A genome-wide association study identifies new susceptibility loci for non-cardia gastric cancer at 3q13.31 and 5p13.1

Gastric cancer, including the cardia and non-cardia types, is the second leading cause of cancer-related deaths worldwide. To identify genetic risk variants for non-cardia gastric cancer, we performed a genome-wide association study in 3,279 individuals (1,006 with non-cardia gastric cancer and 2,273 controls) of Chinese descent. We replicated significant associations in an additional 6,897 subjects (3,288 with non-cardia gastric cancer and 3,609 controls). We identified two new susceptibility loci for non-cardia gastric cancer at 5p13.1 (rs13361707 in the region including PTGER4 and PRKAA1; odds ratio (OR) = 1.41; P = 7.6 × 10(-29)) and 3q13.31 (rs9841504 in ZBTB20; OR = 0.76; P = 1.7 × 10(-9)). Imputation analyses also confirmed previously reported associations of rs2294008 and rs2976392 on 8q24, rs4072037 on 1q22 and rs13042395 on 20p13 with non-cardia gastric cancer susceptibility in the Han Chinese population.     

Genome-wide association study identifies two new susceptibility loci for atopic dermatitis in the Chinese Han population

Atopic dermatitis is a chronic, relapsing form of inflammatory skin disorder that is affected by genetic and environmental factors. We performed a genome-wide association study of atopic dermatitis in a Chinese Han population using 1,012 affected individuals (cases) and 1,362 controls followed by a replication study in an additional 3,624 cases and 12,197 controls of Chinese Han ethnicity, as well as 1,806 cases and 3,256 controls from Germany. We identified previously undescribed susceptibility loci at 5q22.1 (TMEM232 and SLC25A46, rs7701890, P(combined) = 3.15 × 10(-9), odds ratio (OR) = 1.24) and 20q13.33 (TNFRSF6B and ZGPAT, rs6010620, P(combined) = 3.0 × 10(-8), OR = 1.17) and replicated another previously reported locus at 1q21.3 (FLG, rs3126085, P(combined) = 5.90 × 10(-12), OR = 0.82) in the Chinese sample. The 20q13.33 locus also showed evidence for association in the German sample (rs6010620, P = 2.87 × 10(-5), OR = 1.25). Our study identifies new genetic susceptibility factors and suggests previously unidentified biological pathways in atopic dermatitis.     

The pathogenic role of interleukin-27 in autoimmune diabetes

Interleukin (IL)-27 is an IL-12-related cytokine that can promote both anti- and pro-inflammatory immune responses. This study investigated the potential role of IL-27 in autoimmune diabetes. We detected a high level of IL-27 in diabetic NOD mice. In addition, blockade of IL-27 significantly delayed the onset of diabetic splenocyte-transferred diabetes, while IL-27-treated diabetic splenocytes promoted the onset of the disease, compared with untreated controls. Furthermore, IL-27 up-regulated pro-inflammatory cytokines IFN-γ and IL-17 and down-regulated anti-inflammatory cytokines IL-4, TGF-β, and IL-10 secreted by diabetic splenocytes. These results demonstrate a pathogenic role of IL-27 in T cell-mediated autoimmune diabetes. Received 02 September 2008; received after revision 27 September 2008; accepted 01 October 2008 R. Wang, G. Han: These authors contributed equally to this work.     

Relationship among the secretion of extracellular polymeric substances,heat resistance,and bioleaching ability of Metallosphaera sedula

This paper describes the investigation of the secretion of extracellular polymeric substances (EPS) by an extremely thermoacidophilic archaea, Metallosphaera sedula (M. sedula), during the bioleaching of pyrite under different temperatures and discusses the relationship among the EPS secretion, its heat resistance, and its ability to bioleach pyrite. The investigation results indicate that the amount of extracellular proteins is significantly higher than the amount of extracellular polysaccharides in the extracted EPS whether free cells or attached cells; these results are quite different from the behavior of mesophilic Acidithiobacillus ferrooxidans. Although the growth of M. sedula is inhibited at 80℃, the bioleaching ability of M. sedula is only slightly lower than that at the optimum growth temperature of 72℃ because of the heat resistance mechanism based on EPS secretion. The secretion of more extracellular proteins is an important heat resistance mechanism of M. sedula.     

