bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple, single trait GWAS and supervised machine learning reveal the genetic architecture ofFraxinus excelsiortolerance to ash dieback in Europe
Authors: Doonan JM , Budde KB , Kosawang C , Lobo A , Verbylaite R , Brealey JC , Martin MD , Pliūra A , Thomas K , Konrad H , Seegmüller S , Liziniewicz M , Cleary M , Nemesio-Gorriz M , Fussi B , Kirisits T , Gilbert MTP , Heuertz MTP , Kjær ED , Nielsen LR 
Published: December 2023

AbstractCommon ash (Fraxinus excelsior) is under intensive attack from the invasive alien pathogenic fungusHymenoscyphus fraxineus, causing ash dieback at epidemic levels throughout Europe. Previous studies have found significant genetic variation among clones in ash dieback susceptibility and that host phenology, such as autumn yellowing, is correlated with susceptibility of ash trees toH. fraxineus; however, the genomic basis of ash dieback tolerance inF. excelsiorremains poorly understood. Here, we integrate quantitative genetics and genome-wide association analyses with machine learning to reveal the genetic architecture of ash dieback tolerance and its relationship to phenological traits inF. excelsiorpopulations in six European countries (Austria, Denmark, Germany, Ireland, Lithuania, Sweden). We use whole-genome sequencing of 486F. excelsiorgenotypes to confirm the genotypic correlation between crown damage caused by ash dieback and intensity of autumn leaf yellowing within multiple sampling sites. Although, our results suggest that the examined traits are polygenic, a relatively small number of single nucleotide polymorphisms (SNPs) explained a large proportion of the variation in both disease tolerance and autumn leaf yellowing. We could explain up to 63% (based on 9155 unlinked SNPs) of variation in individual response to ash dieback crown damage and up to 72% (based on 3740 unlinked SNPs) of variation in autumn yellowing. We identified eight SNPs encoding non-synonymous substitutions, of which those with the highest predictive power were located within genes related to plant defence (pattern triggered immunity, pathogen detection) and phenology (regulation of flowering and seed maturation, auxin transport). Overall, our results provide insights of a multifaceted defence response, according to which a combination of direct defence mechanisms and phenological avoidance of pathogen spread constitute tolerance to ash dieback.
Methylmercury demethylation and volatilization by animals expressing microbial enzymes
Authors: Tepper K , King J , Cholan PM , Pfitzner C , Morsch M , Apte SC , Maselko M 
Published: December 2023

AbstractMethylmercury is a highly toxic pollutant that accumulates in food webs where it is inaccessible to current remediation technologies. We demonstrate that animals can be engineered to express the microbial enzymes, organomercurial lyase (MerB) and mercuric reductase (MerA), to bioremediate methylmercury. MerA and MerB fromEscherichia coliwere functional in invertebrate (Drosophila melanogaster) and vertebrate (Danio rerio) model systems and converted methylmercury into volatile Hg0. The engineered animals tolerated higher exposures to methylmercury and accumulated less than half as much mercury relative to their wild-type counterparts. The outcomes of this research could be applied to reduce mercury contamination in farmed and recreationally caught fish, for species conservation, and to restore value to organic wastes contaminated with mercury.
Subspecies divergence, hybridisation and the spatial environment shape phylosymbiosis in the microbiome of house mice
Authors: Ferreira Susana C. M. , Jarquín-Díaz Víctor Hugo , Planillo Aimara , Ďureje Ľudovít , Martincová Iva , Kramer-Schadt Stephanie , Forslund Sofia K. , Heitlinger Emanuel 
Published: December 2023

