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Search Results: 1 - 10 of 285 matches for " Onofre Combarros "
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The synergy factor: a statistic to measure interactions in complex diseases
Mario Cortina-Borja, A David Smith, Onofre Combarros, Donald J Lehmann
BMC Research Notes , 2009, DOI: 10.1186/1756-0500-2-105
Abstract: The synergy factor (SF) allows assessment of binary interactions in case-control studies. In this paper we describe its properties and its novel characteristics, e.g. in calculating the power to detect a synergistic effect and in its application to meta-analyses. We illustrate these functions with real examples in Alzheimer's disease, e.g. a meta-analysis of the potential interaction between a BACE1 polymorphism and APOE4: SF = 2.5, 95% confidence interval: 1.5–4.2; p = 0.0001.Synergy factors are easy to use and clear to interpret. Calculations may be performed through the Excel programmes provided within this article. Unlike logistic regression analysis, the method can be applied to datasets of any size, however small. It can be applied to primary or summarised data, e.g. published data. It can be used with any type of susceptibility factor, provided the data are dichotomised. Novel features include power estimation and meta-analysis.The remarkable progress made in the understanding of single-cause diseases has not yet been matched in the study of complex conditions. One problem is that susceptibility factors, e.g. genetic and environmental, all contribute risk that is to varying extents contingent on the presence of other factors [1-4]. Complex diseases cannot therefore be simply seen as due to the accumulation of many small independent effects. Rather, their very complexity lies in the interactions between contingent effects. Important effects may thus be missed if only single factors are independently examined (Discussion). The study of interactions between risk factors is thus central to the study of complex diseases.Yet, unravelling interactions has proved confusing (Discussion). There is a need for a readily accessible method of measuring their strength, available to non-statisticians and applicable to summarised data and to datasets of any size. Methods are also needed to calculate the power to detect an interaction and to perform meta-analyses of interactio
Riesgos competitivos de muerte y equilibrio de Hardy-Weinberg en estudios de casos y controles sobre asociación entre genes y enfermedades
Llorca,Javier; Prieto-Salceda,Dolores; Combarros,Onofre; Dierssen-Sotos,Trinidad; Berciano,José;
Gaceta Sanitaria , 2005, DOI: 10.1590/S0213-91112005000400009
Abstract: objective: to study the impact of competing risks on hardy-weinberg equilibrium and their consequences in case-control studies of gene-late onset disease association. methods: based on a population born in hardy-weinberg equilibrium for a particular gene, the genetic composition when the gene is associated with a lethal early-onset disease and its consequences on a late-onset disease can be deduced. odds ratios estimates are unbiased in case-control studies when controls are sampled by density, even if the controls are in hardy-weinberg disequilibrium. results: an example in which a mutant gene is associated with early mortality is presented, producing a departure from hardy-weinberg equilibrium; as a result, controls in later ages are in disequilibrium, producing an odds ratio equal to 1.61. conclusion: although the main causes of hardy-weinberg disequilibrium in controls are selection bias or genotyping error, a competing risk of death associated with the mutant gene would also result in hardy-weinberg disequilibrium among controls.
