bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stone Age anthropogenic impacts to forest development in the interior Scandinavian Peninsula
Authors: Bertheussen Anastasia , Wright David K. , Dahl Svein Olaf , Birk Jago J. , Bergman Jonas , Buckby Joseph , Fiedler Sabine , Mjærum Axel 
Published: January 2025

AbstractForest growth and development is a highly studied phenomenon in which humans have proven to be influential in shaping structure and composition. Delineating the long-term processes of human-environment interactions is crucial for understanding the history and trajectory of landscape formation and vegetation development. Yet, extensive knowledge of the ecological impacts of Stone Age anthropogenic activity is still lacking, particularly from Fennoscandian sites. A sediment core from South Mesna lake from the interior Scandinavian Peninsula was extracted to investigate the long-term evolutionary effects of human-environment interactions following deglaciation (c. 10,500 cal. BP) and initial colonization of the region. Analysis of the core involved microscopic/trace analytical methods, including geochemical analysis, stable isotope analysis, fecal biomarker analysis, and pollen analysis. The combined evidence demonstrates that anthropogenic impacts are prominent shapers of the ecological trajectory and landscape development of the region since the Early Neolithic (c. 5900 cal. BP), which has left a footprint on modern-day land cover.SignificanceAnthropogenic impacts on the environment have been observed to have had notable consequences on global and regional ecological trajectories and environmental development. Yet, how coupled human-environment interactions affect the long-term ecological complexion of boreal landscapes, such as those of the interior Scandinavian Peninsula, is not widely studied. This article presents evidence of early anthropogenic impacts to a forest’s ecology during the Holocene. Fecal biomarker and pollen analyses make it possible to provide micro-archaeological evidence of human activity and correlate it with noteworthy changes in forest structure. Our data points to a specific co-evolutionary forest development trajectory which is connected to millennial-scale human settlement patterns.
Patagonian fjords/channels vs. open ocean: phytoplankton molecular diversity in Southern Chilean coast
Authors: Fuenzalida Gonzalo , Sanchez Roland , Silva Andrea , Figueroa Alvaro , Artal Osvaldo , Jorquera Milko , Trefault Nicole , Espinoza Oscar , Guzman Leonardo 
Published: January 2025

AbstractEnvironmental filtering hypothesis studies have revealed immense diversity of microorganisms across oceans; however, these studies are scarce along the Southeast Pacific coast. In this work, we describe the molecular diversity of phytoplankton communities from two biogeographic areas with contrasting oceanographic characteristics, namely fjords and channels versus the open Pacific Ocean (36°S to 53°S). Both areas have seen an increase in the frequency and intensity of Harmful Algal Bloom events (HABs). Using a molecular approach based on metabarcoding of the SSU ribosomal gene, we retrieve micro-phytoplankton diversity, community composition, and biogeographical patterns. The ASVs assigned to Dinophyceae and Bacillariophyta classes show differences in richness and dominance between both studied areas. The diversity pattern described in this work shows a higher harmful potential in fjord/channel areas versus the open ocean, which provides grounds for future studies about the factors triggering temporal variations in phytoplankton communities within these two contrasting environments.
Comparing the Seasonal Diets of Buff-tailed Bumblebees and Honey Bees in a Forest Landscape: A Metabarcoding Approach
Authors: Gay Claire , Cochard Précillia , Thouin Julien , Morin Elie , Moreau Fabienne , Poirot Benjamin 
Published: January 2025

