bluuebunny/crossref_metadata_2025_split huggingface dataset:
The counterpart congenital overgrowth syndromes Beckwith-Wiedemann Syndrome in human and large offspring syndrome in bovine involve alterations in DNA methylation, transcription, and chromatin configuration
Authors: Li Yahan , Xiao Ping , Boadu Frimpong , Goldkamp Anna K. , Nirgude Snehal , Cheng Jianlin , Hagen Darren E. , Kalish Jennifer M. , Rivera Rocío Melissa 
Published: December 2023

AbstractBeckwith-Wiedemann Syndrome (BWS, OMIM #130650) is a congenital epigenetic disorder in humans which affects approximately 1 in 10,340 children. The incidence is likely an underestimation as the condition is usually recognized based on observable phenotypes at birth. BWS children have up to a 28% risk of developing tumors and currently, only 80% of patients can be corroborated molecularly (epimutations/variants). It is unknown how the subtypes of this condition are molecularly similar/dissimilar globally, therefore there is a need to deeply characterize the syndrome at the molecular level. Here we characterize the methylome, transcriptome and chromatin configuration of 18 BWS individuals together with the animal model of the condition, the bovine large offspring syndrome (LOS). Sex specific comparisons are performed for a subset of the BWS patients and LOS. Given that this epigenetic overgrowth syndrome has been characterized as a loss-of-imprinting condition, parental allele-specific comparisons were performed using the bovine animal model. In general, the differentially methylated regions (DMRs) detected in BWS and LOS showed significant enrichment for CTCF binding sites. Altered chromosome compartments in BWS and LOS were positively correlated with gene expression changes, and the promoters of differentially expressed genes showed significant enrichment for DMRs, differential topologically associating domains, and differential A/B compartments in some comparisons of BWS subtypes and LOS. We show shared regions of dysregulation between BWS and LOS, including several HOX gene clusters, and also demonstrate that altered DNA methylation differs between the clinically epigenetically identified BWS patients and those identified as having DNA variants (i.e.CDKN1Cmicrodeletion). Lastly, we highlight additional genes and genomic regions that have the potential to serve as targets for biomarker development to improve current molecular methodologies. In summary, our results suggest that genome-wide alternation of chromosome architecture, which is partially caused by DNA methylation changes, also contribute to the development of BWS and LOS.
Levodopa reduces consumption of multiple classes of addictive substances in rats
Authors: Farero Ryan D. , Holtz Nathan A. , Lee Suhjung J. , Kruse Lauren C. , Clark Jeremy J. , Phillips Paul E. M. 
Published: December 2023

AbstractDopamine transmission is implicated in aberrant behaviors associated with substance use disorders. Previous research revealed a causal link between excessive drug consumption and the loss of dopamine signaling to stimuli associated with psychostimulant use. The emerging change in dopamine signaling is specific to stimuli associated with the substance rather than the pharmacological properties of the drug itself. Because the change in dopamine signaling was specific to the associated stimuli and not the pharmacological properties of the substance, we examined if treatment with the dopamine precursor, L-DOPA, alters alcohol and opioid self-administration. Therefore, we trained rats to orally self-administer ethanol or the synthetic opioid fentanyl and found that treating animals with L-DOPA significantly reduced consumption of both alcohol and fentanyl. These data suggest dopamine signaling has a vital role in mediating the amount of drug animals will voluntarily take, across multiple classes of drugs. Importantly, these data are preclinical demonstrations of L-DOPA being utilized as a harm reducing treatment in substance use disorders.
‘Are you even listening?’ - EEG-based decoding of absolute auditory attention to natural speech
Authors: Roebben Arnout , Heintz Nicolas , Geirnaert Simon , Francart Tom , Bertrand Alexander 
Published: December 2023

