bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural basis of the signalling through a bacterial membrane receptor HasR deciphered by an integrative approach
Authors: Wojtowicz Halina , Prochnicka-Chalufour Ada , de Amorim Gisele Cardoso , Roudenko Olga , Simenel Catherine , Malki Idir , Pehau-Arnaudet Gérard , Gubellini Francesca , Koutsioubas Alexandros , Pérez Javier , Delepelaire Philippe , Delepierre Muriel , Fronzes Rémi , Izadi-Pruneyre Nadia 
Published: May 2016

Bacteria use diverse signalling pathways to adapt gene expression to external stimuli. In Gram-negative bacteria, the binding of scarce nutrients to membrane transporters triggers a signalling process that up-regulates the expression of genes of various functions, from uptake of nutrient to production of virulence factors. Although proteins involved in this process have been identified, signal transduction through this family of transporters is not well understood. In the present study, using an integrative approach (EM, SAXS, X-ray crystallography and NMR), we have studied the structure of the haem transporter HasR captured in two stages of the signalling process, i.e. before and after the arrival of signalling activators (haem and its carrier protein). We show for the first time that the HasR domain responsible for signal transfer: (i) is highly flexible in two stages of signalling; (ii) extends into the periplasm at approximately 70–90 Å (1 Å=0.1 nm) from the HasR β-barrel; and (iii) exhibits local conformational changes in response to the arrival of signalling activators. These features would favour the signal transfer from HasR to its cytoplasmic membrane partners.
Substituent Effects on Reduction Potentials of Meta-substituted and Para-substituted Benzylideneanilines
Authors: Wang Lin-yan , Cao Chao-tun , Cao Chen-zhong 
Published: May 2016

Effects of meta-substituent of 3,4′/4,3′/3,3′-substituted benzylideneanilines (XBAYs) on the electrochemical reduction potentials (E(Red)) were investigated, in which 49 samples of target compounds were synthesized, and their reduction potentials were measured by cyclic voltammetry. The substituent effects on the E(Red) of target compounds were analyzed and an optimality equation with four parameters (Hammett constant σ of X, Hammett constant σ of Y, excited-state substituent constant σCCex of X, and the substituent specific cross-interaction effect ΔσCCex 2 between X and Y) was obtained. The results show that the factors affecting the E(Red) of 3,4′/4,3′/3,3′-substituted XBAYs are different from those of 4,4′-substituted XBAYs. For 3,4′/4,3′/3,3′-substituted XBAYs, σ(X) and σ(Y) must be employed, and the contribution of ΔσCCex 2 is important and not negligible. Compared with 4,4′-substituted XBAYs, X group contributes less to 3,4′/4,3′/3,3′-substituted XBAYs, while Y group contributes more to them. Additionally, it was observed that either para-substituted XBAYs or meta-substituted XBAYs, the substituent effects of X are larger than those of Y on the E(Red) of substituted XBAYs.
Spatiotemporal strategies that facilitate recruitment in a habitat specialist tree species
Authors: Krishna Shivani , Somanathan Hema 
Published: May 2016

Abstract
Our understanding of processes underlying plant recruitment emerges from species and habitats that are widely distributed at regional and global scales. However, the applicability of dispersal-recruitment models and the role of dispersal limitation versus microsite limitation have not been examined for specialized habitats. In patchy, freshwater Myristica swamp forests (Western Ghats, India), we examine the roles of primary seed dispersal, secondary seed removal and microsite suitability for the establishment of a swamp specialist tree, Myristica fatua . We estimated primary seed shadows, performed secondary removal experiments and enumerated recruits in swamp sites. Steady-state fruiting was observed with the extended production (&gt;7 months) of small numbers of fruits. Frugivores dropped most of the large and heavy seeds under parent crowns, while a few seeds were transported over short distances by hornbills. Seed placement experiments indicated that removal, germination and establishment were similar within swamp microsites, while seeds failed to survive in matrix habitats surrounding the swamp. Crabs, which were major secondary removers of M. fatua , did not alter the initial seed dispersal patterns substantially, which led to the retention of seeds within the swamp. Distribution of saplings and adults from previous seasons also suggest that dispersal-recruitment dynamics in the swamp specialist M. fatua did not strictly follow predictions of Janzen-Connell model while abiotic effects were significant. Large seeds, steady-state fruiting and small crop sizes may be significant selective forces facilitating escape from density and distance-dependent effects in space and time in specialist plant species such as M. fatua .
Calculating and scoring high quality multiple flexible protein structure alignments
Authors: Ritchie David W. 
Published: May 2016

