bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial Phylogenetics with Continuous Data: an Application to California Bryophytes
Authors: Kling Matthew M. , González-Ramírez Ixchel S. , Carter Benjamin , Borokini Israel , Mishler Brent D.
Published: January 2025

Spatial phylogenetics is premised on the idea that species are not discrete categorical entities but instead lie on a hierarchical evolutionary continuum that contains rich biological information valuable for quantifying spatial biodiversity patterns. Yet while spatial phylogenetic approaches use quantitative information to represent phylogenetic patterns, most have continued to rely on methods that discard valuable information about spatial patterns by converting continuous variables into binary categories. This includes representing geographic ranges using binary presence-absence data, classifying statistical significance into categories, and quantifying biogeographic gradients into discrete regions. In this paper we show how a full suite of spatial phylogenetic analyses, including analyses of alpha and beta diversity, neo- and paleo-endemism, biogeographic hypothesis testing, and spatial conservation prioritization, can be implemented with “smooth” methods that never remove information content by categorizing continuous data. Our analysis focuses on the bryophytes of California, an understudied group in a global plant biodiversity hotspot. Using a time-calibrated phylogeny and species distribution models for 548 species of mosses and liverworts, we profile the evolutionary diversity, compositional turnover, and conservation value of bryophyte communities across the state. Our results highlight important patterns in the diversity of this key plant group, while our methods can serve as a model for future studies seeking to maximize the information content of spatial phylogenetic analyses.
Hamsters with long Covid exhibits a neurodegenerative signature in the brainstem
Authors: Coleon Anthony , Larrous Florence , Kergoat Lauriane , Tichit Magali , Hardy David , Obadia Thomas , Kornobis Etienne , Bourhy Hervé , de Melo Guilherme Dias
Published: January 2025

After infection with SARS-CoV-2, patients may present with one or more symptoms that appear or persist over time, including fatigue, respiratory, cardiovascular and neurological disorders. Neurological symptoms include anxiety, depression and impaired short-term memory. However, the exact underlying mechanisms of long Covid are not yet decrypted. Using the golden hamster as a model, we provide further evidence that SARS-CoV-2 is neuroinvasive and can persist in the central nervous system, as we found viral RNA and replicative virus in the brainstem after 80 days of infection. Infected hamsters presented a neurodegenerative signature in the brainstem, with overexpression of innate immunity genes, impacted dopaminergic and glutamatergic synapses, altered energy metabolism. Finally, the infected hamsters manifested persistent signs of depression and impaired short-term memory, as well as late-onset signs of anxiety, as a valuable model to study long Covid. Conclusively, we provide evidence that virus-related and neurodegenerative and immunometabolic mechanisms coexist in the brainstem of infected hamsters and contribute to the manifestation of neuropsychiatric and cognitive symptoms.

Highlights

SARS-CoV-2 infects and persists in the brainstem of intranasally-inoculated hamsters

Persistent neuropsychiatric and cognitive consequences are observed in SARS-CoV-2-infected hamsters

The brainstem present distinct transcriptome profiles in acute and in long Covid

The dopaminergic and glutamatergic systems are affected in long Covid

The SARS-CoV-2 infection affects the expression of genes related to neurodegenerative processes in acute and in long Covid
The anti-inflammatory activity of IgG requires the co-engagement of types I and II Fc receptors
Authors: Jones Andrew T. , Martynyuk Tetyana , Marino Alessandra E. , Bournazos Stylianos , Ravetch Jeffrey V.
Published: January 2025

Intravenous immunoglobulin administered at high doses has been used for decades as an effective anti-inflammatory preparation to treat a wide array of autoimmune diseases. Studies in murine models have found this activity to be dependent on 1) sialylation of the N-linked glycan on the CH2 domain of IgG, 2) the type I IgG inhibitory Fc receptor FcγRIIB, and 3) the type II Fc receptor DC-SIGN. Here, we demonstrate that the ectodomain glycan on FcγRIIB interacts with the lectin domain of DC-SIGN to form a cell surface complex, thereby enabling the binding of sialylated IgG1. We have exploited this observation to Fc-engineer sialylated IgG1 to enhance its affinity for FcγRIIB and demonstrate that the resulting molecule is at least 100-fold more potent in reducing the inflammatory sequelae of antibody or T cell mediated autoimmune diseases, providing the basis for a new class of anti-inflammatory therapeutics.
Inhibition of the metalloprotease ADAM19 as a Novel Senomorphic Strategy to Ameliorate gut permeability and senescence markers by modulating senescence-associated secretory phenotype (SASP)
Authors: Bar Sudipta , Hilsabeck Tyler A.U , Pattavina Baline , Dominguez Jose Alberto Lopez , Basisty Nathan , Bons Joanna , Watson Mark , Schilling Birgit , Campisi Judith , Kapahi Pankaj , Sharma Amit
Published: January 2025

