bluuebunny/crossref_metadata_2025 huggingface dataset:
Diffuse retro-reflective imaging for improved video tracking of mosquitoes at human baited bednets
Authors: Voloshin Vitaly , Kröner Christian , Seniya Chandrabhan , Murray Gregory P. D. , Guy Amy , Towers Catherine E. , McCall Philip J. , Towers David P.
Published: July 2019

Robust imaging techniques for tracking insects have been essential tools in numerous laboratory and field studies on pests, beneficial insects and model systems. Recent innovations in optical imaging systems and associated signal processing have enabled detailed characterisation of nocturnal mosquito behaviour around bednets and improvements in bednet design, a global essential for protecting populations against malaria. Nonetheless, there remain challenges around ease of use for large scale in situ recordings and extracting data reliably in the critical areas of the bednet where the optical signal is attenuated. Here we introduce a retro-reflective screen at the back of the measurement volume, which can simultaneously provide diffuse illumination, and remove optical alignment issues whilst requiring only one-sided access to the measurement space. The illumination becomes significantly more uniform, although, noise removal algorithms are needed to reduce the effects of shot noise particularly across low intensity bednet regions. By systematically introducing mosquitoes in front and behind the bednet in lab experiments we are able to demonstrate robust tracking in these challenging areas. Overall, the retro-reflective imaging setup delivers mosquito segmentation rates in excess of 90% compared to less than 70% with back-lit systems.
Meiosis-specific functions of kinesin motors in cohesin removal and maintenance of chromosome integrity in budding yeast
Authors: Mittal Priyanka , Prajapati Hemant Kumar , Ghule Komal , Ghosh Santanu K.
Published: July 2019

Kinesin motors provide the molecular forces at the kinetochore-microtubule interface and along the spindle to control chromosome segregation. During meiosis with the two rounds of microtubule assembly-disassembly, the roles of motor proteins remain unexplored. We observed that in contrast to mitosis Cin8 (kinesin 5) and Kip3 (kinesin 8) together are indispensable in meiosis. Examining the meiosis incin8∆kip3∆ cells, we detected chromosome breakage in the meiosis II cells. The double mutant exhibits delay in the cohesin removal and spindle elongation during anaphase I. Consequently, some cells abrogate meiosis II and form dyads while some, as they progress through meiosis II, cause defect in chromosome integrity. We believe that in the latter cells, an imbalance of spindle mediated force and simultaneous persistent cohesin on the chromosomes cause their breakage. We provide evidence that tension generated by Cin8 and Kip3 through microtubule cross-linking is essential for signaling efficient cohesin removal and maintenance of chromosome integrity during meiosis.

Molecular motors generate forces that facilitate chromosome segregation. Unlike mitosis, in meiosis, two times chromosome segregation occur with twice microtubule assembly/disassembly. This work reports that the motor mediated forces are crucial for cohesin removal in meiosis and thus maintain genome integrity.
Estimating and testing the microbial causal mediation effect with high-dimensional and compositional microbiome data
Authors: Wang Chan , Hu Jiyuan , Blaser Martin J. , Li Huilin
Published: July 2019

Motivation

Recent microbiome association studies have revealed important associations between microbiome and disease/health status. Such findings encourage scientists to dive deeper to uncover the causal role of microbiome in the underlying biological mechanism, and have led to applying statistical models to quantify causal microbiome effects and to identify the specific microbial agents. However, there are no existing causal mediation methods specifically designed to handle high dimensional and compositional microbiome data.

Results

We propose a rigorous Sparse Microbial Causal Mediation Model (SparseMCMM) specifically designed for the high dimensional and compositional microbiome data in a typical three-factor (treatment, microbiome and outcome) causal study design. In particular, linear log-contrast regression model and Dirichlet regression model are proposed to estimate the causal direct effect of treatment and the causal mediation effects of microbiome at both the community and individual taxon levels. Regularization techniques are used to perform the variable selection in the proposed model framework to identify signature causal microbes. Two hypothesis tests on the overall mediation effect are proposed and their statistical significance is estimated by permutation procedures. Extensive simulated scenarios show that SparseMCMM has excellent performance in estimation and hypothesis testing. Finally, we showcase the utility of the proposed SparseMCMM method in a study which the murine microbiome has been manipulated by providing a clear and sensible causal path among antibiotic treatment, microbiome composition and mouse weight.
Transcriptional and genomic parallels between the monoxenous parasiteHerpetomonas muscarumandLeishmania
Authors: Sloan Megan A. , Brooks Karen , Otto Thomas D. , Sanders Mandy J. , Cotton James A. , Ligoxygakis Petros
Published: July 2019

Trypanosomatid parasites are causative agents of important human and animal diseases such as sleeping sickness and leishmaniasis. Most trypanosomatids are transmitted to their mammalian hosts by insects, often belonging to Diptera (or true flies). These are called dixenous trypanosomatids since they infect two different hosts, in contrast to those that infect just insects (monoxenous). However, it is still unclear whether dixenous and monoxenous trypanosomatids interact similarly with their insect host, as fly-monoxenous trypanosomatid interaction systems are rarely reported and under-studied – despite being common in nature. Here we present the genome of monoxenous trypanosomatidHerpetomonas muscarumand discuss its transcriptome duringin vitroculture and during infection of its natural insect hostDrosophila melanogaster. TheH. muscarumgenome is broadly syntenic with that of human parasiteLeishmania major. We also found strong similarities between theH. muscarumtranscriptome during fruit fly infection, and those ofLeishmaniaduring sand fly infections. Overall this suggestsDrosophila-Herpetomonasis a suitable model for less accessible insect-trypanosomatid host-parasite systems such as sandfly-Leishmania.

