bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dopamine waves as a mechanism for spatiotemporal credit assignment
Authors: Hamid Arif A. , Frank Michael J. , Moore Christopher I. 
Published: August 2019

AbstractSignificant evidence supports the view that dopamine shapes reward-learning by encoding prediction errors. However, it is unknown whether dopamine decision-signals are tailored to the functional specialization of target regions. Here, we report a novel set of wave-like spatiotemporal activity-patterns in dopamine axons across the dorsal striatum. These waves switch between different activational motifs and organize dopamine transients into localized clusters within functionally related striatal subregions. These specific motifs are associated with distinct task contexts: At reward delivery, dopamine signals rapidly resynchronize into propagating waves with opponent directions depending on instrumental task contingencies. Moreover, dopamine dynamics during reward pursuit signal the extent to which mice have instrumental control and interact with reward waves to predict future behavioral adjustments. Our results are consistent with a computational architecture in which striatal dopamine signals are sculpted by inference about instrumental controllability and provide evidence for a spatiotemporally “vectorized” role of dopamine in credit assignment.
Rethinking global carbon storage potential of trees. A comment on Bastin et al. 2019
Authors: Taylor Shawn D. , Marconi Sergio 
Published: August 2019

AbstractKey MessageBastin et al. 2019 used flawed assumptions in calculating the carbon storage of restored forests worldwide, resulting in a gross overestimate.ContextBastin et al. 2019 use two flawed assumptions: 1) that the area suitable for restoration does not contain any carbon currently, and 2) that soil organic carbon (SOC) from increased canopy cover will accumulate quickly enough to mitigate anthropogenic carbon emissions.AimsWe re-evaluated the potential carbon storage worldwide using empirical relationships of tree cover and carbon.Methods and ResultsWe use global datasets of tree cover, soil organic carbon, and above ground biomass to estimate the empirical relationships of tree cover and carbon stock storage. A more realistic range of global carbon storage potential is between 71.7 and 75.7 GtC globally, with a large uncertainty associated with SOC. This is less than half of the original 205 GtC estimate.ConclusionThe potential global carbon storage of restored forests is much less than that estimated by Bastin et al. 2019. While we agree on the value of assessing global reforestation potential, we suggest caution in considering it the most effective strategy to mitigate anthropogenic emissions.
Mechanotransduction-dependent control of stereocilia dimensions and row identity in inner hair cells
Authors: Krey Jocelyn F. , Chatterjee Paroma , Dumont Rachel A. , Choi Dongseok , Bird Jonathan E. , Barr-Gillespie Peter G. 
Published: August 2019

SummaryActin-rich structures like stereocilia and microvilli are assembled with precise control of length, diameter, and relative spacing. We found that developmental widening of the second-tallest stereocilia rank (row 2) of mouse inner hair cells correlated with the appearance of mechanotransduction. Correspondingly, Tmc1KO/KO;Tmc2KO/KO or TmieKO/KO hair cells, which lack transduction, have significantly altered stereocilia lengths and diameters. EPS8 and the short splice isoform of MYO15A, identity markers for row 1 (tallest), lost their row exclusivity in transduction mutants, a result that was mimicked by block of transduction channels. Likewise, the heterodimeric capping protein subunit CAPZB and its partner TWF2 lost their row 2 tip localization in mutants, and GNAI3 failed to accumulate at row 1 tips. Redistribution of marker proteins was accompanied by increased variability in stereocilia height. Transduction channels thus specify and maintain row identity and control addition of new actin filaments to increase stereocilia diameter.
Adaptive Introgression Promotes Fast Adaptation In Oaks Marginal Populations
Authors: Goicoechea Pablo G , Guillardín Laura , Fernández-Ibarrodo Lierni , Valbuena-Carabaña Maria , González-Martínez Santiago C , Alía Ricardo , Kremer Antoine 
Published: August 2019

