A Common Variant in CLDN14 is Associated with Primary Biliary Cirrhosis and Bone Mineral Density.

Primary biliary cirrhosis (PBC), a chronic autoimmune liver disease, has been associated with increased incidence of osteoporosis. Intriguingly, two PBC susceptibility loci identified through genome-wide association studies are also involved in bone mineral density (BMD). These observations led us to investigate the genetic variants shared between PBC and BMD. We evaluated 72 genome-wide significant BMD SNPs for association with PBC using two European GWAS data sets (n = 8392), with replication of significant findings in a Chinese cohort (685 cases, 1152 controls). Our analysis identified a novel variant in the intron of the CLDN14 gene (rs170183, Pfdr = 0.015) after multiple testing correction. The three associated variants were followed-up in the Chinese cohort; one SNP rs170183 demonstrated consistent evidence of association in diverse ethnic populations (Pcombined = 2.43 × 10(-5)). Notably, expression quantitative trait loci (eQTL) data revealed that rs170183 was correlated with a decline in CLDN14 expression in both lymphoblastoid cell lines and T cells (Padj = 0.003 and 0.016, respectively). In conclusion, our study identified a novel PBC susceptibility variant that has been shown to be strongly associated with BMD, highlighting the potential of pleiotropy to improve gene discovery

Study on the Variation of Terrestrial Water Storage and the Identification of Its Relationship with Hydrological Cycle Factors in the Tarim River Basin, China

The terrestrial water storage anomalies (TWSAs) in the Tarim River Basin (TRB) were investigated and the related factors of water variations in the mountain areas were analyzed based on Gravity Recovery and Climate Experiment (GRACE) data, in situ river discharge, and precipitation during the period of 2002–2015. The results showed that three obvious flood events in 2005, 2006, and 2010 resulted in significant water surplus, although TWSA decreased in the TRB during 2002–2015. However, while the significant water deficits in 2004, 2009, and 2011 were associated with obvious negative river discharge anomalies at the hydrological stations, the significant water deficits were not well consistent with the negative anomalies of precipitation. While the river discharge behaved with low correlations with TWSA, linear relationships between TWSA and climate indices were insignificant in the TRB from 2002 to 2015. The closest relationship was found between TWSA and Pacific Decadal Oscillation (PDO), with correlations of -0.56 and 0.58 during January 2010–December 2015 and during January 2006–December 2009, respectively. Meanwhile, the correlation coefficient between TWSA and El Niño-Southern Oscillation (ENSO) index in the period of April 2002–December 2005 was -0.25, which reached the significant level (p<0.05)

Non-Fossil Origin Explains the Large Seasonal Variation of Highly Processed Organic Aerosol in the Northeastern Tibetan Plateau (3,200 m a.s.l.)

Carbonaceous aerosol plays an important role in climate, but its sources and atmospheric processes are least understood in the Tibetan Plateau (TP), a remote yet climatically sensitive region. This study presents the first seasonal cycle of radiocarbon and stable isotope 13C of organic and elemental carbon (OC and EC) in the atmosphere of the northeastern TP. Large seasonal variations of EC and OC concentrations were explained by non-fossil sources. Regardless of the season, fossil contribution to OC was strongly correlated with inverse OC concentrations. This allowed the separating a constant background source and a source responsible for OC variability that was mostly of non-fossil origin. The 13C signature of OC shows that OC was highly atmospherically processed and thus less volatile than OC found near sources or in urban areas. The 13C-depleted secondary sources contributed strongly to more volatile OC, whereas the 13C-enriched less volatile OC suggests the influence of atmospheric aging.</p

A novel ZRS variant causes preaxial polydactyly type I by increased sonic hedgehog expression in the developing limb bud.

PurposePreaxial polydactyly (PPD) is a common congenital hand malformation classified into four subtypes (PPD I-IV). Variants in the zone of polarizing activity regulatory sequence (ZRS) within intron 5 of the LMBR1 gene are linked to most PPD types. However, the genes responsible for PPD I and the underlying mechanisms are unknown.MethodsA rare large four-generation family with isolated PPD I was subjected to genome-wide genotyping and sequence analysis. In vitro and in vivo functional studies were performed in Caco-2 cells, 293T cells, and a knockin transgenic mouse model.ResultsA novel g.101779T&gt;A (reference sequence: NG_009240.2; position 446 of the ZRS) variant segregates with all PPD I-affected individuals. The knockin mouse with this ZRS variant exhibited PPD I phenotype accompanying ectopic and excess expression of Shh. We confirmed that HnRNP K can bind the ZRS and SHH promoters. The ZRS mutant enhanced the binding affinity for HnRNP K and upregulated SHH expression.ConclusionOur results identify the first PPD I disease-causing variant. The variant leading to PPD I may be associated with enhancing SHH expression mediated by HnRNP K. This study adds to the ZRS-associated syndromes classification system for PPD and clarifies the underlying molecular mechanisms

Visualized Experiment of Bubble Behaviors in a Vertical Narrow Rectangular Channel Under Natural Circulation Condition

The characteristics of bubble behavior have been in particular interest for decades due to its significant contribution to understanding the mechanism of heat transfer. In the present work, visualized experiment is conducted to study the bubble characteristics in subcooled flow boiling of a narrow rectangular channel under natural circulation. The experiments were performed at pressures of 0.2 MPa, with inlet subcooling ranging from 20 to 60 K and heat flux ranging from 100 to 300 kW/m2. A high-speed digital camera is used to capture the pictures of bubble behaviors. A sequence of image processing algorithms is used deal with the original bubble images to get relevant bubble parameters. We observe the whole process of a single sliding bubble lifetime and found most of bubbles slide along the heating surface after detaching the nucleation sites. Five typical sliding bubble growth paths are observed in the present experimental conditions. According to the analysis of the experimental data, it can be found that the liquid subcooling and wall superheat are the main factors that affect the bubble size during sliding in narrow rectangular channel under natural circulation condition. Due to the difference of driving force, the sliding velocity of bubble in forced circulation is always larger than that in natural circulation. At the same time, the bubble velocity changes significantly at different heat flux and shooting location

