bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in psychological adjustment over the course of treatment for breast cancer: the predictive role of social sharing and social support
Authors: Boinon Diane , Sultan Serge , Charles Cécile , Stulz Alexandra , Guillemeau Claire , Delaloge Suzette , Dauchy Sarah 
Published: October 2013

AbstractBackgroundAlthough research on social sharing suggests it could be an important factor in subsequent adjustment, it has rarely been examined in combination with the nature of the support received by patients. The goal of this study was to determine whether and to what extent social sharing concerning the disease and perceived social support after breast surgery explain psychological adjustment at the end of the treatment.MethodsOne hundred two participants were recruited consecutively at a large cancer care center (Gustave Roussy, France). After surgery (T1) and at the end of the adjuvant treatment (T2), patients responded to self‐report questionnaires assessing psychological adjustment (depressive symptoms and cancer‐related distress), social sharing concerning the illness, and perceived social support (generic and cancer specific).ResultsWhen the initial levels of adjustment were controlled for, hierarchical multiple regression models showed that greater instrumental support at T1 accounted for favorable changes in depressive symptoms at T2. In contrast, the perception of aversive attitudes in the environment and the avoidance of social sharing explained an increase in intrusive cancer‐related thoughts.ConclusionThe results suggest a negative impact of aversive attitudes from the environment on adjustment during treatment. It also confirms the importance of practical aspects of social support after surgery. In line with Lepore theory, sharing about the illness in a supportive environment may be of primary importance in the cognitive processing of cancer and thus may promote adjustment. These results have original implications for the counseling of patients and their relatives. Copyright © 2013 John Wiley & Sons, Ltd.
The choice of whether to participate in a phase I clinical trial: increasing the awareness of patients with cancer. An exploratory study
Authors: Catania C. , Radice D. , Spitaleri G. , Adamoli L. , Noberasco C. , Delmonte A. , Vecchio F. , de Braud F. , Toffalorio F. , Goldhirsch A. , De Pas T. 
Published: October 2013

AbstractObjectiveIn a previous study, we found that patients who were offered the possibility of participation in a clinical trial had unexpressed concerns and fears that prevented them from making free or fully knowledgeable choices about their trial participation. In a selected population of patients who were offered participation in a phase I trial, we prospectively investigated whether a face‐to‐face discussion about their unexpressed fears might lead to a more conscious decision about whether to accept/refuse participation in the trial.MethodsAfter the presentation of the trial, a questionnaire was administered to assess the presence of specific fears. Before the patients decided whether to participate in the trial, they discussed any fears that they had; finally, the impact of the discussion on the patients' choice to participate was evaluated.ResultsThe majority (86%) of the patients thought that physicians conduct clinical trials for scientific interest, 13% felt exploited as ‘guinea pigs’ and 20% believed they were offered participation because they had no further hope for improvement. These existing fears were not elicited during the trial interview because the patients were themselves unaware of having them (28%) and because of fear of the doctors (3%). The possibility of discussing these fears was felt as an opportunity and made patients feel more conscious (92%) and freer (97%) when making their choice.ConclusionsRecognising and discussing misconceptions and fears, often unexpressed, make patients freer and more aware when facing the choice of whether or not \to participate in a phase I clinical trial. Copyright © 2013 John Wiley & Sons, Ltd.
Ten‐year follow up of hydroxychloroquine treatment for ABCA3 deficiency
Authors: Williamson Michael , Wallis Colin 
Published: October 2013

SummaryWe present a child with interstitial lung disease (ILD) who was diagnosed with desquamative interstitial pneumonitis following CT thorax and open lung biopsy aged 2 years. Subsequently, surfactant protein gene analysis revealed mutations in the ABCA3 gene. This case of ABCA3 deficient ILD describes a stable clinical course over 10 years and highlights the potential benefit of hydroxychloroquine for this condition. Pediatr Pulmonol. 2014; 49:299–301. © 2013 Wiley Periodicals, Inc.
A case for early bronchoscopic airway assessment after disc battery ingestion
Authors: Wurzel Danielle F. , Masters I. Brent , Choo Kelvin L. , Isles Alan F. 
Published: October 2013

