bluuebunny/crossref_metadata_2025_split huggingface dataset:
A highly contiguous genome assembly reveals sources of genomic novelty in the symbiotic fungusRhizophagus irregularis
Authors: Manley Bethan F. , Lotharukpong Jaruwatana S. , Barrera-Redondo Josué , Yildirir Gokalp , Sperschneider Jana , Corradi Nicolas , Paszkowski Uta , Miska Eric A. , Dallaire Alexandra 
Published: October 2022

AbstractThe root systems of most plant species are aided by the soil foraging capacities of symbiotic Arbuscular Mycorrhizal (AM) fungi of the Glomeromycotina subphylum. Despite recent advances in our knowledge of the ecology and molecular biology of this mutualistic symbiosis, our understanding of the AM fungi genome biology is just emerging. Presented here are the most contiguous and highest-quality nuclear and mitochondrial genome assemblies of an arbuscular mycorrhizal fungus to date, achieved through Nanopore long-read DNA sequencing and Hi-C data. This haploid genome assembly ofRhizophagus irregularis, alongside short- and long-read RNA-Sequencing data, was used to produce a comprehensive annotation catalogue of gene models, repetitive elements, small RNA loci, and DNA cytosine methylome. A phylostratigraphic gene age inference framework revealed that the birth of genes associated with nutrient transporter activity and transmembrane ion transport systems predates the emergence of Glomeromycotina. While symbiotic nutrient cycling in AM fungi relies on genes that existed in ancestor lineages, a burst of Glomeromycotina-restricted genetic innovation is also detected. Analysis of the chromosomal distribution of genetic and epigenetic features highlights evolutionarily young genomic regions that produce abundant small RNAs, suggesting active RNA-based monitoring of genetic sequences surrounding recently evolved genes. This chromosome-scale view of the genome of an AM fungus genome reveals previously unexplored sources of genomic novelty in an organism evolving under an obligate symbiotic life cycle.HighlightsAssembly of 32 highly contiguous chromosomal scaffolds forR. irregularis, with 23 complete and gaplessGene annotation based on short- and long-read RNA-Seq data from different developmental stagesComplete annotation set including mitochondrial genes, DNA methylome, small RNAome, repetitive/transposable elements, functional annotationIdentification of a burst of lineage-restricted genetic innovation in the Glomeromycotina subphylum
Trellis Single-Cell Screening Reveals Stromal Regulation of Patient-Derived Organoid Drug Responses
Authors: Zapatero María Ramos , Tong Alexander , Sufi Jahangir , Vlckova Petra , Rodriguez Ferran Cardoso , Nattress Callum , Qin Xiao , Hochhauser Daniel , Krishnaswamy Smita , Tape Christopher J. 
Published: October 2022

AbstractPatient-derived organoids (PDOs) can model personalized therapy responses, however current screening technologies cannot reveal drug response mechanisms or study how tumor microenvironment cells alter therapeutic performance. To address this, we developed a highly-multiplexed mass cytometry platform to measure post translational modification (PTM) signaling in >2,500 colorectal cancer (CRC) PDOs and cancer-associated fibroblasts (CAFs) in response to clinical therapies at single-cell resolution. To compare patient- and microenvironment-specific drug responses in thousands of single-cell datasets, we developedTrellis— a highly-scalable, hierarchical tree-based treatment effect analysis method. Trellis single-cell screening revealed that on-target cell-cycle blockage and DNA-damage drug effects are common, even in chemorefractory PDOs. However, drug-induced apoptosis is patient-specific. We found drug-induced apoptosis does not correlate with genotype or clinical staging but does align with cell-intrinsic PTM signaling in PDOs. CAFs protect chemosensitive PDOs by shifting cancer cells into a slow-cycling cell-state and CAF chemoprotection can be reversed by inhibiting YAP.Highlights>2,500 single-cell PTM signaling, DNA-damage, cell-cycle, and apoptosis responses from drug-treated PDOs and CAFs.Trellis: hierarchical tree-based treatment effect method for single-cell screening analysis.PDOs have patient-specific drug responses that align with cell-intrinsic PTM signaling states.CAFs chemoprotect PDOs by altering PDO cell-state via YAP signaling.
Impact of neurons on patient derived-cardiomyocytes using organ-on-a-chip and iPSC biotechnologies
Authors: Bernardin Albin A. , Colombani Sarah , Rousselot Antoine , Andry Virginie , Goumon Yannick , Pasqualin Côme , Brugg Bernard , Jacotot Etienne , Pasquié Jean-Luc , Lacampagne Alain , Meli Albano C. 
Published: October 2022

