bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation of an Occupational Sun Safety Intervention
Authors: Buller David B. , Buller Mary Klein , Meenan Richard , Cutter Gary R. , Berteletti Julia , Henry Kimberly L. , Kinsey Alishia , Adjei Irene , Chirico Noah
Published: October 2024

Objective

Two methods for scaling up an evidence-based occupational sun protection program were compared.

Methods

Regional districts (n = 138) in 21 state Departments of Transportation throughout the United States were randomized to receive the Go Sun Smart at Work program via in-person or digital scalability methods in 2019–2022 in 1:2 ratio. Managers completed pretest and posttest surveys and employees completed posttest surveys. Because of the COVID pandemic, only posttest measures were analyzed (n = 255 managers; n = 1387 employees).

Results

After scale-up, more employees reported training (b = 0.381, P = 0.021) and communication (b = 0.112, P = 0.049) at workplaces in in-person rather than digital strategy. There were no differences in managers’ reports of sun protection training, communication, or actions by scalability method (P > 0.05).

Conclusions

Occupational sun protection was implemented during program scale up and employees recalled training/communication more in the in-person than digital strategy.
Mining the CRBN Target Space Redefines Rules for Molecular Glue-induced Neosubstrate Recognition
Authors: Petzold Georg , Gainza Pablo , Annunziato Stefano , Lamberto Ilaria , Trenh Peter , McAllister Laura , Demarco Bradley , Schwander Laura , Bunker Richard D. , Zlotosch Mary , SriRamaratnam Rohitha , Gilberto Samuel , Langousis Gerasimos , Donckele Etienne J. , Quan Chao , Strande Vaik , Donatis Gian Marco De , Alabi Shanique B. , Alers Jessica , Matysik Michelle , Staehly Camille , Dubois Aurélie , Osmont Arnaud , Garskovas Mackenzie , Lyon David , Wiedmer Lars , Oleinikovas Vladimiras , Lieberherr Raphael , Rubin Nooreen T. , Lam Daniel T. , Widlund Nina Ilic , Ritzén Andreas , Caceres Ramon Miguel , Vigil Dominico , Tsai Jennifer , Wallace Owen , Peluso Marisa , Sadok Amine , Paterson Alison M. , Zarayskiy Vladislav , Fasching Bernhard , Bonenfant Debora , Warmuth Markus , Castle John , Townson Sharon A.
Published: October 2024

The CRL4CRBNubiquitin ligase is leveraged by molecular glue degraders, small molecules that reprogram ligase specificity to induce degradation of clinically relevant neosubstrate proteins. Known CRBN neosubstrates share a generalizable β-hairpin G-loop recognition motif, yet systematic exploration of the CRBN target landscape is still pending. Through computational mining of the human proteome using structure-based approaches, we predict over 1,400 CRBN-compatible β-hairpin G-loop proteins across diverse target classes, identify novel mechanisms of neosubstrate recognition through structurally differentiated helical motifs and molecular surface mimicry, and validate 22 representative neosubstrates with clinical implications. This work broadens the CRBN target space, redefines rules for neosubstrate recognition and establishes a platform for the elimination of challenging drug targets by repurposing CRL4CRBNthrough next-generation molecular glue degraders.
Fluorescent-based sex-separation technique in major invasive crop pest,Drosophila suzukii
Authors: Liu Junru , Rayes Danny , Yang Minzhe , Akbari Omar S.
Published: October 2024

Insect population biocontrol methods such as the sterile insect technique (SIT), represent promising alternatives to traditional pesticide-based control applications. To use these strategies efficiently requires scalable sex separation techniques which are currently lacking inDrosophila suzukii, a prominent crop pest species. Having previously characterized a fluorescence-based sex-sorting technique in other pests, termed SEPARATOR (SexingElementProduced byAlternativeRNA-splicing ofA TransgenicObservableReporter), here we explore its potential applicability toDrosophila suzukii. Here, we engineer several strains ofDrosophila suzukiiencoding SEPARATOR constructs that allow for efficient sex selection in early larval stages.
A Combined Computational Fluid Dynamics Modeling and Geometric Morphometrics Methods Approach to Quantifying Hemodynamic and Anatomical Features of Embryonic Chick Heart Anatomies Reconstructed from Light Sheet Fluorescence Microscopy Imaging
Authors: Giesbrecht Kirsten , Rossi Simone , Liu Sophie , Mukherjee Shourya , Bressan Michael , Griffith Boyce
Published: October 2024

Although congenital heart defects occur in approximately 1% of newborns in the US annually, their pathogenesis remains largely unknown. Less than a third of congenital heart defects are traced a known genetic or environmental cause. It has been demonstrated that hemodynamic forces such as wall shear stress are critical for heart development. However, measuring these hemodynamic factorsin vivois infeasible due to physical limitations, such as the small size and constant motion of the embryonic heart. An alternative approach is to recapitulate the hemodynamic environment by simulating blood flow and calculating the resulting hemodynamic forces through computational fluid dynamics modeling. We use computational fluid dynamics modeling to quantify hemodynamics in a cohort of cell-accurate embryonic chick heart anatomies reconstructed using light sheet fluorescent microscopy. Additionally, we perform a quantitative analysis on geometric features using geometric morphometric methods. Together, the high-resolution but accessible imaging technique of light sheet fluorescence microscopy to reconstruct the anatomies paired with computational fluid dynamics modeling and geometric morphometrics methods produces a fast and accessible pipeline for quantitative hemodynamic and anatomical analysis in embryonic heart development.
Deep Learning enabled discovery of kinase drug targets in Pharos
Authors: Halász Ádám M. , Mathias Stephen L. , Das Srinjoy , Edwards Jeremy S.
Published: October 2024

Abstract

We use machine learning with standardized molecular structure and gene ontology data to predict ligand interactions for a set of human kinases. We realize this by leveraging information from the TCRD / Pharos database, developed and maintained within the Illuminating the Druggable Genome (IDG) project.

