bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can leafhoppers help us trace the impact of climate change on agriculture?
Authors: Plante Nicolas , Durivage Jeanne , Brochu Anne-Sophie , Dumonceaux Tim , Torres Dagoberto , Bahder Brian , Kits Joel , Dionne Antoine , Légaré Jean-Philippe , Tellier Stéphanie , Mcune Frédéric , Goulet Charles , Fournier Valérie , Pérez-López Edel 
Published: June 2023

SUMMARYClimate change is reshaping agriculture and insect biodiversity worldwide. With rising temperatures, insect species with narrow thermal margins are expected to be pushed beyond their thermal limits, and losses related to herbivory and diseases transmitted by them will be experienced in new regions. Several previous studies have investigated this phenomenon in tropical and temperate regions, locally and globally; however, here, it is proposed that climate change’s impact on agriculture can be traced through the study of Nearctic migratory insects, specifically leafhoppers. To test this hypothesis, leafhoppers in strawberry fields located in the province of Québec, eastern Canada, were evaluated. The strawberry-leafhopper pathosystem offers a unique opportunity because leafhoppers can transmit, among other diseases, strawberry green petal disease (SbGP), which is associated with pathogenic phytoplasmas. Here, we found that in the last ten years, the number of leafhoppers has been increasing in correspondence with the number of SbGP cases detected in eastern Canada, reporting for the first time ten species new to eastern Canada and two to the country, although the leafhopper diversity has been seriously affected. Our model using more than 34 000 leafhoppers showed that their abundance is influenced by temperature, a factor that we found also influences the microbiome associated withMacrosteles quadrilineatus, which was one of the most abundant leafhoppers we observed. One of our most striking findings is that none of the insecticides used by strawberry growers can control leafhopper incidence, which could be linked to microbiome changes induced by changing temperatures. We suggest that Nearctic leafhoppers can be used as sentinels to trace the multilayered effects of climate change in agriculture.GRAPHICAL ABSTRACTIN BRIEFThe current climate crisis is reshaping insect biodiversity and abundance, but little is known about the direct effect of this phenomenon on agriculture. In this study, we explored leafhoppers, a group of agriculturally important insect pests and disease vectors, as sentinels of the effect of climate change on agriculture. Our findings indicate that this group of insects can help us to understand the effect of the current climate crisis on insect invasions, diversity, abundance, disease dynamics and insecticide resistance and to take quick action to ensure food security while achieving more sustainable agriculture.HIGHLIGHTSMigratory leafhoppers benefit from temperature increasesLeafhopper-transmitted diseases have increased in the last decadeNew non-migratory leafhoppers can be found now in Nearctic regionsLeafhopper insecticide resistance could be linked to the insect microbiome
Evidence for a chromosomal inversion maintaining divergent plumage phenotypes between extensively hybridizing yellowhammers (Emberiza citrinella) and pine buntings (E. leucocephalos)
Authors: Nikelski Ellen , Rubtsov Alexander S. , Irwin Darren 
Published: June 2023

AbstractIn an allopatric speciation model, populations of a species become isolated by a geographic barrier and develop reproductive isolation through genetic differentiation. When populations meet in secondary contact, the strength of evolved reproductive barriers determines the extent of hybridization and whether the populations will continue to diverge or merge back together. The yellowhammer (Emberiza citrinella) and pine bunting (E. leucocephalos) are avian sister species that diverged in allopatry during the Pleistocene glaciations. Though they differ greatly in plumage and form distinct genetic clusters in allopatry, these taxa show negligible mitochondrial DNA differentiation and hybridize extensively in sympatry lending uncertainty to the state of reproductive isolation in the system. To assess the strength of reproductive barriers between taxa, we examined genomic differentiation across the yellowhammer and pine bunting system. We found that extensive admixture has occurred in sympatry, indicating that reproductive barriers between taxa are weak. We also identified a putative Z chromosome inversion that underlies plumage variation in the system, with the “pine bunting” inversion form showing dominance over the “yellowhammer” form. Our results suggest that yellowhammers and pine buntings are currently at a crossroads and that evolutionary forces may push this system towards either continued differentiation or population merging. However, even if these taxa merge, recombination suppression between chromosome Z inversion forms may maintain divergent plumage phenotypes within the system. In this way, our findings highlight the important role hybridization plays in increasing the genetic and phenotypic variation as well as the evolvability of a system.
Reactive Oxygen Species Mediate Transcriptional Responses to Dopamine and Cocaine in Human Cerebral Organoids
Authors: Rudibaugh Thomas T. , Keung Albert J. 
Published: June 2023

