bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population genomics and molecular epidemiology of wheat powdery mildew in Europe
Authors: Jigisha Jigisha , Ly Jeanine , Minadakis Nikolaos , Freund Fabian , Kunz Lukas , Piechota Urszula , Akin Beyhan , Balmas Virgilio , Ben-David Roi , Bencze Szilvia , Bourras Salim , Bozzoli Matteo , Cotuna Otilia , Couleaud Gilles , Cséplő Mónika , Czembor Paweł , Desiderio Francesca , Dörnte Jost , Dreiseitl Antonín , Feechan Angela , Gadaleta Agata , Gauthier Kevin , Giancaspro Angelica , Giove Stefania Lucia , Handley-Cornillet Alain , Hubbard Amelia , Karaoglanidis George , Kildea Steven , Koc Emrah , Liatukas Žilvinas , Lopes Marta S. , Mascher Fabio , McCabe Cathal , Miedaner Thomas , Martìnez-Moreno Fernando , Nellist Charlotte F. , Okoń Sylwia , Praz Coraline , Sánchez-Martín Javier , Sărăţeanu Veronica , Schulz Philipp , Schwartz Nathalie , Seghetta Daniele , Solís Martel Ignacio , Švarta Agrita , Testempasis Stefanos , Villegas Dolors , Widrig Victoria , Menardo Fabrizio 
Published: October 2024

AbstractAgricultural diseases are a major threat to sustainable food production. Yet, for many pathogens we know exceptionally little about their epidemiological and population dynamics, and this knowledge gap is slowing the development of efficient control strategies. Here we study the population genomics and molecular epidemiology of wheat powdery mildew, a disease caused by the biotrophic fungusBlumeria graminis forma specialis tritici(Bgt). We sampled Bgt for two consecutive years, 2022 and 2023, from 22 countries in Europe and surrounding regions, and compiled a genomic dataset of 415 Bgt isolates. We found one single epidemic unit in the north of Europe, consisting of a highly homogeneous population. Conversely, the south of Europe hosts smaller local populations which are less interconnected. In addition, we show that the population structure can be largely predicted by the prevalent wind patterns. We identified several loci that were under selection in the recent past, including fungicide targets and avirulence genes. Some of these loci are common between populations, while others are not, suggesting different local selective pressures. We reconstructed the evolutionary history of one of these loci,AvrPm17, coding for an effector recognized by the wheat receptor Pm17. We found evidence for a soft sweep on standing genetic variation. MultipleAvrPm17haplotypes, which can partially escape recognition by Pm17, spread rapidly throughout the continent upon its introduction in the early 2000s. We also identified a new virulent variant, which emerged more recently and can evadePm17resistance altogether. Overall, we highlight the potential of genomic surveillance in resolving the evolutionary and epidemiological dynamics of agricultural pathogens, as well as in guiding control strategies.
DrosophilaTrus, the orthologue of mammalian PDCD2L, is required for proper cell proliferation, larval developmental timing, and oogenesis
Authors: Takada Saeko , Bolkan Bonnie J. , O’Connor MaryJane , Goldberg Michael , O’Connor Michael B. 
Published: October 2024

