bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reassessment and typification ofOpuntia canterae(Opuntioideae, Cactaceae), an endemic prickly-pear cactus of Uruguay
Authors: Köhler Matias , Majure Lucas C. 
Published: March 2020

Background and aimsOpuntiais the most widespread genus of Cactaceae, naturally occurring throughout arid and semi-arid areas of the Americas. Many of the species have taxonomic problems owed to incomplete original descriptions, lack of type designations, a paucity of taxonomic revisions and in general, difficult species delimitation resulting from hybridization, morphological plasticity and poor specimen preparation. However, efforts are being undertaken to fill in the gaps in our distributional, morphological and phylogenetic knowledge of the group. Here, we reassess the nameOpuntia canterae, providing an updated description, typification, photographs, distribution map, conservation assessment and additional notes.Material and methodsExtensive fieldwork was conducted, along with comprehensive herbarium and literature review. Morphological characters were assessed based on the commonly used characters used for prickly pears. Species delimitation is proposed based on our morphological studies, taxonomic and literature revision, as well as preliminary phylogenetic studies. The IUCN guidelines were followed to provide a conservation assessment of the species.Key resultsOpuntia canteraeis reassessed as a distinct species separated from its previous synonym (O. elata) by the elliptic to long-oblanceolate stem segments, acute to conical flower bud apex and long-obconic fruits. An epitype is here designate for purposes of the precise designation of the name to the taxon. The species is considered endemic to Uruguay and is assessed as Vulnerable (VU) using IUCN criteria, but more fieldwork will be necessary to provide a more precise conservation status.
Goal-dependent tuning of muscle spindle receptors during movement preparation
Authors: Papaioannou Stylianos , Dimitriou Michael 
Published: March 2020

AbstractVoluntary movements are believed to be advantageously prepared before they are executed, but the neural mechanisms at work have been unclear. For example, there are no overt changes in skeletal muscle activity during movement preparation. Here, using a delayed-reach manual task, we demonstrate a decrease in the firing rate of human muscle afferents (primary spindles) when preparing stretch rather than shortening of the spindle-bearing muscle. This goal-dependent modulation of proprioceptors begun early after target onset but was markedly stronger at the latter parts of the preparatory period. In two additional experiments, whole-arm perturbations during reach preparation revealed a congruent modulation of stretch reflex gains of shoulder and upper arm muscles. Our study shows that movement preparation can involve sensory elements of the peripheral nervous system. We suggest that central preparatory activity can also reflect sensory control, and preparatory tuning of muscle spindle mechanoreceptors is a component of planned reaching movements.
Eukaryotic transposable elements as “cargo carriers”: the forging of metal resistance in the fungusPaecilomyces variotii
Authors: Urquhart Andrew S. , Chong Nicholas F. , Yang Yongqing , Idnurm Alexander 
Published: March 2020

ABSTRACTThe horizontal transfer of large gene clusters by mobile elements is a key driver of prokaryotic adaptation in response to environmental stresses. Eukaryotic microbes face similar environmental stresses yet a parallel role for mobile elements has not yet been established. A stress faced by all microorganisms is the prevalence of toxic metals in their environment. In fungi, identified mechanisms for protection against metals generally rely on genes that are dispersed within an organism’s genome. Here we have discovered a large (∼85 kb) region that confers resistance to several metals in the genomes of some, but not all, strains of a fungus,Paecilomyces variotii. We name this regionHEPHAESTUS(Hϕ) and present evidence that this region is mobile within theP. variotiigenome with features highly characteristic of a transposable element. While large gene clusters including those for the synthesis of secondary metabolites have been widely reported in fungi, these are not mobile within fungal genomes.HEPHAESTUScontains the greatest complement of host-beneficial genes carried by a transposable element in eukaryotes. This suggests that eukaryotic transposable elements might play a role analogous to their bacterial counterparts in the horizontal transfer of large regions of host-beneficial DNA. Genes withinHEPHAESTUSresponsible for individual metal resistances include those encoding a P-type ATPase transporter, PcaA, required for cadmium and lead resistance, a transporter, ZrcA, providing resistance to zinc, and a multicopper oxidase, McoA, conferring resistance to copper. Additionally, a subregion ofHϕconferring resistance to arsenate was identified. The presence of a strikingly similar cluster in the genome of another fungus,Penicillium fuscoglaucum, suggests thatHEPHAESTUSarrived inP. variotiivia horizontal gene transfer.
Quantitative differences in neuronal subpopulations between mouse and human dorsal root ganglia demonstrated with RNAscopein situhybridization
Authors: Shiers Stephanie , Klein Rebecca M. , Price Theodore J 
Published: March 2020

