bluuebunny/crossref_metadata_2025_split huggingface dataset:
A distinct mitochondrial myopathy, lactic acidosis and sideroblastic anemia (MLASA) phenotype associates with YARS2 mutations
Authors: Shahni Rojeen , Wedatilake Yehani , Cleary Maureen A. , Lindley Keith J. , Sibson Keith R. , Rahman Shamima 
Published: August 2013

ABSTRACTNuclear‐encoded disorders of mitochondrial translation are clinically and genetically heterogeneous. Genetic causes include defects of mitochondrial aminoacyl‐tRNA synthetases, and factors required for initiation, elongation and termination of protein synthesis as well as ribosome recycling. We report on a new case of myopathy, lactic acidosis and sideroblastic anemia (MLASA) syndrome caused by defective mitochondrial tyrosyl aminoacylation. The patient presented at 1 year with anemia initially attributed to iron deficiency. Bone marrow aspirate at 5 years revealed ringed sideroblasts but transfusion dependency did not occur until 11 years. Other clinical features included lactic acidosis, poor weight gain, hypertrophic cardiomyopathy and severe myopathy leading to respiratory failure necessitating ventilatory support. Long‐range PCR excluded mitochondrial DNA rearrangements. Clinical diagnosis of MLASA prompted direct sequence analysis of the YARS2 gene encoding the mitochondrial tyrosyl‐tRNA synthetase, which revealed homozygosity for a known pathogenic mutation, c.156C>G;p.F52L. Comparison with four previously reported cases demonstrated remarkable clinical homogeneity. First line investigation of MLASA should include direct sequence analysis of YARS2 and PUS1 (encoding a tRNA modification factor) rather than muscle biopsy. Early genetic diagnosis is essential for counseling and to facilitate appropriate supportive therapy. Reasons for segregation of specific clinical phenotypes with particular mitochondrial aminoacyl tRNA‐synthetase defects remain unknown. © 2013 Wiley Periodicals, Inc.
Molecular etiology of hearing impairment associated with nonsyndromic enlarged vestibular aqueduct in East China
Authors: Chai Yongchuan , Huang Zhiwu , Tao Zheng , Li Xiaohua , Li Lei , Li Yun , Wu Hao , Yang Tao 
Published: August 2013

AbstractRecessive mutations in SLC26A4 and in rarer cases double heterozygous mutations of FOXI1/SLC26A4 and KCNJ10/SLC26A4 lead to hearing impairment associated with enlarged vestibular aqueduct (EVA), the most common inner ear malformation. In our large cohort study, we addressed several important questions to the molecular etiology of this disorder. The overall prevalence of SLC26A4 mutations in nonsyndromic childhood sensorineural hearing loss (11.2%, 37/330) were determined by sequencing of SLC26A4 in 330 hearing impaired children who did not undergo inner ear radiologic imaging prior to their genetic test. The penetrance of EVA in bi‐allelic SLC26A4 mutation carriers (100%, 37/37) was determined by follow‐up computed tomography scanning. Combined with the study of 140 additional probands diagnosed with nonsyndromic EVA, we characterized the mutation spectrum of SLC26A4 in East China, which consisted of 19 novel SLC26A4 mutations and differed from those reported in other regions of China. © 2013 Wiley Periodicals, Inc.
Learning and memory in children with Noonan syndrome
Authors: Pierpont Elizabeth I. , Tworog‐Dube Erica , Roberts Amy E. 
Published: August 2013

AbstractGenetic syndromes resulting from molecular alterations of the RAS–MAPK signaling cascade have become the focus of heightened interest among behavioral scientists due to discoveries that proteins within this pathway play an important role in memory formation and consolidation. Individuals with Noonan syndrome (NS), caused by germline mutations in the RAS–MAPK pathway, exhibit wide variability in cognitive and memory skills. The current study aimed to characterize memory deficits that occur in some affected individuals as a key step toward understanding the neurocognitive effects of dysregulated Ras signaling. Learning and memory skills were assessed among 29 children and adolescents with NS using the Wide Range Assessment of Memory and Learning, Second Edition. Performance across subdomains (verbal memory, visual memory and working memory) was compared, as well as the effect of response type (free recall vs. recognition). For immediate memory, children with NS performed significantly better on verbal memory tasks than on visual memory or working memory tasks. For delayed memory, verbal free recall tasks that depend heavily on prefrontal‐hippocampal networks were more challenging than recognition tasks that rely on more distributed temporal cortical regions. Additionally, verbal information presented in context was more easily retained than that presented in a rote format. The current study contributes to our knowledge of the effects of dysregulated RAS–MAPK signaling on the brain and behavior. Continued research on neurocognitive skills in NS has the potential to generate a novel conceptualization of how learning disabilities can arise from altered molecular processes within a specific biological pathway. © 2013 Wiley Periodicals, Inc.
Interstitial 12p13.1 deletion involving GRIN2B in three patients with intellectual disability
Authors: Dimassi Sarra , Andrieux Joris , Labalme Audrey , Lesca Gaétan , Cordier Marie‐Pierre , Boute Odile , Neut Dorothée , Edery Patrick , Sanlaville Damien , Schluth‐Bolard Caroline 
Published: August 2013

