bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanosensitive Rap1 activation promotes barrier function of lung vascular endothelium under cyclic stretch
Authors: Ke Yunbo , Karki Pratap , Zhang Chenou , Li Yue , Nguyen Trang , Birukov Konstantin G. , Birukova Anna A.
Published: February 2019

Mechanical ventilation remains an imperative treatment for the patients with acute respiratory distress syndrome, but can also exacerbate lung injury. We have previously described a key role of RhoA GTPase in high cyclic stretch (CS)–induced endothelial cell (EC) barrier dysfunction. However, cellular mechanotransduction complexes remain to be characterized. This study tested a hypothesis that recovery of a vascular EC barrier after pathologic mechanical stress may be accelerated by cell exposure to physiologic CS levels and involves Rap1-dependent rearrangement of endothelial cell junctions. Using biochemical, molecular, and imaging approaches we found that EC pre- or postconditioning at physiologically relevant low-magnitude CS promotes resealing of cell junctions disrupted by pathologic, high-magnitude CS. Cytoskeletal remodeling induced by low CS was dependent on small GTPase Rap1. Protective effects of EC preconditioning at low CS were abolished by pharmacological or molecular inhibition of Rap1 activity. In vivo, using mice exposed to mechanical ventilation, we found that the protective effect of low tidal volume ventilation against lung injury caused by lipopolysaccharides and ventilation at high tidal volume was suppressed in Rap1 knockout mice. Taken together, our results demonstrate a prominent role of Rap1-mediated signaling mechanisms activated by low CS in acceleration of lung vascular EC barrier restoration.
Actin turnover ensures uniform tension distribution during cytokinetic actomyosin ring contraction
Authors: Cheffings Thomas H. , Burroughs Nigel J. , Balasubramanian Mohan K.
Published: February 2019

In many eukaryotes, cytokinesis is facilitated by the contraction of an actomyosin ring (AMR). The exact mechanisms that lead to this contractility are unknown, although some models posit that actin turnover in the AMR is essential. The effect of reduced actin dynamics during AMR formation has been well studied in Schizosaccharomyces pombe; however, the corresponding effects on AMR contraction are not well understood. By using mutants of the fission yeast actin severing protein Adf1, we observed that contracting AMRs display a “peeling” phenotype, where bundles of actin and myosin peel off from one side of the AMR, and are pulled across to the opposite side. This occurs multiple times during cytokinesis and is dependent on the activity of myosins Myo2, Myp2, and Myo51. We found that the distribution of Myo2 in the AMR anticorrelates with the location of peeling events, suggesting that peeling is caused by a nonuniform tension distribution around the AMR, and that one of the roles of actin turnover is to maintain a uniform tension distribution around the AMR.
Gsmodutils: a python based framework for test-driven genome scale metabolic model development
Authors: Gilbert James , Pearcy Nicole , Norman Rupert , Millat Thomas , Winzer Klaus , King John , Hodgman Charlie , Minton Nigel , Twycross Jamie
Published: February 2019

Motivation

Genome scale metabolic models (GSMMs) are increasingly important for systems biology and metabolic engineering research as they are capable of simulating complex steady-state behaviour. Constraints based models of this form can include thousands of reactions and metabolites, with many crucial pathways that only become activated in specific simulation settings. However, despite their widespread use, power and the availability of tools to aid with the construction and analysis of large scale models, little methodology is suggested for their continued management. For example, when genome annotations are updated or new understanding regarding behaviour is discovered, models often need to be altered to reflect this. This is quickly becoming an issue for industrial systems and synthetic biotechnology applications, which require good quality reusable models integral to the design, build, test and learn cycle.

Results

As part of an ongoing effort to improve genome scale metabolic analysis, we have developed a test-driven development methodology for the continuous integration of validation data from different sources. Contributing to the open source technology based around COBRApy, we have developed the gsmodutils modelling framework placing an emphasis on test-driven design of models through defined test cases. Crucially, different conditions are configurable allowing users to examine how different designs or curation impact a wide range of system behaviours, minimizing error between model versions.

Availability and implementation

The software framework described within this paper is open source and freely available from http://github.com/SBRCNottingham/gsmodutils.

Supplementary information

Supplementary data are available at Bioinformatics online.
refineD: improved protein structure refinement using machine learning based restrained relaxation
Authors: Bhattacharya Debswapna
Published: February 2019

Motivation

Protein structure refinement aims to bring moderately accurate template-based protein models closer to the native state through conformational sampling. However, guiding the sampling towards the native state by effectively using restraints remains a major issue in structure refinement.

Results

Here, we develop a machine learning based restrained relaxation protocol that uses deep discriminative learning based binary classifiers to predict multi-resolution probabilistic restraints from the starting structure and subsequently converts these restraints to be integrated into Rosetta all-atom energy function as additional scoring terms during structure refinement. We use four restraint resolutions as adopted in GDT-HA (0.5, 1, 2 and 4 Å), centered on the Cα atom of each residue that are predicted by ensemble of four deep discriminative classifiers trained using combinations of sequence and structure-derived features as well as several energy terms from Rosetta centroid scoring function. The proposed method, refineD, has been found to produce consistent and substantial structural refinement through the use of cumulative and non-cumulative restraints on 150 benchmarking targets. refineD outperforms unrestrained relaxation strategy or relaxation that is restrained to starting structures using the FastRelax application of Rosetta or atomic-level energy minimization based ModRefiner method as well as molecular dynamics (MD) simulation based FG-MD protocol. Furthermore, by adjusting restraint resolutions, the method addresses the tradeoff that exists between degree and consistency of refinement. These results demonstrate a promising new avenue for improving accuracy of template-based protein models by effectively guiding conformational sampling during structure refinement through the use of machine learning based restraints.

