bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ventral Pallidum is Essential for Cocaine Reinstatement After Voluntary Abstinence
Authors: Farrell Mitchell R. , Ruiz Christina M. , Castillo Erik , Faget Lauren , Khanbijian Christine , Liu Siyu , Schoch Hannah , Rojas Gerardo , Hnasko Thomas S. , Mahler Stephen V. 
Published: May 2019

AbstractAddiction is a chronic relapsing disorder, and during recovery many people experience several relapse events as they attempt to voluntarily abstain from drug. New preclinical relapse models have emerged which capture this common human experience of relapse after voluntary abstinence, and mounting evidence indicates that reinstatement of drug seeking after voluntary abstinence recruits neural circuits distinct from reinstatement following experimenter-imposed abstinence, or abstinence due to extinction training. Ventral pallidum (VP), a key limbic node involved in drug seeking, has well-established roles in conventional reinstatement models tested following extinction training, but it is unclear whether this region also participates in more translationally-relevant models of relapse. Here we show that chemogenetic inhibition of VP neurons strongly attenuates cocaine-, context-, and cue-induced reinstatement tested after voluntary, punishment-induced abstinence. This effect was strongest in the most compulsive, punishment-resistant rats, and reinstatement was associated with neural activity in anatomically-defined VP subregions. VP inhibition also attenuated the propensity of rats to display ‘hesitations,’ a risk assessment behavior seen during punished drug taking that is likely due to concurrent approach and avoidance motivations. These results indicate that VP, unlike other connected limbic brain regions, is essential for reinstatement of drug seeking after voluntary abstinence. Since VP inhibition effects were strongest in the most compulsively cocaine-seeking individuals, this could indicate that VP plays a particularly important role in the most pathological, addiction-like behavior, making it an attractive target for future therapeutic interventions.
Neutrophils promote CXCR3-dependent itch in the development of atopic dermatitis
Authors: Walsh Carolyn M. , Hill Rose Z. , Schwendinger-Schreck Jamie , Deguine Jacques , Brock Emily C. , Kucirek Natalie , Rifi Ziad , Wei Jessica , Gronert Karsten , Brem Rachel B. , Barton Gregory M. , Bautista Diana M. 
Published: May 2019

AbstractChronic itch remains a highly prevalent disorder with limited treatment options. Most chronic itch diseases are thought to be driven by both the nervous and immune systems, but the fundamental molecular and cellular interactions that trigger the development of itch and the acute-to-chronic itch transition remain unknown. Here, we show that skin-infiltrating neutrophils are key initiators of itch in atopic dermatitis, the most prevalent chronic itch disorder. Neutrophil depletion significantly attenuated itch-evoked scratching in a mouse model of atopic dermatitis. Neutrophils were also required for several key hallmarks of chronic itch, including skin hyperinnervation, enhanced expression of itch signaling molecules, and upregulation of inflammatory cytokines, activity-induced genes, and markers of neuropathic itch. Finally, we demonstrate that neutrophils are required for induction of CXCL10, a ligand of the CXCR3 receptor that promotes itch via activation of sensory neurons, and we find that that CXCR3 antagonism attenuates chronic itch.
Multi-ethnic genome-wide association study of decomposed cardioelectric phenotypes illustrates strategies to identify and characterize evidence of shared genetic effects for complex traits
Authors: Baldassari Antoine R. , Sitlani Colleen M. , Highland Heather M. , Arking Dan E. , Buyske Steve , Darbar Dawood , Gondalia Rahul , Graff Misa , Guo Xiuqing , Heckbert Susan R. , Hindorff Lucia A. , Hodonsky Chani J. , Ida Chen Yii-Der , Kaplan Robert C. , Peters Ulrike , Post Wendy , Reiner Alex P. , Rotter Jerome I. , Shohet Ralph V. , Seyerle Amanda A. , Sotoodehnia Nona , Tao Ran , Taylor Kent D. , Wojcik Genevieve L , Yao Jie , Kenny Eimear E. , Lin Henry J. , Soliman Elsayed Z. , Whitsel Eric A. , North Kari E. , Kooperberg Charles , Avery Christy L. 
Published: May 2019