AbstractClosely related host species share similar symbionts, yet how host genetics and the environment affect symbiont communities at different stages of host genetic divergence remains largely unknown. Similarly, it is unclear whether host-symbiont associations result from or contribute to host divergence.We examined the intestinal community of 619 wild-caught mice from Germany’s European house mouse hybrid zone. Here, hybridisation upon secondary contact reflects divergence and could be traced gradually.Temporal and spatial factors were strong predictors of microbiome composition. Subspecies divergence predicted the composition similarity of the overall microbiome, specifically in the bacteria, parasite and fungal components. The effect of hybridisation was generally weak but significant for the fungal component. We confirmed our results in experiments with wild-derived inbred mice: subspecies’ genetic distances and hybridisation predicted the overall microbiome composition, and hybridisation further predicted fungal similarities among individuals. Fungi seemed more stable to the community perturbation of infection than other components of the microbiome.Differences between subspecies were more substantial across different microbiome components than those associated with hybridisation. Diverged microbiomes are a product of host divergence and are maintained by host genetics upon large environmental effects. These results provide a unique perspective into the ecoevolutionary processes shaping phylosymbiosis.
A cross-attention transformer encoder for paired sequence data
Authors: Dens Ceder , Laukens Kris , Meysman Pieter , Bittremieux Wout 
Published: December 2023

AbstractTransformer-based sequence encoding architectures are often limited to a single-sequence input while some tasks require a multi-sequence input. For example, the peptide–MHCII binding prediction task where the input consists of two protein sequences. Current workarounds to solve this input-type mismatch lack resemblance with the biological mechanisms behind the task. As a solution, we propose a novel cross-attention transformer encoder that creates a cross-attended embedding of both input sequences. We compare its classification performance on the peptide–MHCII binding prediction task to a baseline logistic regression model and a default transformer encoder. Finally, we make visualizations of the attention layers to show how the different models learn different patterns.
Larval growth rate affects wing shape more than eyespot size in the seasonally polyphenic butterflyMelanitis leda
Authors: Molleman Freerk , Moore Elizabeth M. , Halali Sridhar , Kodandaramaiah Ullasa , Halali Dheeraj , van Bergen Erik , Brakefield Paul M. , Oostra Vicencio 
Published: December 2023

AbstractButterflies often show adaptive phenotypic plasticity where environmental cues during early stages are used to produce a phenotype that maximizes fitness in the environment experienced by adults. Many tropical satyrine butterflies (Nymphalidae: Satyrinae) are seasonally polyphenic and produce distinct wet- and dry-season form adults providing tight environment-phenotype matching in seasonal environments. Dry-season forms, which are expressed in the dry season, can be induced in the laboratory by growing larvae at low temperatures or on poor food quality. Since both these factors also tend to reduce larval growth rate, larval growth rate may be an internal cue that translates the environmental cues into the expression of phenotypes. If this is the case, we predict that slower-growing larvae would be more likely to develop a dry-season phenotype. To test this hypothesis, we measured both larval growth rate and adult phenotype (eyespot size and wing shape) of individuals of the common evening brown butterfly (Melanitis leda), reared at various temperatures and on various host-plant species. We found that among treatments, larvae with lower growth rates (low temperature, particular host plants) were more likely to develop dry-season phenotypes (small eyespots, falcate wing tips), but within treatments, larval growth rate was mainly linked to wing shape, not eyespot size. These relationships tended to be stronger for males than females as males showed a wider range of eyespot sizes and wing shapes. Overall, only plasticity in wing shape appears to be (partly) mediated by larval growth, and in a sex-specific manner.
Spatial transcriptomics of a parasitic flatworm provides a molecular map of vaccine candidates, drug targets and drug resistance genes
Authors: Gramberg Svenja , Puckelwaldt Oliver , Schmitt Tobias , Lu Zhigang , Haeberlein Simone 
Published: December 2023

