bluuebunny/crossref_metadata_2025_split huggingface dataset:
The fate of carbon in a mature forest under carbon dioxide enrichment
Authors: Jiang M. , Medlyn B.E. , Drake J.E. , Duursma R.A. , Anderson I.C. , Barton C.V.M. , Boer M.M. , Carrillo Y. , Castañeda-Gómez L. , Collins L. , Crous K.Y. , De Kauwe M.G. , Emmerson K.M. , Facey S.L. , Gherlenda A.N. , Gimeno T.E. , Hasegawa S. , Johnson S.N. , Macdonald C.A. , Mahmud K. , Moore B.D. , Nazaries L. , Nielsen U.N. , Noh N.J. , Ochoa-Hueso R. , Pathare V.S. , Pendall E. , Pineiro J. , Powell J.R. , Power S.A. , Reich P.B. , Renchon A.A. , Riegler M. , Rymer P. , Salomón R.L. , Singh B.K. , Smith B. , Tjoelker M.G. , Walker J.K.M. , Wujeska-Klause A. , Yang J. , Zaehle S. , Ellsworth D.S. 
Published: July 2019

AbstractAtmospheric carbon dioxide enrichment (eCO2) can enhance plant carbon uptake and growth1,2,3,4,5, thereby providing an important negative feedback to climate change by slowing the rate of increase of the atmospheric CO2concentration6. While evidence gathered from young aggrading forests has generally indicated a strong CO2fertilization effect on biomass growth3,4,5, it is unclear whether mature forests respond to eCO2in a similar way. In mature trees and forest stands7,8,9,10, photosynthetic uptake has been found to increase under eCO2without any apparent accompanying growth response, leaving an open question about the fate of additional carbon fixed under eCO24, 5, 7,8,9,10,11. Here, using data from the first ecosystem-scale Free-Air CO2Enrichment (FACE) experiment in a mature forest, we constructed a comprehensive ecosystem carbon budget to track the fate of carbon as the forest responds to four years of eCO2exposure. We show that, although the eCO2treatment of ambient +150 ppm (+38%) induced a 12% (+247 gCm-2yr-1) increase in carbon uptake through gross primary production, this additional carbon uptake did not lead to increased carbon sequestration at the ecosystem level. Instead, the majority of the extra carbon was emitted back into the atmosphere via several respiratory fluxes, with increased soil respiration alone contributing ∼50% of the total uptake surplus. Our results call into question the predominant thinking that the capacity of forests to act as carbon sinks will be generally enhanced under eCO2, and challenge the efficacy of climate mitigation strategies that rely on CO2fertilization as a driver of increased carbon sinks in standing forests and afforestation projects.
Machine-learning classification suggests that many alphaproteobacterial prophages may instead be gene transfer agents
Authors: Kogay Roman , Neely Taylor B. , Birnbaum Daniel P. , Hankel Camille R. , Shakya Migun , Zhaxybayeva Olga 
Published: July 2019

AbstractMany of the sequenced bacterial and archaeal genomes encode regions of viral provenance. Yet, not all of these regions encode bona fide viruses. Gene transfer agents (GTAs) are thought to be former viruses that are now maintained in genomes of some bacteria and archaea and are hypothesized to enable exchange of DNA within bacterial populations. In Alphaproteobacteria, genes homologous to the ‘head-tail’ gene cluster that encodes structural components of the Rhodobacter capsulatus GTA (RcGTA) are found in many taxa, even if they are only distantly related to Rhodobacter capsulatus. Yet, in most genomes available in GenBank RcGTA-like genes have annotations of typical viral proteins, and therefore are not easily distinguished from their viral homologs without additional analyses. Here, we report a ‘support vector machine’ classifier that quickly and accurately distinguishes RcGTA-like genes from their viral homologs by capturing the differences in the amino acid composition of the encoded proteins. Our open-source classifier is implemented in Python and can be used to scan homologs of the RcGTA genes in newly sequenced genomes. The classifier can also be trained to identify other types of GTAs, or even to detect other elements of viral ancestry. Using the classifier trained on a manually curated set of homologous viruses and GTAs, we detected RcGTA-like ‘head-tail’ gene clusters in 57.5% of the 1,423 examined alphaproteobacterial genomes. We also demonstrated that more than half of the in silico prophage predictions are instead likely to be GTAs, suggesting that in many alphaproteobacterial genomes the RcGTA-like elements remain unrecognized.Data depositionSequence alignments and phylogenetic trees are available in a FigShare repository at DOI 10.6084/m9.figshare.8796419. The Python source code of the described classifier and additional scripts used in the analyses are available via a GitHub repository at https://github.com/ecg-lab/GTA-Hunter-v1
Iterative Hard Thresholding in GWAS: Generalized Linear Models, Prior Weights, and Double Sparsity
Authors: Chu Benjamin B. , Keys Kevin L. , German Christopher A. , Zhou Hua , Zhou Jin J. , Sobel Eric , Sinsheimer Janet S. , Lange Kenneth 
Published: July 2019

