bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extensive genomic and transcriptomic variation defines the chromosome-scale assembly ofHaemonchus contortus, a model gastrointestinal worm
Authors: Doyle Stephen R. , Tracey Alan , Laing Roz , Holroyd Nancy , Bartley David , Bazant Wojtek , Beasley Helen , Beech Robin , Britton Collette , Brooks Karen , Chaudhry Umer , Maitland Kirsty , Martinelli Axel , Noonan Jennifer D. , Paulini Michael , Quail Michael A. , Redman Elizabeth , Rodgers Faye H. , Sallé Guillaume , Shabbir Muhammad Zubair , Sankaranarayanan Geetha , Wit Janneke , Howe Kevin L. , Sargison Neil , Devaney Eileen , Berriman Matthew , Gilleard John S. , Cotton James A. 
Published: February 2020

AbstractBackgroundHaemonchus contortusis a globally distributed and economically important gastrointestinal pathogen of small ruminants, and has become the key nematode model for studying anthelmintic resistance and other parasite-specific traits among a wider group of parasites including major human pathogens. Two draft genome assemblies forH. contortuswere reported in 2013, however, both were highly fragmented, incomplete, and differed from one another in important respects. While the introduction of long-read sequencing has significantly increased the rate of production and contiguity ofde novogenome assemblies broadly, achieving high quality genome assemblies for small, genetically diverse, outcrossing eukaryotic organisms such asH. contortusremains a significant challenge.ResultsHere, we report using PacBio long read and OpGen and 10X Genomics long-molecule methods to generate a highly contiguous 283.4 Mbp chromosome-scale genome assembly including a resolved sex chromosome. We show a remarkable pattern of almost complete conservation of chromosome content (synteny) withCaenorhabditis elegans, but almost no conservation of gene order. Long-read transcriptome sequence data has allowed us to define coordinated transcriptional regulation throughout the life cycle of the parasite, and refine our understanding ofcis- andtrans-splicing relative to that observed inC. elegans. Finally, we use this assembly to give a comprehensive picture of chromosome-wide genetic diversity both within a single isolate and globally.ConclusionsTheH. contortusMHco3(ISE).N1 genome assembly presented here represents the most contiguous and resolved nematode assembly outside of theCaenorhabditisgenus to date, together with one of the highest-quality set of predicted gene features. These data provide a high-quality comparison for understanding the evolution and genomics ofCaenorhabditisand other nematodes, and extends the experimental tractability of this model parasitic nematode in understanding pathogen biology, drug discovery and vaccine development, and important adaptive traits such as drug resistance.
Cystin gene mutations cause autosomal recessive polycystic kidney disease associated with alteredMycexpression
Authors: Yang Chaozhe , O’Connor Amber K. , Kesterson Robert A. , Watts Jacob A. , Majmundar Amar J. , Braun Daniela A. , Lek Monkol , Laricchia Kristen M. , Fathy Hanan M. , Shril Shirlee , Hildebrandt Friedhelm , Guay-Woodford Lisa M. 
Published: February 2020

AbstractMutation of theCys1gene underlies the renal cystic disease in theCys1cpk/cpk(cpk)mouse that phenocopies human autosomal recessive polycystic kidney disease (ARPKD). Cystin, the protein product ofCys1, is expressed in the primary apical cilia of renal ductal epithelial cells. In previous studies, we showed that cystin regulatesMycexpression via interaction with the tumor suppressor, necdin. Here, we demonstrate rescue of thecpkrenal phenotype by kidney-specific expression of a cystin-GFP fusion protein encoded by a transgene integrated into theRosa26locus. In addition, we show that expression of the cystin-GFP fusion protein in collecting duct cells down-regulates expression ofMycincpkkidneys. Finally, we report the first human patient with an ARPKD phenotype due to homozygosity for a predicted deleterious splicing defect inCYS1. These findings suggest that mutations in theCys1mouse andCYS1human orthologues cause an ARPKD phenotype that is driven by overexpression of theMycproto-oncogene.Translational StatementThe cystin-deficientcpkmouse is a model for the study of autosomal recessive polycystic kidney disease (ARPKD). We show that thecpkmouse phenotype is associated with alteredMycexpression. To date, the clinical relevance of cystin deficiency to human disease was unclear, due to the absence of ARPKD cases associated withCYS1mutations. We report the first case of ARPKD linked to aCYS1mutation disrupting normal splicing. These findings confirm the relevance of cystin deficiency to human ARPKD, implicateMycin disease initiation or progression, and validate thecpkmouse as a translationally relevant disease model.
Love at first flight: Wing interference patterns are species-specific and sexually dimorphic in blowflies (Diptera: Calliphoridae)
Authors: Butterworth Nathan J. , White Thomas E. , Byrne Phillip G. , Wallman James F. 
Published: February 2020

