Molecular epidemiology of HFE gene polymorphic variants (C282Y, H63D and S65C) in the population of Espírito Santo, Brazil.

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Alves, L N R; Santos, E V W; Stur, E; Silva Conforti, A M A; Louro, I D

2016-04-27

Hereditary hemochromatosis (HH) is an autosomal recessive disorder that leads to progressive iron accumulation and may cause cirrhosis, hepatocellular carcinoma, diabetes, and heart failure. Most cases of HH have been linked to mutations in genes associated with iron homeostasis. There have been three major variants in the high Fe (HFE) gene associated with the disease: C282Y, H63D and S65C. In this context, we aimed to evaluate the prevalence of the polymorphic variants (C282Y, H63D and S65C) of the HFE gene in the population of the Espírito Santo State (ES), Brazil by analyzing three different groups: general population (N = 120), Pomeranian descendants (N = 59), and patients with HH (N = 20). Using genomic DNA extracted from peripheral blood, polymorphic variant identification was performed by polymerase chain reaction-restriction fragment length polymorphism. Statistically significant differences were observed for genotype distribution of C282Y (P HFE gene allele frequencies for the general population, Pomeranian subpopulation, and patients with HH of ES, Brazil.

Interleucina-18 (IL-18 y otros parámetros inmunológicos como marcadores de gravedad en la pancreatitis aguda Interleukin 18 (IL-18 and other immunological parameters as markers of severity in acute pancreatitis

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M. A. Martín

2008-12-01

Full Text Available Objetivo: se trata de comparar prospectivamente el comportamiento durante la primera semana del ingreso de los niveles de interleucina-18 (IL-18, y otros parámetros inmunológicos entre pacientes con pancreatitis aguda con y sin criterios de gravedad, así como entre pacientes con y sin desarrollo ulterior de seudoquiste. Pacientes y métodos: se compararon en 36 pacientes con pancreatitis aguda los resultados de sTNF-RI, IL-1Ra, IL-6 e IL-18 los días 1, 2, 3 y 7 desde el ingreso entre pancretitis leve, grave y un grupo control (13 pacientes con cólico biliar simple, así como entre pacientes con o sin seudoquiste. Resultados: al comparar pancreatitis leve con grave, IL-18 fue significativamente superior sólo el primer día en las pancreatitis graves y los otros parámetros a partir del segundo día de forma mantenida. También en pacientes que desarrollaron seudoquiste, IL-18 estuvo significativamente elevada el primer día. Conclusiones: IL-18 resultó el marcador más precoz de complicaciones y gravedad de la pancreatitis aguda a nivel sistémico y local (seudoquiste.Objective: our aim was to prospectively compare the behavior of interleukin 18 (IL-18 levels and other immunological parameters during the first week of hospitalization between acute pancreatitis patients with and without severity criteria, as well as between patients with and without late pseudocyst development. Patients and methods: in 36 patients with acute pancreatitis we compared sTNF-RI, IL-1Ra, IL-6, and IL-18 levels at days 1, 2, 3 and 7 after hospitalization between mild pancreatitis, severe pancreatitis, and a "control" group (13 patients with uncomplicated biliary colic, as well as between patients with and without pseudocyst. Results: on comparing mild to severe pancreatitis, IL-18 was significantly higher only the first day in severe pancreatitis, while the other parameters were steadily higher after the second day. In patients developing pseudocyst, IL-18 was

Variantes del ADNmt en isleños del lago Titicaca: máxima frecuencia del haplotipo B1 y evidencia de efecto fundador

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José Sandoval

2013-06-01

Full Text Available Los polimorfismos del ADN mitocondrial son herramientas en el estudio comparativo de poblaciones modernas y antiguas. Entre los más usados están los haplotipos mitocondriales basados en RFLP (polimorfismo de longitud de fragmentos de restricción y un sistema de inserción /deleción. El presente estudio establece la frecuencia de estos haplotipos y compara un total de 144 individuos representativos de las islas Taquile y Amantaní (lengua quechua y de las islas de Los Uros y Anapia (lengua aymara del lago Titicaca, Perú. Nuestros resultados revelan la predominancia del haplotipo B1: 100% en Taquile (n=57; 88,6% en Amantaní (n=35; 75% en Los Uros (n=28 y 87,5% en Anapia (n=24, siendo las frecuencias más altas registradas en el mundo. Otros haplotipos se observan en menor proporción: 17,9% de A2 y 7,1% de D1 en Los Uros; 11,4% de la variante C1 en Amantaní; 4,2% de cada haplotipo C1, C2 y D1 en Anapia. La alta frecuencia de B1 indica que las poblaciones de Taquile, Amantaní y Anapia provienen de un grupo fundador reducido. Aunque hay afinidad entre las poblaciones aymaras de Anapia y Los Uros; la proporción de algunos alelos en los últimos, sugiere la persistencia de un acervo genético uru en contraposición a la idea de su extinción.

Furaldehyde substrate specificity and kinetics of Saccharomyces cerevisiae alcohol dehydrogenase 1 variants.

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Laadan, Boaz; Wallace-Salinas, Valeria; Carlsson, Åsa Janfalk; Almeida, João Rm; Rådström, Peter; Gorwa-Grauslund, Marie F

2014-08-09

A previously discovered mutant of Saccharomyces cerevisiae alcohol dehydrogenase 1 (Adh1p) was shown to enable a unique NADH-dependent reduction of 5-hydroxymethylfurfural (HMF), a well-known inhibitor of yeast fermentation. In the present study, site-directed mutagenesis of both native and mutated ADH1 genes was performed in order to identify the key amino acids involved in this substrate shift, resulting in Adh1p-variants with different substrate specificities. In vitro activities of the Adh1p-variants using two furaldehydes, HMF and furfural, revealed that HMF reduction ability could be acquired after a single amino acid substitution (Y295C). The highest activity, however, was reached with the double mutation S110P Y295C. Kinetic characterization with both aldehydes and the in vivo primary substrate acetaldehyde also enabled to correlate the alterations in substrate affinity with the different amino acid substitutions. We demonstrated the key role of Y295C mutation in HMF reduction by Adh1p. We generated and kinetically characterized a group of protein variants using two furaldehyde compounds of industrial relevance. Also, we showed that there is a threshold after which higher in vitro HMF reduction activities do not correlate any more with faster in vivo rates of HMF conversion, indicating other cell limitations in the conversion of HMF.

Mapping of Epitopes Occurring in Bovine α(s1)-Casein Variants by Peptide Microarray Immunoassay.

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Lisson, Maria; Erhardt, Georg

2016-01-01

Immunoglobulin E epitope mapping of milk proteins reveals important information about their immunologic properties. Genetic variants of αS1-casein, one of the major allergens in bovine milk, are until now not considered when discussing the allergenic potential. Here we describe the complete procedure to assess the allergenicity of αS1-casein variants B and C, which are frequent in most breeds, starting from milk with identification and purification of casein variants by isoelectric focusing (IEF) and anion-exchange chromatography, followed by in vitro gastrointestinal digestion of the casein variants, identification of the resulting peptides by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), in silico analysis of the variant-specific peptides as allergenic epitopes, and determination of their IgE-binding properties by microarray immunoassay with cow's milk allergic human sera.

Genes y variantes polimórficas asociadas a la enfermedad cardiovascular

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Eliana C. Portilla

2014-09-01

Full Text Available La aterosclerosis se considera como la principal causante de enfermedades cardiovasculares. Es una enfermedad multifactorial, caracterizada por procesos inflamatorios y la internalización continua de moléculas lipídicas al interior del vaso. Los estudios de genes candidato han proporcionado conocimiento acerca de la fisiopatología de esta enfermedad y han permitido la postulación de algunos polimorfismos como responsables de la susceptibilidad genética en diversas poblaciones. En particular, estos polimorfismos que modulan ciertas vías moleculares tales como el estrés oxidativo, el metabolismo lipídico y la trombogénesis se asocian con el desarrollo de las enfermedades cardiovasculares. Se han conducido varios estudios para identificar nuevas variantes asociadas con la enfermedad que han permitido el descubrimiento de nuevas vías de la enfermedad. Aunque el hallazgo de nuevos genes asociados a la enfermedad cardiovascular a través de enfoques como el escaneo global del genoma ha contribuido al entendimiento del desarrollo de esta condición, el conocimiento aún es limitado y poco concluyente. El objetivo de esta revisión es identificar los genes y las variantes polimórficas asociadas a la enfermedad cardiovascular, de acuerdo con los diferentes enfoques de análisis de asociación genética.

Significance of ubiquitin carboxy-terminal hydrolase L1 elevations in athletes after sub-concussive head hits.

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Vikram Puvenna

Full Text Available The impact of sub-concussive head hits (sub-CHIs has been recently investigated in American football players, a population at risk for varying degrees of post-traumatic sequelae. Results show how sub-CHIs in athletes translate in serum as the appearance of reporters of blood-brain barrier disruption (BBBD, how the number and severity of sub-CHIs correlate with elevations of putative markers of brain injury is unknown. Serum brain injury markers such as UCH-L1 depend on BBBD. We investigated the effects of sub-CHIs in collegiate football players on markers of BBBD, markers of cerebrospinal fluid leakage (serum beta 2-transferrin and markers of brain damage. Emergency room patients admitted for a clinically-diagnosed mild traumatic brain injury (mTBI were used as positive controls. Healthy volunteers were used as negative controls. Specifically this study was designed to determine the use of UCH-L1 as an aid in the diagnosis of sub-concussive head injury in athletes. The extent and intensity of head impacts and serum values of S100B, UCH-L1, and beta-2 transferrin were measured pre- and post-game from 15 college football players who did not experience a concussion after a game. S100B was elevated in players experiencing the most sub-CHIs; UCH-L1 levels were also elevated but did not correlate with S100B or sub-CHIs. Beta-2 transferrin levels remained unchanged. No correlation between UCH-L1 levels and mTBI were measured in patients. Low levels of S100B were able to rule out mTBI and high S100B levels correlated with TBI severity. UCH-L1 did not display any interpretable change in football players or in individuals with mild TBI. The significance of UCH-L1 changes in sub-concussions or mTBI needs to be further elucidated.

[Preparation and spectral characterization of CdS(y)Te(1-y) thin films].

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Li, Wei; Feng, Liang-Huan; Wu, Li-Li; Zhang, Jing-Quan; Li, Bing; Lei, Zhi; Cai, Ya-Ping; Zheng, Jia-Gui; Cai, Wei; Zhang, Dong-Min

2008-03-01

CdS(y)Te(1-y) (0 co-evaporation of powders of CdTe and CdS. For the characterization of the structure and composition of the CdS(y)Te(1-y) thin films the X-ray diffraction (XRD) and energy-dispersive spectroscopy (EDS) were used. The results indicate that the values of sulfur content y detected and controlled by the quartz wafer detector show good agreement with the EDS results. The films were found to be cubic for x or = 0.3. The 20-50 nm of grain sizes for CdS(y)Te(1-y) thin films were calculated using a method of XRD analysis. Finally, the optical properties of CdS(y)Te(1-y) thin films were characterized by UV-Vis-NIR spectroscopy alone. According to a method from Swanepoel, together with the first-order Sellmeier model, the thickness, of d-535 nm, energy gap of E(g)-1.41 eV, absorption coefficient, alpha(lambda) and refractive index, n(lambda) of CdS(0.22) Te(0.78) thin films were determined from the transmittance at normal incidence of light in the wavelength range 300-2 500 nm. The results also indicate that the CdS(y)Te(1-y) thin films with any composition (0 co-evaporation, and the method to characterize the optical properties of CdS(y)Te(1-y) thin films can be implemented for other semiconductor thin films.

Variantes moleculares en el gen L1 del virus del papiloma humano tipo 16, y regiones de la proteína L1 probablemente involucradas en la interacción virus-célula epitelial

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María Mercedes Bravo

2004-03-01

Full Text Available

La infección con virus del papiloma humano de alto riesgo es considerada como el principal factor de riesgo en el desarrollo del cáncer de cuello uterino. Entre los HPV de alto riesgo, el tipo 16 es el más frecuente tanto en mujeres con citología normal, como en mujeres con lesiones premalignas y en cáncer invasivo. Se ha demostrado la existencia de variaciones en la secuencia del genoma de HPV16, estos polimorfismos se han agrupado en cinco ramas filogenéticas denominadas según su distribución geográfica: Europeas (E, Asiaticas-Americanas (AA, Asiáticas (As, Africanas (Af y Norteamericanas (NA; determinadas por sustituciones nucleotídicas en los genes E6, L1 y L2 y la región larga de control.

Varios estudios han sugerido que las variantes no Europeas son más agresivas que las Europeas, esto puede ser el reflejo de una interacción diferente con el huésped y por tanto implicar diferencias en el resultado final de la infección (mayor persistencia o mayor oncogenicidad.

Particularmente se ha demostrado que las variaciones en la secuencia de aminoácidos de la proteína L1, la proteína principal de la cápside viral, pueden modificar las epítopes neutralizantes del virus afectando la efectividad de la respuesta inmune, también estas variaciones pueden afectar la capacidad de ensamble de las cápsides y la afinidad por receptores a nivel epitelial.

El propósito de este estudio fue identificar las variaciones moleculares del gen L1 de HPV16 en aislamientos provenientes de cepillados cervicales de mujeres colombianas con citología normal y con cáncer de cuello uterino, con el fin de analizar si existen variaciones que alteren las regiones

Regulation of synaptic structure by ubiquitin C-terminal hydrolase L1.

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Cartier, Anna E; Djakovic, Stevan N; Salehi, Afshin; Wilson, Scott M; Masliah, Eliezer; Patrick, Gentry N

2009-06-17

Ubiquitin C-terminal hydrolase L1 (UCH-L1) is a deubiquitinating enzyme that is selectively and abundantly expressed in the brain, and its activity is required for normal synaptic function. Here, we show that UCH-L1 functions in maintaining normal synaptic structure in hippocampal neurons. We found that UCH-L1 activity is rapidly upregulated by NMDA receptor activation, which leads to an increase in the levels of free monomeric ubiquitin. Conversely, pharmacological inhibition of UCH-L1 significantly reduces monomeric ubiquitin levels and causes dramatic alterations in synaptic protein distribution and spine morphology. Inhibition of UCH-L1 activity increases spine size while decreasing spine density. Furthermore, there is a concomitant increase in the size of presynaptic and postsynaptic protein clusters. Interestingly, however, ectopic expression of ubiquitin restores normal synaptic structure in UCH-L1-inhibited neurons. These findings point to a significant role of UCH-L1 in synaptic remodeling, most likely by modulating free monomeric ubiquitin levels in an activity-dependent manner.

The D313Y variant in the GLA gene - no evidence of a pathogenic role in Fabry disease

DEFF Research Database (Denmark)

Hasholt, Lis; Ballegaard, Martin; Bundgaard, Henning

2017-01-01

Fabry disease is an X- linked inherited lysosomal storage disease caused by mutations in the GLA gene encoding the lysosomal enzyme alpha-galactosidase A (α-Gal A). The possible pathological significance of the D313Y variant in the GLA gene has not been verified and it may be a Fabry variant. Our......, and the presence in Fabry females did not significantly enhance the phenotype of a known causative mutation in the GLA gene (G271S). Our findings indicate that the D313Y variant is not causative to nor enhancing Fabry disease phenotype. The D313Y variant in the GLA gene was not disease causative in 2 Danish...... families. Investigating male family members were crucial in excluding the Fabry phenotype, and thus very important for proper genetic counceling of all family members, as well as overdiagnosing a devastating genetic disease....

Influence of HFE variants and cellular iron on monocyte chemoattractant protein-1

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Simmons Zachary

2009-02-01

Full Text Available Abstract Background Polymorphisms in the MHC class 1-like gene known as HFE have been proposed as genetic modifiers of neurodegenerative diseases that include neuroinflammation as part of the disease process. Variants of HFE are relatively common in the general population and are most commonly associated with iron overload, but can promote subclinical cellular iron loading even in the absence of clinically identified disease. The effects of the variants as well as the resulting cellular iron dyshomeostasis potentially impact a number of disease-associated pathways. We tested the hypothesis that the two most common HFE variants, H63D and C282Y, would affect cellular secretion of cytokines and trophic factors. Methods We screened a panel of cytokines and trophic factors using a multiplexed immunoassay in human neuroblastoma SH-SY5Y cells expressing different variants of HFE. The influence of cellular iron secretion on the potent chemokine monocyte chemoattractant protein-1 (MCP-1 was assessed using ferric ammonium citrate and the iron chelator, desferroxamine. Additionally, an antioxidant, Trolox, and an anti-inflammatory, minocycline, were tested for their effects on MCP-1 secretion in the presence of HFE variants. Results Expression of the HFE variants altered the labile iron pool in SH-SY5Y cells. Of the panel of cytokines and trophic factors analyzed, only the release of MCP-1 was affected by the HFE variants. We further examined the relationship between iron and MCP-1 and found MCP-1 secretion tightly associated with intracellular iron status. A potential direct effect of HFE is considered because, despite having similar levels of intracellular iron, the association between HFE genotype and MCP-1 expression was different for the H63D and C282Y HFE variants. Moreover, HFE genotype was a factor in the effect of minocycline, a multifaceted antibiotic used in treating a number of neurologic conditions associated with inflammation, on MCP-1

Studies of CTNNBL1 and FDFT1 variants and measures of obesity: analyses of quantitative traits and case-control studies in 18,014 Danes

DEFF Research Database (Denmark)

Andreasen, Camilla Helene; Mogensen, Mette Sloth; Borch-Johnsen, Knut

2009-01-01

of obesity-related quantitative traits, and case-control studies in large study samples of Danes. METHODS: The FDFT1 rs7001819, CTNNBL1 rs6013029 and rs6020846 were genotyped, using TaqMan allelic discrimination, in a combined study sample comprising 18,014 participants ascertained from; the population...... and a previous study. FDFT1 rs7001819 showed no association with obesity, neither when analysing quantitative traits nor when performing case-control studies of obesity.......). The most significantly associating variants within CTNNBL1 including rs6013029 and rs6020846 were additionally confirmed to associate with morbid obesity in a French Caucasian case-control sample. The aim of this study was to investigate the impact of these three variants on obesity, through analyses...

C282Y-HFE gene variant affects cholesterol metabolism in human neuroblastoma cells.

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Ali-Rahmani, Fatima; Huang, Michael A; Schengrund, C-L; Connor, James R; Lee, Sang Y

2014-01-01

Although disruptions in the maintenance of iron and cholesterol metabolism have been implicated in several cancers, the association between variants in the HFE gene that is associated with cellular iron uptake and cholesterol metabolism has not been studied. The C282Y-HFE variant is a risk factor for different cancers, is known to affect sphingolipid metabolism, and to result in increased cellular iron uptake. The effect of this variant on cholesterol metabolism and its possible relevance to cancer phenotype was investigated using wild type (WT) and C282Y-HFE transfected human neuroblastoma SH-SY5Y cells. Expression of C282Y-HFE in SH-SY5Y cells resulted in a significant increase in total cholesterol as well as increased transcription of a number of genes involved in its metabolism compared to cells expressing WT-HFE. The marked increase in expression of NPC1L1 relative to that of most other genes, was accompanied by a significant increase in expression of NPC1, a protein that functions in cholesterol uptake by cells. Because inhibitors of cholesterol metabolism have been proposed to be beneficial for treating certain cancers, their effect on the viability of C282Y-HFE neuroblastoma cells was ascertained. C282Y-HFE cells were significantly more sensitive than WT-HFE cells to U18666A, an inhibitor of desmosterol Δ24-reductase the enzyme catalyzing the last step in cholesterol biosynthesis. This was not seen for simvastatin, ezetimibe, or a sphingosine kinase inhibitor. These studies indicate that cancers presenting in carriers of the C282Y-HFE allele might be responsive to treatment designed to selectively reduce cholesterol content in their tumor cells.

NMNAT1 variants cause cone and cone-rod dystrophy.

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Nash, Benjamin M; Symes, Richard; Goel, Himanshu; Dinger, Marcel E; Bennetts, Bruce; Grigg, John R; Jamieson, Robyn V

2018-03-01

Cone and cone-rod dystrophies (CD and CRD, respectively) are degenerative retinal diseases that predominantly affect the cone photoreceptors. The underlying disease gene is not known in approximately 75% of autosomal recessive cases. Variants in NMNAT1 cause a severe, early-onset retinal dystrophy called Leber congenital amaurosis (LCA). We report two patients where clinical phenotyping indicated diagnoses of CD and CRD, respectively. NMNAT1 variants were identified, with Case 1 showing an extremely rare homozygous variant c.[271G > A] p.(Glu91Lys) and Case 2 compound heterozygous variants c.[53 A > G];[769G > A] p.(Asn18Ser);(Glu257Lys). The detailed variant analysis, in combination with the observation of an associated macular atrophy phenotype, indicated that these variants were disease-causing. This report demonstrates that the variants in NMNAT1 may cause CD or CRD associated with macular atrophy. Genetic investigations of the patients with CD or CRD should include NMNAT1 in the genes examined.

Variants in SLC18A3, vesicular acetylcholine transporter, cause congenital myasthenic syndrome

NARCIS (Netherlands)

O'Grady, Gina L.; Verschuuren, Corien; Yuen, Michaela; Webster, Richard; Menezes, Manoj; Fock, Johanna M.; Pride, Natalie; Best, Heather A.; Damm, Tatiana Benavides; Turner, Christian; Lek, Monkol; Engel, Andrew G.; North, Kathryn N.; Clarke, Nigel F.; MacArthur, Daniel G.; Kamsteeg, Erik-Jan; Cooper, Sandra T.

2016-01-01

Objective: To describe the clinical and genetic characteristics of presynaptic congenital myasthenic syndrome secondary to biallelic variants in SLC18A3. Methods: Individuals from 2 families were identified with biallelic variants in SLC18A3, the gene encoding the vesicular acetylcholine transporter

Variantes histológicas y factores pronósticos del carcinoma papilar de tiroides en el Instituto Nacional de Cancerología de Colombia, 2006-2012

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Alfredo Romero-Rojas

2015-09-01

Full Text Available Introducción. El cáncer de tiroides es la neoplasia más común y el subtipo papilar es el más frecuente; hay factores histológicos y clínicos asociados con un mayor riesgo de recidiva y metástasis. Objetivo. Examinar las características histológicas, clínicas y de pronóstico de los carcinomas papilares de tiroides diagnosticados en el Instituto Nacional de Cancerología de Colombia. Materiales y métodos. Se llevó a cabo un estudio de cohorte retrospectiva que incluyó a 619 pacientes con carcinoma papilar de tiroides entre 2006 y 2012; se analizaron las características sociodemográficas, histológicas, de pronóstico y clínicas. Resultados. El 87,7% de casos correspondió a mujeres. La presencia de dos o más variantes histológicas en un mismo caso se consideró como una variante a la cual se denominó patrón combinado; esta fue la más frecuente (50,9 %, seguida de la variante folicular (23,4 %, incluidos los subtipos encapsulados o no encapsulado y la variante clásica (22,1 %. El promedio del tamaño tumoral fue de 20,8 mm. En más de la mitad de los casos se evidenció invasión capsular, invasión extratiroidea y metástasis en ganglios linfáticos. Comparados con otras variantes histológicas, los carcinomas con patrón combinado presentaron mayor riesgo de invasión de la cápsula tiroidea, de invasión extraganglionar y de metástasis. Conclusión. En muchos aspectos los resultados fueron similares a los reportados previamente; sin embargo, se encontró que la presencia del patrón combinado aumentaba el riesgo de invasión capsular, metástasis en nódulos linfoides y extensión extratiroidea en comparación con los que tenían una sola variante. Sería necesario hacer estudios acerca del mecanismo biológico de la diferenciación en células cancerosas con el fin de ahondar sobre este fenómeno.

Ternary gallides RE_4Rh_9Ga_5, RE_5Rh_1_2Ga_7 and RE_7Rh_1_8Ga_1_1 (RE=Y, La-Nd, Sm, Gd, Tb). Intergrowth structures with MgCu_2 and CaCu_5 related slabs

International Nuclear Information System (INIS)

Seidel, Stefan; Rodewald, Ute C.; Poettgen, Rainer; Janka, Oliver

2017-01-01

Fourteen ternary gallides RE_4Rh_9Ga_5, RE_5Rh_1_2Ga_7 and RE_7Rh_1_8Ga_1_1 (RE=Y, La-Nd, Sm, Gd, Tb) were synthesized from the elements by arc-melting, followed by different annealing sequences either in muffle or induction furnaces. The samples were characterized through Guinier powder patterns and the crystal structures of Ce_4Rh_9Ga_5, Ce_5Rh_1_2Ga_7, Ce_7Rh_1_8Ga_1_1, Nd_5Rh_1_0_._4_4_(_4_)Ga_8_._5_6_(_4_), Nd_4Rh_9Ga_5 and Gd_4Rh_9Ga_5 were refined from single crystal X-ray diffractometer data. The new gallides are the n=2, 3 and 5 members of the RE_2_+_n Rh_3_+_3_n Ga_1_+_2_n structure series in the Parthe intergrowth concept. The slabs of these intergrowth structures derive from the cubic Laves phase MgCu_2 (Mg_2Ni_3Si as ternary variant) and CaCu_5 (CeCo_3B_2 as ternary variant). Only the Nd_5Rh_1_0_._4_4_(_4_)Ga_8_._5_6_(_4_) crystal shows Rh/Ga mixing within the Laves type slabs. Magnetic susceptibility measurements reveal Pauli paramagnetism for Y_4Rh_9Ga_5 and Curie-Weiss paramagnetism for Gd_4Rh_9Ga_5 and Tb_4Rh_9Ga_5. Low-temperature data show ferromagnetic ordering at T_C=78.1 (Gd_4Rh_9Ga_5) and 55.8 K (Tb_4Rh_9Ga_5).

Affinity purification of human factor H on polypeptides derived from streptococcal m protein: enrichment of the Y402 variant.

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O Rickard Nilsson

Full Text Available Recent studies indicate that defective activity of complement factor H (FH is associated with several human diseases, suggesting that pure FH may be used for therapy. Here, we describe a simple method to isolate human FH, based on the specific interaction between FH and the hypervariable region (HVR of certain Streptococcus pyogenes M proteins. Special interest was focused on the FH polymorphism Y402H, which is associated with the common eye disease age-related macular degeneration (AMD and has also been implicated in the binding to M protein. Using a fusion protein containing two copies of the M5-HVR, we found that the Y402 and H402 variants of FH could be efficiently purified by single-step affinity chromatography from human serum containing the corresponding protein. Different M proteins vary in their binding properties, and the M6 and M5 proteins, but not the M18 protein, showed selective binding of the FH Y402 variant. Accordingly, chromatography on a fusion protein derived from the M6-HVR allowed enrichment of the Y402 protein from serum containing both variants. Thus, the exquisite binding specificity of a bacterial protein can be exploited to develop a simple and robust procedure to purify FH and to enrich for the FH variant that protects against AMD.

HFE p.C282Y gene variant is associated with varicose veins in Russian population.

Science.gov (United States)

Sokolova, Ekaterina A; Shadrina, Alexandra S; Sevost'ianova, Kseniya S; Shevela, Andrey I; Soldatsky, Evgenii Yu; Seliverstov, Evgenii I; Demekhova, Marina Yu; Shonov, Oleg A; Ilyukhin, Evgenii A; Smetanina, Mariya A; Voronina, Elena N; Zolotukhin, Igor A; Filipenko, Maxim L

2016-08-01

Recently, the association of polymorphism rs1800562 (p.C282Y) in the hemochromatosis (HFE) gene with the increased risk of venous ulceration was shown. We hypothesized that HFE gene polymorphism might be involved not only in ulceration process, but also in susceptibility to primary varicose veins. We genotyped HFE p.C282Y (rs1800562) and p.H63D (rs1799945) variants in patients with primary varicose veins (n = 463) and in the control group (n = 754). In our study, p.282Y variant (rs1800562 A allele) was significantly associated with the risk of varicose veins (OR 1.79, 95 % CI = 1.11-2.89, P = 0.02). A borderline significant reverse association of p.63D variant (rs1799945 G allele) with venous leg ulcer development was revealed in Russians (OR 0.25, 95 % CI = 0.06-1.00, P = 0.05), but not in the meta-analysis (P = 0.56). We conclude that the HFE gene polymorphism can affect the risk of developing primary varicose veins.

A S52P mutation in the 'α-crystallin domain' of Mycobacterium leprae HSP18 reduces its oligomeric size and chaperone function.

Science.gov (United States)

Nandi, Sandip K; Rehna, Elengikal A A; Panda, Alok K; Shiburaj, Sugathan; Dharmalingam, Kuppamuthu; Biswas, Ashis

2013-12-01

Mycobacterium leprae HSP18 is a small heat shock protein (sHSP). It is a major immunodominant antigen of M. leprae pathogen. Previously, we have reported the existence of two M. leprae HSP18 variants in various leprotic patients. One of the variants has serine at position 52, whereas the other one has proline at the same position. We have also reported that HSP18 having proline at position 52 (HSP18P(52)) is a nonameric protein and exhibits chaperone function. However, the structural and functional characterization of wild-type HSP18 having serine at position 52 (HSP18S(52)) is yet to be explored. Furthermore, the implications of the S52P mutation on the structure and chaperone function of HSP18 are not well understood. Therefore, we cloned and purified these two HSP18 variants. We found that HSP18S(52) is also a molecular chaperone and an oligomeric protein. Intrinsic tryptophan fluorescence and far-UV CD measurements revealed that the S52P mutation altered the tertiary and secondary structure of HSP18. This point mutation also reduced the oligomeric assembly and decreased the surface hydrophobicity of HSP18, as revealed by HPLC and 4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid binding studies, respectively. Mutant protein was less stable against thermal and chemical denaturation and was more susceptible towards tryptic cleavage than wild-type HSP18. HSP18P(52) had lower chaperone function and was less effective in protecting thermal killing of Escherichia coli than HSP18S(52). Taken together, our data suggest that serine 52 is important for the larger oligomerization and chaperone function of HSP18. Because both variants differ in stability and function, they may have different roles in the survival of M. leprae in infected hosts. © 2013 FEBS.

Observation of spin reorientation in layered manganites La1.2Sr1.8(Mn1-yRuy)2O7 (0.0=<y=<0.2) by Lorentz transmission electron microscopy

International Nuclear Information System (INIS)

Yu, X.Z.; Uchida, M.; Onose, Y.; He, J.P.; Kaneko, Y.; Asaka, T.; Kimoto, K.; Matsui, Y.; Arima, T.; Tokura, Y.

2006-01-01

The effect of Ru substitution for Mn in bilayered oxides La 1.2 Sr 1.8 (Mn 1-y Ru y ) 2 O 7 (0= for the y=0 crystal to the c-axis for y=0.2, and it rotates away from the c-axis for the y=0.05 and y=0.07 crystals with decreasing temperature. Furthermore, maze-shaped magnetic domain structures were observed in the (001) thin crystals with 0.05=< y=<0.2. Changes in domain size and structure indicate that the uniaxial magnetic anisotropy becomes stronger as Ru content y increases

Ubiquitin carboxyl terminal hydrolase L1 negatively regulates TNFα-mediated vascular smooth muscle cell proliferation via suppressing ERK activation

International Nuclear Information System (INIS)

Ichikawa, Tomonaga; Li, Jinqing; Dong, Xiaoyu; Potts, Jay D.; Tang, Dong-Qi; Li, Dong-Sheng; Cui, Taixing

2010-01-01

Deubiquitinating enzymes (DUBs) appear to be critical regulators of a multitude of processes such as proliferation, apoptosis, differentiation, and inflammation. We have recently demonstrated that a DUB of ubiquitin carboxyl terminal hydrolase L1 (UCH-L1) inhibits vascular lesion formation via suppressing inflammatory responses in vasculature. However, the precise underlying mechanism remains to be defined. Herein, we report that a posttranscriptional up-regulation of UCH-L1 provides a negative feedback to tumor necrosis factor alpha (TNFα)-mediated activation of extracellular signal-regulated kinases (ERK) and proliferation in vascular smooth muscle cells (VSMCs). In rat adult VSMCs, adenoviral over-expression of UCH-L1 inhibited TNFα-induced activation of ERK and DNA synthesis. In contrast, over-expression of UCH-L1 did not affect platelet derived growth factor (PDGF)-induced VSMC proliferation and activation of growth stimulating cascades including ERK. TNFα hardly altered UCH-L1 mRNA expression and stability; however, up-regulated UCH-L1 protein expression via increasing UCH-L1 translation. These results uncover a novel mechanism by which UCH-L1 suppresses vascular inflammation.

HFE gene C282Y variant is associated with colorectal cancer in Caucasians: a meta-analysis.

Science.gov (United States)

Chen, Weidong; Zhao, Hua; Li, Tiegang; Yao, Hongliang

2013-08-01

The HFE gene has been suggested to play an important role in the pathogenesis of colorectal cancer. However, the results have been conflicting. In this study, we performed a meta-analysis to clarify the association of HFE gene C282Y variant with colorectal cancer. PubMed and Embase were retrieved to identify the potential literature. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated using fixed- or random-effects model. A total of eight papers including nine studies (7,588 colorectal cancer cases and 81,571 controls) for HFE gene C282Y variant were included in the meta-analysis. The result indicated that HFE gene C282Y variant was significantly associated with colorectal cancer under recessive model (OR = 2.00, 95 % CI = 1.32-3.04), with no evidence of between-study heterogeneity (I (2) = 0.2 %, p = 0.432). Further subgroup analysis by number of cases suggested the effect was significant in studies with more than 500 cases (OR = 2.51, 95 % CI = 1.58-3.98, I (2) = 0.0 %, p = 0.921), but not in studies with less than 500 cases (OR = 0.75, 95 % CI = 0.28-1.97, I (2) = 0.0 %, p = 0.622). The current meta-analysis supported the positive association of HFE gene C282Y variant with colorectal cancer. Further large-scale studies with the consideration for gene-gene/gene-environment interactions should be conducted to investigate the association.

The MLH1 c.1852_1853delinsGC (p.K618A variant in colorectal cancer: genetic association study in 18,723 individuals.

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Anna Abulí

Full Text Available Colorectal cancer is one of the most frequent neoplasms and an important cause of mortality in the developed world. Mendelian syndromes account for about 5% of the total burden of CRC, being Lynch syndrome and familial adenomatous polyposis the most common forms. Lynch syndrome tumors develop mainly as a consequence of defective DNA mismatch repair associated with germline mutations in MLH1, MSH2, MSH6 and PMS2. A significant proportion of variants identified by screening these genes correspond to missense or noncoding changes without a clear pathogenic consequence, and they are designated as "variants of uncertain significance", being the c.1852_1853delinsGC (p.K618A variant in the MLH1 gene a clear example. The implication of this variant as a low-penetrance risk variant for CRC was assessed in the present study by performing a case-control study within a large cohort from the COGENT consortium-COST Action BM1206 including 18,723 individuals (8,055 colorectal cancer cases and 10,668 controls and a case-only genotype-phenotype correlation with several clinical and pathological characteristics restricted to the Epicolon cohort. Our results showed no involvement of this variant as a low-penetrance variant for colorectal cancer genetic susceptibility and no association with any clinical and pathological characteristics including family history for this neoplasm or Lynch syndrome.

Una variante del gen CAPN10 y los factores ambientales muestran asociación con el exceso de peso en jóvenes colombianos

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Ana C. Orozco

2014-12-01

Full Text Available Introducción. La obesidad resulta de la interacción entre factores de riesgo genéticos y ambientales. Objetivo. Evaluar el efecto de tres variantes genéticas y factores ambientales en el exceso de peso en jóvenes de 10 a 18 años de Medellín, Colombia. Materiales y métodos. Se hizo un estudio transversal en 424 jóvenes divididos en tres grupos: 100 obesos, 112 jóvenes con sobrepeso, y, pareados con ellos, 212 jóvenes con peso adecuado, que conformaron el grupo de control. Se evaluó la asociación entre tres polimorfismos genéticos (UCP3-rs1800849, FTO-rs17817449 y CAPN10-rs3842570 y el exceso de peso, así como su interacción con antecedentes familiares de enfermedad, el tiempo dedicado a ver televisión y a jugar videojuegos y el consumo de alimentos. Resultados. Los antecedentes familiares de obesidad, la dedicación de más de dos horas al día a ver televisión y jugar videojuegos, la falta de lactancia materna, el bajo consumo de cereales, legumbres, frutas y verduras y el gran consumo de comidas rápidas fueron más frecuentes entre los obesos que en los controles. Se observó una asociación significativa entre el genotipo I/I (SNP19 del CAPN10 y el exceso de peso, incluso en los jóvenes que llevaban una vida activa. Además, se encontró una asociación significativa entre los genotipos C/C del UCP3 y G/G y T/T del FTO y el exceso de peso, pero solo en los jóvenes sedentarios. Conclusiones. En esta población, la alimentación inadecuada y el sedentarismo aumentaron el riesgo de exceso de peso. El genotipo I/I de SNP19 del CAPN10 se asoció significativamente con el exceso de peso. Algunas variantes del FTO y el UCP3 mostraron tener efecto solo en jóvenes sedentarios.

Investigação de variantes gênicas de canais iônicos em pacientes com síndrome do QT longo Investigación de variantes génicas de canales iónicos en pacientes con síndrome del QT largo Investigation of ion channel gene variants in patients with long QT syndrome

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Ernesto Curty

2011-03-01

Full Text Available FUNDAMENTO: A síndrome do QT longo (SQTL é uma síndrome arrítmica herdada com aumento do intervalo QT e risco de morte súbita. Mutações nos genes KCNQ1, KCNH2 e SCN5A respondem por 90% dos casos com genótipo determinado, e a genotipagem é informativa para aconselhamento genético e melhor manejo da doença. OBJETIVO: Investigação molecular e análise computacional de variantes gênicas de KCNQ1, KCNH2 e SCN5A associadas à SQTL em famílias portadoras da doença. MÉTODOS: As regiões codificantes dos genes KCNQ1, KCNH2 e SCN5A de pacientes com SQTL e familiares foram sequenciadas e analisadas utilizando o software Geneious ProTM. RESULTADOS: Foram investigadas duas famílias com critérios clínicos para SQTL. A probanda da Família A apresentava QTC = 562 ms, Escore de Schwartz = 5,5. A genotipagem identificou a mutação G1714A no gene KCNH2. Foi observado QTC = 521 ± 42 ms nos familiares portadores da mutação contra QTC = 391 ± 21 ms de não portadores. A probanda da Família B apresentava QTc = 551 ms, Escore de Schwartz = 5. A genotipagem identificou a mutação G1600T, no mesmo gene. A análise dos familiares revelou QTC = 497 ± 42 ms nos portadores da mutação, contra QTC = 404 ± 29 ms nos não portadores. CONCLUSÃO: Foram encontradas duas variantes gênicas previamente associadas à SQTL em duas famílias com diagnóstico clínico de SQTL. Em todos os familiares portadores das mutações foi observado o prolongamento do intervalo QT. Foi desenvolvida uma estratégia para identificação de variantes dos genes KCNQ1, KCNH2 e SCN5A, possibilitando o treinamento de pessoal técnico para futura aplicação na rotina diagnóstica.FUNDAMENTO: El síndrome del QT largo (SQTL es un síndrome arrítmico heredado con aumento del intervalo QT y riesgo de muerte súbita. Mutaciones en los genes KCNQ1, KCNH2 y SCN5A responden por 90% de los casos con genotipo determinado, y el genotipaje es informativo para aconsejamiento gen

Meta-analysis of rare and common exome chip variants identifies S1PR4 and other loci influencing blood cell traits

DEFF Research Database (Denmark)

Pankratz, Nathan; Schick, Ursula M; Zhou, Yi

2016-01-01

with Illumina HumanExome BeadChip genotypes. We then performed replication analyses of new discoveries in 18,018 European-American women and 5,261 Han Chinese. We identified and replicated four new erythrocyte trait-locus associations (CEP89, SHROOM3, FADS2, and APOE) and six new WBC loci for neutrophil count...... (S1PR4), monocyte count (BTBD8, NLRP12, and IL17RA), eosinophil count (IRF1), and total WBC count (MYB). The association of a rare missense variant in S1PR4 supports the role of sphingosine-1-phosphate signaling in leukocyte trafficking and circulating neutrophil counts. Loss-of-function experiments...... for S1pr4 in mouse and s1pr4 in zebrafish demonstrated phenotypes consistent with the association observed in humans and altered kinetics of neutrophil recruitment and resolution in response to tissue injury....

UCH-L1 and GFAP Serum Levels in Neonates with Hypoxic-Ischemic Encephalopathy: A single center pilot study

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Martha V. Douglas-Escobar

2014-12-01

Full Text Available Objective - We examined two potential biomarkers of brain damage in HIE neonates: glial fibrillary acidic protein (GFAP; a marker of gliosis and ubiquitin C-terminal hydrolase L1 (UCH-L1; a marker of neuronal injury. We hypothesized the biomarkers would be measurable in cord blood of healthy neonates and could serve as a normative reference for brain injury in HIE infants. Further, we hypothesized that serum samples of HIE neonates would have higher levels and would correlate with brain damage on MRI and later developmental outcomes.Study Design - Serum UCH - L1 and GFAP concentrations from HIE neonates(n = 16 were compared with controls(n = 11.Pearson correlation coefficients and a mixed model design examined the relationship between biomarker concentrations of HIE neonates and brain damage(MRI and developmental outcomes(Bayley - III.Result– Both biomarkers were detected in cord blood from control subjects.UCH - L1 concentrations were higher in HIE neonates(p < 0.001 and associated with cortical injury(p < 0.055 and later motor and cognitive developmental outcomes(p < 0.05.The temporal change in GFAP concentrations from birth to 96 hours of age predicted motor developmental outcomes(p < 0.05 and injury to the basal ganglia and white matter.Conclusion– UCH - L1 concentrations correlated with cortical injury and developmental delays and GFAP concentrations correlated with basal ganglia and white matter injury and motor delay in HIE affected patients.Researchers should continue to explore UCH - L1 and GFAP as promising serum biomarkers of brain damage and predictors of neurodevelopmental outcomes in neonates with HIE.

Phase conversion from hexagonal CuS(y)Se(1-y) to cubic Cu(2-x)S(y)Se(1-y): composition variation, morphology evolution, optical tuning, and solar cell applications.

Science.gov (United States)

Xu, Jun; Yang, Xia; Yang, Qingdan; Zhang, Wenjun; Lee, Chun-Sing

2014-09-24

In this work, we report a simple and low-temperature approach for the controllable synthesis of ternary Cu-S-Se alloys featuring tunable crystal structures, compositions, morphologies, and optical properties. Hexagonal CuS(y)Se(1-y) nanoplates and face centered cubic (fcc) Cu(2-x)S(y)Se(1-y) single-crystal-like stacked nanoplate assemblies are synthesized, and their phase conversion mechanism is well investigated. It is found that both copper content and chalcogen composition (S/Se atomic ratio) of the Cu-S-Se alloys are tunable during the phase conversion process. Formation of the unique single-crystal-like stacked nanoplate assemblies is resulted from oriented stacking coupled with the Ostwald ripening effect. Remarkably, optical tuning for continuous red shifts of both the band-gap absorption and the near-infrared localized surface plasmon resonance are achieved. Furthermore, the novel Cu-S-Se alloys are utilized for the first time as highly efficient counter electrodes (CEs) in quantum dot sensitized solar cells (QDSSCs), showing outstanding electrocatalytic activity for polysulfide electrolyte regeneration and yielding a 135% enhancement in power conversion efficiency (PCE) as compared to the noble metal Pt counter electrode.

The interaction of glutathione S-transferase M1-null variants with tobacco smoke exposure and the development of childhood asthma

DEFF Research Database (Denmark)

Rogers, A J; Brasch-Andersen, C; Ionita-Laza, I

2009-01-01

BACKGROUND: The glutathione S-transferase M1 (GSTM1)-null variant is a common copy number variant associated with adverse pulmonary outcomes, including asthma and airflow obstruction, with evidence of important gene-by-environment interactions with exposures to oxidative stress. OBJECTIVE: To exp...

Ontología para la gestión unificada de variantes y versiones de productos

OpenAIRE

Sonzini, María Soledad; Vegetti, Marcela

2015-01-01

El objetivo de este trabajo es presentar una ontología para gestionar la variación temporal de una familia de productos a través de versiones. La propuesta permite identificar los puntos variantes, la causa, el tiempo de validez y el control de la propagación/ impacto de los cambios. Es una ontología genérica que puede ser integrada con distintos modelos de representación de variantes de productos. A fin de validar la propuesta, se muestra la integración de la ontología de versiones propuesta...

Y2 receptor gene variants reduce the risk of hypertension in obese children and adolescents.

Science.gov (United States)

Santoro, Nicola; Del Giudice, Emanuele Miraglia; Grandone, Anna; Marzuillo, Pierluigi; Cozzolino, Domenico; Di Salvo, Giovanni; Pacileo, Giuseppe; Calabrò, Raffaele; Perrone, Laura

2008-08-01

To verify whether peptide YY (PYY) and its Y2 receptor (Y2R) gene variants can be associated with obesity or hypertension or both in a cohort of obese children and adolescents. Two hundred and twenty-nine obese children (105 girls, mean z-score BMI 5.1 +/- 2.4; mean age 10.5 +/- 2.9 years) and 250 age and sex-matched lean controls (130 women, mean z-score BMI 0.5 +/- 1.1; mean age 10.3 +/- 2.8) were enrolled in the study. Height, weight, BMI, waist circumference and 24-h systolic and diastolic blood pressure were measured. Night-time, day-time and 24-h systolic and diastolic blood pressures were evaluated by 24 h ambulatory blood pressure measurement, and appropriate standard deviation scores according to sex, age and height were calculated. Molecular screening of the PYY and Y2R genes was performed. No new mutations were found. We observed three previously described polymorphisms: G767C on PYY and T585C and T936C on Y2R. An association study was carried out in obese patients. No associations were found between the PYY genotypes and the studied phenotypes. The Y2R gene variants, T585C and T936C, which are in almost complete linkage disequilibrium, were found to be associated with night-time, day-time and 24-h systolic and diastolic blood pressures. In particular, subject homozygotes for the T allele showed lower systolic and diastolic blood pressure values compared with the other genotypes. Moreover, obese children homozygous for the T585 allele showed a lower risk of developing hypertension than patients carrying the CC and CT genotypes (chi 6.9; df = 1, P = 0.03; odds ratio = 0.5, 95% confidence interval: 0.27-0.88). Our results suggest that Y2R gene variants are involved in blood pressure regulation in obese children and adolescents.

Stability of Cd_1_–_xZn_xO_yS_1_–_y Quaternary Alloys Assessed with First-Principles Calculations

International Nuclear Information System (INIS)

Varley, Joel B.; He, Xiaoqing; Rockett, Angus; Lordi, Vincenzo

2017-01-01

One route to decreasing the absorption in CdS buffer layers in Cu(In,Ga)Se_2 and Cu_2ZnSn(S,Se)_4 thin-film photovoltaics is by alloying. Here we use first-principles calculations based on hybrid functionals to assess the energetics and stability of quaternary Cd, Zn, O, and S (Cd_1_–_xZn_xO_yS_1_–_y) alloys within a regular solution model. Our results identify that full miscibility of most Cd_1_–_xZn_xO_yS_1_–_y compositions and even binaries like Zn(O,S) is outside typical photovoltaic processing conditions. Finally, the results suggest that the tendency for phase separation of the oxysulfides may drive the nucleation of other phases such as sulfates that have been increasingly observed in oxygenated CdS and ZnS.

Variantes en los factores de transcripción para IFNγ, TBET, STAT1, STAT4 y HLX, y el riesgo de desarrollar tuberculosis pulmonar en un estudio de casos y controles de una población colombiana

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María Dulfary Sánchez

2013-06-01

Full Text Available Introducción. El interferón gama (IFNγ es la citocina más potente para controlar la infección por Mycobacterium tuberculosis, el agente etiológico de la tuberculosis humana. Los pacientes con tuberculosis activa presentan reducción de los niveles de IFNγ, lo cual parece explicar la inmunidad poco efectiva contra el bacilo. La disminución de su expresión o alteraciones funcionales de los factores transactivadores del promotor del gen de IFNγ, podrían explicar la reducción de los niveles de IFNγ enlos pacientes con tuberculosis. Objetivo. Determinar la asociación de variantes genéticas en los factores de transcripción TBET,STAT1, STAT4 y HLX con sensibilidad o resistencia a tuberculosis pulmonar. Materiales y métodos. Se seleccionaron ocho polimorfismos de un solo nucleótido (Single-NucleotidePolymorphism, SNP y se estableció su genotipo, en 466 pacientes con tuberculosis pulmonar y 300 controles sanos en Colombia; además, se hizo un análisis de asociación alélica y genética. Resultados. Los resultados indican que los SNP de los factores de transcripción estudiados no están asociados con tuberculosis; sin embargo, el polimorfismo rs11650354 en TBET puede estar implicado en la disminución de riesgo de tuberculosis. El genotipo TT de TBET se asoció significativamente con protección contra tuberculosis usando un modelo genético recesivo (OR=0,089; CI95%: 0,01-0,73;p=0,0069; sin embargo, la corrección mediante pruebas múltiples de ajuste abolió esta asociación (Empirical P Value, EMP2=0,61. Conclusión. En este estudio se sugiere un efecto de la variante rs11650354 de TBET sobre la resistencia a la tuberculosis en la población colombiana. Es necesario desarrollar un estudio de replicación usando muestras adicionales para confirmar esta asociación sugestiva. doi: http://dx.doi.org/10.7705/biomedica.v33i2.790

Rare HFE variants are the most frequent cause of hemochromatosis in non-c282y homozygous patients with hemochromatosis.

Science.gov (United States)

Hamdi-Rozé, Houda; Beaumont-Epinette, Marie-Pascale; Ben Ali, Zeineb; Le Lan, Caroline; Loustaud-Ratti, Véronique; Causse, Xavier; Loreal, Olivier; Deugnier, Yves; Brissot, Pierre; Jouanolle, Anne-Marie; Bardou-Jacquet, Edouard

2016-12-01

p.Cys282Tyr (C282Y) homozygosity explains most cases of HFE-related hemochromatosis, but a significant number of patients presenting with typical type I hemochromatosis phenotype remain unexplained. We sought to describe the clinical relevance of rare HFE variants in non-C282Y homozygotes. Patients referred for hemochromatosis to the National Reference Centre for Rare Iron Overload Diseases from 2004 to 2010 were studied. Sequencing was performed for coding region and intronic flanking sequences of HFE, HAMP, HFE2, TFR2, and SLC40A1. Nine private HFE variants were identified in 13 of 206 unrelated patients. Among those, five have not been previously described: p.Leu270Argfs*4, p.Ala271Valfs*25, p.Tyr52*, p.Lys166Asn, and p.Asp141Tyr. Our results show that rare HFE variants are identified more frequently than variants in the other genes associated with iron overload. Rare HFE variants are therefore the most frequent cause of hemochromatosis in non-C282Y homozygote HFE patients. Am. J. Hematol. 91:1202-1205, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Assessing pathogenicity of MLH1 variants by co-expression of human MLH1 and PMS2 genes in yeast

Energy Technology Data Exchange (ETDEWEB)

Vogelsang, Matjaz; Comino, Aleksandra; Zupanec, Neja [Department for Biosynthesis and Biotransformation, National Institute of Chemistry, Hajdrihova 19, SI-1001 Ljubljana (Slovenia); Hudler, Petra [Medical Center for Molecular Biology, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, SI-1000 Ljubljana (Slovenia); Komel, Radovan [Department for Biosynthesis and Biotransformation, National Institute of Chemistry, Hajdrihova 19, SI-1001 Ljubljana (Slovenia); Medical Center for Molecular Biology, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, SI-1000 Ljubljana (Slovenia)

2009-10-28

Loss of DNA mismatch repair (MMR) in humans, mainly due to mutations in the hMLH1 gene, is linked to hereditary nonpolyposis colorectal cancer (HNPCC). Because not all MLH1 alterations result in loss of MMR function, accurate characterization of variants and their classification in terms of their effect on MMR function is essential for reliable genetic testing and effective treatment. To date, in vivo assays for functional characterization of MLH1 mutations performed in various model systems have used episomal expression of the modified MMR genes. We describe here a novel approach to determine accurately the functional significance of hMLH1 mutations in vivo, based on co-expression of human MLH1 and PMS2 in yeast cells. Yeast MLH1 and PMS1 genes, whose protein products form the MutLα complex, were replaced by human orthologs directly on yeast chromosomes by homologous recombination, and the resulting MMR activity was tested. The yeast strain co-expressing hMLH1 and hPMS2 exhibited the same mutation rate as the wild-type. Eight cancer-related MLH1 variants were introduced, using the same approach, into the prepared yeast model, and their effect on MMR function was determined. Five variants (A92P, S93G, I219V, K618R and K618T) were classified as non-pathogenic, whereas variants T117M, Y646C and R659Q were characterized as pathogenic. Results of our in vivo yeast-based approach correlate well with clinical data in five out of seven hMLH1 variants and the described model was thus shown to be useful for functional characterization of MLH1 variants in cancer patients found throughout the entire coding region of the gene.