AbstractWe report on three patients presenting moderate intellectual disability, delayed language acquisition, and mild facial dysmorphia. Array‐CGH studies revealed overlapping interstitial 12p13.1 microdeletions encompassing all or part of GRIN2B. GRIN2B encodes the NR2B subunit of the N‐methyl‐D‐aspartate (NMDA) receptor. This receptor is a heteromeric glutamate‐activated ion channel, present throughout the central nervous system. It plays a critical role in corticogenesis, neuronal migration, and synaptogenesis during brain development. GRIN2B alterations, including mutation and gene disruption by apparently balanced chromosomal rearrangements, have been described in patients with intellectual disability and autism spectrum disorder. We report here on the first cases of GRIN2B deletion, enlarging the spectrum of GRIN2B abnormalities. Our findings confirm the involvement of this gene in neurodevelopmental disorders. © 2013 Wiley Periodicals, Inc.
Prevalence of beckwith–wiedemann syndrome in North West of Italy
Authors: Mussa Alessandro , Russo Silvia , De Crescenzo Agostina , Chiesa Nicoletta , Molinatto Cristina , Selicorni Angelo , Richiardi Lorenzo , Larizza Lidia , Silengo Margherita Cirillo , Riccio Andrea , Ferrero Giovanni Battista 
Published: August 2013

ABSTRACTAlthough Beckwith–Wiedemann syndrome (BWS, OMIM #130650) is the most common genetic overgrowth disorder, data on its epidemiology are scanty and the estimates of its occurrence show wide variability. The aim of this study is to assess its prevalence in Piedmont Region (Italy). We included in the study all patients diagnosed with BWS born in Piedmont from 1997 to 2009 through a search in the Italian Registry for Rare Diseases. This source was further validated with data from the network of Regional Clinical Genetics services and surveys in extra‐regional Clinical Genetics centres, laboratories and the Italian BWS patients association. All cases were further ascertained through physical exam, medical history and specific molecular tests. The search identified 46 clear‐cut cases of BWS born across the 13‐year period, providing a prevalence of 1:10 340 live births (95% confidence interval 1:7,752–13,698 live births). Among the 41 patients who underwent molecular tests, 70.7% were positive, showing hypomethylation of the IC2 imprinting center (29.3%), paternal chromosome 11 uniparental disomy (pUPD11, 24.4%), IC1 hypermethylation (14.6%), CDKN1c mutation (2.4%), whereas 29.3% had negative molecular tests. The study provides an approximate BWS prevalence of 1:10,000 live birth, the highest reported to date. © 2013 Wiley Periodicals, Inc.
A Genome‐Wide Association Study Reveals ARL15, a Novel Non‐HLA Susceptibility Gene for Rheumatoid Arthritis in North Indians
Authors: Negi Sapna , Juyal Garima , Senapati Sabyasachi , Prasad Pushplata , Gupta Aditi , Singh Shalini , Kashyap Sujit , Kumar Ashok , Kumar Uma , Gupta Rajiva , Kaur Satbir , Agrawal Suraksha , Aggarwal Amita , Ott Jurg , Jain Sanjay , Juyal Ramesh C. , Thelma B. K. 
Published: August 2013

