bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nonsyndromic brachydactyly type D and type E mapped to 7p15 in healthy children and adults from the jirel ethnic group in eastern nepal
Authors: Williams Kimberly D. , Blangero John , Subedi Janardan , Jha Bharat , Dyer Thomas , Vandeberg John L. , Towne Bradford , Williams‐Blangero Sarah 
Published: September 2013

ObjectivesThere is phenotypic overlap between Brachydactyly Type D (BDD) and Brachydactyly Type E (BDE) that suggests a possible common underlying etiology. We seek to understand the genetic underpinnings of, and relationship between, these skeletal anomalies.MethodsThe Jirel ethnic group of eastern Nepal participates in various genetic epidemiologic studies, including those in which hand‐wrist radiographs have been taken to examine skeletal development. Nearly 2,130 individuals (969 males; 1,161 females) were phenotyped for BDD/BDE. Of these, 1,722 individuals (773 males; 949 females) were genotyped for 371 STR markers spanning the autosomal genome. Variance components‐based linkage analysis was used to conduct a genome‐wide linkage scan for QTL influencing the BDD/BDE phenotype.ResultsBDD was present in 3.55%, and BDE was present in 0.39%, of the study sample. Because of the phenotypic overlap between two traits, affecteds of either type were considered as affected by a single combined phenotype (BDD/BDE) having a prevalence of 3.94%. The additive genetic heritability of BDD/BDE was highly significant (h2 ± SE = 0.89 ± 0.13; P = 1.7 × 10−11). Significant linkage of BDD/BDE was found to markers on chromosome 7p21‐7p14 (peak LOD score = 3.74 at 7p15 between markers D7S493 and D7S516).ConclusionsPossible positional candidate genes in the one‐lod support interval of this QTL include TWIST and the HOXA1‐A13 cluster. This is the first study to report significant linkage results for BDD/BDE using a large extended pedigree, and the first to suggest that mutations in TWIST and/or the HOXA1‐A13 cluster may contribute to these specific skeletal anomalies. Am. J. Hum. Biol. 25:743–750, 2013. © 2013 Wiley Periodicals, Inc.
Sex‐specific control of central nervous system autoimmunity by p38 mitogen‐activated protein kinase signaling in myeloid cells
Authors: Krementsov Dimitry N. , Noubade Rajkumar , Dragon Julie A. , Otsu Kinya , Rincon Mercedes , Teuscher Cory 
Published: September 2013

ObjectiveMultiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS), characterized by a global increasing incidence driven by relapsing–remitting disease in females. Investigators have described p38 mitogen‐activated protein kinase (MAPK) as a key regulator of inflammatory responses in autoimmunity, but its role in the sexual dimorphism in MS or MS models remains unexplored.MethodsToward this end, we used experimental autoimmune encephalomyelitis (EAE), the principal animal model of MS, combined with pharmacologic and genetic inhibition of p38 MAPK activity and transcriptomic analyses.ResultsPharmacologic inhibition of p38 MAPK selectively ameliorated EAE in female mice. Conditional deletion studies demonstrated that p38α signaling in macrophages/myeloid cells, but not T cells or dendritic cells, mediated this sexual dimorphism, which was dependent on the presence of adult sex hormones. Analysis of CNS inflammatory infiltrates showed that female but not male mice lacking p38α in myeloid cells exhibited reduced immune cell activation compared with controls, whereas peripheral T‐cell priming was unaffected in both sexes. Transcriptomic analyses of myeloid cells revealed differences in p38α‐controlled transcripts comprising female‐ and male‐specific gene modules, with greater p38α dependence of proinflammatory gene expression in females.InterpretationOur findings demonstrate a key role for p38α in myeloid cells in CNS autoimmunity and uncover important molecular mechanisms underlying sex differences in disease pathogenesis. Taken together, our results suggest that the p38 MAPK signaling pathway represents a novel target for much needed disease‐modifying therapies for MS. Ann Neurol 2014;75:50–66
Activation of the Ubiquitin Proteasome Pathway in a Mouse Model of Inflammatory Myopathy: A Potential Therapeutic Target
Authors: Rayavarapu Sree , Coley William , Van der Meulen Jack H. , Cakir Erdinc , Tappeta Kathyayini , Kinder Travis B. , Dillingham Blythe C. , Brown Kristy J. , Hathout Yetrib , Nagaraju Kanneboyina 
Published: September 2013

