bluuebunny/crossref_metadata_2025_split huggingface dataset:
PhylEx: Accurate reconstruction of clonal structure via integrated analysis of bulk DNA-seq and single cell RNA-seq data
Authors: Jun Seong-Hwan , Toosi Hosein , Mold Jeff , Engblom Camilla , Chen Xinsong , O’Flanagan Ciara , Hagemann-Jensen Michael , Sandberg Rickard , Aparicio Samuel , Hartman Johan , Roth Andrew , Lagergren Jens 
Published: February 2021

AbstractWe propose PhylEx: a clonal-tree reconstruction method that integrates bulk genomics and single-cell transcriptomics data. In addition to the clonal-tree, PhylEx also assigns single-cells to clones, which effectively produce clonal expression profiles, and generates clonal genotypes. By analyzing scRNA-seq integrated with bulk DNA-seq, PhylEx can take advantage of co-occurrences of the mutations found in the cells. In the probabilistic model underlying PhylEx, the raw read counts from scRNA-seq follow a mixture of Beta-Binomial distributions, which accounts for the sparse nature of single-cell gene expression data; the mixture lessens the penalty caused by mutations not observed due to mono-allelic expression. We rigorously evaluated PhylEx on simulated datasets as well as a biological dataset consisting of a previously well-characterized high-grade serous ovarian cancer (HGSOC) cell line. PhylEx outperformed the state-of-the-art methods by a wide margin both when comparing capacity for clonal-tree reconstruction and capacity for correctly clustering mutations. By analyzing HGSOC and HER2+ breast cancer data, we also show that PhylEx clears the way for phylo-phenotypic analysis of cancer, i.e., that the clonal expression profiles, induced by the cell-to-clone assignments, can be exploited in a manner beyond what is possible with only expression-based clustering.
Bisphenol S and bisphenol F are less disruptive to cardiac electrophysiology and potentially safer for use in medical products, as compared to bisphenol A
Authors: Prudencio Tomas , Swift Luther , Guerrelli Devon , Cooper Blake , Reilly Marissa , Ciccarrelli Nina , Sheng Jiansong , Jaimes Rafael , Posnack Nikki Gillum 
Published: February 2021

ABSTRACTBackgroundBisphenol A (BPA) is a high-production volume chemical that is commonly used to manufacture consumer and medical-grade plastic products. Due to its ubiquity, the general population can incur daily environmental exposure to BPA, while heightened BPA exposure has been reported in intensive care patients and industrial workers. Due to health concerns, structural analogues are being explored as replacements for BPA.ObjectiveThis study aimed to examine the direct nongenomic effects of BPA on cardiac electrophysiology and compare its safety profile to recently developed alternatives, including BPS (bisphenol S) and BPF (bisphenol F).MethodsWhole-cell voltage-clamp recordings were performed on cell lines transfected with Nav1.5, hERG, or Cav1.2. Results of single channel experiments were validated by conducting electrophysiology studies on human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) and intact, whole heart preparations.ResultsOf the chemicals tested, BPA was the most potent inhibitor of both fast (INa-P) and late (INa-L) sodium channel (IC50= 55.3 and 23.6 μM, respectively), L-type calcium channel (IC50= 30.8 μM) and hERG channel current (IC50= 127 μM). The inhibitory effects of BPA and BPF on L-type calcium channels were supported by microelectrode array recordings, which revealed shortening of the extracellular field potential (akin to QT interval). Further, BPA and BPF exposure impaired atrioventricular conduction in intact, whole heart experiments. BPS did not alter any of the cardiac electrophysiology parameters tested.DiscussionResults of this study demonstrate that BPA and BPF exert an immediate inhibitory effect on cardiac ion channels, and that BPS may be a safer alternative. Intracellular signaling or genomic effects of bisphenol analogues were not investigated; therefore, additional mechanistic studies are necessary to fully elucidate the safety profile of bisphenol analogues on the heart.
Psilocin acutely disrupts sleep and affects local but not global sleep homeostasis in laboratory mice
Authors: Thomas Christopher W. , Blanco-Duque Cristina , Bréant Benjamin , Goodwin Guy M. , Sharp Trevor , Bannerman David M. , Vyazovskiy Vladyslav V. 
Published: February 2021

