bluuebunny/crossref_metadata_2025_split huggingface dataset:
Small Extracellular Vesicles Secreted by Region-specific Astrocytes Ameliorate the Mitochondrial Function in a Cellular Model of Parkinson’s Disease
Authors: Leggio Loredana , L’Episcopo Francesca , Magrì Andrea , Ulloa-Navas María José , Paternò Greta , Vivarelli Silvia , Bastos Carlos A. P. , Tirolo Cataldo , Testa Nunzio , Caniglia Salvatore , Risiglione Pierpaolo , Pappalardo Fabrizio , Faria Nuno , Peruzzotti-Jametti Luca , Pluchino Stefano , García-Verdugo José Manuel , Messina Angela , Marchetti Bianca , Iraci Nunzio 
Published: April 2021

AbstractExtracellular vesicles (EVs) are emerging as powerful players in cell-to-cell communication both in health and diseased brain. In Parkinson’s disease (PD) – characterized by selective dopaminergic (DAergic) neuron death in ventral midbrain (VMB) and degeneration of DAergic terminals in striatum (STR) – astrocytes (AS) exert dual harmful/protective functions. When activated by chemokine CCL3, AS promote a robust DAergic neuroprotection both in cellular and pre-clinical models of PD, with mechanisms not fully elucidated. Here we used a combination of techniques to characterize AS-EVs derived from VMB and STR, and investigated their potential to exert neuroprotection. First, we show that: (i) AS of both regions secrete small EVs of ~100 nm; (ii) VMB-AS release more EVs per cell than STR-AS under basal conditions; and (iii) only VMB-AS respond to CCL3 by producing more EVs, suggesting differential AS-EV secretion rate according to PD brain region. Next, addressing AS-EV potential against oxidative stress and mitochondrial toxicity, we found that AS-EVs, especially CCL3-AS-EVs, fully counteract H2O2-induced caspase-3 activation. Furthermore, using high resolution respirometry, we demonstrated that AS-EVs rescue the neuronal mitochondrial complex I function impaired by MPP+, with VMB-AS-EVs fully restoring ATP production in MPP+-injured neurons, highlighting a regional diversity of AS-EVs with neuroprotective implications for PD.
Jasmonate inhibits adventitious root initiation through transcriptional repression ofCKX1and activation ofRAP2.6Ltranscription factor in Arabidopsis
Authors: Dob Asma , Lakehal Abdellah , Novak Ondrej , Bellini Catherine 
Published: April 2021

AbstractAdventitious rooting is ade novoorganogenesis process that enables plants to propagate clonally and cope with environmental stresses. Adventitious root initiation (ARI) is controlled by interconnected transcriptional and hormonal networks, but there is little knowledge of the genetic and molecular programs orchestrating these networks. Thus, we have applied genome-wide transcriptome profiling to elucidate the profound transcriptional reprogramming events preceding ARI. These reprogramming events are associated with downregulation of cytokinin (CK) signaling and response genes, which could be triggers for ARI. Interestingly, we found that CK free-base content declined during ARI, due to downregulation ofde novoCK biosynthesis and upregulation of CK inactivation pathways. We also found that MYC2-dependent jasmonate (JA) signaling inhibits ARI by downregulating expression of theCYTOKININ OXIDASE/DEHYDROGENASE1gene. We also demonstrated that JA and CK synergistically activate expression ofRELATED to APETALA2.6 LIKE(RAP2.6L) transcription factor, and constitutive expression of this transcription factor strongly inhibits ARI. Collectively, our findings reveal that previously unknown genetic interactions between JA and CK play key roles in ARI
Exquisite Sensitivity to Dual BRG1/BRM ATPase Inhibitors Reveals Broad SWI/SNF Dependencies in Acute Myeloid Leukemia
Authors: Rago Florencia , Rodrigues Lindsey Ulkus , Bonney Megan , Sprouffske Kathleen , Kurth Esther , Elliott GiNell , Ambrose Jessi , Aspesi Peter , Oborski Justin , Chen Julie T. , McDonald E. Robert , Mapa Felipa A , Ruddy David A. , Kauffmann Audrey , Abrams Tinya , Bhang Hyo-eun C. , Jagani Zainab 
Published: April 2021

