bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sarm1 is not necessary for activation of neuron-intrinsic growth programs yet required for the Schwann cell repair response and peripheral nerve regeneration
Authors: Schmitd Ligia B. , Hafner Hannah , Ward Ayobami , Adib Elham Asghari , Biscola Natalia P. , Kohen Rafi , Patel Manav , Williamson Rachel E. , Desai Emily , Bennett Julianna , Saxman Grace , Athaiya Mitre , Wilborn David , Shumpert Jaisha , Zhao Xiao-Feng , Kawaguchi Riki , Geschwind Daniel H. , Hoke Ahmet , Shrager Peter , Collins Catherine A. , Havton Leif A. , Kalinski Ashley L. , Giger Roman J. 
Published: March 2024

AbstractUpon peripheral nervous system (PNS) injury, severed axons undergo rapid SARM1-dependent Wallerian degeneration (WD). In mammals, the role of SARM1 in PNS regeneration, however, is unknown. Here we demonstrate thatSarm1is not required for axotomy induced activation of neuron-intrinsic growth programs and axonal growth into a nerve crush site. However, in the distal nerve,Sarm1is necessary for the timely induction of the Schwann cell (SC) repair response, nerve inflammation, myelin clearance, and regeneration of sensory and motor axons. InSarm1-/-mice, regenerated fibers exhibit reduced axon caliber, defective nerve conduction, and recovery of motor function is delayed. The growth hostile environment ofSarm1-/-distal nerve tissue was demonstrated by grafting ofSarm1-/-nerve into WT recipients. SC lineage tracing in injured WT andSarm1-/-mice revealed morphological differences. In theSarm1-/-distal nerve, the appearance of p75NTR+, c-Jun+ SCs is significantly delayed.Ex vivo, p75NTRand c-Jun upregulation inSarm1-/-nerves can be rescued by pharmacological inhibition of ErbB kinase. Together, our studies show thatSarm1is not necessary for the activation of neuron intrinsic growth programs but in the distal nerve is required for the orchestration of cellular programs that underlie rapid axon extension.
Beyond homogeneity: Charting the landscape of heterogeneity in psychiatric electroencephalography
Authors: Ebadi Aida , Allouch Sahar , Mheich Ahmad , Tabbal Judie , Kabbara Aya , Robert Gabriel , Lefebvre Aline , Iftimovici Anton , Rodríguez-Herreros Borja , Chabane Nadia , Hassan Mahmoud 
Published: March 2024

AbstractElectroencephalography (EEG) has been thoroughly studied for decades in psychiatry research. Yet its integration into clinical practice as a diagnostic/prognostic tool remains unachieved. We hypothesize that a key reason is the underlying patient’s heterogeneity, overlooked in psychiatric EEG research relying on a case-control approach. We combine HD-EEG with normative modeling to quantify this heterogeneity using two well-established and extensively investigated EEG characteristics -spectral power and functional connectivity-across a cohort of 1674 patients with attention-deficit/hyperactivity disorder, autism spectrum disorder, learning disorder, or anxiety, and 560 matched controls. Normative models showed that deviations from population norms among patients were highly heterogeneous and frequency-dependent. Deviation spatial overlap across patients did not exceed 40% and 24% for spectral and connectivity, respectively. Considering individual deviations in patients has significantly enhanced comparative analysis, and the identification of patient-specific markers has demonstrated a correlation with clinical assessments, representing a crucial step towards attaining precision psychiatry through EEG.
AlGrow: a graphical interface for easy, fast and accurate area and growth analysis of heterogeneously colored targets
Authors: McHale Marcus , Sulpice Ronan 
Published: March 2024

AbstractImage analysis is widely used in plant biology to determine growth rates and other phenotypic characters, with segmentation into foreground and background being a primary challenge. Statistical clustering and learning approaches can reduce the need for user input into this process, though these are computationally demanding, can generalise poorly and are not intuitive to end users. As such, simple strategies that rely on the definition of a range of target colors are still frequently adopted. These are limited by the geometries in color space that are implicit to their definition; i.e. thresholds define cuboid volumes and selected colors with a radius define spheroid volumes. A more comprehensive specification of target color is a hull, in color space, enclosing the set of colors in the image foreground. We developed AlGrow, a software tool that allows users to easily define hulls by clicking on the source image or a three-dimensional projection of its colors. We implemented convex hulls and then alpha-hulls, i.e. a limit applied to hull edge length, to support concave surfaces and disjoint color volumes. AlGrow also provides automated annotation by detecting internal circular markers, such as pot margins, and applies relative indexes to support movement. Analysis of publicly available Arabidopsis image series and metadata demonstrated effective automated annotation and mean Dice coefficients of >0.95 following training on only the first and last images in each series. AlGrow provides both graphical and command line interfaces and is released free and open-source with compiled binaries for the major operating systems.
EDC-3 and EDC-4 Regulate Embryonic mRNA Clearance and Biomolecular Condensate Specialization
Authors: Vidya Elva , Jami-Alahmadi Yasaman , Mayank Adarsh K. , Rizwan Javeria , Xu Jia Ming Stella , Cheng Tianhao , Leventis Rania , Sonenberg Nahum , Wohlschlegel James A. , Vera Maria , Duchaine Thomas F. 
Published: March 2024

