bluuebunny/crossref_metadata_2025_split huggingface dataset:
Corylus avellananon-specific lipid-transfer protein Cor a 8 is a moonlighting enzyme with a new lipase activity
Authors: Alex Fissore , Giulia Di Napoli , Maria Laura De Sciscio , Valentina Santoro , Edoardo Salladini , Mauro Marengo , Simonetta Oliaro-Bosso , Gaia Vanzetti , Andrea Caratti , Fabrizio Dal Piaz , Francesco Piazza , Maela Manzoli , Giuseppe Genova , Giuseppe Barbiroli Alberto , Stefania Iametti , Franca Fraternali , Salvatore Adinolfi 
Published: November 2024

AbstractThe high-fat content of hazelnuts, mainly triglycerides, makes them prone to lipid oxidation during storage, which has a big impact on their sensory and nutritional quality. The chemical pathways leading to hazelnut oxidative rancidity have been well characterized and it are faster on free fatty acids. Lipase(s) enzymes are required, in oilseed, to hydrolyze the ester bond to free the single molecule of fatty acids. This step, necessary for germination, is the first event to trigger rancidity. Identifying the lipase(s) enzyme and the biochemical pathways involved in rancidity would lead to an effective strategy to prevent fat deterioration. Different proteins have been characterized in hazelnut seed and great interest has been risen towards the non-specific lipid transfer protein family because they were identified as human allergens. Here we show that Cor a 8 – a member of nsLTP – is a novel non-regiospecific lipase that is able to bind to oil-water interfaces and hydrolyze the triacylglycerol (TAGs) ester bonds by a non-canonical active site (non-serine dependent). Molecular modelling and molecular dynamics suggest that Cor a 8 is a moonlighting enzyme not only able to catalyze the hydrolysis of TAGs but also to stabilize the resulting free fatty acids and transport it.Cor a 8 homologues are present in all land plants, but the specific catalytic amino acids are found only in angiosperms, suggesting an evolutionary adaptation for lipid metabolism unique to flowering plants. This study sets the foundation for understanding this new lipid metabolism in plants and its role in rancidity development.
Comparison of genomic assembly and annotation based on two clones of avian pathogenicEscherichia coli
Authors: Zhao Yufei , Olsen John Elmerdahl , Poulsen Louise , Christensen Henrik 
Published: November 2024

AbstractMethods for assembly and annotation of whole genomic sequences were compared for six strains of avian pathogenicEscherichia coli(APEC). Two vertically transferredE. coliclones, represented by three isolates all belonging to pulse field genome electrophoresis (PFGE) type 65- sequence type (ST)95 and three isolates belonging to PFGE type 47- ST131, were selected for Illumina short read sequencing. There was no significant difference between SPAdes and CLC Genomic Workbench for benchmark parameters to assemble the short reads. The six strains were also sequenced by long read sequencing (Nanopore) and these reads were hybrid assembled with the short reads. Unicycler provided a lower number of contigs and higher N50 compared to Flye. No significant differences between total length of genomes were obtained from the four assemblers. At least 2.1 and 0.9% of coding gene sequences (CDSs) annotated with RAST and PROKKA, respectively were wrongly annotated. The errors were most often associated to CDS of shorter length (< 150 nt) with functions such as transposases, mobile genetic elements or being hypothetical. The investigation points out the importance of controlling automatic annotations and suggest further work to improve annotations in strains not belonging to the K12 or B lineages.
Whole-genome sequencing ofHyphopichia burtoniifrom isolated yeast recovered from zebra dove droppings in Thailand
Authors: Indoang Saowakon , Chumtong Sanicha , Prachantasena Sakaoporn , Wiriyaprom Ratchakul , Surachart Komwit , Promwised Rattanaruji , Ngasaman Ruttayaporn 
Published: November 2024