AbstractObjectiveIn this study, we use electroencephalography (EEG) recordings to determine whether a subject is actively listening to a presented speech stimulus. More precisely, we aim to discriminate between an active listening condition, and a distractor condition where subjects focus on an unrelated distractor task while being exposed to a speech stimulus. We refer to this task as absolute auditory attention decoding.ApproachWe re-use an existing EEG dataset where the subjects watch a silent movie as a distractor condition, and introduce a new dataset with two distractor conditions (silently reading a text and performing arithmetic exercises). We focus on two EEG features, namely neural envelope tracking (NET) and spectral entropy (SE). Additionally, we investigate whether the detection of such an active listening condition can be combined with a selective auditory attention decoding task, where the goal is to decide to which of multiple competing speakers the subject is attending. The latter is a key task in so-called neuro-steered hearing devices that aim to suppress unattended audio, while preserving the attended speaker.Main resultsContrary to a previous hypothesis of higher SE being related with actively listening rather than passively listening (without any distractors), we find significantly lower SE in the active listening condition compared to the distractor conditions. Nevertheless, the NET is consistently significantly higher when actively listening. Similarly, we show that the accuracy of a selective auditory attention decoding task improves when evaluating the accuracy only on the highest NET segments. However, the reverse is observed when evaluating the accuracy only on the lowest SE segments.SignificanceWe conclude that the NET is more reliable for decoding absolute auditory attention as it is consistently higher when actively listening, whereas the relation of the SE between actively and passively listening seems to depend on the nature of the distractor.
Scm6A: A fast and low-cost method for quantifying m6A modifications at the single-cell level
Authors: Li Yueqi , Li Jingyi , Li Wenxing , Liang Shuaiyi , Wei Wudi , Chu Jiemei , Lai Jingzhen , Lin Yao , Chen Hubin , Su Jinming , Hu Xiaopeng , Wang Gang , Meng Jun , Jiang Junjun , Ye Li , An Sanqi 
Published: December 2023

AbstractIt is widely accepted that m6A exhibits significant intercellular specificity, which poses challenges for its detection using existing m6A quantitative methods. In this study, we introduce Scm6A, a machine learning-based approach for single-cell m6A quantification. Scm6A leverages input features derived from the expression levels of m6Atransregulators andcissequence features, and found that Scm6A offers remarkable prediction efficiency and reliability. To further validate the robustness and precision of Scm6A, we applied a winscore-based m6A calculation method to conduct m6A-seq analysis on CD4+and CD8+T-cells isolated through magnetic-activated cell sorting (MACS). Subsequently, we employed Scm6A for analysis on the same samples. Notably, the m6A levels calculated by Scm6A exhibited a significant positive correlation with m6A quantified through m6A-seq in different cells isolated by MACS, providing compelling evidence for Scm6A’s reliability. We also used the scm6A-seq method to validate the reliability of our approach. Additionally, we performed single-cell level m6A analysis on lung cancer tissues as well as blood samples from COVID-19 patients, and demonstrated the landscape and regulatory mechanisms of m6A in different T-cell subtypes from these diseases. In summary, our work has yielded a novel, dependable, and accurate method for single-cell m6A detection. We are confident that Scm6A will have broad applications in the realm of m6A-related research.
Single-cell Total-RNA Profiling Unveils Regulatory Hubs of Transcription Factors
Authors: Niu Yichi , Luo Jiayi , Zong Chenghang 
Published: December 2023

AbstractRecent development of RNA velocity uses master equations to establish the kinetics of the life cycle of RNAs from nascent RNA to mature RNA to degradation. To feed this kinetic analysis, simultaneous measurement of nascent RNA and mature RNA in single cells is greatly desired. However, the majority of single-cell RNA-seq chemistry only captures mature RNA species to measure gene expressions. Here, we develop a one-step total-RNA chemistry-based scRNA-seq method: snapTotal-seq. We benchmarked this method with multiple single-cell RNA-seq assays in their performance in kinetic analysis of cell cycle by RNA velocity. Next, with LASSO regression between transcription factors, we identified the critical regulatory hubs mediating the cell cycle dynamics. We also applied snapTotal-seq to profile the oncogene-induced senescence and identified the key regulatory hubs governing the entry of senescence. Furthermore, from the comparative analysis of nascent RNA and mature RNA, we identified a significant portion of genes whose expression changes occurred in mature RNA but not to the same degree in nascent RNA, indicating these gene expression changes are mainly controlled by post-transcriptional regulation. Overall, we demonstrate that snapTotal-seq can provide enriched information about gene regulation, especially during the transition between cell states.
NK cells contribute to resistance to anti-PD1 therapy in immune-excluded melanomas
Authors: Landeloos Ewout , Pozniak Joanna , Roda Niccoló , Visscher Amber De , Martinez Asier Antoranz , Herck Yannick Van , Bervoets Greet , Bosisio Francesca , Boecxstaens Veerle , Bassez Ayse , Lambrechts Diether , Matthys Patrick , Bechter Oliver , Marine Jean-Christophe 
Published: December 2023

