187 research outputs found

    Genetic testing of epileptic encephalopathies of infancy: An approach

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    The epileptic encephalopathies of infancy are a group of disorders characterized by intractable seizures, persistent abnormality of cortical function documented on EEG, and consequently impaired neuro-developmental outcomes. The etiologies vary and include; structural brain malformations, acquired brain insults, and inborn errors of metabolism in the majority of the affected patients. In a proportion of these cases no obvious etiology is identifiable on investigation. Recent advances in molecular diagnostics have led to the discovery of a number of gene defects that may be causal in many epileptic encephalopathies. Identification of the causative mutation is important for prognostic and genetic counseling, and may also carry treatment implications. The recently described genes include; Cyclin-Dependent Kinase-Like 5 gene (CDKL5), Protocadherin 19 (PCDH19), Sodium channel neuronal type 1a subunit gene (SCN1A), Aristaless-Related Homeobox Gene (ARX), and Syntaxin binding protein 1 gene (STXBP1), amongst others. Distinct electro-clinical syndromes are increasingly being identified amongst patients carrying the various mutations. In this review, we outline the approach to clinical evaluation and genetic testing of epileptic encephalopathies in infancy

    Drug compliance in children with epilepsy: Cross-sectional study, New Delhi

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    Background: For individuals with epilepsy, adherence to medication is crucial in preventing or minimizing seizures and their cumulative impact on everyday life. Compliance studies in adult patients are many, but few in children with epilepsy. Objective: This study tries to find the prevalence of noncompliance in children with epilepsy and causes leading to it. Method: The study was conducted in a tertiary care super specialty children hospital of New Delhi. Children, age 1-12 years, who were already diagnosed cases of epilepsy and were all on drug therapy for at least 3 months were included in the study. After obtaining clearance from the hospital’s Ethical Committee, a total of 100 parents of epileptic children were interviewed as per the prepared questionnaire. Results: Out of 100 children (63 males, 37 females) with epilepsy, 71% were compliant. Most of the noncompliant parents (82.7%) felt that there is the harmful effect of long-term anti-epileptic drugs. They believed in stopping medications on their own once signs and symptoms disappear and did not like to give medication to their child in public place. No significant association of noncompliance could be seen with etiology of epilepsy, monotherapy versus polytherapy, and duration of disease, mother’s age and parental education (p>0.05). Conclusion: Compliance in this study group of children with epilepsy was 71%. Further improvement of health and well-being of children with epilepsy can be attempted by education of parents, distribution of written instructions in the form of pamphlets, counseling, group discussions, and exchange of personal experience. Public awareness drive should help in reducing the associated taboos

    Exploring the secretome of Corynebacterium glutamicum ATCC 13032

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    The demand for alternative sources of food proteins is increasing due to the limitations and challenges associated with conventional food production. Advances in biotechnology have enabled the production of proteins using microorganisms, thus prompting the exploration of attractive microbial hosts capable of producing functional proteins in high titers. Corynebacterium glutamicum is widely used in industry for the production of amino acids and has many advantages as a host organism for recombinant protein production. However, its performance in this area is limited by low yields of target proteins and high levels of native protein secretion. Despite representing a challenge for heterologous protein production, the C. glutamicum secretome has not been fully characterized. In this study, state-of-the-art mass spectrometry-based proteomics was used to identify and analyze the proteins secreted by C. glutamicum. Both the wild-type strain and a strain that produced and secreted a recombinant ÎČ-lactoglobulin protein were analyzed. A total of 427 proteins were identified in the culture supernatants, with 148 predicted to possess a secretion signal peptide. MS-based proteomics on the secretome enabled a comprehensive characterization and quantification (based on abundance) of the secreted proteins through label-free quantification (LFQ). The top 12 most abundant proteins accounted for almost 80% of the secretome. These are uncharacterized proteins of unknown function, resuscitation promoting factors, protein PS1, Porin B, ABC-type transporter protein and hypothetical membrane protein. The data can be leveraged for protein production by, e.g., utilizing the signal peptides of the most abundant proteins to improve secretion of heterologous proteins. In addition, secretory stress can potentially be alleviated by inactivating non-essential secreted proteins. Here we provide targets by identifying the most abundant, secreted proteins of which majority are of unknown function. The data from this study can thus provide valuable insight for researchers looking to improve protein secretion and optimize C. glutamicum as a host for secretory protein production

    Cavitating Leukoencephalopathy With Posterior Predominance Caused by a Deletion in the APOPT1 Gene in an Indian Boy.

