bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recovery of trait heritability from whole genome sequence data
Authors: Wainschtein Pierrick , Jain Deepti , Zheng Zhili ,   TOPMed Anthropometry Working Group,   NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Cupples L. Adrienne , Shadyab Aladdin H. , McKnight Barbara , Shoemaker Benjamin M. , Mitchell Braxton D. , Psaty Bruce M. , Kooperberg Charles , Liu Ching-Ti , Albert Christine M. , Roden Dan , Chasman Daniel I. , Darbar Dawood , Lloyd-Jones Donald M , Arnett Donna K. , Regan Elizabeth A. , Boerwinkle Eric , Rotter Jerome I. , O’Connell Jeffrey R. , Yanek Lisa R. , de Andrade Mariza , Allison Matthew A. , McDonald Merry-Lynn N. , Chung Mina K , Fornage Myriam , Chami Nathalie , Smith Nicholas L. , Ellinor Patrick T. , Vasan Ramachandran S. , Mathias Rasika A. , Loos Ruth J.F. , Rich Stephen S. , Lubitz Steven A. , Heckbert Susan R. , Redline Susan , Guo Xiuqing , Chen Y.-D Ida , Laurie Cecelia A. , Hernandez Ryan D. , McGarvey Stephen T. , Goddard Michael E. , Laurie Cathy C. , North Kari E. , Lange Leslie A. , Weir Bruce S. , Yengo Loic , Yang Jian , Visscher Peter M. 
Published: March 2019

AbstractHeritability, the proportion of phenotypic variance explained by genetic factors, can be estimated from pedigree data 1, but such estimates are uninformative with respect to the underlying genetic architecture. Analyses of data from genome-wide association studies (GWAS) on unrelated individuals have shown that for human traits and disease, approximately one-third to two-thirds of heritability is captured by common SNPs 2–5. It is not known whether the remaining heritability is due to the imperfect tagging of causal variants by common SNPs, in particular if the causal variants are rare, or other reasons such as overestimation of heritability from pedigree data. Here we show that pedigree heritability for height and body mass index (BMI) appears to be largely recovered from whole-genome sequence (WGS) data on 25,465 unrelated individuals of European ancestry. We assigned 33.7 million genetic variants to groups based upon their minor allele frequencies (MAF) and linkage disequilibrium (LD) with variants nearby, and estimated and partitioned genetic variance accordingly. The estimated heritability was 0.68 (SE 0.10) for height and 0.30 (SE 0.10) for BMI, with a range of ~0.60 – 0.71 for height and ~0.25 – 0.35 for BMI, depending on quality control and analysis strategies. Low-MAF variants in low LD with neighbouring variants were enriched for heritability, to a greater extent for protein-altering variants, consistent with negative selection thereon. Cumulatively variants with 0.0001 < MAF < 0.1 explained 0.47 (SE 0.07) and 0.30 (SE 0.10) of heritability for height and BMI, respectively. Our results imply that rare variants, in particular those in regions of low LD, is a major source of the still missing heritability of complex traits and disease.
Magnus Representation of Genome Sequences
Authors: Wu Chengyuan , Ren Shiquan , Wu Jie , Xia Kelin 
Published: March 2019

AbstractWe introduce an alignment-free method, the Magnus Representation, to analyze genome sequences. The Magnus Representation captures higher-order information in genome sequences. We combine our approach with the idea ofk-mers to define an effectively computable Mean Magnus Vector. We perform phylogenetic analysis on three datasets: mosquito-borne viruses, filoviruses, and bacterial genomes. Our results on ebolaviruses are consistent with previous phylogenetic analyses, and confirm the modern viewpoint that the 2014 West African Ebola outbreak likely originated from Central Africa. Our analysis also confirms the close relationship betweenBundibugyo ebolavirusandTaï Forest ebolavirus. For bacterial genomes, our method is able to classify relatively well at the family and genus level, as well as at higher levels such as phylum level. The bacterial genomes are also separated well into Gram-positive and Gram-negative subgroups.
Bioorthogonal non-canonical amino acid tagging reveals translationally active subpopulations of the cystic fibrosis lung microbiota
Authors: Valentini Talia D. , Lucas Sarah K. , Binder Kelsey A. , Cameron Lydia C. , Motl Jason A. , Dunitz Jordan M. , Hunter Ryan C. 
Published: March 2019