AbstractVarious subunits of mammalian SWI/SNF chromatin remodeling complexes display loss-of-function mutations characteristic of tumor suppressors in different cancers, but an additional role for SWI/SNF supporting cell survival in distinct cancer contexts is emerging. In particular, genetic dependence on the catalytic subunit BRG1/SMARCA4 has been observed in acute myeloid leukemia (AML), yet the feasibility of direct therapeutic targeting of SWI/SNF catalytic activity in leukemia remains unknown. Here, we evaluated the activity of dual BRG1/BRM ATPase inhibitors across a genetically diverse panel of cancer cell lines and observed that hematopoietic cancer cell lines were among the most sensitive compared to other lineages. This result was striking in comparison to data from pooled short hairpin RNA screens, which showed that only a subset of leukemia cell lines display sensitivity to BRG1 knockdown. We demonstrate that combined genetic knockdown of BRG1 and BRM is required to recapitulate the effects of dual inhibitors, suggesting that SWI/SNF dependency in human leukemia extends beyond a predominantly BRG1-driven mechanism. Through gene expression and chromatin accessibility studies, we show that the dual inhibitors act at genomic loci associated with oncogenic transcription factors, and observe a downregulation of leukemic pathway genes includingMYC, a well-established target of BRG1 activity in AML. Overall, small molecule inhibition of BRG1/BRM induced common transcriptional responses across leukemia models resulting in a spectrum of cellular phenotypes. Our studies reveal the breadth of SWI/SNF dependency and support targeting SWI/SNF catalytic function as a potential therapeutic strategy in AML.
Annual dynamics ofZymoseptoria triticipopulations in wheat cultivar mixtures: a compromise between the efficiency and durability of a recently broken-down resistance gene?
Authors: Orellana-Torrejon Carolina , Vidal Tiphaine , Boixel Anne-Lise , Gélisse Sandrine , Saint-Jean Sébastien , Frédéric Suffert 
Published: April 2021

AbstractCultivar mixtures slow polycyclic epidemics but may also affect the evolution of pathogen populations by diversifying the selection pressures exerted by their plant hosts at field scale. We compared the dynamics of natural populations of the fungal pathogenZymoseptoria triticiin pure stands and in three binary mixtures of wheat cultivars (one susceptible cultivar and one cultivar carrying the recently broken-downStb16qgene) over two annual field epidemics. We combined analyses of population ‘size’ based on disease severity, and of population ‘composition’ based on changes in the frequency of virulence againstStb16qin seedling assays with more than 3000 strains. Disease reductions were observed in mixtures late in the epidemic, at the whole canopy scale and on both cultivars, suggesting the existence of a reciprocal ‘protective’ effect. The three cultivar proportions in the mixtures (0.25, 0.5 and 0.75) modulated the decrease in (i) the size of the pathogen population relative to the two pure stands, (ii) the size of the virulent subpopulation, and (iii) the frequency of virulence relative to the pure stand of the cultivar carryingStb16q. Our findings suggest that optimal proportions may differ slightly between the three indicators considered. We argued potential trade-offs that should be taken into account when deploying a resistance gene in cultivar mixtures: between the dual objectives ‘efficacy’ and ‘durability’, and between the ‘size’ and ‘frequency’ of the virulent subpopulation. Based on current knowledge, it remains unclear whether virulent subpopulation size or frequency has the largest influence on interepidemic virulence transmission.
A Computational and Biochemical Study of -1 Ribosomal Frameshifting in Human mRNAs
Authors: Zhou Xia , Huang Xiaolan , Du Zhihua 
Published: April 2021

Abstract−1 programmed ribosomal frameshifting (−1 PRF) is a translational recoding mechanism used by many viral and cellular mRNAs. −1 PRF occurs at a heptanucleotide slippery sequence and is stimulated by a downstream RNA structure, most often in the form of a pseudoknot. The utilization of −1 PRF to produce proteins encoded by the −1 reading frame is wide-spread in RNA viruses, but relatively rare in cellular mRNAs. In human, only three such cases of −1 PRF events have been reported, all involving retroviral-like genes and protein products. To evaluate the extent of −1 PRF utilization in the human transcriptome, we have developed a computational scheme for identifying putative pseudoknot-dependent −1 PRF events and applied the method to a collection of 43,191 human mRNAs in the NCBI RefSeq database. In addition to the three reported cases, our study identified more than two dozen putative −1 PRF cases. The genes involved in these cases are genuine cellular genes without a viral origin. Moreover, in more than half of these cases, the frameshift site locates far upstream (>250 nt) from the stop codon of the 0 reading frame, which is nonviral-like. Using dual luciferase assays in HEK293T cells, we confirmed that the −1 PRF signals in the mRNAs of CDK5R2 and SEMA6C are functional in inducing efficient frameshifting. Our findings have significant implications in expanding the repertoire of the −1 PRF phenomenon and the protein-coding capacity of the human transcriptome.
Generalization of Cortical MOSTest Genome-Wide Associations Within and Across Samples
Authors: Loughnan Robert J. , Shadrin Alexey A. , Frei Oleksandr , van der Meer Dennis , Zhao Weiqi , Palmer Clare E. , Thompson Wesley K. , Makowski Carolina , Jernigan Terry L. , Andreassen Ole A. , Fan Chun Chieh , Dale Anders M. 
Published: April 2021

