bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parkin coordinates mitochondrial lipid remodeling to execute mitophagy
Authors: Lin Chao-Chieh , Yan Jin , Kapur Meghan D. , Norris Kristi L. , Hsieh Cheng-Wei , Lai Chun-Hsiang , Vitale Nicolas , Lim Kah-Leong , Guan Ziqiang , Chi Jen-Tsan , Yang Wei-Yuan , Yao Tso-Pang 
Published: February 2020

AbstractMitochondrial failure caused by Parkin mutations contributes to Parkinson’s disease. Parkin binds, ubiquitinates, and targets impaired mitochondria for autophagic destruction. Robust mitophagy involves peri-nuclear concentration of Parkin-tagged mitochondria, followed by dissemination of juxtanuclear mitochondrial aggregates, and efficient sequestration of individualized mitochondria by autophagosomes. Here, we report that the execution of complex mitophagic events requires active mitochondrial lipid remodeling. Parkin recruits phospholipase D2 to the depolarized mitochondria and generate phosphatidic acid (PA). Mitochondrial PA is subsequently converted to diacylglycerol (DAG) by Lipin-1 phosphatase-a process that further requires mitochondrial ubiquitination and ubiquitin-binding autophagic receptors, NDP52 and Optineurin. We show that Optineurin transports, via Golgi-derived vesicles, a PA-binding factor EndoB1 to ubiquitinated mitochondria, thereby facilitating DAG production. Mitochondrial DAG activates both F-actin assembly to drive mitochondrial individualization, and autophagosome biogenesis to efficiently restrict impaired mitochondria. Thus Parkin, autophagic receptors and the Golgi complex orchestrate mitochondrial lipid remodeling to execute robust mitophagy.
Core and Matrix Thalamic Sub-Populations Relate to Spatio-Temporal Cortical Connectivity Gradients
Authors: Müller Eli , Munn Brandon , Hearne Luke J. , Smith Jared B. , Fulcher Ben , Cocchi Luca , Shine James M. 
Published: February 2020

AbstractRecent neuroimaging experiments have defined low-dimensional gradients of functional connectivity in the cerebral cortex that subserve a spectrum of capacities that span from sensation to cognition. Despite well-known anatomical connections to the cortex, the subcortical areas that support cortical functional organization have been relatively overlooked. One such structure is the thalamus, which maintains extensive anatomical and functional connections with the cerebral cortex across the cortical mantle. The thalamus has a heterogeneous cytoarchitecture, with at least two distinct cell classes that send differential projections to the cortex: granular-projecting ‘Core’ cells and supragranular-projecting ‘Matrix’ cells. Here we use high-resolution 7T resting-state fMRI data and the relative amount of two calcium-binding proteins, parvalbumin and calbindin, to infer the relative distribution of these two cell-types (Core and Matrix, respectively) in the thalamus. First, we demonstrate that thalamocortical connectivity recapitulates large-scale, low-dimensional connectivity gradients within the cerebral cortex. Next, we show that diffusely-projecting Matrix regions preferentially correlate with cortical regions with longer intrinsic fMRI timescales. We then show that the Core–Matrix architecture of the thalamus is important for understanding network topology in a manner that supports dynamic integration of signals distributed across the brain. Finally, we replicate our main results in a distinct 3T resting-state fMRI dataset. Linking molecular and functional neuroimaging data, our findings highlight the importance of the thalamic organization for understanding low-dimensional gradients of cortical connectivity.
Gene Networks and Pathways for Plasma Lipid Traits via Multi-tissue Multi-omics Systems Analysis
Authors: Blencowe Montgomery , Ahn In Sook , Saleem Zara , Luk Helen , Cely Ingrid , Mäkinen Ville-Petteri , Zhao Yuqi , Yang Xia 
Published: February 2020

