bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between the ACE I/D gene polymorphism and progressive renal failure in autosomal dominant polycystic kidney disease: A meta-analysis
Authors: Pabalan Noel , Tharabenjasin Phuntila , Parcharoen Yardnapar , Tasanarong Adis 
Published: August 2019

AbstractObjectiveThe angiotensin converting enzyme insertion/deletion (ACE I/D) gene polymorphism is involved in a wide range of clinical outcomes. This makes ACE I/D an important genetic marker. Updating the genetic profile of ACE I/D and raising the evidence for its role in renal disease is therefore needed. Reported associations of ACE I/D with progressive renal failure (PRF) in autosomal dominant polycystic kidney disease (ADPKD) have been inconsistent, prompting a meta-analysis to obtain more precise estimates.MethodsMulti-database search yielded 18 articles for inclusion in the meta-analysis. Risks (odds ratios [ORs] and 95% confidence intervals) were estimated by comparing the ACE genotypes (heterozygote ID, homozygotes DD and II). Heterogeneous (random-effects) pooled associations were subjected to outlier treatment which yielded fixed-effects outcomes and split the findings into pre- (PRO) and post- (PSO) outlier status. Subgroup analysis was based on ethnicity (Asian/Caucasian) and minor allele frequency (maf). The ≥ 0.50 maf subgroup indicates higher frequency of the variant II genotype over that of the common DD genotype, otherwise, the subgroup is considered < 0.50 maf. Stability of the associative effects was assessed with sensitivity treatment. Temporal trend of association was examined with cumulative meta-analysis.ResultsIn the PSO analysis, overall effects were null (ORs 0.99-1.02) but not in the subgroups (Asian and ≥ 0.50 maf), where in presence of the D allele (DD/ID) and the I allele (II), increased (ORs 1.63-5.62) and reduced (OR 0.22) risks were observed, respectively. Of these pooled effects, the Asian and ≥ 0.50 maf homozygous DD genotypes had high ORs (5.01-5.63) indicating elevated magnitude of effects that were highly significant (Pa < 10−5) and homogeneous (I2 = 0%), in addition to their robustness. In contrast, the Caucasian and < 0.50 maf subgroup effects were: (i) non-heterogeneous (fixed-effects) at the outset, which did not require outlier treatment and (ii) non-significant (ORs 0.91-1.10, Pa = 0.15-0.79). Cumulative meta-analysis revealed increased precision of effects over time.ConclusionsPRF in ADPKD impacted the Asian and ≥ 0.50 maf subgroups where DD homozygote carriers were up to 6-fold susceptible. The high magnitude of these effects were highly significant, homogeneous and robust indicating strong evidence of association.
The Effects of Metronome Frequency Differentially Affects Gait on a Treadmill and Overground in People with Parkinson’s Disease
Authors: Wygand Madelon , Chawla Guneet , Browner Nina , Lewek Michael D 
Published: August 2019

AbstractObjectiveTo determine the effect of different metronome cue frequencies on spatiotemporal gait parameters when walking overground compared to walking on a treadmill in people with Parkinson’s diseaseDesignRepeated-measures, within-subject designSettingResearch laboratoryParticipantsTwenty-one people with Parkinson’s disease (Hoehn & Yahr stage 1-3)InterventionsParticipants walked overground and on a treadmill with and without metronome cues of 85%, 100%, and 115% of their baseline cadence for one minute each.Main Outcome MeasuresGait speed, step length, and cadenceResultsAn interaction effect between cue frequency and walking environment revealed that participants took longer steps during the 85% condition on the treadmill only. When walking overground, metronome cues of 85% and 115% of baseline cadence yielded decreases and increases, respectively, in both cadence and gait speed with no concomitant change in step length.ConclusionsThese data suggest that people with PD are able to alter spatiotemporal gait parameters immediately when provided the appropriate metronome cue and walking environment. We propose to target shortened step lengths by stepping to the beat of slow frequency auditory cues while walking on a treadmill, whereas the use of fast frequency cues during overground walking can facilitate faster walking speeds.
Increasing Heroin, Cocaine, and Buprenorphine Arrests Reported to the Maine Diversion Alert Program
Authors: Simpson Kevin J , Moran Matthew T , McCall Kenneth L , Herbert John , Foster Michelle , Simoyan Olapeju M , Shah Dipam T , Desrosiers Clare , Nichols Stephanie D , Piper Brian J 
Published: August 2019

