bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated evaluation of payments for ecosystem services programs in China: a systematic review
Authors: Yang Wu , Lu Qiaoling
Published: April 2018

Introduction:
During the past two decades, payments for ecosystem services (PES) program has become a popular conservation paradigm for realigning socioeconomic costs and benefits among different stakeholders. As billions of investment flows into the natural capital pool, there is growing interest to understand the ecological, economic, and social outcomes of PES programs. China is one of the countries that extensively implements PES programs. Although there is a growing interest to perform impact evaluation of China’s massive PES programs, it is unclear that what existing literature has done, has not done, and should do in the future. Therefore, to guide further research and practices, we conduct a systematic review of studies on China’s PES programs.

Results:
Our review shows that there are growing impact evaluation studies of PES programs in China. However, the spatial and ecosystem distributions of existing studies are quite uneven. Most case studies were poorly designed, rarely quantified, and evaluated without sophisticated methods. Among the three dimensions of ecological effectiveness, economic efficiency, and social equity, economic efficiency is the least studied.

Discussion and Conclusion:
We further discuss the challenges and opportunities and provide insights for future research. To improve the understanding and management of natural capital, we call for mainstreaming impact evaluation of ecosystem service policies in China and beyond following the state-of-art procedures.
Methods of engagement: On civic participation formats as composition devices in urban planning
Authors: Meilvang Marie Leth , Carlsen Hjalmar Bang , Blok Anders
Published: April 2018

This article evaluates and develops the contribution of pragmatic sociology to the study of urban life and politics, by way of analysing recent shifts in the cultural-political forms of civic participation in formal urban planning. In doing so, it seeks to stage a critical test of the diagnosis of a ‘certified’, (neo-)liberal city that has recently emerged from work with Laurent Thévenot’s sociology of engagements and commonalities. Drawing on extensive empirical materials on the methods and formats of civic participation in contemporary Danish urban planning, we identify three dominant civic participation formats: the hearing, the dialogue meeting, and the workshop. These formats, we argue, work as composition devices that stabilise certain figures of the urban (quasi-)’citizen’, endowed with circumscribed possibilities for political engagement. Rather than a monolithic process of ‘certification’, we conclude, recent years have witnessed a partial and contested translation of the urban citizen into more manageable, liberal shapes.
Effect of substrates on Zinc Oxide thin films fabrication using sol-gel method
Authors: Kadir Rosmalini Ab , Mohd Taib Nurmalina , Wan Ahmad Wan Rosmaria , Aziz Anees Abdul , Zoolfakar Ahmad Sabirin
Published: April 2018

The properties of ZnO thin films were deposited on three different substrates via dip coating method was investigated. The films were prepared on glass, ITO and p-type silicon. Characterization of the film revealed that the properties of the dip coated ZnO thin films were influenced by the type of substrates. The grains on ITO and glass were ∼10 nm in size while the grains on wafer agglomerate together to form a denser film. Studies of the optical properties using UV-VIS-NIR of the fabricated films demonstrated that glass has the highest transmittance compared to ITO.
Inference of the human polyadenylation code
Authors: Leung Michael K K , Delong Andrew , Frey Brendan J
Published: April 2018

Motivation

Processing of transcripts at the 3′-end involves cleavage at a polyadenylation site followed by the addition of a poly(A)-tail. By selecting which site is cleaved, the process of alternative polyadenylation enables genes to produce transcript isoforms with different 3′-ends. To facilitate the identification and treatment of disease-causing mutations that affect polyadenylation and to understand the sequence determinants underlying this regulatory process, a computational model that can accurately predict polyadenylation patterns from genomic features is desirable.

Results

Previous works have focused on identifying candidate polyadenylation sites and classifying tissue-specific sites. By training on how multiple sites in genes are competitively selected for polyadenylation from 3′-end sequencing data, we developed a deep learning model that can predict the tissue-specific strength of a polyadenylation site in the 3′ untranslated region of the human genome given only its genomic sequence. We demonstrate the model’s broad utility on multiple tasks, without any application-specific training. The model can be used to predict which polyadenylation site is more likely to be selected in genes with multiple sites. It can be used to scan the 3′ untranslated region to find candidate polyadenylation sites. It can be used to classify the pathogenicity of variants near annotated polyadenylation sites in ClinVar. It can also be used to anticipate the effect of antisense oligonucleotide experiments to redirect polyadenylation. We provide analysis on how different features affect the model’s predictive performance and a method to identify sensitive regions of the genome at the single-based resolution that can affect polyadenylation regulation.

Supplementary information

Supplementary data are available at Bioinformatics online.
LipidPedia: a comprehensive lipid knowledgebase
Authors: Kuo Tien-Chueh , Tseng Yufeng Jane
Published: April 2018

Motivation

Lipids are divided into fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, saccharolipids, sterols, prenol lipids and polyketides. Fatty acyls and glycerolipids are commonly used as energy storage, whereas glycerophospholipids, sphingolipids, sterols and saccharolipids are common used as components of cell membranes. Lipids in fatty acyls, glycerophospholipids, sphingolipids and sterols classes play important roles in signaling. Although more than 36 million lipids can be identified or computationally generated, no single lipid database provides comprehensive information on lipids. Furthermore, the complex systematic or common names of lipids make the discovery of related information challenging.