AbstractImmune checkpoint blockade (ICB) has become a standard of care in the treatment of metastatic melanoma (MM). Although ICB is particularly successful in some MM patients, more than half do not obtain a durable benefit. Biomarkers that predict response are urgently needed and overcoming intrinsic resistance is key to improving the success of ICB therapy. Using single cell RNA sequencing, we characterized the immune landscape of pre- and early on-treatment biopsies taken from a cohort of MM patients (n>20) exposed to ICB therapy. Our analysis identified >20 immune cell types and confirmed previously described associations between the abundance of various CD8 T cell populations and ICB outcome. Unexpectedly, we found that lack of response was associated with an increased occurrence of a granulysin-expressing (GNLY+) natural killer (NK) cell population. This observation was replicated in other MM cohorts and in a breast cancer cohort in which paired biopsies were also collected pre and early-on ICB therapy. Spatial proteomics revealed that whereas NK cells colocalized with CD8 T cells within the tumour bed in responding lesions, these cells accumulated at the tumour margin in non-responding lesions. Strikingly, depletion of NK cells in an NRAS-driven melanoma mouse model, which exhibits an immune-excluded phenotype and is refractory to ICB, promoted massive immune cell infiltration and tumour clearance upon anti-PD1 exposure. These data highlight a differential immune cell topography between early on-treatment responding and nonresponding MM lesions, which could be exploited to develop a robust stratification biomarker, and unravel an unexpected contribution of NK cells in primary resistance to ICB.
VCD-induced menopause mouse model reveals reprogramming of hepatic metabolism
Authors: Kumari Roshan , Ponte Michael E. , Franczak Edziu , Prom John C. , O’Neil Maura F. , Sardiu Mihaela E. , Lutkewitte Andrew J. , Shankar Kartik , Morris E. Matthew , Thyfault John P. 
Published: December 2023

ABSTRACTMenopause adversely impacts systemic energy metabolism and increases the risk of metabolic disease(s) including hepatic steatosis, but the mechanisms are largely unknown. Dosing female mice with vinyl cyclohexene dioxide (VCD) selectively causes follicular atresia in ovaries, leading to a murine menopause-like phenotype. In this study, we treated female C57BL6/J mice with VCD (160mg/kg i.p. for 20 consecutive days followed by verification of the lack of estrous cycling) to investigate changes in body composition, energy expenditure (EE), hepatic mitochondrial function, and hepatic steatosis across different dietary conditions. VCD treatment induced ovarian follicular loss and increased follicle-stimulating hormone (FSH) levels in female mice, mimicking a menopause-like phenotype. VCD treatment did not affect body composition, or EE in mice on a low-fat diet or in response to a short-term (1-week) high-fat, high sucrose diet (HFHS). However, the transition to a HFHS lowered cage activity in VCD mice. A chronic HFHS diet (16 weeks) significantly increased weight gain, fat mass, and hepatic steatosis in VCD-treated mice compared to HFHS-fed controls. In the liver, VCD mice showed suppressed hepatic mitochondrial respiration on LFD, while chronic HFHS diet resulted in compensatory increases in hepatic mitochondrial respiration. Also, liver RNA sequencing revealed that VCD promoted global upregulation of hepatic lipid/cholesterol synthesis pathways. Our findings suggest that the VCD- induced menopause model compromises hepatic mitochondrial function and lipid/cholesterol homeostasis that sets the stage for HFHS diet-induced steatosis while also increasing susceptibility to obesity.
Whole group tracking reveals that relatedness drives consistent subgrouping patterns in white-nosed coatis
Authors: Grout Emily M. , Ortega Josué , Minasandra Pranav , Quin Matthew J. , Crofoot Margaret C. , Strandburg-Peshkin Ariana , Hirsch Ben T. 
Published: December 2023

