bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell resolution analysis of the crosstalk between chemogenically activated astrocytes and microglia
Authors: Philtjens Stéphanie , Turnbull Marion T. , Thedy Brian P. , Moon Younghye , Kim Jungsu 
Published: April 2020

SummaryAstrocytes are the most common glial cell type in the brain, yet, it is unclear how their activation affects the transcriptome of neighboring cells. Engineered G protein-coupled receptors (GPCRs) called Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) enable selective activation of specific cell types, such as astrocytes. Here, we combine activation of astrocytes in the hippocampus and cortex of healthy mice with single-cell RNA sequencing. Our data show that long-term activation of astrocytes dramatically alters the transcriptome of astrocytes and microglia. Genes that were differentially expressed in Gq-DREADD-activated astrocytes are involved in neurogenesis and low-density lipoprotein particle biology, while those in the microglia were involved in lipoprotein handling, purinergic receptor activity, and immune cell migration and chemotaxis. Furthermore, network analysis showed that Gq-DREADD-mediated activation in astrocytes resulted in an upregulation of genes involved in the GPCR signaling pathways and calcium ion homeostasis, confirming astrocyte activation. This dataset will serve as a resource for the broader neuroscience community, and our findings highlight the importance of studying transcriptomic alterations in microglia after astrocyte activationin vivo.
DNA damage independent inhibition of NF-κB transcription by anthracyclines
Authors: Chora Ângelo Ferreira , Pedroso Dora , Kyriakou Eleni , Pejanovic Nadja , Colaço Henrique , Gozzelino Raffaella , Barros André , Willmann Katharina , Velho Tiago , Moita Catarina F. , Santos Isa , Pereira Pedro , Carvalho Sílvia , Martins Filipa Batalha , Ferreira João A. , Fernandes de Almeida Sérgio , Benes Vladimir , Anrather Josef , Weis Sebastian , Soares Miguel P. , Geerlof Arie , Neefjes Jacques , Sattler Michael , Messias Ana C. , Neves-Costa Ana , Moita Luís Ferreira 
Published: April 2020

AbstractAnthracyclines are among the most used and effective anticancer drugs. Their activity has been attributed to DNA double-strand breaks resulting from topoisomerase II poisoning and to eviction of histones from select sites in the genome. Here we show that the extensively used anthracyclines Doxorubicin, Daunorubicin and Epirubicin, decrease the transcription of nuclear factor kappa B (NF-κB)-dependent gene targets, but not interferon responsive genes. Using an NMR-based structural approach, we demonstrate that anthracyclines disturb the complexes formed between the NF-κB subunit RelA and its DNA binding sites. The variant anthracyclines Aclarubicin, Doxorubicinone and the newly developed Dimethyl-doxorubicin, which share anticancer properties with the other anthracyclines but do not induce DNA damage, also suppressed inflammation, thus uncoupling DNA damage from the effects on inflammation. These findings have implications for anticancer therapy and for the development of novel anti-inflammatory drugs with limited side effects for life-threatening conditions such as sepsis.
Genetic dissection of the fermentative and respiratory contributions supportingVibrio choleraehypoxic growth
Authors: Bueno Emilio , Sit Brandon , Waldor Matthew K. , Cava Felipe 
Published: April 2020

