bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of catabolic rates of fatty acids using stable isotope and isotope‐ratio mass spectrometry
Authors: Gotoh Naohiro , Nagai Toshiharu , Yoshinaga Kazuaki , Mizobe Hoyo , Watanabe Hiroyuki 
Published: May 2013

AbstractThe catabolic rates of individual fatty acids in mice were compared using stable isotope (13C)‐labeled fatty acids and isotope‐ratio mass spectrometry (IRMS). The catabolic rates were evaluated from the ratio of 13C and 12C in carbon dioxide expired by mice. The results showed that the catabolic rate of octanoic acid is three times faster than that of palmitic acid. This result is consistent with previous reports using radioisotope 14C showing that medium‐chain fatty acids are more easily beta‐oxidized than long‐chain fatty acids. The catabolic rates of odd‐numbered fatty acids such as pentadecanoic acid and heptadecanoic acid were significantly lower compared to those of even‐numbered fatty acids such as palmitic acid. These findings support previous reports that show odd‐numbered fatty acids easily accumulating in body fat. The high accumulation of odd‐numbered fatty acids in body fat thus directly reflects a low degree of beta‐oxidization. The combination of stable isotope‐labeled compounds and IRMS serves as a powerful tool in lipid analysis.
Balancing triacylglycerol production and utilization in the liver
Authors: Stanley John 
Published: May 2013

AbstractThe accumulation of triacylglycerols in the liver or steatosis can evolve into more destructive pathological conditions. Understanding how the metabolic pathways of triacylglycerol production and utilisation are balanced and how this balance is lost in insulin resistant states characterised by steatosis is crucial to understanding non‐alcoholic fatty liver disease (NAFLD). Available evidence suggests that oversupply of fatty acids to the liver probably from de novo lipogenesis in the liver itself accounts for steatosis. In addition, steatosis can stimulate de novo lipogenesis by the same mechanism as insulin setting up a vicious circle which may be very hard to break. More research is needed to determine how this vicious circle is initiated.
Tolfenamic acid inhibits colon cancer cell and tumor growth and induces degradation of specificity protein (Sp) transcription factors
Authors: Pathi Satya , Li Xi , Safe Stephen 
Published: May 2013

AbstractTolfenamic acid (TA) is a non‐steroidal anti‐inflammatory drug (NSAID) that inhibits lung, esophageal, breast and pancreatic cancer cell and tumor growth, and this study investigated the anticancer activity of TA in colon cancer. TA inhibited growth and induced apoptosis in RKO, SW480, HT‐29, and HCT‐116 colon cancer cells, and TA (50 mg/kg/d) also inhibited tumor growth in athymic nude mice bearing RKO cells as xenografts. TA downregulated expression of Sp proteins (Sp1, Sp3, and Sp4) in colon cancer cells and this was accompanied by decreased expression of several Sp‐regulated growth promoting (cyclin D1, hepatocyte growth factor receptor), angiogenic (vascular endothelial growth factor (VEGF) and its receptor 1), survival (survivin and bcl‐2), and inflammatory (NFκBp65/p50) gene products. The mechanism of TA‐mediated effects on Sp proteins was due to activation of caspases. These results now extend the number of NSAIDs that may have clinical potential for colon cancer chemotherapy and show that the anticancer activity of TA is due, in part, to targeting Sp transcription factors. © 2013 Wiley Periodicals, Inc.
The many faces of alpha‐synuclein mutations
Authors: Kasten Meike , Klein Christine 
Published: May 2013

ABSTRACTSince the first description of alpha‐synuclein (SNCA) mutations in 1997, this gene has probably become the most intensely investigated one associated with monogenic Parkinson disease (PD). Prompted by the finding of a novel SNCA mutation, H50Q, we systematically explored the 145 published SNCA mutation carriers for a possible mutation (type)‐specific clinical expression, which appears to be rather unique to SNCA mutations compared with other PD genes. The A53T mutation is associated with an approximately 10‐year earlier age at onset than the other 3 known missense mutations, including the new H50Q mutation. Similarly, SNCA triplication carriers have an approximately 10‐year earlier onset and a more rapid disease course than duplication carriers, who, overall closely resemble patients with idiopathic PD. Furthermore, higher order SNCA multiplications are associated with additional neurologic features, such as myoclonus. For the nonmotor features, their mere frequency appears less striking than their severity, with an early age of onset of depression or dementia, suicidal ideation, and multimodal hallucinations. We conclude that, (1) although SNCA mutations are a rare cause of PD, it remains worth testing for new mutations in this gene; (2) a differential view of SNCA mutations and variants may allow important pathophysiologic inferences even beyond monogenic PD and is warranted in the context of clinical counseling. © 2013 Movement Disorder Society
Somatic alpha‐synuclein mutations in Parkinson's disease: Hypothesis and preliminary data
Authors: Proukakis Christos , Houlden Henry , Schapira Anthony H. 
Published: May 2013

