Updated mortality analysis of radiation workers at Rocketdyne (Atomics International), 1948-2008

Updated analyses of mortality data are presented on 46,970 workers employed 1948-1999 at Rocketdyne (Atomics International). Overall, 5,801 workers were involved in radiation activities, including 2,232 who were monitored for intakes of radionuclides, and 41,169 workers were engaged in rocket testing or other non-radiation activities. The worker population is unique in that lifetime occupational doses from all places of employment were sought, updated and incorporated into the analyses. Further, radiation doses from intakes of 14 different radionuclides were calculated for 16 organs or tissues using biokinetic models of the International Commission on Radiation Protection (ICRP). Because only negligible exposures were received by the 247 workers monitored for radiation activities after 1999, the mean dose from external radiation remained essentially the same at 13.5 mSv (maximum 1 Sv) as reported previously, as did the mean lung dose from external and internal radiation combined at 19.0 mSv (maximum 3.6 Sv). An additional 9 years of follow-up, from December 31,1999 through 2008, increased the person-years of observation for the radiation workers by 21.7% to 196,674 (mean 33.9 years) and the number of cancer deaths by 50% to 684. Analyses included external comparisons with the general population and the computation of standardized mortality ratios (SMRs) and internal comparisons using proportional hazards models and the computation of relative risks (RRs). A low SMR for all causes of death (SMR 0.82; 95% CI 0.78-0.85) continued to indicate that the Rocketdyne radiation workers were healthier than the general population and were less likely to die. The SMRs for all cancers taken together (SMR 0.88; 95% CI 0.81-0.95), lung cancer (SMR 0.87; 95% CI 0.76-1.00) and leukemia other than chronic lymphocytic leukemia (CLL) (SMR 1.04; 95% 0.67-1.53) were not significantly elevated. Cox regression analyses revealed no significant dose-response trends for any cancer. For all cancers excluding leukemia, the RR at 100 mSv was estimated as 0.98 (95% CI 0.82-1.17), and for all leukemia other than CLL it was 1.06 (95% CI 0.50-2.23). Uranium was the primary radionuclide contributing to internal exposures, but no significant increases in lung and kidney disease were seen. The extended follow-up reinforces the findings in the previous study in failing to observe a detectable increase in cancer deaths associated with radiation, but strong conclusions still cannot be drawn because of small numbers and relatively low career doses. Larger combined studies of early workers in the United States using similar methodologies are warranted to refine and clarify radiation risks after protracted exposures.     

Thick and thin fingers point out Turing waves

Mouse genetics and computer simulations demonstrate that digit number and width are controlled by a Turing-type mechanism in which distal Hox genes modulate periodicity.     

甲亢甲低患者肝纤维化指标检测的临床意义分析

目的:探讨甲状腺功能亢进(甲亢)、甲状腺功能减低(甲低)与肝纤维化指标的关系及其可能的机制。方法:采用放射免疫分析法(R1A)检测57例甲亢患者、43例甲低患者、39例甲亢治疗后甲状腺激素正常者和50例健康成人的血清Ⅳ型胶原(1V-C)、Ⅲ型前胶原(PCⅢ)、透明质酸(HA)、层粘连蛋白(LN)、T3、T4、FT3、FT4、TSH、TGA、TMA含量。结果:甲亢患者组血清中1V-C、PCⅢ含量比正常对照组及甲低患者组显著性增高(P<0.05);治疗后甲状腺激素下降,1V-C、PCⅢ含量也随之下降(与治疗前比较P<0.01);HA、LN在四组中无显著性差异(P>0.05),在甲亢治疗前后无显著性差异(P>0.05)。各项肝纤维化指标与TGA、TMA的阳性率无关。结论:甲亢患者可有不同程度的肝功能损害,血清中甲状腺激素水平增高时,1V-C、PCⅢ水平也增高,在用1V-C、PCⅢ判断肝纤维化时应注意有无甲状腺疾病特别是甲亢。未发现HA、LN含量与甲状腺激素水平的关系。     

塔里木盆地西北缘核桃坚果生化成分多样性分析

该研究收集新疆塔里木盆地西北缘44份核桃资源,其中树龄超过50 a的实生资源41份、主栽良种3个,并对其主要生化成分蛋白质、糖、脂肪、氨基酸、油酸、亚油酸、亚麻酸、棕榈酸、硬脂酸进行了多样性分析。结果表明:44份资源的生化成分变异幅度大,存在着丰富的多样性。各指标变异幅度由4.93%~30.93%,香农-维纳指数(H')变幅为1.38~2.02。17种氨基酸变异幅度由10.07%~35.71%,香农-维纳指数(H')变幅为1.85~2.20。主要生化成分主成分分析显示蛋白质、糖、脂肪三个主要成分的累计贡献率达81.67%。聚类分析表明,群组间生化成分存在显著差异,群组的聚类与地理分布有明显相关性,流域相同的资源的生化成分构成比例具有相似性。与主栽品种相比,实生资源在糖、蛋白质、脂肪等方面具有更高的变异幅度,因而具有一定的开发潜力。     

The axial channel of the proteasome core particle is gated by the Rpt2 ATPase and controls both substrate entry and product release.

Substrates enter the proteasome core particle (CP) through a channel that opens upon association with the regulatory particle (RP). Using yeast mutants, we show that channel opening is mediated by the ATPase domain of Rpt2, one of six ATPases in the RP. To test whether degradation products exit through this channel, we analyzed their size distribution. Their median length from an open-channel CP mutant was 40% greater than that from the wild-type. Thus, channel opening may enhance the yield of peptides long enough to function in antigen presentation. These experiments demonstrate that gating of the RP channel controls both substrate entry and product release, and is specifically regulated by an ATPase in the base of the RP.     