ABSTRACTBoth fermentative and respiratory processes contribute to bacterial metabolic adaptations to low oxygen tension (hypoxia). In the absence of O2as a respiratory electron sink, many bacteria utilize alternative electron acceptors such as nitrate (NO3−). During canonical NO3−respiration, NO3−is reduced in a stepwise manner to N2by a dedicated set of reductases.Vibrio cholerae,the etiological agent of cholera, only requires a single periplasmic NO3−reductase (NapA) to undergo NO3−respiration, suggesting that the pathogen possesses a non-canonical NO3−respiratory chain. Here, we used complementary transposon-based screens to identify genetic determinants of general hypoxic growth and NO3−respiration inV. cholerae. We found that while theV. choleraeNO3−respiratory chain is primarily composed of homologues of established NO3−respiratory genes, it also includes components previously unlinked to this process, such as the Na+-NADH dehydrogenase Nqr. The ethanol-generating enzyme AdhE was shown to be the principal fermentative branch required during hypoxic growth inV. cholerae. Relative to singleadhEornapAmutant strains, aV. choleraestrain lacking both genes exhibited severely impaired hypoxic growthin vitroandin vivo.Our findings reveal the genetic bases for interactions between disparate energy production pathways that support pathogen fitness in shifting conditions. Such metabolic specializations inV. choleraeand other pathogens are potential targets for antimicrobial interventions.IMPORTANCEBacteria reprogram their metabolism in environments with low oxygen levels (hypoxia). Typically, this occurs via regulation of two major, but largely independent, metabolic pathways-fermentation and respiration. Here, we found that the diarrheal pathogenVibrio choleraehas a respiratory chain for NO3−that consists largely of components found in other NO3−respiratory systems, but also contains several proteins not previously linked to this process. Both AdhE-dependent fermentation and NO3−respiration were required for efficient pathogen growth in both laboratory conditions and in an animal infection model. These observations provide genetic evidence for fermentative-respiratory interactions and identify metabolic vulnerabilities that may be targetable for new antimicrobial agents inV. choleraeand related pathogens.
A Ribosome Interaction Surface Sensitive to mRNA GCN Periodicity
Authors: Scopino Kristen , Williams Elliot , Elsayed Abdelrahman , Barr William A. , Krizanc Daniel , Thayer Kelly M. , Weir Michael P. 
Published: April 2020

ABSTRACTGCN codons are over-represented in initial codons of ORFs of prokaryote and eukaryote mRNAs. We describe a ribosome rRNA-protein surface that interacts with an mRNA GCN codon when next-in-line for the ribosome A site. The interaction surface is comprised of the edges of two stacked rRNA bases: the Watson-Crick edge of 16S/18S rRNA C1054 and adjacent Hoogsteen edge of A1196 (Escherichia coli16S rRNA numbering). Also part of the interaction surface, the planar guanidinium group of a conserved Arginine (R146 of yeast ribosomal protein Rps3) is stacked adjacent to A1196. On its other side, the interaction surface is anchored to the ribosome A site through base stacking of C1054 with the wobble anticodon base of the A-site tRNA. Using Molecular Dynamics simulations of a 495-residue subsystem of translocating ribosomes, we observe base pairing of C1054 to nucleotide G at position 1 of the next-in-line codon, consistent with previous cryo-EM observations, and hydrogen bonding of A1196 and R146 to C at position 2. Hydrogen bonding to both of these codon positions is significantly weakened when C at position 2 is changed to G, A or U. These sequence-sensitive mRNA-ribosome interactions at theC1054-A1196-R146 (CAR) surface potentially contribute to GCN-mediated regulation of protein translation.
Kingdom-wide analysis of the evolution of the plant type III polyketide synthase superfamily
Authors: Naake Thomas , Maeda Hiroshi A. , Proost Sebastian , Tohge Takayuki , Fernie Alisdair R. 
Published: April 2020

AbstractThe emergence of type III polyketide synthases (PKSs) was a pre-requisite for the conquest of land by the green lineage. To study the deep evolutionary history of this key family, we used phylogenomic synteny network and phylogenetic analyses of whole-genome data from 126 species spanning the green lineage. This study thereby combined study of genomic location and context with changes in gene sequences. We found that two major clades, CHS and LAP5/6 homologs, evolved early by a segmental duplication event prior to the divergence of Bryophytes and Tracheophytes. We propose that the macroevolution of the type III PKS superfamily is governed by whole-genome duplications and triplications. Intriguingly, the combined phylogenetic and synteny analyses in this study shed new insights into changes in the genomic location and context that are retained for a longer time scale with more recent functional divergence captured by gene sequence alterations.
RNA-GPS Predicts SARS-CoV-2 RNA Localization to Host Mitochondria and Nucleolus
Authors: Wu Kevin , Zou James , Chang Howard Y. 
Published: April 2020

