bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cancer therapy via neoepitope-specific monoclonal antibody cocktails
Authors: Hartman Colin J. , Mohamed Asmaa O. , Shukla Girja S. , Pero Stephanie C. , Sun Yu-Jing , Rodríguez Roberto S. , Genovese Nicholas F. , Kohler Nico M. , Hemphill Thomas R. , Huang Yina H. , Krag David N. , Ackerman Margaret E. 
Published: August 2024

ABSTRACTBackgroundCellular heterogeneity presents a significant challenge to cancer treatment. Antibody therapies targeting individual tumor-associated antigens can be extremely effective but are not suited for all patients and often fail against tumors with heterogeneous expression as tumor cells with low or no antigen expression escape targeting and develop resistance. Simultaneously targeting multiple tumor-specific proteins with multiple antibodies has the potential to overcome this barrier and improve efficacy, but relatively few widely expressed cancer-specific antigens are known. In contrast, neoepitopes, which arise from mutations unique to tumor cells, are considerably more abundant. However, since neoepitopes are not commonly shared between individuals, a patient-customized approach is necessary and motivates efforts to develop an efficient means to identify suitable target mutations and isolate neoepitope-specific monoclonal antibodies.MethodsHere, focusing on the latter goal, we use directed evolution in yeast and phage display systems to engineer antibodies from non-immune, human antibody fragment libraries that are specific for neoepitopes previously reported in the B16F10 melanoma model.ResultsWe demonstrate proof-of-concept for a pipeline that supports rapid isolation and functional enhancement of multiple neoepitope peptide-targeted monoclonal antibodies and demonstrate their robust binding to B16F10 cells and potent effector functionsin vitro. These antibodies were combined and evaluatedin vivofor anti-cancer activity in tumor-bearing mice, where they suppressed B16F10 tumor growth and prolonged survival.ConclusionsThese findings emphasize the potential for clinical application of patient-customized antibody cocktails in the treatment of the many cancers poorly addressed by current therapies.
Fallow deer approaching humans are also more likely to be seropositive forToxoplasma gondii
Authors: Ryan Andrew R. , Zintl Annetta , Griffin Laura L. , Quinn Matthew , Haigh Amy , Sabbatini Pietro , Amin Bawan , Ciuti Simone 
Published: August 2024

AbstractToxoplasma gondii(T. gondii) is a trophically-transmitted protozoan parasite that has been suggested to facilitate its transmission by altering intermediate hosts’ anti-predator behaviour, thus increasing the likelihood of completing the cycle inside its definitive host i.e. domestic and wild felines.T. gondiihas been linked to reduced risk-aversion, slower reaction times, and more exploratory behaviours in intermediate hosts, including most famously weakened aversion to the scent of feline predators in mice. Studies examining this phenomenon, however, have almost exclusively been carried out in laboratory conditions with small mammals, whereas little is known about the role ofT. gondiiwithin more complex ecological contexts involving large mammals in the wild. Under such scenario, the goals of our study were three-fold. Firstly, to determine the prevalence ofT. gondiiinfection in a population of free-living fallow deer (Dama dama) living in a park at the edge of a metropolis. Secondly, to find a link between deer seropositivity and space use in the park, namely proximity to buildings with domestic cats, where deer may have been more likely to contract the disease. Finally, to determine whether infection withT. gondiiwas linked to risk taking behaviour in these free ranging large mammals, namely likelihood to approach park visitors. To achieve our goals, we estimated seropositivity and combined it with spatial distribution and behavioural data of individually-recognizable deer ranging from those that avoid humans (risk-avoiders) to those who beg for food (risk-takers). We foundT. gondiito be quite widespread in this population with a seropositive of 20% (24 out of 120 individuals). Contrary to our expectations, we found no correlation betweenT. gondiiseropositivity and space use in the park, therefore not allowing us to engage with the dynamics of disease contraction. We did however find that fallow deer taking the risk of approaching humans were also more likely to be seropositive. Are risk taking individuals more likely to contract the disease? Or, alternatively, do they take more risk because they have contracted the disease? The causal mechanism behind our result has yet to be disentangled, opening new scenarios in research aimed at tackling host manipulation in this parasite. It is a fact, however, that those animals that were more likely to be in contact with the public were also those more likely to be seropositive, adding key empirical evidence to the study of zoonotic diseases. Our study is a significant contribution on the transmission and maintenance dynamics ofT. gondii, offering new insights on the need to conduct longitudinal studies able to disentangle the causal mechanism andT. gondii’s ability to manipulate its intermediate host.
Movement responses to lethal risk: an integrative analysis of proactive and reactive antipredator behaviours in a large herbivore
Authors: Vanderlocht Charlotte , Robira Benjamin , Corradini Andrea , Farra Simone Dal , Ossi Federico , Righetti Davide , Hauffe Heidi C. , Pedrotti Luca , Cagnacci Francesca 
Published: August 2024