AbstractRange shifts and species range limits are two fundamental, related processes in population and evolutionary genetics that have received much attention since a large impact of climate change in species’ distributions was predicted. In general, there is a broad consensus on the effects of abiotic interactions on range limits, but comprehensive evidence supporting/rejecting the impact of biotic interactions is lacking. Hybridization has long been recognized as a biotic interaction favoring marginal populations establishment and range expansion through transgressive segregation or adaptive introgression, but recently new roles have been claimed for hybridization, such as the trigger of adaptive radiations, or indirect effects on population sizes that would allow persistence until new mutations arises or the environment changes. In this work, we selected two Mediterranean oak species with ecological discrimination based on soil pH, and intensively sampled three interspecific pairs of marginal populations from taxon-extreme environments under heterogeneous climate conditions. We genotyped 110 EST-SSR markers evenly distributed across their genomes and applied a variety of population and landscape genetics models to validate candidate genes for local adaptation. Then, several introgression screens on shared candidates showed that the three inter-specific population pairs contain evidences of adaptive introgression and that events occur in both directions. Other significant findings from our work are: (i) Aproximate Bayesian Computation coupled to coalescent simulations supports small hybridization rates since recent secondary contact in two population pairs affected by Quaternary climatic oscillations but continuous old interspecific gene flow in the pair less affected by climate, (ii) introgression at loci involved in local adaptations leads to strong geographic structure of marginal oak populations when sampling is large enough, and (iii) sampling efforts can be targeted to reveal different components of populations structure. Finally, we review evidences that support our conclusions and discuss some evolutionary implications of adaptive introgression on range expansion.
Spatiotemporal refinement of signal flow through association cortex during learning
Authors: Gilad Ariel , Helmchen Fritjof 
Published: August 2019

AbstractAssociation areas in neocortex encode novel stimulus-outcome relationships but the principles of their engagement during task learning remain elusive. Using chronic wide-field calcium imaging we reveal two phases of spatiotemporal refinement of layer 2/3 cortical activity in mice learning whisker-based texture discrimination. Even before mice reach learning threshold, association cortex—including rostro-lateral (RL), posteromedial (PM), and retrosplenial dorsal (RD) areas—is generally suppressed early during trials (between auditory start cue and whisker-texture touch). As learning proceeds, a spatiotemporal activation sequence builds up, spreading from auditory areas to RL immediately before texture touch (whereas PM and RD remain suppressed) and continuing into barrel cortex, which eventually efficiently discriminates between textures. Additional correlation analysis substantiates this diverging learning-related refinement within association cortex. Our results indicate that a pre-learning phase of general suppression in association cortex precedes a learning-related phase of task-specific signal flow enhancement.
Structural basis of reiterative transcription from the pyrG and pyrBI promoters by bacterial RNA polymerase
Authors: Shin Yeonoh , Hedglin Mark , Murakami Katsuhiko S. 
Published: August 2019

ABSTRACTReiterative transcription is a non-canonical form of RNA synthesis by RNA polymerase in which a ribonucleotide specified by a single base in the DNA template is repetitively added to the nascent RNA transcript. We previously determined the X-ray crystal structure of the bacterial RNA polymerase engaged in reiterative transcription from the pyrG promoter, which contains 8 poly-G RNA bases synthesized using 3 C bases in the DNA as a template and extends RNA without displacement of the promoter recognition σ factor from the core enzyme. In this study, we determined a series of transcript initiation complex structures from the pyrG promoter using soak trigger freeze X-ray crystallography. We also performed biochemical assays to monitor template DNA translocation during RNA synthesis from the pyrG promoter and in vitro transcription assays to determine the length of poly-G RNA from the pyrG promoter variants. Structures and biochemical assays revealed how the RNA transcript from the pyrG promoter is guided toward the Rifampin-binding pocket then the main channel of RNA polymerase and provided insight into RNA slippage during reiterative transcription of the pyrG promoter. Lastly, we determined a structure of a reiterative transcription complex at the pyrBI promoter and revealed an alternative mechanism of RNA slippage and extension requiring the σ dissociation from the core enzyme.SIGNIFICANCE STATEMENTRNA polymerase synthesizes multiple bases of RNA using a single base of the template DNA due to slippage between RNA transcript and template DNA. This noncanonical RNA synthesis is called “reiterative transcription,” playing several regulatory roles cellular organisms and viruses. In this study, we determined a series of X-ray crystal structures of a bacterial RNA polymerase engaged in reiterative transcription and characterized a role of template DNA during reiterative transcription by biochemical assays. Our study revealed how RNA slips on template DNA and how RNA polymerase and template DNA determine length of reiterative RNA product. We also provide insights into the regulation of gene expression using two alternative ways of reiterative transcription.
Developing T cells form an immunological synapse for passage through the β−selection checkpoint
Authors: Allam Amr H. , Charnley Mirren , Pham Kim , Russell Sarah M. 
Published: August 2019

