bluuebunny/crossref_metadata_2025 huggingface dataset:
Eliciting priors and relaxing the single causal variant assumption in colocalisation analyses
Authors: Wallace Chris
Published: November 2019

Horizontal integration of summary statistics from different GWAS traits can be used to evaluate evidence for their shared genetic causality. One popular method to do this is a Bayesian method, coloc, which is attractive in requiring only GWAS summary statistics and no linkage disequilibrium estimates and is now being used routinely to perform thousands of comparisons between traits.

Here we show that while most users do not adjust default software values, misspecification of prior parameters can substantially alter posterior inference. We suggest data driven methods to derive sensible prior values, and demonstrate how sensitivity analysis can be used to assess robustness of posterior inference.

The flexibility of coloc comes at the expense of an unrealistic assumption of a single causal variant per trait. This assumption can be relaxed by stepwise conditioning, but this requires external software and an LD matrix aligned to study alleles. We have now implemented conditioning within coloc, and propose a new alternative method, masking, that does not require LD and approximates conditioning when causal variants are independent. Importantly, masking can be used in combination with conditioning where allelically aligned LD estimates are available for only a single trait.

We have implemented these developments in a new version of coloc which we hope will enable more informed choice of priors and overcome the restriction of the single causal variant assumptions in coloc analysis.

Author Summary

Determining whether two traits share a genetic cause can be helpful to identify mechanisms underlying genetically-influenced risk of disease or other traits. One method for doing this is “coloc”, which updates prior knowledge about the chance of two traits sharing a causal variant with observed genetic association data in a Bayesian statistical framework. To do this using only summary genetic association data that is commonly shared, the method makes certain assumptions, in particular about the number of genetic causal variants that may underly each measured trait in a genomic region.

We walk through several data-driven approaches to summarise the prior knowledge required for this technique, and propose sensitivity analysis as a means of checking that inference is robust to uncertainty about that prior knowledge. We also show how the assumptions about number of causal variants in a region may be relaxed, and that this improves inferential accuracy.
Synapsin is required for dense core vesicle capture and cAMP-dependent neuropeptide release
Authors: Yu Szi-chieh , Steuer Costa Wagner , Liewald Jana F. , Shao Jiajie , Gottschalk Alexander
Published: November 2019

Release of neuropeptides from dense core vesicles (DCVs) is important for neuromodulation. By optogenetics, behavioral analysis, electrophysiology, and electron microscopy, we show that synapsin SNN-1 is required for cAMP-dependent neuropeptide release inCaenorhabditis eleganscholinergic motor neurons. In synapsin mutants, behaviors induced by the photoactivated adenylyl cyclase bPAC, which we previously showed to depend on acetylcholine and neuropeptides, are altered like in animals with reduced cAMP. While synapsin mutants have slight alterations in synaptic vesicle distribution, DCVs were affected much more: DCVs were ~30% reduced in synaptic terminals, and not released following bPAC stimulation. Imaging axonal DCV trafficking, also in genome-engineered mutants in the serine-9 protein kinase A phosphorylation site, showed that synapsin captures DCVs at synapses, making them available for release. In non-phosphorylatable SNN-1B(S9A) mutants, DCVs traffic less and accumulate, likely by enhanced tethering to the actin cytoskeleton. Our work establishes synapsin as a key mediator of neuropeptide release.
6mer seed toxicity in viral microRNAs
Authors: Murmann Andrea E. , Bartom Elizabeth T. , Schipma Matthew J. , Vilker Jacob , Chen Siquan , Peter Marcus E.
Published: November 2019

Micro(mi)RNAs are short double stranded noncoding RNAs (19-23nts) that regulate gene expression by suppressing mRNAs through RNA interference. Targeting is determined by the seed sequence (position 2-7/8) of the mature miRNA. A minimal G-rich seed of just 6 nucleotides is highly toxic to cells by targeting genes essential for cell survival. A screen of 215 miRNAs encoded by 17 human pathogenic viruses (v-miRNAs) now suggests that a number of v-miRNAs can kill cells through a G-rich 6mer sequence embedded in their seed. Specifically, we demonstrate that miR-K12-6-5p, an oncoviral mimic of the tumor suppressive miR-15/16 family encoded by human Kaposi’s sarcoma-associated herpes virus, harbors a noncanonical toxic 6mer seed (position 3-8) and that v-miRNAs are more likely than cellular miRNAs to utilize a noncanonical 6mer seed. Our data suggest that during evolution viruses evolved to use 6mer seed toxicity to kill cells.
Adhesion modulates cell morphology and migration within dense fibrous networks
Authors: Moreira-Soares Maurício , Cunha Susana P. , Bordin José Rafael , Travasso Rui D. M.
Published: November 2019