AbstractToys are us (Trus) is theDrosophila melanogasterortholog of mammalian Programmed Cell Death 2-Like (PDCD2L), a protein that has been implicated in ribosome biogenesis, cell cycle regulation, and oncogenesis. In this study, we examined the function of Trus duringDrosophiladevelopment. CRISPR/Cas9 generated null mutations intruslead to partial embryonic lethality, significant larval developmental delay, and complete pre-pupal lethality. In mutant larvae, we found decreased cell proliferation and growth defects in the brain and imaginal discs. Mapping relevant tissues for Trus function usingtrus RNAiandtrusmutant rescue experiments revealed that imaginal disc defects are primarily responsible for the developmental delay, while the pre-pupal lethality is likely associated with faulty central nervous system (CNS) development. Examination of the molecular mechanism behind the developmental delay phenotype revealed thattrusmutations induce the Xrp1-Dilp8 ribosomal stress-response in growth-impaired imaginal discs, and this signaling pathway attenuates production of the hormone ecdysone in the prothoracic gland. Additional Tap-tagging and mass spectrometry of components in Trus complexes isolated fromDrosophilaKc cells identified Ribosomal protein subunit 2 (RpS2), which is coded bystring of pearls (sop)inDrosophila,and Eukaryotic translation elongation factor 1 alpha 1 (eEF1α1) as interacting factors. We discuss the implication of these findings with respect to the similarity and differences intrusgenetic null mutant phenotypes compared to the haplo-insufficiency phenotypes produced by heterozygosity for mutants in Minute genes and other genes involved in ribosome biogenesis.Authors SummaryRibosomes are essential macromolecular machines required for decoding mRNA to make proteins, the major biomolecules that carry out all central cellular functions. As such, their structural and operational integrity is critical to organismal survival, and mutations that disrupt proper stoichiometry or assembly of ribosomes produce serious pathological consequences during an organism’s development and/or adult life. The ribosome assembly factor PDCD2L is highly conserved from yeast to man, yet its overall function and requirement during development is poorly understood. By examining the developmental consequences of null mutations intrus, which encodes theDrosophilaPDCD2L homolog, we demonstrate an essential role for this factor in cell-cycle regulation. Furthermore, disruption of Trus function in mitotically dividing imaginal tissue activates the Xrp1-dilp8 stress response pathway which limits production of ecdysone, the major arthropod molting hormone, leading to severe developmental delay during larval stages. These studies provide new insights on the requirements of this highly conserved ribosome assemble factor during development.
Inhibiting the cholesterol storage enzyme ACAT1/SOAT1 in aging Apolipoprotein E4 mice alter their brains inflammatory profiles
Authors: Huynh Thao N. , Fikse Emma N. , Havrda Matthew C. , Chang Catherine C.Y. , Chang Ta Yuan 
Published: October 2024

AbstractAging and Apolipoprotein E4 (APOE4) are the two most significant risk factors for late-onset Alzheimer’s disease (LOAD). Compared to APOE3, APOE4 disrupts cholesterol homeostasis, increases cholesteryl esters (CEs), and exacerbates neuroinflammation in brain cells including microglia. Targeting CEs and neuroinflammation could be a novel strategy to ameliorate APOE4 dependent phenotypes. Toll-like receptor 4 (TLR4) is a key player in inflammation, its regulation is associated with cholesterol content of lipid rafts in cell membranes. We previously demonstrated that in normal microglia expressing APOE3, inhibiting the cholesterol storage enzyme acylCoA:cholesterol acyltransferase 1 (ACAT1/SOAT1) reduces CEs, dampened neuroinflammation via modulating the fate of TLR4. We also showed that treating myelin debris-loaded normal microglia with ACAT inhibitor F12511 reduced cellular CEs and activated ABC transporter 1 (ABCA1) for cholesterol efflux. In this study, we found that treating primary microglia expressing APOE4 with F12511 also reduces CEs, activated ABCA1, and dampened LPS dependent NFkB activation. In vivo, a two-week injections of nanoparticle F12511, which consists of DSPE-PEG2000, phosphatidylcholine, and F12511, to aged female APOE4 mice reduced TLR4 protein content and decreased proinflammatory cytokines including IL-1β in APOE4 mice brains. Overall, our work suggests nanoparticle F12511 is a novel agent to ameliorate LOAD.
Functional organization and natural scene responses across mouse visual cortical areas revealed with encoding manifolds
Authors: Dyballa Luciano , Field Greg D. , Stryker Michael P. , Zucker Steven W. 
Published: October 2024

AbstractA challenge in sensory neuroscience is understanding how populations of neurons operate in concert to represent diverse stimuli. To meet this challenge, we have created “encoding manifolds” that reveal the overall responses of brain areas to diverse stimuli with the resolution of individual neurons and their response dynamics. Here we use encoding manifold to compare the population-level encoding of primary visual cortex (VISp) with five higher visual areas (VISam, VISal, VISpm, VISlm, and VISrl). We used data from the Allen Institute Visual Coding–Neuropixels dataset from the mouse. We show that the encoding manifold topology computed only from responses to grating stimuli is continuous, for V1 and for higher visual areas, with smooth coordinates spanning it that include orientation selectivity and firing-rate magnitude. Surprisingly, the manifolds for each visual area revealed novel relationships between how natural scenes are encoded relative to static gratings—a relationship that was conserved across visual areas. Namely, neurons preferring natural scenes preferred either low or high spatial frequency gratings, but not intermediate ones. Analyzing responses by cortical layer reveals a preference for gratings concentrated in layer 6, whereas preferences for natural scenes tended to be higher in layers 2/3 and 4. The results reveal how machine learning approaches can be used to organize and visualize the structure of sensory coding, thereby revealing novel relationships within and across brain areas and sensory stimuli.Significance StatementManifolds have become a commonplace for analyzing and visualizing neural responses. However, prior work has focused on building manifolds that organize diverse stimuli in neural response coordinates. Here, we demonstrate the utility of an alternative approach: building manifolds to represent neurons in stimulus/response coordinates, which we term ‘encoding manifolds’. This approach has several advantages, such as being able to directly visualize and compare how different brain areas encode diverse stimulus ensembles. We use the approach to reveal novel relationships between layer-specific responses and the encoding of natural versus artificial stimuli.
Uterine stromal but not epithelial PTGS2 is critical for murine pregnancy success
Authors: Massri Noura , Arora Ripla 
Published: October 2024