ABSTRACTBackgroundPublished genome-wide association studies (GWAS) are mainly European-centric, examine a narrow view of phenotypic variation, and infrequently interrogate genetic effects shared across traits. We therefore examined the extent to which a multi-ethnic, combined trait GWAS of phenotypes that map to well-defined biology can enable detection and characterization of complex trait loci.MethodsWith 1000 Genomes Phase 3 imputed data in 34,668 participants (15% African American; 3% Chinese American; 51% European American; 30% Hispanic/Latino), we performed covariate-adjusted univariate GWAS of six contiguous electrocardiogram (ECG) traits that decomposed an average heartbeat and two commonly reported composite ECG traits that summed contiguous traits. Combined phenotype testing was performed using the adaptive sum of powered scores test (aSPU).ResultsWe identified six novel and 87 known ECG trait loci (aSPU p-value < 5E-9). Lead SNP rs3211938 at novel locus CD36 was common in African Americans (minor allele frequency=10%) and near-monomorphic in European Americans, with effect sizes for the composite trait, QT interval, among the largest reported. Only one novel locus was detected for the composite traits, due to opposite directions of effects across contiguous traits that summed to near-zero. Combined phenotype testing did not detect novel loci unapparent by univariate testing. However, this approach aided locus characterization, particularly when loci harbored multiple independent signals that differed by trait.ConclusionsDespite including one-third as few participants as the largest published GWAS of ECG traits, our study identifies multiple novel ECG genetic loci, emphasizing the importance of ancestral diversity and phenotype measurement in this era of ever-growing GWAS.AUTHOR SUMMARYWe leveraged a multiethnic cohort with precise measures of cardioelectric function to identify novel genetic loci affecting this complex, multifaceted phenotype. The success of our approach stresses the importance of phenotypic precision and participant diversity for future locus discovery and characterization efforts, and cautions against compromises made in genome-wide association studies to pursue ever-growing sample sizes.
HBV seroepidemiology data for Africa provides insights into transmission and prevention
Authors: McNaughton Anna L , Lourenço José , Bester Phillip Armand , Mokaya Jolynne , Lumley Sheila F , Forde Donall , Maponga Tongai G , Katumba Kenneth R , Goedhals Dominique , Gupta Sunetra , Seeley Janet , Newton Robert , Ocama Ponsiano , Matthews Philippa C 
Published: May 2019

ABSTRACTInternational goals for elimination of hepatitis B virus (HBV) infection set ambitious targets for 2030. In many African populations, HBV prevalence remains high (≥8%) despite the roll-out of infant HBV immunisation from the mid-1990’s onwards. Enhanced efforts are now urgently required to improve an understanding of population epidemiology, in order to determine which interventions are most likely to be effective in advancing populations towards elimination goals. In populations with a high prevalence of infection, catch-up HBV vaccination of adults has sometimes been deployed as a preventive strategy. An alternative approach of ‘test and treat’ could be applied as a tool to interrupt transmission. We used a systematic approach to investigate the relationship between prevalence of HBV infection (HBsAg) and exposure (anti-HBc) in Africa, and then applied a mathematical model to investigate the impact of catch-up vaccination and a ‘test and treat’ strategy in Uganda, representing a high prevalence setting. We demonstrate a strong relationship between the prevalence of HBsAg and anti-HBc (p<0.0001), but with region-specific differences that may reflect different patterns of transmission. In high prevalence settings, catch-up vaccination may have a transient effect but this intervention does not contribute to a sustained decline in prevalence. In contrast, diagnosing and treating infection has a marked impact on reducing prevalence, equivalent to that of infant immunisation. Conclusion: We have developed a high-resolution picture of HBV epidemiology across Africa. Developing insights into regional differences provides an evidence base for the most effective interventions. In combination with robust neonatal immunisation programmes, testing and treating infection is likely to be of most impact in making advances towards elimination targets.
Predicting spread and effective control measures for African swine fever– should we blame the boars?
Authors: Taylor Rachel A. , Podgórski Tomasz , Simons Robin R. L. , Ip Sophie , Gale Paul , Kelly Louise A. , Snary Emma L. 
Published: May 2019