AbstractThis study aimed to characterise zoonotic yeasts from zebra dove (Geopelia striata) droppings in small farms in Songkhla province, Thailand. Four contaminated isolates were found with morphology and biochemical test results like those of Cryptococcus spp., but they exhibited different results from the positive control in nested polymerase chain reaction (PCR); the first step was negative, but the nested PCR step was positive. All isolates were subjected to antifungal susceptibility testing. The resistance isolate (Tip11) was subjected to whole genome sequencing. Only the Tip11 isolate showed high resistance to itraconazole and ketoconazole, with minimum inhibitory concentrations of >32.0 and 32.0 μg/mL, respectively, corresponding to high levels of minimum fungicidal concentrations for both drugs (>32 μg/mL). Consequently, Tip11 was selected as a representative of the contaminated isolates and subjected to whole-genome sequencing analysis. The results identified the Tip11 isolate as Hyphopichia burtonii (99.30% identity), with a genome length of 12,360,159 bp, a GC content of 35.16%, and 2,146 protein groups closely related to the Saccharomycetaceae family. This is the first report of H. burtonii in zebra doves in Thailand. This yeast has been previously identified as a cause of human infection leading to peritonitis in Thailand, and its resistance to antifungal drugs may pose a public health risk. Therefore, the application of biosecurity measures on farms, such as regular removal of droppings and cage sanitisation, should be implemented according to good agricultural practices. Moreover, further characterisation and functional analysis of the proteins identified should be considered.
Ethanol alters mechanosensory habituation inC. elegansby way of the BK potassium channel through a novel mechanism
Authors: Kokan Nikolas , Lin Conny , Luna Alvaro , Viliunas Joani , Rankin Catharine H. 
Published: November 2024

AbstractIn this research, we investigated how alcohol modulates the simplest form of learning, habituation, inCaenorhabditis elegans. We used our high throughput Multi-Worm Tracker to conduct a large scale study of more than 21,000 wild-type worms to assess the effects of different doses of alcohol on habituation of the well-characterized tap withdrawal response. We found that the effect of alcohol on habituation of the reversal response to repeated mechanosensory stimuli (taps) differed depending on the component of the reversal response assessed. Furthermore, we discovered that alcohol shifted the dominant response to tap from a backward reversal to a brief forward movement. Because the large conductance potassium (BK) channel has been shown to be important for alcohol’s effects on behaviour in a variety of organisms, includingC. elegans, we investigated whether theC. elegansBK channel ortholog, SLO-1, mediated the effects of alcohol on habituation. We tested several different strains of worms with mutations inslo-1along with wild-type controls; null mutations inslo-1made animals resistant to alcohol induced changes in learning. However, a mutation in the putative ethanol binding site on SLO-1 did not disrupt ethanol’s impact on habituation. Finally, by degrading SLO-1 in different parts of the nervous system we found that SLO-1’s function in ethanol’s impact on habituation is likely distributed throughout the neural circuit that responds to tap. Based on these results, our main conclusions are 1) ethanol is not a general facilitator or inhibitor of habituation but rather a complex modulator, 2) SLO-1 is required for ethanol’s effect on habituation, 3) ethanol is interacting (directly or indirectly) with SLO-1 through a novel unidentified mechanism to influence response plasticity.
diaPASEF-Powered Chemoproteomics Enables Deep Kinome Interaction Profiling
Authors: Woods Kathryn , Rants’o Thankhoe A. , Chan Alexandria M. , Sapre Tanmay , Mastin Grace E. , Maguire Kathleen M. , Ong Shao-En , Golkowski Martin 
Published: November 2024

ABSTRACTProtein-protein interactions (PPIs) underlie most biological functions. Devastating human conditions like cancers, neurological disorders, and infections, hijack PPI networks to initiate disease, and to drive disease progression. Understanding precisely how diseases remodel PPI networks can, therefore, help clarify disease mechanisms and identify therapeutic targets. Protein kinases control most cellular processes through protein phosphorylation. The 518 human kinases, known as the kinome, are frequently dysregulated in disease and highly druggable with ATP-competitive inhibitors. Kinase activity, localization, and substrate recognition are regulated by dynamic PPI networks composed of scaffolding and adapter proteins, other signaling enzymes like small GTPases and E3 ligases, and phospho-substrates. Accordingly, mapping kinase PPI networks can help determine kinome activation states, and, in turn, cellular activation states; this information can be used for studying kinase-mediated cell signaling, and for prioritizing kinases for drug discovery. Previously, we have developed a high-throughput method for kinome PPI mapping based on mass spectrometry (MS)-based chemoproteomics that we named kinobead competition and correlation analysis (kiCCA). Here, we introduce 2ndgeneration (gen) kiCCA which utilizes data-independent acquisition (dia) with parallel accumulation serial fragmentation (PASEF) MS and a re-designed CCA algorithm with improved selection criteria and the ability to predict multiple kinase interaction partners of the same proteins. Using neuroblastoma cell line models of the noradrenergic-mesenchymal transition (NMT), we demonstrate that 2ndgen kiCCA(1)identified 6.1-times more kinase PPIs in native cell extracts compared to our 1stgen approach,(2)determined kinase-mediated signaling pathways that underly the neuroblastoma NMT, and(3)accurately predicted pharmacological targets for manipulating NMT states. Our 2ndgen kiCCA method is broadly useful for cell signaling research and kinase drug discovery.
A reference genome forTrichogramma kaykai: A tiny desert-dwelling parasitoid wasp with competing sex-ratio distorters
Authors: Culotta Jack , Lindsey Amelia RI 
Published: November 2024