Cementitious property of NaAlO2-activated Ge slag as cement supplement

Germanium (Ge), a waste residue leaching from zinc (Zn) smelting process, has potential cementitious properties and could be recycled as a cement supplement activated by chemical reagents. In this work, a test was conducted to determine the hydration properties of Ge slag-cement-based composites with Ge slag (GS)/ordinary Portland cement (PC) contents of 0wt%, 5wt%, 10wt%, 15wt%, 20wt%, and 25wt% and water-to-binder ratio (w/b) of 0.4. The activators Ca(OH)₂, AlCl₃, NaAlO₂, and Na₂CO₃ were mixed under 1wt%, 2wt%, 3wt%, and 4wt% dosages of GS weight. The composition and microstructure of the hydration products were investigated by the combined approaches of X-ray diffraction (XRD), thermogravimetry-differential scanning calorimetry (TG-DSC), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDS). First, the GS cementitious property is attributed to the high content of CaSO₄·2H₂O. Second, the activators affected the acceleration performance in the following order:NaAlO₂, Na₂CO₃, AlCl₃, and Ca(OH)₂. More importantly, the 28-day unconfined compressive strength (UCS) is 45.34 MPa at the optimum formula of 0.6wt% NaAlO₂, 15wt% GS, and 85wt% PC, which is 9.16% higher than the control. Thus, NaAlO₂ is beneficial for the ettringite (AFt) generation, resulting in the C-S-H structure compaction. However, the Zn2+ residue inhibited the AFt formation, representing an important challenge to the strength growth with curing age. Consequently, the GS could be recycled as a supplement to the cement under the activator NaAlO₂.     

西藏措勤盆地晚中生代构造—岩相演化

措勤盆地的坟要形成、发育期为中生代。由于受南、北两条特提斯构造带的影响,盆地内东西向构造岩相分带比较明显,并与一定的沉积环境相对应,即由海相－三角洲相－滨滩相－台地相－陆相沉积。晚中生代措勤盆地的地层说明了分盆地的演化经历了从沉陷－稳定－隆起的构造旋回过程,从而反映了从裂谷－洋盆－残余海封闭及断陷盆地发育的９沉积历史。在盆地内,川巴－色林错地区发育了一套具有一定生油条件、富含有机质的残留海盆沉积,     

Cauchy问题概率解法收敛性

对于抛物型偏微分方程中的Ｃａｕｃｈｙ问题,本文给出了用Ｍｏｎｔｅ－Ｃａｒｌｏ方法计算出某布朗运动中ｔ时刻前之期望值的数值解法,并证明了此数值解的依概率收敛性。     

Exome sequencing identifies somatic mutations of DNA methyltransferase gene DNMT3A in acute monocytic leukemia

Abnormal epigenetic regulation has been implicated in oncogenesis. We report here the identification of somatic mutations by exome sequencing in acute monocytic leukemia, the M5 subtype of acute myeloid leukemia (AML-M5). We discovered mutations in DNMT3A (encoding DNA methyltransferase 3A) in 23 of 112 (20.5%) cases. The DNMT3A mutants showed reduced enzymatic activity or aberrant affinity to histone H3 in vitro. Notably, there were alterations of DNA methylation patterns and/or gene expression profiles (such as HOXB genes) in samples with DNMT3A mutations as compared with those without such changes. Leukemias with DNMT3A mutations constituted a group of poor prognosis with elderly disease onset and of promonocytic as well as monocytic predominance among AML-M5 individuals. Screening other leukemia subtypes showed Arg882 alterations in 13.6% of acute myelomonocytic leukemia (AML-M4) cases. Our work suggests a contribution of aberrant DNA methyltransferase activity to the pathogenesis of acute monocytic leukemia and provides a useful new biomarker for relevant cases.