Availability and implementation

http://watson.cse.eng.auburn.edu/refineD/.

Supplementary information

Supplementary data are available at Bioinformatics online.
ST-Steiner: a spatio-temporal gene discovery algorithm
Authors: Norman Utku , Cicek A Ercument
Published: February 2019

Motivation

Whole exome sequencing (WES) studies for autism spectrum disorder (ASD) could identify only around six dozen risk genes to date because the genetic architecture of the disorder is highly complex. To speed the gene discovery process up, a few network-based ASD gene discovery algorithms were proposed. Although these methods use static gene interaction networks, functional clustering of genes is bound to evolve during neurodevelopment and disruptions are likely to have a cascading effect on the future associations. Thus, approaches that disregard the dynamic nature of neurodevelopment are limited.

Results

Here, we present a spatio-temporal gene discovery algorithm, which leverages information from evolving gene co-expression networks of neurodevelopment. The algorithm solves a prize-collecting Steiner forest-based problem on co-expression networks, adapted to model neurodevelopment and transfer information from precursor neurodevelopmental windows. The decisions made by the algorithm can be traced back, adding interpretability to the results. We apply the algorithm on ASD WES data of 3871 samples and identify risk clusters using BrainSpan co-expression networks of early- and mid-fetal periods. On an independent dataset, we show that incorporation of the temporal dimension increases the predictive power: predicted clusters are hit more and show higher enrichment in ASD-related functions compared with the state-of-the-art.

Availability and implementation

The code is available at http://ciceklab.cs.bilkent.edu.tr/st-steiner.

Supplementary information

Supplementary data are available at Bioinformatics online.
Finding enzyme cofactors in Protein Data Bank
Authors: Mukhopadhyay Abhik , Borkakoti Neera , Pravda Lukáš , Tyzack Jonathan D , Thornton Janet M , Velankar Sameer
Published: February 2019

Motivation

Cofactors are essential for many enzyme reactions. The Protein Data Bank (PDB) contains >67 000 entries containing enzyme structures, many with bound cofactor or cofactor-like molecules. This work aims to identify and categorize these small molecules in the PDB and make it easier to find them.

Results

The Protein Data Bank in Europe (PDBe; pdbe.org) has implemented a pipeline to identify enzyme cofactor and cofactor-like molecules, which are now part of the PDBe weekly release process.

Availability and implementation

Information is made available on the individual PDBe entry pages at pdbe.org and programmatically through the PDBe REST API (pdbe.org/api).

Supplementary information

Supplementary data are available at Bioinformatics online.
The DECam minute cadence survey – II. 49 variables but no planetary transits of a white dwarf
Authors: Dame Kyra , Belardi Claudia , Kilic Mukremin , Rest Armin , Gianninas A , Barber Sara , Brown Warren R
Published: February 2019

We present minute cadence photometry of 31 732 point sources observed in one 3 $\rm deg^{2}$ DECam pointing centred at RA = 09:03:02 and Dec. = −04:35:00 over eight consecutive half-nights. We use these data to search for eclipse-like events consistent with a planetary transit of a white dwarf and other sources of stellar variability within the field. We do not find any significant evidence for minute-long transits around our targets, hence we rule out planetary transits around ∼370 white dwarfs that should be present in this field. Additionally, we identify 49 variables, including 40 new systems. These include 23 detached or contact stellar binaries, one eclipsing white dwarf + M dwarf binary, 16 δ Scuti, three RR Lyrae, and two ZZ Ceti pulsators. Results from the remaining two fields in our survey will allow us to place more stringent constraints on the frequency of planets orbiting white dwarfs in the habitable zone.
Prevalence of Smoking and Knowledge About the Hazards of Smoking Among 170 000 Chinese Adults, 2013–2014
Authors: Zhang Mei , Liu Shiwei , Yang Ling , Jiang Yong , Huang Zhengjing , Zhao Zhenping , Deng Qian , Li Yichong , Zhou Maigeng , Wang Linhong , Chen Zhengming , Wang Limin
Published: February 2019

Introduction

Periodic population surveys of smoking behavior can inform development of effective tobacco control strategies. We investigated smoking patterns, cessation, and knowledge about smoking hazards in China.

Methods

A nationally representative cross-sectional survey recruited 176 318 people aged ≥18 years across 31 provinces of China in 2013–2014, using multi-stage stratified cluster sampling methods. The smoking patterns, cessation, and knowledge about smoking hazards were analyzed, overall and in population subgroups, adjusting for sample selection weight and post-stratification factors.