AbstractCulture-independent studies of cystic fibrosis lung microbiota have provided few mechanistic insights into the polymicrobial basis of disease. Deciphering the specific contributions of individual taxa to CF pathogenesis requires a comprehensive understanding of theirin situecophysiology. We applied bioorthogonal non-canonical amino acid tagging (BONCAT), a ‘click’ chemistry-based metabolic labeling approach, to quantify and visualize translational activity among CF microbiota. Using BONCAT-based fluorescent imaging on sputum collected from stable CF subjects, we reveal that only a subset of bacteria are translationally active. We also combined BONCAT with fluorescent activated cell sorting (FACS) and 16S rRNA gene sequencing to assign taxonomy to the active subpopulation and found that the most dominant taxa are indeed translationally active. On average, only ∼12-18% of bacterial cells were BONCAT labeled, suggesting a heterogeneous growth strategy widely employed by most airway microbiota. Differentiating translationally active populations from those that are dormant adds to our evolving understanding of the polymicrobial basis of CF lung disease and may help guide patient-specific therapeutic strategies targeting active bacterial populations that are most likely to be susceptible.
Low-background Acyl-biotinyl Exchange Largely Eliminates the Co-isolation of Non-S-acylated Proteins and Enables Deep S-acylproteomic Analysis
Authors: Zhou Bo , Wang Yang , Yan Yiwu , Mariscal Javier , Di Vizio Dolores , Freeman Michael R. , Yang Wei 
Published: March 2019

ABSTRACTProteinS-acylation (also called palmitoylation) is a common post-translational modification whose deregulation plays a key role in the pathogenesis of many diseases. Acyl-biotinyl exchange (ABE), a widely used method for the enrichment ofS-acylated proteins, has the potential of capturing the entireS-acylproteome in any types of biological samples. Here, we showed that current ABE methods suffer from high background arising from the co-isolation of non-S-acylated proteins. The background can be substantially reduced by an additional blockage of residual free cysteine residues with 2,2’-dithiodipyridine prior to biotin-HPDP reaction. Coupling the low-background ABE (LB-ABE) method with label-free quantitative proteomics, 2,895 high-confidence candidateS-acylated proteins (including 1,591 knownS-acylated proteins) were identified from human prostate cancer LNCaP cells, representing so-far the largestS-acylproteome dataset identified in a single study. Immunoblotting analysis confirmed theS-acylation of five known and five novel prostate cancer-relatedS-acylated proteins in LNCaP cells and suggested that theirS-acylation levels were about 0.6-1.8%. In summary, the LB-ABE method largely eliminates the co-isolation of non-S-acylated proteins and enables deepS-acylproteomic analysis. It is expected to facilitate much more comprehensive and accurate quantification ofS-acylproteomes than previous ABE methods.
A major role for Eco1 in regulating cohesin-mediated mitotic chromosome folding
Authors: Dauban Lise , Montagne Rémi , Thierry Agnès , Lazar-Stefanita Luciana , Gadal Olivier , Cournac Axel , Koszul Romain , Beckouët Frederic 
Published: March 2019

AbstractUnderstanding how chromatin organizes spatially into chromatid and how sister chromatids are maintained together during mitosis is of fundamental importance in chromosome biology. Cohesin, a member of the Structural Maintenance of Chromosomes (SMC) complex family, holds sister chromatids together 1–3 and promotes long-range intra-chromatid DNA looping 4,5. These cohesin-mediated DNA loops are important for both higher-order mitotic chromatin compaction6,7 and, in some organisms, compartmentalization of chromosomes during interphase into topologically associating domains (TADs) 8,9. Our understanding of the mechanism(s) by which cohesin generates large DNA loops remains incomplete. It involves a combination of molecular partners and active expansion/extrusion of DNA loops. Here we dissect the roles on loop formation of three partners of the cohesin complex: Pds5 10, Wpl1 11 and Eco1 acetylase 12, during yeast mitosis. We identify a new function for Eco1 in negatively regulating cohesin translocase activity, which powers loop extrusion. In the absence of negative regulation, the main barrier to DNA loop expansion appears to be the centromere. Those results provide new insights on the mechanisms regulating cohesin dependent DNA looping.
Gene-level quantitative trait mapping in an expandedC. elegansmultiparent experimental evolution panel
Authors: Noble Luke M. , Rockman Matthew V. , Teotónio Henrique 
Published: March 2019