AbstractIn the heart, cardiac function is regulated by the autonomic nervous system (ANS) that extends through the myocardium and establish junctions at the sinus node and ventricular levels. Thus, an increase or decrease of neuronal activity acutely affects myocardial function and chronically affects its structure through remodeling processes. The neuro-cardiac junction (NCJ), which is the major structure of this system, is poorly understood and only few cell models allow us to study it. Here we present an innovant neuro-cardiac organ-on-chip model to study this structure to better understand the mechanisms involved in the establishment of NCJ. To create such a system, we used microfluidic devices composed of two separate cells compartment interconnected by asymmetric microchannels. Rat PC12 cells, were differentiated to recapitulate the characteristics of sympathetic neurons, and cultivated with cardiomyocytes derived from human induced pluripotent stem cells (hiPSC). We confirmed the presence of specialized structure between the two cell types that allow neuromodulation and observed that the neuronal stimulation impacts the excitation-contraction coupling properties including the intracellular calcium handling. Finally, we also co-cultivated human neurons (hiPSC-NRs) with human cardiomyocytes (hiPSC-CMs) both obtained from the same hiPSC line. Hence, we have developed a neuro-cardiac compartmentalized in vitro model system that allows to recapitulate structural and functional properties of neuro-cardiac junction and that can be used to better understand interaction between heart and brain in humans, as well as to evaluate the impact of drugs on a reconstructed human neuro-cardiac system.
Strawberry additive increases nicotine vapor sampling and systemic exposure but does not enhance Pavlovian-based nicotine reward in mice
Authors: Patten Theresa , Johnson Natalie L. , Shaw Jessica K. , Dossat Amanda M. , Dreier Allison , Kimball Bruce A. , Wesson Daniel W. , De Biasi Mariella 
Published: October 2022

AbstractNicotine is an addictive drug whose popularity has recently increased, particularly among adolescents, due to the availability of electronic nicotine devices (i.e., “vaping”) and nicotine e-liquids containing additives with rich chemosensory properties. Some efforts to understand the role of these additives in nicotine reward suggest that they increase nicotine reward and reinforcement, but the sensory contributions of additives, especially in their vapor forms, are largely untested. Here, to better understand how a fruit-flavored (i.e., strawberry) additive influences nicotine reward and aversion, we used a conditioned place preference (CPP) procedure in which nicotine and a strawberry additive were delivered as a vapor to male and female adolescent mice. We found that nicotine vapor alone can lead to dose-dependent CPP when using a biased design. The strawberry additive did not produce CPP on its own, and we did not observe an effect of the strawberry additive on nicotine vapor-induced reward. Nevertheless, mice exposed to nicotine + strawberry additive vapor had higher plasma cotinine concentrations, which did not appear to reflect altered nicotine metabolism. Instead, by directly measuring vapor sampling through respiration monitoring, we uncovered an increase in the amount of sniffing toward strawberry-containing nicotine vapor compared to nicotine vapor alone. Together these data indicate that chemosensory-rich e-liquid additives may enhance the perceived sensory profile of nicotine vapors rather than the reward valueper se, which leads to overall increased nicotine exposure.Significance StatementWith the rise in popularity of flavored e-cigarette products, many have considered the possibility that flavor volatiles will enhance nicotine reward; however, the possibility that flavor additives have chemosensory properties that can affect nicotine intake has been largely overlooked. Here, by delivering nicotine to adolescent mice as a vapor we were able to consider both possibilities. We found that mice had increased sniffing intensity and nicotine exposure when vapors contained a strawberry additive, despite the fact that the same additive was unable to enhance Pavlovian nicotine reward using a CPP paradigm. This research highlights the importance of considering the chemosensory properties of e-cigarette additives as a mechanism for their effect on nicotine use.
Unique and shared proteome responses of rice plants (Oryza sativa) to individual abiotic stresses
Authors: Habibpourmehraban Fatemeh , Atwell Brian J. , Haynes Paul A. 
Published: October 2022