AbstractSerotonergic psychedelic drugs, such as psilocin (4-hydroxy-N,N-dimethyltryptamine), profoundly alter the quality of consciousness through mechanisms which are incompletely understood. Growing evidence suggests that a single psychedelic experience can positively impact long-term psychological well-being, with relevance for the treatment of psychiatric disorders, including depression. A prominent factor associated with psychiatric disorders is disturbed sleep, and the sleep-wake cycle is implicated in the regulation of neuronal firing and activity homeostasis. It remains unknown to what extent psychedelic agents directly affect sleep, in terms of both acute arousal and homeostatic sleep regulation. Here, chronicin vivoelectrophysiological recordings were obtained in mice to track sleep-wake architecture and cortical activity after psilocin injection. Administration of psilocin led to delayed REM sleep onset and reduced NREM sleep maintenance for up to approximately 3 hours after dosing, and the acute EEG response was associated primarily with an enhanced oscillation around 4 Hz. No long-term changes in sleep-wake quantity were found. When combined with sleep deprivation, psilocin did not alter the dynamics of homeostatic sleep rebound during the subsequent recovery period, as reflected in both sleep amount and EEG slow wave activity. However, psilocin decreased the recovery rate of sleep slow wave activity following sleep deprivation in the local field potentials of electrodes targeting medial prefrontal and surrounding cortex. It is concluded that psilocin affects both global vigilance state control and local sleep homeostasis, an effect which may be relevant for its antidepressant efficacy.
A visual tour of carbon export by sinking particles
Authors: Durkin Colleen A. , Buesseler Ken O. , Cetinić Ivona , Estapa Margaret L. , Kelly Roger P. , Omand Melissa 
Published: February 2021

AbstractTo better quantify the ocean’s biological carbon pump, we resolved the diversity of sinking particles that transport carbon into the ocean’s interior, their contribution to carbon export, and their attenuation with depth. Sinking particles collected in sediment trap gel layers from 4 distinct ocean ecosystems were imaged, measured, and classified. The size and identity of particles was used to model their contribution to particulate organic carbon (POC) flux. Measured POC fluxes were reasonably predicted by particle images. Nine particle types were identified, and most of the compositional variability was driven by the relative contribution of aggregates, long cylindrical fecal pellets, and salp fecal pellets. While particle composition varied across locations and seasons, the entire range of compositions was measured at a single well-observed location in the subarctic North Pacific over 1 month, across 500 m of depth. The magnitude of POC flux was not consistently associated with a dominant particle class, but particle classes did influence flux attenuation. Long fecal pellets attenuated most rapidly with depth whereas certain other classes attenuated little or not at all with depth. Small particles (<100μm) consistently contributed ∼5% to total POC flux in samples with higher magnitude fluxes. The relative importance of these small particle classes (spherical mini pellets, short oval fecal pellets, and dense detritus) increased in low flux environments (up to 46% of total POC flux). Imaging approaches that resolve large variations in particle composition across ocean basins, depth, and time will help to better parameterize biological carbon pump models.
Dynamic Auditory Remapping Across the Sleep-Wake Cycle
Authors: Arzi Anat , Trentin Caterina , Laudini Annamaria , Krugliak Alexandra , Nikolla Dritan , Bekinschtein Tristan 
Published: February 2021

AbstractIn a single day we transition from vigilant wakefulness to unconscious sleep and dreaming, undergoing diverse behavioural, physiological and neural changes. While during the awake state, exogenous stimuli and endogenous changes lead to sensory reorganisation, this remapping has not been charted throughout the sleep-wake cycle. We recorded neural activity in response to a range of tones using electroencephalography during a full night’s sleep, and examined whether auditory responses become more similar, dissimilar or remain unchanged between wakefulness, non-rapid (NREM) and rapid eye movement (REM) sleep. We found that neural similarities between pairs of auditory evoked potentials differed by conscious state in both early and late auditory processing stages. Furthermore, tone-pairs neural similarities were modulated by conscious state as a function of tone frequency, where some tone-pairs changed similarity between states and others continued unaffected. These findings demonstrate a state-, stimulus- and time-dependent functional reorganization of auditory processing across the sleep-wake cycle.
Targeting Diacylglycerol Lipase to Reduce Alcohol Consumption
Authors: Bedse Gaurav , Winters Nathan D. , Astafyev Anastasia , Patrick Toni A. , Mahajan Vikrant R. , Uddin Md. Jashim , Centanni Samuel W. , Samuels David C. , Marnett Lawrence J. , Winder Danny G. , Patel Sachin 
Published: February 2021

