute myocardial infarction (AMI).

Methods and Results

We performed a systematic review of randomized controlled trials (RCTs) comparing treatment with nicorandil prior to reperfusion therapy with control (placebo or no nicorandil) in patients who suffered from AMI and performed primary PCI. PubMed, EMBASE and CENTRAL databases and other sources were searched without language and publication restriction. 14 trials involving 1680 patients were included into this meta-analysis. Nicorandil significantly reduced the incidence of thrombolysis in myocardial infarction (TIMI) flow grade ≤2 (risk ratio [RR], 0.57; 95% confidence interval [CI]: 0.42 to 0.79), the Timi frame count (TFC) (mean difference [MD], -5.19; 95% CI: -7.13 to -3.26), increased left ventricular ejection fraction (LVEF) (%) (MD, 3.08; 95% CI: 0.79 to 5.36), and reduced the incidence of ventricular arrhythmia (RR, 0.53; 95% CI: 0.37 to 0.76) and congestive heart failure (CHF) (RR, 0.41; 95% CI: 0.22 to 0.75). No difference in the pear creatine kinase (CK) value (MD, -290.19; 95% CI: -793.75 to 213.36) or cardiac death (RR, 0.39; 95% CI: 0.09 to 1.67) was observed.

Conclusions

Nicorandil prior to reperfusion is associated with improvement of coronary reflow as well as suppression of ventricular arrhythmia, and further improves left ventricular function in patients who suffered from AMI and underwent primary PCI. But the definite clinical benefits of nicorandil were not found, which may be due to the small sample size of the selected studies.     

兔病毒性出血症病毒基因组结构与功能研究进展

兔病毒性出血症病毒(Rabbit hemorrhagic disease virus,RHDV)是一种对兔具有高度致病性和致死性的病毒,所引发的疫病俗称"兔瘟",其病死率高达100%,是一种对养兔业危害性比较严重的重要传染病.RHDV在分类地位上属于杯状病毒科(Caliciviridae),兔病毒属(Lagovirus).     

Quantify patient-specific coronary material property and its impact on stress/strain calculations using in vivo IVUS data and 3D FSI models: a pilot study

Biomechanics and Modeling in Mechanobiology - Computational models have been used to calculate plaque stress and strain for plaque progression and rupture investigations. An intravascular...     

Homeotic gene expression in the wild-type and a homeotic mutant of the moth Manduca sexta

Antibodies were used to examine the expression patterns of Antennapedia (Antp), Ultrabithorax (Ubx), Ubx and abdominal-A combined(Ubx/abd-A),and Distalless (Dll) in the embryos of the moth Manduca sexta. We found that the spatial and temporal pattern of Antp expression in Manduca was correlated with the anterior migration of two patches of epithelium that include the anterior-most tracheal pits, and with the development of functional spiracles. Ubx expression showed an intricate pattern which suggests complex regulation during development. Throughout Manduca embryogenesis the expression of Ubx/Abd-A and Dll was similar to that reported for other insects. However, there was no apparent reduction in Ubx/Abd-A expression in the Manduca abdominal proleg primordia that expressed Dll. The expression of these four proteins was also examined in embryosof the Manduca homozygous homeotic mutant Octopod (Octo). The Octo mutation results in the transformation of A1 and A2 in the anterior direction, with homeotic legs appearing on A1 and occasionally A2. Our results suggest that in Octo animals there is a reduction in the level of Ubx protein expression throughout its domain. Based on homeotic gene expression in wild-type and mutant Manduca and in other insects, we discuss potential roles of homeotic genes in insect morphological evolution. Received: 21 September 1998 / Accepted: 5 March 1999     

福建万木林天然马尾松林分特征

福建万木林天然马尾松林为以马尾松占绝对优势的松阀混交林,物种多样性与四周的天然阔叶林相近,林分蓄积量高达９８４．２ｍ３ｈｍ－２,是罕见的、典型的天然马尾松丰产林,为珍贵的自然资源。