AbstractGenome-wide association studies (GWAS) have implicated ∼380 genetic loci for plasma lipid regulation. However, these loci only explain 17-27% of the trait variance and a comprehensive understanding of the molecular mechanisms has not been achieved. In this study, we utilized an integrative genomics approach leveraging diverse genomic data from human populations to investigate whether genetic variants associated with various plasma lipid traits, namely total cholesterol (TC), high and low density lipoprotein cholesterol (HDL and LDL), and triglycerides (TG), from GWAS were concentrated on specific parts of tissue-specific gene regulatory networks. In addition to the expected lipid metabolism pathways, gene subnetworks involved in ‘interferon signaling’, ‘autoimmune/immune activation’, ‘visual transduction’, and ‘protein catabolism’ were significantly associated with all lipid traits. Additionally, we detected trait-specific subnetworks, including cadherin-associated subnetworks for LDL, glutathione metabolism for HDL, valine, leucine and isoleucine biosynthesis for TC, and insulin signaling and complement pathways for TG. Finally, utilizing gene-gene relations revealed by tissue-specific gene regulatory networks, we detected both known (e.g.APOH, APOA4, andABCA1) and novel (e.g.F2in adipose tissue) key regulator genes in these lipid-associated subnetworks. Knockdown of theF2gene (Coagulation Factor II, Thrombin) in 3T3-L1 and C3H10T1/2 adipocytes reduced gene expression ofAbcb11, Apoa5, Apof, Fabp1, Lipc, andCd36, reduced intracellular adipocyte lipid content, and increased extracellular lipid content, supporting a link between adipose thrombin and lipid regulation. Our results shed light on the complex mechanisms underlying lipid metabolism and highlight potential novel targets for lipid regulation and lipid-associated diseases.
An original model of brain infection identifies the hijacking of host lipoprotein import as a bacterial strategy for blood-brain barrier crossing
Authors: Benmimoun Billel , Papastefanaki Florentia , Périchon Bruno , Segklia Katerina , Roby Nicolas , Miriagou Vivi , Schmitt Christine , Dramsi Shaynoor , Matsas Rebecca , Spéder Pauline 
Published: February 2020

AbstractPathogens able to cross the blood-brain barrier (BBB) induce long-term neurological sequelae and death. Understanding how neurotropic pathogens bypass this strong physiological barrier is a prerequisite to devise therapeutic strategies. Here we propose an innovative model of infection in the developing Drosophila brain, combining whole brain explants within vivosystemic infection. We identified several mammalian pathogens able to cross the Drosophila BBB, including Group B Streptococcus (GBS). Amongst GBS surface components, lipoproteins, and in particular the B leucin-rich Blr, were important for BBB crossing and virulence in Drosophila. Further, we identified (V)LDL receptor LpR2, expressed in the BBB, as a host receptor for Blr, allowing GBS translocation through endocytosis. Finally, we demonstrated that Blr is required for BBB crossing and pathogenicity in a murine model of infection. Our results support the relevance of Drosophila for studying host-pathogen interactions and identify a new mechanism by which pathogens exploit host barriers to generate brain infection.
Genomic and phenotypic heterogeneity of clinical isolates of the human pathogensAspergillus fumigatus, Aspergillus lentulusandAspergillus fumigatiaffinis
Authors: dos Santos Renato Augusto Corrêa , Steenwyk Jacob L. , Rivero-Menendez Olga , Mead Matthew E. , Silva Lilian Pereira , Bastos Rafael Wesley , Alastruey-Izquierdo Ana , Goldman Gustavo Henrique , Rokas Antonis 
Published: February 2020

