bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved molecular characterization of the Klebsiella oxytoca complex reveals the prevalence of the kleboxymycin biosynthetic gene cluster
Authors: Shibu Preetha , McCuaig Frazer , McCartney Anne L. , Kujawska Magdalena , Hall Lindsay J. , Hoyles Lesley 
Published: July 2020

ABSTRACTAs part of ongoing studies with clinically relevant Klebsiella spp., we characterized the genomes of three clinical GES-5-positive ST138 strains originally identified as Klebsiella oxytoca. blaOXY gene, average nucleotide identity and phylogenetic analyses showed the strains to be Klebsiella michiganensis. Affiliation of the strains to ST138 led us to demonstrate that the current multi-locus sequence typing scheme for K. oxytoca can be used to speciate members of this genetically diverse complex of bacteria. The strains encoded the kleboxymycin biosynthetic gene cluster (BGC), previously only found in K. oxytoca strains and one strain of Klebsiella grimontii. The finding of this BGC, associated with antibiotic-associated haemorrhagic colitis, in K. michiganensis led us to carry out a wide-ranging study to determine the prevalence of this BGC in Klebsiella spp. Of 7,170 publicly available Klebsiella genome sequences screened, 88 encoded the kleboxymycin BGC. All BGC-positive strains belonged to the K. oxytoca complex, with strains of four (K. oxytoca, K. pasteurii, K. grimontii, K. michiganensis) of the six species of the complex found to encode the complete BGC. In addition to being found in K. grimontii strains isolated from preterm infants, the BGC was found in K. oxytoca and K. michiganensis metagenome-assembled genomes recovered from neonates. Detection of the kleboxymycin BGC across the K. oxytoca complex may be of clinical relevance and this cluster should be included in databases characterizing virulence factors, in addition to those characterizing BGCs.IMPACT STATEMENTMembers of the Klebsiella oxytoca complex are difficult to speciate using phenotypic and chemotaxonomic methods. Consequently, many genomes deposited in public databases are misclassified as K. oxytoca. Here we demonstrate that the current multi-locus sequence typing (MLST) system for the complex can be used to accurately speciate many strains, which will be of use to clinical laboratories in resource-limited settings which rely on the MLST scheme for typing and epidemiological tracking of isolates. In addition, extended analyses of the genomes of Klebsiella spp. have revealed the kleboxymycin biosynthetic gene cluster (BGC) is restricted to species of the Klebsiella oxytoca complex (K. oxytoca, K. michiganensis, K. pasteurii and K. grimontii). Species- and/or gene-specific differences in the cluster’s sequences may be relevant to virulence of K. oxytoca and related species. The finding of the kleboxymycin BGC in the preterm infant gut microbiota may have implications for disease presentation in a subset of neonates.
Genomic network analysis of an environmental and livestock IncF plasmid population
Authors: Matlock William , Chau Kevin K. , AbuOun Manal , Stubberfield Emma , Barker Leanne , Kavanagh James , Pickford Hayleah , Gilson Daniel , Smith Richard P. , Gweon H. Soon , Hoosdally Sarah J. , Swann Jeremy , Sebra Robert , Bailey Mark J. , Peto Timothy E. A. , Crook Derrick W. , Anjum Muna F. , Read Daniel S. , Walker A. Sarah , Stoesser Nicole , Shaw Liam P. ,   on behalf of the REHAB consortium
Published: July 2020

AbstractIncF plasmids are diverse and of great clinical significance, often carrying genes conferring antimicrobial resistance (AMR) such as extended-spectrum β-lactamases, particularly inEnterobacteriaceae. Organising this plasmid diversity is challenging, and current knowledge is largely based on plasmids from clinical settings. Here, we present a network community analysis of a large survey of IncF plasmids from environmental (influent, effluent, and upstream/downstream waterways surrounding wastewater treatment works) and livestock settings. We use a tractable and scalable methodology to examine the relationship between plasmid metadata and network communities. This reveals how niche (sampling compartment and host genera) partition and shape plasmid diversity. We also perform pangenome-style analyses on network communities. We show that such communities define unique combinations of core genes, with limited overlap. Building plasmid phylogenies based on alignments of these core genes, we demonstrate that plasmid accessory function is closely linked to core gene content. Taken together, our results suggest that stable IncF plasmid backbone structures can persist in environmental settings while allowing dramatic variation in accessory gene content that may be linked to niche adaptation. The recent association of IncF plasmids with AMR likely reflects their suitability for rapid niche adaptation.
Musical expertise shapes functional and structural brain networks independent of absolute pitch ability
Authors: Leipold Simon , Klein Carina , Jäncke Lutz 
Published: July 2020

