Derivation of induced pluripotent stem cells (iPSCs) by retroviral transduction of skin fibroblasts from four patients suffering 7q11.23 microduplication syndrome

Skin fibroblasts were obtained from four patients with 7q11.23 microduplication syndrome carrying the reciprocal rearrangement of Williams-Beuren syndrome at the 7q11.23 genomic region. Induced pluripotent stem cells (iPSCs) were generated by retroviral infection of fibroblasts with polycystronic vectors. The generated iPSC clones ESi058B, ESi057B, ESi070A and ESi071A had the 7q11.23 duplication with no additional genomic alterations, a stable karyotype, expressed pluripotency markers and could differentiate towards the three germ layers in vitro via embryoid body formation and in vivo by teratoma formation. Patient's derived iPSCs are a valuable resource for in vitro modeling of 7q11.23 microduplication syndrome

Defective minor spliceosome mRNA processing results in isolated familial growth hormone deficiency

The molecular basis of a significant number of cases of isolated growth hormone deficiency remains unknown. We describe three sisters affected with severe isolated growth hormone deficiency and pituitary hypoplasia caused by biallelic mutations in the RNPC3 gene, which codes for a minor spliceosome protein required for U11/U12 small nuclear ribonucleoprotein (snRNP) formation and splicing of U12-type introns. We found anomalies in U11/U12 di-snRNP formation and in splicing of multiple U12-type introns in patient cells. Defective transcripts include preprohormone convertases SPCS2 and SPCS3 and actin-related ARPC5L genes, which are candidates for the somatotroph-restricted dysfunction. The reported novel mechanism for familial growth hormone deficiency demonstrates that general mRNA processing defects of the minor spliceosome can lead to very narrow tissue-specific consequences.Peer reviewe

Acute Effects of Beetroot Juice Supplements on Resistance Training: A Randomized Double-Blind Crossover

The ingestion of beetroot juice (BJ) has been associated with improvements in physical performance in endurance sports, however the literature on resistance training (RT) is scarce. The aim of this study was to investigate the acute effects of BJ compared to a placebo (PLA) on muscular endurance and movement concentric velocity during RT. Twelve healthy men performed an incremental RT test (back squat and bench press) with three sets, at 60%, 70%, and 80% of their repetition maximum (1-RM). Movement velocity variables, total number of repetitions performed until concentric failure, blood lactate, and ratings of perceived effort post-training were measured. A higher number of repetitions were recorded with BJ compared to those with PLA (13.8 ± 14.4; p 0.05). Acute supplementation of BJ improved muscular endurance performance in RT

X-chromosome tiling path array detection of copy number variants in patients with chromosome X-linked mental retardation

Contiene 3 ficheros adicionales con información suplementaria.-- et al.[Background] Aproximately 5–10% of cases of mental retardation in males are due to copy number variations (CNV) on the X chromosome. Novel technologies, such as array comparative genomic hybridization (aCGH), may help to uncover cryptic rearrangements in X-linked mental retardation (XLMR) patients. We have constructed an X-chromosome tiling path array using bacterial artificial chromosomes (BACs) and validated it using samples with cytogenetically defined copy number changes. We have studied 54 patients with idiopathic mental retardation and 20 controls subjects.[Results] Known genomic aberrations were reliably detected on the array and eight novel submicroscopic imbalances, likely causative for the mental retardation (MR) phenotype, were detected. Putatively pathogenic rearrangements included three deletions and five duplications (ranging between 82 kb to one Mb), all but two affecting genes previously known to be responsible for XLMR. Additionally, we describe different CNV regions with significant different frequencies in XLMR and control subjects (44% vs. 20%).[Conclusion] This tiling path array of the human X chromosome has proven successful for the detection and characterization of known rearrangements and novel CNVs in XLMR patients.The authors thank the "Genoma España" and Genome Canada joint R+D+I projects in human health, plants and aquiculture; the former "Departament d'Universitats i Societat de la Informació" (DURSI) and the "Departament de Salut", from the Catalan Autonomous Government (2005SGR00008 - Generalitat de Catalunya); the Instituto de Salud Carlos III (PI041126, CIBER-ESP), the EU's Sixth Framework Programme [FP6-2005-LIFESCIHEALTH-7; ANEUPLOIDY No. 037627] and Fundación Areces (U-2006-FARECES-O).Peer reviewe