AbstractThe spatial organization of gene expression dictates tissue functions in multicellular parasites. Here, we present the first spatial transcriptome of a parasitic flatworm, the common liver flukeFasciola hepatica.We identified gene expression profiles and marker genes for eight distinct tissues and validated the latter byin situhybridization. To demonstrate the power of our spatial atlas, we focused on genes with substantial medical importance, including vaccine candidates (Ly6 proteins), drug targets (β-tubulins, protein kinases) and drug resistance genes (glutathione S-transferases, ABC transporters). Several of these genes exhibited unique expression patterns, indicating tissue-specific biological functions. Notably, the prioritization of tegumental protein kinases identified a PKCβ, for which small-molecule targeting caused parasite death. Our comprehensive gene expression map provides unprecedented molecular insights into the organ systems of this complex parasitic organism, serving as a valuable tool for both basic and applied research.
Transformation of cereal grains: Botanical and chemical analysis of food residues encrusted on pottery from the Funnel Beaker settlement of Oldenburg LA 77, northern Germany
Authors: Kubiak-Martens Lucy , Oudemans Tania F.M. , Brozio Jan Piet , Filipović Dragana , Müller Johannes , Kirleis Wiebke 
Published: December 2023

AbstractAn integrated botanical and chemical approach is used to study surface residues on Funnel Beaker ceramics from the site of Oldenburg LA 77, in northern Germany. Organic residues were discovered adhering to fragments of thick-walled, undecorated ceramic vessels (n=19) and ceramic discs (n=2). The surface residues were studied using scanning electron microscopy (SEM), to examine remains of cereals and other plant tissues that survived food preparation and cooking, and using attenuated total reflectance Fourier transform infrared spectroscopy (ATR–FTIR) and direct time-resolved mass spectrometry (DTMS), to chemically identify specific food components. The SEM results show a reoccurring presence of cereal grain (emmer and barley) and one case of co-occurrence of emmer and fat-hen seeds. The SEM evidence for the use of sprouted emmer grain and milk-ripe barley from the Oldenburg residues greatly enhances our understanding of Neolithic foodways in northwestern Europe. The ATR-FTIR results showed that roughly a third of the surface residues contain traces of the original foods prepared or processed and DTMS results confirm that most of the residues primarily contain polysaccharides and a minimal amount of plant protein and that they lack lipids. Only one residue presents minor indications for a (partly) animal origin. The ceramic vessels were thus used almost exclusively for the processing or cooking of cereal grains. This study offers an intimate view of the cuisine and cooking practices (and in some cases their seasonal timing) in an early agricultural village located in a marginal farming region on the south coast of the Baltic Sea.
Distinct latitudinal patterns of shifting spring phenology across the Appalachian Trail Corridor
Authors: Tourville Jordon , Murray Georgia , Nelson Sarah 
Published: December 2023

AbstractWarming associated with climate change will likely continue to advance the onset of spring phenology for many forest plants across the eastern United States. Understory forbs and spring ephemerals which fix a disproportionate amount of carbon during spring may be negatively affected by earlier canopy closure (i.e., phenological windows), however, information on the spatial patterns of phenological change for these communities is still lacking. To assess the potential for changes in spring phenological windows we synthesized observations from the Appalachian Mountain Club’s (AMC) Mountain Watch (MW) project, the National Phenology Network (NPN), and AMC’s iNaturalist projects between 2004 and 2022 (n = 118,250) across the length of the Appalachian Trail (AT) Corridor (34°N-46°N latitude). We used hierarchical Bayesian modeling to examine the sensitivity of day of year of flowering and leaf-out for 11 understory species and 14 canopy tree species to mean spring temperature (April-June). We conducted analyses across the AT Corridor, partitioned by regions of 4° latitude (South, Mid-Atlantic, and North). Spring phenologies for both understory plants and canopy trees advanced with warming (∼6 days/°C and ∼3 days/°C, respectively). However, sensitivity of each group varied by latitude, with phenology of trees and understory plants advancing to a greater degree in the mid-Atlantic region (∼10 days/°C) than the southern or northern regions (∼5 days/°C). While we find evidence that phenological windows remain stable in southern and mid-Atlantic portions of the AT, we observed an expansion of the spring phenological window in the north where there was greater understory temperature sensitivity compared to trees (∼1.6 days/°C). Our analyses indicate differential sensitivity of forest plant phenology to potential warming across a large latitudinal gradient in the eastern United States. Further, evidence for a temperature-driven expansion of the spring phenological window suggests a potential beneficial effect for understory plants, although phenological mismatch with potential pollinators is possible. Using various extensive citizen-science derived datasets allows us to synthesize regional- and continental-scale data to explore spatial and temporal trends in spring phenology related to warming. Such data can help to standardize approaches in phenological research and its application to forest climate resiliency.
Radical pairs and superoxide amplification can explain magnetic field effects on planarian regeneration
Authors: Rishabh  , Zadeh-Haghighi Hadi , Simon Christoph 
Published: December 2023