ObjectiveMyositis is characterized by severe muscle weakness. We and others have previously shown that endoplasmic reticulum (ER) stress plays a role in the pathogenesis of myositis. The present study was undertaken to identify perturbed pathways and assess their contribution to muscle disease in a mouse myositis model.MethodsStable isotope labeling with amino acids in cell culture (SILAC) was used to identify alterations in the skeletal muscle proteome of myositic mice in vivo. Differentially altered protein levels identified in the initial comparisons were validated using a liquid chromatography tandem mass spectrometry spike‐in strategy and further confirmed by immunoblotting. In addition, we evaluated the effect of a proteasome inhibitor, bortezomib, on the disease phenotype, using well‐standardized functional, histologic, and biochemical assessments.ResultsWith the SILAC technique we identified significant alterations in levels of proteins belonging to the ER stress response, ubiquitin proteasome pathway (UPP), oxidative phosphorylation, glycolysis, cytoskeleton, and muscle contractile apparatus categories. We validated the myositis‐related changes in the UPP and demonstrated a significant increase in the ubiquitination of muscle proteins as well as a specific increase in ubiquitin carboxyl‐terminal hydrolase isozyme L1 (UCHL‐1) in myositis, but not in muscle affected by other dystrophies or normal muscle. Inhibition of the UPP with bortezomib significantly improved muscle function and also significantly reduced tumor necrosis factor α expression in the skeletal muscle of mice with myositis.ConclusionOur findings indicate that ER stress activates downstream UPPs and contributes to muscle degeneration and that UCHL‐1 is a potential biomarker for disease progression. UPP inhibition offers a potential therapeutic strategy for myositis.
Estrogen Receptor α Regulates Tripartite Motif–Containing Protein 21 Expression, Contributing to Dysregulated Cytokine Production in Systemic Lupus Erythematosus
Authors: Smith Siobhán , Ní Gabhann Joan , McCarthy Eoghan , Coffey Barbara , Mahony Rebecca , Byrne Jennifer C. , Stacey Kevin , Ball Elizabeth , Bell Aubrey , Cunnane Gaye , Doran Michele F. , Molloy Eamonn S. , Lee Ruth Z. , Harvey Brian , Kearns Grainne , Jefferies Caroline A. 
Published: September 2013

ObjectiveTo examine the role of 17β‐estradiol in the regulation of the autoantigen tripartite motif–containing protein 21 (TRIM‐21) in patients with systemic lupus erythematosus (SLE).MethodsMonocytes isolated from healthy control subjects and patients with SLE were stimulated with 17β‐estradiol and/or the estrogen receptor α (ERα) antagonist methyl‐piperidino‐pyrazole dihydrochloride. TRIM‐21, ERα, and CREMα expression was determined by real‐time polymerase chain reaction (PCR) analysis. MatInspector software was used to identify putative binding sites within the TRIM‐21 promoter. ERα binding to the TRIM‐21 gene promoter region in monocytes was analyzed by chromatin immunoprecipitation (ChIP) assay. TRIM‐21 and interferon regulatory factor 3 protein levels were analyzed by Western blotting.ResultsReal‐time PCR analysis demonstrated a role of estrogen in the regulation of TRIM‐21 expression in monocytes, which correlated positively with ERα gene expression in patients with SLE. Investigations into the human TRIM‐21 promoter revealed the presence of an estrogen response element, with ChIP assays confirming ERα binding to this site. Studies into estrogen‐induced TRIM‐21 expression revealed a hyperresponsiveness of SLE patients to 17β‐estradiol, which led to the enhanced levels of TRIM‐21 observed in these individuals.ConclusionOur results demonstrate a role of estrogen in the regulation of TRIM‐21 expression through an ERα‐dependent mechanism, a pathway that we observed to be overactive in SLE patients. Treatment of monocytes with an ERα antagonist abrogated estrogen‐induced TRIM‐21 expression and, as a consequence, decreased the expression of interleukin‐23. These findings identify TRIM‐21 as a novel ERα‐regulated gene and provide novel insights into the link between estrogen and the molecular pathogenesis of SLE.
Reactivity of Fluoro‐Substituted Bis(thiocarbonyl) Donors with Diiodine: An XRD, FT–Raman, and DFT Investigation
Authors: Mancini Annalisa , Aragoni M. Carla , Bingham Ann L. , Castellano Carlo , Coles (née Huth) Susanne L. , Demartin Francesco , Hursthouse Michael B. , Isaia Francesco , Lippolis Vito , Maninchedda Giuseppe , Pintus Anna , Arca Massimiliano 
Published: September 2013

