bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure-based prediction of ligand–protein interactions on a genome-wide scale
Authors: Hwang Howook , Dey Fabian , Petrey Donald , Honig Barry 
Published: December 2017

Significance
The ability to identify protein targets for different ligands would have enormous impact on drug discovery, both in the repurposing of known drugs and in the identification of off-targets. Moreover, identifying small-molecule binding sites and associating potential ligands with those sites is important in protein function annotation. The methods described in this paper are designed to accomplish these goals. They rely heavily on the use of protein structural alignment to detect relationships not available from sequence alone and use a measure of protein–ligand interaction similarity to determine whether proteins with similar shapes are likely to bind similar ligands. We present results that compare favorably with existing methods using an approach that can be applied on a genome-wide scale.
Network analysis identifies chromosome intermingling regions as regulatory hotspots for transcription
Authors: Belyaeva Anastasiya , Venkatachalapathy Saradha , Nagarajan Mallika , Shivashankar G. V. , Uhler Caroline 
Published: December 2017

Significance
We develop a network analysis approach for identifying clusters of interactions between chromosomes, which we validate experimentally. Our method integrates 1D features of the genome, such as epigenetic marks, with 3D interactions, allowing us to study spatially colocalized regions between chromosomes that are functionally relevant. We observe that clusters of interchromosomal regions fall into active and inactive categories. We find that active clusters share transcription factors and are enriched for transcriptional machinery, suggesting that chromosome intermingling regions play a key role in genome regulation. Our method provides a unique quantitative framework that can be broadly applied to study the principles of genome organization and regulation during processes such as cell differentiation and reprogramming.
Perception and misperception of surface opacity
Authors: Marlow Phillip J. , Kim Juno , Anderson Barton L. 
Published: December 2017

Significance
One of the most perplexing problems in vision science is to understand how the visual system computes the reflectance and transmittance properties of different materials despite variability in 3D shape and illumination. We show that 3D shape can play a decisive role in the perception of surface opacity and that gross misperceptions of surface opacity can arise for specific surface geometries and light fields. We argue that the perception of surface opacity depends on the relationship between intensity and 3D surface orientation and show that this relationship can play a decisive role in modulating the perception of surface opacity, independently of the true physical characteristics of materials.
Impact of insecticide resistance in
Anopheles arabiensis
on malaria incidence and prevalence in Sudan and the costs of mitigation
Authors: Kafy Hmooda Toto , Ismail Bashir Adam , Mnzava Abraham Peter , Lines Jonathan , Abdin Mogahid Shiekh Eldin , Eltaher Jihad Sulieman , Banaga Anuar Osman , West Philippa , Bradley John , Cook Jackie , Thomas Brent , Subramaniam Krishanthi , Hemingway Janet , Knox Tessa Bellamy , Malik Elfatih M. , Yukich Joshua O. , Donnelly Martin James , Kleinschmidt Immo 
Published: December 2017

Significance
Emerging insecticide resistance in malaria vectors could presage a catastrophic rebound in malaria morbidity and mortality. In areas of moderate levels of resistance to pyrethroids, long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) with a carbamate insecticide were significantly more effective than IRS with pyrethroid insecticide. The impact on the effectiveness of LLINs could not be quantified. The incremental cost of using a carbamate insecticide to which vectors are susceptible was US $0.65 per person protected per year, which is considered acceptable by international standards. While the WHO recommends that different interventions, where possible, should use different insecticide classes, these data alone should not be used as the basis for a policy change in vector control interventions.
Early endosome as a pathogenic target for antiphosphatidylethanolamine antibodies
Authors: Hou Songwang , Fölsch Heike , Ke Ke , Cook Mills Joan , Ramsey-Goldman Rosalind , Zhao Ming 
Published: December 2017

