bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid evaluation of habitat connectivity change to safeguard multispecies persistence in human-transformed landscapes
Authors: Oehri Jacqueline , Wood Sylvia L.R. , Touratier Eluna , Leung Brian , Gonzalez Andrew 
Published: November 2023

AbstractProtecting habitat connectivity in fragmented landscapes is essential for safeguarding biodiversity and nature’s contributions to people. Following the Post-2020 Kunming-Montreal Global Biodiversity Framework (KM-GBF) of the Convention on Biological Diversity (CBD) there is a clear science-policy need to assess habitat connectivity and track its change over time to inform conservation planning.In response to this need we describe an analytical, multi-indicator and multispecies approach for the rapid assessment of habitat connectivity at fine spatial grain and at the extent of an entire ecoregion. Out of 69 connectivity indicators we found through a literature review, we identified a key-set of nine indicators that align with the Essential Biodiversity Variables framework and that are suitable to guide rapid action for connectivity and conservation targets in the KM-GBF. Using these selected indicators, we mapped and evaluated connectivity change from 2011 to 2021 across the ecoregion of the St-Lawrence Lowlands in Quebec (∼30,000 km2) for seven ecoprofile species representing regional forest habitat needs. For the majority of these ecoprofile species, trends over the last decade indicate a decline in effective connected area and metapopulation carrying capacity, mainly via a division of large contiguous habitat into smaller fragments, whereas total habitat area largely remained unchanged.These results highlight that trends in habitat area and connectivity are not necessarily correlated and the urgent need to conserve and restore connectivity in the St-Lawrence Lowlands, in order to meet regional targets under the KM-GBF. Our general approach enables a comprehensive evaluation of connectivity for regional spatial planning for biodiversity. We develop an R-tool to support this analysis and that can be extended to other conservation planning efforts for connectivity.
A comparative study between a power and a connectivity sEEG biomarker for seizure-onset zone identification in temporal lobe epilepsy
Authors: Vila-Vidal Manel , Corominas Ferran Craven-Bartle , Gilson Matthieu , Zucca Riccardo , Principe Alessandro , Rocamora Rodrigo , Deco Gustavo , Campo Adrià Tauste 
Published: November 2023

AbstractBackgroundIctal stereo-encephalography (sEEG) biomarkers for seizure onset zone (SOZ) localization can be classified depending on whether they target abnormalities in signal power or functional connectivity between signals, and they may depend on the frequency band and time window at which they are estimated.New methodThis work aimed to compare and optimize the performance of a power and a connectivity-based biomarkers to identify SOZ contacts from ictal sEEG recordings. To do so, we used a previously introduced power-based measure, the normalized mean activation (nMA), which quantifies the ictal average power activation. Similarly, we defined the normalized mean strength (nMS), to quantify the ictal mean functional connectivity of every contact with the rest. The optimal frequency bands and time windows were selected based on optimizing AUC and F2-score.ResultsThe analysis was performed on a dataset of 67 seizures from 10 patients with pharmacoresistant temporal lobe epilepsy. Our results suggest that the power-based biomarker generally performs better for the detection of SOZ than the connectivity-based one. However, an equivalent performance level can be achieved when both biomarkers are independently optimized. Optimal performance was achieved in the beta and lower-gamma range for the power biomarker and in the higher-gamma range for connectivity, both using a 30 s period after seizure onset.ConclusionsThe results of this study highlight the importance of this optimization step over frequency and time windows when comparing different SOZ discrimination biomarkers. This information should be considered when training SOZ classifiers on retrospective patients’ data for clinical applications.
A deep learning convolutional neural network distinguishes neuronal models of Parkinson’s disease from matched controls
Authors: Thomas Rhalena A. , Cai Eddie , Reintsch Wolfgang , Han Chanshaui , Shinde Sneha , Larivière Roxanne , Krahn Andrea , Chen Carol X.Q. , Nguyen-Renou Emmanuelle , Deneault Eric , You Zhipeng , Durcan Thomas M. , Fon Edward A. 
Published: November 2023

