bluuebunny/crossref_metadata_2025 huggingface dataset:
Osteopontin binding to lipopolysaccharide lowers tumor necrosis factor-α and prevents early alcohol-induced liver injury in mice
Authors: Ge Xiaodong , Leung Tung-Ming , Arriazu Elena , Lu Yongke , Urtasun Raquel , Christensen Brian , Fiel Maria Isabel , Mochida Satoshi , Sφrensen Esben S. , Nieto Natalia
Published: November 2013

Although osteopontin (OPN) is induced in alcoholic patients, its role in the pathophysiology of alcoholic liver disease (ALD) remains unclear. Increased translocation of lipopolysaccharide (LPS) from the gut is key for the onset of ALD because it promotes macrophage infiltration and activation, tumor necrosis factor-α (TNFα) production, and liver injury. Since OPN is protective for the intestinal mucosa, we postulated that enhancing OPN expression in the liver and consequently in the blood and/or in the gut could protect from early alcohol-induced liver injury. Wild-type (WT), OPN knockout (Opn−/−
), and transgenic mice overexpressing OPN in hepatocytes (Opn
HEPTg) were fed either the control or the ethanol Lieber-DeCarli diet. Ethanol increased hepatic, plasma, biliary, and fecal OPN more in Opn
HEPTg than in WT mice. Steatosis was less in ethanol-treated Opn
HEPTg mice as shown by decreased liver-to-body weight ratio, hepatic triglycerides, the steatosis score, oil red-O staining, and lipid peroxidation. There was also less inflammation and liver injury as demonstrated by lower alanine aminotransferase (ALT) activity, hepatocyte ballooning degeneration, LPS levels, the inflammation score, and the number of macrophages and TNFα+ cells. To establish if OPN could limit LPS availability and its noxious effects in the liver, binding studies were performed. OPN showed binding affinity for LPS which prevented macrophage activation, reactive oxygen, and nitrogen species generation and TNFα production. Treatment with milk OPN (m-OPN) blocked LPS translocation in vivo and protected from early alcohol-induced liver injury. Conclusion: Natural induction plus forced overexpression of OPN in the liver or treatment with m-OPN protect from early alcohol-induced liver injury by blocking the gut-derived LPS and TNFα effects in the liver. (HEPATOLOGY 2014;59:1600-1616)
Vitamin D‐binding protein, circulating vitamin D and risk of renal cell carcinoma
Authors: Mondul Alison M. , Weinstein Stephanie J. , Moy Kristin A. , Männistö Satu , Albanes Demetrius
Published: November 2013

Cell culture experiments suggest that vitamin D may inhibit renal carcinogenesis, but human studies of circulating 25‐hydroxyvitamin D [25(OH)D], the accepted measure of vitamin D status, and kidney cancer have been null. Limited research has examined the role of circulating vitamin D‐binding protein (DBP) in the association between 25(OH)D and disease risk, and it is unclear whether free 25(OH)D in circulation is a better measure of effective exposure, or if DBP may independently impact outcomes. We conducted a nested case–control analysis within the Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention (ATBC) Study to examine whether circulating DBP concentration was prospectively associated with risk of renal cell carcinoma, and whether it modified the association with 25(OH)D. Renal cell carcinoma cases (n = 262) were matched 1:1 to controls on age (±1 year) and date of blood collection (± 30 days). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) of renal cell carcinoma risk by quartiles of 25(OH)D, DBP and the molar ratio of 25(OH)D:DBP, a proxy for free circulating 25(OH)D. Men with higher DBP concentrations were at significantly decreased risk of kidney cancer (Q4 vs. Q1: OR = 0.17, 95% CI = 0.08–0.33; p‐trend < 0.0001), a finding unchanged by adjustment for 25(OH)D. Although we observed no association with total 25(OH)D, we found slightly increased risk with higher levels of estimated free 25(OH)D [Q4 vs. Q1 of the 25(OH)D:DBP ratio, OR = 1.61, 95% CI = 0.95–2.73; p‐trend = 0.09]. The strong protective association observed between higher circulating DBP concentration and kidney cancer risk requires replication but suggests a vitamin D‐independent influence of DBP.
Cultured beef: medical technology to produce food
Authors: Post Mark J
Published: November 2013