AbstractWing interference patterns (WIPs) are stable structural colours displayed on insect wings which are only visible at specific viewing geometries and against certain backgrounds. These patterns are widespread among flies and wasps, and growing evidence suggests that they may function as species- and sex-specific mating cues in a range of taxa. As such, it is expected that WIPs should differ between species and show clear sexual dimorphisms. However, the true extent to which WIPs vary between species, sexes, and individuals is currently unclear, as previous studies have only taken a qualitative approach, without considering how WIPs might be perceived by the insect. Here, we perform the first quantitative analysis of inter- and intra-specific variation in WIPs across seven Australian species of the blowfly genusChrysomya. Using multispectral digital imaging and a tentative model of blowfly colour vision, we provide quantitative evidence that WIPs are species-specific, highlight that the extent of divergence is greater in males than in females, and demonstrate sexual dimorphisms in several species. These data provide evidence that WIPs have diversified substantially in blowflies and suggests that sexual selection may have played a role in this process.
Exon probe sets and bioinformatics pipelines for all levels of fish phylogenomics
Authors: Hughes Lily C. , Ortí Guillermo , Saad Hadeel , Li Chenhong , White William T. , Baldwin Carole C. , Crandall Keith A. , Arcila Dahiana , Betancur-R. Ricardo 
Published: February 2020

AbstractExon markers have a long history of use in phylogenetics of ray-finned fishes, the most diverse clade of vertebrates with more than 35,000 species. As the number of published genomes increases, it has become easier to test exons and other genetic markers for signals of ancient duplication events and filter out paralogs that can mislead phylogenetic analysis. We present seven new probe sets for current target-capture phylogenomic protocols that capture 1,104 exons explicitly filtered for paralogs using gene trees. These seven probe sets span the diversity of teleost fishes, including four sets that target five hyper-diverse percomorph clades which together compriseca. 17,000 species (Carangaria, Ovalentaria, Eupercaria, and Syngnatharia + Pelagiaria combined). We additionally included probes to capture exon markers that have been commonly used in fish phylogenetics, despite some being flagged for paralogs, to facilitate integration of old and new molecular phylogenetic matrices. We tested these probes and merged new exon-capture sequence data into an existing data matrix of 1,105 exons and 300 ray-finned fish species. We provide an optimized bioinformatics pipeline to assemble exon capture data from raw reads to alignments for downstream analysis. We show that loci with known paralogs are at risk of assembling duplicated sequences with target-capture, but we also assembled many useful orthologous sequences. These probe sets are a valuable resource for advancing fish phylogenomics because they can be easily extracted from increasingly available whole genome and transcriptome datasets, and also may be integrated with existing PCR-based exon and mitochondrial datasets.
COMPOSITUM 1 (COM1) contributes to the architectural simplification of barley inflorescence via meristem identity signals
Authors: Poursarebani N. , Trautewig C. , Melzer M. , Nussbaumer T. , Lundqvist U. , Rutten T. , Schmutzer T. , Brandt R. , Himmelbach A. , Altschmied L. , Koppolu R. , Youssef H. M. , Sibout R. , Dalmais M. , Bendahmane A. , Stein N. , Xin Z. , Schnurbusch T. 
Published: February 2020

AbstractGrasses have varying inflorescence shapes; however, little is known about the genetic mechanisms specifying such shapes among tribes. We identified the grass-specific TCP transcription factor COMPOSITUM 1 (COM1) expressed in inflorescence meristematic boundaries of different grasses. COM1 specifies branch-inhibition in Triticeae (barley) versus branch-formation in non-Triticeae grasses. Analyses of cell size, cell walls and transcripts revealed barley COM1 regulates cell growth, affecting cell wall properties and signaling specifically in meristematic boundaries to establish identity of adjacent meristems.COM1acts upstream of the boundary geneLiguleless1and confers meristem identity partially independent of theCOM2pathway. Furthermore, COM1 is subject to purifying natural selection, thereby contributing to specification of the spike inflorescence shape. This meristem identity pathway has conceptual implications for both inflorescence evolution and molecular breeding in Triticeae.
Distinct representations of finger movement and force in human motor and premotor cortices
Authors: Flint Robert D. , Tate Matthew C. , Li Kejun , Templer Jessica W. , Rosenow Joshua M. , Pandarinath Chethan , Slutzky Marc W. 
Published: February 2020

