bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic and prognostic value of the gasdermins in gastric cancer
Authors: Xu Yeqiong , Wan Chuandan , Wang Ping , Gu yulan 
Published: October 2023

AbstractBackgroundPyroptosis has been drawn attention owing to its contributory role in various cancers. Recently, the participator of pyroptosis, gasdermins (GSDMs) have been reported associated with of multiple types of cancers. However, the role of GSDMs expression in diagnosis and prognosis of gastric cancer (GC) has not been well elucidated. Moreover, the mechanisms underlying the carcinogenesis of GC are still obscure.MethodsHerein we analyzed the transcriptional, prognostic information and the role of GSDMs in patients with GC from TIMER, UALCAN, Human Protein Atlas (HPA), GEPIA and Kaplan-Meier plotter databases. The cBioPortal online tool was used to analyze the GSDMs alterations, correlations, and networks. Furthermore, String, Cytoscape and TIMER were conducted to explore the functional enrichment and immune modulation. The statistical analysis was carried out in the R environment, andP-value < 0.05 was considered statistically significant.ResultsGSDMB, GSDMC, GSDMD, GSDME were with higher expression in GC than normal tissue in TIMER database. Moreover, survival analyses via two databases both demonstrated that high expression of GSDME was related to shorter overall survival (OS) in patients with GC. Additionally, functional enrichment revealed that GSDMs might be involved in endopeptidase activity, peptidase regulator activity, cysteine-type peptidase activity. Besides, GSDMs were correlated with infiltration levels of immune cells in GC, and GSDME was correlated with the infiltrating level of CD4+ T, CD8+ T, neutrophils, macrophages and dendritic cells.ConclusionsThe study systematically indicated the potential diagnostic and prognostic value of GSDMs in GC. Our results showed that GSDME might play a considerably oncogenic role in GC diagnosis and prognosis. However, our bioinformatics analyses should be further validated in more prospective studies.
A Deep Dive into Single-Cell RNA Sequencing Foundation Models
Authors: Boiarsky Rebecca , Singh Nalini , Buendia Alejandro , Getz Gad , Sontag David 
Published: October 2023

AbstractLarge-scale foundation models, which are pre-trained on massive, unlabeled datasets and subsequently fine-tuned on specific tasks, have recently achieved unparalleled success on a wide array of applications, including in healthcare and biology. In this paper, we explore two foundation models recently developed for single-cell RNA sequencing data, scBERT and scGPT. Focusing on the fine-tuning task of cell type annotation, we explore the relative performance of pre-trained models compared to a simple baseline, L1-regularized logistic regression, including in the few-shot setting. We perform ablation studies to understand whether pretraining improves model performance and to better understand the difficulty of the pre-training task in scBERT. Finally, using scBERT as an example, we demonstrate the potential sensitivity of fine-tuning to hyperparameter settings and parameter initializations. Taken together, our results highlight the importance of rigorously testing foundation models against well established baselines, establishing challenging fine-tuning tasks on which to benchmark foundation models, and performing deep introspection into the embeddings learned by the model in order to more effectively harness these models to transform single-cell data analysis. Code is available athttps://github.com/clinicalml/sc-foundation-eval.
High pathogenicity avian influenza A (H5N1) clade 2.3.4.4b virus infection in a captive Tibetan black bear (Ursus thibetanus): investigations based on paraffin-embedded tissues, France, 2022
Authors: Bessière Pierre , Gaide Nicolas , Croville Guillaume , Crispo Manuela , Fusade-Boyer Maxime , Abou Monsef Yanad , Dirat Malorie , Beltrame Marielle , Dendauw Philippine , Lemberger Karin , Guérin Jean-Luc , Le Loc’h Guillaume 
Published: October 2023