Author Summary

Trypanosomes andLeishmaniaare parasites that cause serious Neglected Tropical Diseases (NTDs) in the world’s poorest people. Both of these are dixenous trypanosomatids, transmitted to humans and other mammals by biting flies. They are called dixenous as they can establish infections in two different types of hosts – insect vectors and mammals. In contrast, monoxenous trypanosomatids usually only infect insects. Despite establishment in the insect’s midgut being key to transmission of NTDs, events during early establishment inside the insect are still unclear in both dixenous and monoxenous parasites. Here, we study the interaction between a model insect – the fruit flyDrosophila melanogaster– and its natural monoxenous trypanosomatid parasiteHerpetomonas muscarum. We show that both the genome of this parasite, and gene regulation at early stages of infection have strong parallels withLeishmania. This work has begun to identify evolutionarily conserved aspects of the process by which trypanosomatids establish in insects, thus potentially highlighting key checkpoints necessary for transmission of dixenous parasites. In turn, this might inform new strategies to control trypanosomatid NTDs.
Genome-wide rare variant analysis for thousands of phenotypes in 54,000 exomes
Authors: Cirulli Elizabeth T. , White Simon , Read Robert W. , Elhanan Gai , Metcalf William J , Schlauch Karen A. , Grzymski Joseph J. , Lu James , Washington Nicole L.
Published: July 2019

Defining the effects that rare variants can have on human phenotypes is essential to advancing our understanding of human health and disease. Large-scale human genetic analyses have thus far focused on common variants, but the development of large cohorts of deeply phenotyped individuals with exome sequence data has now made comprehensive analyses of rare variants possible. We analyzed the effects of rare (MAF<0.1%) variants on 3,166 phenotypes in 40,468 exome-sequenced individuals from the UK Biobank and performed replication as well as meta-analyses with 1,067 phenotypes in 13,470 members of the Healthy Nevada Project (HNP) cohort who underwent Exome+ sequencing at Helix. Our analyses of non-benign coding and loss of function (LoF) variants identified 78 gene-based associations that passed our statistical significance threshold (p<5×10-9). These are associations in which carrying any rare coding or LoF variant in the gene is associated with an enrichment for a specific phenotype, as opposed to GWAS-based associations of strictly single variants. Importantly, our results do not suffer from the test statistic inflation that is often seen with rare variant analyses of biobank-scale data because of our rare variant-tailored methodology, which includes a step that optimizes the carrier frequency threshold for each phenotype based on prevalence. Of the 47 discovery associations whose phenotypes were represented in the replication cohort, 98% showed effects in the expected direction, and 45% attained formal replication significance (p<0.001). Six additional significant associations were identified in our meta-analysis of both cohorts. Among the results, we confirm known associations of PCSK9 and APOB variation with LDL levels; we extend knowledge of variation in the TYRP1 gene, previously associated with blonde hair color only in Solomon Islanders to blonde hair color in individuals of European ancestry; we show that PAPPA, a gene in which common variants had previously associated with height via GWAS, contains rare variants that decrease height; and we make the novel discovery that STAB1 variation is associated with blood flow in the brain. Our results are available for download and interactive browsing in an app (https://ukb.research.helix.com). This comprehensive analysis of the effects of rare variants on human phenotypes marks one of the first steps in the next big phase of human genetics, where large, deeply phenotyped cohorts with next generation sequence data will elucidate the effects of rare variants.
Molecular and structural mechanism of pan-genotypic HCV NS3/4A protease inhibition by glecaprevir
Authors: Timm Jennifer , Kosovrasti Klajdi , Henes Mina , Leidner Florian , Hou Shurong , Ali Akbar , Kurt-Yilmaz Nese , Schiffer Celia A.
Published: July 2019

Hepatitis C virus (HCV), causative agent of chronic viral hepatitis, infects 71 million people worldwide and is divided into seven genotypes and multiple subtypes with sequence identities between 68 to 82%. While older generation direct-acting antivirals (DAAs) had varying effectiveness against different genotypes, the newest NS3/4A protease inhibitors including glecaprevir (GLE) have pan-genotypic activity. The structural basis for pan-genotypic inhibition and effects of polymorphisms on inhibitor potency were not well known due to lack of crystal structures of GLE-bound NS3/4A or genotypes other than 1. In this study, we determined the crystal structures of NS3/4A from genotypes 1a, 3a, 4a and 5a in complex with GLE. Comparison with the highly similar grazoprevir (GZR) indicated the mechanism of GLE’s drastic improvement in potency. We found that while GLE is highly potent against wild type NS3/4A of all genotypes, specific resistance-associated substitutions (RASs) confer orders of magnitude loss in inhibition. Our crystal structures reveal molecular mechanisms behind pan-genotypic activity of GLE, including potency loss due to RASs at D168. Our structures permit for the first time analysis of changes due to polymorphisms among genotypes, providing insights into design principles that can aid future drug development and potentially can be extended to other proteins.
Compound stimuli reveal the structure of visual motion selectivity in macaque MT neurons
Authors: Zaharia Andrew D , Goris Robbe L T , Movshon J Anthony , Simoncelli Eero P
Published: July 2019