SummaryAfrican swine fever (ASF) has been causing multiple outbreaks in Russia, Poland and the Baltic countries in recent years and is currently spreading westwards throughout Europe and eastwards into China, with cases occurring in wild boar and domestic pigs. Curtailing further spread of ASF requires full understanding of the transmission pathways of the disease. Wild boars have been implicated as a potential reservoir for the disease and one of the main modes of transmission within Europe. We developed a spatially explicit model to estimate the risk of infection with ASF in boar and pigs due to the natural movement of wild boar that is applicable across the whole of Europe. We demonstrate the model by using it to predict the probability that early cases of ASF in Poland were caused by wild boar dispersion. The risk of infection in 2015 is computed due to wild boar cases in Poland in 2014, compared against the reported cases in 2015 and then the procedure is repeated for 2015-2016. We find that long- and medium-distance spread of ASF (i.e. >30km) is very unlikely to have occurred due to boar dispersal, due in part to the generally short distances boar will travel (<20km on average). We also predict what the relative success of different control strategies would have been in 2015, if they were implemented in 2014. Results suggest that hunting of boar reduces the number of new cases, but a larger region is at risk of ASF compared to no control measure. Alternatively, introducing boar-proof fencing reduces the size of the region at risk in 2015, but not the total number of cases. Overall, our model suggests wild boar movement is only responsible for local transmission of disease, thus other pathways are more dominant in medium and long distance spread of the disease.
Sensitive detection of circular DNAs at single-nucleotide resolution using guided realignment of partially aligned reads
Authors: Prada-Luengo Iñigo , Krogh Anders , Maretty Lasse , Regenberg Birgitte 
Published: May 2019

AbstractCircular DNA has recently been identified across different species including human normal and cancerous tissue, but short-read mappers are unable to align many of the reads crossing circle junctions and hence limits their detection from short-read sequencing data. Here, we propose a new method, Circle-Map, that guides the realignment of partially aligned reads using information from discordantly mapped reads. We demonstrate how this approach dramatically increases sensitivity for detection of circular DNA on both simulated and real data while retaining high precision.
The Avocado Genome Informs Deep Angiosperm Phylogeny, Highlights Introgressive Hybridization, and Reveals Pathogen-Influenced Gene Space Adaptation
Authors: Rendón-Anaya Martha , Ibarra-Laclette Enrique , Méndez Bravo Alfonso , Lan Tianying , Zheng Chunfang , Carretero-Paulet Lorenzo , Perez-Torres Claudia Anahí , Chacón-López Alejandra , Hernandez-Guzmán Gustavo , Chang Tien-Hao , Farr Kimberly M. , Barbazuk W. Brad , Chamala Srikar , Mutwil Marek , Shivhare Devendra , Alvarez-Ponce David , Mitter Neena , Hayward Alice , Fletcher Stephen , Rozas Julio , Sánchez Gracia Alejandro , Kuhn David , Barrientos-Priego Alejandro F. , Salojärvi Jarkko , Librado Pablo , Sankoff David , Herrera-Estrella Alfredo , Albert Victor A. , Herrera-Estrella Luis 
Published: May 2019