AbstractThe reactions of 1,3,8,10‐tetrakis(4′‐fluorophenyl)‐4,5,6,7‐tetrathiocino[1,2‐b:3,4‐b′]diimidazolyl‐2,9‐dithione (4) and molecular diiodine afforded spoke adducts with stoichiometries 4·I2 and 4⋅3I2, isolated in the compound 4⋅3I2⋅xCH2Cl2⋅(1−x)I2 (x=0.70), and characterized by single‐crystal XRD and FT–Raman spectroscopy. The nature of the reaction products was investigated under the prism of theoretical calculations carried out at the DFT level. The structural data, FT–Raman spectroscopy, and quantum mechanical calculations agree in indicating that the introduction of fluorophenyl substituents results in a lowering of the Lewis basicity of this class of bis(thiocarbonyl) donors compared with alkyl‐substituted tetrathiocino donors and fluorine allows for extended interactions that are responsible for solid‐state crystal packing.
Parametric Solutions to the Generalized Discrete Yakubovich‐Transpose Matrix Equation
Authors: Song Caiqin , Feng Jun‐e , Wang Xiaodong , Zhao Jianli 
Published: September 2013

AbstractThis paper is concerned with the complete parametric solutions to the generalized discrete Yakubovich‐transpose matrix equation X − AXTB = CY. which is related with several types of matrix equations in control theory. One of the parametric solutions has a neat and elegant form in terms of the Krylov matrix, a block Hankel matrix and an observability matrix. In addition, the special case of the generalized discrete Yakubovich‐transpose matrix equation, which is called the Karm‐Yakubovich‐transpose matrix equation, is considered. The explicit solutions to the Karm‐Yakubovich‐transpose matrix equation are also presented by the so‐called generalized Leverrier algorithm. At the end of the paper, two examples are given to show the efficiency of the proposed algorithm.
Circularly Polarized Luminescence in Supramolecular Assemblies of Chiral Bichromophoric Perylene Bisimides
Authors: Kumar Jatish , Nakashima Takuya , Tsumatori Hiroyuki , Mori Midori , Naito Masanobu , Kawai Tsuyoshi 
Published: September 2013

AbstractChiral bichromophoric perylene bisimides are demonstrated as active materials of circularly polarized emission. The bichromophoric system exhibited circularly polarized luminescence with dissymmetry factors typical of that of similar organic chiral chromophoric systems in the monomeric state. Variation in solvent composition led to the formation of stably soluble helical aggregates through intermolecular interactions. A large enhancement in the dissymmetry of circularly polarized luminescence was exhibited by the aggregated structures both in the solution and solid states. The sum of excitonic couplings between the individual chromophoric units in the self‐assembled state results in relatively large dissymmetry in the circularly polarized luminescence, thereby giving rise to enhanced dissymmetry factors for the aggregated structures. The spacer between chiral center and chromophoric units played a crucial role in the effective enhancement of chiroptical properties in the self‐assembled structures. These materials might provide opportunities for the design of a new class of functional bichromophoric organic nanoarchitectures that can find potential applications in the field of chiroptical memory and light‐emitting devices based on supramolecular electronics.
Ammonia‐Annealed TiO2 as a Negative Electrode Material in Li‐Ion Batteries: N Doping or Oxygen Deficiency?
Authors: Ventosa Edgar , Xia Wei , Klink Stefan , Mantia Fabio La , Mei Bastian , Muhler Martin , Schuhmann Wolfgang 
Published: September 2013

