bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electrostatic interactions play an essential role in the binding of oleic acid with α‐lactalbumin in the HAMLET‐like complex: A study using charge‐specific chemical modifications
Authors: Xie Yongjing , Min Soyoung , Harte Níal P. , Kirk Hannah , O'Brien John E. , Voorheis H. Paul , Svanborg Catharina , Hun Mok K. 
Published: February 2013

AbstractHuman α‐lactalbumin made lethal to tumor cells (HAMLET) and its analogs are partially unfolded protein‐oleic acid (OA) complexes that exhibit selective tumoricidal activity normally absent in the native protein itself. To understand the nature of the interaction between protein and OA moieties, charge‐specific chemical modifications of lysine side chains involving citraconylation, acetylation, and guanidination were employed and the biophysical and biological properties were probed. Upon converting the original positively‐charged lysine residues to negatively‐charged citraconyl or neutral acetyl groups, the binding of OA to protein was eliminated, as were any cytotoxic activities towards osteosarcoma cells. Retention of the positive charges by converting lysine residues to homoarginine groups (guanidination); however, yielded unchanged binding of OA to protein and identical tumoricidal activity to that displayed by the wild‐type α‐lactalbumin‐oleic acid complex. With the addition of OA, the wild‐type and guanidinated α‐lactalbumin proteins underwent substantial conformational changes, such as partial unfolding, loss of tertiary structure, but retention of secondary structure. In contrast, no significant conformational changes were observed in the citraconylated and acetylated α‐lactalbumins, most likely because of the absence of OA binding. These results suggest that electrostatic interactions between the positively‐charged basic groups on α‐lactalbumin and the negatively‐charged carboxylate groups on OA molecules play an essential role in the binding of OA to α‐lactalbumin and that these interactions appear to be as important as hydrophobic interactions. Proteins 2013. © 2012 Wiley Periodicals, Inc.
Nucleotide recognition by the initiation factor aIF5B: Free energy simulations of a neoclassical GTPase
Authors: Simonson Thomas , Satpati Priyadarshi 
Published: February 2013

AbstractThe GTPase aIF5B is a universally conserved initiation factor that assists ribosome assembly. Crystal structures of its nucleotide complexes, X‐ray(GTP) and X‐ray(GDP), are similar in the nucleotide vicinity, but differ in the orientation of a distant domain IV. This has led to two, contradictory, mechanistic models. One postulates that X‐ray(GTP) and X‐ray(GDP) are, respectively, the active, “ON” and the inactive, “OFF” states; the other postulates that both structures are OFF, whereas the ON state is still uncharacterized. We study GTP/GDP binding using molecular dynamics and a continuum electrostatic free energy method. We predict that X‐ray(GTP) has a ≈ 3 kcal/mol preference to bind GDP, apparently contradicting its assignment as ON. However, the preference arises mainly from a single, nearby residue from the switch 2 motif: Glu81, which becomes protonated upon GTP binding, with a free energy cost of about 4 kcal/mol. We then propose a different model, where Glu81 protonation/deprotonation defines the ON/OFF states. With this model, the X‐ray(GTP):GTP complex, with its protonated Glu81, is ON, whereas X‐ray(GTP):GDP is OFF. The model postulates that distant conformational changes such as domain IV rotation are “uncoupled” from GTP/GDP exchange and do not affect the relative GTP/GDP binding affinities. We analyze the model using a general thermodynamic framework for GTPases. It yields rather precise predictions for the nucleotide specificities of each state, and the state specificities of each nucleotide, which are roughly comparable to the homologues IF2 and aIF2, despite the lack of any conformational switching in the model. © 2012 Wiley Periodicals, Inc.
CAD‐score: A new contact area difference‐based function for evaluation of protein structural models
Authors: Olechnovič Kliment , Kulberkytė Eleonora , Venclovas Česlovas 
Published: February 2013