AbstractDopamine signaling in the adult ventral forebrain regulates behavior, stress response, and memory formation and in neurodevelopment regulates neural differentiation and cell migration. Excessive dopamine levels including due to cocaine use both in utero and in adults could lead to long-term adverse consequences. The mechanisms underlying both homeostatic and pathological changes remain unclear, partly due to the diverse cellular responses elicited by dopamine and the reliance on animal models that exhibit species- specific differences in dopamine signaling. To address these limitations, 3-D cerebral organoids have emerged as human-derived models, recapitulating salient features of human cell signaling and neurodevelopment. Organoids have demonstrated responsiveness to external stimuli, including substances of abuse, making them valuable investigative models. In this study we utilize the Xiang-Tanaka ventral forebrain organoid model and characterize their response to acute and chronic dopamine or cocaine exposure. The findings revealed a robust immune response, novel response pathways, and a potential critical role for reactive oxygen species (ROS) in the developing ventral forebrain. These results highlight the potential of cerebral organoids asin vitrohuman models for studying complex biological processes in the brain.
Dectin-1/CARD9-induction of the TFEB and TFE3 gene network is dispensable for phagocyte anti-Aspergillusactivity in the lung
Authors: Aufiero Mariano A. , Shlezinger Neta , Gjonbalaj Mergim , Mills Kathleen A.M. , Ballabio Andrea , Hohl Tobias M. 
Published: June 2023

ABSTRACTMyeloid phagocytes of the respiratory immune system, such as neutrophils, monocytes, and alveolar macrophages, are essential for immunity toAspergillus fumigatus, the most common etiologic agent of mold pneumonia worldwide. Following engulfment ofA. fumigatusconidia, fusion of the phagosome with the lysosome, is a critical process for killing conidia. TFEB and TFE3 are transcription factors that regulate lysosomal biogenesis under stress and are activated by inflammatory stimuli in macrophages, but it is unknown whether TFEB and TFE3 contribute to anti-Aspergillusimmunity during infection. We found that lung neutrophils express TFEB and TFE3, and their target genes were upregulated duringA. fumigatuslung infection. Additionally,A. fumigatusinfection induced nuclear accumulation of TFEB and TFE3 in macrophages in a process regulated by Dectin-1 and CARD9 signaling. Genetic deletion ofTfebandTfe3impaired macrophage killing ofA. fumigatusconidia. However, in a murine immune competentAspergillusinfection model with genetic deficiency ofTfebandTfe3in hematopoietic cells, we surprisingly found that lung myeloid phagocytes had no defects in conidial phagocytosis or killing. Loss of TFEB and TFE3 did not impact murine survival or clearance ofA. fumigatusfrom the lungs. Our findings indicate that myeloid phagocytes activate TFEB and TFE3 in response toA. fumigatus, and while this pathway promotes macrophage fungicidal activityin vitro, genetic loss can be functionally compensated at the portal of infection in the lung, resulting in no measurable defect in fungal control and host survival.
Top-down modulation in canonical cortical circuits with short-term plasticity
Authors: Waitzmann Felix , Wu Yue Kris , Gjorgjieva Julijana 
Published: June 2023