Results

Among men, 60.7% were ever-smokers, with proportions of regular, occasional and former smokers being 46.3%, 5.5%, and 8.8% respectively. Among women, only 2.8% had ever smoked. The prevalence of ever smoking in men was higher in rural than urban areas (63.2% vs. 57.6%) and varied from 39.5% to 67.4% across 31 provinces. Among male regular smokers, the mean daily number of cigarettes smoked was 17.8, with mean age at first starting to smoke daily being 20.1 years. Among current smokers, one-third (32.6% men, 32.1% women) had tried to quit before and 36.8% (36.8% men, 35.5% women) intended to quit in the future. Of the Chinese adults, 75.9% recognized that smoking was hazardous, with the proportions believing that smoking could cause lung cancer, heart attack or stroke being 67.0%, 33.2%, and 29.5%, respectively and with 26.0% reporting that smoking could cause all these conditions.

Conclusion

Among Chinese adults, the smoking prevalence remained high in men but was low in women. In both men and women, knowledge about smoking hazards was poor.

Implications

This study showed that tobacco smoking remained highly prevalent among adult men in China in 2013–2014. Moreover, men born in recent decades were more likely to start smoking at younger ages and to smoke more cigarettes than those born in previous generations. There was a large regional variation in male smoking prevalence, with the least economically developed regions having higher prevalence. In contrast, few women in China smoked, especially among those born in recent decades. The contrasting smoking patterns in men and women is likely to result in an increasingly large gender disparity in life expectancy in the coming decades.
Characterization of Volatile Organic Compound Metabolites in Cigarette Smokers, Electronic Nicotine Device Users, Dual Users, and Nonusers of Tobacco
Authors: Keith Rachel J , Fetterman Jessica L , Orimoloye Olusola A , Dardari Zeina , Lorkiewicz Pawel K , Hamburg Naomi M , DeFilippis Andrew P , Blaha Michael J , Bhatnagar Aruni
Published: February 2019

Introduction

Limited research exists about the possible cardiovascular effects of electronic nicotine delivery systems (ENDS). We therefore sought to compare exposure to known or potentially cardiotoxic volatile organic compounds (VOCs) in ENDS users, smokers, and dual users.

Methods

A total of 371 individuals from the Cardiovascular Injury due to Tobacco Use study, a cross-sectional study of healthy participants aged 21–45 years, were categorized as nonusers of tobacco (n = 87), sole ENDS users (n = 17), cigarette smokers (n = 237), and dual users (n = 30) based on 30-day self-reported tobacco product use patterns. Participants provided urine samples for VOC and nicotine metabolite measurement. We assessed associations between tobacco product use and VOC metabolite measures using multivariable-adjusted linear regression models.

Results

Mean (SD) age of the population was 32 (±6.8) years, 55% men. Mean urinary cotinine level in nonusers of tobacco was 2.6 ng/mg creatinine, whereas cotinine levels were similar across all tobacco product use categories (851.6–910.9 ng/mg creatinine). In multivariable-adjusted models, sole ENDS users had higher levels of metabolites of acrolein, acrylamide, acrylonitrile, and xylene compared with nonusers of tobacco, but lower levels of most VOC metabolites compared with cigarette smokers or dual users. In direct comparison of cigarettes smokers and dual users, we found lower levels of metabolites of styrene and xylene in dual users.

Conclusion

Although sole ENDS use may be associated with lower VOC exposure compared to cigarette smoking, further study is required to determine the potential health effects of the higher levels of certain reactive aldehydes, including acrolein, in ENDS users compared with nonusers of tobacco.

Implications

ENDS use in conjunction with other tobacco products may not significantly reduce exposure to VOC, but sole use does generally reduce some VOC exposure and warrants more in-depth studies.
Smoking Among Immigrant Groups in the United States: Prevalence, Education Gradients, and Male-to-Female Ratios
Authors: Pampel Fred , Khlat Myriam , Bricard Damien , Legleye Stéphane
Published: February 2019

Introduction

Immigrants in the United States are less likely to smoke than those born in the United States, but studies have not fully described the diversity of their smoking patterns. We investigate smoking by world region of birth and duration of residence in the United States, with a comprehensive approach covering current prevalence levels, education gradients, and male-to-female ratios.

Methods

The data originate from the National Health Interview Surveys, 2000–2015, and the sample of 365 404 includes both US-born and foreign-born respondents aged 25–70 years. World region of birth and duration of residence in the United States measure immigrant characteristics. Current cigarette smoking was analyzed using logistic regression.

Results

Immigrant groups were protected from smoking and had weaker education gradients in smoking and larger male-to-female smoking ratios than the US-born population. However, large differences emerged among the immigrant groups for region of birth but less so for duration of residence in the United States. For example, immigrants from sub-Saharan Africa and the Indian subcontinent have low prevalence, weak education gradients, and high male-to-female ratios. Immigrants from Europe have the opposite pattern, and immigrants from Latin America fall between those two extremes.

Conclusion

The stage of the cigarette epidemic in the region of birth helps explain the diverse group profiles. Duration of residence in the United States does less to account for the differences in smoking than region of birth. The findings illustrate the heterogeneity of immigrant populations originating from diverse regions across the world and limited convergence with the host population after immigration.

