bluuebunny/crossref_metadata_2025_split huggingface dataset:
Soil carbon in the world’s tidal marshes
Authors: Maxwell Tania L. , Spalding Mark D. , Friess Daniel A. , Murray Nicholas J. , Rogers Kerrylee , Rovai Andre S. , Smart Lindsey S. , Weilguny Lukas , Adame Maria Fernanda , Adams Janine B. , Copertino Margareth S. , Cott Grace M. , Costa Micheli Duarte de Paula , Holmquist James R. , Ladd Cai J.T. , Lovelock Catherine E. , Ludwig Marvin , Moritsch Monica M. , Navarro Alejandro , Raw Jacqueline L. , Ruiz-Fernández Ana-Carolina , Serrano Oscar , Smeaton Craig , Broek Marijn Van de , Windham-Myers Lisamarie , Landis Emily , Worthington Thomas A. 
Published: April 2024

AbstractTidal marshes are threatened coastal ecosystems known for their capacity to store large amounts of carbon in their water-logged soils. Accurate quantification and mapping of global tidal marshes soil organic carbon (SOC) stocks is of considerable value to conservation efforts. Here, we used training data from 3,710 unique locations, landscape-level environmental drivers and a newly developed global tidal marsh extent map to produce the first global, spatially-explicit map of SOC storage in tidal marshes at 30 m resolution. We estimate the total global SOC stock to 1 m to be 1.44 Pg C, with a third of this value stored in the United States of America. On average, SOC in tidal marshes’ 0-30 and 30-100 cm soil layers are estimated at 83.1 Mg C ha-1(average predicted error 44.8 Mg C ha-1) and 185.3 Mg C ha-1(average predicted error 105.7 Mg C ha-1), respectively. Our spatially-explicit model is able to capture 59% of the variability in SOC density, with elevation being the strongest driver aside from soil depth. Our study reveals regions with high prediction uncertainty and therefore highlights the need for more targeted sampling to fully capture SOC spatial variability.
Forestwalk: A machine learning workflow brings new insights into posture and balance in rodent beam walking
Authors: Tozzi Francesca , Zhang Yan-Ping , Narayanan Ramanathan , Roquiero Damian , O’Connor Eoin C. 
Published: April 2024

AbstractThe beam walk is widely used to study coordination and balance in rodents. While the task has ethological validity, the main endpoints of ‘foot slip counts’ and ‘time to cross’ are prone to human-rater variability and offer limited sensitivity and specificity. We asked if machine learning-based methods could reveal previously hidden, but biologically relevant, insights from the task. Marker-less pose estimation, using DeepLabCut, was deployed to label 13 anatomical points on mice traversing the beam. Next, we automated classical endpoint detection, including foot slips, with high recall (>90%) and precision (>80%). A total of 395 features were engineered and a random-forest classifier deployed that, together with skeletal visualizations, could test for group differences and identify determinant features. This workflow, named Forestwalk, uncovered pharmacological treatment effects in C57BL/6J mice, revealed phenotypes in transgenic mice used to study Angelman syndrome and SLC6A1-related neurodevelopmental disorder, and will facilitate a deeper understanding of how the brain controls balance in health and disease.
Population genomic analysis reveals cryptic population structure in the commercially important Lake Malawi cichlidCopadichromis mloto
Authors: Sawasawa Wilson , van Huysduynen Alexander Hooft , Gresham Sophie , Sungani Harold , Rusuwa Bosco , De Boeck Gudrun , Turner George F. , Ngochera Maxon , Svardal Hannes 
Published: April 2024