AbstractBackgroundThe opioid overdose crisis is especially pronounced in Maine. The Diversion Alert Program (DAP) was developed to combat illicit drug use and prescription drug diversion by facilitating communication between law enforcement and healthcare providers with the goal of limiting drug-related harms and criminal behaviors. Our objectives in this report were to analyze 2014-2017 DAP for: 1) trends in drug arrests and, 2) differences in arrests by offense, demographics (sex and age) and by region.MethodsDrug charges (N = 8,193, 31.3% female, age = 33.1 ± 9.9) reported to the DAP were examined by year, demographics, and location.ResultsThe most common substances of the 10,064 unique arrests reported were heroin (N = 2,203, 21.9%), crack/cocaine (N = 945, 16.8%), buprenorphine (N = 812, 8.1%), and oxycodone (N = 747, 7.4%). While the overall number of arrests reported to the DAP declined in 2017, the proportion of arrests involving opioids (heroin, buprenorphine, or fentanyl) and stimulants (cocaine/crack cocaine, or methamphetamine), increased (p < .05). Women had significantly increased involvement in arrests involving sedatives and miscellaneous pharmaceuticals (e.g. gabapentin) while men had an elevation in stimulant arrests. Heroin accounted for a lower percentage of arrests among individuals age > 60 (6.6%) relative to young-adults (18-29, 22.3%, p < .0001). Older-adults had significantly more arrests than younger-adults for oxycodone, hydrocodone, and marijuana.ConclusionHeroin had the most arrests from 2014-2017. Buprenorphine, fentanyl and crack/cocaine arrests increased appreciably suggesting that improved treatment is needed to prevent further nonmedical use and overdoses. The Diversion Alert Program provided a unique data source for research, a harm-reduction tool for health care providers, and an informational resource for law enforcement.
Pyntheon: A Functional Analysis Framework for Protein Modifications and Mutations of 83 Model Organisms
Authors: Arslan Ahmed 
Published: August 2019

AbstractMotivationPosttranslational modifications (PTMs) modulate proteins activity depending on the dynamics of cellular conditions, in the highly regulated processes that control the reversible nature of these modifications and a cellular state. Due to the unique importance of PTMs, a number of resources are available to analyze the protein modification data for different organisms. These databases are quite informative on a limited number of popular organisms, mostly human and yeast. However there has not been a single database to date that makes it possible to analyze the modified protein residue data for up to 83 model organisms. Moreover, there are limited resources that rely on both protein mutations and modifications in evaluating a phenotype.ResultsI am presenting a comprehensive python toolPyntheonthat enables users to analyze protein modifications and mutations data. This resource can be used in different ways to know: (i) if the proteins of interest have modifications and (ii) if the modified residues overlap with mutated sites. Additional functions include, analyzing if a PTM-site is present in a functional protein region, like domain and structural regions. In summary, Pyntheon makes it possible for a larger community of researchers to evaluate their curated proteomics data and interpret the impact of mutations on phenotypes.ConclusionPyntheon has multifold functions that can help analyzing the protein mutations impact on the modified residues for a large number of popular model organisms.Code-Availabilityhttps://github.com/AhmedArslan/pyntheonContactaarslan@stanford.edu
In situ Fucosylation for Modulating Wnt Signaling in Live Cells
Authors: Hong Senlian , Feng Lei , Jiang Hao , Hou Xiaomeng , Guo Peng , Marlow Florence L. , Stanley Pamela , Wu Peng 
Published: August 2019