Pharos collects relevant biochemical and clinically relevant information of a large set of biologically important (human) proteins from publicly available sources, including scientific publications as well as specialized databases. The 635 kinases listed in Pharos are classified into levels reflecting the relative amount and type of accumulated information. Importantly, molecular structure and Gene Ontology annotations are available for the entire set, but only 455 of the kinases have recorded ligand affinity data.

We developed a deep neural network-based framework to predict the ligand affinity profile for kinases using generally available information (molecular structure and Gene Ontology annotations) as input. The input data is organized into a 2,770 – dimensional vector with binary entries. The output data are predicted affinity values for interactions between the respective kinase and possible ligands.

To address the very large number of possible ligands (58,800) and the sparsity of available binding data, we organized the ligands into 5,275 clusters based on structural similarity measures. Our model framework is trained to predict likely interactions between kinases and these ligand clusters.

We aim to identify sets of likely ligand partners associated with high predicted relative affinities for a given kinase. We measure performance by evaluating the efficiency in identifying known ligand partners for documented kinases that were not included in the training data. Our results indicate that our model framework can identify sets of ligands that will contain a significant fraction of the correct (known) ligand partners.
BioFunctional: A Comprehensive App for Interpreting and Visualizing Functional Analysis of KEGG Pathways and Gene Ontologies
Authors: Rodriguez Alejandro , Monleon Getino Antonio
Published: October 2024

A comprehensive application designed for the interpretation and visualization of the functional analysis related to KEGG pathways and gene ontologies gives researchers and specialists a tool to get detailed functional information about their data, specifically going deep into biological pathways and gene functions information. By using a variety of techniques and libraries, such as Shiny, htrr, dplyr, tibble, and rvest, we have developed an application that provides a well-designed user-oriented interface with all the facilities to assess their data and start analyzing it directly from scratch through a few steps.

The software allows an exhaustive exploration of KEGG pathways and Gene Ontologies, facilitating the analysis of complex biological processes. To achieve this, functions described in the scripts integrate data manipulation methods and web scraping techniques to extract the necessary information from online official databases, Kyoto Encyclopedia of Genes and Genomes (KEGG) and QuickGo. Furthermore, those functions are computed by parallel processing, resulting in efficient petitions to the database servers and allowing the user to get quick results from a large dataset.

A crucial feature of BioFunctional is its ability to obtain ancestral information for KEGG pathways and gene ontologies, using the techniques described above. This makes it easier to understand the hierarchy of these ontologies and how each sample in a dataset is classified within them, offering users a way to study the dataset at different taxonomic levels directly from the raw data. Additionally, the app implements the capability to create interactive networks, representing all experimental data to visualize the relationships between groups and ontologies without neglecting the established classification. This is a primary tool for understanding the meaning of the relationships observed within the displayed system.

Key features of Biofunctional include

Interactive visualization: Create and explore networks to visualize relationships between groups and ontologies.

Hierarchical analysis: Trace ancestral information for KEGG pathways and Gene Ontologies to understand hierarchical classifications.

Efficient processing: Employ parallel processing for rapid data analysis, even with large datasets.

Intuitive interface: A user-friendly design simplifies data exploration and analysis.

Due to these attributes, the software represents a valuable tool for analysts involved in the study of KEGG pathways and Gene Ontologies. By providing an intuitive interface with advanced data processing techniques, it empowers researchers to unravel the intricacies of biological functions and gain insights into the relationships between genes or molecular components.

Supplementary information

https://github.com/alexrodriguezmena/BIOFunctional
Exploration of the Metabolic Potential of the Corallococcus Genus: A Rich Source of Secondary Metabolites, and CAZymes
Authors: Hossain Md. Saddam , Tuli Shanjana Rahman , Fatima Nigar , Tanim Md. Tauhidul Islam , Hashem Abu
Published: October 2024