Significance
Autoimmunity against phosphatidylethanolamine (PE) was first reported more than three decades ago. Since then, a growing body of literature has documented the prevalence of aPE in a number of clinical conditions including thrombosis and repeated pregnancy loss, but the cellular target of anti-PE antibodies has remained elusive. The study presented here shows that the cellular vulnerability to PE binding is mediated by interactions that occur in the endosomal compartment, which lead to the activation of inflammatory mechanisms. Thus, our results provide knowledge about the pathogenic mechanism of aPE and have important implications for the diagnosis and treatment of this autoimmune condition.
Proteasomes tether to two distinct sites at the nuclear pore complex
Authors: Albert Sahradha , Schaffer Miroslava , Beck Florian , Mosalaganti Shyamal , Asano Shoh , Thomas Henry F. , Plitzko Jürgen M. , Beck Martin , Baumeister Wolfgang , Engel Benjamin D. 
Published: December 2017

Significance
This study compares the native structures of cytosolic and nuclear proteasomes, visualized directly within cells. The assembly states and functional states of proteasomes in each compartment were similar, indicating comparable levels of proteolytic activity per proteasome. Nuclear proteasomes were tethered to two different sites at the nuclear pore complex (NPC): the inner nuclear membrane and the NPC basket. Structural analysis revealed mechanistic details of the two tethering interactions. These results present direct evidence that proteasomes bind at NPCs, establishing a cellular hub for protein degradation at the gateway between the nucleus and cytoplasm. This work demonstrates how cryo-electron tomography can reveal biological mechanisms by directly observing the interactions between molecular complexes within the native cellular environment.
Status and function of the English language in Qatar: a social semiotic perspective
Authors: Alkhatib Hadeel 
Published: December 2017

ABSTRACT
This paper gives an overview of the role(s) that the English language plays in the Qatari community. Firstly, it reviews the areas displaying the decisive role of the English language in Qatari society through a social semiotic analysis of a set of political cartoons published in the two best-selling Qatari newspapers, Al Sharq (The East) and Al Raya (The Banner), during the period of 2011–2014 in which a flurry of activity, in terms of both economic and linguistic changes, took place in Qatar. Secondly, it discusses the implications that the unequivocal priority given to the English language may have for Arab native speakers in the country by utilizing Foucault's concept of heterotopia. This paper concludes that English has occupied an influential role in Qatari society and has created a sense of estrangement among Arabic native residents of the country.
Quantifying carbon fluxes from primary production to mesopelagic fish using a simple food web model
Authors: Anderson Thomas R , Martin Adrian P , Lampitt Richard S , Trueman Clive N , Henson Stephanie A , Mayor Daniel J 
Published: December 2017

Abstract
An ecosystem-based flow analysis model was used to study carbon transfer from primary production (PP) to mesopelagic fish via three groups of copepods: detritivores that access sinking particles, vertical migrators, and species that reside in the surface ocean. The model was parameterized for 40°S to 40°N in the world ocean such that results can be compared with recent estimates of mesopelagic fish biomass in this latitudinal range, based on field studies using acoustic technologies, of ∼13 Gt (wet weight). Mesopelagic fish production was predicted to be 0.32% of PP which, assuming fish longevity of 1.5 years, gives rise to predicted mesopelagic fish biomass of 2.4 Gt. Model ensembles were run to analyse the uncertainty of this estimate, with results showing predicted biomass &gt;10 Gt in only 8% of the simulations. The work emphasizes the importance of migrating animals in transferring carbon from the surface ocean to the mesopelagic zone. It also highlights how little is known about the physiological ecology of mesopelagic fish, trophic pathways within the mesopelagic food web, and how these link to PP in the surface ocean. A deeper understanding of these interacting factors is required before the potential for utilizing mesopelagic fish as a harvestable resource can be robustly assessed.
Vitamin D Supplementation Does Not Affect Metabolic Changes Seen With ART Initiation
Authors: Muhammad Josh , Chan Ellen S , Brown Todd T , Tebas Pablo , McComsey Grace A , Melbourne Kathleen , Hardin Royce , Willig Amanda L , Yin Michael T , Ribaudo Heather , Overton Edgar Turner 
Published: December 2017

Abstract

Background
Insulin resistance and lipid changes are common after antiretroviral therapy (ART) initiation. Observational studies suggest that vitamin D supplementation reduces the risk of developing diabetes and improves lipid profiles.

