bluuebunny/crossref_metadata_2025_split huggingface dataset:
Symbiotic cyanobacteria communities in hornworts across time, space, and host species
Authors: Nelson Jessica M. , Hauser Duncan A. , Li Fay-Wei 
Published: June 2020

SummaryRationaleWhile plant-microbe interactions have been intensively studied in mycorrhizal and rhizobial symbioses, much less is known about plant symbioses with nitrogen-fixing cyanobacteria. Here we focused on hornworts (a bryophyte lineage), and investigated the diversity of their cyanobionts and how these communities are shaped by spatial, temporal, and host factors.MethodWe carried out repeated samplings of hornwort and soil samples in upstate New York throughout the growing season. Three sympatric hornwort species were included, allowing us to directly compare partner specificity and selectivity. To profile cyanobacteria communities, we established a new metabarcoding protocol targetingrbcL-Xwith PacBio long reads.ResultsHornwort cyanobionts have a high phylogenetic diversity, including clades that do not contain other known plant or lichen symbionts. While the sympatric hornwort species have similarly low specificity, they exhibit different preferences toward cyanobionts, although this depended on what cyanobacteria were present in the soil. Cyanobacterial communities varied spatially, even at small scales, but time did not play a major organizing role.Conclusion.This study highlights the importance of sampling soil and sympatric species to infer partner compatibility and preference, and marks a critical step toward better understanding the ecology and evolution of plant-cyanobacteria symbiosis.
The Mammalian Target of Rapamycin (mTOR) Kinase Mediates Haloperidol-Induced Cataleptic Behavior
Authors: Ramírez-Jarquín Uri Nimrod , Shahani Neelam , Pryor William , Usiello Alessandro , Subramaniam Srinivasa 
Published: June 2020

ABSTRACTThe mammalian target of rapamycin (mTOR) is a ubiquitously expressed serine/threonine kinase protein complex (mTORC1 or mTORC2) that orchestrates diverse functions ranging from embryonic development to aging. However, its brain tissue-specific roles remain less explored. Here, we have identified that the depletion of themTORgene in the mice striatum completely prevented the extrapyramidal motor side-effects (catalepsy) induced by the dopamine 2 receptor (D2R) antagonist haloperidol, which is the most widely used typical antipsychotic drug. Conversely, a lack of striatal mTOR in mice did not affect catalepsy triggered by the dopamine 1 receptor (D1R) antagonist SCH23390. Along with the lack of cataleptic effects, the administration of haloperidol in mTOR mutants failed to increase striatal phosphorylation levels of ribosomal protein pS6 (S235/236) as seen in control animals. To confirm the observations of the genetic approach, we used a pharmacological method and determined that the mTORC1 inhibitor rapamycin has a profound influence upon post-synaptic D2R-dependent functions. We consistently found that pretreatment with rapamycin entirely prevented (in a time-dependent manner) the haloperidol-induced catalepsy in wild-type mice. Collectively, our data indicate that striatal mTORC1 blockade may offer therapeutic benefits with regard to the prevention of D2R-dependent extrapyramidal motor side-effects of haloperidol in psychiatric illness.
Pre-meiotic, 24-nt reproductive phasiRNAs are abundant in anthers of wheat and barley but not rice and maize
Authors: Bélanger Sébastien , Pokhrel Suresh , Czymmek Kirk , Meyers Blake C. 
Published: June 2020