Different secondary metabolites take on important roles. They can also transport metals, function as sexual hormones, facilitate harmonious coexistence of microbes and living beings, and induce differentiation, besides being used as competitive weapons against other bacteria, fungi, amoebae, plants, insects, and large animals. Progress in next-generation sequencing methods, together with microbial genome sequencing, has unveiled a wealth of natural products (NPs) with yet-untapped potential. Genome mining of Corallococcus species and C. exiguus subspecies that can make secondary metabolites that are clinically important has not been studied very much. The goal of this study is to look into Corallococcus genomes' biosynthetic gene clusters (BGCs) and carbohydrate-active enzyme gene clusters. We fully characterize BGCs from Corallococcus reference genome sequences that are publicly available using bioinformatic tools in addition to phylogenetic and genomic comparisons. Our results show that there is a huge range of BGCs in different Corallococcus genomes, but the species or subspecies level affects the ability to make NPs. Additionally, we investigated unknown and less comparable BGCs at the species level and found that C. llansteffanensis has more potential as a reservoir of new secondary metabolites. These insights will pave the way for the algorithmic identification of species- and subspecies-specific pathways for NP development. Keywords: Coralloccus; Genome Mining; Secondary Metabolites; Antimicrobial Peptides; Carbohydrate-Active Enzymes (CAZymes);
Evidence that the cell glycocalyx envelops respiratory syncytial virus (RSV) particles that form on the surface of RSV-infected human airway cells
Authors: Lai Soak Kuan , Lee Zhi Qi , Tan Trina Isabel , Tan Boon Huan , Sugrue Richard J
Published: October 2024

We examined how respiratory syncytial virus (RSV) particles circumvent the overlying glycocalyx on virus-infected A549 cells. The glycocalyx was detected using the lectin WGA-AL488 probe, and the antibodies anti-HS and anti-syndecan-4 that detect heparin sulphate (HS) and the syndecan-4 protein (SYND4) respectively. Imaging of RSV-infected cells provided evidence that the glycocalyx envelopes the virus filaments as they form, and that components of the glycocalyx such as HS moieties and SYND4 are displayed on the surface of the mature virus filaments. Using recombinant expression of the G protein we also demonstrated that the G protein was trafficked into pre-existing filamentous cellular structures with a well-defined glycocalyx, suggesting that the glycocalyx is maintained at the site of virus particle assembly. These data provide evidence that during RSV particle assembly the virus filaments become enveloped by the glycocalyx, and that the glycocalyx should be considered as a structural component of RSV particles.
Reproductive experience drives changes in behavior and physiology in male California mice (Peromyscus californicus)
Authors: Colt Maria E. , Agarwal Priyanka , Kolb David , Glasper Erica R. , Fisher Heidi S.
Published: October 2024

Paternal experience improves memory and reduces anxiety-like behavior in males, but it is unclear whether these changes are due to mating, siring offspring, or caregiving behavior. Likewise, paternal males have larger testes, a measure of sperm production, but again, the effects of siring and caregiving experience are difficult to disentangle. We examined behavioral and physiological outcomes in three groups of male mice: 1) virgins, 2) males paired with sterile females (‘non-fathers’), and 3) experienced fathers (Experiment 1). Compared to virgins and non-fathers, experienced fathers exhibited increased recognition memory (novel object recognition) and decreased anxiety-like behavior (elevated plus maze). Virgin males, however, had smaller testes and fewer sperm compared to non-fathers. We then compared the same traits in three additional groups of male mice: 1) non-fathers, 2) non-fathers with experience caring for unrelated pups (‘pup-sensitized non-fathers’), and 3) first-time fathers, to determine whether the behavioral and physiological observations in Experiment 1 were due to siring offspring or caregiving, and how rapidly these changes occur (Experiment 2). Recognition memory and anxiety-like behavior did not differ among these three groups, suggesting that caring for a single litter does not recapitulate the behavioral changes observed in experienced fathers (Experiment 1). Despite equal mating opportunity, we observed larger testes in first-time fathers compared to non-fathers, suggesting that investment in sperm production may be more plastic than behavioral changes. Finally, we compared pup interactions in pup-sensitized non-fathers and first-time fathers. While pup-sensitized non-fathers were slower to approach pups than first-time fathers, they spent more time grooming pups, whereas first-time fathers invested more time in nest building, suggesting different caregiving behaviors in pup-sensitized males and biological fathers. Taken together, our study revealed that mating, siring, and caregiving experience contributes to changes in memory, anxiety-like behavior, and reproductive investment in males of a biparental species.
Torsion-Induced Traumatic Optic Neuropathy (TITON): A Physiologically Relevant Animal Model of Traumatic Optic Neuropathy
Authors: Ryan Annie K. , Asemota Brooke I. , Heisler-Taylor Tyler , Mello Claire , Rodriguez Luis , Sponsel William E. , Racine Julie , Rex Tonia S. , Glickman Randolph D. , Reilly Matthew A.
Published: October 2024

Traumatic optic neuropathy (TON) is a common cause of irreversible blindness following head injury. TON is characterized by axon damage in the optic nerve followed by retinal ganglion cell death in the days and weeks following injury. At present, no therapeutic or surgical approach has been found to offer any benefit beyond observation alone. This is due in part to the lack of translational animal models suitable for understanding mechanisms and evaluating candidate treatments. In this study, we developed a rat model of TON in which the eye is rapidly rotated, inflicting mechanical stress on the optic nerve and leading to significant visual deficits. These functional deficits were thoroughly characterized up to one week after injury using electrophysiology and immunohistochemistry. The photopic negative response (PhNR) of the light adapted full field electroretinogram (LA ffERG) was significantly altered following injury. This correlated with increased biomarkers of retinal stress, axon disruption, and cell death. Together, this evidence suggests the utility of our model for mimicking clinically relevant TON and that the PhNR may be an early diagnostic for TON. Future studies will utilize this animal model for evaluation of candidate treatments.
An atlas of conserved transcription factor binding sites reveals the cell type-resolved gene regulatory landscape of flowering plants
Authors: Baumgart Leo A , Morales-Cruz Abraham , Greenblum Sharon I , Wang Peng , Zhang Yu , Yang Lin , Chen Cindy , Dilworth David J , Garretson Alexis C , Grosjean Nicolas , He Guifen , Savage Emily , Yoshinaga Yuko , Blaby Ian K , Daum Chris G , O’Malley Ronan C
Published: October 2024

