bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential impact of climate change on Nearctic leafhopper distribution and richness in North America
Authors: Santos Abraão Almeida , Jacques Jordanne , Pérez-López Edel 
Published: December 2023

ABSTRACTClimate change significantly contributes to shifts in the geographical range of pests and diseases. Leafhoppers (Hemiptera: Cicadellidae), known vectors of phytoplasmas pathogens, are linked to the transmission of more than 600 diseases affecting a thousand plant species worldwide. Despite this, the potential effects of climate change on leafhopper vectors of phytoplasmas remain a critical knowledge gap. To address this gap, our study investigated the potential impact of climate change on 14 species of Nearctic leafhoppers previously associated with phytoplasma-related diseases. Using the MaxEnt species distribution algorithm and other ecological niche modeling techniques, we assessed(i)the expected species richness under current climate conditions and four future scenarios and(ii)the environmental niche similarity among these species across these scenarios. Our projections suggest that the eastern region of North America holds the potential for the highest species richness, a trend expected to persist across all future scenarios, gradually expanding eastward. Notably, our findings indicate the increasing suitability of northern Canada for more species. Network analysis further revealed a remarkable similarity in environmental niches among most leafhopper species. Moreover, across the four future scenarios, there is a tendency for an increase in this similarity. Altogether, our study underscores the potential persistent presence of Nearctic leafhoppers in their current habitats while pointing to a shift toward northern North America in future scenarios. These findings have significant implications for sustainable pest management practices, prompting a necessary discussion on strategies to mitigate climate change and pest migration’s impact on agricultural systems.
Repurposing Hsp90 inhibitors as antimicrobials targeting two-component systems identifies compounds leading to loss of bacterial membrane integrity
Authors: Fernandez-Ciruelos Blanca , Albanese Marco , Adhav Anmol , Solomin Vitalii , Ritchie-Martinez Arabela , Taverne Femke , Velikova Nadya , Jirgensons Aigars , Marina Alberto , Finn Paul W. , Wells Jerry M. 
Published: December 2023

AbstractThe discovery of antimicrobials with novel mechanisms of action is crucial to tackle the foreseen global health crisis due to antimicrobial resistance. Bacterial two-component signalling systems (TCS) are attractive targets for the discovery of novel antibacterial agents. TCS-encoding genes are found in all bacterial genomes and typically consist of a sensor histidine kinase (HK) and a response regulator (RR). Due to the conserved Bergerat fold in the ATP-binding domain of the TCS HK and the human chaperone Hsp90, there has been much interest in repurposing inhibitors of Hsp90 as antibacterial compounds. In this study, we explore the chemical space of the known Hsp90 inhibitor scaffold 3,4-diphenylpyrazole (DPP), building on previous literature to further understand their potential for HK inhibition. Six DPP analogues inhibited HK autophosphorylationin vitroand had good antimicrobial activity against Gram-positive bacteria. However, mechanistic studies showed that their antimicrobial activity was related to damage of bacterial membranes. In addition, DPP analogues were cytotoxic to mammalian cancer cell lines and induced the cell arrest phenotype shown for other Hsp90 inhibitors. We conclude that these DPP structures can be further optimized as specific disruptors of bacterial membranes providing binding to Hsp90 and cytotoxicity are lowered. With respect to the original hypothesis, the X-ray crystal structure of resorcinol, a substructure of the DPP derivatives, bound to the HK CheA represents a promising starting point for the fragment-based design of novel HK inhibitors.
Intraspecies interactions ofStreptococcus mutansimpact biofilm architecture and virulence determinants in childhood dental caries
Authors: Momeni Stephanie S. , Cao Xixi , Xie Baotong , Rainey Katherine , Childers Noel K. , Wu Hui 
Published: December 2023