Accumulation of DNA damage can accelerate aging through cellular senescence. Previously, we established a Drosophila model to investigate the effects of radiation-induced DNA damage on the intestine. In this model, we examined irradiation-responsive senescence in the fly intestine. Through an unbiased genome-wide association study (GWAS) utilizing 156 strains from the Drosophila Genetic Reference Panel (DGRP), we identified meltrin β (the drosophila orthologue of mammalian ADAM19) as a potential modulator of the senescence-associated secretory phenotype (SASP). Knockdown of meltrin β resulted in reduced gut permeability, DNA damage, and expression of the senescence marker β-galactosidase (SA-β-gal) in the fly gut following irradiation. Additionally, inhibition of ADAM19 in mice using batimastat-94 reduced gut permeability and inflammation in the gut. Our findings extend to human primary fibroblasts, where ADAM19 knockdown or pharmacological inhibition decreased expression of specific SASP factors and SA-β-gal. Furthermore, proteomics analysis of the secretory factor of senescent cells revealed a significant decrease in SASP factors associated with the ADAM19 cleavage site. These data suggest that ADAM19 inhibition could represent a novel senomorphic strategy.
GPCRchimeraDB: A database of chimeric G-Protein Coupled Receptors (GPCRs) to assist their design
Authors: Crauwels Charlotte , Díaz Adrián , Vranken Wim
Published: January 2025

G-Protein Coupled Receptors (GPCRs) are membrane proteins implicated in numerous diseases that have been studied for decades. However, despite their significance, many GPCRs remain poorly characterized and untargeted by drugs. Chimeric GPCRs have emerged as valuable tools for elucidating GPCR function by facilitating the identification of signaling pathways, resolving structures, and discovering novel ligands of poorly understood GPCRs. Such chimeric GPCRs are obtained by merging a well-characterized and a less-well-characterized GPCR at the intracellular loops, leveraging knowledge transfer from the well-characterized GPCR. However, despite the 170 chimeric GPCRs engineered to date, the design process remains largely trial-and-error and lacks a standardized approach. To address this gap, we introduce GPCRchimeraDB (https://www.bio2byte.be/gpcrchimeradb/), the first comprehensive database dedicated to chimeric GPCRs. It catalogs 170 chimeric receptors, identified through extensive literature review, and includes 1,758 natural GPCRs, enabling connections between chimeras and their parent receptors while facilitating the exploration of novel parent combinations. Both chimeric and natural GPCR entries are extensively described at the sequence, structural, and biophysical level through a range of visualization tools, with annotations from resources like UniProt and GPCRdb and predictions from AlphaFold, ESMFold and b2btools. Additionally, GPCRchimeraDB offers a GPCR sequence aligner and a feature comparator to investigate differences between natural and chimeric receptors as well as guidelines to support the design of novel chimeras. GPCRchimeraDB is therefore a resource to facilitate and optimize the design of new chimeras, so helping to gain insights into poorly characterized receptors and contributing to advances in GPCR therapeutic development.

Graphical Abstract
A modelling framework to estimate vector dispersal and disease spread in an important agricultural pathosystem
Authors: Preedy Katharine F. , Namara Louise Mc , Mostafiz Md Munir , Schughart Maximilian , Bramham Lawrence E. , Leybourne Daniel J.
Published: January 2025

Cereals are some of the most agriculturally important crops grown worldwide. Cereal aphids are small sap-feeding insects that infest cereals and vector devastating cereal pathogens, principally the yellow dwarf viruses, with severe infection reducing yields by 20−80%. Currently, farmers are advised to apply insecticide if a single cereal aphid is found within the crop. However, this is an oversimplification of the biology and ecology of the vector-virus system: Each aphid species can transmit a range of yellow dwarf virus species with variable efficiency, and intra-species diversity within a vector species (genotype) can influence this further. Accounting for this variation in decision-making processes has the potential to help with developing bespoke management options based on the composition of the local vector-virus population, and represents a novel avenue that could be explored to develop more sustainable management strategies. Here we describe a stage-structured model that can estimate vector dispersal and disease spread. We use data for the two main cereal aphid species and the two yellow dwarf virus species of greatest concern in Europe to examine how diversity at each level of the vector-virus system impacts disease spread. More broadly, our modelling framework represents a tool that can be used to explore vector-virus-host interactions in greater detail, and we use cereal systems as a case study. Our modelling scenarios highlight diversity at each scale as an important factor. We show that the two main vector species have contrasting dispersal patterns, and that this interacts with virus transmission efficacy to influence disease spread; genetic variation within a vector population is a key driver behind disease spread and disease risk; and for vector species that transmit multiple virus species, the specific vector-virus species combination is a key risk factor to consider.
Localized translation of cell junction mRNAs is required for epithelial cell polarity
Authors: Chin Ashley , Bergeman Jonathan , Communal Laudine , Boulais Jonathan , Mes-Masson Anne-Marie , Lécuyer Eric
Published: January 2025

Epithelial cells exhibit a highly polarized organization along their apico-basal axis, a feature that is critical to their function and frequently perturbed in cancer. One less explored process modulating epithelial cell polarity is the subcellular localization of mRNA molecules. In the present study, we report that several mRNAs encoding evolutionarily conserved epithelial polarity regulatory proteins, includingZo-1,AfdnandScrib, are localized to cell junction regions inDrosophilaepithelial tissues and human epithelial cells. Targeting of these mRNAs is coincident with the robust junctional distribution of their encoded proteins, and we demonstrate that they are locally translated at cell junction regions. To identify RNA binding proteins (RBPs) potentially implicated in junctional mRNA regulation, we performed systematic immuno-labeling with a collection of validated RBP antibodies, identifying a dozen RBPs with consistent junctional distribution patterns, several of which directly bind junctional transcripts. Strikingly, depletion of these RBP candidates, including MAGOH, a core component of the exon-junction complex (EJC), perturbed the junctional distribution and localized translation ofZo-1andScribmRNAs, as well as the junctional accumulation of their protein products. Functional disruption of MAGO, or its interaction partner Y14, inDrosophilafollicular epithelial cells perturbs the distribution of junctional transcripts and proteins. Finally, tissue microarray analysis of ovarian cancer tumor specimens revealed that expression of MAGOH and ZO-1 is positively correlated and that both proteins are potential biomarkers of good prognosis. Altogether, this work reveals that localized mRNA translation at cell junction regions is important for modulating epithelial cell polarity.