Transcription factors (TFs) play a central role in regulating gene expression, a process fundamental to cellular function. Characterizing transcription factor binding sites (TFBSs) is essential for understanding TF functions and identifying TF target genes, but many predicted TFBSs lack clear biological significance. We generated an atlas of TFBSs across ten flowering plants and demonstrated that conserved TFBSs are strongly enriched for genomic and epigenomic signatures of functional regulatory elements. We uncovered conserved properties of TFBSs, including TF family-specific clustering of binding sites in distinct promoter and gene body locations. By integrating this atlas with single nuclei RNA and chromatin profiles, we elucidated conserved TF activity underlying development and stress responses and annotated key cell type-specific regulatory pathways. Finally, we found that TF ortholog binding specificity is preserved over long evolutionary times, suggesting that divergence of regulatory sequences, rather than TFs, is a primary driver of regulatory evolution.
Rational design of peak calling parameters for TIP-seq based on pA-Tn5 insertion patterns improves predictive power
Authors: Roberts Thomas , Dash Hiranyamaya , Rönkkö Teemu K. E. , Weinert Maria , Skene Nathan
Published: October 2024

Epigenomic profiling provides insights into the regulatory mechanisms that govern gene expression. At a fundamental level, these mechanisms are determined by proteins that bind the DNA or modify the chromatin. Techniques such as ChIP-seq and CUT&Tag have been instrumental in mapping the binding sites of such proteins across the genome. Recent advances have led to the development of TIP-seq, a highly sensitive method devised to increase the number of unique reads per sample. Its design results in novel library features, which have not yet been explored with comparative analytics. Through the extensive assessment of bioinformatics tools and parameters we have developed an analysis pipeline that is ideally suited for TIP-seq data, including linear deduplication, read prioritisation and read shifting. Using transcription factor binding profiles (TFs), we show that our optimised pipeline greatly reduces the width of peaks to below 50% and more precisely aligns the peak summit with known motifs. A tutorial of the optimised peak calling is available on GitHub athttps://github.com/neurogenomics/peak_calling_tutorial.git. Our methodological advancement substantially improves TIP-seq data quality, and the thoughtful design of analysis parameters is widely applicable to all pA-Tn5 based profiling assays.
Basic fibroblast growth factor helps protect facial nerve cells in a freeze-induced paralysis model
Authors: Iwata Shinji , Yamada Hiroyuki , Teraoka Masato , Tanaka Takemichi , Kimura Takuya , Joko Tomonori , Tabata Yasuhiko , Wakisaka Hiroyuki , Hato Naohito
Published: October 2024

Severe axonal damage in the peripheral nerves results in retrograde degeneration towards the central side, leading to neuronal cell death, eventually resulting in incomplete axonal regeneration and functional recovery. Therefore, it is necessary to evaluate the facial nerve nucleus in models of facial paralysis and investigate the efficacy of treatments, to identify treatment options for severe paralysis. Consequently, we aimed to examine the percentage of facial nerve cell reduction and the extent to which intratympanic administration of a basic fibroblast growth factor (bFGF) inhibits neuronal cell death in a model of severe facial paralysis. A severe facial paralysis model was induced in Hartley guinea pigs by freezing the facial canal. Animals were divided into two groups: one group was treated with gelatin hydrogel impregnated with bFGF and the other was treated with saline. Facial movement scoring, electrophysiological testing, and histological assessment of facial neurons were performed at different postoperative time points. The freezing-induced facial paralysis model showed a facial neuronal cell death rate of 29.0%; however, bFGF administration reduced neuronal cell death to 15.8%. Facial movement scores also demonstrated improvement in the bFGF group compared with those in the control group. Intratympanic bFGF administration has a protective effect on facial neurons in a model of severe facial paralysis. These findings suggest a potential therapeutic approach for treating patients with refractory facial paralysis. Further studies are required to explore the clinical applicability of this treatment.
Effects of feeding water hyacinth (Eichhornia crassipes) fodder with or without commercial concentrate on zoo-technical performance and profitability in tropical goats and sheep
Authors: Fanta Yared , Kechero Yisehak , Yemane Nebiyu
Published: October 2024