ABSTRACTThe tiny parasitoid waspTrichogramma kaykaiinhabits the Mojave Desert of the southwest United States. Populations of this tiny insect variably host up to two different sex-distorting genetic elements: (1) the endosymbiotic bacteriumWolbachiawhich induces the parthenogenetic reproduction of females, and (2) a B-chromosome, “Paternal Sex Ratio” (PSR), which converts would-be female offspring to PSR-transmitting males. We report here the genome of aWolbachia-infectedTrichogramma kaykaiisofemale colony KSX58. Using Oxford Nanopore sequencing we produced a final genome assembly of 203 Mbp with 45x coverage, consisting of 213 contigs with an N50 of 1.9 Mbp. The assembly is quite complete, with 91.41% complete BUSCOs recovered: a very high score for Trichogrammatids that have been previously characterized for having high levels of core gene losses. We also report a complete mitochondrial genome forT. kaykai,and an assembly of the associatedWolbachia, strainwTkk. We identified copies of the parthenogenesis-inducing genespifAandpifBin a remnant prophage region of thewTkk genome. TheTrichogramma kaykaiassembly is the highest quality genome assembly for the genus to-date and will serve as a great resource for understanding the evolution of sex and selfish genetic elements.
Buprenorphine Induces Human Fetal Membrane Sterile Inflammation
Authors: Lynn Tatyana , Kelleher Megan E , Georges Hanah M , McCauley Elle M , Logan Ryan W , Yonkers Kimberly A , Abrahams Vikki M 
Published: November 2024

AbstractOpioid-use disorder (OUD) during pregnancy has increased in the United States to critical levels and is a leading cause of maternal morbidity and mortality. Untreated OUD is associated with pregnancy complications in particular, preterm birth. Medications for OUD, such as buprenorphine, are recommended with the added benefit that treatment during pregnancy increases treatment post-partum. However, the rate of preterm birth in individuals using illicit opioids or being treated with opioid agonist therapeutics is double that of the general population. Since inflammation in the placenta and the associated fetal membranes (FM) is a common underlying cause of preterm birth, we sought to determine if the opioid, buprenorphine, induces sterile inflammation in human FMs and to examine the mechanisms involved. Using an establishedin vitrohuman FM explant system, we report that buprenorphine significantly increased FM secretion of the inflammatory cytokine IL-6; the neutrophilic chemokine IL-8; and the inflammasome-mediated cytokine IL-1β, mirroring the inflammatory profile commonly seen at the maternal-fetal interface in preterm birth. Other factors that were elevated in FMs exposed to buprenorphine included the mediators of membrane weakening, prostaglandin E2 (PGE2), and matrix metalloproteinases, MMP1 and MMP9. Furthermore, this sterile inflammatory and weakening FM response induced by buprenorphine was mediated in part by innate immune Toll-like receptor 4 (TLR4), the NLRP3 inflammasome, the μ-opioid receptor, and downstream NFκB and ERK/JNK/MAPK signaling. This may provide the mechanistic link between opioid use in pregnancy and the elevated risk for preterm birth. Since there are adverse consequences of not treating OUD, our findings may help identify ways to mitigate the impact opioids have on pregnancy outcomes while allowing the continuation of maintenance therapy.
Maximizing immunopeptidomics-based bacterial epitope discovery by multiple search engines and rescoring
Authors: Willems Patrick , Thery Fabien , Van Moortel Laura , De Meyer Margaux , Staes An , Gul Adillah , Kovalchuke Lyudmila , Declercq Arthur , Devreese Robbe , Bouwmeester Robbin , Gabriels Ralf , Martens Lennart , Impens Francis 
Published: November 2024