AbstractCortical dynamics and computations are strongly influenced by diverse GABAergic interneurons, including those expressing parvalbumin (PV), somatostatin (SST), and vasoactive intestinal peptide (VIP). Together with excitatory (E) neurons, they form a canonical microcircuit and exhibit counterintuitive nonlinear phenomena. One instance of such phenomena is response reversal, whereby SST neurons show opposite responses to top-down modulation via VIP depending on the presence of bottom-up sensory input, indicating that the network may function in different regimes under different stimulation conditions. Combining analytical and computational approaches, we demonstrate that model networks with multiple interneuron subtypes and experimentally identified short-term plasticity mechanisms can implement response reversal. Surprisingly, despite not directly affecting SST and VIP activity, PV-to-E short-term depression has a decisive impact on SST response reversal. We show how response reversal relates to inhibition stabilization and the paradoxical effect in the presence of several short-term plasticity mechanisms demonstrating that response reversal coincides with a change in the indispensability of SST for network stabilization. In summary, our work suggests a role of short-term plasticity mechanisms in generating nonlinear phenomena in networks with multiple interneuron subtypes and makes several experimentally testable predictions.
Dopamine D2 receptors in the bed nucleus of the stria terminalis modulate alcohol-related behaviors
Authors: Pati Dipanwita , Lee Sophia I. , Conley Sara Y. , Sides Tori , Boyt Kristen M. , Hunker Avery C. , Zweifel Larry S. , Kash Thomas L. 
Published: June 2023

AbstractDysregulation of the dopamine (DA) system is a hallmark of substance abuse disorders, including alcohol use disorder (AUD). Of the DA receptor subtypes, the DA D2 receptors (D2Rs) play a key role in the reinforcing effects of alcohol. D2Rs are expressed in numerous brain regions associated with the regulation of appetitive behaviors. One such region is the bed nucleus of the stria terminalis (BNST), which has been linked to the development and maintenance of AUD. Recently, we identified alcohol withdrawal-related neuroadaptations in the periaqueductal gray/dorsal raphe to BNST DA circuit in male mice. However, the role of D2R-expressing BNST neurons in voluntary alcohol consumption is not well characterized. In this study, we used a CRISPR-Cas9-based viral approach, to selectively reduce the expression of D2Rs in BNST VGAT neurons and interrogated the impact of BNST D2Rs in alcohol-related behaviors. In male mice, reduced D2R expression potentiated the stimulatory effects of alcohol and increased voluntary consumption of 20% w/v alcohol in a two-bottle choice intermittent access paradigm. This effect was not specific to alcohol, as D2R deletion also increased sucrose intake in male mice. Interestingly, cell-specific deletion of BNST D2Rs in female mice did not alter alcohol-related behaviors but lowered the threshold for mechanical pain sensitivity. Collectively, our findings suggest a role for postsynaptic BNST D2Rs in the modulation of sex-specific behavioral responses to alcohol and sucrose.
Lysinoalanine crosslinking is a conserved post-translational modification in the spirochete flagellar hook
Authors: Lynch Michael J. , Deshpande Maithili , Kyrniyati Kurni , Zhang Kai , James Milinda , Miller Michael , Zhang Sheng , Passalia Felipe J. , Wunder Elsio A. , Charon Nyles W. , Li Chunhao , Crane Brian R. 
Published: June 2023

AbstractSpirochete bacteria cause Lyme disease, leptospirosis, syphilis and several other human illnesses. Unlike other bacteria, spirochete flagella are enclosed within the periplasmic space where the filaments distort and push the cell body by action of the flagellar motors. We previously demonstrated that the oral pathogenTreponema denticola(Td) catalyzes the formation of covalent lysinoalanine (Lal) crosslinks between conserved cysteine and lysine residues of the FlgE protein that composes the flagellar hook. Although not necessary for hook assembly, Lal is required for motility of Td, presumably due to the stabilizing effect of the crosslink. Herein, we extend these findings to other, representative spirochete species across the phylum. We confirm the presence of Lal crosslinked peptides in recombinant andin vivo-derived samples fromTreponemaspp.,Borreliellaspp.,Brachyspiraspp., andLeptospiraspp.. Like with Td, a mutant strain of the Lyme disease pathogenBorreliella burgdorferiunable to form the crosslink has impaired motility. FlgE fromLeptospiraspp. does not conserve the Lal-forming cysteine residue which is instead substituted by serine. Nevertheless,Leptospira interrogansalso forms Lal, with several different Lal isoforms being detected between Ser-179 and Lys-145, Lys-148, and Lys-166, thereby highlighting species or order-specific differences within the phylum. Our data reveals that the Lal crosslink is a conserved and necessary post-translational modification across the spirochete phylum and may thus represent an effective target for spirochete-specific antimicrobials.Significance StatementThe phylum Spirochaetota contains bacterial pathogens responsible for a variety of diseases, including Lyme disease, syphilis, periodontal disease, and leptospirosis. Motility of these pathogens is a major virulence factor that contributes to infectivity and host colonization. The oral pathogenTreponema denticolaproduces a post-translational modification (PTM) in the form of a lysinoalanine (Lal) crosslink between neighboring subunits of the flagellar hook protein FlgE. Herein, we demonstrate that representative spirochetes species across the phylum all form Lal in their flagellar hooks.T. denticolaandB. burgdorfericells incapable of forming the crosslink are non-motile, thereby establishing the general role of the Lal PTM in the unusual type of flagellar motility evolved by spirochetes.
CRISPR screening by AAV episome-sequencing (CrAAVe-seq) is a highly scalable cell type-specificin vivoscreening platform
Authors: Ramani Biswarathan , Rose Indigo V.L. , Teyssier Noam , Pan Andrew , Danner-Bocks Spencer , Sanghal Tanya , Yadanar Lin , Tian Ruilin , Ma Keran , Palop Jorge J. , Kampmann Martin 
Published: June 2023

