bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenomics and genotype-phenotype association analyses reveal conserved genetic architecture of complex traits in cattle and human
Authors: Liu Shuli , Yu Ying , Zhang Shengli , Cole John B. , Tenesa Albert , Wang Ting , McDaneld Tara G. , Ma Li , Liu George E. , Fang Lingzhao 
Published: July 2020

AbstractBackgroundLack of comprehensive functional annotations across a wide range of tissues and cell types severely hinders the biological interpretations of phenotypic variation, adaptive evolution, and domestication in livestock. Here we used a combination of comparative epigenomics, genome-wide association study (GWAS), and selection signature analysis, to shed light on potential adaptive evolution in cattle.ResultsWe cross-mapped 8 histone marks of 1300 samples from human to cattle, covering 178 unique tissues/cell types. By uniformly analyzing 723 RNA-seq and 40 whole genome bisulfite sequencing (WGBS) datasets in cattle, we validated that cross-mapped histone marks captured tissue-specific expression and methylation, reflecting tissue-relevant biology. Through integrating cross-mapped tissue-specific histone marks with large-scale GWAS and selection signature results, we for the first time detected relevant tissues and cell types for 45 economically important traits and artificial selection in cattle. For instance, immune tissues are significantly associated with health and reproduction traits, multiple tissues for milk production and body conformation traits (reflecting their highly polygenic architecture), and thyroid for the different selection between beef and dairy cattle. Similarly, we detected relevant tissues for 58 complex traits and diseases in humans and observed that immune and fertility traits in humans significantly correlated with those in cattle in terms of relevant tissues, which facilitated the identification of causal genes for such traits. For instance,PIK3CG, a gene highly specifically expressed in mononuclear cells, was significantly associated with both age-at-menopause in human and daughter-still-birth in cattle.ICAM, a T cell-specific gene, was significantly associated with both allergic diseases in human and metritis in cattle.ConclusionCollectively, our results highlighted that comparative epigenomics in conjunction with GWAS and selection signature analyses could provide biological insights into the phenotypic variation and adaptive evolution. Cattle may serve as a model for human complex traits, by providing additional information beyond laboratory model organisms, particularly when more novel phenotypes become available in the near future.
The roles of hybridization and habitat fragmentation in the evolution of Brazil’s enigmatic longwing butterflies, Heliconius nattereri and H. hermathena
Authors: Massardo Darli , VanKuren Nicholas W. , Nallu Sumitha , Ramos Renato R. , Ribeiro Pedro G. , Silva-Brandão Karina L. , Brandão Marcelo M. , Lion Marília B. , Freitas André V. L. , Cardoso Márcio Z. , Kronforst Marcus R. 
Published: July 2020

AbstractBackgroundHeliconiusbutterflies are widely distributed across the Neotropics and have evolved a stunning array of wing color patterns that mediate Müllerian mimicry and mating behavior. Their rapid radiation has been strongly influenced by hybridization, which has created new species and allowed sharing of color patterning alleles between mimetic species pairs. While these processes have frequently been observed in widespread species with contiguous distributions, manyHeliconiusspecies inhabit patchy or rare habitats that may strongly influence the origin and spread of species and color patterns. Here, we assess the effects of historical population fragmentation and unique biology on the origins, genetic health, and color pattern evolution of two rare and sparsely distributed Brazilian butterflies,Heliconius hermathenaandHeliconius nattereri.ResultsWe assembled genomes and re-sequenced whole genomes of eightH. nattereriand 71H. hermathenaindividuals. These species harbor little genetic diversity, skewed site frequency spectra, and high deleterious mutation loads consistent with recent population bottlenecks.Heliconius hermathenaconsists of discrete, strongly isolated populations that likely arose from a single population that dispersed after the last glacial maximum. Despite having a unique color pattern combination that suggested a hybrid origin, we found no genome-wide evidence thatH. hermathenais a hybrid species. However,H. hermathenamimicry evolved via introgression, from co-mimeticHeliconius erato, of a small genomic region upstream of the color patterning genecortex.ConclusionsHeliconius hermathenaandH. nattereripopulation fragmentation, potentially driven by historical climate change and recent deforestation, has significantly reduced the genetic health of these rare species. Our results contribute to a growing body of evidence that introgression of color patterning alleles between co-mimetic species appears to be a general feature ofHeliconiusevolution.
Analysis of H3K4me3 and H3K27me3 bivalent promotors in HER2+ breast cancer cell lines reveals variations depending on estrogen receptor status and significantly correlates with gene expression
Authors: Kaukonen Damien , Kaukonen Riina , Polit Lélia , Hennessy Bryan T. , Lund Riikka , Madden Stephen F. 
Published: July 2020