Methods
This 48-week prospective, randomized, double-blind, placebo-controlled study evaluated high-dose vitamin D3 (4000 IU daily) plus calcium supplementation (1000 mg calcium carbonate daily) in HIV-infected participants initiating ART with efavirenz/emtricitabine/tenofovir (EFV/FTC/TDF). Changes in insulin resistance (as estimated by homeostatic model assessment), fasting lipid profile, and components of the metabolic syndrome were assessed at baseline, 24 weeks, and 48 weeks. Stratified Wilcoxon rank sum tests and stratified normal score tests were used to evaluate differences between treatment arms, stratified by screening 25-OH vitamin D stratum (≤/&gt;20 ng/mL).

Results
A total of 165 participants enrolled: 79 in the vitamin D/calcium (Vit D/Cal) arm and 86 in the placebo arm. Only the placebo arm experienced a modest increase in insulin resistance at week 24 (P &lt; .001). While increases in total and high-density lipoprotein cholesterol were significant in both arms at weeks 24 and 48, increases in low-density lipoprotein cholesterol at week 24 were only identified in the placebo arm (P = .011). Body mass index remained stable, whereas modest increases in waist circumference were observed in the placebo arm. Metabolic syndrome was present in 19 participants (12%) at baseline and 20 participants (14%) at week 48, without differences between arms.

Conclusions
Vit D/Cal supplementation over 48 weeks did not alter the lipid profile or glucose metabolism experienced with initiation of EFV/FTC/TDF in ART-naïve persons. Vitamin D supplementation is unlikely to be an effective strategy to attenuate metabolic dysregulations with ART initiation.
Characterizing the Liquid-liquid Phase Co-existence in Biomembrane: Insights from Local Non-affine Deformation and Topological Rearrangements
Authors: Iyer Sahithya S. , Tripathy Madhusmita , Srivastava Anand 
Published: December 2017

AbstractLateral heterogeneities in bio-membranes play a crucial role in various physiological functions of the cell. Such heterogeneities lead to demixing of lipid constituents and formation of distinct liquid domains in the membrane. We study lateral heterogeneities in terms of the topological rearrangements of lipids, to identify liquid-liquid phase co-existence in model membranes. By quantifying the degree of non-affineness associated with individual lipid, we are able to characterize the liquid ordered (Lo) and liquid disordered (Ld) phases in model lipid bilayers, without any prior knowledge on chemical identity of the lipids. We explore the usage of this method on all atom and coarse-grained lipid bilayer trajectories. This method is helpful in defining the instantaneous Lo-Ld domain boundaries in complex multi-component bilayer systems. The characterization can also highlight the effect of line-active molecules on the phase boundaries and domain mixing. Overall, we propose a framework to explore the molecular origin of spatial and dynamical heterogeneity in bio-membranes systems, which can not only be exploited in computer simulation, but also in experiments.
Effects of latent toxoplasmosis on olfactory functions of men and women
Authors: Flegr Jaroslav , Milinski Manfred , Kaňková Šárka , Hůla Martin , Hlaváčová Jana , Sýkorová Kateřina 
Published: December 2017

SUMMARYThe prevalence of toxoplasmosis is higher in schizophrenics than in the general population. It has been suggested that certain symptoms of schizophrenia, including changes in olfactory functions, are in fact symptoms of toxoplasmosis that can be easily detected in schizophrenics only due to the increased prevalence of toxoplasmosis in this population. Schizophrenics have impaired identification of odors and lower sensitivity of odor detection. Here we searched for differences in olfactory functions between 62 infected and 61 noninfected non-schizophrenic subjects. The infected men scored better in the standard odor-identification test. The infected women rated all smells as more intensive while the infected men rated nearly all smells as less intensive. Infected women rated the pleasantness of the smell of undiluted cat urine as higher than the non-infected women and the opposite was true for the men (the opposite direction shifts in men and women were described earlier for highly diluted cat urine). Toxoplasmosis had no effect on the rated pleasantness of the smell of other stimuli. Our results suggest that latent toxoplasmosis is associated with changes in the olfactory functions in humans; however, the observed changes differ from those observed in schizophrenics.Key findingsInfected men but not women show better odor identification ability than the non-infected controls.The infected women rated all smells as more and men as less intensive than the controls.The infected women rated smell of cat urine as more and men as less pleasurable than the controls.Toxoplasmosis had no effect on the rated pleasantness of the smell of other stimuli.We found no new evidence for the toxoplasmosis hypothesis of schizophrenia.
Behavioral variation correlates with differences in single neuron serotonin receptor subtype expression within and across species
Authors: Tamvacakis A.N. , Senatore A. , Katz P.S. 
Published: December 2017