AbstractImproving the chemical diffusion of Li ions in anatase TiO2 is essential to enhance its rate capability as a negative electrode for Li‐ion batteries. Ammonia annealing has been used to improve the rate capability of Li4Ti5O12. Similarly, ammonia annealing improves the Li‐ion storage performance of anatase TiO2 in terms of the stability upon cycling and the C‐rate capability. In order to distinguish whether N doping or oxygen deficiencies, both introduced upon ammonia annealing, are more relevant for the observed improvement, a systematic electrochemical study was performed. The results suggest that the creation of oxygen vacancies upon ammonia annealing is the main reason for the improvement of the stability and C‐rate capability.
Quality changes during spouted bed drying of Pepper‐Rosmarin extract
Authors: Benelli Lucimara , Souza Claudia R. F. , Oliveira Wanderley P. 
Published: September 2013

AbstractThis study was undertaken in order to evaluate the effects of processing and feed composition variables on the retention of volatile compounds and product properties during spouted bed drying of pepper‐rosmarin extract (Lippia sidoides Cham.). The product loss on drying, LD, moisture content, Xp, water activity, Aw, concentration of bioactive markers (flavonoid, TF, polyphenol, TPF and thymol contents, TT), antioxidant activity, IC50, powder flow properties, powder morphology and crystalline state were the responses analysed. Processing conditions and feed composition significantly affected the product quality, leading to noticeable changes in the retention of bioactive substances. Results of this study show that the concentration of bioactive markers in the dried product tended to increase with the feed flow rate of the feed composition relative to the maximum dryer evaporation capacity, Ws/Wmax, and conversely with the concentration of drying carriers added to the feed composition. The dried extract showed significant antioxidant activity, although significant losses of bioactive marker compounds (TF, TPF and TT) were observed in some processing conditions.
Native and rearranged ALK copy number and rearranged cell count in non–small cell lung cancer
Authors: Camidge D. Ross , Skokan Margaret , Kiatsimkul Porntip , Helfrich Barbara , Lu Xian , Barón Anna E. , Schulte Nathan , Maxson DeLee , Aisner Dara L. , Franklin Wilbur A. , Doebele Robert C. , Varella‐Garcia Marileila 
Published: September 2013