AbstractFood safety of staple crops such as rice is of global concern and is at the top of the policy agenda worldwide. Abiotic stresses are one of the main limitations to optimizing yields for sustainability, food security and food safety. We analyzed proteome changes inOryza sativassp. Nipponbare in response to three adverse abiotic treatments, including three levels of drought (mild, moderate, and severe), soil salinization, and non-optimal temperatures. All treatments had modest, negative effects on plant growth, enabling us to identify proteins that were common to all stresses, or unique to one. More than 75% of the total of differentially abundant proteins in response to abiotic stresses were specific to individual stresses, while fewer than 5% of stress-induced proteins were shared across all abiotic constraints. Stress-specific and non-specific stress-responsive proteins identified were categorized in terms of core biological processes, molecular functions, and cellular localization.Data AccessAll data have also been submitted to the PRIDE data repository, and will be available with project identifier PXD037280.
An evolutionary conserved division-of-labor between hippocampal and neocortical sharp-wave ripples organizes information transfer during sleep
Authors: van Schalkwijk Frank J. , Weber Jan , Hahn Michael A. , Lendner Janna D. , Inostroza Marion , Lin Jack J. , Helfrich Randolph F. 
Published: October 2022

AbstractThe hippocampal sharp-wave ripple (SW-R) is the key substrate of the hippocampal-neocortical dialogue underlying memory formation. Recently, it became evident that SW-R are not unique to archicortex, but constitute a wide-spread neocortical phenomenon. To date, little is known about morphological and functional similarities between archi- and neocortical SW-R. Leveraging intracranial recordings from the human hippocampus and prefrontal cortex during sleep, our results reveal region-specific functional specializations, albeit a near-uniform morphology. While hippocampal SW-R trigger directional hippocampal-to-neocortical information flow, neocortical SW-R reduce information flow to minimize interference. At the population level, hippocampal SW-R confined population dynamics to a low-dimensional subspace, while neocortical SW-R diversified the population response; functionally uncoupling the hippocampal-neocortical network. Critically, our replication in rodents demonstrated the same division-of-labor between archi-and neocortical SW-R. These results uncover an evolutionary preserved mechanism where coordinated interplay between hippocampal and neocortical SW-R temporally segregates hippocampal information transfer from neocortical processing.
Plant YTHDF proteins are direct effectors of antiviral immunity against an m6A-containing RNA virus
Authors: Martínez-Pérez Mireya , Aparicio Frederic , Arribas-Hernández Laura , Due Tankmar Mathias , Rennie Sarah , Brodersen Peter , Pallas Vicente 
Published: October 2022

SUMMARYIn virus-host interactions, nucleic acid-directed first lines of defense that allow viral clearance without compromising growth are of paramount importance. Plants use the RNA interference pathway as such a basal antiviral immune system, but additional RNA-based mechanisms of defense also exist. The infectivity of the plant positive strand RNA virus alfalfa mosaic virus (AMV) relies on demethylation of viral RNA by recruitment of the cellularN6-methyladenosine (m6A) demethylase ALKBH9B, but how demethylation of viral RNA promotes AMV replication remains unknown. Here, we show that inactivation of the cytoplasmic YT521-B homology domain (YTH)-containing m6A-binding proteins, ECT2, ECT3, and ECT5 is sufficient to restore AMV infectivity in partially resistantalkbh9bmutants. We also show that the antiviral function of ECT2 is distinct from its previously demonstrated function in promotion of proliferation of primordial cells, because an ECT2 mutant carrying a small deletion in its intrinsically disordered region is partially compromised for antiviral defense, but not for developmental functions. These results indicate that the m6A-YTH axis constitutes a novel branch of basal antiviral immunity in plants.
Metabolic evolution in response to interspecific competition in a eukaryote
Authors: Ghedini Giulia , Marshall Dustin J. 
Published: October 2022