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    A 5-year-old Indian boy presented with subacute onset regression of milestones associated with seizures and spasticity. The symptoms started after an attack of measles. The magnetic resonance imaging (MRI) of the brain showed cavitating leukodystrophy with posterior predominance. Molecular analysis of the APOPT1 gene, a recently described gene associated with mitochondrial leukodystrophy, showed the patient to be homozygous for a 12.82-kilobase deletion, including coding exon 3. Deletion of exon 3 produces a frameshift, predicting the translation of a truncated protein (p.Glu121Valfs*4). The patient was started on mitochondrial cocktail regimen of thiamine, riboflavin, coenzyme Q and carnitine. Although he initially showed some improvement, he died 6 months after the onset of his illness.Genetic testing for the patient was done as part of the APOPT1 research project funded by MRC (MRC-QQR grant 2015-2020 and ERC advanced grant ERC FP7-322424

    Electronic structure investigation of CeB6 by means of soft X-ray scattering

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    The electronic structure of the heavy fermion compound CeB6 is probed by resonant inelastic soft X-ray scattering using photon energies across the Ce 3d and 4d absorption edges. The hybridization between the localized 4f orbitals and the delocalized valence-band states is studied by identifying the different spectral contributions from inelastic Raman scattering and normal fluorescence. Pronounced energy-loss structures are observed below the elastic peak at both the 3d and 4d thresholds. The origin and character of the inelastic scattering structures are discussed in terms of charge-transfer excitations in connection to the dipole allowed transitions with 4f character. Calculations within the single impurity Anderson model with full multiplet effects are found to yield consistent spectral functions to the experimental data.Comment: 9 pages, 4 figures, 1 table, http://link.aps.org/doi/10.1103/PhysRevB.63.07510

    Metamagnetic Quantum Criticality in Sr3Ru2O7

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    We consider the metamagnetic transition in the bilayer ruthenate, Sr3Ru2O7{\rm Sr_3Ru_2O_7}, and use this to motivate a renormalization group treatment of a zero-temperature quantum-critical end-point. We summarize the results of mean field theory and give a pedagogical derivation of the renormalization-group equations. These are then solved to yield numerical results for the susceptibility, the specific heat and the resistivity exponent which can be compared with measured data on Sr3Ru2O7{\rm Sr_3Ru_2O_7} to provide a powerful test for the standard framework of metallic quantum criticality. The observed approach to the critical point is well-described by our theory explaining a number of unusual features of experimental data. The puzzling behaviour very near to the critical point itself, though, is not accounted for by this, or any other theory with a Fermi surface

    Altered Cellular Protein Quality Control System Modulates Cardiomyocyte Function in Volume Overload-Induced Hypertrophy

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    Volume-induced hypertrophy is one of the risk factors for cardiac morbidity and mortality. In addition, mechanical and metabolic dysfunction, aging, and cellular redox balance are also contributing factors to the disease progression. In this study, we used volume overload (VO), which was induced by an aortocaval fistula in 2-month-old male Wistar rats, and sham-operated animals served as control. Functional parameters were measured by transthoracic echocardiography at termination 4- or 8-months after VO. The animals showed hypertrophic remodeling that was accompanied by mechanical dysfunction and increased cardiomyocyte stiffness. These alterations were reversible upon treatment with glutathione. Cardiomyocyte dysfunction was associated with elevated oxidative stress markers with unchanged inflammatory signaling pathways. In addition, we observed altered phosphorylation status of small heat shock proteins 27 and 70 and diminished protease expression caspases 3 compared to the matched control group, indicating an impaired protein quality control system. Such alterations might be attributed to the increased oxidative stress as anticipated from the enhanced titin oxidation, ubiquitination, and the elevation in oxidative stress markers. Our study showed an early pathological response to VO, which manifests in cardiomyocyte mechanical dysfunction and dysregulated signaling pathways associated with enhanced oxidative stress and an impaired protein quality control system
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