AbstractThe ability to grasp and manipulate objects requires controlling both finger movement kinematics and isometric force. Previous work suggests that these behavioral modes are controlled separately, but it is unknown whether the cerebral cortex represents them differently. Here, we investigated this question by recording high-density electrocorticography from the motor and premotor cortices of seven human subjects performing a sequential movement-force motor task. We decoded finger movement (0.7±0.3 fractional variance account for; FVAF) and force (0.7±0.2 FVAF) with high accuracy, yet found different spatial representations. We also found clear distinctions in electrocorticographic activity by using deep learning methods to uncover state-space representations, and by developing a new metric, the neural vector angle. Thus, state-space techniques can help to investigate broad cortical networks. Finally, we were able to classify the behavioral mode from neural signals with high accuracy (90±6%). Thus, finger movement and force have distinct representations in motor/premotor cortices. This will inform our understanding of the neural control of movement as well as the design of grasp brain-machine interfaces.
Using computational modeling to teach metabolism as a dynamic system improves student performance
Authors: Booth Christine S. , Song Changsoo , Howell Michelle E. , Rasquinha Achilles , Saska Aleš , Helikar Resa , Sikich Sharmin M. , Couch Brian A. , Dijk Karin van , Roston Rebecca L. , Helikar Tomáš 
Published: February 2020

AbstractUnderstanding metabolic function requires knowledge of the dynamics, interdependence, and regulation of biochemical networks. However, current approaches are not optimal to develop the needed mechanistic understanding, and misconceptions about biological processes persist even after graduation. To address these issues, we developed a computational modeling and simulation approach that employs scaffolded learning to teach biochemistry students about the regulation of metabolism. The power of the approach lies in students’ abilities to alter any component or connection in a modeled system and instantly observe the effects of their changes. We find that students who use our approach perform better on biochemistry metabolism questions compared to students in a course that did not use this approach. We also investigated performance by gender and found that our modules may have the potential to increase equity in education. We noted that students are generally positive about the approach and appreciate its benefits. Our modules provide life science instructors with a dynamic and systems-driven approach to teach metabolic regulation and control that improves learning and also equips students with important technical skills.
Towards domain-general predictive coding: Expected TMS excites the motor system less effectively than unexpected stimulation
Authors: Tran Dominic M. D. , McNair Nicolas A. , Harris Justin A. , Livesey Evan J. 
Published: February 2020

AbstractThe brain’s response to sensory input is modulated by prediction. For example, sounds that are produced by one’s own actions, or those that are strongly predicted by environmental cues, are perceived as less salient and elicit an attenuated N1 component in the auditory evoked potential. Here we examined whether the neural response to direct stimulation of the brain is attenuated by prediction in a similar manner. Transcranial magnetic stimulation (TMS) applied over primary motor cortex can be used to gauge the excitability of the motor system. Motor-evoked potentials (MEPs), elicited by TMS and measured in peripheral muscles, are larger when actions are being prepared and smaller when actions are voluntarily suppressed. We tested whether the amplitude of MEPs was attenuated under circumstances where the TMS pulse can be reliably predicted, even though control of the relevant motor effector was never required. Self-initiation of the TMS pulse and reliable cuing of the TMS pulse both attenuated MEP amplitudes, compared to MEPs generated programmatically in an unpredictable manner. These results suggest that predictive coding may be governed by domain-general mechanisms responsible for all forms predictive learning.
Specific Inhibition of GSK-3β by Tideglusib: Potential Therapeutic Target for Neuroblastoma Cancer Stem Cells
Authors: Bahmad Hisham F. , Chalhoub Reda M. , Harati Hayat , Bou-Gharios Jolie , Ballout Farah , Monzer Alissar , Msheik Hiba , Assi Sahar , Araji Tarek , Elajami Mohamad K. , Ghanem Paola , Chamaa Farah , Kadara Humam , Abou-Antoun Tamara , Daoud Georges , Fares Youssef , Abou-Kheir Wassim 
Published: February 2020