ObjectiveGenome‐wide association studies (GWAS) and their subsequent meta‐analyses have changed the landscape of genetics in rheumatoid arthritis (RA) by uncovering several novel genes. Such studies are heavily weighted by samples from Caucasian populations, but they explain only a small proportion of total heritability. Our previous studies in genetically distinct North Indian RA cohorts have demonstrated apparent allelic/genetic heterogeneity between North Indian and Western populations, warranting GWAS in non‐European populations. We undertook this study to detect additional disease‐associated loci that may be collectively important in the presence or absence of genes with a major effect.MethodsHigh‐quality genotypes for >600,000 single‐nucleotide polymorphisms (SNPs) in 706 RA patients and 761 controls from North India were generated in the discovery stage. Twelve SNPs showing suggestive association (P < 5 × 10−5) were then tested in an independent cohort of 927 RA patients and 1,148 controls. Additional disease‐associated loci were determined using support vector machine (SVM) analyses. Fine‐mapping of novel loci was performed by using imputation.ResultsIn addition to the expected association of the HLA locus with RA, we identified association with a novel intronic SNP of ARL15 (rs255758) on chromosome 5 (Pcombined = 6.57 × 10−6; odds ratio 1.42). Genotype–phenotype correlation by assaying adiponectin levels demonstrated the functional significance of this novel gene in disease pathogenesis. SVM analysis confirmed this association along with that of a few more replication stage genes.ConclusionIn this first GWAS of RA among North Indians, ARL15 emerged as a novel genetic risk factor in addition to the classic HLA locus, which suggests that population‐specific genetic loci as well as those shared between Asian and European populations contribute to RA etiology. Furthermore, our study reveals the potential of machine learning methods in unraveling gene–gene interactions using GWAS data.
Copy Number Variations of Complement Component C4 Are Associated With Behçet's Disease but Not With Ankylosing Spondylitis Associated With Acute Anterior Uveitis
Authors: Hou Shengping , Qi Jian , Liao Dan , Zhang Qi , Fang Jing , Zhou Yan , Liu Yunjia , Bai Lin , Zhang Meifen , Kijlstra Aize , Yang Peizeng 
Published: August 2013

ObjectiveComplement component C4 copy number variations are associated with various inflammatory diseases. This study was undertaken to investigate whether copy number variations of C4 are also involved in the pathogenesis of Behçet's disease (BD).MethodsGene expression was examined by enzyme‐linked immunosorbent assay (ELISA) or real‐time polymerase chain reaction (PCR). Copy number variations of C4 isotypes (C4A and C4B) were detected by real‐time PCR in 905 patients with BD, 205 patients with ankylosing spondylitis (AS) and acute anterior uveitis, and 1,238 controls. The activation of CD4+ T cells was analyzed by flow cytometry, and cytokine production was detected by ELISA.ResultsProtein expression of total C4 in serum was significantly increased in patients with active BD compared with those with inactive BD or controls (Bonferroni corrected P [Pcorr] = 1.64 × 10−4 and Pcorr = 0.037, respectively), but not in patients with AS and acute anterior uveitis. Copy number variation analysis identified a significantly increased frequency of more than 2 copies of C4A in BD patients (P = 1.65 × 10−7, odds ratio [OR] 2.84). HLA–B51, which is located on the same chromosome as C4, showed a strong association with BD in the Han Chinese population (P = 8.90 × 10−65, OR 5.05), but logistic regression showed that C4A copy number variation was an independent risk factor for BD. A significantly increased expression of C4A was observed in the high copy number groups (>2 copies or 2 copies) versus the low copy number group (Pcorr = 0.019 and Pcorr = 0.044, respectively). Increased production of interleukin‐6 (IL‐6) was also observed in the high C4A copy number group (Pcorr = 0.037). No effect of C4 copy number variation on the expression of T cell activation markers was detected.ConclusionOur findings indicate that a high copy number of C4A confers risk for BD by modulating the expression of C4A and enhancing IL‐6 production.
LC‐MS/MS method for the determination of agomelatine in human plasma and its application to a pharmacokinetic study
Authors: Wang Xiaolin , Zhang Dan , Liu Man , Zhao Hongna , Du Aihua , Meng Lingjie , Liu Huichen 
Published: August 2013