AbstractThe declining diversity of pollinating insects is a major threat to ecosystem conservation, pollination services, and global food security. Honeybees dominate managed pollination, but their dominance can affect other pollinators. Competition for resources can lead to decreased foraging success and survival rates for wild bees, especially bumblebees. This study explores the dietary composition of honeybees and bumblebees using molecular metabarcoding techniques with three primers (ITS2, TrnLgh, and TrnLch) in an agricultural and forest land, Avensan, France. It aims to characterize pollen diversity within their diets, allowing for the inference of floral diversity in the study site. The primers detected pools of different species, indicating a high diversity of floral species in the plants visited by both species. The “primer” effect was more important than the “pollinator” effect in segregating plants found. The Schoener index revealed a slight diet overlap in plant species used by honeybees and bumblebees, depending on the primer. Correspondence analyses showed a high segregation between species associated with honeybees and species associated with bumblebees, regardless of the primer. However, the metabarcoding technique was found to be accurate in separating different pollinator food niches, and did not find a significant overlap in the diet of these two insects. The study provides a good approach to study their floral resources sharing in the same geographical area and time scale, but it is not powerful enough to infer floral diversity.
Negative frequency-dependent selection contributes to modular structure of effector repertoires inPseudomonas syringae
Authors: Li Shuanger , Laderman Eric , Märkle Hanna , Yang Yunze , Bergelson Joy , Pascual Mercedes 
Published: January 2025

AbstractThe evolutionary fate of multi-strain pathogens is shaped by host-pathogen ecological interactions. In bacterial pathogens of plants, enhanced strain characterization and advances in our understanding of molecular mechanisms underlying defense pathways open the door for revisiting the role of negative frequency-dependent selection (NFDS) in strain structure, including its interplay with genetic exchange. NFDS arising from specific defense is one potential mechanism for generating, maintaining, and structuring pathogen diversity. In plants, specific protection against microbial pathogens involves Resistance proteins (R-proteins) that recognize virulence factors (effectors) secreted by pathogens, typically to subvert the initial line of host defense. Here we formulate a stochastic computational co-evolution model that explicitly incorporates variable length R-gene and effector repertoires, and migration from their regional pools. We use this model to understand potential mechanisms shaping effector repertoire structure and associated strain coexistence in the generalist plant pathogenP. syringae. The demonstration of a modular structure in our numerical simulations motivates the analysis of genome sequences from 76 strains collected in the Midwestern US and 1104 strains from global sources. We find that effector repertories both locally and globally exhibit a modular structure, with higher similarity within than between clusters. The observed modules are consistent with the core genome phylogeny and are unexplained by plant host species, location of isolation, and genetic linkage between effectors. An extension of the model is needed to take into account the evidence for genetic exchange and the phylogenetic congruence of effector modules. We initialize the system with a phylogenetically congruent modular structure and include recombination rates decreasing as a function of phylogenetic distance. We show that NFDS can counter-balance the effects of mixing due to recombination and in so doing, contributes to the maintenance of strain structure. These findings indicate that the observed similarity clusters may constitute, in part, emergent niches arising from eco-evolutionary dynamics that contribute to strain coexistence.
KILDA: identifying KIV-2 repeats from kmers
Authors: Corentin Molitor , Timothy Labidi , Antoine Rimbert , Bertrand Cariou , Mathilde Di Filippo , Claire Bardel 
Published: January 2025

AbstractMotivationHigh concentration of lipoprotein(a), a lipoprotein with proatherogenic properties, is an important risk factor for cardiovascular disease. This concentration is mostly genetically determined by a complex interplay between the number of Kringle-IV type 2 repeats and Lipoprotein(a)-affecting variants. Besides lipoprotein(a) plasma concentration, there is an unmet need to identify individuals most at risk based on theirLPAgenotype.ResultsWe developed KILDA, a Nextflow pipeline, to identify the number of Kringle-IV type 2 repeats and Lp(a)-affecting variants directly from kmers generated from FASTQ files. The pipeline was tested on the 1000 Genomes Project (n=2459) and results were equivalent to DRAGEN-LPA (R2=0.93).In-silicodatasets proved the robustness of KILDA’s predictions under different scenarios of sequencing coverage and quality.ConclusionKILDA is an open-source and free-to-use pipeline to identify the number of Kringle-IV type 2 repeats and lipoprotein(a)-associated variants. Its results are equivalent to DRAGEN-LPA, offering a free and robust tool for determining theLPAkringle number even when inputting low coverage libraries.AvailabilityKILDA is publicly available athttps://github.com/HCL-HUBL/KILDAalong with a recipe to build an Apptainer image containing all the required dependencies.Contact:corentin.molitor@chu-lyon.frSupplementary informationSupplementary data are available atBioinformaticsonline.
Disease-associated Kv1.3 variants are energy compromised with impaired nascent chain folding
Authors: Sykes Aaron , Caruth Lannawill , Setia Verma Shefali , Hoshi Toshinori , Deutsch Carol 
Published: January 2025