BACKGROUNDPatients with anaplastic lymphoma kinase (ALK)‐positive non–small cell lung cancer (NSCLC) respond to ALK inhibitors. Clinically, the presence of ≥15% cells with rearrangements identified on break‐apart fluorescence in situ hybridization (FISH) classifies tumors as positive. Increases in native and rearranged ALK copy number also occur.METHODSIn total, 1426 NSCLC clinical specimens (174 ALK‐positive specimens and 1252 ALK‐negative specimens) and 24 ALK‐negative NSCLC cell lines were investigated. ALK copy number and genomic status were assessed by FISH.RESULTSClinical specimens with 0% to 9%, 10% to 15%, 16% to 30%, 31% to 50%, and >50% ALK‐positive cells were identified in 79.3%, 8.5%, 1.4%, 2.7%, and 8.1%, respectively. An increased native ALK copy number (≥3 copies per cell in ≥40% of cells) was detected in 19% of ALK‐positive tumors and in 62% of ALK‐negative tumors. In ALK‐negative tumors, abundant, focal amplification of native ALK was rare (0.8%). Other atypical patterns occurred in approximately 6% of tumors. The mean native ALK copy number ranged from 2.1 to 6.9 copies in cell lines and was not correlated with crizotinib sensitivity (50% inhibitory concentration, 0.34‐2.8 μM; r = 0.279; P = .1764). Neither native or rearranged ALK copy number nor the percentage of positive cells correlated with extra‐central nervous system progression‐free survival in ALK‐positive patients who were receiving crizotinib.CONCLUSIONSOverall, 8.5% of tumors fell below the established positivity threshold by ≤5%. Further investigation of ALK by other diagnostic techniques in such cases may be warranted. Native ALK copy number increases alone were not associated with sensitivity to ALK inhibition in vitro. However, rare, complex patterns of increased native ALK in patients should be studied further; because, otherwise, atypical rearrangements contained within these may be missed. Cancer 2013;119:3968–3975. © 2013 American Cancer Society.
A NEIL1 single nucleotide polymorphism (rs4462560) predicts the risk of radiation‐induced toxicities in esophageal cancer patients treated with definitive radiotherapy
Authors: Chen Yun , Zhu Meiling , Zhang Zhen , Jiang Guoliang , Fu Xiaolong , Fan Min , Sun Menghong , Wei Qingyi , Zhao Kuaile 
Published: September 2013

BACKGROUNDTo assess the association between single nucleotide polymorphisms (SNPs) of base‐excision repair genes and clinical outcomes, the roles of genetic variants of 3 selected genes—flap structure‐specific endonuclease 1 (FEN1), 8‐hydroxyguanine DNA glycosylase (hOGG1), and nei endonuclease VIII‐like 1 (NEIL1)—were investigated in radiation‐induced esophageal toxicity (RIET), radiation pneumonitis (RP), and overall survival (OS) after radio(chemo)therapy in patients with esophageal squamous cell carcinoma (ESCC).METHODSNEIL1 reference SNP 4462560 (rs4462560) and rs7402844, hOGG1 rs1052133 and rs293795, and FEN1 rs4246215 and rs174538 were genotyped in 187 patients with ESCC who received definitive radiotherapy with or without chemotherapy. Kaplan‐Meier cumulative probabilities and Cox proportional hazards regression models were used to assess the effect of the genotypes on the risk of RIET, RP, and OS.RESULTSThe authors observed that patients who had the NEIL1 rs4462560 GC/CC genotype had a statistically significantly lower risk of both grade ≥2 acute radiation‐induced esophageal toxicity (RIET) (adjusted hazard ratio [HR], 0.421; 95% confidence interval [CI], 0.207‐0.856; P = .017) and grade ≥2 acute radiation pneumonitis (RP) (adjusted HR, 0.392; 95% CI, 0.163‐0.946; P = .037) compared with patients who had the GG genotype, but the genotype did not affect OS (adjusted HR, 0.778; 95% CI, 0.471‐1.284; P = .326). There were no significant findings for other the SNPs under investigation.CONCLUSIONSThe NEIL1 rs4462560 SNP may serve as a predictor of acute RIET and RP risk but not of OS. Larger prospective studies are needed to validate these findings. Cancer 2013;119:4205–4211. © 2013 American Cancer Society.
Selective Hydrogenation of Phenol and Derivatives over Polymer‐Functionalized Carbon‐Nanofiber‐Supported Palladium Using Sodium Formate as the Hydrogen Source
Authors: Chen Aibing , Li Yonglei , Chen Jinzhu , Zhao Guoying , Ma Longlong , Yu Yifeng 
Published: September 2013