AbstractGenome-Wide Association studies have typically been limited to single phenotypes, given that high dimensional phenotypes incur a large multiple comparisons burden: ~1 million tests across the genome times the number of phenotypes. Recent work demonstrates that a Multivariate Omnibus Statistic Test (MOSTest) is well powered to discover genomic effects distributed across multiple phenotypes. Applied to cortical brain MRI morphology measures, MOSTest has resulted in a drastic improvement in power to discover loci when compared to established approaches (min-P). One question that arises is how well these discovered loci replicate in independent data. Here we perform 10 times cross validation within 35,644 individuals from UK Biobank for imaging measures of cortical area, thickness and sulcal depth (>1,000 dimensionality for each). By deploying a replication method that aggregates discovered effects distributed across multiple phenotypes, termed PolyVertex Score (PVS), we demonstrate a higher replication yield and comparable replication rate of discovered loci for MOSTest (# replicated loci: 348-845, replication rate: 94-95%) in independent data when compared with the established min-P approach (# replicated loci: 31-68, replication rate: 65-80%). An out-of-sample replication of discovered loci was conducted with a sample of 8,336 individuals from the Adolescent Brain Cognitive Development®(ABCD) study, who are on average 50 years younger than UK Biobank individuals. We observe a higher replication yield and comparable replication rate of MOSTest compared to min-P. This finding underscores the importance of using well-powered multivariate techniques for both discovery and replication of high dimensional phenotypes in Genome-Wide Association studies.
An ancient clade ofPenelope-like retroelements with permuted domains is present in the green lineage and protists, and dominates many invertebrate genomes
Authors: Craig Rory J. , Yushenova Irina A. , Rodriguez Fernando , Arkhipova Irina R. 
Published: April 2021

ABSTRACTPenelope-like elements (PLEs) are an enigmatic clade of retroelements whose reverse transcriptases (RTs) share a most recent common ancestor with telomerase RTs. The single ORF of canonical EN+ PLEs encodes RT and a C-terminal GIY-YIG endonuclease (EN) that enables intrachromosomal integration, while EN–PLEs lack endonuclease and are generally restricted to chromosome termini. EN+ PLEs have only been found in animals, except for one case of horizontal transfer to conifers, while EN–PLEs occur in several kingdoms. Here we report a new, deep-branching PLE clade with a permuted domain order, whereby an N-terminal GIY-YIG endonuclease is linked to a C-terminal RT by a short domain with a characteristic Zn-finger-like motif. These N-terminal EN+ PLEs share a structural organization, including pseudo-LTRs and complex tandem/inverted insertions, with canonical EN+ PLEs fromPenelope/Poseidon,NeptuneandNematisclades, and show insertion bias for microsatellites, but lack hammerhead ribozyme motifs. However, their phylogenetic distribution is much broader. TheNaiadclade is found in numerous invertebrate phyla, where they can reach tens of thousands of copies per genome.Naiadsin spiders and clams independently evolved to encode selenoproteins.Chlamys, which lack the CCHH motif universal to PLE endonucleases, occur in green algae, spike mosses (targeting ribosomal DNA) and the slime moldPhysarum. Unlike canonical PLEs, RTs of N-terminal EN+ PLEs contain the insertion-in-fingers domain, strengthening the link between PLEs and telomerases. Additionally, we describeHydra, a novel metazoan C-terminal EN+ clade. Overall, we conclude that PLE diversity, distribution and abundance is comparable to non-LTR and LTR-retrotransposons.
Quorum sensing signals from epibiont mediate the induction of bioactive peptides in mat-forming cyanobacteriaNostoc
Authors: Saha Subhasish , Bulzu Paul-Adrian , Urajová Petra , Mareš Jan , Konert Grzegorz , Câmara Manoel João , Macho Markéta , Ewe Daniela , Hrouzek Pavel , Masojídek Jiří , Ghai Rohit , Saurav Kumar 
Published: April 2021