Culturing beef from bovine satellite cells can be done and the urgent need for alternative beef production requires full‐scale research into this interesting possibility. © 2013 Society of Chemical Industry
Effects of bacteriophage on the quality and shelf life of Paralichthys olivaceus during chilled storage
Authors: Li Meng , Lin Hong , Khan Muhammad Naseem , Wang Jingxue , Kong Linghong
Published: November 2013

BACKGROUND

The microbiological spoilage of fishery foods is mainly due to specific spoilage organisms (SSOs), with Shewanella putrefaciens being the SSO of most chilled marine fish. Bacteriophages have shown excellent capability to control micro‐organisms. The aim of this study was to determine a specific bacteriophage to prevent spoilage by reducing SSO (S. putrefaciens) levels in the marine fish Paralichthys olivaceus (olive flounder) under chilled storage.

RESULTS

Chilled flounder fillets were inoculated with S. putrefaciens and treated with different concentrations of bacteriophage Spp001 ranging from 104 to 108 plaque‐forming units (pfu) mL−1. Bacterial growth (including total viable count and SSO) of the bacteriophage‐treated groups was significantly inhibited compared with that of the negative control group (P < 0.05). Sensory evaluation and biochemical parameters revealed that the bacteriophage could extend the shelf life of chilled flounder fillets (from <4 to 14 days) with good esthetic quality, even at low temperature (4 °C). Furthermore, bacteriophage concentrations of 106 and 108 pfu mL−1 were more effective than the chemical preservative potassium sorbate (5 g L−1).

CONCLUSION

The bacteriophage Spp001 offered effective biocontrol of S. putrefaciens under chilled conditions, retaining the quality characteristics of spiked fish fillets, and thus could be a potential candidate for use in chilled fish fillet biopreservation. © 2013 Society of Chemical Industry
Structure elucidation of ACE‐inhibitory and antithrombotic peptides isolated from mackerel skin gelatine hydrolysates
Authors: Khiari Zied , Rico Daniel , Martin‐Diana Ana Belen , Barry‐Ryan Catherine
Published: November 2013

BACKGROUND

The fish‐processing industry generates significant amounts of waste and by‐products that are usually discarded. This study investigated the preparation of bioactive gelatine peptides from fish skin. Gelatine was extracted from mackerel (Scomber scombrus) skin and hydrolysed by pepsin for 1, 2, 6 and 24 h. All hydrolysates were screened for antioxidant, ACE‐inhibitory and antithrombotic activities.

RESULTS

Gelatine peptides obtained after 24 h of hydrolysis exhibited the highest antioxidant activity (DPPH reduction ∼80%, FRAP ∼130 µmol Trolox equivalent L−1). These hydrolysates had high ACE‐inhibitory activity (>70%) and were able to significantly (P < 0.05) inhibit platelet aggregation by about 30%, corresponding to moderate antithrombotic activity.

CONCLUSION

The bioactive properties were mainly due to the presence of low‐molecular‐weight peptides of 337 and 423 Da. © 2013 Society of Chemical Industry
DNA methylation and demethylation: A pathway to gametogenesis and development
Authors: Dean Wendy
Published: November 2013