HIGHLIGHTS

Cell junction mRNA targeting is conserved between tissues and species

These mRNAs undergo localized translation at areas of cell-cell contact

A diversity of RBPs localize to cell junction regions and interact with junctional transcripts.

Disruption of junctional RBPs impacts epithelial cell polarity and localized translation

MAGOH and ZO-1 expression is correlated in ovarian tumor specimens and are potential biomarkers of good prognosis
Orthogonal RNA-regulated destabilization domains for three-color RNA imaging with minimal RNA perturbation
Authors: Pham Tien G. , Ajayi Omoyemi , Wu Jiahui
Published: January 2025

RNA-regulated destabilization domain allows live-cell imaging of single RNA. However, this method is limited to single-color RNA imaging and its long RNA tag induces destabilization of the tagged RNA. Here, we describe two orthogonal RNA-regulated destabilization domains that enable three-color mRNA imaging in living mammalian cells. One of these destabilizations can be combined with a short RNA tag (9XMS2) for single-molecule RNA imaging without perturbation of RNA stability.
High potential contribution of intercropping to soybean and maize self-sufficiency in Europe
Authors: Chen Mathilde , Guilpart Nicolas , Makowski David
Published: January 2025

The European Union is currently not self-sufficient in soybean and maize,1thus relying on imports.2According to results of fields experiments,3the simultaneous cultivation of soybeans and cereals – intercropping – could improve food self-sufficiency without increasing cultivated land, but this strategy has yet to be evaluated at the scale of the European Union. Here, we examine the potential for maize-soybean intercropping to improve the European Union’s self-sufficiency in soybean and maize without cropland expansion and by minimizing crop substitution. Our results suggest that achieving 50% (75%) soybean self-sufficiency in the European Union would require 13.1 (20.1) Mha under maize-soybean intercropping. When comparing the areas of cultivated land obtained either by growing the two species separately or together, we demonstrate that intercropping saves 27-30% of land compared with sole crops as soon as more soybean is produced in 1 ha of intercropping than in 0.5 ha of sole soybean. Ensuring European Union’s self-sufficiency in a sustainable way is a challenge requiring multiple solutions. Our results underline that intercropping is an effective strategy for improving the European Union’s soybean self-sufficiency, while satisfying maize needs and saving cultivated lands.
The role of prooxidants and antioxidants in shaping life-history and parasite tolerance inAnophelesmosquitoes
Authors: Zeferino Tiago G. , Mora Alfonso Rojas , Koella Jacob C.
Published: January 2025

Oxidative homeostasis plays important roles in physiology, for reactive oxygen species not only lead to damaging oxidative stress, but also regulate important physiological processes like immunity and longevity. ROS are therefore expected to be a key factor underlying many host-parasite interactions. We evaluated the role of the host’s oxidative status on the outcome of infection with the mosquitoAnopheles gambiaeinfected by the microsporidianVavraia culicis. To do so, we manipulated the oxidative status of the mosquitoes by feeding them early (the first four days after emergence) or late (from five days after emergence onwards) either a standard sugar source or one supplemented with a prooxidant (hydrogen peroxide) or antioxidant (vitamin C), and then measured the longevity and fecundity of uninfected and infected mosquitoes and (for infected mosquitoes) the parasite load at a given day (13 days after emergence) or when the mosquitoes died. The prooxidant generally increased longevity, but if consumed early after emergence its impact was lessened by the infection byVavraia. In contrast the antioxidant increased fecundity, and the impact was not affected by the status of infection or by the timing of consumption. Finally, early consumption of both supplements increasedVavraia’s spore load at 13 days after emergence and at death. In contrast, late consumption enhanced the parasite’s growth late in the mosquito’s life. Thus, our experiment revealed complex effects of prooxidant and antioxidant consumption, emphasising the critical role of timing and context in shaping their influence on biological traits.
Detecting Amino Acid Variants Using Next-Generation Protein Sequencing (NGPS)
Authors: Chinnaraj Mathivanan , Lin Jianan , Blacklock Kristin , Hermes Eric , Meyer Michael , Pike Douglas , Vieceli John , Chorny Ilya
Published: January 2025

Next-Generation Protein Sequencing™(NGPS™) is a single-molecule approach for characterizing protein variants, offering detailed insight into proteoforms and amino acid substitutions not easily discerned by mass spectrometry. The novel data type produced by NGPS, which is based on binding of N-terminal amino acids by fluorescently tagged recognizer proteins, requires the development of new data analysis methods and bioinformatic tools. Here, we present ProteoVue™, a comprehensive bioinformatics pipeline for Single Amino Acid Variant (SAAV) detection and quantification using the Quantum-Si Platinum®NGPS platform. ProteoVue integrates multiple analytical components, including robust pulse-calling, recognition segment detection, fluorescence dye classification, and a neural network-driven kinetic signature database for pulse duration prediction. These components feed into a scoring-based alignment and clustering framework that enables accurate variant calling within binary peptide mixtures. We demonstrate that ProteoVue recovers expected variant ratios across diverse substitution types including residues that lack direct amino acid recognizers. While some extreme cases remain challenging, the pipeline consistently captures the key kinetic features required for variant discrimination, underscoring its potential as a versatile and powerful tool for proteomic studies. As NGPS technology matures and recognizer libraries expand, ProteoVue provides a foundation for increasingly refined variant analysis in basic research, biomarker discovery, and clinical applications.
OPUS-GO: An interpretable protein/RNA sequence annotation framework based on biological language model
Authors: Xu Gang , Lv Ying , Zhang Ruoxi , Xia Xinyuan , Wang Qinghua , Ma Jianpeng
Published: January 2025

