bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phased chromosome-level genome of the annelid tubewormGaleolaria caespitosa
Authors: van Dorssen Monique , Belcher Emily K. , Gallegos Cristóbal , Hodgins Kathryn A. , Monro Keyne 
Published: November 2024

AbstractHaplotype-resolved (phased) genome assemblies are emerging as important assets for genomic studies of species with high heterozygosity, but remain lacking for key animal lineages. Here, we use PacBio HiFi and Omni-C technologies to assemble the first phased, annotated, chromosome-level genome for any annelid: the reef-building tubewormGaleolaria caespitosa(Serpulidae). The assembly is 803.5 Mbp long (scaffold N50 = 76.5 Mbp) for haplotype 1 and 789.3 Mbp long (scaffold N50 = 75.4 Mbp) for haplotype 2, which are arranged into 11 pairs of chromosomes showing no sign of sex chromosomes. This compares with cytological analyses reporting 12–13 pairs inGaleolaria’s closest relatives, including species that are protandrous hermaphrodites. We combined long-read and short-read transcriptome sequencing to annotate both haplotypes, resulting in 43,191 predicted proteins for haplotype 1, 39,675 proteins for haplotype two, and 55.5% of proteins with at least one functional annotation. We also assembled a mitochondrial genome 23 Kbp long, annotating all genes typically found in mitochondrial DNA apart from those coding the16Sribosomal subunit and the proteinatp8— a short, fast-evolving mitochondrial gene missing in other metazoans. ComparingGaleolaria’s genome to those of three other annelids reveals limited collinearity despite 32.2% of shared orthologous gene clusters (4,248 of 13,174 clusters counted inGaleolaria), suggesting extensive chromosomal rearrangements among lineages. New high-quality annelid genomes may help resolve the genetic and evolutionary basis of this diversity.
Unveiling the Hidden Feast: from molecular detection to predation rate – An example on biological control by generalist predators
Authors: Masson Abel Louis , Rastello Kevan , Sacco-Martret de Preville Ambre , Tricault Yann , Poggi Sylvain , Canard Elsa , Etienne Marie-Pierre , Plantegenest Manuel 
Published: November 2024

AbstractVery few processes are as decisive as predation in shaping the structure and dynamics of ecological communities. For most predator species, the number of prey items killed by a predator in a day (predation rate) remains impossible to assess because direct observations are scarce or impossible to acquire. To fill this gap, we propose here a Hierarchical Bayesian Model that integrates data on the molecular detection of prey in predators (e.g. PCR results), on individuals captured in the field on the one hand, and on individuals fed in the laboratory, on the other, in a novel mechanistic framework. By explicitly combining the processes of predation and digestion, model fit provides an estimate of the slope and intercept of the digestion curve, and an estimate of the number of prey consumed by a predator in a day. In a case study targeting 25 carabid beetle species and 5 types of prey in agricultural fields (winter wheat), we use our model to estimate predation rates at species and community scales and demonstrate its advantages for studies on biocontrol and beyond.Code and Data are available on this repository :/r/HBM_PredationCode-C725/
Striking Departures from Polygenic Architecture in the Tails of Complex Traits
Authors: Souaiaia Tade , Wu Hei Man , Ori Anil P.S. , Choi Shing Wan , Hoggart Clive J. , O’Reilly Paul F. 
Published: November 2024

AbstractUnderstanding the genetic architecture of human traits is of key biological, medical and evolutionary importance[1]. Despite much progress, little is known about how genetic architecture varies across the trait continuum and, in particular, if it differs in the tails of complex traits, where disease often occurs. Here, applying a novel approach based on polygenic scores, we reveal striking departures from polygenic architecture across 148 quantitative trait tails, consistent with distinct concentrations of high-impact rare alleles in one or both tails of most of the traits. We demonstrate replication of these results across ancestries, cohorts, repeat measures, and using an orthogonal family-based approach[2]. Furthermore, trait tails with inferred enrichment of rare alleles are associated with more exome study hits, reduced fecundity, advanced paternal age, and lower predictive accuracy of polygenic scores. Finally, we find evidence of ongoing selection consistent with the observed departures in polygenicity and demonstrate, via simulation, that traits under stabilising selection are expected to have tails enriched for rare, large-effect alleles. Overall, our findings suggest that while common variants of small effect likely account for most of the heritability in complex traits[3], rare variants of large effect are often more important in the trait tails, particularly among individuals at highest risk of disease. Our study has implications for rare variant discovery, the utility of polygenic scores, the study of selection in humans, and for the relative importance of common and rare variants to complex traits and diseases.
Cancer-associated DAXX mutations reveal a critical role for ATRX localization in ALT suppression
Authors: Clatterbuck Soper Sarah F. , Walker Robert L. , Pineda Marbin A. , Zhu Yuelin J. , Dalgleish James L. T. , Wang Jasmine , Meltzer Paul S. 
Published: November 2024