Perfiles de valores interpersonales y análisis de conductas y actitudes sociales de adolescentes

The aims of this study are to identify the interpersonal value profiles and analyze whether there are differences with respect to behavior and social attitude in a sample made up of 885 Compulsory Secondary Education (ESO) students (14-17 years), of whom 49.8% (n = 441) were males and 50.2% (n = 444) were females. The results show the identification of three different interpersonal value profiles corresponding to different levels of antisocial and criminal behavior. Thus the ARL-BCB (high recognition and leadership – low conformity and benevolence) group had the most antisocial and criminal behavior, low levels of social sensitivity, conformity and helpfulness-collaboration, and high levels of dominance, aggressiveness-stubbornness and apathy-isolation. Points that need to be worked on in preventive intervention of antisocial and criminal behavior of students by improving their social attitudes are highlighted.; Los objetivos de este trabajo son identificar los diferentes perfiles de valores interpersonales y analizar si entre ellos, existen diferencias respecto a la conducta y actitud social. Todo ello, en una muestra formada por 885 alumnos de Educación Secundaria (14 a 17 años), de los cuales, el 49.8% (n= 441) son hombres y el 50.2% (n = 444) mujeres. Los resultados muestran la identificación de tres perfiles de valores interpersonales diferentes, correspondiéndose con diferentes niveles de conductas delictivas y antisociales. Así, el grupo con mayor presencia de ambas conductas, antisociales y delictivas, bajos niveles de sensibilidad social, conformidad y ayuda- colaboración, y altos niveles de dominancia, agresividad-terquedad y apatía-retraimiento es el ARL-BCB (alto reconocimiento y liderazgo -baja conformidad y benevolencia-). Finalmente, se ponen de relieve los aspectos a trabajar en la intervención preventiva de las conductas antisociales y delictivas del alumnado a través de la mejora de las actitudes sociales

Essential role of the N-terminal region of TFII-I in viability and behavior

<p>Abstract</p> <p>Background</p> <p><it>GTF2I </it>codes for a general intrinsic transcription factor and calcium channel regulator TFII-I, with high and ubiquitous expression, and a strong candidate for involvement in the morphological and neuro-developmental anomalies of the Williams-Beuren syndrome (WBS). WBS is a genetic disorder due to a recurring deletion of about 1,55-1,83 Mb containing 25-28 genes in chromosome band 7q11.23 including <it>GTF2I</it>. Completed homozygous loss of either the <it>Gtf2i </it>or <it>Gtf2ird1 </it>function in mice provided additional evidence for the involvement of both genes in the craniofacial and cognitive phenotype. Unfortunately nothing is now about the behavioral characterization of heterozygous mice.</p> <p>Methods</p> <p>By gene targeting we have generated a mutant mice with a deletion of the first 140 amino-acids of TFII-I. mRNA and protein expression analysis were used to document the effect of the study deletion. We performed behavioral characterization of heterozygous mutant mice to document <it>in vivo </it>implications of TFII-I in the cognitive profile of WBS patients.</p> <p>Results</p> <p>Homozygous and heterozygous mutant mice exhibit craniofacial alterations, most clearly represented in homozygous condition. Behavioral test demonstrate that heterozygous mutant mice exhibit some neurobehavioral alterations and hyperacusis or odynacusis that could be associated with specific features of WBS phenotype. Homozygous mutant mice present highly compromised embryonic viability and fertility. Regarding cellular model, we documented a retarded growth in heterozygous MEFs respect to homozygous or wild-type MEFs.</p> <p>Conclusion</p> <p>Our data confirm that, although additive effects of haploinsufficiency at several genes may contribute to the full craniofacial or neurocognitive features of WBS, correct expression of <it>GTF2I </it>is one of the main players. In addition, these findings show that the deletion of the fist 140 amino-acids of TFII-I altered it correct function leading to a clear phenotype, at both levels, at the cellular model and at the <it>in vivo </it>model.</p