ABSTRACTEarly childhood dental caries (ECC) is the most common chronic disease among children with a heavy disease burden among low socioeconomic populations.Streptococcus mutansis most frequently associated with initiation of ECC. Many studies report children with multipleS. mutansstrains (i.e., genotypes) having greater odds of developing ECC, studies investigating intraspecies interactions in dental caries are lacking. In this study, the impact of intraspecies interactions on cariogenic and fitness traits of clinicalS. mutansisolates are investigated usingin-vitroandin-vivoapproaches.Initially clinicalS. mutansisolates of 10 children from a longitudinal epidemiological study were evaluated.S. mutansstrains (G09 and G18, most prevalent) isolated from one child were used for subsequent analysis. Association analysis was used to determine if presence of multipleS. mutansgenotypes within the first-year of colonization was associated with caries. Biofilm analysis was performed for single and mixed cultures to assess cariogenic traits, including biofilm biomass, intra-polysaccharide, pH, and glucan. Confocal Laser Scanning Microscopy (CLSM) and time-lapse imaging were used to evaluate spatial and temporal biofilm dynamics, respectively. ADrosophilamodel was used to assess colonizationin-vivo.Mean biofilm pH was significantly lower in co-cultured biofilms as compared with monoculture biofilms. Doubling ofS. mutans in-vitrobiofilms was observed by CLSM andin-vivocolonization inDrosophilafor co-culturedS. mutans. Individual strains occupied specific domains in co-culture and G09 contributed most to increased co-culture biofilm thickness and colonization inDrosophila. Biofilm formation and acid production displayed distinct signatures in time-lapsed experiments.IMPORTANCEThis study sheds light on the complex dynamics of a key contributor to early childhood dental caries (ECC) by exploring intraspecies interactions of differentS. mutansstrains and their impact on cariogenic traits. Utilizing clinical isolates from children with ECC, the research highlights significant differences in biofilm architecture and acid production in mixed versus single genotype cultures. The findings reveal that co-culturedS. mutansstrains exhibit increased cell density and acidity, with individual strains occupying distinct domains. These insights, enhanced by use of time-lapsed Confocal Laser Scanning Microscopy and a Drosophila model, offer a deeper understanding of ECC pathogenesis and potential avenues for targeted interventions.
Modulation of cell differentiation and growth dynamics underlie the shift from bud protection to light capture in cauline leaves
Authors: Le Gloanec C. , Gómez-Felipe A. , Alimchandani V. , Branchini E. , Routier-Kierzkowska A-L. , Kierzkowski D. 
Published: December 2023

ABSTRACTPlant organs have evolved into diverse shapes for specialized functions despite emerging as simple protrusions at the shoot apex. Cauline leaves serve both as photosynthetic organs and protective structures for emerging floral buds. However, the growth patterns underlying this dual function remain unknown. Here, we investigate the developmental dynamics shaping cauline leaves underlying their functional diversification from other laminar organs. We show that cauline leaves display a significant delay in overall elongation compared to rosette leaves. Using live imaging, we reveal that their functional divergence hinges on early modulation of the timing of cell differentiation and cellular growth rates. In contrast to rosette leaves and sepals, cell differentiation is delayed in cauline leaves, fostering extended proliferation, prolonged morphogenetic activity, and growth redistribution within the organ. Notably, cauline leaf growth is transiently suppressed during the early stages, keeping the leaf small and unfolded during the initiation of the first flowers. Our findings highlight the unique developmental timing of cauline leaves, underlying their shift from an early protective role to a later photosynthetic function.ONE SENTENCE SUMMARYThe dual function of the cauline leaf in protection and light capture is achieved during development through a delay of cell differentiation, growth redistribution, and transient growth decrease.
Small molecule inhibitor binds to NLRP3 and prevents inflammasome activation
Authors: Lackner Angela , Cabral Julia Elise , Qiu Yanfei , Zhou Haitian , Leonidas Lemuel , Pham Minh Anh , Macapagal Alijah , Lin Sophia , Armanus Emy , McNulty Reginald 
Published: December 2023

AbstractDespite recent advances in the mechanism of oxidized DNA activating NLRP3, the molecular mechanism and consequence of oxidized DNA associating with NLRP3 remains unknown. Cytosolic NLRP3 binds oxidized DNA which has been released from the mitochondria, which subsequently triggers inflammasome activation. Human glycosylase (hOGG1) repairs oxidized DNA damage which inhibits inflammasome activation. The fold of NLRP3 pyrin domain contains amino acids and a protein fold similar to hOGG1. Amino acids that enable hOGG1 to bind and cleave oxidized DNA are conserved in NLRP3. We found NLRP3 could bind and cleave oxidized guanine within mitochondrial DNA. The binding of oxidized DNA to NLRP3 was prevented by small molecule drugs which also inhibit hOGG1. These same drugs also inhibited inflammasome activation. Elucidating this mechanism will enable design of drug memetics that treat inflammasome pathologies, illustrated herein by NLRP3 pyrin domain inhibitors which suppressed interleukin-1β (IL-1β) production in macrophages.One-Sentence SummaryNLRP3 cleaves oxidized DNA and small molecule drug binding inhibits inflammasome activation.
Benchmarking tRNA-Seq quantification approaches by realistic tRNA-Seq data simulation identifies two novel approaches with higher accuracy
Authors: Smith Tom , Monti Mie , Willis Anne E , Kalmár Lajos 
Published: December 2023

