bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mosquitoes self-medicate according to the dynamics of a microsporidian infection
Authors: Zeferino Tiago G. , Mora Alfonso Rojas , Vallat Armelle , Koella Jacob C. 
Published: December 2024

AbstractImmune responses protect against infectious diseases but often incur costs, such as oxidative stress. In mosquitoes, these costs may drive behaviours that manage oxidative homeostasis, such as self-medicating by consuming nectar containing biologically active substances, including prooxidants and antioxidants. We examined whetherAnopheles gambiaemosquitoes adjust their dietary preferences when infected with the microsporidian parasiteVavraia culicis. Using sugar solutions supplemented or not with hydrogen peroxide (a prooxidant) or ascorbic acid (an antioxidant), we assessed the feeding preferences of uninfected and infected mosquitoes at different ages and measured the effects of these diets on oxidative homeostasis and parasite load. Uninfected mosquitoes preferred sugar alone, possibly to avoid oxidative stress caused by the supplemented diets. In contrast, infected mosquitoes initially preferred the prooxidant diet, which reduced parasite load and oxidative stress, but later shifted towards the antioxidant diet, which had little effect on parasite load or oxidative stress. These findings demonstrate that mosquitoes can self-medicate by consuming nectar with appropriate levels of prooxidants and antioxidants, adjusting their preference dynamically with infection progression. Given the role of mosquitoes as major vectors of infectious diseases, these results may have significant public health implications.
Non-mulberry silk fibroin functionalization enhances charge-transfer efficiency in aligned polypyrrole-silk composites for electrically stimulated neurite outgrowth
Authors: Borah Rajiv , Moses Joseph Christakiran , Upadhyay Jnanendra , Das Jitu Moni , Mandal Biman B. 
Published: December 2024

AbstractElectroconductive biomaterials (ECBs) replicate the natural bioelectrical environment of nerve tissue, promoting action potential propagation after injury and enhancing nerve regeneration through therapeutic electrical stimulation (ES). We present a highly electroactive Faradaic ECB with exceptional electrical conductivity and charge density, alongside low electrochemical impedance. These ECBs trigger action potentials at low stimulation voltages by regulating redox reactions through their intrinsic reversible behavior, thereby preventing electrode degradation and tissue damage. Our biohybrid scaffold consists of aligned microfibrous matrices of polypyrrole (PPy) andBombyx morisilk fibroin (BmSF), functionalized withAntheraea assamensissilk fibroin (AaSF) rich in the cell-affinitive RGD tripeptide. Serving as an anionic dopant for PPy, AaSF significantly enhances the scaffold’s electrical properties (∼9.18 mS cm-1) and charge-transfer efficiency (∼25.27 Ω). The scaffolds exhibit superior charge injection capacity at low potentials compared to conventional bioelectrodes (e.g., 0.46 mC cm-2at 50 mV). Under pulsed ES at 50 mV cm-1, these scaffolds support remarkable neurite outgrowth of dorsal root ganglion (DRG) neurons up to 830 μm (7 days). Notably, higher current densities and voltages decrease the rate of neurite outgrowth, highlighting the importance of optimizing ES parameters to effectively evoke functional action potentials without causing any neuronal damage. Biocompatibility assessments reveal that AaSF functionalization improves cellular behavior while minimizing immunomodulatory responses. Enhanced neuronal and glial differentiation is attributed to better cell communication facilitated by excellent adhesion and increased conductivity. In essence, this study provides a strategy for selecting optimal ES parameters for electrically excitable tissues using established electrochemical techniques. The fabricated biohybrid scaffolds hold significant promise as smart nerve guidance channels (NGCs) for future nerve regeneration therapies.
A Wearable Spiral Ultrasound Patch for Focused Ultrasound Peripheral Neuromodulation of Diabetic Neuropathic Pain
Authors: Pu Cong , Fu Ben , Lu Pengda , Guan Xin , Zhang Jiayi , Shen Yuting , Li Xiao , Guo Lehang , Xu Huixiong , Jiang Xiaoning , Peng Chang 
Published: December 2024

