Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus.

Both obesity and being underweight have been associated with increased mortality. Underweight, defined as a body mass index (BMI) ≤ 18.5 kg per m(2) in adults and ≤ -2 standard deviations from the mean in children, is the main sign of a series of heterogeneous clinical conditions including failure to thrive, feeding and eating disorder and/or anorexia nervosa. In contrast to obesity, few genetic variants underlying these clinical conditions have been reported. We previously showed that hemizygosity of a ∼600-kilobase (kb) region on the short arm of chromosome 16 causes a highly penetrant form of obesity that is often associated with hyperphagia and intellectual disabilities. Here we show that the corresponding reciprocal duplication is associated with being underweight. We identified 138 duplication carriers (including 132 novel cases and 108 unrelated carriers) from individuals clinically referred for developmental or intellectual disabilities (DD/ID) or psychiatric disorders, or recruited from population-based cohorts. These carriers show significantly reduced postnatal weight and BMI. Half of the boys younger than five years are underweight with a probable diagnosis of failure to thrive, whereas adult duplication carriers have an 8.3-fold increased risk of being clinically underweight. We observe a trend towards increased severity in males, as well as a depletion of male carriers among non-medically ascertained cases. These features are associated with an unusually high frequency of selective and restrictive eating behaviours and a significant reduction in head circumference. Each of the observed phenotypes is the converse of one reported in carriers of deletions at this locus. The phenotypes correlate with changes in transcript levels for genes mapping within the duplication but not in flanking regions. The reciprocal impact of these 16p11.2 copy-number variants indicates that severe obesity and being underweight could have mirror aetiologies, possibly through contrasting effects on energy balance.

Alteración del centro de gravedad y riesgo de caída en pacientes con trastornos neurológicos. Bogotá. 2014

Introducción: el objetivo de la rehabilitación en los pacientes neurológicos es reducir su discapacidad, potencializar su funcionalidad y promover su independencia para así permitirle desempeñar un rol activo en la comunidad. Por esta razón, es de gran importancia prevenir la aparición de eventos adversos en esta población mediante la detección temprana de factores de riesgo que conllevan a pacientes con enfermedad cerebro vascular a presentar caídas y a su vez le permita a los profesionales de la salud generar estrategias para minimizar su incidencia, complicaciones y/o secuelas. Objetivo: determinar los factores relacionados con la alteración del centro de gravedad y riesgos de caída en paciente con trastornos neurológicos Metodología: se realizó un estudio cuantitativo descriptivo exploratorio retrospectivo donde se tuvieron en cuenta pacientes diagnóstico de enfermedades neurológicas que presentaron o no antecedentes de caídas junto con otros criterios de inclusión y exclusión, tomados de las bases de datos de la institución Mobility Group. Resultados: Se evaluaron en total 19 sujetos (52,6 % hombres) con edad media de 48,37 años. Se clasificaron en dos grupos (alto y bajo riesgo de caída ) de pacientes según la aplicación de la escala de riesgo de caída de J.H. Downton a los cuales se aplicó estadística descriptiva para describir su comportamiento en referencia a factores como diagnóstico clínico, presencia de dolor, fuerza y tono de miembros inferiores en los principales grupos musculares , clasificación de espasticidad y finalmente con la alteración de la trayectoria del centro de gravedad según la valoración realizada con el dispositivo THERA-TRAINER BALANCE.

Deletion 5q12: Delineation of a Phenotype Including Mental Retardation and Ocular Defects

Array-CGH enables the detection of submicroscopic chromosomal deletions and duplications and leads to an accurate delineation of the imbalances, raising the possibility of correlating genotype to phenotype and mapping minimal critical regions associated with particular patterns of clinical features. We report here on four patients sharing common clinical features (psychomotor retardation, coarse facies and ocular anomalies), with proximal 5q deletions identified by oligo array-CGH. The deletions range from 5.75 to 17.26-Mb in size and occurred de novo. A common 2.63-Mb region between the deletions described here can be defined in 5q12.1 (59,390,122-62,021,754 bp bp from 5pter, hg18) and includes 12 genes. Among them, KIF2A, which encodes a kinesin superfamily protein, is a particularly interesting candidate for the phenotype, as it suppresses the growth of axonal collateral branches and is involved in normal brain development. Ocular defects, albeit unspecific, seem to be common in the 5q12.1 deletion. Identification of additional cases of deletions involving the 5q12.1 region will allow more accurate genotype-phenotype correlations. (C) 2011 Wiley-Liss, Inc.

Metamorphic and geochronogical study of the Triassic El Oro metamorphic complex, Ecuador: Implications for high-temperature metamorphism in a forearc zone

In the forearc of the Andean active margin in southwest Ecuador, the El Oro metamorphic complex exhibits a well exposed tilted forearc section partially migmatized. We used Raman spectroscopy on carbonaceous matter (RSCM) thermometry and pseudosections coupled with mineralogical and textural studies to constrain the pressure–temperature (P–T) evolution of the El Oro metamorphic complex during Triassic times. Our results show that anatexis of the continental crust occurred by white-mica and biotite dehydration melting along a 10 km thick crustal domain (from 4.5 to 8 kbar) with increasing temperature from 650 to 700 °C. In the biotite dehydration melting zone, temperature was buffered at 750–820 °C in a 5 km thick layer. The estimated average thermal gradient during peak metamorphism is of 30 °C/km within the migmatitic domain can be partitioned into two apparent gradients parts. The upper part from surface to 7 km depth records a 40–45 °C/km gradient. The lower part records a quasi-adiabatic geotherm with a 10 °C/km gradient consistent with an isothermal melting zone. Migmatites U–Th–Pb geochronology yielded zircon and monazite ages of 229.3 ± 2.1 Ma and 224.5 ± 2.3 Ma, respectively. This thermal event generated S-type magmatism (the Marcabeli granitoid) and was immediately followed by underplating of the high-pressure low-temperature (HP-LT) Arenillas–Panupalí unit at 225.8 ± 1.8 Ma. The association of high-temperature low-pressure (HT-LP) migmatites with HP-LT unit constitutes a new example of a paired metamorphic belt along the South American margin. We propose that in addition to crustal thinning, underplating of the Piedras gabbroic unit before 230 Ma provided the heat source necessary to foster crustal anatexis. Furthermore, its MORB signature shows that the asthenosphere was involved as the source of the heat anomaly. S-type felsic magmatism is widespread during this time and suggests that a large-scale thermal anomaly affected a large part of the South American margin during the late Triassic. We propose that crustal anatexis is related to an anomaly that arose during subduction of the Panthalassa ocean under the South American margin. Slab verticalization or slab break-off can be invoked as the origin of the upwelling of the asthenosphere.

Eclipses, razón y superstición en las vidas de Nicias y Dión de Plutarco

A partir de un abordaje retórico-literario, nuestro objetivo es indagar las representaciones discursivas de los elementos supersticiosos en la biografía de Nicias y en la de Dión. Tomaremos como ejemplo el eclipse de luna narrado en Nicias 23 y reiterado en Dión 24, para demostrar que mediante la repetición del ejemplo en dos contextos distintos Plutarco nos invita a reflexionar sobre la superstición de un modo más atractivo que la mera exposición teórica de doctrinas filosóficas.