ABSTRACTWnt/β-catenin signaling, also known as canonical Wnt signaling, regulates critical, context-dependent transcription in numerous (patho) physiological events. Amongst the well-documented mechanisms of canonical Wnt signaling, modification of N-glycans by L-fucose (Fuc) is the newest and the least understood. Using a combination of Chinese Hamster Ovary (CHO) cell mutants with different fucosylation levels andin situcell-surface Fuc editing (ISF), we report that α(1-3)-fucosylation of N-acetylglucosamine in the LacNAc (Galβ(1-4)-GlcNAc) sequences of complex N-glycans modulates Wnt signaling by regulating the endocytosis of low density lipoprotein receptor-related protein 6 (LRP6). Pulse-chase experiments reveal that increasing N-glycan LacNAc fucosylation elevates endocytosis of lipid-raft-localized LRP6, leading to the suppression of Wnt-β-catenin signaling. Inhibiting endocytosis by inhibiting dynamin 1, a GTPase responsible for endocytosis in eukaryotic cells, partially rescues Wnt signaling. Remarkably, inhibition of Wnt signaling by N-glycan LacNAc fucosylation is fully rescued by the addition of free Fuc to the medium, suggesting that endocytosis of N-glycan fucosylated LRP6 may be mediated by a receptor that recognizes the bound α(1-3)-Fuc. This work provides the first evidence thatin situcell-surface fucosylation can be exploited to regulate a specific signaling pathway via endocytosis, revealing a novel regulatory mechanism linking glycosylation of a cell surface receptor with its intracellular signaling.
Histone ChIP-Seq identifies differential enhancer usage during chondrogenesis as critical for defining cell-type specificity
Authors: Cheung Kathleen , Barter Matthew J. , Falk Julia , Proctor Carole , Reynard Louise N. , Young David A. 
Published: August 2019

AbstractEpigenetic mechanisms are known to regulate gene expression during chondrogenesis. In this study, we have characterised the epigenome during in vitro differentiation of human mesenchymal stem cells (hMSCs) into chondrocytes. Chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) was used to assess a range of N-terminal post-transcriptional modifications (marks) to histone H3 lysines (H3K4me3, H3K4me1, H3K27ac, H3K27me3 and H3K36me3) in both hMSCs and differentiated chondrocytes. Chromatin states were characterised using histone ChIP-seq and cis-regulatory elements were identified in chondrocytes. Chondrocyte enhancers were associated with chondrogenesis related gene ontology (GO) terms. In silico analysis and integration of DNA methylation data with chondrogenesis chromatin states revealed that enhancers marked by histone marks H3K4me1 and H3K27ac were de-methylated during in vitro chondrogenesis. Similarity analysis between hMSC and chondrocyte chromatin states defined in this study with epigenomes of cell-types defined by the Roadmap Epigenomics project revealed that enhancers are more distinct between cell-types compared to other chromatin states. Motif analysis revealed that the transcription factor SOX9 is enriched in chondrocyte enhancers. Luciferase reporter assays confirmed that chondrocyte enhancers characterised in this study exhibited enhancer activity which may be modulated by inducing DNA methylation and SOX9 overexpression. Altogether, these integrated data illustrate the cross-talk between different epigenetic mechanisms during chondrocyte differentiation.SummaryHuman mesenchymal stem cells are able to differentiate into chondrocytes, the cell type found in cartilage, making them an accessible system to study gene regulation during this process. Epigenetic mechanisms such as histone modifications and DNA methylation together with transcription factor binding play a role in activating and repressing gene expression. In this study, we investigated the genome-wide histone modification changes during chondrocyte differentiation. Integration of this data with DNA methylation and SOX9 transcription factor ChIP-seq revealed epigenetic changes at gene enhancer elements. Regions of the genome that transition from non-enhancers to enhancers in chondrocytes are enriched for SOX9 transcription factor binding sites. Luciferase reporter assays revealed that enhancer activity may be modulated by manipulating DNA methylation and SOX9 expression. This study has defined important regulatory elements in chondrocytes which could serve as targets for future mechanistic studies.
Prioritizing persistent microbiome members in the common bean rhizosphere: an integrated analysis of space, time, and plant genotype
Authors: Stopnisek Nejc , Shade Ashley 
Published: August 2019

AbstractThe full potential of managing microbial communities to support plant health is yet-unrealized, in part because it remains difficult to ascertain which members are most important for the plant. However, microbes that consistently associate with a plant species across varied field conditions and over plant development likely engage with the host or host environment. Here, we applied abundance-occupancy concepts from macroecology to quantify the core membership of bacterial/archaeal and fungal communities in the rhizosphere of the common bean (Phaseolus vulgaris). Our study investigated the microbiome membership that persisted over multiple dimensions important for plant agriculture, including major growing regions, plant development, annual plantings, and divergent genotypes, and also included re-analysis of public data. We found 48 core bacterial taxa that were consistently detected in all samples, inclusive of all datasets and dimensions. This suggests reliable enrichment of these taxa to the plant environment and time-independence of their association with the plant. More generally, this work provides a robust approach for systematically prioritizing core microbiome memberships in any host or system.
3D mapping of host-parasite-microbiome interactions reveals metabolic determinants of tissue tropism and disease tolerance in Chagas disease
Authors: Hossain Ekram , Khanam Sharmily , Wu Chaoyi , Lostracco-Johnson Sharon , Thomas Diane , Katemauswa Mitchelle , Gosmanov Camil , Li Danyang , Woelfel-Monsivais Christine , Sankaranarayanan Krithivasan , McCall Laura-Isobel 
Published: August 2019