Results

Here, we present LipidPedia, a comprehensive lipid knowledgebase. The content of this database is derived from integrating annotation data with full-text mining of 3923 lipids and more than 400 000 annotations of associated diseases, pathways, functions and locations that are essential for interpreting lipid functions and mechanisms from over 1 400 000 scientific publications. Each lipid in LipidPedia also has its own entry containing a text summary curated from the most frequently cited diseases, pathways, genes, locations, functions, lipids and experimental models in the biomedical literature. LipidPedia aims to provide an overall synopsis of lipids to summarize lipid annotations and provide a detailed listing of references for understanding complex lipid functions and mechanisms.

Availability and implementation

LipidPedia is available at http://lipidpedia.cmdm.tw.

Supplementary information

Supplementary data are available at Bioinformatics online.
Whole-genome resequencing reveals signatures of selection and timing of duck domestication
Authors: Zhang Zebin , Jia Yaxiong , Almeida Pedro , Mank Judith E , van Tuinen Marcel , Wang Qiong , Jiang Zhihua , Chen Yu , Zhan Kai , Hou Shuisheng , Zhou Zhengkui , Li Huifang , Yang Fangxi , He Yong , Ning Zhonghua , Yang Ning , Qu Lujiang
Published: April 2018

Background

The genetic basis of animal domestication remains poorly understood, and systems with substantial phenotypic differences between wild and domestic populations are useful for elucidating the genetic basis of adaptation to new environments as well as the genetic basis of rapid phenotypic change. Here, we sequenced the whole genome of 78 individual ducks, from two wild and seven domesticated populations, with an average sequencing depth of 6.42X per individual.

Results

Our population and demographic analyses indicate a complex history of domestication, with early selection for separate meat and egg lineages. Genomic comparison of wild to domesticated populations suggests that genes that affect brain and neuronal development have undergone strong positive selection during domestication. Our FST analysis also indicates that the duck white plumage is the result of selection at the melanogenesis-associated transcription factor locus.

Conclusions

Our results advance the understanding of animal domestication and selection for complex phenotypic traits.
Field of genes: using Apache Kafka as a bioinformatic data repository
Authors: Lawlor Brendan , Lynch Richard , Mac Aogáin Micheál , Walsh Paul
Published: April 2018

Background

Bioinformatic research is increasingly dependent on large-scale datasets, accessed either from private or public repositories. An example of a public repository is National Center for Biotechnology Information's (NCBI's) Reference Sequence (RefSeq). These repositories must decide in what form to make their data available. Unstructured data can be put to almost any use but are limited in how access to them can be scaled. Highly structured data offer improved performance for specific algorithms but limit the wider usefulness of the data. We present an alternative: lightly structured data stored in Apache Kafka in a way that is amenable to parallel access and streamed processing, including subsequent transformations into more highly structured representations. We contend that this approach could provide a flexible and powerful nexus of bioinformatic data, bridging the gap between low structure on one hand, and high performance and scale on the other. To demonstrate this, we present a proof-of-concept version of NCBI's RefSeq database using this technology. We measure the performance and scalability characteristics of this alternative with respect to flat files.

Results

The proof of concept scales almost linearly as more compute nodes are added, outperforming the standard approach using files.

Conclusions

Apache Kafka merits consideration as a fast and more scalable but general-purpose way to store and retrieve bioinformatic data, for public, centralized reference datasets such as RefSeq and for private clinical and experimental data.
The draft genome sequence of forest musk deer (Moschus berezovskii)
Authors: Fan Zhenxin , Li Wujiao , Jin Jiazheng , Cui Kai , Yan Chaochao , Peng Changjun , Jian Zuoyi , Bu Ping , Price Megan , Zhang Xiuyue , Shen Yongmei , Li Jing , Qi Wenhua , Yue Bisong
Published: April 2018

Background

The forest musk deer, Moschus berezovskii, is one of seven musk deer (Moschus spp.) and is distributed in Southwest China. Akin to other musk deer, the forest musk deer has been traditionally and is currently hunted for its musk (i.e., global perfume industry). Considerable hunting pressure and habitat loss have caused significant population declines. Consequently, the Chinese government commenced captive breeding programs for musk harvesting in the 1950s. However, the prevalence of fatal diseases is considerably restricting population increases. Disease severity and extent are exacerbated by inbreeding and genetic diversity declines in captive musk deer populations. It is essential that knowledge of captive and wild forest musk deer populations' immune system and genome be gained in order to improve their physical and genetic health. We have thus sequenced the whole genome of the forest musk deer, completed the genomic assembly and annotation, and performed preliminary bioinformatic analyses.

Findings

A total of 407 Gb raw reads from whole-genome sequencing were generated using the Illumina HiSeq 4000 platform. The final genome assembly is around 2.72 Gb, with a contig N50 length of 22.6 kb and a scaffold N50 length of 2.85 Mb. We identified 24,352 genes and found that 42.05% of the genome is composed of repetitive elements. We also detected 1,236 olfactory receptor genes. The genome-wide phylogenetic tree indicated that the forest musk deer was within the order Artiodactyla, and it appeared as the sister clade of four members of Bovidae. In total, 576 genes were under positive selection in the forest musk deer lineage.

Conclusions

We provide the first genome sequence and gene annotation for the forest musk deer. The availability of these resources will be very useful for the conservation and captive breeding of this endangered and economically important species and for reconstructing the evolutionary history of the order Artiodactyla.
Comparative whole genome DNA methylation profiling of cattle sperm and somatic tissues reveals striking hypomethylated patterns in sperm
Authors: Zhou Yang , Connor Erin E , Bickhart Derek M , Li Congjun , Baldwin Ransom L , Schroeder Steven G , Rosen Benjamin D , Yang Liguo , Van Tassell Curtis P , Liu George E
Published: April 2018

Background

Although sperm DNA methylation has been studied in humans and other species, its status in cattle is largely unknown.