The utilization of unconventional feed resources, such as water hyacinth is an effective strategy to address feed shortages in tropical and subtropical regions, particularly where access to conventional feeds is limited. In this study, tropical sheep (Doyogena rams) and goats (Woyito-Guji bucks) fed diets containing different amounts of WH were examined for their zoo-technical performance and profitability sing a 2 × 4 × 4 randomized crossover design with two animal species, four nutritional treatments, and four feeding intervals. The dietary treatments consisted of 50% hay + 0% WH + 50% commercial concentrate (CC, T1), 50% hay + 12.5% WH + 37.5% CC (T2), 50% hay + 25% WH + 25% CC (T3), and 50% hay + 37.5% WH + 12.5% CC (T4). The findings showed that compared to goats, sheep had the highest energy and nutrient intake (P<0.001), nutrient digestibility (P<0.001), average daily gain (ADG, g/day), and body weight change (BWC (kg) (P<0.05). Regarding energy and nutritional intake, there was a substantial difference (P < 0.001) between treatment groups for both animal species, with the exception of goats’ consumption of DM, OM, CHO, GE, and ADL (P <0.05). Likewise, significant differences existed between treatment groups for nutritional digestibility, ADG, BWC, and FCE for both species (P <0.001). Moreover, significant interactions (P < 0.005) were seen in all energy and nutrient intake parameters between species and treatment. Furthermore, in tropical sheep and goat breeds, water hyacinth can replace up to 37.5% of the commercial concentrate used for growth and fattening, but it has a major comparative effect on sheep. Feed prices for the T4 group fed sheep and goats were 37.2% and 36.8% lower, respectively, than for the T1 group. Therefore, farmers in the tropics who cannot afford commercial concentrates can still benefit economically by using the dry biomass of water hyacinth in their diet, either with or without it.
Gut Bacteria Metabolize Natural and Synthetic Steroid Hormones via the Reductive OsrABC Pathway
Authors: Jacoby Christian , Scorza Kaylie , Ecker Lia , McMillin Mary , Ramaswamy Ramanujam , Sundararajan Anitha , Sidebottom Ashley M. , Lin Huaiying , Dufault-Thompson Keith , Hall Brantley , Jiang Xiaofang , Light Samuel H.
Published: October 2024

Steroid hormone metabolism by the gut microbiome has multiple implications for mammalian physiology, but the underlying mechanisms and broader significance of this activity remains largely unknown. Here, we isolate a novel human gut bacterium,Clostridium steroidoreducensTstrain HCS.1, that reduces cortisol, progesterone, testosterone, and related steroid hormones to 3β,5β-tetrahydrosteroid products. Through transcriptomics and heterologous enzyme profiling, we identify and biochemically characterize theC. steroidoreducensOsrABC reductive steroid hormone pathway. OsrA is a 3-oxo-Δ1-steroid hormone reductase that selectively targets the Δ1-bond present in synthetic steroid hormones, including the anti-inflammatory corticosteroids prednisolone and dexamethasone. OsrB is a promiscuous 3-oxo-Δ4-steroid hormone reductase that converts steroid hormones to 5β-dihydrosteroid intermediates. OsrC is a 3-oxo-5β-steroid hormone oxidoreductase that reduces 5β-intermediates to 3β,5β-tetrahydro products. We find thatosrAandosrBhomologs predict steroid hormone reductase activity in diverse gut bacteria and are enriched in Crohn’s disease fecal metagenomes. These studies thus identify the basis of reductive steroid hormone metabolism in the gut and establish a link between inflammatory disease and microbial enzymes that deplete anti-inflammatory corticosteroids.
DNA methylation of transposons pattern aging differences across a diverse cohort of dogs from the Dog Aging Project
Authors: Mariner Blaise L. , McCoy Brianah M. , Greenier Ashlee , Brassington Layla , Slikas Elizabeth , Adjangba Christine , Marye Abbey , Harrison Benjamin R. , Bamberger Tal , Algavi Yadid , Muller Efrat , Harris Adam , Rout Emily ,   The Dog Aging Project Consortium, Avery Anne , Borenstein Elhanan , Promislow Daniel , Snyder-Mackler Noah
Published: October 2024

Within a species, larger individuals often have shorter lives and higher rates of age-related disease. Despite this well-known link, we still know little about underlying age-related epigenetic differences, which could help us better understand inter-individual variation in aging and the etiology, onset, and progression of age-associated disease. Dogs exhibit this negative correlation between size, health, and longevity and thus represent an excellent system in which to test the underlying mechanisms. Here, we quantified genome-wide DNA methylation in a cohort of 864 dogs in the Dog Aging Project. Age strongly patterned the dog epigenome, with the majority (66% of age-associated loci) of regions associating age-related loss of methylation. These age effects were non-randomly distributed in the genome and differed depending on genomic context. We found the LINE1 (long interspersed elements) class of TEs (transposable elements) were the most frequently hypomethylated with age (FDR < 0.05, 40% of all LINE1 regions). This LINE1 pattern differed in magnitude across breeds of different sizes– the largest dogs lost 0.26% more LINE1 methylation per year than the smallest dogs. This suggests that epigenetic regulation of TEs, particularly LINE1s, may contribute to accelerated age and disease phenotypes within a species. Since our study focused on the methylome of immune cells, we looked at LINE1 methylation changes in golden retrievers, a breed highly susceptible to hematopoietic cancers, and found they have accelerated age-related LINE1 hypomethylation compared to other breeds. We also found many of the LINE1s hypomethylated with age are located on the X chromosome and are, when considering X chromosome inactivation, counter-intuitively more methylated in males. These results have revealed the demethylation of LINE1 transposons as a potential driver of intra-species, demographic-dependent aging variation.
Metabolomic profiles of stony coral species from the Dry Tortugas National Park display inter- and intraspecies variation
Authors: Deutsch Jessica M. , Demko Alyssa M. , Jaiyesimi Olakunle A. , Foster Gabriel , Kindler Adelaide , Pitts Kelly A. , Vekich Tessa , Williams Gareth , Walker Brian K. , Paul Valerie J. , Garg Neha
Published: October 2024