AbstractAnimal development is dictated by the selective and timely decay of mRNAs in developmental transitions, but the impact of mRNA decapping scaffold proteins in development is unknown. This study unveils the roles and interactions of the DCAP-2 decapping scaffolds EDC-3 and EDC-4 in the embryonic development ofC. elegans. EDC-3 facilitates the timely removal of specific embryonic mRNAs, includingcgh-1, car-1,andifet-1by reducing their expression, and preventing excessive accumulation of DCAP-2 condensates in somatic cells. We further uncover a novel role for EDC-3 in defining the boundaries between P-bodies, germ granules, and stress granules. Lastly, we show that EDC-4 counteracts EDC-3 and engenders the assembly of DCAP-2 with the GID (CTLH) complex, a ubiquitin ligase involved in maternal-to-zygotic transition (MZT). Our findings support a model wherein multiple RNA decay mechanisms temporally partake in the clearance of maternal and zygotic mRNAs throughout embryonic development.
Targeted Long-Read Bisulfite Sequencing for Promoter Methylation Analysis in Severe Preterm Birth
Authors: Pereyra Silvana , Sardina Angela , Neumann Rita , May Celia , Sapiro Rossana , Bertoni Bernardo , Cappetta Mónica 
Published: March 2024

AbstractDNA methylation plays a critical role in the dynamics of gene expression regulation and the development of various disorders. Whole-genome bisulfite sequencing can provide single base resolution of CpG methylation levels and is the “gold standard” for DNA methylation quantification, but it also has a high cost. In contrast, targeted sequencing is optimal when focusing on specific candidate regions, while providing sufficient sequencing depth. Here, we present a targeted bisulfite sequencing approach to study the methylation status of regions of interest. We amplify selected regions from bisulfite-treated DNA and sequence them using Nanopore sequencing. In this work, we applied this workflow to candidate gene promoters for severe premature labor in a Latin American population.We successfully amplified fragments over 1 Kb in length using long PCR conditions for 12 genes that were barcoded per sample and pooled to be sequenced on MinION flow cells. This approach achieved high sequencing depths, ensuring reliable DNAm estimation. We found significant hypomethylation of theMIR155HGgene promoter in severe preterm birth samples, which is concordant with reported gene expression changes.We demonstrate that combining bisulfite DNA treatment with pooled long-read sequencing is a cost- and time-effective method to evaluate DNAm in several targeted regions and several samples in parallel. This study provides proof-of-concept for larger studies, demonstrating the applicability and high scalability of our assay to any locus of interest. Our experience suggests that this approach can be easily transferred to other diagnostic questions.
GP-HTNLoc: A Graph Prototype Head-Tail Network-based Model for Multi-label Subcellular Localization Prediction of ncRNAs
Authors: Han Shuangkai , Liu Lin 
Published: March 2024

AbstractNumerous research findings demonstrated that understanding the subcellular localization of non-coding RNAs (ncRNAs) is pivotal in elucidating their roles and regulatory mechanisms in cells. Despite the existence of over ten computational models dedicated to predicting the subcellular localization of ncRNAs, a majority of these models are designed solely for single-label prediction. In reality, ncRNAs often exhibit localization across multiple subcellular compartments. Furthermore, the existing multi-label localization prediction models are insufficient in addressing the challenges posed by the scarcity of training samples and class imbalance in ncRNA dataset. This study addresses the limitations of existing models by introducing a novel multi-label localization prediction model for ncRNAs, termed GP-HTNLoc. To alleviate class imbalance, the model adopts a separate training approach for head and tail class labels. In GP-HTNLoc, a pioneering graph prototype module is introduced for capturing potential association of ncRNA samples with labels. This module efficiently learns the graph structure and aggregates sample features. Notably, only few samples are required to obtain label prototypes containing rich information. These prototypes are then utilized to train a transfer learner, facilitating the transfer of meta-knowledge from the head class to the tail class. Experimental results demonstrate that GP-HTNLoc surpasses current state-of-the-art models across all datasets. Ablation study underscore the vital role played by the graph prototype module in enhancing the performance of GP-HTNLoc. The user-friendly online GP-HTNLoc web server can be accessed athttps://56s8y85390.goho.co.
Testing a Method for Quantifying Microplastic Content inMytilus californianus
Authors: Sidhu Ajeetesh S. , Sun William , Helal Mariam B. , Gupta Aryaman , Mittal Aarsh , Ramanathan Serena , Thakur Manu , Jain Bhoomi , Wang Dylan , Benson Andrew , Adams Connor T. 
Published: March 2024