ABSTRACTThe avocado,Persea americana, is a fruit crop of immense importance to Mexican agriculture with an increasing demand worldwide. Avocado lies in the anciently-diverged magnoliid clade of angiosperms, which has a controversial phylogenetic position relative to eudicots and monocots. We sequenced the nuclear genomes of the Mexican avocado race,P. americanavar.drymifolia, and the most commercially popular hybrid cultivar, Hass, and anchored the latter to chromosomes using a genetic map. Resequencing of Guatemalan and West Indian varieties revealed that ∼39% of the Hass genome represents Guatemalan source regions introgressed into a Mexican race background. Some introgressed blocks are extremely large, consistent with the recent origin of the cultivar. The avocado lineage experienced two lineage-specific polyploidy events during its evolutionary history. Although gene-tree/species-tree phylogenomic results are inconclusive, syntenic ortholog distances to other species place avocado as sister to the enormous monocot and eudicot lineages combined. Duplicate genes descending from polyploidy augmented the transcription factor diversity of avocado, while tandem duplicates enhanced the secondary metabolism of the species. Phenylpropanoid biosynthesis, known to be elicited byColletotrichum(anthracnose) pathogen infection in avocado, is one enriched function among tandems. Furthermore, transcriptome data show that tandem duplicates are significantly up- and down-regulated in response to anthracnose infection, whereas polyploid duplicates are not, supporting the general view that collections of tandem duplicates contribute evolutionarily recent “tuning knobs” in the genome adaptive landscapes of given species.SIGNIFICANCE STATEMENTAvocado is a nutritious, economically important fruit species that occupies an unresolved position near the earliest evolutionary branchings of flowering plants. Our nuclear genome sequences of Mexican and Hass variety avocados inform ancient evolutionary relationships and genome doublings, the admixed nature of Hass, and provide a look at how pathogen interactions have shaped avocado’s more recent genomic evolutionary history.
Hepatitis C Virus Regulates its Replication by Maturing miR-122 Through Akt-Dependent Phosphorylation of KSRP
Authors: Baudesson Camille , Amadori Céline , Danso Hassan , Donati Flora , Nevers Quentin , Durand Tony , Lemasson Matthieu , Rosenberg Arielle R. , Trabucchi Michele , Ahmed-Belkacem Abdelhakim , Bruscella Patrice , Pawlotsky Jean-Michel , Féray Cyrille 
Published: May 2019

AbstractThe liver-specific micro-RNA-122 (miR-122) is required for the replication of hepatitis C virus (HCV). The direct interaction between miR-122 and the 5’ untranslated region of the HCV genome promotes viral replication and protects HCV RNA from degradation. Because HCV RNA is its own substrate for replication, infected cells are submitted to the sequestration of increasing levels of miR-122 and to global de-repression of host miR-122 mRNA targets. Whether and how HCV regulates miR-122 maturation to create an environment favorable to its replication remains unexplored. We discovered that Akt-dependent phosphorylation of KSRP host protein at Serine residue 193 is essential for miR-122 maturation in hepatocytes. Moreover, we showed the existence of a reciprocal regulation loop where HCV replication can modulate the proviral effect mediated by KSRP-dependent maturation of miR-122. These data support a mechanism by which HCV regulates the expression of miR-122 by hijacking KSRP, thereby fueling its own replication.
Mitonuclear interactions influence Alzheimer’s disease risk
Authors: Andrews Shea J , Fulton-Howard Brian , Patterson Christopher , McFall G Peggy , Gross Alden , Michaelis Elias K , Goate Alison , Swerdlow Russell H , Pa Judy ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: May 2019

AbstractWe examined the associations between mitochondrial DNA haplogroups (MT-hg) and their interactions with a polygenic risk score based on nuclear-encoded mitochondrial genes (nMT-PRS) with risk of dementia and age of onset of dementia (AOO). Logistic regression was used to determine the effect of MT-hgs and nMT-PRS on dementia at baseline (332 controls / 204 cases). Cox proportional hazards models were used to model dementia AOO (n=1047; 433 incident cases). Additionally, we tested for interactions between MT-hg and nMT-PRS in the logistic and Cox models. MT-hg K and a one SD larger nMT-PRS were associated with elevated odds of dementia. Significant antagonistic interactions between the nMT-PRS and MT-hg K and T were observed. Individual MT-hg were not associated with AOO; however, a significant antagonistic interactions was observed between the nMT-PRS and MT-hg T and a synergistic interaction between the nMT-PRS and MT-hg V. These results suggest that MT-hgs influence dementia risk, and that variants in the nuclear and mitochondrial genome interact to influence the age of onset of dementia.HighlightsMitochondrial dysfunction has been proposed to influence dementia riskMT-hg K and T interacted with a genetic risk score to reduce dementia riskMT-hg T and V interacted with a genetic risk score to influence dementia age of onset
Neglectful maternal caregiving involves altered brain plasticity in empathy-related areas
Authors: Rodrigo María José , León Inmaculada , García Lorna , Hernández-Cabrera Juan Andrés , Quiñones Ileana 
Published: May 2019