ABSTRACTMass spectrometry-based discovery of bacterial immunopeptides presented by infected cells allows untargeted discovery of bacterial antigens that can serve as vaccine candidates. However, reliable identification of bacterial epitopes is challenged by their extreme low abundance. Here, we describe an optimized bioinformatical framework to enhance the confident identification of bacterial immunopeptides. Immunopeptidomics data of cell cultures infected withListeria monocytogeneswere searched by four different search engines, PEAKS, Comet, Sage and MSFragger, followed by data-driven rescoring with MS2Rescore. Compared to individual search engine results, this integrated workflow boosted immunopeptide identification by an average of 27% and led to the high-confidence detection of 18 additional bacterial peptides (+27%) matching 15 differentListeriaproteins (+36%). Despite the strong agreement between the search engines, a small number of spectra (< 1%) had ambiguous matches to multiple peptides and were excluded to ensure high-confident identifications. Finally, we demonstrate our workflow with sensitive timsTOF SCP data acquisition and find that rescoring, now with inclusion of ion mobility features, identifies 76% more peptides compared to Q Exactive HF acquisition. Together, our results demonstrate how integration of multiple search engine results along with data-driven rescoring maximizes immunopeptide identification, boosting the detection of high-confidence bacterial epitopes for vaccine development.
Depletion of all platelet integrins impacts hemostasis, thrombosis and tumor metastasis
Authors: Janus-Bell Emily , Liboni Cristina , Yakusheva Alexandra , Mittelheisser Vincent , Mouriaux Clarisse , Bourdon Catherine , Bochler Louis , Hyenne Vincent , Garcia-Leon Maria , Lefebvre Olivier , Goetz Jacky G. , Mangin Pierre H. 
Published: November 2024

ABSTRACTPlatelet integrins, in addition to other platelet receptors, are known to control hemostasis, thrombosis but also metastatic progression. Yet, their exclusive but combined deficiency has never been tested in these processes. Taking advantage of PF4Cre-β1−/−/β3−/−mouse strain, we show that platelets are exclusively depleted for all integrins. While they displayed impaired binding to fibrinogen and annexin-V, P-selectin exposure was normal. Platelet adhesion was abrogated on immobilized fibrinogen and fibrillar fibronectin under shear flow. PF4Cre-β1−/−/β3−/−mice presented an increased bleeding time and a profound defect in experimental models of arterial thrombosis. Platelet adhesion to tumor cells was also reduced, with a profound impact on tumor growth and metastatic burden in a model of triple negative breast cancer. Overall, these results confirm the central role of platelet integrins in hemostasis and thrombosis, and define their role in tumor growth and metastasis formation.40-word summary:Depletion of all platelet integrins in PF4Cre-β1−/−/β3−/−mice leads to increased bleeding time and inhibitsin vivoarterial thrombosis. Integrin-null platelets reduce tumor growth and metastatic burden in orthotopic and experimental metastasis models. Platelet integrins control hemostasis, thrombosis and metastasis.
Phage DisCo: targeted discovery of bacteriophages by co-culture
Authors: Rand Eleanor A. , Owen Siân V. , Quinones-Olvera Natalia , Jean Kesther D. C. , Hernandez-Perez Carmen , Baym Michael 
Published: November 2024

AbstractPhages interact with many components of bacterial physiology from the surface to the cytoplasm. Although there are methods to determine the receptors and intracellular systems a specified phage interacts with retroactively, finding a phage that interacts with a chosen piece of bacterial physiologya prioriis very challenging. Variation in phage plaque morphology does not to reliably distinguish distinct phages and therefore many potentially redundant phages may need to be isolated, purified, and individually characterized to find phages of interest. Here, we present a method in which multiple bacterial strains are co-cultured on the same screening plate to add an extra dimension to plaque morphology data. In this method, PhageDiscovery byCo-culture (Phage DisCo), strains are isogenic except for fluorescent tags and one perturbation expected to impact phage infection. Differential plaquing on the strains is easily detectable by fluorescent signal and implies that the perturbation made to the surviving strain in a plaque prevents phage infection. We validate the phage DisCo method by showing that characterized phages have the expected plaque morphology on Phage DisCo plates and demonstrate the power of Phage DisCo for multiple targeted discovery applications, from receptors to phage defense systems.
Phyllobacterium melilotisp. nov. a novel non-symbiotic bacterium isolated from root nodules ofMelilotus albus(white sweet clover) grown in Canada
Authors: Bromfield Eden S. P. , Cloutier Sylvie , Hynes Michael F. 
Published: November 2024