Assessing pathogenicity of MLH1 variants by co-expression of human MLH1 and PMS2 genes in yeast

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Hudler Petra

2009-10-01

Full Text Available Abstract Background Loss of DNA mismatch repair (MMR in humans, mainly due to mutations in the hMLH1 gene, is linked to hereditary nonpolyposis colorectal cancer (HNPCC. Because not all MLH1 alterations result in loss of MMR function, accurate characterization of variants and their classification in terms of their effect on MMR function is essential for reliable genetic testing and effective treatment. To date, in vivo assays for functional characterization of MLH1 mutations performed in various model systems have used episomal expression of the modified MMR genes. We describe here a novel approach to determine accurately the functional significance of hMLH1 mutations in vivo, based on co-expression of human MLH1 and PMS2 in yeast cells. Methods Yeast MLH1 and PMS1 genes, whose protein products form the MutLα complex, were replaced by human orthologs directly on yeast chromosomes by homologous recombination, and the resulting MMR activity was tested. Results The yeast strain co-expressing hMLH1 and hPMS2 exhibited the same mutation rate as the wild-type. Eight cancer-related MLH1 variants were introduced, using the same approach, into the prepared yeast model, and their effect on MMR function was determined. Five variants (A92P, S93G, I219V, K618R and K618T were classified as non-pathogenic, whereas variants T117M, Y646C and R659Q were characterized as pathogenic. Conclusion Results of our in vivo yeast-based approach correlate well with clinical data in five out of seven hMLH1 variants and the described model was thus shown to be useful for functional characterization of MLH1 variants in cancer patients found throughout the entire coding region of the gene.

Assessing pathogenicity of MLH1 variants by co-expression of human MLH1 and PMS2 genes in yeast

International Nuclear Information System (INIS)

Vogelsang, Matjaz; Comino, Aleksandra; Zupanec, Neja; Hudler, Petra; Komel, Radovan

2009-01-01

Loss of DNA mismatch repair (MMR) in humans, mainly due to mutations in the hMLH1 gene, is linked to hereditary nonpolyposis colorectal cancer (HNPCC). Because not all MLH1 alterations result in loss of MMR function, accurate characterization of variants and their classification in terms of their effect on MMR function is essential for reliable genetic testing and effective treatment. To date, in vivo assays for functional characterization of MLH1 mutations performed in various model systems have used episomal expression of the modified MMR genes. We describe here a novel approach to determine accurately the functional significance of hMLH1 mutations in vivo, based on co-expression of human MLH1 and PMS2 in yeast cells. Yeast MLH1 and PMS1 genes, whose protein products form the MutLα complex, were replaced by human orthologs directly on yeast chromosomes by homologous recombination, and the resulting MMR activity was tested. The yeast strain co-expressing hMLH1 and hPMS2 exhibited the same mutation rate as the wild-type. Eight cancer-related MLH1 variants were introduced, using the same approach, into the prepared yeast model, and their effect on MMR function was determined. Five variants (A92P, S93G, I219V, K618R and K618T) were classified as non-pathogenic, whereas variants T117M, Y646C and R659Q were characterized as pathogenic. Results of our in vivo yeast-based approach correlate well with clinical data in five out of seven hMLH1 variants and the described model was thus shown to be useful for functional characterization of MLH1 variants in cancer patients found throughout the entire coding region of the gene

Circulating Levels of sFlt1 Splice Variants as Predictive Markers for the Development of Preeclampsia

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Colby A. Souders

2015-06-01

Full Text Available Angiogenic biomarkers, including soluble fms-like tyrosine kinase 1 (sFlt1, are thought to be predictors of preeclampsia onset; however, improvement is needed before a widespread diagnostic test can be utilized. Here we describe the development and use of diagnostic monoclonal antibodies specific to the two main splice variants of sFlt1, sFlt1-1 and sFlt1-14. These antibodies were selected for their sensitivity and specificity to their respective sFlt1 isoform in a capture ELISA format. Data from this pilot study suggest that sFlt1-1 may be more predictive of preeclampsia than total sFlt1. It may be possible to improve current diagnostic platforms if more specific antibodies are utilized.

Análisis de variantes de HPV-16 como marcador molecular antropólogico

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Badano, Ines

2007-01-01

Full Text Available El Virus Papiloma Humano tipo 16 (HPV16 es el principal responsable del desarrollo del cáncer de cuello uterino. Además de su significado clínico, el estudio de la variación genética en las regiones E6, L1 y LCR de este virus ha permitido identificar variantes específicas de diferentes áreas geográficas. Este descubrimiento sugiere una antigua propagación del HPV16 y su coevolución con el género humano. En este contexto, las variantes podrían servir como marcador molecular antropológico, aportando nuevos datos al análisis de patrones migratorios humanos. El objetivo del trabajo fue determinar las variantes de HPV16 en las regiones genéticas E6 y L1 que infectan mujeres guaraníes de Misiones. Para ello se analizaron 39 muestras de cepillados cervicales de mujeres guaraníes infectadas con HPV16. Las variantes en E6 y L1 se identificaron por PCR e hibridación en dot blot. Los resultados obtenidos fueron: el 77% de las variantes Europeas, 20% Africanas y 3% Asiático Americanas. La baja prevalencia de variantes Asiático Americanas coincide con lo reportado por Picconi y col, 2002 para mujeres quechuas, y haría suponer una limitada diseminación del HPV16 durante la época prehispánica. El predominio de las variantes Europeas podría ser resultado de la colonización española y la inmigración europea, mientras que el tráfico de esclavos negros explicaría la presencia de variantes Africanas. Por otra parte, la hipótesis de competencia viral tampoco puede ser descartada.

Analysis of Hepatitis C Virus Genotype 1b Resistance Variants in Japanese Patients Treated with Paritaprevir-Ritonavir and Ombitasvir.

Science.gov (United States)

Krishnan, Preethi; Schnell, Gretja; Tripathi, Rakesh; Beyer, Jill; Reisch, Thomas; Zhang, Xinyan; Setze, Carolyn; Rodrigues, Lino; Burroughs, Margaret; Redman, Rebecca; Chayama, Kazuaki; Kumada, Hiromitsu; Collins, Christine; Pilot-Matias, Tami

2016-02-01

Treatment of HCV genotype 1b (GT1b)-infected Japanese patients with paritaprevir (NS3/4A inhibitor boosted with ritonavir) and ombitasvir (NS5A inhibitor) in studies M12-536 and GIFT-I demonstrated high sustained virologic response (SVR) rates. The virologic failure rate was 3% (13/436) across the two studies. Analyses were conducted to evaluate the impact of baseline resistance-associated variants (RAVs) on treatment outcome and the emergence and persistence of RAVs in patients experiencing virologic failure. Baseline paritaprevir resistance-conferring variants in NS3 were infrequent, while Y93H in NS5A was the most prevalent ombitasvir resistance-conferring variant at baseline. A comparison of baseline prevalence of polymorphisms in Japanese and western patients showed that Q80L and S122G in NS3 and L28M, R30Q, and Y93H in NS5A were significantly more prevalent in Japanese patients. In the GIFT-I study, the prevalence of Y93H in NS5A varied between 13% and 21% depending on the deep-sequencing detection threshold. Among patients with Y93H comprising 40% of their preexisting viral population, the 24-week SVR (SVR24) rates were >99% (276/277), 93% (38/41), and 76% (25/33), respectively, indicating that the prevalence of Y93H within a patient's viral population is a good predictor of treatment response. The predominant RAVs at the time of virologic failure were D168A/V in NS3 and Y93H alone or in combination with other variants in NS5A. While levels of NS3 RAVs declined over time, NS5A RAVs persisted through posttreatment week 48. Results from these analyses are informative in understanding the resistance profile of an ombitasvir- plus paritaprevir/ritonavir-based regimen in Japanese GT1b-infected patients. Copyright © 2016 Krishnan et al.

Lack of association between the S447X variant of the lipoprotein lipase gene and plasma lipids: A preliminary study

OpenAIRE

Zambrano Morales, Mariana; Fernández Salgado, Erika; Balzán Urdaneta, Ligia; Labastidas, Neila; Aranguren-Méndez, José; Connell, Lissette; Molero Paredes, Tania; Rojas, Alicia; Panunzio, Amelia

2014-01-01

El aumento en los valores de los lípidos sanguíneos, constituye un importante factor de riesgo cardiovascular. La lipoproteína lipasa (LPL) juega un papel importante en el metabolismo lipoproteico. Factores metabólicos y genéticos pueden influir en la función de la LPL. La variante S447X de la LPL se ha asociado con cambios en el perfil lipídico en diferentes poblaciones. El objetivo de esta investigación fue analizar la relación entre la variante S447X del gen de la LPL y lípidos plasmáticos...

Glial Fibrillary Acidic Protein and Ubiquitin C-Terminal Hydrolase-L1 as Outcome Predictors in Traumatic Brain Injury.

Science.gov (United States)

Takala, Riikka S K; Posti, Jussi P; Runtti, Hilkka; Newcombe, Virginia F; Outtrim, Joanne; Katila, Ari J; Frantzén, Janek; Ala-Seppälä, Henna; Kyllönen, Anna; Maanpää, Henna-Riikka; Tallus, Jussi; Hossain, Md Iftakher; Coles, Jonathan P; Hutchinson, Peter; van Gils, Mark; Menon, David K; Tenovuo, Olli

2016-03-01

Biomarkers ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) may help detect brain injury, assess its severity, and improve outcome prediction. This study aimed to evaluate the prognostic value of these biomarkers during the first days after brain injury. Serum UCH-L1 and GFAP were measured in 324 patients with traumatic brain injury (TBI) enrolled in a prospective study. The outcome was assessed using the Glasgow Outcome Scale (GOS) or the extended version, Glasgow Outcome Scale-Extended (GOSE). Patients with full recovery had lower UCH-L1 concentrations on the second day and patients with favorable outcome had lower UCH-L1 concentrations during the first 2 days compared with patients with incomplete recovery and unfavorable outcome. Patients with full recovery and favorable outcome had significantly lower GFAP concentrations in the first 2 days than patients with incomplete recovery or unfavorable outcome. There was a strong negative correlation between outcome and UCH-L1 in the first 3 days and GFAP levels in the first 2 days. On arrival, both UCH-L1 and GFAP distinguished patients with GOS score 1-3 from patients with GOS score 4-5, but not patients with GOSE score 8 from patients with GOSE score 1-7. For UCH-L1 and GFAP to predict unfavorable outcome (GOS score ≤ 3), the area under the receiver operating characteristic curve was 0.727, and 0.723, respectively. Neither UCHL-1 nor GFAP was independently able to predict the outcome when age, worst Glasgow Coma Scale score, pupil reactivity, Injury Severity Score, and Marshall score were added into the multivariate logistic regression model. GFAP and UCH-L1 are significantly associated with outcome, but they do not add predictive power to commonly used prognostic variables in a population of patients with TBI of varying severities. Copyright © 2016 Elsevier Inc. All rights reserved.

Variantes polimórficas Ala513Pro y Gly972Arg del gen IRS-1 no se asocian a la diabetes mellitus tipo 2 en un grupo de la población cubana The Ala513Pro and Gly972ARg polymorphous variants of IRS-1 gen are not associated with type diabetes mellitus in a group of the Cuban population

Directory of Open Access Journals (Sweden)

Luis Miguel Pérez

2011-08-01

Full Text Available Introducción: la diabetes mellitus tipo 2 es una enfermedad heterogénea y multifactorial, que está determinada por factores genéticos y no genéticos. El sustrato 1 del receptor de la insulina (IRS-1 cumple una función fundamental en la transmisión de la señal insulínica, por tanto sus variantes génicas constituyen blancos importantes en el estudio de la susceptibilidad genética a esta enfermedad en las diferentes poblaciones. Objetivo: explorar el papel de las variantes polimórficas Gly972Arg y Ala513Pro del gen IRS-1 en la susceptibilidad genética de la diabetes mellitus tipo 2 en un grupo de la población cubana. Métodos: se determinó la frecuencia de los polimorfismos Gly972Arg y Ala513Pro del IRS-1 en 499 ciudadanos cubanos, con un índice de masa corporal entre 22-30, con edades comprendidas entre los 40 y 70 años: de ellos 272 (54,5 % diabéticos y 227 (45,5 % no diabéticos. Resultados: la frecuencia del alelo Pro513 fue baja (1,2 % y similar para ambos grupos (1,1 % vs. 1,3 % para el grupo de diabéticos y el grupo control, respectivamente. La frecuencia del polimorfismo Gly972Arg fue de 16,2%, superior a la reportada para la mayoría de las poblaciones estudiadas. No se encontraron diferencias significativas en la frecuencia del alelo Arg972 entre el grupo de diabéticos y el grupo control (15,4 % vs. 17,3 %, ni cambios en los niveles de glucemia e insulinemia asociados a la presencia del alelo polimórfico Arg972. Conclusiones: en este grupo de sujetos de la población cubana, las variantes polimórficas Ala513Pro y Gly972Arg del gen IRS-1 no participan en la etiología de la diabetes mellitus tipo 2.Introduction: the type 2 diabetes mellitus is a heterogeneous and multifactor disease determined by genetic and no-genetic factors. The substrate 1 of insulin receptor (IRS-1 has a fundamental function in transmission of insulin signal, thus its genic variants are significant targets in study of genetic susceptibility to

Heterozygous RTEL1 variants in bone marrow failure and myeloid neoplasms.

Science.gov (United States)

Marsh, Judith C W; Gutierrez-Rodrigues, Fernanda; Cooper, James; Jiang, Jie; Gandhi, Shreyans; Kajigaya, Sachiko; Feng, Xingmin; Ibanez, Maria Del Pilar F; Donaires, Flávia S; Lopes da Silva, João P; Li, Zejuan; Das, Soma; Ibanez, Maria; Smith, Alexander E; Lea, Nicholas; Best, Steven; Ireland, Robin; Kulasekararaj, Austin G; McLornan, Donal P; Pagliuca, Anthony; Callebaut, Isabelle; Young, Neal S; Calado, Rodrigo T; Townsley, Danielle M; Mufti, Ghulam J

2018-01-09

Biallelic germline mutations in RTEL1 (regulator of telomere elongation helicase 1) result in pathologic telomere erosion and cause dyskeratosis congenita. However, the role of RTEL1 mutations in other bone marrow failure (BMF) syndromes and myeloid neoplasms, and the contribution of monoallelic RTEL1 mutations to disease development are not well defined. We screened 516 patients for germline mutations in telomere-associated genes by next-generation sequencing in 2 independent cohorts; one constituting unselected patients with idiopathic BMF, unexplained cytopenia, or myeloid neoplasms (n = 457) and a second cohort comprising selected patients on the basis of the suspicion of constitutional/familial BMF (n = 59). Twenty-three RTEL1 variants were identified in 27 unrelated patients from both cohorts: 7 variants were likely pathogenic, 13 were of uncertain significance, and 3 were likely benign. Likely pathogenic RTEL1 variants were identified in 9 unrelated patients (7 heterozygous and 2 biallelic). Most patients were suspected to have constitutional BMF, which included aplastic anemia (AA), unexplained cytopenia, hypoplastic myelodysplastic syndrome, and macrocytosis with hypocellular bone marrow. In the other 18 patients, RTEL1 variants were likely benign or of uncertain significance. Telomeres were short in 21 patients (78%), and 3' telomeric overhangs were significantly eroded in 4. In summary, heterozygous RTEL1 variants were associated with marrow failure, and telomere length measurement alone may not identify patients with telomere dysfunction carrying RTEL1 variants. Pathogenicity assessment of heterozygous RTEL1 variants relied on a combination of clinical, computational, and functional data required to avoid misinterpretation of common variants.

Serum concentration of ubiquitin c-terminal hydrolase-L1 in detecting severity of traumatic brain injury

Science.gov (United States)

Siahaan, A. M. P.; Japardi, I.; Hakim, A. A.

2018-03-01

One of the main problems with ahead injury is assessing the severity. While physical examination and imaging had limitations, neuronal damage markers, ubiquitin C-terminal hydrolase-L1 (UCH-L1), released in theblood may provide valuable information about diagnosis the traumatic brain injury (TBI).Analyzing the concentrations of serum ubiquitin C-terminal hydrolase-L1 (UCH-L1), there must have a neuronal injury biomarker, in theTBI patients serum and their association with clinical characteristics and outcome. There were 80 TBI subjects, and there are mild, moderate, and severe involved in this study of case- control. By using ELISA, we studied the profile of serum UCH-L1 levels for TBI patients. TheUCH-L1 serum level of moderate and severe head injury is higher than in mild head injury (pinjury patients. There is no particular correlation found between serum UCH-L1 level and outcome. Serum levels of UCH-L1 appear to have potential clinical utility in diagnosing TBI but do not correlate with outcome.

Association of ubiquitin carboxy-terminal hydrolase-L1 in cerebrospinal fluid with clinical severity in a cohort of patients with Guillain-Barré syndrome.

Science.gov (United States)

Nagamine, Satoshi; Fujiwara, Yuuki; Shimizu, Toshio; Kawata, Akihiro; Wada, Keiji; Isozaki, Eiji; Kabuta, Tomohiro

2015-06-01

Guillain-Barré syndrome (GBS) is an acute immune-mediated polyneuropathy. Although its pathogenic mechanism has been revealed and various therapeutic trials have been performed, a proportion of patients experience the severe sequelae associated with GBS. In this paper, we investigated whether the amount of the neuron-specific protein, ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1), in the cerebrospinal fluid of patients with GBS was correlated with the clinical course of the disease. UCH-L1 protein levels were greater in patients with GBS than in controls. The patients with GBS whose UCH-L1 protein levels were higher than those of the controls presented with more severe symptoms at peak. UCH-L1 protein levels tended to become elevated as the total protein levels were increased; however, elevated UCH-L1 without an increase in total protein might be correlated with severe disease course (bedridden or ventilator supported). These results suggest that UCH-L1 could be a biomarker associated with the severity of the disease at the acute phase of GBS.

Tropical calcific pancreatitis and its association with CTRC and SPINK1 (p.N34S) variants.

NARCIS (Netherlands)

Derikx, M.H.; Szmola, R.; Morsche, R.H.M. te; Sunderasan, S.; Chacko, A.; Drenth, J.P.H.

2009-01-01

BACKGROUND: Tropical calcific pancreatitis (TCP) is a relatively common form of chronic pancreatitis in parts of Asia and Africa. The SPINK1 variant p.N34S is strongly associated with TCP, but other genetic factors remain to be defined. Chymotrypsinogen C (CTRC) degrades trypsinogen and

Engineered Cpf1 variants with altered PAM specificities.

Science.gov (United States)

Gao, Linyi; Cox, David B T; Yan, Winston X; Manteiga, John C; Schneider, Martin W; Yamano, Takashi; Nishimasu, Hiroshi; Nureki, Osamu; Crosetto, Nicola; Zhang, Feng

2017-08-01

The RNA-guided endonuclease Cpf1 is a promising tool for genome editing in eukaryotic cells. However, the utility of the commonly used Acidaminococcus sp. BV3L6 Cpf1 (AsCpf1) and Lachnospiraceae bacterium ND2006 Cpf1 (LbCpf1) is limited by their requirement of a TTTV protospacer adjacent motif (PAM) in the DNA substrate. To address this limitation, we performed a structure-guided mutagenesis screen to increase the targeting range of Cpf1. We engineered two AsCpf1 variants carrying the mutations S542R/K607R and S542R/K548V/N552R, which recognize TYCV and TATV PAMs, respectively, with enhanced activities in vitro and in human cells. Genome-wide assessment of off-target activity using BLISS indicated that these variants retain high DNA-targeting specificity, which we further improved by introducing an additional non-PAM-interacting mutation. Introducing the identified PAM-interacting mutations at their corresponding positions in LbCpf1 similarly altered its PAM specificity. Together, these variants increase the targeting range of Cpf1 by approximately threefold in human coding sequences to one cleavage site per ∼11 bp.

Upper limit for the emission of monoenergetic photons in Y(1S)- and Y(2S)-meson decays

International Nuclear Information System (INIS)

Albrecht, H.; Binder, U.; Harder, G.; Lembke-Koppitz, I.; Philipp, A.; Schmidt-Parzefall, W.; Schroeder, H.; Schulz, H.D.; Wurth, R.; Drescher, H.; Graewe, B.; Matthiesen, U.; Scheck, H.; Spengler, J.; Wegener, D.; Edwards, K.W.; Kapitza, H.; Yun, J.C.; Frisken, W.R.; Fukunaga, C.; Goddard, M.; Gilkinson, D.J.; Gingrich, D.M.; Kim, P.C.H.; Kutschke, R.; MacFarlane, D.B.; McKenna, J.A.; Orr, R.S.; Padley, P.; Prentice, J.D.; Seywerd, H.C.J.; Stacey, B.J.; Yoon, T.S.; Ammar, R.; Coppage, D.; Davis, R.; Kanekal, S.; Kwak, N.; Kernel, G.; Plesko, M.; Childers, R.; Darden, C.W.; Gennow, H.

1985-08-01

We report the results of a search for monoenergetic photons in the decay of both the Y(1S)- and the Y(2S)-meson. Photons converted in the beam tube or the drift chamber inner wall, and photons detected with the barrel shower counters of the ARGUS detector, respectively, have been used in the analysis. No narrow peak is observed in the energy interval 0.5 GeV<=Esub(γ)<=4.0 GeV. (orig.)

Production Cross Sections of $J/\\Psi$(1S) and $Y$(1S) at $\\sqrt{s}$ = 7 TeV with CMS

CERN Document Server

Beranek, Sarah

Measurements of the production cross sections of $J/\\Psi$(1S) and $Υ$(1S) resonances in the dimuon channel in proton-proton collisions with a $\\sqrt{s}$ = 7 TeV at the CMS experiment at LHC (CERN) are presented. The efficiencies are obtained via data-driven methods. The differential cross sections are presented as a function of the transverse momentum. The total inclusive $J/\\Psi$(1S) production cross section for an integrated luminosity of 36 pb$^{−1}$ is measured with (50.61 $\\pm$ 0.04$_{stat}$ $\\pm$ 3.09$_{sys}$ $\\pm$ 2.02$_{lumi}$ ) $nb$ for a transverse momentum between 8 and 30 GeV/c and a rapidity range of |y| < 2.4. The total production cross section for the $Υ$(1S) resonance is measured for an integrated luminosity of 36 pb$^{−1}$ in the rapidity range of |y| < 2.0 and a transverse momentum range between 3 and 30 GeV/c with (4.96 $\\pm$ 0.06$_{stat}$ $\\pm$ 0.47$_{sys}$ $\\pm$ 0.20$_{lumi}$ ) $nb$.

Inclusive muon and b quark production cross sections in p bar p collisions at √s = 1.8 TeV

International Nuclear Information System (INIS)

Abachi, S.

1995-07-01

We report on the measurement of inclusive muon and b quark production by the D0 collaboration in p bar p collisions at √s = 1.8 TeV at the Fermilab Tevatron Collider. The results represent a refined analysis of the previously published 1992--93 data. We measure the muon cross section due to b quark decays over the kinematic range 4 T μ μ | T μ > 6 GeV/c and |y b | < 1.0

Association of usf1s2 variant in the upstream stimulatory factor 1 gene with premature coronary artery disease in southern population of Iran

Directory of Open Access Journals (Sweden)

Najmeh Jouyan

2015-03-01

Conclusion: It appears that the usf1s2 variant in upstream transcription factor 1 gene is an independent predictor of premature coronary artery disease in our population and applies its effects without affecting blood sugar and lipid levels.

Percepción del estrés competitivo y cultura en futbolistas profesionales de Brasil y Portugal

OpenAIRE

M. Regina F. Brand\\u00E3o; Hiram Vald\\u00E9s Casal; Alfonso Antonio Machado; Ana Ramires

2006-01-01

El objetivo del presente estudio fue comparar jugadores de fútbol con diferentes perspectivas culturales y similar nivel de experiencia, en la percepción del estrés. Fueron evaluados 18 jugadores Brasileños de la Selección Nacional Brasileña, y 20 jugadores Portugueses de la Selección Nacional Portuguesa, con una media de edad de 26,69 + 4,1 y 26,05 + 2,3 años respectivamente, mediante el Inventario de Estrés en Fútbol. Aparece una tendencia resulta muy marcada, los ítems que son evaluados co...

Inclusive dimuon and b-quark production cross sections in pp-bar collisions at √ s = 1.8 TeV

International Nuclear Information System (INIS)

Alitti, J.; Chevalier, L.; Ducros, Y.; Lebrat, J.F.; Mangeot, P.

1995-01-01

We report on a preliminary measurement of the inclusive dimuon cross section in pp-bar collisions at √ s = 1.8 TeV using the DΦ detector at the Fermilab Tevatron. From these results, we extract the inclusive b-quark production cross section for the kinematic range |y b | bmin T < 25 GeV / c. The difference in azimuthal angle in the transverse plane for dimuon pairs from bb-bar production is also shown. (author). 10 refs., 6 figs

Inclusive χc and b-quark production in bar pp collisions at √s =1.8 TeV

International Nuclear Information System (INIS)

Abe, F.; Albrow, M.; Amidei, D.; Anway-Wiese, C.; Apollinari, G.; Atac, M.; Auchincloss, P.; Azzi, P.; Bacchetta, N.; Baden, A.R.; Badgett, W.; Bailey, M.W.; Bamberger, A.; de Barbaro, P.; Barbaro-Galtieri, A.; Barnes, V.E.; Barnett, B.A.; Bauer, G.; Baumann, T.; Bedeschi, F.; Behrends, S.; Belforte, S.; Bellettini, G.; Bellinger, J.; Benjamin, D.; Benlloch, J.; Bensinger, J.; Beretvas, A.; Berge, J.P.; Bertolucci, S.; Biery, K.; Bhadra, S.; Binkley, M.; Bisello, D.; Blair, R.; Blocker, C.; Bodek, A.; Bolognesi, V.; Booth, A.W.; Boswell, C.; Brandenburg, G.; Brown, D.; Buckley-Geer, E.; Budd, H.S.; Busetto, G.; Byon-Wagner, A.; Byrum, K.L.; Campagnari, C.; Campbell, M.; Caner, A.; Carey, R.; Carithers, W.; Carlsmith, D.; Carroll, J.T.; Cashmore, R.; Castro, A.; Cen, Y.; Cervelli, F.; Chadwick, K.; Chapman, J.; Chiarelli, G.; Chinowsky, W.; Cihangir, S.; Clark, A.G.; Cobal, M.; Connor, D.; Contreras, M.; Cooper, J.; Cordelli, M.; Crane, D.; Cunningham, J.D.; Day, C.; DeJongh, F.; Dell'Agnello, S.; Dell'Orso, M.; Demortier, L.; Denby, B.; Derwent, P.F.; Devlin, T.; Dickson, M.; Drucker, R.B.; Dunn, A.; Einsweiler, K.; Elias, J.E.; Ely, R.; Eno, S.; Errede, S.; Etchegoyen, A.; Farhat, B.; Frautschi, M.; Feldman, G.J.; Flaugher, B.; Foster, G.W.; Franklin, M.; Freeman, J.; Frisch, H.; Fuess, T.; Fukui, Y.; Garfinkel, A.F.; Gauthier, A.; Geer, S.; Gerdes, D.W.; Giannetti, P.; Giokaris, N.; Giromini, P.; Gladney, L.; Gold, M.; Gonzalez, J.; Goulianos, K.; Grassmann, H.; Grieco, G.M.; Grindley, R.; Grosso-Pilcher, C.; Haber, C.; Hahn, S.R.; Handler, R.; Hara, K.; Harral, B.; Harris, R.M.; Hauger, S.A.; Hauser, J.; Hawk, C.; Hessing, T.; Hollebeek, R.; Holloway, L.; Hoelscher, A.; Hong, S.; Houk, G.; Hu, P.; Hubbard, B.; Huffman, B.T.; Hughes, R.; Hurst, P.; Huth, J.; Hylen, J.; Incagli, M.; Ino, T.; Iso, H.; Jensen, H.; Jessop, C.P.; Johnson, R.P.; Joshi, U.; Kadel, R.W.; Kamon, T.; Kanda, S.; Kardelis, D.A.; Karliner, I.; Kearns, E.; Keeble, L.; Kephart, R.

1993-01-01

We report the full reconstruction of χ c mesons through the decay chain χ c →J/ψ γ, J/ψ→μ + μ - , using data obtained at the Collider Detector at Fermilab in 2.6±0.2 pb -1 of bar pp collisions at √s =1.8 TeV. This exclusive χ c sample is used to measure the χ c -meson production cross section times branching fractions. We obtain σxB=3.2±0.4(stat) -1.1 +1.2 (syst) nb for χ c mesons decaying to J/ψ with p T >6.0 GeV/c and pseudorapidity |η| T b >8.5 GeV/c and |y b |<1

Y-box protein-1/p18 fragment identifies malignancies in patients with chronic liver disease

International Nuclear Information System (INIS)

Tacke, Frank; Kanig, Nicolas; En-Nia, Abdelaziz; Kaehne, Thilo; Eberhardt, Christiane S; Shpacovitch, Victoria; Trautwein, Christian; Mertens, Peter R

2011-01-01

Immunohistochemical detection of cold shock proteins is predictive for deleterious outcome in various malignant diseases. We recently described active secretion of a family member, denoted Y-box (YB) protein-1. We tested the clinical and diagnostic value of YB-1 protein fragment p18 (YB-1/p18) detection in blood for malignant diseases. We used a novel monoclonal anti-YB-1 antibody to detect YB-1/p18 by immunoblotting in plasma samples of healthy volunteers (n = 33), patients with non-cancerous, mostly inflammatory diseases (n = 60), hepatocellular carcinoma (HCC; n = 25) and advanced solid tumors (n = 20). YB-1/p18 was then tested in 111 patients with chronic liver diseases, alongside established tumor markers and various diagnostic measures, during evaluation for potential liver transplantation. We developed a novel immunoblot to detect the 18 kD fragment of secreted YB-1 in human plasma (YB-1/p18) that contains the cold-shock domains (CSD) 1-3 of the full-length protein. YB-1/p18 was detected in 11/25 HCC and 16/20 advanced carcinomas compared to 0/33 healthy volunteers and 10/60 patients with non-cancerous diseases. In 111 patients with chronic liver disease, YB-1/p18 was detected in 20 samples. Its occurrence was not associated with advanced Child stages of liver cirrhosis or liver function. In this cohort, YB-1/p18 was not a good marker for HCC, but proved most powerful in detecting malignancies other than HCC (60% positive) with a lower rate of false-positive results compared to established tumor markers. Alpha-fetoprotein (AFP) was most sensitive in detecting HCC, but simultaneous assessment of AFP, CA19-9 and YB-1/p18 improved overall identification of HCC patients. Plasma YB-1/p18 can identify patients with malignancies, independent of acute inflammation, renal impairment or liver dysfunction. The detection of YB-1/p18 in human plasma may have potential as a tumor marker for screening of high-risk populations, e.g. before organ transplantation, and should

Investigation of the role of interleukin-1 receptor antagonist VNTR variant on the Behçet’s disease

Science.gov (United States)

Dursun, Gül; Demir, Helin Deniz; Karakuş, Nevin; Demir, Osman; Yiğit, Serbülent

2018-01-01

Objective Behçet’s disease (BD), a chronic multisystem inflammatory disorder, is mainly characterized by relapsing periods of a wide range of clinical symptoms. Several cytokine genes may play important roles in the pathogenesis of BD. Therefore, interleukin-1 receptor antagonist (IL-1Ra) gene 86bp variable number tandem repeat (VNTR) variant was investigated in patients with BD in a Turkish population. Methods One hundred nine patients (60 females, 49 males; the mean age±standard deviation [SD] was 36.56±9.571 years) with BD and one hundred healthy individuals (54 females, 46 males; the mean age±SD was 36.64±2.294 years) were examined in the study. For genotyping, polymerase chain reaction-restriction fragment length polymorphism analysis was employed. Data were analyzed using Statistical Package for Social Sciences (SPSS) 22.0 (IBM Corp.; Armonk, NY, USA) (p0.05). The frequency of the a1/a1, a1/a2 genotypes and a1, a2 alleles were the most common both in patients and healthy controls (p=0.37, p=0.26, and p=0.53, respectively). Also, no statistically significant difference was found between the IL-1Ra VNTR variant genotypes and clinical characteristics (p>0.05). Conclusion The results of this study do not support an association between the IL-1Ra VNTR variant and the risk of BD in a Turkish population. However, further studies of this variant with larger sample sizes and different ethnicities are required for confirmation. PMID:29657871

Comprehensive analysis of the MLH1 promoter region in 480 patients with colorectal cancer and 1150 controls reveals new variants including one with a heritable constitutional MLH1 epimutation.

Science.gov (United States)

Morak, Monika; Ibisler, Ayseguel; Keller, Gisela; Jessen, Ellen; Laner, Andreas; Gonzales-Fassrainer, Daniela; Locher, Melanie; Massdorf, Trisari; Nissen, Anke M; Benet-Pagès, Anna; Holinski-Feder, Elke

2018-04-01

Germline defects in MLH1 , MSH2 , MSH6 and PMS2 predisposing for Lynch syndrome (LS) are mainly based on sequence changes, whereas a constitutional epimutation of MLH1 (CEM) is exceptionally rare. This abnormal MLH1 promoter methylation is not hereditary when arising de novo, whereas a stably heritable and variant-induced CEM was described for one single allele. We searched for MLH1 promoter variants causing a germline or somatic methylation induction or transcriptional repression. We analysed the MLH1 promoter sequence in five different patient groups with colorectal cancer (CRC) (n=480) composed of patients with i) CEM (n=16), ii) unsolved loss of MLH1 expression in CRC (n=37), iii) CpG-island methylator-phenotype CRC (n=102), iv) patients with LS (n=83) and v) MLH1-proficient CRC (n=242) as controls. 1150 patients with non-LS tumours also served as controls to correctly judge the results. We detected 10 rare MLH1 promoter variants. One novel, complex MLH1 variant c.-63_-58delins18 is present in a patient with CRC with CEM and his sister, both showing a complete allele-specific promoter methylation and transcriptional silencing. The other nine promoter variants detected in 17 individuals were not associated with methylation. For four of these, a normal, biallelic MLH1 expression was found in the patients' cDNA. We report the second promoter variant stably inducing a hereditary CEM. Concerning the classification of promoter variants, we discuss contradictory results from the literature for two variants, describe classification discrepancies between existing rules for five variants, suggest the (re-)classification of five promoter variants to (likely) benign and regard four variants as functionally unclear. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Microstrain engineered magnetic properties in Bi1-x Ca x Fe1-y Ti y O3-δ nanoparticles: deviation from Néel’s 1/d size-dependent magnetization behaviour

Science.gov (United States)

Mocherla, Pavana S. V.; Sahana, M. B.; Gopalan, R.; Ramachandra Rao, M. S.; Nanda, B. R. K.; Sudakar, C.

2017-10-01

Magnetization of antiferromagnetic nanoparticles is known to generally scale up inversely to their diameter (d) according to Néel’s model. Here we report a deviation from this conventional linear 1/d dependence, altered significantly by the microstrain, in Ca and Ti substituted BiFeO3 nanoparticles. Magnetic properties of microstrain-controlled Bi1-x Ca x Fe1-y Ti y O3-δ (y  =  0 and x  =  y) nanoparticles are analyzed as a function of their size ranging from 18 nm to 200 nm. A complex interdependence of doping concentration (x or y), annealing temperature (T), microstrain (ɛ) and particle size (d) is established. X-ray diffraction studies reveal a linear variation of microstrain with inverse particle size, 1/d nm-1 (i.e. ɛ · d  =  16.5 nm·%). A rapid increase in the saturation magnetization below a critical size d c ~ 35 nm, exhibiting a (1/d) α (α  ≈  2.6) dependence, is attributed to the influence of microstrain. We propose an empirical formula M \\propto (1/d)ɛ β (β  ≈  1.6) to highlight the contributions from both the size and microstrain towards the total magnetization in the doped systems. The magnetization observed in nanoparticles is thus, a result of the competing magnetic contribution from the terminated spin cycloid on the surface and counteracting microstrain present at a given size.

Non-coding keratin variants associate with liver fibrosis progression in patients with hemochromatosis.

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Pavel Strnad

Full Text Available BACKGROUND: Keratins 8 and 18 (K8/K18 are intermediate filament proteins that protect the liver from various forms of injury. Exonic K8/K18 variants associate with adverse outcome in acute liver failure and with liver fibrosis progression in patients with chronic hepatitis C infection or primary biliary cirrhosis. Given the association of K8/K18 variants with end-stage liver disease and progression in several chronic liver disorders, we studied the importance of keratin variants in patients with hemochromatosis. METHODS: The entire K8/K18 exonic regions were analyzed in 162 hemochromatosis patients carrying homozygous C282Y HFE (hemochromatosis gene mutations. 234 liver-healthy subjects were used as controls. Exonic regions were PCR-amplified and analyzed using denaturing high-performance liquid chromatography and DNA sequencing. Previously-generated transgenic mice overexpressing K8 G62C were studied for their susceptibility to iron overload. Susceptibility to iron toxicity of primary hepatocytes that express K8 wild-type and G62C was also assessed. RESULTS: We identified amino-acid-altering keratin heterozygous variants in 10 of 162 hemochromatosis patients (6.2% and non-coding heterozygous variants in 6 additional patients (3.7%. Two novel K8 variants (Q169E/R275W were found. K8 R341H was the most common amino-acid altering variant (4 patients, and exclusively associated with an intronic KRT8 IVS7+10delC deletion. Intronic, but not amino-acid-altering variants associated with the development of liver fibrosis. In mice, or ex vivo, the K8 G62C variant did not affect iron-accumulation in response to iron-rich diet or the extent of iron-induced hepatocellular injury. CONCLUSION: In patients with hemochromatosis, intronic but not exonic K8/K18 variants associate with liver fibrosis development.

HFE gene variants modify the association between maternal lead burden and infant birthweight: a prospective birth cohort study in Mexico City, Mexico.

Science.gov (United States)

Cantonwine, David; Hu, Howard; Téllez-Rojo, Martha Maria; Sánchez, Brisa N; Lamadrid-Figueroa, Héctor; Ettinger, Adrienne S; Mercado-García, Adriana; Hernández-Avila, Mauricio; Wright, Robert O

2010-07-26

Neonatal growth is a complex process involving genetic and environmental factors. Polymorphisms in the hemochromatosis (HFE) iron regulatory genes have been shown to modify transport and toxicity of lead which is known to affect birth weight. We investigated the role of HFE C282Y, HFE H63 D, and transferrin (TF) P570 S gene variants in modifying the association of lead and infant birthweight in a cohort of Mexican mother-infant pairs. Subjects were initially recruited between 1994-1995 from three maternity hospitals in Mexico City and 411 infants/565 mothers had archived blood available for genotyping. Multiple linear regression models, stratified by either maternal/infant HFE or TF genotype and then combined with interaction terms, were constructed examining the association of lead and birthweight after controlling for covariates. 3.1%, 16.8% and 17.5% of infants (N=390) and 1.9%, 14.5% and 18.9% of mothers (N=533) carried the HFE C282Y, HFE H63D, and TF P570 S variants, respectively. The presence of infant HFE H63 D variants predicted 110.3 g (95% CI -216.1, -4.6) decreases in birthweight while maternal HFE H63 D variants predicted reductions of 52.0 g (95% CI -147.3 to 43.2). Interaction models suggest that both maternal and infant HFE H63 D genotype may modify tibia lead's effect on infant birthweight in opposing ways. In our interaction models, maternal HFE H63 D variant carriers had a negative association between tibia lead and birthweight. These results suggest that the HFE H63 D genotype modifies lead's effects on infant birthweight in a complex fashion that may reflect maternal-fetal interactions with respect to the metabolism and transport of metals.

Inclusive dimuon and b-quark production cross sections in p bar p collisions at √s = 1.8 TeV

International Nuclear Information System (INIS)

Abachi, S.; Abbott, B.; Abolins, M.

1995-07-01

We report on a preliminary measurement of the inclusive dimuon cross section in p bar p collisions at √s = 1.8 TeV using the D0 detector at the Fermilab Tevatron. From these results, we extract the inclusive b-quark production cross section for the kinematic range |y b | T b min < 25 GeV/c. The difference in azimuthal angle in the transverse plane for dimuon pairs from b bar b production is also shown

Detección de mutaciones de los genes hMLH1 y hMSH2 del sistema de reparación de malos apareamientos del ADN en familias colombianas sospechosas de cancer colorrectal no polipósico hereditario (síndrome de Lynch.

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Andrea Gómez

2005-09-01

Full Text Available Introducción. El cáncer colorrectal es la segunda causa de morbilidad y mortalidad por cáncer en los países desarrollados. En Colombia es la quinta causa de muerte entre los diferentes cánceres. Cerca del 75% de éstos corresponde a cánceres esporádicos, alrededor del 25% son familiares, y son claramente hereditarios el 5%. De éstos, el más importantes es el cáncer colorrectal no polipósico hereditario o síndrome de Lynch. Objetivo. Analizar los dos genes más importantes involucrados en el síndrome de Lynch, el hMLH1 y el hMSH2. Materiales y métodos. En 17 familias colombianas que cumplían con los criterios de Ámsterdam II o las pautas de Bethesda, se analizaron por SSCP los 35 exones de estos dos genes y las variantes electroforéticas se secuenciaron. Resultados. Se detectaron 8 mutaciones de línea germinal en las familias analizadas, 7 en el gen hMLH1 y 1 en hMSH2, y se encontró una tasa de detección de mutaciones del 47%. Seis de las 8 mutaciones encontradas en este estudio han sido previamente reportadas en la literatura. Un cambio de una base en el sitio donador de empalme en el exón 9 del gen hMLH1 (G>A (dos familias, un cambio A>G en el codón 755 del exón 17, y un cambio G>A en el exón 18. Se detectaron dos nuevas mutaciones, una en el exón 17, un cambio C>T en el codón 640, y una deleción de TG en el codón 184 del exón 3 del gen hMSH2. También se detectó en dos familias un polimorfismo del intrón 13 del hMLH1. Conclusión. Este es el primer estudio realizado en Colombia que detecta mutaciones en el síndrome de Lynch y pretende establecer un programa integral de manejo y prevención.

Anatomical variants of lister's tubercle; A new morphological classification based on magnetic resonance imaging

Energy Technology Data Exchange (ETDEWEB)

Chan, Wan Ying; Chong, Le Roy [Dept. of Radiology, Changi General Hospital, Singapore (Singapore)

2017-11-15

Lister's tubercle is used as a standard anatomical landmark in hand surgery and arthroscopy procedures. In this study, we aimed to evaluate and propose a classification for anatomical variants of Lister's tubercle. Between September 2011 and July 2014, 360 MRI examinations for wrists performed using 1.5T scanners in a single institution were retrospectively evaluated. The prevalence of anatomical variants of Lister's tubercle based on the heights and morphology of its radial and ulnar peaks was assessed. These were classified into three distinct types: radial peak larger than ulnar peak (Type 1), similar radial and ulnar peaks (Type 2) and ulnar peak larger than radial peak (Type 3). Each type was further divided into 2 subtypes (A and B) based on the morphology of the peaks. The proportions of Type 1, Type 2, and Type 3 variants in the study population were 69.2, 21.4, and 9.5%, respectively. For the subtypes, the Type 1A variant was the most common (41.4%) and conformed to the classical appearance of Lister's tubercle; whereas, Type 3A and 3B variants were rare configurations (6.4% and 3.1%, respectively) wherein the extensor pollicis longus tendon coursed along the radial aspect of Lister's tubercle. Anatomical variations of Lister's tubercle have potential clinical implications for certain pathological conditions and pre-procedural planning. The proposed classification system facilitates a better understanding of these anatomical variations and easier identification of at-risk and rare variants.

Identification of a truncated splice variant of IL-18 receptor alpha in the human and rat, with evidence of wider evolutionary conservation

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Chris S. Booker

2014-09-01

Full Text Available Interleukin-18 (IL-18 is a pro-inflammatory cytokine which stimulates activation of the nuclear factor kappa beta (NF-κB pathway via interaction with the IL-18 receptor. The receptor itself is formed from a dimer of two subunits, with the ligand-binding IL-18Rα subunit being encoded by the IL18R1 gene. A splice variant of murine IL18r1, which has been previously described, is formed by transcription of an unspliced intron (forming a ‘type II’ IL18r1 transcript and is predicted to encode a receptor with a truncated intracellular domain lacking the capacity to generate downstream signalling. In order to examine the relevance of this finding to human IL-18 function, we assessed the presence of a homologous transcript by reverse transcription-polymerase chain reaction (RT-PCR in the human and rat as another common laboratory animal. We present evidence for type II IL18R1 transcripts in both species. While the mouse and rat transcripts are predicted to encode a truncated receptor with a novel 5 amino acid C-terminal domain, the human sequence is predicted to encode a truncated protein with a novel 22 amino acid sequence bearing resemblance to the ‘Box 1’ motif of the Toll/interleukin-1 receptor (TIR domain, in a similar fashion to the inhibitory interleukin-1 receptor 2. Given that transcripts from these three species are all formed by inclusion of homologous unspliced intronic regions, an analysis of homologous introns across a wider array of 33 species with available IL18R1 gene records was performed, which suggests similar transcripts may encode truncated type II IL-18Rα subunits in other species. This splice variant may represent a conserved evolutionary mechanism for regulating IL-18 activity.

Measurement of the Y(1S) production cross-section in pp collisions at {radical}(s)=7 TeV in ATLAS

Energy Technology Data Exchange (ETDEWEB)

Aad, G [Fakultaet fuer Mathematik und Physik, Albert-Ludwigs-Universitaet, Freiburg i.Br. (Germany); Abbott, B [Homer L. Dodge Department of Physics and Astronomy, University of Oklahoma, Norman, OK (United States); Abdallah, J [Institut de Fisica d' Altes Energies and Universitat Autonoma de Barcelona and ICREA, Barcelona (Spain); Abdelalim, A A [Section de Physique, Universite de Geneve, Geneva (Switzerland); Abdesselam, A [Department of Physics, Oxford University, Oxford (United Kingdom); Abdinov, O [Institute of Physics, Azerbaijan Academy of Sciences, Baku (Azerbaijan); Abi, B [Department of Physics, Oklahoma State University, Stillwater, OK (United States); Abolins, M [Department of Physics and Astronomy, Michigan State University, East Lansing, MI (United States); Abramowicz, H [Raymond and Beverly Sackler School of Physics and Astronomy, Tel Aviv University, Tel Aviv (Israel); Abreu, H [LAL, Univ. Paris-Sud and CNRS/IN2P3, Orsay (France); Acerbi, E [INFN Sezione di Milano (Italy); Dipartimento di Fisica, Universita di Milano, Milano (Italy); Acharya, B S [INFN Gruppo Collegato di Udine (Italy); ICTP, Trieste [Italy; Adams, D L [Physics Department, Brookhaven National Laboratory, Upton, NY (United States); Addy, T N [Department of Physics, Hampton University, Hampton, VA (United States); Adelman, J [Department of Physics, Yale University, New Haven, CT (United States); Aderholz, M [Max-Planck-Institut fuer Physik (Werner-Heisenberg-Institut), Muenchen (Germany); Adomeit, S [Fakultaet fuer Physik, Ludwig-Maximilians-Universitaet Muenchen, Muenchen (Germany); Adragna, P [Department of Physics, Queen Mary University of London, London (United Kingdom); Adye, T [Particle Physics Department, Rutherford Appleton Laboratory, Didcot (United Kingdom); Aefsky, S [Department of Physics, Brandeis University, Waltham, MA (United States)

2011-11-03

A measurement of the cross-section for Y(1S){yields}{mu}{sup +}{mu}{sup -} production in proton-proton collisions at centre of mass energy of 7 TeV is presented. The cross-section is measured as a function of the Y(1S) transverse momentum in two bins of rapidity, |y{sup Y(1S)}|<1.2 and 1.2<|y{sup Y(1S)}|<2.4. The measurement requires that both muons have transverse momentum p{sub T}{sup {mu}>}4 GeV and pseudorapidity |{eta}{sup {mu}|}<2.5 in order to reduce theoretical uncertainties on the acceptance, which depend on the poorly known polarisation. The results are based on an integrated luminosity of 1.13 pb{sup -1}, collected with the ATLAS detector at the Large Hadron Collider. The cross-section measurement is compared to theoretical predictions: it agrees to within a factor of two with a prediction based on the NRQCD model including colour-singlet and colour-octet matrix elements as implemented in PYTHIA while it disagrees by up to a factor of ten with the next-to-leading order prediction based on the colour-singlet model.

A review of variant hemoglobins interfering with hemoglobin A1c measurement.

Science.gov (United States)

Little, Randie R; Roberts, William L

2009-05-01

Hemoglobin A1c (HbA1c) is used routinely to monitor long-term glycemic control in people with diabetes mellitus, as HbA1c is related directly to risks for diabetic complications. The accuracy of HbA1c methods can be affected adversely by the presence of hemoglobin (Hb) variants or elevated levels of fetal hemoglobin (HbF). The effect of each variant or elevated HbF must be examined with each specific method. The most common Hb variants worldwide are HbS, HbE, HbC, and HbD. All of these Hb variants have single amino acid substitutions in the Hb beta chain. HbF is the major hemoglobin during intrauterine life; by the end of the first year, HbF falls to values close to adult levels of approximately 1%. However, elevated HbF levels can occur in certain pathologic conditions or with hereditary persistence of fetal hemoglobin. In a series of publications over the past several years, the effects of these four most common Hb variants and elevated HbF have been described. There are clinically significant interferences with some methods for each of these variants. A summary is given showing which methods are affected by the presence of the heterozygous variants S, E, C, and D and elevated HbF. Methods are divided by type (immunoassay, ion-exchange high-performance liquid chromatography, boronate affinity, other) with an indication of whether the result is artificially increased or decreased by the presence of a Hb variant. Laboratorians should be aware of the limitations of their method with respect to these interferences. 2009 Diabetes Technology Society.

An Evaluation of Factors Associated With Pathogenic PRSS1, SPINK1, CTFR, and/or CTRC Genetic Variants in Patients With Idiopathic Pancreatitis.

Science.gov (United States)

Jalaly, Niloofar Y; Moran, Robert A; Fargahi, Farshid; Khashab, Mouen A; Kamal, Ayesha; Lennon, Anne Marie; Walsh, Christi; Makary, Martin A; Whitcomb, David C; Yadav, Dhiraj; Cebotaru, Liudmila; Singh, Vikesh K

2017-08-01

We evaluated factors associated with pathogenic genetic variants in patients with idiopathic pancreatitis. Genetic testing (PRSS1, CFTR, SPINK1, and CTRC) was performed in all eligible patients with idiopathic pancreatitis between 2010 to 2015. Patients were classified into the following groups based on a review of medical records: (1) acute recurrent idiopathic pancreatitis (ARIP) with or without underlying chronic pancreatitis; (2) idiopathic chronic pancreatitis (ICP) without a history of ARP; (3) an unexplained first episode of acute pancreatitis (AP)pancreatitis. Logistic regression analysis was used to determine the factors associated with pathogenic genetic variants. Among 197 ARIP and/or ICP patients evaluated from 2010 to 2015, 134 underwent genetic testing. A total of 88 pathogenic genetic variants were found in 64 (47.8%) patients. Pathogenic genetic variants were identified in 58, 63, and 27% of patients with ARIP, an unexplained first episode of AP <35 years of age, and ICP without ARP, respectively. ARIP (OR: 18.12; 95% CI: 2.16-151.87; P=0.008) and an unexplained first episode of AP<35 years of age (OR: 2.46; 95% CI: 1.18-5.15; P=0.017), but not ICP, were independently associated with pathogenic genetic variants in the adjusted analysis. Pathogenic genetic variants are most likely to be identified in patients with ARIP and an unexplained first episode of AP<35 years of age. Genetic testing in these patient populations may delineate an etiology and prevent unnecessary diagnostic testing and procedures.