AbstractEvaluation of protein models against the native structure is essential for the development and benchmarking of protein structure prediction methods. Although a number of evaluation scores have been proposed to date, many aspects of model assessment still lack desired robustness. In this study we present CAD‐score, a new evaluation function quantifying differences between physical contacts in a model and the reference structure. The new score uses the concept of residue–residue contact area difference (CAD) introduced by Abagyan and Totrov (J Mol Biol 1997; 268:678–685). Contact areas, the underlying basis of the score, are derived using the Voronoi tessellation of protein structure. The newly introduced CAD‐score is a continuous function, confined within fixed limits, free of any arbitrary thresholds or parameters. The built‐in logic for treatment of missing residues allows consistent ranking of models of any degree of completeness. We tested CAD‐score on a large set of diverse models and compared it to GDT‐TS, a widely accepted measure of model accuracy. Similarly to GDT‐TS, CAD‐score showed a robust performance on single‐domain proteins, but displayed a stronger preference for physically more realistic models. Unlike GDT‐TS, the new score revealed a balanced assessment of domain rearrangement, removing the necessity for different treatment of single‐domain, multi‐domain, and multi‐subunit structures. Moreover, CAD‐score makes it possible to assess the accuracy of inter‐domain or inter‐subunit interfaces directly. In addition, the approach offers an alternative to the superposition‐based model clustering. The CAD‐score implementation is available both as a web server and a standalone software package at http://www.ibt.lt/bioinformatics/cad‐score/. Proteins 2013. © 2012 Wiley Periodicals, Inc.
Thermodynamics of binding by calmodulin correlates with target peptide α‐helical propensity
Authors: Dunlap Tori B. , Kirk Jessime M. , Pena Emily A. , Yoder Meghan S. , Creamer Trevor P. 
Published: February 2013

AbstractIn this work, we have examined contributions to the thermodynamics of calmodulin (CaM) binding from the intrinsic propensity for target peptides to adopt an α‐helical conformation. CaM target sequences are thought to commonly reside in disordered regions within proteins. Using the ability of TFE to induce α‐helical structure as a proxy, the six peptides studied range from having almost no propensity to adopt α‐helical structure through to a very high propensity. This despite all six peptides having similar CaM‐binding affinities. Our data indicate there is some correlation between the deduced propensities and the thermodynamics of CaM binding. This finding implies that molecular recognition features, such as CaM target sequences, may possess a broad range of propensities to adopt local structure. Given that these peptides bind to CaM with similar affinities, the data suggest that having a higher propensity to adopt α‐helical structure does not necessarily result in tighter binding, and that the mechanism of CaM binding is very dependent on the nature of the substrate sequence. Proteins 2013. © 2012 Wiley Periodicals, Inc.
Identification of mycobacterial lectins from genomic data
Authors: Abhinav K. V. , Sharma Alok , Vijayan M. 
Published: February 2013

AbstractSixty‐four sequences containing lectin domains with homologs of known three‐dimensional structure were identified through a search of mycobacterial genomes. They appear to belong to the β‐prism II, the C‐type, the Microcystis virdis (MV), and the β‐trefoil lectin folds. The first three always occur in conjunction with the LysM, the PI‐PLC, and the β‐grasp domains, respectively while mycobacterial β‐trefoil lectins are unaccompanied by any other domain. Thirty heparin binding hemagglutinins (HBHA), already annotated, have also been included in the study although they have no homologs of known three‐dimensional structure. The biological role of HBHA has been well characterized. A comparison between the sequences of the lectin from pathogenic and nonpathogenic mycobacteria provides insights into the carbohydrate binding region of the molecule, but the structure of the molecule is yet to be determined. A reasonable picture of the structural features of other mycobacterial proteins containing one or the other of the four lectin domains can be gleaned through the examination of homologs proteins, although the structure of none of them is available. Their biological role is also yet to be elucidated. The work presented here is among the first steps towards exploring the almost unexplored area of the structural biology of mycobacterial lectins. Proteins 2013. © 2012 Wiley Periodicals, Inc.
Solution structure of the SH3 domain of DOCK180
Authors: Liu Xiangrong , Li Fengjuan , Pan Zhu , Wang Wenning , Wen Wenyu 
Published: February 2013

AbstractDOCK180 family proteins are Rho guanine nucleotide exchange factors. DOCK1‐5 contains an N‐terminal SH3 domain implicated in their autoinhibition. Release of the closed conformation requires the interaction between SH3 and engulfment and cell motility (ELMO). Here, we solved the solution structure of DOCK180 SH3 domain, which shares similar target binding features with the SH3 domain of DOCK2. The conserved N‐terminal extension packs with the SH3 core domain and forms a new target binding site distinct from the canonical “PxxP” site. Our results demonstrate that the bidentate target binding mode of DOCK180 SH3 domain might be a general feature in all DOCK proteins. Proteins 2013. © 2012 Wiley Periodicals, Inc.
Ab initio structure prediction of the antibody hypervariable H3 loop
Authors: Zhu Kai , Day Tyler 
Published: February 2013

