Timeless preserves telomere length by promoting efficient DNA replication through human telomeres

A variety of telomere protection programs are utilized to preserve telomere structure. However, the complex nature of telomere maintenance remains elusive. The Timeless protein associates with the replication fork and is thought to support efficient progression of the replication fork through natural impediments, including replication fork block sites. However, the mechanism by which Timeless regulates such genomic regions is not understood. Here, we report the role of Timeless in telomere length maintenance. We demonstrate that Timeless depletion leads to telomere shortening in human cells. This length maintenance is independent of telomerase, and Timeless depletion causes increased levels of DNA damage, leading to telomere aberrations. We also show that Timeless is associated with Shelterin components TRF1 and TRF2. Timeless depletion slows telomere replication in vitro, and Timeless-depleted cells fail to maintain TRF1-mediated accumulation of replisome components at telomeric regions. Furthermore, telomere replication undergoes a dramatic delay in Timeless-depleted cells. These results suggest that Timeless functions together with TRF1 to prevent fork collapse at telomere repeat DNA and ensure stable maintenance of telomere length and integrity.     

头颅CT、头颅MRI 在结核性脑膜炎诊断中应用

结核性脑膜炎是中枢神经系统感染性疾病中常见病,且致死率、致残率都很高.结核性脑膜炎的临床表现具有非特异性性,因此临床上容易引起误诊、漏诊.目前结核性脑膜炎的诊断主要是依据临床资料,脑脊液检查、生化及病原学和影像学检查等综合诊断方法.早期诊断及治疗和结核性脑膜炎的预后有着密切的关系,提高早期诊断是改善结核性脑膜炎顸后关键.头颅CT、头颅MR在结核性脑膜炎诊断中有着重要的作用,对结核性脑膜炎的诊断可提供重要的价值.本文就头颅CT及头颅MR在结核性脑膜炎中的作用做一综述.     

Role of the RuvAB protein in avoiding spontaneous formation of deletion mutations in the Escherichia coli K-12 endogenous tonB gene

The endogenous tonB gene of Escherichia coli was used as a target for spontaneous deletion mutations which were isolated from ruvAB-, recG-, and ruvC- cells. The rates of tonB mutation were essentially the same in ruv+, ruvAB-, recG-, and ruvC- cells. We analyzed tonB mutants by sequencing. In the ruv+, recG-, and ruvC- strains, the spectra were different from those obtained from the ruvAB- cells, where deletions dominated followed by IS insertions, base substitutions, and frameshifts, in that order. We then analyzed the tonB-trp large deletion, due to simultaneous mutations of the trp operon, and found that the frequency in ruvAB- was higher than those in ruv+, recG-, and ruvC- cells. To characterize deletion formation further, we analyzed all the tonB mutants from one colicin plate. Seven deletions were identified at five sites from the 45 tonB mutants of ruv+ cells and 24 deletions at 11 sites from the 43 tonB mutants of ruvAB- cells. Thus, the ruvAB- strain is a deletion mutator. We discuss the role of RuvAB in avoiding deletions.     

超高龄患者填充骨水泥型人工股骨头置换术后的凝血功能 变化及意义

目的:观察骨水泥填充对人工股骨头置换术术后超高龄老年患者凝血系统的影响。方法:选择80岁以上骨水泥型人工股骨头置换术患者29例,于术前、术后当天及术后第3天空腹抽取静脉血,测定凝血功能相关指标,包括凝血酶原时间(PT)、部分凝血活酶时间(APTT)、凝血酶时间(TT)、凝血酶原活动度(PTA)、国际标准化比值(INR)、纤维蛋白原(FIB)、D二聚体(DD)、抗凝血酶Ⅲ(ATⅢ)、血小板(PLT)水平,并对结果进行比较分析。结果:患者术后当天FIB、DD、显著升高(P<0.05),ATⅢ降低(P<0.05),提示高凝状态,且纤溶亢进,此时段TT、PT延长(P<0.05),血小板明显降低,提示存在出血风险;术后第3天TT、PT显著延长(P<0.05),ATⅢ恢复到术前水平,FIB,DD水平较手术后当天下降,提示术后第3天有明显的出血倾向,凝血与纤溶系统逐渐恢复平衡。结论:骨水泥型人工股骨头置换术对80岁以上超高龄患者凝血功能有显著影响,术后当天高凝状态、纤溶亢进,存在潜在出血风险,术后第3天有明显出血倾向,提示高龄患者术后应适当补充凝血因子且须谨慎使用抗凝药物。     

Type II diabetes and metabolic syndrome in relation to head and neck squamous cell carcinoma risk: A SEER-Medicare database study