AbstractTo maintain genome stability, proliferating cells must enact a program of telomere maintenance. While most tumors maintain telomeres through the action of telomerase, a subset of tumors utilize a DNA-templated process termed Alternative Lengthening of Telomeres or ALT. ALT is associated with mutations in the ATRX/DAXX/H3.3 histone chaperone complex, which is responsible for deposition of non-replicative histone variant H3.3 at heterochromatic regions of the genome including telomeres. We wished to better understand the role DAXX plays in ALT suppression, and to determine which disease-associated DAXX mutations are unable to suppress ALT. To answer this question, we have leveraged the G292 cell line, in which ATRX is wild type but DAXX has undergone a fusion event with the non-canonical kinesin KIFC3. Restoration of wild-type DAXX in G292 localizes ATRX and abrogates ALT. Using this model system, we tested the ability of a panel of disease-associated DAXX missense variants to suppress ALT. Missense mutations in the ATRX binding domain, the histone binding domain, and the C-terminal SUMO interaction motif reduce the ability of DAXX to suppress ALT. Unexpectedly, we find that mutations in the DAXX histone binding domain lead to failure of ATRX localization. We conclude that a key function of DAXX in ALT suppression is the localization of ATRX to nuclear foci.
Network toxicology focused investigation on the impacts of inorganic arsenic and cadmium on human and ecosystem health
Authors: Chivukula Nikhil , Madgaonkar Shreyes Rajan , Ramesh Kundhanathan , Mangot Swetha , Karthikeyan Panneerselvam , Marigoudar Shambanagouda Rudragouda , Sharma Krishna Venkatarama , Samal Areejit 
Published: November 2024

AbstractHeavy metals like arsenic and cadmium are persistent environmental pollutants that pose serious health risks to humans and ecosystems due to their toxicity, bioaccumulation potential, and frequent presence in consumer products. Network toxicology offers a holisticin silicoframework to elucidate the complex biological mechanisms of toxicity, thereby supporting New Approach Methodologies (NAMs) for toxicity assessment. In this study, network toxicological tools were utilized to investigate arsenic- and cadmium-induced toxicities. Toxicity endpoints associated with inorganic arsenic and cadmium compounds were curated from six exposome-relevant databases and mapped to key events (KEs) across adverse outcome pathways (AOPs) cataloged in AOP-Wiki. This led to construction of stressor-AOP networks, revealing 51 AOPs associated with arsenic and 78 with cadmium, and facilitated mechanistic case studies of pathways relevant to human and ecological health. Toxicity concentrations and bioconcentration factors from the ECOTOX database were then used to construct stressor-species networks, that helped identify species that are vulnerable and potentially bioaccumalate these chemicals. Further, the construction of species sensitivity distributions (SSDs) and toxicity-normalized SSDs (SSDn), provided a comparative framework for prioritizing these compounds in risk assessments. Further, integrating SSD data with stressor-species networks identified species groups particularly sensitive to arsenic and cadmium exposure, enhancing these networks’ utility for ecological risk assessment. The networks and related data generated in this study are freely available for further research athttps://cb.imsc.res.in/heavymetaltox/. Overall, this study offers a comprehensive perspective on the toxicological impact of inorganic arsenic and cadmium compounds, supporting a One Health approach to their regulatory and mitigation strategies.
A proposed framework for evaluating meat alternatives
Authors: Semper Cameron , Kolta Caroline , Kinney MJ , Giali Jordan , Rogers Michaella , Blaustein-Rejto Dan , Rowat Amy C. , Ogilvie Olivia J. , Hutmacher Ryan , Wee Josephine , Emery Isaac , Domigan Laura J. , Shelke Kantha 
Published: November 2024