AbstractFish is an important source of animal protein for many people living around Lake Malawi. The evaluation of population structure and genetic diversity can yield useful information for management and conservation of fish species but is complicated in Lake Malawi by the close genetic relatedness of species of the recent cichlid adaptive radiation. In this study, we analysed whole-genome sequencing data of “true utaka”, a group of cichlids previously common in fisheries, but that has faced strong decline due to overfishing. Our analysis of 223 individuals collected from fishermen’s catches along the western shoreline of Lake Malawi confirmed thatCopadichromis mloto(C. sp. “virginalis kajose”) is the true utaka most targeted by fisheries. Genetic principal component analysis, phylogenetic inference, and admixture analysis revealed complex patterns of population structure. The presence of at least three geographically widespread genetic clades that have remained separate despite gene flow and partial sympatry hints at the presence of currently undescribed, cryptic species diversity inC. mloto. This result leads us to suggest that, despite the lack of obvious habitat barriers, benthic and pelagic species of Malawi cichlids might harbour unidentified species diversity and calls for further genetic and taxonomic research to define appropriate conservation units.
Insights into dynamic sound localisation: A direction-dependent comparison between human listeners and a Bayesian model
Authors: McLachlan Glen , Majdak Piotr , Reijniers Jonas , Mihocic Michael , Peremans Herbert 
Published: April 2024

AbstractSelf-motion is an essential but often overlooked component of sound localisation. While the directional information of a source is implicitly contained in head-centred acoustic cues, that acoustic input needs to be continuously combined with sensorimotor information about the head orientation in order to decode these cues to a world-centred frame of reference. On top of that, the use of head movement significantly reduces ambiguities in the directional information provided by the incoming sound. In this work, we evaluate a Bayesian model that predicts dynamic sound localisation, by comparing its predictions to human performance measured in a behavioural sound-localisation experiment. Model parameters were set a-priori, based on results from various psychoacoustic and sensorimotor studies, i.e., without any post-hoc parameter fitting to behavioral results. In a spatial analysis, we evaluated the model’s capability to predict spatial localisation responses. Further, we investigated specific effects of the stimulus duration, the spatial prior and sizes of various model uncertainties on the predictions. The spatial analysis revealed general agreement between the predictions and the actual behaviour. The altering of the model uncertainties and stimulus duration revealed a number of interesting effects providing new insights on modelling the human integration of acoustic and sensorimotor information in a localisation task.Author summaryIn everyday life, sound localisation requires both interaural and monaural acoustic information. In addition to this, sensorimotor information about the position of the head is required to create a stable and accurate representation of our acoustic environment. Bayesian inference is an effective mathematical framework to model how humans combine information from different sources and form beliefs about the world. Here, we compare the predictions from a Bayesian model for dynamic sound localisation with data from a localisation experiment. We show that we can derive the model parameter values from previous psychoacoustic and sensorimotor experiments and that the model without any post-hoc fitting, can predict general dynamic localisation performance. Finally, the discrepancies between the modelled data and behavioural data are analysed by testing the effects of adjusting the model parameters.
Myelin regulatory factor(Myrf) is a critical early regulator of retinal pigment epithelial development
Authors: Brinkmeier Michelle L. , Wang Su Qing , Pittman Hannah , Cheung Leonard Y. , Prasov Lev 
Published: April 2024

ABSTRACTMyelin regulatory factor (Myrf) is a critical transcription factor in early retinal and retinal pigment epithelial development, and human variants inMYRFare a cause for nanophthalmos. Single cell RNA sequencing (scRNAseq) was performed onMyrfconditional knockout mice (Rx>Cre Myrffl/fl) at 3 developmental timepoints.Myrfwas expressed specifically in the RPE, and expression was abrogated inRx>Cre Myrffl/fleyes. scRNAseq analysis revealed a loss of RPE cells at all timepoints resulting from cell death. GO-term analysis in the RPE revealed downregulation of melanogenesis and anatomic structure morphogenesis pathways, which were supported by electron microscopy and histologic analysis. Novel structural target genes includingErmnandUpk3b, along with macular degeneration and inherited retinal disease genes were identified as downregulated, and a strong upregulation of TGFß/BMP signaling and effectors was observed. Regulon analysis placedMyrfdownstream ofPax6andMitfand upstream ofSox10in RPE differentiation. Together, these results suggest a strong role for Myrf in the RPE maturation by regulating melanogenesis, cell survival, and cell structure, in part acting through suppression of TGFß signaling and activation ofSox10.SUMMARY STATEMENTMyrfregulates RPE development, melanogenesis, and is important for cell structure and survival, in part through regulation ofErmn,Upk3bandSox10,and BMP/TGFb signaling.
The allosteric landscape of the Src kinase
Authors: Beltran Antoni , Faure Andre J. , Lehner Ben 
Published: April 2024