AbstractPrey species can display antipredation movement behaviours to reduce predation risk including proactive responses to chronic or predictable risk, and reactive responses to acute or unpredictable risk. Thus, at any given time, prey movement choice may reflect the trade-off between proaction and reaction. In previous studies, proaction and reaction have generally been considered separately, which neglects their simultaneous influence on animal decisions. In this study, we analysed how proaction and reaction interact to shape the movements of GPS-collared red deer (Cervus elaphus), in response to human hunting of conspecifics. Our results show that red deer proactively selected canopy cover where and when risk was predictably high. However, when they were unable to avoid risk, canopy cover was no longer selected, but only modulated a reactive response along a freeze-to-escape continuum. This reaction was even more evident when the environment was unfamiliar, underlining the importance of memory in such reaction patterns. Therefore, to our knowledge, for the first time, we describe how proaction and reaction fuse in anantipredation sequenceof interconnected movement decisions in a large herbivore, and we lay the foundations for further investigations into the evolutionary origins of similarities and differences between proactive and reactive behaviours.
UniPTM: Multiple PTM site prediction on full-length protein sequence
Authors: Meng Lingkuan , Lin Jiecong , Cheng Ke , Xu Kui , Sun Hongyan , Wong Ka-Chun 
Published: August 2024

AbstractPost-translational modifications (PTMs) enrich the functional diversity of proteins by attaching chemical groups to the side chains of amino acids. In recent years, a myr-iad of AI models have been proposed to predict many specific types of PTMs. However, those models typically adopt the sliding window approach to extract short and equal-length protein fragments from full-length proteins for model training. Unfortunately, such a subtle step results in the loss of long-range information from distal amino acids, which may impact the PTM formation process. In this study, we introduce UniPTM, a window-free model designed to train and test on natural and full-length protein sequences, enabling the prediction of multiple types of PTMs in a holistic manner. Moreover, we established PTMseq, the first comprehensive dataset of full-length pro-tein sequences with annotated PTMs, to train and validate our model. UniPTM has undergone extensive validations and significantly outperforms existing models, eluci-dating the influence of protein sequence completeness on PTM. Consequently, UniPTM offers interpretable and biologically meaningful predictions, enhancing our understand-ing of protein functionally and regulation. The source code and PTMseq dataset for UniPTM are available athttps://www.github.com/TransPTM/UniPTM.
3D histology reveals that immune response to pancreatic precancers is heterogeneous and depends on global pancreas structure
Authors: Kiemen Ashley L. , Almagro-Pérez Cristina , Matos Valentina , Forjaz Andre , Braxton Alicia M. , Dequiedt Lucie , Parksong Jeeun , Cannon Courtney D. , Yuan Xuan , Shin Sarah M. , Babu Jaanvi Mahesh , Thompson Elizabeth D. , Cornish Toby C. , Ho Won Jin , Wood Laura D. , Wu Pei-Hsun , Muñoz Barrutia Arrate , Hruban Ralph H. , Wirtz Denis 
Published: August 2024

SUMMARYPancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer for which few effective therapies exist. Immunotherapies specifically are ineffective in pancreatic cancer, in part due to its unique stromal and immune microenvironment. Pancreatic intraepithelial neoplasia, or PanIN, is the main precursor lesion to PDAC. Recently it was discovered that PanINs are remarkably abundant in the grossly normal pancreas, suggesting that the vast majority will never progress to cancer. Here, through construction of 48 samples of cm3-sized human pancreas tissue, we profiled the immune microenvironment of 1,476 PanINs in 3D and at single-cell resolution to better understand the early evolution of the pancreatic tumor microenvironment and to determine how inflammation may play a role in cancer progression.We found that bulk pancreatic inflammation strongly correlates to PanIN cell fraction. We found that the immune response around PanINs is highly heterogeneous, with distinct immune hotspots and cold spots that appear and disappear in a span of tens of microns. Immune hotspots generally mark locations of higher grade of dysplasia or locations near acinar atrophy. The immune composition at these hotspots is dominated by naïve, cytotoxic, and regulatory T cells, cancer associated fibroblasts, and tumor associated macrophages, with little similarity to the immune composition around less-inflamed PanINs. By mapping FOXP3+ cells in 3D, we found that regulatory T cells are present at higher density in larger PanIN lesions compared to smaller PanINs, suggesting that the early initiation of PanINs may not exhibit an immunosuppressive response.This analysis demonstrates that while PanINs are common in the pancreases of most individuals, inflammation may play a pivotal role, both at the bulk and the microscopic scale, in demarcating regions of significance in cancer progression.
Circular RNAs exhibit exceptional stability in the aging brain and serve as reliable age and experience indicators
Authors: Kirio Ken , Patop Ines , Anduaga Ane Martin , Harris Jenna , Pamudurti Nagarjuna , Martel Claire , Kadener Sebastian 
Published: August 2024

ABSTRACTCircular RNAs (circRNAs) comprise a large class of stable RNAs produced through backsplicing. While circRNAs have been shown to be very stable in cell culture, it is unknown how stable they arein vivo. Interestingly, studies across various animal systems demonstrated that circRNAs levels increase with age in neural tissue. However, the underlying reasons for this age-related accumulation are still unclear. To address these questions, we profiled circRNAs from fly heads at six timepoints across their lifespan. We found that circRNA levels increase linearly with age, independent of changes in mRNA levels, overall transcription, intron retention, or host genes splicing. This indicates that the age-related accumulation is attributed to their extraordinary stability in neural tissue rather than changes in biosynthesis. Furthermore, exposure to environmental stimuli like different temperatures, resulted in the increase but not decrease of circRNAs subsets, further confirming their stabilityin vivo. This exceptional stability implies that circRNAs can serve as markers of environmental experience. Indeed, flies subjected to a ten-day regimen at 29°C exhibit higher levels of specific brain circRNAs even six weeks after returning to standard conditions, indicating that circRNAs can reveal past environmental stimuli. Additionally, circRNA half-life measurements revealed values exceeding 20 days, with some showing no degradation over the animal’s lifetime. These findings demonstrate the extreme stability of circRNAsin vivoand their use as markers for aging, stress and life experiences.
Quantifying irreversibility of ecological systems
Authors: Li Junang , Munch Stephan B. , Tan Tzer Han , Song Chuliang 
Published: August 2024

AbstractIrreversibility—the asymmetry of population dynamics when played forward versus backward in time—is a fundamental property of ecological dynamics. Despite its early recognition in ecology, irreversibility has remained a high-level and unquantifiable concept. Here, we introduce a quantitative framework rooted in non-equilibrium statistical physics to measure irreversibility in general ecological systems. Through theoretical analyses, we demonstrate that irreversibility quantifies the degree to which a system is out of equilibrium, a property not captured by traditional ecological metrics. We validate this prediction empirically across diverse ecological systems structured by different forces, such as rapid evolution, nutrient availability, and temperature. In sum, our study provides a rigorous formalism for quantifying irreversibility in ecological systems, with the potential to integrate dynamical, energetic, and informational perspectives in ecology.
Nanopore sequencing from protozoa to phages: decoding biological information on a string of biochemical molecules into human-readable signals
Authors: Hunter Branden , Cromwell Timothy , Shim Hyunjin 
Published: August 2024