AbstractProfessional musicians are a popular model for investigating experience-dependent plasticity in human large-scale brain networks. A minority of musicians possess absolute pitch, the ability to name a tone without reference. The study of absolute pitch musicians provides insights into how a very specific talent is reflected in brain networks. Previous studies of the effects of musicianship and absolute pitch on large-scale brain networks have yielded highly heterogeneous findings regarding the localization and direction of the effects. This heterogeneity was likely influenced by small samples and vastly different methodological approaches. Here, we conducted a comprehensive multimodal assessment of effects of musicianship and absolute pitch on intrinsic functional and structural connectivity using a variety of commonly employed and state-of-the-art multivariate methods in the largest sample to date (n = 153 female and male human participants; 52 absolute pitch musicians, 51 non-absolute pitch musicians, and 50 non-musicians). Our results show robust effects of musicianship in inter- and intrahemispheric connectivity in both structural and functional networks. Crucially, most of the effects were replicable in both musicians with and without absolute pitch when compared to non-musicians. However, we did not find evidence for an effect of absolute pitch on intrinsic functional or structural connectivity in our data: The two musician groups showed strikingly similar networks across all analyses. Our results suggest that long-term musical training is associated with robust changes in large-scale brain networks. The effects of absolute pitch on neural networks might be subtle, requiring very large samples or task-based experiments to be detected.Significance StatementA question that has fascinated neuroscientists, psychologists, and musicologists for a long time is how musicianship and absolute pitch, the rare talent to name a tone without reference, are reflected in large-scale networks of the human brain. Much is still unknown as previous studies have reported widely inconsistent results based on small samples. Here, we investigate the largest sample of musicians and non-musicians to date (n = 153) using a multitude of established and novel analysis methods. Results provide evidence for robust effects of musicianship on functional and structural networks that were replicable in two separate groups of musicians and independent of absolute pitch ability.
Adopting STING agonist cyclic dinucleotides as a potential adjuvant for SARS-CoV-2 vaccine
Authors: Wu Jun-Jun , Chen Yong-Xiang , Li Yan-Mei 
Published: July 2020

AbstractA novel STING agonist CDGSF unilaterally modified with phosphorothioate and fluorine was synthesized. CDGSF displayed better STING activity over dithio CDG. Immunization of SARS-CoV-2 Spike protein with CDGSF as an adjuvant elicited an exceptional high antibody titer and a robust T cell response, which were better than the group using aluminium hydroxide as a adjuvant. These results highlighted the adjuvant potential of STING agonist in SARS-CoV-2 vaccine preparation for the first time.
Multiplexed quantitative screens of single cell shape and YAP/TAZ localisation identify DOCK5 as a coincident detector of polarity and adhesion during migration
Authors: Pascual-Vargas Patricia , Arias-Garcia Mar , Roumeliotis Theodoros I. , Choudhary Jyoti S. , Bakal Chris 
Published: July 2020

AbstractYAP and TAZ are transcriptional co-activators that are often constitutively active in triple negative breast cancer (TNBC) cells driving proliferation, invasion, and drug resistance. Through multiplexed quantitative genetic screens for YAP/TAZ localisation and cell shape, we found that the RhoGEF DOCK5 is essential for YAP/TAZ activation in metastatic cells and is required for the maintenance of polarity during migration. DOCK5 regulates cell shape and thus YAP/TAZ through different genetic interactions with CDC42, RAC, and RHOA GTPases. DOCK5 regulates focal adhesion (FA) morphogenesis in RAC-dependent fashions that promote RHOA mediated actomyosin engagement of FA. Using unbiased systems-level quantification of protein levels by mass spectrometry we show that DOCK5 maintains polarity by stabilising protein levels of the CDC42 effector GSK3β. We conclude DOCK5 acts as a coincidence detector to promote leading edge persistence in subcellular locations where there is both RAC and RHOA dependent FA morphogenesis and active CDC42 mediated cell polarisation.
Structure of human sodium leak channel NALCN in complex with FAM155A
Authors: Xie Jiongfang , Ke Meng , Xu Lizhen , Lin Shiyi , Zhang Jiabei , Yang Fan , Wu Jianping , Yan Zhen 
Published: July 2020

