bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blocking mitochondrial pyruvate import causes energy wasting via futile lipid cycling in brown fat
Authors: Veliova Michaela , Ferreira Caroline M. , Benador Ilan Y. , Jones Anthony E. , Desousa Brandon R. , Mahdaviani Kiana , Acín-Pérez Rebeca , Petcherski Anton , Divakaruni Ajit S. , Prentki Marc , Corkey Barbara E. , Liesa Marc , Oliveira Marcus F. , Shirihai Orian S. 
Published: November 2019

ABSTRACTFutile lipid cycling is an ATP-wasting process proposed to participate in energy expenditure of mature fat-storing white adipocytes, given their inability to oxidize fat. The hallmark of activated brown adipocytes is to increase fat oxidation by uncoupling respiration from ATP synthesis. Whether ATP-consuming lipid cycling can contribute to BAT energy expenditure has been largely unexplored. Here we find that pharmacological inhibition of the mitochondrial pyruvate carrier (MPC) in brown adipocytes is sufficient to increase ATP-synthesis fueled by fatty acid oxidation, even in the absence of adrenergic stimulation. We find that elevated ATP-demand induced by MPC inhibition results from activation of futile lipid cycling. Furthermore, we identify that glutamine consumption and theMalate-AspartateShuttle are required for the increase inEnergyExpenditure induced by MPC inhibition inBrownAdipocytes (MAShEEBA). These data demonstrate that futile energy expenditure through lipid cycling can be activated in BAT by altering fuel availability to mitochondria. Therefore, we identify a new mechanism to increase fat oxidation and energy expenditure in BAT that bypasses the need for adrenergic stimulation of mitochondrial uncoupling.
Neuromodulation of astrocytic K+ clearance
Authors: Bellot-Saez Alba , Kékesi Orsolya , Ben-Abu Yuval , Morley John W. , Buskila Yossi 
Published: November 2019

ABSTRACTPotassium homeostasis is a fundamental requirement for normal brain function. Therefore, effective removal of excessive K+accumulation from the synaptic cleft during neuronal activity is paramount. Astrocytes, one of the most common subtype of glial cells in the brain, play a key role in K+clearance from the extracellular milieu using various mechanisms, including uptake via Kir channels and the Na+-K+ATPase, and spatial buffering through the astrocytic gap-junction coupled network. Recently we showed that alterations in the concentrations of extracellular potassium ([K+]°) or impairments of the astrocytic clearance mechanism effect the resonance and oscillatory behaviour of both individual and networks of neurons recorded from C57/BL6 mice of both sexes. These results indicate that astrocytes have the potential to modulate neuronal network activity, however the cellular effectors that may affect the astrocytic K+clearance process are still unknown. In this study, we have investigated the impact of neuromodulators, which are known to mediate changes in network oscillatory behaviour, on the astrocytic clearance process. Our results suggest that some neuromodulators (5-HT; NA) affect astrocytic spatial buffering via gap-junctions, while others (DA; Histamine) affect the uptake mechanism via Kir channels. These results suggest that neuromodulators can affect network oscillatory activity through parallel activation of both neurons and astrocytes, establishing a synergistic mechanism to recruitment of neurons into ensamble of networks to maximise the synchronous network activity.Significance statementNeuromodulators are known to mediate changes in network oscillatory behaviour and thus impact on brain states. In this study we show that certain neuromodulators directly affect distinct stages of astrocytic K+clearance, promoting neuronal excitability and network oscillations through parallel activation of both neurons and astrocytes, thus establishing a synergistic mechanism to maximise the synchronous network activity.
Experts, but not novices, exhibit StartReact indicating experts use the reticulospinal system more than novices
Authors: Bartels Brandon M. , Quezada Maria Jose , Ravichandran Vengateswaran J. , Honeycutt Claire F. 
Published: November 2019