AbstractCompetition can drive rapid evolution which, in turn, alters the trajectory of ecological communities. The role of eco-evolutionary dynamics in ecological communities is increasingly well-appreciated, but a mechanistic framework for identifying the types of traits that will evolve, and their trajectories, is required. Metabolic theory makes explicit predictions about how competition should shape the evolution of metabolism and size but these predictions have gone largely untested, particularly in eukaryotes. We use experimental evolution of a eukaryotic phototroph to examine how metabolism, size, and demography coevolve under both inter- and intra-specific competition. We find that the focal species evolves a smaller body size in response to competition, reducing density-dependence and maximizing carrying capacity. Metabolic theory successfully predicted most of these adaptations, but we also find important departures from theory. Longer-term evolution (70 generations) led to Pareto improvements in both population growth rate and carrying capacity, suggesting that classic r-K trade-offs observed among species can be evaded within species. The evasion of this trade-off appeared to arise due to the rapid evolution of enhanced metabolic plasticity: lineages exposed to competition evolved more labile metabolisms that tracked resource availability more effectively than lineages that were competition-free. We predict that rapid evolution in both size and metabolism may be a ubiquitous feature of adaptation to changing resource regimes that occurviaspecies invasions and environmental change.
Differential reduction of neuropathic pain symptoms by mGlu4-mediated neuromodulation of amygdala circuits
Authors: Pereira Vanessa , Arias Juri Aparicio , Llebaria Amadeu , Goudet Cyril 
Published: October 2022

ABSTRACTNeuropathic pain is a common health problem, resulting in exacerbated response to noxious and non noxious stimuli, as well as impaired emotional and cognitive responses. Unfortunately, neuropathic pain is also one of the most difficult pain syndromes to manage, highlighting the importance of better understanding of the brain regions and neuromodulatory mechanisms involved in its regulation. Among the many interconnected brain areas which process pain, the amygdala is known to play an important role in the integration of sensory and emotional pain signals. Here, we questioned the ability of a recently identified neuromodulatory mechanisms associated to the metabotropic glutamate receptors mGlu4in the amygdala to modulate neuropathic pain. In a murine model of peripheral mononeuropathy induced by a chronic constriction of the sciatic nerve, we demonstrate that pharmacological activation of amygdala mGlu4receptors efficiently alleviates sensory and depressive-like symptoms in both male and female mice. Moreover, we reveal a differential modulation of those symptoms, activating mGlu4receptors in the controlateral amygdala, relatively to the side of the mononeuropathy, is necessary and sufficient to relieve both sensory and depressive-like symptoms while ipsilateral activation solely reduces depressive-like symptoms. Furthermore, using photopharmacology, a recent strategy allowing a precise spatiotemporal photocontrol of deep brain endogenous targets, we further demonstrate the rapid and reversible action of mGlu4-mediated neuromodulation on neuropathic pain symptoms. Finally, coupling photopharmacology and analgesic conditioned place preference, we show an important pain-reducing effect of mGlu4 activation. Taken together, these data highlight the analgesic potential of enhancing amygdala mGlu4activity to counteract neuropathy in the hope of improving existing treatments.
Assisting walking balance using a bio-inspired exoskeleton controller
Authors: Afschrift M. , Van Asseldonk E. , Van Mierlo M. , Bayon C. , Keemink A. , van der Kooij H. , De Groote F. 
Published: October 2022