One of the most fundamental abilities required for the sustainability of complex life forms is active cell migration, since it is essential in diverse processes from morphogenesis to leukocyte chemotaxis in immune response. The movement of a cell is the result of intricate mechanisms, that involve the coordination between mechanical forces, biochemical regulatory pathways and environmental cues. In particular, epithelial cancer cells have to employ mechanical strategies in order to migrate through the tissue’s basement membrane and infiltrate the bloodstream during the invasion stage of metastasis. In this work we explore how mechanical interactions such as spatial restriction and adhesion affect migration of a self-propelled droplet in dense fibrous media. We have performed a systematic analysis using a phase-field model and we propose a novel approach to simulate cell migration with Dissipative Particle Dynamics (DPD) modelling. With this purpose we have measured the cell’s velocity and quantified its morphology as a function of the fibre density and of its adhesiveness to the matrix fibres. Furthermore, we have compared our results to a previous in vitro migration assay of fibrosacorma cells in fibrous matrices. The results are model independent and show good agreement between the two methodologies and experiments in the literature, which indicates that these minimalist descriptions are able to capture the main features of the system. Our results indicate that adhesiveness is critical for cell migration, by modulating cell morphology in crowded environments and by enhancing cell velocity. In addition, our analysis suggests that matrix metalloproteinases (MMPs) play an important role as adhesiveness modulators. We propose that new assays should be carried out to address the role of adhesion and the effect of different MMPs in cell migration under confined conditions.
Cross-kingdom signalling regulates spore germination in the moss Physcomitrella patens
Authors: Vesty Eleanor F. , Whitbread Amy L. , Needs Sarah , Tanko Wesal , Jones Kirsty , Halliday Nigel , Ghaderiardakani Fatemeh , Liu Xiaoguang , Cámara Miguel , Coates Juliet C.
Published: November 2019

Plants live in close association with microorganisms that can have beneficial or detrimental effects. The activity of bacteria in association with flowering plants has been extensively analysed. Bacteria use quorum-sensing as a way of monitoring their population density and interacting with their environment. A key group of quorum sensing molecules in Gram-negative bacteria are the N-acylhomoserine lactones (AHLs), which are known to affect the growth and development of both flowering plants, including crops, and marine algae. Thus, AHLs have potentially important roles in agriculture and aquaculture. Nothing is known about the effects of AHLs on the earliest-diverging land plants, thus the evolution of AHL-mediated bacterial-plant- and algal interactions is unknown. In this paper, we show that AHLs can affect spore germination in a representative of the earliest plants on land, the Bryophyte moss Physcomitrella patens. Furthermore, we demonstrate that sporophytes of wild isolates of Physcomitrella patens are associated with AHL-producing bacteria.
Design to Data for mutants of β-glucosidase B from Paenibacillus polymyxa: M319C, T431I, and K337D
Authors: Huang Peishan , Contreras Stephanie C. , Bloomfield Eliana , Schmitz Kristine , Arredondo Augustine , Siegel Justin B.
Published: November 2019

The use of computational tools has become an increasingly popular tool for engineering protein function. While there are numerous examples of computational tools enabling the design of novel protein functions, there remains room for improvement in both prediction accuracy and success. To improve algorithms for functional and stability predictions, we have initiated the development of a data set designed to be used for training new computational algorithms for enzyme design. To date our dataset is composed of over 129 mutants with associated expression levels, kinetic data, and thermal stability for the enzyme β-glucosidase B (BglB) from Paenibacillus polymyxa. In this study, we introduced three new variants (M319C, T431I, and K337D) to our existing dataset with the goal of cultivating a larger dataset to train new design algorithms and more broadly explore structure-function relationships in BglB.
Cellular life from the three domains and viruses are transcriptionally active in a hypersaline desert community
Authors: Uritskiy Gherman , Tisza Michael J. , Gelsinger Diego R , Munn Adam , Taylor James , DiRuggiero Jocelyne
Published: November 2019

Microbial communities play essential roles in the biosphere and understanding the mechanisms underlying their functional adaptations to environmental conditions is critical for predicting their behavior. This aspect of microbiome function has not been well characterized in natural high-salt environments. To address this knowledge gap, and to build a general framework of relating the genomic and transcriptomic components in a microbiome, we performed a meta-omic survey of extremophile communities inhabiting halite (salt) nodules in the Atacama Desert. We found that the major phyla of this halophilic community have very different levels of total transcriptional activity and that different metabolic pathways were activated in their transcriptomes. We report that a novelDolichomastixalga – the only eukaryote found in this system – was by far the most active community member. It produced the vast majority of the community’s photosynthetic transcripts despite being outnumbered by members of theCyanobacteria. The divergence in the transcriptional landscapes of these segregated communities, compared to the relatively stable metagenomic functional potential, suggests that microbiomes in each salt nodule undergo unique transcriptional adjustments to adapt to local conditions. We also report the characterization of several previously unknown halophilic viruses, many of which exhibit transcriptional activity indicative of host infection.

Originality-Significance Statement

While the metagenomics of hypersaline environments have already led to many discoveries, the transcriptional adaptations and functions of halophilic microbial communities in natural environments remains understudied. We perform the first robust meta-omic investigation of a hypersaline desert ecosystem, linking the genomic and transcriptional elements of the community. Our analysis unexpectedly revealed that Eukaryotes may be the main primary producers in this extreme environment, despite halophilic Archaea and Bacteria dominating the biomass. We also expand on the existing known diversity of halophilic viruses and demonstrate abundance (copies per million reads) and metatranscriptomic activity (transcripts per million reads); putative hosts are shown on the right.
RASflow: An RNA-Seq Analysis Workflow with Snakemake
Authors: Zhang Xiaokang , Jonassen Inge
Published: November 2019

Background

With the cost of DNA sequencing decreasing, increasing amounts of RNA-Seq data are being generated giving novel insight into gene expression and regulation. Prior to analysis of gene expression, the RNA-Seq data has to be processed through a number of steps resulting in a quantification of expression of each gene / transcript in each of the analyzed samples. A number of workflows are available to help researchers perform these steps on their own data, or on public data to take advantage of novel software or reference data in data re-analysis. However, many of the existing workflows are limited to specific types of studies. We therefore aimed to develop a maximally general workflow, applicable to a wide range of data and analysis approaches and at the same time support research on both model and non-model organisms. Furthermore, we aimed to make the workflow usable also for users with limited programming skills.