Splicing analysis of 14 BRCA1 missense variants classifies nine variants as pathogenic

DEFF Research Database (Denmark)

Ahlborn, Lise B; Dandanell, Mette; Steffensen, Ane Y

2015-01-01

by functional analysis at the protein level. Results from a validated mini-gene splicing assay indicated that nine BRCA1 variants resulted in splicing aberrations leading to truncated transcripts and thus can be considered pathogenic (c.4987A>T/p.Met1663Leu, c.4988T>A/p.Met1663Lys, c.5072C>T/p.Thr1691Ile, c......Pathogenic germline mutations in the BRCA1 gene predispose carriers to early onset breast and ovarian cancer. Clinical genetic screening of BRCA1 often reveals variants with uncertain clinical significance, complicating patient and family management. Therefore, functional examinations are urgently...... needed to classify whether these uncertain variants are pathogenic or benign. In this study, we investigated 14 BRCA1 variants by in silico splicing analysis and mini-gene splicing assay. All 14 alterations were missense variants located within the BRCT domain of BRCA1 and had previously been examined...

Variantes del Papilomavirus Humano 16 y su asociación con el HLA en cáncer cervical Variants of Human Papillomavirus 16 and its association with HLA in cervical cancer

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Jehidys Montiel Ramos

2010-12-01

Full Text Available El cáncer cervical es el segundo cáncer más común en mujeres en el mundo y es el principal cáncer en mujeres en países en desarrollo. La infección persistente por los genotipos oncogénicos del Virus del Papiloma Humano (VPH es la causa necesaria para el desarrollo del cáncer cervical, siendo el VPH-16 el genotipo responsable del 50-60% de los casos. Las variantes No Europeas del VPH-16 han sido asociadas con infección persistente, lesiones de alto grado y cáncer. Los polimorfismos del Antígeno Leucocitario Humano (HLA están también asociados con la susceptibilidad al cáncer cervical y se ha postulado una relación entre variantes del VPH y ciertos alelos del HLA. La presente revisión hace referencia a la relación entre los polimorfismos de HLA y el desarrollo de cáncer cervical y la evidencia que documenta la interrelación de este factor con la variabilidad del VPH-16. Salud UIS 2010; 42: 272-280Cervical cancer is the second most common cancer in women worldwide and the most frequent cancer in women of the majority of developing countries. Persistent infection with Human Papillomavirus (HPV oncogenic types of HPV is necessary to develop cervical, cancer, with HPV-16 responsible for 50-60% of cases. Non-European variants of HPV-16 have been associated with persistant infection and high degree cervical cancer. Human Leucocyte Antigen (HLA polymorphisms are also associated with susceptibility to cervical cancer. It has been suggested relationship between HPV-16 variability and some HLA Alleles., This revision refers to the relation between HLA polymorphisms and cervical cancer development, and present evidence that may explain its relation with HPV-16 variability. Salud UIS 2010; 42: 272-280

Dos variantes de la alfabetización académica cuando se entrelazan la lectura y la escritura en las materias

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Paula Carlino

2017-01-01

Full Text Available ste trabajo reexamina datos de tres investigaciones realizadas por el Grupo para la Inclusión y Calidad Educativas a través de Ocuparnos de la Lectura y la Escritura en todas las Materias (Giceolem, que versan sobre los modos en que escribir y leer se incluyen en distintos espacios curriculares de la educación superior. Mediante una encuesta nacional, identificamos que existen dos modalidades de trabajo con la lectura y la escritura en cada materia: la periférica y la entrelazada. A través del análisis de registros observacionales en clases de Historia y de Biología, distinguimos, a su vez, dos variantes de la modalidad entrelazada, correspon - dientes a situaciones en las que se dialoga en torno a lo leído y escrito sobre temas disciplinares. El análisis de las observaciones de clase permite caracterizar las prácticas de enseñanza, y triangularlas con lo que de ellas se declara en la encuesta. Se busca con ello aportar al debate sobre la alfabetización académica, precisando cómo, con qué fin y por qué ocuparse de la escritura y lectura a través del currículum.

Tipificación Molecular del Vibrio cholerae O1 en el Perú

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Huguet T José

2000-01-01

Full Text Available Este estudio de ribotipificación en 75 cepas de Vibrio cholerae O1 permitió identificar tres variantes ribotípicas, referidas como Per1, Per2 y Per3, aisladas durante el periodo 1991- 1999 en el Perú. La variante Per1 fue reportada tanto en la etapa epidémica y endémica del cólera, mientras que Per2 y Per3 se relacionaron sólo con la etapa endémica. Los resultados mostraron además una aparición constante y mayoritaria de la variante Per1, poniendo en evidencia la emergencia de un mismo grupo clonal en los brotes epidémicos del Perú. Las variantes ribotípicas encontradas fueron comparadas con los ribotipos de diferentes cepas referenciales de V. cholerae previamente caracterizadas. Se observó una identidad total del ribotipo Per1 con la variante ribotípica de aislamientos Asiáticos (Tailandia, encontrándose además altos índices de similitud entre los ribotipos Per1, Per2 y Per3, y evidenciándose una estrecha relación entre las cepas peruanas y los aislamientos asiáticos.

Estudio basal de prevalencia de sífilis y VIH y comportamientos asociados en población privada de libertad, Perú 1999

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César Cárcamo C

2003-03-01

Full Text Available Objetivos: Estimar la prevalencia de sífilis y VIH e identificar los comportamientos de riesgo asociados en personas privadas de libertad (PPL. Materiales y métodos: Estudio transversal realizado durante el año 1999 en 22 establecimientos penitenciarios peruanos. Se realizó RPR para la detección de sífilis (datos ligados y ELISA para tamizaje de VIH (datos no ligados, confirmándose con IFI o Western Blot. Se realizó una encuesta estructurada y se analizaron los datos mediante los programas SPSS 9,0 y AMOS 4. Resultados: Participaron 6963 PPL. La prevalencia de VIH fue 1,1% y de sífilis 4,1%. Los comportamientos de riesgo asociados a VIH más significativos fueron: consumo de drogas (OR:2,7, infecciones de transmisión sexual (OR: 2,3, relaciones sexuales entre hombres (OR: 2,2, uso de cocaína (OR: 2,1, úlcera genital (OR: 2,1, haber sido encarcelado previamente (OR: 2 y tener tatuajes (OR: 1,99. Mientras los asociados a sífilis fueron: tener relaciones sexuales entre hombres OR: (2,8, infecciones de transmisión sexual (OR: 2,4, úlcera genital (OR:1,8, haber tenido relaciones sexuales con trabajadora sexual (OR: 1,5 y tener más de dos parejas sexuales (OR: 1,5. Utilizando un modelo de ecuaciones estructurales se asoció VIH con el reporte de tener tatuaje, más de dos parejas sexuales, más de un encarcelamiento previo y úlcera genital. Conclusiones: Se encontraron importantes valores de prevalencia de VIH y sífilis en este grupo de personas, siendo necesario continuar realizando estudios similares que nos permitan conocer las tendencias (vigilancia de segunda generación y conocer el impacto de posibles intervenciones.

Prevalência de talassemias e hemoglobinas variantes no estado de Goiás, Brasil Prevalence of thalassemias and variant hemoglobins in the state of Goiás, Brazil

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Paulo Roberto de Melo-Reis

2006-12-01

Full Text Available As anemias hereditárias, em especial as talassemias e hemoglobinas (Hb variantes, são as mais comuns das alterações genéticas humanas; sua freqüência na população brasileira é muito variável, dependendo dos grupos raciais formadores de cada região. O povoamento de Goiás, que teve início logo após o seu descobrimento, em 1726, motivado pela procura de ouro, foi composto principalmente por portugueses e escravos africanos, contexto que favoreceu a mestiçagem entre eles. Considerando que esses povos apresentam genes para as hemoglobinas anormais com freqüências variadas, é esperado que se encontrem essas alterações genéticas na nossa população. O objetivo deste trabalho foi avaliar a prevalência de talassemias e hemoglobinas variantes na população de Goiás. Para isso a casuística foi composta por 404 alunos participantes dos diversos cursos da Universidade Católica de Goiás (UCG, oriundos de 55 cidades do estado de Goiás. A prevalência de anemia hereditária por talassemias e hemoglobinas variantes em Goiás foi de 10,1%, cuja ordem decrescente foi a seguinte: talassemia alfa heterozigótica (5,2%, heterozigose para hemoglobina S (Hb AS (2,2%, heterozigose para hemoglobina C (Hb AC (1%, talassemia beta menor (0,7%, associação entre talassemia alfa e heterozigose para Hb S (0,5%, associação entre talassemia alfa e heterozigose para Hb C (0,3% e heterozigose para hemoglobina D (Hb AD (0,3%. Nenhum caso de homozigose foi encontrado no presente estudo. Este trabalho demonstrou a dispersão dos genes para Hb S, Hb C e Hb D, bem como de talassemias alfa e beta em uma população do estado de Goiás. Por essa razão, concluímos que é importante realizar programas com maior abrangência da população para estudo da epidemiologia das talassemias e hemoglobinas variantes no estado de Goiás.The hereditary anemias, especially the thalassemies and hemoglobinopathies are the most common human genetic abnormalities. Their

Y-type urethral duplication with posterior perineal fistula: A new variant

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Sandesh V Parelkar

2017-05-01

Full Text Available 13 months old boy presented with constipation and straining during micturition with poor urinary stream and voiding of urine per rectum. Perineal examination revealed posterior perineal fistula. Voiding cysto-urethrogram showed bilateral vesicoureteral reflux with bladder diverticuli, normal dorsal urethra and dye going from urethra to rectum suggestive of Y type urethral duplication. Under stoma cover, he underwent excision of posterior perineal fistula with accessory ventral urethra and anorectoplasty was done. At present patient is passing urine in good stream without straining. The uniqueness of our case is the presence of Y type of urethral duplication with normal calibre dorsal urethra and presence of posterior perineal fistula. Therefore, we consider our case to be an unusual variant of Y type of urethral duplication that has not been described before.

Obtención de Variantes Hiperactivas e Inactivas de la Endocelulasa Cel9 de Myxobacter Sp. Al-1 Obtención de Variantes Hiperactivas e Inactivas de la Endocelulasa Cel9 de Myxobacter Sp. Al-1

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Mario Pedraza-Reyes

2012-02-01

Full Text Available Debido a su aplicación industrial, existe un gran interés en la producción de celulasas con propiedades bioquímicas novedosas. Por ello, en el presente trabajo se utilizó una estrategia basada en un método de mutagénesis aleatoria in vivo para la obtención de variantes de la endocelulasa Cel9 del microorganismo gram-negativo Myxobacter Sp. AL-1. Siguiendo este enfoque, se obtuvieron cepas transformantes de Escherichia coli capaces de secretar variantes de la proteína Cel9 cuyas actividades específicas fueron incrementadas hasta 7.5 veces con respecto a la actividad mostrada por la enzima nativa. Del mismo modo, se generaron cepas de E. coli productoras de variantes de la proteína Cel9 con baja o nula actividad enzimática. Experimentos de subclonación y fraccionamiento celular revelaron que las mutaciones asociadas con los fenotipos de las variantes de la enzima Cel9 ocurrieron en la secuencia del gen cel9. Así mismo, se demostró que los fenotipos de las cepas mutantes carentes de actividad enzimática no dependen de su incapacidad para secretar las proteínas mutantes. Además de su potencial aplicación biotecnológica, los resultados obtenidos en este trabajo permiten avanzar en el entendimiento de la relación estructura-función de la celulasa Cel9 de Myxobacter Sp. AL-1.Due to its biotechnological impact, there is currently a growing interest in the production of cellulases with novel biochemical properties. Here, multiple generations of random mutagenesis in vivo and screening were employed to generate variants of the modular cellulase Cel9 from Myxobacter Sp. AL-1. Following this approach, Cel9 variants which showed increases upto 7.5 fold of cellulase activity were obtained. In addition, Cel9 mutants which completely lost the ability to degrade cellulose were also obtained. Results revealed that mutations associated with the phenotype of the Cel9 variants occurred on the mutant gene sequence and that themutants with null

Detection of new variant “Off-ladder” at the D12S391, D19S433 and ...

African Journals Online (AJOL)

Detection of new variant “Off-ladder” at the D12S391, D19S433 and D1S1656 ... African Journal of Biotechnology ... PCR products were detected by genetic analyzer 3130xL then, the data processed and analyzed by PowerStatsV1.2 software.

Measurement of the $b \\bar{b}$ Cross-Section and Correlations using Dimuon Events in $p \\bar{p}$ Collisions at $\\sqrt{s}$ = 1.8-TeV

Energy Technology Data Exchange (ETDEWEB)

Fein, David Kevin [Arizona U.

1996-01-01

We have measured the b-quark production cross section for $\\mid y \\mid$ < 1 using a sample of dimuon events collected with the D0 detector in $p\\bar{p}$ collisions at $\\sqrt{s}$ = 1:8 TeV at the Fermilab Tevatron. The measured b-quark cross section is consistent with $O(\\alpha^3_s$) QCD predictions, but lies at the upper limit of the theoretical uncertainties which is a factor of 1.5 above the mean value. A study of the difference in azimuthal angle of the two muons is in good qualitative agreement with the $O(\\alpha^3_s$) QCD predictions

Genome-wide association study identifies variants associated with autoimmune hepatitis type 1.

Science.gov (United States)

de Boer, Ynto S; van Gerven, Nicole M F; Zwiers, Antonie; Verwer, Bart J; van Hoek, Bart; van Erpecum, Karel J; Beuers, Ulrich; van Buuren, Henk R; Drenth, Joost P H; den Ouden, Jannie W; Verdonk, Robert C; Koek, Ger H; Brouwer, Johannes T; Guichelaar, Maureen M J; Vrolijk, Jan M; Kraal, Georg; Mulder, Chris J J; van Nieuwkerk, Carin M J; Fischer, Janett; Berg, Thomas; Stickel, Felix; Sarrazin, Christoph; Schramm, Christoph; Lohse, Ansgar W; Weiler-Normann, Christina; Lerch, Markus M; Nauck, Matthias; Völzke, Henry; Homuth, Georg; Bloemena, Elisabeth; Verspaget, Hein W; Kumar, Vinod; Zhernakova, Alexandra; Wijmenga, Cisca; Franke, Lude; Bouma, Gerd

2014-08-01

Autoimmune hepatitis (AIH) is an uncommon autoimmune liver disease of unknown etiology. We used a genome-wide approach to identify genetic variants that predispose individuals to AIH. We performed a genome-wide association study of 649 adults in The Netherlands with AIH type 1 and 13,436 controls. Initial associations were further analyzed in an independent replication panel comprising 451 patients with AIH type 1 in Germany and 4103 controls. We also performed an association analysis in the discovery cohort using imputed genotypes of the major histocompatibility complex region. We associated AIH with a variant in the major histocompatibility complex region at rs2187668 (P = 1.5 × 10(-78)). Analysis of this variant in the discovery cohort identified HLA-DRB1*0301 (P = 5.3 × 10(-49)) as a primary susceptibility genotype and HLA-DRB1*0401 (P = 2.8 × 10(-18)) as a secondary susceptibility genotype. We also associated AIH with variants of SH2B3 (rs3184504, 12q24; P = 7.7 × 10(-8)) and CARD10 (rs6000782, 22q13.1; P = 3.0 × 10(-6)). In addition, strong inflation of association signal was found with single-nucleotide polymorphisms associated with other immune-mediated diseases, including primary sclerosing cholangitis and primary biliary cirrhosis, but not with single-nucleotide polymorphisms associated with other genetic traits. In a genome-wide association study, we associated AIH type 1 with variants in the major histocompatibility complex region, and identified variants of SH2B3and CARD10 as likely risk factors. These findings support a complex genetic basis for AIH pathogenesis and indicate that part of the genetic susceptibility overlaps with that for other immune-mediated liver diseases. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Intragenomic sequence variation at the ITS1 - ITS2 region and at the 18S and 28S nuclear ribosomal DNA genes of the New Zealand mud snail, Potamopyrgus antipodarum (Hydrobiidae: mollusca)

Science.gov (United States)

Hoy, Marshal S.; Rodriguez, Rusty J.

2013-01-01

Molecular genetic analysis was conducted on two populations of the invasive non-native New Zealand mud snail (Potamopyrgus antipodarum), one from a freshwater ecosystem in Devil's Lake (Oregon, USA) and the other from an ecosystem of higher salinity in the Columbia River estuary (Hammond Harbor, Oregon, USA). To elucidate potential genetic differences between the two populations, three segments of nuclear ribosomal DNA (rDNA), the ITS1-ITS2 regions and the 18S and 28S rDNA genes were cloned and sequenced. Variant sequences within each individual were found in all three rDNA segments. Folding models were utilized for secondary structure analysis and results indicated that there were many sequences which contained structure-altering polymorphisms, which suggests they could be nonfunctional pseudogenes. In addition, analysis of molecular variance (AMOVA) was used for hierarchical analysis of genetic variance to estimate variation within and among populations and within individuals. AMOVA revealed significant variation in the ITS region between the populations and among clones within individuals, while in the 5.8S rDNA significant variation was revealed among individuals within the two populations. High levels of intragenomic variation were found in the ITS regions, which are known to be highly variable in many organisms. More interestingly, intragenomic variation was also found in the 18S and 28S rDNA, which has rarely been observed in animals and is so far unreported in Mollusca. We postulate that in these P. antipodarum populations the effects of concerted evolution are diminished due to the fact that not all of the rDNA genes in their polyploid genome should be essential for sustaining cellular function. This could lead to a lessening of selection pressures, allowing mutations to accumulate in some copies, changing them into variant sequences.                   

Lesiones de causa externa en menores y mayores de 18 años en un hospital colombiano Injuries from external causes in minors (less than 18 years of age and adults at a hospital in Colombia

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Mónica Bejarano

2009-03-01

Full Text Available OBJETIVOS: Definir y comparar las características de las lesiones de causa externa entre los pacientes menores y mayores de 18 años que consultaron al Hospital Mario Correa Rengifo. MÉTODOS: Se realizó un análisis de la información recabada mediante el Sistema de Vigilancia de Lesiones de Causa Externa del hospital Mario Correa Rengifo de Cali, Colombia, comparando menores y mayores de edad, entre enero de 2004 y diciembre de 2007. RESULTADOS: Se atendieron 4 507 menores de 18 años, la mayoría varones (69,3%, con 75,5% de las lesiones no intencionales (aunque 88% de las lesiones intencionales fueron interpersonales y 12% autoinfligidas. Las lesiones se presentaron con mayor frecuencia en la residencia (44,1% y la calle (39,5%; la actividad más frecuente fue la recreación (53,3%. Los menores de 18 años tuvieron más lesiones en el cráneo (razón de posibilidades [OR] = 1,62; P = 0,0000 y la región maxilofacial (OR = 1,49; P = 0,0000 que los mayores. En 5,8% hubo consumo de alcohol y en 2,6% de drogas, lo que incrementó la ocurrencia de lesiones intencionales (alcohol OR = 4,25 y drogas OR = 1,56. CONCLUSIONES: El número de pacientes menores de 18 años de edad con lesiones de causa externa que son atendidos en el hospital Mario Correa Rengifo aumenta cada vez más. El comportamiento de las lesiones en la niñez y adolescencia es diferente al de los mayores, pues tienen más lesiones no intencionales, que ocurren en el lugar de residencia o en las calles, donde habitualmente juegan. Es importante implementar diversas estrategias, educativas y estructurales para la prevención de este tipo de lesiones.OBJECTIVES: To define and compare the types of injuries from external causes in patients more than and less than 18 years of age treated by the Mario Correa Rengifo Hospital. METHODS: An analysis was conducted of data retrieved from the Sistema de Vigilancia de Lesiones de Causa Externa (Surveillance System for Injuries from External

Radiosynthesis of (S)-["1"8F]T1: The first PET radioligand for molecular imaging of α3β4 nicotinic acetylcholine receptors

International Nuclear Information System (INIS)

Sarasamkan, Jiradanai; Fischer, Steffen; Deuther-Conrad, Winnie; Ludwig, Friedrich-Alexander; Scheunemann, Matthias; Arunrungvichian, Kuntarat; Vajragupta, Opa; Brust, Peter

2017-01-01

Recent pharmacologic data revealed the implication of α3β4 nicotinic acetylcholine receptors (nAChRs) in nicotine and drug addiction. To image α3β4 nAChRs in vivo, we aimed to establish the synthesis of a ["1"8F]-labelled analog of the highly affine and selective α3β4 ligand (S)-3-(4-(4-fluorophenyl)-1H-1,2,3-triazol-1-yl)quinuclidine ((S)-T1). (S)-["1"8F]T1 was synthesized from ethynyl-4-["1"8F]fluorobenzene (["1"8F]5) and (S)-azidoquinuclidine by click reaction. After a synthesis time of 130 min (S)-["1"8F]T1 was obtained with a radiochemical yield (non-decay corrected) of 4.3±1.3%, a radiochemical purity of >99% and a molar activity of >158 GBq/μmol. The brain uptake and the brain-to-blood ratio of (S)-["1"8F]T1 in mice at 30 min post injection were 2.02 (SUV) and 6.1, respectively. According to an ex-vivo analysis, the tracer remained intact (>99%) in brain. Only one major radiometabolite was detected in plasma and urine samples. In-vitro autoradiography on pig brain slices revealed binding of (S)-["1"8F]T1 to brain regions associated with the expression of α3β4 nAChRs, which could be reduced by the α3β4 nAChR selective drug AT-1001. These findings make (S)-["1"8F]T1 a potential tool for the non-invasive imaging of α3β4 nAChRs in the brain by PET. - Highlights: • (S)-["1"8F]T1 is a promising α3ß4 nAChR ligand for PET imaging. • The novel radioligand (S)-["1"8F]T1 was synthesized by click reaction. • The potential of (S)-["1"8F]T1 was shown by in vitro autoradiography and in vivo evaluation in mice.

Índice cintura-cadera contra perímetro cintura para el diagnóstico del síndrome metabólico en niños y adolescentes con familiares de primer grado diabéticos tipo 1 Waist-hip index versus waist circumference for diagnosis of metabolic syndrome in first degree-children and adolescents relatives of persons with type 1 diabetes

Directory of Open Access Journals (Sweden)

Eduardo Cabrera-Rode

2011-12-01

Full Text Available Objetivo: comparar las mediciones de perímetro cintura e índice cintura-cadera para determinar la frecuencia del síndrome metabólico en familiares de primer grado de personas con diabetes tipo 1, utilizando diferentes definiciones pediátricas. Métodos: se estudiaron 224 familiares de primer grado de personas con diabetes tipo 1, en edades comprendidas entre los 4 y los 19 años. Se les determinó peso, talla, perímetro cintura y perímetro cadera, tensión arterial, glucemia, triglicéridos y HDL-colesterol. Se aplicaron las definiciones de síndrome metabólico según los criterios de Cook, Ford, la Federación Internacional de Diabetes y del consenso cubano. Se realizó una variante del consenso cubano utilizando: índice de masa corporal e índice cintura-cadera, según tablas cubanas, valores de glucosa ³ 5,6 mmol/L y tensión arterial ³ 90 percentil (tablas cubanas. Se tomaron, de forma independiente, los criterios de HDL-colesterol y triglicéridos. Empleamos el índice cintura-cadera de las tablas cubanas, el perímetro cintura sugerido por la Asociación Latinoamericana de Diabetes y el europeo para las definiciones estudiadas. Para la comparación de las frecuencias del síndrome metabólico, se usó la prueba exacta de Fisher. Resultados: la frecuencia del síndrome metabólico al aplicar la variante del consenso cubano fue de 9,37 % (21/224. Al comparar la variante del consenso cubano con las definiciones de Cook, Ford y la Federación Internacional de Diabetes (que utiliza el perímetro cintura de la Asociación Latinoamericana de Diabetes, se observó diferencia significativa con Cook y la Federación Internacional de Diabetes (4,01 %, p= 0,0360; 1,33 %, p= 0,0002 respectivamente. Al confrontar la presencia del síndrome metabólico de la variante del consenso cubano con Cook (8,48 %; 19/224 y Ford (8,93 %; 20/224, teniendo en cuenta el índice cintura-cadera de las tablas cubanas, podemos detectar frecuencias similares de

Investigation of luminescence mechanism in La{sub 0.2}Y{sub 1.8}O{sub 3} scintillator

Energy Technology Data Exchange (ETDEWEB)

Sahi, Sunil [Department of Physics, The University of Texas at Arlington, Arlington, TX 76019-0059 (United States); Wang, Zhiqiang [Department of Chemistry, The University of Western Ontario, London, Ontario, Canada N6A 5B7 (Canada); Luo, Junming [School of Materials Science and Engineering, Nanchang Hangkong University, Nanchang 330063 (China); Groza, Michael [Department of Life and Physical Sciences, Fisk University, Nashville, TN 37208-3051 (United States); Li, Jiang [Key Laboratory of Transparent Opto-functional Inorganic Materials, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050 (China); Zhang, Junying [Department of Physics, Beihang University, Beijing 100191 (China); Chen, Wei, E-mail: weichen@uta.edu [Department of Physics, The University of Texas at Arlington, Arlington, TX 76019-0059 (United States); Pan, Yubai [Key Laboratory of Transparent Opto-functional Inorganic Materials, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050 (China); Burger, Arnold [Department of Life and Physical Sciences, Fisk University, Nashville, TN 37208-3051 (United States); Sham, Tsun-Kong [Department of Chemistry, The University of Western Ontario, London, Ontario, Canada N6A 5B7 (Canada)

2016-05-15

La{sub 0.2}Y{sub 1.8}O{sub 3} is a new and promising scintillator which is based on the host material without doping. Here the time gated X-ray excited optical luminescence is measured by using the excitation energy below, above and at the La L{sub 3}-edge. A relatively slow and broad emission with peak at 415 nm has been observed as the dominant emission. Also, a weak emission at 360 nm is observed at the fast window, associated with the recombination of trapped excitons in Y{sub 2}O{sub 3} host. The observations show that the broad emission at 415 nm is most likely due to the recombination of trapped excitons associated with the La{sup 3+} doping into Y{sub 2}O{sub 3} sites.

Evolution of simeprevir-resistant variants over time by ultra-deep sequencing in HCV genotype 1b.

Science.gov (United States)

Akuta, Norio; Suzuki, Fumitaka; Sezaki, Hitomi; Suzuki, Yoshiyuki; Hosaka, Tetsuya; Kobayashi, Masahiro; Kobayashi, Mariko; Saitoh, Satoshi; Ikeda, Kenji; Kumada, Hiromitsu

2014-08-01

Using ultra-deep sequencing technology, the present study was designed to investigate the evolution of simeprevir-resistant variants (amino acid substitutions of aa80, aa155, aa156, and aa168 positions in HCV NS3 region) over time. In Toranomon Hospital, 18 Japanese patients infected with HCV genotype 1b, received triple therapy of simeprevir/PEG-IFN/ribavirin (DRAGON or CONCERT study). Sustained virological response rate was 67%, and that was significantly higher in patients with IL28B rs8099917 TT than in those with non-TT. Six patients, who did not achieve sustained virological response, were tested for resistant variants by ultra-deep sequencing, at the baseline, at the time of re-elevation of viral loads, and at 96 weeks after the completion of treatment. Twelve of 18 resistant variants, detected at re-elevation of viral load, were de novo resistant variants. Ten of 12 de novo resistant variants become undetectable over time, and that five of seven resistant variants, detected at baseline, persisted over time. In one patient, variants of Q80R at baseline (0.3%) increased at 96-week after the cessation of treatment (10.2%), and de novo resistant variants of D168E (0.3%) also increased at 96-week after the cessation of treatment (9.7%). In conclusion, the present study indicates that the emergence of simeprevir-resistant variants after the start of treatment could not be predicted at baseline, and the majority of de novo resistant variants become undetectable over time. Further large-scale prospective studies should be performed to investigate the clinical utility in detecting simeprevir-resistant variants. © 2014 Wiley Periodicals, Inc.

AdS{sub 3} holography for 1/4 and 1/8 BPS geometries

Energy Technology Data Exchange (ETDEWEB)

Giusto, Stefano [Dipartimento di Fisica ed Astronomia “Galileo Galilei”, Università di Padova,Via Marzolo 8, 35131 Padova (Italy); I.N.F.N. Sezione di Padova,Via Marzolo 8, 35131 Padova (Italy); Moscato, Emanuele; Russo, Rodolfo [Centre for Research in String Theory,School of Physics and Astronomy, Queen Mary University of London,Mile End Road, London, E1 4NS (United Kingdom)

2015-11-04

Recently a new class of 1/8-BPS regular geometries in type IIB string theory was constructed in arXiv:1503.01463. In this paper we provide a precise description of the semiclassical states dual, in the AdS/CFT sense, to these geometries. In explicit examples we show that the holographic 1-point functions and the Ryu-Takayanagi’s Entanglement Entropy for a single small interval match the corresponding CFT calculations performed by using the proposed dual states. We also discuss several new examples of such precision holography analysis in the 1/4-BPS sector and provide an explicit proof that the small interval derivation of the Entanglement Entropy used in arXiv:1405.6185 is fully covariant.

New genetic variants of LATS1 detected in urinary bladder and colon cancer.

Science.gov (United States)

Saadeldin, Mona K; Shawer, Heba; Mostafa, Ahmed; Kassem, Neemat M; Amleh, Asma; Siam, Rania

2014-01-01

LATS1, the large tumor suppressor 1 gene, encodes for a serine/threonine kinase protein and is implicated in cell cycle progression. LATS1 is down-regulated in various human cancers, such as breast cancer, and astrocytoma. Point mutations in LATS1 were reported in human sarcomas. Additionally, loss of heterozygosity of LATS1 chromosomal region predisposes to breast, ovarian, and cervical tumors. In the current study, we investigated LATS1 genetic variations including single nucleotide polymorphisms (SNPs), in 28 Egyptian patients with either urinary bladder or colon cancers. The LATS1 gene was amplified and sequenced and the expression of LATS1 at the RNA level was assessed in 12 urinary bladder cancer samples. We report, the identification of a total of 29 variants including previously identified SNPs within LATS1 coding and non-coding sequences. A total of 18 variants were novel. Majority of the novel variants, 13, were mapped to intronic sequences and un-translated regions of the gene. Four of the five novel variants located in the coding region of the gene, represented missense mutations within the serine/threonine kinase catalytic domain. Interestingly, LATS1 RNA steady state levels was lost in urinary bladder cancerous tissue harboring four specific SNPs (16045 + 41736 + 34614 + 56177) positioned in the 5'UTR, intron 6, and two silent mutations within exon 4 and exon 8, respectively. This study identifies novel single-base-sequence alterations in the LATS1 gene. These newly identified variants could potentially be used as novel diagnostic or prognostic tools in cancer.

NUDT15, FTO, and RUNX1 genetic variants and thiopurine intolerance among Japanese patients with inflammatory bowel diseases

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Toshiyuki Sato

2017-07-01

Full Text Available Background/Aims: Recent genome-wide analyses have provided strong evidence concerning adverse events caused by thiopurine drugs such as azathioprine (AZA and 6-mercaptopurine. The strong associations identified between NUDT15 p.Arg139Cys and thiopurine-induced leukopenia and severe hair loss have been studied and confirmed over the last 2 years. However, other coding variants, including NUDT15 p.Val18_Val19insGlyVal, NUDT15 p.Val18Ile, and FTO p.Ala134Thr, and a noncoding variation in RUNX1 (rs2834826 remain to be examined in detail in this respect. Therefore, we investigated the correlation between these adverse events and the 5 recently identified variants mentioned above among Japanese patients with inflammatory bowel diseases (IBD.Methods: One hundred sixty thiopurine-treated patients with IBD were enrolled. Genotyping was performed using TaqMan SNP Genotyping Assays or Sanger sequencing.Results: None of the 5 variants were associated with gastrointestinal intolerance to AZA. However, NUDT15 p.Arg139Cys was significantly associated with the interval between initiation and discontinuation of AZA among patients with gastrointestinal intolerance. This variant was strongly associated with early (<8 weeks and late (≥8 weeks leukopenia and severe hair loss. Moreover, it correlated with the interval between initiation of thiopurine therapy and leukopenia occurrence, and average thiopurine dose. NUDT15 p.Val18_Val19insGlyVal, NUDT15 p.Val18Ile, FTO p.Ala134Thr, and RUNX1 rs2834826 exhibited no significant relationship with the adverse events examined.Conclusions: Of the 5 variants investigated, NUDT15 p.Arg139Cys had the strongest impact on thiopurine-induced leukopenia and severe hair loss; therefore, its genotyping should be prioritized over that of other variants in efforts to predict these adverse events in Japanese patients with IBD.

Genomic diversity of human papillomavirus-16, 18, 31, and 35 isolates in a Mexican population and relationship to European, African, and Native American variants

International Nuclear Information System (INIS)

Calleja-Macias, Itzel E.; Kalantari, Mina; Huh, John; Ortiz-Lopez, Rocio; Rojas-Martinez, Augusto; Gonzalez-Guerrero, Juan F.; Williamson, Anna-Lise; Hagmar, Bjoern; Wiley, Dorothy J.; Villarreal, Luis; Bernard, Hans-Ulrich; Barrera-Saldana, Hugo A.

2004-01-01

Cervical cancer, mainly caused by infection with human papillomaviruses (HPVs), is a major public health problem in Mexico. During a study of the prevalence of HPV types in northeastern Mexico, we identified, as expected from worldwide comparisons, HPV-16, 18, 31, and 35 as highly prevalent. It is well known that the genomes of HPV types differ geographically because of evolution linked to ethnic groups separated in prehistoric times. As HPV intra-type variation results in pathogenic differences, we analyzed genomic sequences of Mexican variants of these four HPV types. Among 112 HPV-16 samples, 14 contained European and 98 American Indian (AA) variants. This ratio is unexpected as people of European ethnicity predominate in this part of Mexico. Among 15 HPV-18 samples, 13 contained European and 2 African variants, the latter possibly due to migration of Africans to the Caribbean coast of Mexico. We constructed phylogenetic trees of HPV-31 and 35 variants, which have never been studied. Forty-six HPV-31 isolates from Mexico, Europe, Africa, and the United States (US) contained a total of 35 nucleotide exchanges in a 428-bp segment, with maximal distances between any two variants of 16 bp (3.7%), similar to those between HPV-16 variants. The HPV-31 variants formed two branches, one apparently the European, the other one an African branch. The European branch contained 13 of 29 Mexican isolates, the African branch 16 Mexican isolates. These may represent the HPV-31 variants of American Indians, as a 55% prevalence of African variants in Mexico seems incomprehensible. Twenty-seven HPV-35 samples from Mexico, Europe, Africa, and the US contained 11 mutations in a 893-bp segment with maximal distances between any two variants of only 5 mutations (0.6%), including a characteristic 16-bp insertion/deletion. These HPV-35 variants formed several phylogenetic clusters rather than two- or three-branched trees as HPV-16, 18, and 31. An HPV-35 variant typical for American

Measurement of Drell-Yan electron and muon pair differential cross sections in bar pp collisions at √s =1.8 TeV

International Nuclear Information System (INIS)

Abe, F.; Albrow, M.; Amidei, D.; Anway-Wiese, C.; Apollinari, G.; Atac, M.; Auchincloss, P.; Azzi, P.; Bacchetta, N.; Baden, A.R.; Badgett, W.; Bailey, M.W.; Bamberger, A.; de Barbaro, P.; Barbaro-Galtieri, A.; Barnes, V.E.; Barnett, B.A.; Bauer, G.; Baumann, T.; Bedeschi, F.; Behrends, S.; Belforte, S.; Bellettini, G.; Bellinger, J.; Benjamin, D.; Benlloch, J.; Bensinger, J.; Beretvas, A.; Berge, J.P.; Bertolucci, S.; Biery, K.; Bhadra, S.; Binkley, M.; Bisello, D.; Blair, R.; Blocker, C.; Bloom, K.; Bodek, A.; Bolognesi, V.; Booth, A.W.; Boswell, C.; Brandenburg, G.; Brown, D.; Buckley-Geer, E.; Budd, H.S.; Busetto, G.; Byon-Wagner, A.; Byrum, K.L.; Campagnari, C.; Campbell, M.; Caner, A.; Carey, R.; Carithers, W.; Carlsmith, D.; Carroll, J.T.; Cashmore, R.; Castro, A.; Cen, Y.; Cervelli, F.; Chadwick, K.; Chapman, J.; Chiarelli, G.; Chinowsky, W.; Cihangir, S.; Clark, A.G.; Cobal, M.; Connor, D.; Contreras, M.; Cooper, J.; Cordelli, M.; Crane, D.; Cunningham, J.D.; Day, C.; DeJongh, F.; Dell'Agnello, S.; Dell'Orso, M.; Demortier, L.; Denby, B.; Derwent, P.F.; Devlin, T.; DiBitonto, D.; Dickson, M.; Drucker, R.B.; Dunn, A.; Einsweiler, K.; Elias, J.E.; Ely, R.; Eno, S.; Errede, S.; Etchegoyen, A.; Farhat, B.; Frautschi, M.; Feldman, G.J.; Flaugher, B.; Foster, G.W.; Franklin, M.; Freeman, J.; Frisch, H.; Fuess, T.; Fukui, Y.; Garfinkel, A.F.; Gauthier, A.; Geer, S.; Gerdes, D.W.; Giannetti, P.; Giokaris, N.; Giromini, P.; Gladney, L.; Gold, M.; Gonzalez, J.; Goulianos, K.; Grassmann, H.; Grieco, G.M.; Grindley, R.; Grosso-Pilcher, C.; Haber, C.; Hahn, S.R.; Handler, R.; Hara, K.; Harral, B.; Harris, R.M.; Hauger, S.A.; Hauser, J.; Hawk, C.; Hessing, T.; Hollebeek, R.; Holloway, L.; Hoelscher, A.; Hong, S.; Houk, G.; Hu, P.; Hubbard, B.; Huffman, B.T.; Hughes, R.; Hurst, P.; Huth, J.; Hylen, J.; Incagli, M.; Ino, T.; Iso, H.; Jensen, H.; Jessop, C.P.; Johnson, R.P.; Joshi, U.; Kadel, R.W.; Kamon, T.; Kanda, S.; Kardelis, D.A.; Karliner, I.; Kearns, E.

1994-01-01

We measure the Drell-Yan differential cross section d 2 σ/dM dy| |y| over the mass range 11 2 using dielectron and dimuon data from bar pp collisions at a center-of-mass energy of √s =1.8 TeV. Our results show the 1/M 3 dependence that is expected from the naive Drell-Yan model. In comparison to the predictions of recent QCD calculations we find our data favor those parton distribution functions with the largest quark contributions in the x interval 0.006 to 0.03

Novel P-TEN-induced putative kinase 1 (PINK1) variant in Indian Parkinson's disease patient.

Science.gov (United States)

Halder, Tamali; Raj, Janak; Sharma, Vivek; Das, Parimal

2015-09-25

Loss-of-function mutation in PINK1 is known for causing autosomal recessive early onset Parkinsonism accounting approximately 6.5% of PD cases. Recently, PINK1 has also been shown to cause Parkinson's disease (PD) in eastern India. Present study is aimed to see its contribution in north-Indian PD patients. A total of 106 PD patients and 60 ethnically matched healthy controls were included in the study. All the patients were screened for mutation in PINK1 by direct DNA sequence analysis of the PCR amplicons covering all exons and exon-intron boundaries. Identified novel variant was reconfirmed by DNA sequencing of 10 randomly selected TA clones containing the variant amplicon. In vitro functional assay of the mutant protein was performed by transfecting COS-7 cell line with wild type and mutant (created by site-directed-mutagenesis) cDNA construct of PINK1 fused to N' terminal GFP followed by western blot analysis. Two potentially pathogenic, one being novel (p.Q267X) and 6 other apparently non-pathogenic variants were identified. Western blot analysis reveals production of truncated PINK1 fusion protein of ∼55kDa in p.Q267X mutant instead of 82/93kDa of wild type PINK1 fusion protein (molecular weight of GFP is ∼27kDa). Our study concludes that PINK1 variants are prevalent for causing Parkinson's disease (PD) in India, as revealed by the occurrence of 1.8% (2/106) in PD patients from north Indian population. The novel homozygous variant of PINK1 (c.799C>T) reported here is the plausible cause for disease manifestation in this patient. Future study, however, would be helpful to understand the functional mechanism how this premature PINK1 protein (p.Q267X) responds to cellular stress leading to the PD pathophysiology. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

In vitro metabolism studies of 18F-labeled 1-phenylpiperazine using mouse liver S9 fraction

International Nuclear Information System (INIS)

Ryu, Eun Kyoung; Choe, Yearn Seong; Kim, Dong Hyun; Ko, Bong-Ho; Choi, Yong; Lee, Kyung-Han; Kim, Byung-Tae

2006-01-01

The in vitro metabolism of 1-(4-[ 18 F]fluoromethylbenzyl)-4-phenylpiperazine ([ 18 F]1) and 1-(4-[ 18 F]fluorobenzyl)-4-phenylpiperazine ([ 18 F]2) was investigated using mouse liver S9 fraction. Results were compared to those of in vivo metabolism using mouse blood and bone and to in vitro metabolism using mouse liver microsomes. Defluorination was the main metabolic pathway for [ 18 F]1 in vitro and in vivo. Based on TLC, HPLC and LC-MS data, [ 18 F]fluoride ion and less polar radioactive metabolites derived from aromatic ring oxidation were detected in vitro, and the latter metabolites were rapidly converted into the former with time, whereas only the [ 18 F]fluoride ion was detected in vivo. Similarly, the in vitro metabolism of [ 18 F]2 using either S9 fraction or microsomes showed the same pattern as the in vivo method using blood; however, the radioactive metabolites derived from aromatic ring oxidation were not detected in vivo. These results demonstrate that liver S9 fraction can be widely used to investigate the intermediate radioactive metabolites and to predict the in vivo metabolism of radiotracers

Fotometría y polarimetría de Lynga 1

Science.gov (United States)

Brusasco, M. A.; Baume, G.; Vázquez, R. A.

Se presentan los resultados de las observaciones fotométricas CCD-UBVRI hasta magnitud aproximadamente V = 18 y polarimétricas hasta V = 13 en la zona del cúmulo abierto Lynga 1. El mismo se halla en una dirección cercana a un remanente de supernova y fue estudiado previamente por Peterson y FitzGerald (1988) mediante fotometría fotoeléctrica. Se ha redeterminado el enrojecimiento, la distancia y la edad de dicho objeto. Se han hallado además los valores de las pendientes de las funciones de luminosidad y de masa comparándoselas con las de otros cúmulos de edades similares.

Fracturas orbitocigomáticas, valor de la clasificación de Knight y North en su terapéutica Orbitozygomatic fractures and the value of Knight and North´s classification.

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Oscar N. García-Roco Pérez

2006-08-01

Full Text Available Se realizó un estudio observacional descriptivo de 230 pacientes intervenidos quirúrgicamente por fracturas orbitocigomáticas en el Servicio de Cirugía Maxilofacial del Hospital Provincial Docente "Manuel Ascunce Domenech" de Camagüey, en el período de enero 1999 a diciembre 2003, con el propósito de describir el valor de la clasificación de Knight y North en la selección de variantes quirúrgicas terapéuticas de las fracturas orbitocigomáticas, a través de la experiencia del servicio. Se utilizó la clasificación de Knight y North para la selección de las variantes de tratamiento, determinándose las variables edad, sexo, clasificación, terapéutica quirúrgica, complicaciones y resultados posoperatorios. Se observó un predominio del sexo masculino con el 75,7 %, y dicha cirugía se realizó con mayor frecuencia entre los 25-34 años (34,3 %. La clase III de Knight y North fue la más frecuente (45,6 %, seguida por la II y IV, con el 31,6 y 10,1 %, respectivamente. Basados en esta clasificación y teniendo en cuenta el grado de inestabilidad posreducción esperado, se seleccionó adecuadamente la variante terapéutica a emplear en el 98,8 % de los casos. Se llega a la conclusión de que la incidencia de fracturas orbitocigomáticas es alta, y dentro de ellas, la clase III de Knight y North es la más frecuente. Se recomienda esta clasificación para su tratamiento, ya que permite seleccionar la variante de tratamiento más adecuada de acuerdo con el grado de inestabilidad posreducción esperado, lográndose resultados estéticos y funcionales adecuados con escasas complicaciones posoperatorias no inherentes a esta.A descriptive observational study of 250 patients, who were operated on from orbitozygomatic fractures at the Maxillofacial Surgery Service of “Manuel Ascunce Domenech” provincial teaching hospital in Camaguey from January 1999 to December 2003, was conducted . The objective was to describe the importance of Knight

DINÁMICA DE LA RESPUESTA HUMORAL ESPECÍFICA Y FRECUENCIA DE VARIANTES DEL VIRUS DE PRRS EN TRES GRANJAS PORCINAS CON DIFERENTES ESTRATEGIAS DE CONTROL, EN YUCATÁN, MÉXICO

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Pilar Gómez-Ruiz

2014-04-01

Full Text Available El objetivo de este estudio fue describir la dinámica de la respuesta humoral específica y la frecuencia de variantes del virus del PRRS en tres granjas con diferentes estrategias de control. Treinta cerdos en cada granja fueron estudiados. Los animales se muestrearon y los sueros se procesaron mediante ELISA y RT-PCR in tiempo real usando tecnología Sybr Green para detectar las variantes del virus del PRRS. La media de los valores de S/P, RT-PCR y temperatura de desnaturalización se compararon a los 21, 49, 77,105 y 160 días de edad. Los cerdos de las granja A fueron positivos a la prueba de ELISA en todas las edades; en la granja B los cerdos fueron positivos a los 77, 105 y 160 días de edad, y los cerdos de la granja C fueron positivos a los 105 y 160 días de edad. Las temperaturas de desnaturalización, mostraron cuatro diferentes tiempos de desnaturalización en cada granja, correspondiendo a cuatro tipos de virus: virus vacunal, inóculo y dos tipos silvestres de virus. En conclusión, las diferentes estrategias utilizadas en las granjas indujeron una respuesta inmune en la mayoría de los animales. En la granja A se obtuvieron las medias más altas de S/P. Las estrategias de control no evitaron la presencia de variantes del virus del PRRS por lo que pudieran representar un riesgo para la población animal.

Genetic variant of AMD1 is associated with obesity in urban Indian children.

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Rubina Tabassum

Full Text Available Hyperhomocysteinemia is regarded as a risk factor for cardiovascular diseases, diabetes and obesity. Manifestation of these chronic metabolic disorders starts in early life marked by increase in body mass index (BMI. We hypothesized that perturbations in homocysteine metabolism in early life could be a link between childhood obesity and adult metabolic disorders. Thus here we investigated association of common variants from homocysteine metabolism pathway genes with obesity in 3,168 urban Indian children.We genotyped 90 common variants from 18 genes in 1,325 children comprising of 862 normal-weight (NW and 463 over-weight/obese (OW/OB children in stage 1. The top signal obtained was replicated in an independent sample set of 1843 children (1,399 NW and 444 OW/OB in stage 2. Stage 1 association analysis revealed association between seven variants and childhood obesity at P<0.05, but association of only rs2796749 in AMD1 [OR = 1.41, P = 1.5×10(-4] remained significant after multiple testing correction. Association of rs2796749 with childhood obesity was validated in stage 2 [OR = 1.28, P = 4.2×10(-3] and meta-analysis [OR = 1.35, P = 1.9×10(-6]. AMD1 variant rs2796749 was also associated with quantitative measures of adiposity and plasma leptin levels that was also replicated and corroborated in combined analysis.Our study provides first evidence for the association of AMD1 variant with obesity and plasma leptin levels in children. Further studies to confirm this association, its functional significance and mechanism of action need to be undertaken.

Prácticas sexuales y seroprevalencia de infección por VIH, HTLV-1 sífilis en meretrices clandestinas de Lima

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Luis Trujillo

1996-10-01

Full Text Available Objetivo: Investigar la prevalencia de prácticas sexuales de riesgo para infección por Enfermedades de Transmisión Sexual (ETS y la seroprevalencia de infección por VIH-1, HTLV-1 y Treponema pallidum en meretrices de los burdeles clandestinos de Lima. Material y métodos: Estudio de diseño transversal, descriptivo y no probabilístico. Se realizó una encuesta anónima por entrevista directa sobre prácticas sexuales y antecedentes de ETS y se tomó una muestra de sangre para análisis serológico de anticuerpos contra VIH-1, HTLV-1 y T. Pallidum de 158 meretrices voluntarias en 15 burdeles clandestinos de Lima Metropolitana entre marzo y junio de 1994. Resultados: Todas las muestras de suero fueron negativas para VIH-1 (IC 95%, 0.0 - 1.8 pero dos resultaron indeterminadas (ELISA positivo y WB banda p24 presente. Seis (3.8% positivas para HTLV-1 (IC 95%, 1.4 - 8.1. Cinco (3.2% fueron VDRL reactivas (IC 95%, 1.0 - 7.3. El uso consistente de condón con los clientes fue 75% (119/158. Sólo 3% (4/137 lo usan con su pareja sexual estable. Las prácticas sexuales de riesgo encontradas fueron: coito anal 7.6%, relaciones sexuales durante la menstruación 37%, felación 93%, relaciones sexuales con clientes portadores de úlceras genitales 19%; pero refirieron un mayor uso del condón en las mismas. El 25% tuvo antecedentes de alguna ETS en los últimos 5 años, siendo gonorrea, la más frecuente (22%. Conclusiones: La población de meretrices de los burdeles clandestinos de Lima tiene un elevado uso consistente del condón con clientes, y la prevalencia de infección retroviral y de sífilis es baja. (Rev Med Hered 1996; 7: 162-171.

Minor drug-resistant HIV type-1 variants in breast milk and plasma of HIV type-1-infected Ugandan women after nevirapine single-dose prophylaxis.

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Pilger, Daniel; Hauser, Andrea; Kuecherer, Claudia; Mugenyi, Kizito; Kabasinguzi, Rose; Somogyi, Sybille; Harms, Gundel; Kunz, Andrea

2011-01-01

Nevirapine single-dose (NVP-SD) reduces mother-to-child transmission of HIV type-1 (HIV-1), but frequently induces resistance mutations in the HIV-1 genome. Little is known about drug-resistant HIV-1 variants in the breast milk of women who have taken NVP-SD. Blood and breast milk samples of 39 HIV-1-infected Ugandan women were taken 6-12 weeks after NVP-SD intake. Samples were analysed by population sequencing and allele-specific real-time PCR (AS-PCR) with detection limits for NVP-resistant HIV-1 variants (K103N and Y181C) of D n = 5, G n = 2 and C n = 1). A total of 7 (37%) and 10 (53%) women carried NVP-resistant virus in breast milk and plasma, respectively. Overall, 71% (5/7) women with NVP-resistant HIV-1 in breast milk displayed >1 drug-resistant variant. Resistance in breast milk was higher at week 6 (6/13 samples [46%]) compared with week 12 (1/6 samples [17%]). In total, 10 drug-resistant populations harbouring the K103N and/or Y181C mutation were detected in the 19 breast milk samples; 7 (70%) were caused by resistant minorities (< 5% of the total HIV-1 population). In the four women with drug-resistant virus in both plasma and breast milk, the mutation patterns differed between the two compartments. Minor populations of drug-resistant HIV-1 were frequently found in breast milk of Ugandan women after exposure to NVP-SD. Further studies need to explore the role of minor drug-resistant variants in the postnatal transmission of (resistant) HIV-1.