AbstractHigh pathogenicity avian influenza viruses H5Nx (HPAIVs) of clade 2.3.4.4b have been circulating increasingly in both wild and domestic birds in recent years. In turn, this has led to an increase in the number of spillovers events affecting mammals. In November 2022, a HPAIV H5N1 caused an outbreak in a zoological park in the south of France, resulting in the death of a Tibetan black bear (Ursus thibetanus) and several captive and wild bird species. We detected the virus in various tissues of the bear and a wild black-headed gull found dead in its enclosure using histopathology, two differentin-situdetection techniques and next generation sequencing, all performed on formalin fixed paraffin embedded tissues. Phylogenetic analysis performed on HA gene segment showed that bear and gull strains shared 99.998% genetic identity, making the bird strain the closest related one. We detected the PB2 E627K mutation in minute quantities in the gull, whereas it predominated in the bear, which suggests that this mammalian adaptation marker was selected during the bear infection. Our results provide the first molecular and histopathological characterization of an H5N1 virus infection in this bear species.
Assessing Perceptual Chromatic Equiluminance Using a Reflexive Pupillary Response
Authors: Ye Liu , Mahony Bridget W. , Wang Xiaochun , Daye Pierre , Wang Wei , Cavanagh Patrick , Pouget Pierre , Andolina Ian Max 
Published: October 2023

AbstractEquiluminant stimuli help assess the integrity of colour perception and the relationship of colour to other visual features. As a result of individual variation, it is necessary to calibrate experimental visual stimuli to suit each individual’s unique equiluminant ratio. Most traditional methods rely on training observers to report their subjective equiluminance point. Such paradigms cannot easily be implemented on pre-verbal or non-verbal observers. Here, we present a novel Pupil Frequency-Tagging Method (PFTM) for detecting a participant’s unique equiluminance point without verbal instruction and with minimal training. PFTM analyses reflexive pupil oscillations induced by slow (< 2 Hz) temporal alternations between coloured stimuli. Two equiluminant stimuli will induce a similar pupil dilation response regardless of colour; therefore, an observer’s equiluminant point can be identified as the luminance ratio between two colours for which the oscillatory amplitude of the pupil at the tagged frequency is minimal. We compared pupillometry-based equiluminance ratios to those obtained with two established techniques in humans: minimum flicker and minimum motion. In addition, we estimated the equiluminance point in non-human primates, demonstrating that this new technique can be successfully employed in non-verbal subjects.Key PointsMeasuring equiluminance is challenging in non-verbal subjects.The pupil diameter varies as perceived brightness changes.Utilising oscillatory pupillometry, PFTM provides a way to measure equiluminance points without training or the need for a subjective report.
First Genome-Scale Metabolic Modeling ofBrucella abortusPredicts Pathogen Gene Essentiality and New Drug Target
Authors: Pinto Bruno Ribeiro , Guimarães de Oliveira Filipe Vilaça , Fernandes Miquéias , Ranieri Lima Alex Jerônimo , de Oliveira Mendes Tiago Antônio 
Published: October 2023

AbstractBovine brucellosis, a globally widespread disease, imposes substantial economic burdens on livestock production. The pathogen,Brucella abortus, has a particular affinity for infecting cattle and can also impact humans, potentially posing a public health risk in regions where the disease persists. To gain a deeper understanding of the pathogen’s biology and its interactions with the host, Pathogen-specific Genome-Scale Metabolic Models offer valuable insights. They aid in identifying novel pharmacological targets and biomarkers, which can inform innovative brucellosis control strategies. In this study, we developed and validated the first Genome-Scale Metabolic Model ofB. abortus2308, named iBP932, encompassing 932 genes, 1,140 reactions, and 999 metabolites. Furthermore, iBP932 capability to predict potential drug targets was demonstrated.
It’s not the spoon that bends: Internal states of the observer determine serial dependence
Authors: Ozkirli Ayberk , Pascucci David 
Published: October 2023

AbstractTraditional views suggest that human perception handles uncertainty using optimal strategies. For instance, when prior stimuli are more reliable than current ones, perceptual decisions rely more on the past, leading to stronger serial dependence. Here, we report findings that challenge this view. We asked human observers to reproduce the average orientation of an ensemble of stimuli under varying stimulus uncertainty. Contrary to optimal strategies, we found that serial dependence is stronger when prior stimuli are more uncertain. We hypothesize that fluctuations in stimulus uncertainty may influence internal states of observers, such as participants expectations about uncertainty and beliefs about their own performance. A striking finding is that manipulating these internal states through rigged feedback can yield drastic effects on serial dependence, even when external input (i.e., stimulus uncertainty) remained constant. Our findings suggest that phenomena like serial dependence can be better understood by considering internal states of the observer, beyond fixed computations and optimal strategies.
Mammalian circadian clock proteins form dynamic interacting microbodies distinct from phase separation
Authors: Xie Pancheng , Xie Xiaowen , Ye Congrong , Dean Kevin M. , Laothamatas Isara , Taufique S K Tahajjul , Takahashi Joseph , Yamazaki Shin , Xu Ying , Liu Yi 
Published: October 2023

