bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding the paradoxical mechanical response of in-phase A-tracts at different force regimes
Authors: Marin-Gonzalez Alberto , Pastrana Cesar L. , Bocanegra Rebeca , Martín-González Alejandro , Vilhena J.G. , Pérez Rubén , Ibarra Borja , Aicart-Ramos Clara , Moreno-Herrero Fernando 
Published: November 2019

ABSTRACTA-tracts are A:T rich DNA sequences that exhibit unique structural and mechanical properties associated with several functions in vivo. The crystallographic structure of A-tracts has been well characterized. However, their response to forces remains unknown and the variability of their flexibility reported for different length scales has precluded a comprehensive description of the mechanical properties of these molecules. Here, we rationalize the mechanical properties of A-tracts across multiple length scales using a combination of single-molecule experiments and theoretical polymer models applied to DNA sequences present in the C. elegans genome. Atomic Force Microscopy imaging shows that phased A-tracts induce long-range (∼200 nm) bending. Moreover, the enhanced bending originates from an intrinsically bent structure rather than as a consequence of larger flexibility. In support of this, our data were well described with a theoretical model based on the worm-like chain model that includes intrinsic bending. Magnetic tweezers experiments confirm that the observed bent is intrinsic to the sequence and does not rely on particular ionic conditions. Using optical tweezers, we assess the local rigidity of A-tracts at high forces and unravel an unusually stiff character of these sequences, as quantified by their large stretch modulus. Our work rationalizes the complex multiscale flexibility of A-tracts, shedding light on the cryptic character of these sequences.
Description ofCorynebacterium rouxiisp. nov., a novel member of thediphtheriaespecies complex
Authors: Badell Edgar , Hennart Mélanie , Rodrigues Carla , Passet Virginie , Dazas Melody , Panunzi Leonardo , Bouchez Valérie , Carmi-Leroy Annick , Toubiana Julie , Brisse Sylvain 
Published: November 2019

AbstractA group of six clinical isolates previously identified asCorynebacterium diphtheriaebiovar Belfanti, isolated from human cutaneous or peritoneum infections and from one dog, were characterized by genomic sequencing, biochemical analysis and mass spectrometry (MALDI-TOF MS). The six isolates were negative for the diphtheria toxin gene. Phylogenetic analyses showed that the six isolates (including FRC0190T) are clearly demarcated fromC. diphtheriae, C. belfantii, C. ulceransandC. pseudotuberculosis. The average nucleotide identity of FRC0190TwithC. diphtheriaeNCTC 11397Twas 92.6%, and was 91.8% withC. belfantiiFRC0043T.C. diphtheriaesubsp.lausannensestrain CHUV2995Tappeared to be a later heterotypic synonym ofC. belfantii(ANI, 99.3%). Phenotyping data revealed an atypical negative or heterogeneous intermediate maltose fermentation reaction for the six isolates. MALDI-TOF MS differentiated the new group from the otherCorynebacteriumtaxa by the presence of specific spectral peaks.rpoBsequences showed identity to atypical, maltose-negativeC. diphtheriaebiovar Belfanti isolates previously described from two cats in the USA. We propose the nameCorynebacterium rouxiisp. nov. for the novel group, with FRC0190T(= CIP 111752T= DSM 110354T) as type strain.
Neuro-functional correlates of protective effects of wheel-running exercise against cocaine locomotor sensitization in mice: a [18F]fallypride microPET study
Authors: Becker Guillaume , Lespine Louis-Ferdinand , Bahri Mohamed Ali , Serrano Maria Elisa , Lemaire Christian , Luxen André , Tirelli Ezio , Plenevaux Alain 
Published: November 2019