AbstractThe SARS-CoV-2 coronavirus is driving a global pandemic, but its biological mechanisms are less well understood. SARS-CoV-2 is an RNA virus whose multiple genomic and sub-genomic RNA (sgRNA) transcripts hijack the host cell’s machinery, located across distinct cytotopic locations. Subcellular localization of its viral RNA could play important roles in viral replication and host antiviral immune response. Here we perform computational modeling of SARS-CoV-2 viral RNA localization across eight subcellular neighborhoods. We compare hundreds of SARS-CoV-2 genomes to the human transcriptome and other coronaviruses and perform systematic sub-sequence analyses to identify the responsible signals. Using state-of-the-art machine learning models, we predict that the SARS-CoV-2 RNA genome and all sgRNAs are enriched in the host mitochondrial matrix and nucleolus. The 5’ and 3’ viral untranslated regions possess the strongest and most distinct localization signals. We discuss the mitochondrial localization signal in relation to the formation of double-membrane vesicles, a critical stage in the coronavirus life cycle. Our computational analysis serves as a hypothesis generation tool to suggest models for SARS-CoV-2 biology and inform experimental efforts to combat the virus.
Magnetoencephalographic Signatures of Hierarchical Rule Learning in Newborns
Authors: Moser Julia , Schleger Franziska , Weiss Magdalene , Sippel Katrin , Dehaene-Lambertz Ghislaine , Preissl Hubert 
Published: April 2020

AbstractEstimating the extent to which newborn humans process input from their environment, especially regarding the depth of processing, is a challenging question. To approach this problem, we measured brain responses in 20 newborns with magnetoencephalography (MEG) in a “local-global” auditory oddball paradigm in which two-levels of hierarchical regularities are presented. Results suggest that infants in the first weeks of life are able to learn hierarchical rules, yet a certain level of vigilance seems to be necessary. Newborns detected violations of the first-order regularity and displayed a mismatch response between 200-400ms. Violations of the second-order regularity only evoked a late response in newborns in an active state, which was expressed by a high heart rate variability. These findings are in line with those obtained in human adults and older infants suggesting a continuity in the functional architecture from term- birth on, despite the important immaturity of the human brain at this age.
A transient role of primary cilia in controlling direct versus indirect neurogenesis in the developing cerebral cortex
Authors: Hasenpusch-Theil Kerstin , Laclef Christine , Colligan Matt , Fitzgerald Eamon , Howe Katherine , Carroll Emily , Abrams Shaun R. , Reiter Jeremy F. , Schneider-Maunoury Sylvie , Theil Thomas 
Published: April 2020

ABSTRACTDuring the development of the cerebral cortex, neurons are generated directly from radial glial cells or indirectly via basal progenitors. The balance between these division modes determines the number and types of neurons formed in the cortex thereby affecting cortical functioning. Here, we investigate the role of primary cilia in this process. We show that a mutation in the ciliary geneInpp5eleads to a transient increase in direct neurogenesis and subsequently to an overproduction of layer V neurons in newborn mice. Loss ofInpp5ealso affects ciliary structure coinciding with increased Akt and mTOR signalling and reduced Gli3 repressor levels. Genetically re-storing Gli3 repressor rescues the decreased indirect neurogenesis inInpp5emutants. Overall, our analyses reveal how primary cilia determine neuronal subtype composition of the cortex by controlling direct vs indirect neurogenesis. These findings have implications for understanding cortical malformations in ciliopathies withINPP5Emutations.
ROS in tobacco stigma exudate affect pollen proteome and provoke membrane hyperpolarization
Authors: Maria Breygina , Ekaterina Klimenko , Eugeny Shilov , Anna Mamaeva , Viktor Zgoda , Igor Fesenko 
Published: April 2020

1.AbstractROS are known to be accumulated in stigmas of different species and can possibly perform different functions in plant reproduction. Here we confirm the assumption that they affect pollen by altering ion transport through the plasma membrane; as a more deferred effect, pollen proteome is modified. We detected ROS in stigma exudate, found hyperpolarization in exudate-treated growing pollen tubes and used flow cytometry of pollen protoplasts to compare the effects of fresh exudate and exogenous H2O2on pollen tube plasmalemma. Exudate causes plasmalemma hyperpolarization similar to the one provoked by H2O2, which is abolished by catalase treatment and ROS quencher MnTMPP. Inhibitory analysis indicates the participation of Ca2+- and K+-conducting channels in the observed hyperpolarization, linking obtained data with previous patch-clamp studiesin vitro. For a deeper understanding of pollen response to ROS we analyzed proteome alterations in H2O2-treated pollen grains. We found 50 unique proteins and 20 differently accumulated proteins that are mainly involved in cell metabolism, energetics, protein synthesis and folding. Thus, pollen is getting ready for effective resource usage, construction of cellular components and rapid growth.HighlightsThe active substance in stigma exudate is H2O2H2O2causes hyperpolarization mediated by the activation of cation channels.H2O2affects pollen proteome; we found 50 unique proteins.
Clearance of senescent cells following cardiac ischemia-reperfusion injury improves recovery
Authors: Dookun Emily , Walaszczyk Anna , Redgrave Rachael , Palmowski Pawel , Tual-Chalot Simon , Suwana Averina , Chapman James , Jirkovsky Eduard , Sosa Leticia Donastorg , Gill Eleanor , Yausep Oliver E , Santin Yohan , Mialet-Perez Jeanne , Owens W Andrew , Grieve David , Spyridopoulos Ioakim , Taggart Michael , Arthur Helen M. , Passos João F. , Richardson Gavin D. 
Published: April 2020