Detection of early Alzheimer's disease in MCI patients by the combination of MMSE and an episodic memory test
Ana Pozueta, Eloy Rodríguez-Rodríguez, José Vazquez-Higuera, Ignacio Mateo, Pascual Sánchez-Juan, Soraya González-Perez, José Berciano, Onofre Combarros
BMC Neurology , 2011, DOI: 10.1186/1471-2377-11-78
Abstract: All patients underwent a complete clinical and neuropsychological evaluation at baseline and every 6 months during a two-year follow-up period, with 54 out of 109 MCI patients progressing to dementia (50 of them progressed to AD dementia), and 55 remaining as stable MCI (S-MCI).A combination of MMSE and California Verbal Learning Test Long Delayed Total Recall (CVLT-LDTR) constituted the best predictive model: subjects scoring above 26/30 on MMSE and 4/16 on CVLT-LDTR had a negative predictive value of 93.93% at 2 years, whereas those subjects scoring below both of these cut-off scores had a positive predictive value of 80.95%.Pr-AD might be distinguished from S-MCI at baseline using the combination of MMSE and CVLT-LDTR. These two neuropsychological predictors are relatively brief and may be readily completed in non-specialist clinical settings.Different biomarkers have been thoroughly studied in order to establish which ones best predict the progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia. With current evidence, medial temporal lobe and hippocampal atrophy on MRI, glucose metabolism reduction measured by FDG-PET and CSF biomarkers reflecting AD pathology, are useful in detecting prodromal AD (Pr-AD) patients [1]. Nevertheless, these new biomarkers are still not universally available in routine clinical practice. A neuropsychological profile differentiating Pr-AD from stable MCI (S-MCI) has been investigated, and episodic memory impairment seems to be a strong predictor of progression to dementia [2-4], although it is not specific as some patients will not develop AD. Impairment in other cognitive domains (executive function and language) has been described in Pr-AD, but there are discrepancies about which additional impaired area will most improve sensitivity and specificity for detecting Pr-AD [5-7]. We aim to investigate the clinical variables and neuropsychological measures at the moment of MCI diagnosis, which will better
No association of CDK5 genetic variants with Alzheimer's disease risk
José Vázquez-Higuera, Ignacio Mateo, Pascual Sánchez-Juan, Eloy Rodríguez-Rodríguez, Jon Infante, José Berciano, Onofre Combarros
BMC Medical Genetics , 2009, DOI: 10.1186/1471-2350-10-68
Abstract: We examined genetic variations of CDK5 by genotyping haplotype tagging SNPs (htSNPs) (rs9278, rs2069459, rs891507, rs2069454, rs1549759 and rs2069442) in a group of 408 Spanish AD cases and 444 controls.There were no differences in the genotypic, allelic or haplotypic distributions between cases and controls in the overall analysis or after stratification by APOE ε4 allele.Our negative findings in the Spanish population argue against the hypothesis that CDK5 genetic variations are causally related to AD risk. Still, additional studies using different sets of patients and control subjects deserve further attention, since supporting evidence for association between CDK5 gene and AD risk in the Dutch population exists.One of the neuropathological hallmarks in Alzheimer's disease (AD) is the presence of neurofibrillary tangles, which are composed of the microtubule-binding protein tau that is hyperphosphorylated [1]. Cyclin-dependent kinase 5 (CDK5) has been implicated as one of the major protein kinases involved in the abnormal hyperphosphorylation of tau in AD [2], the activity of CDK5 has been shown to be higher in the prefrontal cortex of AD brains [3], and CDK5 has been described to be associated with all stages of neurofibrillary pathology in AD brains [4]. In addition, transgenic mice overexpressing CDK5 show a dramatic increase in hyperphosphorylated, aggregated tau [5]. CDK5 is an interesting genetic target for association analysis of AD, and there are data available from 5 independent samples [6-9]. To facilitate comparisons with the Rotterdam Study that found a specific CDK5 haplotype influencing the risk for AD in a Dutch population, we examined the haplotype tagging SNPs identified by Arias-Vásquez et al. [8] (rs2069442, rs2069454, rs891507, rs2069459, and rs9278) and one additional htSNP (rs1549759), covering the complete genomic region of CDK5, in a large series of Spanish AD cases and controls.The study included 408 AD patients (66% women; mean age at th