AbstractMotivation: Calculating multiple protein structure alignments (MSAs) is important for understanding functional and evolutionary relationships between protein families, and for modeling protein structures by homology. While incorporating backbone flexibility promises to circumvent many of the limitations of rigid MSA algorithms, very few flexible MSA algorithms exist today. This article describes several novel improvements to the Kpax algorithm which allow high quality flexible MSAs to be calculated. This article also introduces a new Gaussian-based MSA quality measure called ‘M-score’, which circumvents the pitfalls of RMSD-based quality measures.Results: As well as calculating flexible MSAs, the new version of Kpax can also score MSAs from other aligners and from previously aligned reference datasets. Results are presented for a large-scale evaluation of the Homstrad, SABmark and SISY benchmark sets using Kpax and Matt as examples of state-of-the-art flexible aligners and 3DCOMB as an example of a state-of-the-art rigid aligner. These results demonstrate the utility of the M-score as a measure of MSA quality and show that high quality MSAs may be achieved when structural flexibility is properly taken into account.Availability and Implementation: Kpax 5.0 may be downloaded for academic use at http://kpax.loria.fr/ .Contact: dave.ritchie@inria.frSupplementary information: Supplementary data are available at Bioinformatics online.
PRESS: PRotEin S-Sulfenylation server
Authors: Sakka Marianna , Tzortzis Grigorios , Mantzaris Michalis D. , Bekas Nick , Kellici Tahsin F. , Likas Aristidis , Galaris Dimitrios , Gerothanassis Ioannis P. , Tzakos Andreas G. 
Published: May 2016

Abstract
Motivation: Transient S-sulfenylation of cysteine thiols mediated by reactive oxygen species plays a critical role in pathology, physiology and cell signaling. Therefore, discovery of new S-sulfenylated sites in proteins is of great importance towards understanding how protein function is regulated upon redox conditions.
Results: We developed PRESS (PRotEin S-Sulfenylation) web server, a server which can effectively predict the cysteine thiols of a protein that could undergo S-sulfenylation under redox conditions. We envisage that this server will boost and facilitate the discovery of new and currently unknown functions of proteins triggered upon redox conditions, signal regulation and transduction, thus uncovering the role of S-sulfenylation in human health and disease.
Availability and implementation: The PRESS web server is freely available at http://press-sulfenylation.cse.uoi.gr/
Contacts: agtzakos@gmail.com or gtzortzi@cs.uoi.gr
Supplementary information: Supplementary data are available at Bioinformatics online.
A simple yet accurate correction for winner's curse can predict signals discovered in much larger genome scans
Authors: Bigdeli T. Bernard , Lee Donghyung , Webb Bradley Todd , Riley Brien P. , Vladimirov Vladimir I. , Fanous Ayman H. , Kendler Kenneth S. , Bacanu Silviu-Alin 
Published: May 2016

AbstractMotivation: For genetic studies, statistically significant variants explain far less trait variance than ‘sub-threshold’ association signals. To dimension follow-up studies, researchers need to accurately estimate ‘true’ effect sizes at each SNP, e.g. the true mean of odds ratios (ORs)/regression coefficients (RRs) or Z -score noncentralities. Naïve estimates of effect sizes incur winner’s curse biases, which are reduced only by laborious winner’s curse adjustments (WCAs). Given that Z -scores estimates can be theoretically translated on other scales, we propose a simple method to compute WCA for Z -scores, i.e. their true means/noncentralities.Results: WCA of Z -scores shrinks these towards zero while, on P -value scale, multiple testing adjustment (MTA) shrinks P -values toward one, which corresponds to the zero Z -score value. Thus, WCA on Z -scores scale is a proxy for MTA on P -value scale. Therefore, to estimate Z -score noncentralities for all SNPs in genome scans, we propose F DR I nverse Q uantile T ransformation (FIQT). It (i) performs the simpler MTA of P -values using FDR and (ii) obtains noncentralities by back-transforming MTA P -values on Z -score scale. When compared to competitors, realistic simulations suggest that FIQT is more (i) accurate and (ii) computationally efficient by orders of magnitude. Practical application of FIQT to Psychiatric Genetic Consortium schizophrenia cohort predicts a non-trivial fraction of sub-threshold signals which become significant in much larger supersamples.Conclusions : FIQT is a simple, yet accurate, WCA method for Z -scores (and ORs/RRs, via simple transformations).Availability and Implementation: A 10 lines R function implementation is available at https://github.com/bacanusa/FIQT .Contact: sabacanu@vcu.eduSupplementary information: Supplementary data are available at Bioinformatics online.
seqlm: an MDL based method for identifying differentially methylated regions in high density methylation array data
Authors: Kolde Raivo , Märtens Kaspar , Lokk Kaie , Laur Sven , Vilo Jaak 
Published: May 2016