AbstractWeak magnetic field exposure can affect many biological processes across a wide range of living organisms. Recently, it has been observed that weak magnetic fields can modulate reactive oxygen species (ROS) concentration, affecting regeneration in planaria. These effects show unusual nonlinear dependence on magnetic field strength, including a sign change. In another study by the same group, superoxide is identified as the particular ROS being modulated. We propose a radical pair mechanism based on a flavin-superoxide radical pair to explain the modulation of superoxide production and its effect on planarian regeneration. The results of our calculations favor a triplet-born radical pair. Our yield calculations can reproduce the observed magnetic field dependence, including the sign change. Moreover, to explain the size of the effect on ROS concentration, we suggest a simple amplification model inspired by known biochemical mechanisms and lay out the conditions for such a model to work. Further, we also make empirical predictions concerning the hypomagnetic field effects on planarian regeneration.
Leveraging large language models for data analysis automation
Authors: Jansen Jacqueline A , Manukyan Artür , Al Khoury Nour , Akalin Altuna 
Published: December 2023

AbstractData analysis is constrained by a shortage of skilled experts, particularly in biology, where detailed data interpretation is vital for understanding complex biological processes and developing new treatments and diagnostics. To address this, we developedmergen, an R package that leverages Large Language Models (LLMs) for data analysis code generation and execution. Our primary goal is to enable humans to conduct data analysis by simply describing their objectives and the desired analyses for specific datasets through clear text. Our approach improves code generation via specialized prompt engineering and error feedback mechanisms. In addition, our system can execute the data analysis workflows prescribed by the LLM providing the results of the data analysis workflow for human review. We evaluated the performance of this data analysis system using various data analysis tasks. Our evaluation revealed that while LLMs effectively generate code for some data analysis tasks, challenges remain in executable code generation, especially for complex data analysis tasks. Our study contributes to a better understanding of LLM capabilities and limitations, providing software infrastructure and practical insights for their effective integration into data analysis workflows.
Facile generation of biepitopic antibodies with intrinsic agonism for activating receptors in the tumor necrosis factor superfamily
Authors: Jhajj Harkamal S. , Schardt John S. , Khalasawi Namir , Yao Emily L. , Lwo Timon S. , Kwon Na-Young , O’Meara Ryen L , Desai Alec A. , Tessier Peter M. 
Published: December 2023

SummaryAgonist antibodies that activate cellular receptors are being pursued for therapeutic applications ranging from neurodegenerative diseases to cancer. For the tumor necrosis factor (TNF) receptor superfamily, higher-order clustering of three or more receptors is key to their potent activation. This can be achieved using antibodies that recognize two unique epitopes on the same receptor and mediate receptor superclustering. However, identifying compatible pairs of antibodies to generate biepitopic antibodies (also known as biparatopic antibodies) for activating TNF receptors typically requires animal immunization and is a laborious and unpredictable process. Here, we report a simple method for systematically identifying biepitopic antibodies that potently activate TNF receptors without the need for additional animal immunization. Our approach uses off-the-shelf, receptor-specific IgG antibodies, which lack intrinsic (Fc-gamma receptor-independent) agonist activity, to first block their corresponding epitopes. Next, we perform selections for single-chain antibodies from human nonimmune libraries that bind accessible epitopes on the same ectodomains using yeast surface display and fluorescence-activated cell sorting. The selected single-chain antibodies are finally fused to the light chains of IgGs to generate human tetravalent antibodies that engage two different receptor epitopes and mediate potent receptor activation. We highlight the broad utility of this approach by converting several existing clinical-stage antibodies against TNF receptors, including ivuxolimab and pogalizumab against OX40 and utomilumab against CD137, into biepitopic antibodies with highly potent agonist activity. We expect that this widely accessible methodology can be used to systematically generate biepitopic antibodies for activating other receptors in the TNF receptor superfamily and many other receptors whose activation is dependent on strong receptor clustering.
Vitamin D attenuates diabetic myocardial injury via the Erbb4/ferroptosis axis
Authors: Song Hanlu , Miao Yufan , Zhang Yujing , Zhang Luoya , Chen Hao , Tang Lulu , Li Wenjie , Gu Chenxi , Li Xing 
Published: December 2023