Accurate annotation of protein and RNA sequences is essential for understanding their structural and functional attributes. However, due to the relative ease of obtaining whole sequence-level annotations compared to residue-level annotations, existing biological language model (BLM)-based methods often prioritize enhancing sequence-level classification accuracy while neglecting residue-level interpretability. To address this, we introduce OPUS-GO, which exclusively utilizes sequence-level annotations to provide both sequence-level and residue-level classification results. In other words, OPUS-GO not only provides the sequence-level annotations but also offers the rationale behind these predictions by pinpointing their corresponding most critical residues within the sequence. Our results show that, by leveraging features derived from BLMs and our modified Multiple Instance Learning (MIL) strategy, OPUS-GO exhibits superior sequence-level classification accuracy compared to baseline methods in most downstream tasks. Furthermore, OPUS-GO demonstrates robust interpretability by accurately identifying the residues associated with the corresponding labels. Additionally, the OPUS-GO framework can be seamlessly integrated into any language model, enhancing both accuracy and interpretability for their downstream tasks.
Transitory impact of subclinicalShigellainfections on biomarkers of environmental enteropathy in children under 2 years
Authors: Liakakos Haley A. , Platts-Mills James A. , Quesada Maria Garcia , Liu Jie , Houpt Eric R. , Rogawski McQuade Elizabeth T.
Published: January 2025

Clinical and subclinicalShigellainfections among children living in low- and middle-income countries (LMICs) have been associated with long-term adverse effects such as impaired linear growth. The mechanism for the impact of subclinical infections has been theorized to occur through contributions to environmental enteropathy (EE). WhileShigellahas previously been associated with biomarkers of EE at the time of infection, we evaluated whether this impact was sustained after infections, which would support EE being the mechanism for the effects ofShigellaon growth. A prospective birth cohort study of 1,715 children living in 8 different LMICs was conducted. Over the course of 24 months, monthly non-diarrheal stool samples were analyzed for subclinicalShigellainfections through quantitative PCR methods. EE was reflected by elevated concentrations of 3 fecal biomarkers: myeloperoxidase (MPO), neopterin (NEO), and alpha-1-antitrypsin (AAT). MPO concentrations were found to be significantly higher by 0.30 log(nm/mL) (95% CI: 0.23, 0.37) in the initial month ofShigelladetection among stools with subclinicalShigellainfections. After theShigellainfection, MPO concentrations declined throughout the following 6 months, and concentrations were lower by 6 months post-infection [MPO 6-month difference: -0.16 log(nm/mL) (95% CI: -0.26, -0.04)]. SubclinicalShigellainfections had no effect on NEO concentration levels within the initial month ofShigelladetection but did decrease post-infection. SubclinicalShigellainfections had no effect on AAT concentration levels until 6 months post-infection [AAT difference: -0.13 log(mg/g) (95% CI: - 0.24, -0.03)]. These findings did not differ by antibiotic use around time of index infection. The impact ofShigellaon biomarkers of EE was not sustained, suggesting the negative association betweenShigellaand growth could be explained by the accumulation of time-limited rather than persistent effects on inflammation.
Architectural singularities in wild Coffea (Baracoffea) species: integrated morphological perspectives for climate-resilient coffee cultivation
Authors: Bezandry Rickarlos , Guyot Romain , Ranarijaona Hery Lisy Tiana , Sabatier Sylvie , Vavitsara Marie Elodie , Anest Artemis
Published: January 2025

Global coffee production faces increasing threats from climate change, including rising temperatures, prolonged droughts, and spreads of diseases. Wild coffee species, notably those growthing in highly constrained environments in Madagascar, offer a critical genetic resource to address these challenges. Understanding adaptive traits allowing these species to establish into arid environments is essential to implement guid breeding strategies into create resilient coffee varieties. Here, we hypothesize that these wild Coffee species display unique traits compared to other Coffea species, reflecting adaptations to arid and seasonally dry environments. We used the architectural analysis to describe three Baracoffea species and compare them to known cultivated Coffee.

Field studies were conducted in two contrasting sites in Madagascar, focusing on three wild coffee species, natively growing into arid environments: Coffea ambongensis, C. bissetiae, and C. boinensis. Structural traits at the whole plant scale were measured across developmental stages using morphological and architectural analyses.