ABSTRACTTheCaenorhabditis elegansmultiparental experimental evolution (CeMEE) panel is a collection of genome-sequenced, cryopreserved recombinant inbred lines useful for mapping the genetic basis and evolution of quantitative traits. We have expanded the resource with new lines and new populations, and here report updated additive and epistatic mapping simulations and the genetic and haplotypic composition of CeMEE version 2. Additive QTL explaining 3% of trait variance are detected with >80% power, and the median detection interval is around the length of a single gene on the highly recombinant chromosome arms. Although CeMEE populations are derived from a long-term evolution experiment, genetic structure is dominated by variation present in the ancestral population and is not obviously associated with phenotypic differentiation.C. elegansprovides exceptional experimental advantages for the study of phenotypic evolution.
Phase separation of zonula occludens proteins drives formation of tight junctions
Authors: Beutel Oliver , Maraspini Riccardo , Pombo-Garcia Karina , Martin-Lemaitre Cécilie , Honigmann Alf 
Published: March 2019

AbstractTight junctions are cell adhesion complexes that seal tissues and are involved in cell polarity and signalling. Supra-molecular assembly and positioning of tight junctions as continuous networks of adhesion strands is dependent on the two membrane associated scaffolding proteins ZO1 and ZO2. To understand how ZO proteins organize junction assembly, we performed quantitative cell biology andin vitroreconstitution experiments. We discovered that ZO proteins self-organize membrane attached compartments via phase separation. We identified the multivalent interactions of the conserved PDZ-SH3-GuK supra-domain as the driver of phase separation. These interactions are regulated by phosphorylation and intra-molecular binding. Formation of condensed ZO protein compartments is sufficient to specifically enrich and localize tight junction proteins including adhesion receptors, cytoskeletal adapters and transcription factors. Our results suggest that an active phase transition of ZO proteins into a condensed membrane bound compartment drives claudin polymerization and coalescence of a continuous tight junction belt.
Near-optimal combination of disparity across a log-polar scaled visual field
Authors: Maiello Guido , Chessa Manuela , Bex Peter J. , Solari Fabio 
Published: March 2019

AbstractThe human visual system is foveated: we can see fine spatial details in central vision, whereas resolution is poor in our peripheral visual field, and this loss of resolution follows an approximately logarithmic decrease. Additionally, our brain organizes visual input in polar coordinates. Therefore, the image projection occurring between retina and primary visual cortex can be mathematically described by the log-polar transform. Here, we test and model how this space-variant visual processing affects how we process binocular disparity, a key component of human depth perception. We observe that the fovea preferentially processes disparities at fine spatial scales, whereas the visual periphery is tuned for coarse spatial scales, in line with the naturally occurring distributions of depths and disparities in the real-world. We further show that the visual field integrates disparity information across the visual field, in a near-optimal fashion. We develop a foveated, log-polar model that mimics the processing of depth information in primary visual cortex and that can process disparity directly in the cortical domain representation. This model takes real images as input and recreates the observed topography of disparity sensitivity in man. Our findings support the notion that our foveated, binocular visual system has been moulded by the statistics of our visual environment.Author summaryWe investigate how humans perceive depth from binocular disparity at different spatial scales and across different regions of the visual field. We show that small changes in disparity-defined depth are detected best in central vision, whereas peripheral vision best captures the coarser structure of the environment. We also demonstrate that depth information extracted from different regions of the visual field is combined into a unified depth percept. We then construct an image-computable model of disparity processing that takes into account how our brain organizes the visual input at our retinae. The model operates directly in cortical image space, and neatly accounts for human depth perception across the visual field.
A Simple way to Improve a Conventional A/O-MBR for High Simultaneous Carbon and Nutrients Removal from Synthetic Municipal Wastewater
Authors: Dome Adoonsook , Chang Chia-Yuan , Aunnop Wongrueng , Chayakorn Pumas 
Published: March 2019