AbstractBackgroundHyperglycemia and hyperlipidemia lead to the ferroptosis, well as the phosphorylation of Erbb4, and thereby increase the risk of cardiac hypertrophy. Thus, our investigation aims to explore whether vitamin D could mitigate diabetic cardiac injury through modulation of the Erbb4/ferroptosis axis.Methods and resultsKKAy mice fed on a high-fat diet were utilized to construct the prediabetic model, which showed an up-regulated phosphorylation of Erbb4, with concurrent ferroptosis in cardiac tissues. Following the intervention with vitamin D for 16 weeks, the activity of Erbb4/YAP signaling was suppressed and the severeness of ferroptosis was improved. Meanwhile disturbances in glucose-lipid metabolism and insulin secretion induced by high fat were alleviated, along with improvements in cardiac hypertrophy and myocardial function. Moreover, we established anin vitrodamage model by introducing H9c2 myocardial cells to high glucose (HG, 33.3 mM) and palmitic acid (PA, 0.25 mM). Unsurprisingly, similar results have been acquired after vitamin D supplementation. Subsequently, selective inhibitors of Erbb4 (Dacomitinib) and ferroptosis (Ferrostatin-1) were applied to evaluate the efficiency of Erbb4 signaling on modulating ferroptosisin vitro, and conclusively confirming that inhibiting of Erbb4 indeed reduce ferroptosis under HG and PA stimulus. Additionally, treatment of vitamin D was found to reduce cardiomyocyte hypertrophy and prevent cell death by inhibiting Erbb4 activity. Interestingly, the combined intervention of Vitamin D and Dacomitinib exerted a synergistic effect on ameliorating the abnormal conditions.ConclusionsOur study unveils, the correlation between Erbb4 and ferroptosis in diabetic heart. Providing evidences that vitamin D supplementation can improve ferroptosis related diabetic cardiac injury through inactivation of Erbb4. Proposing that the combination treatment of vitamin D and Erbb4 inhibitors may emerge as a highly feasible clinical strategy for diabetic myocardial injury.
Identifying the dimensions of philanthropic CSR in the FMCG sector: agenda for the sustainability of business
Authors: Soni Vibha , Saxena Priti , Moid Sana , Saxena Abhineet , Mehta Mita 
Published: December 2023

Purpose
This study aims to use a multi-stage scale development process to identify the dimensions of philanthropic corporate social responsibility (PCSR) in India’s fast-moving consumer goods (FMCG) sector.

Design/methodology/approach
The authors conducted a study to develop a comprehensive, reliable and valid scale for measuring PCSR based on the customer perception of FMCG product manufacturers. This research adopted a comprehensive and detailed scale development process using multi-stage sampling for scale development. This final study was conducted on a sample of 402 respondents from the city of Jaipur, India.

Findings
The results have underlined the multi-dimensional aspect of PCSR; these dimensions are: altruism towards society, volunteering for local community development, generosity towards ecology, benevolent spirit and problem-solving charity.

Practical implications
This study gives valuable insights into philanthropic scale development in the FMCG sector that can immensely help domestic and international marketers to formulate CSR as a strategy. This research provides insights into a wide range of scales which can be base for future research studies that aim to explore different organizational settings.

Originality/value
PCSR and CSR are important for developing strategies for sustainable businesses across the globe. Dimensions of PCSR will be useful for practitioners and researchers in developing second-order constructs for future studies.