SummaryNALCN, a sodium leak channel mainly expressed in the central nervous systems, is responsible for the resting Na+ permeability that controls neuronal excitability. Dysfunctions of the NALCN channelosome, NALCN with several auxiliary subunits, are associated with a variety of human diseases. Here, we reported the cryo-EM structure of human NALCN in complex with FAM155A, at an overall resolution of 3.1 angstrom. FAM155A forms extensive interactions with the extracellular loops of NALCN that help stabilize NALCN in the membrane. A Na+ ion-binding site, reminiscent of a Ca2+ binding site in Cav channels, is identified in the unique EEKE selectivity filter. Despite its ‘leaky’ nature, the intracellular gate is sealed by S6I, II-III linker and III-IV linker. Our study establishes the molecular basis of Na+ permeation and voltage sensitivity, and provides important clues to the mechanistic understanding of NALCN regulation and NALCN channelosome-related diseases.
Introgression, hominin dispersal and megafaunal survival in Late Pleistocene Island Southeast Asia
Authors: Teixeira João C. , Jacobs Guy S. , Stringer Chris , Tuke Jonathan , Hudjashov Georgi , Purnomo Gludhug A. , Sudoyo Herawati , Cox Murray P. , Tobler Ray , Turney Chris S.M. , Cooper Alan , Helgen Kristofer M. 
Published: July 2020

AbstractThe hominin fossil record of Island Southeast Asia (ISEA) indicates that at least two endemic ‘super-archaic’ species –Homo luzonensisandH. floresiensis– were present around the time anatomically modern humans (AMH) arrived in the region >50,000 years ago. Contemporary human populations carry signals consistent with interbreeding events with Denisovans in ISEA – a species that is thought to be more closely related to AMH than the super-archaic endemic ISEA hominins. To query this disparity between fossil and genetic evidence, we performed a comprehensive search for super-archaic introgression in >400 modern human genomes. Our results corroborate widespread Denisovan ancestry in ISEA populations but fail to detect any super-archaic admixture signals. By highlighting local megafaunal survival east of the Wallace Line as a potential signature of deep, pre-H. sapienshominin-faunal interaction, we propose that this understudied region may hold the key to unlocking significant chapters in Denisovan prehistory.
Phenotypic plasticity underlies local invasion and distant metastasis in colon cancer
Authors: Sacchetti Andrea , Teeuwssen Miriam , Verhagen Mathijs , Joosten Rosalie , Xu Tong , Stabile Roberto , van der Steen Berdine , Watson Martin M. , Gusinac Alem , Kim Won Kyu , Ubink Inge , van de Werken Harmen J.G. , Fumagalli Arianna , Paauwe Madelon , van Rheenen Jacco , Sansom Owen , Kranenburg Onno , Fodde Riccardo 
Published: July 2020

AbstractPhenotypic plasticity represents the most relevant hallmark of the carcinoma cell as it bestows it with the capacity of transiently altering its morphologic and functional features whileen routeto the metastatic site. However, the study of phenotypic plasticity is hindered by the rarity of these events within primary lesions and by the lack of experimental models. Here, we identified a subpopulation of phenotypic plastic colon cancer cells: EpCAMlocells are motile, invasive, chemo-resistant, and highly metastatic. EpCAMlobulk and single-cell RNAseq analysis indicated 1. enhanced Wnt/β-catenin signaling, 2. a broad spectrum of degrees of EMT activation including hybrid E/M states (partial EMT) with highly plastic features, and 3. high correlation with the CMS4 subtype, accounting for colon cancer cases with poor prognosis and a pronounced stromal component. Of note, a signature of genes specifically expressed in EpCAMlocancer cells is highly predictive of overall survival in tumors other than CMS4, thus highlighting the relevance of quasi-mesenchymal tumor cells across the spectrum of colon cancers. Enhanced Wnt and the downstream EMT activation represent key events in eliciting phenotypic plasticity along the invasive front of primary colon carcinomas. Distinct sets of epithelial and mesenchymal genes define transcriptional trajectories through which state transitions arise. pEMT cells, often earmarked by the extracellular matrix glycoprotein SPARC together with nuclear ZEB1 and β-catenin along the invasive front of primary colon carcinomas, are predicted to represent the origin of these (de)differentiation routes through biologically-distinct cellular states, and to underlie the phenotypic plasticity of colon cancer cells.
Quantitative detection of sleep apnea with wearable watch device
Authors: Hayano Junichiro , Yamamoto Hiroaki , Nonaka Izumi , Komazawa Makoto , Itao Kenichi , Udea Norihiro , Tanaka Haruhito , Yuda Emi 
Published: July 2020