ABSTRACTThe regulation of oligopeptides production is essential in understanding their ecological role in complex microbial communities including harmful cyanobacterial blooms. The role of chemical communication between the cyanobacterium and the microbial community harboured as epibionts within its phycosphere is at an initial stage of research and little is understood about its specificity. Herein, we present insight into the role of a bacterial epibiont in regulating production of cyanobacterial oligopeptides microviridins, well-known elastase inhibitors with presumed anti-grazing effects, in an ecologically important cyanobacterial genusNostoc. Heterologous expression and identification of specific signal molecules from the epibiont suggest the role of a quorum sensing-based interaction. Further, physiological experiments show an increase in microviridin production without affecting cyanobacterial growth and photosynthetic activity. Simultaneously, oligopeptides presenting a selective inhibition pattern provide support for their specific function in response to the presence of cohabitant epibionts. Thus, the chemical interaction revealed in our study provides an example of an interspecies signalling pathway monitoring the bacterial flora around the cyanobacterial filaments and induction of intrinsic species-specific metabolic responses.IMPORTANCEThe regulation of cyanopeptide production beyond microcystin is essential to understand their ecological role in complex microbial communities, e.g. harmful cyanobacterial blooms. The role of chemical communication between the cyanobacterium and the epibionts within its phycosphere is at an initial stage of research and little is understood about its specificity. The frequency of cyanopeptide occurrence also demonstrates the need to understand the contribution of cyanobacterial peptides to the overall biological impact of cyanopeptides on aquatic organisms and vertebrates including humans. Our results shed light on the epibiont control of cyanopeptide production via quorum sensing mechanisms and we posit that such mechanisms may be widespread in natural cyanobacterial bloom community regulation.
Detection of porcine enteric viruses (Kobuvirus, Mamastrovirus and Sapelovirus) in domestic pigs in Corsica, France
Authors: Capai Lisandru , Piorkowski Géraldine , Maestrini Oscar , Casabianca François , Masse Shirley , de Lamballerie Xavier , Charrel Rémi N. , Falchi Alessandra 
Published: April 2021

AbstractMany enteric viruses are found in pig farms around the world and can cause death of animals or important production losses for breeders. Among the wide spectrum of enteric viral species, porcine Sapelovirus (PSV), porcine Kobuvirus (PKoV) and porcine Astrovirus (PAstV) are frequently found in pig feces. In this study we investigated sixteen pig farms in Corsica, France, to evaluate the circulation of three enteric viruses (PKoV, PAstV-1 and PSV). In addition to the three viruses studied by RT–qPCR (908 pig feces samples), 26 stool samples were tested using the Next Generation Sequencing method (NGS). Our results showed viral RNA detection rates (i) of 62.0% [58.7–65.1] (n = 563/908) for PSV, (ii) of 44.8% [41.5–48.1] (n = 407/908) for PKoV and (iii) of 8.6% [6.8–10.6] (n = 78/908) for PAstV-1. Significant differences were observed for all three viruses according to age (P-value = 2.4e–13 for PAstV-1; 2.4e–12 for PKoV and 0.005 for PSV). The type of breeding was significantly associated with RNA detection only for PAstV-1 (P-value = 9.6e–6). Among the 26 samples tested with NGS method, consensus sequences corresponding to 10 different species of virus were obtained This study provides first insight on the presence of three common porcine enteric viruses in France. We also showed that they are frequently encountered in pigs born and bred in Corsica, which demonstrates endemic local circulation.ImportanceThis study provides important information in the comprehension of the epidemiology of different viruses circulating in swine farms. We have shown the great diversity of viruses that could be present in extensive farms. Moreover, to our knowledge, this is the first detection of these different viruses in France. So far, this study has to be considered as a first step in the study of enteric viruses in Corsican pig farms.
Aspartate in the intestine: dual service as anaerobic electron acceptor and nitrogen source
Authors: Conway Tyrrell 
Published: April 2021

SummaryFumarate was previously known to serve as an anaerobic electron acceptor by E. coli when colonizing the mammalian intestine, but the source of that fumarate was elusive. In this issue, Unden and coworkers demonstrate that l‐aspartic acid is the source of fumarate that drives anaerobic respiration by colonized E. coli (Schubert et al., 2021). Moreover, Schubert et al., establish that E. coli is able to grow anaerobically by using aspartate as a sole source of nitrogen. These groundbreaking findings indicate that a single amino acid – aspartate – supports anaerobic respiration and acquisition of nitrogen by E. coli in the intestine.
Social status, political priorities and unequal representation
Authors: TRABER DENISE , HÄNNI MIRIAM , GIGER NATHALIE , BREUNIG CHRISTIAN 
Published: April 2021