AbstractMotor skill acquisition utilizes a wide array of neural structures; however, few articles evaluate how the relative contributions of these structures shift over the course of learning. Recent evidence from rodents and songbirds suggests there is a transfer from cortical to subcortical structures following intense, repetitive training. Evidence from humans indicate that the reticulospinal system is modulated over the course of skill acquisition and may be a subcortical facilitator of learning. The objective of this study was to evaluate how reticulospinal contributions are modulated by task expertise. Reticulospinal contributions were assessed using StartReact (SR). We hypothesized that expert typists would show SR during an individuated, keystroke task but SR would be absent in novices. Expert (75.2 ± 9.8 WPM) and novice typists (41.6 ± 8.2 WPM) were evaluated during an individuated, keystroke movements. In experts, SR was present in all fingers (except the middle) but was absent in novices (except the little). Together, these results suggest that experts use reticulospinal contributions more for movement than novices indicating that the reticular formation becomes increasingly important for movement execution in highly trained, skilled tasks even those that require individuated movement of the fingers.
The neocortical progenitor specification program is established through combined modulation of SHH and FGF signaling
Authors: Yabut Odessa R. , Ng Hui-Xuan , Yoon Keejung , Arela Jessica C. , Ngo Thomas , Pleasure Samuel J. 
Published: November 2019

ABSTRACTNeuronal progenitors in the developing forebrain undergo dynamic competence states to ensure timely generation of specific excitatory and inhibitory neuronal subtypes from distinct neurogenic niches of the dorsal and ventral forebrain, respectively. Here we show evidence of progenitor plasticity when Sonic hedgehog (SHH) signaling is left unmodulated in the embryonic neocortex of the dorsal forebrain. At early stages of corticogenesis, loss of Suppressor of Fused (Sufu), a potent inhibitor of SHH signaling, in neocortical progenitors, altered their transcriptomic landscape. Ectopic activation of SHH signaling occurred, via degradation of Gli3R, resulting in significant upregulation of Fibroblast Growth Factor 15 (FGF15) gene expression. Consequently, activation of FGF signaling, and its downstream effector the MAPK signaling, facilitated expression of genes characteristic of ventral forebrain progenitors. Our studies identify the importance of modulating extrinsic niche signals such as SHH and FGF15 to maintain the competency and specification program of neocortical progenitors throughout corticogenesis.SIGNIFICANCE STATEMENTLow levels of FGF15 control progenitor proliferation and differentiation during neocortical development but little is known on how FGF15 expression is maintained. Our studies identified SHH signaling as a critical activator of FGF15 expression during corticogenesis. We found that Sufu, via Gli3R, ensured low levels of FGF15 was expressed to prevent abnormal specification of neocortical progenitors. These studies advance our knowledge on the molecular mechanisms guiding the generation of specific neocortical neuronal lineages, their implications in neurodevelopmental diseases, and may guide future studies on how progenitor cells may be utilized for brain repair.
Specific hippocampal interneurons shape consolidation of recognition memory
Authors: Oliveira da Cruz Jose F. , Busquets-Garcia Arnau , Zhao Zhe , Varilh Marjorie , Lavanco Gianluca , Bellocchio Luigi , Robin Laurie , Cannich Astrid , Julio-Kalajzić Francisca , Drago Filippo , Marsicano Giovanni , Soria-Gomez Edgar 
Published: November 2019

SUMMARYA complex array of different inhibitory interneurons tightly controls hippocampal activity, but how such diversity specifically impacts on memory processes is scantly known. We found that a small subclass of type-1 cannabinoid receptor (CB1)-expressing hippocampal interneurons determines episodic-like memory consolidation by linking dopamine D1 receptor signaling to GABAergic transmission.Mice lacking CB1 in D1-positive cells (D1-CB1-KO) displayed impaired long-term, but not short-term, object recognition memory. Re-expression of CB1 in hippocampal, but not striatal, D1-positive cells rescued this memory impairment. Learning induced a facilitation of in vivo hippocampal long-term potentiation (LTP), which was abolished in mutant mice. Chemogenetic and pharmacological experiments revealed that both CB1-mediated memory and associated LTP facilitation involves the local control of GABAergic inhibition in a D1-dependent manner.This study reveals that CB1-/D1-expressing interneurons shape hippocampal circuits to sustain recognition memory, thereby identifying a mechanism linking the diversity of hippocampal interneurons to specific behavioral and cognitive outcomes.
Inversions shape the divergence ofDrosophila pseudoobscuraandD. persimilison multiple timescales
Authors: Korunes Katharine L , Machado Carlos A , Noor Mohamed AF 
Published: November 2019