Motion selectivity in primary visual cortex (V1) is approximately separable in orientation, spatial frequency, and temporal frequency (“frequency-separable”). Models for area MT neurons posit that their selectivity arises by combining direction-selective V1 afferents whose tuning is organized around a tilted plane in the frequency domain, specifying a particular direction and speed (“velocity-separable”). This construction explains “pattern direction selective” MT neurons, which are velocity-selective but relatively invariant to spatial structure, including spatial frequency, texture and shape. Surprisingly, when tested with single drifting gratings, most MT neurons’ responses are fit equally well by models with either form of separability. However, responses to plaids (sums of two moving gratings) tend to be better described as velocity-separable, especially for pattern neurons. We conclude that direction selectivity in MT is primarily computed by summing V1 afferents, but pattern-invariant velocity tuning for complex stimuli may arise from local, recurrent interactions.

Significance Statement

How do sensory systems build representations of complex features from simpler ones? Visual motion representation in cortex is a well-studied example: the direction and speed of moving objects, regardless of shape or texture, is computed from the local motion of oriented edges. Here we quantify tuning properties based on single-unit recordings in primate area MT, then fit a novel, generalized model of motion computation. The model reveals two core properties of MT neurons — speed tuning and invariance to local edge orientation — result from a single organizing principle: each MT neuron combines afferents that represent edge motions consistent with a common velocity, much as V1 simple cells combine thalamic inputs consistent with a common orientation.
Diverse dynamics of glutamatergic input from sensory neurons underlie heterogeneous responses of olfactory bulb outputs in vivo
Authors: Moran Andrew K. , Eiting Thomas P. , Wachowiak Matt
Published: July 2019

Mitral/tufted (MT) cells of the olfactory bulb (OB) show diverse temporal responses to odorant stimulation that are thought to encode odor information. To understand the role of sensory input dynamics versus OB circuit mechanisms in generating this diversity, we imaged glutamate signaling onto MT cell dendrites in anesthetized and awake mice. We found surprising diversity in the dynamics of these signals, including excitatory, suppressive, and biphasic responses as well as nonlinear changes in glutamate signaling across inhalations. Simultaneous imaging of glutamate and calcium signals from MT cell dendrites revealed highly correlated responses for both signals. Glutamate responses were only weakly impacted by blockade of postsynaptic activity, implicating sensory neurons as a primary source of glutamate signaling onto MT cells. Thus, the dynamics of sensory input alone, rather than emergent features of OB circuits, may account for much of the diversity in MT cell responses that underlies OB odor representations.
Stable and widespread structural heteroplasmy in chloroplast genomes revealed by a new long-read quantification method
Authors: Wang Weiwen , Lanfear Robert
Published: July 2019

The chloroplast genome usually has a quadripartite structure consisting of a large single copy region and a small single copy region separated by two long inverted repeats. It has been known for some time that a single cell may contain at least two structural haplotypes of this structure, which differ in the relative orientation of the single copy regions. However, the methods required to detect and measure the abundance of the structural haplotypes are labour-intensive, and this phenomenon remains understudied. Here we develop a new method, Cp-hap, to detect all possible structural haplotypes of chloroplast genomes of quadripartite structure using long-read sequencing data. We use this method to conduct a systematic analysis and quantification of chloroplast structural haplotypes in 61 land plant species across 19 orders of Angiosperms, Gymnosperms and Pteridophytes. Our results show that there are two chloroplast structural haplotypes which occur with equal frequency in most land plant individuals. Nevertheless, species whose chloroplast genomes lack inverted repeats or have short inverted repeats have just a single structural haplotype. We also show that the relative abundance of the two structural haplotypes remains constant across multiple samples from a single individual plant, suggesting that the process which maintains equal frequency of the two haplotypes operates rapidly, consistent with the hypothesis that flip-flop recombination mediates chloroplast structural heteroplasmy. Our results suggest that previous claims of differences in chloroplast genome structure between species may need to be revisited.

Significance Statement

Chloroplast genome consists of a large single copy region, a small single copy region, and two inverted repeats. Some decades ago, a discovery showed that there are two types chloroplast genome in some plants, which differ the way that the four regions are put together. However, this phenomenon has been shown in just a small number of species, and many open questions remain. Here, we develop a fast method to measure the chloroplast genome structures, based on long-reads. We show that almost all plants we analysed contain two possible genome structures, while a few plants contain only one structure. Our findings hint at the causes of the phenomenon, and provide a convenient new method with which to make rapid progress.
Regulating Soil Bacterial Diversity, Enzyme Activities and Community Composition Using Residues from Golden Apple Snails
Authors: Wang Jiaxin , Lu Xuening , Zhang Jiaen , Wei Guangchang , Xiong Yue
Published: July 2019