Results

Utilizing the workflow management system Snakemake and the package management system Conda, we have developed a modular, flexible and user-friendly RNA-Seq analysis pipeline: RNA-Seq Analysis Snakemake Workflow (RASflow). Utilizing Snakemake and Conda alleviates challenges with library dependencies and version conflicts and also supports reproducibility. To be applicable for a wide variety of applications, RASflow supports mapping of reads to both genomic and transcriptomic assemblies. RASflow has a broad range of potential users: it can be applied by researchers interested in any organism and since it requires no programming skills, it can be used by researchers with different backgrounds. RASflow is an open source tool and source code as well as documentation, tutorials and example data sets can be found on GitHub: https://github.com/zhxiaokang/RASflow

Conclusions

RASflow is a simple and reliable RNA-Seq analysis workflow which is a full pack of RNA-Seq analysis.
Practical parameter identifiability for spatiotemporal models of cell invasion
Authors: Simpson Matthew J , Baker Ruth E , Vittadello Sean T , Maclaren Oliver J
Published: November 2019

We examine the practical identifiability of parameters in a spatiotemporal reaction-diffusion model of a scratch assay. Experimental data involves fluorescent cell cycle labels, providing spatial information about cell position and temporal information about the cell cycle phase. Cell cycle labelling is incorporated into the reaction–diffusion model by treating the total population as two interacting subpopulations. Practical identifiability is examined using a Bayesian Markov chain Monte Carlo (MCMC) framework, confirming that the parameters are identifiable when we assume the diffusivities of the subpopulations are identical, but that the parameters are practically non-identifiable when we allow the diffusivities to be distinct. We also assess practical identifiability using a profile likelihood approach, providing similar results to MCMC with the advantage of being an order of magnitude faster to compute. Therefore, we suggest that the profile likelihood ought to be adopted as a screening tool to assess practical identifiability before MCMC computations are performed.
Real-time tracking reveals the catalytic process of Rad51-driven DNA strand exchange
Authors: Ito Kentaro , Murayama Yasuto , Kurokawa Yumiko , Kanamaru Shuji , Kokabu Yuichi , Maki Takahisa , Argunhan Bilge , Tsubouchi Hideo , Ikeguchi Mitsunori , Takahashi Masayuki , Iwasaki Hiroshi
Published: November 2019

During homologous recombination, Rad51 forms a nucleoprotein filament on single-stranded DNA to promote DNA strand exchange. This filament binds to double-stranded DNA (dsDNA), searches for homology, and promotes transfer of the complementary strand, producing a new heteroduplex. Strand exchange proceeds via two distinct three-strand intermediates, C1 and C2. C1 contains the intact donor dsDNA whereas C2 contains newly formed heteroduplex DNA. Here, we show that conserved DNA binding motifs, loop 1 (L1) and loop 2 (L2) in site I of Rad51, play distinct roles in this process. L1 is involved in formation of the C1 complex whereas L2 mediates the C1-C2 transition, producing the heteroduplex. Another DNA binding motif, site II, serves as the DNA entry position for initial Rad51 filament formation, as well as for second donor dsDNA incorporation. Our study provides a comprehensive molecular model for the catalytic process of strand exchange mediated by eukaryotic RecA family recombinases.
Mechanism of the secretion of the lanthipeptide nisin
Authors: Lagedroste Marcel , Reiners Jens , Smits Sander H.J. , Schmitt Lutz
Published: November 2019

Lanthipeptides are ribosomally synthesized and post-translationally modified peptides containing dehydrated amino acids and (methyl-)lanthionine rings. One of the best-studied example is nisin, which is synthesized as a precursor peptide comprising of an N-terminal leader peptide and a C-terminal core peptide. Amongst others, the leader peptide is crucial for enzyme recognition and acts as a secretion signal for the ABC transporter NisT which secrets nisin in a proposed channeling mechanism. Here, we present anin vivosecretion analysis of this process in the presence and absence of the maturation machinery composed of the dehydratase NisB and the cyclase NisC. The data clearly demonstrated that the function of NisC, but the mere presence of NisB modulated the apparent secretion rates. Additional in vitro studies of detergent-solubilized NisT revealed how the activity of this ABC transporter is again influenced by the enzymes of the maturation machinery, but not the substrate.
eyes absentin the cockroach panoistic ovaries regulates proliferation and differentiation through ecdysone signalling
Authors: Ramos S. , Chelemen F. , Pagone V. , Elshaer N. , Irles P. , Piulachs M.D.
Published: November 2019

Eyes absent (Eya), is a protein structurally conserved from hydrozoans to humans, for which two basic roles have been reported: it can act as a transcription cofactor and as a protein tyrosine phosphatase. Eya was discovered in the flyDrosophila melanogasterin relation to its function in eye development, and the same function was later reported in other insects. Eya is also involved in insect oogenesis, although studies in this sense are limited toD. melanogaster, which has meroistic ovaries, and whereeyamutations abolish gonad formation.