AbstractNext generation transcriptomics in combination with imaging-based approaches have emerged as powerful tools for the characterization of dorsal root ganglion (DRG) neuronal subpopulations. The mouse DRG has been well-characterized by many independently conducted studies with convergent findings, but few studies have directly compared expression of population markers between mouse and human. This is important because of our increasing reliance on the mouse as a preclinical model for translational studies. While calcitonin gene-related peptide (CGRP) and P2X purinergic ion channel type 3 receptor (P2X3R) have been used to define peptidergic and non-peptidergic nociceptor subpopulations, respectively, in mouse DRG, these populations may be different in other species. To directly test this, as well as a host of other markers, we used multiplex RNAscopein-situhybridization to elucidate the distribution of a multitude of unique and classic neuronal mRNAs in peptidergic (CGRP expressing) and non-peptidergic (P2X3R expressing) nociceptor subpopulations in mouse and human DRG. We found a large overlapping CGRP and P2X3R neuronal subpopulation in human, lumbar DRG that was not present in mouse. We also found differential expression in a variety of mRNAs for Trp-channels, cholinergic receptors, potassium channels, sodium channels, other markers/targets. These data offer insights into the spatial and functional organization of neuronal cell subpopulations in the rodent and human DRG and support the idea that sensory system organizational principles are likely different between both species.
The mesolimbic dopamine signatures of relapse to alcohol-seeking
Authors: Liu Yu , Jean-Richard-dit-Bressel Philip , Yau Joanna Oi-Yue , Willing Alexandra , Prasad Asheeta A. , Power John M. , Killcross Simon , Clifford Colin W.G. , McNally Gavan P. 
Published: March 2020

AbstractThe mesolimbic dopamine system comprises distinct compartments supporting different functions in learning and motivation. Less well understood is how complex addiction-related behaviors emerge from activity patterns across these compartments. Here we show how different forms of relapse to alcohol-seeking are assembled from activity across the ventral tegmental area and the nucleus accumbens. Using gCaMP and dLight fibre photometry, we show that self-administration and two forms of relapse (renewal/context-induced reinstatement and reacquisition) are associated with recruitment across the mesolimbic dopamine system. Using a variety of interventions, we show that this activity is causal to both forms of relapse. Finally, we use dissimilarity matrices to identify mesolimbic dopamine signatures of self-administration, extinction, and relapse. We show that signatures of relapse can be identified from heterogeneous activity profiles across the mesolimbic dopamine system and that these signatures differ for different forms of relapse.
CircGLCE alleviates intervertebral disc degeneration by regulating apoptosis and matrix degradation through the targeting of miR-587/STAP1
Authors: Chen Zhonghui , Zhang Weibing , Deng Ming , Zhou Yan , Li Yaming 
Published: March 2020