Our results suggest that unique traits characterize Barracoffea species, such as rhythmic growth, terminal flowering on short shoots, and species-specific developmental strategies. These findings highlight the architectural diversity of Baracoffea, identify potential key drivers of ecological adaptation and therefore highlights the potential of this group of species for breeding climate- resilient coffee varieties.
An updated proteomic analysis ofDrosophilahemolymph after bacterial infection
Authors: Rommelaere Samuel , Schüpfer Fanny , Armand Florence , Hamelin Romain , Lemaitre Bruno
Published: January 2025

Using an in-depth Mass Spectrometry based proteomics approach, we provide a comprehensivecharacterization of the hemolymphatic proteome of adult flies upon bacterial infection. We detected and quantified changes in abundance of several known immune regulators and effectors, including multiple antimicrobial peptides, peptidoglycan-binding proteins and serine proteases. Comparison to previously published transcriptomic analyses reveals a partial overlap with our dataset, indicating that many proteins released into the hemolymph upon infection may not be regulated at the transcript level. Among them, we identify a set of muscle-derived proteins released into the hemolymph upon infection. Finally, our analysis reveals that infection induces major changes in the abundance of proteins associated with mitochondrial respiration. This study uncovers a large number of previously undescribed proteins potentially involved in the immune response.
Negative selection on baboon admixture is strongest on chromosome X
Authors: Sørensen Erik F. , Hellenthal Garrett , Munch Kasper
Published: January 2025

The six admixing baboon species offer a natural experiment to study negative selection on admixture and potentially genetic incompatibility in species with divergence resembling that between anatomically modern and extinct human subspecies such as Neanderthals. We analyze 156 high-coverage genomes sampled from seven olive and four yellow baboon populations shaped by admixture in two different reticulation events. In Tanzania, olive and yellow baboons admix despite 1.3 million years of divergence. In Ethiopia, olive baboons have invaded and displaced an ancient Hamadryas-like population separated by 0.6 million years, thus mirroring the displacement of Neanderthals by modern humans. Analyzing local ancestry across whole genome, we find evidence of negative selection on minor parent ancestry in Tanzanian yellow and olive baboon populations reaching far behind the hybrid zone and in Ethiopian olive baboons. We find that evidence of selection against admixture is up to seven times stronger on the X chromosome. The proportion of minor parent ancestry is substantially higher on the X chromosome in Ethiopian olive and yellow baboon populations, which displaced the populations now representing their minor parent ancestry. This additional MPA is concentrated in a few genomic regions with high frequency. This indicates that this original ancestry was retained by negative selection on the invading ancestry, suggesting that these loci play a role in emerging reproductive barriers in the Papio as well as the Homo genus.
Identification of ketotic cattle based on milk spectroscopic characteristics: a chemometric modelling approach built upon the principles of Aquaphotomics
Authors: Giovinazzo Simone , Bisaglia Carlo , Cattaneo Tiziana M.P. , Marinoni Laura , Cabassi Giovanni , Brambilla Massimo
Published: January 2025

The early diagnosis of metabolic disorders in intensive farms, such as ketosis, allows a timely health treatment, resulting in improved animal welfare and reduced productivity and economic losses for farmers. This approach represents an opportunity for more sustainable animal production practices.

For these reasons, we developed a chemometric processing model based on GNU Octave capable of identifying milk sample categories based on the chemo-physical characteristics of their near-infrared signature. Such a characterisation relies on the innovative approach of aquaphotomics, which investigates the interaction between light and water molecules in any biological system. Aquaphotomics leverages the properties of water as a biomarker and amplifier to identify changes in the system indicative of a perturbation, such as the onset of a metabolic disorder.

The realised package allows spectral data elaborations, including preprocessing methods like the calculation of spectrum derivatives, noise removal and scatter correction techniques, as well as chemometric analysis like Principal Component Analysis (PCA), Linear Discriminant Analysis (LDA), Quadratic Discriminant Analysis (QDA), and Partial Least Squares Regression (PLSR). In this way, the code enables the identification of the most significant water bands implicated in the origin of the disease, with the potential to represent an innovative approach for monitoring the health status of animals.
Integration of spatial and single nucleus transcriptomics to map gene expression in the developing mouse kidney
Authors: Chaney Christopher P. , Fusco Alexandria N. , Grilli Elyse D. , Warshaw Jane N. , Luo Peter M. , Cleaver Ondine , Marciano Denise K. , Carroll Thomas J.
Published: January 2025

The kidney is a complex organ requiring tightly coordinated interactions between epithelial, endothelial, and mesenchymal cells during development. Congenital kidney defects can result in kidney disease and renal failure, highlighting the importance of understanding kidney formation mechanisms. Advances in RNA sequencing have revealed remarkable cellular heterogeneity, especially in the kidney stroma, though relationships between stromal, epithelial, and endothelial cells remain unclear.

This study presents a comprehensive gene expression atlas of embryonic and postnatal kidneys, integrating single-nucleus and in situ RNA sequencing data. We developed the Kidney Spatial Transcriptome Analysis Tool (KSTAT), enabling researchers to identify cell locations, predict cell-cell communication, and map gene pathway activity. KSTAT revealed significant heterogeneity among embryonic kidney pericytes, providing a critical resource for hypothesis generation and advancing knowledge of kidney development and disease.
Glandular Trichome Rupture in Tomato Plants is an Ultra-Fast & Sensitive Defense Mechanism Against Insects
Authors: Popowski Jared , Warma Lucas , Cifuentes Alicia Abarca , Bleeker Petra , Jalaal Maziyar
Published: January 2025