Abstract
Background
The role of histone modifications is poorly characterized in breast cancer, especially within the major subtypes. While epigenetic modifications may enhance the adaptability of a cell to both therapy and the surrounding environment, the mechanisms by which this is accomplished remains unclear. In this study we focus on the HER2 subtype and investigate two histone trimethylations that occur on the histone 3; the trimethylation located at lysine 4 (H3K4me3) found in active promoters and the trimethylation located at lysine 27 (H3K27me3) that correlates with gene repression. A bivalency state is the result of the co-presence of these two marks at the same promoter.

Methods
In this study we investigated the relationship between these histone modifications in promoter regions and their proximal gene expression in HER2+ breast cancer cell lines. In addition, we assessed these patterns with respect to the presence or absence of the estrogen receptor (ER). To do this, we utilized ChIP-seq and matching RNA-seq from publicly available data for the AU565, SKBR3, MB361 and UACC812 cell lines. In order to visualize these relationships, we used KEGG pathway enrichment analysis, and Kaplan-Meyer plots.

Results
We found that the correlation between the three types of promoter trimethylation statuses (H3K4me3, H3K27me3 or both) and the expression of the proximal genes was highly significant overall, while roughly a third of all genes are regulated by this phenomenon. We also show that there are several pathways related to cancer progression and invasion that are associated with the bivalent status of the gene promoters, and that there are specific differences between ER+ and ER- HER2+ breast cancer cell lines. These specific differences that are differentially trimethylated are also shown to be differentially expressed in patient samples. One of these genes, HIF1AN, significantly correlates with patient outcome.

Conclusions
This study highlights the importance of looking at epigenetic markings at a subtype specific level by characterizing the relationship between the bivalent promoters and gene expression. This provides a deeper insight into a mechanism that could lead to future targets for treatment and prognosis, along with oncogenesis and response to therapy of HER2+ breast cancer patients.
Gait improvements by assisting hip movements with the robot in children with cerebral palsy: a pilot randomized controlled trial
Authors: Kawasaki Shihomi , Ohata Koji , Yoshida Takeshi , Yokoyama Atsushi , Yamada Shigehito 
Published: July 2020