ABSTRACTAlpha‐synuclein (SNCA) is crucial in the pathogenesis of Parkinson's disease (PD), yet mutations in the SNCA gene are rare. Evidence for somatic genetic variation in normal humans, also involving the brain, is increasing, but its role in disease is unknown. Somatic SNCA mutations, arising in early development and leading to mosaicism, could contribute to PD pathogenesis and yet be absent or undetectable in DNA derived from peripheral lymphocytes. Such mutations could underlie the widespread pathology in PD, with the precise clinical outcome dependent on their type and the timing and location of their occurrence. We recently reported a novel SNCA mutation (c.150T>G, p.H50Q) in PD brain‐derived DNA. To determine if there was mosaicism for this, a PCR and cloning strategy was used to take advantage of a nearby heterozygous intronic polymorphism. No evidence of mosaicism was found. High‐resolution melting curve analysis of SNCA coding exons, which was shown to be sensitive enough to detect low proportions of 2 known mutations, did not reveal any further mutations in DNA from 28 PD brain‐derived samples. We outline the grounds that make the somatic SNCA mutation hypothesis consistent with genetic, embryological, and pathological data. Further studies of brain‐derived DNA are warranted and should include DNA from multiple regions and methods for detecting other types of genomic variation. © 2013 The Authors. International Parkinson and Movement Disorder Society published by Wiley Periodicals, Inc.
The 6‐minute walk test and other clinical endpoints in duchenne muscular dystrophy: Reliability, concurrent validity, and minimal clinically important differences from a multicenter study
Authors: McDonald Craig M. , Henricson Erik K. , Abresch R. Ted , Florence Julaine , Eagle Michelle , Gappmaier Eduard , Glanzman Allan M. ,   PTC124‐GD‐007‐DMD Study Group, Spiegel Robert , Barth Jay , Elfring Gary , Reha Allen , Peltz Stuart W. 
Published: May 2013

ABSTRACTIntroduction: An international clinical trial enrolled 174 ambulatory males ≥5 years old with nonsense mutation Duchenne muscular dystrophy (nmDMD). Pretreatment data provide insight into reliability, concurrent validity, and minimal clinically important differences (MCIDs) of the 6‐minute walk test (6MWT) and other endpoints. Methods: Screening and baseline evaluations included the 6‐minute walk distance (6MWD), timed function tests (TFTs), quantitative strength by myometry, the PedsQL, heart rate–determined energy expenditure index, and other exploratory endpoints. Results: The 6MWT proved feasible and reliable in a multicenter context. Concurrent validity with other endpoints was excellent. The MCID for 6MWD was 28.5 and 31.7 meters based on 2 statistical distribution methods. Conclusions: The ratio of MCID to baseline mean is lower for 6MWD than for other endpoints. The 6MWD is an optimal primary endpoint for Duchenne muscular dystrophy (DMD) clinical trials that are focused therapeutically on preservation of ambulation and slowing of disease progression. Muscle Nerve 48: 357–368, 2013
Predictors of neoplastic disease in children with isolated pituitary stalk thickening
Authors: Robison Nathan J. , Prabhu Sanjay P. , Sun Pengling , Chi Susan N. , Kieran Mark W. , Manley Peter E. , Cohen Laurie E. , Goumnerova Liliana , Smith Edward R. , Scott R. Michael , London Wendy B. , Ullrich Nicole J. 
Published: May 2013