ABSTRACTFungal pathogens are a global threat to human health. For example, fungi from the genusAspergilluscause a spectrum of diseases collectively known as aspergillosis. Most of the >200,000 life-threatening aspergillosis infections per year worldwide are caused byAspergillus fumigatus. Recently, molecular typing techniques have revealed that aspergillosis can also be caused by organisms that are phenotypically similar toA. fumigatusbut genetically distinct, such asAspergillus lentulusandAspergillus fumigatiaffinis. Importantly, some of these so-called cryptic species exhibit different virulence and drug susceptibility profiles thanA. fumigatus, however, our understanding of their biology and pathogenic potential has been stymied by the lack of genome sequences and phenotypic profiling. To fill this gap, we phenotypically characterized the virulence and drug susceptibility of 15 clinical strains ofA. fumigatus, A. lentulus, andA. fumigatiaffinisfrom Spain and sequenced their genomes. We found heterogeneity in virulence and drug susceptibility across species and strains. Genes known to influence drug susceptibility (cyp51Aandfks1) vary in paralog number and sequence among these species and strains and correlate with differences in drug susceptibility. Similarly, genes known to be important for virulence inA. fumigatusshowed variability in number of paralogs across strains and across species. Characterization of the genomic similarities and differences of clinical strains ofA. lentulus, A. fumigatiaffinis, and A. fumigatusthat vary in disease-relevant traits will advance our understanding of the variance in pathogenicity betweenAspergillusspecies and strains that are collectively responsible for the vast majority of aspergillosis infections in humans.
Modeling cannabinoids from a large-scale sample ofCannabis sativachemotypes
Authors: Vergara Daniela , Gaudino Reggie , Blank Thomas , Keegan Brian 
Published: February 2020

AbstractThe accelerating legalization ofCannabishas opened the industry to using contemporary analytical techniques. The gene regulation and pharmacokinetics of dozens of cannabinoids remain poorly understood. Because retailers in many medical and recreational jurisdictions are required to report chemical concentrations of cannabinoids, commercial laboratories have growing chemotype datasets of diverseCannabiscultivars. Using a data set of 17,600 cultivars tested by Steep Hill Inc., we apply machine learning techniques to interpolate missing chemotype observations and cluster cultivars together based on similarity. Our results show that cultivars cluster based on their chemotype, and that some imputation methods work better than others at grouping these cultivars based on chemotypic identity. However, due to the missing data for some of the cannabinoids their behavior could not be accurately predicted. These findings have implications for characterizing complex interactions in cannabinoid biosynthesis and improving phenotypical classification ofCannabiscultivars.
In vivodiscovery of RNA proximal proteins in human cells via proximity-dependent biotinylation
Authors: Lin Xianzhi , Fonseca Marcos A. S. , Corona Rosario I. , Lawrenson Kate 
Published: February 2020

AbstractRNA molecules function as messengers or noncoding adaptor molecules, structural components, and regulators of genome organization and gene expression. Their roles and regulation are mediated by other molecules they interact with, especially RNA binding proteins (RBPs). Here we report RNA proximity labeling (RPL), an RNA-centric method based on fusion of an endonuclease-deficient Type VI CRISPR-Cas protein (dCas13b) and engineered ascorbate peroxidase (APEX2) to discoverin vivotarget RNA proximal proteins (RPPs) through proximity-based biotinylation.U1RPPs enriched by proximity-based biotinylation included bothU1snRNA canonical and noncanonical functions-related proteins. In addition, profiling of poly(A) tail proximal proteins uncovered expected categories of RBPs for poly(A) tails and also provided novel evidence for poly(A)+ RNA 5’-3’ proximity and expanded subcellular localizations. Our results suggest that RPL is a rapid approach for identifying both interacting and neighboring proteins associated with target RNA molecules in their native cellular contexts.
Induced mutagenesis by the DNA cytosine deaminase APOBEC3H Haplotype I protects against lung cancer
Authors: Hix Mark A. , Wong Lai , Flath Ben , Chelico Linda , Cisneros G. Andrés 
Published: February 2020

SummaryThe DNA cytosine deaminases APOBEC3A, APOBEC3B, and APOBEC3H Haplotype I can induce mutations in cells that lead to cancer evolution. The database of cancer biomarkers in DNA repair genes (DNArCdb) identified a single nucleotide polymorphism (rs139298) of APOBEC3H Haplotype I that is involved in lung cancer1. Here, we show that this single nucleotide polymorphism causes the destabilization of APOBEC3H Haplotype I. Computational analysis suggests that the resulting K121E change affects the structure of APOBEC3H leading to active site disruption and destabilization of the RNA-mediated dimer interface. A K117E mutation in a K121E background stabilized the APOBEC3H Haplotype I, enabled biochemical study, and showed that the K121E affected catalytic activity, single-stranded DNA binding, and oligomerization on single-stranded DNA. That the destabilization of a DNA mutator would be associated with lung cancer suggests that too much mutation could result in immune recognition or death of tumor cells, suggesting that multiple APOBEC3s would not be expressed in the same tumor cells. In support of this hypothesis, stably expressed APOBEC3H Haplotype I caused a high amount of double-stranded DNA breaks in a lung cancer cell line that endogenously expressed APOBEC3B. Altogether, the data support the model that high APOBEC3 mutations in tumors are protective.
Video Recording Can Conveniently Assay Mosquito Locomotor Activity
Authors: da Silva Araujo Maisa , Guo Fang , Rosbash Michael 
Published: February 2020