ABSTRACTA sensitive and selective LC‐MS/MS method for the determination of agomelatine in human plasma was developed and validated. After simple liquid–liquid extraction, the analytes were separated on a Zorbax SB‐C18 column (150 × 2.1 mm i.d., 5 µm) with an isocratic mobile phase consisting of 5 mm ammonium acetate solution (containing 0.1% formic acid) and methanol (30:70, v/v) at a flow‐rate of 0.3 mL/min. The MS acquisition was performed in multiple reaction monitoring mode with a positive electrospray ionization source. The mass transitions monitored were m/z 244.1 → 185.3 and m/z 285.2 → 193.2 for agomelatine and internal standard, respectively. The methods were validated for selectivity, carry‐over, matrix effects, calibration curves, accuracy and precision, extraction recoveries, dilution integrity and stability. The validated method was successfully applied to a pharmacokinetic study of agomelatine in Chinese volunteers following a single oral dose of 25 mg agomelatine tablet. Copyright © 2013 John Wiley & Sons, Ltd.
Negotiating Reintegration and Meanings of Space: Formerly Abducted Youth in Uganda
Authors: Paaskesen Lise 
Published: August 2013

ABSTRACTThe war in Northern Uganda has ended, and youth who were abducted by the Lord's Resistance Army continue to return to communities. Research conducted in the summer of 2010 in two locations in Uganda, Gulu and Masindi, shows that the process of reintegration is an ongoing process in which formerly abducted youth (FAY) negotiate social relations for reintegration in a very interactive way. FAY consciously decide to stay quiet about their past to avoid compromising social reintegration. The experience‐oriented approach has allowed for an in‐depth exploration and understanding of the reintegration process from the perspective of FAY. In Northern Ugandan cosmology, meaning given to FAY personal spaces dominates. With FAY facing social exclusion by community members and the need to overcome boundaries to reintegration, coping mechanisms are adopted to facilitate reintegration and to carve out personal space within the Northern Ugandan cosmology. In the exploration of the process of negotiating reintegration, a conceptual model is adopted and adjusted to represent personal space within Northern Ugandan cosmology. The main findings suggest that FAY negotiate social relations for reintegration in a very interactive way and that they consciously decide to stay quiet about their past so as to not compromise social reintegration. Copyright © 2013 John Wiley & Sons, Ltd.
Squarylium‐Triazine Dyad as a Highly Sensitive Photoradical Generator for Red Light
Authors: Kawamura Koichi , Schmitt Julien , Barnet Maxime , Salmi Hanene , Ley Christian , Allonas Xavier 
Published: August 2013

AbstractNew dyads, based on squarylium dye and substituted‐triazine, were synthesized that exhibit an intramolecular photodissociative electron‐transfer reaction. The compounds were used as a red‐light photoradical generator. The photochemical activity of the dyad was compared to the corresponding unlinked systems (S+T) by determining the rate constant of electron transfer. The efficiency of the radical generation from the dyad compared to the unlinked system was demonstrated by measuring the maximum rate of free radical polymerization of acrylates in film. An excellent relationship between the rate of electron transfer and the rate of polymerization was found, evidencing the interest of this new approach to efficiently produce radicals under red light.
The role of electrode material in capturing power generated in Pseudomonas catalysed fuel cells
Authors: Jayapriya J. , Ramamurthy V. 
Published: August 2013

AbstractHigh efficiency electrodes (e.g. metal coated, carbon‐polymer composites and noble‐metal catalyst, etc.) used in conventional fuel cells are commercially available; however they are not being used in microbial fuel cells (MFCs). These electrodes are not biocompatible and more susceptible to catalyst poisoning when industrial effluents/aquatic sediments are used as a fuel. There is a need for unique electrode materials for MFCs that should be highly conductive material with enhanced active surface area, cheap, easy to process, biocompatible and scalable. In this study, the performance of mediator‐less microbial fuel cells (MFC) using Pseudomonas aeruginosa as a biocatalyst using different electrodes such as graphite blocks, carbon cloth, carbon fibre reinforced plate and graphite sheet was evaluated. Different metal salt doped graphite epoxy composites (MS‐GECE) and chemically modified carbon electrodes (CMCE) were also tested. Among the different combinations of the electrodes tested, Fe3+ graphite cathode produced significantly higher power density (1679.9 ± 98.04 µW/m2). These studies indicate the feasibility of the improvement in electrode design on the performance of MFC for wider applications.
Structure–Activity Relationship Studies of Pyrrolone Antimalarial Agents
Authors: Murugesan Dinakaran , Kaiser Marcel , White Karen L. , Norval Suzanne , Riley Jennifer , Wyatt Paul G. , Charman Susan A. , Read Kevin D. , Yeates Clive , Gilbert Ian H. 
Published: August 2013