Trichomes, specialized hair-like structures on the surfaces of many plants, play a crucial role in defense against herbivorous insects. We investigated the biomechanics of type VI glandular trichomes in cultivated tomato (Solanum lycopersicum) and its wild relative (Solanum habrochaites). Using micropipette force sensors and high-speed imaging, we uncovered the rupture mechanics underlying gland bursting, highlighting the small forces and short time-scales involved in this process. Additionally, we observed larvae of the Western flower thrips (Frankliniella occidentalis), a major pest in tomato cultivation, inadvertently triggering trichome rupture and accumulating glandular secretions on their bodies. These findings demonstrate how rapid gland bursting and the fluid dynamics of glandular secretions act as an efficient and swift plant defense mechanism against insect herbivory.
Regulation of epigenetics and chromosome structure by human ORC2
Authors: Su Zhangli , Tian Mengxue , Shibata Etsuko , Shibata Yoshiyuki , Yang Tianyi , Wang Zhenjia , Jin Fulai , Zang Chongzhi , Dutta Anindya
Published: January 2025

The six subunit Origin Recognition Complex (ORC) is a DNA replication initiator that also promotes heterochromatinization in some species. A multi-omics study in a human cell line with mutations in three subunits of ORC, reveals that the subunits bind to DNA independent of each other rather than as part of a common six-subunit ORC. While DNA-bound ORC2 was seen to compact chromatin and attract repressive histone marks, the activation of chromatin and protection from repressive marks was seen at a large number of sites. The epigenetic changes regulate hundreds of genes, including some epigenetic regulators, adding an indirect mechanism by which ORC2 regulates epigenetics without local binding. DNA-bound ORC2 also prevents the acquisition of CTCF at focal sites in the genome to regulate chromatin loops. Thus, individual ORC subunits are major regulators, in both directions, of epigenetics, gene expression and chromosome structure, independent of the role of ORC in replication.
Termination sequence between an inducible promoter and ubiquitous chromatin opening element (UCOE) reduces gene expression leakage and silencing
Authors: Yanagi Tomoki , Phen Shean Fu , Ayala Jonah , Aydin Deniz Ece , Truong David M.
Published: January 2025

Abstract

Inducible gene expression circuits offer precise control over target gene activation, making them essential tools for direct reprogramming, where cells are guided to differentiate into specific cell types. However, stable circuit function and consistent expression of key inducible proteins are crucial for effective reprogramming, and DNA methylation-induced silencing hinders this stability. To address this issue, A2-ubiquitous chromatin opening elements (A2UCOE) have gained attention for their ability to maintain open chromatin and prevent methylation, thereby stabilizing gene expression. In this study, we aimed to forward program iPSCs into thymic epithelial cells (TECs) using a compact, all-in-one gene circuit composed of a doxycycline-inducible Tet-On system, 863-bp A2UCOE (0.9 UCOE), andFOXN1, a master transcription factor for TEC differentiation. This compact construct enables site-specific genome integration and stable inducible expression within iPSCs for renewably generating TECs. While the 0.9 UCOE promoted stable expression of constitutively expressed genes, it also caused unintendedFOXN1gene leakage, leading to unprogrammed gradual differentiation of the iPSCs. We generated A2UCOE fragments of varying lengths and found that gene leakage persisted regardless of fragment size. We tested spacer sequences between the A2UCOE and the Tet-On promoter consisting of varying AT-nucleotide content (35, 50, and 65%) and the 65% AT-rich SV40 poly-A terminator sequence and found that only the SV40 poly-A mitigated this leakage, and surprisingly, enhanced desired anti-silencing effects. These findings highlight the benefits and potential risks of using A2UCOE in iPSCs, and provides insights into a regulatory DNA architecture optimal for compact forward programming circuits for controlled iPSC differentiation.

Graphical abstract
Cross-site imputation for recovering variables without individual pooled data
Authors: Thiesmeier Robert , Madley-Dowd Paul , Orsini Nicola , Ahlqvist Viktor H.
Published: January 2025

In multi-site studies, it is common for some sites not to have recorded key variables. Although it is theoretically possible to use data from sites with recorded observations to impute the missing values, this process becomes challenging when data pooling is not feasible due to logistic or legal constraints. We therefore propose a multiple imputation approach — cross-site imputation — to recover any variables across sites without the need to pool individual-level data. The solution involves transporting predicted regression coefficients and variances from studies with observed data to impute missing variables at sites without data. The approach is illustrated in an applied example of recovering confounders across Swedish hospitals, and theoretical considerations are outlined. Given the increasing importance of multi-site studies in observational research, cross-site imputation could offer a practical approach for imputing variables that have not been recorded in some study sites.
Self-Perceived Decline in Memory and Concentration 9 and 12 months post COVID-19 infection
Authors: Ruivinho Carolina , Moniz Marta , Goes Ana Rita , Soares Patrícia , Leite Andreia ,   LOCUS group
Published: January 2025

Introduction

COVID-19 infection caused by SARS-CoV-2 has led to significant long-term health challenges, including Long COVID or Post-COVID condition, that can include symptoms such as cognitive decline, memory loss, and concentration issues. This study investigates the prevalence and risk factors of post-COVID cognitive symptoms among individuals tested for COVID-19.

Methods

A cross-sectional study was conducted in Lisbon and Tagus Valley, targeting individuals tested for COVID-19 in August 2022. Participants were selected from a random sample of 10,000 individuals. Data were collected via computer-assisted telephone interviews at 9 and 12 months post-test, covering sociodemographic details, health behaviors, pre-existing conditions, and COVID-19 symptoms. The primary outcome was the presence of at least one cognitive symptom (memory loss and/or concentration issues) at 9 and 12 months. Additionally, each symptom was assessed individually, along with a composite outcome of both symptoms concurrently.