AbstractThe formation of subgroups can allow group-living animals flexibility to balance the costs and benefits of sociality over time. Subgrouping dynamics emerge from individual decisions about whether and with whom to maintain cohesion, with these decisions potentially influenced by ecological, physiological, and social factors. We GPS-tracked the movements of nearly all members of three wild white-nosed coati (Nasua narica) social groups that differed in their demographic profiles to better understand how these highly social, frugivorous carnivores weight the relative importance of these different factors in their grouping decisions. Quantifying group movements and subgrouping patterns, we found that two of the three groups we tracked exhibited fission-fusion behaviours, with groups splitting into subgroups that persisted over varying timespans from minutes to days. In contrast, the third group remained together across the entire observation period. When groups split, they did not do so randomly; instead, individuals tended to form subgroups with the same individuals consistently over time. Assessing the drivers of subgrouping patterns revealed that subgroup membership was associated with genetic relatedness, but not physiological similarity as quantified by age and sex homophily. Our results demonstrate great variation in subgrouping patterns within a single species, while also highlighting a consistent role of relatedness in driving social preferences when subgroups form.
TurboID mapping reveals exportome of secreted intrinsically disordered proteins in the transforming parasiteTheileria annulata
Authors: Brühlmann Francis , Perry Carmen , Griessen Charlotte , Gunasekera Kapila , Reymond Jean-Louis , Naguleswaran Arunasalam , Rottenberg Sven , Woods Kerry , Olias Philipp 
Published: December 2023

ABSTRACTTheileria annulatais a tick-transmitted apicomplexan parasite that gained the unique ability among parasitic eukaryotes to transform its host cell, inducing a fatal cancer-like disease in cattle. Understanding the mechanistic interplay driving this transformation between the host cell and malignantTheileriaspecies requires the identification of responsible parasite effector proteins. In this study, we used TurboID-based proximity labelling, which unbiasedly identified secreted effector proteins within host cell compartments. By fusing TurboID to nuclear export or localization signals, we biotinylated proteins in the vicinity of the ligase enzyme in the nucleus or cytoplasm of infected macrophages, followed by mass spectrometry analysis. Our approach revealed with high confidence nine nuclear and four cytosolic candidate effector proteins within the host cell compartments, eight of which had no orthologues in non-transformingT. orientalis. Strikingly, all eight of these proteins are predicted to be highly intrinsically disordered proteins (IDPs). We discovered a novel tandem arrayed protein family, Nuclear Intrinsically Disordered Proteins (NIDP) 1 - 4, featuring diverse functions predicted by conserved protein domains. Particularly, NIDP2 exhibited a biphasic host cell-cycle dependent localization, interacting with the EB1/CD2AP/CLASP1 parasite membrane complex during mitosis and the tumor suppressor Stromal Antigen 2 (STAG2), a cohesion complex subunit, in the host nucleus. In addition to STAG2, numerous NIDP2-associated host nuclear proteins implicated in various cancers were identified, shedding light on the potential role of theT. annulataexported protein family NIDP in host cell transformation and cancer-related pathways.IMPORTANCETurboID proximity labelling was used to unveil the secreted proteins ofTheileria annulata, an apicomplexan parasite responsible for a fatal, proliferative disorder in cattle, representing a significant socio-economic burden particularly in north Africa, central Asia, and India. Our investigation has provided important insights into the unique host-parasite interaction, revealing effector proteins characterized by high intrinsically disordered protein (IDP) structures. Remarkably, these proteins are conspicuously absent in non-transformingTheileriaspecies, strongly suggesting their central role in the transformative processes within host cells. In addition, our study identified a novel tandem arrayed protein family, with Nuclear Intrinsically Disordered Protein (NIDP) 2 emerging as a central player interacting with established tumor genes. Significantly, this work represents the first unbiased screening for exported effector proteins inTheileriaand contributes essential insights into the molecular intricacies behind the malignant transformation of immune cells.
Abundant microorganisms in soil are mainly controlled by stochastic processes, while bacteria and fungi differ in rare taxa
Authors: Qian Guo , Gong Lu 
Published: December 2023