AbstractBackgroundRecently, rehabilitation robots are expected to improve the gait of cerebral palsy (CP) children. However, only few previous studies have reported the kinematic and kinetic changes by using wearable exoskeleton robots. The aim of this study was to investigate the change in gait parameters in CP children by training with the wearable robot-assisted gait training.Methods10 spastic CP children with Gross Motor Function Classification Scale levels I-III completed a sham-controlled crossover randomized trial. Robot-assisted gait training (RAGT) and non-assisted gait training (NAGT) were performed on the treadmill with the Honda Walking Assist (HWA) in two different days. To examine the carry-over effect from treadmill walking to overground walking, participants also performed 5.5 m overground-walks without the HWA before and after treadmill training (pre- and post-trial). During treadmill walking, peak of both hip and knee angles were measured. Also, we calculated the limb symmetry of hip range of motion. In addition, gait speed and ground reaction force were measured in overground trials.ResultsThe maximum hip angle on the limb with fewer hip movements, which was defined as the affected limb, showed a significant interaction between ASSIST (RAGT and NAGT) and TIME (pre- and post-trial) (p < 0.05). Limb symmetry significantly improved after RAGT (p < 0.05), but not in NAGT. Furthermore, the affected limb showed a significant increase in the positive peak of the anterior-posterior ground reaction force during 70–100% of the gait cycle (p < 0.05). However, there was no change in gait speed.ConclusionBy assisting the both hip movements with the HWA, maximum hip flexion and extension angle of the affected limb improved. Also, limb symmetry and propulsion force of the affected limb improved. Our results suggest that assisting both hip movements with the HWA might be an effective method for improving gait in CP children.Trial registrationUMIN-CTR, UMIN000030667. Registered 3 January 2018,https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000033737
Building knowledge translation competency in a community-based hospital: a practice-informed curriculum for healthcare providers, researchers, and leadership
Authors: Provvidenza Christine , Townley Ashleigh , Wincentak Joanne , Peacocke Sean , Kingsnorth Shauna 
Published: July 2020

Abstract
Background
Enacting knowledge translation (KT) in healthcare settings is a complex process that requires organizational facilitation. In addition to addressing organizational-level barriers, targeting individual-level factors such as KT competencies are a necessary component of this aim. While literature on KT competency training is rapidly growing, there has been little exploration of the potential benefits of training initiatives delivered from an intra-organizational perspective. Addressing this gap, we developed the Knowledge Translation Facilitator Network (KTFN) to meet the KT needs of individuals expected to use and produce knowledge (e.g., healthcare providers, research staff, managers, family advisors) within an academic health sciences center. The aim of this study is to describe the development, implementation, and evaluation of the KTFN curriculum.

Methods
An educational framework was used to guide creation of the KTFN curriculum. Stakeholder interviews, a literature review of KT competency, and environmental scan of capacity building initiatives plus adult learning principles were combined with in-house experience of KT practitioners to inform content and delivery. An evaluation strategy consisting of pre/post-test curriculum and post-session satisfaction surveys, as well as post-curriculum interviews assessed impact on participant knowledge and skills and captured perceived value of KFTN.

Results
The curriculum has been delivered three times over 3 years, with 30 individuals trained, representing healthcare providers, graduate level research trainees, managers, and family advisors. Using the New World Kirkpatrick Model as an analysis framework, we found that the KTFN curriculum was highly valued and shifted learners’ perceptions of KT. Participants identified enhanced knowledge and skills that could be applied to different facets of their work; increased confidence in their ability to execute KT tasks; and intention to use the content in future projects. Barriers to future use included time to plan and conduct KT activities.

Conclusion
KTFN was developed to enhance KT competency among organizational members. This initiative shows promise as a highly valued training program that meets both individual and organizational KT needs and speaks to the importance of investing in tailored KT competency initiatives as an essential building block to support moving evidence into practice.
CagA orchestrates eEF1A1 and PKCδ to induce interleukin-6 expression in Helicobacter pylori-infected gastric epithelial cells
Authors: Xu Shaohan , Wu Xiaoqian , Zhang Xiaoyan , Chen Chu , Chen Hao , She Feifei 
Published: July 2020

Abstract
Background
Helicobacter pylori colonises the stomach of approximately 50% of the global population. Cytotoxin-associated gene A protein (CagA) is one of the important virulent factors responsible for the increased inflammation and increases the risk of developing peptic ulcers and gastric carcinoma. The cytokine interleukin-6 (IL-6) has particularly important roles in the malignant transformation of gastric and intestinal epithelial cells as it is upregulated in H. pylori-infected gastric mucosa. In this study, we investigated the underlying mechanisms of CagA-induced IL-6 up-regulation during H. pylori infection. AGS cells, a human gastric adenocarcinoma cell line, lacking eEF1A1 were infected with CagA+H. pylori (NCTC11637), CagA−H. pylori (NCTC11637ΔcagA), or transduced by Ad-cagA/Ad-GFP. The expression and production of IL-6 were measured by quantitative real-time reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The interactions among CagA, eukaryotic translation elongation factor 1-alpha 1 (eEF1A1), protein kinase Cδ (PKCδ), and signal transducer and activator of transcription 3 (STAT3) were determined by western blot or co-immunoprecipitation.

