A somitic Wnt16/Notch pathway specifies haematopoietic stem cells

Haematopoietic stem cells (HSCs) are a self-renewing population of cells that continuously replenish all blood and immune cells during the lifetime of an individual. HSCs are used clinically to treat a wide array of diseases, including acute leukaemias and congenital blood disorders, but obtaining suitable numbers of cells and finding immune-compatible donors remain serious problems. These difficulties have led to an interest in the conversion of embryonic stem cells or induced pluripotent stem cells into HSCs, which is not possible using current methodologies. To accomplish this goal, it is critical to understand the native mechanisms involved in the specification of HSCs during embryonic development. Here we demonstrate in zebrafish that Wnt16 controls a novel genetic regulatory network required for HSC specification. Non-canonical signalling by Wnt16 is required for somitic expression of the Notch ligands deltaC (dlc) and deltaD (dld), and these ligands are, in turn, required for the establishment of definitive haematopoiesis. Notch signalling downstream of Dlc and Dld is earlier than, and distinct from, known cell-autonomous requirements for Notch, strongly suggesting that novel Notch-dependent relay signal(s) induce the first HSCs in parallel to other established pathways. Our results demonstrate that somite-specific gene expression is required for the production of haemogenic endothelium.     

基于MODIS数据的2001-2018年黑龙江省林火时空分布

[目的]黑龙江省是中国重要的林业省份之一,也是受林火危害最严重的地区之一.通过遥感数据获取森林火点信息,充分了解近年来黑龙江省林火发生的时空分布格局,探索林火发生规律.[方法]根据黑龙江省2001—2018年MODIS(分辨率成像光谱仪)遥感图像的MCD64A1火烧迹地产品数据集,提取林火火点信息,结合历史火灾记录资料...     

事务处理技术及在煤矿安全信息管理系统中的应用

事务处理是重要的数据库完整性保证技术,本文结合煤矿安全信息管理系统的研制,介绍了事务概念、MS SQL Server事务处理语句、ASP事务处理及编程实现.将事务处理技术用于网络数据库系统的开发,将有效地保证系统数据的完整性.     

MA法制备复合材料常用设备的比较分析(综述)

简述了机械合金化常用设备的工作原理及特点,分析了机械合金化设备对制备颗粒增强金属基复合材料的影响因素,为制备复合材料的设备选用及工艺的设计提供依据,并对球磨机的研究与开发提出了技术展望.     

状态方程计算高分子共混物的比体积

基于一个简单的非均核链流体分子热力学模型,采用不同形式的微扰项,可构筑不同形式的高分子共混物系统的状态方程。方程已被应用于关联聚苯乙烯/聚2,6-二甲基苯醚(PS/PPO)、聚苯乙烯/聚乙烯甲醚(PS/PVME)、聚苯乙烯/聚丁二烯(PS/PBD)、聚醚砜/聚氧乙烯(PESP/PEO)等高分子共混物的比体积。结果显示,用一个与温度无关的二元相互作用可调参数可满意关联所选体系的比体积,并可预测所选体系的比体积。     

The coming-to-be of Hansen’s method

This article by Curtis Wilson is an account of the origin of Hansen’s powerful systematic method for finding contributions of higher order perturbations in celestial mechanics. Hansen’s method was developed in the course of improving on Laplace’s treatment of the mutual perturbations of Jupiter and Saturn. This method, an entirely new way of doing celestial mechanics when it first appeared, later made possible the successful treatment of the complicated motions of our moon (see Wilson 2010). In this paper Wilson gives a brief historical introduction followed by an account of relevant technical details of the Laplacian background, an account illustrating technical details in Hansen’s initial development in his Disquisitions of 1829, and a treatment illustrating details contributing to the achievement of Hansen’s more refined development in his Untersuchung of 1831. These details include conditional equations Hansen provides for checking the accuracy of calculations. Wilson also includes a detailed assessment showing the extraordinary improvement in empirical accuracy of Hansen’s treatment over the best earlier treatment of the Jupiter-Saturn  interactions.     

Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas

To identify somatic mutations in pediatric diffuse intrinsic pontine glioma (DIPG), we performed whole-genome sequencing of DNA from seven DIPGs and matched germline tissue and targeted sequencing of an additional 43 DIPGs and 36 non-brainstem pediatric glioblastomas (non-BS-PGs). We found that 78% of DIPGs and 22% of non-BS-PGs contained a mutation in H3F3A, encoding histone H3.3, or in the related HIST1H3B, encoding histone H3.1, that caused a p.Lys27Met amino acid substitution in each protein. An additional 14% of non-BS-PGs had somatic mutations in H3F3A causing a p.Gly34Arg alteration.     

Dominant missense mutations in ABCC9 cause Cantú syndrome

Cantú syndrome is characterized by congenital hypertrichosis, distinctive facial features, osteochondrodysplasia and cardiac defects. By using family-based exome sequencing, we identified a de novo mutation in ABCC9. Subsequently, we discovered novel dominant missense mutations in ABCC9 in 14 of the 16 individuals with Cantú syndrome examined. The ABCC9 protein is part of an ATP-dependent potassium (K(ATP)) channel that couples the metabolic state of a cell with its electrical activity. All mutations altered amino acids in or close to the transmembrane domains of ABCC9. Using electrophysiological measurements, we show that mutations in ABCC9 reduce the ATP-mediated potassium channel inhibition, resulting in channel opening. Moreover, similarities between the phenotype of individuals with Cantú syndrome and side effects from the K(ATP) channel agonist minoxidil indicate that the mutations in ABCC9 result in channel opening. Given the availability of ABCC9 antagonists, our findings may have direct implications for the treatment of individuals with Cantú syndrome.     

SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout

Uric acid is the end product of purine metabolism in humans and great apes, which have lost hepatic uricase activity, leading to uniquely high serum uric acid concentrations (200-500 microM) compared with other mammals (3-120 microM). About 70% of daily urate disposal occurs via the kidneys, and in 5-25% of the human population, impaired renal excretion leads to hyperuricemia. About 10% of people with hyperuricemia develop gout, an inflammatory arthritis that results from deposition of monosodium urate crystals in the joint. We have identified genetic variants within a transporter gene, SLC2A9, that explain 1.7-5.3% of the variance in serum uric acid concentrations, following a genome-wide association scan in a Croatian population sample. SLC2A9 variants were also associated with low fractional excretion of uric acid and/or gout in UK, Croatian and German population samples. SLC2A9 is a known fructose transporter, and we now show that it has strong uric acid transport activity in Xenopus laevis oocytes.