AbstractAntibodies have the capability of binding a wide range of antigens due to the diversity of the six loops constituting the complementarity determining region (CDR). Among the six loops, the H3 loop is the most diverse in structure, length, and sequence identity. Prediction of the three‐dimensional structures of antibodies, especially the CDR loops, is an important step in the computational design and engineering of novel antibodies for improved affinity and specificity. Although it has been demonstrated that the conformation of the five non‐H3 loops can be accurately predicted by comparing their sequences against databases of canonical loop conformations, no such connection has been established for H3 loops. In this work, we present the results for ab initio structure prediction of the H3 loop using conformational sampling and energy calculations with the program Prime on a dataset of 53 loops ranging in length from 4 to 22 residues. When the prediction is performed in the crystal environment and including symmetry mates, the median backbone root mean square deviation (RMSD) is 0.5 Å to the crystal structure, with 91% of cases having an RMSD of less than 2.0 Å. When the prediction is performed in a noncrystallographic environment, where the scaffold is constructed by swapping the H3 loops between homologous antibodies, 70% of cases have an RMSD below 2.0 Å. These results show promise for ab initio loop predictions applied to modeling of antibodies. © 2012 Wiley Periodicals, Inc.
Highly covarying residues have a functional role in antibody constant domains
Authors: Proctor Elizabeth A. , Kota Pradeep , Demarest Stephen J. , Caravella Justin A. , Dokholyan Nikolay V. 
Published: February 2013

AbstractThe ability to generate and design antibodies recognizing specific targets has revolutionized the pharmaceutical industry and medical imaging. Engineering antibody therapeutics in some cases requires modifying their constant domains to enable new and altered interactions. Engineering novel specificities into antibody constant domains has proved challenging due to the complexity of inter‐domain interactions. Covarying networks of residues that tend to cluster on the protein surface and near binding sites have been identified in some proteins. However, the underlying role these networks play in the protein resulting in their conservation remains unclear in most cases. Resolving their role is crucial, because residues in these networks are not viable design targets if their role is to maintain the fold of the protein. Conversely, these networks of residues are ideal candidates for manipulating specificity if they are primarily involved in binding, such as the myriad interdomain interactions maintained within antibodies. Here, we identify networks of evolutionarily‐related residues in C‐class antibody domains by evaluating covariation, a measure of propensity with which residue pairs vary dependently during evolution. We computationally test whether mutation of residues in these networks affects stability of the folded antibody domain, determining their viability as design candidates. We find that members of covarying networks cluster at domain‐domain interfaces, and that mutations to these residues are diverse and frequent during evolution, precluding their importance to domain stability. These results indicate that networks of covarying residues exist in antibody domains for functional reasons unrelated to thermodynamic stability, making them ideal targets for antibody design. Proteins 2013. © 2012 Wiley Periodicals, Inc.
Guest Editorial on Meeting and Mating Across Borders: Union Formation in the European Union Single Market
Authors: de Valk Helga A. G. , Medrano Juan Díez 
Published: February 2013

ABSTRACTThis editorial introduces a special issue and its different contributions. We provide an overarching background for the special issue by situating it in the context of the European Union integration process and through a general discussion of the role of intermarriage in establishing links across borders. The importance of studying union formation, that is, marriages between Europeans in the context of the European Single Market is discussed. We argue that marriages between Europeans can promote the development of trans‐European solidarity ties and may in this regard contribute to European identity formation. This article introduces the goals of the different research pieces in the special issue and outlines the overarching issues that are demonstrated by the papers collectively. We conclude that European binational marriages are still rather rare and that binational European couples are not a homogenous group. Our findings point towards the continued relevance of local geography, migrant history and patterns, as well as cultural and linguistic similarities for partner choice in a unified Europe. We call for a more integrated approach and a clear research agenda setting for the further study of union formation and dissolution in the European single market. Copyright © 2013 John Wiley & Sons, Ltd.
Robotic Anderson–Hynes dismembered pyeloplasty: initial experience
Authors: Moreno‐Sierra Jesús , Castillon‐Vela Ignacio , Ortiz‐Oshiro Elena , Galante‐Romo Isabel , Fernandez‐Perez Cristina , Senovilla‐Perez Jose L. , Casado‐Varela Javier , Garde‐Garcia Hector , Chavez‐Roa Cesar , Vera‐Gonzalez Vicente 
Published: February 2013