AbstractConcerns surrounding the environmental, economic, and ethical consequences of meat production and industrial agriculture have prompted substantial research and capital investment into the production of meat alternatives. Alternative meat production encompasses a variety of technological approaches including plant-based meats, cell-based or cultivated meats, meat alternatives relying on fungal protein sources, and hybrids thereof; each of which offers unique advantages and disadvantages and has been associated with a myriad of claims supporting it as the preferred alternative to animal-derived meats. As part of XPRIZE Foundation’s Feed the Next Billion competition, we developed a framework for evaluating meat alternatives by measuring their structural, nutritional, and organoleptic properties while also assessing safety and their purported environmental and economic benefits compared to animal-derived meats. The framework is technologically agnostic and can be used to evaluate meat alternatives of all types. The output of the framework enables a data-driven comparison to animal-derived meat and/or other alternative meats, allowing a range of stakeholders (e.g., food startups, investors, government) to assess technological readiness, competitive advantage, and impact potential. This framework can assist this nascent industry as it moves towards standardizing approaches to evaluating the quality, safety and proposed benefits of meat alternatives.
The role of secondary structures of peptide polymers on antimicrobial efficacy and antibiotic potentiation
Authors: Barman Swagatam , Abiodun Alimi , Hossain Md Waliullah , Parris Adam , Chandrasseril Aiswarya Banshidhar , Older Ethan A. , Li Jie , Decho Alan W. , Tang Chuanbing 
Published: November 2024

ABSTRACTThe rise of antibiotic resistance, biofilm formation, and dormant bacterial populations poses serious global health threats. Synthetic antimicrobial peptide (AMP) mimics offer promising alternatives, though the impact of secondary structures in polymeric AMP mimics on antimicrobial efficacy is underexplored. This study investigates chirality-controlled α-peptide polymers (D-PP and DL-PP), synthesized via ring-opening polymerization of allylglycineN-carboxy anhydrides and post-polymerization modification through thiol-ene click chemistry. D-PP adopts a stable helical structure under biomimetic conditions, whereas DL-PP remains random. This helical structure enhanced D-PP’s antibacterial and antibiotic potentiation activities, amplifying antibiotic efficacy by 2- to 256-fold across various classes—including tetracyclines, ansamycins, fusidanes, macrolides, cephalosporins, and monobactams—against multidrug-resistant Gram-negative pathogens, while maintaining low hemolytic activity and high protease stability. Mechanistic investigations revealed that D-PP exhibited greater membrane interaction. D-PP and antibiotic combinations eradicated dormant bacterial populations and disrupted biofilms with minimal antimicrobial resistance development. This study paves the way for the rational design of polypeptide-based antimicrobial agents, harnessing chirality and secondary structural features to enhance the efficacy of synthetic antimicrobial peptide mimics.
Engineered mitochondrial A-to-G editors with enhanced efficiency and targeting scope
Authors: Chen Liang , Hong Mengjia , Luan Changming , Yuan Meng , Wang Yiming , Guo Xinyuan , Fang Yue , Huang Hao , Dong Xiaohua , Gao Hongyi , Zhang Dan , Chen Xi , Meng Dihao , Huang Molin , Yi Zongyi , Liu Mingyao , Gao Liangcai , Song Gaojie , Zhou Xiaoming , Wei Wensheng , Li Dali 
Published: November 2024

SummaryMitochondrial base editing is a powerful technology, but the current A-to-G mitochondrial DNA (mtDNA) base editors are reluctant to achieve high efficiency, which is critical for mtDNA engineering. Through laboratory evolution, TadA-8e variants were discovered with substantially increased activity and expanded targeting compatibility, especially for previously unfavorite sequence contexts, when applied to both nuclear and mitochondrial ABEs. Further engineering of the mtDNA editors (eTd-mtABEs) dramatically reduced both DNA and RNA off-targeting effects and enhanced strand-selective A-to-G editing with substitution of DddA to DNA nickases. Moreover, the eTd-mtABEs induced up to 145-fold editing frequencies compared to previous mtDNA adenine base editors in rat cells, and installed targeted mutations in all injected rat embryos with up to 74% efficiency in founders, resulting generation of SNHL and Leigh syndrome models with severe defects. It suggests that eTd-mtABEs are promising mtDNA engineering technology for basic research and for translational studies.HighlightsEngineered TadA variants enhance nuclear and mitochondrial ABE activity in all sequence contexts.Additional mutations in eTd-mtABEs further minimize both DNA and RNA off-targeting effects.Engineered TadA variants are compatible to DNA nickase assisted strand-selective mtDNA editing.eTd-mtABEs enable highly efficient generation of rat mtDNA disease models with severe phenotypes.
Golgins support extracellular matrix secretion by collectively maintaining the Golgi structure-function relationship
Authors: Thompson George , Hoyle Anna , Lewis Philip A. , Esther Prada-Sanchez M. , Swift Joe , Heesom Kate , Lowe Martin , Stephens David , Stevenson Nicola 
Published: November 2024