AbstractDiabetic foot disease, a severe complication of diabetes, frequently results in diabetic neuropathic pain, which diminishes quality of life and increases the risk of amputation. Current treatment options are limited in their effectiveness and can present adverse effects. We have demonstrated a first-of-its-kind wearable spiral ultrasound patch for focused ultrasound peripheral neuromodulation to alleviate diabetic neuropathic pain. This innovative, stretchable ultrasound device reliably delivers focused ultrasound to peripheral nerves. The device’s ultrasound elements are arranged in a phyllotaxis spiral pattern, enhancing transmitted acoustic focus performance and minimizing grating and side lobes. Using a diabetic foot rat model, we confirmed peripheral neuropathy through behavioral assessments of mechanical allodynia and heat hyperalgesia, which showed significant pain relief after two weeks of ultrasound treatment. Additionally, nerve conduction velocity improved. Biological safety tests indicated no adverse effects on nerve tissues or cells. Our approach offers a non-invasive solution for managing diabetic neuropathic pain and provides critical insights into its underlying mechanisms, paving the way for more effective therapies.
Telomere-to-Telomere Genome Assembly UncoversWolbachia-Driven Sex-Specific Demography and Challenges Fisher’s Principle in a Sawfly
Authors: Zhang Mingpeng , Zhai Ruoyu , Niu Gengyun , Chen Jiaqi , Tan Beibei , Wu Duo , Meng Guanliang , Wei Meicai 
Published: December 2024

AbstractWolbachia, a widespread endosymbiotic bacterium, can reshape the evolutionary fates of its insect hosts by distorting reproduction and altering population dynamics. Despite extensive laboratory research, its long-term effects on host evolution in nature remain poorly understood, particularly regarding genetic mechanisms underlying changes in sex determination and reproduction. Here, we report the first telomere-to-telomere (T2T) genome assembly of the sawflyAnalcellicampa danfengensisand the complete genome of it symbioticWolbachia. Comparative population genomics of six closely relatedAnalcellicampaspecies revealed thatWolbachia-infected populations experience marked changes in sex-specific demography. While uninfected species maintain balanced genetic features between males and females, infected species show a persistent reduction in male effective population size alongside a stable or even growing female population, ultimately driving males toward extinction. Genomic scans identified positively selected genes associated with reproductive functions, sensory perception, neural development, and longevity, suggesting thatWolbachiamanipulates critical host biological pathways to promote its transmission. These findings provide direct genomic evidence thatWolbachiaacts as a powerful evolutionary force, reshaping host genomes in a way that disrupts Fisher’s principle, ultimately driving female-biased demography and the extinction of males at evolutionary timescales. This work provides deeper insights into host– endosymbiont coevolution and has important implications for evolutionary theory and pest management strategies.
Genotyping Short Tandem Repeats Across Copy Number Alterations, Aneuploidies, and Polyploid Organisms
Authors: Verbiest Max A. , Grassi Elena , Bertotti Andrea , Anisimova Maria 
Published: December 2024

AbstractShort tandem repeats (STRs) are a rich source of genetic variation, but are difficult to genotype. While specialized repeat variant callers exist, they typically assume a euploid human genome. This means recent findings regarding phenotypic effects of STR variants in human health and disease cannot be readily extended to polyploid organisms or cancer, which is characterised by copy number alterations (CNAs). Here we present ConSTRain, a novel STR variant caller that explicitly accounts for the copy number of loci in its genotyping approach. We benchmark ConSTRain using a euploid human 100X whole genome sequencing sample where it calls STR allele lengths for over 1.7×106loci in under 20 minutes with an accuracy of 98.28%. Subsequently, we show that ConSTRain resolves complex STR genotypes in an artificial trisomy 21 sample and a polyploid Dwarf Cavendish banana harbouring a large duplication. Finally, we analyse a microsatellite instable colorectal cancer tumoroid, where ConSTRain tackles CNAs and whole-genome duplications. ConSTRain is the first STR variant caller that allows for the investigation of repeats affected by CNAs, aneuploidies, and polyploid genomes. This unlocks the investigation of STRs across a wide range of contexts and organisms where they previously could not be easily studied.
Repeated head-exposures to a 5G-3.5 GHz signal do not alter behavior but modify intracerebral gene expression in adult male mice
Authors: Lameth Julie , Royer Juliette , Martin Alexandra , Marie Corentine , Cormos Délia Arnaud- , Lévêque Philippe , Poirier Roseline , Edeline Jean-Marc , Mallat Michel 
Published: December 2024