Results

At 9 months, memory loss was reported by 24.87% of COVID-19 positive cases versus 10.20% of negatives, and concentration issues by 15.45% of positives versus 7.45% of negatives. At 12 months, memory loss prevalence was 16.67% for positives and 9.45% for negatives, while concentration issues were 9.82% for positives and 2.99% for negatives. Additionally, the prevalence of at least one cognitive symptom was 28.24% in positive cases at 9 months compared to 12.16% in negatives, and 17.81% versus 9.95% at 12 months. Female sex was significantly associated with a higher prevalence of cognitive symptoms at both time points.

Discussion

These findings underscore the enduring cognitive impact of COVID-19, with significant disparities in cognitive symptoms between COVID-19 positive and negative individuals observed at both 9 and 12 months post-infection. The higher prevalence of memory loss and concentration issues among COVID-19 positives suggests potential neurological sequelae linked to SARS-CoV-2 infection. Notably, the association of female sex with increased cognitive symptom prevalence warrants further investigation into gender-specific vulnerabilities or biological mechanisms underlying these disparities. Addressing these persistent cognitive symptoms is crucial for long-term patient management and underscores the need for targeted interventions and comprehensive post-COVID care strategies to mitigate long-lasting health implications.
The structural basis forde novoDNA methylation in chromatin
Authors: Xie Xiaoyan , Liu Minmin , Zhou X. Edward , Dykstra Michelle L. , Jones Peter A. , Worden Evan J.
Published: January 2025

De novocytosine methylation is essential for mammalian development and is deposited by DNMT3A and DNMT3B. In cells, DNA methylation occurs in the context of chromatin, where nucleosomes are connected by DNA linkers. Here, we report Cryo-EM structures of DNMT3A2/3B3 bound to di-nucleosomes with different linker lengths. We show that DNMT3A2/3B3 preferentially binds di-nucleosomes separated by short DNA linkers by inducing large-scale changes to the di-nucleosome structure, enabling each DNMT3B3 subunit to bind each nucleosome. Linker length and the position of cytosines within the linker control DNA methylation, indicating that a significant fraction of linkers in chromatin are naturally resistant to DNMT3A2/3B3 activity. Finally, DNMT3A2/3B3 scans for H3K36me2-3 modifications, explaining how H3K36 methylation simulates DNMT3A2 activity. Our structure is the first example of a DNA methyltransferase interacting with higher-order nucleosome substrates and provides new insights on how DNA methylation takes place in chromatin.
Suaeda Salsa Hyperspectral Index (SSHI) for mapping S. salsa in coastal wetlands using hyperspectral satellite imagery
Authors: zhang mengyao , Ke Yinghai , Shang Kun , Zhuo Zhaojun , Liu Han , Li Peng , Zhao Nana , Sha Jinghan , Li Jinyuan
Published: January 2025

Suaeda Salsa (S. salsa), a pioneer species with short and red-purplish plants in the intertidal zones, has significant ecological, economic, recreational and tourism values. Timely monitoring of S. salsa is crucial for understanding its dynamics and sustainable management of coastal wetlands. Hyperspectral satellite offers valuable opportunities due to its detailed spectral information. This study proposed a Suaeda Salsa Hyperspectral Index (SSHI) for S. salsa mapping based on hyperspectral satellite imagery. The SSHI was developed by considering the large within-class spectral variations of cover types at coastal wetlands, accounting for the spectral correlations in hyperspectral data, and employing dynamic band selection on a per-pixel basis to optimize the separation of S. salsa from other land covers. , where i∈[499nm, 611nm], j∈[628nm, 851nm], . We applied SSHI on ZY1-02D/E AHSI images over Yellow River Delta (YRD) and Liao River Delta (LRD), China during 2021 to 2023. Based on SSHI, a simple thresholding method and a random forest (RF) model were used to map S. salsa. Our results showed that the overall accuracies of S. salsa maps achieved 87.96%~89.43% (YRD) and 92.03%~93.36% (LRD) using thresholds, and 92.62%~94.05% (YRD) and 94.74%~94.79% (LRD) using RF. For RF, incorporating SSHI improves S. salsa producer's accuracies (user's accuracies) by 1.02%~6.85% (2.26%~6.25%) compared to those without SSHI, proving the effectiveness of SSHI. The S. salsa maps reveal notable temporal variations, reflecting the impacts of climate change and human activities. SSHI is also applicable to other hyperspectral imagery, such as GF-5B and PRISMA.
Optimizing Family Self-Efficacy Through Self-Care Guidelines To Reduce Rehospitalization Rates In Stroke Patients: A Quasi-experimental study
Authors: Putra Komang Ardidhana Nugraha , Pandin Moses Glorino Rumambo , Dewi Ni Luh Putu Ayu Ratna , Shari Alfi
Published: January 2025

Introduction

Since 2007, there has been an alarming spike in stroke cases in Indonesia, leading to an increase in rehospitalization due to complications and recurrent stroke attacks. Self-care with family support has been proven effective in supporting stroke recovery.

Objective

This study aims to assess the effectiveness of self-care guidelines to prevent rehospitalization of stroke patients on family self- efficacy.

Method

A quasi-experimental research design was used in this study. A total of 80 respondents were involved, consisting of 40 respondents in each group. Data collection was carried out using observation sheets and the General Self-Efficacy Scale (GSE).