ABSTRACTAlcohol use disorder (AUD) is associated with substantial morbidity, mortality, and societal cost, and pharmacological treatment options for AUD are limited. The endogenous cannabinoid (eCB) signaling system is critically involved in reward processing and alcohol intake is positively correlated with release of the eCB ligand 2-Arachidonoylglycerol (2-AG) within reward neurocircuitry. Here we show that genetic and pharmacological inhibition of diacylglycerol lipase (DAGL), the rate limiting enzyme in the synthesis of 2-AG, reduces alcohol consumption in a variety of preclinical models ranging from a voluntary free-access model to aversion resistant-drinking, and dependence-like drinking induced via chronic intermittent ethanol vapor exposure in mice. DAGL inhibition also prevented ethanol-induced suppression of GABAergic transmission onto midbrain dopamine neurons, providing mechanistic insight into how DAGL inhibition could affect alcohol reward. Lastly, DAGL inhibition during either chronic alcohol consumption or protracted withdrawal was devoid of anxiogenic and depressive-like behavioral effects. These data suggest reducing 2-AG signaling via inhibition of DAGL could represent a novel approach to reduce alcohol consumption across the spectrum of AUD severity.
Mapping densely packed GPIIb/IIIa receptors in murine blood platelets with expansion microscopy
Authors: Heil Hannah S. , Aigner Max , Maier Sophia , Gupta Prateek , Evers Luise M.C. , Göb Vanessa , Kusch Charly , Meub Mara , Nieswandt Bernhard , Stegner David , Heinze Katrin G. 
Published: February 2021

AbstractInterrogating small platelets and their densely packed, highly abundant receptor landscape is key to understand platelet clotting, a process that can save lives when stopping blood loss after an injury, but also kill when causing heart attack, stroke or pulmonary embolism. The underlying key receptor distributions and interactions, in particular the relevance of integrin clustering, are not fully understood is because of highly abundant and densely distributed GPIIb/IIIa receptors. This makes receptor distributions difficult to assess even by super-resolution fluorescence microscopy. Here, we combine dual-color expansion and confocal microscopy with colocalization analysis to assess platelet receptor organization without the need of a super-resolution microscope. We show that 4x expansion is highly straight-forward for super-resolution microscopy of platelets, while 10x expansion provides higher precision at the price of increased efforts in sample preparation and imaging. Quantifying various receptor colocalization scenarios we demonstrate that expansion microscopy can pinpoint receptor distributions and interactions in resting and activated platelets being superior to conventional methods that fail in such dense 3D scenarios with highly abundant receptors. We reveal the presence of GPIIb/IIIa clusters in resting platelets, which are not affected by platelet activation indicating that they contribute to the rapid platelet response during platelet clotting.Graphical Abstract
The PMT-drivenp-coumaroylation of poplar lignins impacts lignin structure and improves wood saccharification
Authors: Lapierre Catherine , Sibout Richard , Laurans Françoise , Lesage-Descauses Marie-Claude , Déjardin Annabelle , Pilate Gilles 
Published: February 2021