ABSTRACTUse of non-steroidal anti-inflammatory drugs that target prostaglandin synthase (PTGS) enzymes have been implicated in miscarriage. Further, PTGS2-derived prostaglandins are reduced in the endometrium of patients with a history of implantation failure. However, in the mouse model of pregnancy, peri-implantation PTGS2 function is controversial. Some studies suggest thatPtgs2-/-mice display deficits in ovulation, fertilization, and implantation, while other studies suggest a role for PTGS2 only in ovulation but not implantation. Further, the uterine cell type responsible for PTGS2 function and role of PTGS2 in regulating implantation chamber formation is not known. To address this we generated tissue-specific deletion models ofPtgs2. We observed that PTGS2 ablation from the epithelium alone inLtfcre/+; Ptgs2f/fmice and in both the epithelium and endothelium of thePax2cre/+; Ptgs2f/fmice does not affect embryo implantation. Further, deletion of PTGS2 in the ovary, oviduct, and the uterus usingPgrcre/+; Ptgs2f/fdoes not disrupt pre-implantation events but instead interferes with post-implantation chamber formation, vascular remodeling and decidualization. While all embryos initiate chamber formation, more than half of the embryos fail to transition from blastocyst to epiblast stage, resulting in embryo death and resorbing decidual sites at mid-gestation. Thus, our results suggest no role for uterine epithelial PTGS2 in early pregnancy but instead highlight a role for uterine stromal PTGS2 in modulating post-implantation embryo and implantation chamber growth. Overall, our study provides clarity on the compartment-specific role of PTGS2 and provides a valuable model for further investigating the role of stromal PTGS2 in post-implantation embryo development.
Integrated systems biology identifies disruptions in mitochondrial function and metabolism as key contributors to heart failure with preserved ejection fraction (HFpEF)
Authors: Gibb Andrew A. , LaPenna Kyle , Gaspar Ryan B. , Latchman Nadina R. , Tan Yinfei , Choya-Foces Carmen , Doiron Jake E. , Li Zhen , Xia Huijing , Lazaropoulos Michael P. , Conwell Mariell , Sharp Thomas E. , Goodchild Traci T. , Lefer David J. , Elrod John W. 
Published: October 2024