ABSTRACTTwo classes of pre-meiotic (21-nt) and meiotic (24-nt) phasiRNAs and their patterns of accumulation have been described in maize and rice anthers. Their precise function remains unclear, but some studies have shown that they support male fertility. The important role of phasiRNAs in anthers underpins our current study to their characterization in wheat and barley anthers. In this study, we staged anthers at every 0.2 mm of development for one wheat and two barley varieties. We isolated pre-meiotic (0.2 mm, 0.4 mm and 0.6 mm), meiotic (0.8 mm, 1.0 mm and 1.4 mm) and post-meiotic (1.8 mm) anthers for which we then investigated accumulation patterns of RNAs, including reproductive phasiRNAs. We annotated a total 12,821 and 2,897PHASloci in the wheat and barley genomes, respectively. When comparing the total number ofPHASloci in genomes of maize, rice, barley and wheat, we characterized an expansion of reproductivePHASloci in the genomes ofPoaceaesubfamilies fromPanicoideaetoOryzoideaeand toPoideae. In addition to the two classes of pre-meiotic (21-nt) and meiotic (24-nt) phasiRNAs, previously described in maize and rice anthers, we described a group of 24-nt phasiRNAs that accumulate in pre-meiotic anthers. The absence of pre-meiotic 24-nt phasiRNAs in maize and rice suggests a divergence in grass species of thePoideaesubfamily. Additionally, we performed a co-expression gene analysis describing the regulation of phasiRNA biogenesis in wheat and barley anthers. We highlightAGO9andAGO6as candidate binding partners of pre-meiotic and meiotic 24-nt phasiRNAs, respectively.One sentence summaryIn wheat and barley anthers, 24-nt reproductive phasiRNAs are abundant in both meiotic and pre-meiotic stages.
Generalized correlation-based dynamical network analysis: a new high-performance approach for identifying allosteric communications in molecular dynamics trajectories
Authors: Melo Marcelo C. R. , Bernardi Rafael C. , de la Fuente-Nunez Cesar , Luthey-Schulten Zaida 
Published: June 2020

AbstractMolecular interactions are essential for regulation of cellular processes, from the formation of multiprotein complexes, to the allosteric activation of enzymes. Identifying the essential residues and molecular features that regulate such interactions is paramount for understanding the biochemical process in question, allowing for suppression of a reaction through drug interventions, or optimization of a chemical process using bioengineered molecules. In order to identify important residues and information pathways within molecular complexes, the Dynamical Network Analysis method was developed and has since been broadly applied in the literature. However, in the dawn of exascale computing, this method is generally limited to relatively small biomolecular systems. In this work we provide an evolution of the method, application and interface. All data processing and analysis is conducted through Jupyter notebooks, providing automatic detection of important solvent and ion residues, an optimized and parallel generalized correlation implementation that is linear with respect to the number of nodes in the system, and subsequent community clustering, calculation of betweenness of contacts, and determination optimal paths. Using the popular visualization program VMD, high-quality renderings of the networks over the biomolecular structures can be produced. Our new implementation was employed to investigate three different systems, with up to 2.5 M atoms, namely the OMP-decarboxylase, the Leucyl-tRNA synthetase complexed with its cognate tRNA and adenylate, and the respiratory complex I in a membrane environment. Our enhanced and updated protocol provides the community with an intuitive and interactive interface, which can be easily applied to large macromolecular complexes.
Mechanism and inhibition of SARS-CoV-2 PLpro
Authors: Klemm Theresa , Ebert Gregor , Calleja Dale J. , Allison Cody C. , Richardson Lachlan W. , Bernardini Jonathan P. , Lu Bernadine G. C. , Kuchel Nathan W. , Grohmann Christoph , Shibata Yuri , Gan Zhong Yan , Cooney James P. , Doerflinger Marcel , Au Amanda E. , Blackmore Timothy R. , Geurink Paul P. , Ovaa Huib , Newman Janet , Riboldi-Tunnicliffe Alan , Czabotar Peter E. , Mitchell Jeffrey P. , Feltham Rebecca , Lechtenberg Bernhard C. , Lowes Kym N. , Dewson Grant , Pellegrini Marc , Lessene Guillaume , Komander David 
Published: June 2020

AbstractCoronaviruses, including SARS-CoV-2, encode multifunctional proteases that are essential for viral replication and evasion of host innate immune mechanisms. The papain-like protease PLpro cleaves the viral polyprotein, and reverses inflammatory ubiquitin and anti-viral ubiquitin-like ISG15 protein modifications1,2. Drugs that target SARS-CoV-2 PLpro (hereafter, SARS2 PLpro) may hence be effective as treatments or prophylaxis for COVID-19, reducing viral load and reinstating innate immune responses3. We here characterise SARS2 PLpro in molecular and biochemical detail. SARS2 PLpro cleaves Lys48-linked polyubiquitin and ISG15 modifications with high activity. Structures of PLpro bound to ubiquitin and ISG15 reveal that the S1 ubiquitin binding site is responsible for high ISG15 activity, while the S2 binding site provides Lys48 chain specificity and cleavage efficiency. We further exploit two strategies to target PLpro. A repurposing approach, screening 3727 unique approved drugs and clinical compounds against SARS2 PLpro, identified no compounds that inhibited PLpro consistently or that could be validated in counterscreens. More promisingly, non-covalent small molecule SARS PLpro inhibitors were able to inhibit SARS2 PLpro with high potency and excellent antiviral activity in SARS-CoV-2 infection models.
Nucleocapsid protein of SARS-CoV-2 phase separates into RNA-rich polymerase-containing condensates
Authors: Savastano Adriana , de Opakua Alain Ibáñez , Rankovic Marija , Zweckstetter Markus 
Published: June 2020