ABSTRACTWheel-running exercise in laboratory rodents (animal model useful to study the neurobiology of aerobic exercise) decreases behavioral markers of vulnerability to addictive properties of various drugs of abuse including cocaine. However, neurobiological mechanisms underpinning this protective effect are far from being fully characterized and understood. Here, 28-day-old female C57BL/6J mice were housed with (n=48) or without (n=48) a running wheel for 6 weeks before being tested for acute locomotor responsiveness and initiation of locomotor sensitization to intraperitoneal injections of 8 mg/kg cocaine. The long-term expression of sensitization took place 3 weeks after the last session. On the day after, all mice underwent a microPET imaging session with [18F]fallypride radiotracer (dopamine 2/3 receptor (D2/3R) antagonist). Exercised mice were less sensitive to acute and sensitized cocaine hyperlocomotor effects, such attenuation being particularly well-marked for long-term expression of sensitization (η2p = 0.262). Additionally, we found that chronic administrations of cocaine was associated with a clear-cut increase of [18F]fallypride binding potential in mouse striatum (η2p = 0.170), presumably reflecting an increase in postsynaptic D2/3R density in this region. Finally, we found evidence that wheel-running exercise was associated with a moderate decrease in D2/3R density in striatum (η2p = 0.075), a mechanism that might contribute to protective properties of such form of exercise against drugs of abuse vulnerability.
Out of the Mediterranean Region: worldwide biogeography of snapdragons and relatives (tribe Antirrhineae, Plantaginaceae)
Authors: Gorospe Juan Manuel , Monjas David , Fernández-Mazuecos Mario 
Published: November 2019

ABSTRACTAimThe tribe Antirrhineae, including snapdragons, toadflaxes and relatives, is a model group for plant evolutionary research. It is widely distributed across the Northern Hemisphere and the Neotropics, but displays an uneven distribution of diversity, with more than 50% of species and subspecies in the Mediterranean Region. Here we conducted the first detailed, worldwide biogeographic analysis of the Antirrhineae and tested two alternative hypotheses (time-for-speciation vs. diversification rate differences) to explain the uneven distribution of diversity.LocationWorldwide, with a focus on the Mediterranean Region.Taxontribe Antirrhineae (Plantaginaceae).MethodsA phylogenetic biogeographic approach was taken, accounting for area connections through time. Ancestral ranges, dispersal events, speciation and lineage accumulation within areas were estimated. Diversification rates for taxa present and absent in the Mediterranean Region were compared, accounting for the effect of a floral key innovation (nectar spur).ResultsA proto-Mediterranean origin in the Late Eocene was estimated, and the Mediterranean Region stood out as the main centre for speciation and dispersal. Congruent patterns of long-distance dispersal from the Mediterranean Region to North America were recovered for at least two amphiatlantic clades. A significant floristic exchange between the Mediterranean and south-western Asia was detected. We found no evidence of different diversification rates between lineages inside and outside the Mediterranean Region.Main conclusionsThe Mediterranean Region played a key role in the origin of the current distribution of the Antirrhineae. However, the higher species richness found in this region appears to be the result of a time-for-speciation effect rather than of increased diversification rates. The establishment of current mediterranean climates in the Northern Hemisphere appears to have contributed to the recent diversification of the group, in combination with colonisation of adjacent regions with arid and semi-arid climates.
Sox2 and Sox3 are essential for development and regeneration of the zebrafish lateral line
Authors: Undurraga Cristian A. , Gou Yunzi , Sandoval Pablo C. , Nuñez Viviana A. , Allende Miguel L. , Riley Bruce B. , Hernández Pedro P. , Sarrazin Andres F. 
Published: November 2019

