bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histone H3 tail binds a unique sensing pocket in EZH2 to activate the PRC2 methyltransferase
Authors: Jani Krupa S. , Jain Siddhant U. , Ge Eva J. , Diehl Katharine L. , Lundgren Stefan M. , Müller Manuel M. , Lewis Peter W. , Muir Tom W. 
Published: April 2019

Significance
Polycomb Repressor Complex 2 (PRC2) is an epigenetic effector enzyme with key roles in gene silencing and establishment of facultative heterochromatin. Mutations of this histone lysine methyltransferase and its substrate H3K27 are linked to multiple human pathologies, and PRC2 has been identified as a therapeutic target in cancer treatment. The H3K27 methylation activity of PRC2 is sensitive to the chromatin environment, including the methylation state of H3K36 on the same histone tail. The mechanistic basis of this negative cross-talk is poorly understood. The present work sheds light on this question by identifying a regulatory feature on the catalytic subunit of PRC2, EZH2, which acts as a specific sensor for H3K36 methylation state. The work reveals an unusual mode of enzyme modulation by a substrate molecule.
Blind tests of RNA–protein binding affinity prediction
Authors: Kappel Kalli , Jarmoskaite Inga , Vaidyanathan Pavanapuresan P. , Greenleaf William J. , Herschlag Daniel , Das Rhiju 
Published: April 2019

SignificanceRNA and protein molecules interact to perform translation, splicing, and other fundamental processes. These interactions are defined by their strength and specificity, but it remains infeasible to experimentally measure these properties for all biologically important RNA–protein complexes. Development of computational strategies for calculating RNA–protein energetics has been hindered by unique complexities of RNA–protein binding, particularly the propensity of RNA to adopt multiple conformations in the unbound state. We describe a method, Rosetta-Vienna RNP-ΔΔG, combining 3D structure modeling with RNA secondary structure-based energetic calculations to predict RNA–protein relative binding affinities. For several diverse systems and in rigorous blind tests, the accuracy of Rosetta-Vienna RNP-ΔΔG compared with experimental measurements is significantly better than that of prior approaches.
Immune tolerance in multiple sclerosis and neuromyelitis optica with peptide-loaded tolerogenic dendritic cells in a phase 1b trial
Authors: Zubizarreta Irati , Flórez-Grau Georgina , Vila Gemma , Cabezón Raquel , España Carolina , Andorra Magi , Saiz Albert , Llufriu Sara , Sepulveda Maria , Sola-Valls Nuria , Martinez-Lapiscina Elena H. , Pulido-Valdeolivas Irene , Casanova Bonaventura , Martinez Gines Marisa , Tellez Nieves , Oreja-Guevara Celia , Español Marta , Trias Esteve , Cid Joan , Juan Manel , Lozano Miquel , Blanco Yolanda , Steinman Lawrence , Benitez-Ribas Daniel , Villoslada Pablo 
Published: April 2019

Significance
Application of antigen-specific immune tolerance in autoimmune disease is a long-sought goal. We studied diseases with abundant information on the autoimmune target: in multiple sclerosis (MS), various myelin antigens are known targets of T cells and antibodies, whereas in neuromyelitis optica (NMO), the aquaporin-4 channel is attacked by T cells and antibodies. We tested whether engineered dendritic cells might induce a tolerogenic immune response in these two conditions. In this in-human clinical study, individual regulatory T cells, secreting IL-10, a key tolerogenic cytokine, were detected after treatment. These results might lead to more extensive trials with this approach in autoimmune conditions where the antigenic target has been identified, including MS, NMO, myasthenia gravis, and Graves disease.
Designer covalent heterobivalent inhibitors prevent IgE-dependent responses to peanut allergen
Authors: Deak Peter E. , Kim Baksun , Abdul Qayum Amina , Shin Jaeho , Vitalpur Girish , Kloepfer Kirsten M. , Turner Matthew J. , Smith Neal , Shreffler Wayne G. , Kiziltepe Tanyel , Kaplan Mark H. , Bilgicer Basar 
Published: April 2019