1AbstractBackgroundConsecutive testing of single nucleotide polymorphisms (SNPs) is usually employed to identify genetic variants associated with complex traits. Ideally one should model all covariates in unison, but most existing analysis methods for genome-wide association studies (GWAS) perform only univariate regression.ResultsWe extend and efficiently implement iterative hard thresholding (IHT) for multiple regression, treating all SNPs simultaneously. Our extensions accommodate generalized linear models (GLMs), prior information on genetic variants, and grouping of variants. In our simulations, IHT recovers up to 30% more true predictors than SNP-by-SNP association testing, and exhibits a 2 to 3 orders of magnitude decrease in false positive rates compared to lasso regression. We also test IHT on the UK Biobank hypertension phenotypes and the Northern Finland Birth Cohort of 1966 cardiovascular phenotypes. We find that IHT scales to the large datasets of contemporary human genetics and recovers the plausible genetic variants identified by previous studies.ConclusionsOur real data analysis and simulation studies suggest that IHT can (a) recover highly correlated predictors, (b) avoid over-fitting, (c) deliver better true positive and false positive rates than either marginal testing or lasso regression, (d) recover unbiased regression coefficients, (e) exploit prior information and group-sparsity and (f) be used with biobank sized data sets. Although these advances are studied for GWAS inference, our extensions are pertinent to other regression problems with large numbers of predictors.
Critical Role for the Unique N-Terminus of Chlamydial MreB in Directing Its Membrane Association and Interaction with Elements of the Divisome
Authors: Lee Junghoon , Cox John V. , Ouellette Scot P. 
Published: July 2019

AbstractChlamydiaelack the conserved central coordinator protein of cell division FtsZ, a tubulin-like homolog. Current evidence indicatesChlamydiauses the actin-like homolog, MreB, to substitute for the role of FtsZ. Interestingly, we observed MreB as a ring at the septum in dividing cells ofChlamydia. We hypothesize that MreB, to substitute for FtsZ inChlamydia, must possess unique properties compared to canonical MreB orthologs. Sequence differences between chlamydial MreB and orthologs in other bacteria revealed that chlamydial MreB possesses an extended N-terminal region and the conserved amphipathic helix found in other bacterial MreBs. The extended N-terminal region was sufficient to restore the localization of a truncatedE. coliMreB mutant lacking its amphipathic helix to the membrane and was crucial for interactions with cell division components RodZ and FtsK, though the region was not required for homotypic interactions. Importantly, the N-terminal region was sufficient to direct GFP to the membrane when expressed inChlamydia. A mutant N-terminal region with reduced amphipathicity was unable to perform these functions. From these data, the extended N-terminal region of chlamydial MreB is critical for localization and interactions of this protein. Our data provide mechanistic support for chlamydial MreB to serve as a substitute for FtsZ.ImportanceChlamydia trachomatisis an obligate intracellular pathogen, causing sexual transmitted diseases and trachoma. Studying chlamydial physiology, especially its cell division mechanism, is important for developing novel therapeutic strategies for the treatment of these diseases. Since chlamydial cell division has unique features, including a polarized cell division process independent of FtsZ, a canonical cell division coordinator, studying the subject is helpful for understanding undefined aspects of chlamydial growth. In this study, we characterized MreB, a substitute for FtsZ, as a cell division coordinator. It forms a filamentous ring at the septum, like FtsZ inE. coli. We show that the localization of MreB is dependent upon the amphipathic nature of its extended N-terminus. Furthermore, this region is crucial for its interaction with other proteins involved in cell division. Given these results, chlamydial MreB may function as a scaffold for cell divisome proteins at the septum and regulate cell division in this organism.
Forced isoform switching of Neat1_1 to Neat1_2 leads to the loss of Neat1_1 and the hyperformation of paraspeckles but does not affect the development and growth of mice
Authors: Isobe Momo , Toya Hikaru , Mito Mari , Chiba Tomoki , Asahara Hiroshi , Hirose Tetsuro , Nakagawa Shinichi 
Published: July 2019