AbstractBy shaping meiotic recombination, chromosomal inversions can influence genetic exchange between hybridizing species. Despite the recognized importance of inversions in evolutionary processes such as divergence and speciation, teasing apart the effects of inversions over time remains challenging. For example, are their effects on sequence divergence primarily generated through creating blocks of linkage-disequilibrium pre-speciation or through preventing gene flux after speciation? We provide a comprehensive look into the influence of chromosomal inversions on gene flow throughout the evolutionary history of a classic system:Drosophila pseudoobscuraandD. persimilis. We use extensive whole-genome sequence data to report patterns of introgression and divergence with respect to chromosomal arrangements. Overall, we find evidence that inversions have contributed to divergence patterns betweenDrosophila pseudoobscuraandD. persimilisover three distinct timescales: 1) pre-speciation segregation of ancestral polymorphism, 2) post-speciation ancient gene flow, and 3) recent gene flow. We discuss these results in terms of our understanding of evolution in this classic system and provide cautions for interpreting divergence measures in similar datasets in other systems.
UPCLASS: a Deep Learning-based Classifier for UniProtKB Entry Publications
Authors: Teodoro Douglas , Knafou Julien , Naderi Nona , Pasche Emilie , Gobeill Julien , Arighi Cecilia N. , Ruch Patrick 
Published: November 2019

AbstractIn the UniProt Knowledgebase (UniProtKB), publications providing evidence for a specific protein annotation entry are organized across different categories, such as function, interaction and expression, based on the type of data they contain. To provide a systematic way of categorizing computationally mapped bibliography in UniProt, we investigate a Convolution Neural Network (CNN) model to classify publications with accession annotations according to UniProtKB categories. The main challenge to categorize publications at the accession annotation level is that the same publication can be annotated with multiple proteins, and thus be associated to different category sets according to the evidence provided for the protein. We propose a model that divides the document into parts containing and not containing evidence for the protein annotation. Then, we use these parts to create different feature sets for each accession and feed them to separate layers of the network. The CNN model achieved a F1-score of 0.72, outperforming baseline models based on logistic regression and support vector machine by up to 22 and 18 percentage points, respectively. We believe that such approach could be used to systematically categorize the computationally mapped bibliography in UniProtKB, which represents a significant set of the publications, and help curators to decide whether a publication is relevant for further curation for a protein accession.
Motif V acts as a Regulator of Energy Transduction Between the Flavivirus NS3 ATPase and RNA Binding Cleft
Authors: Du Pont Kelly E. , Davidson Russell , McCullagh Martin , Geiss Brian J. 
Published: November 2019

ABSTRACTThe unwinding of double-stranded RNA intermediates is a critical component for the replication of flavivirus RNA genomes. This function is achieved by the C-terminal helicase domain of nonstructural protein 3 (NS3). As a member of the superfamily 2 (SF2) helicases, NS3 is known to require the binding and hydrolysis of ATP/NTP to translocate along and unwind double-stranded nucleic acids. However, the mechanism of energy transduction between the ATP and RNA binding pockets is not well understood. Previous molecular dynamics simulations published by our group have identified Motif V as a potential “communication hub” for this energy transduction pathway. In order to investigate the role of Motif V in this process, a study combining molecular dynamics, biochemistry and virology has been employed. Mutations of Motif V were tested in both replicon and recombinant protein systems to investigate viral genome replication, RNA binding affinity, ATP hydrolysis activity and helicase unwinding activity. Using these analyses, we found that T407A and S411A in Motif V demonstrated increased turnover rates, suggesting that the mutations causes the helicase to unwind dsRNA more quickly than WT. Additionally, simulations of each mutant were used to probe structural changes within NS3 caused by each mutation. These simulations indicate that Motif V controls communication between the ATP binding pocket and the helical gate. These data help define the linkage between ATP hydrolysis and helicase activity within NS3 and provide insight into the biophysical mechanisms for ATPase driven NS3 helicase function.
Dimensions of passerine biodiversity along an elevational gradient: a nexus for historical biogeography and contemporary ecology
Authors: Burgio Kevin R. , Presley Steven J. , Cisneros Laura M. , Davis Katie E. , Dreiss Lindsay M. , Klingbeil Brian T. , Willig Michael R. 
Published: November 2019