SummaryDisc battery ingestion in children is becoming increasingly common with the proliferation of small battery‐powered electronic devices. In the case of esophageal impaction, the likelihood and severity of complications are proportionate to the time between ingestion and removal. Tracheo‐esophageal fistulae (TOF) are a recognized complication and can be life‐threatening. We describe an interesting case of disc battery ingestion with delayed recognition of a TOF. We document the tracheal mucosal healing process of a large airway defect and describe the role of bronchoscopy in guiding the timing of surgical intervention. This case highlights the important role of early bronchoscopic assessment in management of these patients. Pediatr Pulmonol. 2014; 49:E72–E74. © 2013 Wiley Periodicals, Inc.
Effect of Homolog Doping on Surface Morphology and Mass‐Loss Rates from PETN Crystals: Studies using Atomic Force Microscope and Thermogravimetric Analysis
Authors: Bhattacharia Sanjoy K. , Maiti Amitesh , Gee Richard H. , Nunley Jay , Weeks Brandon L. 
Published: October 2013

AbstractPentaerythritol tetranitrate (PETN) is an important energetic material, whose performance as a secondary explosive depends strongly on the density as well as flow porosity of powdered material, which in turn is governed by the size and surface properties of the PETN crystallite particles. Historically there has been evidence that the surface properties of PETN particles can be strongly influenced by the presence of homolog impurities of PETN, in particular, dipentaerythritol hexanitrate (diPEHN) and tripentaerythritol octanitrate (triPEON), although not many systematic studies characterizing such influence exist. In this work we employ thermogravimetric analysis (TGA) to measure mass‐loss rates at elevated temperatures and show that doping with a small amount of diPEHN and triPEON can reduce the mass‐loss rate from PETN single‐crystal surfaces by as much as 35 % as compared to undoped crystals. Arrhenius plots of mass‐loss rates as a function of temperature suggest that the reduction in evaporation is not due to the change in activation barrier of the molecular evaporation process, but perhaps due to the impedance to the receding motion of the steps by the immobile impurities on the surface. Removal of surface impurities through gentle washing with ethanol leads to enhanced mass‐loss rate relative to pure PETN suggesting a roughened surface morphology. Some surface roughening in doped crystals is supported by Atomic force microscopy (AFM) images of growth layers that show evidences of growth layer stacking and rough edges. We also find that a larger amount of impurity added to the original solution does not necessarily lead to a more highly doped crystal, which could perhaps be interpreted as PETN crystals being able to accommodate only up to a certain weight percent of homolog impurities.
Recombinant human lecithin‐cholesterol acyltransferase Fc fusion: Analysis of N‐ and O‐linked glycans and identification and elimination of a xylose‐based O‐linked tetrasaccharide core in the linker region
Authors: Spahr Chris , Kim Justin J. , Deng Sihong , Kodama Paul , Xia Zhen , Tang Jay , Zhang Richard , Siu Sophia , Nuanmanee Noi , Estes Bram , Stevens Jennitte , Zhou Mingyue , Lu Hsieng S. 
Published: October 2013

AbstractRecombinant human lecithin‐cholesterol acyltransferase Fc fusion (huLCAT‐Fc) is a chimeric protein produced by fusing human Fc to the C‐terminus of the human enzyme via a linker sequence. The huLCAT‐Fc homodimer contains five N‐linked glycosylation sites per monomer. The heterogeneity and site‐specific distribution of the various glycans were examined using enzymatic digestion and LC‐MS/MS, followed by automatic processing. Almost all of the N‐linked glycans in human LCAT are fucosylated and sialylated. The predominant LCAT N‐linked glycoforms are biantennary glycans, followed by triantennary sugars, whereas the level of tetraantennary glycans is much lower. Glycans at the Fc N‐linked site exclusively contain typical asialobiantennary structures. HuLCAT‐Fc was also confirmed to have mucin‐type glycans attached at T407 and S409. When LCAT‐Fc fusions were constructed using a G‐S‐G‐G‐G‐G linker, an unexpected +632 Da xylose‐based glycosaminoglycan (GAG) tetrasaccharide core of Xyl‐Gal‐Gal‐GlcA was attached to S418. Several minor intermediate species including Xyl, Xyl‐Gal, Xyl‐Gal‐Gal, and a phosphorylated GAG core were also present. The mucin‐type O‐linked glycans can be effectively released by sialidase and O‐glycanase; however, the GAG could only be removed and localized using chemical alkaline β‐elimination and targeted LC‐MS/MS. E416 (the C‐terminus of LCAT) combined with the linker sequence is likely serving as a substrate for peptide O‐xylosyltransferase. HuLCAT‐Fc shares some homology with the proposed consensus site near the linker sequence, in particular, the residues underlined PPPE416GS418GGGGDK. GAG incorporation can be eliminated through engineering by shifting the linker Ser residue downstream in the linker sequence.
Probing impact of active site residue mutations on stability and activity of Neisseria polysaccharea amylosucrase
Authors: Daudé David , Topham Christopher M. , Remaud‐Siméon Magali , André Isabelle 
Published: October 2013