Results

Using whole-genome bisulfite sequencing (WGBS), we profiled the DNA methylome of cattle sperm through comparison with three somatic tissues (mammary gland, brain, and blood). Large differences between cattle sperm and somatic cells were observed in the methylation patterns of global CpGs, pericentromeric satellites, partially methylated domains (PMDs), hypomethylated regions (HMRs), and common repeats. As expected, we observed low methylation in the promoter regions and high methylation in the bodies of active genes. We detected selective hypomethylation of megabase domains of centromeric satellite clusters, which may be related to chromosome segregation during meiosis and their rapid transcriptional activation upon fertilization. We found more PMDs in sperm cells than in somatic cells and identified meiosis-related genes such asKIF2B and REPIN1, which are hypomethylated in sperm but hypermethylated in somatic cells. In addition to the common HMRs around gene promoters, which showed substantial differences between sperm and somatic cells, the sperm-specific HMRs also targeted to distinct spermatogenesis-related genes, including BOLL, MAEL, ASZ1, SYCP3, CTCFL, MND1, SPATA22, PLD6, DDX4, RBBP8, FKBP6, and SYCE1. Although common repeats were heavily methylated in both sperm and somatic cells, some young Bov-A2 repeats, which belong to the SINE family, were hypomethylated in sperm and could affect the promoter structures by introducing new regulatory elements.

Conclusions

Our study provides a comprehensive resource for bovine sperm epigenomic research and enables new discoveries about DNA methylation and its role in male fertility.
Are We Delivering Optimal Pulmonary Rehabilitation? The Importance of Quality Indicators in Evaluating Clinical Practice
Authors: Camp Pat G , Cheung Walden
Published: April 2018

Pulmonary rehabilitation (PR) is a complex intervention that has been shown to improve exercise capacity and quality of life, reduce dyspnea, and decrease the risk of exacerbations and hospitalization. Although the evidence for PR is strong, the translation of this evidence into clinical practice remains a challenge, and important gaps in care exist. To date, most research in PR has focused on questions related to treatment efficacy. Less attention has been paid to confirming whether the strong evidence base of PR has been effectively translated to this complex clinical setting. Policy makers and other stakeholders in PR are calling for the establishment of core standards and quality indicators in PR to evaluate existing programs and improve patient care. However, what are quality indicators, and how are they used? This Perspective explores quality assurance in the context of PR and introduces the concepts and uses of quality indicators that can be used to evaluate and improve the quality of care.
The ERBB network facilitates KRAS-driven lung tumorigenesis
Authors: Kruspig Björn , Monteverde Tiziana , Neidler Sarah , Hock Andreas , Kerr Emma , Nixon Colin , Clark William , Hedley Ann , Dick Craig , Vousden Karen , Martins Carla , Murphy Daniel J.
Published: April 2018

KRAS is the most frequently mutated driver oncogene in human adenocarcinoma of the lung. There are presently no clinically proven strategies for treatment of KRAS-driven lung cancer. Activating mutations in KRAS are thought to confer independence from upstream signaling, however recent data suggest that this independence may not be absolute. Here we show that initiation and progression of KRAS-driven lung tumors requires input from ERBB family RTKs: Multiple ERBB RTKs are expressed and active from the earliest stages of KRAS driven lung tumor development, and treatment with a multi-ERBB inhibitor suppresses formation of KRasG12D-driven lung tumors. We present evidence that ERBB activity amplifies signaling through the core RAS pathway, supporting proliferation of KRAS mutant tumor cells in culture and progression to invasive disease in vivo. Importantly, brief pharmacological inhibition of the ERBB network significantly enhances the therapeutic benefit of MEK inhibition in an autochthonous tumor setting. Our data suggest that lung cancer patients with KRAS-driven disease may benefit from inclusion of multi-ERBB inhibitors in rationally designed treatment strategies.

One Sentence Summary

G12 Mutant KRAS requires tonic ERBB network activity for initiation and maintenance of lung cancer
Snapshot: clustering and visualizing epigenetic history during cell differentiation
Authors: Xiang Guanjue , Giardine Belinda , An Lin , Sun Chen , Keller Cheryl A. , Heuston Elisabeth , Bodine David , Hardison Ross C , Zhang Yu
Published: April 2018

Epigenetic modification of chromatin plays a pivotal role in regulating gene expression during cell differentiation. The scale and complexity of epigenetic data pose significant challenges for biologists to identify the regulatory events controlling cell differentiation. Here, we present a new method, called Snapshot, that uses epigenetic data to generate a hierarchical visualization for DNA regions with epigenetic features segregating along any given cell differentiation hierarchy of interest. Different hierarchies of cell types may be used to highlight the epigenetic history specific to any particular cell lineage. We demonstrate the utility of Snapshot using data from the VISION project, an international project for ValIdated Systematic IntegratiON of epigenomic data in mouse and human hematopoiesis.

