bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular mechanism of substrate specificity in the bacterial neutral amino acid transporter LeuT
Authors: Noskov Sergei Y. 
Published: June 2008

AbstractThe recently published X‐ray structure of LeuT, a Na+/Cl−‐dependent neurotransmitter transporter, has provided fresh impetus to efforts directed at understanding the molecular principles governing specific neurotransmitter transport. The combination of the LeuT crystal structure with the results of molecular simulations enables the functional data on specific binding and transport to be related to molecular structure. All‐atom FEP and molecular dynamics (MD) simulations of LeuT embedded in an explicit membrane were performed alongside a decomposition analysis to dissect the molecular determinants of the substrate specificity of LeuT. It was found that the ligand must be in a zwitterionic (ZW) form to bind tightly to the transporter. The theoretical results on the absolute binding‐free energies for leucine, alanine, and glycine show that alanine can be a potent substrate for LeuT, although leucine is preferred, which is consistent with the recent experimental data (Singh et al., Nature 2007;448:952–956). Furthermore, LeuT displays robust specificity for leucine over glycine. Interestingly, the ability of LeuT to discriminate between substrates relies on the dynamics of residues that form its binding pocket (e.g., F253 and Q250) and the charged side chains (R30‐D404) from a second coordination shell. The water‐mediated R30‐D404 salt bridge is thought to be part of the extracellular (EC) gate of LeuT. The introduction of a polar ligand such as glycine to the water‐depleted binding pocket of LeuT gives rise to structural rearrangements of the R30‐D404‐Q250 hydrogen‐bonding network and leads to increased hydration of the binding pocket. Conformational changes associated with the broken hydrogen bond between Q250 and R30 are shown to be important for tight and selective ligand binding to LeuT. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Structure‐based approach to pharmacophore identification, in silico screening, and three‐dimensional quantitative structure–activity relationship studies for inhibitors of Trypanosoma cruzi dihydrofolate reductase function
Authors: Schormann N. , Senkovich O. , Walker K. , Wright D.L. , Anderson A.C. , Rosowsky A. , Ananthan S. , Shinkre B. , Velu S. , Chattopadhyay D. 
Published: June 2008

AbstractWe have employed a structure‐based three‐dimensional quantitative structure–activity relationship (3D‐QSAR) approach to predict the biochemical activity for inhibitors of T. cruzi dihydrofolate reductase‐thymidylate synthase (DHFR‐TS). Crystal structures of complexes of the enzyme with eight different inhibitors of the DHFR activity together with the structure in the substrate‐free state (DHFR domain) were used to validate and refine docking poses of ligands that constitute likely active conformations. Structural information from these complexes formed the basis for the structure‐based alignment used as input for the QSAR study. Contrary to indirect ligand‐based approaches the strategy described here employs a direct receptor‐based approach. The goal is to generate a library of selective lead inhibitors for further development as antiparasitic agents. 3D‐QSAR models were obtained for T. cruzi DHFR‐TS (30 inhibitors in learning set) and human DHFR (36 inhibitors in learning set) that show a very good agreement between experimental and predicted enzyme inhibition data. For crossvalidation of the QSAR model(s), we have used the 10% leave‐one‐out method. The derived 3D‐QSAR models were tested against a few selected compounds (a small test set of six inhibitors for each enzyme) with known activity, which were not part of the learning set, and the quality of prediction of the initial 3D‐QSAR models demonstrated that such studies are feasible. Further refinement of the models through integration of additional activity data and optimization of reliable docking poses is expected to lead to an improved predictive ability. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Mapping α‐helical induced folding within the intrinsically disordered C‐terminal domain of the measles virus nucleoprotein by site‐directed spin‐labeling EPR spectroscopy
Authors: Belle Valérie , Rouger Sabrina , Costanzo Stéphanie , Liquière Elodie , Strancar Janez , Guigliarelli Bruno , Fournel André , Longhi Sonia 
Published: June 2008