AbstractEnzymes catalyze the reactions of life and are the targets of most small molecule drugs. Most drugs target conserved enzyme active sites, often causing problems of specificity and toxicity. Targeting allosteric sites can increase specificity, overcome resistance mutations, and allow fine-tuning of activity. However, most enzymes have no known allosteric sites and methods do not exist to comprehensively identify them. Here we present a general and fast approach to chart allosteric communication in enzymes and apply it to the Src kinase to produce the first comprehensive map of negative and positive allosteric control of an enzymatic activity. Allostery in the Src kinase domain is pervasive, anisotropic, partially predictable, and modulated by regulatory domains. Multiple surface pockets of Src are allosterically active and so genetically-prioritized for the development of inhibitory and activating drugs. Using this approach it should be possible to chart global allosteric maps of many kinases and other enzymes important for medicine and biotechnology.HighlightsFirst comprehensive map of negative and positive allosteric control of an enzymatic activity, the Src kinase.Allosteric communication is pervasive, distance dependent, and anisotropic.Allostery is conserved and modulated in the presence of the Src regulatory domains.Genetic prioritization of druggable surface pockets for Src inhibition and activation.Allosteric maps can now be constructed for many medically and industrially important kinases and enzymes.
Resolved vs. uncontrolled inflammation: a mathematical model to decipher the role of innate immunity
Authors: García-Martínez Karina , Ledón Nuris , Lage Agustín 
Published: April 2024

ABSTRACTNeutrophils and macrophages related processes have been described as relevant during the inflammation resolution after an acute damage. Nevertheless, understanding the impact of both cells and the processes in which they are involved is still an open debate. Specifically, several studies have been focused on elucidate their impact in the dynamic outcome of resolution vs uncontrolled response. In this work, we develop a mathematical model that describe the dynamic of the innate immune response after an acute damage. Our model includes all the described processes that mediate this response, including the regulatory mechanisms carried out by type-2 macrophages (M2). Additionally, we estimate the resolution indices to quantify the efficiency of resolution mechanisms by controlling the initial expansion of Neutrophils and/or the subsequent contraction kinetics of the cell response. We predict that the processes of cells influx into the inflamed site, Neutrophil apoptosis and type-1 macrophage (M1)-mediated efferocytosis, are the ones that have an impact on the final outcome, but interfering in different resolution indices. In particular, we predict that the partial reduction of Neutrophil influx and the increase of M1-mediated efferocytosis rate are the best strategies to control the Neutrophil initial expansion. On the other hand, the partial reduction of M1 cells influx or the increase of Neutrophil apoptosis rate are predicted as good strategies to accelerate the Neutrophils decay during the contraction phase of the response.
Transcription of HIV-1 at sites of intact latent provirus integration
Authors: Teixeira Ana Rafaela , Bittar Cintia , Silva Santos Gabriela S. , Oliveira Thiago Y. , Huang Amy S. , Linden Noemi , Ferreira Isabella A.T.M. , Murdza Tetyana , Muecksch Frauke , Jones R. Brad , Caskey Marina , Jankovic Mila , Nussenzweig Michel C. 
Published: April 2024