AbstractAnopheles gambiaeandAedes aegyptiare perhaps the best studied mosquito species and important carriers of human malaria and arbovirus, respectively. Mosquitoes have daily rhythms in behaviors and show a wide range of activity patterns. AlthoughAnophelesis known to be principally nocturnal andAedesprincipally diurnal, details of mosquito activity are not easily assayed in the laboratory. We recently described FlyBox, a simple tracking system for assayingDrosophilalocomotor activity rhythms and thought that it might also be applicable to monitoring mosquito activity. Indeed, we show here that FlyBox can easily, conveniently, affordably and accurately measure the activity ofAnophelesas well asAedesover several days. The resulting profiles under light-dark as well as constant darkness conditions are compatible with results in the literature, indicating that this or similar systems will be useful in the future for more detailed studies on a range of insect species and under more diverse laboratory conditions.
Host genotype and colonist arrival order jointly govern plant microbiome composition and function
Authors: Leopold Devin R. , Busby Posy E. 
Published: February 2020

SummaryThe composition of host-associated microbiomes can have important consequences for host health and fitness [1–3]. Yet, we still lack understanding of many fundamental processes that determine microbiome composition [4,5]. There is mounting evidence that historical contingency during microbiome assembly may overshadow more deterministic processes, such as the selective filters imposed by host traits [6–8]. More specifically, species arrival order has been frequently shown to affect microbiome composition [9–12], a phenomenon known as priority effects [13–15]. However, it is less clear whether priority effects during microbiome assembly are consequential for the host [16], or whether intraspecific variation in host traits can alter the trajectory of microbiome assembly under priority effects. In a greenhouse inoculation experiment using the black cottonwood (Populus trichocarpa) foliar microbiome, we manipulated host genotype and the colonization order of common foliar fungi. We quantified microbiome assembly outcomes using fungal marker-gene sequencing and measured susceptibility of the colonized host to a leaf rust pathogen, Melampsora × columbiana. We found that the effect of species arrival order on microbiome composition, and subsequent disease susceptibility, depended on the host genotype. Additionally, we found that microbiome assembly history can affect host disease susceptibility independent of microbiome composition at the time of pathogen exposure, suggesting that the interactive effects of species arrival order and host genotype can decouple community composition and function. Overall, these results highlight the importance of a key process underlying stochasticity in microbiome assembly while also revealing which hosts are most likely to experience these effects.
Bacterial infections in the early period after liver transplantation in adults: A prospective single‐center cohort study
Authors: Jafarpour Zahra , Pouladfar Gholamreza , Malek Hosseini Seyed Ali , Firoozifar Mohammad , Jafari Peyman 
Published: February 2020