Associations between eating speed, diet quality, adiposity, and cardiometabolic risk factors

Objective: To assess the associations between eating speed, adiposity, cardiometabolic risk factors, and diet quality in a cohort of Spanish preschool-children. Study design: A cross-sectional study in 1371 preschool age children (49% girls; mean age, 4.8 ± 1.0 years) from the Childhood Obesity Risk Assessment Longitudinal Study (CORALS) cohort was conducted. After exclusions, 956 participants were included in the analyses. The eating speed was estimated by summing the total minutes used in each of the 3 main meals and then categorized into slow, moderate, or fast. Multiple linear and logistic regression models were fitted to assess the β-coefficient, or OR and 95% CI, between eating speed and body mass index, waist circumference, fat mass index (FMI), blood pressure, fasting plasma glucose, and lipid profile. Results: Compared with participants in the slow-eating category, those in the fast-eating category had a higher prevalence risk of overweight/obesity (OR, 2.9; 95% CI, 1.8-4.4; P < .01); larger waist circumference (β, 2.6 cm; 95% CI, 1.5-3.8 cm); and greater FMI (β, 0.3 kg/m2; 95% CI, 0.1-0.5 kg/m2), systolic blood pressure (β, 2.8 mmHg; 95% CI, 0.6-4.9 mmHg), and fasting plasma glucose levels (β, 2.7 mg/dL, 95% CI, 1.2-4.2 mg/dL) but lower adherence to the Mediterranean diet (β, −0.5 points; 95% CI, −0.9 to −0.1 points). Conclusions: Eating fast is associated with higher adiposity, certain cardiometabolic risk factors, and lower adherence to a Mediterranean diet. Further long-term and interventional studies are warranted to confirm these associations

Use of an orthovoltage X-ray treatment unit as a radiation research system in a small-animal cancer model

<p>Abstract</p> <p>Background</p> <p>We explore the use of a clinical orthovoltage X-ray treatment unit as a small-animal radiation therapy system in a tumoral model of cervical cancer.</p> <p>Methods</p> <p>Nude mice were subcutaneously inoculated with 5 × 10⁶HeLa cells in both lower limbs. When tumor volume approximated 200 mm³treatment was initiated. Animals received four 2 mg/kg intraperitoneal cycles (1/week) of cisplatin and/or 6.25 mg/kg of gemcitabine, concomitant with radiotherapy. Tumors were exposed to 2.5 Gy/day nominal surface doses (20 days) of 150 kV X-rays. Lead collimators with circular apertures (0.5 to 1.5 cm diameter) were manufactured and mounted on the applicator cone to restrict the X-ray beam onto tumors. X-ray penetration and conformality were evaluated by measuring dose at the surface and behind the tumor lobe by using HS GafChromic film. Relative changes in tumor volume (RTV) and a clonogenic assay were used to evaluate the therapeutic response of the tumor, and relative weight loss was used to assess toxicity of the treatments.</p> <p>Results</p> <p>No measurable dose was delivered outside of the collimator apertures. The analysis suggests that dose inhomogeneities in the tumor reach up to ± 11.5% around the mean tumor dose value, which was estimated as 2.2 Gy/day. Evaluation of the RTV showed a significant reduction of the tumor volume as consequence of the chemoradiotherapy treatment; results also show that toxicity was well tolerated by the animals.</p> <p>Conclusion</p> <p>Results and procedures described in the present work have shown the usefulness and convenience of the orthovoltage X-ray system for animal model radiotherapy protocols.</p