Results

There was an increase in self-efficacy in the intervention group before and after the implementation of self-care guidelines in families caring for stroke patients with a p value <0.001.

Conclusion

The implementation of self-care guidelines is effective in increasing family self-efficacy in long-term care to prevent rehospitalization of stroke patients. Evaluation of the long-term impact of implementing guidelines on rehospitalization and quality of life of stroke patients is important to do.
KIF18A in HCC Metastasis: Dual Role in Anoikis Resistance and Chromosome Instability
Authors: Kan Changhao , Bai Weiyu , Yang Xinru , Hamdy Hayam , Yang Xianghui , Liu Xin , Lv Yan , Shen Junling , Sun Jianwei
Published: January 2025

The study explores the role of KIF18A, a gene linked to whole-genome doubling (WGD) and chromosomal instability (CIN), in the metastatic progression of hepatocellular carcinoma (HCC). We found that KIF18A is a critical link between CIN and anoikis resistance, key factors in HCC metastasis. Through the bulk-seq analysis, we identified the pressures of anoikis and CIN faced by tumor cells during HCC metastasis and identified hub genes central to this process. Our results reveal that E2F activation during HCC progression leads to the transcription of KIF18A, promoting the survival and metastasis of CIN tumors. Overexpression of KIF18A leads to longer tumor life, more micronuclei, and increased survival and metastasis through non-canonical NF-kB activation. Deletion of KIF18A stabilizes the nuclear membrane of the micronucleus, silences cGAS-STING and PI3K-AKT pathways, and inhibits classical NF-kB. The study’s limitations include the need for further animal studies to validate the findings and explore the transient activation of the cGAS-STING pathway. Additionally, future research could focus on the potential therapeutic implications of targeting KIF18A in cancer treatment.
Joint models reveal human subcortical underpinnings of choice and learning behaviour
Authors: Miletić Steven , Stevenson Niek , Bazin Pierre-Louis , Alkemade Anneke , Isherwood Scott J. S. , Trutti Anne C. , Tse Desmond H. Y. , Håberg Asta K. , Forstmann Birte U.
Published: January 2025

Decision making and learning processes together enable adaptive goal-oriented behaviour. Animal studies demonstrated the importance of subcortical regions in these cognitive processes, but the human subcortical contributions remain poorly characterised. Here, we study choice and learning processes in the human subcor-tex, using a tailored ultra-high field 7 T fMRI imaging protocol combined with joint models. Joint models provide unbiased estimates of brain-behaviour rela-tions by simultaneously including behavioural and neural data at the participant and group level. Results demonstrate relations between subcortical regions and the adjustment of decision urgency. Value-related BOLD differences were found with opposite BOLD polarity in different parts of the striatum. Multiple sub-cortical regions showed BOLD signatures of reward prediction error processing, but contrary to expectations, these did not include the dopaminergic midbrain. Combined, this study characterises the human subcortical contributions to choice and learning, and demonstrates the feasibility and value of joint modelling in facilitating our understanding of brain-behaviour relationships.
Protein kinase G inhibition preserves photoreceptor viability and function in a new mouse model for autosomal dominant retinitis pigmentosa
Authors: Zhu Yu , Peiroten Lucia , Nanda Kumar Pranav , Hottin Catherine , Haq Wadood , Paquet-Durand François
Published: January 2025

Retinitis Pigmentosa (RP) is the most common inherited retinal degeneration, characterized by an initial loss of rod photoreceptor cells. Photoreceptor cell death has been associated with high levels of cyclic guanosine-3′, 5′-monophosphate (cGMP) in animal models of autosomal recessive RP (ARRP) and autosomal dominant RP (ADRP). cGMP analogues inhibiting protein kinase G (PKG) have been found to prevent rod degeneration in ARRP disease models, but their effects on ADRP are unknown. Here, we used the recently generated rhodopsin-mutantRhoI255d/+ADRP mouse model to investigate cGMP-signaling and the effects of cGMP analogues targeting PKG.

cGMP accumulation was investigated by retinal immunostaining in wild-type (WT),RhoI255d/+, andRhoI255d/I255dmice. The therapeutic efficacy of the cGMP analogues CN03 and CN238 was evaluated on organotypic retinal explant cultures derived from WT andRhoI255d/+mice. Readouts included the TUNEL assay and immunostaining for cone arrestin-3. Downstream effectors of cell death were visualized using calpain, poly-ADP-ribose polymerase (PARP), and histone deacetylase (HDAC)in situassays, as well as caspase-3 immunostaining. Photoreceptor function was assessed using micro-electroretinogram (µERG) recordings. When compared with WT,RhoI255dphotoreceptors displayed cGMP accumulation in outer segments. In theRhoI255d/+ADRP model, CN03 and CN238 significantly reduced the number of dying photoreceptors. However, the relatively small number of photoreceptors exhibiting caspase-3 activity was not changed by the treatment. Remarkably, CN238 effectively provided long-lasting neuroprotection of cone photoreceptors and preserved retinal light responsiveness ofRhoI255d/+retina.

Overall, this study suggests caspase-independent but cGMP-dependent cell death as a dominant degenerative mechanism in theRhoI255d/+ADRP mouse model. PKG inhibition demonstrated robust neuroprotection of both rod and cone photoreceptors, while the marked preservation of retinal function, especially with the compound CN238, highlighted cGMP analogues for the treatment of ADRP.