AbstractThe maternal brain undergoes functional and structural adaptations to sensitive caregiving that are critical for ensuring infant wellbeing. This study investigates brain structural alterations in neglectful caregiving and their impact on mother-child interactive behavior. High-resolution 3D volumetric images were obtained on 25 neglectful (NM) and 23 non-neglectful control (CM) mothers. Using Voxel-Based Morphometry, we compared gray and white matter volume (GMV/WMV) between the two groups. Mothers also completed an empathy scale and participated with their children in a standardized play task (Emotional Availability Scale, EA). NM, as compared to CM, showed GMV reductions in right insula, anterior/middle cingulate, and right inferior frontal gyrus (IFG), as well as WMV reductions in bilateral frontal regions. A GMV increase was observed in the right fusiform and cerebellum. Regression analyses showed a negative effect of fusiform GMV and a positive effect of right frontal WMV on EA Mediation analyses showed the mediating role of emotional empathy in the positive effect of insula and IFG, and the negative effect of cerebellum on EA. Neglectful mothering involves an altered plasticity in emotional empathy-related areas and in frontal areas associated with poor mother-child interactive bonding, indicating how critical the structural changes in these areas are for infant wellbeing.
The Impact of Pathway Database Choice on Statistical Enrichment Analysis and Predictive Modeling
Authors: Mubeen Sarah , Hoyt Charles Tapley , Gemünd Andre , Hofmann-Apitius Martin , Fröhlich Holger , Domingo-Fernández Daniel 
Published: May 2019

AbstractBackgroundPathway-centric approaches are widely used to interpret and contextualize -omicsdata. However, databases contain different representations of the same biological pathway, which may lead to different results of statistical enrichment analysis and predictive models in the context of precision medicine.ResultsWe have performed an in-depth benchmarking of the impact of pathway database choice on statistical enrichment analysis and predictive modeling. We analyzed five cancer datasets using three major pathway databases and developed an approach to merge several databases into a single integrative database: MPath. Our results show that equivalent pathways from different databases yield disparate results in statistical enrichment analysis. Moreover, we observed a significant dataset-dependent impact on performance of machine learning models on different prediction tasks. Further, MPath significantly improved prediction performance and reduced the variance of prediction performances in some cases. At the same time, MPath yielded more consistent and biologically plausible results in the statistical enrichment analyses. Finally, we implemented a software package designed to make our comparative analysis with these and additional databases fully reproducible and to facilitate the update of our integrative pathway resource in the future.ConclusionThis benchmarking study demonstrates that pathway database choice can influence the results of statistical enrichment analysis and prediction modeling. Therefore, we recommend the use of multiple pathway databases or the use of integrative databases.
MolNetEnhancer: enhanced molecular networks by integrating metabolome mining and annotation tools
Authors: Ernst Madeleine , Kang Kyo Bin , Caraballo-Rodríguez Andrés Mauricio , Nothias Louis-Felix , Wandy Joe , Wang Mingxun , Rogers Simon , Medema Marnix H. , Dorrestein Pieter C. , van der Hooft Justin J.J. 
Published: May 2019

AbstractMetabolomics has started to embrace computational approaches for chemical interpretation of large data sets. Yet, metabolite annotation remains a key challenge. Recently, molecular networking and MS2LDA emerged as molecular mining tools that find molecular families and substructures in mass spectrometry fragmentation data. Moreover, in silico annotation tools obtain and rank candidate molecules for fragmentation spectra. Ideally, all structural information obtained and inferred from these computational tools could be combined to increase the resulting chemical insight one can obtain from a data set. However, integration is currently hampered as each tool has its own output format and efficient matching of data across these tools is lacking. Here, we introduce MolNetEnhancer, a workflow that combines the outputs from molecular networking, MS2LDA, in silico annotation tools (such as Network Annotation Propagation or DEREPLICATOR) and the automated chemical classification through ClassyFire to provide a more comprehensive chemical overview of metabolomics data whilst at the same time illuminating structural details for each fragmentation spectrum. We present examples from four plant and bacterial case studies and show how MolNetEnhancer enables the chemical annotation, visualization, and discovery of the subtle substructural diversity within molecular families. We conclude that MolNetEnhancer is a useful tool that greatly assists the metabolomics researcher in deciphering the metabolome through combination of multiple independent in silico pipelines.