ABSTRACTTransgenic poplars (Populus tremula x Populus alba, clone INRA 717-1B4) were produced by introducing theBrachypodium distachyon Bradi2g36910(BdPMT1) gene driven by the Arabidopsis (Arabidopsis thaliana)Cinnamate 4-Hydroxylase (AtC4H) promoter in the wild-type (WT) line and in a line overexpressing the Arabidopsis Ferulate 5-Hydroxylase (AtF5H). BdPMT1encodes a transferase which catalyzes the acylation of monolignols byp-coumaric acid (CA). SeveralBdPMT1- OE/WT andBdPMT1-OE/AtF5H-OEtransgenic lines were grown in the greenhouse andBdPMT1expression in xylem was confirmed by RT-PCR. The analysis of the cell walls (CW) of poplar stems and of corresponding purified dioxan lignins (DL) revealed that theBdPMT1-OE lignins were asp-coumaroylated as the lignins of C3 grass straws. For some transformants, CA levels even reached about 11 mg/g CW and 66 mg/g DL, which by far exceeds those ofBrachypodiumor wheat samples. This unprecedentedly highp-coumaroylation of poplar lignins affected neither the poplar growth, nor the stem lignin content. By contrast, the transgenic lignins were structurally modified, with an increase of terminal units with free phenolic groups. Relative to controls, this increase argues for a reduced polymerization degree ofBdPMT1-OE lignins and makes them more soluble in cold NaOH solution. Thep-coumaroylation of poplar samples, up to the levels of C3 grasses, improved the saccharification yield of alkali-pretreated poplar CW. These results establish that the genetically-drivenp-coumaroylation of lignins is a promising strategy to make wood lignins more susceptible to the alkaline treatments that can be used during the industrial processing of lignocellulosics.One-sentence summaryThe expression of a grass p-coumaroyl-CoA:monolignol transferase induces a high p-coumaroylation of poplar lignins and a better saccharification of alkali-pretreated poplar wood without growth penalty
Capturing actively produced microbial volatile organic compounds from human associated samples with vacuum assisted sorbent extraction
Authors: Phan Joann , Kapcia Joseph , Rodriguez Cynthia I. , Vogel Victoria L. , Dunham Sage J. B. , Whiteson Katrine 
Published: February 2021

ABSTRACTVolatile organic compounds (VOC) from biological samples have unknown origins. VOCs may originate from the host or different microbial organisms from a microbial community. In order to disentangle the origin of microbial VOCs, we performed volatile headspace analysis of bacterial mono- and co-cultures ofStaphylococcus aureus, Pseudomonas aeruginosa, andAcinetobacter baumannii, and stable isotope probing in biological samples of feces, saliva, sewage, and sputum. We utilized mono- and co-cultures to identify volatile production from individual bacterial species or in combination with stable isotope probing to identify the active metabolism of microbes from the biological samples. To extract the VOCs, we employed vacuum assisted sorbent extraction (VASE). VASE is an easy-to-use commercialized solvent-free headspace extraction method for semi-volatile and volatile compounds. The lack of solvents and the near vacuum conditions used make developing a method relatively easy and fast when compared to other extraction options like tert-butylation and solid phase microextraction. However, VASE does not work on nonvolatile compounds, thus excluding many protein analyses and heavy stable isotope labelling experiments. Using the workflow described here, we identified volatile signatures from mono- and co-cultures indicating there were volatiles specific to certain microbes or co-cultures. Furthermore, analysis of the stable isotope probing of biological samples identified VOCs that were either commonly or uniquely produced from the different human derived biological samples. Here we present the general workflow and experimental considerations of VASE.SUMMARYFrom this protocol, readers will be able to extract volatile organic compounds from a biological sample with the vacuum assisted sorbent extraction method, run samples on a GC-MS with the use of the Entech autosampler, and analyze data.
Fossil data do not support a long pre-Cretaceous history of flowering plants
Authors: Budd Graham E. , Mann Richard P. , Doyle James A. , Coiro Mario , Hilton Jason 
Published: February 2021

AbstractThe origin of angiosperms is a classic macroevolutionary problem, because of their rapid rise in the Early Cretaceous fossil record, beginning about 139 Ma ago, and the conflict this creates with older crown-group ages based on molecular clock dating1. Silvestro et al.2use a novel methodology to model past angiosperm diversity based on a Bayesian Brownian Bridge model of fossil finds assigned to extant families, concluding that a Cretaceous origin is vanishingly unlikely. However, their results strongly conflict with the known temporal distribution of angiosperm fossils, and, while we agree that statistical analysis aids interpretation of the fossil record, here we show the conclusions of Silvestro et al.2are unsound.
Polymorphism of Genetic Ambigrams
Authors: Dudas Gytis , Huber Greg , Wilkinson Michael , Yllanes David 
Published: February 2021