SUMMARYThe etiologic agent of the Covid-19 pandemic is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The viral membrane of SARS-CoV-2 surrounds a helical nucleocapsid in which the viral genome is encapsulated by the nucleocapsid protein. The nucleocapsid protein of SARS-CoV-2 is produced at high levels within infected cells, enhances the efficiency of viral RNA transcription and is essential for viral replication. Here we show that RNA induces cooperative liquid-liquid phase separation of the SARS-CoV-2 nucleocapsid protein. In agreement with its ability to phase separate in vitro, we show that the protein associates in cells with stress granules, cytoplasmic RNA/protein granules that form through liquid-liquid phase separation and are modulated by viruses to maximize replication efficiency. Liquid-liquid phase separation generates high-density protein/RNA condensates that recruit the RNA-dependent RNA polymerase complex of SARS-CoV-2 providing a mechanism for efficient transcription of viral RNA. Inhibition of RNA-induced phase separation of the nucleocapsid protein by small molecules or biologics thus can interfere with a key step in the SARS-CoV-2 replication cycle.
Identification of a critical horseshoe-shaped region in the nsp5 (Mpro, 3CLpro) protease interdomain loop (IDL) of coronavirus mouse hepatitis virus (MHV)
Authors: Nick Benjamin C. , Pandya Mansi C. , Lu Xiaotao , Franke Megan E. , Callahan Sean M. , Hasik Emily F. , Berthrong Sean T. , Denison Mark R. , Stobart Christopher C. 
Published: June 2020

AbstractHuman coronaviruses are enveloped, positive-strand RNA viruses which cause respiratory diseases ranging in severity from the seasonal common cold to SARS and COVID-19. Of the 7 human coronaviruses discovered to date, 3 emergent and severe human coronavirus strains (SARS-CoV, MERS-CoV, and SARS-CoV-2) have recently jumped to humans in the last 20 years. The COVID-19 pandemic spawned by the emergence of SARS-CoV-2 in late 2019 has highlighted the importance for development of effective therapeutics to target emerging coronaviruses. Upon entry, the replicase genes of coronaviruses are translated and subsequently proteolytically processed by virus-encoded proteases. Of these proteases, nonstructural protein 5 (nsp5, Mpro, or 3CLpro), mediates the majority of these cleavages and remains a key drug target for therapeutic inhibitors. Efforts to develop nsp5 active-site inhibitors for human coronaviruses have thus far been unsuccessful, establishing the need for identification of other critical and conserved non-active-site regions of the protease. In this study, we describe the identification of an essential, conserved horseshoe-shaped region in the nsp5 interdomain loop (IDL) of mouse hepatitis virus (MHV), a common coronavirus replication model. Using site-directed mutagenesis and replication studies, we show that several residues comprising this horseshoe-shaped region either fail to tolerate mutagenesis or were associated with viral temperature-sensitivity. Structural modeling and sequence analysis of these sites in other coronaviruses, including all 7 human coronaviruses, suggests that the identified structure and sequence of this horseshoe regions is highly conserved and may represent a new, non-active-site regulatory region of the nsp5 (3CLpro) protease to target with coronavirus inhibitors.ImportanceIn December 2019, a novel coronavirus (SARS-CoV-2) emerged in humans and triggered a pandemic which has to date resulted in over 8 million confirmed cases of COVID-19 across more than 180 countries and territories (June 2020). SARS-CoV-2 represents the third emergent coronavirus in the past 20 years and the future emergence of new coronaviruses in humans remains certain. Critically, there remains no vaccine nor established therapeutics to treat cases of COVID-19. The coronavirus nsp5 protease is a conserved and indispensable virus-encoded enzyme which remains a key target for therapeutic design. However, past attempts to target the active site of nsp5 with inhibitors have failed stressing the need to identify new conserved non-active-site targets for therapeutic development. This study describes the discovery of a novel conserved structural region of the nsp5 protease of coronavirus mouse hepatitis virus (MHV) which may provide a new target for coronavirus drug development.
Cryptosporulation inKurthiaspp. forces a rethinking of asporogenesis in Firmicutes
Authors: Filippidou Sevasti , Fatton Mathilda , Junier Thomas , Berge Matthieu , Poppleton Daniel , Blum Thorsten B , Kaminek Marek , Odriozola Adolfo , Blom Jochen , Johnson Shannon L , Abrahams Jan Pieter , Chain Patrick S , Gribaldo Simonetta , Tocheva Elitza I. , Zuber Benoît , Viollier Patrick H , Junier Pilar 
Published: June 2020