AbstractUsing site‐directed spin‐labeling EPR spectroscopy, we mapped the region of the intrinsically disordered C‐terminal domain of measles virus nucleoprotein (NTAIL) that undergoes induced folding. In addition to four spin‐labeled NTAIL variants (S407C, S488C, L496C, and V517C) (Morin et al. (2006), J Phys Chem 110: 20596‐20608), 10 new single‐site cysteine variants were designed, purified from E. coli, and spin‐labeled. These 14 spin‐labeled variants enabled us to map in detail the gain of rigidity of NTAIL in the presence of either the secondary structure stabilizer 2,2,2‐trifluoroethanol or the C‐terminal domain X (XD) of the viral phosphoprotein. Different regions of NTAIL were shown to contribute to a different extent to the binding to XD, while the mobility of the spin labels grafted at positions 407 and 460 was unaffected upon addition of XD; that of the spin labels grafted within the 488–502 and the 505–522 regions was severely and moderately reduced, respectively. Furthermore, EPR experiments in the presence of 30% sucrose allowed us to precisely map to residues 488–502, the NTAIL region undergoing α‐helical folding. The mobility of the 488–502 region was found to be restrained even in the absence of the partner, a behavior that could be accounted for by the existence of a transiently populated folded state. Finally, we show that the restrained motion of the 505–522 region upon binding to XD is due to the α‐helical transition occurring within the 488–502 region and not to a direct interaction with XD. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Molecular dynamics studies of the energetics of translocation in model T7 RNA polymerase elongation complexes
Authors: Woo Hyung‐June , Liu Yuemin , Sousa Rui 
Published: June 2008

AbstractTranslocation in the single subunit T7 RNA polymerase elongation complex was studied by molecular dynamics simulations using the posttranslocated crystal structure with the fingers domain open, an intermediate stable in the absence of pyrophosphate, magnesium ions, and nucleotide substrate. Unconstrained and umbrella sampling simulations were performed to examine the energetics of translocations. The extent of translocation was quantified using reaction coordinates representing the average and individual displacements of the RNA‐DNA hybrid base pairs with respect to a reference structure. In addition, an unconstrained simulation was also performed for the product complex with the fingers domain closed, but with the pyrophosphate and magnesium removed, in order to examine the local stability of the pretranslocated closed state after the pyrophosphate release. The average spatial movement of the entire hybrid was found to be energetically costly in the post‐ to pretranslocated direction in the open state, while the pretranslocated state was stable in the closed complex, supporting the notion that the conformational state dictates the global stability of translocation states. However, spatial fluctuations of the RNA 3′‐end in the open conformation were extensive, with the typical range reaching 3–4 Å. Our results suggest that thermal fluctuations play more important roles in the translocation of individual nucleotides than in the movement of large sections of nucleotide strands: RNA 3′‐end can move into and out of the active site within a single conformational state, while a global movement of the hybrid may be thermodynamically unfavorable without the conformational change. Proteins 2008. © 2008 Wiley‐Liss, Inc.
A study of the electric quadrupole Raman processes of the proton‐conducting KHSeO4 and KDSeO4 single crystals using 1H, 2H and 39K NMR
Authors: Lim Ae Ran , Yoon Choon Sup 
Published: June 2008

AbstractThe spin–lattice relaxation time, T1, and the spin–spin relaxation time, T2, of the 1H, 2H, and 39K nuclei in KHSeO4 and KDSeO4 crystals were determined in the temperature range 160–420 K. The T1 of the 39K nuclei in the two crystals were found to decrease with increasing temperature, and the spin–lattice relaxation rate, T1–1, for 39K is proportional to Tk. In the case of KHSeO4, T1–1 for the 39K nuclei was found to have a very strong temperature dependence, i.e. it is proportional to T7. The temperature dependence of the 39K relaxation rate in KDSeO4 is in accordance with a Raman process, as T1–1 ∝ T2. Thus, for the 39K nuclei in the two crystals, Raman processes with k = 2 and 7 is due to the coupling of electric quadrupole moments to the thermal fluctuations of the local electric field gradients. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Strategic resources and performance: a meta‐analysis
Authors: Crook T. Russell , Ketchen David J. , Combs James G. , Todd Samuel Y. 
Published: June 2008