ABSTRACTHuman Kv1.3, encoded byKCNA3, is expressed in neuronal and immune cells. Its impaired expression or function produces chronic inflammatory disease and autoimmune disorders, the severity of which correlates with Kv1.3 protein expression. The intersubunit recognition domain, T1, at the cytosolic N-terminus of Kv1.3, acquires secondary, tertiary, and quaternary structures during early biogenesis while the nascent protein is attached to the ribosome and/or the ER membrane. In this study, we ask whether nativeKCNA3gene variants in T1 are associated with human disease and whether they manifest early-stage folding defects, energetic instabilities, and conformational distortion of subunits. We use three approaches: first, the unbiased “genome-first” approach to determine phenotype associations of specificKCNA3rare variants. Second, we use biochemical assays to assess early-stage tertiary and quaternary folding and membrane association of these variants during early biogenesis. Third, we use all-atom molecular dynamics simulations of the T1 tetramer to assess structural macroscopic and energetic stability differences between wildtype (WT) Kv1.3 and a single-point variant, R114G. Measured folding probabilities and membrane associations are dramatically reduced in several of the native variants compared to WT. Simulations strikingly show that the R114G variant produces more energetically unstable and dynamic T1 domains, concomitant with tertiary unwinding and impaired formation of symmetrical tetramers. Our findings identify molecular mechanisms by which rare variants influence channel assembly, potentially contributing to diverse clinical phenotypes underlying human disease.
Evolutionary trajectories of immune escape across cancers
Authors: Chen Wenjie , Baker Toby , Zhang Zhihui , Ogilvie Huw A. , Van Loo Peter , Gu Shengqing (Stan) 
Published: January 2025

AbstractImmune escape is a critical hallmark of cancer progression and underlies resistance to multiple immunotherapies. However, it remains unclear when the genetic events associated with immune escape occur during cancer development. Here, we integrate functional genomics studies of immunomodulatory genes with a tumor evolution reconstruction approach to infer the evolution of immune escape across 38 cancer types from the Pan-Cancer Analysis of Whole Genomes dataset. Different cancers favor mutations in different immunomodulatory pathways. For example, the antigen presentation machinery is highly mutated in colorectal adenocarcinoma, lung squamous cell carcinoma, and chromophobe renal cell carcinoma, and the protein methylation pathway is highly mutated in bladder transitional cell carcinoma and lung adenocarcinoma. We also observe different timing patterns in multiple immunomodulatory pathways. For instance, mutations impacting genes involved in cellular amino acid metabolism were more likely to happen late in pancreatic adenocarcinoma. Mutations in the glucocorticoid receptor regulatory network pathway tended to occur early, while mutations in the TNF pathways were more likely to occur late in B-cell non-Hodgkin lymphoma. Mutations in the NOD1/2 signaling pathway and DNA binding transcription factor activity tended to happen late in breast adenocarcinoma and ovarian adenocarcinoma. Together, these results delineate the evolutionary trajectories of immune escape in different cancer types and highlight opportunities for improved immunotherapy of cancer.SignificanceDespite its critical role in cancer progression, the evolution of immune escape is poorly understood. We integrate functional genomics and tumor evolution reconstruction and infer immune escape trajectories across cancer types. Our results have important implications for developing biomarkers for immunoprevention and treatment strategies for immune escape of cancer.
Genome diversity and phylogeny of the sectionAlataeof genusLemna(Lemnaceae), comprising the presumed speciesLemna aequinoctialis, Le. perpusillaandLe. aoukikusa
Authors: Stepanenko Anton , Braglia Luca , Fuchs Jörg , Schubert Veit , Hoang Phuong TN , Lee Yuri , Chen Guimin , Gianì Silvia , Morello Laura , Schubert Ingo 
Published: January 2025