AbstractParkinson’s disease (PD) is a neurodegenerative disorder that results in the loss of dopaminergic neurons in the substantia nigra pars compacta. Despite advances in understanding PD, there is a critical need for novel therapeutics that can slow or halt its progression. Induced pluripotent stem cell (iPSC)-derived dopaminergic neurons have been used to model PD but measuring differences between PD and control cells in a robust, reproducible, and scalable manner remains a challenge. In this study, we developed a binary classifier convolutional neural network (CNN) to accurately classify microscopy images of PD models and matched control cells. We acquired images of iPSC-derived neural precursor cells (NPCs) and dopaminergic (DANs) and trained multiple CNN models comparing control cells to genetic and chemical models of PD. Our CNN accurately predicted whether control NPC cells were treated with the PD-inducing pesticide rotenone with 97.60% accuracy. We also compared control to a genetic model of PD (deletion of the Parkin gene) and found a predictive accuracy of 86.77% and 95.47% for NPC and DAN CNNs, respectively. Our cells were stained for nuclei, mitochondria, and plasma membrane, and we compared the contribution of each to the CNN’s accuracy. Using all three features together produced the best accuracy, but nuclear staining alone produced a highly predictive CNN. Our study demonstrates the power of deep learning and computer vision for analyzing complex PD-related phenotypes in DANs and suggests that these tools hold promise for identifying new targets for therapy and improving our understanding of PD.
EmbedGEM: A framework to evaluate the utility of embeddings for genetic discovery
Authors: Mukherjee Sumit , McCaw Zachary R , Pei Jingwen , Merkoulovitch Anna , Soare Tom , Tandon Raghav , Amar David , Somineni Hari , Klein Christoph , Satapati Santhosh , Lloyd David , Probert Christopher ,   Insitro Research Team, Koller Daphne , O’Dushlaine Colm , Karaletsos Theofanis 
Published: November 2023

AbstractMachine learning (ML)-derived embeddings are a compressed representation of high content data modalities. Embeddings can capture detailed information about disease states and have been qualitatively shown to be useful in genetic discovery. Despite their promise, embeddings have a major limitation: it is unclear if genetic variants associated with embeddings are relevant to the disease or trait of interest. In this work we describe EmbedGEM (EmbeddingGeneticEvaluationMethods), a framework to systematically evaluate the utility of embeddings in genetic discovery. EmbedGEM focuses on comparing embeddings along two axes: heritability and disease relevance. As measures of heritability, we consider the number of genome-wide significant associations and the meanχ2statistic at significant loci. For disease relevance, we compute polygenic risk scores for each embedding principal component, then evaluate their association with high-confidence disease or trait labels in a held-out evaluation patient set. While our development of EmbedGEM is motivated by embeddings, the approach is generally applicable to multivariate traits, and can readily be extended to accommodate additional metrics along the evaluation axes. We demonstrate EmbedGEM’s utility by evaluating embeddings and multivariate traits in two separate datasets: i) a synthetic dataset simulated to demonstrate the ability of the framework to correctly rank traits based on their heritability and disease relevance, and ii) a real data from the UK Biobank including metabolic and liver-related traits. Importantly, we show that greater disease relevance does not automatically follow from greater heritability.
A fast and inexpensive plate-based NGS library preparation method for insect genomics
Authors: Cobb Lauren , de Muinck Erik , Kollias Spyros , Skage Morten , Gilfillan Gregor D. , Sydenham Markus A. K. , Qiao Shuo-Wang , Star Bastiaan 
Published: November 2023

AbstractEntomological sampling and storage conditions often prioritise efficiency, practicality and conservation of morphological characteristics, and may therefore be suboptimal for DNA preservation. This practice can impact downstream molecular applications, such as the generation of high-throughput genomic libraries, which often requires substantial DNA input amounts. Here, we investigate a fast and economical Tn5 transposase tagmentation-based library preparation method optimised for 96-well plates and low yield DNA extracts from insect legs stored under different conditions. Using a standardised input of 6ng DNA, library preparation costs were significantly reduced through the 6-fold dilution of a commercially available tagmentation enzyme. Costs were further suppressed by direct post-amplification pooling, skipping quality assessment of individual libraries. We find that reduced DNA yields associated with ethanol-based storage do not impede overall sequencing success. Furthermore, we find that the efficiency of tagmentation-based library preparation can be improved by thorough post-amplification bead clean-up which selects against both short and large DNA fragments. By lowering data generation costs, broadening the scope of whole genome studies to include low yield DNA extracts and increasing throughput, we expect this protocol to be of significant value for a range of applications in the field of insect genomics.
Embryonic lymphocytes contribute to a genetic form of autoimmune inflammation
Authors: Cascione Sara , Fontana Elena , Scarfò Rebecca , Rigoni Rosita , Capo Valentina , Draghici Elena , Dobbs Kerry , Notarangelo Luigi D. , Villa Anna , Ditadi Andrea 
Published: November 2023