AbstractBackgroundIntervertebral disc degeneration (IDD) can induce profound global socioeconomic burdens. Recent studies have suggested that circular RNAs might have crucial functions in the progression of IDD. The purpose of this study was to identify a specific circular RNA and to investigate its regulatory mechanism in IDD.MethodsCircGLCE was selected after microarray analyses and was further analysed by RT-qPCR and FISH. After silencing CircGLCE, its function was assessed with RT-qPCR, immunofluorescence analysis and flow cytometry. Based on Sanger sequencing, miR-587 was identified as a direct target of CircGLCE, and it was further examined with RNA pulldown assays, RT-qPCR, dual luciferase assays and FISH. After silencing CircGLCE or miR-587, western blotting, immunofluorescence analysis, and flow cytometry were conducted. STAP1 was assessed by RT-qPCR and luciferase assay, and experiments with silenced and overexpressed miR-587 were performed. A rescue experiment was also included. In an IDD rat model, the in vivo effects of overexpressing CircGLCE on IDD were analysed with imaging techniques, TUNEL staining, FISH, western blotting, H&E staining and immunohistochemistry.ResultsCircGLCE was found to stably exist in the cytoplasm of nucleus pulposus (NP) cells. It was downregulated in IDD. Knockdown of CircGLCE promoted apoptosis and induced the expression of matrix-degrading enzymes in NP cells. CircGLCE served as a miR-587 sponge in NP cells. Inhibiting miR-587 counteracted the IDD-enhancing effect caused by silencing CircGLCE. STAP1 served as the miRNA target that mediated the functions of miR-587. Overexpressing CircGLCE alleviated IDD in vivo.ConclusionsCircGLCE attenuates IDD by regulating the apoptosis of NP cells and by regulating ECM degradation through the targeting of miR-587/STAP1. CircGLCE may be a potential therapeutic target for IDD treatments.
SPINK1-induced amelioration of impaired autophagy contributes to suppression of trypsinogen activation in a model of acute pancreatitis
Authors: Zhao Yuxiao , Jia Jianlong , Shopit Abdullah , Liu Yang , Wang Jun 
Published: March 2020

AbstractSPINK1 has been regarded as a reversible trypsinogen inhibitor for the inappropriate activation of trypsin, a key step in the initiation of acute pancreatitis (AP). However, the mechanisms of its action remains largely unclear and controversial. Here, we reported an unexpected effects of SPINK1 on inhibiting trypsinogen activation through the regulation of impaired autophagy in cerulein-stimulated AR42J cells, a well-established in vitro model of acute pancreatitis. Firstly, we found that the impaired autophagic flux was induced and trypsinogen activity enhanced in the above setting. Then, we showed that SPINK1 overexpression could inhibit the level of increased autophagic activity, improving the hindered autophagy flux, and significantly decreased the trypsinogen activity, whereas shRNA-caused downregulation of SPINK1 exacerbated the impairment of autophagic flux and trypsin activity, in the same cerulein-processed cells. More importantly, the trypsinogen activation in this model could be ameliorated by 3-Methyladenine(3-MA), an autophagy inhibitor. Thus, this study revealed, possibly for the first time, that SPINK1 greatly blocked the trypsinogen activation possibly through the modulation of impaired autophagy in cerulein-induced in vitro model of acute pancreatitis.
High-Throughput Stool Metaproteomics: Method and Application to Human Specimens
Authors: Gonzalez Carlos G. , Wastyk Hannah C. , Topf Madeline , Gardner Christopher D. , Sonnenburg Justin L. , Elias Joshua E. 
Published: March 2020

AbstractStool-based proteomics is capable of significantly augmenting our understanding of host-gut microbe interactions. However, in comparison to competing technologies such as metagenomics and 16S rRNA sequencing, it is under-utilized due to its low throughput and the negative impact sample contaminants can have on highly sensitive mass spectrometry equipment. Here, we present a new stool proteomic processing pipeline that addresses these shortcomings in a highly reproducible and quantitative manner. Using this method, 290 samples from a dietary intervention study were processed in approximately 1.5 weeks, largely done by a single researcher. These data indicated a subtle but distinct monotonic increase in the number of significantly altered proteins between study participants on fiber- or fermented food-enriched diets. Lastly, we were able to classify study participants based on their diet-altered proteomic profiles, and demonstrated that classification accuracies of up to 89% could be achieved by increasing the number of subjects considered. Taken together, this study represents the first high throughout proteomic method for processing stool samples in a technically reproducible manner, and has the potential to elevate stool-based proteomics as an essential tool for profiling host-gut microbiome interactions in a clinical setting.ImportanceWidely available technologies based on DNA sequencing have been used to describe the kinds of microbes that might correlate with health and disease. However, mechanistic insight might be best achieved through careful study of the dynamic proteins at the interface between the foods we eat, our microbes, and ourselves. Mass-spectrometry-based proteomics has the potential to revolutionize our understanding of this complex system but its application to clinical studies has been hampered by low-throughput and laborious experimentation pipelines. In response, we developed SHT-Pro, the first high-throughput pipeline designed to rapidly handle large stool sample sets. With it, a single researcher can process over one hundred stool samples per week for mass spectrometry analysis, roughly 10 times faster than previous methods. Since SHT-Pro is fairly simple to implement using commercially available reagents, it should be easily adaptable to large-scale clinical studies.
Assessment of the Clinical Utility of Plasma Metagenomic Next-Generation Sequencing in a Pediatric Hospital Population
Authors: Lee Rose A. , Al Dhaheri Fatima , Pollock Nira R. , Sharma Tanvi S. 
Published: March 2020