AbstractLiquid-liquid phase separation (LLPS) underlies diverse biological processes. Because most LLPS studies were performed in vitro or in cells that overexpress protein, the physiological relevance of LLPS is unclear. PERIOD proteins are central mammalian circadian clock components and interact with other clock proteins in the core circadian negative feedback loop. Different core clock proteins were previously shown to form large complexes. Here we show that when transgene was stably expressed, PER2 formed nuclear phosphorylation-dependent LLPS condensates that recruited other clock proteins. Super-resolution microscopy of endogenous PER2, however, revealed formation of circadian-controlled, rapidly diffusing microbodies that were resistant to protein concentration changes, hexanediol treatment, and loss of phosphorylation, indicating that they are distinct from the LLPS condensates caused by overexpression. Surprisingly, only a small fraction of endogenous PER2 microbodies transiently interact with endogenous BMAL1 and CRY1, a conclusion that was confirmed in cells and in mice tissues, suggesting an enzyme-like mechanism in the circadian negative feedback process. Together, these results demonstrate that the dynamic interactions of core clock proteins is a key feature of mammalian circadian clock mechanism and the importance of examining endogenous proteins in LLPS and circadian studies.
CryoTransformer: A Transformer Model for Picking Protein Particles from Cryo-EM Micrographs
Authors: Dhakal Ashwin , Gyawali Rajan , Wang Liguo , Cheng Jianlin 
Published: October 2023

AbstractCryo-electron microscopy (cryo-EM) is a powerful technique for determining the structures of large protein complexes. Picking single protein particles from cryo-EM micrographs (images) is a crucial step in reconstructing protein structures from them. However, the widely used template-based particle picking process requires some manual particle picking and is labor-intensive and time-consuming. Though machine learning and artificial intelligence (AI) can potentially automate particle picking, the current AI methods pick particles with low precision or low recall. The erroneously picked particles can severely reduce the quality of reconstructed protein structures, especially for the micrographs with low signal-to-noise (SNR) ratios. To address these shortcomings, we devised CryoTransformer based on transformers, residual networks, and image processing techniques to accurately pick protein particles from cryo-EM micrographs. CryoTransformer was trained and tested on the largest labelled cryo-EM protein particle dataset - CryoPPP. It outperforms the current state-of-the-art machine learning methods of particle picking in terms of the resolution of 3D density maps reconstructed from the picked particles as well as F1-score and is poised to facilitate the automation of the cryo-EM protein particle picking.
Fast myosin binding protein C knockout in skeletal muscle alters length-dependent activation and myofilament structure
Authors: Hessel Anthony L. , Kuehn Michel , Han Seong-Won , Ma Weikang , Irving Thomas C. , Momb Brent A. , Song Taejeong , Sadayappan Sakthivel , Linke Wolfgang A. , Palmer Bradley M. 
Published: October 2023

AbstractIn striated muscle, some sarcomere proteins regulate crossbridge cycling by varying the propensity of myosin heads to interact with actin. Myosin-binding protein C (MyBP-C) is bound to the myosin thick filament and is predicted to interact and stabilize myosin heads in a docked position against the thick filament and limit crossbridge formation, the so-called OFF state. Via an unknown mechanism, MyBP-C is thought to release heads into the so-called ON state, where they are more likely to form crossbridges. To study this proposed mechanism, we used the C2-/-mouse line to knock down fast-isoform MyBP-C completely and total MyBP-C by ∼24%, and conducted mechanical functional studies in parallel with small-angle X-ray diffraction to evaluate the myofilament structure. We report that C2−/−fibers presented deficits in force production and reduced calcium sensitivity. Structurally, passive C2-/-fibers presented altered SL-independent and SL-dependent regulation of myosin head ON/OFF states, with a shift of myosin heads towards the ON state. Unexpectedly, at shorter sarcomere lengths, the thin filament was axially extended in C2-/-vs. non-transgenic controls, which we postulate is due to increased low-level crossbridge formation arising from relatively more ON myosins in the passive muscle that elongates the thin filament. The downstream effect of increasing crossbridge formation in a passive muscle on contraction performance is not known. Such widespread structural changes to sarcomere proteins provide testable mechanisms to explain the etiology of debilitating MyBP-C-associated diseases.
Mu opioid receptors gate the locus coeruleus pain generator
Authors: Norris Makenzie R. , Kuo Chao-Cheng , Dunn Samantha S. , Kim Jenny R. , Becker Léa J. , Borges Gustavo , Thang Loc V. , Parker Kyle E. , McCall Jordan G. 
Published: October 2023

