Genome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2

A combined genome-wide association and linkage study was used to identify loci causing variation in cystic fibrosis lung disease severity. We identified a significant association (P = 3.34 × 10(-8)) near EHF and APIP (chr11p13) in p.Phe508del homozygotes (n = 1,978). The association replicated in p.Phe508del homozygotes (P = 0.006) from a separate family based study (n = 557), with P = 1.49 × 10(-9) for the three-study joint meta-analysis. Linkage analysis of 486 sibling pairs from the family based study identified a significant quantitative trait locus on chromosome 20q13.2 (log(10) odds = 5.03). Our findings provide insight into the causes of variation in lung disease severity in cystic fibrosis and suggest new therapeutic targets for this life-limiting disorder.     

The cross-talk between the urokinase receptor and fMLP receptors regulates the activity of the CXCR4 chemokine receptor

The receptor (CXCR4) for the stromal-derived factor-1 (SDF1) and the urokinase-receptor (uPAR) are up-regulated in various tumors. We show that CXCR4-transfected cells migrate toward SDF1 on collagen (CG) and do not on vitronectin (VN). Co-expression of cell-surface uPAR, which is a VN receptor, impairs SDF1-induced migration on CG and allows migration on VN. Blocking fMLP receptors (fMLP-R), alpha-v integrins or the uPAR region capable to interact with fMLP-Rs, impairs migration of uPAR/CXCR4-transfected cells on VN and restores their migration on CG. uPAR co-expression also reduces the adherence of CXCR4-expressing cells to various components of the extracellular matrix (ECM) and influences the partitioning of beta1 and alpha-v integrins to membrane lipid-rafts, affecting ECM-dependent signaling. uPAR interference in CXCR4 activity has been confirmed in cells from prostate carcinoma. Our results demonstrate that uPAR expression regulates the adhesive and migratory ability of CXCR4-expressing cells through a mechanism involving fMLP receptors and alpha-v integrins.     

H2 receptor antagonists and human granulopoiesis

Summary The effect of 2 H₂ receptor antagonists (ranitidine and cimetidine) on the in vitro growth of human granulomonopoietic precursors (CFU-GM) was studied. Ranitidine, although having an anti H₂ receptor activity much greater than that of cimetidine, displays the same toxicity for CFU-GM.Acknowledgments. This work was supported by CNR, Rome, PFCCN and AIRC, Milan.     

Effect of lithium on normal and chronic granulocytic leukemia colony forming cells (CFU-GM)

The effect of lithium on normal and chronic granulocytic leukemia (CGL) granulo-monocytic precursors (CFU-GM) has been studied. Lithium slightly increases normal CFU-GM growth whereas it is without effect or moderately inhibitory for CGL CFU-GM. It is suggested that it is unlikely that lithium therapy enhances the proliferation of a silent leukemic clone.     

多硫化钠浸金研究

本文中研究了用多硫化钠作浸出剂浸出锑锍中的金。根据实验和理论分析,认为多硫化物浸金具有如下反应: 6Au 2S~(2-) S_4~(2-)=6AuS~- 8Au 3S~(2-) S_5~(2-)=8AuS~- 6Au 2HS~- 2OH~- S_4~(2-)=6AuS~- 2H_2O 8Au 3HS~- 3OH~- S_5~(2-)=8AuS~- 3H_2O考察了粒度、温度、硫化钠用量、加硫量、氢氧化钠浓度、液固比、时间等因素对金浸出率的影响。在研究所得的最佳条件下,金的浸出率稳定在93％以上。     

基于遗传BP神经网络的区域物流需求预测

针对当前区域物流需求预测数据复杂且可变性较大、预测方法环境适应性较差的问题,提出了基于遗传BP神经网络的区域物流需求预测模型。首先,分析区域物流需求预测影响因素,并建立区域物流需求预测指标体系;其次,采用遗传算法优化预测网络中的可变参数,并建立多输入-多输出的BP神经网络多元预测模型;最后,通过实例结果表明该模型具有较高的预测精度和有效度。     

Decondensation of nuclear chromatin under the influence ofTris buffer

Résumé Des petits fragments de foie de rat ont été maintenus dans un tampon 2 mM tris HCl avec ou sans saccharose (concentration final 0,25M). L'incubation du tissus pendant au moins 1 h dans le tampontris cause une décondensation de la chromatine, qui peut être retardée par le saccharose. Les changements morphologiques des types de chromatine n'ont pas l'effet d'incorporer l'uridine dans le noyaux interphasiques du foie.     

低成本热芯盒树脂的研制

热芯盒树脂是在铸造技术中应用比较广泛的一种粘结剂，但是成本较高，本文介绍的一种通过加入低成本的改性剂而研制成的低成本热芯盒树脂，基本上达到国内外同类产品水平，在生产上原料来源广泛，有一定的实际意义。     

Multiple apical plasma membrane constituents are associated with susceptibility to meconium ileus in individuals with cystic fibrosis

Variants associated with meconium ileus in cystic fibrosis were identified in 3,763 affected individuals by genome-wide association study (GWAS). Five SNPs at two loci near SLC6A14 at Xq23-24 (minimum P = 1.28 × 10(-12) at rs3788766) and SLC26A9 at 1q32.1 (minimum P = 9.88 × 10(-9) at rs4077468) accounted for ~5% of phenotypic variability and were replicated in an independent sample of affected individuals (n = 2,372; P = 0.001 and 0.0001, respectively). By incorporating the knowledge that disease-causing mutations in CFTR alter electrolyte and fluid flux across surface epithelium into a hypothesis-driven GWAS (GWAS-HD), we identified associations with the same SNPs in SLC6A14 and SLC26A9 and established evidence for the involvement of SNPs in a third solute carrier gene, SLC9A3. In addition, GWAS-HD provided evidence of association between meconium ileus and multiple genes encoding constituents of the apical plasma membrane where CFTR resides (P = 0.0002; testing of 155 apical membrane genes jointly and in replication, P = 0.022). These findings suggest that modulating activities of apical membrane constituents could complement current therapeutic paradigms for cystic fibrosis.     

tRNA in developing human placenta

Summary Amino acid acceptor activity of tRNA in the human placenta as measured throughout gestation was found to be the lowest in post-term placenta. Aminoacylation of tRNA proceeded with maximum activity in the stage of formation of the placenta.