AbstractQuantification of transfer RNA (tRNA) using illumina sequencing based tRNA-Seq is complicated due to their degree of redundancy and extensive modifications. As such, no tRNA-Seq method has become well established, while various approaches have been proposed to quantify tRNAs from sequencing reads. Here, we use realistic tRNA-Seq simulations to benchmark tRNA-Seq quantification approaches, including two novel approaches. We demonstrate that these novel approaches are consistently the most accurate, using data simulated to mimic five different tRNA-Seq methods. This simulation-based benchmarking also identifies specific shortfalls for each quantification approach and suggests that up to 13% of the variance observed between cell lines in real tRNA-Seq data could be due to systematic differences in quantification accuracy.
Transcriptional correlates of cocaine-associated learning in striatal ARC ensembles
Authors: Salery Marine , Godino Arthur , Xu Yu Qing , Fullard John F , Durand-de Cuttoli Romain , LaBanca Alexa R , Holt Leanne M , Russo Scott J , Roussos Panos , Nestler Eric J 
Published: December 2023

AbstractLearned associations between the rewarding effects of drugs and the context in which they are experienced underlie context-induced relapse. Previous work demonstrates the importance of sparse neuronal populations – called neuronal ensembles – in associative learning and cocaine seeking, but it remains unknown whether the encoding vs. retrieval of cocaine-associated memories involves similar or distinct mechanisms of ensemble activation and reactivation in nucleus accumbens (NAc). We use ArcCreERT2mice to establish that mostly distinct NAc ensembles are recruited by initial vs. repeated exposures to cocaine, which are then differentially reactivated and exert distinct effects during cocaine-related memory retrieval. Single-nuclei RNA-sequencing of these ensembles demonstrates predominant recruitment of D1 medium spiny neurons and identifies transcriptional properties that are selective to cocaine-recruited NAc neurons and could explain distinct excitability features. These findings fundamentally advance our understanding of how cocaine drives pathological memory formation during repeated exposures.
Knockdown of PHOX2B in the retrotrapezoid nucleus reduces the central CO2chemoreflex in rats
Authors: Cardani Silvia , Janes Tara A. , Betzner William , Pagliardini Silvia 
Published: December 2023

ABSTRACTPHOX2B is a transcription factor essential for the development of the autonomic nervous system. Heterozygous mutations in the PHOX2B coding region are responsible for the occurrence of Congenital Central Hypoventilation Syndrome (CCHS), a rare neurological disorder characterised by inadequate chemosensitivity and life-threatening sleep-related hypoventilation. Animal studies suggest that chemoreflex defects are caused in part by the improper development or function of PHOX2B expressing neurons in the retrotrapezoid nucleus (RTN), a central hub for CO2chemosensitivity.Although the function of PHOX2B in rodents during development is well established, its role in the adult respiratory network remains unknown. In this study, we investigated whether reduction in PHOX2B expression in chemosensitive neuromedin-B (NMB) expressing neurons in the RTN altered respiratory function. Four weeks following local RTN injection of a lentiviral vector expressing the short hairpin RNA (shRNA) targetingPhox2bmRNA, a reduction of PHOX2B expression was observed inNmbneurons compared to both naïve rats and rats injected with the non-target shRNA. PHOX2B knockdown did not affect breathing in room air or under hypoxia, but ventilation was significantly impaired during hypercapnia. PHOX2B knockdown did not alterNmbexpression but reduced the expression of bothTask2andGpr4, two CO2sensors in the RTN. We conclude that PHOX2B in the adult brain has an important role in CO2chemoreception and reduced PHOX2B expression in CCHS beyond the developmental period may contribute to the impaired central chemoreflex function.
How to barcode (almost all) freshwater biodiversity
Authors: Tournayre Orianne , Tian Haolun , Lougheed David R. , Windle Matthew J.S. , Lambert Sheldon , Carter Jennipher , Sun Zhengxin , Ridal Jeff , Wang Yuxiang , Cumming Brian F. , Arnott Shelley E. , Lougheed Stephen C. 
Published: December 2023