AbstractThe spread of wearable watch devices with photoplethysmography (PPG) sensors has made it possible to use continuous pulse wave data during daily life. We examined if PPG pulse wave data can be used to detect sleep apnea, a common but underdiagnosed health problem associated with impaired quality of life and increased cardiovascular risk. In 41 patients undergoing diagnostic polysomnography (PSG) for sleep apnea, PPG was recorded simultaneously with a wearable watch device. The pulse interval data were analyzed by an automated algorithm called auto-correlated wave detection with adaptive threshold (ACAT) which was developed for electrocardiogram (ECG) to detect the cyclic variation of heart rate (CVHR), a characteristic heart rate pattern accompanying sleep apnea episodes. The median (IQR) apnea-hypopnea index (AHI) was 17.2 (4.4-28.4) and 22 (54%) subjects had AHI ≥15. The hourly frequency of CVHR (Fcv) detected by the ACAT algorithm closely correlated with AHI (r= 0.81), while none of the time-domain, frequency-domain, or non-linear indices of pulse interval variability showed significant correlation. The Fcv was greater in subjects with AHI ≥15 (19.6 ± 12.3 /h) than in those with AHI <15 (6.4 ± 4.6 /h), and was able to discriminate them with 82% sensitivity, 89% specificity, and 85% accuracy. The classification performance was comparable to that obtained when the ACAT algorithm was applied to ECG R-R intervals during the PSG. The analysis of wearable watch PPG by the ACAT algorithm could be used for the quantitative screening of sleep apnea.
Absence of reliable physiological signature of illusory body ownership revealed by fine-grained autonomic measurement during the rubber hand illusion
Authors: Critchley Hugo D , Botan Vanessa , Ward Jamie 
Published: July 2020

AbstractThe neural representation of a ‘biological self’ is linked theoretically to the control of bodily physiology. In an infleuntial model, selfhood relates to internal agency and higher-order interoceptive representation, inferred from the predicted impact of efferent autonomic nerves on afferent viscerosensory feedback. Here we tested if an altered representation of physical self (illusory embodiment of an artificial hand) is accompanied by sustained shifts in autonomic activity.Participants (N=37) underwent procedures for induction of the rubber hand illusion (synchronous stroking of own unseen hand and observed stroking of artificial hand) and a control condition (asychronous stroking). We recorded electrodermal activity, electrocardiography, and non-invasive measurement of multiunit skin sympathetic nerve activity (SKNA) from the chest. We compared measures between task conditions, and between individuals who did and did not experience the illusion. Bayes factors quantified the strength of evidence for and against null hypotheses.Subjective reports and observed proprioceptive drift confirmed the efficacy of synchronous vs asynchronous condition in inducing illusory hand ownership. Stringent discriminant analysis classified 24 /37 individuals as experiencing the rubber hand illusion. Electrodermal activity, heart rate, heart rate variability, and SKNA measures revealed no autonomic differences between synchronous vs asynchronous conditions, nor between individuals who did or did not experience the rubber hand illusion. Bayes factors confirmed there was substantial evidence for no physiological differences.In contrast to earlier reports, our cardiac and electrodermal autonomic data, including fine grained SKNA measurement, provide substantial evidence for the absence of a reliable change in physiological state during induction or experience of the rubber hand illusion. If illusory body ownership is coupled to, or facilitated by, changes in efferent autonomic activity and afferent viscerosensory feedback, our findings suggest that such changes in bodily physiology are not sustained as an obligatory component of the illusion.
The bakers’s yeast Msh4-Msh5 associates with double-strand break hotspots and chromosome axis during meiosis to promote crossovers
Authors: Nandanan Krishnaprasad G. , Pankajam Ajith V. , Salim Sagar , Shinohara Miki , Lin Gen , Chakraborty Parijat , Steinmetz Lars M. , Shinohara Akira , Nishant Koodali T. 
Published: July 2020