Implications

The study identifies immigrant groups that, because of high smoking prevalence related to levels in the host country, should be targeted for cessation efforts. It also identifies immigrant groups with low prevalence for which anti-smoking programs should encourage maintenance of healthy habits. Many immigrant groups show strong education disparities in smoking, further suggesting that smokers with lower levels of education be targeted by public health programs.
Influence of Tattoo Ink on Hepatitis C Virus Infectiousness
Authors: Behrendt Patrick , Brüning Janina , Todt Daniel , Steinmann Eike
Published: February 2019

Hepatitis C virus (HCV) is a blood-borne virus and is most frequently transmitted through large or repeated direct percutaneous exposures to infected blood. The 2 most common exposures associated with transmission of HCV are blood transfusion and intravenous drug abuse. The association between HCV transmission and other suspected risk factors such as tattooing is more controversial. Although HCV can survive for days to weeks in suspension or on inanimate surfaces, its stability in tattooing supplies remains elusive. Here, we analyzed the influence of tattoo ink on HCV infectiousness.
Comparative Performance of Fungicides, Biofungicides, and Host Plant Defense Inducers in Suppression of Phytophthora Root Rot in Flowering Dogwood During Simulated Root Flooding Events
Authors: Brown Matthew S. , Baysal-Gurel Fulya , Oliver Jason B. , Addesso Karla M.
Published: February 2019

During flooding events in nurseries, Phytophthora root rot caused by Phytophthora cinnamomi Rands often causes damage that leads to complete crop loss. In this study, we evaluated the efficacy of fungicides, biofungicides, and host plant defense inducers for preventive and curative control of Phytophthora root rot on flowering dogwood (Cornus florida L.) seedlings exposed to a simulated flood event of 1, 3, or 7 days. In two greenhouse trials, preventive (7 days before flooding) or curative (1 day after flooding) drench treatments were applied to dogwood seedlings artificially inoculated with P. cinnamomi. The plants were flooded by maintaining standing water for 1, 3, or 7 days. After the trials, plant growth data (total plant weight, root weight, plant height, and plant width) were recorded, and root systems were assessed for disease severity using a scale of 0 to 100% of roots affected, and subsamples were plated on PARPH-V8 medium to determine the percent recovery of the Phytophthora pathogen. Plants preventively treated with Subdue MAXX had reduced disease severity relative to the nontreated, inoculated plants (positive control) flooded 1, 3, or 7 days in both trials. Pageant Intrinsic and Segovis treatments also had lower disease severity than the positive control at all flooding durations in trial two, but not trial one. In trial one, preventive and curative treatments of Orkestra Intrinsic had reduced disease severity compared with the positive control at 1 and 3 days of flooding, whereas curative treatments of Empress Intrinsic and Tartan Stressgard also were effective at 1 and 3 days of flooding in trial one. The host plant defense inducers (Aliette 80 WDG, Signature Xtra, and Actigard) were inconsistent and ineffective at reducing disease severity when applied as preventive or curative treatments. Preventive treatments of the biofungicides RootShield Plus+ and MBI-110 had consistently lower disease severity than the positive control at 1 day of flooding but not 3 or 7 days of flooding. Potentially, growers can use information from this study to manage Phytophthora root rot during flooding or in areas of the nursery that often experience high soil moisture levels.
Peter Neil Temple Wells CBE. 19 May 1936—22 April 2017
Authors: Thomas Hywel R.
Published: February 2019

Peter Wells will be remembered internationally for his many outstanding contributions in the field of medical ultrasound. He pioneered the development of non-invasive imaging techniques in the development of ultrasonics as a diagnostic and surgical tool. He was the originator and developer of instruments for ultrasonic surgery and ultrasonic power measurement, as well as the two-dimensional, articulated-arm ultrasonic general purpose scanner and the water-immersion ultrasonic breast scanner. He demonstrated ultrasonic-pulsed Doppler range-gating, and was the discoverer of the ultrasonic Doppler signal characteristic of malignant tumour neovascularization. He investigated ultrasonic bioeffects and formulated ultrasonic safety guidelines and conditions for prudent use of ultrasonic diagnosis. His outstanding and sustained achievements in the medical applications of ultrasound extend continuously from the 1960s until a few days before his death at the age of 80. Anyone who has ever benefited from an ultrasound procedure owes a debt of gratitude to Peter Wells.
David Godfrey Pettifor. 9 March 1945—16 October 2017
Authors: Sutton Adrian P. , Drautz Ralf , Vitek Vaclav
Published: February 2019

David Pettifor was a theoretical physicist who changed the nature of materials science by raising the status of materials modelling to that of materials characterization and processing. He believed that the subject advanced through the development of simple models that withstood rigorous testing against experiments and the most accurate numerical computations. Having been a pioneer of total energy density functional theory calculations, he went on to derive analytic interatomic potentials for transition metals and nearly-free-electron metals and alloys from quantum mechanical principles. He is probably best known for the development of highly successful structure maps for binary and pseudo-binary alloys that were used by alloy developers in industry to create intermetallic alloys with improved properties. At Oxford he established the first materials modelling laboratory, bringing together physicists, chemists, materials scientists and engineers to model materials across length and time scales, which became a flagship laboratory for materials scientists world-wide.
One-directional flow of ionic solutions along fine electrodes under an alternating current electric field
Authors: Shin Jung Hwal , Kim Kanghyun , Woo Hyeonsu , Kang In Seok , Kang Hyun-Wook , Choi WooSeok , Lim Geunbae
Published: February 2019