AbstractSporulation is a complex morphophysiological process resulting in a cellular structure that is more resistant than the vegetative form. In Firmicutes, this structure is produced within the mother cell, and is called an endospore. Endospore formation is thought to have evolved in the common ancestor of Firmicutes. However, sporulation has apparently been lost in some extant lineages that are defined asasporogenic. We isolated strain 11kri321, a representative of the genusKurthia, from an oligotrophic geothermal reservoir. WhileKurthiaspp. is considered to comprise only asporogenic species, strain 11kri321 produced spores. Genomic reconstruction of the sporulation pathway shows elements typical of sporulation in Bacilli, including the signaling for sporulation onset. However, key genes were missing, including those involved in engulfment and dipicolinic acid synthesis. Based on the results for strain 11kri321, sporulation was investigated in otherKurthiastrains. Genes involved in signaling, cell division and spore coat formation were detected in three availableKurthiagenomes. Moreover, endosporulation was clearly visualized in at least two of the four strains tested. These results show thatKurthiais an endospore-forming Firmicute lineage. However, the genetic background of sporulation in this genus deviates from the known sporulation pathway in Firmicutes and even within Bacilli, suggesting that a revision of the minimal set of genes used for genomic detection of sporulation is required. Based on our findings we propose the termcryptosporulantto refer to putative asporogenic Firmicutes for which a detailed genomic and physiological characterization of sporulating is missing.ImportanceEndospore-forming Firmicutes include many environmental and medical relevant bacterial clades. In these microorganisms, the ability to produce endospores is essential for survival in the environment and even for pathogenesis. The minimum core of genes required to produce a viable and resistant spore, the distinction between endospore-forming and asporogenic groups, as well as the evolution of sporulation have been a subject of investigation and debate for decades. Here, we demonstrate endosporulation in the genusKurthia,considered as asporogenic. Morphological, physiological and genomic analyses were undertaken to demonstrate that sporulation is not lost within this lineage. Based on our results we propose a re-examination of the minimal genetic requirements of sporulation and the use of the termcryptosporulantto describe lineages of Firmicutes that have not previously been observed to sporulate, but for which a detailed analysis is still missing.
Analysis of Gene Expression from Systemic Lupus Erythematosus Synovium Reveals a Profile of Activated Immune Cells and Inflammatory Pathways
Authors: Hubbard Erika L. , Catalina Michelle D. , Heuer Sarah , Bachali Prathyusha , Robl Robert , Geraci Nicholas S. , Grammer Amrie C. , Lipsky Peter E. 
Published: June 2020

ABSTRACTArthritis is a common manifestation of systemic lupus erythematosus (SLE) yet understanding of the underlying pathogenic mechanisms remains incomplete. We, therefore, interrogated gene expression profiles of SLE synovium to gain insight into the nature of lupus arthritis (LA), using osteoarthritis (OA) and rheumatoid arthritis (RA) as comparators. Knee synovia from SLE, OA, and RA patients were analyzed for differentially expressed genes (DEGs) and also by Weighted Gene Co-expression Network Analysis (WGCNA) to identify modules of highly co-expressed genes. Genes upregulated and/or co-expressed in LA revealed numerous immune/inflammatory cells dominated by a myeloid phenotype, whereas OA was characteristic of fibroblasts and RA of T- and B-cells. Upstream regulator analysis identifiedCD40Land inflammatory cytokines as drivers of the LA gene expression profile. Genes governing trafficking of immune cells into the synovium by chemokines were identified, but notin situgeneration of germinal centers. GSVA confirmed activation of specific myeloid and lymphoid cell types in LA. Numerous therapies were predicted to target LA, including TNF, NFκB, MAPK, and CDK inhibitors. Detailed gene expression analysis identified a unique pattern of cellular components and physiologic pathways operative in LA, as well as drugs potentially able to target this common manifestation of SLE.
Can expectation suppression be explained by reduced attention to predictable stimuli?
Authors: Alink Arjen , Blank Helen 
Published: June 2020

