Novel Compound Heterozygous Mutations Expand the Recognized Phenotypes of \u3cem\u3eFARS2\u3c/em\u3e-linked Disease

Mutations in mitochondrial aminoacyl-tRNA synthetases are an increasingly recognized cause of human diseases, often arising in individuals with compound heterozygous mutations and presenting with system-specific phenotypes, frequently neurologic. FARS2 encodes mitochondrial phenylalanyl transfer ribonucleic acid (RNA) synthetase (mtPheRS), perturbations of which have been reported in 6 cases of an infantile, lethal disease with refractory epilepsy and progressive myoclonus. Here the authors report the case of juvenile onset refractory epilepsy and progressive myoclonus with compound heterozygous FARS2 mutations. The authors describe the clinical course over 6 years of care at their institution and diagnostic studies including electroencephalogram (EEG), brain magnetic resonance imaging (MRI), serum and cerebrospinal fluid analyses, skeletal muscle biopsy histology, and autopsy gross and histologic findings, which include features shared with Alpers-Huttenlocher syndrome, Leigh syndrome, and a previously published case of FARS2 mutation associated infantile onset disease. The authors also present structure-guided analysis of the relevant mutations based on published mitochondrial phenylalanyl transfer RNA synthetase and related protein crystal structures as well as biochemical analysis of the corresponding recombinant mutant proteins

Erratum to: Delta rhythmicity is a reliable EEG biomarker in Angelman syndrome: a parallel mouse and human analysis

After publication of our article [1], we became aware that there were two minor data loading and analysis scripting errors in the human EEG data processing pipeline. These errors affected the channel loading/grouping and sleep/ wake coding of EEG data. We have re-analysed all the data affected by these errors. The errors do not affect any interpretations or conclusions, thus no changes to the text are required apart from correcting p values and raw values affected by the errors. There are no changes to statistical significance or lack-thereof. The errors affect data presented in Fig. 3, Fig. 4, Fig. 5, and Additional file 3: Figure S3 and thus we have re-plotted these figures (see below)

Power Line Arbitrary Waveform Generator

Import 05/08/2014Tato bakalářská práce je zaměřena na generování libovolných průběhů napájecích napětí a simulaci poruchových stavů zdroje Kikusui PCR 1000 LA. V práci jsem se věnoval jak teoretickému popisu, tak praktickým zapojením a programování napájecích průběhů. V závěru jsem zhodnotil dosažené výsledky.This work is focused on generating abitrary waveform supply voltages and simulation of fault conditions Kikusui PCR 1000 LA. In my work I paid attention to theoretical description, practical wiring and programming of the supply waveforms. In the end, I reviewed the results.460 - Katedra informatikyvýborn

Cuesta 0 : Guy Blackburn, Claudine Cotton, Ronald Thibert, Yves Tremblay

In a book characterized by an elaborate presentation (punctured rice paper and oculus, cardboard separators and fold-outs), the works of four Saguenay-based artists are assembled in the context of a two-year project that explores our relationship to territorial environment. Harvey studies the impact of modes of presentation on the reception of art works, while Sioui Durand expounds how the artist's book functions as a non social strategy. With texts by and about the artists. Biographical notes. 1 bibl. ref

Identification of a distinct developmental and behavioral profile in children with Dup15q syndrome.

BackgroundOne of the most common genetic variants associated with autism spectrum disorder (ASD) are duplications of chromosome 15q11.2-q13.1 (Dup15q syndrome). To identify distinctive developmental and behavioral features in Dup15q syndrome, we examined the social communication, adaptive, and cognitive skills in clinic-referred subjects and compared the characteristics of children with Dup15q syndrome to age/IQ-matched children with non-syndromic ASD. Behavior and development were also analyzed within the Dup15q group for differences related to copy number or epilepsy.MethodsParticipants included 13 children with Dup15q syndrome and 13 children with non-syndromic ASD, matched on chronological and mental age, ages 22 months-12 years. In the Dup15q group, ten participants had isodicentric and three had interstitial duplications. Four children had active epilepsy (all isodicentric). Participants were assessed for verbal and non-verbal cognition, ASD characteristics based on the Autism Diagnostic Observation Schedule (ADOS), and adaptive function based on the Vineland Adaptive Behavior Scales (VABS). Group comparisons were performed between Dup15q and ASD participants, as well as within the Dup15q group based on duplication type and epilepsy status.ResultsAll children with Dup15q syndrome met the criteria for ASD; ASD severity scores were significantly lower than children in the non-syndromic ASD group. ADOS profiles demonstrated a relative strength in items related to social interest. Children with Dup15q syndrome also demonstrated significantly more impairment in motor and daily living skills. Within the Dup15q group, children with epilepsy demonstrated significantly lower cognitive and adaptive function than those without epilepsy.ConclusionsThe relative strength observed in social interest and responsiveness in the context of impaired motor skills represents an important avenue for intervention, including aggressive treatment of epilepsy, early and consistent focus on motor skills, and intervention targeting joint attention and language within a play context, in order to build on social interest to further develop social communication abilities. Longitudinal research beginning in early development will elucidate the temporal relationships between developmental domains and neurological comorbidities in these children at high risk for neurodevelopmental disorders