AbstractNeuroblastoma is an embryonic tumor that represents the most common extracranial solid tumor in children. Resistance to therapy is attributed, in part, to the persistence of a subpopulation of slowly dividing cancer stem cells (CSCs) within those tumors. Glycogen synthase kinase (GSK)-3β is an active proline-directed serine/threonine kinase, well-known to be involved in different signaling pathways entangled in the pathophysiology of neuroblastoma. This study aims to assess the potency of an irreversible GSK-3β inhibitor drug, Tideglusib (TDG), in suppressing proliferation, viability, and migration of human neuroblastoma cell lines, as well as its effects on their CSCs subpopulationin vitroandin vivo. Our results showed that treatment with TDG significantly reduced cell proliferation, viability, and migration of SK-N-SH and SH-SY5Y cells. TDG also significantly inhibited neurospheres formation capability in both cell lines, eradicating the self-renewal ability of highly resistant CSCs. Importantly, TDG potently inhibited neuroblastoma tumor growth and progressionin vivo. In conclusion, TDG proved to be an effectivein vitroandin vivotreatment for neuroblastoma cell lines and may hence serve as a potential adjuvant therapeutic agent for this aggressive nervous system tumor.
Transcription-associated topoisomerase activities control DNA-breaks production by G-quadruplex ligands
Authors: Pipier A. , Bossaert M. , Riou J.F. , Noirot C. , Nguyễn L-T. , Serre R-F. , Bouchez O. , Defrancq E. , Calsou P. , Britton S. , Gomez D. 
Published: February 2020

AbstractG-quadruplexes (G4), non-canonical DNA structures, are involved in several essential processes. Stabilization of G4 structures by small compounds (G4 ligands) affects almost all DNA transactions, including telomere maintenance and genomic stability. Here, thanks to a powerful and unbiased genetic approach, we identify topoisomerase 2-alpha (TOP2A) as the main effector of cell cytotoxicity induced by CX5461, a G4 ligand currently undergoing phase I/II clinical trials. This approach also allowed to identify new point mutations affecting TOP2A activity without compromising cell viability. Moreover, based on cross-resistance studies and siRNA-based protein depletion we report that TOP2A plays a major role in cell cytotoxicity induced by two unrelated clastogenic G4 ligands, CX5461 and pyridostatin (PDS). We also report that cytotoxic effects induced by both compounds are associated with topoisomerase 2-mediated DNA breaks production. Finally, we show that TOP2-mediated DNA breaks production is strongly associated with RNA Pol II-dependent transcription and is countered by topoisomerase 1 (TOP1). Altogether our results indicate that clastogenic G4 ligands act as DNA structure-driven TOP2-poisons at transcribed regions bearing G-quadruplex structures.
The stress-induced protein NUPR1 orchestrates protein translation during ER-stress by interacting with eIF2α
Authors: Borrello Maria Teresa , Santofimia-Castaño Patricia , Bocchio Marco , Listi Angela , Fraunhoffer Nicolas , Soubeyran Philippe , Chevet Eric , Pin Christopher , Iovanna Juan 
Published: February 2020

AbstractNUPR1 is a stress response protein overexpressed upon cell injury in virtually all organs including the exocrine pancreas. Despite NUPR1’s well established role in the response to cell stress, the molecular and structural machineries triggered by NUPR1 activation remain largely unknown. In this study, we uncover an important role for NUPR1 in participating in the unfolded protein response pathway and the endoplasmic reticulum stress response. Biochemical results, confirmed by ultrastructural morphological observation, revealed alterations in the UPR in acinar cells of germline-deleted NUPR1 murine models, consistent with the inability to restore general protein translation. Bioinformatical analysis of NUPR1 interacting partners showed significant enrichment in translation initiation factors, including eukaryotic initiation factor (eIF) 2α. Co-immunoprecipitation and proximity ligation assays both confirmed interaction between NUPR1 and eIF2α and its phosphorylated form (p-eIF2α). Our. Moreover, our data also suggest loss of NUPR1 in cells results in maintained eIF2α phosphorylation and evaluation of nascent proteins by (peIF2α), and click chemistry revealed that NUPR1-depleted PANC-1 cells displayed a slower post stress protein translational recovery compared to wild-type. Combined, this data proposes a novel role for NUPR1 in the integrated stress response pathway, at least partially through promoting efficient PERK-branch activity and resolution through a unique interaction with eIF2α.SignificanceIn the pancreas, NUPR1 is required for a resolution of the ER stress response. During ER stress response, NUPR1 binds both eIF2α allowing for its dephosphorylation and restoration of new protein synthesis.HighlightsBiochemical analysis revealed a general reduction in the protein expression of downstream mediators of the unfolded protein response in the pancreas of mice lackingNupr1. This finding suggests a novel role for NUPR1 in the UPR/ER stress response.Ultrastructural analysis of pancreata revealed reduced morphological alterations in tunicamycin-treatedNupr1-/-mice compared toNupr1+/+mice consistent with a maintained block in general protein translation.Co-immunoprecipitation of tagged NUPR1 confirmed a novel interaction with eIF2α. Depletion of NUPR1 prolonged phosphorylation of eIF2α, suggesting it may be involved in attenuation of the PERK branch of the UPR.NUPR1-depleted PANC-1 cells displayed a slower recovery of protein translation following UPR activation
A supernumerary designer chromosome for modularin vivopathway assembly inSaccharomyces cerevisiae
Authors: Postma Eline D. , Dashko Sofia , van Breemen Lars , Taylor Parkins Shannara K. , van den Broek Marcel , Daran Jean-Marc , Daran-Lapujade Pascale 
Published: February 2020