AbstractThe 5thgeneration (5G) of mobile communications promotes human exposures to electromagnetic fields exploiting the 3.5 GHz frequency band. We have analyzed behaviors, cognitive functions and gene expression in mice submitted to asymmetrical head-exposures to a 5G-modulated 3.5 GHz signal. The exposures were applied 1h daily, 5 days per week over a six-week period, at a specific absorption rate (SAR) averaging 0.19 W/kg over the brain. Locomotor activity in an open-field, object-place and object recognition memories were assessed repeatedly after four weeks of exposure and did not reveal any significant effect on the locomotion/exploration, anxiety level or memory processes. mRNA profiling was performed at the end of the exposure period in two symmetrical areas of the right and left cerebral cortex in which the SAR values were 0.43 and 0.14 W/kg, respectively. We found significant changes in the expression of less than 1% of the expressed genes with over-representations of genes related to glutamatergic synapses. The right cortical area differed from the left one by an over-representation of responsive genes encoded by the mitochondrial genome. Our data show that repeated head-exposures to a 5G-3.5 GHz signal can trigger mild transcriptome alterations without change in memory capacities or emotional state.
Expanding the Landscape of Aging via Orbitrap Astral Mass Spectrometry and Tandem Mass Tag (TMT) Integration
Authors: Keele Gregory R. , Dou Yue , Kodikara Seth P. , Jeffery Erin D. , Bai Dina , Paulo Joao A. , Gygi Steven P. , Tian Xiao , Zhang Tian 
Published: December 2024

AbstractAging results in a progressive decline in physiological function due to the deterioration of essential biological processes, such as transcription and RNA splicing, ultimately increasing mortality risk. Although proteomics is emerging as a powerful tool for elucidating the molecular mechanisms of aging, existing studies are constrained by limited proteome coverage and only observe a narrow range of lifespan. To overcome these limitations, we integrated the Orbitrap Astral Mass Spectrometer with the multiplex tandem mass tag (TMT) technology to profile the proteomes of three brain tissues (cortex, hippocampus, striatum) and kidney in the C57BL/6JN mouse model, achieving quantification of 8,954 to 9,376 proteins per tissue (cumulatively 12,749 across all tissues). Our sample population represents balanced sampling across both sexes and three age groups (3, 12, and 20 months), comprising young adulthood to early late life (approximately 20-60 years of age for human lifespan). To enhance quantitative accuracy, we developed a peptide filtering strategy based on resolution and signal-to-noise thresholds. Our analysis uncovered distinct tissue-specific patterns of protein abundance, with age and sex differences in the kidney, while brain tissues exhibit notable age changes and limited sex differences. In addition, we identified both proteomic changes that are linear with age (i.e., continuous) and that have a non-linear pattern (i.e., non-continuous), revealing complex protein dynamics over the adult lifespan. Integrating our findings with early developmental proteomic data from brain tissues highlighted further divergent age-related trajectories, particularly in synaptic proteins. This study not only provides a robust data analysis workflow for TMT datasets generated using the Orbitrap Astral mass spectrometer but also expands the proteomic landscape of aging, capturing proteins with age and sex effects with unprecedented depth.
Genetic basis of an adaptive polymorphism controlling butterfly silver iridescence
Authors: Livraghi Luca , Hanly Joseph J. , Loh Ling Sheng , Henry Albie , Keck Chloe M.T. , Shirey Vaughn M. , Tsai Cheng-Chia , Yu Nanfang , Van Belleghem Steven M. , Roberts W. Mark , Boggs Carol L. , Martin Arnaud 
Published: December 2024