Biological N fixation but not mineral N fertilization enhances the accumulation of N in peanut soil in maize/peanut intercropping system

Legume/cereal intercropping has the potential to maximize the use of resources to raise yields due to enhanced nitrogen (N) fixation by legume root nodules, while high N fertilization may inhibit the nodulation of legume. However, whether legume/cereal intercropping can promote the accumulation of soil N storage with N fertilization and its underlying mechanism are less clear. Here, we evaluated the long-term (5 years) effects of maize/peanut intercropping and mineral N fertilization on peanut soil total N content and soil N cycling functional genes. The experiment includes two planting patterns (peanut maize intercropping and peanut monocropping) with three N fertilization rates (0, 150, and 300 kg N ha−1). Intercropping increased soil total N content (STN) by average 18.2%, and the positive effect of intercropping on STN decreased with N application rate. Highest N application decreased the nodule fresh weight (NFW) by 64.3% and 46.0% in intercropping and monocropping system, respectively. However, intercropping has no effect on NFW. Intercropping increased the nifH gene abundance by average 26.5%. SEM analysis indicated that NFW and nifH gene abundance combined can explain 46% of the variance of STN. Our results indicate that biological N fixation but not mineral N fertilization enhances the accumulation of N in soil planted with peanut in maize/peanut intercropping system.info:eu-repo/semantics/publishedVersio

Faktor-Faktor Yang Mempengaruhi Pengungkapan Tanggung Jawab Sosial

Penelitian ini bertujuan untuk menentukan faktor-faktor yang mempengaruhi luasnya tingkat pengungkapan tanggung jawab sosial Perusahaan (Corporate Social Responsibility) dengan menguji pengaruh ukuran Perusahaan, profitabilitas, leverage, kepemilikan insti­tusional, ukuran dewan komisaris, ukuran dewan direksi, dan ukuran komite audit. Sampel yang digunakan adalah Perusahaan sektor pertambangan terdaftar di Bursa Efek Indonesia selama 2010-2012. Data diperoleh dari laporan keuangan auditan dan laporan tahunan serta laporan keberlanjutan (sustainability report) jika ada. Penelitian ini menggunakan pendekatan kuantitatif dengan analisis regresi linear berganda. Penelitian ini menunjukkan bahwa ukuran Perusahaan dan komite audit memiliki pengaruh positif terhadap peng­ungkapan tanggung jawab sosial. Tidak ditemukan bukti pengaruh profitabilitas, leverage, kepemilikan institusional, ukuran dewan komisaris, dan ukuran dewan direksi terhadap terhadap pengungkapan tanggung jawab sosial

Potential biomarkers for the early detection of bone metastases

The clinical manifestations of bone metastases are diversified while many sites remain asymptomatic at early stage. As the early diagnosis method is not perfect and the early symptoms of tumor bone metastasis are not typical, bone metastasis is not easy to be detected. Therefore, the search for bone metastasis-related markers is effective for timely detection of tumor bone metastases and the development of drugs to inhibit bone metastases. As a result, bone metastases can only be diagnosed when symptoms are found, increasing the risk of developing skeletal-related event (SREs), which significantly impairs the patient’s quality of life. Therefore, the early diagnosis of bone metastases is of great importance for the treatment and prognosis of cancer patients. Changes of bone metabolism indexes appear earlier in bone metastases, but the traditional biochemical indexes of bone metabolism lack of specificity and could be interfered by many factors, which limits their application in the study of bone metastases. Some new biomarkers of bone metastases have good diagnostic value, such as proteins, ncRNAs, circulating tumor cells (CTCs). Therefore, this study mainly reviewed the initial diagnostic biomarkers of bone metastases which were expected to provide references for the early detection of bone metastases

Health-related quality of life as measured with EQ-5D among populations with and without specific chronic conditions: A population-based survey in Shaanxi province, China

© 2013 Tan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Introduction: The aim of this study was to examine health-related quality of life (HRQoL) as measured by EQ-5D and to investigate the influence of chronic conditions and other risk factors on HRQoL based on a distributed sample located in Shaanxi Province, China. Methods: A multi-stage stratified cluster sampling method was performed to select subjects. EQ-5D was employed to measure the HRQoL. The likelihood that individuals with selected chronic diseases would report any problem in the EQ-5D dimensions was calculated and tested relative to that of each of the two reference groups. Multivariable linear regression models were used to investigate factors associated with EQ VAS. Results: The most frequently reported problems involved pain/discomfort (8.8%) and anxiety/depression (7.6%). Nearly half of the respondents who reported problems in any of the five dimensions were chronic patients. Higher EQ VAS scores were associated with the male gender, higher level of education, employment, younger age, an urban area of residence, access to free medical service and higher levels of physical activity. Except for anemia, all the selected chronic diseases were indicative of a negative EQ VAS score. The three leading risk factors were cerebrovascular disease, cancer and mental disease. Increases in age, number of chronic conditions and frequency of physical activity were found to have a gradient effect. Conclusion: The results of the present work add to the volume of knowledge regarding population health status in this area, apart from the known health status using mortality and morbidity data. Medical, policy, social and individual attention should be given to the management of chronic diseases and improvement of HRQoL. Longitudinal studies must be performed to monitor changes in HRQoL and to permit evaluation of the outcomes of chronic disease intervention programs. © 2013 Tan et al.National Nature Science Foundation (No. 8107239