Golden apple snails (GAS) have become a serious pest for agricultural production in Asia. A sustainable method for managing GAS is urgently needed, including potentially using them to produce commercial products. In this study, we evaluate the effects of GAS residues (shell and meat) on soil pH, bacterial diversity, enzyme activities, and other soil characteristics. Results showed that the amendment of GAS residues significantly elevated soil pH (to near-neutral), total organic carbon (TOC) (by 10-134%), NO3-N (by 46-912%), NH4-N (by 18-168%) and total nitrogen (TN) (by 12-132%). Bacterial diversity increased 13% at low levels of amendment and decreased 5% at high levels, because low-levels of GAS residues increased soil pH to near-neutral, while high-levels of amendment substantially increased soil nutrients and subsequently suppressed bacterial diversity. The dominant phyla of bacteria were: Proteobacteria (about 22%), Firmicutes (15-35%), Chloroflexi (12%-22%), Actinobacteria (8%-20%) Acidobacteria, Gemmatimonadetes, Cyanobacteria and Bacterioidetes. The amendment of GAS residues significantly increased the relative abundance of Firmicutes, Gemmatimonadetes, Bacterioidetes and Deinococcus-Thermus, but significantly decreased the relative abundance of Chloroflexi, Actinobacteria, Acidobacteria, Cyanobacteria and Planctomycetes. Our results suggest that GAS residues treatment induces a near-neutral and nutrient-rich soil. In this soil, soil pH may not be the best predictor of bacterial community composition or diversity; rather soil nutrients (ie., NH4-N and NO3-N) and soil TOC showed stronger correlations with bacterial community composition. Overall, GAS residues could replace lime for remediation of acidic and degraded soils, not only to remediate physical soil properties, but also microbial communities.

Importance

The wide spreading golden apple snail (GAS) is a harmful pest to crop productions and could result in soil and air pollutions after death. In the previous study, we developed a biocontrol method: adding GAS residues to acidic soil to mitigate the living GAS invasion and spread, improve soil quality, and reduce soil and air pollution. However, the effects of GAS residues amendment on bacterial diversity and community still remain unclear. This study provided insights into bacterial diversity and community compositions to facilitate the evaluation of GAS residues application.
Novel genetic loci affecting facial shape variation in humans
Authors: Xiong Ziyi , Dankova Gabriela , Howe Laurence J. , Lee Myoung Keun , Hysi Pirro G. , de Jong Markus A. , Zhu Gu , Adhikari Kaustubh , Li Dan , Li Yi , Pan Bo , Feingold Eleanor , Marazita Mary L. , Shaffer John R. , McAloney Kerrie , Xu Shuhua , Jin Li , Wang Sijia , de Vrij Femke M. , Lendemeijer Bas , Richmond Stephen , Zhurov Alexei , Lewis Sarah , Sharp Gemma , Paternoster Lavinia , Thompson Holly , Gonzalez-Jose Rolando , Bortolini Maria Catira , Canizales-Quinteros Samuel , Gallo Carla , Poletti Giovanni , Bedoya Gabriel , Rothhammer Francisco , Uitterlinden André G. , Ikram M. Arfan , Wolvius Eppo B. , Kushner Steven A. , Nijsten Tamar , Palstra Robert-Jan , Boehringer Stefan , Medland Sarah E , Tang Kun , Ruiz-Linares Andrés , Martin Nicholas G. , Spector Timothy D. , Stergiakouli Evie , Weinberg Seth M. , Liu Fan , Kayser Manfred ,   on behalf of the International Visible Trait Genetics (VisiGen) Consortium
Published: July 2019

The human face represents a combined set of highly heritable phenotypes, but knowledge on its genetic architecture remains limited despite the relevance for various fields of science and application. A series of genome-wide association studies on 78 facial shape phenotypes quantified from 3-dimensional facial images of 10,115 Europeans identified 24 genetic loci reaching genome-wide significant association, among which 17 were previously unreported. A multi-ethnic study in additional 7,917 individuals confirmed 13 loci including 8 unreported ones. A global map of polygenic face scores assembled facial features in major continental groups consistent with anthropological knowledge. Analyses of epigenomic datasets from cranial neural crest cells revealed abundant cis-regulatory activities at the face-associated genetic loci. Luciferase reporter assays in neural crest progenitor cells highlighted enhancer activities of several face-associated DNA variants. These results substantially advance our understanding of the genetic basis underlying human facial variation and provide candidates for future in-vivo functional studies.
YAP nuclear translocation through dynein and acetylated microtubule controls fibroblast activation
Authors: You Eunae , Ko Panseon , Jeong Jangho , Keum Seula , Kim Jung-Woong , Seo Young-Jin , Song Woo Keun , Rhee Sangmyung
Published: July 2019

Myofibroblasts are the major cell type that are responsible for increase the mechanical stiffness in fibrotic tissues. It has well documented that the TGF-β/Smad axis is required for myofibroblast differentiation under the rigid substrate condition. However, the mechanism driving myofibroblast differentiation in soft substrates remains unknown. In this research, we demonstrated that interaction of yes-associated protein (YAP) and acetylated microtubule via dynein, a microtubule motor protein drives nuclear localization of YAP in soft matrix, which in turn increased TGF-β1 induced transcriptional activity of Smad for myofibroblast differentiation. Pharmacological and genetical disruption of dynein impaired the nuclear translocation of YAP and decreased the TGF-β1 induced Smad activity even though phosphorylation and nuclear localization of Smad occurred normally in α-tubulin acetyltransferase (α-TAT1) knockout cell. Moreover, microtubule acetylation prominently appeared in the fibroblast-like cells nearby the blood vessel in the fibrotic liver induced by CCl4 administration which were conversely decreased by TGF-β receptor inhibitor. As a result, quantitative inhibition of microtubule acetylation may be suggested as a new target for overcome the fibrotic diseases.
Deriving stratified effects from joint models investigating Gene-Environment Interactions
Authors: Laville Vincent , Majarian Timothy , de Vries Paul S. , Bentley Amy R. , Feitosa Mary F. , Sung Yun J. , Rao DC , Manning Alisa , Aschard Hugues ,   on behalf of the CHARGE Gene-Lifestyle Interactions Working Group
Published: July 2019

Background

Models including an interaction term and performing a joint test of SNP and/or interaction effect are often used to discover Gene-Environment (GxE) interactions. When the environmental exposure is a binary variable, analyses from exposure-stratified models which consist of estimating genetic effect in unexposed and exposed individuals separately can be of interest. In large-scale consortia focusing on GxE interactions in which only the joint test has been performed, it may be challenging to get summary statistics from both exposure-stratified and marginal (i.e not accounting for interaction) models.