ABSTRACTThe recovery of injured or lost sensory neurons after trauma, disease or aging is a major scientific challenge. Upon hearing loss or balance disorder, regeneration of mechanosensory hair cells has been observed in fish, some amphibians and under special circumstances in birds, but is absent in adult mammals. In aquatic vertebrates, hair cells are not only present in the inner ear but also in neuromasts of the lateral line system. The zebrafish lateral line neuromast has an almost unlimited capacity to regenerate hair cells. This remarkable ability is possible due to the presence of neural stem/progenitor cells within neuromasts. In order to further characterize these stem cells, we use the expression of the neural progenitor markers Sox2 and Sox3, transgenic reporter lines, and morphological and topological analysis of the different cell types within the neuromast. We reveal new sub-populations of supporting cells, the sustentacular supporting cells and the neuromast stem cells. In addition, using loss-of-function and mutants ofsox2andsox3, we find that the combined activity of both genes is essential for lateral line development and regeneration. The capability of sox2/sox3 expressing stem cells to produce new hair cells, hair cell-precursors, and supporting cells after damage was analyzed in detail by time-lapse microscopy and immunofluorescence. We are able to provide evidence that sox2/3 expressing cells are the main contributors to the regenerated neuromast, and that their daughter cells are able to differentiate into most cell types of the neuromast.
Modeling time-varying brain networks with a self-tuning optimized Kalman filter
Authors: Pascucci D. , Rubega M. , Plomp G. 
Published: November 2019

AbstractBrain networks are complex dynamical systems in which directed interactions between different areas evolve at the sub-second scale of sensory, cognitive and motor processes. Due to the highly non-stationary nature of neural signals and their unknown noise components, however, modeling dynamic brain networks has remained one of the major challenges in contemporary neuroscience. Here, we present a new algorithm based on an innovative formulation of the Kalman filter that is optimized for tracking rapidly evolving patterns of directed functional connectivity under unknown noise conditions. The Self-Tuning Optimized Kalman filter (STOK) is a novel adaptive filter that embeds a self-tuning memory decay and a recursive regularization to guarantee high network tracking accuracy, temporal precision and robustness to noise. To validate the proposed algorithm, we performed an extensive comparison against the classical Kalman filter, in both realistic surrogate networks and real electroencephalography (EEG) data. In both simulations and real data, we show that the STOK filter estimates time-frequency patterns of directed connectivity with significantly superior performance. The advantages of the STOK filter were even clearer in real EEG data, where the algorithm recovered latent structures of dynamic connectivity from epicranial EEG recordings in rats and human visual evoked potentials, in excellent agreement with known physiology. These results establish the STOK filter as a powerful tool for modeling dynamic network structures in biological systems, with the potential to yield new insights into the rapid evolution of network states from which brain functions emerge.Author summaryDuring normal behavior, brains transition between functional network states several times per second. This allows humans to quickly read a sentence, and a frog to catch a fly. Understanding these fast network dynamics is fundamental to understanding how brains work, but up to now it has proven very difficult to model fast brain dynamics for various methodological reasons. To overcome these difficulties, we designed a new Kalman filter (STOK) by innovating on previous solutions from control theory and state-space modelling. We show that STOK accurately models fast network changes in simulations and real neural data, making it an essential new tool for modelling fast brain networks in the time and frequency domain.
Chronic loss of STAG2 leads to altered chromatin structure contributing to de-regulated transcription in AML
Authors: Smith James S , Craig Stephanie G , Liberante Fabio G , Lappin Katrina M , Crean Clare M , McDade Simon S , Thompson Alexander , Mills Ken I , Savage Kienan I 
Published: November 2019

ABSTRACTThe cohesin complex plays a major role in folding the human genome into 3D structural domains. Mutations in members of the cohesin complex are known early drivers of myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML), with STAG2 the most frequently mutated complex member. Here we use functional genomics to investigate the impact of chronic STAG2 loss on three-dimensional genome structure and transcriptional programming in a clinically relevant model of chronic STAG2 loss. The chronic loss of STAG2 led to loss of smaller loop domains and the maintenance/formation of large domains which in turn led to altered genome compartmentalisation. These changes in genome structure were linked with altered gene expression, including deregulation of the HOXA locus and the MAPK signalling pathway, which may contribute to disease development and response to therapy.AUTHOR SUMMARYAcute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS) are clonal malignant diseases that affect the myeloid blood cell lineage. Around 40 different mutations have been identified as being associated with MDS and AML; several mutations effect genes in the cohesin complex particularly STAG2. STAG2 is an X-linked gene that is pivotal to the cohesin complex and the mutations result in a truncated gene and loss of function. We have introduced a clinically relevant truncating mutation into an isogeneic AML model. This has shown that changes in the sizes of loop and domains formed in the genome resulting in appropriate gene compartmentalisations. The associated changes in gene transcription has resulted in deregulation of HOX genes, essential for development and differentiation, and in the MAPK signalling pathway that could a therapeutic target.
Suppression of homeostatic gene expression and increased expression of metabolism-related genes are early features of glaucoma in optic nerve head microglia
Authors: Tribble James R , Harder Jeffrey M , Williams Pete A , John Simon W M 
Published: November 2019

