Molecular Characterization of NRXN1 Deletions from 19,263 Clinical Microarray Cases Identifies Exons Important for Neurodevelopmental Disease Expression

PURPOSE: The purpose of the current study was to assess the penetrance of NRXN1 deletions. METHODS: We compared the prevalence and genomic extent of NRXN1 deletions identified among 19,263 clinically referred cases to that of 15,264 controls. The burden of additional clinically relevant copy-number variations (CNVs) was used as a proxy to estimate the relative penetrance of NRXN1 deletions. RESULTS: We identified 41 (0.21%) previously unreported exonic NRXN1 deletions ascertained for developmental delay/intellectual disability that were significantly greater than in controls (odds ratio (OR) = 8.14; 95% confidence interval (CI): 2.91-22.72; P \u3c 0.0001). Ten (22.7%) of these had a second clinically relevant CNV. Subjects with a deletion near the 3\u27 end of NRXN1 were significantly more likely to have a second rare CNV than subjects with a 5\u27 NRXN1 deletion (OR = 7.47; 95% CI: 2.36-23.61; P = 0.0006). The prevalence of intronic NRXN1 deletions was not statistically different between cases and controls (P = 0.618). The majority (63.2%) of intronic NRXN1 deletion cases had a second rare CNV at a prevalence twice as high as that for exonic NRXN1 deletion cases (P = 0.0035). CONCLUSIONS: The results support the importance of exons near the 5\u27 end of NRXN1 in the expression of neurodevelopmental disorders. Intronic NRXN1 deletions do not appear to substantially increase the risk for clinical phenotypes.Genet Med 19 1, 53-61

Modeling the vacuolar storage of malate shed lights on pre- and post-harvest fruit acidity

Background: Malate is one of the most important organic acids in many fruits and its concentration plays a critical role in organoleptic properties. Several studies suggest that malate accumulation in fruit cells is controlled at the level of vacuolar storage. However, the regulation of vacuolar malate storage throughout fruit development, and the origins of the phenotypic variability of the malate concentration within fruit species remain to be clarified. In the present study, we adapted the mechanistic model of vacuolar storage proposed by Lobit et al. in order to study the accumulation of malate in pre and postharvest fruits. The main adaptation concerned the variation of the free energy of ATP hydrolysis during fruit development. Banana fruit was taken as a reference because it has the particularity of having separate growth and post-harvest ripening stages, during which malate concentration undergoes substantial changes. Moreover, the concentration of malate in banana pulp varies greatly among cultivars which make possible to use the model as a tool to analyze the genotypic variability. The model was calibrated and validated using data sets from three cultivars with contrasting malate accumulation, grown under different fruit loads and potassium supplies, and harvested at different stages. Results: The model predicted the pre and post-harvest dynamics of malate concentration with fairly good accuracy for the three cultivars (mean RRMSE = 0.25-0.42). The sensitivity of the model to parameters and input variables was analyzed. According to the model, vacuolar composition, in particular potassium and organic acid concentrations, had an important effect on malate accumulation. The model suggested that rising temperatures depressed malate accumulation. The model also helped distinguish differences in malate concentration among the three cultivars and between the pre and post-harvest stages by highlighting the probable importance of proton pump activity and particularly of the free energy of ATP hydrolysis and vacuolar pH. Conclusions: This model appears to be an interesting tool to study malate accumulation in pre and postharvest fruits and to get insights into the ecophysiological determinants of fruit acidity, and thus may be useful for fruit quality improvement. (Résumé d'auteur

Consensus recommendations on organization of care for individuals with Phelan-McDermid syndrome

The manifestations of Phelan-McDermid syndrome (PMS) are complex, warranting expert and multidisciplinary care in all life stages. In the present paper we propose consensus recommendations on the organization of care for individuals with PMS. We indicate that care should consider all life domains, which can be done within the framework of the International Classification of Functioning, Disability and Health (ICF). This framework assesses disability and functioning as the outcome of the individual's interactions with other factors. The different roles within care, such as performed by a centre of expertise, by regional health care providers and by a coordinating physician are addressed. A surveillance scheme and emergency card is provided and disciplines participating in a multidisciplinary team for PMS are described. Additionally, recommendations are provided for transition from paediatric to adult care. This care proposition may also be useful for individuals with other rare genetic neurodevelopmental disorders.</p

Tendencias de la cultura y cambio organizacional: estudio de caso

La imagen corporativa en relación con el medio se evidencia en el informe de Deloitte (2018) sobre tendencias del capital humano, en donde se reportan alrededor de 11.000 cuestionarios aplicados a gerentes de 140 países y 150 líderes de empresas colombianas, el planteamiento realizado sugiere que el capital social cobra tanto importancia como el físico y el financiero. Estos aspectos están relacionados con la identidad corporativa y cómo se relaciona a su vez con la cultura y la gestión del en la organización. La cultura y la gestión del cambio han cobrado mucho interés para las personas que guían las organizaciones, los estudios realizados por Deloitte en 2017 se focalizaron en la relación de la cultura y el compromiso como elementos importantes del empleado; los resultados del estudio dejan en evidencia cómo la habilidad de las organizaciones para afrontar inconvenientes de compromiso y cultura tenían una reducción del 14% con respecto al año anterior, estos datos permiten entender la complejidad del ambiente en el ámbito laboral y dan cuenta de la importancia de desarrollar conocimiento válido que oriente a académicos y empresarios para que puedan abordar de una manera adecuada estos aspectos.1a edició

High resolution investigation of the 26Mg(p,p)26Mg reaction

Differential cross sections for elastic scattering of protons on 26Mg in the Ep = 1–2 MeV region, were measured with surface barrier counters at four angles. In this energy range 42 26Mg(p, γ) 27Al resonances are known. Of 19 (p, γ) resonances the corresponding 26Mg(p,p) 26Mg resonance was also observed; three (p,p) resonances were found which had no (p, γ) counterpart. The measured widths range from 6 keV down to 6 eV. The spins of 14 of these resonances and the proton orbital momenta of 20 resonances could be determined unambiguously. Partial widths for proton and γ-ray emission are computed from the observed widths and the (p, γ) yields. Upper limits are given for the widths of unobserved resonances

High resolution investigation of the 26Mg(p,p)26Mg reaction

Differential cross sections for elastic scattering of protons on 26Mg in the Ep = 1–2 MeV region, were measured with surface barrier counters at four angles. In this energy range 42 26Mg(p, γ) 27Al resonances are known. Of 19 (p, γ) resonances the corresponding 26Mg(p,p) 26Mg resonance was also observed; three (p,p) resonances were found which had no (p, γ) counterpart. The measured widths range from 6 keV down to 6 eV. The spins of 14 of these resonances and the proton orbital momenta of 20 resonances could be determined unambiguously. Partial widths for proton and γ-ray emission are computed from the observed widths and the (p, γ) yields. Upper limits are given for the widths of unobserved resonances

The isobaric analogue state in 31P of the 3.13 MeV level in 31Si

The differential cross section for elastic scattering of protons on 30Si was measured with surface barrier counters at four angles. The Ep = 2187 keV resonance known from 30Si((p,γ)31P was observed in the 30Si(p,p)30Si reaction and the parity, the proton width and the reduced proton width were determined. A confirmation of the f-wave character was obtained. The resonance level in 31P was identified as the analogue state of the 3.13 MeV level in 31Si. The observed reduced width is in accord with this assumption