The generation of gametes falls between two reprogramming phases. These phases are characterised by profound periods of transcriptional activity, which define and reinforce lineage decisions. The control of these transcriptional programs and the interpretation of the underlying genetic instruction is the task of the epigenome. As such, dynamic processes during reprogramming are critical for the development of the germ line and its resetting, which propels that developmental process forward and provides the transfer of genetic and epigenetic information between generations. Central in this reprogramming is the addition and subtraction of DNA methylation and its oxidative products, coupled to the mechanisms at play to achieve this goal. The activities competent to add DNA methylation, and identification of those enzymes able to modify it, have heralded a new chapter in our understanding of the complexities that dictate and direct cellular fates. How the early embryos makes use of these marks and how they are modulated will give us insight into cellular differentiation and reprogramming critical for health and into the process of aging. This review details some of these processes and the activities essential to achieve the immortality of the mammalian germ line. Mol. Reprod. Dev. 81: 113–125, 2014. © 2013 Wiley Periodicals, Inc.
Palmitoyl‐protein thioesterase 1 (PPT1): An obesity‐induced rat testicular marker of reduced fertility
Authors: Liu Yue , Zhao Wenzhen , Gu Guobao , Lu Liming , Feng Jingsheng , Guo Qiangsu , Ding Zhide
Published: November 2013

Male obesity may lead to declines in testosterone levels, reproductive hormonal profile, and semen quantity. To assess the effects of obesity on spermatogenesis, Sprague–Dawley rats fed a high‐fat diet served as a model of induced obesity. The litter sizes for females mated to obese males were significantly lower as compared to females mated with normal‐diet‐fed controls. Their serum high‐density lipoprotein, low‐density lipoprotein, cholesterol, and estradiol levels increased in obese males, but testosterone and follicle‐stimulating hormone levels decreased. Testicular morphology disruptions included Sertoli‐cell atrophy, disrupted tight junctions, and mitochondrial degeneration in spermatogenic cells. To further investigate the molecular mechanisms leading to high‐fat‐diet‐induced changes, we employed testicular proteomic analysis on rats fed both types of diet. Three spots were up‐regulated in rats fed a high‐fat diet whereas two others were downregulated. One of the upregulated spots was palmitoyl‐protein thioesterase 1 (PPT1), a lipoprotein metabolizing related enzyme localized to Sertoli cells. In a Sertoli‐cell line cultured in a high‐fat supplemented medium, PPT1 abundance was accompanied by increases in the endocytic vesicle‐associated protein, clathrin, and decreases in the tight junctional proteins, ZO‐1 and occludin. In conclusion, declines in rat male fertility induced by a high‐fat diet are associated with an altered testicular protein expression pattern as well as disruption of testicular Sertoli‐cell and spermatogenic‐cell morphology. PPT1 expression may provide a testicular marker of reduced fertility in obese males, as increases in its expression may be detrimental to Sertoli‐cell function during spermatogenesis. Mol. Reprod. Dev. 81: 55–65, 2014. © 2013 Wiley Periodicals, Inc.
Eight‐year weight losses with an intensive lifestyle intervention: The look AHEAD study
Authors:   The Look AHEAD Research Group
Published: November 2013

Objective

To evaluate 8‐year weight losses achieved with intensive lifestyle intervention (ILI) in the Look AHEAD (Action for Health in Diabetes) study.

Design and Methods

Look AHEAD assessed the effects of intentional weight loss on cardiovascular morbidity and mortality in 5,145 overweight/obese adults with type 2 diabetes, randomly assigned to ILI or usual care (i.e., diabetes support and education [DSE]). The ILI provided comprehensive behavioral weight loss counseling over 8 years; DSE participants received periodic group education only.

Results

All participants had the opportunity to complete 8 years of intervention before Look AHEAD was halted in September 2012; ≥88% of both groups completed the 8‐year outcomes assessment. ILI and DSE participants lost (mean ± SE) 4.7% ± 0.2% and 2.1 ± 0.2% of initial weight, respectively (P < 0.001) at year 8; 50.3% and 35.7%, respectively, lost ≥5% (P < 0.001), and 26.9% and 17.2%, respectively, lost ≥10% (P < 0.001). Across the 8 years ILI participants, compared with DSE, reported greater practice of several key weight‐control behaviors. These behaviors also distinguished ILI participants who lost ≥10% and kept it off from those who lost but regained.