AbstractGlaucoma is the leading cause of irreversible vision loss. Ocular hypertension is a major risk factor for glaucoma and recent work has demonstrated critical early neuroinflammatory insults occur in the optic nerve head following ocular hypertension. Microglia and infiltrating monocytes are likely candidates to drive these neuroinflammatory insults. However, the exact molecular identity / transcriptomic profile of microglia early following ocular hypertensive insults is unknown. To elucidate the molecular identity of microglia during early glaucoma pathogenesis, we performed RNA-sequencing of microglia mRNA from the optic nerve head of a genetic mouse model of glaucoma (DBA/2J) at a time point following ocular hypertensive insults, but preceding detectable neurodegeneration (with microglia identified as being CD45lo/CD11b+/CD11c−). Furthermore, RNA-sequencing was performed on optic nerve head microglia from mice treated with radiation therapy, a potent therapy preventing neuroinflammatory insults. Transcriptomic profiling of optic nerve head microglia mRNA identifies early metabolic priming with marked changes in mitochondrial gene expression, and changes to phagocytosis, inflammatory, and sensome pathways. The data predict that many functions of microglia that help maintain tissue homeostasis are affected. Comparative analysis of these data with data from previously published whole optic nerve head tissue or monocyte-only samples from DBA/2J mice demonstrate that many of the neuroinflammatory signatures in these data sets arise from infiltrating monocytes and not reactive microglia. Finally, our data demonstrate that radiation therapy of DBA/2J mice potently abolishes these microglia metabolic transcriptomic changes at the same time points. Together, our data provide a unique resource for the community to help drive further hypothesis generation and testing in glaucoma.
Visual Cell Sorting: A High-throughput, Microscope-based Method to Dissect Cellular Heterogeneity
Authors: Hasle Nicholas , Cooke Anthony , Srivatsan Sanjay , Huang Heather , Stephany Jason J. , Krieger Zachary , Jackson Dana , Tang Weiliang , Pendyala Sriram , Monnat Raymond J. , Trapnell Cole , Hatch Emily M. , Fowler Douglas M. 
Published: November 2019

AbstractMicroscopy is a powerful tool for characterizing complex cellular phenotypes, but linking these phenotypes to genotype or RNA expression at scale remains challenging. Here, we present Visual Cell Sorting, a method that physically separates hundreds of thousands of live cells based on their visual phenotype. Visual Cell Sorting uses automated imaging and phenotypic analysis to direct selective illumination of Dendra2, a photoconvertible fluorescent protein expressed in live cells; these photoactivated cells are then isolated using fluorescence-activated cell sorting. First, we use Visual Cell Sorting to assess the effect of hundreds of nuclear localization sequence variants in a pooled format, identifying variants that improve nuclear localization and enabling annotation of nuclear localization sequences in thousands of human proteins. Second, we use Visual Cell Sorting to recover cells that retain normal nuclear morphologies after paclitaxel treatment, then derive their single cell transcriptomes to identify multiple pathways associated with paclitaxel resistance in human cancers. Unlike alternative methods, Visual Cell Sorting depends on inexpensive reagents and commercially available hardware. As such, it can be readily deployed to uncover the relationships between visual cellular phenotypes and internal states, including genotypes and gene expression programs.
Transcriptional regulatory network controlling the ontogeny of hematopoietic stem cells
Authors: Gao Peng , Chen Changya , Howell Elizabeth D. , Li Yan , Tober Joanna , Uzun Yasin , He Bing , Gao Long , Zhu Qin , Siekmann Arndt , Speck Nancy A. , Tan Kai 
Published: November 2019