AbstractThe amylosucrase from Neisseria polysaccharea is a transglucosidase from the GH13 family of glycoside‐hydrolases that naturally catalyzes the synthesis of α‐glucans from the widely available donor sucrose. Interestingly, natural molecular evolution has modeled a dense hydrogen bond network at subsite −1 responsible for the specific recognition of sucrose and conversely, it has loosened interactions at the subsite +1 creating a highly promiscuous subsite +1. The residues forming these subsites are considered to be likely involved in the activity as well as the overall stability of the enzyme. To assess their role, a structure‐based approach was followed to reshape the subsite −1. A strategy based on stability change predictions, using the FoldX algorithm, was considered to identify the best candidates for site‐directed mutagenesis and guide the construction of a small targeted library. A miniaturized purification protocol was developed and both mutant stability and substrate promiscuity were explored. A range of 8°C between extreme melting temperature values was observed and some variants were able to synthesize series of oligosaccharides with distributions differing from that of the parental enzyme. The crucial role of subsite −1 was thus highlighted and the biocatalysts generated can now be considered as starting points for further engineering purposes.
Selective CGRP and adrenomedullin peptide binding by tethered RAMP‐calcitonin receptor‐like receptor extracellular domain fusion proteins
Authors: Moad Heather E. , Pioszak Augen A. 
Published: October 2013

AbstractCalcitonin gene‐related peptide (CGRP) and adrenomedullin (AM) are related peptides that are potent vasodilators. The CGRP and AM receptors are heteromeric protein complexes comprised of a shared calcitonin receptor‐like receptor (CLR) subunit and a variable receptor activity modifying protein (RAMP) subunit. RAMP1 enables CGRP binding whereas RAMP2 confers AM specificity. How RAMPs determine peptide selectivity is unclear and the receptor stoichiometries are a topic of debate with evidence for 1:1, 2:2, and 2:1 CLR:RAMP stoichiometries. Here, we describe bacterial production of recombinant tethered RAMP‐CLR extracellular domain (ECD) fusion proteins and biochemical characterization of their peptide binding properties. Tethering the two ECDs ensures complex stability and enforces defined stoichiometry. The RAMP1‐CLR ECD fusion purified as a monomer, whereas the RAMP2‐CLR ECD fusion purified as a dimer. Both proteins selectively bound their respective peptides with affinities in the low micromolar range. Truncated CGRP(27‐37) and AM(37‐52) fragments were identified as the minimal ECD complex binding regions. The CGRP C‐terminal amide group contributed to, but was not required for, ECD binding, whereas the AM C‐terminal amide group was essential for ECD binding. Alanine‐scan experiments identified CGRP residues T30, V32, and F37 and AM residues P43, K46, I47, and Y52 as critical for ECD binding. Our results identify CGRP and AM determinants for receptor ECD complex binding and suggest that the CGRP receptor functions as a 1:1 heterodimer. In contrast, the AM receptor may function as a 2:2 dimer of heterodimers, although our results cannot rule out 2:1 or 1:1 stoichiometries.
The interdomain interface in bifunctional enzyme protein 3/4A (NS3/4A) regulates protease and helicase activities
Authors: Aydin Cihan , Mukherjee Sourav , Hanson Alicia M. , Frick David N. , Schiffer Celia A. 
Published: October 2013