AbstractChagas disease (CD) is a parasitic infection caused by Trypanosoma cruzi protozoa. Over 8 million people worldwide are T. cruzi-positive, 20-30% of which will develop cardiomyopathy, megaoesophagus and/or megacolon. The mechanisms leading to gastrointestinal (GI) symptom development are however poorly understood. To address this issue, we systematically characterized the spatial impact of experimental T. cruzi infection on the microbiome and metabolome across the GI tract. The largest microbiota perturbations were observed in the proximal large intestine in both acute and chronic disease, with chronic-stage effects also observed in the cecum. Strikingly, metabolomic impact of acute-to-chronic stage transition differed depending on the organ, with persistent large-scale effects of infection primarily in the oesophagus and large intestine, providing a potential mechanism for GI pathology tropism in CD. Infection particularly affected acylcarnitine and lipid metabolism. Building on these observations, treatment of infected mice with carnitine-supplemented drinking water prevented acute-stage mortality with no changes in parasite burden. Overall, these results identified a new mechanism of disease tolerance in CD, with potential for the development of new therapeutic regimens. More broadly, these results highlight the potential of spatially-resolved metabolomic approaches to provide insight into disease pathogenesis, with translational applications for infectious disease drug development.
Freezing and water availability structure the evolutionary diversity of trees across the Americas
Authors: Segovia R. A. , Pennington R. T. , Baker T. R. , de Souza F. Coelho , Neves D. M. , Davis C. C. , Armesto J. J. , Olivera-Filho A. T. , Dexter K. G. 
Published: August 2019

AbstractThe historical course of evolutionary diversification shapes the current distribution of biodiversity, but the main forces constraining diversification are unclear. We unveil the evolutionary structure of tree species diversity across the Americas to assess whether an inability to move (dispersal limitation) or to evolve (niche conservatism) is the predominant constraint in plant diversification and biogeography. We find a fundamental divide in tree lineage composition between tropical and extratropical environments, defined by the absence versus presence of freezing temperatures. Within the Neotropics, we uncover a further evolutionary split between moist and dry forests. Our results demonstrate that American tree lineages, though broadly distributed geographically, tend to retain their ancestral environmental relationships and that phylogenetic niche conservatism is the primary force structuring the distribution of tree biodiversity.
A low-cost, open-source evolutionary bioreactor and its educational use
Authors: Gopalakrishnan Vishhvaan , Crozier Dena , Card Kyle J. , Chick Lacy D. , Krishnan Nikhil P. , McClure Erin , Pelesko Julia , Williamson Drew F.K. , Nichol Daniel , Mandal Soumyajit , Bonomo Robert A. , Scott Jacob G. 
Published: August 2019

AbstractThe morbidostat automatically adjusts antibiotic concentration as a bacterial population evolves resistance. Although this device has advanced our understanding of the evolutionary and ecological processes that drive antibiotic resistance, no low-cost and open-source systems are available for educators. Here, we present the EVolutionary biorEactor (EVE), an accessible alternative to other morbidostats for use in low-resource classrooms that requires minimal engineering and programming experience. We first compare our system to others, emphasizing how it differs in design and cost. We then describe how we validated the EVE by evolving replicate Escherichia coli populations under chloramphenicol challenge and comparing our results to those in the published literature. Lastly, we detail how high school students used the EVE to learn about bacterial growth and antibiotic resistance.
Genomic profiling of PML bodies reveals transcriptional regulation by PML bodies through the DNMT3A exclusion
Authors: Kurihara Misuzu , Kato Kagayaki , Sanbo Chiaki , Shigenobu Shuji , Ohkawa Yasuyuki , Fuchigami Takeshi , Miyanari Yusuke 
Published: August 2019