Abstract
Motivation : One of the main goals of large scale methylation studies is to detect differentially methylated loci. One way is to approach this problem sitewise, i.e. to find differentially methylated positions (DMPs). However, it has been shown that methylation is regulated in longer genomic regions. So it is more desirable to identify differentially methylated regions (DMRs) instead of DMPs. The new high coverage arrays, like Illuminas 450k platform, make it possible at a reasonable cost. Few tools exist for DMR identification from this type of data, but there is no standard approach.
Results : We propose a novel method for DMR identification that detects the region boundaries according to the minimum description length (MDL) principle, essentially solving the problem of model selection. The significance of the regions is established using linear mixed models. Using both simulated and large publicly available methylation datasets, we compare seqlm performance to alternative approaches. We demonstrate that it is both more sensitive and specific than competing methods. This is achieved with minimal parameter tuning and, surprisingly, quickest running time of all the tried methods. Finally, we show that the regional differential methylation patterns identified on sparse array data are confirmed by higher resolution sequencing approaches.
Availability and Implementation : The methods have been implemented in R package seqlm that is available through Github: https://github.com/raivokolde/seqlm
Contact: rkolde@gmail.com
Supplementary information: Supplementary data are available at Bioinformatics online.
The impact of alternative rebuilding strategies to rebuild overfished stocks
Authors: Wetzel Chantel R. , Punt André E. ,   Handling editor: Emory Anderson
Published: May 2016

Abstract
Ending overfishing and rebuilding fish stocks to levels that provide for optimum sustainable yield is a concern for fisheries management worldwide. In the United States, fisheries managers are legally mandated to end overfishing and to implement rebuilding plans for fish stocks that fall below minimum stock size thresholds. Rebuilding plans should lead to recovery to target stock sizes within 10 years, except in situations where the life history of the stock or environmental conditions dictate otherwise. Federally managed groundfish species along the US West Coast have diverse life histories where some are able to rebuild quickly from overfished status, while others, specifically rockfish (Sebastes spp.), may require decades for rebuilding. A management strategy evaluation which assumed limited estimation error was conducted to evaluate the performance of alternative strategies for rebuilding overfished stocks for these alternative US West Coast life histories. Generally, the results highlight the trade-off between the reduction of catches during rebuilding vs. the length of rebuilding. The most precautionary rebuilding plans requiring the greatest harvest reduction resulted in higher average catches over the entire projection period compared with strategies that required a longer rebuilding period with less of a reduction in rebuilding catch. Attempting to maintain a 50% probability of rebuilding was the poorest performing rebuilding strategy for all life histories, resulting in a large number of changes to the rebuilding plan, increased frequency of failing to meet rebuilding targets, and higher variation in catch. The rebuilding plans that implemented a higher initial rebuilding probability (≥60%) for determining rebuilding fishing mortality and targets generally resulted in fewer changes to the rebuilding plans and rebuilt by the target rebuilding year, particularly for stocks with the longer rebuilding plans (e.g. rockfishes).
Changing Times, Changing Relationships At Work … Changing Law?
Authors: Langstaff Sir Brian 
Published: May 2016