Frequency of the Hemochromatosis Gene (HFE Variants in a Jordanian Arab Population and in Diabetics from the Same Region

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Asem Alkhateeb

2009-01-01

Full Text Available Hereditary HFE-linked hemochromatosis is a frequent recessive disorder among individuals of northern European ancestry. The clinical characteristic of this disease is the gradual accumulation of iron in internal organs, which ultimately may lead to organ damage and death. Three allelic variants of HFE gene have been correlated with hereditary hemochromatosis: C282Y is significantly associated with hereditary hemochromatosis in populations of Celtic origin, H63D and S65C are associated with milder form of iron overload. In this study we performed mutation analysis to identify allele frequency of the three variants of HFE gene in Jordanian Arab population, to assess deviations of these frequencies from those detected elsewhere, and to determine if there is an increased frequency of these variants in a diabetic population (Type 2 diabetes from the same area. DNA was extracted from blood samples of 440 individuals attending King Abdullah University Hospital for ambulatory services. We used polymerase chain reaction (PCR to amplify exons 2 and 4 of the HFE gene then restriction fragment length polymorphism (RFLP method to detect the variants. There were neither homozygous nor heterozygous for C282Y variant. For the H63D variant, 0.68% were homozygous and 21.1% were heterozygous. For the S65C variant, there were no homozygous and 0.23% were heterozygous. Allelic frequencies were, 0%, 11.25%, and 0.11% for C282Y, H63D, and S65C, respectively. Our samples were subdivided into two categories of type 2 diabetic (89 cases and controls (blood donors, 204 cases and compared with regard to the H63D variant. Both groups did not have homozygous H63D variant. H63D heterozygous in diabetics were 23.60% and in blood donor controls 22.55%. Allelic frequency of the mutant H63D allele was 11.80% in diabetics and 11.27% for the blood donor controls. This is the first study to show the frequency of the three hemochromatosis gene variants in Jordan with the interesting

Relación entre el feedback emocional, feedback cognitivo-verbal y percepción emocional en la variante frontal de demencia frontotemporal resultados preliminares Relationship Between Emotional Feedback, Verbal-Cognitive Feedback And Emotional Perception In The Frontal Variant Of Frontotemporal Dementia Preliminary Results

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Florencia Calodolce

2008-12-01

Full Text Available Numerosos estudios hallaron disociaciones, tanto entre las pruebas de cognición social entre sí, como entre éstas y las que evalúan funciones ejecutivas, lo cual apoya la idea de que el feedback emocional, la percepción emocional y el feedback cognitivo-verbal constituyen dominios cognitivos independientes. Sin embargo en la literatura actual existe controversia respecto de aquella disociación. Con el objetivo de estudiar dicha relación se evaluaron 15 sujetos con variante frontal de Demencia Frontotemporal (DFTvf con una batería neuropsicológica, y además utilizando: Wisconsin Card Sorting Test (WCST, Iowa Gamblig Task (IGT y Test de Lectura de Mente en Ojos (LMO. Se encontró un correlación inversa entre IGT y WCST, correlación directa entre LMO y WCST y falta de correlación entre IGT y LMO. Estos resultados apoyan la hipótesis de que los dominios cognitivos estudiados se encuentran disociados (Bechara, A., Damasio, A.R. y Lough, S..Several studies found dissociations, both between social cognition tests among themselves, and between these and those evaluating executive functions, which supports the idea that emotional feedback, emotional perception and verbal-cognitive feedback are independent cognitive domains. Nevertheless in present literature there is a controversy respect to that dissosciation. With the objective to study the relation between these processes a group of 15 subjects with frontal variant of Frontotemporal Dementia (DFTvf, was evaluated with a neuropsycological battery and in addition using: Wisconsin Card Sorting Test (WCST, Iowa Gamblig Task (IGT and The Reading the mind in Eyes Test (LMO. There was found: an inverse correlation between IGT and WCST, a direct correlation between LMO and WCST and a lack of correlation between IGT and LMO. These results support the hypothesis that the studied cognitive domains are dissociated (Bechara,A., Damasio, A.R. y Lough, S..

Percepción del estrés competitivo y cultura en futbolistas profesionales de Brasil y Portugal

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M. Regina F. Brand\\u00E3o

2006-01-01

Full Text Available El objetivo del presente estudio fue comparar jugadores de fútbol con diferentes perspectivas culturales y similar nivel de experiencia, en la percepción del estrés. Fueron evaluados 18 jugadores Brasileños de la Selección Nacional Brasileña, y 20 jugadores Portugueses de la Selección Nacional Portuguesa, con una media de edad de 26,69 + 4,1 y 26,05 + 2,3 años respectivamente, mediante el Inventario de Estrés en Fútbol. Aparece una tendencia resulta muy marcada, los ítems que son evaluados como positivos por los dos grupos, los Brasileños tienden a evaluarlos significativamente más positivos que los Portugueses y en los evaluados como negativos por las dos nacionalidades, los Brasileños tienden a evaluarlos como más negativos. Quizás más interesante aún resulta la gran cantidad de ítems que son evaluados como influyentes en tendencias totalmente inversas, lo que los Brasileños consideran negativo es considerado por los Portugueses como positivo o neutro. Muy probablemente la variable cultural puede explicar la variabilidad de percepción del estrés.

Haplotype analysis of common variants in the BRCA1 gene and risk of sporadic breast cancer

International Nuclear Information System (INIS)

Cox, David G; Kraft, Peter; Hankinson, Susan E; Hunter, David J

2005-01-01

Truncation mutations in the BRCA1 gene cause a substantial increase in risk of breast cancer. However, these mutations are rare in the general population and account for little of the overall incidence of sporadic breast cancer. We used whole-gene resequencing data to select haplotype tagging single nucleotide polymorphisms, and examined the association between common haplotypes of BRCA1 and breast cancer in a nested case-control study in the Nurses' Health Study (1323 cases and 1910 controls). One haplotype was associated with a slight increase in risk (odds ratio 1.18, 95% confidence interval 1.02–1.37). A significant interaction (P = 0.05) was seen between this haplotype, positive family history of breast cancer, and breast cancer risk. Although not statistically significant, similar interactions were observed with age at diagnosis and with menopausal status at diagnosis; risk tended to be higher among younger, pre-menopausal women. We have described a haplotype in the BRCA1 gene that was associated with an approximately 20% increase in risk of sporadic breast cancer in the general population. However, the functional variant(s) responsible for the association are unclear

eCD4-Ig variants that more potently neutralize HIV-1.

Science.gov (United States)

Fetzer, Ina; Gardner, Matthew R; Davis-Gardner, Meredith E; Prasad, Neha R; Alfant, Barnett; Weber, Jesse A; Farzan, Michael

2018-03-28

utility of antibodies as a treatment for HIV-1 infection or part of an effort to eradicate latently infected cells. eCD4-Ig is an antibody-like entry inhibitor that closely mimics HIV-1's obligate receptors. eCD4-Ig appears to be qualitatively different from antibodies since it neutralizes all HIV-1, HIV-2, and SIV isolates. Here we characterize three new structurally distinct eCD4-Ig variants, and show that each excels in a key property useful to prevent, treat or cure an HIV-1 infection. For example, one variant neutralized HIV-1 most efficiently, while others best enlisted natural killer cells to eliminate infected cells. These observations will help generate eCD4-Ig variants optimized for different clinical applications. Copyright © 2018 American Society for Microbiology.

Fine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants.

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Mengmeng Du

Full Text Available Genome-wide association studies (GWAS have identified many common single nucleotide polymorphisms (SNPs associated with colorectal cancer risk. These SNPs may tag correlated variants with biological importance. Fine-mapping around GWAS loci can facilitate detection of functional candidates and additional independent risk variants. We analyzed 11,900 cases and 14,311 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. To fine-map genomic regions containing all known common risk variants, we imputed high-density genetic data from the 1000 Genomes Project. We tested single-variant associations with colorectal tumor risk for all variants spanning genomic regions 250-kb upstream or downstream of 31 GWAS-identified SNPs (index SNPs. We queried the University of California, Santa Cruz Genome Browser to examine evidence for biological function. Index SNPs did not show the strongest association signals with colorectal tumor risk in their respective genomic regions. Bioinformatics analysis of SNPs showing smaller P-values in each region revealed 21 functional candidates in 12 loci (5q31.1, 8q24, 11q13.4, 11q23, 12p13.32, 12q24.21, 14q22.2, 15q13, 18q21, 19q13.1, 20p12.3, and 20q13.33. We did not observe evidence of additional independent association signals in GWAS-identified regions. Our results support the utility of integrating data from comprehensive fine-mapping with expanding publicly available genomic databases to help clarify GWAS associations and identify functional candidates that warrant more onerous laboratory follow-up. Such efforts may aid the eventual discovery of disease-causing variant(s.

Mass spectrometry analysis of the variants of histone H3 and H4 of soybean and their post-translational modifications

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Lam Hon-Ming

2009-07-01

Full Text Available Abstract Background Histone modifications and histone variants are of importance in many biological processes. To understand the biological functions of the global dynamics of histone modifications and histone variants in higher plants, we elucidated the variants and post-translational modifications of histones in soybean, a legume plant with a much bigger genome than that of Arabidopsis thaliana. Results In soybean leaves, mono-, di- and tri-methylation at Lysine 4, Lysine 27 and Lysine 36, and acetylation at Lysine 14, 18 and 23 were detected in HISTONE H3. Lysine 27 was prone to being mono-methylated, while tri-methylation was predominant at Lysine 36. We also observed that Lysine 27 methylation and Lysine 36 methylation usually excluded each other in HISTONE H3. Although methylation at HISTONE H3 Lysine 79 was not reported in A. thaliana, mono- and di-methylated HISTONE H3 Lysine 79 were detected in soybean. Besides, acetylation at Lysine 8 and 12 of HISTONE H4 in soybean were identified. Using a combination of mass spectrometry and nano-liquid chromatography, two variants of HISTONE H3 were detected and their modifications were determined. They were different at positions of A31F41S87S90 (HISTONE variant H3.1 and T31Y41H87L90 (HISTONE variant H3.2, respectively. The methylation patterns in these two HISTONE H3 variants also exhibited differences. Lysine 4 and Lysine 36 methylation were only detected in HISTONE H3.2, suggesting that HISTONE variant H3.2 might be associated with actively transcribing genes. In addition, two variants of histone H4 (H4.1 and H4.2 were also detected, which were missing in other organisms. In the histone variant H4.1 and H4.2, the amino acid 60 was isoleucine and valine, respectively. Conclusion This work revealed several distinct variants of soybean histone and their modifications that were different from A. thaliana, thus providing important biological information toward further understanding of the histone

Next generation sequencing identifies abnormal Y chromosome and candidate causal variants in premature ovarian failure patients.

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Lee, Yujung; Kim, Changshin; Park, YoungJoon; Pyun, Jung-A; Kwack, KyuBum

2016-12-01

Premature ovarian failure (POF) is characterized by heterogeneous genetic causes such as chromosomal abnormalities and variants in causal genes. Recently, development of techniques made next generation sequencing (NGS) possible to detect genome wide variants including chromosomal abnormalities. Among 37 Korean POF patients, XY karyotype with distal part deletions of Y chromosome, Yp11.32-31 and Yp12 end part, was observed in two patients through NGS. Six deleterious variants in POF genes were also detected which might explain the pathogenesis of POF with abnormalities in the sex chromosomes. Additionally, the two POF patients had no mutation in SRY but three non-synonymous variants were detected in genes regarding sex reversal. These findings suggest candidate causes of POF and sex reversal and show the propriety of NGS to approach the heterogeneous pathogenesis of POF. Copyright © 2016 Elsevier Inc. All rights reserved.

5-Gb/s 0.18-{mu}m CMOS 2:1 multiplexer with integrated clock extraction

Energy Technology Data Exchange (ETDEWEB)

Zhang Changchun; Wang Zhigong; Shi Si; Miao Peng [Institute of RF- and OE-ICs, Southeast University, Nanjing 210096 (China); Tian Ling, E-mail: zgwang@seu.edu.c [School of Science and Engineering, Southeast University, Nanjing 210096 (China)

2009-09-15

A 5-Gb/s 2:1 MUX (multiplexer) with an on-chip integrated clock extraction circuit which possesses the function of automatic phase alignment (APA), has been designed and fabricated in SMIC's 0.18 {mu}m CMOS technology. The chip area is 670 x 780 {mu}m{sup 2}. At a single supply voltage of 1.8 V, the total power consumption is 112 mW with an input sensitivity of less than 50 mV and an output single-ended swing of above 300 mV. The measurement results show that the IC can work reliably at any input data rate between 1.8 and 2.6 Gb/s with no need for external components, reference clock, or phase alignment between data and clock. It can be used in a parallel optic-fiber data interconnecting system.

Engineered Cpf1 variants with altered PAM specificities increase genome targeting range

Science.gov (United States)

Gao, Linyi; Cox, David B.T.; Yan, Winston X.; Manteiga, John C.; Schneider, Martin W.; Yamano, Takashi; Nishimasu, Hiroshi; Nureki, Osamu; Crosetto, Nicola; Zhang, Feng

2017-01-01

The RNA-guided endonuclease Cpf1 is a promising tool for genome editing in eukaryotic cells1–7. However, the utility of the commonly used Acidaminococcus sp. BV3L6 Cpf1 (AsCpf1) and Lachnospiraceae bacterium ND2006 Cpf1 (LbCpf1) is limited by their requirement of a TTTV protospacer adjacent motif (PAM) in the DNA substrate. To address this limitation, we performed a structure-guided mutagenesis screen to increase the targeting range of Cpf1. We engineered two AsCpf1 variants carrying the mutations S542R/K607R and S542R/K548V/N552R, which recognize TYCV and TATV PAMs, respectively, with enhanced activities in vitro and in human cells. Genome-wide assessment of off-target activity using BLISS7 assay indicated that these variants retain high DNA targeting specificity, which we further improved by introducing an additional non-PAM-interacting mutation. Introducing the identified mutations at their corresponding positions in LbCpf1 similarly altered its PAM specificity. Together, these variants increase the targeting range of Cpf1 by approximately three-fold in human coding sequences to one cleavage site per ~11 bp. PMID:28581492

Alloying as a Route to Monolayer Transition Metal Dichalcogenides with Improved Optoelectronic Performance: Mo(S1–xSex)2 and Mo1–yWyS2

KAUST Repository

Shi, Zhiming; Zhang, Qingyun; Schwingenschlö gl, Udo

2018-01-01

–xSex)2 and Mo1–yWyS2 with x = 1/3, 2/3 and y = 1/3, 1/2, 2/3 are stable according to phonon calculations and realize 1T′ or 1T″ phases. The transition barriers from the 2H phase are lower than for monolayer MoS2, implying that the 1T′ or 1T″ phases

GBA Variants Influence Motor and Non-Motor Features of Parkinson’s Disease

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Jesús, Silvia; Huertas, Ismael; Cáceres-Redondo, María Teresa; Vargas-González, Laura; Gómez-Llamas, Myriam; Carrillo, Fátima; Calderón, Enrique; Carballo, Manuel; Gómez-Garre, Pilar; Mir, Pablo

2016-01-01

The presence of mutations in glucocerebrosidase (GBA) gene is a known factor increasing the risk of developing Parkinson’s disease (PD). Mutations carriers have earlier disease onset and are more likely to develop neuropsychiatric symptoms than other sporadic PD cases. These symptoms have primarily been observed in Parkinson’s patients carrying the most common pathogenic mutations L444P and N370S. However, recent findings suggest that other variants across the gene may have a different impact on the phenotype as well as on the disease progression. We aimed to explore the influence of variants across GBA gene on the clinical features and treatment related complications in PD. In this study, we screened the GBA gene in a cohort of 532 well-characterised PD patients and 542 controls from southern Spain. The potential pathogeniticy of the identified variants was assessed using in-silico analysis and subsequently classified as benign or deleterious. As a result, we observed a higher frequency of GBA variants in PD patients (12.2% vs. 7.9% in controls, p = 0.021), earlier mean age at disease onset in GBA variant carriers (50.6 vs. 56.6 years; p = 0.013), as well as more prevalent motor and non-motor symptoms in patients carrying deleterious variants. In addition, we found that dopaminergic motor complications are influenced by both benign and deleterious variants. Our results highlight the fact that the impact on the phenotype highly depends on the potential pathogenicity of the carried variants. Therefore, the course of motor and non-motor symptoms as well as treatment-related motor complications could be influenced by GBA variants. PMID:28030538

Microarray Analysis of Copy Number Variants on the Human Y Chromosome Reveals Novel and Frequent Duplications Overrepresented in Specific Haplogroups.

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Martin M Johansson

Full Text Available The human Y chromosome is almost always excluded from genome-wide investigations of copy number variants (CNVs due to its highly repetitive structure. This chromosome should not be forgotten, not only for its well-known relevance in male fertility, but also for its involvement in clinical phenotypes such as cancers, heart failure and sex specific effects on brain and behaviour.We analysed Y chromosome data from Affymetrix 6.0 SNP arrays and found that the signal intensities for most of 8179 SNP/CN probes in the male specific region (MSY discriminated between a male, background signals in a female and an isodicentric male containing a large deletion of the q-arm and a duplication of the p-arm of the Y chromosome. Therefore, this SNP/CN platform is suitable for identification of gain and loss of Y chromosome sequences. In a set of 1718 males, we found 25 different CNV patterns, many of which are novel. We confirmed some of these variants by PCR or qPCR. The total frequency of individuals with CNVs was 14.7%, including 9.5% with duplications, 4.5% with deletions and 0.7% exhibiting both. Hence, a novel observation is that the frequency of duplications was more than twice the frequency of deletions. Another striking result was that 10 of the 25 detected variants were significantly overrepresented in one or more haplogroups, demonstrating the importance to control for haplogroups in genome-wide investigations to avoid stratification. NO-M214(xM175 individuals presented the highest percentage (95% of CNVs. If they were not counted, 12.4% of the rest included CNVs, and the difference between duplications (8.9% and deletions (2.8% was even larger.Our results demonstrate that currently available genome-wide SNP platforms can be used to identify duplications and deletions in the human Y chromosome. Future association studies of the full spectrum of Y chromosome variants will demonstrate the potential involvement of gain or loss of Y chromosome sequence in

Quantitative determination of casein genetic variants in goat milk: Application in Girgentana dairy goat breed.

Science.gov (United States)

Montalbano, Maria; Segreto, Roberta; Di Gerlando, Rosalia; Mastrangelo, Salvatore; Sardina, Maria Teresa

2016-02-01

The study was conducted to develop a high-performance liquid chromatographic (HPLC) method to quantify casein genetic variants (αs2-, β-, and κ-casein) in milk of homozygous individuals of Girgentana goat breed. For calibration experiments, pure genetic variants were extracted from individual milk samples of animals with known genotypes. The described HPLC approach was precise, accurate and highly suitable for quantification of goat casein genetic variants of homozygous individuals. The amount of each casein per allele was: αs2-casein A = 2.9 ± 0.8 g/L and F = 1.8 ± 0.4 g/L; β-casein C = 3.0 ± 0.8 g/L and C1 = 2.0 ± 0.7 g/L and κ-casein A = 1.6 ± 0.3 g/L and B = 1.1 ± 0.2 g/L. A good correlation was found between the quantities of αs2-casein genetic variants A and F, and β-casein C and C1 with other previously described method. The main important result was obtained for κ-casein because, till now, no data were available on quantification of single genetic variants for this protein. Copyright © 2015 Elsevier Ltd. All rights reserved.

Short communication: The gain-of-function Y581S polymorphism of the ABCG2 transporter increases secretion into milk of danofloxacin at the therapeutic dose for mastitis treatment.

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Otero, J A; Barrera, B; de la Fuente, A; Prieto, J G; Marqués, M; Álvarez, A I; Merino, G

2015-01-01

The ATP-binding cassette transporter ABCG2 restricts the exposure of certain drugs and natural compounds in different tissues and organs. Its expression in the mammary gland is induced during lactation and is responsible for the active secretion of many compounds into milk, including antimicrobial agents. This particular function of ABCG2 may affect drug efficacy against mastitis and the potential presence of drug residues in the milk. Previous in vitro and in vivo studies showed increased transport of several compounds, including fluoroquinolones, by the bovine ABCG2 Y581S polymorphism. Our main purpose was to study the potential effect of this bovine ABCG2 polymorphism on the secretion into milk of the antimicrobial danofloxacin administered at the therapeutic dose of 6mg/kg used for mastitis treatment. In addition, the effect of this polymorphism on the relative mRNA and protein levels of ABCG2 by quantitative real-time PCR and Western blot were studied. Danofloxacin 18% (6mg/kg) was administered to 6 Y/Y homozygous and 5 Y/S heterozygous cows. Danofloxacin levels in milk and milk-to-plasma concentration ratios were almost 1.5- and 2-fold higher, respectively, in Y/S cows compared with the Y/Y cows, showing a higher capacity of this variant to transport danofloxacin into milk. Furthermore, the higher activity of this polymorphism is not linked to higher ABCG2 mRNA or protein levels. These results demonstrate the relevant effect of the Y581S polymorphism of the bovine ABCG2 transporter in the secretion into milk of danofloxacin after administration of 6mg/kg, with potentially important consequences for mastitis treatment and for milk residue handling. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

[Variability of nuclear 18S-25S rDNA of Gentiana lutea L. in nature and in tissue culture in vitro].

Science.gov (United States)

Mel'nyk, V M; Spiridonova, K V; Andrieiev, I O; Strashniuk, N M; Kunakh, V A

2004-01-01

18S-25S rDNA sequence in genomes of G. lutea plants from different natural populations and from tissue culture has been studied with blot-hybridization method. It was shown that ribosomal repeats are represented by the variants which differ for their size and for the presence of additional HindIII restriction site. Genome of individual plant usually possesses several variants of DNA repeats. Interpopulation variability according to their quantitative ratio and to the presence of some of them has been shown. Modifications of the range of rDNA repeats not exceeding intraspecific variability were observed in callus tissues in comparison with the plants of initial population. Non-randomness of genome modifications in the course of cell adaptation to in vitro conditions makes it possible to some extent to forecast these modifications in tissue culture.

Functional and clinical relevance of novel and known PCSK1 variants for childhood obesity and glucose metabolism

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Dennis Löffler

2017-03-01

Full Text Available Objective: Variants in Proprotein Convertase Subtilisin/Kexin Type 1 (PCSK1 may be causative for obesity as suggested by monogenic cases and association studies. Here we assessed the functional relevance in experimental studies and the clinical relevance through detailed metabolic phenotyping of newly identified and known PCSK1 variants in children. Results: In 52 obese children selected for elevated proinsulin levels and/or impaired glucose tolerance, we found eight known variants and two novel heterozygous variants (c.1095 + 1G > A and p.S24C by sequencing the PCSK1 gene. Patients with the new variants presented with extreme obesity, impaired glucose tolerance, and PCOS. Functionally, c.1095 + 1G > A caused skipping of exon8 translation and a complete loss of enzymatic activity. The protein was retained within the endoplasmic reticulum (ER causing ER stress. The p.S24C variant had no functional effect on protein size, cell trafficking, or enzymatic activity. The known variants rs6230, rs35753085, and rs725522 in the 5′ end did not affect PCSK1 promoter activity.In clinical association studies in 1673 lean and obese children, we confirmed associations of rs6232 and rs6234 with BMI-SDS and of rs725522 with glucose stimulated insulin secretion and Matsuda index. We did not find the new variants in any other subjects. Conclusions: We identified and functionally characterized two rare novel PCSK1 variants of which c.1095 + 1G > A caused complete loss of protein function. In addition to confirming rs6232 and rs6234 in PCSK1 as polygenic risk variants for childhood obesity, we describe an association of rs725522 with insulin metabolism. Our results support the contribution of PCSK1 variants to obesity predisposition in children. Keywords: PCSK1, PC1/3, Obesity, Children, Prohormone convertase 1/3

La pérdida lexical en la variante wanky en la ciudad de Bilwi: barrio “Filemón Rivera” y las comunidades de Uhri y Saklín, río Coco.

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Germín Baldeáramos Solano

2012-02-01

Full Text Available Las razones para la realización de este estudio se fundamentan en el deterioro y pérdida de la lengua miskitu, variante wank y, entre el grupo de hablantes dentro de la ciudad de Bilwi, Puerto Cabezas y comunidades del río Coco –Wangki Awala–, lo cual debe ser una preocupación para las autoridades gubernamentales de nuestra región y el país, profesionales en el área de educación, sociología y la cultura en general.El estudio es descriptivo, cualitativo y de corte longitudinal con el cual se permite identificar los aspectos que han generado a la pérdida lexical de la lengua miskitu, para lo que se tomó en cuenta a la población del barrio “Filimon Rivera” (sector No. 3 y las comunidades de Uhri y Saklin en el municipio de Waspam, río Coco. En el presente estudio se realizaron entrevistas abiertas y observación participante, compartiendo con los hablantes en su lengua materna.Los resultados fueron los siguientes: Entre algunas de las palabras que están en desuso son: yamni, aisa, yapti, suapan, batanka,li klaswan, krukrutara, snik, pukrus, saurka. Sins watla, titan yamni, tutti yamni, tihmia yamni, yapti.Entre los elementos que afectan la pérdida lexical en la variante wanky se encuentran el mestizaje, la migración, los medio de comunicación radial, televisiva, emisoras quienes en un gran porcentaje emiten informaciones en la lengua que no es el miskitu y poco uso de la lengua miskitu ancestral en el hogar por parte de madres y padres de familia con sus hijas e hijos.

Detección Serológica y Molecular del Virus PVY N y su variante PVY NTN en Papa (Solanum tuberosum L.) y Hospedantes Alternos en Tapalpa, México

OpenAIRE

Hernández-de la Cruz, Miguel; Gómez-Leyva, Juan Florencio; López-Muraira, Irma Guadalupe; Dimas-Estrada, María Susana; Andrade-González, Isaac; Ireta-Moreno, Javier

2007-01-01

Se realizó un muestreo en cultivos de papa (Solanum tuberosum) para semilla en la zona productora de Tapalpa, Jalisco, México, así como de maleza e insectos asociados al cultivo con el objetivo de determinar la presencia del virus PVY N y su variante PVY NTN. Mediante técnicas serológicas y moleculares se analizaron 41 variedades de papa, 19 de Tapalpa, y 22 provenientes de Toluca, Estado de México. Con la técnica de DAS-ELISA, la variedad Malinche de Tapalpa fue positiva a PVY N, mientras qu...

4s24p3--4s4p4 and 4s24p3--4s2fp25s transitions in Y VII, Zr VIII, Nb IX, and MoX

International Nuclear Information System (INIS)

Reader, J.; Acquista, N.

1981-01-01

Spectra of ionized Y, Zr, Nb, and Mo have been observed in sliding-spark and triggered-spark discharges on 10.7-m normal- and grazing-incidence spectrographs at the National Bureau of Standards in Washington, D. C. From these observations the 4s 2 4p 3 --4s4p 4 transitions in Y VII, Zr VIII, Nb IX, and Mo X have been identified. The 4s 2 4p 3 --4s 2 4p 2 5s transitions in Y VII-Mo X, previously identified by Rahimullah et al. [Phys. Scr. 14, 221--223 (1976); 18, 96--106 (1978)], have been confirmed. In Y VII the 4s 2 4p 3 --4s 2 4p 2 6s and 4s4p 4 --4p 5 transition also have been found. The parameters obtained from least-squares fits to the energy levels are compared with Hartree--Fock calculations. Preliminary values of the ionization energies have been determined as 110.02 +- 0.15 eV for Y VII, 133.7 +- 0.5 eV for Zr VIII, 159.2 +- 0.7 eV for Nb IX, and 186.4 +- 1.2 eV for Mo X

Structure of conkunitzin-S1, a neurotoxin and Kunitz-fold disulfide variant from cone snail

International Nuclear Information System (INIS)

Dy, Catherine Y.; Buczek, Pawel; Imperial, Julita S.; Bulaj, Grzegorz; Horvath, Martin P.

2006-01-01

Most Kunitz proteins like BPTI and α-dendrotoxin are stabilized by three disulfide bonds. The crystal structure shows how subtle repacking of non-covalent interactions may compensate for disulfide bond loss in a naturally occurring two-disulfide variant, conkunitzin-S1, the first discovered member of a new conotoxin family. Cone snails (Conus) are predatory marine mollusks that immobilize prey with venom containing 50–200 neurotoxic polypeptides. Most of these polypeptides are small disulfide-rich conotoxins that can be classified into families according to their respective ion-channel targets and patterns of cysteine–cysteine disulfides. Conkunitzin-S1, a potassium-channel pore-blocking toxin isolated from C. striatus venom, is a member of a newly defined conotoxin family with sequence homology to Kunitz-fold proteins such as α-dendrotoxin and bovine pancreatic trypsin inhibitor (BPTI). While conkunitzin-S1 and α-dendrotoxin are 42% identical in amino-acid sequence, conkunitzin-S1 has only four of the six cysteines normally found in Kunitz proteins. Here, the crystal structure of conkunitzin-S1 is reported. Conkunitzin-S1 adopts the canonical 3 10 –β–β–α Kunitz fold complete with additional distinguishing structural features including two completely buried water molecules. The crystal structure, although completely consistent with previously reported NMR distance restraints, provides a greater degree of precision for atomic coordinates, especially for S atoms and buried solvent molecules. The region normally cross-linked by cysteines II and IV in other Kunitz proteins retains a network of hydrogen bonds and van der Waals interactions comparable to those found in α-dendrotoxin and BPTI. In conkunitzin-S1, glycine occupies the sequence position normally reserved for cysteine II and the special steric properties of glycine allow additional van der Waals contacts with the glutamine residue substituting for cysteine IV. Evolution has thus defrayed the

Frequency and spectrum of mitochondrial 12S rRNA variants in 440 Han Chinese hearing impaired pediatric subjects from two otology clinics

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Zhou Jianjin

2011-01-01

Full Text Available Abstract Background Aminoglycoside ototoxicity is one of the common health problems. Mitochondrial 12S rRNA mutations are one of the important causes of aminoglycoside ototoxicity. However, the incidences of 12S rRNA mutations associated with aminoglycoside ototoxicity are less known. Methods A total of 440 Chinese pediatric hearing-impaired subjects were recruited from two otology clinics in the Ningbo and Wenzhou cities of Zhejiang Province, China. These subjects underwent clinical, genetic evaluation and molecular analysis of mitochondrial 12S rRNA. Resultant mtDNA variants were evaluated by structural and phylogenetic analysis. Results The study samples consisted of 227 males and 213 females. The age of all participants ranged from 1 years old to 18 years, with the median age of 9 years. Ninety-eight subjects (58 males and 40 females had a history of exposure to aminoglycosides, accounting for 22.3% cases of hearing loss in this cohort. Molecular analysis of 12S rRNA gene identified 41 (39 known and 2 novel variants. The incidences of the known deafness-associated 1555A > G, 1494C > T and 1095T > C mutations were 7.5%, 0.45% and 0.91% in this entire hearing-impaired subjects, respectively, and 21.4%, 2% and 2% among 98 subjects with aminoglycoside ototoxicity, respectively. The structural and phylogenetic evaluations showed that a novel 747A > G variant and known 839A > G, 1027A > G, 1310C > T and 1413T > C variants conferred increased sensitivity to aminoglycosides or nonsyndromic deafness as they were absent in 449 Chinese controls and localized at highly conserved nucleotides of this rRNA. However, other variants were polymorphisms. Of 44 subjects carrying one of definite or putative deafness-related 12S rRNA variants, only one subject carrying the 1413T > C variant harbored the 235DelC/299DelAT mutations in the GJB2 gene, while none of mutations in GJB2 gene was detected in other 43 subjects. Conclusions Mutations in mitochondrial 12S r

Myopathy With SQSTM1 and TIA1 Variants: Clinical and Pathological Features

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Zhiyv Niu

2018-03-01

Full Text Available ObjectiveThe aim of this study is to identify the molecular defect of three unrelated individuals with late-onset predominant distal myopathy; to describe the spectrum of phenotype resulting from the contributing role of two variants in genes located on two different chromosomes; and to highlight the underappreciated complex forms of genetic myopathies.Patients and methodsClinical and laboratory data of three unrelated probands with predominantly distal weakness manifesting in the sixth-seventh decade of life, and available affected and unaffected family members were reviewed. Next-generation sequencing panel, whole exome sequencing, and targeted analyses of family members were performed to elucidate the genetic etiology of the myopathy.ResultsGenetic analyses detected two contributing variants located on different chromosomes in three unrelated probands: a heterozygous pathogenic mutation in SQSTM1 (c.1175C>T, p.Pro392Leu and a heterozygous variant in TIA1 (c.1070A>G, p.Asn357Ser. The affected fraternal twin of one proband also carries both variants, while the unaffected family members harbor one or none. Two unrelated probands (family 1, II.3, and family 3, II.1 have a distal myopathy with rimmed vacuoles that manifested with index extensor weakness; the other proband (family 2, I.1 has myofibrillar myopathy manifesting with hypercapnic respiratory insufficiency and distal weakness.ConclusionThe findings indicate that all the affected individuals have a myopathy associated with both variants in SQSTM1 and TIA1, respectively, suggesting that the two variants determine the phenotype and likely functionally interact. We speculate that the TIA1 variant is a modifier of the SQSTM1 mutation. We identify the combination of SQSTM1 and TIA1 variants as a novel genetic defect associated with myofibrillar myopathy and suggest to consider sequencing both genes in the molecular investigation of myopathy with rimmed vacuoles and myofibrillar myopathy

Myopathy With SQSTM1 and TIA1 Variants: Clinical and Pathological Features.

Science.gov (United States)

Niu, Zhiyv; Pontifex, Carly Sabine; Berini, Sarah; Hamilton, Leslie E; Naddaf, Elie; Wieben, Eric; Aleff, Ross A; Martens, Kristina; Gruber, Angela; Engel, Andrew G; Pfeffer, Gerald; Milone, Margherita

2018-01-01

The aim of this study is to identify the molecular defect of three unrelated individuals with late-onset predominant distal myopathy; to describe the spectrum of phenotype resulting from the contributing role of two variants in genes located on two different chromosomes; and to highlight the underappreciated complex forms of genetic myopathies. Clinical and laboratory data of three unrelated probands with predominantly distal weakness manifesting in the sixth-seventh decade of life, and available affected and unaffected family members were reviewed. Next-generation sequencing panel, whole exome sequencing, and targeted analyses of family members were performed to elucidate the genetic etiology of the myopathy. Genetic analyses detected two contributing variants located on different chromosomes in three unrelated probands: a heterozygous pathogenic mutation in SQSTM1 (c.1175C>T, p.Pro392Leu) and a heterozygous variant in TIA1 (c.1070A>G, p.Asn357Ser). The affected fraternal twin of one proband also carries both variants, while the unaffected family members harbor one or none. Two unrelated probands (family 1, II.3, and family 3, II.1) have a distal myopathy with rimmed vacuoles that manifested with index extensor weakness; the other proband (family 2, I.1) has myofibrillar myopathy manifesting with hypercapnic respiratory insufficiency and distal weakness. The findings indicate that all the affected individuals have a myopathy associated with both variants in SQSTM1 and TIA1 , respectively, suggesting that the two variants determine the phenotype and likely functionally interact. We speculate that the TIA1 variant is a modifier of the SQSTM1 mutation. We identify the combination of SQSTM1 and TIA1 variants as a novel genetic defect associated with myofibrillar myopathy and suggest to consider sequencing both genes in the molecular investigation of myopathy with rimmed vacuoles and myofibrillar myopathy although additional studies are needed to investigate the

[Hemoglobin variants in Colombian patients referred to discard hemoglobinopathies].

Science.gov (United States)

Romero-Sánchez, Consuelo; Gómez Gutiérrez, Alberto; Duarte, Yurani; Amazo, Constanza; Manosalva, Clara; Chila M, Lorena; Casas-Gómez, María Consuelo; Briceño Balcázar, Ignacio

2015-10-01

Oxygen transport is altered in hemoglobinopathies. To study the distribution of hemoglobinopathies in Andean subjects without African ancestry. We analyzed blood samples of 1,407 subjects aged 18 to 59 years (58% females), living in the central Andean region of Colombia, referred to discard hemoglobinopathies. The frequency and type of hemoglobinopathy was established by capillary and agarose gel electrophoresis. The frequency of hemoglobinopathies was 34.5% and higher among females. The structural variants found were: AS-heterozygous hemoglobin (8.1%), homozygous SS (3.7%), heterozygous SC (2.2%), AC heterozygotes (0.5%) and heterozygous AE (0.3%). Quantitative variants found were Hb A-Beta thalassemia (13.91%) and Hb H (0.06%), Beta-thalassemia heterozygotes C (0.88%), S-Beta thalassemia heterozygotes (6.07%) and compound heterozygous SC/Beta thalassemia (0.25%), with a persistence of fetal hemoglobin 0. Composite thalassemia was also found in 31%. All techniques showed good correlation and capillary electrophoresis demonstrated a greater detection of hemoglobin variants. The frequency of hemoglobin variants in the analyzed population was high, which is an important public health indicator. The most common hemoglobin variant was HbA/Increased structural Hb A2 and the mos frequent structural hemoglobinopathy was sickle cell trait. Capillary electrophoresis can discern any Hb variants present in the population.

Two-jet invariant-mass distribution at √s =1.8 TeV

International Nuclear Information System (INIS)

Abe, F.; Amidei, D.; Apollinari, G.; Ascoli, G.; Atac, M.; Auchincloss, P.; Baden, A.R.; Barbaro-Galtieri, A.; Barnes, V.E.; Bedeschi, F.; Behrends, S.; Belforte, S.; Bellettini, G.; Bellinger, J.; Bensinger, J.; Beretvas, A.; Berge, P.; Bertolucci, S.; Bhadra, S.; Binkley, M.; Blair, R.; Blocker, C.; Bofill, J.; Booth, A.W.; Brandenburg, G.; Brown, D.; Byon, A.; Byrum, K.L.; Campbell, M.; Carey, R.; Carithers, W.; Carlsmith, D.; Carroll, J.T.; Cashmore, R.; Cervelli, F.; Chadwick, K.; Chapin, T.; Chiarelli, G.; Chinowsky, W.; Cihangir, S.; Cline, D.; Connor, D.; Contreras, M.; Cooper, J.; Cordelli, M.; Curatolo, M.; Day, C.; DelFabbro, R.; Dell'Orso, M.; DeMortier, L.; Devlin, T.; DiBitonto, D.; Diebold, R.; Dittus, F.; DiVirgilio, A.; Elias, J.E.; Ely, R.; Errede, S.; Esposito, B.; Flaugher, B.; Focardi, E.; Foster, G.W.; Franklin, M.; Freeman, J.; Frisch, H.; Fukui, Y.; Garfinkel, A.F.; Giannetti, P.; Giokaris, N.; Giromini, P.; Gladney, L.; Gold, M.; Goulianos, K.; Grosso-Pilcher, C.; Haber, C.; Hahn, S.R.; Handler, R.; Harris, R.M.; Hauser, J.; Hessing, T.; Hollebeek, R.; Hu, P.; Hubbard, B.; Hurst, P.; Huth, J.; Jensen, H.; Johnson, R.P.; Joshi, U.; Kadel, R.W.; Kamon, T.; Kanda, S.; Kardelis, D.A.; Karliner, I.; Kearns, E.; Kephart, R.; Kesten, P.; Keutelian, H.; Kim, S.; Kirsch, L.; Kondo, K.; Kruse, U.; Kuhlmann, S.E.; Laasanen, A.T.; Li, W.; Liss, T.; Lockyer, N.; Marchetto, F.; Markeloff, R.; Markosky, L.A.; McIntyre, P.; Menzione, A.; Meyer, T.; Mikamo, S.; Miller, M.; Mimashi, T.; Miscetti, S.; Mishina, M.; Miyashita, S.; Mondal, N.; Mori, S.; Morita, Y.; Mukherjee, A.; Newman-Holmes, C.; Nodulman, L.; Paoletti, R.; Para, A.; Patrick, J.; Phillips, T.J.; Piekarz, H.; Plunkett, R.; Pondrom, L.; Proudfoot, J.; Punzi, G.; Quarrie, D.; Ragan, K.; Redlinger, G.; Rhoades, J.; Rimondi, F.; Ristori, L.; Rohaly, T.; Roodman, A.; Sansoni, A.; Sard, R.; Scarpine, V.; Schlabach, P.; Schmidt, E.E.; Schoessow, P.; Schub, M.H.; Schwitters, R.; Scribano, A.

1990-01-01

We present the dijet invariant-mass distribution in the region between 60 and 500 GeV, measured in 1.8-TeV bar pp collisions in the Collider Detector at Fermilab. Jets are restricted to the pseudorapidity interval |η| A A =Nα s M A /6, with N=5

Functional Investigations of HNF1A Identify Rare Variants as Risk Factors for Type 2 Diabetes in the General Population

Science.gov (United States)

Najmi, Laeya Abdoli; Aukrust, Ingvild; Flannick, Jason; Molnes, Janne; Burtt, Noel; Molven, Anders; Groop, Leif; Altshuler, David; Johansson, Stefan; Njølstad, Pål Rasmus

2017-01-01

Variants in HNF1A encoding hepatocyte nuclear factor 1α (HNF-1A) are associated with maturity-onset diabetes of the young form 3 (MODY 3) and type 2 diabetes. We investigated whether functional classification of HNF1A rare coding variants can inform models of diabetes risk prediction in the general population by analyzing the effect of 27 HNF1A variants identified in well-phenotyped populations (n = 4,115). Bioinformatics tools classified 11 variants as likely pathogenic and showed no association with diabetes risk (combined minor allele frequency [MAF] 0.22%; odds ratio [OR] 2.02; 95% CI 0.73–5.60; P = 0.18). However, a different set of 11 variants that reduced HNF-1A transcriptional activity to diabetes in the general population (combined MAF 0.22%; OR 5.04; 95% CI 1.99–12.80; P = 0.0007). Our functional investigations indicate that 0.44% of the population carry HNF1A variants that result in a substantially increased risk for developing diabetes. These results suggest that functional characterization of variants within MODY genes may overcome the limitations of bioinformatics tools for the purposes of presymptomatic diabetes risk prediction in the general population. PMID:27899486

Trissomia 18: revisão dos aspectos clínicos, etiológicos, prognósticos e éticos Trisomía 18 (síndrome de Edwards: revisión de los aspectos clínicos, etiológicos, pronósticos y éticos Trisomy 18: review of the clinical, etiologic, prognostic, and ethical aspects

Directory of Open Access Journals (Sweden)

Rafael Fabiano M. Rosa

2013-03-01

Full Text Available OBJETIVO: Revisar as características clínicas, etiológicas, diagnósticas e prognósticas da trissomia do cromossomo 18 (síndrome de Edwards. FONTES DE DADOS: Foram pesquisados artigos científicos presentes nos portais MedLine, Lilacs e SciELO, utilizando-se os descritores 'trisomy 18' e 'Edwards syndrome'. A pesquisa não se limitou a um período determinado e englobou artigos presentes nestes bancos de dados. SÍNTESE DOS DADOS: A síndrome de Edwards é uma doença caracterizada por um quadro clínico amplo e prognóstico bastante reservado. Há descrição na literatura de mais de 130 anomalias diferentes, as quais podem envolver praticamente todos os órgãos e sistemas. Seus achados são resultantes da presença de três cópias do cromossomo 18. A principal constituição cromossômica observada entre estes pacientes é a trissomia livre do cromossomo 18, que se associa ao fenômeno de não disjunção, especialmente na gametogênese materna. A maioria dos fetos com síndrome de Edwards acaba indo a óbito durante a vida embrionária e fetal. A mediana de sobrevida entre nascidos vivos tem usualmente variado entre 2,5 e 14,5 dias. CONCLUSÕES: O conhecimento do quadro clínico e do prognóstico dos pacientes com a síndrome de Edwards tem grande importância no que diz respeito aos cuidados neonatais e à decisão de instituir ou não tratamentos invasivos. A rapidez na confirmação do diagnóstico é importante para a tomada de decisões referentes às condutas médicas. Muitas vezes, as intervenções são realizadas em condições de emergência, sem muita oportunidade de reflexão ou discussão, e envolvem questões médicas e éticas difíceis.OBJETIVO: Revisar las características clínicas, etiológicas, diagnósticas y pronósticas de la trisomía del cromosoma 18 (síndrome de Edwards. FUENTES DE DATOS: Fueron investigados artículos científicos presentes en los portales MedLine, Lilacs y SciELO, utilizando los

Responses of synchronous L5178Y S/S cells to heavy ions and their significance for radiobiological theory

International Nuclear Information System (INIS)

Lett, J.T.; Cox, A.B.; Story, M.D.; Blakely, E.A.

1989-01-01

Synchronous suspensions of the radiosensitive S/S variant of the L5178Y murine leukaemic lymphoblast at different positions in the cell cycle were exposed aerobically to segments of heavy-ion beams 20 Ne, 28 Si, 40 Ar, 56 Fe and 93 Nb) in the Bragg plateau regions of energy deposition. The incident energies of the ion beams were in the range of 460±95 MeV u -1 , and the calculated values of linear energy transfer (LET ∞ for the primary nuclei in the irradiated samples were 33±3, 60±3, 95±5, 213±21 and 478±''36 keV ''mu''m -1 , respectively; 280 kVp X-rays were used as the base-line radiation. Generally, the maxima or inflections in relations between relative biological effectiveness (RBE) and LET ∞ were dependent upon the cycle position at which the cells were irradiated. Certain of those relations were influenced by post-irradiation hypothermia. (author)

Small-angle X-ray titration study on the complex formation between 5-S RNA and the L18 protein of the Escherichia coli 50-S ribosome particle

International Nuclear Information System (INIS)

Oesterberg, R.; Garrett, A.

1977-01-01

The 5-S RNA (A) and the L 18 protein (B) from Escherichia coli ribosomes form one single AB complex in the concentration ranges supposed to prevail in vivo; at concentrations of L 18 higher than 40 mM there is some indication for a minor species, most probably an AB 2 species. This is indicated from the X-ray scattering titration data of the 5-S RNA/L 18 system recorded at 21 0 C in ribosomal reconstitution buffer. As a result of the 1 : 1 complex formation, there is a relatively small but defined increase in the radius of gyration from 3.61 to 3.85 nm. This result as well as the experimental scattering curve can be explained by models where it is assumed that the elongated L 18 model is quite far from the electron density centre and where protein L 18 interacts with one or both of the minor arms of the supposed Y-shaped 5-S RNA molecule. (orig.) [de

5-Gb/s 0.18-μm CMOS 2:1 multiplexer with integrated clock extraction

International Nuclear Information System (INIS)

Zhang Changchun; Wang Zhigong; Shi Si; Miao Peng; Tian Ling

2009-01-01

A 5-Gb/s 2:1 MUX (multiplexer) with an on-chip integrated clock extraction circuit which possesses the function of automatic phase alignment (APA), has been designed and fabricated in SMIC's 0.18 μm CMOS technology. The chip area is 670 x 780 μm 2 . At a single supply voltage of 1.8 V, the total power consumption is 112 mW with an input sensitivity of less than 50 mV and an output single-ended swing of above 300 mV. The measurement results show that the IC can work reliably at any input data rate between 1.8 and 2.6 Gb/s with no need for external components, reference clock, or phase alignment between data and clock. It can be used in a parallel optic-fiber data interconnecting system.

5-Gb/s 0.18-μm CMOS 2:1 multiplexer with integrated clock extraction

Science.gov (United States)

Changchun, Zhang; Zhigong, Wang; Si, Shi; Peng, Miao; Ling, Tian

2009-09-01

A 5-Gb/s 2:1 MUX (multiplexer) with an on-chip integrated clock extraction circuit which possesses the function of automatic phase alignment (APA), has been designed and fabricated in SMIC's 0.18 μm CMOS technology. The chip area is 670 × 780 μm2. At a single supply voltage of 1.8 V, the total power consumption is 112 mW with an input sensitivity of less than 50 mV and an output single-ended swing of above 300 mV. The measurement results show that the IC can work reliably at any input data rate between 1.8 and 2.6 Gb/s with no need for external components, reference clock, or phase alignment between data and clock. It can be used in a parallel optic-fiber data interconnecting system.

Defect structure, electronic conductivity and expansion of properties of (La1−xSrx)sCo1−yNiyO3−δ

DEFF Research Database (Denmark)

Hjalmarsson, Per; Søgaard, Martin; Mogensen, Mogens Bjerg

2010-01-01

This study reports on oxygen nonstoichiometry, electronic conductivity and lattice expansion of three compositions as function of T and PO2 in the (La1−xSrx)sCo1−yNiyO3−δ (x=0.1, y=0.4; x=0.1, y=0.3; x=0.2, y=0.2) materials system. The nonstoichiometry data were successfully fitted using the itin......This study reports on oxygen nonstoichiometry, electronic conductivity and lattice expansion of three compositions as function of T and PO2 in the (La1−xSrx)sCo1−yNiyO3−δ (x=0.1, y=0.4; x=0.1, y=0.3; x=0.2, y=0.2) materials system. The nonstoichiometry data were successfully fitted using...... the itinerant electron model which indicates the existence of delocalized electronic states. This was also reflected in the high electronic conductivities, above 1000 S cm−1, measured for all three compositions. The electronic conductivity was shown to decrease linearly with the oxygen nonstoichiometry...... parameter, δ, supporting that the conductivity is dependent on p-type charge carriers. Comparing calculated p-type mobilities with data reported in literature on La1−xSrxCoO3 indicated that Ni-substitution into (La1−xSrx)sCoO3−δ increases the p-type mobility. The electronic conductivity was also found...

DIVERSITY OF THE TYPE 1 INTRON-ITS REGION OF THE 18S rRNA GENE IN PSEUDOGYMNOASCUS SPECIES FROM THE RED HILLS OF KANSAS.

Science.gov (United States)

Chen, Xi; Crupper, Scott S

2016-09-01

Gypsum caves found throughout the Red Hills of Kansas have the state's most diverse and largest population of cave-roosting bats. White-nose syndrome (WNS), a disease caused by the fungus Pseudogymnoascus destructans, which threatens all temperate bat species, has not been previously detected in the gypsum caves as this disease moves westward from the eastern United States. Cave soil was obtained from the gypsum caves, and using the polymerase chain reaction, a 624-nucleotide DNA fragment specific to the Type 1 intron-internal transcribed spacer region of the 18S rRNA gene from Pseudogymnoascus species was amplified. Subsequent cloning and DNA sequencing indicated P. destructans DNA was present, along with 26 uncharacterized Pseudogymnoascus DNA variants. However, no evidence of WNS was observed in bat populations residing in these caves.

Manejo y aprovechamiento de la agrobiodiversidad en el sistema milpa del sureste de México

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Lourdes Mateos-Maces

2016-10-01

Full Text Available En este trabajo, se describió y clasificó la agrobiodiversidad del sistema milpa en la región tropical de San Felipe Usila, Oaxaca, México, a partir de la percepción de agricultores sobre la diversidad fenotípica y usos de la variabilidad intraespecífica y biodiversidad recolectada a nivel de parcela. Bajo un enfoque de agroecosistemas, se obtuvo información de tres sistemas de producción, denominados: laderas pedregosas (> 18° de pendiente, lomeríos irregulares y pedregosos con pendientes entre 6 y 18°, y terrenos planos (< 6° de zonas ribereñas. Así, con el objetivo de registrar la percepción de diversidad y usos de la agrobiodiversidad, se aplicaron entrevistas a 200 agricultores de once comunidades indígenas Chinantecas de San Felipe Usila, mediante un cuestionario semiestructurado. En el análisis de ji-cuadrada, se determinaron relaciones significativas (P < 0.05 entre agroecosistemas y variantes fenotípicas de frijol y maíz, cultivos intercalados, regímenes de humedad para la siembra, superficie sembrada y fechas de siembra, de floración y cosecha de maíz. En el análisis de correspondencia múltiple, se distinguen patrones de diversidad, uso y manejo en relación a regiones geográfico-culturales de localización de los agroecosistemas y parcelas. En las parcelas de producción se siembran, cultivan y recolectan hasta 26 especies, las principales son: maíz (cinco variantes fenotípicas, frijol (21 variedades y poblaciones nativas, calabaza (cuatro variantes y yuca (tres variantes. También fue notorio el alto uso de pesticidas y fertilizantes químicos, hasta 22 productos diferentes.