Results
During H. pylori infection, CagA-M (residues 256‒871aa) was found to interact with eEF1A1-I (residues 1‒240aa). NCTC11637 increased the expression of IL-6 in AGS cells compared with NCTC11637ΔcagA whereas knockdown of eEF1A1 in AGS cells completely abrogated these effects. Moreover, the CagA-eEF1A1 complex promoted the expression of IL-6 in AGS cells. CagA and eEF1A1 cooperated to mediate the expression of IL-6 by affecting the activity of p-STATS727 in the nucleus. Further, CagA-eEF1A1 affected the activity of STAT3 by recruiting PKCδ. However, blocking PKCδ inhibited the phosphorylation of STAT3S727 and induction of IL-6 by CagA.

Conclusions
CagA promotes the expression of IL-6 in AGS cells by recruiting PKCδ through eEF1A1 in the cytoplasm to increase the phosphorylation of STAT3S727 in the nucleus. These findings provide new insights into the function of CagA-eEF1A1 interaction in gastric adenocarcinoma.
Nucleo–cytoplasmic transport defects and protein aggregates in neurodegeneration
Authors: Bitetto Giacomo , Di Fonzo Alessio 
Published: July 2020

AbstractIn the ongoing process of uncovering molecular abnormalities in neurodegenerative diseases characterized by toxic protein aggregates, nucleo-cytoplasmic transport defects have an emerging role. Several pieces of evidence suggest a link between neuronal protein inclusions and nuclear pore complex (NPC) damage. These processes lead to oxidative stress, inefficient transcription, and aberrant DNA/RNA maintenance. The clinical and neuropathological spectrum of NPC defects is broad, ranging from physiological aging to a suite of neurodegenerative diseases. A better understanding of the shared pathways among these conditions may represent a significant step toward dissecting their underlying molecular mechanisms, opening the way to a real possibility of identifying common therapeutic targets.
Syntrophic acetate oxidation replaces acetoclastic methanogenesis during thermophilic digestion of biowaste
Authors: Dyksma Stefan , Jansen Lukas , Gallert Claudia 
Published: July 2020

Abstract
Background
Anaerobic digestion (AD) is a globally important technology for effective waste and wastewater management. In AD, microorganisms interact in a complex food web for the production of biogas. Here, acetoclastic methanogens and syntrophic acetate-oxidizing bacteria (SAOB) compete for acetate, a major intermediate in the mineralization of organic matter. Although evidence is emerging that syntrophic acetate oxidation is an important pathway for methane production, knowledge about the SAOB is still very limited.

Results
A metabolic reconstruction of metagenome-assembled genomes (MAGs) from a thermophilic solid state biowaste digester covered the basic functions of the biogas microbial community. Firmicutes was the most abundant phylum in the metagenome (53%) harboring species that take place in various functions ranging from the hydrolysis of polymers to syntrophic acetate oxidation. The Wood-Ljungdahl pathway for syntrophic acetate oxidation and corresponding genes for energy conservation were identified in a Dethiobacteraceae MAG that is phylogenetically related to known SAOB. 16S rRNA gene amplicon sequencing and enrichment cultivation consistently identified the uncultured Dethiobacteraceae together with Syntrophaceticus, Tepidanaerobacter, and unclassified Clostridia as members of a potential acetate-oxidizing core community in nine full-scare digesters, whereas acetoclastic methanogens were barely detected.