Genetic variation in the tau protein phosphatase-2A pathway is not associated with Alzheimer's disease risk
José L Vázquez-Higuera, Ignacio Mateo, Pascual Sánchez-Juan, Eloy Rodríguez-Rodríguez, Ana Pozueta, Miguel Calero, José L Dobato, Ana Frank-García, Fernando Valdivieso, José Berciano, Maria J Bullido, Onofre Combarros
BMC Research Notes , 2011, DOI: 10.1186/1756-0500-4-327
Abstract: In a group of 729 Spanish late-onset Alzheimer's disease (AD) patients and 670 healthy controls, we examined variations into a set of candidate genes (PPP2CA, PPP2R2A, ANP32A, LCMT1, PPME1 and PIN1) in the tau protein phosphatase-2A (PP2A) pathway, to address hypotheses of genetic variation that might influence AD risk.There were no differences in the genotypic, allelic or haplotypic distributions between cases and controls in the overall analysis or after stratification by age, gender or APOE ε4 allele.Our negative findings in the Spanish population argue against the hypothesis that genetic variation in the tau protein phosphatase-2A (PP2A) pathway is causally related to AD riskOne of the neuropathological hallmarks in Alzheimer's disease (AD) is neurofibrillary tangles (NFTs), which are composed of the microtubule-binding protein tau that is hyperphosphorylated [1]. Tau phosphorylation is catalysed by tau protein kinases and reversed by tau protein phosphatases [2]. It has been reported that the expression and activity of the major tau phosphatase in human brain, protein phosphatase-2A (PP2A), is decreased in the affected areas of AD brain [3,4], suggesting that a downregulation of tau phosphatases in AD brain might underlie the abnormal hyperphosphorylation of tau. The overall PP2A activity is determined by composition of the holoenzyme from the catalytic subunit alpha (PP2CA) and the regulatory subunit B alpha (PP2R2A), the level of PP2A inhibitors such as ANP32A (inhibitor-1 of protein phosphatase-2A), and changes in PP2A methylation regulated by the leucine carboxyl methytransferase-1 (LCMT1) and the protein phosphatase methylesterase-1 (PPME1); in addition, the peptidyl-prolyl cis/trans isomerase PIN1 induces conformational changes in tau that can facilitate tau dephosphorylation by PP2A (Figure 1). Consequently, PPP2CA, PPP2R2A, ANP32A, LCMT1, PPME1 and PIN1 are good candidate genes for the analysis of AD susceptibility. The largest genome wide association (
DYRK1A genetic variants are not linked to Alzheimer's disease in a Spanish case-control cohort
José Vázquez-Higuera, Pascual Sánchez-Juan, Eloy Rodríguez-Rodríguez, Ignacio Mateo, Ana Pozueta, Ana Frank, Isabel Sastre, Fernando Valdivieso, José Berciano, María J Bullido, Onofre Combarros
BMC Medical Genetics , 2009, DOI: 10.1186/1471-2350-10-129
Abstract: We examined genetic variations of DYRK1A by genotyping haplotype tagging SNPs (htSNPs) (rs11701483, rs2835740, rs1137600, rs2835761, rs2835762, rs2154545 and rs8132976) in a group of 634 Spanish AD cases and 733 controls.There were no differences in the genotypic, allelic or haplotypic distributions between cases and controls in the overall analysis or after stratification by APOE ε4 allele.Our negative findings in the Spanish population argue against the hypothesis that DYRK1A genetic variations are causally related to AD risk. Still, additional studies using different sets of patients and control subjects deserve further attention, since supporting evidence for association between DYRK1A gene and AD risk in the Japanese population exists.Abnormal tau hyperphosphorylation has been suggested as being one of the central events in the development of neurofibrillary tangles (NFTs), which are one of the characteristic neuropathological lesions found in Alzheimer's disease (AD) brains [1]. Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) phosphorylates tau in vitro at the Thr212 residue [2], which is hyperphosphorylated in AD brains, and a significant increase in the amount of phosphor-Thr212-tau is also found in the brains of transgenic mice that overexpress human DYRK1A [3]. In addition, transgenic mice bearing a triple tau mutation and expressing hyperphosphorylated tau in neurons of the hippocampus and neocortex show increased expression of DYRK1A in individual neurons in the same regions [4]. Moreover, DYRK1A accumulates in NFTs in brains of subjects with sporadic AD and in subjects with trisomy of chromosome 21 and Down syndrome (DS) [5]. The increase dosage of DYRK1A in DS brain due to trisomy of chromosome 21 correlates to an increase in three microtubule-binding domain repeats-tau level [6], which on abnormal hyperphosphorylation and aggregation of tau results in neurofibrillary degeneration [7]. All this data postulates a role for DYRK1A a
Caspase-1 genetic variation is not associated with Alzheimer's disease risk
José Vázquez-Higuera, Eloy Rodríguez-Rodríguez, Pascual Sánchez-Juan, Ignacio Mateo, Ana Pozueta, Ana Martínez-García, Ana Frank, Fernando Valdivieso, José Berciano, María J Bullido, Onofre Combarros
BMC Medical Genetics , 2010, DOI: 10.1186/1471-2350-11-32
Abstract: We examined genetic variations of CASP1 by genotyping haplotype tagging SNPs (htSNPs) (rs501192, rs556205 and rs530537) in a group of 628 Spanish AD cases and 722 controls.There were no differences in the genotypic, allelic or haplotypic distributions between cases and controls in the overall analysis or after stratification by age, gender or APOE ε4 allele.Our negative findings in the Spanish population argue against the hypothesis that CASP1 genetic variations are causally related to AD risk.A chronic inflammatory process might contribute to the neurodegeneration associated with Alzheimer's disease (AD), by overexpression of cytokines, such as interleukin-1 (IL-1), and other inflammatory molecules in activated microglia surrounding amyloid plaques [1]. Increased expression of IL-1 in AD has been implicated in the formation of amyloid plaques and neurofibrillary tangles, the spread of these neuropathological lesions across cerebral cortical regions, and the accompanying neuronal cell injury and loss [2]. The predominant β isoform of IL-1 is generated from an inactive precursor through the action of caspase-1 (CASP1), a cystein protease formerly called IL-1β converting enzyme (ICE), and CASP1 expression appears to be significantly increased in post-mortem brain tissue from patients with AD [3-5]. In addition, CASP1 messenger RNA expression has been closely associated with neurofibrillary tangle and, to a lesser extent, amyloid plaque density [4]. Several studies have reported associations between IL-1β genetic polymorphisms and AD, but findings from different studies have been controversial [6]. Although genetic markers of the CASP1 region were not found associated to AD in recent genome-wide association studies [7-10], Blankenberg et al. [11] sequenced the CASP1 gene in a case-control study of myocardial infarction (MI), and found that CASP1 genetic variation is associated with cardiovascular risk. The present study investigated the genetic variability of the CASP1
Replication by the Epistasis Project of the interaction between the genes for IL-6 and IL-10 in the risk of Alzheimer's disease
Onofre Combarros, Cornelia M van Duijn, Naomi Hammond, Olivia Belbin, Alejandro Arias-Vásquez, Mario Cortina-Borja, Michael G Lehmann, Yurii S Aulchenko, Maaike Schuur, Heike K?lsch, Reinhard Heun, Gordon K Wilcock, Kristelle Brown, Patrick G Kehoe, Rachel Harrison, Eliecer Coto, Victoria Alvarez, Panos Deloukas, Ignacio Mateo, Rhian Gwilliam, Kevin Morgan, Donald R Warden, A David Smith, Donald J Lehmann
Journal of Neuroinflammation , 2009, DOI: 10.1186/1742-2094-6-22