Electric fields are widely used for controlling liquids in various research fields. To control a liquid, an alternating current (AC) electric field can offer unique advantages over a direct current (DC) electric field, such as fast and programmable flows and reduced side effects, namely the generation of gas bubbles. Here, we demonstrate one-directional flow along carbon nanotube nanowires under an AC electric field, with no additional equipment or frequency matching. This phenomenon has the following characteristics: First, the flow rates of the transported liquid were changed by altering the frequency showing Gaussian behaviour. Second, a particular frequency generated maximum liquid flow. Third, flow rates with an AC electric field (approximately nanolitre per minute) were much faster than those of a DC electric field (approximately picolitre per minute). Fourth, the flow rates could be controlled by changing the applied voltage, frequency, ion concentration of the solution and offset voltage. Our finding of microfluidic control using an AC electric field could provide a new method for controlling liquids in various research fields.
Hydrological controls on river network connectivity
Authors: Garbin Silvia , Celegon Elisa Alessi , Fanton Pietro , Botter Gianluca
Published: February 2019

This study proposes a probabilistic approach for the quantitative assessment of reach- and network-scale hydrological connectivity as dictated by river flow space–time variability. Spatial dynamics of daily streamflows are estimated based on climatic and morphological features of the contributing catchment, integrating a physically based approach that accounts for the stochasticity of rainfall with a water balance framework and a geomorphic recession flow analysis. Ecologically meaningful minimum stage thresholds are used to evaluate the connectivity of individual stream reaches, and other relevant network-scale connectivity metrics. The framework allows a quantitative description of the main hydrological causes and the ecological consequences of water depth dynamics experienced by river networks. The analysis shows that the spatial variability of local-scale hydrological connectivity is strongly affected by the spatial and temporal distribution of climatic variables. Depending on the underlying climatic settings and the critical stage threshold, loss of connectivity can be observed in the headwaters or along the main channel, thereby originating a fragmented river network. The proposed approach provides important clues for understanding the effect of climate on the ecological function of river corridors.
Microbeam two-dimensional small-angle X-ray scattering investigating the effects of reduced graphene oxide on local microstructures of high-density polyethylene/reduced graphene oxide nanocomposite bars
Authors: Yao Guibin , Duan Tianchen , Chi Enyi , Guo Pengran , Li Yiguo , Wang Zongbao
Published: February 2019

It has been reported that the introduction of reduced graphene oxide (RGO) can enhance the crystallization and orientation of high-density polyethylene (HDPE) matrix and thus improve the mechanical properties of HDPE/RGO nanocomposites. In this study, the local microstructures and orientations in different regions of HDPE/RGO bars with varied RGO contents were further explored by two-dimensional small-angle X-ray scattering using a microbeam technique. It is unveiled that the orientation orderings of each position is intensified with increasing RGO amount, and of particular interest is the observation of the slight change of the ordering degrees in diverse zones of HDPE/RGO nanocomposite bars, indicating that RGO imposes a uniform enhancing effect upon HDPE matrix within different areas and consequently induces an effective increase of the mechanical properties of HDPE/RGO nanocomposites.
Electrophysiological evidence for light-activated cation transport in calcifying corals
Authors: Taubner Isabelle , Hu Marian Y. , Eisenhauer Anton , Bleich Markus
Published: February 2019

Light has been demonstrated to enhance calcification rates in hermatypic coral species. To date, it remains unresolved whether calcifying epithelia change their ion transport activity during illumination, and whether such a process is mediated by the endosymbiotic algae or can be controlled by the coral host itself. Using a modified Ussing chamber in combination with H+sensitive microelectrode measurements, the present work demonstrates that light triggers the generation of a skeleton positive potential of up to 0.9 mV in the hermatypic coralStylophora pistillata. This potential is generated by a net flux of cations towards the skeleton and reaches its maximum at blue (450 nm) light. The effects of pharmacological inhibitors targeting photosynthesis 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) and anion transport 4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS) were investigated by pH microelectrode measurements in coral tissues demonstrating a rapid decrease in tissue pH under illumination. However, these inhibitors showed no effect on the electrophysiological light response of the coral host. By contrast, metabolic inhibition by cyanide and deoxyglucose reversibly inhibited the light-induced cation flux towards the skeleton. These results suggest that ion transport across coral epithelia is directly triggered by blue light, independent of photosynthetic activity of algal endosymbionts. Measurements of this very specific and quantifiable physiological response can provide parameters to identify photoreception mechanisms and will help to broaden our understanding of the mechanistic link between light stimulation and epithelial ion transport, potentially relevant for calcification in hermatypic corals.
Inferring the model and onset of natural selection under varying population size from the site frequency spectrum and haplotype structure
Authors: Nakagome Shigeki , Hudson Richard R. , Di Rienzo Anna
Published: February 2019