ABSTRACTAimThe incorporation of functional and phylogenetic information is necessary to comprehensively characterize spatial patterns of biodiversity and to evaluate the relative importance of ecological and evolutionary mechanisms in molding such patterns. We evaluated the relative importance of mechanisms that shape passerine biodiversity along an extensive elevational gradient.LocationManu Biosphere Reserve in the Peruvian AndesTaxonSongbirds (order Passeriformes)MethodsWe quantified elevational gradients of species richness, phylogenetic biodiversity, and functional biodiversity for all passerines as well as separately for suboscines and oscines; determined if phylogenetic or functional biodiversity was consistent with random selection or if there was evidence of particular mechanisms dominating community assembly; and compared patterns for each dimension of biodiversity for the two suborders.ResultsFor all passerines and for suboscines, species richness decreased in a saturating fashion, phylogenetic biodiversity declined linearly, and functional biodiversity was stochastic along the elevation gradient. For oscines, species richness and phylogenetic biodiversity decreased linearly, and functional biodiversity decreased in a saturating fashion.Main conclusionsElevational gradients of biodiversity at Manu result from a combination of adaptations associated with radiations that occurred elsewhere (suboscines in Amazonian lowlands, oscines in colder climes of North America) and an in situ radiation in the Andes (tanagers). Our results suggest a combination of temperature-related physiological constraints and a reduction in functional redundancy associated with decreasing resource abundance at higher elevations molded the passerine assemblages along this elevational gradient. Explicit consideration of historical biogeography and conservatism of ancestral niches is necessary to comprehensively understand the mechanisms that mold gradients of biodiversity.
Dielectrophoresis assisted rapid, selective and single cell detection of antibiotic resistant bacteria with G-FETs
Authors: Kumar Narendra , Wang Wenjian , Ortiz-Marquez Juan C. , Catalano Matthew , Gray Mason , Biglari Nadia , Hikari Kitadai , Ling Xi , Gao Jianmin , Opijnen Tim van , Burch Kenneth S 
Published: November 2019

AbstractThe rapid increase in antibiotic resistant pathogenic bacteria has become a global threat, which besides the development of new drugs, requires rapid, cheap, scalable, and accurate diagnostics. Label free biosensors relying on electrochemical, mechanical, and mass based detection of whole bacterial cells have attempted to meet these requirements. However, the trade-off between selectivity and sensitivity of such sensors remains a key challenge. In particular, point-of-care diagnostics that are able to reduce and/or prevent unneeded antibiotic prescriptions require highly specific probes with sensitive and accurate transducers that can be miniaturized and multiplexed, and that are easy to operate and cheap. Towards achieving this goal, we present a number of advances in the use of graphene field effect transistors (G-FET) including the first use of peptide probes to electrically detect antibiotic resistant bacteria in a highly specific manner. In addition, we dramatically reduce the needed concentration for detection by employing dielectrophoresis for the first time in a G-FET, allowing us to monitor changes in the Dirac point due to individual bacterial cells. Specifically, we realized rapid binding of bacterial cells to a G-FET by electrical field guiding to the device to realize an overall 3 order of magnitude decrease in cell-concentration enabling a single-cell detection limit, and 9-fold reduction in needed time to 5 minutes. Utilizing our new biosensor and procedures, we demonstrate the first selective, electrical detection of the pathogenic bacterial species Staphylococcus aureus and antibiotic resistant Acinetobacter baumannii on a single platform.
Deletion ofcftrleads to an excessive neutrophilic response and defective tissue repair in a zebrafish model of sterile inflammation
Authors: Bernut Audrey , Loynes Catherine A. , Floto R. Andres , Renshaw Stephen A. 
Published: November 2019