AbstractHIV-1 anti-retroviral therapy is highly effective but fails to eliminate a reservoir of latent proviruses leading to a requirement for life-long treatment. How the site of integration of authentic intact latent proviruses might impact their own or neighboring gene expression or reservoir dynamics is poorly understood. Here we report on proviral and neighboring gene transcription at sites of intact latent HIV-1 integration in cultured T cells obtained directly from people living with HIV, as well as engineered primary T cells and cell lines. Proviral gene expression was correlated to the level of endogenous gene expression under resting but not activated conditions. Notably, latent proviral promoters were 100-10,000X less active than in productively infected cells and had little or no measurable impact on neighboring gene expression under resting or activated conditions. Thus, the site of integration has a dominant effect on the transcriptional activity of intact HIV-1 proviruses in the latent reservoir thereby influencing cytopathic effects and proviral immune evasion.
Temperature-modulated maternal effects vary with offspring developmental stage inDrosophila melanogaster
Authors: Kohlmeier P , Van Schaik B , Pen I , Billeter JC , Groothuis TGG 
Published: April 2024

ABSTRACTAn organism’s phenotype has the potential to vary in response to environmental factors, allowing it to adjust to environmental fluctuations. Maternal effects on offspring phenotypes have been recognized as important contributors to this phenotypic plasticity, although the extent and duration of this contribution remain elusive. At more advanced developmental stages, offspring may be able to assess their current environment more accurately than at earlier developmental stages, and therefore their reliance on maternal effects may decline over time. This study investigates how the magnitude and direction of maternal effects change between early and late development using the fruit flyDrosophila melanogasteras a model. We employed a split brood design to disentangle the effects of maternal ambient temperature from the effects of offspring ambient temperature at the larval vs. the pupal or early adulthood stage. We subsequently measured offspring phenotypes such as heat shock and cold shock recovery times, survival, and developmental time. Maternal effects on these traits were often substantial during early offspring development, but these effects either diminished in magnitude or even changed direction as development progressed. In conclusion, our study reveals a dynamic shift in the magnitude and direction of maternal effects on offspring phenotypes inD. melanogaster, highlighting the interplay between maternal influence and offspring developmental stage in shaping adaptive responses to environmental variation.
First whole genome assembly ofVaccinium floribundumKunth, an emblematic Andean species
Authors: Albuja-Quintana Martina , Pozo Gabriela , Gordillo-Romero Milton , Armijos Carolina E. , Torres María de Lourdes 
Published: April 2024

AbstractBackgroundVaccinium floribundumKunth, known as "mortiño," is an endemic shrub species of the Andean region adapted to harsh conditions in high-altitude ecosystems. It plays an important ecological role as a pioneer species in the aftermath of deforestation and human-induced fires within paramo ecosystems, emphasizing its conservation value. While previous studies have offered insights into the genetic diversity of mortiño, comprehensive genomic studies are still missing to fully understand the unique adaptations of this species and its population status, highlighting the importance of generating a reference genome for this plant.ResultsONT and Illumina sequencing were used to establish a reference genome for this species. Three differentde novogenome assemblies were generated and compared for quality, continuity and completeness. The Flye assembly was selected as the best and refined by filtering out short ONT reads, screening for contaminants and genome scaffolding. The final assembly has a genome size of 529 MB, containing 1,317 contigs and 97% complete BUSCOs, indicating a high level of integrity of the genome. Additionally, the LAI Index of 12.93, further categorizes this assembly as a reference genome.ConclusionsThe genome ofV. floribundumreported in this study is the first reference genome generated for this species, providing a valuable tool for further studies. This high-quality genome, based on the quality and completeness parameters obtained, will not only help uncover the genetic mechanisms responsible for its unique traits and adaptations to high-altitude ecosystems, but will also contribute to conservation strategies for a species endemic to the Andes.
Riluzole reverses blood-testis barrier loss to rescue chemotherapy-induced male infertility by binding to TRPC
Authors: Huang Rufei , Xia Huan , Lin Wanqing , Wang Zhaoyang , Li Lu , Deng Jingxian , Ye Tao , Li Ziyi , Yang Yan , Huang Yadong 
Published: April 2024