Abstract: We examined this interaction in the Epistasis Project, a collaboration of 7 AD research groups, contributing DNA samples from 1,757 cases of AD and 6,295 controls.We replicated the interaction. For IL6 rs2069837 AA × IL10 rs1800871 CC, the synergy factor (SF) was 1.63 (95% confidence interval: 1.10–2.41, p = 0.01), controlling for centre, age, gender and apolipoprotein E ε4 (APOEε4) genotype. Our results are consistent between North Europe (SF = 1.7, p = 0.03) and North Spain (SF = 2.0, p = 0.09). Further replication may require a meta-analysis. However, association due to linkage disequilibrium with other polymorphisms in the regulatory regions of these genes cannot be excluded.We suggest that dysregulation of both IL-6 and IL-10 in some elderly people, due in part to genetic variations in the two genes, contributes to the development of AD. Thus, inflammation facilitates the onset of sporadic AD.Alzheimer's disease (AD) is accompanied by a chronic inflammatory process, including activation of microglia and astrocytes that express pro-inflammatory cytokines [1,2]. It is unclear to what extent this inflammation is a reaction to the pathology of AD, and to what extent it contributes to the onset or progression of the disease.Two multi-functional cytokines, interleukin-6 (IL-6) and interleukin-10 (IL-10), may be relevant to this question. IL-6 is a potent pro-inflammatory cytokine [3], while IL-10 acts to limit inflammation in the brain [4]. Both are produced by activated microglia and astrocytes [3,4]. Two single nucleotide polymorphisms (SNPs), rs1800795 (-174G/C) and rs1800896 (-1082G/A), in the regulatory regions of the genes, IL6 and IL10, respectively, have been widely studied. However, the ongoing AlzGene meta-analyses of the two SNPs [5]http://www.alzforum.org/res/com/gen/alzgene/ webcite are both currently negative (4 July 2009): pooled odds ratios for Caucasians in single-locus analyses of IL6-174C versus G alleles = 0.93 (95% confidence interval: 0.79–1.08,
Behavior of the Fungus Colletotrichum gloeosporioides (Penz & Sacc.), Which Causes Bitter Rot in Apples after Harvesting  [PDF]
Sideney Becker Onofre, Dirlane Antoniazzi
Advances in Microbiology (AiM) , 2014, DOI: 10.4236/aim.2014.44026
Abstract:

The apple is the second most important fruit in Brazil. However, apple cultivars are susceptible to several diseases that can cause losses after harvesting. Bitter rot is caused by the fungus Colletotrichum gloeosporioides and is one of the most damaging summer diseases. The goal of this work was to evaluate the behavior of this fungus in four apple cultivars grown in Brazil (Fuji, Gala, Golden and Green) under two treatments: direct inoculation and isolated fungus. The fungus was isolated by taking fragments from infected fruits, which were stored on Potato Dextrose Agar (PDA) in a laboratory. For the direct treatment, the fungus was removed from infected fruits and directly inoculated into healthy fruits. After inoculation, the fruits were kept at room temperature and the halos of degradation were evaluated every 48 hours. The results demonstrated that direct inoculation was more pathogenic, that the Gala cultivar was the most resistant to the pathogen, and that the Golden cultivar was the most susceptible.

Al compás de la revolución Interactiva: Un mundo de conexiones
Onofre,Elena;
Cuadernos del Centro de Estudios en Dise?±o y Comunicaci?3n. Ensayos , 2012,
Abstract: the impact produced by interactive revolution in the current scenario is equivalent to that produced by the industrial revolution, the advent of the printing press or the copernican revolution. the big difference between these events that have led to changes in paradigm and worldview in history is that the interactive revolution in society has been installed in just two decades, while the penetration of industrialism, mass and access to the printed word, and further, the acceptance of the copernican theory, needed dozens of generations to anchor in society. the signals that characterize the stage dominated by information technology and communication, are a constant and sustained pressure on the model of the professional field approach proposed by academic institutions.in this scenario dominated by multi-directional communication and multitasking colaborative audiences, institutional dynamics should take the "rythm" demanded by a society governed by the giddiness of disposal.we need to be continuously informed about many subjects and this forces us to provide new meanings not only to the objects of consumption, but to what we do as professionals.
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