Significance
IgE antibody interaction with allergen proteins is the main driver for life-threating allergic responses. Using a nanoparticle-based method, we identified the most crucial binding sites for IgEs on peanut proteins by testing a small population of patient serum with a clinical history of severe allergies to peanuts. We then synthesized inhibitors, we call covalent heterobivalent inhibitors, which specifically and permanently prevent IgEs from binding to peanut proteins and triggering allergic responses. This is significant as it seems that only a few binding sites on peanut allergen proteins drive allergic responses. Also, this is a functional example of selective IgE inhibition to a relevant food allergen and establishes cHBIs as a class of allergy therapeutics.
Mechanistic basis for impaired ferroptosis in cells expressing the African-centric S47 variant of p53
Authors: Leu Julia I-Ju , Murphy Maureen E. , George Donna L. 
Published: April 2019

Significance
The p53 tumor suppressor protein is a critical stress response mediator. Polymorphisms in the human TP53 gene can alter protein function. We investigated an African-centric variant affecting codon 47 (P47S). Compared with those with the P47 variant, cells and mice expressing the serine 47 (S47) variant exhibit increased levels of coenzyme A (CoA) and glutathione (GSH). These molecules inhibit the induction of ferroptosis in S47 cells and mice. Elevated levels of CoA and GSH feedback on the p53 protein to negatively regulate the structure and function of this tumor suppressor protein. We identify CoA as a regulator of ferroptosis and show that the control of cell fate in response to certain ferroptosis inducers and p53 is reversible by altering the redox environment.
Early tropical crop production in marginal subtropical and temperate Polynesia
Authors: Prebble Matthew , Anderson Atholl J. , Augustinus Paul , Emmitt Joshua , Fallon Stewart J. , Furey Louise L. , Holdaway Simon J. , Jorgensen Alex , Ladefoged Thegn N. , Matthews Peter J. , Meyer Jean-Yves , Phillipps Rebecca , Wallace Rod , Porch Nicholas 
Published: April 2019

SignificanceFossil evidence shows that Polynesians introduced the tropical crop taro (Colocasia esculenta) during initial colonization of the subtropical South Pacific islands and temperate New Zealand after 1200 CE, establishing garden ecosystems with similar commensal plants and invertebrates. Sedimentary charcoal and fossil remains indicate how frequent burning and perennial cultivation overcame the ecological constraints for taro production, particularly the temperate forest cover of New Zealand. An increase in short-lived plants, indicating a transition toward higher-intensity production, followed rapid woody forest decline and species extinctions on all islands. The relatively recent fossil records from the subtropical and temperate islands of Polynesia provide unique insights into the ecological processes behind the spread of Neolithic crops into areas marginal for production.
Myosin Va transport of liposomes in three-dimensional actin networks is modulated by actin filament density, position, and polarity
Authors: Lombardo Andrew T. , Nelson Shane R. , Kennedy Guy G. , Trybus Kathleen M. , Walcott Sam , Warshaw David M. 
Published: April 2019

SignificanceIntracellular transport of critical cellular components (e.g. vesicles, organelles, mRNA, chromosomes) is accomplished by myosin Va molecular motors along complicated 3D networks of actin filaments. Disruption of these transport processes leads to debilitating human disease (e.g. Griscelli syndrome), while rearrangement of the 3D actin cytoskeleton is a hallmark of malignant cancers. We found that the various modes of motion (stationary, diffusive-like, or directed) describing how teams of myosin Va transport 350-nm liposome cargos are determined by the 3D position and polarity of the actin filaments within the network that the myosin Va motors interact with. This study demonstrates that the 3D actin filament organization within the network can serve as a potent regulator of myosin Va motor-based intracellular transport.
Effective detection of spatio-temporal carrier dynamics by carrier capture
Authors: Rosati R , Lengers F , Reiter D E , Kuhn T 
Published: April 2019

Abstract
The spatio-temporal dynamics of electrons moving in a 2D plane is challenging to detect when the required resolution shrinks simultaneously to nanometer length and subpicosecond time scale. We propose a detection scheme relying on phonon-induced carrier capture from 2D unbound states into the bound states of an embedded quantum dot. This capture process happens locally and here we explore if this locality is sufficient to use the carrier capture process as detection of the ultrafast diffraction of electrons from an obstacle in the 2D plane. As an example we consider an electronic wave packet traveling in a semiconducting monolayer of the transition metal dichalcogenide MoSe2, and we study the scattering-induced dynamics using a single particle Lindblad approach. Our results offer a new way to high resolution detection of the spatio-temporal carrier dynamics.
Noise spectroscopy to study the 1D electron transport properties in InAs nanowires
Authors: Petrychuk M , Zadorozhnyi I , Kutovyi Y , Karg S , Riel H , Vitusevich S 
Published: April 2019

