bluuebunny/crossref_metadata_2025_split huggingface dataset:
A molten globule intermediate of the Von Willebrand factor A1 domain firmly tethers platelets under shear flow
Authors: Tischer Alexander , Madde Pranathi , Blancas‐Mejia Luis. M. , Auton Matthew 
Published: November 2013

ABSTRACTClinical mutations in patients diagnosed with Type 2A von Willebrand disease (VWD) have been identified that break the single disulfide bond linking N‐ and C‐termini in the vWF A1 domain. We have modeled the effect of these mutations on the disulfide‐bonded structure of A1 by reducing and carboxy‐amidating these cysteines. Solution biophysical studies show that loss of this disulfide bond induces a molten globule conformational state lacking global tertiary structure but retaining residual secondary structure. The conformational dependence of platelet adhesion to these native and molten globule states of A1 is quantitatively compared using real‐time high‐speed video microscopy analysis of platelet translocation dynamics under shear flow in a parallel plate microfluidic flow chamber. While normal platelets translocating on surface‐captured native A1 domain retain the catch‐bond character of pause times that increase as a function of shear rate at low shear and decrease as a function of shear rate at high shear, platelets that interact with A1 lacking the disulfide bond remain stably attached and do not translocate. Based on these findings, we propose that the shear stress‐sensitive regulation of the A1‐GPIb interaction is due to folding the tertiary structure of this domain. Removal of the tertiary structure by disrupting the disulfide bond destroys this regulatory mechanism resulting in high‐strength interactions between platelets and vWF A1 that are dependent only on residual secondary structure elements present in the molten globule conformation. Proteins 2014; 82:867–878. © 2013 Wiley Periodicals, Inc.
Mapping disease‐related missense mutations in the immunoglobulin‐like fold domain of lamin A/C reveals novel genotype–phenotype associations for laminopathies
Authors: Scharner Juergen , Lu Hui‐Chun , Fraternali Franca , Ellis Juliet A. , Zammit Peter S. 
Published: November 2013

ABSTRACTMutations in A‐type nuclear lamins cause laminopathies. However, genotype–phenotype correlations using the 340 missense mutations within the LMNA gene are unclear: partially due to the limited availability of three‐dimensional structure. The immunoglobulin (Ig)‐like fold domain has been solved, and using bioinformatics tools (including Polyphen‐2, Fold X, Parameter OPtimized Surfaces, and PocketPicker) we characterized 56 missense mutations for position, surface exposure, change in charge and effect on Ig‐like fold stability. We find that 21 of the 27 mutations associated with a skeletal muscle phenotype are distributed throughout the Ig‐like fold, are nonsurface exposed and predicted to disrupt overall stability of the Ig‐like fold domain. Intriguingly, the remaining 6 mutations clustered, had higher surface exposure, and did not affect stability. The majority of 9 lipodystrophy or 10 premature aging syndrome mutations also did not disrupt Ig‐like fold domain stability and were surface exposed and clustered in distinct regions that overlap predicted binding pockets. Although buried, the 10 cardiac mutations had no other consistent properties. Finally, most lipodystrophy and premature aging mutations resulted in a ‐1 net charge change, whereas skeletal muscle mutations caused no consistent net charge changes. Since premature aging, lipodystrophy and the subset of 6 skeletal muscle mutations cluster tightly in distinct, charged regions, they likely affect lamin A/C –protein/DNA/RNA interactions: providing a consistent genotype–phenotype relationship for mutations in this domain. Thus, this subgroup of skeletal muscle laminopathies that we term the ‘Skeletal muscle cluster’, may have a distinct pathological mechanism. These novel associations refine the ability to predict clinical features caused by certain LMNA missense mutations. Proteins 2014; 82:904–915. © 2013 Wiley Periodicals, Inc.
Intuitive, but not simple: Including explicit water molecules in protein–protein docking simulations improves model quality
Authors: Parikh Hardik I. , Kellogg Glen E. 
Published: November 2013