AbstractIn this study, two anoxic-oxic-MBR systems (conventional and biofilm) were operated in parallel under complete SRT to compare system performance and microbial community composition. Moreover, with the microbial communities, comparisons were made between adhesive stage and suspended stage. High average removal of COD, NH4+-N and TN was achieved in both systems. However, TP removal efficiency was remarkably higher in BF-A/O-MBR when compared with C-A/O-MBR. TP mass balance analysis suggested that under complete SRT, sponges play a key role in both phosphorus release and accumulation. The qPCR analysis showed that sponge biomass could maintain higher abundance of total bacteria than suspended sludge. Meanwhile, AOB and denitrifiers were enriched in the suspended sludge rather than the sponge biomass. Results of pyrosequencing reveal that the compacted sponge in BF-A/O-MBR could promote the growth of bacteria involved in nutrient removal and reduce the filamentous and bacterial related to membrane fouling in the suspended sludge.
Poor seed quality, reduced germination, and decreased seedling vigor in soybean is linked to exposure of the maternal lines to drought stress
Authors: Wijewardana Chathurika , Reddy K. Raja , Krutz L. Jason , Gao Wei , Bellaloui Nacer 
Published: March 2019

AbstractEffects of environmental stressors on the parent may be transmitted to the F1 generation of plants that support global food, oil, and energy production for humans and animals. This study was conducted to determine if the effects of drought stress on parental soybean plants are transmitted to the F1 generation. The germination and seedling vigor of F1 soybean whose maternal parents, Asgrow AG5332 and Progeny P5333RY, were exposed to soil moisture stress, that is, 100, 80, 60, 40, and 20% replacement of evapotranspiration (ET) during reproductive growth, were evaluated under controlled conditions. Pooled over cultivars, effects of soil moisture stress on the parents caused a reduction in the seed germination rate, maximum seed germination, and overall seedling performance in the F1 generation. The effect of soil moisture stress on the parent induced an irreversible change in the seed quality in the F1 generation and the effects on seed quality in the F1 generation were exasperated when exposed to increasing levels of drought stress. Results indicate that seed weight and storage reserve are key factors influencing germination traits and seedling growth. Our data confirm that the effects of drought stress on soybean are transferable, causing reduced germination, seedling vigor, and seed quality in the F1 generation.
Computational prediction and analysis of very high risk single nucleotide polymorphisms in human cytochrome P450 oxidoreductase gene
Authors: Benet Bosco Dhas D , Rajalakshmi K , Suganya S , Pavani P , Yaswanth K 
Published: March 2019

ABSTRACTCytochrome P450 oxidoreductase (POR) is a highly polymorphic gene which is involved in metabolism of drugs and steroids through transfer of electron from NADPH to all CYP enzymes. In this study, we attempt to identify the very high risk single nucleotide polymorphisms in POR gene that would affect phenotype of the enzyme. The genetic variants in POR gene were retrieved from databases and analyzed with appropriate online computation tools. Very high risk non-synonymous SNPs were identified with 12 different sequence and structure homology based tools and evolutionary conservation tool (Consurf). Further the phenotype effect of the variant was assessed with MutPred2 and LigPlot. The very high risk non-coding variants were predicted with HaploReg V4 and RegulomeDB tools. The very high risk SNPs that may affect miRNA target sites were screened using PolymiRTs v3.0, miRNA SNP v2.0 and MirSNP. Among 4,601 variants in POR gene, 58 missense variants, 8 non-coding variants and three SNPs in miRNA target sites were found to be very high risk. These very high risk variants may regulate the expression and activity of cytochrome P450 oxidoreductase enzyme leading to differential drug and steroid metabolism by CYP enzymes.
Design and control of a climbing robot for inspection of high mast lighting
Authors: Li Peng , Duan Xingguang , Sun Guangli , Li Xiang , Zhou Yang , Liu Yunhui 
Published: March 2019

Purpose
This paper aims to develop a climbing robot to help people inspect lamps of high-mast lighting.

Design/methodology/approach
The robot consists of driving mechanism, suspension mechanism and compression mechanism. The driving mechanism is realized by link chains and sprockets, which are arranged opposite to each other, to form a dual caterpillar mechanism. The compression mechanism squeezes the caterpillar, and rubber feet “grasps” the steel rope to generate enough adhesion forces. The suspension mechanism is used to compensate the contraction or extension of the chains. The robot is equipped with a DC motor with a rated power of 250 W and a wireless module to communicate with the operator’s console. The dynamic model of the robot and the control strategy is derived, and the stability of the controller is proofed.