ABSTRACTSegregation of homologous chromosomes during the first meiotic division requires at least one obligate crossover/exchange event between the homolog pairs. In the baker’s yeastSaccharomyces cerevisiaeand mammals, the mismatch repair-related factors, Msh4-Msh5 and Mlh1-Mlh3 generate the majority of the meiotic crossovers from programmed double-strand breaks (DSBs). To understand the mechanistic role of Msh4-Msh5 in meiotic crossing over, we performed genome-wide ChIP-sequencing and cytological analysis of the Msh5 protein in cells synchronized for meiosis. We observe that Msh5 associates with DSB hotspots, chromosome axis, and centromeres. We found that the initial recruitment of Msh4-Msh5 occurs following DSB resection. A two-step Msh5 binding pattern was observed: an early weak binding at DSB hotspots followed by enhanced late binding upon the formation of double Holliday junction structures. Msh5 association with the chromosome axis is Red1 dependent, while Msh5 association with the DSB hotspots and axis is dependent on DSB formation by Spo11. Msh5 binding was enhanced at strong DSB hotspots consistent with a role for DSB frequency in promoting Msh5 binding. These data on thein vivolocalization of Msh5 during meiosis have implications for how Msh4-Msh5 may work with other crossover and synapsis promoting factors to ensure Holliday junction resolution at the chromosome axis.AUTHOR SUMMARYDuring meiosis, crossovers facilitate physical linkages between homologous chromosomes that ensure their accurate segregation. Meiotic crossovers are initiated from programmed DNA double-strand breaks (DSBs). In the baker’s yeast and mammals, DSBs are repaired into crossovers primarily through a pathway involving the highly conserved mismatch repair related Msh4-Msh5 complex along with other crossover promoting factors.In vitroand physical studies suggest that the Msh4-Msh5 heterodimer facilitates meiotic crossover formation by stabilizing Holliday junctions. We investigated the genome-widein vivobinding sites of Msh5 during meiotic progression. Msh5 was enriched at DSB hotspots, chromosome axis, and centromere sites. Our results suggest Msh5 associates with both DSB sites on the chromosomal loops and with the chromosome axis to promote crossover formation. These results on thein vivodynamic localization of the Msh5 protein provide novel insights into how the Msh4-Msh5 complex may work with other crossover and synapsis promoting factors to facilitate crossover formation.
The ParA’s function is realized by two separate proteins in the partitioning system ofMyxococcusplasmid pMF1
Authors: Sheng Duohong , Chen Xiaojing , Li Yajie , Wang Jingjing , Zhuo Li , Li Yuezhong 
Published: July 2020

AbstractTheparoperon in the sole myxobacterial plasmid pMF1 includes a function-unknownparCgene in front of the classicalparAandparBgenes. Removal ofparCseverely reduced plasmid stability, but ex-situ compensations ofparCdid not restore theparsystem function. Individual expression ofparAformed insoluble proteins, while co-expression ofparCbeforeparAproduced a soluble ParC-ParA heterodimer. ParA alone had no ATPase activity and no polymerization, while ParC addition aided ParA to restore the activities. Fusing ParC and ParA in different ways all produced soluble proteins and some restored ATPase activity or increased plasmid stability. Protein interaction model analysis and experiments revealed that ParC structurally mimics the N-terminal of Ia-type SopA (ParA), endowing theMyxococcusParA protein to play functions by shifting of ParC between two sites on ParA surface. The present results highlight that ParC functions as a part of ParA to support its soluble expression and function, and the separation of ParC and ParA into two proteins in structure enables the ParC ‘fragment’ to shift in a larger range around ParA to function during partitioning.Author summaryOur work on ParC here provides a new example for the evolution of multi-domain protein. ParC and ParA are two proteins, but their expression and function act as a whole, which proposes a new regulatory model for bacterialparsystem, and also provides research ideas and materials for the study of functional coordination and evolution of ParA domains in the future.
Opposing macroevolutionary and trait-mediated patterns of threat and naturalization in flowering plants
Authors: Schmidt J. P. , Davies T. J. , Farrell M. J. 
Published: July 2020

AbstractDue to expanding global trade and movement, new plant species are establishing in exotic ranges at increasing rates while the number of native species facing extinction from multiple threats grows. Yet, how species losses and gains globally may together be linked to traits and macroevolutionary processes is poorly understood. Here we show that, adjusting for diversification rate and age, the proportion of threatened species across flowering plant families is negatively related to the proportion of naturalized species. Moreover, naturalization is positively associated with climate variability, short generation time, autonomous seed production, and interspecific hybridization, but negatively with age and diversification; whereas threat is negatively associated with climate variability and hybridization, and positively with biotic pollination, age and diversification. Such a pronounced signature of naturalization and threat across plant families suggests that both trait syndromes have coexisted over deep evolutionary time and that neither strategy is necessarily superior to the other.