AbstractBackgroundMetagenomic next-generation sequencing (mNGS) of plasma cell-free DNA (cfDNA) is commercially available, but its role in the workup of infectious diseases is unclear.MethodsTo understand the clinical utility of plasma mNGS, we retrospectively reviewed patients tested at a pediatric institution over 2 years to evaluate the clinical relevance of the organism(s) identified and impact on antimicrobial management. We also investigated the effect of pre-test antimicrobials and interpretation of molecules of microbial cfDNA per microliter (MPM) plasma.Results29/59 (49%) mNGS tests detected organism(s), and 28/51 (55%) organisms detected were clinically relevant. Median MPM of clinically relevant organisms was 1533 versus 221 for irrelevant organisms (p=0.01). mNGS test sensitivity and specificity were 53% and 79%, respectively, with a positive predictive value (PPV) of 72% and negative predictive value (NPV) of 50%. 14% of tests impacted clinical management by changing antimicrobial therapy. Immunocompromised status was the only patient characteristic that trended towards a significant clinical impact (p=0.056). No patients with culture-negative endocarditis had organisms identified by mNGS. There were no significant differences in antimicrobial pre-test duration between tests with clinically relevant organism(s) versus those that returned negative, nor was the MPM different between pre-treated and un-treated organisms, suggesting that 10 days of antimicrobial therapy as observed in this cohort did not sterilize testing; however, no pre-treated organisms identified resulted in a new diagnosis impacting clinical managementConclusionsPlasma mNGS demonstrated higher utility for immunocompromised patients, but given the low PPV and NPV, cautious interpretation and Infectious Diseases consultation are prudent.SummaryWe evaluate the test performance characteristics and clinical utility of plasma metagenomic next-generation sequencing in a pediatric hospital cohort and demonstrate sensitivity and specificity of 53% and 79%, with 14% of tests impacting antimicrobial management.
Mechanistic Insights into Crosstalk of Tet(X) and MCR-1, Two Resistance Enzymes Co-produced by A Single Plasmid
Authors: Xu Yongchang , Liu Lizhang , Zhang Huimin , Feng Youjun 
Published: March 2020

AbstractTigecycline and colistin are few of last-resort defenses used in anti-infection therapies against carbapenem-resistant bacterial pathogens. The successive emergence of plasmid-bornetet(X) tigecycline resistance mechanism and mobile colistin resistance (mcr) determinant, renders them clinically ineffective, posing a risky challenge to global public health. Here, we report that co-carriage oftet(X6) andmcr-1gives co-resistance to both classes of antibiotics by a single plasmid inE. coli. Genomic analysis suggested that transposal transfer ofmcr-1proceeds into the plasmid pMS8345A, in which a new varianttet(X6) is neighbored with Class I integron. The structure-guided mutagenesis finely revealed the genetic determinants of Tet(X6) in the context of phenotypic tigecycline resistance. The combined evidencein vitroandin vivodemonstrated its enzymatic action of Tet(X6) in the destruction of tigecycline. The presence of Tet(X6) (and/or MCR-1) robustly prevents the accumulation of reactive oxygen species (ROS) induced by tigecycline (and/or colistin). Unlike thatmcr-1exerts fitness cost inE. coli, tet(X6) does not. In thetet(X6)-positive strain that co-harborsmcr-1, tigecycline resistance is independently of colistin resistance caused by MCR-1-mediated lipid A remodeling, and vice versa. Co-production of Tet(X6) and MCR-1 gives no synergistic delayed growth of the recipientE. coli. Similar to that MCR-1 behaves in the infection model ofG. mellonella, Tet(X6) renders the treatment of tigecycline ineffective. Therefore, co-transfer of such two AMR genes is of great concern in the context of “one health” comprising environmental/animal/human sectors, and heightened efforts are required to monitor its dissemination.Author summaryWe report thattet(X6), a new tigecycline resistance gene, is co-carried with the other resistance genemcr-1by a single plasmid. Not only have we finely mapped genetic determinants oftet(X6), but also revealed its biochemical action of tigecycline destruction. Crosstalk of Tet(X6) with MCR-1 is addressed. Tet(X6) tigecycline resistance is independently of MCR-1 colistin resistance, and vice versa. Similar to MCR-1 that renders colistin clinically ineffective, Tet(X6) leads to the failure of tigecycline treatment in the infection model ofG. mellonella. This study extends mechanistic understanding mechanism and interplay of Tet(X6) and MCR-1, coproduced by a single plasmid. It also heightens the need to prevent rapid and large-scaled spread of AMR.
Genomic islands of differentiation in a rapid avian radiation have been driven by recent selective sweeps
Authors: Hejase Hussein A. , Salman-Minkov Ayelet , Campagna Leonardo , Hubisz Melissa J. , Lovette Irby J. , Gronau Ilan , Siepel Adam 
Published: March 2020