ABSTRACTBackgroundHeart failure with preserved ejection fraction (HFpEF) accounts for ∼50% of HF cases, with no effective treatments. The ZSF1-obese rat model recapitulates numerous clinical features of HFpEF including hypertension, obesity, metabolic syndrome, exercise intolerance, and LV diastolic dysfunction. Here, we utilized a systems-biology approach to define the early metabolic and transcriptional signatures to gain mechanistic insight into the pathways contributing to HFpEF development.MethodsMale ZSF1-obese, ZSF1-lean hypertensive controls, and WKY (wild-type) controls were compared at 14w of age for extensive physiological phenotyping and LV tissue harvesting for unbiased metabolomics, RNA-sequencing, and assessment of mitochondrial morphology and function. Utilizing ZSF1-lean and WKY controls enabled a distinction between hypertension-driven molecular changes contributing to HFpEF pathology, versus hypertension + metabolic syndrome.ResultsZSF1-obese rats displayed numerous clinical features of HFpEF. Comparison of ZSF1-lean vs WKY (i.e., hypertension-exclusive effects) revealed metabolic remodeling suggestive of increased aerobic glycolysis, decreased β-oxidation, and dysregulated purine and pyrimidine metabolism with few transcriptional changes. ZSF1-obese rats displayed worsened metabolic remodeling and robust transcriptional remodeling highlighted by the upregulation of inflammatory genes and downregulation of the mitochondrial structure/function and cellular metabolic processes. Integrated network analysis of metabolomic and RNAseq datasets revealed downregulation of nearly all catabolic pathways contributing to energy production, manifesting in a marked decrease in the energetic state (i.e., reduced ATP/ADP, PCr/ATP). Cardiomyocyte ultrastructure analysis revealed decreased mitochondrial area, size, and cristae density, as well as increased lipid droplet content in HFpEF hearts. Mitochondrial function was also impaired as demonstrated by decreased substrate-mediated respiration and dysregulated calcium handling.ConclusionsCollectively, the integrated omics approach applied here provides a framework to uncover novel genes, metabolites, and pathways underlying HFpEF, with an emphasis on mitochondrial energy metabolism as a potential target for intervention.
Microglia respond to elevated intraocular pressure and synapse loss in the visual thalamus in a mouse model of glaucoma
Authors: Thompson Jennifer L. , McCool Shaylah , Smith Jennie C. , Schaal Victoria , Pendyala Gurudutt , Yelamanchili Sowmya , Van Hook Matthew J. 
Published: October 2024

AbstractMicroglia are resident immune cells of the central nervous system and mediate a broad array of adaptations and responses during disease, injury, and development. Typically, microglia morphology is understood to provide a window into their functional state. However, it is apparent that they have the capacity to adopt a broad spectrum of functional phenotypes characterized by numerous morphological profiles and associated gene expression profiles. Glaucoma, which leads to blindness from retinal ganglion cell (RGC) degeneration, is commonly associated with elevated intraocular pressure and has been shown to trigger microglia responses within the retinal layers, at the optic nerve head, and in retinal projection targets in the brain. The goal of this study was to determine the relationship of microglia morphology to intraocular pressure and the loss of retinal ganglion cell output synapses in the dorsolateral geniculate nucleus (dLGN), a RGC projection target in the thalamus that conveys information to the primary visual cortex. We accomplished this by analyzing dLGN microglia morphologies in histological sections from DBA/2J mice, which develop a form of inherited glaucoma. Microglia morphology was analyzed using skeletonized Iba1-fluorescence images and fractal analyses of individually reconstructed microglia cells. We found that microglia adopted more simplified morphologies, characterized by fewer endpoints and less total process length per microglia cell. There was an age-dependent shift in microglia morphology in tissue from control mice (DBA/2JGpnmb+) that was accelerated in DBA/2J mice. Microglia morphological measurements correlated with cumulative intraocular pressure, immunofluorescence labeling for the complement protein C1q, and density of vGlut2-labeled RGC axon terminals. Additionally, fractal analysis revealed a clear distinction between control and glaucoma dLGN, with microglia from ocular hypertensive DBA/2J dLGN tissue showing an elongated rod-like morphology. RNA-sequencing of dLGN tissue samples showed an upregulation of immune system-related gene expression and several specific genes associated with microglia activation and potential neuroprotective functions. These results suggest that microglia in the dLGN alter their physiology to respond to RGC degeneration in glaucoma, potentially contributing to CNS adaptations to neurodegenerative vision loss.
From raw footage to behaviour: an automated pipeline for activity monitoring and behaviour identification in the wild
Authors: Silva Liliana R. , Ferreira André C. , Doutrelant Claire , Covas Rita 
Published: October 2024

ABSTRACTStudies of animal behaviour usually rely on direct observations or manual annotations of video recordings for data collection. However, such methods can be very time-consuming and inefficient, leading to sub-optimal sample sizes. Recent advances in deep-learning have shown great potential to overcome such limitations. Nonetheless, for behavioural recognition, solutions currently available are mostly focused on laboratory and/or standardized settings.Here, we present a pipeline to guide researchers in building their own behavioural recognition system from their video data. Our pipeline is replicable and especially useful for studies in the wild. We take advantage of over 12215hs of manually annotated behaviours of sociable weavers (Philetarius socius). As behaviour classifiers we used long-short term neural networks (LSTMs) known to be suitable to classify temporal sequences of data such as video-based behavioural data.LSTMs allowed us to: 1) monitor nest activity by detecting the birds’ presence and simultaneously classifying the type of trajectory: i.e., nest-chamber entrance or exit; and 2) identify the respective behaviour performed: provisioning, building or aggression. With our pipeline we reduced the behavioural annotation error by 21%, while increasing by eight times the analyses speed.This work demonstrates how previously analysed long-term data can be used to develop highly-efficient automated behavioural analyses, whereas this pipeline is easily adaptable to other species and behaviours, requiring only labelled video data.
RNA toehold switch-based reporter assay to assess bacterial uptake of antisense oligomers
Authors: Sarkar Paramita , Popella Linda , Pérez-Jiménez Sandra , Vogel Jörg 
Published: October 2024