A fundamental question about adaptation in a population is the time of onset of the selective pressure acting on beneficial alleles. Inferring this time, in turn, depends on the selection model. We develop a framework of approximate Bayesian computation (ABC) that enables the use of the full site frequency spectrum and haplotype structure to test the goodness-of-fit of selection models and estimate the timing of selection under varying population size scenarios. We show that our method has sufficient power to distinguish natural selection from neutrality even if relatively old selection increased the frequency of a pre-existing allele from 20% to 50% or from 40% to 80%. Our ABC can accurately estimate the time of onset of selection on a new mutation. However, estimates are prone to bias under the standing variation model, possibly due to the uncertainty in the allele frequency at the onset of selection. We further extend our approach to take advantage of ancient DNA data that provides information on the allele frequency path of the beneficial allele. Applying our ABC, including both modern and ancient human DNA data, to four pigmentation alleles in Europeans, we detected selection on standing variants that occurred after the dispersal from Africa even though models of selection on a new mutation were initially supported for two of these alleles without the ancient data.
Parsing human and biophysical drivers of coral reef regimes
Authors: Jouffray Jean-Baptiste , Wedding Lisa M. , Norström Albert V. , Donovan Mary K. , Williams Gareth J. , Crowder Larry B. , Erickson Ashley L. , Friedlander Alan M. , Graham Nicholas A. J. , Gove Jamison M. , Kappel Carrie V. , Kittinger John N. , Lecky Joey , Oleson Kirsten L. L. , Selkoe Kimberly A. , White Crow , Williams Ivor D. , Nyström Magnus
Published: February 2019

Coral reefs worldwide face unprecedented cumulative anthropogenic effects of interacting local human pressures, global climate change and distal social processes. Reefs are also bound by the natural biophysical environment within which they exist. In this context, a key challenge for effective management is understanding how anthropogenic and biophysical conditions interact to drive distinct coral reef configurations. Here, we use machine learning to conduct explanatory predictions on reef ecosystems defined by both fish and benthic communities. Drawing on the most spatially extensive dataset available across the Hawaiian archipelago—20 anthropogenic and biophysical predictors over 620 survey sites—we model the occurrence of four distinct reef regimes and provide a novel approach to quantify the relative influence of human and environmental variables in shaping reef ecosystems. Our findings highlight the nuances of what underpins different coral reef regimes, the overwhelming importance of biophysical predictors and how a reef's natural setting may either expand or narrow the opportunity space for management interventions. The methods developed through this study can help inform reef practitioners and hold promises for replication across a broad range of ecosystems.
Profundibacter amoris gen. nov., sp. nov., a new member of the Roseobacter clade isolated from Loki’s Castle Vent Field on the Arctic Mid-Ocean Ridge.
Authors: Le Moine Bauer Sven , Sjøberg Andreas Gilje , L'Haridon Stéphane , Stokke Runar , Roalkvam Irene , Steen Ida Helene , Dahle Håkon
Published: February 2019

A bacterial strain, designated BAR1T, was isolated from a microbial mat growing on the surface of a barite chimney at the Loki’s Castle Vent Field, at a depth of 2216 m. Cells of strain BAR1T were rod-shaped, Gram-reaction-negative and grew on marine broth 2216 at 10–37 °C (optimum 27–35 °C), pH 5.5–8.0 (optimum pH 6.5–7.5) and 0.5–5.0 % NaCl (optimum 2 %). The DNA G+C content was 57.38 mol%. The membrane-associated major ubiquinone was Q-10, the fatty acid profile was dominated by C18 : 1ω7c (91 %), and the polar lipids detected were phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine, one unidentified aminolipid, one unidentified lipid and one unidentified phospholipid. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain BAR1T clustered together with Rhodobacterales bacterium PRT1, as well as the genera

Halocynthiibacter

and Pseudohalocynthiibacter in a polyphyletic clade within the

Roseobacter

clade. Several characteristics differentiate strain BAR1T from the aforementioned genera, including its motility, its piezophilic behaviour and its ability to grow at 35 °C and under anaerobic conditions. Accordingly, strain BAR1T is considered to represent a novel genus and species within the Roseobacter clade, for which the name Profundibacter amoris gen. nov., sp. nov. is proposed. The type strain is Profundibacter amoris BAR1T (=JCM 31874T=DSM 104147T).
Taibaiella helva sp. nov., isolated from farmland soil in China
Authors: Chen Ling-Ling , Hu Ting , Xing Zi-Yu , Lu Jia-Sen , Yang Han , Huang Xing
Published: February 2019

A yellow-coloured bacterial strain, designated F-4T, was isolated from a farmland soil sample from Qianshan, Anhui province, China. Strain F-4T was Gram-stain-negative, strictly aerobic, oval-shaped, motile (by gliding) and non-spore-forming. Growth occurred at 20–35 °C (optimum, 30 °C), at pH 6.0–8.0 (pH 7.0) and with 0–1.0 % (w/v) NaCl (0 %). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain F-4T belonged to the genus

Taibaiella
. 16S rRNA gene sequence similarity values between strain F-4T and the type strains of the three recognized species of the genus