MSX1 gene variant - its presence in tooth absence - a case control genetic study.

Science.gov (United States)

Reddy, Naveen Admala; Adusumilli, Gopinath; Devanna, Raghu; Pichai, Saravanan; Rohra, Mayur Gobindram; Arjunan, Sharmila

2013-10-01

Non Syndromic tooth agenesis is a congenital anomaly with significant medical, psychological and social ramifications. There is sufficient evidence to hypothesize that locus for this condition can be identified by candidate genes. The aim of this study was to test whether MSX1 671 T>C gene variant was involved in etiology of Non Syndromic tooth agenesis in Raichur Patients. Blood samples were collected with informed consent from 50 subjects having Non Syndromic tooth agenesis and 50 controls. Genomic DNA was extracted from the blood samples, Polymerase Chain Reaction was performed (PCR) and Restriction Fragment Length Polymorphism (RFLP) was performed for digestion products that were evaluated. The RESULTS showed positive correlation between MSX1671 T>C gene variant and Non Syndromic tooth agenesis in Raichur Patients. MSX1 671 T>C gene variant may be a good screening marker for Non Syndromic tooth agenesis in Raichur Patients . How to cite this article:Reddy NA, Adusumilli G, Devanna R, Pichai S, Rohra MG, Arjunan S. Msx1 Gene Variant - Its Presence in Tooth Absence - A Case Control Genetic Study. J Int Oral Health 2013; 5(5):20-6.

Essential role of maternal UCHL1 and UCHL3 in fertilization and preimplantation embryo development

Czech Academy of Sciences Publication Activity Database

Mtango, N.R.; Sutovsky, M.; Šušor, Andrej; Zhong, Z.S.; Latham, K.E.; Šutovský, P.

2012-01-01

Roč. 227, č. 4 (2012), s. 1592-1603 ISSN 0021-9541 R&D Projects: GA ČR GA524/07/1087 Institutional research plan: CEZ:AV0Z50450515 Keywords : UBIQUITIN-PROTEASOME PATHWAY * ANTI-POLYSPERMY DEFENSE * IN-VITRO FERTILIZATION Subject RIV: ED - Physiology Impact factor: 4.218, year: 2012

Comparison of Ion Personal Genome Machine Platforms for the Detection of Variants in BRCA1 and BRCA2.

Science.gov (United States)

Hwang, Sang Mee; Lee, Ki Chan; Lee, Min Seob; Park, Kyoung Un

2018-01-01

Transition to next generation sequencing (NGS) for BRCA1 / BRCA2 analysis in clinical laboratories is ongoing but different platforms and/or data analysis pipelines give different results resulting in difficulties in implementation. We have evaluated the Ion Personal Genome Machine (PGM) Platforms (Ion PGM, Ion PGM Dx, Thermo Fisher Scientific) for the analysis of BRCA1 /2. The results of Ion PGM with OTG-snpcaller, a pipeline based on Torrent mapping alignment program and Genome Analysis Toolkit, from 75 clinical samples and 14 reference DNA samples were compared with Sanger sequencing for BRCA1 / BRCA2 . Ten clinical samples and 14 reference DNA samples were additionally sequenced by Ion PGM Dx with Torrent Suite. Fifty types of variants including 18 pathogenic or variants of unknown significance were identified from 75 clinical samples and known variants of the reference samples were confirmed by Sanger sequencing and/or NGS. One false-negative results were present for Ion PGM/OTG-snpcaller for an indel variant misidentified as a single nucleotide variant. However, eight discordant results were present for Ion PGM Dx/Torrent Suite with both false-positive and -negative results. A 40-bp deletion, a 4-bp deletion and a 1-bp deletion variant was not called and a false-positive deletion was identified. Four other variants were misidentified as another variant. Ion PGM/OTG-snpcaller showed acceptable performance with good concordance with Sanger sequencing. However, Ion PGM Dx/Torrent Suite showed many discrepant results not suitable for use in a clinical laboratory, requiring further optimization of the data analysis for calling variants.

A Novel Nonsense Variant in Nav1.5 Cofactor MOG1 Eliminates Its Sodium Current Increasing Effect and May Increase the Risk of Arrhythmias

DEFF Research Database (Denmark)

Olesen, Morten S; Jensen, Niels F; Holst, Anders G

2011-01-01

at a lower frequency (1.8% vs 0.4%, P = 0.078). Electrophysiological investigation showed that the p.E61X variant completely eliminates the sodium current-increasing effect of MOG1 and thereby causes loss of function in the sodium current. When mimicking heterozygosity by coexpression of Nav1.5 with wild......BACKGROUND: The protein MOG1 is a cofactor of the cardiac sodium channel, Nav1.5. Overexpression of MOG1 in Nav1.5-expressing cells increases sodium current markedly. Mutations in the genes encoding Nav1.5 and its accessory proteins have been associated with cardiac arrhythmias of significant...... and 23 were patients with Brugada syndrome. The effect of one variant was investigated functionally by patch-clamping CHO-K1 cells coexpressing Nav1.5 with MOG1. RESULTS: We uncovered a novel heterozygous nonsense variant, c.181G>T (p.E61X), that, however, was also present in control subjects, albeit...

Lorentz transmission electron microscopy on nanometric magnetic bubbles and skyrmions in bilayered manganites La{sub 1.2}Sr{sub 1.8}(Mn{sub 1−y}Ru{sub y}){sub 2}O{sub 7} with controlled magnetic anisotropy

Energy Technology Data Exchange (ETDEWEB)

Morikawa, D.; Yu, X. Z.; Kaneko, Y. [RIKEN Center for Emergent Matter Science (CEMS), Wako 351-0198 (Japan); Tokunaga, Y.; Arima, T. [RIKEN Center for Emergent Matter Science (CEMS), Wako 351-0198 (Japan); Department of Advanced Materials Science, University of Tokyo, Kashiwa 277-8561 (Japan); Nagai, T.; Kimoto, K. [Transmission Electron Microscopy Station and Surface Physics and Structure Unit, National Institute for Materials Science (NIMS), Tsukuba 305-0044 (Japan); Tokura, Y. [RIKEN Center for Emergent Matter Science (CEMS), Wako 351-0198 (Japan); Department of Applied Physics, University of Tokyo, Tokyo 113-8656 (Japan)

2015-11-23

We have investigated nanometric magnetic textures in thin (<150 nm) plates of Ru-doped bilayered manganites La{sub 1.2}Sr{sub 1.8}(Mn{sub 1−y}Ru{sub y}){sub 2}O{sub 7}. Ru substitution for Mn site changes the magnetic anisotropy from in-plane to out-of-plane easy axis type without any significant change of global magnetic and crystal structures. The combination of conventional and Lorentz transmission electron microscopy observations confirms the emergence of magnetic bubbles and skyrmions in the absence of magnetic field. With the changing Ru concentration, systematic changes in the type of magnetic bubbles are observed. A tiny residual magnetic field also affects the generation and the type-change of magnetic bubbles.

Variantes quirúrgicas para el tratamiento del linfedema primario de pene y escroto

Directory of Open Access Journals (Sweden)

Orestes Díaz Hernández

2000-12-01

Full Text Available Se presentan 2 variantes técnicas del tratamiento quirúrgico del linfedema primario de pene y escroto en 2 pacientes con características clínicas diferentes. Una de las técnicas quirúrgicas empleadas consistió en 2 incisiones laterales en las bolsas escrotales con resección del tejido linfedematoso y la otra con una incisión única en la bolsa y reimplantación de la base del pene con resección de todo el tejido linfedematoso. En ambos casos antes de intentar la resección del tejido linfedematoso se extrajeron de su lecho el cordón espermático y los testículos para facilitar la operación, minimizar el tiempo quirúrgico y producir menos complicaciones. La propia piel del cuello de la bolsa escrotal se emplea en su reconstrucción e incluso para acomodar los testículos. No se hizo necesario, con estas técnicas, realizar injerto libre ni pediculado de piel. Los pacientes recuperaron la capacidad funcional del pene, tuvieron mejoría estética y desapareció la angustia que esta enfermedad les ocasionabaTwo technical variants of the surgical treatment of primary penile and scrotal lymphoedema used in 2 patients with different clinical characteristics are presented. One of the surgical techniques used consisted in 2 lateral incisions in the scrotal bursae with resection of the lymphoedematous tissue and the other in a single incision in the bursa and reimplantation of the basis of the penis with resection of all the lymphoedematous tissue. In both cases, before attempting the resection of the lymphoedematous tissue the spermatic cord and the testes were removed from their bed to facilitate the operation, to reduce the surgical time and to cause less complications. The own skin of the neck of the scrotal bursa is used in its reconstruction and even to accomodate the testes. By using these techniques, it was not necessary to make a free or pediculate skin graft. Patients recovered the functional capacity of the penis, had an aesthetic

ADULT VARIANT BARTTER’S SYNDROME- A CASE REPORT

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Ishwar Sidappa Hasabi

2017-02-01

Full Text Available BACKGROUND Bartter syndrome is a group of channelopathies with different genetic origins and molecular pathophysiologies, but sharing common feature of decreased tubular transport of sodium chloride in thick ascending loop of Henle (TAL, 1 although more common in antenatal group. Classic adult variant of Bartter syndrome is a rare entity. We hereby present a rare adult variant of classic Bartter syndrome.

Frecuencia de los grupos sanguíneos A1, A2, Aint, B y O en individuos normales

Directory of Open Access Journals (Sweden)

García Rosasco, Marcela

2001-01-01

Full Text Available Se definen como A intermedio (Aint los hematíes que comparten caracteres con A1 y A2. Existen diferencias cualitativas y cuantitativas en los epitopes A. Los hematíes A1 son aglutinados por la lectina de Dolichus biflorus (anti-A1, los A2 por la lectina de Ulex europaeus (anti-H, en tanto los hematíes Aint, son variablemente aglutinados por ambas de manera inesperada. El objetivo del presente trabajo fue determinar la frecuencia de fenotipos A1, Aint, A2, B y O en individuos normales de la ciudad de Rosario (Argentina.Se realizó una búsqueda de individuos Aint en estos individuos de acuerdo a la reacción con las lectinas mencionadas. Se estudiaron 1301 muestras frente a reactivos monoclonales comerciales anti-A, anti-B, anti-AB y lectinas anti-A1 y anti-H. De las muestras estudiadas resultaron 703 O (54,04%, 468 A (35,97%; 106 B (8,15%; 18 A1B (1,38% y 6 A2B (0,46%. Las muestras A se subdividieron en 346 A1 (73,93%; 82 A2 (17,52% y 40 Aint (8,55%. Nuestros resultados concuerdan con observaciones previas sobre la marcada heterogeneidad de los hematíes Aint. El reconocimiento de subgrupos débiles del grupo A reviste importancia en la práctica forense y en el estudio de la dinámica de poblaciones. El estudio de la variante Aint es relevante en Inmunogenética Poblacional, por su contribución al conocimiento del mestizaje con poblaciones negras.

Inhibition of Lassa virus glycoprotein cleavage and multicycle replication by site 1 protease-adapted alpha(1-antitrypsin variants.

Directory of Open Access Journals (Sweden)

Anna Maisa

2009-06-01

Full Text Available Proteolytic processing of the Lassa virus envelope glycoprotein precursor GP-C by the host proprotein convertase site 1 protease (S1P is a prerequisite for the incorporation of the subunits GP-1 and GP-2 into viral particles and, hence, essential for infectivity and virus spread. Therefore, we tested in this study the concept of using S1P as a target to block efficient virus replication.We demonstrate that stable cell lines inducibly expressing S1P-adapted alpha(1-antitrypsin variants inhibit the proteolytic maturation of GP-C. Introduction of the S1P recognition motifs RRIL and RRLL into the reactive center loop of alpha(1-antitrypsin resulted in abrogation of GP-C processing by endogenous S1P to a similar level observed in S1P-deficient cells. Moreover, S1P-specific alpha(1-antitrypsins significantly inhibited replication and spread of a replication-competent recombinant vesicular stomatitis virus expressing the Lassa virus glycoprotein GP as well as authentic Lassa virus. Inhibition of viral replication correlated with the ability of the different alpha(1-antitrypsin variants to inhibit the processing of the Lassa virus glycoprotein precursor.Our data suggest that glycoprotein cleavage by S1P is a promising target for the development of novel anti-arenaviral strategies.

Interleukin-18 alters protein expressions of neurodegenerative diseases-linked proteins in human SH-SY5Y neuron-like cells

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Elina M Sutinen

2014-08-01

Full Text Available Chronic inflammation and oxidative stress (OS are present in Alzheimer´s disease (AD brains in addition to neuronal loss, Amyloid-β (Aβ plaques and hyperphosphorylated tau-protein neurofibrillary tangles. Previously we showed that levels of the pro-inflammatory cytokine, interleukin-18 (IL-18, are elevated in post-mortem AD brains. IL-18 can modulate the tau kinases, Cdk5 and GSK3β, as well as Aβ-production. IL-18 levels are also increased in AD risk diseases, including type-2 diabetes and obesity. Here, we explored other IL-18 regulated proteins in neuron-like SH-SY5Y cells. Differentiated SH-SY5Y cells, incubated with IL-18 for 24, 48 or 72h, were analyzed by two-dimensional gel electrophoresis (2D-DIGE. Specific altered protein spots were chosen and identified with mass spectrometry and verified by western immunoblotting. IL-18 had time-dependent effects on the SH-SY5Y proteome, modulating numerous protein levels/modifications. We concentrated on those related to OS (DDAH2, peroxiredoxins 2, 3 and 6, DJ-1, BLVRA, Aβ-degradation (MMP14, TIMP2, Aβ-aggregation (Septin-2 and modifications of axon growth and guidance associated, collapsing response mediator protein 2 (CRMP2. IL-18 significantly increased antioxidative enzymes, indicative of OS, and altered levels of glycolytic α- and γ-enolase and multifunctional 14-3-3γ and -ε, commonly affected in neurodegenerative diseases. MMP14, TIMP2, α-enolase and 14-3-3ε, indirectly involved in Aβ metabolism, as well as Septin-2 showed changes that increase Aβ levels. Increased 14-3-3γ may contribute to GSK3β driven tau hyperphosphorylation and CRMP2 Thr514 and Ser522 phosphorylation with the Thr555-site, a target for Rho kinase, showing time-dependent changes. IL-18 also increased caspase-1 levels and vacuolization of the cells. Although our SH-SY5Y cells were not aged, as neurons in AD, our work suggests that heightened or prolonged IL-18 levels can drive protein changes of known

Unusual variant of Cantrell′s pentalogy?

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Kumar Basant

2008-01-01

Full Text Available A 12-hour-old male infant presented with prolapsed abdominal content through a defect on left side of chest wall with respiratory distress. A thorough clinical examination suggested absence of ectopia cordis, abdominal wall defect, and any bony anomaly. The child expired after 6 hours of admission because of respiratory distress and electrolyte imbalance. Is congenital defect of chest wall associated with diaphragmatic hernia without ectopia cordis and omphalocele, an unusual variant of Cantrell′s pentalogy?

Endocarditis infecciosa por S. aureus en la Argentina: EIRA-2. Análisis comparativo luego de 10 años de los estudios EIRA 1 y 2

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Ernesto R. Ferreirós

2006-01-01

Full Text Available Objetivo Comparar el perfil y la evolución de la endocarditis infecciosa (EI en nuestro país a lo largo de 10 años, a través de los registros EIRA-1 y EIRA-2. Determinar las características clínicas y epidemiológicas y la evolución hospitalaria de la EI por Staphylococcus aureus (EISA en la Argentina. Métodos El estudio EIRA-2 fue un registro prospectivo multicéntrico conducido en 82 hospitales de 16 provincias de la Argentina. En el presente análisis se incluyeron pacientes con EI definidas (clasificación de Duke relevados en un período de 18 meses. Resultados Se registraron 390 episodios de EI definidas (108 EISA y 282 no EISA; edad media 58,5 ± 17,3 años, sexo masculino 70%. No existieron diferencias estadísticamente significativas entre las 108 EISA y las 282 no EISA con respecto a edad, sexo, endocarditis de válvula protésica, enfermedad valvular degenerativa, presencia de insuficiencia cardíaca y frecuencia de tratamiento quirúrgico. La comparación de los registros EIRA-2 y EIRA-1 demostró cambios importantes en el perfil de la enfermedad en la última década, actualmente caracterizada por pacientes de mayor edad (58 versus 51 años, mayor prevalencia de cardiopatía subyacente 67% versus 55% (en particular prótesis valvulares 19,2% versus 8,5%, enfermedades valvulares degenerativas 12,4% versus 4,8% y cardiopatías congénitas 9,5% versus 4,2%, mayor frecuencia de infección causada por S. aureus (30% versus 26% y menor por Streptococcus viridans (30,8% versus 26,8%, con una reducción del tiempo hasta el diagnóstico definitivo (21,5 versus 33 días. No se encontraron modificaciones en la tasa de mortalidad de la enfermedad. Se observó una diferencia estadísticamente significativa (p < 0,01 de las EISA con respecto a las no EISA en la prevalencia de cardiopatía subyacente [58,3% versus 67,4% (OR 0,7 IC 95% 0,4-0,99]; la EISA presentó una prevalencia menor de enfermedad valvular reumática [0,9% versus 7,1% (OR

Alloying as a Route to Monolayer Transition Metal Dichalcogenides with Improved Optoelectronic Performance: Mo(S1–xSex)2 and Mo1–yWyS2

KAUST Repository

Shi, Zhiming

2018-04-26

On the basis of first-principles and cluster expansion calculations, we propose an effective approach to realize monolayer transition metal dichalcogenides with sizable band gaps and improved optoelectronic performance. We show that monolayer Mo(S1–xSex)2 and Mo1–yWyS2 with x = 1/3, 2/3 and y = 1/3, 1/2, 2/3 are stable according to phonon calculations and realize 1T′ or 1T″ phases. The transition barriers from the 2H phase are lower than for monolayer MoS2, implying that the 1T′ or 1T″ phases can be achieved experimentally. Furthermore, it turns out that the 1T″ monolayer alloys with x = 1/3, 2/3 and y = 1/3, 2/3 are semiconductors with band gaps larger than 1 eV, due to trimerization. The visible light absorption and carrier mobility are strongly improved as compared to 2H monolayer MoS2, MoSe2, and WS2. Thus, the 1T″ monolayer alloys have the potential to expand the applications of transition metal dichalcogenides, for example, in solar cells.

Assessment of polymorphic variants in the melanocortin-1 receptor gene with cutaneous pigmentation using an evolutionary approach.

Science.gov (United States)

Kanetsky, Peter A; Ge, Fan; Najarian, Derek; Swoyer, Jennifer; Panossian, Saarene; Schuchter, Lynn; Holmes, Robin; Guerry, DuPont; Rebbeck, Timothy R

2004-05-01

The melanocortin-1 receptor gene (MC1R) encodes a membrane-bound receptor protein that is central to melanin synthesis. The coding region of MC1R is highly polymorphic and associations of variants with pigmentation phenotypes and risk for cutaneous neoplasms have been reported. We sought to determine the distribution and frequency of MC1R variants and their relationship to pigmentation characteristics in 179 Caucasian controls from the United States. One hundred thirty-five (75.4%) subjects carried one or more variants, and we determined that carriage of the previously designated "red hair color" (RHC) alleles, R151C, R160W, and D294H was strongly associated with fair pigmentation phenotypes including light hair and eye color, tendency to burn, decreased tendency to tan, and freckling. We used SIFT software to define MC1R protein positions that were predicted intolerant to amino acid substitutions; detected variants that corresponded to intolerant substitutions were D84E, R142H, R151C, I155T, R160W, and D294H. Carriage of one or more of these putative functionally important variants or the frameshift variant ins86A was significantly associated with fair pigmentation phenotypes. Analyses limited to carriage of ins86A and the three non-RHC alleles identified by SIFT were attenuated and no longer reached statistical significance. This is the first study to describe MC1R variants among control subjects from the U.S. Our results indicate that the frequency of variants is similar to that previously observed among non-U.S. Caucasians. Risk variants defined by either the published literature or by evolutionary criteria are strongly and significantly associated with all fair pigmentation phenotypes that were measured.

Actitudes y comportamientos preventivos durante la pandemia degripe (H1N1 2009 en España

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Fernando Agüero Santagelo

2011-01-01

Full Text Available Fundamentos: En la primavera de 2009 la aparición del nuevo virus de la gripe (H1N1 2009 causó una enorme alarma social. El objetivo de este estudio es describir los conocimientos y las percepciones de riesgo sobre la enfermedad y su vacuna así como las medidas preventivas adoptadas por la población general en España. Métodos: Encuesta telefónica en dos oleadas a una muestra de teléfonos fijos con cuotas por edad, sexo, Comunidades Autonómicas y tamaño de municipio. El cuestionario incluía preguntas sobre percepciones, medidas preventivas y vacunación contra la gripe (H1N1 2009. Se realizó un análisis estadístico descriptivo de las principales variables del estudio y se aplicó la prueba chi-cuadrado para estudiar la relación estadística para datos categóricos. Resultados: Respondieron el cuestionario 1.627 personas. 823 (51,6% eran mujeres; 502 (30,9% tenían entre 18 y 35 años y 580 (35,6% entre 35 y 55. 729 (49,1% eran trabajadores manuales y 857 (52,7% vivían en municipios de más de 50.000 habitantes. Únicamente un 15,7% de los que respondieron se sentía a riesgo de contraer la enfermedad, percepción que disminuyó al 3,9% en la segunda oleada, tra el pico epidémico. En conjunto, más del 80% (n=1.353 pensaba que se había generado alarma social, y el 77% adoptó al menos una medida preventiva. Las medidas preventivas más frecuentemente adoptadas fueron cubrirse la boca y la nariz con un pañuelo al toser o estornudar (n=951 ; 58,5% y la higiene de manos (n= 624 ; 38,4%. Conclusión: Las principales medidas adoptadas fueron las recomendadas por las autoridades sanitarias.

Interactions among variants in TXA2R, P2Y12 and GPIIIa are associated with carotid plaque vulnerability in Chinese population.

Science.gov (United States)

Yi, Xingyang; Lin, Jing; Luo, Hua; Zhou, Ju; Zhou, Qiang; Wang, Yanfen; Wang, Chun

2018-04-03

The associations between variants in platelet activation-relevant genes and carotid plaque vulnerability are not fully understood. The aim of the present study was to investigate the associations of the variants in platelet activation-relevant genes and interactions among these variants with carotid plaque vulnerability. There were no significant differences in the frequencies of genotypes of the 11 variants between patients and controls. Among 396 patients, 102 patients had not carotid plaque, 106 had VP, and 188 had SP. The 11 variants were not independently associated with risk of carotid plaque vulnerability after adjusting for potential confounding variables. However, the GMDR analysis showed that there were synergistic effects of gene-gene interactions among TXA2Rr s1131882, GPIIIa rs2317676 and P2Y12 rs16863323 on carotid plaque vulnerability. The high-risk interactions among the three variants were associated with high platelet activation, and independently associated with the risk of carotid plaque vulnerability. Eleven variants in platelet activation-relevant genes were examined using mass spectrometry methods in 396 ischemic stroke patients and 291controls. Platelet-leukocyte aggregates and platelet aggregation were also measured. Carotid plaques were assessed by B-mode ultrasound. According to the results of ultrasound, the patients were stratified into three groups: non-plaque group, vulnerable plaque (VP) group and stable plaque (SP) group. Furthermore, gene-gene interactions were analyzed using generalized multifactor dimensionality reduction (GMDR) methods. The rs1131882, rs2317676, and rs16863323 three-loci interactions may confer a higher risk of carotid plaque vulnerability, and might be potential markers for plaque instability.

Functional Characterization of Rare RAB12 Variants and Their Role in Musician’s and Other Dystonias

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Eva Hebert

2017-10-01

Full Text Available Mutations in RAB (member of the Ras superfamily genes are increasingly recognized as cause of a variety of disorders including neurological conditions. While musician’s dystonia (MD and writer’s dystonia (WD are task-specific movement disorders, other dystonias persistently affect postures as in cervical dystonia. Little is known about the underlying etiology. Next-generation sequencing revealed a rare missense variant (c.586A>G; p.Ile196Val in RAB12 in two of three MD/WD families. Next, we tested 916 additional dystonia patients; 512 Parkinson’s disease patients; and 461 healthy controls for RAB12 variants and identified 10 additional carriers of rare missense changes among dystonia patients (1.1% but only one carrier in non-dystonic individuals (0.1%; p = 0.005. The detected variants among index patients comprised p.Ile196Val (n = 6; p.Ala174Thr (n = 3; p.Gly13Asp; p.Ala148Thr; and p.Arg181Gln in patients with MD; cervical dystonia; or WD. Two relatives of MD patients with WD also carried p.Ile196Val. The two variants identified in MD patients (p.Ile196Val; p.Gly13Asp were characterized on endogenous levels in patient-derived fibroblasts and in two RAB12-overexpressing cell models. The ability to hydrolyze guanosine triphosphate (GTP, so called GTPase activity, was increased in mutants compared to wildtype. Furthermore, subcellular distribution of RAB12 in mutants was altered in fibroblasts. Soluble Transferrin receptor 1 levels were reduced in the blood of all three tested p.Ile196Val carriers. In conclusion, we demonstrate an enrichment of missense changes among dystonia patients. Functional characterization revealed altered enzyme activity and lysosomal distribution in mutants suggesting a contribution of RAB12 variants to MD and other dystonias.

Ciberbullying en adolescentes y jóvenes del País Vasco: cambios con la edad

OpenAIRE

Garaigordobil, Maite

2015-01-01

El estudio tuvo como objetivo analizar cambios con la edad en ciberbullying. La muestra fue de 3026 participantes del País Vasco de 12 a 18 años. Se administró el Test Cyberbullying para evaluar la frecuencia con la que 15 conductas han sido sufridas, realizadas y observadas durante el último año, y permite obtener 4 indicadores psicométricos: victimización, agresión, observación, victimización-agresiva. Los resultados evidenciaron: 1) Similar porcentaje de víctimas de 12 a 18 años en las 15 ...

(2S,7S-10-Ethyl-1,8,10,12-tetraazatetracyclo[8.3.1.18,12.02,7]pentadecan-10-ium iodide

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Augusto Rivera

2012-10-01

Full Text Available The title chiral quaternary ammonium salt, C13H25N4+·I−, was synthesized through the Menschutkin reaction between the cage aminal (2S,7S-1,8,10,12-tetraazatetracyclo[8.3.1.18,12.02,7]pentadecane and ethyl iodide. The quaternization occurred regioselectively on the nitrogen with major sp3 character. The crystal structure consists of anions and cations separated by normal distances. Ions are not linked through C—H...I hydrogen bonds.

Aborto inducido, séptico y shock séptico

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Omar Sandoval Muñoz

2016-07-01

Full Text Available El aborto provocado séptico en Chile estuvo por varias décadas dentro de las primeras causas de mortalidad materna, y en 1960 la tasa de mortalidad materna por aborto era de 107/100.000 NV. El desarrollo y progreso en diversas áreas de nuestro país, sumado a las políticas sanitarias implementadas gubernamentalmente, han logrado disminuir la mortalidad materna por aborto de manera muy significativa, siendo ésta de 0.8/100.000 NV en 2005 y manteniéndose estable y por debajo de 1.5/100.000 NV desde el 2001 en adelante. En el presente artículo se revisa y compara el perfil epidemiológico de la mujer que actualmente se realiza un aborto y además se aborda el diagnóstico y tratamiento médico desde la perspectiva gineco-obstétrica.

Aborto inducido, séptico y shock séptico

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Omar Sandoval Muñoz

2009-06-01

Full Text Available El aborto provocado séptico en Chile estuvo por varias décadas dentro de las primeras causas de mortalidad materna, y en 1960 la tasa de mortalidad materna por aborto era de 107/100.000 NV. El desarrollo y progreso en diversas áreas de nuestro país, sumado a las políticas sanitarias implementadas gubernamentalmente, han logrado disminuir la mortalidad materna por aborto de manera muy significativa, siendo ésta de 0.8/100.000 NV en 2005 y manteniéndose estable y por debajo de 1.5/100.000 NV desde el 2001 en adelante. En el presente artículo se revisa y compara el perfil epidemiológico de la mujer que actualmente se realiza un aborto y además se aborda el diagnóstico y tratamiento médico desde la perspectiva gineco-obstétrica.

TIAM1 variants improve clinical outcome in neuroblastoma.

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Sanmartín, Elena; Yáñez, Yania; Fornés-Ferrer, Victoria; Zugaza, José L; Cañete, Adela; Castel, Victoria; Font de Mora, Jaime

2017-07-11

Identification of tumor driver mutations is crucial for improving clinical outcome using a personalized approach to the treatment of cancer. Neuroblastoma is a tumor of the peripheral sympathetic nervous system for which only a few driver alterations have been described including MYCN amplification and ALK mutations. We assessed 106 primary neuroblastoma tumors by next generation sequencing using a customized amplicon-based gene panel. Our results reveal that genetic variants in TIAM1 gene associate with better clinical outcome, suggesting a role for these TIAM1 variants in preventing progression of this disease. The detected variants are located within the different domains of TIAM1 that signal to the upstream regulator RAS and downstream effector molecules MYC and RAC, which are all implicated in neuroblastoma etiology and progression. Clinical outcome was improved in tumors where a TIAM1 variant was present concomitantly with either ALK mutation or MYCN amplification. Given the function of these signaling molecules in cell survival, proliferation, differentiation and neurite outgrowth, our data suggest that the TIAM1-mediated network is essential to neuroblastoma and thus, inhibiting TIAM1 reflects a rational strategy for improving therapy efficacy in neuroblastoma.

Exome-Wide Association Study Identifies New Low-Frequency and Rare UGT1A1 Coding Variants and UGT1A6 Coding Variants Influencing Serum Bilirubin in Elderly Subjects

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Oussalah, Abderrahim; Bosco, Paolo; Anello, Guido; Spada, Rosario; Guéant-Rodriguez, Rosa-Maria; Chery, Céline; Rouyer, Pierre; Josse, Thomas; Romano, Antonino; Elia, Maurizzio; Bronowicki, Jean-Pierre; Guéant, Jean-Louis

2015-01-01

Abstract Genome-wide association studies (GWASs) have identified loci contributing to total serum bilirubin level. However, no exome-wide approaches have been performed to address this question. Using exome-wide approach, we assessed the influence of protein-coding variants on unconjugated, conjugated, and total serum bilirubin levels in a well-characterized cohort of 773 ambulatory elderly subjects from Italy. Coding variants were replicated in 227 elderly subjects from the same area. We identified 4 missense rare (minor allele frequency, MAF bilirubin level (P = 2.34 × 10−34, P = 7.02 × 10−34, and P = 8.27 × 10−34), as well as unconjugated, and conjugated bilirubin levels. We also identified UGT1A6 variants in association with total (rs6759892, p.Ser7Ala, P = 1.98 × 10−26; rs2070959, p.Thr181Ala, P = 2.87 × 10−27; and rs1105879, p.Arg184Ser, P = 3.27 × 10−29), unconjugated, and conjugated bilirubin levels. All UGT1A1 intronic variants (rs887829, rs6742078, and rs4148325) and UGT1A6 coding variants (rs6759892, rs2070959, and rs1105879) were significantly associated with gallstone-related cholecystectomy risk. The UGT1A6 variant rs2070959 (p.Thr181Ala) was associated with the highest risk of gallstone–related cholecystectomy (OR, 4.58; 95% CI, 1.58–13.28; P = 3.21 × 10−3). Using an exome-wide approach we identified coding variants on UGT1A1 and UGT1A6 genes in association with serum bilirubin level and hyperbilirubinemia risk in elderly subjects. UGT1A1 intronic single-nucleotide polymorphisms (SNPs) (rs6742078, rs887829, rs4148324) serve as proxy markers for the low-frequency and rare UGT1A1 variants, thereby providing mechanistic explanation to the relationship between UGT1A1 intronic SNPs and the UGT1A1 enzyme activity. UGT1A1 and UGT1A6 variants might be potentially associated with gallstone-related cholecystectomy risk. PMID:26039129

Comorbilidad entre abuso/dependencia de drogas y el distrés psicológico en siete países de Latinoamérica y uno del Caribe

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Edgar Merchán-Hamann

2012-01-01

Full Text Available Fue realizado estudio multicéntrico en pacientes bajo tratamento por dependencia de alcohol y substancias ilícitas, en ocho países (Brasil, Chile, Guatemala, Jamaica, Nicaragua, Panamá, Paraguay, Uruguay. El objetivo fue investigar la frecuencia de distrés psicológico, diagnóstico actual de comorbilidades, y disfuncionalidad familiar percibida. Fueron incluídos 1.073 voluntarios adultos, que diligenciaron un cuestionario o fueron entrevistados. El distrés psicológico y la disfuncionalidad familiar fueron evaluados por escalas (Kessler K-10 y APGAR-family. Hombres predominaron en todos los lugares (edades entre 18 y 86. En la mayoría de los sitios, el diagnóstico actual de ansiedad varió entre 30% y 40% y el de depresión entre 20% y 35%. Niveles altos u muy altos de distrés psícológico fueron reportados por más de 70% en Uruguay, Nicaragua, Guatemala y Brasil. La disfuncionalidad familiar severa fue mayor en Panamá 34.7% seguida de los sitios de Nicaragua 20-25%. La prevalencia de distrés psicológico sugiere niveles altos de comorbilidad.

Protease-Activated Receptor 4 Variant p.Tyr157Cys Reduces Platelet Functional Responses and Alters Receptor Trafficking.

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Norman, Jane E; Cunningham, Margaret R; Jones, Matthew L; Walker, Mary E; Westbury, Sarah K; Sessions, Richard B; Mundell, Stuart J; Mumford, Andrew D

2016-05-01

Protease-activated receptor 4 (PAR4) is a key regulator of platelet reactivity and is encoded by F2RL3, which has abundant rare missense variants. We aimed to provide proof of principle that rare F2LR3 variants potentially affect platelet reactivity and responsiveness to PAR1 antagonist drugs and to explore underlying molecular mechanisms. We identified 6 rare F2RL3 missense variants in 236 cardiac patients, of which the variant causing a tyrosine 157 to cysteine substitution (Y157C) was predicted computationally to have the greatest effect on PAR4 structure. Y157C platelets from 3 cases showed reduced responses to PAR4-activating peptide and to α-thrombin compared with controls, but no reduction in responses to PAR1-activating peptide. Pretreatment with the PAR1 antagonist vorapaxar caused lower residual α-thrombin responses in Y157C platelets than in controls, indicating greater platelet inhibition. HEK293 cells transfected with a PAR4 Y157C expression construct had reduced PAR4 functional responses, unchanged total PAR4 expression but reduced surface expression. PAR4 Y157C was partially retained in the endoplasmic reticulum and displayed an expression pattern consistent with defective N-glycosylation. Mutagenesis of Y322, which is the putative hydrogen bond partner of Y157, also reduced PAR4 surface expression in HEK293 cells. Reduced PAR4 responses associated with Y157C result from aberrant anterograde surface receptor trafficking, in part, because of disrupted intramolecular hydrogen bonding. Characterization of PAR4 Y157C establishes that rare F2RL3 variants have the potential to markedly alter platelet PAR4 reactivity particularly after exposure to therapeutic PAR1 antagonists. © 2016 American Heart Association, Inc.

UCH-LI acts as a novel prognostic biomarker in gastric cardiac adenocarcinoma.

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Yang, Honghong; Zhang, Chunhong; Fang, Shan; Ou, Rongying; Li, Wenfeng; Xu, Yunsheng

2015-01-01

Gastric cardiac adenocarcinoma (GCA) accounts for a majority of gastric cancer population and harbors unfavorable outcome. Ubiquitin C-terminal hydrolase L1 (UCH-L1) belongs to the deubiquitinating enzyme family, which could regulate cell growth in human cancers. In the present study, expression of UCH-L1 was evaluated in 196 GCAs by immunohistochemistry using tissue microarray and its function on gastric cancer cells was measured. UCH-L1 expression was increased in GCA specimens, compared with their normal tissues and UCH-L1 overexpression is tightly correlated with tumor size and overall TNM stage. Log-rank analysis showed that UCH-L1 positive is reversely associated with cumulative survival (Pstage that is a known negative factor in gastric cancers (Hazard Ratio=0.33, Pgastric cancer cells. Our findings suggest that UCH-L1 is a promising prognostic biomarker for GCAs and might play an important role in the carcinogenesis of gastric cancer.

La fiesta española de L’Hippodrome de París (18 de diciembre de 1879: toros, flamenco y seudo-folclore español

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José Manuel Pedrosa

2015-04-01

Full Text Available ABSTRACT. On 18th December, 1879, a great charity event was held in Paris. Its aim was to raise funds for flood victims in the region of Murcia. That party brought together all the high society and the French bourgeoisie. Toreros, gypsies, Spanish dances went on stage. And they shaped a «folk» image of Spain that had great influence outside our borders. RESUMEN. El 18 de diciembre de 1879 se celebró en París una gran fiesta benéfica. Su objetivo era recaudar fondos para los damnificados de las inundaciones que unos meses antes había sufrido la región de Murcia. Aquella fiesta reunió a toda la alta sociedad y a la burguesía francesa. Toreros, gitanos, bailes españoles subieron a escena. Y ejerció gran influencia en la configuración de los tópicos folclóricos acerca de España que triunfaron fuera de nuestras fronteras.

Association of Caucasian-identified variants with colorectal cancer risk in Singapore Chinese.

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Lai Fun Thean

Full Text Available Genome-wide association studies (GWAS in Caucasians have identified fourteen index single nucleotide polymorphisms (iSNPs that influence colorectal cancer (CRC risk.We investigated the role of eleven iSNPs or surrogate SNPs (sSNPs, in high linkage disequilibrium (LD, r(2≥ 0.8 and within 100 kb vicinity of iSNPs, in 2,000 age- and gender-matched Singapore Chinese (SCH cases and controls.Only iSNP rs6983267 at 8q24.21 and sSNPs rs6695584, rs11986063, rs3087967, rs2059254, and rs7226855 at 1q41, 8q23.3, 11q23.1, 16q22.1 and 18q21.1 respectively showed evidence of association with CRC risk, with odds ratios (OR ranging from 1.13 to 1.40. sSNP rs827401 at 10p14 was associated with rectal cancer risk (OR = 0.74, 95% CI 0.63-0.88 but not disease prognosis (OR = 0.91, 95% CI 0.69-1.20. Interestingly, sSNP rs3087967 at 11q23.1 was associated with CRC risk in men (OR = 1.34, 95% CI 1.14-1.58 but not women (OR = 1.07, 95% CI: 0.88-1.29, suggesting a gender-specific role. Half of the Caucasian-identified variants, including the recently fine-mapped BMP pathway loci, BMP4, GREM1, BMP2 and LAMA 5, did not show any evidence for association with CRC in SCH (OR ~1; p-value >0.1. Comparing the results of this study with that of the Northern and Hong Kong Chinese, only variants at chromosomes 8q24.21, 10p14, 11q23.1 and 18q21.1 were replicated in at least two out of the three Chinese studies.The contrasting results between Caucasians and Chinese could be due to different LD patterns and allelic frequencies or genetic heterogeneity. The results suggest that additional common variants contributing to CRC predisposition remained to be identified.

CARACTERIZACIÓN BIOLÓGICA DE VARIANTES DE PLACA DE LA CEPA VACUNAL 17D CONTRA LA FIEBRE AMARILLA

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María Rojas

2009-09-01

Full Text Available La vacuna colombiana 17D, contiene por lo menos cuatro fenotipos, denominados pequeño (0.3 – 1.2 mm, mediano (1.3 – 2.1 mm, grande (2.2 – 3.0 mm y extragrande (>3.1 mm. La composición y distribución porcentual de esos fenotipos, varió entre lotes y entre ampolletas de un mismo lote. Cada variante fue clonada por dilución de la vacuna y su efecto virulento fue analizado en ratones; el fenotipo de placa pequeño estuvo ligeramente sub representado en los lotes analizados y mostró una virulencia similar a la de la cepa silvestre neurotrópica Francesa (LD50 > 10-6, mientras que el fenotipo predominante y mas atenuado fue el mediano (LD50: 10-4. Los fenotipos grande y extragrande mostraron una virulencia intermedia (LD 50: 10 – 5  con relación a los anteriores. Los análisis de secuencia de las variantes sobre una región comprendida entre el extremo 3´NS5 y el inicio de 3´NCR, mostró la cercanía entre aquellas variantes con algún grado de virulencia, y entre la variante atenuada y la vacuna colombiana. La heterogeneidad de la vacuna 17D, constituye una evidencia de la estructura de quasiespecies propia de los virus RNA y señala cómo los casos de reacciones post vacunales  adversas pueden estar asociados con la aplicación de vacunas fabricadas a partir de cepas virales atenuadas.  

Sarcoidosis aguda: Variante de Síndrome de Löfgren sin eritema nodoso

OpenAIRE

Pérez, Gerardo; Facal, Jorge

2014-01-01

El síndrome de Löfgren, es una variante aguda de la sarcoidosis, que se caracteriza por fiebre, eritema nodoso, adenomegalias hiliares pulmonares y artritis. En general, tiene un curso benigno y autolimitado, que contrasta con las formas crónicas que requieren uso de corticoides y tienen tendencia a la recidiva. Se describe aquí el caso clínico de un paciente joven, de sexo masculino, con artritis pero sin eritema nodoso, lo que dificultó el planteo diagnóstico de síndrome de Löfgren. Se real...

Variantes alélicas de CYP2D6: *4, *6 y *10 en una muestra de residentes del estado Aragua, Venezuela

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Carlos Flores-Angulo

Full Text Available El objetivo del estudio fue determinar la frecuencia de las variantes del gen CYP2D6: *4, *6 y *10 y predecir el fenotipo metabolizador en una muestra de 145 individuos no consanguíneos, aparentemente sanos, residentes del estado Aragua, Venezuela. Los genotipos fueron determinados mediante ensayos de reacción en cadena de la polimerasa seguidos de digestión con endonucleasas de restricción. La predicción del fenotipo metabolizador se realizó con base al sistema Activity score. Las frecuencias de CYP2D6 *4, *6 y *10 fueron de 14,5%, 0,3% y 1%, respectivamente; un porcentaje significativo de individuos fueron categorizados como metabolizador rápido heterocigoto/metabolizador intermedio (23,5% y metabolizador lento (4,1%. Esta información tiene impacto clínico potencial, porque CYP2D6 interviene en el metabolismo de fármacos de prescripción frecuente como: carvedilol, captopril, cloroquina, codeína, fluoxetina, fluvastatina, haloperidol, idarrubicina, indinavir, imatinib, loperamida, nifedipina, ondansetrón y tamoxifeno

Identification of IFRD1 variant in a Han Chinese family with autosomal dominant hereditary spastic paraplegia associated with peripheral neuropathy and ataxia.

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Lin, Pengfei; Zhang, Dong; Xu, Guangrun; Yan, Chuanzhu

2018-04-01

Spinocerebellar ataxias (SCAs) are a group of autosomal dominant, clinically heterogeneous neurodegenerative disorders. SCA18 is a rare autosomal dominant sensory/motor neuropathy with ataxia (OMIM#607458) associated with a single missense variant c.514 A>G in the interferon related developmental regulator 1 (IFRD1) gene previously reported in a five-generation American family of Irish origin. However, to date, there have been no other reports of the IFRD1 mutation to confirm its role in SCA. Here, we report a Han Chinese family with SCA18; the family members presented with a slowly progressing gait ataxia, pyramidal tract signs, and peripheral neuropathy. We identified a missense variant (c.514 A>G, p.I172V) in IFRD1 gene in the family using targeted next-generation sequencing and Sanger direct sequencing with specific primers. Our results suggest that the IFRD1 gene may be the causative allele for SCA18.

Bulimia nerviosa y factores de riesgo asociados en adolescentes escolarizados de 14 a 18 años en Barranquilla (Colombia

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Mariela Borda Pérez

2015-01-01

Full Text Available Objetivo: establecer la prevalencia de riesgo de bulimia y de factores de riesgo asociados en adolecentes escolarizados de 14 a 18 años de Barranquilla. Materiales y métodos: Estudio transversal partir de una muestra representativa de escolares de cuatro establecimientos educativos de Barranquilla. Participaron 149 sujetos de 14 a 18 años. Se aplicó instrumento para determinar imagen corporal y bulimia (Body Shape Questionarie, el Bulimia Test of Edinburgh, Test de Rosemberg y DASS21, se estimó IMC y se empleó un cuestionario para determinantes personales. Resultados: La prevalencia de riesgo de bulimia fue del 44,3 %. El perfil identifica preferencialmente a 51,3 % mujeres, una de cada cuatro con sobrepeso, y de ellos, el 53 % tenía 16 años o más. Las características relevantes: 18,2 % consumía diuréticos y laxantes para bajar de peso; el 40,9 % tenía problemas económicos; el 56 % manifestó ansiedad; el 53 % depresión y el 53 % insatisfacción con su imagen corporal. Se observó tendencia a la asociación con: sobrepeso, saltar comidas con frecuencia, consumir tres comidas y picar, consumir tres comidas, emplear diuréticos o laxantes para bajar de peso, ansiedad, depresión, estrés e insatisfacción corporal; se obtuvieron razones de disparidad significantes y probabilidad del chi-cuadrado menor de 0.05. Conclusión: El riesgo de bulimia se presentó preferencialmente en el grupo de ≥ 16 años, en mujeres y en el estrato medio. Se aprecia una asociación estadística con sobrepeso saltar comidas con frecuencia, consumir tres comidas y picar, consumir tres comidas, emplear diuréticos o laxantes para bajar de peso, ansiedad, depresión, estrés e insatisfacción corporal.

Low multiple electrode aggregometry platelet responses are not associated with non-synonymous variants in G-protein coupled receptor genes.

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Norman, Jane E; Lee, Kurtis R; Walker, Mary E; Murden, Sherina L; Harris, Jessica; Mundell, Stuart; J Murphy, Gavin; Mumford, Andrew D

2015-10-01

Multiple electrode aggregometry (MEA) improves prediction of thrombosis and bleeding in cardiac patients. However, the causes of inter-individual variation in MEA results are incompletely understood. We explore whether low MEA results are associated with platelet G-protein coupled receptor (GPCR) gene variants. The effects of P2Y12 receptor (P2Y12), thromboxane A2 receptor (TPα) and protease-activated receptor 1 (PAR1) dysfunction on the MEA ADP-test, ASPI-test and TRAP-test were determined using receptor antagonists. Cardiac surgery patients with pre-operative MEA results suggesting GPCR dysfunction were selected for P2Y12 (P2RY12), TPα (TBXA2R) and PAR1 (F2R) sequencing. In control blood samples, P2Y12, TPα or PAR1 antagonists markedly reduced ADP-test, ASPI-test and TRAP-test results respectively. In the 636 patients from a cohort of 2388 cardiac surgery patients who were not receiving aspirin or a P2Y12 blocker, the median ADP-test result was 75.1 U (range 4.8-153.2), ASPI-test 83.7 U (1.4-157.3) and TRAP-test 117.7 U (2.4-194.1), indicating a broad range of results unexplained by anti-platelet drugs. In 238 consenting patients with unexplained low MEA results, three P2RY12 variants occurred in 70/107 (65%) with suspected P2Y12 dysfunction and four TBXA2R variants occurred in 19/22 (86%) with suspected TPα dysfunction although the later group was too small to draw meaningful conclusions about variant frequency. All the variants were synonymous and unlikely to cause GPCR dysfunction. There were no F2R variants in the 109 cases with suspected PAR1 dysfunction. MEA results suggesting isolated platelet GPCR dysfunction were common in cardiac surgery patients, but were not associated with non-synonymous variants in P2RY12 or F2R. Copyright © 2015 Elsevier Ltd. All rights reserved.

The rs3857059 variant of the SNCA gene is associated with Parkinson’s disease in Mexican Mestizos

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S. García

2016-06-01

Full Text Available ABSTRACT Among the candidate genes for Parkinson’s disease (PD, SNCA has replicated association in different populations. Besides other known mutations in the SNCA gene, the rs3857059 variant has also been linked to various neurodegenerative disorders. Therefore, the aim of the present study was to search for association of this variant and sporadic PD in Mexican Mestizo patients. A case-control study was performed including 241 individuals, 106 patients, and 135 healthy controls. Genotyping was performed using real-time PCR. The rs3857059 variant demonstrated an association with PD in Mexican Mestizos (OR = 2.40, CI, 1.1 to 5.1, p = 0.02 under the recessive model. In addition, a gender effect was found for the GG genotype in females (OR = 1.31, CI, 1.01 to 1.7, p = 0.037. This is the first study to confirm an association of the rs3857059 variant with PD and also to show a gender effect. Our data contribute to the elucidation of the link between rs3857059 and susceptibility to PD observed in the Mexican Mestizo population.

Three-dimensional spatial analysis of missense variants in RTEL1 identifies pathogenic variants in patients with Familial Interstitial Pneumonia.

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Sivley, R Michael; Sheehan, Jonathan H; Kropski, Jonathan A; Cogan, Joy; Blackwell, Timothy S; Phillips, John A; Bush, William S; Meiler, Jens; Capra, John A

2018-01-23

Next-generation sequencing of individuals with genetic diseases often detects candidate rare variants in numerous genes, but determining which are causal remains challenging. We hypothesized that the spatial distribution of missense variants in protein structures contains information about function and pathogenicity that can help prioritize variants of unknown significance (VUS) and elucidate the structural mechanisms leading to disease. To illustrate this approach in a clinical application, we analyzed 13 candidate missense variants in regulator of telomere elongation helicase 1 (RTEL1) identified in patients with Familial Interstitial Pneumonia (FIP). We curated pathogenic and neutral RTEL1 variants from the literature and public databases. We then used homology modeling to construct a 3D structural model of RTEL1 and mapped known variants into this structure. We next developed a pathogenicity prediction algorithm based on proximity to known disease causing and neutral variants and evaluated its performance with leave-one-out cross-validation. We further validated our predictions with segregation analyses, telomere lengths, and mutagenesis data from the homologous XPD protein. Our algorithm for classifying RTEL1 VUS based on spatial proximity to pathogenic and neutral variation accurately distinguished 7 known pathogenic from 29 neutral variants (ROC AUC = 0.85) in the N-terminal domains of RTEL1. Pathogenic proximity scores were also significantly correlated with effects on ATPase activity (Pearson r = -0.65, p = 0.0004) in XPD, a related helicase. Applying the algorithm to 13 VUS identified from sequencing of RTEL1 from patients predicted five out of six disease-segregating VUS to be pathogenic. We provide structural hypotheses regarding how these mutations may disrupt RTEL1 ATPase and helicase function. Spatial analysis of missense variation accurately classified candidate VUS in RTEL1 and suggests how such variants cause disease. Incorporating

Prácticas sexuales de riesgo y seroprevalencia de infección por VIH-1. HTLV-1, sífilis y hepatitis B en varones drogadictos no endovenosos de Lima.