巴松措原生动物群落结构季节及垂直分布

为揭示我国西藏高原湖泊原生动物群落结构特征及垂直分布格局,于2017年11月及2018年5月和9月,在巴松措中心分7层设置采样点,利用25号浮游生物网采集原生动物。采用活体观察和固定染色相结合的方法,共鉴定到原生动物195种(其中春季86种,夏季93种,秋季80种),隶属于2门11纲24目43科59属。其中以肉鞭门种类较丰富,砂壳类纤毛虫占优势。垂直分布的物种组成和群落结构复杂表现为：表层>中层>底层,物种多样性、丰富度和优势度指数表现为：表层>中层>底层,均匀度指数大多数为1;季节分布的物种组成和群落结构群复杂程度表现为：夏季>春季>秋季,物种多样性、丰富度指数表现为：夏季>秋季>春季,优势度指数表现为：夏季>秋季>春季,均匀度指数表现为：秋季>春季>夏季;优势物种和群落结构都会随水深的增加而减少。总体呈现出物种多样性较低、均匀度较高,具有明显的时空异质性。     

单细胞测序方法研究进展

近年来,高通量测序技术(Next-generation sequencing,NGS)快速发展,已广泛应用于生命科学各个领域,但传统的混合细胞测序(Bulk cell sequencing)检测的是细胞群体的总平均反应,无法反应每个细胞的真实情况,这会影响研究者对细胞功能认知的准确性。单细胞测序技术(Single cell sequencing,sc-Seq)的出现,从一定程度上解决了传统测序固有的缺陷。单细胞测序是针对单个细胞的RNA或DNA进行测序,能够准确测出单个细胞的基因结构和表达状态,从而分析相同表型细胞的异质性。本文首先介绍单细胞测序的原理、测序类型和测序平台,有助于理解单细胞测序和在进行科研项目时设计合适的项目方案。进一步介绍单细胞转录组测序的分析流程和各种常用的分析工具或软件,并重点阐述单细胞转录组测序分析中的细胞聚类和拟时序分析的原理和研究进展,为进行单细胞转录组测序数据分析提供参考。最后,本文简述了单细胞测序研究热度、单细胞测序的应用、挑战和展望等,有助于更全面地认识单细胞测序。     

Inflammasome Modulation by Chemotherapeutics in Malignant Mesothelioma

Malignant mesothelioma (MM) is a fatal disease in dire need of therapy. The role of inflammasomes in cancer is not very well studied, however, literature supports both pro-and anti-tumorigenic effects of inflammasomes on cancer depending upon the type of cancer. Asbestos is a causative agent for MM and we have shown before that it causes inflammasome priming and activation in mesothelial cells. MM tumor cells/tissues showed decreased levels of inflammasome components like NLRP3 and caspase-1 as compared to human mesothelial cells or normal tissue counterpart of tumor. Based on our preliminary findings we hypothesized that treatment of MMs with chemotherapeutic drugs may elevate the levels of NLRP3 and caspase-1 resulting in increased cell death by pyroptosis while increasing the levels of IL-1β and other pro-inflammatory molecules. Therefore, a combined strategy of chemotherapeutic drug and IL-1R antagonist may play a beneficial role in MM therapy. To test our hypothesis we used two human MM tumor cell lines (Hmeso, H2373) and two chemotherapeutic drugs (doxorubicin, cisplatin). Through a series of experiments we showed that both chemotherapeutic drugs caused increases in NLRP3 levels, caspase-1 activation, pyroptosis and pro-inflammatory molecules released from MM cells. In vivo studies using SCID mice and Hmeso cells showed that tumors were smaller in combined treatment group of cisplatin and IL-1R antagonist (Anakinra) as compared to cisplatin alone or untreated control groups. Taken together our study suggests that chemotherapeutic drugs in combination with IL-1R antagonist may have a beneficial role in MM treatment.     

Reducing Frequent Visits to the Emergency Department: A Systematic Review of Interventions

Objective

The objective of this study was to establish the effectiveness of interventions to reduce frequent emergency department (ED) use among a general adult high ED-use population.

Methods

Systematic review of the literature from 1950-January 2015. Studies were included if they: had a control group (controlled trials or comparative cohort studies), were set in an ED or acute care facility, and examined the impact of an intervention to reduce frequent ED use in a general adult population. Studies reporting non-original data or focused on a specific patient population were excluded. Study design, patient population, intervention, the frequency of ED visits, and costs of frequent ED use and/or interventions were extracted and narratively synthesized.

Results

Among 17 included articles, three intervention categories were identified: case management (n = 12), individualized care plans (n = 3), and information sharing (n = 2). Ten studies examining case management reported reductions in mean (-0.66 to -37) or median (-0.1 to -20) number of ED visits after 12-months; one study reported an increase in mean ED visits (+2.79); and one reported no change. Of these, 6 studies also reported reduced hospital costs. Only 1 study evaluating individualized care plans examined ED utilization and found no change in median ED visits post-intervention. Costs following individualized care plans were also only evaluated in 1 study, which reported savings in hospital costs of $742/patient. Evidence was mixed regarding information sharing: 1 study reported no change in mean ED visits and did not examine costs; whereas the other reported a decrease in mean ED visits (-16.9) and ED cost savings of $15,513/patient.

Conclusions

The impact of all three frequent-user interventions was modest. Case management had the most rigorous evidence base, yielded moderate cost savings, but with variable reductions in ED use. Future studies evaluating non-traditional interventions, tailoring to patient subgroups or socio-cultural contexts, are warranted.