In the present work we studied the function ofeyain the panoistic ovary of the cockroachBlattella germanica. We show thateyais essential for correct development of panoistic ovaries. InB. germanica, eyaacts at different level and in a distinct way in the germarium and the vitellarium. In the germarium,eyacontributes to maintain the correct number of somatic and germinal cells by regulating the expression of steroidogenic genes in the ovary. In the vitellarium,eyafacilitates follicle cells proliferation and contributes to regulate the cell program, in the context of basal ovarian follicle maturation. Thus,eya-depleted females ofB. germanicaarrest the growth and maturation of basal ovarian follicles and become sterile.
N-(tert-Butyl)-2-(2-nitrophenyl)imidazo[1,2-a]pyridin-3-amine
Authors: Dhanalakshmi G. , Mala Ramanjaneyulu , Thennarasu Sathiah , Aravindhan S.
Published: November 2019

In the title compound, C17H18N4O2, the dihedral angle between the pyridine and benzene rings is 55.68 (11)°. In the crystal, N—H...N hydrogen bonds link the molecules into [010] chains.
Serviceability analysis of a cable-supported footbridge subjected to human-induced loads
Authors: Li Zhen , Li Dejian , Lu Yao , Cheng Kepei , Wu Qianqiu
Published: November 2019

Purpose

The purpose of this paper is to obtain the response time history curves of vertical and lateral acceleration in the span of the main beam under different loads through the finite element time-history analysis method, so as to realize the Serviceability Analysis of a Cable-Supported Footbridge Subjected to Human-Induced Loads, taking the long-span cable-supported footbridge over Dongtan River as an example.

Design/methodology/approach

The finite element method is used for analysis of the footbridge.

Findings

It is found that under the condition of low-density pedestrians walking freely, the response of human vertical vibration acceleration and the load conditions of pedestrian overpasses cannot meet the requirements of normal use. Therefore, the vertical acceleration of the footbridge should be designed to reduce vibration. Under these two loading conditions, the lateral acceleration response meets the requirements of normal use.

Originality/value

On the basis of summarizing the research at home and abroad, the analysis of human-induced vibration is mainly considered from two aspects: frequency regulation and dynamic response control. The walking load models mainly include Fourier series model, self-excitation model, impulse model, stochastic model and more; the crowd load models are divided into groups: low-density crowd walking freely, high-density crowd flowing and more. Therefore, it is very important to calculate the structural vibration response in the design of long-span cable-supported footbridges under pedestrian excitation to meet comfort requirements.
A polyhydroxyalkanoate‐based encapsulating strategy for ‘bioplasticizing’ microorganisms
Authors: González Erika , Herencias Cristina , Prieto M. Auxiliadora
Published: November 2019

Over the past few decades, considerable interest has been shown in developing nano‐ and microcarriers with biocompatible and biodegradable materials for medical and biotechnological applications. Microencapsulation is a technology capable of enhancing the survival rate of bacteria, providing stability in harsh environments. In the present paper, we developed a technology to encapsulate microorganisms within polyhydroxyalkanoate (PHA)‐based microcapsules (MPs), employing a modified double emulsion solvent evaporation technique, with Pseudomonas putida KT2440 as a biotechnological model strain. The resulting MPs display a spherical morphology and an average particle size of 10 μm. The stability of the MPs was monitored under different conditions of storage and stress. The MPs remained stable for at least 24 days stored at 4°C in a water suspension. They exhibited greater tolerance to stress conditions; encapsulated cells remained viable for 2 h in alkaline solution and after 24 h of H2O2 exposure at 10 and 20 mM. Results suggested the potential of MPs as a microcontainer of bacterial cells, even for biotechnological applications requiring high alkaline conditions and oxidative stress. We validated the potential applicability of the PHA‐based microencapsulation method in other microorganisms by encapsulating the predatory bacterium Bdellovibrio bacteriovorus.
Diamondoids are not forever: microbial biotransformation of diamondoid carboxylic acids
Authors: Folwell Benjamin D. , McGenity Terry J. , Whitby Corinne
Published: November 2019