Taibaiella

,

Taibaiella koreensis

KACC 17171T,

Taibaiella soli

KCTC 42277T and

Taibaiella chishuiensis

JCM 19637T, were 98.1, 96.4 and 95.9 %, respectively. The predominant respiratory quinone was MK-7, with MK-8 as a minor component. The major polar lipids of strain F-4T were three unidentified lipids, two unidentified aminolipids, three unidentified phospholipids, an unidentified aminophospholipid and phosphatidylethanolamine. The major cellular fatty acids were iso-C15 : 0, iso-C15 : 1 G and iso-C17 : 0. The G+C content of the genomic DNA based on total genome calculations was 51.3 mol%. The major polyamine of strain F-4T was homospermidine. The average nucleotide identity and the digital DNA–DNA hybridization values for draft genomes between strain F-4T and strain THG-DT86T were 79.8 and 22.6 %, respectively. On the basis of the genotypic and phenotypic data presented here, strain F-4T represents a novel species of the genus

Taibaiella

, for which the name

Taibaiella
helva sp. nov. is proposed. The type strain is F-4T (=KCTC 62442T=CGMCC 1.13562T).
Strain-level differences in gut microbiome composition determine fecal IgA levels and are modifiable by gut microbiota manipulation
Authors: Yang Chao , Mogno Ilaria , Contijoch Eduardo J. , Borgerding Joshua N. , Aggarwala Varun , Li Zhihua , Grasset Emilie K. , Helmus Drew S. , Dubinsky Marla C. , Mehandru Saurabh , Cerutti Andrea , Faith Jeremiah J.
Published: February 2019

Fecal IgA production depends on colonization by a gut microbiota. However, the bacterial strains that drive gut IgA production remain largely unknown. By accessing the IgA-inducing capacity of a diverse set of human gut microbial strains, we identified Bacteroides ovatus as the species that best induced gut IgA production. However, this induction varied biomodally across different B. ovatus strains. The high IgA-inducing B. ovatus strains preferentially elicited more IgA production in the large intestine through both T-cell-dependent and T-cell-independent B cell-activation pathways. Remarkably, a low-IgA phenotype in mice could be robustly and consistently converted into a high-IgA phenotype by transplanting a multiplex cocktail of high IgA-inducing B. ovatus strains but not individual ones. Thus, microbial strain specificity is essential for the optimal induction of high-IgA responses in the gut. Our results highlight the critical importance of microbial strains in driving phenotype variation in the mucosal immune system and provide a strategy to robustly modify a gut immune phenotype, including IgA production.
Theta and Gamma Bands Encode Acoustic Dynamics over Wide-ranging Timescales
Authors: Teng Xiangbin , Poeppel David
Published: February 2019

Natural sounds have broadband modulation spectra and contain acoustic dynamics ranging from tens to hundreds of milliseconds. How does the human auditory system encode acoustic information over wide-ranging timescales to achieve sound recognition? Previous work (Teng et al., 2017) demonstrated a temporal coding preference in the auditory system for the theta (4 – 7 Hz) and gamma (30 – 45 Hz) ranges, but it remains unclear how acoustic dynamics between these two ranges is encoded. Here we generated artificial sounds with temporal structures over timescales from ~200 ms to ~30 ms and investigated temporal coding on different timescales in the human auditory cortex. Participants discriminated sounds with temporal structures at different timescales while undergoing magnetoencephalography (MEG) recording. The data show robust neural entrainment in the theta and the gamma bands, but not in the alpha and beta bands. Classification analyses as well as stimulus reconstruction reveal that the acoustic information of all timescales can be differentiated through the theta and gamma bands, but the acoustic dynamics in the theta and gamma ranges are preferentially encoded. We replicate earlier findings of multi-time scale processing and further demonstrate that the theta and gamma bands show generality of temporal coding across all timescales with comparable capacity. The results support the hypothesis that the human auditory cortex primarily encodes auditory information employing neural processes within two discrete temporal regimes.

Significance

Natural sounds contain rich acoustic dynamics over wide-ranging timescales, but perceptually relevant regularities often occupy specific temporal ranges. For instance, speech carries phonemic information on a shorter timescale than syllabic information at ~ 200 ms. How does the brain efficiently ‘sample’ continuous acoustic input to perceive temporally structured sounds? We presented sounds with temporal structures at different timescales and measured cortical entrainment using magnetoencephalography. We found, unexpectedly, that the human auditory system preserves high temporal coding precision on two non-overlapping timescales, the slower (theta) and faster (gamma) bands, to track acoustic dynamics over all timescales. The results suggest that the acoustic environment which we experience as seamless and continuous is segregated by discontinuous neural processing, or ‘sampled.’
Aversive learning strengthens episodic memory in both adolescents and adults
Authors: Cohen Alexandra O. , Matese Nicholas G. , Filimontseva Anastasia , Shen Xinxu , Shi Tracey C. , Livne Ethan , Hartley Catherine A.
Published: February 2019

Adolescence is often filled with positive and negative emotional experiences that may change how individuals remember and respond to stimuli in their environment. In adults, aversive events can both enhance memory for associated stimuli as well as generalize to enhance memory for unreinforced but conceptually related stimuli. The present study tested whether learned aversive associations similarly lead to better memory and generalization across a category of stimuli in adolescents. Participants completed an olfactory Pavlovian category conditioning task in which trial-unique exemplars from one of two categories were partially reinforced with an aversive odor. Participants then returned 24-hours later to complete a surprise recognition memory test. We found better corrected recognition memory for the reinforced versus the unreinforced category of stimuli in both adults and adolescents. Further analysis revealed that enhanced recognition memory was driven specifically by better memory for the reinforced exemplars. Autonomic arousal during learning was also related to subsequent memory. These findings build on previous work in adolescent and adult humans and rodents showing comparable acquisition of aversive Pavlovian conditioned responses across age groups and demonstrate that memory for stimuli with an acquired aversive association is enhanced in both adults and adolescents.
Earth-Gravity Congruent Motion Benefits Visual Gain For Parabolic Trajectories
Authors: Jörges Björn , López-Moliner Joan
Published: February 2019