AbstractResource‐based theory (RBT) has emerged as a key perspective guiding inquiry into the determinants of organizational performance. Since the early 1990s, numerous studies have examined RBT's assertion that the extent to which organizations possess strategic resources is positively related to performance. Although many studies appear to support this assertion, there is no consensus regarding how strongly strategic resources relate to performance. To help resolve this issue, we meta‐analyze 125 studies of RBT that collectively encompass over 29,000 organizations. Our conservative estimate is that the effect size of the strategic resources–performance relationship is r̄c = 0.22. Moderator tests suggest that the resources‐performance link is stronger (1) when resources meet the criteria laid out in RBT and (2) for those performance measures that are not affected by potential value appropriation. When resources meet RBT's criteria and when performance measures are not affected by potential appropriation, the strength of the relationship grows to r̄c = 0.29. This suggests that the identification, development, and distribution of value from strategic resources should be a primary consideration for scholars, managers, and shareholders. Copyright © 2008 John Wiley & Sons, Ltd.
Effects of thermally oxidized triglycerides on the oxidative stability of soybean oil
Authors: Yoon S. H. , Jung M. Y. , Min D. B. 
Published: June 2008

AbstractSoybean oil purified by silicic acid column chromatography did not contain peroxides, free fatty acids, phospholipids or oxidized polar compounds. The purified soybean oil was thermally oxidized at 180°C for 96 hr in the presence of air. The thermally oxidized compounds (31.3%) were separated from the purified soybean oil by gradient elution silicic acid chromatography. Thermally oxidized compounds contained hydroxyl groups, carbonyl groups andtrans double bonds according to the infrared spectrum. Thermally oxidized compounds were added to soybean oil and purified soybean oil at 0, 0.5, 1.0, 1.5 and 2.0% to study the effects of these compounds on the oxidative stability of oil. The oxidative stabilities of oils were determined by gas chromatographic analysis of volatile compound formation and molecular oxygen disappearance in the headspace of oil bottles. The thermally oxidized compounds showed prooxidant effects on the oxidative stabilities of both refined, bleached and deodorized soybean oil and purified soybean oil. Duncan's Multiple Range Test showed that thermally oxidized compounds had a significant effect on the volatile compound formatiion and oxygen disappearance in the headspace of oil at α=0.05.
Malnutrition prevalence in The Netherlands: results of the Annual Dutch National Prevalence Measurement of Care Problems
Authors: Meijers Judith M. M. , Schols Jos M. G. A. , vanBokhorst-de van der Schueren Marian A. E. , Dassen Theo , Janssen Maaike A. P. , Halfens Ruud J. G. 
Published: June 2008

The objective of this study was to provide data on malnutrition prevalence in hospitals, nursing homes and home-care organisations in The Netherlands in a nationally representative sample, and to assess the factors such as age, sex, time since admission, ward type and disease for identifying patients at high risk of malnutrition. A cross-sectional, multi-centre design with a standardised questionnaire was used to measure the prevalence of malnutrition. Nutritional status was assessed by BMI, undesired weight loss and nutritional intake. In this study, 12 883 patients were included. The prevalence of malnutrition was the highest in hospitals (23·8 %), followed by home-care organisations (21·7 %) and nursing homes (19·2 %). Logistic regression analysis revealed no association with age, time since admission and ward type. Being female was associated with malnutrition only in nursing homes. Blood diseases, gastrointestinal tract diseases, infection, chronic obstructive pulmonary disease, dementia and cancer were the factors associated with malnutrition in hospitals. Dementia was associated with malnutrition in nursing homes, while gastrointestinal tract diseases, diabetes mellitus and cancer were the associated factors in home care. This study shows that malnutrition is still a substantial problem in hospitals, nursing homes and home care in The Netherlands. Malnutrition is a problem for more than one in five patients. Despite growing attention to the problem, more continued alertness is required.
Disability and the Implications of the Wellbeing Agenda: Some Reflections from the United Kingdom
Authors: EDWARDS CLAIRE , IMRIE ROB 
Published: June 2008