AbstractBackgroundThe significance of pituitary stalk thickening (PST) on magnetic resonance imaging (MRI) is often unclear. We evaluated presenting symptoms, MRI findings, clinical course, and outcome predictors of patients with PST.ProcedureWe used a computerized search of the medical record from 1995 to 2008 to identify patients with PST without pituitary mass on MRI. Baseline and follow‐up MRIs were reviewed in a blinded fashion. Relevant clinical data were abstracted.Results69 patients with reported PST and adequate imaging for review were identified; 42 met study criteria. Median age at first abnormal MRI was 13.6 years (range: 0.8–19.7); 43% were male. Median follow‐up was 3.4 years (range 0–12.8). Patients with diabetes insipidus (DI) were significantly more likely to have a neoplastic process than those without (P = 0.0008). Of 16 patients with DI, 8 (50%) had a neoplastic process, including germ cell tumor (n = 4), Langerhans cell histiocytosis (n = 3), and lymphoma (n = 1). Among patients with DI, 7 (44%) also developed anterior pituitary hormone dysfunction (APD), either at presentation or on pre‐biopsy follow‐up, including 6/8 patients with stalk neoplasm and only 1/8 patients with non‐neoplastic PST (P = 0.04). Twenty‐six patients presented without DI; none was found to have neoplasm of the stalk except one patient with craniopharyngioma. Progression of PST on follow‐up imaging was significantly associated with a subsequent neoplastic diagnosis (P = 0.04).ConclusionPatients with PST without DI are unlikely to have a neoplastic process. Among patients with DI, APD or progressive stalk increase over time are predictive of neoplasia. Pediatr Blood Cancer 2013;60:1630–1635. © 2013 Wiley Periodicals, Inc.
Glycidyl Azide Polymer Crosslinked Through Triazoles by Click Chemistry: Curing, Mechanical and Thermal Properties
Authors: Reshmi Sasidhara K. , Vijayalakshmi K. P. , Thomas Deepthi , Arunan E. , Reghunadhan Nair C. P. 
Published: May 2013

AbstractGlycidyl azide polymer (GAP) was cured through “click chemistry” by reaction of the azide group with bispropargyl succinate (BPS) through a 1,3‐dipolar cycloaddition reaction to form 1,2,3‐triazole network. The properties of GAP‐based triazole networks are compared with the urethane cured GAP‐systems. The glass transition temperature (Tg), tensile strength, and modulus of the system increased with crosslink density, controlled by the azide to propargyl ratio. The triazole incorporation has a higher Tg in comparison to the GAP‐urethane system (Tg−20 °C) and the networks exhibit biphasic transitions at 61 and 88 °C. The triazole curing was studied using Differential Scanning Calorimetry (DSC) and the related kinetic parameters were helpful for predicting the cure profile at a given temperature. Density functional theory (DFT)‐based theoretical calculations implied marginal preference for 1,5‐addition over 1,4‐addition for the cycloaddition between azide and propargyl group. Thermogravimetic analysis (TG) showed better thermal stability for the GAP‐triazole and the mechanism of decomposition was elucidated using pyrolysis GC‐MS studies. The higher heat of exothermic decomposition of triazole adduct (418 kJ ⋅ mol−1) against that of azide (317 kJ ⋅ mol−1) and better mechanical properties of the GAP‐triazole renders it a better propellant binder than the GAP‐urethane system.
Synthesis and Characterization of 1,5‐Dinitro‐2,6‐bis(trinitromethyl)‐3a,4a,7a,8a‐tetrahydro‐[1,4]dioxino[2,3‐d:5,6‐d′]diimidazole (DNTNDI)
Authors: Wu Minjie , Chen Shusen , Shu Qinghai , Li Lijie , Jin Shaohua 
Published: May 2013