ABSTRACTCharacterizing the nature of interaction between proteins that have not been experimentally cocrystallized requires a computational docking approach that can successfully predict the spatial conformation adopted in the complex. In this work, the Hydropathic INTeractions (HINT) force field model was used for scoring docked models in a data set of 30 high‐resolution crystallographically characterized “dry” protein–protein complexes and was shown to reliably identify native‐like models. However, most current protein–protein docking algorithms fail to explicitly account for water molecules involved in bridging interactions that mediate and stabilize the association of the protein partners, so we used HINT to illuminate the physical and chemical properties of bridging waters and account for their energetic stabilizing contributions. The HINT water Relevance metric identified the “truly” bridging waters at the 30 protein–protein interfaces and we utilized them in “solvated” docking by manually inserting them into the input files for the rigid body ZDOCK program. By accounting for these interfacial waters, a statistically significant improvement of ∼24% in the average hit‐count within the top‐10 predictions the protein–protein dataset was seen, compared to standard “dry” docking. The results also show scoring improvement, with medium and high accuracy models ranking much better than incorrect ones. These improvements can be attributed to the physical presence of water molecules that alter surface properties and better represent native shape and hydropathic complementarity between interacting partners, with concomitantly more accurate native‐like structure predictions. Proteins 2014; 82:916–932. © 2013 Wiley Periodicals, Inc.
Salt effects on hydrophobic‐core formation in folding of a helical miniprotein studied by molecular dynamics simulations
Authors: Yoda Takao , Sugita Yuji , Okamoto Yuko 
Published: November 2013

ABSTRACTWe have investigated effects of salt ions on folding events of a helical miniprotein chicken villin headpiece subdomain HP36. Low concentrations of ions alter electrostatic interactions between charged groups of a protein and can change the populations of conformers. Here, we compare two data sets of folding simulations of HP36 in explicit water solvent with or without ions. For efficient sampling of the conformational space of HP36, the multicanonical replica‐exchange molecular dynamics method was employed. Our analyses suggest that salt alters salt‐bridging nature of the protein at later stages of folding at room temperature. Especially, more nonnative, nonlocal salt bridges are formed at near‐native conformations in pure water. Our analyses also show that such salt‐bridge formation hinders the fully native hydrophobic‐core packing at the final stages of folding. Proteins 2014; 82:933–943. © 2013 Wiley Periodicals, Inc.
The addition of 2,2,2‐trifluoroethanol prevents the aggregation of guanidinium around protein and impairs its denaturation ability: A molecular dynamics simulation study
Authors: Shao Qiang 
Published: November 2013

ABSTRACTTFE, 2,2,2‐trifluoroethanol, and guanidinium (Gdm+) are two typical osmolytes. A great number of experimental and theoretical studies have shown that TFE and Gdm+ can accumulate on protein surface and thus exert their effects on protein structure in their respective solutions. Their accumulation manners are, however, different: the hydrophobic property of TFE makes its accumulation more preferential around hydrophobic side chains than other types whereas Gdm+ prefers to stack strongly against the planar side chains but only weakly binds to the hydrophobic groups. The present molecular dynamics simulation study shows a novel test to investigate the combined effects of TFE and Gdm+ on protein structure in mixed guanidinium/TFE solution. The results indicate that the accumulation of TFE is more competitive than Gdm+ in either GdmSCN/TFE or GdmCl/TFE solution. The preceding accumulation of TFE around protein surface limits the approach of Gdm+ and water to protein. As a result, the hydrogen bonding between Gdm+ and water to protein is highly forbidden and the secondary structure stability of protein is strongly enhanced. In contrast, without the presence of TFE, the protein structure is largely denatured in similarly concentrated GdmSCN or GdmCl solution. Proteins 2014; 82:944–953. © 2013 Wiley Periodicals, Inc.
Analyses of the folding properties of ferredoxin‐like fold proteins by means of a coarse‐grained Gō model: Relationship between the free energy profiles and folding cores
Authors: Sugita Masatake , Kikuchi Takeshi 
Published: November 2013