AbstractA wellbeing agenda has emerged in government that seeks to promote a ‘politics of happiness’, in which citizens are, as the New Economics Foundation put it, ‘happy, healthy, capable and engaged’ (2004: 2). This article explores the wellbeing agenda in the UK, and its implications for disabled people. We argue that it is unlikely, in its present form, to contribute to the development of social theoretical, or more politically progressive, analysis and understanding of disablement in society. This is because of the emphasis on biologism, personality and character traits, and a policy prognosis that revolves around self-help and therapy, or individuated actions and (self) responsibilities.
Judging a Book by its Cover: Did Perceptions of the 1996 US Welfare Reforms Affect Public Support for Spending on the Poor?
Authors: HETLING ANDREA , McDERMOTT MONIKA L. 
Published: June 2008

AbstractResearch into public policy and public opinion demonstrates ample evidence that opinion affects policy, but relatively limited empirical findings regarding how policy might affect opinion: a process dubbed policy feedback. Much of the literature examines aggregate reactions to policy, while related public opinion research emphasises individual findings driven primarily by party affiliation or political ideology. This article takes the research one step further, examining whether individuals' judgements of policy effectiveness contribute to their support for or opposition to government policy spending. Specifically, it examines the case of US welfare reform and public reactions to it using a national survey conducted in 2001. Findings based on multinomial logistic regression analysis demonstrate not only that people's judgements of welfare reform's effectiveness contribute to their support for government spending on the poor, but also that the reasons behind their judgements matter.
Approximating the maximum ergodic average via periodic orbits
Authors: COLLIER D. , MORRIS I. D. 
Published: June 2008

AbstractLet σ:ΣA→ΣA be a subshift of finite type, let $\mathcal {M}_\sigma $ be the set of all σ-invariant Borel probability measures on ΣA, and let $f\colon \Sigma _A \to \mathbb {R}$ be a Hölder continuous observable. There exists at least one σ-invariant measure μ which maximizes $\int f \,d\mu $. The following question was asked by B. R. Hunt, E. Ott and G. Yuan: how quickly can the maximum of the integrals $\int f \,d\mu $ be approximated by averages along periodic orbits of period less than p? We give an example of a Hölder observable f for which this rate of approximation is slower than stretched-exponential in p.
Micron-scale mapping of sulfur cycling across the oxycline of a cyanobacterial mat: a paired nanoSIMS and CARD-FISH approach
Authors: Fike David Andrew , Gammon Crystal Lynn , Ziebis Wiebke , Orphan Victoria Jeanne 
Published: June 2008

Abstract
The metabolic activities of microbial mats have likely regulated biogeochemical cycling over most of Earth's history. However, the relationship between metabolic activity and the establishment of isotopic geochemical gradients in these mats remains poorly constrained. Here we present a parallel microgeochemical and microbiological study of micron-scale sulfur cycling within hypersaline microbial mats from Guerrero Negro, Baja California Sur, Mexico. Dissolved sulfide within the mats was captured on silver discs and analyzed for its abundance and δ34S isotopic composition using high-resolution secondary ion mass spectrometry (nanoSIMS). These results were compared to sulfide and oxygen microelectrode profiles. Two-dimensional microgeochemical mapping revealed well-defined laminations in sulfide concentration (on scales from 1 to 200 μm), trending toward increased sulfide concentrations at depth. Sulfide δ34S decreased from ∼+10‰ to −20‰ in the uppermost 3 mm and oscillated repeatedly between −10‰ and −30‰ down to a depth of 8 mm. These variations are attributed to spatially variable bacterial sulfate reduction within the mat. A parallel examination of the spatial distribution of known sulfate-reducing bacteria within the family Desulfobacteraceae was conducted using catalyzed reporter deposition fluorescence in situ hybridization. Significant concentrations of Desulfobacteraceae were observed in both oxic and anoxic zones of the mat and occurred in several distinct layers, in large aggregates and heterogeneously dispersed as single cells throughout. The spatial distribution of these microorganisms is consistent with the variation in sulfide concentration and isotopic composition we observed. The parallel application of the methodologies developed here can shed light on micron-scale sulfur cycling within microbially dominated sedimentary environments.
Long-term experimental warming alters nitrogen-cycling communities but site factors remain the primary drivers of community structure in high arctic tundra soils
Authors: Walker Jennifer K M , Egger Keith N , Henry Gregory H R 
Published: June 2008