AbstractTwo novel bacterial strains isolated from root-nodules of white sweet clover (Melilotus albus) plants grown at a Canadian site were previously characterized and placed in the genusPhyllobacterium. Here we present phylogenomic and phenotypic data to support the description of strain T1293Tas representative of a novel species and present the first complete closed genome sequence of a bacterial strain (T1018) representing the species ‘P. pellucidum’.Phylogenetic analysis of genome sequences as well as analysis of 53 core genes placed novel strain T1293Tin a highly supported cluster of strains distinct from namedPhyllobacteriumspecies withP. myrsinacearumandP. calauticaeas closest relatives. The highest average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values of genome sequences of T1293Tcompared to closest species type strains (84.1% and 26.5%, respectively) are well below the threshold values for bacterial species circumscription. The genome of strain T1293Thas a size of 5074034 bp with a DNA G+C content of 55 mol% and possesses three plasmids with sizes of 397619 bp, 476847 bp and 519835 bp. Detected in the genome were Type III and Type VI secretion system genes, implicated in plant-microbe and microbe-microbe interactions, but key nodulation, nitrogen-fixation and photosystem genes were not detected. Further analysis revealed that T1293T, like otherPhyllobacteriumspecies, possesses key genes encoding an enzyme complex implicated in the degradation of glyphosate, a widely used broad-spectrum herbicide that has negative consequences for many microorganisms including the human gut microbiome. A novel prophage (size ∼ 41.5 kb) was also detected in the genome of T1293T. Data for multiple phenotypic tests complemented the sequence-based characterization of strain T1293T. The data presented support the description of a new species and the namePhyllobacterium melilotisp. nov. is proposed with T1293T= LMG32641T= HAMBI 3765Tas the species type strain.
Efficient pheromone navigation via antagonistic detectors
Authors: Wan Xuan , Zhou Tingtao , Susoy Vladislav , Park Core Francisco , Groaz Alessandro , Brady John F. , Samuel Aravinthan D.T. , Sternberg Paul W. 
Published: November 2024

AbstractChemotaxis to a potential mate who is moving and emitting a volatile sex pheromone poses a navigation challenge that requires rapid, precise responses to maximize reproductive success. We demonstrate thatCaenorhabditis elegansmales address this challenge by utilizing two pheromone detectors located in head and tail sensory neurons. Despite sharing a receptor SRD-1, AWA head neurons promote forward movement and acceleration, while tail PHD neurons induce reversals and deceleration. In increasing pheromone gradients AWA dominates; whereas weakening gradients inactivate AWAs, allowing PHDs to fine-tune the response and correct the path. Head AWAs are essential for mate-searching, while tail PHDs are crucial for complex tasks. The navigation mode and velocity adapt as males climb a pheromone gradient. A minimal-parameter computational model recapitulates key findings and illuminates the interplay between head and tail signals in adaptive navigation.Graphical abstract:Spatially separated pheromone detection drives adaptive navigation inC. elegansmales.Theupper panelillustrates howC. elegansmales utilize spatially separated pairs of sensory neurons, AWA (head) and PHD (tail), that detect the same volatile sex pheromone molecule via the receptor SRD-1. Despite sharing this receptor, head neurons detect gradient changes and activate when concentration increases, suppressing turning, and promoting forward movement and acceleration. In contrast, tail neurons detect absolute concentration and activate at preferred moderate concentrations, inducing reversals and deceleration. Themiddle panelshows that upon initial pheromone introduction, simultaneous activation of head and tail neurons cancels each other out, causing males to transition from random walking to a stationary anchoring state, preventing them from chasing the concentration wave initially. As pheromone concentration increases, head neurons dominate, driving forward locomotion and acceleration. At the highest concentrations, tail neurons become less active while head neurons are highly activated, leading to rapid, goal-directed movement (sprinting). Incorrect directional choices result in AWA deactivation and persistent PHD activity, inducing pausing and local exploration. Repeated unsuccessful attempts trigger area-restricted searching. Thebottom paneldepicts our computational model which recapitulates these behaviors by integrating inputs from head and tail neurons. A confidence metric, which is positively correlated with directional accuracy and speed and negatively correlated with turning, is introduced. Once confidence surpasses a threshold, the model transitions from more random (kinesis) to more directed (taxis) movement. The depicted trajectories represent simulated behavior based on this confidence-driven model.