AbstractResearchers on inequalities in representation debate about whether governments represent the preferences of the rich better than those of less affluent citizens. We argue that problems of high‐ and low‐status citizens are treated differently already at the agenda‐setting stage. If affluent and less affluent citizens have different priorities about which issues should be tackled by government, then these divergent group priorities explain why government favours high‐ over low‐status citizens. Due to different levels of visibility, resources and social ties, governments pay more attention to what high‐status citizens consider important in their legislative agenda and pay less attention to the issues of low‐status citizens. We combined three types of data for our research design. First, we extracted the policy priorities (most important issues) for all status groups from Eurobarometer data between 2002 and 2016 for 10 European countries and matched this information with data on policy outcomes from the Comparative Agendas Project. We then strengthen our results using a focused comparison of three single country studies over longer time series. We show that a priority gap exists and has representational consequences. Our analysis has important implications for the understanding of the unequal representation of status groups as it sheds light on an important, yet so far unexplored, aspect of the political process. Since the misrepresentation of political agendas occurs at the very beginning of the policy‐making process, the consequences are potentially even more severe than for the unequal treatment of preferences.
Pediatric opioid fatalities: What can we learn for prevention?
Authors: Bishop‐Freeman Sandra C. , Young Kerry A. , Aurelius Michelle B. , Hudson Jason S. 
Published: April 2021

AbstractThe aim of this study was to highlight 19 cases investigated by the North Carolina Office of the Chief Medical Examiner over the last 12 years involving accidental or undetermined manner of death opioid ingestions leading to fatalities in young children. These pediatric ingestions have closely mirrored the opioid epidemic in adults transitioning from prescription medications to illicit drugs including fentanyl and fentanyl analogues. Unlike a typical adult ingestion for purposes of self‐harm or pleasure, poisonings in toddlers and infants are usually the result of curiosity, exploration, a decreased sense of danger, or imitation of adult or older sibling behavior. Eleven of the decedents were between the ages of 8 and 24 months. Among the cases were 12 prescription opioid exposure deaths and 7 illicit drug poisonings. A majority of the decedents were found unresponsive in an unkept home and/or in unsafe sleeping spaces with easy access to drugs or drug materials, which stresses the importance of safe pediatric sleeping conditions. After a complete pathological investigation, several of the cases had physical or scene evidence demonstrating that foil, plastic, or paper small enough to be ingested can contain enough potent opioid to cause death. Details from the toxicological investigation are included for each case to provide postmortem whole blood drug concentrations for forensic practitioners. Accidental pediatric poisonings are preventable. Risk reduction through improving awareness and education of the dangers of opioids is a key factor in mitigating these tragedies.
Unusual cutaneous presentation in a corrosive acid ingestion
Authors: Mittal Chaitanya , Gupta Vaibhav , Meshram Vikas P. , Kanchan Tanuj , Setia Puneet , Bharti Jyotsna Naresh , Sarangi Sujata , Malik Shaloo 
Published: April 2021

AbstractCorrosive digestive tract injuries are considered to be a source of morbidity and mortality worldwide. The cases of acid ingestion in Forensic Medicine practice are not infrequent. Corrosive ingestion usually presents with injuries over the face, oropharynx, esophagus, and gastrointestinal tract. We report a case of a 65‐year‐old woman who was brought to the emergency department with a history of ingestion of toilet cleaner at her home. Following this, she developed blackish‐brown discoloration over the abdomen. The patient survived for less than one day. An autopsy confirmed the perforation of the stomach and small intestine. 500 ml of blackish fluid was present in the peritoneal cavity which resulted in corrosive peritonitis. The chemical examiner's report showed corrosive mixtures comprising sulfate, nitrate, and chloride ions in the peritoneal contents. This case report highlights atypical cutaneous presentation over the abdomen following corrosive acid ingestion, which has not been reported previously. The possible explanation for this cutaneous manifestation was corrosive effects of the underlying viscera due to its close proximation to the abdominal wall and presence of minimal intra‐abdominal fat. A direct physical connection between perforation and cutaneous findings was not identified. The case emphasizes the need for a comprehensive approach in managing such cases, analyzing ingested material, and following standard autopsy protocols in case of death.