AbstractThere is a significant need for scalable CRISPR-based genetic screening methods that can be applied directly in mammalian tissuesin vivowhile enabling cell type-specific analysis. To address this, we developed an adeno-associated virus (AAV)-based CRISPR screening platform, CrAAVe- seq, that incorporates a Cre-sensitive sgRNA construct for pooled screening within targeted cell populations in mouse tissues. We demonstrate the utility of this approach by screening two distinct large sgRNA libraries, together targeting over 5,000 genes, in mouse brains to create a robust profile of neuron-essential genes. We validate two genes as strongly neuron-essential in both primary mouse neurons andin vivo, confirming the predictive power of our platform. By comparing results from individual mice and across different cell populations, we highlight the reproducibility and scalability of the platform and show that it is highly sensitive even for screening smaller neuronal subpopulations. We systematically characterize the impact of sgRNA library size, mouse cohort size, the size of the targeted cell population, viral titer, and multiplicity of infection on screen performance to establish general guidelines for large-scalein vivoscreens.
Profiling the neuroimmune cascade in 3xTg mice exposed to successive mild traumatic brain injuries
Authors: Pybus Alyssa F. , Bitarafan Sara , Brothers Rowan O. , Rohrer Alivia , Khaitan Arushi , Moctezuma Felix Rivera , Udeshi Kareena , Davies Brae , Triplett Sydney , Dammer Eric , Rangaraju Srikant , Buckley Erin M. , Wood Levi B. 
Published: June 2023

ABSTRACTRepetitive mild traumatic brain injuries (rmTBI) sustained within a window of vulnerability can result in long term cognitive deficits, depression, and eventual neurodegeneration associated with tau pathology, amyloid beta (Aβ) plaques, gliosis, and neuronal and functional loss. However, we have limited understanding of how successive injuries acutely affect the brain to result in these devastating long-term consequences. In the current study, we addressed the question of how repeated injuries affect the brain in the acute phase of injury (<24hr) by exposing the 3xTg-AD mouse model of tau and Aβ pathology to successive (1x, 3x, 5x) once-daily weight drop closed-head injuries and quantifying immune markers, pathological markers, and transcriptional profiles at 30min, 4hr, and 24hr after each injury. We used young adult mice (2-4 months old) to model the effects of rmTBI relevant to young adult athletes, and in the absence of significant tau and Aβ pathology. Importantly, we identified pronounced sexual dimorphism, with females eliciting more differentially expressed proteins after injury compared to males. Specifically, females showed: 1) a single injury caused a decrease in neuron-enriched genes inversely correlated with inflammatory protein expression as well as an increase in AD-related genes within 24hr, 2) each injury significantly increased expression of a group of cortical cytokines (IL-1α, IL-1β, IL-2, IL-9, IL-13, IL-17, KC) and MAPK phospho-proteins (phospho-Atf2, phospho-Mek1), several of which were co-labeled with neurons and correlated with phospho-tau, and 3) repetitive injury caused increased expression of genes associated with astrocyte reactivity and immune function. Collectively our data suggest that neurons respond to a single injury within 24h, while other cell types including astrocytes transition to inflammatory phenotypes within days of repetitive injury.
CRISPR-mediated germline mutagenesis for genetic sterilization ofAnopheles gambiaemales
Authors: Smidler Andrea L. , Paton Douglas G. , Church George M. , Esvelt Kevin M. , Shaw W. Robert , Catteruccia Flaminia 
Published: June 2023