Findings
The payload experiment shows the robot can afford up to 3.7 times payload versus its own weight. Even when the payload is 30 kg, the robot can maintain a speed of the 1 m/s. The experiments also show that the tracking error of the robot reaches zero.

Practical implications
The proposed moving mechanism has a high load/weight ratio, which is a verified solution for the cable inspection purpose.

Originality/value
A rope climbing robot for high mast lighting inspection is proposed. The developed mechanism can reach a speed of 1 m/s with the payload of 30 kg, while its own weight is only 15.6 kg. The payload/weight ratio of the robot is 2.24; this value is rather good in many climbing robots reported in other renowned journal.
A hybrid conjugated method for assembly sequence generation and explode view generation
Authors: Bahubalendruni M.V.A. Raju , Gulivindala Anil , Kumar Manish , Biswal Bibhuti Bhusan , Annepu Lakshumu Naidu 
Published: March 2019

Purpose
The purpose of this paper is to develop an efficient hybrid method that can collectively address assembly sequence generation (ASG) and exploded view generation (EVG) problem effectively. ASG is an act of finding feasible collision free movement of components of a mechanical product in accordance with the assembly design. Although the execution of ASG is complex and time-consuming in calculation, it is highly essential for efficient manufacturing process. Because of numerous limitations of the ASG algorithms, a definite method is still unavailable in the computer-aided design (CAD) software, and therefore the explosion of the product is not found to be in accordance with any feasible disassembly sequence (disassembly sequence is reverse progression of assembly sequence). The existing EVG algorithms in the CAD software result in visualization of the entire constituent parts of the product over single screen without taking into consideration the feasible order of assembly operations; thus, it becomes necessary to formulate an algorithm which effectively solves ASG and EVG problem in conjugation. This requirement has also been documented as standard in the “General Information Concerning Patents: 1.84 Standards for drawings” in the United States Patent and Trademark office (2005) which states that the exploded view created for any product should show the relationship or order of assembly of various parts that are permissible.

Design/methodology/approach
In this paper, a unique ASG method has been proposed and is further extended for EVG. The ASG follows a deterministic approach to avoid redundant data collection and calculation. The proposed method is effectively applied on products which require such feasible paths of disassembly other than canonical directions.

Findings
The method is capable of organizing the assembly operations as linear or parallel progression of assembly such that the assembly task is completed in minimum number of stages. This result is further taken for EVG and is found to be proven effective.

Originality/value
Assembly sequence planning (ASP) is performed most of the times considering the geometric feasibility along canonical axes without considering parallel possibility of assembly operations. In this paper, the proposed method is robust to address this issue. Exploded view generation considering feasible ASP is also one of the novel approaches illustrated in this paper.
Helping autistic women thrive
Authors: Zener Dori 
Published: March 2019

Purpose
The purpose of this paper is to outline a clinical framework developed for autistic women. INVEST (Identify Needs, Validate, Educate, Strengthen and Thrive) is a strengths-based neurodiversity therapeutic approach. Autistic individuals are treated with respect and are believed to have the capacity to make meaningful changes in their lives.

Design/methodology/approach
The author’s clinical experiences working as an individual, couple and family therapist specializing in girls and women with autism inform this paper. The innovative therapeutic approach will be described including reasons for seeking therapy, the theoretical underpinnings and case examples that bring each component of INVEST to life.

Findings
Women with autism are very responsive to a therapeutic process that validates their experiences. Helping individuals and their support systems learn more about autism and their unique profile can enhance understanding and self-acceptance. Strategies to increase emotional awareness and reduce victimization are emphasized. Understanding sensory triggers and executive functioning challenges enable individuals to make useful adaptations. Building skills and setting parameters on time and energy help to stave off autistic burnout.

Practical implications
The impact of the INVEST model goes beyond the therapist’s office and can be applied to multiple settings. All professionals have the opportunity to treat autistic women with respect, validation and an assumption of competence.

Originality/value
Clinical program are scarce for individuals with autism, especially women. The INVEST model is the beginning of a discussion of what can help autistic women thrive.