AbstractThe secretion of extracellular matrix (ECM) proteins is vital to the maintenance of tissue health. One major control point of this process is the Golgi apparatus, whose dysfunction causes numerous connective tissue disorders. Golgi function is tightly linked to its structure, which is maintained by the cytoskeleton and Golgi organising proteins. We sought to investigate the role of two of these organising proteins, the golgins GMAP210 and Golgin-160, in ECM secretion. We found that loss of either protein had distinct impacts on Golgi organisation. GMAP210 loss caused cisternal fragmentation and dilation, alongside the accumulation of tubulovesicular structures. Meanwhile, Golgin-160 knockout lead to Golgi fragmentation and vesicle build-up. Nonetheless, loss of each protein had a similar impact on ECM secretion and glycosaminoglycan synthesis. We therefore propose that golgins are collectively required to create the correct physical-chemical space to support efficient ECM protein secretion and modification. This is the first time that Golgin-160 has been shown to be required for ECM secretion.SummaryIn this study, Thompsonet aldemonstrate that two cis-Golgi golgins, GMAP210 and Golgin-160, have distinct, non-redundant roles in maintaining Golgi organisation and that both are required to support the efficient secretion, assembly, and modification of extracellular matrix proteins.
Sensitivity to Vγ9Vδ2TCR T cells is imprinted after single mutations during early oncogenesis
Authors: Cleven Astrid , Meringa Angelo D. , Brazda Peter , Fasci Domenico , Koorman Thijs , Aarts Tineke , Johanna Inez , Beringer Dennis X , Hernandez-Lopez Patricia , Heijhuurs Sabine , Mizutani Tomohiro , Lim Sangho , Huismans Maarten , Bernink Jochem , Diaz David Vargas , Wu Wei , Jose Esther San , Schipper Jelle , Tsakirakis Nikos , Hoorens van Heyningen Lauren , Nouwens Annick , Gatti Lucrezia , Straetemans Trudy , Snippert Hugo , Roodhart Jeanine , Derksen Patrick W.B. , Drost Jarno , Altelaar Maarten , Heck Albert J.R. , Clevers Hans , Kuball Juergen , Sebestyen Zsolt 
Published: November 2024

ABSTRACTVγ9Vδ2T cells have the unique ability to recognize a broad range of malignant transformed cells. The tumor targeting event involving BTN2A1 and BTN3A1 dimers on the tumor cell surface is critical, leading to full activation of the TCR. Although the molecular mechanisms governing TCR engagement and T cell activation are well-characterized, the role of Vγ9Vδ2 T cells in cancer immune surveillance remains to be fully elucidated, particularly the mechanisms that enable these cells to discriminate between healthy and malignant cells at an early stage of malignant transformation. We employed two independent, genetically engineered step-wise mutagenesis models of human colorectal and breast cancer that mimic the transformation steps leading to tumor formation. We demonstrate that various single oncogenic mutations introduced into healthy organoids or cells, are sufficient to upregulate surface expressed BTN2A1 and enable Vγ9Vδ2 TCR binding to tumor cells. However, full activation of T cells through a Vγ9Vδ2TCR required additional subsequent phosphorylation of juxtamembrane (JTM) amino acids of BTN3A1, leading to the activating heterodimerization of BTN2A1 and 3A1. Using a protein interactome mapping pipeline, we identified PHLDB2, SYNJ2 and CARMIL1 as key players in controlling these delicate dual surface dynamics of BTN2A1 and 3A1 during early transformation. This mode of action allowed Vγ9Vδ2TCR T cells to control tumorsin vitroand in vivo, emphasizing the crucial role of these molecules from early mutagenesis, to advanced cancer stages, and highlighting the therapeutic potential of a Vγ9Vδ2TCR.
Quiescent neural stem cells transiently become ‘neurons’ to coordinate reactivation
Authors: Gherghina Laura-Yvonne , Tang Jocelyn L.Y. , Brand Andrea H. 
Published: November 2024