Results

In this work, we developed a simple framework to estimate summary statistics in each stratum of a binary exposure and in the marginal model using summary statistics from the “joint” model. We performed simulation studies to assess our estimators’ accuracy and examined potential sources of bias, such as correlation between genotype and exposure and differing phenotypic variances within exposure strata. Results from these simulations highlight the high theoretical accuracy of our estimators and yield insights into the impact of potential sources of bias. We then applied our methods to real data and demonstrate our estimators’ retained accuracy after filtering SNPs by sample size to mitigate potential bias.

Conclusions

These analyses demonstrated the accuracy of our method in estimating both stratified and marginal summary statistics from a joint model of gene-environment interaction. In addition to facilitating the interpretation of GxE screenings, this work could be used to guide further functional analyses. We provide a user-friendly Python script to apply this strategy to real datasets. The Python script and documentation are available at https://gitlab.pasteur.fr/statistical-genetics/J2S.
An N-terminal motif in NLR immune receptors is functionally conserved across distantly related plant species
Authors: Adachi Hiroaki , Contreras Mauricio , Harant Adeline , Wu Chih-hang , Derevnina Lida , Sakai Toshiyuki , Duggan Cian , Moratto Eleonora , Bozkurt Tolga O , Maqbool Abbas , Win Joe , Kamoun Sophien
Published: July 2019

The molecular codes underpinning the functions of plant NLR immune receptors are poorly understood. We used in vitro Mu transposition to generate a random truncation library and identify the minimal functional region of NLRs. We applied this method to NRC4—a helper NLR that functions with multiple sensor NLRs within a Solanaceae receptor network. This revealed that the NRC4 N-terminal 29 amino acids are sufficient to induce hypersensitive cell death. This region is defined by the consensus MADAxVSFxVxKLxxLLxxEx (MADA motif) that is conserved at the N-termini of NRC family proteins and ~20% of coiled-coil (CC)-type plant NLRs. The MADA motif matches the N-terminal α1 helix of Arabidopsis NLR protein ZAR1, which undergoes a conformational switch during resistosome activation. Immunoassays revealed that the MADA motif is functionally conserved across NLRs from distantly related plant species. NRC-dependent sensor NLRs lack MADA sequences indicating that this motif has degenerated in sensor NLRs over evolutionary time.
A promiscuous kinase inhibitor delineates the conspicuous structural features of protein kinase CK2a1
Authors: Tsuyuguchi Masato , Nakaniwa Tetsuko , Sawa Masaaki , Nakanishi Isao , Kinoshita Takayoshi
Published: July 2019

Protein kinase CK2a1 is a serine/threonine kinase that plays a crucial role in the growth, proliferation and survival of cells and is a well known target for tumour and glomerulonephritis therapies. Here, the crystal structure of the kinase domain of CK2a1 complexed with 5-iodotubercidin (5IOD), an ATP-mimetic inhibitor, was determined at 1.78 Å resolution. The structure shows distinct structural features and, in combination with a comparison of the crystal structures of five off-target kinases complexed with 5IOD, provides valuable information for the development of highly selective inhibitors.
A common mechanism for efficient N2O reduction in diverse isolates of nodule‐forming bradyrhizobia
Authors: Mania Daniel , Woliy Kedir , Degefu Tulu , Frostegård åsa
Published: July 2019

Bradyrhizobia are abundant soil bacteria, which can form nitrogen‐fixing symbioses with leguminous plants, including important crops such as soybean, cowpea and peanut. Many bradyrhizobia can denitrify, but studies have hitherto focused on a few model organisms. We screened 39 diverse Bradyrhizobium strains, isolated from legume nodules. Half of them were unable to reduce N2O, making them sources of this greenhouse gas. Most others could denitrify NO3− to N2. Time‐resolved gas kinetics and transcription analyses during transition to anaerobic respiration revealed a common regulation of nirK, norCB and nosZ (encoding NO2−, NO and N2O reductases), and differing regulation of napAB (encoding periplasmic NO3− reductase). A prominent feature in all N2‐producing strains was a virtually complete hampering of NO3− reduction in the presence of N2O. In‐depth analyses suggest that this was due to a competition between electron transport pathways, strongly favouring N2O over NO3− reduction. In a natural context, bacteria with this feature would preferentially reduce available N2O, produced by themselves or other soil bacteria, making them powerful sinks for this greenhouse gas. One way to augment such populations in agricultural soils is to develop inoculants for legume crops with dual capabilities of efficient N2‐fixation and efficient N2O reduction.
When, How and Why Are Junior Coalition Parties Able to Affect a Government's Foreign Policy? A Study of Swedish Coalition Governments 2006–2014
Authors: Brommesson Douglas , Ekengren Ann‐Marie
Published: July 2019