AbstractThe β-selection checkpoint of T cell development tests whether the cell has recombined its genomic DNA to produce a functional T Cell Receptor β (TCRβ) receptor. Passage through the β-selection checkpoint requires the nascent TCRβ protein to mediate signaling through a pre-TCR complex. In this study, we show that developing T cells at the β-selection checkpoint establish an immunological synapse in in vitro & in situ, resembling that of the mature T cell. The immunological synapse is dependent on two key signaling pathways known to be critical for the transition beyond the β-selection checkpoint, Notch and CXCR4 signaling. In vitro and in situ analyses indicate that the immunological synapse promotes passage through the β-selection checkpoint. Collectively, these data indicate that developing T cells regulate pre-TCR signaling through the formation of an immunological synapse. This signaling platform integrates cues from Notch, CXCR4, and MHC on the thymic stromal cell, to allow transition beyond the β-selection checkpoint.SummaryT cell development requires testing whether genomic rearrangement has produced a T cell receptor capable of transmitting signals. Most T cells fail this test. Here, we show that passage through the β-selection checkpoint requires assembly of a platform to support TCR signaling.
The role of dopaminergic nuclei in predicting and experiencing gains and losses: A 7T human fMRI study
Authors: Fontanesi Laura , Gluth Sebastian , Rieskamp Jörg , Forstmann Birte U. 
Published: August 2019

AbstractThe ability to predict the outcomes of actions based on experience is crucial for making successful decisions in new or dynamic environments. In animal studies using electrophysiology, it was found that dopamine neurons, located in the substantia nigra (SN) and the ventral tegmental area (VTA), have a crucial role in feedback-based learning. However, human neuroimaging studies have provided inconclusive results. The present work used ultrahigh field (7 Tesla) structural and functional MRI and optimized protocols to extract SN and VTA signals in human participants. In a number-guessing task, we found significant correlations with reward prediction error and risk in both the SN and the VTA and no correlation with expected value. We also found a surprise signal in the SN. These results are in line with a recent framework that proposed a differential role for the VTA and the SN in, respectively, learning of values and surprise.
Intersecting vulnerabilities: Climatic and demographic contributions to future population exposure to Aedes-borne viruses in the United States
Authors: Rohat Guillaume , Monaghan Andrew , Hayden Mary H. , Ryan Sadie J. , Wilhelmi Olga 
Published: August 2019

AbstractUnderstanding how climate change and demographic factors may shape future population exposure to viruses such as Zika, dengue, or chikungunya, transmitted by Aedes mosquitoes is essential to improving public health preparedness. In this study, we combine projections of cumulative monthly Aedes-borne virus transmission risk with spatially explicit population projections for vulnerable demographic groups (age and economic factors) to explore future county-level population exposure across the conterminous United States. We employ a scenario matrix – combinations of climate and socioeconomic scenarios (Representative Concentration Pathways and Shared Socioeconomic Pathways) – to assess the full range of uncertainty in emissions, socioeconomic development, and demographic change. Human exposure is projected to increase under most scenarios, up to +177% at the national scale in 2080 relative to 2010. Projected exposure changes are predominantly driven by population changes in vulnerable demographic groups, although climate change is also important, particularly in the western region where future exposure may decrease by >30% under the strongest climate change mitigation scenario. The results emphasize the crucial role that socioeconomic and demographic change play in shaping future population vulnerability and exposure to Aedes-borne virus transmission risk in the United States, and underscore the importance of including socioeconomic scenarios in projections of climate-related vector-borne disease impacts.
Decoding sounds depicting hand-object interactions in primary somatosensory cortex
Authors: Bailey Kerri M , Giordano Bruno L , Kaas Amanda L , Smith Fraser W 
Published: August 2019