AbstractCancer treatments, including cytotoxic therapy, often result in male infertility, necessitating the development of safe and effective strategies to preserve male reproductive potential during chemotherapy. Notably, our study uncovers the potential of repurposing riluzole, an FDA-approved drug for amyotrophic lateral sclerosis (ALS), in enhancing spermatogenesis. Hence, this research aims to explore the feasibility of utilizing riluzole to alleviate male infertility induced by busulfan (BSF), a commonly used chemotherapy drug. We established a BSF-induced oligospermia model in 4-week-old male mice and found that riluzole could effectively countered the detrimental effects of BSF on sperm production in mice with oligospermia. By restoring blood-testis barrier (BTB) functionality, riluzole improves sperm quality and reduces testicular atrophy. Through transcriptomic and molecular docking analyses, we identify transient receptor potential canonical subfamily member 5 (TRPC5) as a potential target for riluzole-mediated regulation of blood-testis barrier function. These findings propose riluzole as a promising therapeutic option for chemotherapy-induced male infertility, thereby addressing the fertility challenges associated with cancer treatments. Moreover, repurposing riluzole could streamline the drug development process, providing a cost-effective approach with reduced risk compared to developing entirely new drugs.
A morphology and secretome map of pyroptosis
Authors: Lippincott Michael J. , Tomkinson Jenna , Bunten Dave , Mohammadi Milad , Kastl Johanna , Knop Johannes , Schwandner Ralf , Huang Jiamin , Ongo Grant , Robichaud Nathaniel , Dagher Milad , Tsuboi Masafumi , Basualto-Alarcón Carla , Way Gregory P. 
Published: April 2024

AbstractPyroptosis represents one type of Programmed Cell Death (PCD). It is a form of inflammatory cell death that is canonically defined by caspase-1 cleavage and Gasdermin-mediated membrane pore formation. Caspase-1 initiates the inflammatory response (through IL-1β processing), and the N-terminal cleaved fragment of Gasdermin D polymerizes at the cell periphery forming pores to secrete pro-inflammatory markers. Cell morphology also changes in pyroptosis, with nuclear condensation and membrane rupture. However, recent research challenges canon, revealing a more complex secretome and morphological response in pyroptosis, including overlapping molecular characterization with other forms of cell death, such as apoptosis. Here, we take a multimodal, systems biology approach to characterize pyroptosis. We treated human Peripheral Blood Mononuclear Cells (PBMCs) with 36 different combinations of stimuli to induce pyroptosis or apoptosis. We applied both secretome profiling (nELISA) and high-content fluorescence microscopy (Cell Painting). To differentiate apoptotic, pyroptotic and healthy cells, we used canonical secretome markers and modified our Cell Painting assay to mark the N-terminus of Gasdermin-D. We trained hundreds of machine learning (ML) models to reveal intricate morphology signatures of pyroptosis that implicate changes across many different organelles and predict levels of many pro-inflammatory markers. Overall, our analysis provides a detailed map of pyroptosis which includes overlapping and distinct connections with apoptosis revealed through a mechanistic link between cell morphology and cell secretome.
GENA-Web - GENomic Annotations Web Inference using DNA language models
Authors: Shmelev Alexey , Petrov Maxim , Penzar Dmitry , Akhmetyanov Nikolay , Tavritskiy Maksim , Mamontov Stepan , Kuratov Yuri , Burtsev Mikhail , Kardymon Olga , Fishman Veniamin 
Published: April 2024

ABSTRACTThe advent of advanced sequencing technologies has significantly reduced the cost and increased the feasibility of assembling high-quality genomes. Yet, the annotation of genomic elements remains a complex challenge. Even for species with comprehensively annotated reference genomes, the functional assessment of individual genetic variants is not straightforward. In response to these challenges, recent breakthroughs in machine learning have led to the development of DNA language models. These transformer-based architectures are designed to tackle a wide array of genomic tasks with enhanced efficiency and accuracy. In this context, we introduce GENA-Web, a web-based platform that consolidates a suite of genome annotation tools powered by DNA language models. The version of GENA-Web presented here encompasses a diverse set of models trained on human data, including the prediction of promoter activity, annotation of splice sites, determination of various chromatin features, and a model for scoring of enhancer activity in Drosophila. GENA-Web is accessible online athttps://dnalm.airi.net/