AbstractSelective hydrogenation of phenol to cyclohexanone over a catalyst of polyaniline‐functionalized carbon‐nanofiber‐supported palladium (Pd‐PANI/CNF) with sodium formate as the hydrogen source has been studied. Phenol conversion exceeding 99 % was achieved with a cyclohexanone selectivity of >99 % in aqueous media. In an extension to Pd‐PANI/CNF, polymers such as polypyrrole (PPY), poly(4‐vinylpyridine) (PVP), and poly(1‐vinylimidazole) (PVI) were further applied to a catalyst of Pd‐polymer/CNF for selective phenol hydrogenation. All of the Pd‐polymer/CNF catalysts showed excellent to good performance toward selective phenol hydrogenation. However, Pd‐PANI/CNF was considerably more active and selective to afford the desired cyclohexanone than Pd‐PPY/CNF, Pd‐PVP/CNF, and Pd‐PVI/CNF. Moreover, a series of phenol‐derived compounds were selectively hydrogenated in high yields under the investigated aqueous conditions. The research highlights an environmentally benign and effective process for the selective reduction of phenol derivatives with sodium formate as an alternative hydrogen source.
Impaired sustained attention in adult patients with type 1 diabetes is related to diabetes per se
Authors: van Dijk Marieke , Donga Esther , van Schie Mojca K. M. , Lammers Gert Jan , van Zwet Erik W. , Corssmit Eleonora P. M. , Romijn Johannes A. , van Dijk J. Gert 
Published: September 2013

AbstractBackgroundPatients with type 1 diabetes have altered sleep characteristics and are thought to have deficits in sustained attention. We compared the sustained attention to response task (SART) of patients with type 1 diabetes to that of healthy controls, and related results with sleep characteristics and disease‐related factors.MethodsSART was applied in 122 patients and 109 controls. Glucoregulation was assessed by HbA1c values and a questionnaire assessing glycaemic history. Clinical parameters were obtained from medical charts. Polyneuropathy was assessed by neurological examination and quantitative sensory testing. Sleep characteristics were assessed with sleep questionnaires. Anxiety and depression scores were assessed by the Hospital Anxiety and Depression Scale.ResultsThe SART reaction time (RT) was significantly longer than in controls (327 ± 5 vs. 285 ± 3 ms, p < 0.001), although there were no significant differences in error scores. Repeated measurement analyses showed that diabetes per se was associated with prolonged RT (p < 0.001) and more commission errors (p = 0.010). None of the sleep‐related and diabetes‐related factors were significantly associated with these SART parameters.ConclusionsPatients with type 1 diabetes had impaired sustained attention, which was associated with diabetes per se but not with disturbed sleep characteristics. Copyright © 2013 John Wiley & Sons, Ltd.
Neonatal injury rapidly alters markers of pain and stress in rat pups
Authors: Victoria Nicole C. , Karom Mary C. , Eichenbaum Hila , Murphy Anne Z. 
Published: September 2013

ABSTRACTLess than 60% of infants undergoing invasive procedures in the neonatal intensive care unit receive analgesic therapy. These infants show long‐term decreases in pain sensitivity and cortisol reactivity. In rats, we have previously shown that inflammatory pain experienced on the day of birth significantly decreases adult somatosensory thresholds and responses to anxiety‐ and stress‐provoking stimuli. These long‐term changes in pain and stress responsiveness are accompanied by two‐fold increases in central met‐enkephalin and β‐endorphin expression. However, the time course over which these changes in central opioid peptide expression occur, relative to the time of injury, are not known. The present studies were conducted to determine whether the observed changes in adult opioid peptide expression were present within the first postnatal week following injury. The impact of neonatal inflammation on plasma corticosterone, a marker for stress reactivity, was also determined. Brain, spinal cord, and trunk blood were harvested at 24 h, 48 h, and 7 d following intraplantar administration of the inflammatory agent carrageenan on the day of birth. Radioimmunoassay was used to determine plasma corticosterone and met‐enkephalin and β‐endorphin levels within the forebrain, cortex, midbrain, and spinal cord. Within 24 h of injury, met‐enkephalin levels were significantly increased in the midbrain, but decreased in the spinal cord and cortex; forebrain β‐endorphin levels were significantly increased as a result of early life pain. Corticosterone levels were also significantly increased. At 7 d post‐injury, opioid peptides remained elevated relative to controls, suggesting a time point by which injury‐induced changes become programmed and permanent. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 74: 42–51, 2014