Junior partners in a coalition government are torn between an eagerness to profile themselves, and to show loyalty to the coalition. We investigate when, how and why junior coalition parties affect foreign policy and profile themselves despite demands for national unity. We study two Swedish centre‐right governments in 2006–2010 and 2010–2014. The parties' foreign policy positions in election manifestos are compared to the foreign policy positions presented in the joint Alliance manifesto and yearly government declarations. An explorative analysis of possible explanations for junior parties' influence is based on elite interviews. The results indicate that junior coalition parties might influence the foreign policy in symbolic value related issues, but less so in issues with real policy implications. Our analysis reveals the importance of the leading member of the coalition and how junior parties converge over time towards the position of the senior coalition member.
Impact of a probiotic product on bowel habits and microbial profile in participants with functional constipation: A randomized controlled trial
Authors: Martoni Christopher J. , Evans Malkanthi , Chow Cheryl‐Emiliane T. , Chan Luisa S. , Leyer Gregory
Published: July 2019

Objective

To investigate the clinical efficacy of a multi‐strain probiotic product on bowel habits and microbial profile in participants with functional constipation.

Methods

This was a randomized, double‐blind, placebo‐controlled and parallel‐arm study. Altogether 94 otherwise healthy adults aged 18 to 65 years with symptoms of functional constipation were randomized as part of the intention‐to‐treat population. The participants received a placebo or the probiotic product (1.5 × 1010 CFU/day), consisting of Lactobacillus acidophilus DDS‐1, Bifidobacterium animalis subsp. lactis UABla‐12, Bifidobacterium longum UABl‐14 and Bifidobacterium bifidum UABb‐10 over 4 weeks. Outcomes included the patient assessment of constipation‐symptom (PAC‐SYM) questionnaire, stool frequency and consistency, and microbial profile.

Results

There were no significant between‐group differences in the PAC‐SYM score, despite significant within‐group differences (P < 0.001) over the study period. The probiotic group showed a faster normalization of stool frequency and consistency, with most participants achieving a normalized profile after 1 week. Fecal samples of the probiotic group exhibited higher relative abundance of Ruminococcaceae (P = 0.0047), including the Ruminococcus genus, and lower relative abundance of Erysipelotrichaceae (P = 0.0172) at end‐point compared with baseline. Placebo group samples showed similar abundance profiles over the study, with the exception of Clostridiaceae, which was lower at the study end‐point (P = 0.0033). Among treated participants, all four probiotic strains were significantly more abundant after the intervention.

Conclusions

No significant differences were observed in symptomology, with both groups showing a more than 20% improvement. However, the probiotic helped modulate bowel function earlier than the placebo, with a corresponding shift to a more fibrolytic microbiota.
Direct effects of organic pollutants on the growth and gene expression of the Baltic Sea model bacteriumRheinheimerasp.BAL341
Authors: Karlsson Christofer M. G. , Cerro‐Gálvez Elena , Lundin Daniel , Karlsson Camilla , Vila‐Costa Maria , Pinhassi Jarone
Published: July 2019

Organic pollutants (OPs) are critically toxic, bioaccumulative and globally widespread. Moreover, severalOPs negatively influence aquatic wildlife. Although bacteria are major drivers of the ocean carbon cycle and the turnover of vital elements, there is limited knowledge ofOPeffects on heterotrophic bacterioplankton. We therefore investigated growth and gene expression responses of the Baltic Sea model bacteriumRheinheimerasp.BAL341 to environmentally relevant concentrations of distinct classes ofOPs in 2‐h incubation experiments. During exponential growth, exposure to a mix of polycyclic aromatic hydrocarbons, alkanes and organophosphate esters (denotedMIX) resulted in a significant decrease (between 9% and 18%) in bacterial abundance and production compared with controls. In contrast, combined exposure to perfluorooctanesulfonic acids and perfluorooctanoic acids (denotedPFAS) had no significant effect on growth. Nevertheless,MIXandPFASexposures both induced significant shifts in gene expression profiles compared with controls in exponential growth. This involved several functional metabolism categories (e.g. stress response and fatty acids metabolism), some of which were pollutant‐specific (e.g. phosphate acquisition and alkane‐1 monooxygenase genes). In stationary phase, only two genes in theMIXtreatment were significantly differentially expressed. The substantial direct influence ofOPs on metabolism during bacterial growth suggests that widespreadOPs could severely alter biogeochemical processes governed by bacterioplankton.
Diabetes news
Authors: Biba Ursula , Teng Rhea W. , Kurian Martin J. , Carracher Ann M. , Close Kelly L.
Published: July 2019

Ursula Biba, Rhea W. Teng, Martin J. Kurian, Ann M. Carracher, and Kelly L. Close are of Close Concerns (http://www.closeconcerns.com), a healthcare information company focused exclusively on diabetes and obesity care. Close Concerns publishes Closer Look, a periodical that brings together news and insights in these areas. Each month, the Journal of Diabetes includes this News feature, in which Biba, Teng, Kurian, Carracher, and Close review the latest developments relevant to researchers and clinicians.
Guidelines for the use of acoustic indices in environmental research
Authors: Bradfer‐Lawrence Tom , Gardner Nick , Bunnefeld Lynsey , Bunnefeld Nils , Willis Stephen G. , Dent Daisy H.
Published: July 2019

Ecoacoustics, the study of environmental sound, is a growing field with great potential for biodiversity monitoring. Audio recordings could provide a rapid, cost‐effective monitoring tool offering novel insights into ecosystem dynamics. More than 60 acoustic indices have been developed to date, which reflect distinct attributes of the soundscape, (i.e. the total acoustic energy at a given location, including noise produced by animals, machinery, wind and rain). However, reported patterns in acoustic indices have been contradictory, possibly because there is no accepted best practice for the collection and analysis of audio recordings.