AbstractNeat1 is a long noncoding RNA (lncRNA) that serves as an architectural component of the nuclear bodies known as paraspeckles. Two isoforms of Neat1, the short isoform Neat1_1 and the long isoform Neat1_2, are generated from the same gene locus by alternative 3’ processing. Neat1_1 is the most abundant and the best conserved isoform expressed in various cell types, whereas Neat1_2 is expressed in a small population of particular cell types, including the tip cells of the intestinal epithelium. To investigate the physiological significance of isoform switching, we created mutant mice that solely expressed Neat1_2 by deleting the upstream polyadenylation (poly-A) signal (PAS) required for the production of Neat1_1. We observed the loss of Neat1_1 and strong upregulation of Neat1_2 in various tissues and cells and the subsequent hyperformation of paraspeckles, especially in cells that normally express Neat1_2. However, the mutant mice were born at the expected Mendelian ratios and did not exhibit obvious external and histological abnormalities. These observations suggested that the hyperformation of paraspeckles does not interfere with the development and growth of these animals under normal laboratory conditions.
Species-specific differences in the susceptibility of fungi towards the antifungal protein AFP depend on C3 saturation of glycosylceramides
Authors: Paege Norman , Warnecke Dirk , Zäuner Simone , Hagen Silke , Rodrigues Ana , Baumann Birgit , Thiess Melanie , Jung Sascha , Meyer Vera 
Published: July 2019

AbstractAFP is an antimicrobial peptide (AMP) produced by the filamentous fungusAspergillus giganteusand a very potent inhibitor of fungal growth without affecting the viability of bacteria, plant or mammalian cells. It targets chitin synthesis and causes plasma membrane permeabilization in many human and plant pathogenic fungi, but its exact mode of action is not known. We have recently proposed adoption of the “damage-response framework of microbial pathogenesis” put forward by Pirofksi and Casadevall in 1999 regarding the analysis of interactions between AMPs and microorganisms, thus, predicting that the cytotoxic capacity of a given AMP is relative and depends not only on the presence/absence of its target(s) in the host and the AMP concentration applied but also on other variables, such as microbial survival strategies. We show here using the examples of three filamentous fungi (Aspergillus niger, Aspergillus fumigatus, Fusarium graminearum) and two yeasts (Saccharomyces cerevisiae, Pichia pastoris) that the important parameters defining the AFP susceptibilities of these fungi are (i) the presence/absence of glycosylceramides, (ii) the presence/absence of Δ3(E)-desaturation of the fatty acid chain therein, and (iii) the (dis)ability of these fungi to respond to AFP inhibitory effects with the fortification of their cell walls via increased chitin and β-(1,3)-glucan synthesis. These observations support the adoption of the damage-response framework to holistically understand the outcome of AFP inhibitory effects.ImportanceOur data suggest a fundamental role of glycosylceramides in the susceptibility of fungi towards AFP. We discovered that only a minor structural difference in these molecules – the saturation level of their fatty acid chain, controlled by a 2-hydroxy fatty N-acyl-Δ3(E)-desaturase – is a key to understanding the inhibitory activity of AFP. As glycosylceramides are important components of fungal plasma membranes, we propose a model which links AFP-mediated inhibition of chitin synthesis in fungi with its potential to disturb plasma membrane integrity.
Separating Measured Genetic and Environmental Effects: Evidence Linking Parental Genotype and Adopted Child Outcomes
Authors: Domingue Benjamin W. , Fletcher Jason 
Published: July 2019

AbstractThere has been widespread adoption of genome wide summary scores (polygenic scores) as tools for studying the importance of genetics and associated lifecourse mechanisms across a range of demographic and socioeconomic outcomes. However, an often unacknowledged issue with these studies is that parental genetics impact both child environments and child genetics, leaving the effects of polygenic scores difficult to interpret. This paper uses multi-generational data containing polygenic scores for parents (n=7,193) and educational outcomes for adopted (n=855) and biological (n=20,939) children, many raised in the same families, which allows us to separate the influence of parental polygenic scores on children outcomes between environmental (adopted children) and environmental and genetic (biological children) effects. Our results complement recent work on “genetic nurture” by showing associations of parental polygenic scores with adopted children’s schooling, providing additional evidence that polygenic scores combine genetic and environmental influences and that research designs are needed to separate these estimated impacts.
Snake deltavirus utilizes envelope proteins of different viruses to generate infectious particles
Authors: Szirovicza Leonora , Hetzel Udo , Kipar Anja , Martinez-Sobrido Luis , Vapalahti Olli , Hepojoki Jussi 
Published: July 2019