Abstract
InAs nanowires (NWs) are recognized as a key material due to their unique transport properties. Despite remarkable progress in designing InAs NW device structures, there are still open questions on device variability. Here, we demonstrate that noise spectroscopy allows us to study not only the parameters of traps, but also to shed light on quantum transport in NW structures. This provides an important understanding of structural behavior as well as the background and strategy required to design NW structures with advanced properties.
Principal component analysis for fast and model-free denoising of multi b-value diffusion-weighted MR images
Authors: Gurney-Champion Oliver J , Collins David J , Wetscherek Andreas , Rata Mihaela , Klaassen Remy , van Laarhoven Hanneke W M , Harrington Kevin J , Oelfke Uwe , Orton Matthew R 
Published: April 2019

Abstract
Despite the utility of tumour characterisation using quantitative parameter maps from multi-b-value diffusion-weighted MRI (DWI), clinicians often prefer the use of the image with highest diffusion-weighting (b-value), for instance for defining regions of interest (ROIs). However, these images are typically degraded by noise, as they do not utilize the information from the full acquisition. We present a principal component analysis (PCA) approach for model-free denoising of DWI data. PCA-denoising was compared to synthetic MRI, where a diffusion model is fitted for each voxel and a denoised image at a given b-value is generated from the model fit. A quantitative comparison of systematic and random errors was performed on data simulated using several diffusion models (mono-exponential, bi-exponential, stretched-exponential and kurtosis). A qualitative visual comparison was also performed for in vivo images in six healthy volunteers and three pancreatic cancer patients. In simulations, the reduction in random errors from PCA-denoising was substantial (up to 55%) and similar to synthetic MRI (up to 53%). Model-based synthetic MRI denoising resulted in substantial (up to 29% of signal) systematic errors, whereas PCA-denoising was able to denoise without introducing systematic errors (less than 2%). In vivo, the signal-to-noise ratio (SNR) and sharpness of PCA-denoised images were superior to synthetic MRI, resulting in clearer tumour boundaries. In the presence of motion, PCA-denoising did not cause image blurring, unlike image averaging or synthetic MRI. Multi-b-value MRI can be denoised model-free with our PCA-denoising strategy that reduces noise to a level similar to synthetic MRI, but without introducing systematic errors associated with the synthetic MRI method.
Verbal Fluency Development Across Childhood: Normative Data from Brazilian–Portuguese Speakers and Underlying Cognitive Processes
Authors: Becker Natalia , Piccolo L R , Salles J F 
Published: April 2019

Abstract

Objective
Verbal fluency (VF) tasks are widely used to investigate children’s lexical knowledge and executive functions skills. Consistency of measurement of the strategic retrieval components is still an issue and performance of Brazilian–Portuguese speaking children are currently not available. A cross-sectional study investigated the effects of age, school type (public × private) and the influence of language, memory and inhibitory control on VF.

Method
We assessed 414 Brazilian children, aged 6–12, in the number of words produced and both clustering and switching components, with two measures of VF: letter (LVF) and semantic (SVF).

Results
Analysis of the number of words produced showed a significant increase between 6–8-year-olds, 9–10-year-olds and 11–12-year-olds in SVF, while in LVF, the differences were significant only in the later age group. In SVF, the numbers of clusters and switches increased with age, whereas in LVF, the number of switches increased in all age groups, but clusters increased only in the older group. Structural equation model analyses showed that oral and written language, verbal memory and inhibitory control are associated with VF performance and IQ, while age mediated VF performance.

Conclusions
The results indicate a different development pattern between LVF and SVF in the number of words produced and in clustering and switching, with the latter predicting VF performance in words produced. VF development is shown to depend on language, memory and inhibitory control. Our results have important implications to clinical neuropsychology.
SurVIndel: improving CNV calling from high-throughput sequencing data through statistical testing
Authors: Rajaby Ramesh , Sung Wing-Kin 
Published: April 2019

Abstract

Motivation
Structural variations (SVs) are large scale mutations in a genome; although less frequent than point mutations, due to their large size they are responsible for more heritable differences between individuals. Two prominent classes of SVs are deletions and tandem duplications. They play important roles in many devastating genetic diseases, such as Smith-Magenis syndrome, Potocki-Lupski syndrome and Williams-Beuren syndrome. Since paired-end whole genome sequencing data have become widespread and affordable, reliably calling deletions and tandem duplications has been a major target in bioinformatics; unfortunately, the problem is far from being solved, since existing solutions often offer poor results when applied to real data.