Availability and implementation: https://github.com/guanjue/snapshot
Analgesia linked to Nav1.7 loss of function requires μ and δ opioid receptors
Authors: Pereira Vanessa , Millet Queensta , Aramburu Jose , Lopez-Rodriguez Cristina , Ruff Claire Gaveriaux , Wood John N
Published: April 2018

Functional deletion of the SCN9A gene encoding sodium channel Nav1.7 makes humans and mice pain-free (1,2). Opioid signaling contributes to this analgesic state (3). Here we show that the pharmacological block or deletion of both μ and δ opioid receptors is required to abolish Nav1.7 null opioid-related analgesia.κ-opioid receptor antagonists were without effect. Enkephalins encoded by the Penk gene are upregulated in Nav1.7 nulls (3). Deleting Nfat5, a transcription factor with binding motifs upstream of Penk (4), induces the same level of enkephalin mRNA expression as found in Nav1.7 nulls, but without consequent analgesia. These data confirm that a combination of events linked to SCN9A gene loss is required for analgesia. Higher levels of endogenous enkephalins (3), potentiated opioid receptors (5), diminished electrical excitability (6,7) and loss of neurotransmitter release (2,1) together contribute to the analgesic phenotype found in Nav1.7 null mouse and human mutants. These observations help explain the failure of Nav1.7 channel blockers alone to produce analgesia and suggest new routes for analgesic drug development.
Strategies for quantitative RNA-seq analyses among closely related species
Authors: Parekh Swati , Vieth Beate , Ziegenhain Christoph , Enard Wolfgang , Hellmann Ines
Published: April 2018

With the growing appreciation for the role of regulatory differences in evolution, researchers need to reliably quantify expression levels within and among species. However, for non-model organisms genome assemblies and annotations are often not available or have inferior quality, biasing the inference of expression changes to an unknown extent. Here, we explore the possibility to map RNA-seq reads from diverged species to one high quality reference genome. As test case, we used a small primate phylogeny ranging from Human to Marmoset spanning 12% nucleotide divergence. To distinguish the effect of sequence divergence and genome quality, we used in silico evolved genomes and existing genomes to simulate RNA-seq reads. These were then mapped to the genome of origin (self-mapping) as well as to one common reference (cross-mapping) to infer the quantification biases. We find that the bias due to cross-mapping is small for the closely related great apes (≤ 4% divergence), and preferable to self-mapping given current genome qualities. For closely related species, cross-mapping provides easy access, high power and a well controlled false discovery rate for both; the analysis of intra-species expression differences as well as the detection of relative differences between species. If divergence increases, so that a substantial fraction of reads exceeds the limits of the mapper used, we find that gene-specific corrections and effect-size cutoffs can limit the bias before self-mapping becomes unavoidable. In summary, for the first time we systematically quantify biases in cross-species RNA-seq studies, providing guidance to best practices for these important evolutionary studies.
RGS14 restricts plasticity in hippocampal CA2 by limiting postsynaptic calcium signaling
Authors: Evans Paul R. , Parra-Bueno Paula , Smirnov Michael S. , Lustberg Daniel J. , Dudek Serena M. , Hepler John R. , Yasuda Ryohei
Published: April 2018

Pyramidal neurons in hippocampal area CA2 are distinct from neighboring CA1 in that they resist synaptic long-term potentiation (LTP) at CA3 Schaffer Collateral synapses. Regulator of G Protein Signaling 14 (RGS14) is a complex scaffolding protein enriched in CA2 dendritic spines that naturally blocks CA2 synaptic plasticity and hippocampus-dependent learning, but the cellular mechanisms by which RGS14 gates LTP are largely unexplored. A previous study has attributed the lack of plasticity to higher rates of calcium (Ca2+) buffering and extrusion in CA2 spines. Additionally, a recent proteomics study revealed that RGS14 interacts with two key Ca2+-activated proteins in CA2 neurons: calcium/calmodulin, and CaMKII. Here, we investigate whether RGS14 regulates Ca2+ signaling in its host CA2 neurons. We find the nascent LTP of CA2 synapses due to genetic knockout (KO) of RGS14 in mice requires Ca2+-dependent postsynaptic signaling through NMDA receptors, CaMK, and PKA, revealing similar mechanisms to those in CA1. We report RGS14 negatively regulates the long-term structural plasticity of dendritic spines of CA2 neurons. We further show that wild-type (WT) CA2 neurons display significantly attenuated spine Ca2+ transients during structural plasticity induction compared with the Ca2+ transients from CA2 spines of RGS14 KO mice and CA1 controls. Finally, we demonstrate that acute overexpression of RGS14 is sufficient to block spine plasticity, and elevating extracellular Ca2+ levels restores plasticity to RGS14-expressing neurons. Together, these results demonstrate for the first time that RGS14 regulates plasticity in hippocampal area CA2 by restricting Ca2+ elevations in CA2 spines and downstream signaling pathways.

Significance Statement

Recent studies of hippocampal area CA2 have provided strong evidence in support of a clear role for this apparently plasticity-resistant subregion of the hippocampus in social, spatial, and temporal aspects of memory. Regulator of G Protein Signaling 14 (RGS14) is a critical factor that inhibits synaptic plasticity in CA2, but the molecular mechanisms by which RGS14 limits LTP remained unknown. Here we provide new evidence that RGS14 restricts spine calcium (Ca2+) in CA2 neurons and that key downstream Ca2+-activated signaling pathways are required for CA2 plasticity in mice lacking RGS14. These results define a previously unrecognized role for RGS14 as a natural inhibitor of postsynaptic Ca2+ signaling in hippocampal area CA2.
Rhizosphere microbes and host plant genotype influence the plant metabolome and reduce insect herbivory
Authors: Hubbard Charley J. , Li Baohua , McMinn Robby , Brock Marcus T. , Maignien Lois , Ewers Brent E. , Kliebenstein Daniel , Weinig Cynthia
Published: April 2018

Rhizosphere microbes affect plant performance, including plant resistance against insect herbivores; yet, the relative influence of rhizosphere microbes vs. plant genotype on herbivory levels and on metabolites related to defense remains unclear.