ABSTRACTAntisense oligomers (ASOs) hold promise as antibiotics for selective targeting of bacterial pathogens and as tools for the modulation of gene function in genetically intractable microbes. However, their efficient delivery across the complex bacterial envelope remains a major challenge. There are few methods to assess the efficiency of carrier-mediated ASO uptake by bacteria. Here, we have developed a “switch-on” reporter assay to measure ASO uptake efficiency in a semi-quantitative manner. The assay uses a synthetic RNA toehold switch fused to the mRNA of a fluorescent reporter protein, which is activatedin vivoby a peptide nucleic acid (PNA)-based ASO upon delivery into the bacterial cytosol. We have used this assay to screen different cell penetrating peptides (CPPs) as ASO carriers inEscherichia coliandSalmonella entericaand observed up to 60-fold activation, depending on the CPP and bacterial strain used. Our assay shows high dynamic range and sensitivity, which should enable high-throughput screens for bacterial ASO carriers. We also show that the reporter can be used to study routes of PNA uptake, as demonstrated by reduced reporter activity in the absence of the inner membrane protein SbmA. In summary, we present a portable tool for the discovery of species-specific and efficient ASO carriers that will also be useful for a broader investigation of cellular uptake mechanisms of antibacterial ASOs.ImportanceThe rise of antimicrobial resistance presents a major global health challenge. If not addressed, the death toll from resistant infections is expected to rise dramatically in the coming years. As a result, it is essential to explore alternative antimicrobial therapies. One promising approach is to target bacterial mRNAs using antisense oligomers (ASOs) to silence genes involved in essential functions, virulence, or resistance. However, delivering ASOs across bacterial membranes remains a major challenge and effective methods to monitor their uptake are limited. In this study, we develop a reporter assay to facilitate the high-throughput discovery of bacterial ASO carriers. This research paves the way for developing novel precision antisense-based antibacterial therapies.
Barley miRNAs and their targets regulation in response to heat stress at the early stage of development
Authors: Kruszka Katarzyna , Pacak Andrzej , Swida-Barteczka Aleksandra , Kesy Jacek , Jarmolowski Artur , Szweykowska-Kulinska Zofia 
Published: October 2024

AbstractMiRNAs are key regulators of gene expression controlling plant development and response to environmental stresses. In this work we studied global dynamics of accumulation of conserved and identified novel barley miRNAs at early stage of plant development during heat stress (1h, 3h and 6h of heat stress). The majority of miRNAs responds to heat stress after 3h and 6h of heat stress duration (124 and 155, respectively). The comparison of heat-induced changes in mature miRNA accumulation to their cognate precursor levels allowed to indicate a smaller group of miRNAs that are controlled at transcriptional level and a larger group that is controlled posttranscriptionally in response to heat stress. For miRNAs with the significant accumulation changes during heat treatment, target mRNAs were identified. Moreover, novel targets have been experimentally assigned for selected miRNAs. mRNA of the effector protein of miRNA activity, AGO1B was found to be downregulated by increased miR168 during heat stress. Importantly, miRNA/mRNA target module miR399c/PHO2 responsible for the phosphorus uptake exhibits dynamic changes under heat stress conditions suggesting adaptation of plant development to stress conditions. This study provides new data for developing miRNA and their mRNA target-based strategies in barley breeding in response to heat stress.Keypoints- Involvement of small RNAs in response to the heat stress conditions have been studied in young barley plants.- The largest number of heat responsive miRNAs was found after 3h and 6h of heat duration.- Heat-induced mature miRNA accumulation and their precursor levels showed complex transcriptional or posttranscriptional regulation.- MiRNA-target modules responsive to heat stress were identified