AbstractInflammation-related progressive lung destruction is the leading causes of premature death in cystic fibrosis (CF), a genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. However, therapeutic targeting of inflammation has been hampered by a lack of understanding of the links between a dysfunctional CFTR and the deleterious innate immune response in CF. Herein, we used CFTR-depleted zebrafish larvae as an innovativein vivovertebrate model, mimicking aspects of the inflammatory pathology of CF-related lung, to understand how CFTR dysfunction leads to abnormal inflammatory status in CF.We show that impaired CFTR-mediated inflammation correlates with an exuberant neutrophilic response after injury: CF zebrafish exhibit enhanced and sustained accumulation of neutrophils at wounds. Excessive epithelial oxidative responses drive enhanced neutrophil recruitment towards wounds. Persistence of neutrophils at inflamed sites is associated with impaired reverse migration of neutrophils and reduction in neutrophil apoptosis. As a consequence, the increased number of neutrophils at wound sites causes tissue damage and abnormal tissue repair. Importantly, the pro-resolution molecule Tanshinone IIA successfully re-balances inflammation both by accelerating inflammation resolution and by improving tissue repair in CFTR-deficient animal.Larval zebrafish giving a unique insight into innate immune cell function in CFTR deficiency, our findings bring important new understanding of the mechanisms underlying the inflammatory pathology in CF, which could be addressed therapeutically to prevent inflammatory lung damage in CF patients with potential improvements in disease outcomes.
Species-level microbiome composition of activated sludge - introducing the MiDAS 3 ecosystem-specific reference database and taxonomy
Authors: Nierychlo Marta , Andersen Kasper Skytte , Xu Yijuan , Green Nick , Albertsen Mads , Dueholm Morten S. , Nielsen Per Halkjær 
Published: November 2019

AbstractThe function of microbial communities in wastewater treatment systems and anaerobic digesters is dictated by the physiological activity of its members and complex interactions between them. Since functional traits are often conserved at low taxonomic ranks (genus, species, strain), the development of high taxonomic resolution and reliable classification is the first crucial step towards understanding the role of microbes in any ecosystem. Here we present MiDAS 3, a comprehensive 16S rRNA gene reference database based on high-quality full-length sequences derived from activated sludge and anaerobic digester systems. The MiDAS 3 taxonomy proposes unique provisional names for all microorganisms down to species level. MiDAS 3 was applied for the detailed analysis of microbial communities in 20 Danish wastewater treatment plants with nutrient removal, sampled over 12 years, demonstrating community stability and many abundant core taxa. The top 50 most abundant species belonged to genera, of which >50% have no known function in the system, emphasizing the need for more efforts towards elucidating the role of important members of wastewater treatment ecosystems. The MiDAS 3 taxonomic database guided an update of the MiDAS Field Guide – an online resource linking the identity of microorganisms in wastewater treatment systems to available data related to their functional importance. The new field guide contains a complete list of genera (>1,800) and species (>4,200) found in activated sludge and anaerobic digesters. The identity of the microbes is linked to functional information, where available. The website also provides the possibility to BLAST the sequences against MiDAS 3 taxonomy directly online. The MiDAS Field Guide is a collaborative platform acting as an online knowledge repository and facilitating understanding of wastewater treatment ecosystem function.
Sex differences in Variability of Brain Structure Across the Lifespan
Authors: Forde Natalie J , Jeyachandra Jerrold , Joseph Michael , Jacobs Grace R , Dickie Erin , Satterthwaite Theodore D , Shinohara Russell T , Ameis Stephanie H , Voineskos Aristotle N 
Published: November 2019

AbstractSeveral brain disorders exhibit sex differences in onset, presentation, and prevalence. Increased understanding of the neurobiology of sex-based differences across the lifespan can provide insight into potential disease risk and protective mechanisms. We focused on sex-related differences in variability, which may be indicative of both disease vulnerability and resilience. In n=3,069 participants, from 8-95 years of age, we first analyzed the variance ratio in females vs. males of cortical surface area and global and subcortical volumes for discrete brain regions, and found widespread greater variability in males. In contrast, variance in cortical thickness was similar for males and females. Multivariate analysis that accounts for structural covariance supported variance ratio findings. Findings were present from early life and stable with age. We then examined variability among brain regions by sex. We found significant age-by-sex interactions across neuroimaging metrics, whereby in very early life males had reduced among-region variability compared to females, while in very late life this was reversed. Overall, our findings of greater regional variability but less among-region variability in males in early life may aid our understanding of sex-based risk for neurodevelopmental disorders. In contrast, our findings in late life may provide a potential sex-based risk mechanism for dementia.