In Boechera stricta, we tested the effects of rhizosphere microbes and plant genotype on herbivore resistance, the primary metabolome, and select secondary metabolites.

Plant populations differed significantly in the concentrations of 6 glucosinolates (GLS), secondary metabolites known to provide herbivore resistance in the Brassicaceae, and the population with lower GLS levels experienced ~60% higher levels of aphid (Aphis spp.) attack; no effect was observed of GLS on damage by a second herbivore, flea beetles (Altica spp.). Rhizosphere microbiome (intact vs. disrupted) had no effect on plant GLS concentrations. However, aphid number and flea beetle damage were respectively ~3-fold and 7-fold higher among plants grown in the disrupted rhizosphere microbiome treatment, and distinct (as estimated from 16s rRNA amplicon sequencing) intact native microbiomes also differed in their effects on herbivore damage. These differences may be attributable to shifts in primary metabolic pathways.

The findings suggest that rhizosphere microbes can play a greater role than plant genotype in defense against insect herbivores, and act through mechanisms independent of plant genotype.
Mendelian randomization does not support serum calcium in prostate cancer risk
Authors: Yarmolinsky James , Berryman Katie , Langdon Ryan , Bonilla Carolina ,   the PRACTICAL consortium, Smith George Davey , Martin Richard M , Lewis Sarah J
Published: April 2018

Background: Observational studies suggest that dietary and serum calcium are risk factors for prostate cancer. However, such studies suffer from residual confounding (due to unmeasured or imprecisely measured confounders), undermining causal inference. Mendelian randomization uses randomly assigned (hence unconfounded and pre-disease onset) germline genetic variation to proxy for phenotypes and strengthen causal inference in observational studies.

Objective: We tested the hypothesis that serum calcium is associated with an increased risk of overall and advanced prostate cancer.

Design: A genetic instrument was constructed using 5 single nucleotide polymorphisms robustly associated with serum calcium in a genome-wide association study (N ≤ 61,079). This instrument was then used to test the effect of a 0.5 mg/dL increase (1 standard deviation, SD) in serum calcium on risk of prostate cancer in 72,729 men in the PRACTICAL (Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome) Consortium (44,825 cases, 27,904 controls) and risk of advanced prostate cancer in 33,498 men (6,263 cases, 27,235 controls).

Results: We found weak evidence for a protective effect of serum calcium on prostate cancer risk (odds ratio [OR] per 0.5 mg/dL increase in calcium: 0.83, 95% CI: 0.63-1.08; P=0.12). We did not find strong evidence for an effect of serum calcium on advanced prostate cancer (OR per 0.5 mg/dL increase in calcium: 0.98, 95% CI: 0.57-1.70; P=0.93).

Conclusions: Our Mendelian randomization analysis does not support the hypothesis that serum calcium increases risk of overall or advanced prostate cancer.
A fast and agnostic method for bacterial genome-wide association studies: bridging the gap between kmers and genetic events
Authors: Jaillard Magali , Lima Leandro , Tournoud Maud , Mahé Pierre , Belkum Alex van , Lacroix Vincent , Jacob Laurent
Published: April 2018

Motivation

Genome-wide association study (GWAS) methods applied to bacterial genomes have shown promising results for genetic marker discovery or fine-assessment of marker effect. Recently, alignment-free methods based on kmer composition have proven their ability to explore the accessory genome. However, they lead to redundant descriptions and results which are hard to interpret.

Methods

Here, we introduce DBGWAS, an extended kmer-based GWAS method producing interpretable genetic variants associated with pheno-types. Relying on compacted De Bruijn graphs (cDBG), our method gathers cDBG nodes identified by the association model into subgraphs defined from their neighbourhood in the initial cDBG. DBGWAS is fast, alignment-free and only requires a set of contigs and phenotypes. It produces annotated subgraphs representing local polymorphisms as well as mobile genetic elements (MGE) and offers a graphical framework to interpret GWAS results.

Results

We validated our method using antibiotic resistance phenotypes for three bacterial species. DBGWAS recovered known resistance determinants such as mutations in core genes in Mycobacterium tuberculosis and genes acquired by horizontal transfer in Staphylococcus aureus and Pseudomonas aeruginosa – along with their MGE context. It also enabled us to formulate new hypotheses involving genetic variants not yet described in the antibiotic resistance literature.

Conclusion

Our novel method proved its efficiency to retrieve any type of phenotype-associated genetic variant without prior knowledge. All experiments were computed in less than two hours and produced a compact set of meaningful subgraphs, thereby outperforming other GWAS approaches and facilitating the interpretation of the results.