AbstractThe locus coeruleus (LC) plays a paradoxical role in chronic pain. Although largely known as a potent source of endogenous analgesia, increasing evidence suggests injury can transform the LC into a chronic pain generator. We sought to clarify the role of this system in pain. Here, we show optogenetic inhibition of LC activity is acutely antinociceptive. Following long-term spared nerve injury, the same LC inhibition is analgesic – further supporting its pain generator function. To identify inhibitory substrates that may naturally serve this function, we turned to endogenous LC mu opioid receptors (LC-MOR). These receptors provide powerful LC inhibition and exogenous activation of LC-MOR is antinociceptive. We therefore hypothesized that endogenous LC-MOR-mediated inhibition is critical to how the LC modulates pain. Using cell type-selective conditional knockout and rescue of LC-MOR receptor signaling, we show these receptors bidirectionally regulate thermal and mechanical hyperalgesia – providing a functional gate on the LC pain generator.
No evidence of “social immune memory” in Acorn ants (Temnothoax nylanderi)
Authors: Robinson Jaya , Pull Christopher D. 
Published: October 2023

ABSTRACTSocial organisms are predicted to experience higher rates of infectious disease, as the likelihood of transmission increases with higher spatial and temporal proximity of potential hosts. In social insects, this risk is counteracted through a social immune system, where altruistic and collective anti-pathogen behaviours reduce or eliminate the impact of disease at the colony, or ‘superorganism’, level. Superorganismal immune strategies are often analogous to immune responses in metazoan organisms, suggesting that disease may have played a crucial role in shaping multiple major evolutionary transitions. In this study, we investigated whether acorn ants use prior experience with a pathogen to perform more efficient social immunity behaviours upon pathogen reencounter, a potential parallel to metazoan immune memory that we term ‘social immune memory’. UsingTemnothorax nylanderiants, we created experience with the fungal pathogenMetarhizium brunneumboth individually and in groups, to investigate the effect of prior experience when presented with the same pathogen. We further examined the effect of prior pathogen experience when groups of ants differ in their pathogen-experience levels. We found no evidence for social immune memory in our experiments, suggesting positive results in previous studies may be due to sublethal infections, rather than cognitive effects. Alternatively, ants may employ different immune defence strategies depending on context or species, with potential differences in immune system flexibility across major evolutionary scales.
Prdm1 Positively Regulates Liver Group 1 ILCs Cancer Immune Surveillance and Preserves Functional Heterogeneity
Authors: He Jitian , Gao Le , Wang Peiying , Chan Wing Keung , Zheng Yiran , Zhang Yumo , Sun Jiaman , Li Xue , Wang Jiming , Li Xiaohong , Chen Huaiyong , Yang Zhouxin , Wang Youwei 
Published: October 2023

AbstractGroup 1 innate lymphoid cells (ILCs) comprise conventional natural killer (cNK) cells and type 1 innate lymphoid cells (ILC1s). The main functions of liver cNK cells and ILC1s not only include directly killing target cells but also regulating local immune microenvironment of the liver through the secretion of cytokines. Uncovering the intricate mechanisms by which transcriptional factors regulate and influence the functions of liver cNK cells and ILC1s, particularly within the context of liver tumors, presents a significant opportunity to amplify the effectiveness of immunotherapies against liver malignancies. Using Ncr1-drived conditional knockout mouse model, our study reveals the regulatory role ofPrdm1in shaping the composition and maturation of cNK cells. AlthoughPrdm1did not affect the killing function of cNK cells in anin vivocytotoxicity model, a significant increase in cancer metastasis was observed inPrdm1knockout mice. Interferon-gamma (IFN-γ), granzyme B, and perforin secretion decreased significantly inPrdm1deficient cNK cells and liver ILC1s. scRNA sequencing data also provided evidences that Prdm1 maintains functional subsets of cNK cells and liver ILC1s and facilitates communications between cNK cells, liver ILC1s and macrophages. The present study unveiled a novel regulatory mechanism of Prdm1 in cNK cells and liver ILC1s, showing promising potential for developing innovative immune therapy strategies against liver cancer.Graphical abstract
Multiomics characterization of cell type repertoires for urine liquid biopsies
Authors: Vorperian Sevahn K. , DeFelice Brian C. , Buonomo Joseph A. , Chinchinian Hagop J. , Gray Ira J. , Yan Jia , Mach Kathleen E. , La Vinh , Lee Timothy J. , Liao Joseph C. , Lafayette Richard , Loeb Gabriel B. , Bertozzi Carolyn R. , Quake Stephen R. 
Published: October 2023