ABSTRACTRapid spread of insecticide resistance among anopheline mosquitoes threatens malaria elimination efforts, necessitating development of alternative vector control technologies. Sterile Insect Technique (SIT) has been successfully implemented in multiple insect pests to suppress field populations by the release of large numbers of sterile males, yet it has proven difficult to adapt toAnophelesvectors. Here we outline adaptation of a CRISPR-based genetic sterilization system to selectively ablate male sperm cells in the malaria mosquitoAnopheles gambiae. We achieve robust mosaic biallelic mutagenesis of zero population growth(zpg, a gene essential for differentiation of germ cells) in F1 individuals after intercrossing a germline-expressing Cas9 transgenic line to a line expressingzpg-targeting gRNAs. Approximately 95% of mutagenized males display complete genetic sterilization, and cause similarly high levels of infertility in their female mates. Using a fluorescence reporter that allows detection of the germline leads to a 100% accurate selection of spermless males, improving the system. These males cause a striking reduction in mosquito population size when released at field-like frequencies in competition cages against wild type males. These findings demonstrate that such a genetic system could be adopted for SIT against important malaria vectors.
Single-cell multiome regression models identify functional and disease-associated enhancers and enable chromatin potential analysis
Authors: Mitra Sneha , Malik Rohan , Wong Wilfred , Rahman Afsana , Hartemink Alexander J. , Pritykin Yuri , Dey Kushal K. , Leslie Christina S. 
Published: June 2023

AbstractWe present a novel gene-level regulatory model called SCARlink that predicts single-cell gene expression from single-cell chromatin accessibility within and flanking (+/-250kb) the genic loci by training on multiome (scRNA-seq and scATAC-seq co-assay) sequencing data. The approach uses regularized Poisson regression on tile-level accessibility data to jointly model all regulatory effects at a gene locus, avoiding the limitations of pairwise gene-peak correlations and dependence on a peak atlas. SCARlink significantly outperformed existing gene scoring methods for imputing gene expression from chromatin accessibility across across high-coverage multiome data sets while giving comparable to improved performance on low-coverage data sets. Shapley value analysis on trained models identified cell-type-specific gene enhancers that are validated by promoter capture Hi-C and are 8x-35x enriched in fine-mapped eQTLs and 22x-35x enriched in fine-mapped GWAS variants across 83 UK Biobank traits. We further show that SCARlink-predicted and observed gene expression vectors provide a robust way to compute a chromatin potential vector field to enable developmental trajectory analysis.
Climate benefits of seaweed farming: estimating regional carbon emission and sequestration pathways
Authors: Bullen Cameron D. , Driscoll John , Burt Jenn , Stephens Tiffany , Hessing-Lewis Margot , Gregr Edward J. 
Published: June 2023

AbstractSeaweed farming is widely promoted as an approach to mitigating climate change despite limited data on carbon removal pathways and uncertainty around benefits and risks at operational scales. We explored the feasibility of seaweed farms to contribute to atmospheric CO2reduction in coastal British Columbia, Canada, a region identified as highly suitable for seaweed farming. Using a place-based, quantitative model, we examined five scenarios spanning a range of industry development. Our intermediate growth scenario sequestered or avoided 0.20 Tg CO2e / year, while our most ambitious scenario (with more cultivation and higher production rates) yielded a reduction of 8.2 Tg CO2e /year, equivalent to 0.3% and 13% of annual greenhouse gas emissions in BC, respectively. Across all scenarios, climate benefits depended on seaweed-based products replacing more emissions-intensive products. Marine sequestration was relatively inefficient in comparison, although production rates and avoided emissions are key uncertainties prioritized for future research. Our results show how seaweed farming could contribute to Canada’s climate goals, and our model illustrates how farmers, regulators, and researchers could accurately quantify the climate benefits of seaweed farming in local contexts.