Results
We developed a novel caller, SurVIndel, which focuses on detecting deletions and tandem duplications from paired next-generation sequencing data. SurVIndel uses discordant paired reads, clipped reads as well as statistical methods. We show that SurVIndel outperforms existing methods on both simulated and real biological datasets.

Availability and implementation
SurVIndel is available at https://github.com/Mesh89/SurVIndel.

Supplementary information
Supplementary data are available at Bioinformatics online.
Hepatitis C Virus (HCV) Treatment With Directly Acting Agents Reduces the Risk of Incident Diabetes: Results From Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES)
Authors: Butt Adeel A , Yan Peng , Aslam Samia , Shaikh Obaid S , Abou-Samra Abdul-Badi 
Published: April 2019

Abstract

Background
The effects of interferon-based therapies for hepatitis C virus (HCV) upon the risk of diabetes are controversial. The effects of newer, directly acting antiviral agents (DAA) upon this risk are unknown. We sought to determine the effects of HCV treatment upon the risk and incidence of diabetes.

Methods
Using the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) database for persons with chronic HCV infection (n = 242 680), we identified those treated with a pegylated interferon and ribavirin regimen (PEG/RBV, n = 4764) or a DAA-containing regimen (n = 21 279), after excluding those with diabetes at baseline, those with a human immunodeficiency virus or hepatitis B virus coinfection, and those treated with both PEG/RBV and DAA regimens. Age-, race-, sex-, and propensity score–matched controls (1:1) were also identified.

Results
Diabetes incidence rates per 1000 person-years were 20.6 (95% confidence interval [CI] 19.6–21.6) among untreated persons, 19.8 (95% CI 18.3–21.4) among those treated with PEG/RBV, and 9.89 (95% CI 8.7–11.1) among DAA-treated persons (P &lt; .001). Among the treated, rates were 13.3 (95% CI 12.2–14.5) for those with a sustained virologic response (SVR) and 19.2 (95% CI 17.4–21.1) for those without an SVR (P &lt; .0001). A larger reduction was observed in persons with more advanced fibrosis/cirrhosis (absolute difference 2.9 for fibrosis severity score [FIB-4] &lt; 1.25; 5.7 for FIB-4 1.26–3.25; 9.8 for FIB-4 &gt;3.25). DAA treatment (hazard ratio [HR] 0.53, 95% CI .46–.63) and SVR (HR 0.81, 95% CI .70–.93) were associated with a significantly reduced risk of diabetes. DAA-treated persons had longer diabetes-free survival rates, compared to untreated and PEG/RBV-treated persons. There was no significant difference in diabetes-free survival rates between untreated and PEG/RBV-treated persons. The results were similar in inverse probability of treatment and censoring weight models.

Conclusions
DAA therapy significantly reduces the incidence and risk of subsequent diabetes. Treatment benefits are more pronounced in persons with more advanced liver fibrosis.
Extant microbial communities in the partially desiccated Rincon de Parangueo maar crater lake in Mexico
Authors: Sánchez-Sánchez Janet , Cerca Mariano , Alcántara-Hernández Rocío J , Lozano-Flores Carlos , Carreón-Freyre Dora , Levresse Gilles , Vega Marina , Varela-Echavarría Alfredo , Aranda-Gómez Jose Jorge 
Published: April 2019