AbstractThe promyelocytic leukaemia (PML) body is a phase-separated nuclear structure involved in various biological processes, including senescence, and tumour suppression1. PML bodies consist of various proteins, including PML proteins and several chromatin regulators2,3and physically associate with chromatin4,5, implying their crucial roles in particular genome functions. However, their roles in transcriptional regulation are largely unknown. Here, we developed APEX-mediated chromatin labelling and purification (ALaP), to identify the genomic regions associated with PML bodies. We find that PML bodies associate with active regulatory regions across the genome and prominently with a ∼300 kb of the short arm of the Y chromosome (YS300) in mouse embryonic stem cells (mESCs). The association with YS300 is essential for the transcriptional activities of neighbouring Y-linked cluster genes. Mechanistically, we show that PML bodies play a novel role in 3D nuclear organization by providing specific nuclear spaces that the de novo DNA methyltransferase DNMT3A cannot access, which results in the robust maintenance of the hypo-methylated states at the Y-linked gene promoters. Our study underscores a new mechanism for gene regulation in the 3D-nuclear space and provides insights into the functional properties of nuclear structures for genome functions.
Patterns of linkage disequilibrium reveal genome architecture in chum salmon
Authors: McKinney Garrett , McPhee Megan V. , Pascal Carita , Seeb James E. , Seeb Lisa W. 
Published: August 2019

AbstractMany studies exclude loci exhibiting linkage disequilibrium (LD); however, high LD can signal reduced recombination around genomic features such as chromosome inversions or sex-determining regions. Chromosome inversions and sex-determining regions are often involved in adaptation, allowing for the inheritance of co-adapted gene complexes and for the resolution of sexually antagonistic selection through sex-specific partitioning of genetic variants. Genomic features such as these can escape detection when loci with LD are removed; in addition, failing to account for these features can introduce bias to analyses. We examined patterns of LD using network analysis to identify an overlapping chromosome inversion and sex-determining region in chum salmon. The signal of the inversion was strong enough to show up as false population substructure when the entire dataset was analyzed, while the signal of the sex-determining region was only obvious after restricting genetic analysis to the sex chromosome. Understanding the extent and geographic distribution of inversions is now a critically important part of genetic analyses of natural populations. The results of this study highlight the importance of analyzing and understanding patterns of LD in genomic dataset and the perils of ignoring or excluding loci exhibiting LD.
Psychotic-like experiences, polygenic risk scores for schizophrenia and structural properties of the salience, default mode and central-executive networks in healthy participants from UK Biobank
Authors: Alloza C. , Blesa-Cábez M. , Bastin M.E. , Madole J.W. , Buchanan C.R. , Janssen J. , Gibson J. , Deary I.J. , Tucker-Drob E.M. , Whalley H.C. , Arango C. , McIntosh A.M , Cox S.R , Lawrie S.M 
Published: August 2019

AbstractSchizophrenia is a highly heritable disorder with considerable phenotypic heterogeneity. Hallmark psychotic symptoms can be considered as existing on a continuum from non-clinical to clinical populations. Assessing genetic risk and psychotic-like experiences (PLEs) in non-clinical populations and their associated neurobiological underpinnings can offer valuable insights into symptom-associated brain mechanisms without the potential confounds of the effects of schizophrenia and its treatment. We leveraged a large population-based cohort (UKBiobank) including information on PLEs, polygenic risk scores for schizophrenia (PRSSZ) and multi-modal brain imaging in combination with network neuroscience. Morphometric (cortical thickness, volume) and water diffusion (fractional anisotropy) properties of the regions and pathways belonging to the salience, default-mode and central-executive networks were computed. We hypothesized that these anatomical concomitants of functional dysconnectivity would be negatively associated with PRSSZand PLEs. PRSSZwas significantly associated with a latent measure of cortical thickness across the salience network (r = −0.069,p= 0.010) and PLEs showed a number of significant associations with properties of the salience and default mode networks (involving the insular cortex, supramarginal gyrus and pars orbitalis,pFDR< 0.050); with the cortical thickness of the insula largely mediating the relationship between PRSSZand auditory hallucinations. These results are consistent with the hypothesis that higher genetic liability for schizophrenia is related to subtle disruptions in brain structure and predisposes to PLEs even among healthy participants. In addition, our study suggests that networks engaged during auditory hallucinations show structural associations with PLEs in the general population.