Conclusions

Look AHEAD's ILI produced clinically meaningful weight loss (≥5%) at year 8 in 50% of patients with type 2 diabetes and can be used to manage other obesity‐related co‐morbid conditions.
Deformation kinetics of pH‐sensitive hydrogels
Authors: Toh William , Ng Teng Yong , Liu Zishun , Hu Jianying
Published: November 2013

Polymeric gels can undergo large deformation when subjected to external solutions of varying pH. It is imperative to understand the deformation process of pH‐sensitive hydrogels for the effective application of these attractive materials in the biomedical and microfluidic fields. In the modeling of these multi‐phase materials, finite element (FE) modeling is a useful tool for the development of future applications, and it allows developers to test a wide variety of material responses in a cost‐effective and efficient manner, reducing the need to conduct extensive laboratory experiments. Although a FE user‐defined material model is available for the equilibrium state, the transient response of pH‐sensitive gels has not been effectively modeled. Based on our recent work using the heat transfer analogy to tap into the readily available coupled temperature–displacement elements available in the commercial FE software ABAQUS for simulation of the transient swelling process of neutral hydrogels, the transient swelling process of a pH‐sensitive hydrogel is studied and a FE model is further developed to simulate the transient phenomena. Some benchmark examples are investigated to demonstrate the model's capabilities in the simulation of nonlinear deformation kinetics relevant to several applications of pH‐sensitive hydrogels. © 2013 Society of Chemical Industry
Functional amphiphilic oligo(ethylene oxide) methacrylate‐based block copolymers: synthesis by an activator regenerated by electron transfer process for atom transfer radical polymerization and aqueous micellization
Authors: Chan Nicky , Jung Hyun Wook , Noh Seung Man , Oh Jung Kwon
Published: November 2013

Well‐defined amphiphilic block copolymers (ABPs) consisting of poly(oligo(ethylene oxide) monomethyl ether methacrylate) (POEOMA) and poly(tert‐butyl methacrylate) (PtBMA) were successfully synthesized using an activator regenerated by electron transfer (ARGET) process for atom transfer radical polymerization (ATRP). Two synthetic routes starting from the synthesis of either PtBMA or POEOMA macroinitiators followed by chain extension with the alternate monomer were examined. The results from a kinetic investigation suggest that both ARGET ATRP of OEOMA and subsequent chain extension with tBMA proceed in a living manner, yielding functional POEOMA‐block‐PtBMA ABPs in the presence of various functional initiators. As a preliminary evaluation for a polymer‐based drug delivery system, the functional ABPs were examined for aqueous micellization through self‐assembly that allows for the preparation of colloidally stable micellar aggregates with various corona morphologies. For flower‐like micelles bearing disulfide linkages in the center of hydrophilic loops, the reductive cleavage of the disulfide linkages enables a facile conversion to thiol‐decorated micelles without a measurable change in particle size. © 2013 Society of Chemical Industry
Solution properties of γ‐crystallins: Compact structure and low frictional ratio are conserved properties of diverse γ‐crystallins
Authors: Chen Yingwei , Zhao Huaying , Schuck Peter , Wistow Graeme
Published: November 2013

γ‐crystallins are highly specialized proteins of the vertebrate eye lens where they survive without turnover under high molecular crowding while maintaining transparency. They share a tightly folded structural template but there are striking differences among species. Their amino acid compositions are unusual. Even in mammals, γ‐crystallins have high contents of sulfur‐containing methionine and cysteine, but this reaches extremes in fish γM‐crystallins with up to 15% Met. In addition, fish γM‐crystallins do not conserve the paired tryptophan residues found in each domain in mammalian γ‐crystallins and in the related β‐crystallins. To gain insight into important, evolutionarily conserved properties and functionality of γ‐crystallins, zebrafish (Danio rerio) γM2b and γM7 were compared with mouse γS and human γD. For all four proteins, far UV CD spectra showed the expected β‐sheet secondary structure. Like the mammalian proteins, γM7 was highly soluble but γM2b was much less so. The heat and denaturant stability of both fish proteins was lower than either mammalian protein. The ability of full‐length and truncated versions of human αB‐crystallin to retard aggregation of the heat denatured proteins also showed differences. However, when solution behavior was investigated by sedimentation velocity experiments, the diverse γ‐crystallins showed remarkably similar hydrodynamic properties with low frictional ratios and partial specific volumes. The solution behavior of γ‐crystallins, with highly compact structures suited for the densely packed environment of the lens, seems to be highly conserved and appears largely independent of amino acid composition.
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