AbstractWith the proliferation of microplastics within the environment, there has been an increased need to quantify them within organic tissues of aquatic species. Several studies have examined the potential role of mussels in filtering these contaminants, prompting interest in characterizing uptake and retention of microplastics in these species. There are a variety of methods to isolate and quantify microplastics, including density separation, enzymatic digestion, and filtration. The applicability of a combined digestion and ultrasonic bath methodology in isolating microplastics from the California mussel (Mytilus californianus Conrad, 1837) was investigated. Microplastics were added to 20-gallon tanks at 0 g (control) 8 mg. Mussel tissues from each tank were digested using potassium hydroxide solutions. These digestions were subjected to vacuum filtration and a sonication bath, then treated with a mixture of sodium hypochlorite and nitric acid. It was found that this method successfully removed organic tissue from the mussels while leaving dyed microplastics intact. The latter were quantified using fluorescent microscopy. This proof-of-principle experiment indicates that this technique can be applied to further studies on environmental impact and retention of microplastics in mussels and may also have utility for other shellfish.
Sensing of dietary amino acids and regulation of calcium dynamics in adipose tissues through Adipokinetic hormone inDrosophila
Authors: Ahmad Muhammad , Wu Shang , Guo Xuan , Perrimon Norbert , He Li 
Published: March 2024

AbstractNutrient sensing and the subsequent metabolic responses are fundamental functions of animals, closely linked to diseases such as type 2 diabetes and various obesity-related diseases.Drosophila melanogasterhas emerged as an excellent model for investigating metabolism and its associated disorders. In this study, we used live-cell imaging to demonstrate that the fly functional homolog of mammalian glucagon, Adipokinetic hormone (AKH), secreted from AKH hormone-producing cells (APCs) in the corpora cardiaca, stimulates intracellular Ca2+waves in the larval fat body/adipose tissue to promote lipid metabolism. Further, we show that specific dietary amino acids activate the APCs, leading to increased intracellular Ca2+and subsequent AKH secretion. Finally, a comparison of Ca2+dynamics in larval and adult fat bodies revealed different mechanisms of regulation, highlighting the interplay of pulses of AKH secretion, extracellular diffusion of the hormone, and intercellular communication through gap junctions. Our study underscores the suitability ofDrosophilaas a powerful model for exploring real-time nutrient sensing and inter-organ communication dynamics.
Unraveling the Genetic Comorbidity Landscape of Alzheimer’s Disease
Authors: Zhang Xueli , Li Dantong , Ye Siting , Liu Shunming , Ma Shuo , Li Min , Peng Qiliang , Hu Lianting , Shang Xianwen , He Mingguang , Zhang Lei 
Published: March 2024

AbstractAlzheimer’s disease (AD) has emerged as the most prevalent and complex neurodegenerative disorder among the elderly population. However, the genetic comorbidity etiology for AD remains poorly understood. In this study, we conducted pleiotropic analysis for 41 AD phenotypic comorbidities, identifying ten genetic comorbidities with 16 pleiotropy genes associated with AD. Through biological functional and network analysis, we elucidated the molecular and functional landscape of AD genetic comorbidities. Furthermore, leveraging the pleiotropic genes and reported biomarkers for AD genetic comorbidities, we identified 50 potential biomarkers for AD diagnosis. Our findings deepen the understanding of the occurrence of AD genetic comorbidities and provide new insights for the search for AD diagnostic markers.HighlightsThe present study has focused on the comorbidities associated with Alzheimer’s disease (AD) by constructing a landscape of these comorbidities at various levels, including diseases, genetics, and pathways.The study findings reveal novel and significant pathways that contribute to the etiology of AD and its comorbidities.By exploring pleiotropic genes and reported biomarkers of AD comorbidities, the study has identified several potential diagnostic biomarker candidates for AD.Abstract FigureGraphic abstract.Study pipeline.
Biochemical properties of chromatin domains define genome compartmentalization
Authors: Lucini Federica , Petrini Cristiano , Salviato Elisa , Pal Koustav , Rosti Valentina , Gorini Francesca , Santarelli Philina , