A high-density association screen of 155 ion transport genes for involvement with common migraine

The clinical overlap between monogenic Familial Hemiplegic Migraine (FHM) and common migraine subtypes, and the fact that all three FHM genes are involved in the transport of ions, suggest that ion transport genes may underlie susceptibility to common forms of migraine. To test this leading hypothesis, we examined common variation in 155 ion transport genes using 5257 single nucleotide polymorphisms (SNPs) in a Finnish sample of 841 unrelated migraine with aura cases and 884 unrelated non-migraine controls. The top signals were then tested for replication in four independent migraine case-control samples from the Netherlands, Germany and Australia, totalling 2835 unrelated migraine cases and 2740 unrelated controls. SNPs within 12 genes (KCNB2, KCNQ3, CLIC5, ATP2C2, CACNA1E, CACNB2, KCNE2, KCNK12, KCNK2, KCNS3, SCN5A and SCN9A) with promising nominal association (0.00041 < P < 0.005) in the Finnish sample were selected for replication. Although no variant remained significant after adjusting for multiple testing nor produced consistent evidence for association across all cohorts, a significant epistatic interaction between KCNB2 SNP rs1431656 (chromosome 8q13.3) and CACNB2 SNP rs7076100 (chromosome 10p12.33) (pointwise P = 0.00002; global P = 0.02) was observed in the Finnish case-control sample. We conclude that common variants of moderate effect size in ion transport genes do not play a major role in susceptibility to common migraine within these European populations, although there is some evidence for epistatic interaction between potassium and calcium channel genes, KCNB2 and CACNB2. Multiple rare variants or trans-regulatory elements of these genes are not ruled out.

MicroRNA-155 Is Required for Mycobacterium bovis BCG-Mediated Apoptosis of Macrophages

Pathogenic rnycobacteria, including Mycobacterium tuberculosis and Mycobacterium bovis, cause significant morbidity and mortality worldwide. However, the vaccine strain Mycobacterium bovis BCG, unlike virulent strains, triggers extensive apoptosis of infected macrophages, a step necessary for the elicitation of robust protective immunity. We here demonstrate that M. bovis BCG triggers Toll-like receptor 2 (TLR2)-dependent microRNA-155 (miR-155) expression, which involves signaling cross talk among phosphatidylinositol 3-kinase (PI3K), protein kinase C delta (PKC delta), and mitogen-activated protein kinases (MAPKs) and recruitment of NF-kappa B and c-ETS to miR-155 promoter. Genetic and signaling perturbations presented the evidence that miR-155 regulates PKA signaling by directly targeting a negative regulator of PKA, protein kinase inhibitor alpha (PKI-alpha). Enhanced activation of PKA signaling resulted in the generation of PKA C-alpha; phosphorylation of MSK1, cyclic AMP response element binding protein (CREB), and histone H3; and recruitment of phospho-CREB to the apoptotic gene promoters. The miR-155-triggered activation of caspase-3, BAK1, and cytochrome c translocation involved signaling integration of MAPKs and epigenetic or posttranslational modification of histones or CREB. Importantly, M. bovis BCG infection-induced apoptosis was severely compromised in macrophages derived from miR-155 knockout mice. Gain-of-function and loss-of-function studies validated the requirement of miR-155 for M. bovis BCG's ability to trigger apoptosis. Overall, M. bovis BCG-driven miR-155 dictates cell fate decisions of infected macrophages, strongly implicating a novel role for miR-155 in orchestrating cellular reprogramming during immune responses to mycobacterial infection.

Oncogenic MicroRNA-155 Down-regulates Tumor Suppressor CDC73 and Promotes Oral Squamous Cell Carcinoma Cell Proliferation IMPLICATIONS FOR CANCER THERAPEUTICS

The CDC73 gene is mutationally inactivated in hereditary and sporadic parathyroid tumors. It negatively regulates beta-catenin, cyclin D1, and c-MYC. Down-regulation of CDC73 has been reported in breast, renal, and gastric carcinomas. However, the reports regarding the role of CDC73 in oral squamous cell carcinoma (OSCC) are lacking. In this study we show that CDC73 is down-regulated in a majority of OSCC samples. We further show that oncogenic microRNA-155 (miR-155) negatively regulates CDC73 expression. Our experiments show that the dramatic up-regulation of miR-155 is an exclusive mechanism for down-regulation of CDC73 in a panel of human cell lines and a subset of OSCC patient samples in the absence of loss of heterozygosity, mutations, and promoter methylation. Ectopic expression of miR-155 in HEK293 cells dramatically reduced CDC73 levels, enhanced cell viability, and decreased apoptosis. Conversely, the delivery of a miR-155 antagonist (antagomir-155) to KB cells overexpressing miR-155 resulted in increased CDC73 levels, decreased cell viability, increased apoptosis, and marked regression of xenografts in nude mice. Cotransfection of miR-155 with CDC73 in HEK293 cells abrogated its pro-oncogenic effect. Reduced cell proliferation and increased apoptosis of KB cells were dependent on the presence or absence of the 3'-UTR in CDC73. In summary, knockdown of CDC73 expression due to overexpression of miR-155 not only adds a novelty to the list of mechanisms responsible for its down-regulation in different tumors, but the restoration of CDC73 levels by the use of antagomir-155 may also have an important role in therapeutic intervention of cancers, including OSCC.

Conductivity noise study of the insulator-metal transition and phase coexistence in epitaxial samarium nickelate thin films

Interaction between the lattice and the orbital degrees of freedom not only makes rare-earth nickelates unusually ``bad metal,'' but also introduces a temperature-driven insulator-metal phase transition. Here we investigate this insulator-metal phase transition in thin films of SmNiO3 using the slow time-dependent fluctuations (noise) in resistivity. The normalized magnitude of noise is found to be extremely large, being nearly eight orders of magnitude higher than thin films of common disordered metallic systems, and indicates electrical conduction via classical percolation in a spatially inhomogeneous medium. The higher-order statistics of the fluctuations indicate a strong non-Gaussian component of noise close to the transition, attributing the inhomogeneity to the coexistence of the metallic and insulating phases. Our experiment offers insight into the impact of lattice-orbital coupling on the microscopic mechanism of electron transport in the rare-earth nickelates.

Sapientia, 1985, Vol. XL, nº 155 (número completo)

Contenido: La verdad (I). La verdad en sí misma y en las cosas / Octavio N. Derisi -- Carácter racional de la libertad / Octavio N. Derisi -- Libertad política : liberalismo y tomismo / Héctor H. Hernández -- Hilemorfismo y corporalidad / J. E. Bolzán -- Fenomenología de la sensación / Gabriel Chalmeta -- La teoría relacional de la personalidad según J. Nuttin / William R. Darós -- Notas y comentarios -- Bibliografía

Diário da Constituinte [gravação de vídeo] : [programa n. 155]

Técnicos em reforma sanitária, representantes da Assembleia Nacional Constituinte (ANC) e o Ministro da Saúde, Sr. Roberto Santos, reuniram-se para debater o tema: a saúde e a Constituinte. Segundo o ministro Roberto Santos o projeto de Constituição atual é um avanço quando coloca a saúde como um direito do cidadão e dever do Estado. A questão da saúde faz parte do título geral do projeto de Constituição, que trata da ordem social. No Artigo 350 fica determinado que o Estado deve criar políticas para eliminar ou reduzir o risco de doenças e garantir o acesso universal e gratuito à saúde. O Deputado José Elias Murad (PTB-MG) esclarece que este princípio significa que, em qualquer parte do país, qualquer brasileiro terá direito ao atendimento médico gratuito. O Deputado Arnaldo Faria de Sá (PTB-SP) vai apresentar um projeto de decisão para colocar já em votação a duração do mandato do Presidente José Sarney. Segundo ele, é necessário votar logo esse tema para que a Constituinte possa trabalhar em paz. Segundo o Regimento da Comissão de Sistematização, um projeto de decisão é todo assunto que precisa ser discutido quando surgir uma ameaça aos trabalhos da Constituinte. O Deputado Nilson Gibson (PMDB-PE) declara que a questão do mandato do presidente como um fato jurídico constituído, um direito adquirido. O Deputado Adolfo Oliveira (PL-RJ) afirma que é preciso caminhar para uma Constituição nova, com tudo reformado, tudo revisado e votação direta para todos os cargos eletivos. O Deputado Augusto Carvalho (PCB-DF), em nome do partido, apoia as eleições diretas para presidente da república em 1988. O Deputado Virgildásio Sena (PMDB-BA) afirma que não é a hora de decidir o mandato do presidente, já que ainda não se decidiu nem o sistema de governo. O Deputado Euclides Scalco (PMDB-PR) entende que é o momento de discutir na Comissão de Sistematização a questão do mandato do presidente e do regime de governo. O Deputado Ulysses Guimarães (PMDB-SP) entende que o Plenário é o fórum próprio para discutir o mandato e o sistema de governo, quando for votado o substitutivo.

Isotope shift studies in the rare earths and lead

Isotope shifts of K_α1 x-ray transitions were measured for the Neodymium isotopes Nd 142, 143, 144, 145, 146, 148 and 150, the Samarium isotopes Sm 147, 148, 149, 150, 152 and 154, the Gadolinium isotopes Gd 154, 155, 156, 157, 158 and 160, the Dysprosium isotopes Dy 162 and 164, the Erbium isotopes Er 166, 168 and 170, the Hafnium isotopes Hf 178 and 180 and the Lead isotopes Pb 204, 206, 207 and 208. A curved crystal Cauchois spectrometer was used. The analysis of the measurement furnished the variation of the mean square charge radius of the nucleus, δ˂r²˃, for 23 isotope pairs. The experimental results were compared with theoretical values from nuclear models. Combining the x-ray shifts and the optical shifts in Nd and Sm yielded the optical mass shifts. An anomaly was observed in the odd-even shifts when the optical and the x-ray shifts were plotted against each other.

Photoluminescence and electroluminescence properties of a samarium complex Sm(TTA)(3)phen

The photoluminescence (PL) and electroluminescence (EL) properties of a samarium complex Sm(TTA)(3)phen (TTA = 2-thenoyltri-fluoroacetonate, phen = 1, 10-phenanthroline) were investigated. The results show that Sm(TTA)3phen could be used as promising luminescent and electron transporting material in the electroluminescent devices. The difference between PL and EL spectra was noticed and discussed. Besides, it is noteworthy that the choice of the hole transporting layer (HTL) showed significant effect on the device performance, which was explained by the low-lying highest occupied molecular orbit (HOMO) level of Sm(TTA)3phen and the different hole injection barrier at the HTL/EML (emitting material layer) interface.

Effect of samarium on Mn activated zinc borosilicate storage glasses

Samarium and manganese co-doped zinc borosilicate storage glasses were prepared by high temperature solid state method. The effect of doping samarium on the defect of Mn activated sample was studied by means of thermoluminescence spectra. It was found that the shallower traps of the sample predominate with the addition of samarium, as a result, the phosphorescence and storage properties of the manganese doped zinc borosilicate glasses were greatly changed.

Study on transfer and interfacial kinetics of neodymium and samarium in membrane based extraction

Extraction and interfacial kinetics of Nd3+ and Sm3+ with HER/EHP-kerosene in a hollow fiber membrane extractor were studied. The results show that the extraction reactions in the hollow fiber membrane extractor are the same as those in the liquid-liquid extraction, which can be expressed as a quasi-first-order reaction. The effect of acidity in aqueous phase, concentrations of extractant, Nd3+ and Sm3+ on extraction rate were discussed and the corresponding reaction series were obtained. The reaction equations, reaction rate constants and the separation constant were obtained.