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.     

Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing

Most patients with acute myeloid leukaemia (AML) die from progressive disease after relapse, which is associated with clonal evolution at the cytogenetic level. To determine the mutational spectrum associated with relapse, we sequenced the primary tumour and relapse genomes from eight AML patients, and validated hundreds of somatic mutations using deep sequencing; this allowed us to define clonality and clonal evolution patterns precisely at relapse. In addition to discovering novel, recurrently mutated genes (for example, WAC, SMC3, DIS3, DDX41 and DAXX) in AML, we also found two major clonal evolution patterns during AML relapse: (1) the founding clone in the primary tumour gained mutations and evolved into the relapse clone, or (2) a subclone of the founding clone survived initial therapy, gained additional mutations and expanded at relapse. In all cases, chemotherapy failed to eradicate the founding clone. The comparison of relapse-specific versus primary tumour mutations in all eight cases revealed an increase in transversions, probably due to DNA damage caused by cytotoxic chemotherapy. These data demonstrate that AML relapse is associated with the addition of new mutations and clonal evolution, which is shaped, in part, by the chemotherapy that the patients receive to establish and maintain remissions.     

Strict evolutionary conservation followed rapid gene loss on human and rhesus Y chromosomes

The human X and Y chromosomes evolved from an ordinary pair of autosomes during the past 200-300 million years. The human MSY (male-specific region of Y chromosome) retains only three percent of the ancestral autosomes' genes owing to genetic decay. This evolutionary decay was driven by a series of five 'stratification' events. Each event suppressed X-Y crossing over within a chromosome segment or 'stratum', incorporated that segment into the MSY and subjected its genes to the erosive forces that attend the absence of crossing over. The last of these events occurred 30 million years ago, 5 million years before the human and Old World monkey lineages diverged. Although speculation abounds regarding ongoing decay and looming extinction of the human Y chromosome, remarkably little is known about how many MSY genes were lost in the human lineage in the 25 million years that have followed its separation from the Old World monkey lineage. To investigate this question, we sequenced the MSY of the rhesus macaque, an Old World monkey, and compared it to the human MSY. We discovered that during the last 25 million years MSY gene loss in the human lineage was limited to the youngest stratum (stratum 5), which comprises three percent of the human MSY. In the older strata, which collectively comprise the bulk of the human MSY, gene loss evidently ceased more than 25 million years ago. Likewise, the rhesus MSY has not lost any older genes (from strata 1-4) during the past 25 million years, despite its major structural differences to the human MSY. The rhesus MSY is simpler, with few amplified gene families or palindromes that might enable intrachromosomal recombination and repair. We present an empirical reconstruction of human MSY evolution in which each stratum transitioned from rapid, exponential loss of ancestral genes to strict conservation through purifying selection.     

Observation of mega-dune evaporation after various rain events in the hinterland of Badain Jaran Desert, China

The formation mechanisms of the mega-dunes and lakes in the hinterland of Badain Jaran Desert,China,is the focus of extensive academic research in the field of geoscience,and an often debated topic is whether atmospheric precipitation on the mega-dune can infiltrate to recharge groundwater.In the present study,the probability distribution functions and the return period analysis of extreme daily precipitation based on long-term precipitation records for the southern margin of Badain Jaran Desert and 2-year observation of hinterland precipitation were used to classify precipitation in the desert region.The data of automatic weather station and eddy covariance system in the desert hinterland were used to analyze evaporation on the mega-dune surface after various rain events.The results showed that the rain events in the desert could be divided into three categories.The first is conventional precipitation(CP),which is below 5 mm,accounting for roughly 90%of all rain events in the desert.The second and third categories are ordinary annual maximum(OAM)and extreme precipitation(EP),in which precipitation is roughly 20 mm and more than 40 mm,respectively.The atmospheric precipitation of CP and OAM evaporated from the megadune surface in 1–3 days and 3–4 weeks,respectively.Following an EP event,the mega-dune evaporation was negatively influenced by the upper dry sand layer,and a lengthy period was required for its complete removal.The accumulative evaporation and accumulative precipitation of all three types of rain events indicated that local atmospheric precipitation had no significant contribution to recharging the groundwater system in the hinterland of Badain Jaran Desert.This research will benefit comprehensive elucidation of the formation mechanism of lakes in the hinterland of Badain Jaran Desert.