AbstractNumerous studies of emerging species have identified genomic “islands” of elevated differentiation against a background of relative homogeneity. The causes of these islands remain unclear, however, with some signs pointing toward “speciation genes” that locally restrict gene flow and others suggesting selective sweeps that have occurred within nascent species after speciation. Here, we examine this question through the lens of genome sequence data for five species of southern capuchino seedeaters, finch-like birds from South America that have undergone a species radiation during the last ∼50,000 generations. By applying newly developed statistical methods for ancestral recombination graph inference and machine-learning methods for the prediction of selective sweeps, we show that previously identified islands of differentiation in these birds appear to be generally associated with relatively recent, species-specific selective sweeps, most of which are predicted to be “soft” sweeps acting on standing genetic variation. Many of these sweeps coincide with genes associated with melanin-based variation in plumage, suggesting a prominent role for sexual selection. At the same time, a few loci also exhibit indications of possible selection against gene flow. These observations shed new light on the complex manner in which natural selection shapes genome sequences during speciation.Significance StatementGenome-wide scans can identify differentiated loci between species that may have promoted speciation. So-called “islands of differentiation” have generally been identified and characterized using standard population genetic summary statistics (e.g.,FSTanddxy), which are limited in distinguishing among possible causes of differentiation, such as selection against gene flow and selective sweeps. We introduce a powerful strategy for analyzing such islands, combining new methods for inferring the full Ancestral Recombination Graph and machine learning methods for identifying selective sweeps. We applied our methods to genomic sequences from closely related southern capuchino seedeaters (Neotropical tanagers) and found signatures of recent selective sweeps around pigmentation genes, including many “soft” sweeps that acted on standing variation.
Global Landscape of Native Protein Complexes inSynechocystissp. PCC 6803
Authors: Xu Chen , Wang Bing , Yang Lin , Hu Lucas Zhongming , Yi Lanxing , Wang Yaxuan , Chen Shenglan , Emili Andrew , Wan Cuihong 
Published: March 2020

AbstractSynechocystissp. PCC 6803 (hereafter:Synechocystis) is a model organism for studying photosynthesis, energy metabolism, and environmental stress. Though known as the first fully sequenced phototrophic organism,Synechocystisstill has almost half of its proteome without functional annotations. In this study, we obtained 291 protein complexes, including 24,092 protein-protein interactions (PPIs) among 2062 proteins by using co–fractionation and LC/MS/MS. The additional level of PPIs information not only revealed the roles of photosynthesis in metabolism, cell motility, DNA repair, cell division, and other physiological processes, but also showed how protein functions vary from bacteria to higher plants due to the changed interaction partner. It also allows us to uncover functions of hypothetical proteins, such as Sll0445, Sll0446, S110447 participating in photosynthesis and cell motility, and Sll1334 regulating the expression of fatty acid. Here we presented the most extensive protein interaction data inSynechocystisso far, which might provide critical insights into the fundamental molecular mechanism in Cyanobacterium.