AbstractUrine is assayed alongside blood in medicine, yet current clinical diagnostic tests utilize only a small fraction of its total biomolecular repertoire, potentially foregoing high-resolution insights into human health and disease. In this work, we characterized the joint landscapes of transcriptomic and metabolomic signals in human urine. We also compared the urine transcriptome to plasma cell-free RNA, identifying a distinct cell type repertoire and enrichment for metabolic signal. Untargeted metabolomic measurements identified a complementary set of pathways to the transcriptomic analysis. Our findings suggest that urine is a promising biofluid yielding prognostic and detailed insights for hard-to-biopsy tissues with low representation in the blood, offering promise for a new generation of liquid biopsies.
Geographic risk assessment ofBatrachochytrium salamandrivoransinvasion in Costa Rica as a means of informing emergence management and mitigation
Authors: Adams Henry C. , Markham Katherine E. , Madden Marguerite , Gray Matthew J. , Vives Federico Bolanos , Chaves Gerardo , Hernandez Sonia M. 
Published: October 2023

AbstractRemotely-sensed risk assessments of emerging, invasive pathogens are key to targeted surveillance and outbreak responses. The recent emergence and spread of the fungal pathogen,Batrachochytrium salamandrivorans(Bsal), in Europe has negatively impacted multiple salamander species. Scholars and practitioners are increasingly concerned about the potential consequences of this lethal pathogen in the Americas, where salamander biodiversity is higher than anywhere else in the world. AlthoughBsalhas not yet been detected in the Americas, certain countries have already proactively implemented monitoring and detection plans in order to identify areas of greatest concern and enable efficient contingency planning in the event of pathogen detection. To predict areas in Costa Rica with a highBsaltransmission risk, we employed ecological niche modeling combined with biodiversity and tourist visitation data to ascertain the specific risk to a country with world renowned biodiversity. Our findings indicate that approximately 23% of Costa Rica’s landmass provides suitable conditions forBsal, posing a threat to 37 salamander species. The Central and Talamanca mountain ranges, in particular, have habitats predicted to be highly suitable for the pathogen. To facilitate monitoring and mitigation efforts, we identified eight specific protected areas that we believe are at the greatest risk due to a combination of high biodiversity, tourist visitation, and suitable habitat forBsal. We advise regular monitoring utilizing remotely-sensed data and ecological niche modeling to effectively targetin-situsurveillance and as places begin implementing educational efforts.
CellTracksColab — A platform for compiling, analyzing, and exploring tracking data
Authors: Gómez-de-Mariscal Estibaliz , Grobe Hanna , Pylvänäinen Joanna W. , Xénard Laura , Henriques Ricardo , Tinevez Jean-Yves , Jacquemet Guillaume 
Published: October 2023

AbstractIn life sciences, tracking objects from movies enables researchers to quantify the behavior of single particles, organelles, bacteria, cells, and even whole animals. While numerous tools now allow automated tracking from video, a significant challenge persists in compiling, analyzing, and exploring the large datasets generated by these approaches. Here, we introduce CellTracksColab, a platform tailored to simplify the exploration and analysis of tracking data. CellTracksColab facilitates the compiling and analysis of results across multiple fields of view, conditions, and repeats, ensuring a holistic dataset overview. CellTracksColab also harnesses the power of high-dimensional data reduction and clustering, enabling researchers to identify distinct behavioral patterns and trends without bias. Finally, CellTracksColab also includes specialized analysis modules enabling spatial analyses (clustering, proximity to specific regions of interest). We demonstrate CellTracksColab capabilities with three use cases, including T-cells and cancer cell migration, as well as filopodia dynamics. CellTracksColab is available for the broader scientific community athttps://github.com/CellMigrationLab/CellTracksColab.