AbstractOmenn Syndrome (OS) is a rare hematological disorder, caused by hypomorphic mutations in genes involved in B-/T-cell receptor (BCR/TCR) rearrangement that result in impaired lymphocyte development and immunodeficiency. Notwithstanding, few T-cell clones enriched in self-reactive specificities expand in peripheral tissues, where they trigger severe inflammation and autoimmune reactions. Interestingly, residual OS lymphocytes display characteristics proper of embryonic lymphocytes that emerge before, and independently from, hematopoietic stem cells (HSCs). This prompted us to hypothesize whether OS autoreactive T-cells are generated in the embryo independently from HSCs. Here we show that in theRag2R229Q/R229QOS mouse model, embryonic but not adult bone marrow-derived hematopoietic progenitors can generate T-cells. T-lymphopoiesis can be rescued in adult OS blood progenitors via their Lin28-mediated reprogramming to an embryonic-like state. Remarkably, when transplanted in immunodeficient mice, embryonic-like OS progenitors trigger tissue morphological alterations and inflammation in the large intestine of the recipients, recapitulating the typical OS inflammatory phenotype. Our study describes the previously unappreciated contribution of embryonic progenitors to the pool of autoreactive infilitrating T-cells, providing a novel platform for both the detailed study of human autoimmune disorders and the design of more targeted therapies.
Age-related structural and functional changes of the intracardiac nervous system
Authors: Sassu Eliza , Tumlinson Gavin , Stefanovska Dragana , Fernández Marbely C. , Iaconianni Pia , Madl Josef , Brennan Tomás , Koch Manuel , Cameron Breanne A. , Preissl Sebastian , Ravens Ursula , Schneider-Warme Franziska , Kohl Peter , Zgierski-Johnston Callum M. , Hortells Luis 
Published: November 2023

AbstractBackgroundAlthough aging is known to be associated with an increased incidence of both atrial and ventricular arrhythmias, there is limited knowledge about how Schwann cells (SC) and the intracardiac nervous system (iCNS) remodel with age. Here we investigate the differences in cardiac SC, parasympathetic nerve fibers, and muscarinic acetylcholine receptor M2 (M2R) expression in young and old mice. Additionally, we examine age-related changes in cardiac responses to sympathomimetic and parasympathomimetic drugs.Methods and ResultsLower SC density, lower SC proliferation and fewer parasympathetic nerve fibers were observed in cardiac and, as a control sciatic nerves from old (20–24 months) compared to young mice (2–3 months). In old mice, CSPG4 was increased in sciatic but not cardiac nerves. Expression of M2R was lower in ventricular myocardium and ventricular conduction system from old mice compared to young mice, while no significant difference was seen in M2R expression in sino-atrial or atrio-ventricular node pacemaker tissue. Heart rate was slower and PQ intervals were longer in Langendorff-perfused hearts from old mice. Ventricular tachycardia and fibrillation were more frequently observed in response to carbachol administration in hearts from old mice versus those from young mice.ConclusionsOn the background of reduced presence of SC and parasympathetic nerve fibers, and of lower M2R expression in ventricular cardiomyocytes and conduction system of aged hearts, the propensity of ventricular arrhythmogenesis upon parasympathomimetic drug application is increased. Whether this is caused by an increase in heterogeneity of iCNS structure and function remains to be elucidated.Graphical abstract
CRISPR antiphage defence mediated by the cyclic nucleotide-binding membrane protein Csx23
Authors: Grüschow Sabine , McQuarrie Stuart , Ackermann Katrin , McMahon Stephen , Bode Bela E. , Gloster Tracey M. , White Malcolm F. 
Published: November 2023