AbstractA key component of cardiac ischemia-reperfusion injury (IRI) is the increased generation of reactive oxygen species, leading to enhanced inflammation and tissue dysfunction in patients following intervention for myocardial infarction. In this study we hypothesized that oxidative stress, due to ischemia-reperfusion, induces senescence which contributes to the pathophysiology of cardiac IRI. We demonstrate that IRI induces cellular senescence in both cardiomyocytes and interstitial cell populations and treatment with the senolytic drug navitoclax after ischemia-reperfusion improves left ventricular function, increases myocardial vascularization, and decreases scar size. SWATH-MS based proteomics reveal that biological processes associated with fibrosis and inflammation, that were increased following ischemia-reperfusion, were attenuated upon senescent cell clearance. Furthermore, navitoclax treatment reduced the expression of proinflammatory, profibrotic and anti-angiogenic cytokines, including interferon gamma-induced protein-10, TGF-β3, interleukin-11, interleukin-16 and fractalkine. Our study provides proof-of-concept evidence that cellular senescence contributes to impaired heart function and adverse remodeling following cardiac ischemia-reperfusion. We also establish that post-IRI senescent cells play a considerable role in the inflammatory response. Subsequently, senolytic treatment, at a clinically feasible time point, attenuates multiple components of this response and improves clinically important parameters. Thus, cellular senescence represents a potential novel therapeutic avenue to improve patient outcomes following cardiac ischemia-reperfusion.
Multidecadal decline and recovery of aspen experiencing contrasting fire regimes: long-unburned, infrequent and frequent mixed-severity wildfire
Authors: Brewen Cerena J. , Berrill John-Pascal , Ritchie Martin W. , Boston Kevin , Dagley Christa M. , Jones Bobette , Coppoletta Michelle , Burnett Coye L. 
Published: April 2020

AbstractQuaking aspen (Populus tremuloides) is a valued, minor component on western landscapes. It provides a wide range of ecosystem services and has been in decline throughout the arid west for the last century. This decline may be explained partially by the lack of fire on the landscape as aspen benefit from fire that eliminates conifer competition and stimulates reproduction through root suckering. Managers are interested in aspen restoration but there is a lack of knowledge about their spatial dynamics in response to fire. Our study area in northeastern California on the Lassen, Modoc and Plumas National Forests has experienced recent large mixed-severity wildfires where aspen was present, providing an opportunity to study the re-introduction of fire. We observed two time periods; a 54-year absence of fire from 1941 to 1993 preceding a 24-year period of wildfire activity from 1993 to 2017. We utilized aerial photos to delineate aspen stand size, location and succession to conifers. We chose aspen stands in areas where wildfires overlapped (twice-burned), where only a single wildfire burned, and areas that did not burn within the recent 24-year period. We looked at these same stands within the first period of fire exclusion for comparison (i.e., 1941-1993). In the absence of fire, all aspen stand areas declined and all stands experienced increases in conifer composition. After wildfire, stands that burned experienced a release from conifer competition and increased in stand area. Stands that burned twice or at high severity experienced a larger removal of conifer competition than stands that burned once at low severity, promoting aspen recovery and expansion. Stands with less edge:area ratio also expanded more with fire present. Across both time periods, stand movement, where aspen stand footprints were mostly in new areas compared to footprints of previous years, was highest in smaller stands. In the fire exclusion period, smaller stands exhibited greater changes in area and location (movement), highlighting their vulnerability to loss in the absence of disturbances that provide adequate growing space for aspen over time.
Systematic hormone-metabolite network provides insights of high salinity tolerance inPongamia pinnata(L.) pierre
Authors: Marriboina Sureshbabu , Sharma Kapil , Sengupta Debashree , Yadavalli Anurupa Devi , Sharma Rameshwar Prasad , Reddy Attipalli Ramachandra 
Published: April 2020