AbstractThe marine mollusc, Pleurobranchaea californica varies daily in whether it swims and this correlates with whether serotonin (5-HT) enhances the strength of synapses made by the swim central pattern generator neuron, C2. Another species, Tritonia diomedea, reliably swims and does not vary in serotonergic neuromodulation. A third species, Hermissenda crassicornis, never produces this behavior and lacks the neuromodulation. We found that expression of particular 5-HT receptor genes in C2 correlates with swimming. Seven 5-HT receptor subtype genes were identified from whole-brain transcriptomes. We isolated individual C2 neurons and sequenced their RNA or measured 5-HT receptor gene expression using quantitative PCR. C2 neurons isolated from Pleurobranchaea individuals that produced a swim motor pattern just prior to isolation expressed the 5-HT2a and 5-HT7 receptor genes, as did the Tritonia samples. These subtypes were absent from C2 neurons isolated from Pleurobranchaea individuals that did not swim that day and from Hermissenda C2 neurons. Expression of other receptors did not correlate with swimming. This suggests that 5-HT2a and 5-HT7 receptors mediate the modulation of C2 synaptic strength and play an important role in swimming. Furthermore, the results suggest that regulation of receptor expression might underlie daily changes in behavior as well as behavioral evolution.
Mechanisms of KCNQ1 Channel Dysfunction in Long QT Syndrome Involving Voltage Sensor Domain Mutations
Authors: Huang Hui , Kuenze Georg , Smith Jarrod A. , Taylor Keenan C. , Duran Amanda M. , Hadziselimovic Arina , Meiler Jens , Vanoye Carlos G. , George Alfred L. , Sanders Charles R. 
Published: December 2017

AbstractLoss-of-function (LOF) mutations in human KCNQ1 are responsible for susceptibility to a life-threatening heart rhythm disorder, the congenital long-QT syndrome (LQTS). Hundreds of KCNQ1 mutations have been identified, but the molecular mechanisms responsible for impaired function are poorly understood. Here, we investigated the impact of 51 KCNQ1 variants located within the voltage sensor domain (VSD), with an emphasis on elucidating effects on cell surface expression, protein folding and structure. For each variant, the efficiency of trafficking to the plasma membrane, the impact of proteasome inhibition, and protein stability were assayed. The results of these experiments, combined with channel functional data, provided the basis for classifying each mutation into one of 6 mechanistic categories. More than half of the KCNQ1 LOF mutations destabilize the structure of the VSD, resulting in mistrafficking and degradation by the proteasome, an observation that underscores the growing appreciation that mutation-induced destabilization of membrane proteins may be a common human disease mechanism. Finally, we observed that 5 of the folding-defective LQTS mutants are located in the VSD S0 helix, where they interact with a number of other LOF mutation sites in other segments of the VSD. These observations reveal a critical role for the S0 helix as a central scaffold to help organize and stabilize the KCNQ1 VSD and, most likely, the corresponding domain of many other ion channels.One Sentence SummaryLong QT syndrome-associated mutations in KCNQ1 most often destabilize the protein, leading to mistrafficking and degradation.
Mitochondrial heteroplasmy is responsible for Atovaquone drug resistance in Plasmodium falciparum
Authors: Siegel Sasha , Rivero Andrea , Adapa Swamy R. , Wang ChengQi , Manetsch Roman , Jiang Rays H.Y. , Kyle Dennis E. 
Published: December 2017