Here, we propose: (a) guidelines for designing studies using audio recordings for the rapid assessment of multiple sites; and (b) a workflow for comparing recordings with seven of the most commonly used indices, permitting discrimination among habitat‐specific soundscapes. We collected and analysed over 26,000 hr of recordings from 117 sites across a range of habitats in a human‐modified tropical landscape in central Panama; an order of magnitude more recordings than used in previously published studies.

We demonstrate that: (a) Standard error variance of indices stabilizes within 120 hr of recordings from a single location. (b) Continuous recording should be used rather than subsample recording on a schedule; sub sampling is a common practice but delays capture of site variability and maximizing total duration of recording should be prioritized. (c) Use of multiple indices to describe soundscape patterns reveals distinct diel and seasonal soundscape patterns among habitats.

We advocate collecting at least 120 hr of continuous recordings per site, and using a range of acoustic indices to categorize the soundscape, including the Acoustic Complexity Index, Acoustic Evenness Index, Acoustic Entropy Index and the Normalized Difference Soundscape Index. Differences among habitat types can be captured if multiple indices are used, and magnitude of variance is often more important than mean values. The workflow we provide will enable successful use of ecoacoustic techniques for environmental monitoring.
Public Deliberation as a Novel Method for an Exception From Informed Consent Community Consultation
Authors: Powers Patricia E. , Shore Karen K. , Perez Susan , Ritley Dominique , Kuppermann Nathan , Holmes James F. , Tzimenatos Leah S. , Shawargga Hiwote , Nishijima Daniel K.
Published: July 2019

Objectives

Community consultation is required for clinical trials considering federal exception from informed consent (EFIC) procedures. Questions remain about the value of the community consult process and whether it adds intended protections to study subjects. Public deliberation methods that provide baseline participant education and elicit values and opinions about consent options is a novel approach for community consultation. This study evaluated the use of structured public deliberation methods to assess a community's values and opinions about informed consent procedures for a pediatric trauma trial.

Methods

This was a mixed‐methods descriptive study of public deliberation sessions assessing participants’ opinions about informed consent procedures for a pediatric trauma randomized controlled trial (RCT). Participants from communities with high rates of pediatric trauma were recruited via community‐based organizations and social media. Deliberation focused on three consent options for a proposed RCT: 1) enrollment using EFIC procedures with no attempt to obtain informed consent, 2) enrollment using EFIC procedures after attempting to reach a parent, or 3) enrollment only with informed consent. Participant demographic data and their opinions about the proposed study and deliberative session were also collected.

Results

There were 102 participants across eight sessions (range of nine to 15/session, mean of 13). Most participants were female (n = 78, 76%) and a plurality were black (n = 48, 47%). The majority of participants preferred enrollment using EFIC procedures only after an attempt was made to reach a parent and informed consent was not possible (n = 56, 55%), followed by enrollment using EFIC procedures with no attempt to obtain informed consent (n = 32, 32%), and enrollment only with written informed consent (n = 13, 13%). One participant declined all options. Eighty‐four participants (82%) agreed or strongly agreed that the RCT was important to do, and 79 participants (77%) said that the sessions provided enough information to make an informed decision about the proposed RCT.

Conclusions

Structured public deliberation is an effective approach when consulting communities for trials considering EFIC procedures. Future studies are needed to evaluate whether public deliberation methods provide participants with enhanced understanding of clinical trials compared to other community consultation methods.
Genome‐wide association studies of the self‐rating of effects of ethanol (SRE)
Authors: Lai Dongbing , Wetherill Leah , Kapoor Manav , Johnson Emma C. , Schwandt Melanie , Ramchandani Vijay A. , Goldman David , Joslyn Geoff , Rao Xi , Liu Yunlong , Farris Sean , Mayfield R. Dayne , Dick Danielle , Hesselbrock Victor , Kramer John , McCutcheon Vivia V. , Nurnberger John , Tischfield Jay , Goate Alison , Edenberg Howard J. , Porjesz Bernice , Agrawal Arpana , Foroud Tatiana , Schuckit Marc
Published: July 2019

The level of response (LR) to alcohol as measured with the Self‐Report of the Effects of Alcohol Retrospective Questionnaire (SRE) evaluates the number of standard drinks usually required for up to four effects. The need for a higher number of drinks for effects is genetically influenced and predicts higher risks for heavy drinking and alcohol problems. We conducted genome‐wide association study (GWAS) in the African‐American (COGA‐AA, N = 1527 from 309 families) and European‐American (COGA‐EA, N = 4723 from 956 families) subsamples of the Collaborative Studies on the Genetics of Alcoholism (COGA) for two SRE scores: SRE‐T (average of first five times of drinking, the period of heaviest drinking, and the most recent 3 months of consumption) and SRE‐5 (the first five times of drinking). We then meta‐analyzed the two COGA subsamples (COGA‐AA + EA). Both SRE‐T and SRE‐5 were modestly heritable (h2: 21%‐31%) and genetically correlated with alcohol dependence (AD) and DSM‐IV AD criterion count (rg: 0.35‐0.76). Genome‐wide significant associations were observed (SRE‐T: chromosomes 6, rs140154945, COGA‐EA P = 3.30E‐08 and 11, rs10647170, COGA‐AA+EA P = 3.53E‐09; SRE‐5: chromosome13, rs4770359, COGA‐AA P = 2.92E‐08). Chromosome 11 was replicated in an EA dataset from the National Institute on Alcohol Abuse and Alcoholism intramural program. In silico functional analyses and RNA expression analyses suggest that the chromosome 6 locus is an eQTL for KIF25. Polygenic risk scores derived using the COGA SRE‐T and SRE‐5 GWAS predicted 0.47% to 2.48% of variances in AD and DSM‐IV AD criterion count in independent datasets. This study highlights the genetic contribution of alcohol response phenotypes to the etiology of alcohol use disorders.
Delivery in the second stage in theatre: Does consultant presence make a difference? A pilot study
Authors: Davis Georgina , Ludlow Joanne
Published: July 2019