AbstractHematopoietic stem cell (HSC) ontogeny is accompanied by dynamic changes in gene regulatory networks. We performed RNA-Seq and histone mark ChIP-Seq to define the transcriptomes and epigenomes of cells representing key developmental stages of HSC ontogeny in the mouse. The five populations analyzed were embryonic day 10.5 (E10.5) endothelium and hemogenic endothelium from the major arteries (dorsal aorta, umbilical and vitelline), an enriched population of pre-hematopoietic stem cells (pre-HSCs), fetal liver HSCs, and adult bone marrow HSCs. We observed dynamic and combinatorial epigenetic changes that mark regulatory DNA sequences including gene promoters and enhancers. Using epigenetic signatures, we identified enhancers for each developmental stage. Only 12% of enhancers are primed, and 78% are active, suggesting the vast majority of enhancers are establishedde novoat the developmental stages where they are required to control their target genes, without prior priming in earlier stages. We constructed developmental-stage-specific transcriptional regulatory networks during HSC ontogeny by linking enhancers and predicted bound transcription factors to their target promoters using a novel computational algorithm. Our computational analyses predicted known transcriptional regulators for the endothelial-to-hematopoietic transition, validating our overall approach, and identified putative novel transcription factors whose regulon activities correlate with the emergence of pre-HSCs. We validated roles for the broadly expressed transcription factors SP3 and MAZ in arterial hemogenic endothelium. Our data and computational analyses provide a useful resource for uncovering regulators of HSC formation.
RADA is a main branch migration factor in plant mitochondrial recombination and its defect leads to mtDNA instability and cell cycle arrest
Authors: Chevigny Nicolas , Weber-Lotfi Frédérique , Nadiras Cédric , Fertet Arnaud , Le Ret Monique , Bichara Marc , Erhardt Mathieu , Dietrich André , Raynaud Cécile , Gualberto José M. 
Published: November 2019

ABSTRACTThe mitochondria of flowering plants have large and complex genomes whose structure and segregation are modulated by recombination activities. The late steps of mitochondrial recombination are still poorly characterized: while the loss of mitochondrial recombination is not viable, a deficiency in RECG1-dependent branch migration has little impact on plant development, implying the existence of alternative pathways. Here we present RADA, an ortholog of bacterial RadA/Sms, which is required for the processing of organellar recombination intermediates. While bacterial RadA is dispensable, RADA-deficient plants are severely impacted in their development and fertility, correlating with increased mtDNA ectopic recombination and replication of recombination-generated subgenomes. The radA mutation is epistatic to recG1, indicating that RADA drives the main branch migration pathway of plant mitochondria. In contrast, the double mutation radA recA3 is lethal, underlining the importance of an alternative RECA3-dependent pathway. Although RADA is dually targeted to mitochondria and chloroplasts, we found little to no effects of radA on the stability of the plastidial genome. The stunted growth of radA mutants could not be correlated with obvious defects in mitochondrial gene expression. Rather, it seems that is partially caused by a retrograde signal that activates nuclear genes repressing cell cycle progression.
Behavioral signatures of a developing neural code
Authors: Avitan Lilach , Pujic Zac , Mölter Jan , McCullough Michael , Zhu Shuyu , Sun Biao , Myhre Ann-Elin , Goodhill Geoffrey J 
Published: November 2019

AbstractDuring early life neural codes must develop to appropriately transform sensory inputs into behavioral outputs. Here we demonstrate a direct link between the maturity of neural coding in the visual brain and developmental changes in visually-guided behavior. In zebrafish larvae we show that visually-driven hunting behavior improves from 4 to 15 days post-fertilization, becoming faster and more accurate. During the same period population activity in the optic tectum refines, leading to improved decoding and information transmission of spatial position, particularly in the representation of the frontal visual field. Remarkably, individual differences in decoding can predict each fish’s hunting success. Together these results show how the neural codes required to subserve a natural behavior emerge during development.