AbstractThe assembly mode of microbial communities helps to explain the ecological processes of soil subsurface groups, and abundant and rare microorganisms have their own unique assembly patterns. In this paper, the effect of changing vegetation types on the assembly of bacteria and fungi with different abundances in soil was investigated by iCAMP in the Tianshan Mountains. The results showed that: (i) there were differences in the distribution of rare and abundant microbial communities among different vegetation types: the main trends were forests>shrubs > grasslands, and the α diversity and variability of rare microorganisms were greater than those of abundant taxa; (ii) abundant taxa were mainly affected by stochastic processes (mainly diffusion limitation), whereas among rare microbes, the main controlling process for bacteria was heterogeneous selection and for fungi was diffusion limitation; (ⅲ)soil carbon, nitrogen and temperature were important determinants driving bacterial community structure. Our results deepen the understanding of the various ecological processes involved in microbial community assembly, reveal the effects of environmental factors on abundant and rare microorganisms, and provide evidence for understanding the mechanisms of soil microbial community construction among different vegetation covers in arid zones.ImportanceThe study compares the response of different vegetation types to soil microbial community processes in the arid zone and deepens the understanding of the mechanisms of soil microbial community composition at different abundances.
Acidic Sphingomyelinase Interactions with Lysosomal Membranes and Cation Amphiphilic Drugs: a Molecular Dynamics Investigation
Authors: Scrima Simone , Lambrughi Matteo , Maeda Kenji , Jäättelä Marja , Papaleo Elena 
Published: December 2023

AbstractLysosomes are pivotal in cellular functions and disease, influencing cancer progression and therapy resistance with Acid Sphingomyelinase (ASM) governing their membrane integrity. Moreover, cation amphiphilic drugs (CADs) are known as ASM inhibitors and have anti-cancer activity, but the structural mechanisms of their interactions with the lysosomal membrane and ASM are poorly explored.Our study, leveraging all-atom explicit solvent molecular dynamics simulations, delves into the interaction of glycosylated ASM with the lysosomal membrane and the effects of one of the CAD representatives, i.e., ebastine on the membrane and ASM.Our results confirm the ASM association to the membrane through the saposin domain, previously only showed with coarse grained models. Furthermore, we elucidated the role of specific residues and ASM-induced membrane curvature in lipid recruitment and orientation. Ebastine also interferes with the association of ASM with the membrane at the level of a loop in the catalytic domain engaging in membrane interactions. Our computational approach, applicable to various CADs or membrane compositions, provides insights into ASM and CAD interaction with the membrane, offering a valuable tool for future studies.
Common anesthetic used in preclinical PET imaging inhibits metabolism of the PET tracer [18F]3F4AP
Authors: Ramos-Torres Karla , Sun Yang , Takahashi Kazue , Zhou Yu-Peng , Brugarolas Pedro 
Published: December 2023

ABSTRACTPET imaging studies in laboratory animals are almost always performed under isoflurane anesthesia to ensure that the subject stays still during the image acquisition. Isoflurane is effective, safe, and easy to use, and it is generally assumed to not have an impact on the imaging results. Motivated by marked differences observed in [18F]3F4AP brain uptake and metabolism between human and nonhuman primate studies, this study investigates the possible effect of isoflurane on [18F]3F4AP metabolism and brain uptake. Isoflurane was found to largely abolish tracer metabolism in mice resulting in a 3.3-fold higher brain uptake in anesthetized mice at 35 min post radiotracer administration, which replicated the observed effect in unanesthetized humans and anesthetized monkeys. This effect is attributed to isoflurane’s interference in the CYP2E1-mediated breakdown of [18F]3F4AP, which was confirmed by reproducing a higher brain uptake and metabolic stability upon treatment with the known CYP2E1 inhibitor disulfiram. These findings underscore the critical need to examine the effect of isoflurane in PET imaging studies before translating tracers to humans that will be scanned without anesthesia.