ABSTRACTHepatitis D virus (HDV) is the only known human satellite virus, and it requires hepatitis B virus (HBV) to form infectious particles. Until 2018 HDV was the sole representative of the genusDeltavirus. The subsequent identification of HDV-like agents in non-human hosts indicated a much longer evolutionary history of deltaviruses than previously hypothesized. Interestingly, none of the HDV-like agents were found in co-infection with an HBV-like agent suggesting that these viruses use different helper virus(es). Here we show, using snake deltavirus (SDeV), that HBV represents only a single example of helper viruses for deltaviruses. We cloned the SDeV genome into a mammalian expression plasmid, and by transfection could initiate SDeV replication in cultured snake and mammalian cells. By superinfecting SDeV infected cells with arenaviruses, or by transfecting different viral surface proteins, we could induce infectious SDeV particle production. Our findings indicate that deltaviruses can likely use a multitude of helper viruses or even viral glycoproteins to form infectious particles. Persistent and recurrent infections would be beneficial for the spread of deltaviruses. It seems plausible that new human and veterinary disease associations with deltavirus infections will be identified in the future.
Mutations in a novel cadherin gene associated with Bt resistance inHelicoverpa zea
Authors: Fritz Megan L. , Nunziata Schyler O. , Guo Rong , Tabashnik Bruce E. , Carrière Yves 
Published: July 2019

AbstractTransgenic corn and cotton produce crystalline (Cry) proteins derived from the soil bacteriumBacillus thuringiensis(Bt) that are toxic to lepidopteran larvae.Helicoverpa zea,a key pest of corn and cotton in the U.S., has evolved widespread resistance to these proteins produced in Bt corn and cotton. While the genomic targets of Cry selection and the mutations that produce resistant phenotypes are known in other lepidopteran species, little is known about how Cry proteins shape the genome ofH. zea. We scanned the genomes of Cry1Ac-selected and unselectedH. zealines, and identified eleven genes on six scaffolds that showed evidence of selection by Cry1Ac, includingcadherin-86C(cad-86C), a gene from a family that is involved in Cry1A resistance in other lepidopterans. Although this gene was expressed in theH. zealarval midgut, the protein it encodes has only 17 to 22% identity with cadherin proteins from other species previously reported to be involved in Bt resistance. An analysis of midgut-expressed cDNAs showed significant between-line differences in the frequencies of putative nonsynonymous substitutions (both SNPs and indels). Our results indicate thatcad-86Cis a target of Cry1Ac selection inH. zea. Future work should investigate phenotypic effects of these nonsynonymous substitutions and their impact on phenotypic resistance in field populations.
Increased Mistranslation ProtectsE. colifrom Protein Misfolding Stress due to Activation of a RpoS-dependent Heat Shock Response
Authors: Evans Christopher R. , Fan Yongqiang , Ling Jiqiang 
Published: July 2019

AbstractThe misincorporation of an incorrect amino acid into a polypeptide during protein synthesis is considered a detrimental phenomenon. Mistranslated protein is often misfolded and degraded or non-functional and results in an increased cost to quality control machinery. Despite these costs, errors during protein synthesis are common in bacteria. Here we report that increased rates of mistranslation inEscherichia coliprovide protection from protein misfolding stress by increasing the level of the heat shock sigma factor, RpoH. Surprisingly, this increase in RpoH due to mistranslation is dependent on the presence of the general stress response sigma factor, RpoS. This report provides evidence for a protective function of mistranslation and suggests a novel regulatory role of RpoS on the RpoH-activated heat shock.
CoGAPS 3: Bayesian non-negative matrix factorization for single-cell analysis with asynchronous updates and sparse data structures
Authors: Sherman Thomas D. , Gao Tiger , Fertig Elana J. 
Published: July 2019