Clinical 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

Mutations 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

Characterizing 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

We 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

TFE, 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

The 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

We 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

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

Human 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.
More on gapped Goldstones at finite density: more gapped Goldstones
Authors: Nicolis Alberto , Penco Riccardo , Piazza Federico , Rosen Rachel A.
Published: November 2013

Abstract

It was recently argued that certain relativistic theories at finite density can exhibit an unconventional spectrum of Goldstone excitations, with gapped Goldstones whose gap is exactly calculable in terms of the symmetry algebra. We confirm this result as well as previous ones concerning gapless Goldstones for non-relativistic systems via a coset construction of the low-energy effective field theory. Moreover, our analysis unveils additional gapped Goldstones, naturally as light as the others, but this time with a model-dependent gap. Their exact number cannot be inferred solely from the symmetry breaking pattern either, but rather depends on the details of the symmetry breaking mechanism — a statement that we explicitly verify with a number of examples. Along the way we provide what we believe to be a particularly transparent interpretation of the so-called inverse-Higgs constraints for spontaneously broken spacetime symmetries.
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

Finite-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.
A NOTE ON THE FORWARD AND THE EQUITY PREMIUM PUZZLES: TWO SYMPTOMS OF THE SAME ILLNESS?
Authors: da Costa Carlos E. , Issler João V. , Matos Paulo F.
Published: November 2013

We build a stochastic discount factor—SDF—using U.S. domestic financial data only, and provide evidence that it accounts for stylized facts about foreign markets that escape SDFs generated by consumption-based models. When our SDF is interpreted as the projection of the pricing kernel from a fully specified model in the space of returns, our results indicate that a model that accounts for the behavior of domestic assets goes a long way toward accounting for the behavior of foreign asset prices. In our tests, we address predictability, a defining feature of the forward premium puzzle—FPP—by using instruments that are known to forecast excess returns in the moment restrictions associated with Euler equations both in the equity and in the foreign markets.
OPTIMAL STABILIZATION POLICY WITH SEARCH EXTERNALITIES
Authors: Berentsen Aleksander , Waller Christopher
Published: November 2013

We study optimal monetary stabilization policy in a DSGE model with microfounded money demand. A search externality creates “congestion,” which causes aggregate output to be inefficient. Because of the informational frictions that give rise to money, households are unable to insure themselves perfectly against aggregate shocks. This gives rise to a welfare-improving role for monetary policy that works by adjusting the nominal interest rate in response to these shocks. Optimal policy is determined by choosing a set of state-contingent nominal interest rates to maximize the expected lifetime utility of the agents subject to the constraints of being an equilibrium.
TEM Investigations on FeF2 based Nanocomposite Battery Materials
Authors: Chakravadhanula V.S.K. , Kübel C. , Munnangi A.R. , Breitung B. , Powell A.K. , Fichtner M. , Hahn H.
Published: November 2013

Extended abstract of a paper presented at Microscopy and Microanalysis 2013 in Indianapolis, Indiana, USA, August 4 – August 8, 2013.
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

Signal 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.
Oxidative C(sp3)–H bond cleavage, C–C and CC coupling at a boron center with O2 as the oxidant mediated by platinum(ii)
Authors: Pal S. , Zavalij P. Y. , Vedernikov A. N.
Published: November 2013