AbstractMalaria is the most significant parasitic disease affecting humans, with 212 million cases and 429,000 deaths in 2 0151, and resistance to existing drugs endangers the global malaria elimination campaign. Atovaquone (ATO) is a safe and potent antimalarial drug that acts on cytochrome b (cyt. b) of the mitochondrial electron transport chain (mtETC) in Plasmodium falciparum, yet treatment failures result in resistance-conferring SNPs in cyt. b. Herein we report that rather than the expected de novo selection of resistance, previously unknown mitochondrial diversity is the genetic mechanism responsible for resistance to ATO, and potentially other cyt. b targeted drugs. We found that P. falciparum harbors cryptic cyt. b. Y268S alleles in the multicopy (∼22 copies) mitochondrial genome prior to drug treatment, a phenomenon known as mitochondrial heteroplasmy. Parasites with cryptic Y268S alleles readily evolve into highly resistant parasites with >95% Y268S copies under in vitro ATO selection. Further we uncovered high mitochondrial diversity in a global collection of 1279 genomes in which heteroplasmic polymorphisms were >3-fold more prevalent than homoplasmic SNPs. Moreover, significantly higher mitochondrial genome copy number was found in Asia (e.g., Cambodia) versus Africa (e.g., Ghana). Similarly, ATO drug selections in vitro induced >3-fold mitochondrial copy number increases in ATO resistant lines. Hidden mitochondrial diversity is a previously unknown mechanism of antimalarial drug resistance and characterization of mitochondrial heteroplasmy will be of paramount importance in combatting resistance to antimalarials targeting the electron transport chain.
CFT & people with intellectual disabilities
Authors: Hardiman Mark , Willmoth Corrina , Walsh James J. 
Published: December 2017

PurposeThe purpose of this paper is to assess the effects of compassion-focussed therapy (CFT) on anxiety in a small sample of adults with intellectual disability.Design/methodology/approachA mixed-methods design was employed. Participants (n=3) completed questionnaire measures of anxiety and self-compassion on three occasions: pre-intervention, post-intervention and, at three months follow-up. Post-intervention, they also took part in recorded interviews that were analysed using interpretive phenomenological analysis. Findings were then synthesised to develop a comprehensive understanding of their overall experience.FindingsFinal data synthesis revealed five themes: participant anxiety decreased (reliable for all participants); the faulty self; improved positive compassionate attitudes; increased sense of common humanity; and mindful distraction techniques.Research limitations/implicationsThis research paper offers in-depth analysis of three participants’ experiences rather than reporting in less detail about a larger number of participants. The self-compassion scale required considerable support and reasonable adaptation to be used with these clients.Originality/valueOnly two other studies have explored the use of CFT with people with intellectual disabilities.
Understanding the nature of processes: an information-processing perspective
Authors: Zelt Sarah , Schmiedel Theresa , vom Brocke Jan 
Published: December 2017

PurposeWhile researchers and practitioners agree on the importance to adapt business process management (BPM) practices to the nature of processes, the authors observe a lack of research on how to most meaningfully distinguish processes in order to apply context-specific BPM practices that increase process efficiency and effectiveness. The purpose of this paper is to systematically analyze the nature of processes as one contextual factor for BPM.Design/methodology/approachBased on a literature review, the authors systematically derive process dimensions that describe the nature of processes and apply an information-processing perspective to the process level as a theoretical lens through which to analyze and structure these process dimensions.FindingsThe authors identified 36 dimensions used to describe process differences that can be consolidated into five generic dimensions based on an information-processing perspective: interdependence of process participants, differentiation of process participants, process analyzability, variability, and importance.Research limitations/implicationsThe paper derives process dimensions from the literature and links them to extant theories as a foundation for context-sensitive BPM. The findings serve as a basis for further conceptualizing BPM and for explaining seemingly contradicting findings about whether management practices increase or decrease organizational performance.Practical implicationsWhile the paper focuses on understanding and explaining process differences, the authors also demonstrate how these dimensions can be used to make strategic management decisions in order to increase the effectiveness and efficiency of processes.Originality/valueThe authors systematically conceptualize process differences as a foundation for contingent process management. In addition, the authors demonstrate that organizational processes provide a new field of application for information-processing theory.