ABSTRACTThe folding mechanisms of proteins with multi‐state transitions, the role of the intermediate states, and the precise mechanism how each transition occurs are significant on‐going research issues. In this study, we investigate ferredoxin‐like fold proteins which have a simple topology and multi‐state transitions. We analyze the folding processes by means of a coarse‐grained Gō model. We are able to reproduce the differences in the folding mechanisms between U1A, which has a high‐free‐energy intermediate state, and ADA2h and S6, which fold into the native structure through two‐state transitions. The folding pathways of U1A, ADA2h, S6, and the S6 circular permutant, S6_p54‐55, are reproduced and compared with experimental observations. We show that the ferredoxin‐like fold contains two common regions consisting folding cores as predicted in other studies and that U1A produces an intermediate state due to the distinct cooperative folding of each core. However, because one of the cores of S6 loses its cooperativity and the two cores of ADA2h are tightly coupled, these proteins fold into the native structure through a two‐state mechanism. Proteins 2014; 82:954–965. © 2013 Wiley Periodicals, Inc.
Assessment of template‐free modeling in CASP10 and ROLL
Authors: Tai Chin‐Hsien , Bai Hongjun , Taylor Todd J. , Lee Byungkook 
Published: November 2013

ABSTRACTWe present the assessment of predictions for Template‐Free Modeling in CASP10 and a report on the first ROLL experiment wherein predictions are collected year round for review at the regular CASP season. Models were first clustered so that duplicated or very similar ones were grouped together and represented by one model in the cluster. The representatives were then compared with targets using GDT_TS, QCS, and three additional superposition‐independent score functions newly developed for CASP10. For each target, the top 15 representatives by each score were pooled to form the Top15Union set. All models in this set were visually inspected by four of us independently using the new plugin, EvalScore, which we developed with the UCSF Chimera group. The best models were selected for each target after extensive debate among the four examiners. Groups were ranked by the number of targets (hits) for which a group's model was selected as one of the best models. The Keasar group had most hits in both categories, with four of 19 FM and eight of 36 ROLL targets. The most successful prediction servers were QUARK from Zhang's group for FM category with three hits and Zhang‐server for the ROLL category with seven hits. As observed in CASP9, many successful groups were not true “template‐free” modelers but used remote templates and/or server models to obtain their winning models. The results of the first ROLL experiment were broadly similar to those of the CASP10 FM exercise. Proteins 2014; 82(Suppl 2):57–83. © 2013 Wiley Periodicals, Inc.
The SUMO Conjugating Enzyme Ubc9 Is Required for Inducing and Maintaining Stem Cell Pluripotency
Authors: Tahmasebi Soroush , Ghorbani Mohammad , Savage Paul , Gocevski Goran , Yang Xiang-Jiao 
Published: November 2013

Abstract
Sumoylation adds a small ubiquitin-like modifier (SUMO) polypeptide to the ε-amino group of a lysine residue. Reminiscent of ubiquitination, sumoylation is catalyzed by an enzymatic cascade composed of E1, E2, and E3. For sumoylation, this cascade uses Ubc9 (ubiquitin conjugating enzyme 9, now officially named ubiquitin conjugating enzyme E2I [UBE2I]) as the sole E2 enzyme. Here, we report that expression of endogenous Ubc9 increases during reprogramming of mouse embryonic fibroblasts (MEFs) into induced pluripotent stem (iPS) cells. In addition, this E2 enzyme is required for reprogramming as its suppression dramatically inhibits iPS cell induction. While Ubc9 knockdown does not affect survival of MEFs and immortalized fibroblasts, Ubc9 is essential for embryonic stem cell (ESC) survival. In addition, we have found that Ubc9 knockdown stimulates apoptosis in ESCs but not in MEFs. Furthermore, the knockdown decreases the expression of the well-known pluripotency marker Nanog and the classical reprogramming factors Klf4, Oct4, and Sox2 in ESCs. Together, these observations indicate that while dispensable for fibroblast survival, the sole SUMO E2 enzyme Ubc9 plays a critical role in reprogramming fibroblasts to iPS cells and maintaining ESC pluripotency. Stem Cells 2014;32:1012–1020
Studies to analyse the relationship between IFNα2b gene dosage and its expression, using a Pichia pastoris‐based expression system
Authors: Khan Mohsin Ahmad , Hassan Nadia , Ahmad Nadeem , Khan Muhammad Islam , Zafar Ahmad Usman , Khan Faidad , Husnain Tayyab 
Published: November 2013