Availability

Open-source tool available at https://gitlab.com/leoisl/dbgwas
Long-read sequence capture of the hemoglobin gene clusters across species
Authors: Hoff Siv Nam Khang , Baalsrud Helle T. , Tooming-Klunderud Ave , Skage Morten , Richmond Todd , Obernosterer Gregor , Shirzadi Reza , Tørresen Ole Kristian , Jakobsen Kjetill S. , Jentoft Sissel
Published: April 2018

Combining high-throughput sequencing with targeted sequence capture has become an attractive tool to study specific genomic regions of interest. Most studies have so far focused on the exome using short-read technology. These approaches are not designed to capture intergenic regions needed to reconstruct genomic organization, including regulatory regions and gene synteny. Here, we demonstrate the power of combining targeted sequence capture with long-read sequencing technology for comparative genomic analyses of the hemoglobin (Hb) gene clusters across eight species separated by up to 70 million years. Guided by the reference genome assembly of the Atlantic cod (Gadus morhua) together with genome information from draft assemblies of selected codfishes, we designed probes covering the two Hb gene clusters. Use of custom-made barcodes combined with PacBio RSII sequencing led to highly continuous assemblies of the LA (~100kb) and MN (~200kb) clusters, which include syntenic regions of coding and intergenic sequences. Our results revealed an overall conserved genetic organization and synteny of the Hb genes within this lineage, yet with several, lineage-specific gene duplications. Moreover, for some of the species examined, we identified amino acid substitutions at two sites in the Hbb1 gene as well as length polymorphisms in its regulatory region, which has previously been linked to temperature adaptation in Atlantic cod populations. This study highlights the use of targeted long-read capture as a versatile approach for comparative genomic studies by generation of a cross-species genomic resource elucidating the evolutionary history of the Hb gene family across the highly divergent group of codfishes.
Androgen Promotes Differentiation of PLZF+Spermatogonia pool via Indirect Regulatory Pattern
Authors: Wang Jingjing , Li Jinmei , Gu Yunzhao , Xia Qin , Song Weixiang , Zhang Xiaoyu , Yang Yang , Wang Wei , Li Hua , Zou Kang
Published: April 2018

Androgen signaling plays a pivotal role in spermatogenesis, but the molecular mechanisms underlying androgen action in this process are unclear. Specifically, it is unknown if the androgen receptor (AR) is expressed in germ cells. Thus it’s interesting to reveal how androgen induces differentiation of spermatogonial progenitor cells (SPCs) in the niche. Here we observed the AR is primarily expressed in pre-spermatogonia of mice 2 days post partum (dpp), absent before spermatogenesis onset, and then expressed in surrounding Sertoli cells. Then we examined a regulatory role of the AR in spermatogenesis using a SPCs-Sertoli cells co-culture system, and demonstrated that androgen negatively regulatedPlzf(the gene for stemness maintenance of SPCs). Additionally, we identified Gata2 as a target of AR in Sertoli cells, and demonstrated that Wilms tumor 1 (WT1) and β1-integrin as two putative intermediate molecules to transfer differentiation signals to SPCs, which was further verified using androgen pharmacological-deprivation mice model. These results demonstrate a regulatory pattern of androgen in SPCs niche in an indirect way via multiple steps of signal transduction.
Systematically investigating the key features of the nuclease deactivated Cpf1 for tunable multiplex genetic regulation
Authors: Miao Chensi , Zhao Huiwei , Qian Long , Lou Chunbo
Published: April 2018

With a unique crRNA processing capability, the CRISPR associated Cpf1 protein holds great potential for multiplex gene regulation. Unlike the well-studied Cas9 protein, however, conversion of Cpf1 to a transcription regulator and its related properties have not been systematically explored yet. In this study, we investigated the mutation schemes and crRNA requirements for the nuclease deactivated Cpf1 (dCpf1). By shortening the direct repeat sequence, we obtained genetically stable crRNA co-transcripts and improved gene repression with multiplex targeting. A screen of diversity-enriched PAM library was designed to investigate the PAM-dependency of gene regulation by dCpf1 from Francisella novicida and Lachnospiraceae bacterium. We found novel PAM patterns that elicited strong or medium gene repressions. Using a computational algorithm, we predicted regulatory outputs for all possible PAM sequences, which spanned a large dynamic range that could be leveraged for regulatory purposes. These newly identified features will facilitate the efficient design of CRISPR-dCpf1 based systems for tunable multiplex gene regulation.
Oxidative Stress Mediates UVC-Induced Increases in Epidermal Autofluorescence of C57 Mouse Ears
Authors: Zhang Mingchao , Maharjan Dhruba Tara , Li Yujia , Ying Weihai
Published: April 2018

Our recent study has reported that UV-induced epidermal autofluorescence (AF) can be used as a novel biomarker for predicting UV-induced skin damage, which is originated from UV-induced, cysteine protease-mediated keratin 1 degradation. A key question regarding these findings is: Does oxidative stress play a significant role in the UV-induced epidermal AF and keratin 1 proteolysis? In our current study, we administered the widely used antioxidant N-acetyl cysteine (NAC) into the skin of mouse ears to test our hypothesis that oxidative stress mediates UV-induced increases in the epidermal AF and keratin 1 degradation. Our study has shown that NAC administration can significantly attenuate the UVC-induced AF increases. The NAC administration can also significantly decrease the UVC-induced keratin 1 degradation. Collectively, our findings have indicated that the oxidative stress induced by UVC is causative to the UVC-induced increases in epidermal AF and keratin 1 proteolysis. Moreover, since oxidative stress is significantly increased in multiple regions of the body in several major diseases, the oxidative stress-induced increases in epidermal AF may become a novel biomarker for diagnosis of major diseases.
Increased green autofluorescence is a marker for non-invasive prediction of H2O2-induced cell death and decreases in the intracellular ATP of HaCaT cells
Authors: Xu Jie , Ying Weihai
Published: April 2018