AbstractThe expectation-suppression effect – reduced stimulus-evoked responses to expected stimuli – is widely considered to be an empirical hallmark of reduced prediction errors in the framework of predictive coding. Here we challenge this notion by proposing that that expectation suppression could be explained by a reduced attention effect. Specifically, we argue that reduced responses to predictable stimuli can also be explained by a reduced saliency-driven allocation of attention. We base our discussion mainly on findings in the visual cortex and propose that resolving this controversy requires the assessment of qualitative differences between the ways in which attention and ‘surprise’ enhance brain responses.
Ecogenomics of key prokaryotes in the arctic ocean
Authors: Royo-Llonch Marta , Sánchez Pablo , Ruiz-González Clara , Salazar Guillem , Pedrós-Alió Carlos , Labadie Karine , Paoli Lucas ,   Tara Oceans Coordinators, Chaffron Samuel , Eveillard Damien , Karsenti Eric , Sunagawa Shinichi , Wincker Patrick , Karp-Boss Lee , Bowler Chris , Acinas Silvia G 
Published: June 2020

SummaryThe Arctic Ocean is a key player in the regulation of climate and at the same time is under increasing pressure as a result of climate change. Predicting the future of this ecosystem requires understanding of the responses of Arctic microorganisms to environmental change, as they are the main drivers of global biogeochemical cycles. However, little is known about the ecology and metabolic potential of active Arctic microbes. Here, we reconstructed a total of 3,550 metagenomic bins from 41 seawater metagenomes collected as part of the Tara Oceans expedition, covering five different Arctic Ocean regions as well as the sub-Arctic North Atlantic Ocean and including various depths and different seasons (spring to autumn). Of these bins, 530 could be classified as Metagenome Assembled Genomes (MAGs) and over 75% of them represented novel species. We describe their habitat range and environmental preferences, as well as their metabolic capabilities, building the most comprehensive dataset of uncultured bacterial and archaeal genomes from the Arctic Ocean to date. We found a prevalence of mixotrophs, while chemolithoautotrophs were mostly present in the mesopelagic Arctic Ocean during spring and autumn. Finally, the catalogue of Arctic MAGs was complemented with metagenomes and metatranscriptomes from the global ocean to identify the most active MAGs present exclusively in polar metagenomes. These polar MAGs, which display a range of metabolic strategies, might represent Arctic sentinels of climate change and should be considered in prospective studies of the future state of the Arctic Ocean.
Transcription factor Sp1 regulates mitotic fidelity through Aurora B kinase-mediated condensin I localization
Authors: Flashner Samuel , Swift Michelle , Sowash Aislinn , Azizkhan-Clifford Jane 
Published: June 2020

AbstractMitotic chromosome assembly is essential for faithful chromosome segregation. Despite their salient role directing interphase chromatin organization, little is known about how transcription factors mediate this process during mitosis. Here, we characterize a mitosis-specific role for transcription factor specificity protein 1 (Sp1). Sp1 localizes to mitotic centromeres and auxin-induced rapid Sp1 degradation results in chromosome segregation errors and aberrant mitotic progression. These defects are driven by anomalous mitotic chromosome assembly. Sp1 degradation results in chromosome condensation defects through reduced condensin complex I localization. Sp1 also mediates the localization and activation of Aurora B kinase early in mitosis, which is essential for condensin complex I recruitment. Underscoring the clinical significance of our findings, aberrant Sp1 expression correlates with aneuploidy in several human cancers, including kidney renal papillary cell carcinoma, ovarian serous cystadenocarcinoma, mesothelioma, cholangiocarcinoma, and hepatocellular carcinoma. Our results suggest that Sp1 protects genomic integrity during mitosis by promoting chromosome assembly.