AbstractHuman interferon α2b (hIFNα2b) is the most important member of the interferon family. Escherichia coli, yeasts, mammalian cell cultures and baculovirus‐infected insect cells have been used for expressing recombinant human interferon. Recently a Pichia pastoris‐based expression system has emerged as an attractive system for producing functional human recombinant IFNα2b. In this regard, gene dosage is considered an important factor in obtaining the optimum expression of recombinant protein, which may vary from one protein to another. In the present study we have shown the effect of IFNα2b gene dosage on extracellular expression of IFNα2b recombinant protein from P. pastoris. Constructs containing from one to five repeats of IFNα2b‐expressing cassettes were created via an in vitro multimerization approach. P. pastoris host strain X‐33 was transformed using these expression cassettes. Groups of P. pastoris clones transformed with different copies of the IFNα2b expression cassette were screened for intrachromosomal integration. The IFNα2b expression level of stable transformants was checked. The copy number of integrated IFNα2b was determined by performing qPCR of genomic DNA of recombinant P. patoris clones. It was observed that an increase in copy number generally had a positive effect on the expression level of IFNα2b protein. Regarding the performance of multicopy strains, those obtained from transformation of multicopy vectors showed relatively high expression, compared to those generated using transformation vector having only one copy of IFNα2b. It was also observed that an increase in drug resistance of a clone did not guarantee its high expression, as integration of a marker gene did not always correlate with integration of the gene of interest. Copyright © 2013 John Wiley & Sons, Ltd.
Simulating the Role of Stellar Rotation in the Spectroscopic Effects of Differential Limb Magnification
Authors: Stevens Adam R. H. , Albrow Michael D. 
Published: November 2013

AbstractFinite-source effects of gravitationally microlensed stars have been well discussed in the literature, but the role that stellar rotation plays has been neglected. A differential magnification map applied to a differentially Doppler-shifted surface alters the profiles of absorption lines, compromising their ordinarily symmetric nature. Herein, we assess the degree to which this finite-source effect of differential limb magnification (DLM), in combination with stellar rotation, alters spectroscopically derived stellar properties. To achieve this, we simulated a grid of high-magnification microlensing events using synthetic spectra. Our analysis shows that rotation of the source generates differences in the measured equivalent widths of absorption lines supplementary to DLM alone, but only of the order of a few per cent. Using the wings of Hα from the same simulated data, we confirmed the result of Johnson and colleagues that DLM alters measurements of effective temperature by ≲100 K for dwarf stars, while showing rotation to bear no additional effect.
Deregulated expression of TANK in glioblastomas triggers pro-tumorigenic ERK1/2 and AKT signaling pathways
Authors: Stellzig J , Chariot A , Shostak K , Ismail Göktuna S , Renner F , Acker T , Pagenstecher A , Schmitz M L 
Published: November 2013

AbstractSignal transmission by the noncanonical IkappaB kinases (IKKs), TANK-binding kinase 1 (TBK1) and IKKɛ, requires interaction with adapter proteins such as TRAF associated NF-κB activator (TANK). Although increased expression or dysregulation of both kinases has been described for a variety of human cancers, this study shows that deregulated expression of the TANK protein is frequently occurring in glioblastomas (GBMs). The functional relevance of TANK was analyzed in a panel of GBM-derived cell lines and revealed that knockdown of TANK arrests cells in the S-phase and prohibits tumor cell migration. Deregulated TANK expression affects several signaling pathways controlling cell proliferation and the inflammatory response. Interference with stoichiometrically assembled signaling complexes by overexpression or silencing of TANK prevented constitutive interferon-regulatory factor 3 (IRF3) phosphorylation. Knockdown of TANK frequently prevents constitutive activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2). TANK-mediated ERK1/2 activation is independent from the canonical MAP kinase or ERK kinase (MEK) 1/2-mediated pathway and utilizes an alternative pathway that uses a TBK1/IKKɛ/Akt signaling axis, thus identifying a novel pathway suitable to block constitutive ERK1/2 activity.
Insights for Undergraduates Seeking an Advanced Degree in Wildlife and Fisheries Sciences
Authors: Kaemingk Mark A , Dembkowski Daniel J , Meyer Hilary A , Gigliotti Larry M 
Published: November 2013