Platinum(ii) 1,5-cyclooctanediyldi(2-pyridyl)borates react with O2via C(sp3)–H bond cleavage and stepwise C–C and CC coupling of the borate ligand.
Wrinkling and Growth Mechanism of CuO Nanowires in Thermal Oxidation of Copper Foil
Authors: Lai Fa-chun , Lin Suan-zhi , Chen Zhi-gao , Hu Hai-long , Lin Li-mei
Published: November 2013

We report a systematic study on wrinkling and CuO nanowires (NWs) growth in the thermal oxidation of copper foil. Copper foils with thickness of 0.5 mm were thermally oxidized in air at 500 °C for 0.5–10 h. It is found that all the samples have wrinkles and the size of the wrinkles increases with the oxidation time increasing. CuO NWs can grow on both the sidehill and hilltop of wrinkle. The CuO NWs on sidehill are longer and denser than those on hilltop. The growth direction of the CuO NWs on sidehill is not vertical to the substrate but vertical to their growth surfaces. The process of wrinkling and CuO NWs growth can be divided into three stages: undulating, voiding, and cracking. The CuO NWs on both sidehill and hilltop grow at the undulating stage. However, only the CuO NWs on sidehill grow and those on hilltop stop growing at the voiding and cracking stages because of the void in hilltop. The local electric field in a wrinkle at undulating stage was calculated, and it is found that the difference of local electric field strengths between hilltop and sidehill is small, which indicates that the predominant driving force for the diffusion of Cu ion during CuO NWs growth is internal stress.
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

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

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.
Use of Geographic Information Systems by Fisheries Management Agencies
Authors: Eder Brandon L , Neely Ben C
Published: November 2013

Use of geographic information systems (GIS) in fisheries science has increased in prevalence since its introduction in the late 1980s, but use among and within fisheries management agencies has not been quantified. We surveyed 89 administrators of fisheries management agencies in the United States and Canada to determine the current status of GIS in fisheries management and received 54 responses (61% return rate). Survey respondents indicated that GIS was used to help manage fish populations, and 63% of respondents believed that GIS was either “very useful” or “extremely useful” for meeting agency objectives. However, most GIS work conducted by fisheries management agencies was executed by few individuals within the agency or by contracted service. Barriers preventing more widespread use by managers within agencies included lack of knowledge or training and limited time to use GIS in job duties. Our results suggest that GIS is an important tool for fisheries management. Further, GIS use within an agency might be increased by focusing on increased biologist participation in training exercises, integration with existing job duties, and recognizing diversity among GIS software.

RESUMEN

desde que se introdujo en la década de los ochenta, los Sistemas de Información Geográfica (GIS) se han utilizado cada vez más en las ciencias pesqueras, sin embargo aún no se ha cuantificado dicha utilización entre y hacia el interior de las agencias de manejo pesquero. Se realizó un sondeo a 89 encargados de agencias manejo pesquero en los Estados Unidos de Norteamérica y Canadá para determinar el estado actual de los GIS en el ámbito de manejo, recibiéndose 54 respuestas (tasa de retorno de 61%). Los encuestados indicaron que los GIS fueron desde “muy útiles” hasta “extremadamente útiles” para cumplir los objetivos de las agencias. No obstante, la mayor parte del trabajo de las agencias basado en los GIS, era realizado por algunos pocos individuos de las propias agencias o bien por servicios contratados. Las barreras que impiden un uso más generalizado de los GIS hacia el interior de las agencias de manejo incluyen la falta de conocimiento o entrenamiento y limitaciones de tiempo para usar este enfoque como parte del trabajo diario. Estos resultados sugieren que los GIS son una herramienta importante para el manejo de pesquerías. Más aún, el uso de los GIS dentro de las agencias, pudiera incrementarse enfocando o aumentando la participación de los biólogos en los ejercicios de entrenamiento, integración a las labores diarias de trabajo y reconociendo la diversidad de software de los GIS.