Oil sands process‐affected waters (OSPW) contain persistent, toxic naphthenic acids (NAs), including the abundant yet little‐studied diamondoid carboxylic acids. Therefore, we investigated the aerobic microbial biotransformation of two of the most abundant, chronically toxic and environmentally relevant diamondoid carboxylic acids: adamantane‐1‐carboxylic acid (A1CA) and 3‐ethyl adamantane carboxylic acid (3EA). We inoculated into minimal salts media with diamondoid carboxylic acids as sole carbon and energy source two samples: (i) a surface water sample (designated TPW) collected from a test pit from the Mildred Lake Settling Basin and (ii) a water sample (designated 2 m) collected at a water depth of 2 m from a tailings pond. By day 33, in TPW enrichments, 71% of A1CA and 50% of 3EA was transformed, with 50% reduction in EC20 toxicity. Similar results were found for 2 m enrichments. Biotransformation of A1CA and 3EA resulted in the production of two metabolites, tentatively identified as 2‐hydroxyadamantane‐1‐carboxylic acid and 3‐ethyladamantane‐2‐ol respectively. Accumulation of both metabolites was less than the loss of the parent compound, indicating that they would have continued to be transformed beyond 33 days and not accumulate as dead‐end metabolites. There were shifts in bacterial community composition during biotransformation, with Pseudomonas species, especially P. stutzeri, dominating enrichments irrespective of the diamondoid carboxylic acid. In conclusion, we demonstrated the microbial biotransformation of two diamondoid carboxylic acids, which has potential application for their removal and detoxification from vast OSPW that are a major environmental threat.
An approach to gut microbiota profile in children with autism spectrum disorder
Authors: Andreo‐Martínez Pedro , García‐Martínez Nuria , Sánchez‐Samper Elvira Pilar , Martínez‐González Agustín Ernesto
Published: November 2019

In recent years, there has been an increase in studies on the implications of gut microbiota (GM) on the behaviour of children with autism spectrum disorders (ASD) due to a dysbiosis in GM that can trigger onset, development or progression of ASD through the microbiota–gut–brain axis. The aim of this study is to carry out a systematic review of articles from the last 6 years that analyse GM in children with ASD compared to GM in control groups. Children with ASD showed a higher abundance of Roseburia and Candida genera, and lower abundance of Dialister, Bilophila, Veillonella, Streptococcus, Coprococcus and Prevotella genera. Those differences can be attributed to factors such as different nationalities, nature of control groups, place where the sample was taken, gastrointestinal (GI) problems or bacterial detection methods. It is still too early to define a specific GM profile of children with ASD, and future studies should focus on homogenizing the characteristics of samples and control groups. Furthermore, new multicentre studies should also focus on the impact of GM on GI physiology, neurophysiology and behaviour of children with ASD, and on performing psychometric analyses of the correlation between the severity of ASD behavioural symptoms and GM profiles.
Cue‐induced effects on decision‐making distinguish subjects with gambling disorder from healthy controls
Authors: Genauck Alexander , Andrejevic Milan , Brehm Katharina , Matthis Caroline , Heinz Andreas , Weinreich André , Kathmann Norbert , Romanczuk‐Seiferth Nina
Published: November 2019

While an increased impact of cues on decision‐making has been associated with substance dependence, it is yet unclear whether this is also a phenotype of non‐substance‐related addictive disorders, such as gambling disorder (GD). To better understand the basic mechanisms of impaired decision‐making in addiction, we investigated whether cue‐induced changes in decision‐making could distinguish GD from healthy control (HC) subjects. We expected that cue‐induced changes in gamble acceptance and specifically in loss aversion would distinguish GD from HC subjects.

Thirty GD subjects and 30 matched HC subjects completed a mixed gambles task where gambling and other emotional cues were shown in the background. We used machine learning to carve out the importance of cue dependency of decision‐making and of loss aversion for distinguishing GD from HC subjects.

Cross‐validated classification yielded an area under the receiver operating curve (AUC‐ROC) of 68.9% (p = .002). Applying the classifier to an independent sample yielded an AUC‐ROC of 65.0% (p = .047). As expected, the classifier used cue‐induced changes in gamble acceptance to distinguish GD from HC. Especially, increased gambling during the presentation of gambling cues characterized GD subjects. However, cue‐induced changes in loss aversion were irrelevant for distinguishing GD from HC subjects. To our knowledge, this is the first study to investigate the classificatory power of addiction‐relevant behavioral task parameters when distinguishing GD from HC subjects. The results indicate that cue‐induced changes in decision‐making are a characteristic feature of addictive disorders, independent of a substance of abuse
Improved assembly and variant detection of a haploid human genome using single‐molecule, high‐fidelity long reads
Authors: Vollger Mitchell R. , Logsdon Glennis A. , Audano Peter A. , Sulovari Arvis , Porubsky David , Peluso Paul , Wenger Aaron M. , Concepcion Gregory T. , Kronenberg Zev N. , Munson Katherine M. , Baker Carl , Sanders Ashley D. , Spierings Diana C.J. , Lansdorp Peter M. , Surti Urvashi , Hunkapiller Michael W. , Eichler Evan E.
Published: November 2019

The sequence and assembly of human genomes using long‐read sequencing technologies has revolutionized our understanding of structural variation and genome organization. We compared the accuracy, continuity, and gene annotation of genome assemblies generated from either high‐fidelity (HiFi) or continuous long‐read (CLR) datasets from the same complete hydatidiform mole human genome. We find that the HiFi sequence data assemble an additional 10% of duplicated regions and more accurately represent the structure of tandem repeats, as validated with orthogonal analyses. As a result, an additional 5 Mbp of pericentromeric sequences are recovered in the HiFi assembly, resulting in a 2.5‐fold increase in the NG50 within 1 Mbp of the centromere (HiFi 480.6 kbp, CLR 191.5 kbp). Additionally, the HiFi genome assembly was generated in significantly less time with fewer computational resources than the CLR assembly. Although the HiFi assembly has significantly improved continuity and accuracy in many complex regions of the genome, it still falls short of the assembly of centromeric DNA and the largest regions of segmental duplication using existing assemblers. Despite these shortcomings, our results suggest that HiFi may be the most effective standalone technology for de novo assembly of human genomes.
Radiologic sinus inflammation and symptoms of chronic rhinosinusitis in a population‐based sample
Authors: Hirsch Annemarie G. , Nordberg Cara , Bandeen‐Roche Karen , Tan Bruce K. , Schleimer Robert P. , Kern Robert C. , Sundaresan Agnes , Pinto Jayant M. , Kennedy Thomas L. , Greene Joseph Scott , Kuiper Jordan R. , Schwartz Brian S.
Published: November 2019

Background

Chronic rhinosinusitis (CRS) epidemiology has been largely studied using symptom‐based case definitions, without assessment of objective sinus findings.