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Dany MUÑOZ

1997-07-01

Full Text Available Objetivo: Investigar la prevalencia de prácticas sexuales de riesgo para infección por Enfermedades de Transmisión Sexual (ETS y la seroprevalencia de infección por VIH-1, HTLV-1, Hepatitis B y Sífilis en varones Drogadictos no Endovenosos (DNEV de Lima e identificar si ellos podrían ser considerados como grupo de alto riesgo de infección para HIV. Material y métodos: Encuesta anónima por entrevista directa sobre practicas sexuales y antecedentes de ETS, y análisis serológico para anticuerpos contra VIH, HTLV-1, HBc y T pallidum de 298 DNEV voluntarios del Instituto de Salud Mental "Honorio Delgado - Hideyo Noguchi" y de 10 Organizaciones No Gubernamentales ("Comunidades Terapéuticas" de Lima Metropolitana entre Abril y Agosto de 1996. Resultados: Cinco (1.7% muestras fueron positivas para VIH y una resultó indeterminada (ELISA positivo y WB banda gp 160 presente. Siete (2.3% positivas para HTLV- 1, treinta y cuatro (11.4% positivas para Ab Anti-HBc; y una (0.3% fue RPR y FTA-Abs positiva. El promedio de edad fué 28.8 ± 8.1 años. El promedio de tiempo de consumo de drogas más frecuente fue 6.9 ± 6.2 años con el 80% más de un año. Durante la etapa de consumo: el promedio del número de parejas sexuales fue 53.9 ± 243 con una mediana de 15. De los DNEV mantuvieron relaciones sexuales con Parejas Sexuales Estables el 79%, con Encuentros Casuales el 82%, con Meretrices el 62.4% y con Homosexuales el 60%; el uso consistente de condón es bajo con todos los tipos de parejas sexuales y en todos los tipos de relaciones sexuales pero aumenta significativamente en las relaciones sexuales con meretrices. Con el uso de drogas existe un aumento en el número de parejas sexuales y mayor frecuencia de algunas prácticas sexuales de riesgo tal como el coito anal con todos los tipos de parejas sexuales, así mismo un elevado porcentaje (75% mantienen relaciones sexuales estando drogados, y el 32.9% intercambian drogas por sexo. El 43

Vitaminas y minerales contra el estrés

OpenAIRE

Espinosa Hernández, Jose Antonio; Cué Brugueras, Manuel

2001-01-01

Se define el estrés como tal, así como los tipos de tratamientos para este. Se expresan las relaciones entre las multivitaminas y minerales y el estr��s y se dan criterios sobre su uso. Se concluye que los principales medicamentos antiestrés encontrados contienen las vitaminas E, B1, B2, B3, B5, B6, B12,C, ácido fólico y minerales cinc y hierro; entre los principales fabricantes se encuentran: Lederle, Rugby, Ayerst, Scherin, Vicks Health Care, Goldline, Squibbs, Miles Inc. y Natural Life.The...

LSD1/KDM1 isoform LSD1+8a contributes to neural differentiation in small cell lung cancer

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Takanobu Jotatsu

2017-03-01

Full Text Available Small cell lung cancer (SCLC is an aggressive neuroendocrine tumor characterized by rapid progression. The mechanisms that lead to a shift from initial therapeutic sensitivity to ultimate therapeutic resistance are poorly understood. Although the SCLC genomic landscape led to the discovery of promising agents targeting genetic alterations that were already under investigation, results have been disappointing. Achievements in targeted therapeutics have not been observed for over 30 years. Therefore, the underlying disease biology and novel targets urgently require a better understanding. Epigenetic regulation is deeply involved in the cellular plasticity that could shift tumor cells to the malignant phenotype. We have focused on a histone modifier, LSD1, that is overexpressed in SCLC and is a potent therapeutic target. Interestingly, the LSD1 splice variant LSD1+8a, the expression of which has been reported to be restricted to neural tissue, was detected and was involved in the expression of neuroendocrine marker genes in SCLC cell lines. Cells with high expression of LSD1+8a were resistant to CDDP and LSD1 inhibitor. Moreover, suppression of LSD1+8a inhibited cell proliferation, indicating that LSD1+8a could play a critical role in SCLC. These findings suggest that LSD1+8a should be considered a novel therapeutic target in SCLC.

Intestinal DMBT1 expression is modulated by Crohn's disease-associated IL23R variants and by a DMBT1 variant which influences binding of the transcription factors CREB1 and ATF-2.

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Julia Diegelmann

Full Text Available OBJECTIVES: DMBT is an antibacterial pattern recognition and scavenger receptor. In this study, we analyzed the role of DMBT1 single nucleotide polymorphisms (SNPs regarding inflammatory bowel disease (IBD susceptibility and examined their functional impact on transcription factor binding and downstream gene expression. METHODS: Seven SNPs in the DMBT1 gene region were analyzed in 2073 individuals including 818 Crohn's disease (CD patients and 972 healthy controls in two independent case-control panels. Comprehensive epistasis analyses for the known CD susceptibility genes NOD2, IL23R and IL27 were performed. The influence of IL23R variants on DMBT1 expression was analyzed. Functional analysis included siRNA transfection, quantitative PCR, western blot, electrophoretic mobility shift and luciferase assays. RESULTS: IL-22 induces DMBT1 protein expression in intestinal epithelial cells dependent on STAT3, ATF-2 and CREB1. IL-22 expression-modulating, CD risk-associated IL23R variants influence DMBT1 expression in CD patients and DMBT1 levels are increased in the inflamed intestinal mucosa of CD patients. Several DMBT1 SNPs were associated with CD susceptibility. SNP rs2981804 was most strongly associated with CD in the combined panel (p = 3.0 × 10(-7, OR 1.42; 95% CI 1.24-1.63. All haplotype groups tested showed highly significant associations with CD (including omnibus P-values as low as 6.1 × 10(-18. The most strongly CD risk-associated, non-coding DMBT1 SNP rs2981804 modifies the DNA binding sites for the transcription factors CREB1 and ATF-2 and the respective genomic region comprising rs2981804 is able to act as a transcriptional regulator in vitro. Intestinal DMBT1 expression is decreased in CD patients carrying the rs2981804 CD risk allele. CONCLUSION: We identified novel associations of DMBT1 variants with CD susceptibility and discovered a novel functional role of rs2981804 in regulating DMBT1 expression. Our data suggest an important

Intestinal DMBT1 expression is modulated by Crohn's disease-associated IL23R variants and by a DMBT1 variant which influences binding of the transcription factors CREB1 and ATF-2.

Science.gov (United States)

Diegelmann, Julia; Czamara, Darina; Le Bras, Emmanuelle; Zimmermann, Eva; Olszak, Torsten; Bedynek, Andrea; Göke, Burkhard; Franke, Andre; Glas, Jürgen; Brand, Stephan

2013-01-01

DMBT is an antibacterial pattern recognition and scavenger receptor. In this study, we analyzed the role of DMBT1 single nucleotide polymorphisms (SNPs) regarding inflammatory bowel disease (IBD) susceptibility and examined their functional impact on transcription factor binding and downstream gene expression. Seven SNPs in the DMBT1 gene region were analyzed in 2073 individuals including 818 Crohn's disease (CD) patients and 972 healthy controls in two independent case-control panels. Comprehensive epistasis analyses for the known CD susceptibility genes NOD2, IL23R and IL27 were performed. The influence of IL23R variants on DMBT1 expression was analyzed. Functional analysis included siRNA transfection, quantitative PCR, western blot, electrophoretic mobility shift and luciferase assays. IL-22 induces DMBT1 protein expression in intestinal epithelial cells dependent on STAT3, ATF-2 and CREB1. IL-22 expression-modulating, CD risk-associated IL23R variants influence DMBT1 expression in CD patients and DMBT1 levels are increased in the inflamed intestinal mucosa of CD patients. Several DMBT1 SNPs were associated with CD susceptibility. SNP rs2981804 was most strongly associated with CD in the combined panel (p = 3.0 × 10(-7), OR 1.42; 95% CI 1.24-1.63). All haplotype groups tested showed highly significant associations with CD (including omnibus P-values as low as 6.1 × 10(-18)). The most strongly CD risk-associated, non-coding DMBT1 SNP rs2981804 modifies the DNA binding sites for the transcription factors CREB1 and ATF-2 and the respective genomic region comprising rs2981804 is able to act as a transcriptional regulator in vitro. Intestinal DMBT1 expression is decreased in CD patients carrying the rs2981804 CD risk allele. We identified novel associations of DMBT1 variants with CD susceptibility and discovered a novel functional role of rs2981804 in regulating DMBT1 expression. Our data suggest an important role of DMBT1 in CD pathogenesis.

The expanding spectrum of COL2A1 gene variants IN 136 patients with a skeletal dysplasia phenotype.

Science.gov (United States)

Barat-Houari, Mouna; Dumont, Bruno; Fabre, Aurélie; Them, Frédéric Tm; Alembik, Yves; Alessandri, Jean-Luc; Amiel, Jeanne; Audebert, Séverine; Baumann-Morel, Clarisse; Blanchet, Patricia; Bieth, Eric; Brechard, Marie; Busa, Tiffany; Calvas, Patrick; Capri, Yline; Cartault, François; Chassaing, Nicolas; Ciorca, Vidrica; Coubes, Christine; David, Albert; Delezoide, Anne-Lise; Dupin-Deguine, Delphine; El Chehadeh, Salima; Faivre, Laurence; Giuliano, Fabienne; Goldenberg, Alice; Isidor, Bertrand; Jacquemont, Marie-Line; Julia, Sophie; Kaplan, Josseline; Lacombe, Didier; Lebrun, Marine; Marlin, Sandrine; Martin-Coignard, Dominique; Martinovic, Jelena; Masurel, Alice; Melki, Judith; Mozelle-Nivoix, Monique; Nguyen, Karine; Odent, Sylvie; Philip, Nicole; Pinson, Lucile; Plessis, Ghislaine; Quélin, Chloé; Shaeffer, Elise; Sigaudy, Sabine; Thauvin, Christel; Till, Marianne; Touraine, Renaud; Vigneron, Jacqueline; Baujat, Geneviève; Cormier-Daire, Valérie; Le Merrer, Martine; Geneviève, David; Touitou, Isabelle

2016-07-01

Heterozygous COL2A1 variants cause a wide spectrum of skeletal dysplasia termed type II collagenopathies. We assessed the impact of this gene in our French series. A decision tree was applied to select 136 probands (71 Stickler cases, 21 Spondyloepiphyseal dysplasia congenita cases, 11 Kniest dysplasia cases, and 34 other dysplasia cases) before molecular diagnosis by Sanger sequencing. We identified 66 different variants among the 71 positive patients. Among those patients, 18 belonged to multiplex families and 53 were sporadic. Most variants (38/44, 86%) were located in the triple helical domain of the collagen chain and glycine substitutions were mainly observed in severe phenotypes, whereas arginine to cysteine changes were more often encountered in moderate phenotypes. This series of skeletal dysplasia is one of the largest reported so far, adding 44 novel variants (15%) to published data. We have confirmed that about half of our Stickler patients (46%) carried a COL2A1 variant, and that the molecular spectrum was different across the phenotypes. To further address the question of genotype-phenotype correlation, we plan to screen our patients for other candidate genes using a targeted next-generation sequencing approach.

Caracterización del inicio de la diabetes mellitus tipo 1 en menores de 18 años

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Yan González Ramos

2016-12-01

Full Text Available Fundamento: la diabetes mellitus tipo 1 es la enfermedad crónico endocrinológica más frecuente en la edad pediátrica y la segunda enfermedad crónica en la infancia después del asma bronquial, en los países desarrollados. Objetivo: identificar los aspectos epidemiológicos en el inicio de la diabetes mellitus tipo 1 en menores de 18 años en la provincia de Cienfuegos en el periodo 1997- octubre 2015. Métodos: se realizó un estudio descriptivo retrospectivo en los pacientes menores de 18 años, diagnosticados con diabetes mellitus tipo 1 en el periodo mencionado. Las variables utilizadas fueron: año y edad del inicio, sexo, color de la piel y municipio de procedencia. Los resultados se presentaron en tablas de frecuencias y porcentajes. Resultados: el porcentaje de pacientes del sexo masculino y femenino fue bastante similar con un leve predominio del masculino (53,5 %. El grupo 5-9 años presentó el mayor número de pacientes (35 casos pero sin diferencias significativas con el de 10-14 años (34 casos. El color de piel blanca predominó con el 75,7 %. El mayor número de casos se mostraron en los meses de otoño con 30. Los municipios de mayor incidencia fueron Cienfuegos con 40 y Cumanayagua con 16 casos respectivamente. Conclusiones: se ha producido un aumento de la incidencia en los últimos años con un leve predominio del sexo masculino y el grupo de 5-9 años. Predominó la raza blanca. El mayor número del inicio ocurrió en otoño y en el municipio de Cienfuegos.

E6 variants of human papillomavirus 18 differentially modulate the protein kinase B/phosphatidylinositol 3-kinase (akt/PI3K) signaling pathway

International Nuclear Information System (INIS)

Contreras-Paredes, Adriana; Cruz-Hernandez, Erick de la; Martinez-Ramirez, Imelda; Duenas-Gonzalez, Alfonso; Lizano, Marcela

2009-01-01

Intra-type genome variations of high risk Human papillomavirus (HPV) have been associated with a differential threat for cervical cancer development. In this work, the effect of HPV18 E6 isolates in Akt/PKB and Mitogen-associated protein kinase (MAPKs) signaling pathways and its implication in cell proliferation were analyzed. E6 from HPV types 16 and 18 are able to bind and promote degradation of Human disc large (hDlg). Our results show that E6 variants differentially modulate hDlg degradation, rebounding in levels of activated PTEN and PKB. HPV18 E6 variants are also able to upregulate phospho-PI3K protein, strongly correlating with activated MAPKs and cell proliferation. Data was supported by the effect of E6 silencing in HPV18-containing HeLa cells, as well as hDlg silencing in the tested cells. Results suggest that HPV18 intra-type variations may derive in differential abilities to activate cell-signaling pathways such as Akt/PKB and MAPKs, directly involved in cell survival and proliferation

Functional significance of SPINK1 promoter variants in chronic pancreatitis.

Science.gov (United States)

Derikx, Monique H M; Geisz, Andrea; Kereszturi, Éva; Sahin-Tóth, Miklós

2015-05-01

Chronic pancreatitis is a progressive inflammatory disorder of the pancreas, which often develops as a result of genetic predisposition. Some of the most frequently identified risk factors affect the serine protease inhibitor Kazal type 1 (SPINK1) gene, which encodes a trypsin inhibitor responsible for protecting the pancreas from premature trypsinogen activation. Recent genetic and functional studies indicated that promoter variants in the SPINK1 gene might contribute to disease risk in carriers. Here, we investigated the functional effects of 17 SPINK1 promoter variants using luciferase reporter gene expression assay in four different cell lines, including three pancreatic acinar cell lines (rat AR42J with or without dexamethasone-induced differentiation and mouse 266-6) and human embryonic kidney 293T cells. We found that most variants caused relatively small changes in promoter activity. Surprisingly, however, we observed significant variations in the effects of the promoter variants in the different cell lines. Only four variants exhibited consistently reduced promoter activity in all acinar cell lines, confirming previous reports that variants c.-108G>T, c.-142T>C, and c.-147A>G are risk factors for chronic pancreatitis and identifying c.-52G>T as a novel risk variant. In contrast, variant c.-215G>A, which is linked with the disease-associated splice-site mutation c.194 + 2T>C, caused increased promoter activity, which may mitigate the overall effect of the pathogenic haplotype. Our study lends further support to the notion that sequence evaluation of the SPINK1 promoter region in patients with chronic pancreatitis is justified as part of the etiological investigation. Copyright © 2015 the American Physiological Society.

Scintillation properties of polycrystalline LaxY1-xO3 ceramic

Science.gov (United States)

Sahi, Sunil; Chen, Wei; Kenarangui, Rasool

2015-03-01

Scintillators are the material that absorbs the high-energy photons and emits visible photons. Scintillators are commonly used in radiation detector for security, medical imaging, industrial applications and high energy physics research. Two main types of scintillators are inorganic single crystals and organic (plastic or liquid) scintillators. Inorganic single crystals are expensive and difficult to grow in desire shape and size. Also, some efficient inorganic scintillator such as NaI and CsI are not environmental friendly. But on the other hand, organic scintillators have low density and hence poor energy resolution which limits their use in gamma spectroscopy. Polycrystalline ceramic can be a cost effective alternative to expensive inorganic single crystal scintillators. Here we have fabricated La0.2Y1.8O3 ceramic scintillator and studied their luminescence and scintillation properties. Ceramic scintillators were fabricated by vacuum sintering of La0.2Y1.8O3 nanoparticles at temperature below the melting point. La0.2Y1.8O3 ceramic were characterized structurally using XRD and TEM. Photoluminescence and radioluminescence studies were done using UV and X-ray as an excitation source. We have used gamma isotopes with different energy to studies the scintillation properties of La0.2Y1.8O3 scintillator. Preliminary studies of La0.2Y1.8O3 scintillator shows promising result with energy resolution comparable to that of NaI and CsI.

Germline-specific H1 variants: the "sexy" linker histones.

Science.gov (United States)

Pérez-Montero, Salvador; Carbonell, Albert; Azorín, Fernando

2016-03-01

The eukaryotic genome is packed into chromatin, a nucleoprotein complex mainly formed by the interaction of DNA with the abundant basic histone proteins. The fundamental structural and functional subunit of chromatin is the nucleosome core particle, which is composed by 146 bp of DNA wrapped around an octameric protein complex formed by two copies of each core histone H2A, H2B, H3, and H4. In addition, although not an intrinsic component of the nucleosome core particle, linker histone H1 directly interacts with it in a monomeric form. Histone H1 binds nucleosomes near the exit/entry sites of linker DNA, determines nucleosome repeat length and stabilizes higher-order organization of nucleosomes into the ∼30 nm chromatin fiber. In comparison to core histones, histone H1 is less well conserved through evolution. Furthermore, histone H1 composition in metazoans is generally complex with most species containing multiple variants that play redundant as well as specific functions. In this regard, a characteristic feature is the presence of specific H1 variants that replace somatic H1s in the germline and during early embryogenesis. In this review, we summarize our current knowledge about their structural and functional properties.

Influence of substitutional disorder on the electrical transport and the superconducting properties of Fe{sub 1+z}Te{sub 1−x−y}Se{sub x}S{sub y}

Energy Technology Data Exchange (ETDEWEB)

Rodríguez, M.G. [Laboratorio de Bajas Temperaturas, Departamento de Física, FCEyNUBA and IFIBA-CONICET, Buenos Aires (Argentina); Polla, G.; Ramos, C.P. [Gerencia de Investigación y Aplicaciones, CAC-CNEA, San Martín (Argentina); Acha, C., E-mail: acha@df.uba.ar [Laboratorio de Bajas Temperaturas, Departamento de Física, FCEyNUBA and IFIBA-CONICET, Buenos Aires (Argentina)

2015-11-15

We have carried out an investigation of the structural, magnetic, transport and superconducting properties of Fe{sub 1+z}Te{sub 1−x−y}Se{sub x}S{sub y} ceramic compounds, for z = 0 and some specific Se (0 ≤ x ≤ 0.5) and S (0 ≤ y ≤ 0.12) contents. The incorporation of Se and S to the FeTe structure produces a progressive reduction of the crystallographic parameters as well as different degrees of structural disorder associated with the differences of the ionic radius of the substituting cations. In the present study, we measure transport properties of this family of compounds and we show the direct influence of disorder in the normal and superconductor states. We notice that the structural disorder correlates with a variable range hopping conducting regime observed at temperatures T > 200 K. At lower temperatures, all the samples except the one with the highest degree of disorder show a crossover to a metallic-like regime, probably related to the transport of resilient-quasi-particles associated with the proximity of a Fermi liquid state at temperatures below the superconducting transition. Moreover, the superconducting properties are depressed only for that particular sample, in accordance to the condition that superconductivity is affected by disorder when the electronic localization length ξ{sub L} becomes smaller than the coherence length ξ{sub SC}. - Highlights: • New Fe(1 + z)Te(1−x−y)Se(x)S(y) ceramic samples were synthesized. • Structural, magnetic, transport and superconducting properties are presented. • Nonmagnetic disorder determines a VRH conduction regime near room temperature. • Superconductivity is affected by disorder.

Measurement of the B Meson Differential Cross Section dσ/dpT in p bar p Collisions at √s=1.8 TeV

International Nuclear Information System (INIS)

Abe, F.; Albrow, M.G.; Amendolia, S.R.; Amidei, D.; Antos, J.; Anway-Wiese, C.; Apollinari, G.; Areti, H.; Atac, M.; Auchincloss, P.; Azfar, F.; Azzi, P.; Bacchetta, N.; Badgett, W.; Bailey, M.W.; Bao, J.; de Barbaro, P.; Barbaro-Galtieri, A.; Barnes, V.E.; Barnett, B.A.; Bartalini, P.; Bauer, G.; Baumann, T.; Bedeschi, F.; Behrends, S.; Belforte, S.; Bellettini, G.; Bellinger, J.; Benjamin, D.; Benlloch, J.; Bensinger, J.; Benton, D.; Beretvas, A.; Berge, J.P.; Bertolucci, S.; Bhatti, A.; Biery, K.; Binkley, M.; Bird, F.; Bisello, D.; Blair, R.E.; Blocker, C.; Bodek, A.; Bokhari, W.; Bolognesi, V.; Bortoletto, D.; Boswell, C.; Boulos, T.; Brandenburg, G.; Bromberg, C.; Buckley-Geer, E.; Budd, H.S.; Burkett, K.; Busetto, G.; Byon-Wagner, A.; Byrum, K.L.; Cammerata, J.; Campagnari, C.; Campbell, M.; Caner, A.; Carithers, W.; Carlsmith, D.; Castro, A.; Cen, Y.; Cervelli, F.; Chao, H.Y.; Chapman, J.; Cheng, M.; Chiarelli, G.; Chikamatsu, T.; Chiou, C.N.; Christofek, L.; Cihangir, S.; Clark, A.G.; Cobal, M.; Contreras, M.; Conway, J.; Cooper, J.; Cordelli, M.; Couyoumtzelis, C.; Crane, D.; Cunningham, J.D.; Daniels, T.; DeJongh, F.; Delchamps, S.; Dell'Agnello, S.; Dell'Orso, M.; Demortier, L.; Denby, B.; Deninno, M.; Derwent, P.F.; Devlin, T.; Dickson, M.; Dittmann, J.R.; Donati, S.; Drucker, R.B.; Dunn, A.; Einsweiler, K.; Elias, J.E.; Ely, R.; Engels, E. Jr.; Eno, S.; Errede, D.; Errede, S.; Fan, Q.; Farhat, B.; Fiori, I.; Flaugher, B.; Foster, G.W.; Franklin, M.; Frautschi, M.; Freeman, J.; Friedman, J.; Fry, A.; Fuess, T.A.; Fukui, Y.; Funaki, S.; Gagliardi, G.; Galeotti, S.; Gallinaro, M.; Garfinkel, A.F.; Geer, S.; Gerdes, D.W.; Giannetti, P.; Giokaris, N.; Giromini, P.; Gladney, L.; Glenzinski, D.; Gold, M.; Gonzalez, J.; Gordon, A.; Goshaw, A.T.; Goulianos, K.; Grassmann, H.; Grewal, A.; Groer, L.; Grosso-Pilcher, C.; Haber, C.; Hahn, S.R.; Hamilton, R.; Handler, R.; Hans, R.M.; Hara, K.; Harral, B.; Harris, R.M.; Hauger, S.A.; Hauser, J.; Hawk, C.

1995-01-01

This paper presents the first direct measurement of the B meson differential cross section dσ/dp T in p bar p collisions at √s=1.8 TeV using a sample of 19.3±0.7 pb --1 accumulated by the Collider Detector at Fermilab. The cross section is measured in the central rapidity region |y| T (B)>6.0 GeV/c by fully reconstructing the B meson decays B + →J/ψK + and B 0 →J/ψK *0 (892), where J/ψ→μ + μ - and K *0 →K + π - . A comparison is made to the theoretical QCD prediction calculated at next-to-leading order

A Novel Therapeutic Modality for Advanced Stage Prostate Cancer Treatment

Science.gov (United States)

2017-10-01

Androgen Receptor Signaling Inhibitors Repress Prostate Cancer Growth by Downregulating Androgen Receptor Splice Variants, EZH2, and Src. Cancer ...research 2015;75(24):5309-17. 18. Wadosky KM, Koochekpour S. Androgen receptor splice variants and prostate cancer : From bench to bedside. Oncotarget...2017;8(11):18550-76. 19. Cao S, Zhan Y, Dong Y. Emerging data on androgen receptor splice variants in prostate cancer . Endocrine-related cancer

Rare coding variants in PLCG2, ABI3 and TREM2 implicate microglial-mediated innate immunity in Alzheimer’s disease

Science.gov (United States)

Sims, Rebecca; van der Lee, Sven J.; Naj, Adam C.; Bellenguez, Céline; Badarinarayan, Nandini; Jakobsdottir, Johanna; Kunkle, Brian W.; Boland, Anne; Raybould, Rachel; Bis, Joshua C.; Martin, Eden R.; Grenier-Boley, Benjamin; Heilmann-Heimbach, Stefanie; Chouraki, Vincent; Kuzma, Amanda B.; Sleegers, Kristel; Vronskaya, Maria; Ruiz, Agustin; Graham, Robert R.; Olaso, Robert; Hoffmann, Per; Grove, Megan L.; Vardarajan, Badri N.; Hiltunen, Mikko; Nöthen, Markus M.; White, Charles C.; Hamilton-Nelson, Kara L.; Epelbaum, Jacques; Maier, Wolfgang; Choi, Seung-Hoan; Beecham, Gary W.; Dulary, Cécile; Herms, Stefan; Smith, Albert V.; Funk, Cory C.; Derbois, Céline; Forstner, Andreas J.; Ahmad, Shahzad; Li, Hongdong; Bacq, Delphine; Harold, Denise; Satizabal, Claudia L.; Valladares, Otto; Squassina, Alessio; Thomas, Rhodri; Brody, Jennifer A.; Qu, Liming; Sanchez-Juan, Pascual; Morgan, Taniesha; Wolters, Frank J.; Zhao, Yi; Garcia, Florentino Sanchez; Denning, Nicola; Fornage, Myriam; Malamon, John; Naranjo, Maria Candida Deniz; Majounie, Elisa; Mosley, Thomas H.; Dombroski, Beth; Wallon, David; Lupton, Michelle K; Dupuis, Josée; Whitehead, Patrice; Fratiglioni, Laura; Medway, Christopher; Jian, Xueqiu; Mukherjee, Shubhabrata; Keller, Lina; Brown, Kristelle; Lin, Honghuang; Cantwell, Laura B.; Panza, Francesco; McGuinness, Bernadette; Moreno-Grau, Sonia; Burgess, Jeremy D.; Solfrizzi, Vincenzo; Proitsi, Petra; Adams, Hieab H.; Allen, Mariet; Seripa, Davide; Pastor, Pau; Cupples, L. Adrienne; Price, Nathan D; Hannequin, Didier; Frank-García, Ana; Levy, Daniel; Chakrabarty, Paramita; Caffarra, Paolo; Giegling, Ina; Beiser, Alexa S.; Giedraitis, Vimantas; Hampel, Harald; Garcia, Melissa E.; Wang, Xue; Lannfelt, Lars; Mecocci, Patrizia; Eiriksdottir, Gudny; Crane, Paul K.; Pasquier, Florence; Boccardi, Virginia; Henández, Isabel; Barber, Robert C.; Scherer, Martin; Tarraga, Lluis; Adams, Perrie M.; Leber, Markus; Chen, Yuning; Albert, Marilyn S.; Riedel-Heller, Steffi; Emilsson, Valur; Beekly, Duane; Braae, Anne; Schmidt, Reinhold; Blacker, Deborah; Masullo, Carlo; Schmidt, Helena; Doody, Rachelle S.; Spalletta, Gianfranco; Longstreth, WT; Fairchild, Thomas J.; Bossù, Paola; Lopez, Oscar L.; Frosch, Matthew P.; Sacchinelli, Eleonora; Ghetti, Bernardino; Sánchez-Juan, Pascual; Yang, Qiong; Huebinger, Ryan M.; Jessen, Frank; Li, Shuo; Kamboh, M. Ilyas; Morris, John; Sotolongo-Grau, Oscar; Katz, Mindy J.; Corcoran, Chris; Himali, Jayanadra J.; Keene, C. Dirk; Tschanz, JoAnn; Fitzpatrick, Annette L.; Kukull, Walter A.; Norton, Maria; Aspelund, Thor; Larson, Eric B.; Munger, Ron; Rotter, Jerome I.; Lipton, Richard B.; Bullido, María J; Hofman, Albert; Montine, Thomas J.; Coto, Eliecer; Boerwinkle, Eric; Petersen, Ronald C.; Alvarez, Victoria; Rivadeneira, Fernando; Reiman, Eric M.; Gallo, Maura; O’Donnell, Christopher J.; Reisch, Joan S.; Bruni, Amalia Cecilia; Royall, Donald R.; Dichgans, Martin; Sano, Mary; Galimberti, Daniela; St George-Hyslop, Peter; Scarpini, Elio; Tsuang, Debby W.; Mancuso, Michelangelo; Bonuccelli, Ubaldo; Winslow, Ashley R.; Daniele, Antonio; Wu, Chuang-Kuo; Peters, Oliver; Nacmias, Benedetta; Riemenschneider, Matthias; Heun, Reinhard; Brayne, Carol; Rubinsztein, David C; Bras, Jose; Guerreiro, Rita; Hardy, John; Al-Chalabi, Ammar; Shaw, Christopher E; Collinge, John; Mann, David; Tsolaki, Magda; Clarimón, Jordi; Sussams, Rebecca; Lovestone, Simon; O’Donovan, Michael C; Owen, Michael J; Behrens, Timothy W.; Mead, Simon; Goate, Alison M.; Uitterlinden, Andre G.; Holmes, Clive; Cruchaga, Carlos; Ingelsson, Martin; Bennett, David A.; Powell, John; Golde, Todd E.; Graff, Caroline; De Jager, Philip L.; Morgan, Kevin; Ertekin-Taner, Nilufer; Combarros, Onofre; Psaty, Bruce M.; Passmore, Peter; Younkin, Steven G; Berr, Claudine; Gudnason, Vilmundur; Rujescu, Dan; Dickson, Dennis W.; Dartigues, Jean-Francois; DeStefano, Anita L.; Ortega-Cubero, Sara; Hakonarson, Hakon; Campion, Dominique; Boada, Merce; Kauwe, John “Keoni”; Farrer, Lindsay A.; Van Broeckhoven, Christine; Ikram, M. Arfan; Jones, Lesley; Haines, Johnathan; Tzourio, Christophe; Launer, Lenore J.; Escott-Price, Valentina; Mayeux, Richard; Deleuze, Jean-François; Amin, Najaf; Holmans, Peter A; Pericak-Vance, Margaret A.; Amouyel, Philippe; van Duijn, Cornelia M.; Ramirez, Alfredo; Wang, Li-San; Lambert, Jean-Charles; Seshadri, Sudha; Williams, Julie; Schellenberg, Gerard D.

2017-01-01

Introduction We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development. PMID:28714976

EFECTO DEL 1-METILCICLOPROPENO (1-MCP Y TRATAMIENTO HIDROTÉRMICO SOBRE LA FISIOLOGÍA Y CALIDAD DEL MANGO 'KEITT'

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J. A. Osuna-García

2007-01-01

Full Text Available El objetivo del presente trabajo fue evaluar el efecto del 1-MCP (0 y 300 nl·litro-1 y diferentes niveles de tratamiento hidrotérmico (0, 52 °C por 5 min y 46 °C por 110 min sobre la fisiología y calidad de mango 'Keitt'. Se analizó velocidad de respiración, pérdida de peso, firmeza, color de pulpa, sólidos solubles totales y porcentaje de frutos enfermos. Se encontró que la efectividad del 1-MCP varió acorde al nivel de tratamiento hidrotérmico. En frutos sin hidrotérmico el 1-MCP disminuyó velocidad de respiración, no influyó en la pérdida de peso, mantuvo cuatro veces más la firmeza y retrasó el cambio de color de pulpa y el aumento de los sólidos solubles. Sin embargo, bajo tratamiento hidrotérmico por 5 min el 1-MCP incrementó velocidad de respiración, no influyó en la pérdida de peso, mantuvo dos veces más la firmeza de pulpa, retrasó el desarrollo del color de pulpa y mantuvo sin cambios los sólidos solubles. La efectividad del 1-MCP sobre firmeza y pérdida de peso fue significativamente afectada por el tratamiento hidrotérmico de 110 min, y no tuvo ningún efecto sobre el control de enfermedades, sin embargo, el tratamiento con agua caliente por 5 min redujo en más de 50 % la presencia de frutos enfermos. El 1-MCP en combinación con el tratamiento hidrotérmico de 5 min alargó en cinco días la vida de anaquel de los frutos y podría ser una alternativa viable en mercados que no requieren tratamiento hidrotérmico cuarentenario para el control de mosca de la fruta.

HFE gene variants affect iron in the brain.

Science.gov (United States)

Nandar, Wint; Connor, James R

2011-04-01

Iron accumulation in the brain and increased oxidative stress are consistent observations in many neurodegenerative diseases. Thus, we have begun examination into gene mutations or allelic variants that could be associated with loss of iron homeostasis. One of the mechanisms leading to iron overload is a mutation in the HFE gene, which is involved in iron metabolism. The 2 most common HFE gene variants are C282Y (1.9%) and H63D (8.9%). The C282Y HFE variant is more commonly associated with hereditary hemochromatosis, which is an autosomal recessive disorder, characterized by iron overload in a number of systemic organs. The H63D HFE variant appears less frequently associated with hemochromatosis, but its role in the neurodegenerative diseases has received more attention. At the cellular level, the HFE mutant protein resulting from the H63D HFE gene variant is associated with iron dyshomeostasis, increased oxidative stress, glutamate release, tau phosphorylation, and alteration in inflammatory response, each of which is under investigation as a contributing factor to neurodegenerative diseases. Therefore, the HFE gene variants are proposed to be genetic modifiers or a risk factor for neurodegenerative diseases by establishing an enabling milieu for pathogenic agents. This review will discuss the current knowledge of the association of the HFE gene variants with neurodegenerative diseases: amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, and ischemic stroke. Importantly, the data herein also begin to dispel the long-held view that the brain is protected from iron accumulation associated with the HFE mutations.

A Measurement of Bottom Quark Production in $p\\bar{p}$ Collisions at $\\sqrt{s}$ = 1.8-TeV.

Energy Technology Data Exchange (ETDEWEB)

Huehn, Thorsten Bernhard [UC, Riverside

1995-12-01

We present a measurement of the bottom quark production cross section at a center of mass energy of 1.8 TeV in the rapidity region $\\mid y \\mid$ < 1 and the transverse momentum range 13 to 37 GeV=c. The measurement is extracted from a dataset of 2707 events containing muons and jets, corresponding to an integrated luminosity of $228nb^{-1}$, taken during the 1992-93 collider run of the Tevatron proton-antiproton collider at Fermilab. The measurement is about two standard deviations above QCD predictions, but is consistent with it within measurement uncertainties and uncertainties in the QCD calculation

Dermatomiositis y síndrome de evans asociado a infección por HTLV-1

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David Loja-Oropeza

2016-01-01

Full Text Available Paciente mujer de 55 años de edad, natural de Ayacucho, con antecedente de dermatomiositis desde hace 3 años, recibió tratamiento irregular con prednisona. Dos meses antes del ingreso presenta anemia hemolítica autoinmune y púrpura trombocitopénica idiopática, recibió pulsos de metilprednisolona y transfusión de paquetes globulares. Al ingreso, soporosa, mal estado general, marcada pérdida ponderal, deshidratada, livedo reticularis en miembros inferiores, onicodistrofia y onicolisis múltiple en los dedos de ambos pies. Western Blot positivo para HTLV-1. Evoluciona con hipoglicemia recurrente. Reportamos un caso de dermatomiositis y síndrome de Evans presentados en el contexto de una infección por virus linfotrópico humano tipo 1.

Apolipoprotein L1 gene variants in deceased organ donors are associated with renal allograft failure.

Science.gov (United States)

Freedman, B I; Julian, B A; Pastan, S O; Israni, A K; Schladt, D; Gautreaux, M D; Hauptfeld, V; Bray, R A; Gebel, H M; Kirk, A D; Gaston, R S; Rogers, J; Farney, A C; Orlando, G; Stratta, R J; Mohan, S; Ma, L; Langefeld, C D; Hicks, P J; Palmer, N D; Adams, P L; Palanisamy, A; Reeves-Daniel, A M; Divers, J

2015-06-01

Apolipoprotein L1 gene (APOL1) nephropathy variants in African American deceased kidney donors were associated with shorter renal allograft survival in a prior single-center report. APOL1 G1 and G2 variants were genotyped in newly accrued DNA samples from African American deceased donors of kidneys recovered and/or transplanted in Alabama and North Carolina. APOL1 genotypes and allograft outcomes in subsequent transplants from 55 U.S. centers were linked, adjusting for age, sex and race/ethnicity of recipients, HLA match, cold ischemia time, panel reactive antibody levels, and donor type. For 221 transplantations from kidneys recovered in Alabama, there was a statistical trend toward shorter allograft survival in recipients of two-APOL1-nephropathy-variant kidneys (hazard ratio [HR] 2.71; p = 0.06). For all 675 kidneys transplanted from donors at both centers, APOL1 genotype (HR 2.26; p = 0.001) and African American recipient race/ethnicity (HR 1.60; p = 0.03) were associated with allograft failure. Kidneys from African American deceased donors with two APOL1 nephropathy variants reproducibly associate with higher risk for allograft failure after transplantation. These findings warrant consideration of rapidly genotyping deceased African American kidney donors for APOL1 risk variants at organ recovery and incorporation of results into allocation and informed-consent processes. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Changes in classification of genetic variants in BRCA1 and BRCA2.

Science.gov (United States)

Kast, Karin; Wimberger, Pauline; Arnold, Norbert

2018-02-01

Classification of variants of unknown significance (VUS) in the breast cancer genes BRCA1 and BRCA2 changes with accumulating evidence for clinical relevance. In most cases down-staging towards neutral variants without clinical significance is possible. We searched the database of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC) for changes in classification of genetic variants as an update to our earlier publication on genetic variants in the Centre of Dresden. Changes between 2015 and 2017 were recorded. In the group of variants of unclassified significance (VUS, Class 3, uncertain), only changes of classification towards neutral genetic variants were noted. In BRCA1, 25% of the Class 3 variants (n = 2/8) changed to Class 2 (likely benign) and Class 1 (benign). In BRCA2, in 50% of the Class 3 variants (n = 16/32), a change to Class 2 (n = 10/16) or Class 1 (n = 6/16) was observed. No change in classification was noted in Class 4 (likely pathogenic) and Class 5 (pathogenic) genetic variants in both genes. No up-staging from Class 1, Class 2 or Class 3 to more clinical significance was observed. All variants with a change in classification in our cohort were down-staged towards no clinical significance by a panel of experts of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC). Prevention in families with Class 3 variants should be based on pedigree based risks and should not be guided by the presence of a VUS.

Prevalence of deleterious germline variants in risk genes including BRCA1/2 in consecutive ovarian cancer patients (AGO-TR-1.

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Philipp Harter

Full Text Available Identification of families at risk for ovarian cancer offers the opportunity to consider prophylactic surgery thus reducing ovarian cancer mortality. So far, identification of potentially affected families in Germany was solely performed via family history and numbers of affected family members with breast or ovarian cancer. However, neither the prevalence of deleterious variants in BRCA1/2 in ovarian cancer in Germany nor the reliability of family history as trigger for genetic counselling has ever been evaluated.Prospective counseling and germline testing of consecutive patients with primary diagnosis or with platinum-sensitive relapse of an invasive epithelial ovarian cancer. Testing included 25 candidate and established risk genes. Among these 25 genes, 16 genes (ATM, BRCA1, BRCA2, CDH1, CHEK2, MLH1, MSH2, MSH6, NBN, PMS2, PTEN, PALB2, RAD51C, RAD51D, STK11, TP53 were defined as established cancer risk genes. A positive family history was defined as at least one relative with breast cancer or ovarian cancer or breast cancer in personal history.In total, we analyzed 523 patients: 281 patients with primary diagnosis of ovarian cancer and 242 patients with relapsed disease. Median age at primary diagnosis was 58 years (range 16-93 and 406 patients (77.6% had a high-grade serous ovarian cancer. In total, 27.9% of the patients showed at least one deleterious variant in all 25 investigated genes and 26.4% in the defined 16 risk genes. Deleterious variants were most prevalent in the BRCA1 (15.5%, BRCA2 (5.5%, RAD51C (2.5% and PALB2 (1.1% genes. The prevalence of deleterious variants did not differ significantly between patients at primary diagnosis and relapse. The prevalence of deleterious variants in BRCA1/2 (and in all 16 risk genes in patients <60 years was 30.2% (33.2% versus 10.6% (18.9% in patients ≥60 years. Family history was positive in 43% of all patients. Patients with a positive family history had a prevalence of deleterious variants

Limit on the $B^0_s \\bar{B}^0_s$ meson oscillation frequency from $p\\bar{p}$ collision data at $\\sqrt{s} = 1.8$-TeV

Energy Technology Data Exchange (ETDEWEB)

Niu, Hong-quan [Brandeis Univ., Waltham, MA (United States)

2003-01-01

This thesis presents a limit on the B$0\\atop{s}$$\\bar{B}$$0\\atop{s}$ oscillation frequency from p$\\bar{p}$ collision data at √s = 1.8 TeV at CDF. The data sample used is the inclusive electron and muon trigger data of approximately 90 pb^-1 collected during the 1993-95 run.

G2S: A web-service for annotating genomic variants on 3D protein structures.

Science.gov (United States)

Wang, Juexin; Sheridan, Robert; Sumer, S Onur; Schultz, Nikolaus; Xu, Dong; Gao, Jianjiong

2018-01-27

Accurately mapping and annotating genomic locations on 3D protein structures is a key step in structure-based analysis of genomic variants detected by recent large-scale sequencing efforts. There are several mapping resources currently available, but none of them provides a web API (Application Programming Interface) that support programmatic access. We present G2S, a real-time web API that provides automated mapping of genomic variants on 3D protein structures. G2S can align genomic locations of variants, protein locations, or protein sequences to protein structures and retrieve the mapped residues from structures. G2S API uses REST-inspired design conception and it can be used by various clients such as web browsers, command terminals, programming languages and other bioinformatics tools for bringing 3D structures into genomic variant analysis. The webserver and source codes are freely available at https://g2s.genomenexus.org. g2s@genomenexus.org. Supplementary data are available at Bioinformatics online. © The Author (2018). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Blended learning y la convergencia entre la educación presencial y a distancia

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Lorenzo García Aretio

2018-01-01

Full Text Available La convergencia, la confluencia, entre las metodologías y recursos de los sistemas educativos presenciales y a distancia está siendo hoy una realidad. Una de las variantes de las instituciones duales o mixtas es la de ofrecer un determinado programa, asignatura o curso con una combinación de tiempos cara a cara, en el aula, y otros tiempos de trabajo fuera del recinto académico, con el apoyo de las tecnologías. Se trataría del blended-learning. Aclaremos que estas mezclas y combinaciones de métodos y recursos, ya se venían realizando por parte de las primeras universidades a distancia con el apoyo de las tutorías presenciales, mucho antes de la llegada de las tecnologías digitales. En este trabajo nos inclinamos más que por mezcla o combinación de modalidades educativas, por la integración de medios, recursos, tecnologías, metodologías, actividades, estrategias y técnicas, tanto presenciales como a distancia, para satisfacer cada necesidad concreta de aprendizaje. Como una variante más de esta integración aparece la flipped classroom en la que se contemplan tiempos en el aula y en el hogar poniendo el énfasis en reorganizar el trabajo de los estudiantes en el aula (más interacción y en su hogar (más trabajo autónomo, de forma inversa a como venía siendo habitual, así como el nuevo rol del profesor.

Novel Variants in Individuals with RYR1-Related Congenital Myopathies: Genetic, Laboratory, and Clinical Findings

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Joshua J. Todd

2018-03-01

Full Text Available The ryanodine receptor 1-related congenital myopathies (RYR1-RM comprise a spectrum of slow, rare neuromuscular diseases. Affected individuals present with a mild-to-severe symptomatology ranging from proximal muscle weakness, hypotonia and joint contractures to scoliosis, ophthalmoplegia, and respiratory involvement. Although there is currently no FDA-approved treatment for RYR1-RM, our group recently conducted the first clinical trial in this patient population (NCT02362425. This study aimed to characterize novel RYR1 variants with regard to genetic, laboratory, muscle magnetic resonance imaging (MRI, and clinical findings. Genetic and histopathology reports were obtained from participant’s medical records. Alamut Visual Software was used to determine if participant’s variants had been previously reported and to assess predicted pathogenicity. Physical exams, pulmonary function tests, T1-weighted muscle MRI scans, and blood measures were completed during the abovementioned clinical trial. Six novel variants (two de novo, three dominant, and one recessive were identified in individuals with RYR1-RM. Consistent with established RYR1-RM histopathology, cores were observed in all biopsies, except Case 6 who exhibited fiber-type disproportion. Muscle atrophy and impaired mobility with Trendelenburg gait were the most common clinical symptoms and were identified in all cases. Muscle MRI revealed substantial inter-individual variation in fatty infiltration corroborating the heterogeneity of the disease. Two individuals with dominant RYR1 variants exhibited respiratory insufficiency: a clinical symptom more commonly associated with recessive RYR1-RM cases. This study demonstrates that a genetics-led approach is suitable for the diagnosis of suspected RYR1-RM which can be corroborated through histopathology, muscle MRI and clinical examination.

The Prevalence and Role of Hemoglobin Variants in Biometric Screening of a Multiethnic Population: One Large Health System's Experience.

Science.gov (United States)

Wilburn, Clayton R; Bernard, David W; Zieske, Arthur W; Andrieni, Julia; Miller, Tara; Wang, Ping

2017-06-01

To characterize and quantitate hemoglobin (Hb) variants discovered during biometric hemoglobin A1c (HbA1c) analyses in a large multiethnic population with a focus on the effect of variants on testing method and results. In total, 13,913 individuals had their HbA1c measured via ion-exchange high-performance liquid chromatography. Samples that had a variant Hb detected or HbF fraction more than 25% underwent variant Hb characterization and confirmation by gel electrophoresis. RBC indices were also evaluated for possible concomitant thalassemia. Of the 13,913 individuals evaluated, 524 (3.77%) had an Hb variant. The prevalence of each variant was as follows: HbS trait (n = 396, 2.85%), HbSS disease (n = 4, 0.03%), HbC trait (n = 85, 0.61%), HbCC disease (n = 2, 0.01%), HbSC disease (n = 5, 0.04%), HbE trait (n = 18, 0.13%), HbD or G trait (n = 9, 0.06%), HbS β-thalassemia + disease (n = 1, 0.01%), hereditary persistence of HbF (n = 2, 0.01%), and HbMontgomery trait (n = 1, 0.01%). Concomitant α-thalassemia was detected in 20 (3.82%) of the 524 individuals with an Hb variant. This study represents one of the largest epidemiologic investigations into the prevalence of Hb variants in a North American metropolitan, multiethnic workforce and their dependents and reinforces the importance of method selection in populations with Hb variants. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Gestión y minimización de los impactos socio ambientales generados fuera del derecho de vía en la etapa de construcción de carreteras caso: variante Fusagasugá - Cundinamarca

OpenAIRE

Patiño Silva, Omar Francisco

2011-01-01

La construcción de la Variante de Fusagasugá, en Cundinamarca, que hace parte del proyecto de transporte departamental denominado Doble Calzada Bogotá - Girardot, vía proyectada en una de las zonas de más desarrollo del país, la cual en su diseño atraviesa una parte del territorio del municipio de Fusagasugá con características propias de ruralidad, por fincas dedicadas a la agricultura y que sirven como sitio de descanso y veraneo en época de vacaciones estudiantiles a una parte de la pob...

Alpha S1-casein polymorphisms in camel (Camelus dromedarius) and descriptions of biological active peptides and allergenic epitopes.

Science.gov (United States)

Erhardt, Georg; Shuiep, El Tahir Salih; Lisson, Maria; Weimann, Christina; Wang, Zhaoxin; El Zubeir, Ibtisam El Yas Mohamed; Pauciullo, Alfredo

2016-06-01

Milk samples of 193 camels (Camelus dromedarius) from different regions of Sudan were screened for casein variability by isoelectric focusing. Kappa-casein and beta-casein were monomorphic, whereas three protein patterns named αs1-casein A, C, and D were identified. The major allele A revealed frequencies of 0.79 (Lahaoi), 0.75 (Shanbali), 0.90 (Arabi Khali), and 0.88 (Arabi Gharbawi) in the different ecotypes. CSN1S1*C shows a single G > T nucleotide substitution in the exon 5, leading to a non-synonymous amino acid exchange (p.Glu30 > Asp30) in comparison to CSN1S1*A and D. At cDNA level, no further single nucleotide polymorphisms could be identified in CSN1S1* A, C, and D, whereas the variants CSN1S1*A and CSN1S1*C are characterized by missing of exon 18 compared to the already described CSN1S1*B, as consequence of DNA insertion of 11 bp at intron 17 which alter the pre-mRNA spliceosome machinery. A polymerase chain-restriction fragment length polymorphism method (PCR-RFLP) was established to type for G > T nucleotide substitution at genomic DNA level. The occurrence and differences of IgE-binding epitopes and bioactive peptides between αs1-casein A, C, and D after digestion were analyzed in silico. The amino acid substitutions and deletion affected the arising peptide pattern and thus modifications between IgE-binding epitopes and bioactive peptides of the variants were found. The allergenic potential of these different peptides will be investigated by microarray immunoassay using sera from milk-sensitized individuals, as it was already demonstrated for bovine αs1-casein variants.

Coexistencia de variantes HIV-1 com insercao dipeptidica no gene da transcriptase reversa

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Aline Aki Tanikawa

2013-08-01

Full Text Available O objetivo desta comunicação foi descrever a detecção de coexistência de variantes HIV-1 com inserções de dois aminoácidos entre os códons 69 e 70 da transcriptase reversa. Tais variantes foram isoladas de paciente do sexo masculino, 16 anos de idade, em tratamento no interior do estado de São Paulo. Após confirmação de falha terapêutica, foi realizado teste de resistência a antirretrovirais, a partir do qual foram detectadas duas variantes contendo inserções dos aminoácidos Ser-Gly/Ser-Ala no códon 69 da transcriptase reversa, além da mutação T69S. Tais inserções possuem baixa prevalência, não foram relatadas em caráter de coexistência no Brasil e estão relacionadas com a resistência a múltiplas drogas, tornando o achado relevante do ponto de vista epidemiológico.

Iron overload in HFE C282Y heterozygotes at first genetic testing: a strategy for identifying rare HFE variants.

Science.gov (United States)

Aguilar-Martinez, Patricia; Grandchamp, Bernard; Cunat, Séverine; Cadet, Estelle; Blanc, François; Nourrit, Marlène; Lassoued, Kaiss; Schved, Jean-François; Rochette, Jacques

2011-04-01

Heterozygotes for the p.Cys282Tyr (C282Y) mutation of the HFE gene do not usually express a hemochromatosis phenotype. Apart from the compound heterozygous state for C282Y and the widespread p.His63Asp (H63D) variant allele, other rare HFE mutations can be found in trans on chromosome 6. We performed molecular investigation of the genes implicated in hereditary hemochromatosis in six patients who presented with iron overload but were simple heterozygotes for the HFE C282Y mutation at first genetic testing. Functional impairment of new variants was deduced from computational methods including molecular modeling studies. We identified four rare HFE mutant alleles, three of which have not been previously described. One mutation is a 13-nucleotide deletion in exon 6 (c.1022_1034del13, p.His341_Ala345 > LeufsX119), which is predicted to lead to an elongated and unstable protein. The second one is a substitution of the last nucleotide of exon 2 (c.340G > A, p.Glu114Lys) which modifies the relative solvent accessibility in a loop interface. The third mutation, p.Arg67Cys, also lies in exon 2 and introduces a destabilization of the secondary structure within a loop of the α1 domain. We also found the previously reported c.548T > C (p.Leu183Pro) missense mutation in exon 3. No other known iron genes were mutated. We present an algorithm at the clinical and genetic levels for identifying patients deserving further investigation. Conclusions Our results suggest that additional mutations in HFE may have a clinical impact in C282Y carriers. In conjunction with results from previously described cases we conclude that an elevated transferrin saturation level and elevated hepatic iron index should indicate the utility of searching for further HFE mutations in C282Y heterozygotes prior to other iron gene studies.

Biochemical characterization of the GM2 gangliosidosis B1 variant

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Tutor J.C.