SummaryIdentifying the genes and mutations that drive phenotypic variation and which are subject to selection is crucial for understanding evolutionary processes. Mormon Fritillary butterflies (Speyeria mormonia) exhibit a striking wing color polymorphism throughout their range: typical morphs bear silver spots on their ventral surfaces, and can co-occur with unsilvered morphs displaying a dull coloration1. Through genome-wide association studies in two polymorphic populations, we fine-map this difference in silvering to the 3’ region of the transcription factor geneoptix. The expression ofoptixis confined to the unsilvered regions that surround the spots, and these patterns are transformed to a silver identity uponoptixRNAi knockdown, implicatingoptixas a repressor of silver scales in this butterfly. We show that the unsilveredoptixhaplotype shows signatures of recent selective sweeps, and that this allele is shared with the monomorphic, unsilvered speciesSpeyeria hydaspe, suggesting that introgressions facilitate the exchange of variants of adaptive potential across species. Remarkably, these findings parallel the role of introgressions andcis-regulatory modulation ofoptixin shaping the aposematic red patterns ofHeliconiusbutterflies2–7, a lineage that separated fromSpeyeria45 million years ago8. The genetic basis of adaptive variation can thus be more predictable than often presumed, even for traits that appear divergent across large evolutionary distances.Graphical Abstract
The sole essential low molecular weight tropomyosin isoform ofCaenorhabditis elegansis essential for pharyngeal muscle function
Authors: Kimmich Michael J. , Geary Meaghan A. , Mi-Mi Lei , Votra SarahBeth D. , Pellenz Christopher D. , Sundaramurthy Sumana , Pruyne David 
Published: December 2024

ABSTRACTTropomyosin is an actin-binding protein that plays roles ranging from regulating muscle contraction to controlling cytokinesis and cell migration. The simple nematodeCaenorhabditis elegansprovides a useful model for studying the core functions of tropomyosin in an animal, having a relatively simple anatomy, and a single tropomyosin gene,lev-11, that produces seven isoforms. Three higher molecular weight isoforms (LEV-11A, D, O) regulate contraction of body wall and other muscles, but comparatively less is known of the functions of four lower molecular weight isoforms (LEV-11C, E, T, U). We demonstrate hereC. eleganscan survive with a single low molecular weight isoform, LEV-11E. Mutants disrupted for LEV-11E die as young larvae, whereas mutants disrupted for all other short isoforms are viable with no overt phenotype. Vertebrate low molecular weight tropomyosins are often considered “nonmuscle” isoforms, but we find LEV-11E localizes to sarcomeric thin filaments in pharyngeal muscle, and co-precipitates from worm extracts with the formin FHOD-1, which is also associated with thin filaments in pharyngeal muscle. Pharyngeal sarcomere organization is grossly normal in larvae lacking LEV-11E, indicating the tropomyosin is not required to stabilize thin filaments, but pharyngeal pumping is absent, suggesting LEV-11E regulates actomyosin activity similar to higher molecular weight sarcomeric tropomyosin isoforms.
A comparative analysis of toxin gene families across diverse sea anemone species
Authors: Smith Hayden L. , Broszczak Daniel A. , van der Burg Chloe A. , Surm Joachim M. , Liggins Libby , Norton Raymond S. , Prentis Peter J. 
Published: December 2024

AbstractAll species from order Actiniaria (sea anemones) are venomous, even though most are of no threat to humans. Currently, we know very little about the toxin gene complement of highly venomous members of this order. To address this gap in knowledge, we sequenced the transcriptome of the highly venomous and medically significant Hell’s Fire sea anemone,Actinodendron plumosum, as well as five distantly related species,Cryptodendrum adhaesivum,Epiactis australiensis,Heteractis aurora,Isactinia olivaceaandStichodactyla mertensii. We used bioinformatic approaches to identify their toxin gene complements and performed a comparative evolutionary analysis of seven understudied toxin families. Of the 16 toxin families identified, 12-40 candidate toxins were found in the six new sea anemone transcriptomes, with only 12 candidates in eight toxin families identified inA. plumosum. Across 26 sea anemone species, six neurotoxin families showed evidence of taxonomic restriction, whereas the phospholipase A2 toxin family was ubiquitously distributed. Additionally, we identified two alternative forms for the phospholipase A2 toxin family, a 10- and 14-cysteine framework, which warrant further structural and functional characterisation. Overall, we have identified a comprehensive list of toxins from a wide diversity of sea anemone species that provides the basis for future research to structurally and functionally characterise novel candidates for use as therapeutics or for agricultural applications.
COVID-19 Reproduction Numbers and Long COVID Prevalences in California State Prisons
Authors: Worden Lee , Wannier Rae , Archer Helena , Blumberg Seth , Kwan Ada , Sears David , Porco Travis C. 
Published: December 2024