Coral reefs are experiencing unprecedented loss in coral cover due to increased incidence of disease and bleaching events. Thus, understanding mechanisms of disease susceptibility and resilience, which vary by species, is important. In this regard, untargeted metabolomics serves as an important hypothesis-building tool enabling delineation of molecular factors underlying disease susceptibility or resilience. In this study, we characterize metabolomes of four species of visually healthy stony corals, includingMeandrina meandrites,Orbicella faveolata,Colpophyllia natans, andMontastraea cavernosa, collected at least a year before stony coral tissue loss disease reached the Dry Tortugas, Florida and demonstrate that both symbiont and host-derived biochemical pathways vary by species. Metabolomes ofMeandrina meandritesdisplayed minimal intraspecies variability and highest biological activity against coral pathogens when compared to other species in this study. Application of advanced metabolite annotation methods enabled delineation of several pathways underlying interspecies variability. Specifically, endosymbiont-derived vitamin E family compounds, betaine lipids, and host-derived acylcarnitines were among the top predictors of interspecies variability. Since several metabolite features that contributed to inter- and intraspecies variation are synthesized by the endosymbiotic Symbiodiniaceae, which could be a major source of these compounds in corals, our data will guide further investigations into these Symbiodiniaceae-derived pathways.

Importance.

Previous research profiling gene expression, proteins, and metabolites produced during thermal stress has reported the importance of endosymbiont-derived pathways in coral bleaching resistance. However, our understanding of interspecies variation in these pathways among healthy corals and their role in diseases is limited. We surveyed the metabolomes of four species of healthy corals with differing susceptibilities to the devastating stony coral tissue loss disease and applied advanced annotation approaches in untargeted metabolomics to determine the interspecies variation in host and endosymbiont-derived pathways. Using this approach, we propose the survey of immune markers such as vitamin E family compounds, acylcarnitines, and other metabolites to infer their role in resilience to coral diseases. As time-resolved multi-omics datasets are generated for disease-impacted corals, our approach and findings will be valuable in providing insight into the mechanisms of disease resistance.
Genome of the enigmatic watering-pot shell reveals adaptations of a living suction anchor
Authors: Sigwart Julia D , Wong Nur Leena W.S. , González Vanessa Liz , Machado Fabrizio Marcondes , Greve Carola , Schell Tilman , Chen Zeyuan
Published: October 2024

The watering pot shells have been rightly called “the weirdest bivalves” for their highly modified body plan and fused tubular shell that resemble the spout of a watering can. This adventitious tube has defied rational explanation as an adaptive pathway and yet arose twice convergently. We present the first genome for the clade Anomalodesmata: an annotated chromosome-scale genome ofVerpa penis(Linnaeus, 1758). The first watering pot shell ever described ranges across southeast Asia but is nonetheless extremely rare and has never previously been sequenced. The assembly length of 507 Mb, with a contig N50 of 5.33 Mb, has 96.5% of sequences anchored onto 19 pseudochromosomes. Contrary to expectations from such a highly modified body plan, there is no evidence of chromosome reduction compared to the ancestral condition of heterodont bivalves (1N=19). A new hypothesis based on analysis of the living animals and literature explains the adaptive significance of this body form: it is structurally optimised for vertical stability in soft sediments, with parallels to engineering principles of a suction anchor. Our study offers new insights to a long-standing mystery in molluscan body forms, and provides genomic resources that are relevant to understanding molluscan evolution, biomineralisation, and biomimetic design.
Evolutionary conserved sap peptides derived from xylem-specific peptide precursors in woody angiosperms
Authors: Chen Chang-Hung , Liou Pin-Chien , Lin Chih-Ching , Kuo Shang-Che , Wu Chia-Chen , Lin Ying-Chung Jimmy , Chen Ying-Lan
Published: October 2024

Peptides act as long-distance mobile signals, transported through vascular sap to coordinate complex developmental processes. Since the tissue-specificity of peptide precursor gene expression is critical in determining peptide signaling function, we integrated vascular sap peptidomes with tissue-level transcriptomes to investigate the roles of sap peptides in two economically important woody plants,Populus trichocarpaandEucalyptus grandis. Xylem exhibited the highest ratio of tissue-specific sap peptide precursor genes. Most of the sap peptides derived from xylem-specific precursor genes ofP. trichocarpaandE. grandiswere highly conserved throughout woody species selected from different clades in angiosperms, including magnoliids, rosids and asterids in eudicots. To further explore the conservation of these peptides, we examined the sap peptidome ofCinnamomum kanehirae(camphor tree), from the ancient clade with three xylem cell types. Approximately 90% of the peptides from xylem-specific precursors that were conserved betweenP. trichocarpaandE. grandis, were also conserved in the vascular sap ofC. kanehirae, demonstrating a remarkably high conservation of these peptides across woody angiosperms. Most of the sap peptides conserved in these three woody species are also highly conserved across land plants, suggesting that these peptides may contribute to plant terrestrialization. Within the sap peptides from xylem- specific precursor genes, a total of 10 peptides were identical across all three woody plants. This substantial enrichment of xylem-specific precursor-derived peptides, along with their high conservation, suggests that these long-distance mobile peptides play a crucial role in secondary xylem development.