AbstractNeurons, even in earliest sensory regions of cortex, are subject to a great deal of contextual influences from both within and across modality connections. Recent work has shown that primary sensory areas can respond to and in some cases discriminate stimuli not of their target modality: for example, primary somatosensory cortex (SI) discriminates visual images of graspable objects. In the present work, we investigated whether SI would discriminate sounds depicting hand-object interactions (e.g. bouncing a ball). In a rapid event-related functional magnetic resonance imaging (fMRI) experiment, participants listened attentively to sounds from three categories: hand-object interactions, and control categories of pure tones and animal vocalizations, while performing a one-back repetition detection task. Multi-voxel pattern analysis revealed significant decoding of different hand-object interactions within SI, but not for either control category. Crucially, in the hand-sensitive voxels defined from an independent tactile localizer, decoding accuracies were significantly higher for hand-object interactions compared to pure tones in left SI. Our findings indicate that simply hearing sounds depicting familiar hand-object interactions elicit different patterns of activity in SI, despite the complete absence of tactile stimulation. These results highlight the rich information that can be transmitted across sensory modalities even to primary sensory areas.
CHD8 regulates the balance between proliferation and differentiation of human iPSCs in neural development
Authors: Liu Wenzhong , Dong Weilai , Hoffman Ellen J. , Fernandez Thomas V. , Gupta Abha R. 
Published: August 2019

ABSTRACTBackgroundChromodomain helicase DNA-binding protein 8 (CHD8), which encodes a chromatin remodeling protein that regulates Wnt/β-catenin mediated gene expression, is one of the most strongly associated genes with autism spectrum disorder (ASD). Characterization of ASD patients with CHD8 disrupting mutations and animal and stem cell models of CHD8 deficiency suggest that CHD8 plays a role in neurodevelopment.MethodsWe generated iPSCs from the T-lymphocytes of a healthy, typically-developing human male and iPSC lines from the same source which were subjected to CRISPR/Cas9-mediated knockdown (KD) of CHD8. We subsequently derived neural progenitor cells (NPCs) and neural cells and examined the effects of CHD8 deficiency on cell proliferation and neural differentiation.ResultsWe observed that, compared to WT, CHD8 KD: (1) increased the number of iPSC colonies formed, (2) suppressed spontaneous differentiation along the edges of iPSC colonies, (3) increased the proliferation of NPCs, (4) delayed the formation of neural rosettes, (5) delayed neurite outgrowth, (6) decreased the percentage of cells in the G0/G1 phase of the cell cycle, (7) increased the percentage of cells in the G2/M phase of the cell cycle, (8) decreased presence of the neuronal marker MAP2 although not the glial marker GFAP, (9) decreased presence for the excitatory neuronal marker VGLUT1, and (10) decreased presence of the synaptic marker SYN1.ConclusionsOur results suggest that CHD8 deficiency causes alterations in the cell cycle. More specifically, CHD8 KD appears to increase cell proliferation and delay neural differentiation. This may contribute to the pathophysiology of ASD.
Theta power and theta-gamma coupling support spatial memory retrieval
Authors: Vivekananda Umesh , Bush Daniel , Bisby James A , Baxendale Sallie , Rodionov Roman , Diehl Beate , Chowdhury Fahmida A , McEvoy Andrew W , Miserocchi Anna , Walker Matthew C , Burgess Neil 
Published: August 2019

AbstractHippocampal theta oscillations have been implicated in spatial memory function in both rodents and humans. What is less clear is how hippocampal theta interacts with higher frequency oscillations during spatial memory function, and how this relates to subsequent behaviour. Here we asked ten human epilepsy patients undergoing intracranial EEG recording to perform a desk-top virtual reality spatial memory task, and found that increased theta power in two discrete bands (‘low’ 2-5Hz and ‘high’ 6-9Hz) during cued retrieval was associated with improved task performance. Similarly, increased coupling between ‘low’ theta phase and gamma amplitude during the same period was associated with improved task performance. These results support a role of theta oscillations and theta-gamma phase-amplitude coupling in human spatial memory function.
Molecular signatures for inflammation vary across cancer types and correlate significantly with tumor stage, gender and vital status of patients
Authors: So Alexandra R. , Si Jeong Min , Lopez David , Pellegrini Matteo 
Published: August 2019