Objective

To describe radiologic sinus opacification and the prevalence of CRS, defined by the co‐occurrence of symptoms and sinus opacification, in a general population‐based sample.

Methods

We collected questionnaires and sinus CT scans from 646 participants selected from a source population of 200 769 primary care patients. Symptom status (CRSS) was based on guideline criteria, and objective radiologic inflammation (CRSO) was based on the Lund‐Mackay (L‐M) score using multiple L‐M thresholds for positivity. Participants with symptoms and radiologic inflammation were classified as CRSS+O. We performed negative binomial regression to assess factors associated with L‐M score and logistic regression to evaluate factors associated with CRSS+O. Using weighted analysis, we calculated estimates for the source population.

Results

The proportion of women with L‐M scores ≥ 3, 4, or 6 (CRSO) was 11.1%, 9.9%, and 5.7%, respectively, and 16.1%, 14.6%, and 8.7% among men. The respective proportion with CRSS+O was 1.7%, 1.6%, and 0.45% among women and 8.8%, 7.5%, and 3.6% among men. Men had higher odds of CRSS+O compared to women. A greater proportion of men (vs women) had any opacification in the frontal, anterior ethmoid, and sphenoid sinuses.

Conclusion

In a general population‐based sample in Pennsylvania, sinus opacification was more common among men than in women and opacification occurred in different locations by sex. Male sex, migraine headache, and prior sinus surgery were associated with higher odds of CRSS+O.
How to understand a development corridor? The case of Lamu Port–South Sudan–Ethiopia‐Transport corridor in Kenya
Authors: Lesutis Gediminas
Published: November 2019

In order to advance the emerging research on development corridors, this paper, drawing on the geographical as well as broader critical social science literatures on infrastructure, offers three different pathways how research on large‐scale infrastructural projects could be conceptually developed. Using the example of Lamu Port–South Sudan–Ethiopia‐Transport corridor in Kenya, the paper discusses how imaginaries and material practices of development corridors could be understood as (1) practices of establishing frontiers of extractive capital accumulation that (2) create fragmented forms of state territoriality characterised by complex interaction between the state and private actors and (3) through ideals of “modernity” valorise some lives over others. Although not exhaustive, taken together these approaches demonstrate that development corridors are not just material practices of infrastructural development that translate into sustainable economic growth and development, as advocated by “win‐win” mainstream development discourses. Instead, the approaches outlined in the paper demonstrate that development corridors are value‐laden practices that play a specific function in creating and sustaining socio‐political orders increasingly dominated by global capitalist expansion, as well as different forms of extraction, state–private actor assemblages, and normative ordering of life that the constitution of these orders sets in motion. Through these analyses, the paper contributes to the geographical scholarship on mega‐infrastructures by indicating how the globally structured politics of infrastructure – such as development corridors – advance capitalist expansion by materialising not just in urban or peri‐urban contexts, as is common to focus within the literature, but also play an important role in producing geographies of states, characterised by extractivism, contested territorialities, and normative ordering of life.
The backroads of AI: The uneven geographies of artificial intelligence and development
Authors: McDuie‐Ra Duncan , Gulson Kalervo
Published: November 2019

Artificial intelligence is being reconfigured as a set of technologies that can address poverty with precision. The impacts of AI will both exacerbate and ameliorate the conditions of uneven development. Recent debates focus on the disruptive effects of AI, particularly to replication of development trajectories that have had success in reducing poverty. In this paper we further these debates by analysing the backroads of AI. The backroads serve as a metaphor for understanding the ways AI will travel from the sites of incubation to the frontlines of uneven development. We explore dialogues between AI and development in two arenas: the World Bank's Development Impact Evaluation initiative (DIME) and the Government of India's national AI strategy, #AIforAll. We argue that both these arenas serve as hubs from which AI will travel out along the backroads to remote, poor, and fragmented polities. While the World Bank utilises AI as technology to empower experts and mobilise a techno‐political authority, what we refer to as precision AI, India seeks to function as a second‐tier AI hub, making AI cheaper and more accessible domestically and for other developing countries, what we refer to as populist AI. We conclude by discussing the interrelations of precision and populist AI along the backroads, and the potential of backroads research for mapping AI, uneven geographies of development and technology and the impacts of AI's disruptions at different scales.
Deregulation and regional specialization: Evidence from Canadian agriculture
Authors: Carter Colin A. , Ferguson Shon M.
Published: November 2019