AbstractPrisons have been hotspots for COVID-19 and likely an important driver of racial disparity in disease burden. From the first COVID-19 case detected through March 25, 2022, 66,684 of 196,652 residents of California’s state prison system were infected, most of them in two large winter waves of outbreaks that reached all 35 of the state prisons. We used individual-level data on disease timing and nightly room assignments in these prisons to reconstruct locations and pathways of transmission statistically, and from that estimated reproduction numbers, locations of unobserved infection events, and the subsequent magnitude and distribution of long COVID prevalence. Where earlier work has recommended smaller cells over large dormitory housing to reduce transmission, recommended use of cells with solid doors over those with bars only, and cautioned against reliance on solid doors (e.g., in cold months when HVAC systems can circulate aerosols), we found evidence of substantial transmission in both dorms and cells regardless of the door and season. Effective reproduction numbers were found to range largely between 0 and 5, in both cells and dorms of all door types. Our estimates of excess case rates suggest that as a result of disparities in incarceration, prison outbreaks contributed to disproportionate disease burden on Black and Indigenous people in California. We estimated that 9,100–11,000 people have developed long COVID as a result of infection in these prison outbreaks, 1,700–2,000 of them with disabling consequences, and that this burden is disproportionately on Black and Indigenous people in comparison to the state as a whole. We urge high-quality medical care for prison residents affected by long COVID, and decarceration to reduce the risk of future outbreaks of both COVID-19 and other diseases.
HCLmNet: A Unified Hybrid Continual Learning Strategy Multimodal Network for Lung Cancer Survival Prediction
Authors: Bappi Ilias , Richter David J. , Kolekar Shivani Sanjay , Kim Kyungbaek 
Published: December 2024

AbstractLung cancer survival prediction is a critical task in healthcare, where accurate and timely predictions can significantly impact patient outcomes. In hospital settings, new patient data is constantly generated, requiring predictive models to adapt without forgetting previously learned knowledge. This challenge is intensified by the need to seamlessly integrate complex multimodal data, such as imaging, DNA, and patient records. Traditional Deep Learning (DL) models, while powerful, often suffer from catastrophic forgetting during incremental learning, further complicating the task of reliable survival prediction in dynamic environments. To address these challenges, we introduce a hybrid Continual Learning (CL) framework that integrates Elastic Weight Consolidation (EWC) with replay-based modules, including EWC Experience Replay (ER), Instance-Level Correlation Replay (EICR), and Class-Level Correlation Replay (ECCR). The ER module preserves knowledge by replaying representative samples from previous data, mitigating interference from new data. The EICR module ensures the retention of fine-grained feature patterns through inter-instance relationship modeling, while the ECCR module consolidates global knowledge across tasks using random triplet probabilities to preserve inter-class correlations. Together, these components create a robust framework, addressing catastrophic forgetting while enhancing adaptability for real-time survival prediction. Another critical challenge is the limitations of Convolutional Neural Networks (CNNs), which tend to miss ground-glass opacities or tiny tumor features in CT and PET images due to their reliance on datasets similar to their pretraining data. To overcome this, we propose a Swin Transformer (SwinT)-based method to extract critical features, addressing CNN shortcomings in such multimodal scenarios. Additionally, XLNet-permutation enriches multimodal analysis by effectively handling small DNA datasets and capturing latent patterns, whereas Fully Connected Network (FCN) process clinical features. A cross-attention fusion mechanism integrates clinical, CT, PET, and DNA data, producing a robust survival prediction model. The final prediction is guided by FCN and Cox Proportional Hazards (CoxPH) techniques, achieves state-of-the-art performance with a 7.7% concordance index (C-Index) improvement (0.84), a mean absolute error (MAE) reduction to 140 days, and minimized forgetting to 0.08. Ablation studies demonstrate the importance of the DNA modality, cross-attention mechanism, and CL strategies, advancing adaptive survival prediction and stability.