AbstractBiological information is encoded in a sequence of biochemical molecules such as nucleic acids and amino acids, and nanopore sequencing is a long-read sequencing technology capable of directly decoding these molecules into human-readable signals. The long reads from nanopore sequencing offer the advantage of obtaining contiguous information, which is particularly beneficial for decoding complex or repetitive regions in a genome. In this study, we investigated the efficacy of nanopore sequencing in decoding biological information from distinctive genomes in metagenomic samples, which pose significant challenges for traditional short-read sequencing technologies. Specifically, we sequenced blood and fecal samples from mice infected withTrypanosoma brucei, a unicellular protozoan known for its hypervariable and dynamic regions that help it evade host immunity. Such characteristics are also prevalent in other host-dependent parasites, such as bacteriophages. The taxonomic classification results showed a high proportion of nanopore reads identified asT. bruceiin the infected blood samples, with no significant identification in the control blood samples and fecal samples. Furthermore, metagenomic de novo assembly of these nanopore reads yielded contigs that mapped to the reference genome ofT. bruceiin the infected blood samples with over 96% accuracy. This exploratory work demonstrates the potential of nanopore sequencing for the challenging task of classifying and assembling hypervariable and dynamic genomes from metagenomic samples.
Chronic cigarette smoke exposure masks pathological features ofHelicobacter pyloriinfection while promoting tumor initiation
Authors: Morris Maeve T. , Piazuelo M Blanca , Olfert I. Mark , Xu Xiaojiang , Hussain Salik , Peek Richard M. , Busada Jonathan T. 
Published: August 2024

AbstractGastric cancer is the fifth most common cancer and the fifth leading cause of cancer deaths worldwide. Chronic infection by the bacteriumHelicobacter pyloriis the most prominent gastric cancer risk factor, but only 1-3% of infected individuals will develop gastric cancer. Cigarette smoking is another independent gastric cancer risk factor, andH. pylori-infected smokers are at a 2-11-fold increased risk of gastric cancer development, but the direct impacts of cigarette smoke onH. pyloripathogenesis remain unknown. In this study, male C57BL/6 mice were infected withH. pyloriand began smoking within one week of infection. The mice were exposed to cigarette smoke (CS) five days/week for 8 weeks. CS exposure had no notable impact on gross gastric morphology or inflammatory status compared to filtered-air (FA) exposed controls in mock-infected mice. However, CS exposure significantly bluntedH. pylori-induced gastric inflammatory responses, reducing gastric atrophy and pyloric metaplasia development. Despite blunting these classic pathological features ofH. pyloriinfection, CS exposures increased DNA damage within the gastric epithelial cells and acceleratedH. pylori-induced dysplasia onset in the INS-GAS gastric cancer model. These data suggest that cigarette smoking may clinically silence classic clinical symptoms ofH. pyloriinfection but enhance the accumulation of mutations and accelerate gastric cancer initiation.
A hidden mark of a troubled past: neuroimaging and transcriptomic analyses reveal interactive effects of maternal immune activation and adolescent THC exposure in the absence of overt behavioural disruptions
Authors: Moreno-Fernández Mario , Luján Víctor , Baliyan Shishir , Poza Celia , Capellán Roberto , de las Heras Natalia , Morcillo Miguel Ángel , Oteo Marta , Ambrosio Emilio , Ucha Marcos , Higuera-Matas Alejandro 
Published: August 2024

ABSTRACTMaternal exposure to infections during gestation has been shown to predispose individuals to the development of schizophrenia. Additionally, clinical data suggest that cannabis use could trigger the onset of schizophrenia in vulnerable individuals. However, the direction of causality remains unclear. To elucidate this issue, we utilised a rat model of maternal immune activation, combined with exposure to increasing doses of THC during adolescence, in both male and female rats. We investigated several behaviours in adulthood that resemble specific symptoms of schizophrenia, including impairments in working memory, deficits in sensorimotor gating, alterations in social behaviour, anhedonia, and potential changes in implicit learning (conditioned taste aversion). Furthermore, we conducted a longitudinal positron emission tomography (PET) study to identify affected brain regions and subsequently collected brain samples from one of these regions (the orbitofrontal cortex) for RNA sequencing analyses. These analyses were also performed on peripheral blood mononuclear cells to identify peripheral biomarkers. Notably, while no overt behavioural disruptions were observed, our PET scans revealed several brain alterations dependent on the combination of both exposures. Additionally, the transcriptomic studies demonstrated that maternal immune activation affected glutamatergic and serotoninergic genes, with the combination of both exposures shifting the expression from down-regulation to up-regulation. In peripheral cells, interactive effects were observed on inflammatory pathways, and some genes were proposed as biomarkers of the disease. These results suggest that the combination of these two vulnerability factors leaves a lasting mark on the body, potentially predisposing individuals to the disease even before behavioural alterations manifest.
Scalable spatial single-cell transcriptomics and translatomics in 3D thick tissue blocks
Authors: Sui Xin , Lo Jennifer A. , Luo Shuchen , He Yichun , Tang Zefang , Lin Zuwan , Zhou Yiming , Wang Wendy Xueyi , Liu Jia , Wang Xiao 
Published: August 2024

