多孔介质中的大尺度多相渗流

在许多工业和环境应用中，不同时空尺度上的多孔介质中的多相渗流都是一个非常重要的过程。因此，了解确定微尺度上的多相渗流和其反应传递过程，并描述其宏观条件下的运动现象是很必要的。目前描述宏观下的多相渗流现象都是基于由达西定律经验公式得到的毛管压力一饱和度一相对渗透率关系式。然而，这些经验模型并不能完全反映实际的物理现象，尤其是大尺度和非均质介质中渗流问题。     

Epigallocatechin-3-gallate affects the growth of LNCaP cells via membrane fluidity and distribution of cellular zinc

Objective: To evaluate effects of epigallocatechin-3-gallate (EGCG) on the viability, membrane properties, and zinc distribution, with and without the presence of Zn²⁺, in human prostate carcinoma LNCaP cells. Methods: We examined changes in cellular morphology and membrane fluidity of LNCaP cells, distribution of cellular zinc, and the incorporated portion of EGCG after treatments with EGCG, Zn²⁺, and EGCG+Zn²⁺. Results: We observed an alteration in cellular morphology and a decrease in membrane fluidity of LNCaP cells after treatment with EGCG or Zn²⁺. The proportion of EGCG incorporated into liposomes treated with the mixture of EGCG and Zn²⁺ at the ratio of 1:1 was 90.57%, which was significantly higher than that treated with EGCG alone (30.33%). Electron spin resonance (ESR) studies and determination of fatty acids showed that the effects of EGCG on the membrane fluidity of LNCaP were decreased by Zn²⁺. EGCG accelerated the accumulation of zinc in the mitochondria and cytosol as observed by atomic absorption spectrometer. Conclusion: These results show that EGCG interacted with cell membrane, decreased the membrane fluidity of LNCaP cells, and accelerated zinc accumulation in the mitochondria and cytosol, which could be the mechanism by which EGCG inhibits proliferation of LNCaP cells. In addition, high concentrations of Zn²⁺ could attenuate the actions elicited by EGCG.     

Constituants amers deBrucea amarissima structures des brucéines A,B et C

Summary Evidence is presented for the structures (II a), (II b) and (II c) for the bruceines A, B and C, the bitter principles isolated from the seeds ofBrucea amarissima.

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18ème Communication sur les constituants amers des Simarubacées; 17ème Communication, voir².     

Isocardenolides

Zusammenfassung Ein einfacher Weg zur Synthese eines von zwei möglichen isomeren Cardenoliden wurde entwickelt und die Reaktionsfolge an Hand der Überführung von Pregnenolon in Isocardenolide V gezeigt.

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Steroids and Related Natural Products XXI. For the previous contribution refer to:G. R. Pettit andP. Hofer, Helv. chim. Acta46, 2142 (1963).

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A preliminary account of this study was presented (December 1963) at the VI. Pan-American Congress of Pharmacy and Biochemistry, Mexico City (Mexico).

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This investigation was supported by PHS Research Grants CY-4074 (C3) to CA-04074-06 from the National Cancer Institute, Public Health Service.     

On the activity of neurosecretory cells in the flesh-flySarcophaga bullata

Résumé L'activité des cellules neurosécretrices dans le cerveau de la femelle deSarcophaga bullata est en corrélation avec le développement des larves dans la femelle et leur position.     

Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci

We carried out a genome-wide association study of type-2 diabetes (T2D) in individuals of South Asian ancestry. Our discovery set included 5,561 individuals with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and Singapore. We identified 20 independent SNPs associated with T2D at P < 10(-4) for testing in a replication sample of 13,170 cases and 25,398 controls, also all of South Asian ancestry. In the combined analysis, we identified common genetic variants at six loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) newly associated with T2D (P = 4.1 × 10(-8) to P = 1.9 × 10(-11)). SNPs at GRB14 were also associated with insulin sensitivity (P = 5.0 × 10(-4)), and SNPs at ST6GAL1 and HNF4A were also associated with pancreatic beta-cell function (P = 0.02 and P = 0.001, respectively). Our findings provide additional insight into mechanisms underlying T2D and show the potential for new discovery from genetic association studies in South Asians, a population with increased susceptibility to T2D.     

Common variants at 12q15 and 12q24 are associated with infant head circumference

To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 × 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 × 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height, their effects on infant head circumference were largely independent of height (P = 3.8 × 10(-7) for rs7980687 and P = 1.3 × 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 × 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume, Parkinson's disease and other neurodegenerative diseases, indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.     

Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids

Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an autosomal-dominant central nervous system white-matter disease with variable clinical presentations, including personality and behavioral changes, dementia, depression, parkinsonism, seizures and other phenotypes. We combined genome-wide linkage analysis with exome sequencing and identified 14 different mutations affecting the tyrosine kinase domain of the colony stimulating factor 1 receptor (encoded by CSF1R) in 14 families with HDLS. In one kindred, we confirmed the de novo occurrence of the mutation. Follow-up sequencing identified an additional CSF1R mutation in an individual diagnosed with corticobasal syndrome. In vitro, CSF-1 stimulation resulted in rapid autophosphorylation of selected tyrosine residues in the kinase domain of wild-type but not mutant CSF1R, suggesting that HDLS may result from partial loss of CSF1R function. As CSF1R is a crucial mediator of microglial proliferation and differentiation in the brain, our findings suggest an important role for microglial dysfunction in HDLS pathogenesis.