Identification of a distinct developmental and behavioral profile in children with Dup15q syndrome.

BackgroundOne of the most common genetic variants associated with autism spectrum disorder (ASD) are duplications of chromosome 15q11.2-q13.1 (Dup15q syndrome). To identify distinctive developmental and behavioral features in Dup15q syndrome, we examined the social communication, adaptive, and cognitive skills in clinic-referred subjects and compared the characteristics of children with Dup15q syndrome to age/IQ-matched children with non-syndromic ASD. Behavior and development were also analyzed within the Dup15q group for differences related to copy number or epilepsy.MethodsParticipants included 13 children with Dup15q syndrome and 13 children with non-syndromic ASD, matched on chronological and mental age, ages 22 months-12 years. In the Dup15q group, ten participants had isodicentric and three had interstitial duplications. Four children had active epilepsy (all isodicentric). Participants were assessed for verbal and non-verbal cognition, ASD characteristics based on the Autism Diagnostic Observation Schedule (ADOS), and adaptive function based on the Vineland Adaptive Behavior Scales (VABS). Group comparisons were performed between Dup15q and ASD participants, as well as within the Dup15q group based on duplication type and epilepsy status.ResultsAll children with Dup15q syndrome met the criteria for ASD; ASD severity scores were significantly lower than children in the non-syndromic ASD group. ADOS profiles demonstrated a relative strength in items related to social interest. Children with Dup15q syndrome also demonstrated significantly more impairment in motor and daily living skills. Within the Dup15q group, children with epilepsy demonstrated significantly lower cognitive and adaptive function than those without epilepsy.ConclusionsThe relative strength observed in social interest and responsiveness in the context of impaired motor skills represents an important avenue for intervention, including aggressive treatment of epilepsy, early and consistent focus on motor skills, and intervention targeting joint attention and language within a play context, in order to build on social interest to further develop social communication abilities. Longitudinal research beginning in early development will elucidate the temporal relationships between developmental domains and neurological comorbidities in these children at high risk for neurodevelopmental disorders

Delta power robustly predicts cognitive function in Angelman syndrome.

ObjectiveAngelman syndrome (AS) is a severe neurodevelopmental disorder caused by loss of function of the maternally inherited UBE3A gene in neurons. Promising disease-modifying treatments to reinstate UBE3A expression are under development and an early measure of treatment response is critical to their deployment in clinical trials. Increased delta power in EEG recordings, reflecting abnormal neuronal synchrony, occurs in AS across species and correlates with genotype. Whether delta power provides a reliable biomarker for clinical symptoms remains unknown.MethodsWe analyzed combined EEG recordings and developmental assessments in a large cohort of individuals with AS (N = 82 subjects, 133 combined EEG and cognitive assessments, 1.08-28.16 years; 32F) and evaluated delta power as a biomarker for cognitive function, as measured by the Bayley Cognitive Score. We examined the robustness of this biomarker to varying states of consciousness, recording techniques and analysis procedures.ResultsDelta power predicted the Bayley Scale cognitive score (P < 10-5 , R2  = 0.9374) after controlling for age (P < 10-24 ), genotype:age (P < 10-11 ), and repeat assessments (P < 10-8 ), with the excellent fit on cross validation (R2  = 0.95). There were no differences in model performance across states of consciousness or bipolar versus average montages (ΔAIC < 2). Models using raw data excluding frontal channels outperformed other models (ΔAIC > 4) and predicted performance in expressive (P = 0.0209) and receptive communication (P < 10-3 ) and fine motor skills (P < 10-4 ).InterpretationDelta power is a simple, direct measure of neuronal activity that reliably correlates with cognitive function in AS. This electrophysiological biomarker offers an objective, clinically relevant endpoint for treatment response in emerging clinical trials