AbstractPreviously reported pyrrolones, such as TDR32570, exhibited potential as antimalarial agents; however, while these compounds have potent antimalarial activity, they suffer from poor aqueous solubility and metabolic instability. Here, further structure–activity relationship studies are described that aimed to solve the developability issues associated with this series of compounds. In particular, further modifications to the lead pyrrolone, involving replacement of a phenyl ring with a piperidine and removal of a potentially metabolically labile ester by a scaffold hop, gave rise to derivatives with improved in vitro antimalarial activities against Plasmodium falciparum K1, a chloroquine‐ and pyrimethamine‐resistant parasite strain, with some derivatives exhibiting good selectivity for parasite over mammalian (L6) cells. Three representative compounds were selected for evaluation in a rodent model of malaria infection, and the best compound showed improved ability to decrease parasitaemia and a slight increase in survival.
2‐Ureido‐4‐Pyrimidone‐Based Hydrogels with Multiple Responses
Authors: Cui Jiaxi , Wang Dapeng , Koynov Kaloian , del Campo Aránzazu 
Published: August 2013

AbstractFunctionalisation of poly[2‐(dimethylamino)ethyl methacrylate] (a responsive methacrylate) with light‐activatable 2‐ureido‐4‐pyrimidone units allows a supramolecular hydrogel to be obtained that combines temperature, light and pH response with self‐healing properties. Whereas the self‐healing properties of this system were described previously, this report focuses on its response to different external stimuli, which is studied by quartz crystal microbalance analysis of thin films of the material. Reversible collapse with increasing temperature, reversible swelling with decreasing pH and irreversible shrinkage with UV exposure are demonstrated. These three stimuli are combined to have externally gated or tuned responses. Thermo‐induced swelling and shrinkage can be reversibly inhibited by changing the pH and irreversibly regulated by exposure to light of different doses. These materials represent the first general strategy to obtain responsive self‐healing hydrogels in which the response and the self‐healing properties are decoupled from each other and can be tuned independently.
Probing Charge Transfer in Benzodifuran–C60 Dumbbell‐Type Electron Donor–Acceptor Conjugates: Ground‐ and Excited‐State Assays
Authors: Li Hui , Schubert Christina , Dral Pavlo O. , Costa Rubén D. , La Rosa Andrea , Thüring Jürg , Liu Shi‐Xia , Yi Chenyi , Filippone Salvatore , Martín Nazario , Decurtins Silvio , Clark Timothy , Guldi Dirk M. 
Published: August 2013

AbstractRigid electron donor–acceptor conjugates (1–3) that combine π‐extended benzodifurans as electron donors and C60 molecules as electron acceptors with different linkers have been synthesized and investigated with respect to intramolecular charge‐transfer events. Electrochemistry, fluorescence, and transient absorption measurements revealed tunable and structure‐dependent charge‐transfer processes in the ground and excited states. Our experimental findings are underpinned by density‐functional theory calculations.
Emotion‐Focused Family Therapy for Eating Disorders in Children and Adolescents
Authors: Robinson Adèle Lafrance , Dolhanty Joanne , Greenberg Leslie 
Published: August 2013

Family‐based therapy (FBT) is regarded as best practice for the treatment of eating disorders in children and adolescents. In FBT, parents play a vital role in bringing their child or adolescent to health; however, a significant minority of families do not respond to this treatment. This paper introduces a new model whereby FBT is enhanced by integrating emotion‐focused therapy (EFT) principles and techniques with the aims of helping parents to support their child's refeeding and interruption of symptoms. Parents are also supported to become their child's ‘emotion coach’; and to process any emotional ‘blocks’ that may interfere with their ability to take charge of recovery. A parent testimonial is presented to illustrate the integration of the theory and techniques of EFT in the FBT model. EFFT (Emotion‐Focused Family Therapy) is a promising model of therapy for those families who require a more intense treatment to bring about recovery of an eating disorder.Key Practitioner Message

More intense therapeutic models exist for treatment‐resistant eating disorders in children and adolescents.
Emotion is a powerful healing tool in families struggling with an eating disorder.
Working with parent's emotions and emotional reactions to their child's struggles has the potential to improve child outcomes. Copyright © 2013 John Wiley & Sons, Ltd.