Abstract
Arctic air temperatures are expected to rise significantly over the next century. Experimental warming of arctic tundra has been shown to increase plant productivity and cause community shifts and may also alter microbial community structure. Hence, the objective of this study was to determine whether experimental warming caused shifts in soil microbial communities by measuring changes in the frequency, relative abundance and/or richness of nosZ and nifH genotypes. Five sites at a high arctic coastal lowland were subjected to a 13-year warming experiment using open-top chambers (OTCs). Sites differed by dominant plant community, soil parent material and/or moisture regimen. Six soil cores were collected from each of four replicate OTC and ambient plots at each site and subdivided into upper and lower samples. Differences in frequency and relative abundance of terminal restriction fragments were assessed graphically by two-way cluster analysis and tested statistically with permutational multivariate analysis of variance (ANOVA). Genotypic richness was compared using factorial ANOVA. The genotype frequency, relative abundance and genotype richness of both nosZ and nifH communities differed significantly by site, and by OTC treatment and/or depth at some sites. The site that showed the most pronounced treatment effect was a wet sedge meadow, where community structure and genotype richness of both nosZ and nifH were significantly affected by warming. Although warming was an important factor affecting these communities at some sites at this high arctic lowland, overall, site factors were the main determinants of community structure.
Indole cell signaling occurs primarily at low temperatures in Escherichia coli
Authors: Lee Jintae , Zhang Xue-Song , Hegde Manjunath , Bentley William E , Jayaraman Arul , Wood Thomas K 
Published: June 2008

Abstract
We have shown that the quorum-sensing signals acylhomoserine lactones, autoinducer-2 (AI-2) and indole influence the biofilm formation of Escherichia coli. Here, we investigate how the environment, that is, temperature, affects indole and AI-2 signaling in E. coli. We show in biofilms that indole addition leads to more extensive differential gene expression at 30 °C (186 genes) than at 37 °C (59 genes), that indole reduces biofilm formation (without affecting growth) more significantly at 25 and 30 °C than at 37 °C and that the effect is associated with the quorum-sensing protein SdiA. The addition of indole at 30 °C compared to 37 °C most significantly repressed genes involved in uridine monophosphate (UMP) biosynthesis (carAB, pyrLBI, pyrC, pyrD, pyrF and upp) and uracil transport (uraA). These uracil-related genes are also repressed at 30 °C by SdiA, which confirms SdiA is involved in indole signaling. Also, compared to 37 °C, indole more significantly decreased flagella-related qseB, flhD and fliA promoter activity, enhanced antibiotic resistance and inhibited cell division at 30 °C. In contrast to indole and SdiA, the addition of (S)-4,5-dihydroxy-2,3-pentanedione (the AI-2 precursor) leads to more extensive differential gene expression at 37 °C (63 genes) than at 30 °C (11 genes), and, rather than repressing UMP synthesis genes, AI-2 induces them at 37 °C (but not at 30 °C). Also, the addition of AI-2 induces the transcription of virulence genes in enterohemorrhagic E. coli O157:H7 at 37 °C but not at 30 °C. Hence, cell signals cause diverse responses at different temperatures, and indole- and AI-2-based signaling are intertwined.