Search results for "abnormal"
showing 10 items of 761 documents
Metabolic and Functional Genomic Studies Identify Deoxythymidylate Kinase as a target in LKB1 Mutant Lung Cancer
2013
Abstract The LKB1/STK11 tumor suppressor encodes a serine/threonine kinase, which coordinates cell growth, polarity, motility, and metabolism. In non–small cell lung carcinoma, LKB1 is somatically inactivated in 25% to 30% of cases, often concurrently with activating KRAS mutations. Here, we used an integrative approach to define novel therapeutic targets in KRAS-driven LKB1-mutant lung cancers. High-throughput RNA interference screens in lung cancer cell lines from genetically engineered mouse models driven by activated KRAS with or without coincident Lkb1 deletion led to the identification of Dtymk, encoding deoxythymidylate kinase (DTYMK), which catalyzes dTTP biosynthesis, as synthetica…
Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus
2012
Coats plus is a highly pleiotropic disorder particularly affecting the eye, brain, bone and gastrointestinal tract. Here, we show that Coats plus results from mutations in CTC1, encoding conserved telomere maintenance component 1, a member of the mammalian homolog of the yeast heterotrimeric CST telomeric capping complex. Consistent with the observation of shortened telomeres in an Arabidopsis CTC1 mutant and the phenotypic overlap of Coats plus with the telomeric maintenance disorders comprising dyskeratosis congenita, we observed shortened telomeres in three individuals with Coats plus and an increase in spontaneous γ 3H2AX-positive cells in cell lines derived from two affected individual…
Parameter Rating by Diffusion Gradient
2014
Anomaly detection is a central task in high-dimensional data analysis. It can be performed by using dimensionality reduction methods to obtain a low-dimensional representation of the data, which reveals the geometry and the patterns that exist and govern it. Usually, anomaly detection methods classify high-dimensional vectors that represent data points as either normal or abnormal. Revealing the parameters (i.e., features) that cause detected abnormal behaviors is critical in many applications. However, this problem is not addressed by recent anomaly-detection methods and, specifically, by nonparametric methods, which are based on feature-free analysis of the data. In this chapter, we provi…
Fragile X-syndrome: literature review and report of two cases
2009
Fragile X-syndrome is caused by a mutation in chromosome X. It is one of the most frequent causes of learning disability. The most frequent manifestations of fragile X-syndrome are learning disability, different orofacial morphological alterations and an increase in testicle size. The disease is associated with cardiac malformations, joint hyperextension and behavioural alterations. We present two male patients aged 17 and 10 years, treated in our Service due to severe gingivitis. Both showed the typical facial and dental characteristics of the syndrome. In addition, we detected the presence of root anomalies such as taurodontism and root bifurcation, which had not been associated with frag…
Relaciones entre gestión corporativa y crisis financiera en el mercado de capitales español
2015
ResumenLa crisis financiera internacional impulsada por las noticias vertidas en agosto de 2007 ha tenido efectos devastadores sobre los mercados de capitales internacionales. El objetivo de este artículo se centra en verificar, en este contexto de crisis, si las empresas del mercado continuo español generan rendimientos anormales negativos, a la par que investigar qué factores ligados al gobierno corporativo podrían justificar estas anomalías. Nuestros resultados confirman que: a)cuando un mismo sujeto asume dirección ejecutiva y presidencia de la junta, en contra de todo pronóstico, ha tenido efectos beneficiosos sobre la gestión corporativa, permitiendo que esas anomalías se vayan diluye…
Congenital secretory diarrhoea caused by activating germline mutations in GUCY2C
2016
Objective Congenital sodium diarrhoea (CSD) refers to a form of secretory diarrhoea with intrauterine onset and high faecal losses of sodium without congenital malformations. The molecular basis for CSD remains unknown. We clinically characterised a cohort of infants with CSD and set out to identify disease-causing mutations by genome-wide genetic testing. Design We performed whole-exome sequencing and chromosomal microarray analyses in 4 unrelated patients, followed by confirmatory Sanger sequencing of the likely disease-causing mutations in patients and in their family members, followed by functional studies. Results We identified novel de novo missense mutations in GUCY2C, the gene encod…
“Diagnosing” the Need or in “Need” of a Diagnosis? Reconceptualizing Educational Need
2017
This chapter is based on compulsory school experiences of students diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) and their parents in the educational context of Finland. Located in the theoretical framework of Disability Studies, the chapter aims to contribute to theory of inclusive education by initiating a new dialogue on conceptual foundations of inclusive schooling. In this regard, the chapter first deconstructs the concept of educational need that stems from the field of traditional special education as contradictory to the original ideals of inclusive education. It then moves on to reconstruct the concept of educational need in accordance with the foundational values …
Is backward disequilibrium in the elderly caused by an abnormal perception of verticality? A pilot study
2007
International audience; OBJECTIVE: We hypothesised that backward disequilibrium (BD), defined by a posterior position of the centre of mass with respect to the base of support, could be caused by a backward tilt in the perception of verticality. METHODS: The relationship between BD, the perception of verticality, and the history of falls in 25 subjects aged 84.5+/-7.4 years was analysed. An original ordinal scale, the BD scale (BDS), was used to quantify BD. Postural (PV) and haptic verticals (HV) were measured in sagittal plane. RESULTS: BDS scores closely correlated with the number of falls (r = 0.81, p =10(-5)). The more the PV was tilted backward, the greater the BDS scores (r = -0.95, …
The aristaless (Arx) gene: one gene for many "interneuronopathies".
2009
The ARX (Aristaless-related (X-linked) homeobox) gene is not only present in arthropods and their ancestors, but also in vertebrates including humans (ARX orthologs). The gene is composed of 5 coding exons and it is expressed predominantly in foetal and adult brain and skeletal muscle. In this review we report on our experience and review the existing literature on the genotype and phenotype heterogeneity associated with ARX abnormalities in humans ranging from severe neuronal migration defects (e.g., lissencephaly), to mild forms of X-linked mental retardation without apparent brain abnormalities. The ARX-related disorders are reviewed focusing on their clinical features and on the role of…
Lip and oral lesions in children with Down syndrome. A controlled study
2015
Background: Down syndrome (DS) is the most common chromosomal abnormality affecting numerous organs, including the orofacial region. The objective of the present study was to assess the prevalence of lip and oral soft tissue lesions, with particular emphasize on the incidence of fissured tongue, lip fissures and angular cheilitis, among individuals with DS in Yemen. Material and Methods: This controlled cross-sectional study included 50 children with DS (6-18 years), and 50 age- and gender-matched healthy controls. The prevalence of orofacial soft tissue lesions was evaluated in both groups. Data were analyzed by Chi-square and Fisher tests, and p <0.05 was considered to be statistically si…