Since oxidative stress plays important pathological roles in numerous diseases, it is of both critical theoretical and clinical significance to search for the approaches for predicting oxidative damage. Cellular models have great value for studying oxidative damage, which would be significantly promoted if non-invasive approaches for predicting oxidative damage can be established without the need of exogenous probes. In our current study, we tested our hypothesis that changes of the autofluorescence (AF) of cells may be used for predicting oxidative cellular damage. Our study found that H2O2 dose-dependently increased the green AF of HaCaT keratinocyte cell line at non-nuclear regions assessed at 1 hr or 3 hrs after the H2O2 exposures, while H2O2 did not affect the green AF of other cell types tested in our study, including PC 12 cells and BV2 microglia. We further found that the increases in the AF of HaCaT cells are highly correlated with the H2O2-induced increases in early-stage apoptosis, late-stage apoptosis and necrosis assessed at 18 hrs after the H2O2 exposures, which are also negatively correlated with the intracellular ATP levels of the H2O2-treated cells assessed at 18 hrs after the H2O2 exposures. Collectively, our study has suggested that increased AF may become the first endogenous marker for non-invasive prediction of oxidative damage selectively for such cell types as HaCaT cells. Compared with traditional approaches, our method may have significant value for studying oxidative damage of keratinocytes with significantly higher efficiency and lower cost.
Genetic control of transition from juvenile to mature wood with respect to microfibril angle (MFA) in Norway spruce (Picea abies) and lodgepole pine (Pinus contorta)
Authors: Hayatgheibi Haleh , Forsberg Nils , Lundqvist Sven-Olof , Mörling Tommy , Mellerowicz Ewa J. , Karlsson Bo , Wu Harry , García Gil M Rosario
Published: April 2018

Genetic control of microfibril angle (MFA) transition from juvenile to mature was evaluated in Norway spruce and lodgepole pine. Increment cores were collected at breast height from 5,618 trees in two 21-year-old Norway spruce progeny trials in southern Sweden, and from 823 trees in two 34-35 – year-old lodgepole pine progeny trials in northern Sweden. Radial variations in MFA from pith to bark were measured for each core using SilviScan. To estimate MFA transition from juvenile to mature, a threshold level of MFA 20° was considered and six different regression functions were fitted to the MFA profile of each tree after exclusion of outliers, following three steps. The narrow-sense heritability estimates (h2) obtained for MFA transition were highest based on the slope function, ranging from 0.21 to 0.23 for Norway spruce and from 0.34 to 0.53 for lodgepole pine, whileh2were mostly non-significant based on the logistic function, under all exclusion methods. Results of this study indicate that it is possible to select for an earlier MFA transition from juvenile to mature in Norway spruce and lodgepole pine selective breeding programs, as the genetic gains (∆G) obtained in direct selection of this trait were very high in both species.
Online customer experience (OCE) in clothing e-retail
Authors: Pandey Shweta , Chawla Deepak
Published: April 2018

Purpose

The purpose of this paper is to explore the dimensions of online customer experience (OCE) and their impact on satisfaction and loyalty in the clothing e-retail context. Furthermore, it explores the influence of gender on the OCE-satisfaction-loyalty chain.

Design/methodology/approach

OCE dimensions were drawn from the literature and then adapted and validated using two samples (217 – exploratory factor analysis, 651 – confirmatory factor analysis) of experienced online clothing shoppers in India. An analysis was done using structured equation modelling.

Findings

Six OCE psychological factors and four OCE functionality factors were revealed. Both OCE dimensions impact loyalty either directly or indirectly through satisfaction. Gender is observed to moderate the relationship among three OCE factors (e-distrust, e-negative beliefs and website interactivity) and satisfaction.

Research limitations/implications

The research results are limited to the factors related to each of the two OCE dimensions explored within the clothing e-retail context in India.

Practical implications

Clothing e-retailers need to focus on both the OCE dimensions to drive business sustenance. Furthermore, their OCE strategies should be in line with the gender-based differences highlighted by the study.

Originality/value

The study facilitates in the adaptation and validation of the OCE dimensions in the clothing e-retail category in an emerging market. While all factors associated with both OCE dimensions are important for driving satisfaction and loyalty, the study underscores the need for a higher focus on visual engagement by e-retailers in the given context. Gender moderates the OCE-satisfaction paths, but does not moderate the OCE-loyalty paths.
Community‐acquired Acute Kidney Injury Among Children Seen in the Pediatric Emergency Department
Authors: Bernardo Erika O. , Cruz Andrea T. , Buffone Gregory J. , Devaraj Sridevi , Loftis Laura L. , Arikan Ayse Akcan
Published: April 2018

Objectives

Acute kidney injury (AKI) is a significant risk factor for morbidity and mortality in children. Little is known about community‐acquired AKI (CA‐AKI) in the pediatric emergency department (PED). Early recognition of AKI allows for nephroprotective measures. The goal of this investigation was to determine the incidence of CA‐AKI and the frequency of clinician identified CA‐AKI to better inform future nephroprotective interventions.