AbstractBalance control is important for mobility, yet exoskeleton research has mainly focused on improving metabolic energy efficiency. Here we present a biomimetic exoskeleton controller that supports walking balance and reduces muscle activity. Humans restore balance after a perturbation by adjusting activity of the muscles actuating the ankle in proportion to deviations from steady-state center of mass kinematics. We designed a controller that mimics the neural control of steady-state walking and the balance recovery responses to perturbations. This controller uses both feedback from ankle kinematics in accordance with an existing model and feedback from the center of mass velocity. Control parameters were estimated by fitting the experimental relation between kinematics and ankle moments observed in humans that were walking while being perturbed by push and pull perturbations. This identified model was implemented on a bilateral ankle exoskeleton. The exoskeleton provided 30% of the estimated ankle moment during steady-state and perturbed walking. Across twelve subjects, exoskeleton support reduced calf muscle activity in steady-state walking by 19 % with respect to a minimal impedance controller. Proportional feedback of the center of mass velocity improved balance support after perturbation. Muscle activity is reduced in response to push and pull perturbations by 10 and 16 % and center of mass deviations by 9 and 18% with respect to the same controller without center of mass feedback. Our control approach implemented on bilateral ankle exoskeletons can thus effectively support steady-state walking and balance control and therefore has the potential to improve mobility in balance-impaired individuals.
Tumor infiltrating iNKT cells sustain neutrophil pro-tumorigenic functions influencing disease progression in human colorectal cancer
Authors: Lattanzi Georgia , Strati Francesco , Díaz-Basabe Angélica , Perillo Federica , Amoroso Chiara , Protti Giulia , Giuffrè Maria Rita , Baldari Ludovica , Cassinotti Elisa , Ghidini Michele , Galassi Barbara , Lopez Gianluca , Noviello Daniele , Porretti Laura , Trombetta Elena , Mazzarella Luca , Iezzi Giandomenica , Nicassio Francesco , Granucci Francesca , Caprioli Flavio , Facciotti Federica 
Published: October 2022

AbstractiNKT cells account for a relevant fraction of effector T-cells in the intestine. Although iNKT cells are cytotoxic lymphocytes, their role in colorectal cancer (CRC) remains controversial. From the analysis of colonic LPMCs of human and murine CRC specimens we report that tumor-infiltrating iNKT cells are characterized by an IL17/GM-CSF pro-tumorigenic phenotype, while maintaining cytotoxic properties in the adjacent non-tumoral tissue. Exposure of iNKT cells to the tumor-associated pathobiontFusobacterium nucleatumblunted their cytotoxic capability and enhanced iNKT cell-mediated neutrophils chemotaxis, which upregulated PMN-MDSC gene signatures and functions. Importantly,in vivostimulation of iNKT cells with αGalCer restored their anti-tumorigenic functions. Survival analyses demonstrated that human CRC co-infiltration by iNKT cells and tumor-associated neutrophils correlates with negative outcomes.Our results reveal a functional plasticity of human intestinal iNKT cells with pro- and anti-tumorigenic activities in CRC, suggesting an iNKT pivotal role in shaping the cancer developmental trajectory.
Long-term responses of life-history strategies to climatic variability in flowering plants
Authors: Boyko James D. , Hagen Eric R. , Beaulieu Jeremy M. , Vasconcelos Thais 
Published: October 2022

SummaryThe evolution of annual or perennial strategies in flowering plants may depend on a broad array of temperature and precipitation variables. Previously documented correlations between life history strategy and climate appear to be clade-specific and fail to consider the coevolution of climatic niches and life history strategies.Here we combine annual and perennial life history data with geographic distribution for 9,939 flowering plant species and utilize a recently developed method that accounts for the joint evolution of continuous and discrete traits to evaluate two hypotheses: (1) annuals tend to evolve in highly seasonal regions prone to extreme heat and drought, and (2) annuals tend to have faster rates of climatic niche evolution than perennials.We find temperature, particularly the maximum temperature of the warmest month, is the most consistent climatic factor influencing life history evolution in flowering plants. Unexpectedly, we find that the rates of climatic niche evolution are faster in perennials than in annual lineages.We propose that annuals are consistently favored in areas prone to extreme heat due to their ability to escape heat stress as seeds, but they tend to be outcompeted by perennials in regions where extreme heat is uncommon or nonexistent.