AbstractMotivationBayesian factorization methods, including Coordinated Gene Activity in Pattern Sets (CoGAPS), are emerging as powerful analysis tools for single cell data. However, these methods have greater computational costs than their gradient-based counterparts. These costs are often prohibitive for analysis of large single-cell datasets. Many such methods can be run in parallel which enables this limitation to be overcome by running on more powerful hardware. However, the constraints imposed by the prior distributions in CoGAPS limit the applicability of parallelization methods to enhance computational efficiency for single-cell analysis.ResultsWe upgraded CoGAPS in Version 3 to overcome the computational limitations of Bayesian matrix factorization for single cell data analysis. This software includes a new parallelization framework that is designed around the sequential updating steps of the algorithm to enhance computational efficiency. These algorithmic advances were coupled with new software architecture and sparse data structures to reduce the memory overhead for single-cell data. Altogether, these updates to CoGAPS enhance the efficiency of the algorithm so that it can analyze 1000 times more cells, enabling factorization of large single-cell data sets.AvailabilityCoGAPS is available as a Bioconductor package and the source code is provided at github.com/FertigLab/CoGAPS. All efficiency updates to enable single-cell analysis available as of version 3.2.Contactejfertig@jhmi.edu
LRRK2 regulates innate immune responses and neuroinflammation during Mycobacterium tuberculosis infection
Authors: Weindel C.G. , Bell S.L. , Huntington T.E. , Vail K.J. , Srinivasan R. , Patrick K.L. , Watson R.O. 
Published: July 2019

SUMMARYDespite many connections between mutations in leucine-rich repeat kinase 2 (LRRK2) and susceptibility to mycobacterial infection, we know little about its function outside of the brain, where it is studied in the context of Parkinson’s Disease (PD). Here, we report that LRRK2 controls peripheral macrophages and brain-resident glial cells’ ability to respond to and express inflammatory molecules. LRRK2 KO macrophages express elevated basal levels of type I interferons, resulting from defective purine metabolism, mitochondrial damage, and engagement of mitochondrial DNA with the cGAS DNA sensing pathway. While LRRK2 KO mice can control Mycobacterium tuberculosis (Mtb) infection, they exhibit exacerbated lung inflammation and altered activation of glial cells in PD-relevant regions of the brain. These results directly implicate LRRK2 in peripheral immunity and support the “multiple-hit hypothesis” of neurodegenerative disease, whereby infection coupled with genetic defects in LRRK2 create an immune milieu that alters activation of glial cells and may trigger PD.
Human induced pluripotent stem cell-derived neuroectodermal epithelial cells mistaken for blood-brain barrier-forming endothelial cells
Authors: Lu Tyler M. , Redmond David , Magdeldin Tarig , Nguyen Duc-Huy T. , Snead Amanda , Sproul Andrew , Xiang Jenny , Shido Koji , Fine Howard A. , Rosenwaks Zev , Rafii Shahin , Agalliu Dritan , Lis Raphaël 
Published: July 2019

AbstractBrain microvascular endothelial cells (BMECs) possess unique properties underlying the blood-brain-barrier (BBB), that are crucial for homeostatic brain functions and interactions with the immune system. Modulation of BBB function is essential for treatment of neurological diseases and effective tumor targeting. Studies to-date have been hampered by the lack of physiological models using cultivated human BMECs that sustain BBB properties. Recently, differentiation of induced pluripotent stem cells (iPSCs) into cells with BBB-like properties has been reported, providing a robust in vitro model for drug screening and mechanistic understanding of neurological diseases. However, the precise identity of these iBMECs remains unclear. Employing single-cell RNA sequencing, bioinformatic analysis and immunofluorescence for several pathways, transcription factors (TFs), and surface markers, we examined the molecular and functional properties of iBMECs differentiated either in the absence or presence of retinoic acid. We found that iBMECs lack both endothelial-lineage genes and ETS TFs that are essential for the establishment and maintenance of EC identity. Moreover, iBMECs fail to respond to angiogenic stimuli and form lumenized vessels in vivo. We demonstrate that human iBMECs are not barrier-forming ECs but rather EpCAM+ neuroectodermal epithelial cells (NE-EpiCs) that form tight junctions resembling those present in BBB-forming BMECs. Finally, overexpression of ETS TFs (ETV2, FLI1, and ERG) reprograms NE-EpiCs to become more like the BBB-forming ECs. Thus, although directed differentiation of human iBMECs primarily gives rise to epithelial cells, overexpression of several ETS TFs can divert them toward a vascular BBB in vitro.