ABSTRACT
In today's job market, having a successful career in the fisheries and wildlife sciences is becoming more dependent on obtaining an advanced degree. As a result, competition for getting accepted into a graduate program is fierce. Our objective for this study was to provide prospective graduate students some insights as to what qualifications or attributes would best prepare them for obtaining a graduate position (M.S.) and to excel once they are enrolled in a graduate program. A survey was sent to 50 universities within the National Association of University Fisheries and Wildlife Programs (NAUFWP) where both faculty and undergraduate students were asked questions relating to graduate school. Faculty rated the importance of various criteria and attributes of graduate school, and students answered the questions according to how they believed faculty members would respond. Overall, undergraduate students shared many of the same graduate school viewpoints as those held by faculty members. However, viewpoints differed on some topics related to admittance and the most important accomplishment of a graduate student while enrolled in a graduate program. These results indicate that undergraduate students may be better prepared for graduate school—and they may understand how to be successful once they are enrolled in a program—than was initially thought.
RESUMEN
en el mercado laboral actual, lograr una carrera exitosa en las ciencias pesqueras y de vida silvestre depende cada vez más de obtener un posgrado. Como resultado, la competencia para ser aceptado en un programa de posgrado es feroz. En objetivo en este estudio es proveer a los prospectos a estudiantes de posgrado de algunos consejos en cuanto a las cualidades y atributos que los preparen de la mejor manera para obtener un posgrado (M. en C.) y destacar una vez que pertenezcan a un programa. Se realizó un sondeo a 50 universidades que se encuentran dentro de la Asociación Nacional de Programas de Universidades en Pesquerías y Vida Silvestre (ANPUPV) en el que se plantearon, tanto facultades como aspirantes, preguntas relativas a las escuelas de posgrado. Las facultades calificaron la importancia de distintos criterios y atributos de las escuelas de posgrado, y los estudiantes contestaron las preguntas de acuerdo a cómo creen que responderían los miembros de las facultades. En general, los estudiantes de licenciatura comparten muchos de los puntos de vista de los miembros de las facultades. Sin embargo, difirieron en algunos temas relacionados con la admisión y con cuáles son los logros más importantes de un estudiante que pertenece a un programa de posgrado. Estos resultados indican que los estudiantes de licenciatura pueden estar mejor preparados para entrar a una escuela de posgrado—y entender mejor cómo tener éxito una vez que entran al programa—de lo que inicialmente se pensaba.
A Retrospective Evaluation of Sustainable Yields for Australia's Northern Prawn Fishery: An Alternative View
Authors: Pascoe Sean , Dichmont Cathy M , Vieira Simon , Kompas Tom , Buckworth Rik C , Carter David 
Published: November 2013

ABSTRACT
The increasing interest in maximum economic yield (MEY) as a management target has been accompanied by considerable debate as to how MEY should be determined. Different interpretations as to how economic costs are treated may lead to different outcomes. For example, a recent paper by Wang and Wang (2012b) provided a retrospective analysis of a recent buyback program in a major Australian fishery aimed at moving the fishery to MEY and concluded that greater economic benefits would have been achieved had the buyback not taken place. However, the economic assumptions underlying this result are debatable. In this article, we provide our own analysis using corrected economic parameters and suggest that, had the buyback not taken place, industry profits from 2006 to 2009 would have been $22–25 million lower. These new findings are placed in the context of the events that led to the buyback taking place and we conclude that the buyback resulted in substantial benefits to the industry.
RESUMEN
El interés creciente de establecer el máximo rendimiento económico (MRE) como objetivo de manejo, ha suscitado un intenso debate en cuanto a cómo éste debe ser calculado. Las diferentes interpretaciones de cómo deben considerarse los costos económicos de una pesquería, han dado lugar a distintos resultados. Por ejemplo un artículo reciente de Wang y Wang (Fisheries, 37(9)) muestra el análisis retrospectivo de un programa de compra de embarcaciones de una de las más importantes pesquerías de Australia, con el objetivo de dirigir a la pesquería hacia el MRE, y se concluye que se hubieran logrado mayores beneficios económicos de no haberse establecido el programa de compra. No obstante, las suposiciones económicas detrás de esto, son controversiales. En este artículo se ofrece un análisis propio utilizando parámetros económicos corregidos y se sugiere que, de no haber tenido lugar la compra de embarcaciones, los beneficios industriales de 2006 a 2009 hubieran sido del orden de $22–25 millones menos. Estos nuevos hallazgos se contextualizan en los eventos que dieron lugar al programa de compra de barcos, y se concluye que dicho programa produjo en importantes beneficios para la industria.