AbstractHepatitis C (HCV) protein 3/4A (NS3/4A) is a bifunctional enzyme comprising two separate domains with protease and helicase activities, which are essential for viral propagation. Both domains are stable and have enzymatic activity separately, and the relevance and implications of having protease and helicase together as a single protein remains to be explored. Altered in vitro activities of isolated domains compared with the full‐length NS3/4A protein suggest the existence of interdomain communication. The molecular mechanism and extent of this communication was investigated by probing the domain–domain interface observed in HCV NS3/4A crystal structures. We found in molecular dynamics simulations that the two domains of NS3/4A are dynamically coupled through the interface. Interestingly, mutations designed to disrupt this interface did not hinder the catalytic activities of either domain. In contrast, substrate cleavage and DNA unwinding by these mutants were mostly enhanced compared with the wild‐type protein. Disrupting the interface did not significantly alter RNA unwinding activity; however, the full‐length protein was more efficient in RNA unwinding than the isolated protease domain, suggesting a more direct role in RNA processing independent of the interface. Our findings suggest that HCV NS3/4A adopts an “extended” catalytically active conformation, and interface formation acts as a switch to regulate activity. We propose a unifying model connecting HCV NS3/4A conformational states and protease and helicase function, where interface formation and the dynamic interplay between the two enzymatic domains of HCV NS3/4A potentially modulate the protease and helicase activities in vivo.
Concerning the structure of apoE
Authors: Frieden Carl , Garai Kanchan 
Published: October 2013

AbstractApolipoprotein E (apoE), first described in 1973, is a truly fascinating protein. While studies initially focused on its role in cholesterol and lipid metabolism, one apoE isoform (apoE4) is a major risk factor for development of late onset Alzheimer's disease. Yet the difference between apoE3, the common form, and apoE4 is a single amino acid of the 299 in this 34 kDa protein. Structure determination of the two domain full length apoE3 protein was only accomplished in 2011 and supports the notion that mutations in the N‐terminal domain can be propagated through the structure to the C‐terminal domain. Understanding the structural differences between apoE3 and apoE4 is critical for finding ways to modulate the deleterious effect of apoE4.
Characterization of human paraoxonase 1 variants suggest that His residues at 115 and 134 positions are not always needed for the lactonase/arylesterase activities of the enzyme
Authors: Bajaj Priyanka , Tripathy Rajan K. , Aggarwal Geetika , Pande Abhay H. 
Published: October 2013

AbstractHuman paraoxonase 1 (h‐PON1) hydrolyzes variety of substrates and the hydrolytic activities of enzyme can be broadly grouped into three categories; arylesterase, phosphotriesterase, and lactonase. Current models of the catalytic mechanism of h‐PON1 suggest that catalytic residues H115 and H134 mediate the lactonase and arylesterase activities of the enzyme. H‐PON1 is a strong candidate for the development of catalytic bioscavenger for organophosphate poisoning in humans. Recently, Gupta et al. (Nat. Chem. Biol. 2011. 7, 120) identified amino acid substitutions that significantly increased the activity of chimeric‐PON1 variant (4E9) against some organophosphate nerve agents. In this study we have examined the effect of these (L69G/S111T/H115W/H134R/R192K/F222S/T332S) and other substitutions (H115W/H134R and H115W/H134R/R192K) on the hydrolytic activities of recombinant h‐PON1 (rh‐PON1) variants. Our results show that the substitutions resulted in a significant increase in the organophosphatase activity of all the three variants of rh‐PON1 enzyme while had a variable effect on the lactonase/arylesterase activities. The results suggest that H residues at positions 115 and 134 are not always needed for the lactonase/arylesterase activities of h‐PON1 and force a reconsideration of the current model(s) of the catalytic mechanism of h‐PON1.
Expression of the cancer‐testis antigen BORIS correlates with prostate cancer
Authors: Cheema Zubair , Hari‐Gupta Yukti , Kita Georgia‐Xanthi , Farrar Dawn , Seddon Ian , Corr John , Klenova Elena 
Published: October 2013