AbstractIntroductionThe introduction of the da Vinci® robotic system in 2000 has been a new step forward in the treatment of ureteropelvic junction obstruction (UPJO). The aim of this study was to analyse our initial experience with robot‐assisted dismembered Anderson–Hynes pyeloplasty and to perform a bibliographic review on the topic.Patients and methodsWe performed 11 robot‐assisted pyeloplasties between March 2007 and April 2011. UPJO diagnosis was made on clinical presentation and imaging techniques (CT scan and intravenous urography). All patients underwent basal and diuretic isotopic renograms to evaluate the degree of obstruction and impaired renal function. Median follow‐up was 10 (range 1–26) months.ResultsMean patient age was 38.8 (range 23‐62) years. There were six women (55%) and five men (45%). All cases were primary surgeries. In four patients the cause of UPJO was a crossing vessel; the other seven patients had intrinsic obstruction. One case was associated with extraction of a calyceal lithiasis. Mean operative time was 189.4 min (125‐270 min). Average time from robotic arms docking was 116.5 (range 55–180) min. Average hospital stay was 4.18 (range 2–8) days. Conversion to open or laparoscopic surgery was not necessary in any case and there were no postoperative complications. Postoperative radiological evaluation and renograms showed good results in all cases.ConclusionsRobotic surgery offers better ergonomics, enhanced three‐dimensional (3D) vision and more precise movements, easing intracorporeal suturing.These advantages make robotic pyeloplasty a reproducible technique that combines the high success rates of open surgery and the benefits of laparoscopic surgery. Copyright © 2013 John Wiley & Sons, Ltd.
Growth of Systems‐Centric Systems Engineering graduate programs in the United States and the role of their non‐tenure‐track faculty
Authors: Lasfer Kahina , Pyster Art 
Published: February 2013

AbstractThis study examines the growth of Systems‐Centric Systems Engineering (SCSE) graduate programs in the United States and the status of full‐time non‐tenure‐track faculty (NTTF) members within these programs. Growth is measured by the number of master's and PhD students who graduated from those programs. The annual production of master's degree graduates has grown by a factor of 5 during the period, increasing from 312 in 2001 to 1535 in 2010. Furthermore, the six largest SE programs accounted for more than half of those graduates. The annual production of PhD degrees has risen as well, though not as dramatically. In spite of such growth, less than 50% of SCSE programs hire NTTF, and, among them, the majority of the programs (65%) have four or fewer NTTF. Only 24% of the total faculty employed by SCSE programs in 2010 are NTTF, and most of them (67%) spend the majority of their time teaching; 65% of the respondents identified industrial experience as the most attractive reason for hiring them. Among SCSE programs that produced a high number of master's degree graduates, the ones that started between 2001 and 2005 employed a higher number of NTTF compared to those that started before 2001. The roles of NTTF are compared to those of tenured and tenure‐track faculty (TTTF). This paper concludes with recommendations on how to best use NTTF. ©2013 Wiley Periodicals, Inc. Syst Eng 16
Separation technologies for current and future biorefineries—status and potential of membrane‐based separation
Authors: Jiang Lan Ying , Zhu Jia Ming 
Published: February 2013