ABSTRACTFreshwater ecosystems are complex, diverse and face a variety of imminent threats that have led to changes in both ecosystem structure and function. It is urgent that we develop and standardize monitoring tools allowing for rapid and comprehensive assessment of freshwater communities to understand their changing dynamics and to inform conservation. Environmental DNA surveys offer a means to inventory and monitor aquatic diversity, yet most studies focus on one or a few taxonomic groups only. In this study, we sought to 1) identify thoroughly validated, cost-efficient primer pair combinations that maximize detection of broad swaths of freshwater diversity, and 2) facilitate future primer pair selection by creating a free online and user-friendly tool. We first evaluated the completeness of public reference sequence databases and the efficiency of 14 primer pairs using anin silicoapproach, and then performed eDNA surveys using five mock communities (mix of DNA from tissues), water samples from aquarium samples with known taxonomic composition, and finally water samples from freshwater systems in Eastern Canada. We highlight the power of eDNA-based metabarcoding for reconstructing freshwater communities, including prey, parasite, pathogen, invasive, and declining species. Our work reveals the importance of the marker choice on species resolution, as well as the importance of degenerate primers, the length of the target fragment and the filtering parameters on detection success in water eDNA samples. Our new online tool SNIPe revealed that 13 to 14 primer pairs are necessary to recover 100% of the species in water samples (aquarium and natural systems), but four primer pairs are sufficient to recover almost 75% of taxa with little overlap. These results highlight the usefulness of eDNA for freshwater monitoring and should prompt more studies on tools to survey all-inclusive communities.
Pharmacometabolomics in TB Meningitis – understanding the pharmacokinetic, metabolic, and immune factors associated with anti-TB drug concentrations in cerebrospinal fluid
Authors: Collins Jeffrey M. , Kipiani Maia , Jin Yutong , Sharma Ashish A. , Tomalka Jeffrey A. , Avaliani Teona , Gujabidze Mariam , Bakuradze Tinatin , Sabanadze Shorena , Avaliani Zaza , Blumberg Henry M. , Benkeser David , Jones Dean P. , Peloquin Charles , Kempker Russell R. 
Published: December 2023

AbstractPoor penetration of many anti-tuberculosis (TB) antibiotics into the central nervous system (CNS) is thought to be a major driver of morbidity and mortality in TB meningitis (TBM). While the amount of a particular drug that crosses into the cerebrospinal fluid (CSF) varies from person to person, little is known about the host factors associated with interindividual differences in CSF concentrations of anti-TB drugs. In patients diagnosed with TBM from the country of Georgia (n=17), we investigate the association between CSF concentrations of anti-TB antibiotics and multiple host factors including serum drug concentrations and CSF concentrations of metabolites and cytokines. We found >2-fold differences in CSF concentrations of anti-TB antibiotics from person to person for all drugs tested including cycloserine, ethambutol, imipenem, isoniazid, levofloxacin, linezolid, moxifloxacin pyrazinamide, and rifampin. While serum drug concentrations explained over 40% of the variation in CSF drug concentrations for cycloserine, isoniazid, linezolid, and pyrazinamide (adjusted R2>0.4, p<0.001 for all), there was no evidence of an association between serum concentrations of imipenem and ethambutol and their respective CSF concentrations. CSF concentrations of carnitines were significantly associated with concentrations of ethambutol and imipenem (q<0.05), and imipenem was the only antibiotic significantly associated with CSF cytokine concentrations. These results indicate that there is high interindividual variability in CSF drug concentrations in patients treated for TBM, which is only partially explained by differences in serum drug concentrations and not associated with concentrations of cytokines and chemokines in the CSF.
Association of urinary peptides with hypertension
Authors: Mavrogeorgis Emmanouil , Kondyli Margarita , Mischak Harald , Vlahou Antonia , Siwy Justyna , Rossing Peter , Campbell Archie , Mels Carina MC , Delles Christian , Staessen Jan A , Latosinska Agnieszka , Persu Alexandre 
Published: December 2023