ABSTRACTThe construction of microbial cell factories for sustainable production of chemicals and pharmaceuticals requires extensive genome engineering. UsingSaccharomyces cerevisiae, this study proposes Synthetic Chromosomes (SynChs) as orthogonal expression platforms for rewiring native cellular processes and implementing new functionalities. Capitalizing the powerful homologous recombination capability ofS. cerevisiae, modular SynChs of 50 and 100 Kb were fully assembledde novofrom up to 44 transcriptional-unit-sized fragments in a single transformation. These assemblies were remarkably efficient and faithful to theirin silicodesign. SynChs made of non-coding DNA were stably replicated and segregated irrespective of their size without affecting the physiology of their host. These non-coding SynChs were successfully used as landing pad and as exclusive expression platform for the essential glycolytic pathway. This work pushes the limit of DNA assembly inS. cerevisiaeand paves the way forde novodesigner chromosomes as modular genome engineering platforms inS. cerevisiae.
Bile Acid pool composition and Gallbladder function are controlled by TGR5 to protect the liver against Bile Acid overload
Authors: Bidault-Jourdainne Valeska , Merlen Grégory , Glénisson Mathilde , Doignon Isabelle , Garcin Isabelle , Péan Noémie , Boisgard Raphael , Ursic-Bedoya José , Serino Matteo , Ullmer Christoph , Humbert Lydie , Abdelrafee Ahmed , Vibert Eric , Duclos-Vallée Jean-Charles , Rainteau Dominique , Tordjmann Thierry 
Published: February 2020

AbstractBackgrounds & AimsAs the bile acid (BA) pool composition is of major impact on liver pathophysiology, we studied its regulation by the BA receptor TGR5, promoting hepatoprotection against BA overload.MethodsWT, total and hepato-specific TGR5-KO, and TGR5-overexpressing mice were used in: partial and 90% extended hepatectomies (EH) upon normal, ursodeoxycholic acid (UDCA)- or cholestyramine (CT)-enriched diet, bile duct ligation (BDL), cholic acid (1%)-enriched diet, and TGR5 agonist (RO) treatments. We thereby studied TGR5 impact on: BA pool composition, liver injury, regeneration and survival. Particular focus was made on gut microbiota (GM) and gallbladder (GB) function analysis. BA pool composition was analyzed in patients undergoing major hepatectomy.ResultsThe TGR5-KO hyperhydrophobic BA pool was not related to BA synthesis alteration, nor to the TGR5-KO GM dysbiosis, as supported by hepatocyte-specific KO mice and cohousing experiments. The TGR5-dependent control of GB dilatation was crucial for BA pool composition, as determined by experiments including RO treatment +/− cholecystectomy. The poor TGR5-KO post-EH survival rate, related with exacerbated peribiliary necrosis and BA overload, was improved by shifting the BA pool towards a more hydrophilic composition (CT and UDCA treatments). After either BDL or CA-enriched diet +/− cholecystectomy, we found that GB dilatation had strong TGR5-dependent hepatoprotective properties. In patients, a more hydrophobic BA pool was correlated with an unfavorable outcome after hepatectomy.ConclusionBA pool composition is crucial for hepatoprotection in mice and humans. We point TGR5 as a key regulator of BA profile and thereby as a potential hepatoprotective target under BA overload conditions.Lay summaryThrough multiple in vivo experimental approaches in mice, together with a patients study, this work brings some new light on the relationships between biliary homeostasis, gallbladder function and liver protection. We showed that the bile acid pool composition is crucial for optimal liver repair, not only in mice but also in human patients undergoing major hepatectomy.