AbstractLiver transplantation (LT) is a potentially curative treatment for terminal stage hepatic diseases. Bacterial infections are the main causes of mortality and morbidity in the early period after LT. Identifying the risk factors could help in minimizing their development. We prospectively investigated the incidence, characteristics, and risk factors of bacterial infections among the recipients during hospitalization after LT and assigned a predictive score. All 389 consecutive adults who underwent LT at the main referral hospital of LT in Iran during 1 year were enrolled prospectively in a cohort study. Infection group consisted of 143 recipients (36.8%). Urinary tract and surgical site infections were the most frequent ones. Gram‐negative bacteria were more prevalent than Gram‐positive ones. Independent risk factors were female sex (relative risks = 2.13), age ≤ 43.5 years (3.70), hospital stay ≥ 9.5 days (5.22), abdominal reoperation (3.03), vancomycin‐resistant Enterococci colonization (5.52), hospitalization 3 months prior to LT (3.25), mechanical ventilation ≥48 hr (4.93), and renal replacement therapies (13.40). We developed a risk score for the prediction of bacterial infections with an area under the receiver operating characteristic curve of 0.85 (95% CI, 0.81–0.89) with sensitivity of 88% and specificity of 64%. In the infection group, mortality was higher than in controls (18.9% vs. 2.0%) with longer hospitalization (16 vs. 10 days; P < 0.001). We detected a high rate of bacterial infections leading to longer hospital stay and higher mortality rate. The formulated risk score can help predict bacterial infections; however, it requires clinical validation in further studies.
Palms and trees resist extreme drought in Amazon forests with shallow water tables
Authors: Sousa Thaiane R. , Schietti Juliana , Coelho de Souza Fernanda , Esquivel‐Muelbert Adriane , Ribeiro Igor O. , Emílio Thaise , Pequeno Pedro A. C. L. , Phillips Oliver , Costa Flavia R. C. 
Published: February 2020

AbstractThe intensity and frequency of severe droughts in the Amazon region have increased in the recent decades. These extreme events are associated with changes in forest dynamics, biomass and floristic composition. However, most studies of drought response have focused on upland forests with deep water tables, which may be especially sensitive to drought. Palms, which tend to dominate the less well‐drained soils, have also been neglected. The relative neglect of shallow water tables and palms is a significant concern for our understanding of tropical drought impacts, especially as one‐third of Amazon forests grow on shallow water tables (<5 m deep).We evaluated the drought response of palms and trees in forests distributed over a 600 km transect in central‐southern Amazonia, where the landscape is dominated by shallow water table forests (SWTF). We compared vegetation dynamics before and following the 2015–2016 El Nino drought, the hottest and driest on record for the region (−214 mm of cumulative water deficit).We observed no change in stand mortality rates and no biomass loss in response to drought in these forests. Instead, we observed an increase in recruitment rates, which doubled to 6.78% year‐1 ± 4.40 (M ± SD) during 2015–2016 for palms and increased by half for trees (to 2.92% year‐1 ± 1.21), compared to rates in the pre‐El‐Nino interval. Within these SWTF, mortality and recruitment rates varied as a function of climatic drought intensity and water table depth for both palms and trees, with mortality being greatest in climatically and hydrologically wetter environments and recruitment greatest in drier environments. Across our transect, there was a significant increase over time in tree biomass.Synthesis. Our results indicate that forests growing over shallow water tables—relatively under‐studied vegetation that nonetheless occupies one‐third of Amazon forests—are remarkably resistant to drought. These findings are consistent with the hypothesis that local hydrology and its interactions with climate strongly constrain forest drought effects, and has implications for climate change feedbacks. This work enhances our understanding of integrated drought effects on tropical forest dynamics and highlights the importance of incorporating neglected forest types into both the modelling of forest climate responses and into public decisions about priorities for conservation.
Back to Stormont: The New Decade, New Approach Agreement and What it Means for Northern Ireland
Authors: Haughey Sean 
Published: February 2020

AbstractThe decision of the Democratic Unionist Party and Sinn Féin to once again share power in Northern Ireland has ended a three‐year hiatus in the region’s devolved government. The deal which resurrects the devolved institutions—New Decade, New Approach—is not short of ambition. It introduces significant institutional reforms which place the institutions on a more sustainable footing and limit the potential for abuse of the Assembly’s infamous Petition of Concern. Nettles have been grasped on issues to do with language, culture, and identity that have long vexed political parties in Northern Ireland. Tucked away in the deal’s appendices are commitments to implement outstanding pledges made in previous agreements, plus ambitious plans for the new Northern Ireland Executive. However, as parties in the region were quick to discover, aspects of this deal are easier said than done. This article considers what New Decade, New Approach promises and, if fully implemented, what its implications are for politics and governance in Northern Ireland.