AbstractBACKGROUNDHypertension is a common condition worldwide, yet its underlying mechanisms remain largely unknown. This study aims at identifying urinary peptides associated with hypertension to further explore its molecular pathophysiology.METHODSPeptidome data from 2876 individuals without end-organ damage were retrieved from the Human Urinary Proteome Database general population (discovery) or type 2 diabetic (validation) cohorts. Participants were divided based on systolic and diastolic blood pressure (SBP and DBP) into hypertensive (SBP≥140mmHg and/or DBP≥90mmHg) and normotensive (SBP<120mmHg and DBP<80mmHg, without antihypertensive treatment) groups. Differences in peptide abundance between the two groups were confirmed using an external cohort (n=420) of participants without end-organ damage, matched for age, body-mass index, eGFR, sex and presence of diabetes. Further, associations of the peptides with BP as a continuous variable were investigated. Findings were compared with peptide biomarkers of chronic diseases and bioinformatics analyses were conducted to potentially highlight the underlying molecular mechanisms.RESULTSBetween hypertensive and normotensive individuals, ninety-six (mostly COL1A1 and COL3A1) peptides were found significantly different in the discovery (adjusted) as well as the validation (nominal significance) cohorts with consistent regulation. Of these peptides, 83 were also consistently regulated in the matched cohort. A weak, yet significant association between their abundance and standardized BP was also observed.CONCLUSIONSHypertension is associated with an altered urinary peptide profile, with evident collagen differential regulation. Peptides related to vascular calcification and sodium regulation are also affected. Whether these modifications reflect the pathophysiology of hypertensionper seand/or early subclinical target organ damage warrants further investigation.Novelty and RelevanceWhat is New?This is the first study demonstrating differential regulation of urinary peptides in hypertensive patients, independent from other co-factors like age, diabetes, or established kidney or cardiovascular disease.What is Relevant?The observed changes in urinary peptides indicate individual differences in molecular changes observed in hypertension, and may guide personalized treatment based on the observed molecular changesClinical/Pathophysiological Implications?The results indicate that collagen homeostasis may be a key molecular feature in hypertension and may serve as an attractive mechanism for pharmacological intervention.
The functional type VI secretion system ofSinorhizobium frediiUSDA257 is required for a successful nodulation withGlycine maxcv Pekin
Authors: Reyes-Pérez Pedro José , Sánchez-Reina Ana , Civantos Cristina , Castro Natalia Moreno-de , Ollero Francisco Javier , Gandullo Jacinto , Jiménez-Guerrero Irene , Bernal Patricia , Pérez-Montaño Francisco 
Published: December 2023

AbstractFor agriculture, the symbiosis carried out by rhizobia with legumes stands out as crucial for both economic and environmental reasons. In this process, the bacteria colonize the roots of the plants, inducing the formation of plant organs called nodules. Within these structures, rhizobia fix the environmental nitrogen into ammonia reducing the demand for this essential element required for plant growth. Various bacterial secretion systems (TXSS, Type X Secretion System) are involved in the establishment of this symbiosis, with the T3SS being the most extensively studied. The T6SS is a nanoweapon present in 25% of gram-negative bacteria, commonly used against other gram-negative bacteria, though some of them use it to manipulate eukaryotic cells.Interestingly, although T6SS is widely distributed among rhizobia, whether it has a specific role in symbiosis with legumes remains elusive.Sinorhizobium frediiUSDA257 is a fast-growing rhizobium with the capacity to nodulate a great variety of legume plants. This strain harbors a single T6SS cluster, containing the genes encoding all the structural components of the system and two genes encoding potential effectors that could target the cell wall of the plants and/or be acting as a toxin/antitoxin system. We have demonstrated that this system is active and can be induced in poor culture media. In addition, we have seen by fluorescence microscopy that the T6SS is active in nodules. Competition assays between USDA257 and different preys have shown that USDA257 cannot kill any of them using its T6SS under tested conditions. By constract, nodulation assays demonstrated that USDA257 utilizes this protein secretion system to enhance nodulation and competitiveness with its hostGlycine maxcv Pekin.