One sentence summary

Integration of sap peptidomic and tissue-level transcriptomic data revealed highly conserved long-distance mobile peptides derived from xylem- specific precursors across woody angiosperms.
Odorant receptors tuned to isothiocyanates inDrosophila melanogasterand their evolutionary expansion in herbivorous relatives
Authors: Matsunaga Teruyuki , Reisenman Carolina E. , Goldman-Huertas Benjamin , Rajshekar Srivarsha , Suzuki Hiromu C. , Tadres David , Wong Joshua , Louis Matthieu , Ramírez Santiago R. , Whiteman Noah K.
Published: October 2024

Plants release complex volatile compounds to attract mutualists, deter herbivores, and deceive pollinators. Here, we used herbivorous specialist flies that feed on mustard plants (Scaptomyzaspp.) and microbe-feeding species (Drosophila melanogasterandScaptomyzaspp.) to investigate how plant-derived electrophilic toxins such as isothiocyanates (ITCs) affect insects, and how flies detect these compounds through olfaction. In survival assays,D. melanogasterexposed to volatile allyl isothiocyanate (AITC), a toxin derived from many Brassicales plants, were acutely intoxicated, demonstrating the high toxicity of this volatile compound to non-specialized insects. Through single sensillum recordings (SSR) from olfactory organs and behavioral assays, we found that the Odorant receptor 42a (Or42a) is necessary for AITC detection and behavioral aversion. Comparative transcriptome and RNA FISH studies across the drosophilid genusScaptomyzarevealed lineage-specific triplication ofOr42ain the Brassicales specialists and a doubling ofOr42a-positive-olfactory sensory neurons. Heterologous expression experiments showed that Or42a paralogs in Brassicales-specialists exhibited broadened sensitivity to ITCs in a paralog-specific manner. Finally, AlphaFold2 modeling followed by site-directed mutagenesis and SSR identified two critical amino acid substitutions that conferredOr42aheighten sensitivity to Brassicales-derived ITCs. Our findings suggest that ITCs, which are toxic to most insects, can be detected and avoided by non-specialists likeD. melanogasterthrough olfaction. In Brassicales specialists, these same Ors experienced gene duplication events that resulted in an expanded sensitivity to ITC compounds. Thus, the insect’s olfactory system can rapidly adapt to toxic ecological niches provided by chemically-defended host plants through co-option of chemosensory capabilities already present in their ancestors.
A neonicotinoid pesticide causes tissue-specific gene expression changes in bumble bees
Authors: Witwicka Alicja , López-Osorio Federico , Chaudhry-Phipps Hannah , Wurm Yannick
Published: October 2024

Pesticides often harm beneficial insect pollinators, impairing their ability to navigate the environment, learn, fight off disease, and reproduce. Understanding the mechanisms behind these disorders is essential for improving pesticide risk assessments. To test whether pesticide exposure induces similar or distinct transcriptional responses across tissues, we administered field-realistic dose of the common neonicotinoid clothianidin toBombus terrestrisbumble bees. We then measured gene expression in brains, hind femurs, and Malpighian tubules. Our analyses revealed that 82% of gene expression differences were tissue-specific. Although genes associated with energy metabolism were consistently down-regulated across all tissues, pesticide exposure primarily affected core tissue functions, namely genes linked to ion transport in the brain, muscle function in the hind femur, and detoxification in Malpighian tubules. Furthermore, while the brain holds the highest abundance of pesticide target receptors, other tissues showed more substantial differences in gene expression magnitude. These findings reveal that pesticide exposure causes complex, tissue-specific effects rather than a uniform body-wide response. Our study provides a mechanistic basis for the severe effects of pesticide exposure on bees and shows how transcriptomics can help pinpoint the most affected areas and processes across the body. Accordingly focusing toxicological assays could significantly improve the precision of pesticide safety evaluations.
Raw materials and manufacturing environment as determinants of miso microbial community
Authors: Ito Kohei , Yamaguchi Marin
Published: October 2024

Miso is a Japanese traditional fermented food with soybeans, salt and kōji, and has gained attention among people for its sophisticated flavor and preservability. Koshu miso is a unique miso made by mixing two types of koji (rice and barley), and is produced primarily in Yamanashi Prefecture, Japan. We characterized the microbiota of miso products from Gomi-shoyu (Yamanashi, Japan) at three distinct fermentation stages: initial (day one), intermediate (four months), and advanced (ten months). All samples, except the ten-month miso, were fermented in wooden barrels. We collected samples from the manufacturing facility, extracted DNA, and performed high-throughput 16S rRNA sequencing to generate amplicon sequence variants (ASVs). Our analysis revealed that the genusStaphylococcusdominated across all miso samples, withMacrococcusandEnterococcusalso showing significant presence, particularly in the four-month miso. Notably,Staphylococcussequences in the miso matched those found in rice and barley koji, indicating the influence of raw ingredients on the initial microbial community. Additionally, the wooden barrels exhibited a microbial profile similar to the miso, suggesting their role in maintaining consistent fermentation conditions. These findings underscore the critical importance of both raw ingredients and manufacturing equipment in shaping the microbial composition and evolution of miso throughout the fermentation process.
A Review and Evaluation of Species Richness Estimation
Authors: Schmitz Johanna Elena , Rahmann Sven
Published: October 2024

Motivation

The statistical problem of estimating the total number of distinct species in a population (or distinct elements in a multiset), given only a small sample, occurs in various areas, ranging from the unseen species problem in ecology to estimating the diversity of immune repertoires. Accurately estimating the true richness from very small samples is challenging, in particular for highly diverse populations with many rare species. Depending on the application, different estimation strategies have been proposed that incorporate explicit or implicit assumptions about either the species distribution or about the sampling process. These methods are scattered across the literature, and an extensive overview of their assumptions, methodology and performance is currently lacking.