AbstractBACKGROUNDBORIS, a paralogue of the transcription factor CTCF, is a member of the cancer‐testis antigen (CT) family. BORIS is normally present at high levels in the testis; however it is aberrantly expressed in various tumors and cancer cell lines. The main objectives of this study were to investigate BORIS expression together with sub‐cellular localization in both prostate cell lines and tumor tissues, and assess correlations between BORIS and clinical/pathological characteristics.METHODSWe examined BORIS mRNA expression, protein levels and cellular localization in a panel of human prostate tissues, cancer and benign, together with a panel prostate cell lines. We also compared BORIS levels and localization with clinical/pathological characteristics in prostate tumors.RESULTSBORIS was detected in all inspected prostate cancer cell lines and tumors, but was absent in benign prostatic hyperplasia. Increased levels of BORIS protein positively correlated with Gleason score, T‐stage and androgen receptor (AR) protein levels in prostate tumors. The relationship between BORIS and AR was further highlighted in prostate cell lines by the ability of ectopically expressed BORIS to activate the endogenous AR mRNA and protein. BORIS localization in the nucleus plus cytoplasm was also associated with higher BORIS levels and Gleason score.CONCLUSIONSDetection of BORIS in prostate tumors suggests potential applications of BORIS as a biomarker for prostate cancer diagnosis, as an immunotherapy target and, potentially, a prognostic marker of more aggressive prostate cancer. The ability of BORIS to activate the AR gene indicates BORIS involvement in the growth and development of prostate tumors. Prostate 74:164–176, 2014. © 2013 Wiley Periodicals, Inc.
Folding 19 proteins to their native state and stability of large proteins from a coarse‐grained model
Authors: Kapoor Abhijeet , Travesset Alex 
Published: October 2013

ABSTRACTWe develop an intermediate resolution model, where the backbone is modeled with atomic resolution but the side chain with a single bead, by extending our previous model (Proteins (2013) DOI: 10.1002/prot.24269) to properly include proline, preproline residues and backbone rigidity. Starting from random configurations, the model properly folds 19 proteins (including a mutant 2A3D sequence) into native states containing β sheet, α helix, and mixed α/β. As a further test, the stability of H‐RAS (a 169 residue protein, critical in many signaling pathways) is investigated: The protein is stable, with excellent agreement with experimental B‐factors. Despite that proteins containing only α helices fold to their native state at lower backbone rigidity, and other limitations, which we discuss thoroughly, the model provides a reliable description of the dynamics as compared with all atom simulations, but does not constrain secondary structures as it is typically the case in more coarse‐grained models. Further implications are described. Proteins 2014; 82:505–516. © 2013 Wiley Periodicals, Inc.
Structural and functional characterization of a novel α/β hydrolase from cariogenic pathogen Streptococcus mutans
Authors: Wang Zixi , Li Lanfen , Su Xiao‐Dong 
Published: October 2013

ABSTRACTThe protein Smu.1393c from Streptococcus mutans is annotated as a putative α/β hydrolase, but it has low sequence identity to the structure‐known α/β hydrolases. Here we present the crystal structure of Smu.1393c at 2.0 Å resolution. Smu.1393c has a fully open alkaline substrate pocket, whose conformation is unique among other similar hydrolase structures. Three residues, Ser101, His251, and Glu125, were identified as the active center of Smu.1393c. By screening a series of artificial hydrolase substrates, we demonstrated Smu.1393c had low carboxylesterase activity towards short‐chain carboxyl esters, which provided a clue for exploring the in vivo function of Smu.1393c. Proteins 2014; 82:695–700. © 2013 Wiley Periodicals, Inc.
SVR_CAF: An integrated score function for detecting native protein structures among decoys
Authors: Zhou Jianhong , Yan Wenying , Hu Guang , Shen Bairong 
Published: October 2013

ABSTRACTAn accurate score function for detecting the most native‐like models among a huge number of decoy sets is essential to the protein structure prediction. In this work, we developed a novel integrated score function (SVR_CAF) to discriminate native structures from decoys, as well as to rank near‐native structures and select best decoys when native structures are absent. SVR_CAF is a machine learning score, which incorporates the contact energy based score (CE_score), amino acid network based score (AAN_score), and the fast Fourier transform based score (FFT_score). The score function was evaluated with four decoy sets for its discriminative ability and it shows higher overall performance than the state‐of‐the‐art score functions. Proteins 2014; 82:556–564. © 2013 Wiley Periodicals, Inc.