Methods

This was a retrospective cross‐sectional study in the PED of a children's hospital. Children 1 month to 18 years of age seen in the PED from January 1 to December 31, 2015, and in whom at least one creatinine level was obtained were included. Patients with chronic kidney disease or end‐stage renal disease or who died in the PED were excluded. Patients had CA‐AKI based on modified Kidney Disease‐Improving Global Outcomes criteria using the creatinine obtained in the PED compared to age‐specific norms. Patients were considered identified if the PED clinician diagnosed AKI. The primary outcome was the incidence of CA‐AKI. Secondary outcomes included frequency of AKI identification, nephrotoxic medication use, hospital length of stay, renal replacement therapy, and death. Fisher exact test or Pearson's chi‐square test was used to calculate odds ratio (OR) with 95% confidence intervals (CIs); multivariable analyses were performed using logistic regression.

Results

In 2015 there were 119,151 PED visits; 15,486 met inclusion criteria. CA‐AKI was present in 239 of 15,486 (1.5%) encounters. AKI was identified by PED clinicians in 46 of 239 (19%) of encounters and by the inpatient team in 123 of 199 (62%) of the encounters admitted. AKI was never recognized by a PED or inpatient clinician in 74 of 199 (37%) encounters. Encounters with AKI correctly diagnosed were older (13 years old vs. 10 years old, p = 0.0114), had more severe (stage 2 or 3) AKI (OR = 5.5, 95% CI = 2.6–11.8), and were more likely to be admitted (OR = 10.3, 95% CI = 1.38–77.4) than encounters with missed AKI.

Conclusions

CA‐AKI remains an underrecognized entity in the PED. Better tools for early recognition of AKI in the busy PED environment are needed.
The Bursts and Lulls of Multimodal Interaction: Temporal Distributions of Behavior Reveal Differences Between Verbal and Non‐Verbal Communication
Authors: Abney Drew H. , Dale Rick , Louwerse Max M. , Kello Christopher T.
Published: April 2018

Recent studies of naturalistic face‐to‐face communication have demonstrated coordination patterns such as the temporal matching of verbal and non‐verbal behavior, which provides evidence for the proposal that verbal and non‐verbal communicative control derives from one system. In this study, we argue that the observed relationship between verbal and non‐verbal behaviors depends on the level of analysis. In a reanalysis of a corpus of naturalistic multimodal communication (Louwerse, Dale, Bard, & Jeuniaux, ), we focus on measuring the temporal patterns of specific communicative behaviors in terms of their burstiness. We examined burstiness estimates across different roles of the speaker and different communicative modalities. We observed more burstiness for verbal versus non‐verbal channels, and for more versus less informative language subchannels. Using this new method for analyzing temporal patterns in communicative behaviors, we show that there is a complex relationship between verbal and non‐verbal channels. We propose a “temporal heterogeneity” hypothesis to explain how the language system adapts to the demands of dialog.
Association of the novel susceptible locus rs9266150 with clinical features of psoriasis vulgaris in the Chinese Han population
Authors: Wu Juan , Huang Yan , Guo Huimin , Ye Lei , Huang Yong , Huang Hequn , Qian Wenjun , Zhang Xuelei , Wang Wenjun , Zheng Xiaodong , Zhang Xuejun , Fan Xing , Liu Jianjun , Yang Sen
Published: April 2018

Psoriasis is a chronic multifactorial disease and is considered to be strongly associated with the major histocompatibility complex (MHC) region. We have discovered an independent, novel and susceptible psoriasis risk HLA loci, rs9266150; P = 4.52 × 10−9 for the first time. In this study, we aimed to verify the relationship between the susceptible locus and the subphenotypes of psoriasis vulgaris (PV), including geographic location, gender, age of onset, family history and present skin lesion types (chronic plaque and guttate). To investigate the distribution and association of the rs9266150 gene with clinical phenotypes of PV in Chinese Han population, we conducted an analysis in case‐control and case‐only subjects in the 9906 controls and 8744 cases by MHC targeted sequencing stratified analysis in this study. Significant associations were found with a northern geographic location in the case‐only (P = 1.97 × 10−4) and the subphenotype‐control analyses (P = 5.57 × 10−5), males in the case‐only (P = 4.77 × 10−3) and the subphenotype‐control analyses (P = 7.31 × 10−4), and guttate psoriasis in the case‐only (P = 4.08 × 10−3) and the subphenotype‐control analyses (P = 1.27 × 10−3). There were no significant differences observed between the age of onset (OR = 1.062, 95% CI: 0.9725‐1.16, P = 1.8 × 10−1) and the family history of psoriasis (OR = 0.981, 95% CI: 0.9048‐1.064, P = 6.43 × 10−1). The recessive model provided the best fit for rs9266150 (P = 4.38 × 10−7). Our results implied that rs9266150 might not only play an important role in the development of psoriasis, but also be positively associated with the geographic location, gender and present skin lesion in the Chinese population.
Autophagy during ageing – from Dr Jekyll to Mr Hyde
Authors: Wilhelm Thomas , Richly Holger
Published: April 2018

Autophagy is a ubiquitous catabolic process, which causes cellular bulk degradation through vesicular engulfment of obsolete, damaged or harmful cytoplasmic components. While autophagy regulates cellular homeostasis during development and in youth, there is mounting evidence that autophagy becomes increasingly dysfunctional with age. Recent work in Caenorhabditis elegans even suggests that late‐life dysfunctional autophagy exhibits detrimental effects that drive the ageing process. Other studies link elevated autophagy closely to increased health and longevity. This review aims to put these apparently opposing views into perspective and define our current understanding of the role of autophagy during ageing.