Results

We comprehensively review and evaluate a variety of existing methods on real and simulated data with different compositions of rare and abundant elements. Our evaluation shows that, depending on species composition, different methods provide the most accurate richness estimates. Simpler methods, like the Chao 1 and Chiu estimators, yield accurate predictions for many of the tested species compositions, but tend to underestimate the true richness for heterogeneous populations and small (containing 1% to 5% of the population) samples. When the population size is known, upsampling estimators such as PreSeq and RichnEst often yield more accurate results.

Availability and implementation

Source code for data simulation and richness estimation is available athttps://gitlab.com/rahmannlab/speciesrichness.
Non-invasive brain-machine interface control with artificial intelligence copilots
Authors: Lee Johannes Y. , Lee Sangjoon , Mishra Abhishek , Yan Xu , McMahan Brandon , Gaisford Brent , Kobashigawa Charles , Qu Mike , Xie Chang , Kao Jonathan C.
Published: October 2024

Motor brain-machine interfaces (BMIs) decode neural signals to help people with paralysis move and communicate. Even with important advances in the last two decades, BMIs face key obstacles to clinical viability. Invasive BMIs achieve proficient cursor and robotic arm control but require neurosurgery, posing significant risk to patients. Non-invasive BMIs do not have neurosurgical risk, but achieve lower performance, sometimes being prohibitively frustrating to use and preventing widespread adoption. We take a step toward breaking this performance-risk tradeoff by building performant non-invasive BMIs. The critical limitation that bounds decoder performance in non-invasive BMIs is their poor neural signal-to-noise ratio. To overcome this, we contribute (1) a novel EEG decoding approach and (2) artificial intelligence (AI) copilots that infer task goals and aid action completion. We demonstrate that with this “AI-BMI,” in tandem with a new adaptive decoding approach using a convolutional neural network (CNN) and ReFIT-like Kalman filter (KF), healthy users and a paralyzed participant can autonomously and proficiently control computer cursors and robotic arms. Using an AI copilot improves goal acquisition speed by up to 4.3×in the standard center-out 8 cursor control task and enables users to control a robotic arm to perform the sequential pick-and-place task, moving 4 randomly placed blocks to 4 randomly chosen locations. As AI copilots improve, this approach may result in clinically viable non-invasive AI-BMIs.
Identification of miR136, miR155, and miR183 in vascular calcification in human peripheral arteries
Authors: Corvec Tom Le , Burgaud Mathilde , Steenman Marja , Tesfaye Robel A , Goueffic Yann , Maurel-Desanlis Blandine , Quillard Thibaut
Published: October 2024

Objective

Vascular calcification (VC) is an independent risk factor for all-cause and cardiovascular mortality. This process contributes to atherosclerotic plaque disruption and thrombosis when close to the lumen, arterial stiffness, and limits endovascular treatment success. Vascular smooth muscle cells (VSMC) in the arterial wall play a major role in VC as they can acquire mineralizing properties when exposed to osteogenic conditions. Despite its clinical impact, there are still no dedicated therapeutic strategies targeting VC.

Design

To address this question, we used human calcified and none-calcified atherosclerotic arteries (ECLAGEN Biocollection) to screen and identify microRNA (miRs) associated with vascular calcification.

Methods

We combined non-biased miRNomic (microfluidic arrays) and transcriptomic analysis to select miR candidates and their putative target genes, with expression associated with vascular calcification and ossification. We further validated miR functional regulation and function on cell mineralization using primary human vascular SMC.

Results

Our study identified 12 miRs associated with vascular calcification in carotid and femoral arteries. Among those, we showed that miR136, miR155, and miR183 expression were regulated during VSMC mineralization and overexpression of these miRs was sufficient to promote smooth muscle cell mineralization. Cross-analysis of this miRNomic and a transcriptomic analysis led to the identification of CD73 and Smad3 pathways as putative target genes responsible for mediating miR155 pro-mineralizing function.

Conclusion

These results highlight the potential benefit of miR155 inhibition in limiting VC development in peripheral atherosclerotic arteries.

What this paper adds

Vascular calcification (VC) is an independent risk factor for all-cause and cardiovascular mortality. No pharmacological treatment is currently available. Our work using human healthy and atherosclerotic peripheral arteries allowed us to non-biasedly identify miR136, miR155, and miR183 as putative players in VC, as they associate with calcification in human atherosclerotic lesions, and are sufficient to induce vascular cell mineralizationin vitro. Among those, miR155 appeared the most important driver of osteogenesisin vitro, making it a candidate for targeting VC in patients.