BackgroundDiabetes and metabolic syndrome have been found to increase the risk of various cancers. Previous studies indicated that diabetes may increase the risk of head and neck squamous cell carcinoma (HNSCC). Metabolic syndrome has not been investigated as a risk factor. We tested whether type II diabetes or metabolic syndrome were associated with HNSCC using a very large database of medical administrative records, providing the ability to investigate relatively weak effects and stratify by subgroups.MethodsWe identified persons diagnosed with HNSCC between 1994 and 2007 in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. We selected controls from a 5% sample of Medicare beneficiaries and frequency matched to cases on sex and duration of enrollment. We estimated odds ratios (OR) and 95% confidence intervals (CI) for the association between type II diabetes/metabolic syndrome and HNSCC, adjusted for potential confounders, among 14,022 cases and 42,066 controls.ResultsWe observed a very weak inverse association between type II diabetes and HNSCC (OR = 0.92; 95% CI, 0.88–0.96) and a moderate inverse association for metabolic syndrome (OR = 0.81; 95% CI, 0.78–0.85). Associations were modified by tobacco use, with null results for type II diabetes among never users (OR = 1.00; 95% CI, 0.95–1.06) and inverse associations among ever users (OR = 0.80; 95% CI, 0.75–0.86).ConclusionsWe observed moderate inverse associations between metabolic syndrome and HNSCC and weak inverse associations between type II diabetes and HNSCC, which was contrary to the evidence to date. Inadequate control for confounding factors, such as overweight/obesity, may have influenced results.     

真核细胞染色体DNA复制起始及复制叉稳定性维持的机制

在真核生物中,DNA复制在染色体上特定的多位点起始．当细胞处在晚M及G1期,多个复制起始蛋白依次结合到DNA复制源,组装形成复制前复合体．pre．RC在Gl-S的转折期得到激活,随后,多个直接参与DNA复制又形成的蛋白结合到DNA复制源,启动DNA的复制,形成两个双向的DNA复制又．在染色体上,移动的DNA复制又经常会碰到复制障碍（二级DNA结构、一些蛋白的结合位点、损伤的碱基等）而暂停下来,此时,需要细胞周期检验点的调控来稳定复制叉,否则,会导致复制又垮塌及基因组不稳定．本文就真核细胞染色体DNA复制起始的机制,以及复制又稳定性的维持机制进行简要综述．     

双极人工股骨头置换治疗老年不稳定股骨粗隆间骨折的临床研究

目的:通过观察我院老年不稳定股骨粗隆间骨折患者临床治疗资料,探讨分析采用双极人工股骨头置换治疗该疾病的临床效果.方法:将我院收治的100例该疾病患者按照手术方法平分为A组与B组两组,分别进行双极人工股骨头置换术与动力髋螺钉手术治疗,对比分析使用两种方法手术时间、出血量情况、术后并发症以及治疗效果等.结果:两组患者经各自手术治疗后,临床症状均有改善,A组患者在手术时间、出血量情况与B组患者相比,差异不显著(P＞0.05),而在术后并发症、髋关节功能对比方面,A组优于B组,差异具有显著性(P＜0.05).结论:采用双极人工股骨头置换手术治疗老年不稳定股骨粗隆间骨折患者,手术并发症少,安全可靠性高.有效改善患者髋关节功能,临床效果显著,值得临床上推广与进一步研究.     

Blood proteome of acute intracranial hemorrhage in infant victims of abusive head trauma

Abusive head trauma (AHT) is a leading cause of mortality and morbidity in infants. While the reported incidence is close to 40 cases per 100′000 births/year, misdiagnoses are commonly observed in cases with atypical, subacute, or chronic presentation. Currently, standard clinical evaluation of inflicted intracranial hemorrhagic injury (ICH) in infants urgently requires a screening test able to identify infants who need additional investigations. Blood biomarkers characteristic of AHT may assist in detecting these infants, improving prognosis through early medical care. To date, the application of innovative omics technologies in retrospective studies of AHT in infants is rare, due also to the blood serum and cerebrospinal fluid of AHT cases being scarce and not systematically accessible. Here, we explored the circulating blood proteomes of infants with severe AHT and their atraumatic controls. We discovered 165 circulating serum proteins that display differential changes in AHT cases compared with atraumatic controls. The peripheral blood proteomes of pediatric AHT commonly reflect: (i) potentially secreted proteome from injured brain, and (ii) proteome dysregulated in the system's circulation by successive biological events following acute ICH. This study opens up a novel opportunity for research efforts in clinical screening of AHT cases.