AbstractReactivation of quiescent neural stem cells (qNSCs) is a coordinated process that generates new neurons and glia. Here, we show that during development reactivation follows a hierarchical sequence, whereby anteriorly located qNSCs control the reactivation of more posterior qNSCs in the central nervous system (CNS). Electrical communication between qNSCs and neurons enables this precise spatial and temporal control of reactivation throughout the entire span of the CNS. Using single-cell RNA-seq we discovered that, remarkably, qNSCs switch on a host of neuronal genes while maintaining a stem cell identity. This transient mixed identity is specific to qNSCs, as neuronal genes are turned off after stem cells resume proliferation. Our results uncover long-range communication between qNSCs to coordinate reactivation, enabled by a transient ‘stem cell-neuron’ fate.
Revealing complex relationships between sex, individuals’ phenotype variation and social signalling in foraging strategies
Authors: Leitão Ana V. , Funghi Caterina , Mota Paulo G. 
Published: November 2024

AbstractIn social living animals, individuals typically use two main strategies to find food: either by exploiting social information (scrounger) or relying on personal knowledge (producer). These tactics are often linked to different life-history strategies. Access to foraging patches in hierarchical social groups may constrain the use of the producer-scrounger strategies, selecting for colour ornaments to act as status badges. In sexual dimorphic species, males and females may exhibit distinct life-history strategies, with females often lacking a clear badge-of-status and occupying subordinate roles. Here we address the question of how differences in social signalling and personality influence foraging behaviour and the individual’s decision to play producer or scrounger, using males and females European serins,Serinus serinus.Specifically, we analysed how individual traits such as sex, plumage colouration, and boldness, relate with foraging strategies in both solitary and social contexts. In solitary contexts, colourful individuals, regardless of sex, were faster to find food, as were bolder males and shyer females. In social contexts, less colourful males and more colourful females adopted the producer strategy, while males’ foraging ability was influenced by their companion’s boldness. Our results reveal that personality and colour differences are linked to social foraging tactics in serins in a sex-dependent manner, highlighting the adaptive value of individual traits in both sexes, and their potential implications for social evolution.
Alcohol Withdrawal Alters the Inhibitory Landscape of the Prelimbic Cortex in an Interneuron- and Sex-specific Manner
Authors: Quadir Sema G , Danyal Zaidi S. , Cone Meredith G , Patel Sachin 
Published: November 2024

ABSTRACTAlcohol use disorder (AUD) is highly prevalent and associated with substantial morbidity and high mortality among substance use disorders. While there are currently three FDA-approved medications for treating AUDs, none specifically target the withdrawal/negative affect stage of AUD, underscoring the need to understand the underlying neurobiology during this critical stage of the addiction cycle. One key region involved in alcohol withdrawal and negative affect is the prelimbic cortex, a subregion of the medial prefrontal cortex. While previous studies have examined alcohol-related adaptations in prefrontal cortical principal glutamatergic neurons, here we used male and female PV:Ai14, SOM:Ai14 and VIP:Ai14 mice to examine synaptic adaptations in all three major classes of prelimbic cortex interneurons following 72 hour withdrawal from a continuous access to two bottle choice model of EtOH drinking in male and female mice. We found that alcohol withdrawal increased excitability of prelimbic PV interneurons in males, but decreased excitability in prelimbic VIP interneurons in females. Additionally, alcohol withdrawal reduced GABA release onto PV interneurons in males while increasing glutamate release onto VIP interneurons in females. In SOM interneurons, alcohol withdrawal had no effect on excitability, but decreased glutamate release onto SOM interneurons in males. Together, our studies identified sex-specific alcohol withdrawal-induced synaptic plasticity in three different types of interneurons and could provide insight into the cellular substrates of negative affective states associated with alcohol withdrawal.