AbstractThe polynitro imidazole derivative 1,5‐dinitro‐2,6‐bis(trinitromethyl)‐3a,4a,7a,8a‐tetrahydro‐[1,4]dioxino[2,3‐d:5,6‐d′]diimidazole (DNTNDI) was synthesized through nitration of 2‐(dinitromethylene)‐1H‐imidazol‐4‐ol in HNO3/Ac2O followed by cyclization of the di‐enol. It was characterized by NMR, IR, elemental analysis, and single‐crystal X‐ray diffraction analysis. Compound DNTNDI crystallizes in the orthorhombic space group P2(1)2(1)2(1). The thermal decomposition was studied with thermogravimetry/derivative thermogravimetry (TG/DTG) in a nitrogen atmosphere with a heating rate of 5 K min−1. The TG/DTG analysis indicated that DNTNDI has 97.64 % mass loss between 127 °C and 173 °C by undergoing exothermic decomposition. The density of DNTNDI was determined as 1.906 g cm−3 at 293 K with an Ultrapycno 1000 Pycnometer. The denotation velocity and denotation pressure of DNTNDI were calculated as 9325 m s−1 and 40 GPa by applying the LOTUSES (version 1.4) code, respectively. The oxygen balance of DNTNDI is 0 and its oxygen content amounts to 51.78 %, which is superior to that of new generation of chlorine‐free oxidizer ammonium dinitramide (ADN).
Molecular function prediction for a family exhibiting evolutionary tendencies toward substrate specificity swapping: Recurrence of tyrosine aminotransferase activity in the Iα subfamily
Authors: Muratore Kathryn E. , Engelhardt Barbara E. , Srouji John R. , Jordan Michael I. , Brenner Steven E. , Kirsch Jack F. 
Published: May 2013

ABSTRACTThe subfamily Iα aminotransferases are typically categorized as having narrow specificity toward carboxylic amino acids (AATases), or broad specificity that includes aromatic amino acid substrates (TATases). Because of their general role in central metabolism and, more specifically, their association with liver‐related diseases in humans, this subfamily is biologically interesting. The substrate specificities for only a few members of this subfamily have been reported, and the reliable prediction of substrate specificity from protein sequence has remained elusive. In this study, a diverse set of aminotransferases was chosen for characterization based on a scoring system that measures the sequence divergence of the active site. The enzymes that were experimentally characterized include both narrow‐specificity AATases and broad‐specificity TATases, as well as AATases with broader‐specificity and TATases with narrower‐specificity than the previously known family members. Molecular function and phylogenetic analyses underscored the complexity of this family's evolution as the TATase function does not follow a single evolutionary thread, but rather appears independently multiple times during the evolution of the subfamily. The additional functional characterizations described in this article, alongside a detailed sequence and phylogenetic analysis, provide some novel clues to understanding the evolutionary mechanisms at work in this family. Proteins 2013. © 2013 Wiley Periodicals, Inc.
Ab initio folding of extended α‐helix: A theoretical study about the role of electrostatic polarization in the folding of helical structures
Authors: Lazim Raudah , Wei Caiyi , Sun Tiedong , Zhang Dawei 
Published: May 2013

ABSTRACTIn this work, we report the ab initio folding of three different extended helical peptides namely 2khk, N36, and C34 through conventional molecular dynamics simulation at room temperature using implicit solvation model. Employing adaptive hydrogen bond specific charge (AHBC) scheme to account for the polarization effect of hydrogen bonds established during the simulation, the effective folding of the three extended helices were observed with best backbone RMSDs in comparison to the experimental structures over the helical region determined to be 1.30 Å for 2khk, 0.73 Å for N36 and 0.72 Å for C34. In this study, 2khk will be used as a benchmark case serving as a means to compare the ability of polarized (AHBC) and nonpolarized force field in the folding of an extended helix. Analyses conducted revealed the ability of the AHBC scheme in effectively folding the extended helix by promoting helix growth through the stabilization of backbone hydrogen bonds upon formation during the folding process. Similar observations were also noted when AHBC scheme was employed during the folding of C34 and N36. However, under Amber03 force field, helical structures formed during the folding of 2khk was not accompanied by stabilization thus highlighting the importance of electrostatic polarization in the folding of helical structures. Proteins 2013. © 2013 Wiley Periodicals, Inc.
Structure‐based engineering of streptavidin monomer with a reduced biotin dissociation rate
Authors: DeMonte Daniel , Drake Eric J. , Lim Kok Hong , Gulick Andrew M. , Park Sheldon 
Published: May 2013