For about 70 years, the Canadian Wheat Board (CWB) was one of the world's largest export “single desk” state traders in agriculture, until it was deregulated in 2012 and stripped of its marketing powers. One of the main crops controlled by the CWB was barley. We estimate the impact of the removal of the CWB's single desk on the spatial pattern of malting barley production in Western Canada. We find that deregulation encouraged growers located closer to malt barley processing plants to increase production relative to growers located further from the plants. This change in cropping patterns after deregulation can be explained by efficiency gains, combined with transportation and handling cost savings.
Current perspectives on recurrent pituitary adenoma: The role and timing of surgery vs adjuvant treatment
Authors: Hayhurst Caroline , Taylor Peter N. , Lansdown Andrew J. , Palaniappan Nachi , Rees Dafydd Aled , Davies John Stephen
Published: November 2019

The clinical course of pituitary adenoma can be highly variable. Aggressive pituitary tumours may require multimodal therapy with multiple operations. Even standard pituitary adenomas exhibit relatively high long‐term recurrence rates and delayed intervention is often required. The indications for revision surgery in the endoscopic era are expanding for both functioning and nonfunctioning tumours, including access to the cavernous sinus and intracranial compartments. Although revision surgery can be challenging, it has been demonstrated to be both safe and effective. The question of the use of early radiotherapy in pituitary adenoma remains controversial. Our increasing understanding of pituitary tumour biology facilitates individualized treatment and surveillance protocols, with early intervention in high‐risk adenoma subtypes. In this review, we discuss the treatment options for recurring pituitary tumours and focus on the role of revision surgery.
Morphological phylogeny of the Tegulinae (Mollusca: Vetigastropoda) reinforces a Turbinidae position
Authors: Dornellas Ana Paula , Couto Diogo Ribeiro , Simone Luiz Ricardo L.
Published: November 2019

A cladistic analysis of the Tegulinae (Turbinidae) is presented using 132 morphological characters and 41 taxa. Tegulinae is recovered and is sister to Prisogaster niger (Prisogasterinae) within the family Turbinidae. This scenario, with Tegulinae as a subfamily within Turbinidae, corroborates with the most molecular analyses. Tegulinae comprises >40 extant species, belonging to eight genera. Morphological studies have not resolved the placement of Tegulinae within Trochoidea sufficiently, and the systematic positions of the genera have never been investigated as a primary objective. The present morphology‐based analysis of genus‐level relationships within Tegulinae provides a robust, phylogenetic diagnosis of each group, rooted on a firm hypothesis of evolutionary relationships. An additional search was performed to include the tegulines Omphalius nigerrimus and Carolesia blakei terminals using unweighted and implied weighting. Our morphological data provide a solid foundation for ensuing systematic research on Tegulinae, as well as Trochoidea, and evidence facilitating the diagnosis of generic and suprageneric groups.
Self‐reported sexual dysfunction in patients with rectal cancer
Authors: Sörensson M. , Asplund D. , Matthiessen P. , Rosenberg J. , Hallgren T. , Rosander C. , González E. , Bock D. , Angenete E.
Published: November 2019

Aim

Patients with rectal cancer often experience sexual dysfunction after treatment. The aim of this study was to evaluate sexual function in a prospective cohort of patients regardless of treatment and tumour stage and explore what factors might affect sexual activity 1 year after diagnosis.

Method

The QoLiRECT study (Quality of Life in RECTal cancer) is a prospective study on the health‐related quality of life in patients with rectal cancer in Denmark and Sweden. Questionnaires were completed at diagnosis and 1 year. Clinical data were retrieved from national quality registries.

Results

Questionnaire data were available from 1085 patients at diagnosis and 920 patients at 1 year. Median age was 69 years (range 25–100). At diagnosis, 29% of the women and 41% of the men were sexually active, which was lower than an age‐matched reference population. This was further reduced to 25% and 34% at 1 year. Risk factors for sexual inactivity were absence of sexual activity prior to the diagnosis and the presence of a stoma. Women experienced reduced lubrication and more dyspareunia at 1 year compared with the time of diagnosis. In men, erectile dysfunction increased from 46% to 55% at 1 year.

Conclusion

Sexual activity in patients with rectal cancer is lower at diagnosis compared with the population norm and is further reduced at 1 year. The presence of a stoma contributed to reduced sexual activity after operation. Sexual dysfunction was difficult to evaluate due to low sexual activity in the cohort. In men, erectile dysfunction is common.
Morbidity associated with the immediate vertical rectus abdominus myocutaneous flap reconstruction after radical pelvic surgery
Authors: Proctor M. J. , Westwood D. A. , Donahoe S. , Chauhan A. , Lynch A. C. , Heriot A. G. , Sent‐Doux K. , Creagh T. , Frizelle F. A. , Wakeman C. J.
Published: November 2019

Aim

Patients who undergo radical pelvic surgery often have problems with perineal wound healing and pelvic collections. While there is recognition of the perineal morbidity, there also remains uncertainty around the benefit of vertical rectus abdominus myocutaneous (VRAM) flaps due to the balance between primary healing and the complications associated with this form of reconstruction. This study aimed to evaluate factors associated with significant flap and donor site related complications following VRAM flap reconstruction for radical pelvic surgery.

Method

A retrospective analysis of VRAM flap related complications was undertaken from prospectively maintained databases for all patients undergoing radical pelvic surgery (2001– 2017) in two cancer centres.