AbstractCancer affects millions of individuals worldwide. One shortcoming of traditional cancer classification systems is that, even for tumors affecting a single organ, there is significant molecular heterogeneity. Precise molecular classification of tumors could be beneficial in personalizing patients’ therapy and predicting prognosis. To this end, here we propose to use molecular signatures to further refine cancer classification. Molecular signatures are collections of genes characterizing particular cell types, tissues or disease. Signatures can be used to interpret expression profiles from heterogeneous samples. Large collections of gene signatures have previously been cataloged in the MSigDB database. We have developed a web-based Signature Visualization Tool (SaVanT) to display signature scores in user-generated expression data. Here we have undertaken a systematic analysis of correlations between inflammatory signatures and cancer samples, to test whether inflammation can differentiate cancer types. Inflammatory response signatures were obtained from MsigDB and SaVanT and a signature score was computed for samples associated with 7 different cancer types. We first identified types of cancers that had high inflammation levels as measured by these signatures. The correlation between signature scores and metadata of these patients (gender, age at initial cancer diagnosis, cancer stage, and vital status) was then computed. We sought to evaluate correlations between inflammation with other clinical parameters and identified four cancer types that had statistically significant association (p-value < 0.05) with at least one clinical characteristic: pancreas adenocarcinoma (PAAD), cholangiocarcinoma (CHOL), kidney chromophobe (KICH), and uveal melanoma (UVM). These results may allow future studies to use these approaches to further refine cancer subtyping and ultimately treatment.
A mechanistic view of collective filament motion in active nematic networks
Authors: Striebel Moritz , Graf Isabella R. , Frey Erwin 
Published: August 2019

ABSTRACTProtein filament networks are structures crucial for force generation and cell shape. A central open question is how collective filament dynamics emerges from interactions between individual network constituents. To address this question we study a minimal but generic model for a nematic network where filament sliding is driven by the action of motor proteins. Our theoretical analysis shows how the interplay between viscous drag on filaments and motor-induced forces governs force propagation through such interconnected filament networks. We find that the ratio between these antagonistic forces establishes the range of filament interaction, which determines how the local filament velocity depends on the polarity of the surrounding network. This force propagation mechanism implies that the polarity-independent sliding observed in Xenopus egg extracts, and in-vitro experiments with purified components, is a consequence of a large force propagation length. We suggest how our predictions can be tested by tangible in vitro experiments whose feasibility is assessed with the help of simulations and an accompanying theoretical analysis.
The BUBR1 pseudokinase domain promotes efficient kinetochore PP2A-B56 recruitment to regulate spindle checkpoint silencing and chromosome alignment
Authors: Braga Luciano Gama , Cisneros Angel F. , Mathieu Michelle , Clerc Maxime , Garcia Pauline , Lottin Baptiste , Garand Chantal , Thebault Philippe , Landry Christian R , Elowe Sabine 
Published: August 2019

ABSTRACTThe balance of phospho-signalling at outer-kinetochores during mitosis is critical for the accurate attachments between kinetochores and the mitotic spindle and timely exit from mitosis. In humans, a major player in determining this balance is the PP2A-B56 phosphatase which is recruited to the Kinase Attachment Regulatory Domain (KARD) of the Spindle Assembly Checkpoint protein Budding Uninhibited by Benzimidazole 1-related 1 (BUBR1) in a phospho-dependent manner. This event unleashes a rapid, switch-like phosphatase relay that reverses phosphorylation at the kinetochore, extinguishing the checkpoint and promoting anaphase entry. Here, we conclusively demonstrate that the pseudokinase domain of human BUBR1 lacks phosphotransfer activity and that it was maintained in vertebrates because it allosterically promotes KARD phosphorylation. Mutation or removal of this domain results in decreased PP2A-B56 recruitment to the outer kinetochore, attenuated checkpoint silencing and errors in chromosome alignment as a result of imbalance in Aurora B activity. We demonstrate that the functions of the BUBR1 pseudokinase and the BUB1 kinase domains are intertwined, providing an explanation for retention of the pseudokinase domain in certain eukaryotes.