ABSTRACT
Rincon de Parangueo is a maar where a perennial lake was present until the 1980s. A conspicuous feature of the lake’s sediments is the presence of bioherms and organo-sedimentary deposits produced by microbial communities. The gradual lake desiccation during the last 40 years has produced dramatic environmental changes inside the maar basin, which resulted in the formation of a highly saline-alkaline system with extant microorganisms. In this paper we succinctly describe the geologic setting where the microbial communities have developed inside of the maar crater and the results obtained from high-throughput sequencing methods to characterize the microbial component (Bacteria, Eukarya and Archaea) in endolithic mats of calcareous sediments, and microbial mats and free-living microorganisms in the soda ponds. The studied sites displayed different microbial communities with a diverse number of phylotypes belonging to Bacteria and Eukarya, contrasting with a much less diverse component in Archaea. The sequences here detected were related to environmental sequences from sites with extreme life conditions such as high alkalinity (alkaliphiles), high salinity (halophiles) and high temperature (thermophiles). Moreover, our results indicate an important unexplored endemic microbial biodiversity in the vestiges of the former lake that need to be studied.
The relationship between an electronic mental health stigma campaign and suicidal thoughts and behaviours: a two-arm randomized controlled trial in the Australian construction industry
Authors: Milner A , Aitken Z , Law P C F , LaMontagne A D , Mann C , Cooper T , Witt K 
Published: April 2019

Abstract
Males employed in the construction industry are at greater risk of suicide than other employed males. It is plausible that a high level of stigma against mental health problems explains the elevated rates of suicide among this group. This study sought to test the effectiveness of an electronic mental health stigma intervention on suicide ideation, communication about suicide and attempts. Participants were randomly assigned to receive either a series of brief contact interventions over a 6-week period or a wait list control. Suicidal ideation, communication about suicide and suicide attempts were assessed using the Suicidal Behaviors Questionnaire-Revised at post-intervention. We used linear regression to assess effectiveness at post-intervention, adjusting for relevant covariates using both conventional methods and a propensity score approach. Results indicate that the intervention had no significant impact on suicidal thoughts, communication or suicide attempts. There was some indication that individuals in the intervention group reported a slight increase in attempts and communication about suicide. These observations underscore an urgent need for more research to understand the complex and nuanced relationship between stigma and suicide in non-clinical populations.
On the Extremal Number of Subdivisions
Authors: Conlon David , Lee Joonkyung 
Published: April 2019

Abstract
One of the cornerstones of extremal graph theory is a result of Füredi, later reproved and given due prominence by Alon, Krivelevich, and Sudakov, saying that if $H$ is a bipartite graph with maximum degree $r$ on one side, then there is a constant $C$ such that every graph with $n$ vertices and $C n^{2 - 1/r}$ edges contains a copy of $H$. This result is tight up to the constant when $H$ contains a copy of $K_{r,s}$ with $s$ sufficiently large in terms of $r$. We conjecture that this is essentially the only situation in which Füredi’s result can be tight and prove this conjecture for $r = 2$. More precisely, we show that if $H$ is a $C_4$-free bipartite graph with maximum degree $2$ on one side, then there are positive constants $C$ and $\delta $ such that every graph with $n$ vertices and $C n^{3/2 - \delta }$ edges contains a copy of $H$. This answers a question of Erd̋s from 1988. The proof relies on a novel variant of the dependent random choice technique which may be of independent interest.
Short-course versus long-course antibiotics in prosthetic joint infections: a systematic review and meta-analysis of one randomized controlled trial plus nine observational studies
Authors: Yen Hung-Teng , Hsieh Ronan W , Huang Chung-yen , Hsu Tzu-Chun , Yeh Timothy , Chen Yee-Chun , Chen Wen-Shan , Lee Chien-Chang 
Published: April 2019

Abstract

Background
Prosthetic joint infections (PJIs) often require long-course antibiotic therapy. However, recent studies argue against the current practice and raise concerns such as the development of antibiotic resistance, side effects of medications and medical costs.

Objectives
To review and compare the outcomes of short-course and long-course antibiotics in PJIs.

Methods
We conducted a systemic review and meta-analysis using a predefined search term in PubMed and EMBASE databases. Studies that met the inclusion criteria from inception to June 2018 were included. The quality of the included studies was assessed.

Results
A total of 10 articles and 856 patients were analysed, comprising 9 observational studies and 1 randomized controlled trial. Our meta-analysis showed no significant difference between short-course and long-course antibiotics (relative risk = 0.87, 95% CI = 0.62–1.22). Additionally, the older the studied group was, the more short-course antibiotics were favoured.

Conclusions
When treating PJI patients following debridement, antibiotics and implant retention, an 8 week course of antibiotic therapy for total hip arthroplasty and a 75 day course for total knee arthroplasty may be a safe approach. For two-stage exchange, a shorter duration of antibiotic treatment during implant-free periods is also generally safe with the usage of antibiotic-loaded cement spacers.