Complex operative obstetrics encompasses a range of clinical acumen, decision‐making and surgical skill requiring training, supervision and practise. A period of mandated consultant presence in theatre in the second stage was prospectively audited at our institution to assess the impact of improved senior supervision on mode of delivery and maternal and neonatal morbidity.
Increasing primary anastomosis rate over time for the operative management of acute diverticulitis
Authors: Ahmadi Nima , Howden William B. , Ahmadi Nazanin , Byrne Christopher M. , Young Christopher J.
Published: July 2019

Background

Over the past two decades, there has been mounting evidence that primary anastomosis (PA) is a safe alternative to Hartmann's procedure (HP) in acute diverticulitis. In addition, specialized colorectal surgeons are more likely to perform PA. This study aimed to analyse if this evidence has led to an increase in the rate of PA in a major tertiary institution over time.

Methods

A retrospective observational study of patients requiring operative management of acute diverticulitis from 1 January 2001 to 31 December 2015 at a tertiary teaching hospital.

Results

One hundred and eighteen patients underwent surgery for acute diverticulitis. Patients who failed initial conservative management were more likely to have PA (43% versus 21%, P = 0.044). There was no difference in medical or surgical complications, readmission rate or mortality between patients who had a PA compared with HP. Patients were more likely to have a PA if a colorectal surgeon was operating compared with a colorectal surgery fellow or general surgeon (36% versus 19% versus 10%, P = 0.039). In patients with modified Hinchey 0–2, there was an increased PA rate within the study period, 21%, 43%, 63% to 57% from the first to the fourth quartile of patients (P = 0.038).

Conclusions

The mounting evidence for the safety of performing PA has led to an increase in the PA rates for acute diverticulitis. Patients who were operated by a colorectal surgeon were more likely to have a PA. The morbidity and mortality were similar in patients who had PA compared with HP.
Decreased neonatal hepatitis B virus (HBV) viremia by maternal tenofovir treatment predicts reduced chronic HBV infection in children born to highly viremic mothers
Authors: Chang Kai‐Chi , Chang Mei‐Hwei , Lee Chien‐Nan , Chang Chin‐Hao , Wu Jia‐Feng , Ni Yen‐Hsuan , Wen Wan‐Hsin , Shyu Ming‐Kwang , Lai Ming‐Wei , Chen Shih‐Ming , Hu Jen‐Jan , Lin Hans Hsienhong , Hsu Jenn‐Jeih , Mu Shu‐Chi , Lin Yu‐Cheng , Liu Chun‐Jen , Chen Ding‐Shinn , Lin Lung‐Huang , Chen Huey‐Ling ,   The Taiwan Study Group for the Prevention of Mother‐to‐Infant Transmission of HBV (PreMIT study)
Published: July 2019

Background

Maternal anti‐viral treatment prevents mother‐to‐infant transmission of hepatitis B virus (HBV), but the role of neonatal viremia on subsequent HBV infection is not clear.

Aims

To investigate the effect of maternal anti‐viral treatment on neonatal serum HBV DNA and hepatitis B surface antigen (HBsAg) in infants born to highly viremic mothers and the roles of neonatal markers in predicting chronic HBV infection in children.

Methods

Serum HBV DNA and HBsAg were tested in children. Of the 201 pregnant mothers, 110 received tenofovir during the third trimester. Chronic infection in children was defined by HBsAg seropositivity at 6 or 12 months lasting more than 6 months.

Results

The maternal HBV viral loads from baseline to delivery were 8.25 ± 0.48 to 4.29 ± 0.98 log10 IU/mL; and 8.29 ± 0.49 to 8.12 ± 0.68 log10 IU/mL in the tenofovir and control group respectively. Of the 208 children, those in the tenofovir group had a lower rate of neonatal HBV DNA seropositivity at birth (5.22% vs 30.11%, P < 0.0001) and HBsAg seropositivity at 6 months (1.74% vs 11.83%, P = 0.003) and 12 months (1.74% vs 10.75%, P = 0.007). In a first multivariate analysis, maternal HBV DNA level at delivery (odds ratio = 1.70, P = 0.0172) and neonatal HBsAg positivity (odds ratio = 19.37, P < 0.0001) were significantly associated with children's chronic HBV infection. In a second model, neonatal HBV DNA positivity was a strong independent influence variable (odds ratio = 61.89, P = 0.0002).

Conclusions

Maternal tenofovir therapy decreased maternal viral load and neonatal viremia. Positive neonatal HBV DNA was highly correlated with chronic HBV infection in children. Clinical Trial Identifier: NCT01312012.