2004-01-01

Full Text Available The deficiency of the A isoenzyme of ß-hexosaminidase (Hex produced by different mutations of the gene that codes for the alpha subunit (Tay-Sachs disease has two variants with enzymological differences: the B variant consists of the absence of Hex A isoenzyme and the B1 variant produces an inactive Hex A isoenzyme for the hydrolysis of the GM2 ganglioside and synthetic substrates with negative charge. In contrast to the early childhood form of the B variant, the B1 variant appears at a later clinical stage (3 to 7 years of age with neurodegenerative symptoms leading to the death of the patient in the second decade of life. The most frequent mutation responsible for the GM2 gangliosidosis B1 variant is R178H, which has a widespread geographic and ethnic distribution. The highest incidence has been described in Portugal, which has been suggested as the point of origin of this mutation. Biochemical characterization of this lysosomal disease is carried out using negatively charged synthetic alpha subunit-specific sulfated substrates, since Hex A isoenzyme heat-inactivation assays are not applicable. However, the determination of the apparent activation energy of Hex using the neutral substrate 3,3'-dichlorophenolsulfonphthaleinyl N-acetyl-ß-D-glucosaminide, may offer a valid alternative. The presence of an alpha subunit in the alphaß heterodimer Hex A means that its activation energy (41.8 kJ/mol is significantly lower than that of the ßß homodimer Hex B (75.1 kJ/mol; however, as mutation inactivates the alpha subunit, the Hex A of the B1 variant presents an activation energy that is similar to that of the Hex B isoenzyme.

Pathogenesis comparison between the United States porcine epidemic diarrhoea virus prototype and S-INDEL-variant strains in conventional neonatal piglets.

Science.gov (United States)

Chen, Qi; Gauger, Phillip C; Stafne, Molly R; Thomas, Joseph T; Madson, Darin M; Huang, Haiyan; Zheng, Ying; Li, Ganwu; Zhang, Jianqiang

2016-05-01

At least two genetically different porcine epidemic diarrhoea virus (PEDV) strains have been identified in the USA: US PEDV prototype and S-INDEL-variant strains. The objective of this study was to compare the pathogenicity differences of the US PEDV prototype and S-INDEL-variant strains in conventional neonatal piglets under experimental infections. Fifty PEDV-negative 5-day-old pigs were divided into five groups of ten pigs each and were inoculated orogastrically with three US PEDV prototype isolates (IN19338/2013, NC35140/2013 and NC49469/2013), an S-INDEL-variant isolate (IL20697/2014), and virus-negative culture medium, respectively, with virus titres of 104 TCID50 ml- 1, 10 ml per pig. All three PEDV prototype isolates tested in this study, regardless of their phylogenetic clades, had similar pathogenicity and caused severe enteric disease in 5-day-old pigs as evidenced by clinical signs, faecal virus shedding, and gross and histopathological lesions. Compared with pigs inoculated with the three US PEDV prototype isolates, pigs inoculated with the S-INDEL-variant isolate had significantly diminished clinical signs, virus shedding in faeces, gross lesions in small intestines, caeca and colons, histopathological lesions in small intestines, and immunohistochemistry staining in ileum. However, the US PEDV prototype and the S-INDEL-variant strains induced similar viraemia levels in inoculated pigs. Whole genome sequences of the PEDV prototype and S-INDEL-variant strains were determined, but the molecular basis of virulence differences between these PEDV strains remains to be elucidated using a reverse genetics approach.

Genetic variants modify the effect of age on APOE methylation in the Genetics of Lipid Lowering Drugs and Diet Network study

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Although apolipoprotein E (APOE) variants are associated with age related diseases, the underlying mechanism is unknown and DNA methylation may be a potential one. With methylation data, measured by the Infinium Human Methylation 450 array, from 993 participants (age ranging from 18 to 87 y) in the ...

Pedidos y saludos en español peruano y en sueco

OpenAIRE

Pettersson, Camilla

2012-01-01

El objetivo de este estudio es mostrar diferencias y similitudes en la comunicación en los actos de habla de pedir y de saludar en el español de la variante peruana y en el sueco, y además acercarnos a eventuales problemas que puedan surgir en el encuentro entre estas dos culturas. Muchos autores han realizado estudios sobre actos de habla en relación con la cortesía, pero ninguno se ha centrado en estos dos actos de habla específicos entre las culturas peruana y sueca, es por ello interesant...

Risk and protective genetic variants in suicidal behaviour: association with SLC1A2, SLC1A3, 5-HTR1B &NTRK2 polymorphisms.

LENUS (Irish Health Repository)

Murphy, Therese M

2012-02-01

BACKGROUND: Suicidal behaviour is known to aggregate in families. Patients with psychiatric disorders are at higher risk for suicide attempts (SA), however protective and risk genetic variants for suicide appear to be independent of underlying psychiatric disorders. Here we investigate genetic variants in genes important for neurobiological pathways linked to suicidal behaviour and\\/or associated endophenotypes, for association with SA among patients with co-existing psychiatric illness. Selected gene-gene and gene-environment interactions were also tested. METHODS: DNA was obtained from bloods of 159 patients (76 suicide attempters and 83 non-attempters), who were profiled for DSM-IV Axis I psychiatric diagnosis. Twenty-eight single nucleotide polymorphisms (SNPs) from 18 candidate genes (COMT, 5-HT2A, 5-HT1A, 5-HTR1B, TPH1, MAO-A, TPH2, DBH, CNR1, BDNF, ABCG1, GABRA5, GABRG2, GABRB2, SLC1A2, SLC1A3, NTRK2, CRHR1) were genotyped. Genotyping was performed by KBioscience. Tests of association between genetic variants and SA were conducted using Chi squared and Armitage Trend tests. Binary logistical regression analyses were performed to evaluate the contribution of individual genetic variants to the prediction of SA, and to examine SNPs for potential gene-gene and gene-environment interactions. RESULTS: Our analysis identified 4 SNPs (rs4755404, rs2269272, rs6296 and rs1659400), which showed evidence of association with SA compared to a non-attempter control group. We provide evidence of a 3-locus gene-gene interaction, and a putative gene-environment interaction, whereby genetic variation at the NTRK2 locus may moderate the risk associated with history of childhood abuse. CONCLUSION: Preliminary findings suggest that allelic variability in SLC1A2\\/3, 5-HTR1B and NTRK2 may be relevant to the underlying diathesis for suicidal acts.

Functional genetic variants in the vesicular monoamine transporter 1 (VMAT1) modulate emotion processing

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Lohoff, Falk W.; Hodge, Rachel; Narasimhan, Sneha; Nall, Aleksandra; Ferraro, Thomas N.; Mickey, Brian J.; Heitzeg, Mary M.; Langenecker, Scott A.; Zubieta, Jon-Kar; Bogdan, Ryan; Nikolova, Yuliya S.; Drabant, Emily; Hariri, Ahmad R.; Bevilacqua, Laura; Goldman, David; Doyle, Glenn A.

2012-01-01

SUMMARY Emotional behavior is in part heritable and often disrupted in psychopathology. Identification of specific genetic variants that drive this heritability may provide important new insight into molecular and neurobiological mechanisms involved in emotionality. Our results demonstrate that the presynaptic vesicular monoamine transporter 1 (VMAT1) Thr136Ile (rs1390938) polymorphism is functional in vitro, with the Ile allele leading to increased monoamine transport into presynaptic vesicles. Moreover, we show that the Thr136Ile variant predicts differential responses in emotional brain circuits consistent with its effects in vitro. Lastly, deep sequencing of bipolar disorder (BPD) patients and controls identified several rare novel VMAT1 variants. The variant Phe84Ser was only present in individuals with BPD and leads to marked increase monoamine transport in vitro. Taken together, our data show that VMAT1 polymorphisms influence monoamine signaling, the functional response of emotional brain circuits, and risk for psychopathology. PMID:23337945

Rare variants in RTEL1 are associated with familial interstitial pneumonia.

Science.gov (United States)

Cogan, Joy D; Kropski, Jonathan A; Zhao, Min; Mitchell, Daphne B; Rives, Lynette; Markin, Cheryl; Garnett, Errine T; Montgomery, Keri H; Mason, Wendi R; McKean, David F; Powers, Julia; Murphy, Elissa; Olson, Lana M; Choi, Leena; Cheng, Dong-Sheng; Blue, Elizabeth Marchani; Young, Lisa R; Lancaster, Lisa H; Steele, Mark P; Brown, Kevin K; Schwarz, Marvin I; Fingerlin, Tasha E; Schwartz, David A; Lawson, William E; Loyd, James E; Zhao, Zhongming; Phillips, John A; Blackwell, Timothy S

2015-03-15

Up to 20% of cases of idiopathic interstitial pneumonia cluster in families, comprising the syndrome of familial interstitial pneumonia (FIP); however, the genetic basis of FIP remains uncertain in most families. To determine if new disease-causing rare genetic variants could be identified using whole-exome sequencing of affected members from FIP families, providing additional insights into disease pathogenesis. Affected subjects from 25 kindreds were selected from an ongoing FIP registry for whole-exome sequencing from genomic DNA. Candidate rare variants were confirmed by Sanger sequencing, and cosegregation analysis was performed in families, followed by additional sequencing of affected individuals from another 163 kindreds. We identified a potentially damaging rare variant in the gene encoding for regulator of telomere elongation helicase 1 (RTEL1) that segregated with disease and was associated with very short telomeres in peripheral blood mononuclear cells in 1 of 25 families in our original whole-exome sequencing cohort. Evaluation of affected individuals in 163 additional kindreds revealed another eight families (4.7%) with heterozygous rare variants in RTEL1 that segregated with clinical FIP. Probands and unaffected carriers of these rare variants had short telomeres (RTEL1 function. Rare loss-of-function variants in RTEL1 represent a newly defined genetic predisposition for FIP, supporting the importance of telomere-related pathways in pulmonary fibrosis.

Vitaminas y minerales contra el estrés

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Jose Antonio Espinosa Hernández

2001-04-01

Full Text Available Se define el estrés como tal, así como los tipos de tratamientos para este. Se expresan las relaciones entre las multivitaminas y minerales y el estr��s y se dan criterios sobre su uso. Se concluye que los principales medicamentos antiestrés encontrados contienen las vitaminas E, B1, B2, B3, B5, B6, B12,C, ácido fólico y minerales cinc y hierro; entre los principales fabricantes se encuentran: Lederle, Rugby, Ayerst, Scherin, Vicks Health Care, Goldline, Squibbs, Miles Inc. y Natural Life.The stress as such, as well as the types of treatment are defined. The relations between the multivitamins and minerals and the stress are described and criteria about their use are given. It is concluded that the main antistress drugs found contain vitamins E, B1, B2, B3, B5, B6, B12, C, folic acid and the minerals zinc and iron. Lederle, Rugny, Ayerst, Scherin, Vicks Health Care, Goldline, Squibbs, Miles Inc. and Natural Life are among the main manufacturers.

Dupuytren’s and Ledderhose Diseases in a Family with LMNA-Related Cardiomyopathy and a Novel Variant in the ASTE1 Gene

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Michael V. Zaragoza

2017-11-01

Full Text Available Dupuytren’s disease (palmar fibromatosis involves nodules in fascia of the hand that leads to flexion contractures. Ledderhose disease (plantar fibromatosis is similar with nodules of the foot. While clinical aspects are well-described, genetic mechanisms are unknown. We report a family with cardiac disease due to a heterozygous LMNA mutation (c.736C>T, p.Gln246Stop with palmar/plantar fibromatosis and investigate the hypothesis that a second rare DNA variant increases the risk for fibrotic disease in LMNA mutation carriers. The proband and six family members were evaluated for the cardiac and hand/feet phenotypes and tested for the LMNA mutation. Fibroblast RNA studies revealed monoallelic expression of the normal LMNA allele and reduced lamin A/C mRNAs consistent with LMNA haploinsufficiency. A novel, heterozygous missense variant (c.230T>C, p.Val77Ala in the Asteroid Homolog 1 (ASTE1 gene was identified as a potential risk factor in fibrotic disease using exome sequencing and family studies of five family members: four LMNA mutation carriers with fibromatosis and one individual without the LMNA mutation and no fibromatosis. With a possible role in epidermal growth factor receptor signaling, ASTE1 may contribute to the increased risk for palmar/plantar fibromatosis in patients with Lamin A/C haploinsufficiency.

Genetic linkage analysis of type 1 diabetes mellitus to markers on chromosomes 2 and 11 in families from Antioquia, Colombia Análisis de ligamiento genético de la diabetes mellitus tipo 1, a marcadores de los cromosomas 2 y 11 en familias antioqueñas

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Gabriel Bedoya Berrío

2004-02-01

la etiología de DM1 han demostrado que ambos subtipos tienen un fuerte componente genético, pero el patrón de herencia es complejo, ya que su patogénesis puede ser el resultado de la interacción de variantes en múltiples genes con factores medioambientales. Los estudios genéticos sobre DM1 han permitido identificar loci de suceptibilidad que se denominan IDDM, así para DM1A se encontró el primer locus (IDDM1 en la región HLA-DR/DQ, situada en 6p21, que modula el efecto de otros genes implicados en la enfermedad, el segundo (IDDM2 se localiza en 11p15 donde se encuentra el gen de la Insulina. Es decir, DM1 presenta gran heterogeneidad genética, de tal manera, que se han identificado más de 18 loci implicados en susceptibilidad a ella, entre ellos 3 en el cromosoma 2 (IDDM 7,12 y 13 y uno en el cromosoma 14 (IDDM11, este último asociado a DM1B. El objetivo de este estudio consistió en la búsqueda de loci en los cromosomas 2 y 11 involucrados en la susceptibilidad a DM, en 3 familias antioqueñas, para lo cual se realizó análisis de ligamiento paramétrico a 23 marcadores microsatélites en el cromosoma 2 y a 18 en el cromosoma 11. A las familias, codificadas como DM1(11afectados, familia 1 (2 afectados y familia10 (3 afectados, se les realizó simulación para determinar el poder para hacer análisis de ligamiento y los resultados mostraron que presentaban suficiente poder para realizarlo, puesto que en DM1 la razón de disparidad máxima (Lod score o Z máximo fue de 3.57, sin recombinación (?=0, el cual es superior a 3, el valor aceptado para determinar ligamiento, y al tomar las tres familias en conjunto se obtuvo un Z máximo de 5.76. Con el análisis de ligamiento para el cromosoma 11, se halló que solo en la familia 10 se presentaba un valor positivo de Z; 1.18 al marcador D11S925 con ?=0, muy superior al de la simulación de esta familia (0.75, con respecto al cromosoma 2, se obtuvieron valores de Z positivos al marcador D2S319 en DM1 y

Diversity and impact of rare variants in genes encoding the platelet G protein-coupled receptors.

Science.gov (United States)

Jones, Matthew L; Norman, Jane E; Morgan, Neil V; Mundell, Stuart J; Lordkipanidzé, Marie; Lowe, Gillian C; Daly, Martina E; Simpson, Michael A; Drake, Sian; Watson, Steve P; Mumford, Andrew D

2015-04-01

Platelet responses to activating agonists are influenced by common population variants within or near G protein-coupled receptor (GPCR) genes that affect receptor activity. However, the impact of rare GPCR gene variants is unknown. We describe the rare single nucleotide variants (SNVs) in the coding and splice regions of 18 GPCR genes in 7,595 exomes from the 1,000-genomes and Exome Sequencing Project databases and in 31 cases with inherited platelet function disorders (IPFDs). In the population databases, the GPCR gene target regions contained 740 SNVs (318 synonymous, 410 missense, 7 stop gain and 6 splice region) of which 70 % had global minor allele frequency (MAF) < 0.05 %. Functional annotation using six computational algorithms, experimental evidence and structural data identified 156/740 (21 %) SNVs as potentially damaging to GPCR function, most commonly in regions encoding the transmembrane and C-terminal intracellular receptor domains. In 31 index cases with IPFDs (Gi-pathway defect n=15; secretion defect n=11; thromboxane pathway defect n=3 and complex defect n=2) there were 256 SNVs in the target regions of 15 stimulatory platelet GPCRs (34 unique; 12 with MAF< 1 % and 22 with MAF≥ 1 %). These included rare variants predicting R122H, P258T and V207A substitutions in the P2Y12 receptor that were annotated as potentially damaging, but only partially explained the platelet function defects in each case. Our data highlight that potentially damaging variants in platelet GPCR genes have low individual frequencies, but are collectively abundant in the population. Potentially damaging variants are also present in pedigrees with IPFDs and may contribute to complex laboratory phenotypes.

Respuesta al estrés, Temperamento y Crianza en niños colombianos de 1 año

OpenAIRE

Marta Martínez, Colombia; María Cristina García, Colombia; Daniel Camilo Aguirre-Acevedo, Colombia

2015-01-01

(analítico):Este estudio busco explorar las relaciones entre el temperamento de una muestra de niños de 1 año (264), las expectativas y prácticas de crianza de sus padres y el cortisol en saliva como respuesta al estrés en una submuestra de la anterior (59). La respuesta al estrés se encontró asociada con la variable prácticas disciplinarias (R=0,31) y se correlaciono negativamente con las variables extroversión (R=-0,35) y regulación (-0,21). No se encontró correlación entre las variables de...

Genome-wide scan of healthy human connectome discovers SPON1 gene variant influencing dementia severity

Science.gov (United States)

Jahanshad, Neda; Rajagopalan, Priya; Hua, Xue; Hibar, Derrek P.; Nir, Talia M.; Toga, Arthur W.; Jack, Clifford R.; Saykin, Andrew J.; Green, Robert C.; Weiner, Michael W.; Medland, Sarah E.; Montgomery, Grant W.; Hansell, Narelle K.; McMahon, Katie L.; de Zubicaray, Greig I.; Martin, Nicholas G.; Wright, Margaret J.; Thompson, Paul M.; Weiner, Michael; Aisen, Paul; Weiner, Michael; Aisen, Paul; Petersen, Ronald; Jack, Clifford R.; Jagust, William; Trojanowski, John Q.; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Saykin, Andrew J.; Morris, John; Liu, Enchi; Green, Robert C.; Montine, Tom; Petersen, Ronald; Aisen, Paul; Gamst, Anthony; Thomas, Ronald G.; Donohue, Michael; Walter, Sarah; Gessert, Devon; Sather, Tamie; Beckett, Laurel; Harvey, Danielle; Gamst, Anthony; Donohue, Michael; Kornak, John; Jack, Clifford R.; Dale, Anders; Bernstein, Matthew; Felmlee, Joel; Fox, Nick; Thompson, Paul; Schuff, Norbert; Alexander, Gene; DeCarli, Charles; Jagust, William; Bandy, Dan; Koeppe, Robert A.; Foster, Norm; Reiman, Eric M.; Chen, Kewei; Mathis, Chet; Morris, John; Cairns, Nigel J.; Taylor-Reinwald, Lisa; Trojanowki, J.Q.; Shaw, Les; Lee, Virginia M.Y.; Korecka, Magdalena; Toga, Arthur W.; Crawford, Karen; Neu, Scott; Saykin, Andrew J.; Foroud, Tatiana M.; Potkin, Steven; Shen, Li; Khachaturian, Zaven; Frank, Richard; Snyder, Peter J.; Molchan, Susan; Kaye, Jeffrey; Quinn, Joseph; Lind, Betty; Dolen, Sara; Schneider, Lon S.; Pawluczyk, Sonia; Spann, Bryan M.; Brewer, James; Vanderswag, Helen; Heidebrink, Judith L.; Lord, Joanne L.; Petersen, Ronald; Johnson, Kris; Doody, Rachelle S.; Villanueva-Meyer, Javier; Chowdhury, Munir; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Morris, John C.; Ances, Beau; Carroll, Maria; Leon, Sue; Mintun, Mark A.; Schneider, Stacy; Marson, Daniel; Griffith, Randall; Clark, David; Grossman, Hillel; Mitsis, Effie; Romirowsky, Aliza; deToledo-Morrell, Leyla; Shah, Raj C.; Duara, Ranjan; Varon, Daniel; Roberts, Peggy; Albert, Marilyn; Onyike, Chiadi; Kielb, Stephanie; Rusinek, Henry; de Leon, Mony J.; Glodzik, Lidia; De Santi, Susan; Doraiswamy, P. Murali; Petrella, Jeffrey R.; Coleman, R. Edward; Arnold, Steven E.; Karlawish, Jason H.; Wolk, David; Smith, Charles D.; Jicha, Greg; Hardy, Peter; Lopez, Oscar L.; Oakley, MaryAnn; Simpson, Donna M.; Porsteinsson, Anton P.; Goldstein, Bonnie S.; Martin, Kim; Makino, Kelly M.; Ismail, M. Saleem; Brand, Connie; Mulnard, Ruth A.; Thai, Gaby; Mc-Adams-Ortiz, Catherine; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Diaz-Arrastia, Ramon; King, Richard; Weiner, Myron; Martin-Cook, Kristen; DeVous, Michael; Levey, Allan I.; Lah, James J.; Cellar, Janet S.; Burns, Jeffrey M.; Anderson, Heather S.; Swerdlow, Russell H.; Apostolova, Liana; Lu, Po H.; Bartzokis, George; Silverman, Daniel H.S.; Graff-Radford, Neill R.; Parfitt, Francine; Johnson, Heather; Farlow, Martin R.; Hake, Ann Marie; Matthews, Brandy R.; Herring, Scott; van Dyck, Christopher H.; Carson, Richard E.; MacAvoy, Martha G.; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Stefanovic, Bojana; Caldwell, Curtis; Hsiung, Ging-Yuek Robin; Feldman, Howard; Mudge, Benita; Assaly, Michele; Kertesz, Andrew; Rogers, John; Trost, Dick; Bernick, Charles; Munic, Donna; Kerwin, Diana; Mesulam, Marek-Marsel; Lipowski, Kristina; Wu, Chuang-Kuo; Johnson, Nancy; Sadowsky, Carl; Martinez, Walter; Villena, Teresa; Turner, Raymond Scott; Johnson, Kathleen; Reynolds, Brigid; Sperling, Reisa A.; Johnson, Keith A.; Marshall, Gad; Frey, Meghan; Yesavage, Jerome; Taylor, Joy L.; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Sabbagh, Marwan; Belden, Christine; Jacobson, Sandra; Kowall, Neil; Killiany, Ronald; Budson, Andrew E.; Norbash, Alexander; Johnson, Patricia Lynn; Obisesan, Thomas O.; Wolday, Saba; Bwayo, Salome K.; Lerner, Alan; Hudson, Leon; Ogrocki, Paula; Fletcher, Evan; Carmichael, Owen; Olichney, John; DeCarli, Charles; Kittur, Smita; Borrie, Michael; Lee, T.-Y.; Bartha, Rob; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M.; Potkin, Steven G.; Preda, Adrian; Nguyen, Dana; Tariot, Pierre; Fleisher, Adam; Reeder, Stephanie; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Scharre, Douglas W.; Kataki, Maria; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Pearlson, Godfrey D.; Blank, Karen; Anderson, Karen; Saykin, Andrew J.; Santulli, Robert B.; Schwartz, Eben S.; Sink, Kaycee M.; Williamson, Jeff D.; Garg, Pradeep; Watkins, Franklin; Ott, Brian R.; Querfurth, Henry; Tremont, Geoffrey; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Rosen, Howard J.; Miller, Bruce L.; Mintzer, Jacobo; Longmire, Crystal Flynn; Spicer, Kenneth; Finger, Elizabeth; Rachinsky, Irina; Rogers, John; Kertesz, Andrew; Drost, Dick

2013-01-01

Aberrant connectivity is implicated in many neurological and psychiatric disorders, including Alzheimer’s disease and schizophrenia. However, other than a few disease-associated candidate genes, we know little about the degree to which genetics play a role in the brain networks; we know even less about specific genes that influence brain connections. Twin and family-based studies can generate estimates of overall genetic influences on a trait, but genome-wide association scans (GWASs) can screen the genome for specific variants influencing the brain or risk for disease. To identify the heritability of various brain connections, we scanned healthy young adult twins with high-field, high-angular resolution diffusion MRI. We adapted GWASs to screen the brain’s connectivity pattern, allowing us to discover genetic variants that affect the human brain’s wiring. The association of connectivity with the SPON1 variant at rs2618516 on chromosome 11 (11p15.2) reached connectome-wide, genome-wide significance after stringent statistical corrections were enforced, and it was replicated in an independent subsample. rs2618516 was shown to affect brain structure in an elderly population with varying degrees of dementia. Older people who carried the connectivity variant had significantly milder clinical dementia scores and lower risk of Alzheimer’s disease. As a posthoc analysis, we conducted GWASs on several organizational and topological network measures derived from the matrices to discover variants in and around genes associated with autism (MACROD2), development (NEDD4), and mental retardation (UBE2A) significantly associated with connectivity. Connectome-wide, genome-wide screening offers substantial promise to discover genes affecting brain connectivity and risk for brain diseases. PMID:23471985

Transmission of single and multiple viral variants in primary HIV-1 subtype C infection.

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Vladimir Novitsky

2011-02-01

Full Text Available To address whether sequences of viral gag and env quasispecies collected during the early post-acute period can be utilized to determine multiplicity of transmitted HIV's, recently developed approaches for analysis of viral evolution in acute HIV-1 infection [1,2] were applied. Specifically, phylogenetic reconstruction, inter- and intra-patient distribution of maximum and mean genetic distances, analysis of Poisson fitness, shape of highlighter plots, recombination analysis, and estimation of time to the most recent common ancestor (tMRCA were utilized for resolving multiplicity of HIV-1 transmission in a set of viral quasispecies collected within 50 days post-seroconversion (p/s in 25 HIV-infected individuals with estimated time of seroconversion. The decision on multiplicity of HIV infection was made based on the model's fit with, or failure to explain, the observed extent of viral sequence heterogeneity. The initial analysis was based on phylogeny, inter-patient distribution of maximum and mean distances, and Poisson fitness, and was able to resolve multiplicity of HIV transmission in 20 of 25 (80% cases. Additional analysis involved distribution of individual viral distances, highlighter plots, recombination analysis, and estimation of tMRCA, and resolved 4 of the 5 remaining cases. Overall, transmission of a single viral variant was identified in 16 of 25 (64% cases, and transmission of multiple variants was evident in 8 of 25 (32% cases. In one case multiplicity of HIV-1 transmission could not be determined. In primary HIV-1 subtype C infection, samples collected within 50 days p/s and analyzed by a single-genome amplification/sequencing technique can provide reliable identification of transmission multiplicity in 24 of 25 (96% cases. Observed transmission frequency of a single viral variant and multiple viral variants were within the ranges of 64% to 68%, and 32% to 36%, respectively.

Whole-Exome Sequencing in Searching for New Variants Associated With the Development of Parkinson’s Disease

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Marina V. Shulskaya

2018-05-01

Full Text Available Background: Parkinson’s disease (PD is a complex disease with its monogenic forms accounting for less than 10% of all cases. Whole-exome sequencing (WES technology has been used successfully to find mutations in large families. However, because of the late onset of the disease, only small families and unrelated patients are usually available. WES conducted in such cases yields in a large number of candidate variants. There are currently a number of imperfect software tools that allow the pathogenicity of variants to be evaluated.Objectives: We analyzed 48 unrelated patients with an alleged autosomal dominant familial form of PD using WES and developed a strategy for selecting potential pathogenetically significant variants using almost all available bioinformatics resources for the analysis of exonic areas.Methods: DNA sequencing of 48 patients with excluded frequent mutations was performed using an Illumina HiSeq 2500 platform. The possible pathogenetic significance of identified variants and their involvement in the pathogenesis of PD was assessed using SNP and Variation Suite (SVS, Combined Annotation Dependent Depletion (CADD and Rare Exome Variant Ensemble Learner (REVEL software. Functional evaluation was performed using the Pathway Studio database.Results: A significant reduction in the search range from 7082 to 25 variants in 23 genes associated with PD or neuronal function was achieved. Eight (FXN, MFN2, MYOC, NPC1, PSEN1, RET, SCN3A and SPG7 were the most significant.Conclusions: The multistep approach developed made it possible to conduct an effective search for potential pathogenetically significant variants, presumably involved in the pathogenesis of PD. The data obtained need to be further verified experimentally.

Descripción de un caso de síndrome del comosoma 18q-

OpenAIRE

Bajo González, Tamara

2010-01-01

Se presenta el estudio de un caso clínico de la deleción terminal del brazo largo del cromosoma 18, también llamado Síndrome de Grouchy, en una niña de siete años de edad. Está clasificada como una enfermedad rara por tener una tasa de incidencia menor o igual a 1 de cada 2000 habitantes de la población. Se analizan los principales problemas que refieren las familias con algún miembro con una enfermedad rara, siendo el más relevante la falta de información y de medios por pa...

Lynch syndrome associated with two MLH1 promoter variants and allelic imbalance of MLH1 expression.

Science.gov (United States)

Hesson, Luke B; Packham, Deborah; Kwok, Chau-To; Nunez, Andrea C; Ng, Benedict; Schmidt, Christa; Fields, Michael; Wong, Jason W H; Sloane, Mathew A; Ward, Robyn L

2015-06-01

Lynch syndrome is a hereditary cancer syndrome caused by a constitutional mutation in one of the mismatch repair genes. The implementation of predictive testing and targeted preventative surveillance is hindered by the frequent finding of sequence variants of uncertain significance in these genes. We aimed to determine the pathogenicity of previously reported variants (c.-28A>G and c.-7C>T) within the MLH1 5'untranslated region (UTR) in two individuals from unrelated suspected Lynch syndrome families. We investigated whether these variants were associated with other pathogenic alterations using targeted high-throughput sequencing of the MLH1 locus. We also determined their relationship to gene expression and epigenetic alterations at the promoter. Sequencing revealed that the c.-28A>G and c.-7C>T variants were the only potentially pathogenic alterations within the MLH1 gene. In both individuals, the levels of transcription from the variant allele were reduced to 50% compared with the wild-type allele. Partial loss of expression occurred in the absence of constitutional epigenetic alterations within the MLH1 promoter. We propose that these variants may be pathogenic due to constitutional partial loss of MLH1 expression, and that this may be associated with intermediate penetrance of a Lynch syndrome phenotype. Our findings provide further evidence of the potential importance of noncoding variants in the MLH1 5'UTR in the pathogenesis of Lynch syndrome. © 2015 The Authors. **Human Mutation published by Wiley Periodicals, Inc.

Functional significance of rare neuroligin 1 variants found in autism.

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Moe Nakanishi

2017-08-01

Full Text Available Genetic mutations contribute to the etiology of autism spectrum disorder (ASD, a common, heterogeneous neurodevelopmental disorder characterized by impairments in social interaction, communication, and repetitive and restricted patterns of behavior. Since neuroligin3 (NLGN3, a cell adhesion molecule at the neuronal synapse, was first identified as a risk gene for ASD, several additional variants in NLGN3 and NLGN4 were found in ASD patients. Moreover, synaptopathies are now known to cause several neuropsychiatric disorders including ASD. In humans, NLGNs consist of five family members, and neuroligin1 (NLGN1 is a major component forming a complex on excitatory glutamatergic synapses. However, the significance of NLGN1 in neuropsychiatric disorders remains unknown. Here, we systematically examine five missense variants of NLGN1 that were detected in ASD patients, and show molecular and cellular alterations caused by these variants. We show that a novel NLGN1 Pro89Leu (P89L missense variant found in two ASD siblings leads to changes in cellular localization, protein degradation, and to the impairment of spine formation. Furthermore, we generated the knock-in P89L mice, and we show that the P89L heterozygote mice display abnormal social behavior, a core feature of ASD. These results, for the first time, implicate rare variants in NLGN1 as functionally significant and support that the NLGN synaptic pathway is of importance in the etiology of neuropsychiatric disorders.

Two new splice variants in porcine PPARGC1A

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Peelman Luc J

2008-12-01

Full Text Available Abstract Background Peroxisome proliferator-activated receptor γ coactivator 1α (PPARGC1A is a coactivator with a vital and central role in fat and energy metabolism. It is considered to be a candidate gene for meat quality in pigs and is involved in the development of obesity and diabetes in humans. How its many functions are regulated, is however still largely unclear. Therefore a transcription profile of PPARGC1A in 32 tissues and 4 embryonic developmental stages in the pig was constructed by screening its cDNA for possible splice variants with exon-spanning primers. Findings This led to the discovery of 2 new splice variants in the pig, which were subsequently also detected in human tissues. In these variants, exon 8 was either completely or partly (the last 66 bp were conserved spliced out, potentially coding for a much shorter protein of respectively 337 and 359 amino acids (aa, of which the first 291 aa would be the same compared to the complete protein (796 aa. Conclusion Considering the functional domains of the PPARGC1A protein, it is very likely these splice variants considerably affect the function of the protein and alternative splicing could be one of the mechanisms by which the diverse functions of PPARGC1A are regulated.

Morbilidad y mortalidad de los pacientes con síndrome de distress respiratorio agudo/injuria pulmonar aguda por Influenza A H1N1 que requirieron soporte cardiopulmonar en un hospital general

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Jaime Zegarra

2012-03-01

Full Text Available Objetivo: Determinar la morbilidad y mortalidad de los pacientes con síndrome de distress respiratorio agudo (SDRA/injuria pulmonar aguda (IPA por Influenza A H1N1 que requirieron soporte cardiopulmonar en un hospital general. Material y métodos: Estudio retrospectivo, descriptivo, tipo serie de casos. Se revisaron las historias clínicas, las hojas de monitoreo ventilatorio y hemodinámico de los pacientes con SDRA/IPA secundario a Influenza A H1N1 atendidos en el Servicio de Cuidados Intensivos Generales (SCIG del Hospital Nacional Cayetano Heredia entre mayo y setiembre de 2009. El diagnóstico de Influenza A H1N1 se realizó por PCR-RT. Resultados: Se atendieron 99 pacientes con Influenza A H1N1, 9 ingresaron al SCIG por SDRA/IPA; cinco requirieron ventilación mecánica invasiva (VMI, tres ventilación mecánica no invasiva y uno no requirió soporte ventilatorio. La edad promedio fue 43,3 ± 18,3 años; el tiempo de enfermedad 8 ± 3 días. Al ingreso, el 100% tuvo fiebre y disnea, el score APACHE II fue 10,5 ± 4,1 y el SOFA 5,6 ± 3,2; el Pa02/Fi02 96,74 ± 28,6. En 4/5 pacientes en VMI el Pa02/Fi02 a las 12 h y al final de la ventilación mecánica fue < 200. La presión en cuña estimada fue 15,69 ± 3,6 y el índice cardiaco por doppler esofágico 2,4 ± 0,34. La TGO fue 160 ± 152,15, DHL 2366,33 ± 1862,13 y CPK 216 ± 298,25. Todos los pacientes recibieron Oseltamivir 150 mg cada 12 h por 10 días. Cuatro pacientes fallecieron. Conclusiones: Los pacientes con SDRA/IPA por Influenza A H1 N1, fueron adultos jóvenes, con tiempo de enfermedad prolongado; con fiebre, disnea y linfopenia; sin compromiso cardiovascular y con hipoxemia refractaria como causa de muerte.

Segregation of virulent influenza A(H1N1 variants in the lower respiratory tract of critically ill patients during the 2010-2011 seasonal epidemic.

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Antonio Piralla

Full Text Available BACKGROUND: Since its appearance in 2009, the pandemic influenza A(H1N1 virus circulated worldwide causing several severe infections. METHODS: Respiratory samples from patients with 2009 influenza A(H1N1 and acute respiratory distress attending 24 intensive care units (ICUs as well as from patients with lower respiratory tract infections not requiring ICU admission and community upper respiratory tract infections in the Lombardy region (10 million inhabitants of Italy during the 2010-2011 winter-spring season, were analyzed. RESULTS: In patients with severe ILI, the viral load was higher in bronchoalveolar lavage (BAL with respect to nasal swab (NS, (p<0.001 suggesting a higher virus replication in the lower respiratory tract. Four distinct virus clusters (referred to as cluster A to D circulated simultaneously. Most (72.7%, n = 48 of the 66 patients infected with viruses belonging to cluster A had a severe (n = 26 or moderate ILI (n = 22. Amino acid mutations (V26I, I116M, A186T, D187Y, D222G/N, M257I, S263F, I286L/M, and N473D were observed only in patients with severe ILI. D222G/N variants were detected exclusively in BAL samples. CONCLUSIONS: Multiple virus clusters co-circulated during the 2010-2011 winter-spring season. Severe or moderate ILI were associated with specific 2009 influenza A(H1N1 variants, which replicated preferentially in the lower respiratory tract.

Microglia P2Y13 Receptors Prevent Astrocyte Proliferation Mediated by P2Y1 Receptors

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Clara Quintas

2018-05-01

Full Text Available Cerebral inflammation is a common feature of several neurodegenerative diseases that requires a fine interplay between astrocytes and microglia to acquire appropriate phenotypes for an efficient response to neuronal damage. During brain inflammation, ATP is massively released into the extracellular medium and converted into ADP. Both nucleotides acting on P2 receptors, modulate astrogliosis through mechanisms involving microglia-astrocytes communication. In previous studies, primary cultures of astrocytes and co-cultures of astrocytes and microglia were used to investigate the influence of microglia on astroglial proliferation induced by ADPβS, a stable ADP analog. In astrocyte cultures, ADPβS increased cell proliferation through activation of P2Y1 and P2Y12 receptors, an effect abolished in co-cultures (of astrocytes with ∼12.5% microglia. The possibility that the loss of the ADPβS-mediated effect could have been caused by a microglia-induced degradation of ADPβS or by a preferential microglial localization of P2Y1 or P2Y12 receptors was excluded. Since ADPβS also activates P2Y13 receptors, the contribution of microglial P2Y13 receptors to prevent the proliferative effect of ADPβS in co-cultures was investigated. The results obtained indicate that P2Y13 receptors are low expressed in astrocytes and mainly expressed in microglia. Furthermore, in co-cultures, ADPβS induced astroglial proliferation in the presence of the selective P2Y13 antagonist MRS 2211 (3 μM and of the selective P2Y12 antagonist AR-C66096 (0.1 μM, suggesting that activation of microglial P2Y12 and P2Y13 receptors may induce the release of messengers that inhibit astroglial proliferation mediated by P2Y1,12 receptors. In this microglia-astrocyte paracrine communication, P2Y12 receptors exert opposite effects in astroglial proliferation as a result of its cellular localization: cooperating in astrocytes with P2Y1 receptors to directly stimulate proliferation and in

Functional characterizations of rare UBA1 variants in X-linked Spinal Muscular Atrophy [version 1; referees: 2 approved

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Chris D. Balak

2017-09-01

Full Text Available Background: X-linked spinal muscular atrophy (XL-SMA results from mutations in the Ubiquitin-Like Modifier Activating Enzyme 1 (UBA1. Previously, four novel closely clustered mutations have been shown to cause this fatal infantile disorder affecting only males. These mutations, three missense and one synonymous, all lie within Exon15 of the UBA1 gene, which contains the active adenylation domain (AAD. Methods: In this study, our group characterized the three known missense variants in vitro. Using a novel Uba1 assay and other methods, we investigated Uba1 adenylation, thioester, and transthioesterification reactions in vitro to determine possible biochemical effects of the missense variants. Results: Our data revealed that only one of the three XL-SMA missense variants impairs the Ubiquitin-adenylating ability of Uba1. Additionally, these missense variants retained Ubiquitin thioester bond formation and transthioesterification rates equal to that found in the wild type. Conclusions: Our results demonstrate a surprising shift from the likelihood of these XL-SMA mutations playing a damaging role in Uba1’s enzymatic activity with Ubiquitin, to other roles such as altering UBA1 mRNA splicing via the disruption of splicing factor binding sites, similar to a mechanism in traditional SMA, or disrupting binding to other important in vivo binding partners.  These findings help to narrow the search for the areas of possible dysfunction in the Ubiquitin-proteasome pathway that ultimately result in XL-SMA. Moreover, this investigation provides additional critical understanding of the mutations’ biochemical mechanisms, vital for the development of future effective diagnostic assays and therapeutics.

Suppression of non-prompt J/psi, prompt J/psi, and Y(1S) in PbPb collisions at sqrt(sNN) = 2.76 TeV

Energy Technology Data Exchange (ETDEWEB)

Chatrchyan, Serguei [Yerevan Physics Inst. (Armenia); et al.

2012-05-01

Yields of prompt and non-prompt J/psi, as well as Y(1S) mesons, are measured by the CMS experiment via their dimuon decays in PbPb and pp collisions at sqrt(sNN) = 2.76 TeV for quarkonium rapidity |y|<2.4. Differential cross sections and nuclear modification factors are reported as functions of y and transverse momentum pt, as well as collision centrality. For prompt J/psi with relatively high pt (6.5Y(1S) mesons are suppressed in PbPb collisions.

Respuesta al estrés, Temperamento y Crianza en niños colombianos de 1 año

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Marta Martínez, Colombia

2015-07-01

Full Text Available (analítico:Este estudio busco explorar las relaciones entre el temperamento de una muestra de niños de 1 año (264, las expectativas y prácticas de crianza de sus padres y el cortisol en saliva como respuesta al estrés en una submuestra de la anterior (59. La respuesta al estrés se encontró asociada con la variable prácticas disciplinarias (R=0,31 y se correlaciono negativamente con las variables extroversión (R=-0,35 y regulación (-0,21. No se encontró correlación entre las variables de temperamento y crianza, lo cual se interpreta con la teoría de la bondad del ajuste. Estos resultados son relevantes en la planificación de los programas de formación de padres y soportan la importancia de erradicar el castigo físico y promover una crianza flexible que se acople a las diferencias individuales.

Respuesta al estrés, Temperamento y Crianza en niños colombianos de 1 año

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Marta Martínez

2015-01-01

Full Text Available Este estudio busco explorar las relaciones entre el temperamento deuna muestra de niños de 1 año (264, las expectativas y prácticas de crianza de sus padres y el cortisolen saliva como respuesta al estrés en una submuestra de la anterior (59. La respuesta al estrés seencontró asociada con la variable prácticas disciplinarias (R=0,31 y se correlaciono negativamentecon las variables extroversión (R=-0,35 y regulación (-0,21. No se encontró correlación entre lasvariables de temperamento y crianza, lo cual se interpreta con la teoría de la bondad del ajuste. Estosresultados son relevantes en la planificación de los programas de formación de padres y soportanla importancia de erradicar el castigo físico y promover una crianza flexible que se acople a lasdiferencias individuales.

Quantification of the beta-adrenoceptor ligand S-1'[F-18]fluorocarazolol in plasma of humans, rats and sheep

NARCIS (Netherlands)

vanWaarde, A; Posthumus, H; Elsinga, PH; Anthonio, RL; van Loenen - Weemaes, Anne-miek; Beaufort-Krol, Gertie C. M.; Paans, AMJ; Vaalburg, W; Visser, Thomas; Visser, Gerben

1996-01-01

Myocardial and pulmonary beta-adrenoceptors can be imaged with 2-(S)-(-)-(9H-carbazol-4-yl-oxy)-3-[1-(fluoromethyl)ethyl]amino-2-propanol (S-1'-[F-18]fluorocarazolol, I). Quantification of unmodified fluorocarazolol in plasma is necessary for analysis of PET images in terms of receptor densities. We

Comportamiento Mecánico Estático de los Instrumentos S1, S2, F1 de Protaper Universal® Bajo Torsión y Doblamiento. Análisis por Elementos Finitos

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Luisa Fernanda Cartagena

2011-10-01

Full Text Available Propósito: Examinar el comportamiento mecánico estático de los instrumentos ProTaper Universal® S1, S2, F1 bajo torsión y doblamiento teniendo en cuenta las propiedades mecánicas del material, mediante el método de elementos finitos. Metodología: Estudio Observacional descriptivo. Las limas investigadas fueron S1, S2, F1 de ProTaper Universal®, modeladas con el software ANSYS 10 y sometidas a fuerzas de torsión empezando en 0.25N/cm hasta alcanzar el torque máximo recomendado por la casa comercial Maillefer® y doblamiento en un ángulo de 600. Resultados:El máximo esfuerzo ocurre en el núcleo de la sección para todos los instrumentos evaluados;  al incrementar el torque el  esfuerzo  se disipa a la periferia para S1 (D5, D10, D14, S2 (D5, D7, D8, D10, F1 (D2, D3, D5.  La lima S1 al ser sometida a  torsión en D0 y D5 independiente del torque que fuese aplicado el máximo de esfuerzo superaba el límite de deformación plástica en el núcleo de la sección  del instrumento. La lima S2 con torques de  1 ó 1,5 N/cm superó  el límite elástico del material. Lima F1 en D0, D2 con torques de  0.25, 0.5, 1, 1.5, 2 N/cm el esfuerzo máximo no supero el límite de deformación plástica. En la prueba de doblamiento la gran mayoría de la estructura de las limas S1, S2, F1, se encuentra  por debajo del esfuerzo de ruptura (línea neutral es bastante ancha.Conclusion: Las fuerzas de  torsión para todas la limas del estudio mostraron tener mayor riesgo de separación del instrumento en comparación con  las fuerzas de doblamiento. 

Babenko’s Approach to Abel’s Integral Equations

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Chenkuan Li

2018-03-01

Full Text Available The goal of this paper is to investigate the following Abel’s integral equation of the second kind: y ( t + λ Γ ( α ∫ 0 t ( t − τ α − 1 y ( τ d τ = f ( t , ( t > 0 and its variants by fractional calculus. Applying Babenko’s approach and fractional integrals, we provide a general method for solving Abel’s integral equation and others with a demonstration of different types of examples by showing convergence of series. In particular, we extend this equation to a distributional space for any arbitrary α ∈ R by fractional operations of generalized functions for the first time and obtain several new and interesting results that cannot be realized in the classical sense or by the Laplace transform.

Search for first-generation leptoquarks in bar pp collisions at √s =1.8 TeV

International Nuclear Information System (INIS)

Abe, F.; Albrow, M.; Amidei, D.; Anway-Wiese, C.; Apollinari, G.; Atac, M.; Auchincloss, P.; Azzi, P.; Baden, A.R.; Bacchetta, N.; Badgett, W.; Bailey, M.W.; Bamberger, A.; de Barbaro, P.; Barbaro-Galtieri, A.; Barnes, V.E.; Barnett, B.A.; Bauer, G.; Baumann, T.; Bedeschi, F.; Behrends, S.; Belforte, S.; Bellettini, G.; Bellinger, J.; Benjamin, D.; Benlloch, J.; Bensinger, J.; Beretvas, A.; Berge, J.P.; Bertolucci, S.; Biery, K.; Bhadra, S.; Binkley, M.; Bisello, D.; Blair, R.; Blocker, C.; Bodek, A.; Bolognesi, V.; Booth, A.W.; Boswell, C.; Brandenburg, G.; Brown, D.; Buckley-Geer, E.; Budd, H.S.; Busetto, G.; Byon-Wagner, A.; Byrum, K.L.; Campagnari, C.; Campbell, M.; Caner, A.; Carey, R.; Carithers, W.; Carlsmith, D.; Carroll, J.T.; Cashmore, R.; Castro, A.; Cen, Y.; Cervelli, F.; Chadwick, K.; Chapman, J.; Chiarelli, G.; Chinowsky, W.; Cihangir, S.; Clark, A.G.; Cobal, M.; Connor, D.; Contreras, M.; Cooper, J.; Cordelli, M.; Crane, D.; Cunningham, J.D.; Day, C.; DeJongh, F.; Dell'Agnello, S.; Dell'Orso, M.; Demortier, L.; Denby, B.; Derwent, P.F.; Devlin, T.; DiBitonto, D.; Dickson, M.; Drucker, R.B.; Einsweiler, K.; Elias, J.E.; Ely, R.; Eno, S.; Errede, S.; Etchegoyen, A.; Farhat, B.; Frautschi, M.; Feldman, G.J.; Flaugher, B.; Foster, G.W.; Franklin, M.; Freeman, J.; Frisch, H.; Fuess, T.; Fukui, Y.; Garfinkel, A.F.; Gauthier, A.; Geer, S.; Gerdes, D.W.; Giannetti, P.; Giokaris, N.; Giromini, P.; Gladney, L.; Gold, M.; Gonzalez, J.; Goulianos, K.; Grassmann, H.; Grieco, G.M.; Grindley, R.; Grosso-Pilcher, C.; Haber, C.; Hahn, S.R.; Handler, R.; Hara, K.; Harral, B.; Harris, R.M.; Hauger, S.A.; Hauser, J.; Hawk, C.; Hessing, T.; Hollebeek, R.; Holloway, L.; Hoelscher, A.; Hong, S.; Houk, G.; Hu, P.; Hubbard, B.; Huffman, B.T.; Hughes, R.; Hurst, P.; Huth, J.; Hylen, J.; Incagli, M.; Ino, T.; Iso, H.; Jensen, H.; Jessop, C.P.; Johnson, R.P.; Joshi, U.; Kadel, R.W.; Kamon, T.; Kanda, S.; Kardelis, D.A.; Karliner, I.; Kearns, E.; Keeble, L.

1993-01-01

We present results of a search for a first-generation leptoquark scrS 1 in bar pp collisions at √s =1.8 TeV at the Fermilab Tevatron. Using 4.05 pb -1 of data collected during the 1988--1989 CDF run, we have searched for evidence of scrS 1 scr bar S1 production assuming that each leptoquark decays to an electron+quark pair with a branching ratio β. Three events with two high energy electrons and two high energy jets were found, but are consistent with Z 0 decay. No events were found in the signal region. Assuming a short lived scalar leptoquark with Yukawa coupling strength λ approx-gt 2x10 -7 , we exclude σβ 2 >55(4.0) pb at 95% C.L. for M scrS =45(125) GeV/c 2 . Using a Monte Carlo prediction for σ(bar pp→scrS 1 scr bar S1+X), we exclude M scrS 2 for β=100(50)%

Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci.