AbstractCRISPR provides adaptive immunity in prokaryotes. Type III CRISPR systems detect invading RNA and activate the catalytic Cas10 subunit, which generates a range of nucleotide second messengers to signal infection. These molecules bind and activate a diverse range of effector proteins that provide immunity by degrading viral components and/or by disturbing key aspects of cellular metabolism to slow down viral replication. Here, we focus on the uncharacterised effector Csx23, which is widespread inVibrio cholerae. Csx23 provides immunity against plasmids and phage when expressed inEscherichia colialong with its cognate type III CRISPR system. The Csx23 protein localises in the membrane using a N-terminal transmembrane α-helical domain and has a cytoplasmic C-terminal domain that binds cyclic tetra-adenylate (cA4), activating its defence function. Structural studies reveal a tetrameric structure with a novel fold that binds cA4specifically. Using pulse EPR, we demonstrate that cA4binding to the cytoplasmic domain of Csx23 results in a major perturbation of the transmembrane domain, consistent with the opening of a pore and/or disruption of membrane integrity. This work reveals a new class of cyclic nucleotide binding protein and provides key mechanistic detail on a membrane-associated CRISPR effector.
Germ granule higher-order organization coordinates their different functions
Authors: Ramat Anne , Haidar Ali , Garret Céline , Simonelig Martine 
Published: November 2023

AbstractMost RNP condensates are composed of heterogeneous immiscible phases. However, how this multiphase organization contributes to their biological functions remains largely unexplored.Drosophilagerm granules, a class of RNP condensates, are the site of mRNA storage and translational activation. Here, using super-resolution microscopy and single-molecule imaging approaches, we show that germ granules have a biphasic organization and that translation occurs in the outer phase and at the surface of the granules. The localization, directionality and compaction of mRNAs within the granule depend on their translation status, translated mRNAs being enriched in the outer phase with their 5’end oriented towards the surface. Altering germ granule biphasic organization represses translation. These findings demonstrate the importance of RNA granule architecture in organizing different functions, highlighting the functional compartmentalization of RNA granules and the key role of higher-order organization.
A cholesterol switch controls phospholipid scrambling by G protein-coupled receptors
Authors: Menon Indu , Sych Taras , Son Yeeun , Morizumi Takefumi , Lee Joon , Ernst Oliver P. , Khelashvili George , Sezgin Erdinc , Levitz Joshua , Menon Anant K. 
Published: November 2023

ABSTRACTClass A G protein-coupled receptors (GPCRs), a superfamily of cell membrane signaling receptors, moonlight as constitutively active phospholipid scramblases. The plasma membrane of metazoan cells is replete with GPCRs, yet has a strong resting trans-bilayer phospholipid asymmetry, with the signaling lipid phosphatidylserine confined to the cytoplasmic leaflet. To account for the persistence of this lipid asymmetry in the presence of GPCR scramblases, we hypothesized that GPCR-mediated lipid scrambling is regulated by cholesterol, a major constituent of the plasma membrane. We now present a technique whereby synthetic vesicles reconstituted with GPCRs can be supplemented with cholesterol to a level similar to that of the plasma membrane and show that the scramblase activity of two prototypical GPCRs, opsin and the β1-adrenergic receptor, is impaired upon cholesterol loading. Our data suggest that cholesterol acts as a switch, inhibiting scrambling above a receptor-specific threshold concentration to disable GPCR scramblases at the plasma membrane.
Seedling microbiota engineering using bacterial synthetic community inoculation on seeds
Authors: Arnault Gontran , Marais Coralie , Préveaux Anne , Briand Martial , Poisson Anne-Sophie , Sarniguet Alain , Barret Matthieu , Simonin Marie 
Published: November 2023