AbstractDouble synonyms in the genetic code can be used as a tool to test competing hypotheses regarding ambigrammatic narnavirus genomes. Applying the analysis to recent observations ofCulex narnavirus 1andZhejiang mosquito virus 3ambigrammatic viruses indicates that the open reading frame on the complementary strand of the segment coding for RNA-dependent RNA polymerase doesnotcode for a functional protein.Culex narnavirus 1has been shown to possess a second segment, also ambigrammatic, termed ‘Robin’. We find a comparable segment forZhejiang mosquito virus 3, a moderately diverged relative ofCulex narnavirus 1. Our analysis of Robin polymorphisms suggests that its reverse open reading frame also does not code for a functional protein. We make a hypothesis about its role.
Leptin regulates glucose homeostasis via the canonical WNT pathway
Authors: Kamstra Kaj , Rizwan Mohammed Z. , Horsfield Julia A. , Pretz Dominik , Shepherd Peter R. , Grattan David R. , Tups Alexander 
Published: February 2021

SummaryLeptin is a body weight regulatory hormone, but it is arguably even more potent at regulating blood glucose levels. To further our understanding of the molecular mechanisms by which leptin controls glucose homeostasis, we have used transgenic zebrafish models and conditional deletion of beta catenin in the mediobasal hypothalamus of adult mice to show that Wnt signalling in the brain mediates glucoregulatory effects of leptin. In zebrafish, under normal feeding conditions, leptin regulates glucose homeostasis but not adipostasis. In times of nutrient excess, we found that leptin also regulates body weight and size in this species. Using a Wnt signalling reporter fish, we show that leptin directly activates the canonical Wnt pathwayin vivo. Pharmacological inhibition of this pathway prevented the leptin-induced improvement in glucose tolerance. In adult mice, conditional deletion of the key Wnt effector molecule, β-catenin, in the mediobasal hypothalamus of male mice confirmed the essential role of the Wnt pathway in mediating leptin action and the neuroendocrine regulation of glucose homeostasis. Adult-onset β-catenin deletion in the mediobasal hypothalamus led to glucose intolerance, exacerbation of caloric intake and body weight gain under high fat diet, as well as resistance to exogenous leptin.
Integrating plant stoichiometry and feeding experiments: state-dependent forage choice and its implications on body mass
Authors: Balluffi-Fry Juliana , Leroux Shawn J. , Wiersma Yolanda F. , Richmond Isabella C. , Heckford Travis R. , Rizzuto Matteo , Kennah Joanie L. , Vander Wal Eric 
Published: February 2021

AbstractIntraspecific feeding choices account for a large portion of herbivore foraging in many ecosystems. Plant resource quality is heterogeneously distributed, affected by nutrient availability and growing conditions. Herbivores navigate landscapes, making feeding decisions according to food qualities, but also energetic and nutritional demands. We test three non-exclusive foraging hypotheses using the snowshoe hare (Lepus americanus): 1) herbivores feeding choices and body conditions respond to intraspecific plant quality variation, 2) feeding responses are mitigated when energetic demands are high, and 3) feeding responses are inflated when nutritional demands are high. We measured black spruce (Picea mariana) nitrogen, phosphorus, and terpene compositions, as indicators of quality, within a snowshoe hare trapping grid and found plant growing conditions to explain spruce quality variation (R2< 0.36). We then offered two qualities of spruce (H1) from the trapping grid to hares in cafeteria-style experiments and measured their feeding and body condition responses (n = 75). We proxied energetic demands (H2) with ambient temperature and coat insulation (% white coat) and nutritional demands (H3) with the spruce quality (nitrogen and phosphorus content) in home ranges. Hares that preferred higher-quality spruce lost less weight during experiments (p = 0.018). The results supported our energetic predictions: hares in colder temperatures and with less-insulative coats (lower % white) consumed more spruce and were less selective towards high-quality spruce. Collectively, we found variation in plant growing conditions within herbivore home ranges substantial enough to affect herbivore body conditions, but any plant-herbivore interactions are also mediated by animal energetic states.