Science.gov (United States)

Aung, Tin; Ozaki, Mineo; Lee, Mei Chin; Schlötzer-Schrehardt, Ursula; Thorleifsson, Gudmar; Mizoguchi, Takanori; Igo, Robert P; Haripriya, Aravind; Williams, Susan E; Astakhov, Yury S; Orr, Andrew C; Burdon, Kathryn P; Nakano, Satoko; Mori, Kazuhiko; Abu-Amero, Khaled; Hauser, Michael; Li, Zheng; Prakadeeswari, Gopalakrishnan; Bailey, Jessica N Cooke; Cherecheanu, Alina Popa; Kang, Jae H; Nelson, Sarah; Hayashi, Ken; Manabe, Shin-Ichi; Kazama, Shigeyasu; Zarnowski, Tomasz; Inoue, Kenji; Irkec, Murat; Coca-Prados, Miguel; Sugiyama, Kazuhisa; Järvelä, Irma; Schlottmann, Patricio; Lerner, S Fabian; Lamari, Hasnaa; Nilgün, Yildirim; Bikbov, Mukharram; Park, Ki Ho; Cha, Soon Cheol; Yamashiro, Kenji; Zenteno, Juan C; Jonas, Jost B; Kumar, Rajesh S; Perera, Shamira A; Chan, Anita S Y; Kobakhidze, Nino; George, Ronnie; Vijaya, Lingam; Do, Tan; Edward, Deepak P; de Juan Marcos, Lourdes; Pakravan, Mohammad; Moghimi, Sasan; Ideta, Ryuichi; Bach-Holm, Daniella; Kappelgaard, Per; Wirostko, Barbara; Thomas, Samuel; Gaston, Daniel; Bedard, Karen; Greer, Wenda L; Yang, Zhenglin; Chen, Xueyi; Huang, Lulin; Sang, Jinghong; Jia, Hongyan; Jia, Liyun; Qiao, Chunyan; Zhang, Hui; Liu, Xuyang; Zhao, Bowen; Wang, Ya-Xing; Xu, Liang; Leruez, Stéphanie; Reynier, Pascal; Chichua, George; Tabagari, Sergo; Uebe, Steffen; Zenkel, Matthias; Berner, Daniel; Mossböck, Georg; Weisschuh, Nicole; Hoja, Ursula; Welge-Luessen, Ulrich-Christoph; Mardin, Christian; Founti, Panayiota; Chatzikyriakidou, Anthi; Pappas, Theofanis; Anastasopoulos, Eleftherios; Lambropoulos, Alexandros; Ghosh, Arkasubhra; Shetty, Rohit; Porporato, Natalia; Saravanan, Vijayan; Venkatesh, Rengaraj; Shivkumar, Chandrashekaran; Kalpana, Narendran; Sarangapani, Sripriya; Kanavi, Mozhgan R; Beni, Afsaneh Naderi; Yazdani, Shahin; Lashay, Alireza; Naderifar, Homa; Khatibi, Nassim; Fea, Antonio; Lavia, Carlo; Dallorto, Laura; Rolle, Teresa; Frezzotti, Paolo; Paoli, Daniela; Salvi, Erika; Manunta, Paolo; Mori, Yosai; Miyata, Kazunori; Higashide, Tomomi; Chihara, Etsuo; Ishiko, Satoshi; Yoshida, Akitoshi; Yanagi, Masahide; Kiuchi, Yoshiaki; Ohashi, Tsutomu; Sakurai, Toshiya; Sugimoto, Takako; Chuman, Hideki; Aihara, Makoto; Inatani, Masaru; Miyake, Masahiro; Gotoh, Norimoto; Matsuda, Fumihiko; Yoshimura, Nagahisa; Ikeda, Yoko; Ueno, Morio; Sotozono, Chie; Jeoung, Jin Wook; Sagong, Min; Park, Kyu Hyung; Ahn, Jeeyun; Cruz-Aguilar, Marisa; Ezzouhairi, Sidi M; Rafei, Abderrahman; Chong, Yaan Fun; Ng, Xiao Yu; Goh, Shuang Ru; Chen, Yueming; Yong, Victor H K; Khan, Muhammad Imran; Olawoye, Olusola O; Ashaye, Adeyinka O; Ugbede, Idakwo; Onakoya, Adeola; Kizor-Akaraiwe, Nkiru; Teekhasaenee, Chaiwat; Suwan, Yanin; Supakontanasan, Wasu; Okeke, Suhanya; Uche, Nkechi J; Asimadu, Ifeoma; Ayub, Humaira; Akhtar, Farah; Kosior-Jarecka, Ewa; Lukasik, Urszula; Lischinsky, Ignacio; Castro, Vania; Grossmann, Rodolfo Perez; Sunaric Megevand, Gordana; Roy, Sylvain; Dervan, Edward; Silke, Eoin; Rao, Aparna; Sahay, Priti; Fornero, Pablo; Cuello, Osvaldo; Sivori, Delia; Zompa, Tamara; Mills, Richard A; Souzeau, Emmanuelle; Mitchell, Paul; Wang, Jie Jin; Hewitt, Alex W; Coote, Michael; Crowston, Jonathan G; Astakhov, Sergei Y; Akopov, Eugeny L; Emelyanov, Anton; Vysochinskaya, Vera; Kazakbaeva, Gyulli; Fayzrakhmanov, Rinat; Al-Obeidan, Saleh A; Owaidhah, Ohoud; Aljasim, Leyla Ali; Chowbay, Balram; Foo, Jia Nee; Soh, Raphael Q; Sim, Kar Seng; Xie, Zhicheng; Cheong, Augustine W O; Mok, Shi Qi; Soo, Hui Meng; Chen, Xiao Yin; Peh, Su Qin; Heng, Khai Koon; Husain, Rahat; Ho, Su-Ling; Hillmer, Axel M; Cheng, Ching-Yu; Escudero-Domínguez, Francisco A; González-Sarmiento, Rogelio; Martinon-Torres, Frederico; Salas, Antonio; Pathanapitoon, Kessara; Hansapinyo, Linda; Wanichwecharugruang, Boonsong; Kitnarong, Naris; Sakuntabhai, Anavaj; Nguyn, Hip X; Nguyn, Giang T T; Nguyn, Trình V; Zenz, Werner; Binder, Alexander; Klobassa, Daniela S; Hibberd, Martin L; Davila, Sonia; Herms, Stefan; Nöthen, Markus M; Moebus, Susanne; Rautenbach, Robyn M; Ziskind, Ari; Carmichael, Trevor R; Ramsay, Michele; Álvarez, Lydia; García, Montserrat; González-Iglesias, Héctor; Rodríguez-Calvo, Pedro P; Fernández-Vega Cueto, Luis; Oguz, Çilingir; Tamcelik, Nevbahar; Atalay, Eray; Batu, Bilge; Aktas, Dilek; Kasım, Burcu; Wilson, M Roy; Coleman, Anne L; Liu, Yutao; Challa, Pratap; Herndon, Leon; Kuchtey, Rachel W; Kuchtey, John; Curtin, Karen; Chaya, Craig J; Crandall, Alan; Zangwill, Linda M; Wong, Tien Yin; Nakano, Masakazu; Kinoshita, Shigeru; den Hollander, Anneke I; Vesti, Eija; Fingert, John H; Lee, Richard K; Sit, Arthur J; Shingleton, Bradford J; Wang, Ningli; Cusi, Daniele; Qamar, Raheel; Kraft, Peter; Pericak-Vance, Margaret A; Raychaudhuri, Soumya; Heegaard, Steffen; Kivelä, Tero; Reis, André; Kruse, Friedrich E; Weinreb, Robert N; Pasquale, Louis R; Haines, Jonathan L; Thorsteinsdottir, Unnur; Jonasson, Fridbert; Allingham, R Rand; Milea, Dan; Ritch, Robert; Kubota, Toshiaki; Tashiro, Kei; Vithana, Eranga N; Micheal, Shazia; Topouzis, Fotis; Craig, Jamie E; Dubina, Michael; Sundaresan, Periasamy; Stefansson, Kari; Wiggs, Janey L; Pasutto, Francesca; Khor, Chiea Chuen

2017-07-01

Exfoliation syndrome (XFS) is the most common known risk factor for secondary glaucoma and a major cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A, have previously been associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results across populations, and to identify new variants associated with XFS. We identified a rare protective allele at LOXL1 (p.Phe407, odds ratio (OR) = 25, P = 2.9 × 10 -14 ) through deep resequencing of XFS cases and controls from nine countries. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 × 10 -8 ). We identified association signals at 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology.

Comparison of the BioRad Variant and Primus Ultra2 high-pressure liquid chromatography (HPLC) instruments for the detection of variant hemoglobins.

Science.gov (United States)

Gosselin, R C; Carlin, A C; Dwyre, D M

2011-04-01

Hemoglobin variants are a result of genetic changes resulting in abnormal or dys-synchronous hemoglobin chain production (thalassemia) or the generation of hemoglobin chain variants such as hemoglobin S. Automated high-pressure liquid chromatography (HPLC) systems have become the method of choice for the evaluation of patients suspected with hemoglobinopathies. In this study, we evaluated the performance of two HPLC methods used in the detection of common hemoglobin variants: Variant and Ultra2. There were 377 samples tested, 26% (99/377) with HbS, 8.5% (32/377) with HbC, 20.7% (78/377) with other hemoglobin variant or thalassemia, and 2.9% with increased hemoglobin A(1) c. The interpretations of each chromatograph were compared. There were no differences noted for hemoglobins A(0), S, or C. There were significant differences between HPLC methods for hemoglobins F, A(2), and A(1) c. However, there was good concordance between normal and abnormal interpretations (97.9% and 96.2%, respectively). Both Variant and Ultra2 HPLC methods were able to detect most common hemoglobin variants. There was better discrimination for fast hemoglobins, between hemoglobins E and A(2), and between hemoglobins S and F using the Ultra2 HPLC method. © 2010 Blackwell Publishing Ltd.

5 CFR 2640.301 - Waivers issued pursuant to 18 U.S.C. 208(b)(1).

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2010-01-01

...(b)(1). 2640.301 Section 2640.301 Administrative Personnel OFFICE OF GOVERNMENT ETHICS GOVERNMENT ETHICS INTERPRETATION, EXEMPTIONS AND WAIVER GUIDANCE CONCERNING 18 U.S.C. 208 (ACTS AFFECTING A PERSONAL... profit or loss or cost of the matter to the company issuing the stock, the change in the value of real...

Sex-specific association between functional neuropeptide S receptor gene (NPSR1) variants and cortisol and central stress responses.

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Streit, Fabian; Akdeniz, Ceren; Haddad, Leila; Kumsta, Robert; Entringer, Sonja; Frank, Josef; Yim, Ilona S; Zänkert, Sandra; Witt, Stephanie H; Kirsch, Peter; Rietschel, Marcella; Wüst, Stefan

2017-02-01

The brain neuropeptide S (NPS) system has recently generated substantial interest and may be of major relevance for central stress regulation. The NPS receptor (NPSR1) is highly expressed in the limbic system, exogenous NPS exerts pronounced anxiolytic and fear-attenuating effects in rodents and extensive close crosstalk between the NPS system and the hypothalamic-pituitary-adrenal (HPA) axis has been demonstrated. In humans, associations between NPSR1 variants and anxiety and panic disorder, as well as amygdala responsiveness to fear- relevant faces and prefrontal cortex activity in a fear conditioning paradigm have been reported. Moreover, a NPSR1 sequence variant was found to be associated with cortisol stress responses in males. Here, we performed a haplotype-based analysis covering three functional NPSR1 single nucleotide polymorphisms in the promoter (rs2530547), in exon 3 (rs324981) and exon 6 (rs727162) in 277 healthy subjects who were exposed to the Trier Social Stress Test (TSST). A significant sex-specific association with salivary cortisol responses to acute psychosocial stress was detected for the common TTC haplotype 2 (frequency of about 20%). In an additional study using an imaging genetics approach, 65 healthy subjects were exposed to a stress paradigm for scanner environments (“ScanSTRESS”). We found a significant and, again, sex-specific interaction between rs324981 (whose minor T-allele is harbored by haplotype 2) and the neural stress response in a cluster close to the parahippocampal gyrus (whole brain corrected). Moreover, as in the TSST sample, NPSR1 variation was associated with salivary cortisol responses (on a trend level) in a sex-specific way. In summary, our preliminary findings in two independent cohorts exposed to different stress paradigms suggest that the NPS system significantly influences acute stress responses and that sequence variation in NPSR1 may contribute to sex differences in stress regulation. Copyright © 2016

Detection of S-gene 'a' determinant variants in hepatitis B patients with both positive HBsAg and HBsAb markers

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Wu Yueping; Ling Yongwu; Huang Songping; Wang Shipeng; Chen Yufeng; Mao Liping; Lu Jianrong

2005-01-01

Objective: To explore the S-gene 'a' determinant variants in hepatitis B patients with both positive HBsAg and HBsAb markers and the effect on the antigenicity of HBsAg. Methods: Quantitative determination of HBV - DNA with competent PCR microfluidic chit method was performed in eight sera specimens from seven hepatitis B patients with both positive HBsAg and HBsAb markers. HBV S-gene was amplified with nested PCR, the PCR product was directly examined for any sequence variant of the amino acids. HBV markers were tested with the very sensitive ELISA/MEIA method in these seven patients. The above rests were also performed in 15 children after failed immunization with hepatitis B vaccine and 9 recipients of liver transplantation for terminal hepatitis B treated with HBIG and lamivudine, serving as controls. Results: The HBsAb contents in the seven patients were all below 80 mIu/ml. Two of the patients with positive HBV-DNA showed no 'a' determinant variant. Two of the four HBV-DNA negative patients demonstrated amino-acid variants (126, 131). One patients who was originally HBV-DNA positive but later turned negative after treatment with interferon and lamivudine demonstrated variant (126). In the 9 patients after successful liver transplantation, the HBsAb contents were all about 150mIu/ml with negative HBV-DNA and no variant. In the 15 immunization failures, HBV-DNA was positive in 14 of them, with 2 cases of variant at 145, 1 case at 126 and 1 case at 134. Conclusion: In some patients with chronic B hepatitis with both positive HBsAg and HBsAb markers, as well as in some vaccine immunization failures, there were 'a' determinant variants, which might alter the antigenicity of HBsAg with escape from the neutralization of low HBsAb. The 'a' determinant variant might also affect the replication of the virus. In this study, no variant was shown in patients after successful liver transplantation. However, the number of patients was too small and the result was of no

Alimentación de la anchoveta (Engraulis ringens en el norte de Chile (18°25'-25°40'S en diciembre de 2010

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Marianela Medina

2015-03-01

Full Text Available Se analiza la dieta de Engraulis ringens para determinar posibles diferencias en su comportamiento alimentario por longitud y gradiente latitudinal. Las muestras se obtuvieron entre 18°25'S y 24°40'S durante el crucero de evaluación hidroacústica del reclutamiento de E. ringens, realizado entre el 1 y 20 de diciembre de 2010. El análisis comprendió la determinación de la dieta contenida en un total de 294 estómagos, provenientes de 18 estaciones de muestreo y distribuidos en tres clases de longitud (pre-reclutas, reclutas y adultos. La dieta se describió mediante los métodos numéricos de frecuencia de ocurrencia e índice de importancia relativa, además de la similitud dietaria por longitud y latitud, y especialización trófica. E. ringens registró un amplio espectro trófico, tanto de presas fitoplanctónicas como zooplanctónicas, con una alta predominancia de fitoplancton por sobre zooplancton en 2,5 órdenes de magnitud, por rango de longitud y latitud. Los componentes de mayor importancia relativa en la dieta fueron las diatomeas de los géneros Rhizosolenia y Chaetoceros, y Copepoda dentro del zooplancton. El análisis de la similitud trófica intraespecífica mostró una alta sobreposición entre los grupos de longitud, conformando una "unidad trófica". Mientras que el análisis latitudinal reveló una alta sobreposición trófica con tendencia a formar dos "unidades tróficas", pero sin seguir un patrón definido. Los resultados, confirman el carácter de depredador generalista y oportunista de E. ringens en la zona norte de Chile durante el periodo analizado.

Valores y lectura(s

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Juan Senís Fernández

2006-01-01

Con dicho proyecto se pretendía, entre otros objetivos, revisar los libros de Lengua del segundo ciclo de Primaria (es decir, de cuarto, quinto y sexto curso con el fin de comprobar cómo se presentaban los valores a través de sus textos y sus paratextos. Con tal cometido, se llevó a cabo una consulta acerca de los manuales usados en los colegios de Cuenca, Albacete y Toledo. De tal consulta provino el corpus de la investigación, que se redujo a los libros de Lengua de las editoriales Anaya, Edelvives, Santillana y SM, que resultaron ser los más utilizados en las tres provincias. El artículo toma estos libros como materia de estudio, y supone un resumen de la investigación. Como tal, será simplificador e incompleto, pero esperamos que resulte lo suficientemente esclarecedor y definitorio en sus ideas y conclusiones como para que el lector se haga una idea de la investigación en su conjunto.

Evaluation of full S1 gene sequencing of classical and variant infectious bronchitis viruses extracted from allantoic fluid and FTA cards.

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Manswr, Basim; Ball, Christopher; Forrester, Anne; Chantrey, Julian; Ganapathy, Kannan

2018-05-01

Sequence variability in the S1 gene determines the genotype of infectious bronchitis virus (IBV) strains. A single RT-PCR assay was developed to amplify and sequence the full S1 gene for six classical and variant IBVs (M41, D274, 793B, IS/885/00, IS/1494/06 and Q1) enriched in allantoic fluid (AF) or the same AF but inoculated onto Flinders Technology Association (FTA) cards. Representative strains from each genotype were grown in SPF eggs and RNA was extracted from AF. Full S1 gene amplification was achieved using primer A and primer 22.51. Products were sequenced using primer A, 1050+, 1380+ and SX3+ to obtain short sequences covering the full gene. Following serial dilutions of AF, detection limits of the partial assay were higher than those of the full S1 gene. Partial S1 sequences exhibited higher than average nucleotide similarity percentages (79%; 352bp) compared to full S1 sequences (77%; 1,756bp), suggesting that full S1 analysis allows greater strain differentiation. For IBV detection from AF inoculated FTA cards, four serotypes were incubated for up to 21 days at three temperatures; 4 o C, 24 o C and 40 o C. RNA was extracted and tested with partial and full S1 protocols. Through partial sequencing, all IBVs were successfully detected at all sampling points and storage temperatures. In contrast, using full S1 sequencing was not possible to amplify the gene beyond 14 days or when stored at 40°C. Data presented shows that for full S1 sequencing, a substantial amount of RNA is needed. Field samples collected onto FTA cards are unlikely to yield such quantity or quality.

HFE gene variants, iron, and lipids: a novel connection in Alzheimer’s disease

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Ali-Rahmani, Fatima; Schengrund, Cara-Lynne; Connor, James R.

2014-01-01

Iron accumulation and associated oxidative stress in the brain have been consistently found in several neurodegenerative diseases. Multiple genetic studies have been undertaken to try to identify a cause of neurodegenerative diseases but direct connections have been rare. In the iron field, variants in the HFE gene that give rise to a protein involved in cellular iron regulation, are associated with iron accumulation in multiple organs including the brain. There is also substantial epidemiological, genetic, and molecular evidence of disruption of cholesterol homeostasis in several neurodegenerative diseases, in particular Alzheimer’s disease (AD). Despite the efforts that have been made to identify factors that can trigger the pathological events associated with neurodegenerative diseases they remain mostly unknown. Because molecular phenotypes such as oxidative stress, synaptic failure, neuronal loss, and cognitive decline, characteristics associated with AD, have been shown to result from disruption of a number of pathways, one can easily argue that the phenotype seen may not arise from a linear sequence of events. Therefore, a multi-targeted approach is needed to understand a complex disorder like AD. This can be achieved only when knowledge about interactions between the different pathways and the potential influence of environmental factors on them becomes available. Toward this end, this review discusses what is known about the roles and interactions of iron and cholesterol in neurodegenerative diseases. It highlights the effects of gene variants of HFE (H63D- and C282Y-HFE) on iron and cholesterol metabolism and how they may contribute to understanding the etiology of complex neurodegenerative diseases. PMID:25071582

Low-frequency nonsynonymous variants in FKBPL and ARPC1B genes are associated with breast cancer risk in Chinese women.

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Zhou, Wen; Jiang, Yue; Zhu, Meng; Hang, Dong; Chen, Jiaping; Zhou, Jing; Dai, Juncheng; Ma, Hongxia; Hu, Zhibin; Jin, Guangfu; Sha, Jiahao; Shen, Hongbing

2017-02-01

Genome-wide association studies have reported more than 100 independent common loci associated with breast cancer risk. The contribution of low-frequency or rare variants to breast cancer susceptibility has not been well explored. Thus, we applied exome chip to genotype >200 000 low-frequency and rare variants in 1064 breast cancer cases and 1125 cancer-free controls and subsequently validated promising associations in another 1040 breast cancer cases and 1240 controls. We identified two low-frequency nonsynonymous variants at FKBPL (rs200847762, OR = 0.34, 95% CI = 0.20-0.57, P = 4.31 × 10 -5 ) and ARPC1B (rs1045012, OR = 0.56, 95% CI = 0.43-0.74, P = 4.30 × 10 -5 ) associated with breast cancer risk. In stratification analyses, we found that the protective effect of rs200847762 was stronger in ER-positive breast cancer (OR = 0.18, 95% CI = 0.06-0.42) than that in ER-negative one (OR = 0.59, 95% CI = 0.31-1.05). Our findings indicate that low-frequency variants may also contribute to breast cancer susceptibility and genetic variants in 6p21.33 and 7q22.1 are important in breast carcinogenesis. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Deficient repair and degradation of DNA in X-irradiated L5178Y S/S cells: cell-cycle and temperature dependence

International Nuclear Information System (INIS)

Ueno, A.M.; Goldin, E.M.; Cox, A.B.; Lett, J.T.

1979-01-01

The rejoining of DNA strand breaks induced by X rays in the radiosensitive S/S variant of the L5178Y murine leukemic lymphoblast has been studied by alkaline-EDTA-sucrose sedimentation using swinging-bucket and zonal rotors. After irradiation, incubation resulted in an increase in DNA size, but the DNA structures were not restored in all cells, even when the x-ray dose was only 50 rad. Subsequently, 10 to 20 h after irradiation, heavily degraded DNA began to appear. When cells were irradiated at different parts of the cycle, the extent of DNA degradation varied in a fashion similar to survival: Least DNA degradation was found after irradiation at the most radioresistant stage (G 1 + 8 h), and most DNA degradation occurred after irradiation at the radiosensitive stage (G 1 ). Changes in cell survival caused by postirradiation hypothermia were also reflected in the extent of DNA degradation. Populations of G 1 cells, which show marked increases in survival after postirradiation hypothermic exposure, exhibited a lower level of DNA degradation, whereas populations of G 1 + 8 h cells, whose survival is affected little by postirradiation hypothermia, showed limited changes in DNA degradation. The onset of degradation was delayed by hypothermia in all cases

Evaluation of Presumably Disease Causing SCN1A Variants in a Cohort of Common Epilepsy Syndromes.

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Lal, Dennis; Reinthaler, Eva M; Dejanovic, Borislav; May, Patrick; Thiele, Holger; Lehesjoki, Anna-Elina; Schwarz, Günter; Riesch, Erik; Ikram, M Arfan; van Duijn, Cornelia M; Uitterlinden, Andre G; Hofman, Albert; Steinböck, Hannelore; Gruber-Sedlmayr, Ursula; Neophytou, Birgit; Zara, Federico; Hahn, Andreas; Gormley, Padhraig; Becker, Felicitas; Weber, Yvonne G; Cilio, Maria Roberta; Kunz, Wolfram S; Krause, Roland; Zimprich, Fritz; Lemke, Johannes R; Nürnberg, Peter; Sander, Thomas; Lerche, Holger; Neubauer, Bernd A

2016-01-01

The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are more likely to be classified as pathogenic if they have already been identified previously in a patient with epilepsy. Here, we critically re-evaluate the pathogenicity of this class of variants in a cohort of patients with common epilepsy syndromes and subsequently ask whether a significant fraction of benign variants have been misclassified as pathogenic. We screened a discovery cohort of 448 patients with a broad range of common genetic epilepsies and 734 controls for previously reported SCN1A mutations that were assumed to be disease causing. We re-evaluated the evidence for pathogenicity of the identified variants using in silico predictions, segregation, original reports, available functional data and assessment of allele frequencies in healthy individuals as well as in a follow up cohort of 777 patients. We identified 8 known missense mutations, previously reported as pathogenic, in a total of 17 unrelated epilepsy patients (17/448; 3.80%). Our re-evaluation indicates that 7 out of these 8 variants (p.R27T; p.R28C; p.R542Q; p.R604H; p.T1250M; p.E1308D; p.R1928G; NP_001159435.1) are not pathogenic. Only the p.T1174S mutation may be considered as a genetic risk factor for epilepsy of small effect size based on the enrichment in patients (P = 6.60 x 10-4; OR = 0.32, fishers exact test), previous functional studies but incomplete penetrance. Thus, incorporation of previous studies in genetic counseling of SCN1A sequencing results is challenging and may produce incorrect conclusions.

SINEUPs are modular antisense long-non coding RNAs that increase synthesis of target proteins in cells

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Silvia eZucchelli

2015-05-01

Full Text Available Despite recent efforts in discovering novel long non-coding RNAs (lncRNAs and unveiling their functions in a wide range of biological processes their applications as biotechnological or therapeutic tools are still at their infancy. We have recently shown that AS Uchl1, a natural lncRNA antisense to the Parkinson’s disease-associated gene Ubiquitin carboxyl-terminal esterase L1 (Uchl1, is able to increase UchL1 protein synthesis at post-transcriptional level. Its activity requires two RNA elements: an embedded inverted SINEB2 sequence to increase translation and the overlapping region to target its sense mRNA. This functional organization is shared with several mouse lncRNAs antisense to protein coding genes. The potential use of AS Uchl1-derived lncRNAs as enhancers of target mRNA translation remains unexplored. Here we define AS Uchl1 as the representative member of a new functional class of natural and synthetic antisense lncRNAs that activate translation. We named this class of RNAs SINEUPs for their requirement of the inverted SINEB2 sequence to UP-regulate translation in a gene-specific manner. The overlapping region is indicated as the Binding Doman (BD while the embedded inverted SINEB2 element is the Effector Domain (ED. By swapping BD, synthetic SINEUPs are designed targeting mRNAs of interest. SINEUPs function in an array of cell lines and can be efficiently directed towards N-terminally tagged proteins. Their biological activity is retained in a miniaturized version within the range of small RNAs length. Its modular structure was exploited to successfully design synthetic SINEUPs targeting endogenous Parkinson’s disease-associated DJ-1 and proved to be active in different neuronal cell lines.In summary, SINEUPs represent the first scalable tool to increase synthesis of proteins of interest. We propose SINEUPs as reagents for molecular biology experiments, in protein manufacturing as well as in therapy of haploinsufficiencies.

The BRCA1 variant p.Ser36Tyr abrogates BRCA1 protein function and potentially confers a moderate risk of breast cancer.

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Christou, Charita M; Hadjisavvas, Andreas; Kyratzi, Maria; Flouri, Christina; Neophytou, Ioanna; Anastasiadou, Violetta; Loizidou, Maria A; Kyriacou, Kyriacos

2014-01-01

The identification of variants of unknown clinical significance (VUS) in the BRCA1 gene complicates genetic counselling and causes additional anxiety to carriers. In silico approaches currently used for VUS pathogenicity assessment are predictive and often produce conflicting data. Furthermore, functional assays are either domain or function specific, thus they do not examine the entire spectrum of BRCA1 functions and interpretation of individual assay results can be misleading. PolyPhen algorithm predicted that the BRCA1 p.Ser36Tyr VUS identified in the Cypriot population was damaging, whereas Align-GVGD predicted that it was possibly of no significance. In addition the BRCA1 p.Ser36Tyr variant was found to be associated with increased risk (OR = 3.47, 95% CI 1.13-10.67, P = 0.02) in a single case-control series of 1174 cases and 1109 controls. We describe a cellular system for examining the function of exogenous full-length BRCA1 and for classifying VUS. We achieved strong protein expression of full-length BRCA1 in transiently transfected HEK293T cells. The p.Ser36Tyr VUS exhibited low protein expression similar to the known pathogenic variant p.Cys61Gly. Co-precipitation analysis further demonstrated that it has a reduced ability to interact with BARD1. Further, co-precipitation analysis of nuclear and cytosolic extracts as well as immunofluorescence studies showed that a high proportion of the p.Ser36Tyr variant is withheld in the cytoplasm contrary to wild type protein. In addition the ability of p.Ser36Tyr to co-localize with conjugated ubiquitin foci in the nuclei of S-phase synchronized cells following genotoxic stress with hydroxyurea is impaired at more pronounced levels than that of the p.Cys61Gly pathogenic variant. The p.Ser36Tyr variant demonstrates abrogated function, and based on epidemiological, genetic, and clinical data we conclude that the p.Ser36Tyr variant is probably associated with a moderate breast cancer risk.

The BRCA1 variant p.Ser36Tyr abrogates BRCA1 protein function and potentially confers a moderate risk of breast cancer.

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Charita M Christou

Full Text Available The identification of variants of unknown clinical significance (VUS in the BRCA1 gene complicates genetic counselling and causes additional anxiety to carriers. In silico approaches currently used for VUS pathogenicity assessment are predictive and often produce conflicting data. Furthermore, functional assays are either domain or function specific, thus they do not examine the entire spectrum of BRCA1 functions and interpretation of individual assay results can be misleading. PolyPhen algorithm predicted that the BRCA1 p.Ser36Tyr VUS identified in the Cypriot population was damaging, whereas Align-GVGD predicted that it was possibly of no significance. In addition the BRCA1 p.Ser36Tyr variant was found to be associated with increased risk (OR = 3.47, 95% CI 1.13-10.67, P = 0.02 in a single case-control series of 1174 cases and 1109 controls. We describe a cellular system for examining the function of exogenous full-length BRCA1 and for classifying VUS. We achieved strong protein expression of full-length BRCA1 in transiently transfected HEK293T cells. The p.Ser36Tyr VUS exhibited low protein expression similar to the known pathogenic variant p.Cys61Gly. Co-precipitation analysis further demonstrated that it has a reduced ability to interact with BARD1. Further, co-precipitation analysis of nuclear and cytosolic extracts as well as immunofluorescence studies showed that a high proportion of the p.Ser36Tyr variant is withheld in the cytoplasm contrary to wild type protein. In addition the ability of p.Ser36Tyr to co-localize with conjugated ubiquitin foci in the nuclei of S-phase synchronized cells following genotoxic stress with hydroxyurea is impaired at more pronounced levels than that of the p.Cys61Gly pathogenic variant. The p.Ser36Tyr variant demonstrates abrogated function, and based on epidemiological, genetic, and clinical data we conclude that the p.Ser36Tyr variant is probably associated with a moderate breast cancer risk.

Hb A1c Determination by Capillary Electrophoresis is an Efficient Method for Detecting β-Thalassemias and Hemoglobin Variants.

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Orts, Juan A; Zúñiga, Ángel; Bello, Yanis; Fabregat, Aleix B; Vicente, Ana I

2016-09-01

Glycated hemoglobin (Hb A 1c ) determination by multicapillary zone electrophoresis (MZE) can additionally be used to detect Hb A 2 , Hb F and most common hemoglobin (Hb) variants. We assessed the effectiveness of this method for detecting β-thalassemia (β-thal), δβ-thalassemia (δβ-thal) and most common Hb variants. Moreover, Hb F/Hb A 2 is evaluated as an index for discriminating between β- and δβ-thal traits. The theoretical β-thalassemia major (β-TM) birth rate in our healthcare area is calculated and contrasted with real data. A MZE technique was used for Hb A 1c measurements in 27,724 patients. Previous criteria for carrier detection were established and subsequently confirmed by molecular biology techniques. Positive predictive value (PPV) was 100.0%. The prevalence of β-thal trait (including δβ-thal) was 0.34%. The most prevalent mutations (estimated per 100,000 population) were HBB: c.118C > T (57.7%), HBB: c.93-21G>A (50.5%), HBB: c.92 + 1G > A (43.3%), HBB: c.92 + 6T > C (32.5%) and HBB: c.20delA (18.0%) for β-thalassemias, and Hb S (HBB: c.20A > T) (32.5%) and Hb J-Baltimore (HBB:c.3880T>A) (28.9%) for Hb variants. We found a paradoxical result between the theoretical β-TM birth rate and real data. We calculated an optimal Hb F/Hb A 2 index cutoff of 0.71 for discriminating between β- and δβ-thal traits. This method is highly cost-effective for detecting β-thalassemias and common Hb variants. Prevalence results match previous data for the Spanish population. Heterogeneity of mutations in Spain has markedly increased as a consequence of migration. The Hb F/Hb A 2 index cutoff could be used to predict δβ-thal trait.

Stability and function of interdomain linker variants of glucoamylase 1 from Aspergillus niger.

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Sauer, J; Christensen, T; Frandsen, T P; Mirgorodskaya, E; McGuire, K A; Driguez, H; Roepstorff, P; Sigurskjold, B W; Svensson, B

2001-08-07

Several variants of glucoamylase 1 (GA1) from Aspergillus niger were created in which the highly O-glycosylated peptide (aa 468--508) connecting the (alpha/alpha)(6)-barrel catalytic domain and the starch binding domain was substituted at the gene level by equivalent segments of glucoamylases from Hormoconis resinae, Humicola grisea, and Rhizopus oryzae encoding 5, 19, and 36 amino acid residues. Variants were constructed in which the H. resinae linker was elongated by proline-rich sequences as this linker itself apparently was too short to allow formation of the corresponding protein variant. Size and isoelectric point of GA1 variants reflected differences in linker length, posttranslational modification, and net charge. While calculated polypeptide chain molecular masses for wild-type GA1, a nonnatural proline-rich linker variant, H. grisea, and R. oryzae linker variants were 65,784, 63,777, 63,912, and 65,614 Da, respectively, MALDI-TOF-MS gave values of 82,042, 73,800, 73,413, and 90,793 Da, respectively, where the latter value could partly be explained by an N-glycosylation site introduced near the linker C-terminus. The k(cat) and K(m) for hydrolysis of maltooligodextrins and soluble starch, and the rate of hydrolysis of barley starch granules were essentially the same for the variants as for wild-type GA1. beta-Cyclodextrin, acarbose, and two heterobidentate inhibitors were found by isothermal titration calorimetry to bind to the catalytic and starch binding domains of the linker variants, indicating that the function of the active site and the starch binding site was maintained. The stability of GA1 linker variants toward GdnHCl and heat, however, was reduced compared to wild-type.

U1 small nuclear RNA variants differentially form ribonucleoprotein particles in vitro.

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Somarelli, Jason A; Mesa, Annia; Rodriguez, Carol E; Sharma, Shalini; Herrera, Rene J

2014-04-25

The U1 small nuclear (sn)RNA participates in splicing of pre-mRNAs by recognizing and binding to 5' splice sites at exon/intron boundaries. U1 snRNAs associate with 5' splice sites in the form of ribonucleoprotein particles (snRNPs) that are comprised of the U1 snRNA and 10 core components, including U1A, U1-70K, U1C and the 'Smith antigen', or Sm, heptamer. The U1 snRNA is highly conserved across a wide range of taxa; however, a number of reports have identified the presence of expressed U1-like snRNAs in multiple species, including humans. While numerous U1-like molecules have been shown to be expressed, it is unclear whether these variant snRNAs have the capacity to form snRNPs and participate in splicing. The purpose of the present study was to further characterize biochemically the ability of previously identified human U1-like variants to form snRNPs and bind to U1 snRNP proteins. A bioinformatics analysis provided support for the existence of multiple expressed variants. In vitro gel shift assays, competition assays, and immunoprecipitations (IPs) revealed that the variants formed high molecular weight assemblies to varying degrees and associated with core U1 snRNP proteins to a lesser extent than the canonical U1 snRNA. Together, these data suggest that the human U1 snRNA variants analyzed here are unable to efficiently bind U1 snRNP proteins. The current work provides additional biochemical insights into the ability of the variants to assemble into snRNPs. Copyright © 2014 Elsevier B.V. All rights reserved.

Search for second generation leptoquarks in p bar p collisions at √s=1.8 TeV

International Nuclear Information System (INIS)

Abe, F.; Albrow, M.G.; Amendolia, S.R.; Amidei, D.; Antos, J.; Anway-Wiese, C.; Apollinari, G.; Areti, H.; Atac, M.; Auchincloss, P.; Azfar, F.; Azzi, P.; Bacchetta, N.; Badgett, W.; Bailey, M.W.; Bao, J.; de Barbaro, P.; Barbaro-Galtieri, A.; Barnes, V.E.; Barnett, B.A.; Bartalini, P.; Bauer, G.; Baumann, T.; Bedeschi, F.; Behrends, S.; Belforte, S.; Bellettini, G.; Bellinger, J.; Benjamin, D.; Benlloch, J.; Bensinger, J.; Benton, D.; Beretvas, A.; Berge, J.P.; Bertolucci, S.; Bhatti, A.; Biery, K.; Binkley, M.; Bird, F.; Bisello, D.; Blair, R.E.; Blocker, C.; Bodek, A.; Bokhari, W.; Bolognesi, V.; Bortoletto, D.; Boswell, C.; Boulos, T.; Brandenburg, G.; Bromberg, C.; Buckley-Geer, E.; Budd, H.S.; Burkett, K.; Busetto, G.; Byon-Wagner, A.; Byrum, K.L.; Cammerata, J.; Campagnari, C.; Campbell, M.; Caner, A.; Carithers, W.; Carlsmith, D.; Castro, A.; Cen, Y.; Cervelli, F.; Chao, H.Y.; Chapman, J.; Cheng, M.; Chiarelli, G.; Chikamatsu, T.; Chiou, C.N.; Christofek, L.; Cihangir, S.; Clark, A.G.; Cobal, M.; Contreras, M.; Conway, J.; Cooper, J.; Cordelli, M.; Couyoumtzelis, C.; Crane, D.; Cunningham, J.D.; Daniels, T.; DeJongh, F.; Delchamps, S.; Dell'Agnello, S.; Dell'Orso, M.; Demortier, L.; Denby, B.; Deninno, M.; Derwent, P.F.; Devlin, T.; Dickson, M.; Dittmann, J.R.; Donati, S.; Drucker, R.B.; Dunn, A.; Einsweiler, K.; Elias, J.E.; Ely, R.; Engels, E. Jr.; Eno, S.; Errede, D.; Errede, S.; Fan, Q.; Farhat, B.; Fiori, I.; Flaugher, B.; Foster, G.W.; Franklin, M.; Frautschi, M.; Freeman, J.; Friedman, J.; Frisch, H.; Fry, A.; Fuess, T.A.; Fukui, Y.; Funaki, S.; Gagliardi, G.; Galeotti, S.; Gallinaro, M.; Garfinkel, A.F.; Geer, S.; Gerdes, D.W.; Giannetti, P.; Giokaris, N.; Giromini, P.; Gladney, L.; Glenzinski, D.; Gold, M.; Gonzalez, J.; Gordon, A.; Goshaw, A.T.; Goulianos, K.; Grassmann, H.; Grewal, A.; Groer, L.; Grosso-Pilcher, C.; Haber, C.; Hahn, S.R.; Hamilton, R.; Handler, R.; Hans, R.M.; Hara, K.; Harral, B.; Harris, R.M.; Hauger, S.A.

1995-01-01

We present the results of a search for second generation leptoquarks S 2 using 19.3pb -1 of data collected at the Collider Detector at Fermilab (CDF) in p bar p collisions at √s=1.8 TeV during the 1992--93 collider run. We have searched for S 2 bar S 2 pairs assuming that each leptoquark decays to a muon + quark with a branching ratio β. We find two candidate events, consistent with an expected background of 1.11±0.48. We obtain upper limits on σ(p bar p→S 2 bar S 2 )β 2 as a function of M S 2 . Using a Monte Carlo prediction for S 2 bar S 2 pair production, we exclude M S 2 2 for β=1 and M S 2 2 for β=0.5 at 95% C.L

Hb variants in Korea: effect on HbA1c using five routine methods.

Science.gov (United States)

Yun, Yeo-Min; Ji, Misuk; Ko, Dae-Hyun; Chun, Sail; Kwon, Gye Cheol; Lee, Kyunghoon; Song, Sang Hoon; Seong, Moon Woo; Park, Sung Sup; Song, Junghan

2017-07-26

Quantification of glycated hemoglobin (HbA1c) is a challenge in patients with hemoglobin (Hb) variants. We evaluated the impact of various Hb variants on five routine HbA1c assays by comparing with the IFCC reference measurement procedure (RMP). Whole blood samples showing warning flags or no results on routine HPLC HbA1c assays were confirmed for Hb variants and were submitted to HbA1c quantification using Sebia Capillarys 2 Flex Piercing, Roche Tina-quant HbA1c Gen. 2, Bio-Rad Variant II Turbo 2.0, ADAMS HA-8180, Tosoh G8 standard mode, and IFCC RMP using LC-MS. Among 114 samples, the most common variants were Hb G-Coushatta (n=47), Queens (n=41), Ube-4 (n=11), Chad (n=4), Yamagata (n=4), G-His-Tsou (n=2), G-Taipei (n=1), Fort de France (n=1), Hoshida (n=1), and two novel variants (Hb α-globin, HBA 52 Gly>Cys and Hb β-globin, HBB 146 His>Asn). In terms of control samples, all the result of HbA1c were "acceptable", within the criteria of ±7% compared to IFCC RMP target values. However, percentage of "unacceptable" results of samples with Hb variants were 16% for Capillarys 2, 7% for Tina-quant, 51% for Variant II Turbo 2.0, 95% for G8 standard mode, and 89% for HA-8180. The Capillarys 2 and HA-8180 assay did not provide the results in 5 and 40 samples with Hb variants, respectively. HbA1c results from five routine assays in patients with relatively common Hb variants in Korea showed various degrees of bias compared to those of IFCC RMP. Therefore, laboratories should be aware of the limitation of their methods with respect to interference from Hb variants found commonly in their local population and suggest an alternative HbA1c quantification method.

Análisis de una nueva variante fenotípica de distrofia del estroma corneal

OpenAIRE

Varela Conde, Yago

2016-01-01

Las distrofias corneales son un conjunto de enfermedades hereditarias de la córnea con base genética demostrable y sin afectación sistémica. Su nomenclatura y clasificación han sido revisadas recientemente, prescindiendo de ciertas patologías y agrupando las distrofias en nuevas categorías. Se ha hallado una variante fenotípica atípica con afectación del estroma corneal, por lo que sólo se han revisado las distrofias corneales localizadas a ese nivel (epiteliales-estromales y estromales). ...

Clinical application of ACMG-AMP guidelines in HNF1A and GCK variants in a cohort of MODY families.

Science.gov (United States)

Santana, L S; Caetano, L A; Costa-Riquetto, A D; Quedas, E P S; Nery, M; Collett-Solberg, P; Boguszewski, M C S; Vendramini, M F; Crisostomo, L G; Floh, F O; Zarabia, Z I; Kohara, S K; Guastapaglia, L; Passone, C G B; Sewaybricker, L E; Jorge, A A L; Teles, M G

2017-10-01

Maturity-onset diabetes of the young (MODY) is a form of monogenic diabetes with autosomal dominant inheritance. GCK -MODY and HNF1A -MODY are the prevalent subtypes. Currently, there is growing concern regarding the correct interpretation of molecular genetic findings. The American College of Medical Genetics and Genomics (ACMG) updated guidelines to interpret and classify molecular variants. This study aimed to determine the prevalence of MODY ( GCK / HNF1A ) in a large cohort of Brazilian families, to report variants related to phenotype, and to classify them according to ACMG guidelines. One hundred and nine probands were investigated, 45% with clinical suspicion of GCK -MODY and 55% with suspicion of HNF1A -MODY. Twenty-five different variants were identified in GCK gene (30 probands-61% of positivity), and 7 variants in HNF1A (10 probands-17% of positivity). Fourteen of them were novel (12- GCK /2- HNF1A ). ACMG guidelines were able to classify a large portion of variants as pathogenic (36%- GCK /86%- HNF1A ) and likely pathogenic (44%- GCK /14%- HNF1A ), with 16% (5/32) as uncertain significance. This allows us to determine the pathogenicity classification more efficiently, and also reinforces the suspected associations with the phenotype among novel variants. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Inclusive Jet Cross Section in pp Collisions at √ (s) =1.8 TeV

International Nuclear Information System (INIS)

Grinstein, S.; Mostafa, M.; Piegaia, R.; Alves, H.; Carvalho, W.; Maciel, A.K.; Motta, H. da; Oliveira, E.; Santoro, A.; Lima, J.G.; Oguri, V.; Gomez, B.; Hoeneisen, B.; Mooney, P.; Negret, J.P.; Ducros, Y.; Beri, S.B.; Bhatnagar, V.; Kohli, J.M.; Singh, J.B.; Shivpuri, R.K.; Acharya, B.S.; Banerjee, S.; Dugad, S.R.; Gupta, A.; Krishnaswamy, M.R.; Mondal, N.K.; Narasimham, V.S.; Parua, N.; Shankar, H.C.; Park, Y.M.; Choi, S.; Kim, S.K.; Castilla-Valdez, H.; Gonzalez Solis, J.L.; Hernandez-Montoya, R.; Magana-Mendoza, L.; Sanchez-Hernandez, A.; Pawlik, B.; Gavrilov, V.; Gershtein, Y.; Kuleshov, S.; Belyaev, A.; Dudko, L.V.; Ermolov, P.; Karmanov, D.; Leflat, A.; Manankov, V.; Merkin, M.; Shabalina, E.; Abramov, V.; Babintsev, V.V.; Bezzubov, V.A.; Bojko, N.I.; Burtovoi, V.S.; Chekulaev, S.V.; Denisov, S.P.; Dyshkant, A.; Eroshin, O.V.; Evdokimov, V.N.; Galyaeav, A.N.; Goncharov, P.I.; Gurzhiev, S.N.; Kostritskiy, A.V.; Kozelov, A.V.; Kozlovsky, E.A.; Mayorov, A.A.; Babukhadia, L.; Davis, K.; Fein, D.; Forden, G.E.; Guida, J.A.; James, E.; Johns, K.; Nang, F.; Narayanan, A.; Rutherfoord, J.; Shupe, M.; Aihara, H.; Barberis, E.; Chen, L.

1999-01-01

We have made a precise measurement of the central inclusive jet cross section at √ (s) =1.8 TeV . The measurement is based on an integrated luminosity of 92 pb -1 collected at the Fermilab Tevatron p p Collider with the D0 detector. The cross section, reported as a function of jet transverse energy (E T ≥ 60 GeV ) in the pseudorapidity interval | η | ≤ 0.5, is in good agreement with predictions from next-to-leading order quantum chromodynamics. copyright 1999 The American Physical Society

Prevalencia del síndrome metabólico en pobladores peruanos por debajo de 1 000 y por encima de los 3 000 msnm

Directory of Open Access Journals (Sweden)

Jaime Pajuelo

2012-04-01

Full Text Available Objetivos: Determinar y comparar la prevalencia del síndrome metabólico y de sus diferentes componentes en población adulta peruana que habita por debajo de 1 000 y por encima de 3 000 msnm. Diseño: Análisis de los datos de la Encuesta Nacional de Indicadores Nutricionales, Bioquímicos, Socioeconómicos y Culturales Relacionados a las Enfermedades Crónicas Degenerativas 2006. Institución: Instituto Nacional de Salud Centro Nacional de Alimentación y Nutrición, Ministerio de Salud, Lima, Perú. Participantes: Personas mayores de 20 años. Métodos: Se incluyó 3 384 personas mayores de 20 años, 2 425 que habitaban por debajo de 1 000 (nivel-I y 959 por encima de los 3 000 msnm (nivel-II. El síndrome metabólico fue definido de acuerdo a los criterios del National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III. Principales medidas de resultados: Prevalencia del síndrome metabólico y sus componentes. Resultados: La prevalencia de síndrome metabólico fue significativamente mayor en el nivel-I (19,7% que en el nivel-II (10,2%, p<0,001. En varones, la prevalencia fue 9,2% en el nivel-I y 5,1% en el nivel-II. En mujeres fue 29,9% en el nivel-I comparado con 15,2% en el nivel-II. La obesidad central (35,5% vs. 21,1%, elevación de presión arterial (20,9% vs. 15,0%, hiperglicemia (3,9% vs. 1,7%, hipertrigliceridemia (31,3% vs. 25,7% y concentraciones bajas de HDLc (57,4% vs. 52,5% fueron significativamente más prevalentes en el nivel-I comparado con el nivel-II (p<0,05. Los componentes del síndrome metabólico más frecuentes en los varones fueron la hipertrigliceridemia y el HDLc bajo, mientras que en las mujeres fueron la obesidad central y el HDLc disminuido. Conclusiones: El síndrome metabólico fue significativamente más prevalente en la población por debajo de los 1 000 msnm; esto podría ser resultado de la transición nutricional, demográfica y socioeconómica en esta área. Las mujeres fueron más

Enrichment of deleterious variants of mitochondrial DNA polymerase gene (POLG1) in bipolar disorder.

Science.gov (United States)

Kasahara, Takaoki; Ishiwata, Mizuho; Kakiuchi, Chihiro; Fuke, Satoshi; Iwata, Nakao; Ozaki, Norio; Kunugi, Hiroshi; Minabe, Yoshio; Nakamura, Kazuhiko; Iwata, Yasuhide; Fujii, Kumiko; Kanba, Shigenobu; Ujike, Hiroshi; Kusumi, Ichiro; Kataoka, Muneko; Matoba, Nana; Takata, Atsushi; Iwamoto, Kazuya; Yoshikawa, Takeo; Kato, Tadafumi

2017-08-01

Rare missense variants, which likely account for a substantial portion of the genetic 'dark matter' for a common complex disease, are challenging because the impacts of variants on disease development are difficult to substantiate. This study aimed to examine the impacts of amino acid substitution variants in the POLG1 found in bipolar disorder, as an example and proof of concept, in three different modalities of assessment: in silico predictions, in vitro biochemical assays, and clinical evaluation. We then tested whether deleterious variants in POLG1 contributed to the genetics of bipolar disorder. We searched for variants in the POLG1 gene in 796 Japanese patients with bipolar disorder and 767 controls and comprehensively investigated all 23 identified variants in the three modalities of assessment. POLG1 encodes mitochondrial DNA polymerase and is one of the causative genes for a Mendelian-inheritance mitochondrial disease, which is occasionally accompanied by mood disorders. The healthy control data from the Tohoku Medical Megabank Organization were also employed. Although the frequency of carriers of deleterious variants varied from one method to another, every assessment achieved the same conclusion that deleterious POLG1 variants were significantly enriched in the variants identified in patients with bipolar disorder compared to those in controls. Together with mitochondrial dysfunction in bipolar disorder, the present results suggested deleterious POLG1 variants as a credible risk for the multifactorial disease. © 2016 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.

Hexagonal perovskites with cationic vacancies. 33. Compounds of type Ba/sub 6-x/Sr/sub x/B/sub 2-y//sup 3 +/SE/sub y//sup 3 +/W/sub 3/vacantO/sub 18/

Energy Technology Data Exchange (ETDEWEB)

Lindner, I; Kemmler-Sack, S [Tuebingen Univ. (Germany, F.R.). Lehrstuhl fuer Anorganische Chemie 2

1982-12-01

In the series Ba/sub 6-x/Sr/sub x/Lu/sub 2-y/SE/sub y//sup 3 +/W/sub 3/vacantO/sub 18/ a substitution of Sr/sup 2 +/ for Ba/sup 2 +/ is possible. According to intensity calculations on powder data of BaSr/sub 5/Lu/sub 1.6/Ho/sub 0.4/W/sub 3/vacantO/sub 18/ the compounds crystallize in a rhombohedral 18 L type with the sequence (hhccc)/sub 3/; space group R-3m. The refined, intensity related R' value is 11.5%. The differences in properties (diffuse reflectance spectra, photoluminescence) between the hexagonal modifications Ba/sub 6/B/sub 2-y//sup 3 +/SE/sub y//sup 3 +/W/sub 3/vacantO/sub 18/ (B/sup 3 +/ = Gd, Y, Lu; SE/sup 3 +/ = Sm, Eu, Tb, Dy, Ho, Er, Tm) and the corresponding cubic HT modifications are discussed.

ASOCIACIÓN ENTRE NIVELES SÉRICOS DE VITAMINA D, RESPUESTA IgE Y VARIANTES GENÉTICAS DEL GEN DEL RECEPTOR DE LA VITAMINA D EN NIÑOS OBESOS DEL CARIBE COLOMBIANO: UN ESTUDIO DE CASOS Y CONTROLES

Directory of Open Access Journals (Sweden)

Eduardo A. Egea Bermejo

2016-07-01

Full Text Available

Introducción: Estudios previos han evaluado la relación entre vitamina D y atopía. En pacientes obesos es incierta esta asociación, sin embargo se acepta hoy que polimorfismos en el receptor de vitamina D pueden asociarse con obesidad. Actualmente son escasos los estudios que han buscado esta asociación en grupos en el litoral Caribe.

Objetivo: Analizar la asociación entre los polimorfismos de los SNPs del receptor de vitamina D con la susceptibilidad para obesidad, su influencia en los niveles séricos de vitamina D e IgE en una población infantil.

Metodología: Se realizó un estudio analítico de casos (n=120 y controles (n=182 con niños obesos entre los 5 y 17 años de edad, procedentes de la costa caribe colombiana. Los niveles séricos de 25(OH vitamina D e IgE Total se midieron mediante ELISA. Valores de p<0.05 fueron estadísticamente significativos.

Resultados y conclusiones: Se encontró asociación entre niveles altos de vitamina-D y obesidad infantil. El 48,3% (n=58 de los casos presentaron niveles >100 ng/mL en comparación a un 0,5% (n = 1 de los controles. Ambos grupos presentaron altos niveles de IgE, (317,07±331,5 vs. 280,6±272.7; p = 0,786. Nuestros resultados no mostraron asociación alguna entre las variantes genéticas con los niveles séricos de vitamina-D con IgE total, como tampoco con obesidad. Todos los SNPs estuvieron en equilibrio Hardy-Weingber. Nuestros resultados no muestran asociación de deficiencia de Vitamina D con obesidad en este grupo poblacional, pero sí IgE elevada en la mayoría de la población, sin tener ninguna relación entre ellos. (Rho spearman: 0,023; p = 0,641.

ASSOCIATION BETWEEN SERUM LEVELS OF VITAMIN D, IgE RESPONSE AND GENETIC VARIANTS OF THE GENE FOR VITAMIN D RECEPTOR IN OBESE CHILDREN IN THE COLOMBIAN CARIBBEAN