AbstractSalinity stress results significant losses in plant productivity, and loss of cultivable lands. AlthoughPongamia pinnatais reported to be a salt tolerant semiarid tree crop, the adaptive mechanisms to saline environment are elusive. The present investigation describes alterations in hormonal and metabolic responses in correlation with physiological and molecular variations in leaves and roots of Pongamia at sea salinity level (3% NaCl) for 8 days. At physiological level, salinity induced adjustments in plant morphology, leaf gas exchange and ion accumulation patterns were observed. Our study also revealed that phytohormones including JAs and ABA play crucial role in promoting the salt adaptive strategies such as apoplasmic Na+sequestration and cell wall lignification in leaves and roots of Pongamia. Correlation studies demonstrated that hormones including ABA, JAs and SA showed a positive interaction with selective compatible metabolites (sugars, polyols and organic acids) to aid in maintaining osmotic balance and conferring salt tolerance to Pongamia. At the molecular level, our data showed that differential expression of transporter genes as well as antioxidant genes regulate the ionic and ROS homeostasis in Pongamia. Collectively, these results shed new insights on an integrated physiological, structural, molecular and metabolic adaptations conferring salinity tolerance to Pongamia.High lightOur data, for the first time, provide new insights for an integrated molecular and metabolic adaptation conferring salinity tolerance in Pongamia. The present investigation describes alterations in hormonal and metabolic responses in correlation with physiological and molecular variations in Pongamia at sea salinity level (3% NaCl) for 8 days.
Plant pathogen infection risk tracks global crop yields under climate change
Authors: Chaloner Thomas M. , Gurr Sarah J. , Bebber Daniel P. 
Published: April 2020

AbstractGlobal food security is strongly determined by crop production. Climate change-induced losses to production can occur directly, or indirectly, including via the distributions and impacts of plant pathogens. However, the likely changes in pathogen pressure in relation to global crop production are poorly understood. Here we show that temperature-dependent infection risk, r(T), for 80 fungal and oomycete crop pathogens will track projected yield changes in 12 crops over the 21st Century. For most crops, both yields and r(T) are likely to increase at high latitudes. In contrast, while the tropics will see little or no productivity gains, r(T) is also likely to decline. In addition, the USA, Europe and China may experience major changes in pathogen assemblages. The benefits of yield gains may therefore be tempered by the increased burden of crop protection due to increased and unfamiliar pathogens.
Random peptides rich in small and disorder-promoting amino acids are less likely to be harmful
Authors: Kosinski Luke , Aviles Nathan , Gomez Kevin , Masel Joanna 
Published: April 2020

AbstractProteins are the workhorses of the cell, yet they carry great potential for harm via misfolding and aggregation. Despite the dangers, proteins are sometimes bornde novofrom non-coding DNA. Proteins are more likely to be born from non-coding regions that produce peptides that do little to no harm when translated than from regions that produce harmful peptides. To investigate which newborn proteins are most likely to “first, do no harm”, we estimate fitnesses from an experiment that competedEscherichia colilineages that each expressed a unique random peptide. A variety of peptide metrics significantly predict lineage fitness, but this predictive power stems from simple amino acid frequencies rather than the ordering of amino acids. Amino acids that are smaller and that promote intrinsic structural disorder have more benign fitness effects. We validate that the amino acids that indicate benign effects in random peptides expressed inE. colialso do so in an independent dataset of random N-terminal tags in which it is possible to control for expression level. The same amino acids are also enriched in young animal proteins.Significance statementProteins are sometimes born de novo. In an experiment to reproduce this process inEscherichia coli, we were able to predict 15% of the variation in random peptide fitness effects from their amino acid frequencies. In contrast, which order the amino acids are in seems to make no difference, adding no predictive power on top of simple amino acid frequencies. Amino acids that are smaller and promote intrinsic structural disorder have more benign fitness effects.