SummaryThe SectionAlataeof genusLemnaof the monocotyledonous aquatic duckweed family (Lemnaceae) consists of rather diverse accessions with unknown phylogeny and unclear taxonomic assignment. In contrast to other duckweeds, someAlataeaccessions, in addition to mainly vegetative propagation, produce readily flowers and viable seeds. We analyzed the genomic diversity and phylogenetic relationship of 52Alataeaccessions.For this purpose, we applied multiple molecular and cytogenetic approaches, including plastid and nuclear sequence polymorphisms, chromosome counting, genome size determination and genomicin situhybridization in combination with geographic distribution.We uncovered ploidy variation, recurrent hybridization, and backcrosses between diploid species and their hybrids. The latter successfully spread over three continents.The results elucidate the evolution ofAlataeaccessions (summarized in Fig. 7) and explain the difficult taxonomic assignment of distinct accessions. Our study might be an example for analogous studies to resolve the hitherto unclear relationships among accessions of the duckweed generaWolffiellaandWolffia.
The ISPpu9 insertion sequence ofPseudomonas putidaKT2440 generates various circular intermediates enabling modular transposition
Authors: Parés-Guillén Elena , Yuste Luis , Rojo Fernando , Moreno Renata 
Published: January 2025

ABSTRACTPseudomonas putidaKT2440 contains seven copies of an insertion sequence (IS) belonging to the IS110family, designated ISPpu9, which are inserted into repetitive extragenic palindromic sequences. Five of these copies include a small RNA,ssr9, located downstream of the transposase gene. Additionally, three separate copies ofssr9are also present. When transferred to a differentP. putidastrain, ISPpu9 inserted at a specific target site highly similar to that of the KT2440 strain. Ssr9 was not needed for transposition. Circular intermediates were detected containing either the transposase, the transposase along withssr9, orssr9alone. This finding explains the presence of these distinct modules in KT2440 chromosome. Minicircle formation required the transposase and short sequences located within the IS ends, which were identified. Unlike other ISs of this family, minicircle formation in ISPpu9 did not produce a hybrid promoter to enhance transcription of the ISPpu9 transposase. Instead, transcription occurred efficiently from its native promoter. In contrast, minicircles formed by ISPpu10, another IS of the same family also present in KT2440, generated a hybrid promoter significantly stronger than its weak native transposase promoter. This suggests that hybrid promoters might only emerge when the native transposase promoter is inherently weak.
Microglial SIRT2 deficiency aggravates cognitive decline and amyloid pathology in Alzheimer’s disease
Authors: Sola-Sevilla Noemi , Garmendia-Berges Maider , Aleixo Mikel , Mera-Delgado MCarmen , Solas Maite , Tordera Rosa M , García-Carracedo Lucía , Expósito Sara , Anaya-Cubero Elena , Fernández-Irigoyen Joaquín , Guruceaga Elisabeth , Santamaria Enrique , Martin Eduardo D. , Puerta Elena 
Published: January 2025

AbstractSirtuin 2 (SIRT2), a NAD+-dependent deacetylase, has been implicated in aging and neurodegenerative diseases such as Alzheimer’s disease (AD). While global SIRT2 inhibition has shown promise in reducing amyloid-beta pathology and cognitive deficits in different mouse models of AD, peripheral SIRT2 inhibition has been associated with adverse effects, such as increased inflammation. This suggests that targeted inhibition of specific cellular populations within the brain may represent a more precise and effective approach for the treatment of AD. To explore this hypothesis, we generated a conditional microglial SIRT2 knockout mouse model in the context of AD. Our results reveal that microglial SIRT2 reduction does not confer protective effects in the APP/PS1 model; rather, it aggravates cognitive decline, accelerates amyloid plaque deposition, and increases levels of pro-inflammatory cytokines at early stages of AD pathology. Transcriptomic analysis further indicates that SIRT2-deficient microglia exhibit altered expression of genes associated with aging and synaptic dysfunction. This phenotype was accompanied by increased phagocytosis of synaptic elements and impaired long-term potentiation. These findings suggest that while SIRT2 inhibition in some contexts may be beneficial, targeted inhibition within microglia could accelerate AD progression, underscoring the need for cell-specific approaches when considering SIRT2 as a therapeutic target.
Post-movement beta rebound reflects strategic re-aiming during motor adaptation, but not re-aiming accuracy
Authors: Will Matthias , Korka Betina , Stenner Max-Philipp 
Published: January 2025