Biorefinery is one of the most important industries in the modern world, as it provides a variety of products, particularly renewable bioenergy, which is highly vital to human existence (?). Among the separation technologies applied in biorefinery, membrane‐based separation has received great attention in past decades as it is in line with the worldwide move toward higher energy efficiency and lower environmental impact. Analysis of the academic and industrial activities being undertaken reveals that porous membranes like nanofiltration, ultrafiltration, and microfiltration are generally associated with pretreatment and hydrolysis procedures where separation is relied on for recovering value‐added materials with wide range of molecular weight and facilitating follow‐up bioconversion. An emerging field that highly appreciates porous membranes is biodiesel purification. Molecular level separations including gas product separation existing in thermal and anaerobic conversions and liquid alcoholic products recovery in microbial/enzymatic process offer more opportunity to membrane‐based gas separation and pervaporation using dense membranes. Membrane distillation and supported liquid membrane, commonly classed as new generation of membrane technology, show the potential in bioethanol recovery and hydrolysis step, respectively. Nonetheless, their competitiveness is to be confirmed. The function of membrane separation is being pushed further. Bearing in mind the importance of membranes with higher quality in terms of separation efficiency and material stability, we must also be prepared for the challenges deriving from some engineering aspects such as membrane fouling, module design, and process optimization.This article is categorized under:

Bioenergy > Science and Materials
Selective Policy of No Drain after Pancreaticoduodenectomy Is a Valid Option in Patients at Low Risk of Pancreatic Fistula: A Case‐Control Analysis
Authors: Lim Chetana , Dokmak Safi , Cauchy François , Aussilhou Beatrice , Belghiti Jacques , Sauvanet Alain 
Published: February 2013

AbstractBackgroundAbdominal drainage is routinely performed after pancreaticoduodenectomy (PD), but this policy has recently been challenged. The aim of the present study was to assess whether abdominal drainage could be omitted after PD in patients at low risk of pancreatic fistula (PF).MethodsFrom 2009 to 2011, 27 consecutive patients underwent PD without abdominal drainage. Their preoperative characteristics and postoperative outcomes were compared to those of 27 matched patients undergoing PD with prophylactic drainage. Patients were matched 1:1 in terms of demographic data, preoperative weight loss, preoperative biliary drainage, surgical indication, and main risk factors of PF (pancreatic texture, main duct size, and body mass index).ResultsOverall morbidity rates (no drainage, 56 % vs. drainage, 70 %; p < 0.4) and operative mortality (1 patient in each group) were similar in both groups. The two groups did not differ significantly in terms of delayed gastric emptying (15 vs. 11 %; p = 0.68), and chylous ascites (4 vs. 15 %; p = 0.35). Radiological or surgical interventions for surgical complications were required in 2 patients (1 in each group). Pancreatic fistula rate (0 vs. 22 %; p = 0.009) and hospital stay (10 vs. 15 days; p = 0.004) were significantly reduced in the no drainage group as compared to the drainage group. The hospital readmission rate was similar in the two groups (no drainage, 3.7 vs. 0 %; p = 0.31).ConclusionsThis study suggests that abdominal drainage should not be considered routinely after PD in patients at low risk of PF. A no drain policy may reduce hospital stay after PD.
Cyclodextrin alleviates neuronal storage of cholesterol in Niemann‐Pick C disease without evidence of detectable blood–brain barrier permeability
Authors: Pontikis Charles C. , Davidson Cristin D. , Walkley Steven U. , Platt Frances M. , Begley David J. 
Published: February 2013

AbstractNiemann‐Pick type C disease is an inherited autosomal recessive neurodegenerative disorder characterised by the accumulation of unesterified cholesterol and sphingolipids within the endosomal/lysosomal compartments. It has been observed that the administration of hydroxypropyl‐β‐cyclodextrin (HPBCD) delays onset of clinical symptoms and reduces accumulation of cholesterol and gangliosides within neuronal cells. It was assumed that HPBCD exerts its action by readily entering the CNS and directly interacting with neurones and other brain cells to facilitate removal of stored cholesterol from the late endosomal/lysosomal compartment. Here, we present evidence that refutes this hypothesis. We use two well established techniques for accurately measuring brain uptake of solutes from blood and show that there is no significant crossing of HPBCD into the brain. The two techniques are brain in situ perfusion and intraperitoneal injection followed by multi‐time‐point regression analysis. Neither study demonstrates significant, time‐dependent uptake of HPBCD in either adult or neonatal mice. However, the volume of distribution available to HPBCD (0.113 ± 0.010 ml/g) exceeds the accepted values for plasma and vascular volume of the brain. In fact, it is nearly three times larger than that for sucrose (0.039 ± 0.006 ml/g). We propose that this indicates cell surface binding of HPBCD to the endothelium of the cerebral vasculature and may provide a mechanism for the mobilisation and clearance of cholesterol from the CNS.