Conclusions
Results presented here provide new insights into a remarkable anaerobic digestion ecosystem where acetate catabolism is mainly realized by Bacteria. Metagenomics and enrichment cultivation revealed a core community of diverse and novel uncultured acetate-oxidizing bacteria and point to a particular niche for them in dry fermentation of biowaste. Their genomic repertoire suggests metabolic plasticity besides the potential for syntrophic acetate oxidation.
Fine-scale succession patterns and assembly mechanisms of bacterial community of Litopenaeus vannamei larvae across the developmental cycle
Authors: Wang Yanting , Wang Kai , Huang Lei , Dong Pengsheng , Wang Sipeng , Chen Heping , Lu Zheng , Hou Dandi , Zhang Demin 
Published: July 2020

Abstract
Background
Microbiome assembly in early life may have a long-term impact on host health. Larval nursery is a crucial period that determines the success in culture of Litopenaeus vannamei, the most productive shrimp species in world aquaculture industry. However, the succession patterns and assembly mechanisms of larval shrimp bacterial community still lack characterization at a fine temporal scale. Here, using a high-frequency sampling strategy and 16S rRNA gene amplicon sequencing, we investigated dynamics of larval shrimp bacterial community and its relationship with bacterioplankton in the rearing water across the whole developmental cycle in a realistic aquaculture practice.

Results
Alpha-diversity of larval shrimp bacteria showed a U-shaped pattern across the developmental cycle with the stages zoea and mysis as the valley. Correspondingly, the compositions of dominant bacterial taxa at the stages nauplius and early postlarvae were more complex than other stages. Remarkably, Rhodobacteraceae maintained the overwhelming dominance after the mouth opening of larvae (zoea I~early postlarvae). The taxonomic and phylogenetic compositions of larval bacterial community both showed stage-dependent patterns with higher rate of taxonomic turnover, suggesting that taxonomic turnover was mainly driven by temporal switching among closely related taxa (such as Rhodobacteraceae taxa). The assembly of larval bacteria was overall governed by neutral processes (dispersal among individuals and ecological drift) at all the stages, but bacterioplankton also had certain contribution during three sub-stages of zoea, when larval and water bacterial communities were most associated. Furthermore, the positive host selection for Rhodobacteraceae taxa from the rearing water during the zoea stage and its persistent dominance and large predicted contribution to metabolic potentials of organic matters at post-mouth opening stages suggest a crucial role of this family in larval microbiome and thus a potential source of probiotic candidates for shrimp larval nursery.

Conclusions
Our results reveal pronounced succession patterns and dynamic assembly processes of larval shrimp bacterial communities during the developmental cycle, highlighting the importance of the mouth opening stage from the perspective of microbial ecology. We also suggest the possibility and potential timing in microbial management of the rearing water for achieving the beneficial larval microbiota in the nursery practice.
Outcomes of inpatient psychological treatments for children and adolescents with eating disorders at time of discharge: a systematic review
Authors: Isserlin Leanna , Spettigue Wendy , Norris Mark , Couturier Jennifer 
Published: July 2020

AbstractBackgroundRecommended first line treatment for children and adolescent eating disorders is outpatient therapy. However, a significant number of children and adolescents with eating disorders continue to require inpatient treatment during the course of their illness. The effect of psychological treatments in an inpatient setting on outcomes at the time of discharge remains unclear. This paper presents the results of a review of the literature on outcomes at the time of discharge following inpatient psychological treatment for children and adolescents with eating disorders.Main bodyThe majority of studies found were observational and of low quality. The most consistently reported positive outcome of inpatient treatment is weight gain. Results related to symptom change and motivation vary between studies. Within the inpatient setting, there is considerable heterogeneity in the types of treatments offered, goals of treatment, length of stay and outcomes measured.ConclusionThere remains a paucity of high-quality studies examining the effect of psychological treatments provided to children and adolescents in an inpatient setting. The significant heterogeneity between studies makes it not possible to compare across studies. Future research should aim to resolve these deficiencies in order to better determine the specific factors that contribute to positive outcomes of inpatient treatment for children and adolescents with eating disorders.