ABSTRACTWe recently reported the engineering of monomeric streptavidin, mSA, corresponding to one subunit of wild type (wt) streptavidin tetramer. The monomer was designed by homology modeling, in which the streptavidin and rhizavidin sequences were combined to engineer a high affinity binding pocket containing residues from a single subunit only. Although mSA is stable and binds biotin with nanomolar affinity, its fast off rate (koff) creates practical challenges during applications. We obtained a 1.9 Å crystal structure of mSA bound to biotin to understand their interaction in detail, and used the structure to introduce targeted mutations to improve its binding kinetics. To this end, we compared mSA to shwanavidin, which contains a hydrophobic lid containing F43 in the binding pocket and binds biotin tightly. However, the T48F mutation in mSA, which introduces a comparable hydrophobic lid, only resulted in a modest 20–40% improvement in the measured koff. On the other hand, introducing the S25H mutation near the bicyclic ring of bound biotin increased the dissociation half life (t½) from 11 to 83 min at 20°C. Molecular dynamics (MD) simulations suggest that H25 stabilizes the binding loop L3,4 by interacting with A47, and protects key intermolecular hydrogen bonds by limiting solvent entry into the binding pocket. Concurrent T48F or T48W mutation clashes with H25 and partially abrogates the beneficial effects of H25. Taken together, this study suggests that stabilization of the binding loop and solvation of the binding pocket are important determinants of the dissociation kinetics in mSA. Proteins 2013. © 2013 Wiley Periodicals, Inc.
Crystal structure of the cataract‐causing P23T γD‐crystallin mutant
Authors: Ji Fangling , Koharudin Leonardus M. I. , Jung Jinwon , Gronenborn Angela M. 
Published: May 2013

ABSTRACTUp to now, efforts to crystallize the cataract‐associated P23T mutant of human γD‐crystallin have not been successful. Therefore, insights into the light scattering mechanism of this mutant have been exclusively obtained from solution work. Here we present the first crystal structure of the P23T mutant at 2.5 Å resolution. The protein exhibits essentially the same overall structure as seen for the wild‐type protein. Based on our structural data, we confirm that no major conformational changes are caused by the mutation, and that solution phase properties of the mutant appear exclusively associated with cataract formation. Proteins 2013. © 2013 Wiley Periodicals, Inc.
Atomistic simulation of phonon and alloy limited hole mobility in Si1–xGex nanowires
Authors: Mehrotra Saumitra , Long Pengyu , Povolotskyi Michael , Klimeck Gerhard 
Published: May 2013

Abstractmagnified imageThe role of alloy and phonon scattering is theoretically explored in 5 nm diameter SiGe nanowires at room temperature. Low‐field mobility calculations are performed by utilizing sp3d5ds*‐spin–orbit‐coupled tight binding model for electronic structure and Boltzmann transport formalism. Three different transport orientations 〈100〉, 〈110〉 and 〈111〉 are considered. Alloy scattering is found to play an important role in these Si1–xGex nanowires, leading to a characteristic ‘U’ shaped mobility curve as a function of alloy composition. It is concluded that to extract any advantage of higher Ge hole mobility by alloying, Ge% > 70% is needed. Furthermore, the 〈111〉 channel orientation exhibits the highest hole mobility while 〈100〉 has the lowest hole mobility for any given alloy composition. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Metabolite profiling using liquid chromatography/quadrupole time‐of‐flight mass spectrometry for the identification of a suitable marker and target matrix of griseofulvin use in bovines
Authors: Tarbin J. A. , Fussell R. J. 
Published: May 2013

RATIONALEGriseofulvin is an antifungal agent with potential for misuse in food‐producing animals. Little is known about its metabolism in ruminants and hence what are suitable marker residues and target matrices for monitoring purposes.METHODSTissues harvested from cattle treated with the antifungal agent griseofulvin were screened using liquid chromatography coupled to positive and negative electrospray ionization (ESI) quadrupole time‐of‐flight mass spectrometry (qToFMS) operated in ToF mode.RESULTSTwenty‐five possible metabolites were detected across all tissue types, but two isomeric compounds with accurate masses corresponding to loss of a methyl group from parent griseofulvin were considered to be the best candidate markers. Data from fragmentation experiments enabled a tentative assignment of the structures of the two compounds as 4‐demethylgriseofulvin and 6‐demethylgriseofulvin. These assignments were confirmed by matching the product ion spectra of incurred residues to those of custom synthesized reference standards.CONCLUSIONS4‐Demethyl‐ and 6‐demethylgriseofulvin have been identified as potential marker compounds of griseofulvin use in cattle. Liver was identified as the target matrix. Hair was shown to have potential for non‐invasive testing. © Crown copyright 2013. Reproduced with the permission of Her Majesty's Stationery Office. Published by John Wiley & Sons, Ltd.