Abstract
As employment law changes and develops, in sometimes surprising ways, this paper considers the possibility that employment law may not be keeping pace with the diversity of working patterns and practices which have rapidly evolved in the past few decades. It therefore poses the question whether labour law needs to change direction to accommodate the work and workers of the twenty-first century. It firstly makes and details the point, against a statistical base, that significant change in the labour market is nothing new, but then turns to the identification of quite radical recent and continuing changes, and goes on to ask whether they demand a changing law. It presents four cases to illustrate where the law appears to fall short, expressing unease that a discriminatory wrong can be done without the law being able to address it, and highlights different ways in which the law of contract may not provide an appropriate model to deal with today’s problems. The possibility is canvassed that if the expression ‘arrangement’ were used in place of the contractual model, the concentration might then be on industrial realities rather than legal niceties. In conclusion, it is emphasised that the answers are ones of policy which are critically dependent upon the guiding political philosophy of the time. (The paper was delivered as a lecture as a general election approached.)
Patient crossover and potentially avoidable repeat computed tomography exams across a health information exchange
Authors: Slovis Benjamin H , Lowry Tina , Delman Bradley N , Beitia Anton Oscar , Kuperman Gilad , DiMaggio Charles , Shapiro Jason S 
Published: May 2016

Objective: The purpose of this study was to measure the number of repeat computed tomography (CT) scans performed across an established health information exchange (HIE) in New York City. The long-term objective is to build an HIE-based duplicate CT alerting system to reduce potentially avoidable duplicate CTs.
Methods: This retrospective cohort analysis was based on HIE CT study records performed between March 2009 and July 2012. The number of CTs performed, the total number of patients receiving CTs, and the hospital locations where CTs were performed for each unique patient were calculated. Using a previously described process established by one of the authors, hospital-specific proprietary CT codes were mapped to the Logical Observation Identifiers Names and Codes (LOINC®) standard terminology for inter-site comparison. The number of locations where there was a repeated CT performed with the same LOINC code was then calculated for each unique patient.
Results: There were 717 231 CTs performed on 349 321 patients. Of these patients, 339 821 had all of their imaging studies performed at a single location, accounting for 668 938 CTs. Of these, 9500 patients had 48 293 CTs performed at more than one location. Of these, 6284 patients had 24 978 CTs with the same LOINC code performed at multiple locations. The median time between studies with the same LOINC code was 232 days (range of 0 to 1227); however, 1327 were performed within 7 days and 5000 within 30 days.
Conclusions: A small proportion (3%) of our cohort had CTs performed at more than one location, however this represents a large number of scans (48 293). A noteworthy portion of these CTs (51.7%) shared the same LOINC code and may represent potentially avoidable studies, especially those done within a short time frame. This represents an addressable issue, and future HIE-based alerts could be utilized to reduce potentially avoidable CT scans.
Extreme asymmetry in the polarized disk of V1247 Orionis
Authors: Ohta Yurina , Fukagawa Misato , Sitko Michael L. , Muto Takayuki , Kraus Stefan , Grady Carol A. , Wisniewski John P. , Swearingen Jeremy R. , Shibai Hiroshi , Sumi Takahiro , Hashimoto Jun , Kudo Tomoyuki , Kusakabe Nobuhiko , Momose Munetake , Okamoto Yoshiko , Kotani Takayuki , Takami Michihiro , Currie Thayne , Thalmann Christian , Janson Markus , Akiyama Eiji , Follette Katherine B. , Mayama Satoshi , Abe Lyu , Brandner Wolfgang , Brandt Timothy D. , Carson Joseph C. , Egner Sebastian E. , Feldt Markus , Goto Miwa , Guyon Olivier , Hayano Yutaka , Hayashi Masahiko , Hayashi Saeko S. , Henning Thomas , Hodapp Klaus W. , Ishii Miki , Iye Masanori , Kandori Ryo , Knapp Gillian R. , Kuzuhara Masayuki , Kwon Jungmi , Matsuo Taro , McElwain Michael W. , Miyama Shoken , Morino Jun-Ichi , Moro-Martín Amaya , Nishimura Tetsuo , Pyo Tae-Soo , Serabyn Eugene , Suenaga Takuya , Suto Hiroshi , Suzuki Ryuji , Takahashi Yasuhiro H. , Takami Hideki , Takato Naruhisa , Terada Hiroshi , Tomono Daigo , Turner Edwin L. , Usuda Tomonori , Watanabe Makoto , Yamada Toru , Tamura Motohide 
Published: May 2016