AbstractCharacterizing the transcriptional and translational gene expression patterns at the single-cell level within their three-dimensional (3D) tissue context is essential for revealing how genes shape tissue structure and function in health and disease. However, most existing spatial profiling techniques are limited to 5-20 µm thin tissue sections. Here, we developed Deep-STARmap and Deep-RIBOmap, which enable 3Din situquantification of thousands of gene transcripts and their corresponding translation activities, respectively, within 200-µm thick tissue blocks. This is achieved through scalable probe synthesis, hydrogel embedding with efficient probe anchoring, and robust cDNA crosslinking. We first utilized Deep-STARmap in combination with multicolor fluorescent protein imaging for simultaneous molecular cell typing and 3D neuron morphology tracing in the mouse brain. We also demonstrate that 3D spatial profiling facilitates comprehensive and quantitative analysis of tumor-immune interactions in human skin cancer.
Endogenous Retrovirus Loci and Induced Changes in Gene Expression in Japanese Indigenous Chickens
Authors: Ishihara Shinya , Shiraishi Jun-ichi , Shimamoto Saki , Ijiri Daichi 
Published: August 2024

AbstractWhen retroviruses infect germ cells and are transmitted to offspring, they become endogenous retroviruses (ERVs), whose insertions influence the expression of nearby genes. This study aimed to identify the genomic loci of ERVs in commercial broiler (Ross308), Tosa-Jidori, and Yakido chickens as well as to elucidate their impact on neighboring gene expression. Whole-genome data were obtained using next-generation sequencing, and candidate ERV loci were identified using the RetroSeq software. The Integrative Genomics Viewer tool was used to confirm target site duplications (TSDs) as evidence of ERV insertions. All reads within 200 bp of these TSDs were extracted to create contigs, confirming the presence of ERV sequences in the contigs using BLASTN. Gene expression levels were estimated by focusing on genes located near the 172 identified ERV loci. Among these, 119 loci were detected in broiler chickens, 80 in Tosa-Jidori chickens, and 86 in Yakido chickens, with 28 loci shared among them. Moreover, of these 172 loci, 75 were located within or near genes. Significant differences in gene expression were observed for N-acetylated alpha-linked acidic dipeptidase 2, glypican 6, and phospholipid scramblase family member 5 depending on the presence of ERV insertions. These results suggest that ERV insertions may influence the expression of certain genes, providing insights into the genetic diversity and evolutionary background of commercial and indigenous chickens. Understanding the effects of ERV insertions on gene expression can inform future genetic research and poultry breeding programs aimed at improving health and productivity.
Ice Finder: Few-Shot Learning for Non-Vitrified Ice Segmentation
Authors: Vivas-Lago Alma , Castaño-Díez Daniel 
Published: August 2024

ABSTRACTThis study introduces Ice Finder, a novel tool for quantifying crystalline ice in tomography, filling a crucial gap in existing methodologies. We establish the first application of the meta-learning paradigm to tomography, demonstrating that various tomographic tasks across datasets can be unified under a single meta-learning framework. Our approach utilizes few-shot learning to enhance domain generalization and adaptability to domain shifts, facilitating rapid adaptation to new datasets with minimal examples. Ice Finder’s performance is evaluated on a comprehensive set of in situ datasets from EMPIAR, proving its ease of use and fast processing capabilities, with inference times in the milliseconds. This tool not only accelerates workflows but also enhances the precision of structural studies in structural biology.