AbstractSynthetic Communities (SynComs) are being developed and tested to manipulate plant microbiota and improve plant health. To date, only few studies proposed the use of SynCom on seed despite its potential for plant microbiota engineering. We developed and presented a simple, reproducible and effective seedling microbiota engineering method using SynCom inoculation on seeds. The method was successful using a wide diversity of SynCom compositions and bacterial strains that are representative of the common bean seed microbiota. First, this method enables the modulation of seed microbiota composition and community size. Then, SynComs strongly outcompeted native seed and potting soil microbiota and contributed on average to 80% of the seedling microbiota. We showed that strain abundance on seed was a main driver of an effective seedling microbiota colonization. Also, selection was partly involved in seed and seedling colonization capacities since strains affiliated to Enterobacteriaceae and Erwiniaceae were good colonizers while Bacillaceae and Microbacteriaceae were poor colonizers. Additionally, the engineered seed microbiota modified the recruitment and assembly of seedling and rhizosphere microbiota through priority effects. This study shows that SynCom inoculation on seeds represents a promising approach to study plant microbiota assembly and its consequence on plant fitness.
Propofol anesthesia destabilizes neural dynamics across cortex
Authors: Eisen Adam J. , Kozachkov Leo , Bastos Andre M. , Donoghue Jacob A. , Mahnke Meredith K. , Brincat Scott L. , Chandra Sarthak , Brown Emery N. , Fiete Ila R. , Miller Earl K. 
Published: November 2023

AbstractEvery day, hundreds of thousands of people undergo general anesthesia. One hypothesis is that anesthesia disrupts dynamic stability, the ability of the brain to balance excitability with the need to be stable and thus controllable. We tested this hypothesis using a new method for quantifying population-level dynamic stability in complex systems,DelayedLinearAnalysis forStabilityEstimation (DeLASE). Propofol was used to transition animals between the awake state and anesthetized unconsciousness. DeLASE was applied to macaque cortex local field potentials (LFPs). We found that neural dynamics were more unstable in unconsciousness compared to the awake state. Cortical trajectories mirrored predictions from destabilized linear systems. We mimicked the effect of propofol in simulated neural networks by increasing inhibitory tone. Paradoxically, increased inhibition also destabilized the networks. Our results suggest that anesthesia disrupts dynamical stability that is required for consciousness.
Exploring the impact of variability in cell segmentation and tracking approaches
Authors: Wiggins Laura , O’Toole Peter J. , Brackenbury William J. , Wilson Julie 
Published: November 2023

AbstractSegmentation and tracking are essential preliminary steps in the analysis of almost all live cell imaging applications. Although the number of open-source software systems that facilitate automated segmentation and tracking continue to evolve, many researchers continue to opt for manual alternatives for samples that are not easily auto-segmented, tracing cell boundaries by hand and re-identifying cells on consecutive frames by eye. Such methods are subject to inter-user variability, introducing idiosyncrasies into the results of downstream analysis that are a result of subjectivity and individual expertise. Such methods are also susceptible to intra-user variability, meaning findings are challenging to reproduce. Here we demonstrate and quantify the degree of intra- and inter-user variability in manual cell segmentation and tracking by comparing the phenotypic metrics extracted from cells segmented and tracked by different members of our research team. Furthermore, we compare the segmentation results for a ptychographic cell image obtained using different automated software and demonstrate the high dependence of performance on their imaging modality optimisation. Our results show that choice of segmentation and tracking methods should be considered carefully in order to enhance the quality and reproducibility of results.
Exposure to bullying between medical and non-medical university students in Bahrain
Authors: Algahtani Haifa Mohammad , Aldandan Laila , Jahrami Haitham , Kamal Dalia , Silverman Henry 
Published: November 2023

PurposeBullying negatively affects victims’ mental health and has been shown to be associated with anxiety and depression. Moreover, many studies have reported the prevalence of mistreatment among medical students (MS), interns and junior physicians. However, there are limited studies on bullying in the Middle East, and no studies on higher education in Bahrain. The authors’ aim was to investigate and compare the prevalence of bullying between MS at a major public university and non-medical students (NMS) at a private university in Bahrain. The authors also sought to explore the associations between bullying, depression and anxiety.Design/methodology/approachThe authors conducted a survey-based cross-sectional study from October 1 to December 31, 2018, using convenient sampling method. A total of 300 students (150 MS and 150 NMS) participated in the study by answering a questionnaire that explored exposure to different types of bullying. In addition, standard anxiety and depression instruments were distributed to students.FindingsThe results showed that MS were more exposed to bullying than NMS, with a significant number (41%) reporting mistreatment from multiple sources, including teachers, consultants and peers. Furthermore, the authors found that bullying was significantly correlated with psychological health, anxiety and depression.Originality/valueThere are limited studies on bullying in the Middle East and no studies on the topic of higher education in Bahrain. Furthermore, the learning environment of tertiary education institutions can be improved by addressing the concerns associated with bullying identified in this study.