The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm

Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD) and type 2 diabetes (T2D), respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) = 1.31, P = 1.2 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 10(-6)), but not with T2D. This variant is the first to be described that affects the risk of AAA and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our samples, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases.     

菲涅耳区板分区规则

根据Huygens-Fresnel的波束管理论,充分利用第1区的有效能量,并利用各个区所贡献的合成场强在焦点处同相的奇数分区,摒弃各合成场强在焦点处反相的偶数分区,导出了平面菲涅耳区板的一维条带的最优分区新规则.从基尔霍夫绕射公式出发进一步研究菲涅耳区板的二维圆环的分区规则.分为标量场(非极化波)绕射和矢量场(极化波)绕射2种情况,得出最优分区与传统分区在短焦距情况下存在差异、而随着焦距的增长渐趋一致的结论.     

Lack of linkage of familial Wilms' tumour to chromosomal band 11p13

Wilms' tumour (WT), a paediatric renal neoplasm, affect approximately 1 in 10,000 children. One or both kidneys can be affected and 5-10% of tumours are bilateral. Most tumours occur sporadically; however, around 1% of the cases are familial, with siblings or cousins most often being affected. Familial cases are more frequently bilateral, and familial and bilateral tumours are diagnosed at an earlier age. On the basis of these observations, it was proposed that the development of WT requires two mutations. In most sporadic unilateral WT, both are somatic; in familial and bilateral tumours the first is thought to be germinal. Cytogenetic and molecular studies have demonstrated germinal mutations in WT/aniridia patients and somatic mutations in sporadic WT at chromosomal band 11p13. To investigate whether familial predisposition to WT is due to a germinal 11p13 mutation, we studied a WT family with seen DNA markers that span the 11p13 region. We found that familial WT predisposition was not genetically linked to any of the 11p13 markers. This suggests that the gene involved in familial WT predisposition is outside 11p13 and is distinct from the gene involved in tumorigensis and in WT predisposition in WT/aniridia 11p13-deletion patients.     

Effect of L-amino-ethyl-cysteine,a sulfur analogue of L-lysine,on virus miltiplication in mammalian cell cultures

Summary L-amino-ethyl-cysteine clearly inhibits replication of Mengovirus; another RNA-virus (vesicular stomatitis virus) is completely insensitive. Protein synthesis is not impaired, but no active viral RNA-polymerase is detected.This work was partly supported by grant No. 73.01407.44 115.0107 of Consiglio Nazionale delle Ricerche, Roma, Italy. The technical collaboration of P. Meo and G. Conciatori is gratefully acknowledged.     

Stimulation of protein kinase C recruits covert calcium channels in Aplysia bag cell neurons

The modulation of voltage-activated calcium currents by protein kinases provides excitable cells with a mechanism for regulating their electrical behaviour. At the single channel level, modulation of calcium current has, to date, been characterized only in cardiac muscle, where beta-adrenergic agonists, acting through cyclic AMP-dependent protein kinase, enhance the calcium current by increasing channel availability and opening. We now report that enhancement of calcium current in the peptidergic bag cell neurons of Aplysia by protein kinase C occurs through a different mechanism, the recruitment of a previously covert class of calcium channel. Under control conditions, bag cell neurons contain only one class of voltage-activated calcium channel with a conductance of approximately 12 pS. After exposure to agents that activate protein kinase C, these neurons also express a second class of calcium channel with a different unitary conductance (approximately 24 pS) that is never seen in untreated cells.     

Effect on non-steroidal anti-inflammatory drugs on Moloney sarcoma virus inoculated mice

Summary Chronic administration of phenylbutazone, flufenamic acid and a new, potent non-steroidal anti-inflammatory agent ITF (3-methyl-5-benzoyl-amino-isothiazole-4-carboxy-p-ethoxyphenylamine) to BALB/c mice inoculated with a Moloney sarcoma virus resulted in a stimulation of tumor growth and increased severity of disease. This treatment, however, had no effect on the spontaneous regression of tumors. Indomethacin in a dose of 5.0 or 2.5 mg per kg suppressed the MSV-induced tumor growth, but this effect was apparently connected with the high toxicity of this drug for mice.     

Studies on the cytochemical localization of adenylate-cyclase activity inDugesia lugubris s.l.

Summary The localization of adenylate-cyclase activity inDugesia lugubris s.l. has been investigated cytochemically using 5-adenylyl-imidodiphosphate as substrate. The enzyme was localized in mucous gland cells, in rhabdite cells, in intercellular spaces and also in nerve endings of this planarian. The presence of adenylate-cyclase on the membrane suggests that it might mediate different stimulus-secretion coupling by increasing cyclic AMP synthesis in specialized areas of the planarian.Supported in part by a grant from Consiglio Nazionale delle Ricerche, Rome.Acknowledgments. This work was performed with the technical assistence of the laboratory of Electron Microscopy of the University of Perugia.     

Climate-driven population divergence in sex-determining systems

Sex determination is a fundamental biological process, yet its mechanisms are remarkably diverse. In vertebrates, sex can be determined by inherited genetic factors or by the temperature experienced during embryonic development. However, the evolutionary causes of this diversity remain unknown. Here we show that live-bearing lizards at different climatic extremes of the species' distribution differ in their sex-determining mechanisms, with temperature-dependent sex determination in lowlands and genotypic sex determination in highlands. A theoretical model parameterized with field data accurately predicts this divergence in sex-determining systems and the consequence thereof for variation in cohort sex ratios among years. Furthermore, we show that divergent natural selection on sex determination across altitudes is caused by climatic effects on lizard life history and variation in the magnitude of between-year temperature fluctuations. Our results establish an adaptive explanation for intra-specific divergence in sex-determining systems driven by phenotypic plasticity and ecological selection, thereby providing a unifying framework for integrating the developmental, ecological and evolutionary basis for variation in vertebrate sex determination.