Abstract
We present the first near-infrared scattered-light detection of the transitional disk around V1247 Ori, which was obtained using high-resolution polarimetric differential imaging observations with Subaru/HiCIAO. Our imaging in the H band reveals the disk morphology at separations of ∼0${^{\prime\prime}_{.}}$14–0${^{\prime\prime}_{.}}$86 (54–330 au) from the central star. The polarized intensity image shows a remarkable arc-like structure toward the southeast of the star, whereas the fainter northwest region does not exhibit any notable features. The shape of the arm is consistent with an arc of 0${^{\prime\prime}_{.}}$28 ± 0${^{\prime\prime}_{.}}$09 in radius (108 au from the star), although the possibility of a spiral arm with a small pitch angle cannot be excluded. V1247 Ori features an exceptionally large azimuthal contrast in scattered, polarized light; the radial peak of the southeastern arc is about three times brighter than the northwestern disk measured at the same distance from the star. Combined with the previous indication of an inhomogeneous density distribution in the gap at ≲46 au, the notable asymmetry in the outer disk suggests the presence of unseen companions and/or planet-forming processes ongoing in the arc.
Do Resting Plasma β-Endorphin Levels Predict Responses to Opioid Analgesics?
Authors: Bruehl Stephen , Burns John W. , Gupta Rajnish , Buvanendran Asokumar , Chont Melissa , Orlowska Daria , Schuster Erik , France Christopher R. 
Published: May 2016

Objectives:Clinically feasible predictors of opioid analgesic responses for use in precision pain medicine protocols are needed. This study evaluated whether resting plasma β-endorphin (BE) levels predicted responses to an opioid analgesic, and whether chronic pain status or sex moderated these effects.Methods:Participants included 73 individuals with chronic low back pain (CLBP) and 88 pain-free controls, all using no daily opioid analgesics. Participants attended 2 identical laboratory sessions during which they received either intravenous morphine (0.08 mg/kg) or saline placebo, with blood samples obtained before drug administration to assay resting plasma BE levels. Once peak drug activity was achieved in each session, participants engaged in an ischemic forearm pain task (ISC) and a heat pain task. Morphine analgesic effects were derived reflecting the difference in pain outcomes between placebo and morphine conditions.Results:In hierarchical regressions, significant Type (CLBP vs. control)×BE interactions (Ps<0.05) were noted for morphine effects on ISC tolerance, ISC intratask pain ratings, and thermal VAS unpleasantness ratings. These interactions derived primarily from associations between higher BE levels and smaller morphine effects restricted to the CLBP subgroup. All other BE-related effects, including sex interactions, for predicting morphine analgesia failed to reach statistical significance.Discussion:BE was a predictor of morphine analgesia for only 3 out of 9 outcomes examined, with these effects moderated by chronic pain status but not sex. On the whole, results do not suggest that resting plasma BE levels are likely to be a clinically useful predictor of opioid analgesic responses.
Immunologic Consequences of Hypoxia during Critical Illness
Authors: Kiers Harmke D. , Scheffer Gert-Jan , van der Hoeven Johannes G. , Eltzschig Holger K. , Pickkers Peter , Kox Matthijs 
Published: May 2016

AbstractAbstract
Hypoxia and immunity are highly intertwined at clinical, cellular, and molecular levels. The prevention of tissue hypoxia and modulation of systemic inflammation are cornerstones of daily practice in the intensive care unit. Potentially, immunologic effects of hypoxia may contribute to outcome and represent possible therapeutic targets. Hypoxia and activation of downstream signaling pathways result in enhanced innate immune responses, aimed to augment pathogen clearance. On the other hand, hypoxia also exerts antiinflammatory and tissue-protective effects in lymphocytes and other tissues. Although human data on the net immunologic effects of hypoxia and pharmacologic modulation of downstream pathways are limited, preclinical data support the concept of tailoring the immune response through modulation of the oxygen status or pharmacologic modulation of hypoxia-signaling pathways in critically ill patients.
Hypoxia affects molecular and cellular inflammatory processes and may thereby affect outcome in critical illness. Modulating oxygenation and pharmacologic interventions in hypoxia-singling pathways could support immunologic functions in these patients.