Results

In all, 154 patients were identified [median age 62 years (range 26–89 years), 80 (52%) men]. Thirty‐three (21%) patients experienced significant donor or flap related complications. Major complications (Clavien–Dindo ≥ 3) related to the abdominal donor site occurred in nine (6%) patients, while those related to the flap or perineal site occurred in 28 (18%) patients. Only smoking (P = 0.003) and neoadjuvant radiotherapy (P = 0.047) were associated with the development of significant flap related complications on univariate analysis. Flap related complications resulted in a significantly longer hospital stay (P < 0.001).

Conclusion

Careful patient selection is required to balance the risks vs the benefits of VRAM flap reconstruction. Immediate VRAM reconstruction in patients undergoing radical pelvic surgery can achieve early healing and stable perineal closure; it has a low but significant morbidity. Major flap related complications are significantly associated with smoking status and neoadjuvant radiotherapy and result in a prolonged length of hospital stay.
The politics of government reorganizations: Evidence from 30 OECD countries, 1980–2014
Authors: Ryu Lanhee , Moon M. Jae , Yang Jae‐jin
Published: November 2019

Revisiting the seminal study of March and Olson (1983), this article aimed to empirically test whether or not government reorganizations at the ministerial level can be better explained by political factors than administrative and functional rhetoric. Government reorganizations have often been understood as functional adaptations to increase organizational efficiency and effectiveness, but little empirical research has been conducted on their political context. By analyzing pooled‐time series data from 30 OECD countries from 1980–2014 taken from the Statesman's Yearbook, this article sought to examine whether changes in political power are associated with government reorganizations and whether their intensity is affected by the country's political system (parliamentarism or presidentialism), transitions of administrative power, and political cycles of the top executive's tenure. The results suggested that government reorganizations are more likely to occur in parliamentary systems, after transitions of political power, and at the beginning of the top executive's tenure.
Communities, health‐care organizations and the contingencies and contradictions of engagement: A case study from Chile
Authors: Montenegro Cristian R. , Mercado Nérida
Published: November 2019

Context

Despite a growing interest in service‐user involvement in mental health services, the interaction between health institutions and local groups is only beginning to receive attention, particularly in global south settings.

Objective

Looking at a participatory initiative in Chile, this study explores how, under unfavourable administrative conditions, health organizations approach and work with communities.

Methods

We interviewed policy‐makers (5), local professionals (10), service users and community representatives (6) linked to a concrete participatory initiative. Participant observation in relevant meetings helped to enrich the interpretations. Thematic analysis was applied to interview transcripts and field notes.

Findings

The findings present a sequence of actions starting with the creation of a network of community‐based groups. A set of problems ensued, related to the group's diversity, internal representation, decision‐making and funding processes. In response, processionals implemented simultaneously bureaucratic and democratic adjustments, developing a vision of community that ignored the particularities—including the motivations—of local groups.

Discussion and conclusion

Based on these findings, we argue that participatory initiatives should be studied as on‐going achievements shaped by broad policy orientations and local configurations of interest. In the process, they produce ad hoc forms of knowledge and visions of community that provide orientation to the agents involved.
Development of a rapid method for codfish identification in processed fish products based on SYBR Green real‐time PCR
Authors: Xiong Xiong , Yuan Fangying , Huang Manhong , Cao Min , Xiong Xiaohui
Published: November 2019

Using species outside the order Gadiformes to prepare codfish products has been widely revealed as a new type of fraud in China, highlighting the necessity to establish proper methods for codfish species identification. This work aimed to develop a new SYBR Green real‐time PCR assay for the detection of codfish ingredient (mainly the eight Gadiformes species, Gadus morhua, Gadus macrocephalus, Theragra chalcogramma, Pollachius virens, Melanogrammus aeglefinus, Merluccius merluccius, Merluccius australis and Albatrossia pectoralis) in processed fish products based on mitochondrial 12S rRNA gene. Results highlighted the positive Cq (cycle quantification value, average value 19.18 ± 1.49) only from the eight Gadiformes species, with no fluorescent signal (Cq > 32) for the other sixty‐seven non‐Gadiformes species. The absolute limit of detection was 0.048 ng genomic DNA. Methodology validation succeeded in twenty‐six commercial products. These results demonstrated that the newly developed method is suitable for the identification of codfish ingredient in processed fish products.
State of Control: Unknown Migrant Children
Authors: Lundstedt Andreas
Published: November 2019

Recently, crises seem to predominate migration policymaking. They are commonly seen as critical junctures which precipitate major policy change. However, rather than creation of something new, crises can instead be vehicles for restoring the order of the past. This article examines the case of asylum‐seeking unaccompanied minors in Sweden, where drastic changes have been made in the aftermath of the perceived “migration crisis” of 2015. Employing historical institutionalist theory, it examines decades of Swedish migration policymaking through analysis of state inquiries, law proposals and court rulings. It argues that the changes introduced 2015 were not qualitatively new, but rather a result of long‐simmering tensions. These tensions lie between state attempts to control migration, particularly of “unidentifiable” individuals, and the rights accorded to migrants. The article shows that Sweden's migration framework of bounded universalism has gradually been altered by tools that categorize migrants, with implications for migration policy as a whole.