TThere is evidence that humans rely on an earth gravity (9.81 m/s2) prior for a series of tasks involving perception and action, the reason being that gravity helps predict future positions of moving objects. Eye-movements in turn are partially guided by predictions about observed motion. Thus, the question arises whether knowledge about gravity is also used to guide eye-movements: If humans rely on a representation of earth gravity for the control of eye movements, earth-gravity-congruent motion should lead to improved visual pursuit. In a pre-registered experiment, we presented participants (n=10) with parabolic motion governed by six different gravities (−1/0.7/0.85/1/1.15/1.3g), two initial vertical velocities and two initial horizontal velocities in a 3D environment. Participants were instructed to follow the target with their eyes. We tracked their gaze and computed the visual gain (velocity of the eyes divided by velocity of the target) as proxy for the quality of pursuit. An LMM analysis with gravity condition as fixed effect and intercepts varying per subject showed that the gain was lower for −1g than for 1g (by −0.13, SE = 0.005). This model was significantly better than a null model without gravity as fixed effect (p<0.001), supporting our hypothesis. A comparison of 1g and the remaining gravity conditions revealed that 1.15g (by 0.043, SE=0.005) and 1.3g (by 0.065, SE=0.005) were associated with lower gains, while 0.7g (by 0.054, SE=0.005) and 0.85g (by 0.029, SE=0.005) were associated with higher gains. This model was again significantly better than a null model (p<0.001), contradicting our hypothesis. Post-hoc analyses reveal that confounds in the 0.7/0.85/1/1.15/1.3g condition may be responsible for these contradicting results. Despite these discrepancies, our data thus provide some support for the hypothesis that internalized knowledge about earth gravity guides eye movements.
lncRNADIGITand BRD3 protein form phase-separated condensates to regulate endoderm differentiation
Authors: Daneshvar Kaveh , Ardehali M. Behfar , Klein Isaac A. , Kratkiewicz Arcadia J. , Zhou Chan , Mahpour Amin , Cook Brett M. , Li Wenyang , Pondick Joshua V. , Moran Sean P. , Young Richard A. , Kingston Robert E. , Mullen Alan C.
Published: February 2019

Gene programs that control differentiation are regulated through the interplay between DNA, RNA, and protein. Cooperation among these fundamental cellular components can occur through highly structured interactions connecting domains formed by specific sequences of nucleotides, ribonucleotides, and/or amino acids and also through the assembly of biomolecular condensates. Here, we show that endoderm differentiation is regulated through the interaction of the long noncoding (lnc) RNADIGITand the bromodomain and extra-terminal (BET) domain family protein BRD3. BRD3 forms phase-separated condensates that containDIGIT, occupies enhancers of endoderm transcription factors, and is required for endoderm differentiation. Purified BRD3 binds to acetylated histone H3 lysine 18 (H3K18ac)in vitroand occupies regions of the genome enriched in H3K18ac during endoderm differentiation, including the key transcription factors that regulate endoderm differentiation.DIGITis also enriched in regions of H3K18ac, and depletion ofDIGITresults in decreased recruitment of BRD3 to these regions. Our findings support a model where cooperation betweenDIGITand BRD3 at regions of H3K18ac regulates the transcription factors that drive endoderm differentiation and suggest a broader role for protein-lncRNA phase-separated condensates as regulators of transcription in development.
Heterozygous missense RAD21 variant in a peripheral sclerocornea pedigree
Authors: Zhang Bi Ning , Yan Chan Tommy Chung , Sin Tam Pancy Oi , Liu Yu , Pang Chi Pui , Jhanji Vishal , Chen Li Jia , Chu Wai Kit
Published: February 2019

Background

Sclerocomea is a rare congenital disorder characterized with cornea opacification. We identified a heterozygous missense RAD21 variant in a non-cons anguineous Chinese family with multiple peripheral sclerocomea patients spanning across three generations inherited in an autosomal dominant manner.

Methods

Comprehensive ophthalmic examinations were conducted on all 14 members. Whole exome sequencing was used to identify the genetic alterations in the affected pedigree members. Lymphoblastoid cell lines (LCLs) were established using blood samples from all members. Cleavage of RAD21 protein was quantified in these cell lines.

Results

All affected individuals showed features of scleralization over the peripheral cornea of both eyes. Mean horizontal and vertical corneal diameter were significantly decreased in the affected members. Significant differences were also observed on mean apex pachymetry between affected and unaffected subjects. A RAD21C1348T variant was co-segregated with affected members. Both the wild-type allele and the missense variant were expressed at the mRNA level. This variant caused RAD21 R450C substitution at the separase cleavage site, which led to reduced RAD21 cleavage.

Conclusion

We believe this is the first report of genetic variant in sclerocornea without other syndromes. Further work is needed to confirm the RAD21R450C variant with sclerocomea.