ABSTRACTMotor adaptation results from several interacting learning mechanisms, including learning via cognitive strategies and implicit adaptation. While strategy-based and implicit learning can be dissociated at a behavioural level, their underlying systems-level physiology is poorly understood. A neural signal that undergoes pronounced changes during motor adaptation is the post-movement beta-rebound (PMBR). However, it is unclear how these changes relate to the specific learning mechanisms that contribute to motor adaptation. We measured electroencephalography (EEG) while healthy participants (N=27) performed reaching movements towards a target. In most trials, a cursor showed the veridical position of the unseen hand, however, for some reaches, the direction of the cursor was rotated relative to the position of the hand. Participants were informed that, once a rotation occurred, it could persist for a single trial (1x condition), or for two consecutive trial (2x condition). In the 2x condition, participants could therefore redirect the rotated cursor through the target in the second rotated trial by re-aiming, while they had to continue aiming at the target in the 1x condition. We observed a stronger decrease of PMBR following the first rotated reach in the 2x condition, compared to the 1x condition, despite similar kinematics. This corroborates our previous results that PMBR reflects strategic re-aiming (Korkaet al., 2023). However, when we collapsed data from the two studies (total N=53), we found that the degree to which the PMBR decreases does not predict re-aiming accuracy. We discuss the role of PMBR in motor adaptation, including implications for clinical disorders.
The mycotoxin Beauvericin is an uncompetitive inhibitor of Cathepsin B
Authors: Yang Xiaoli , Cea-Medina Pablo , Gopalswamy Mohanraj , Vaidya Aparna , Schavier Sonja , Oltzen Shixin , Moßner Sofie , Huang Anfei , Qi Jing , Floss Doreen , Uhrberg Markus , Gohlke Holger , Scheu Stefanie 
Published: January 2025

AbstractBeauvericin (BEA), a cyclic depsipeptide, is a mycotoxin of the enniatin family and the secondary metabolite of various toxigenic fungi. Multiple biological functions of BEA have been well investigated, such as anti-cancer, anti-inflammatory, anti-microbial, and immune-activating functions. In a recent study, we showed that BEA can target Toll-like receptor 4 (TLR4) to induce dendritic cell (DC) activation. In an in silico screen, we identified Cathepsin B (CTSB) as a potential additional interaction partner for BEA, which has been verified recently in a study showing inhibition of CTSB activity by BEA in cell-free assays. The underlying molecular mechanism of BEA-mediated CTSB inhibition remains unknown as do the cellular entities where this inhibition takes place. In this study, we determine the effects of BEA on CTSB within granulocyte-macrophage colony-stimulating factor (GM-CSF)-cultured bone marrow-derived dendritic cells (BMDCs) and human leukemia monocytic cell line THP-1 induced dendritic cells (iDCs). BEA significantly suppresses CTSB activity in both mouse BMDCs and human iDCs. NMR analyses indicate that BEA directly interacts with CTSB. Enzyme kinetics show that BEA can directly inhibit CTSB activity and acts as an uncompetitive inhibitor. Molecular docking analysis revealed a putative binding site for BEA in human CTSB. Collectively, we describe the molecular mechanisms underlying the biological activity of BEA against human CTSB, suggesting that CTSB may be a candidate target for tumor therapy.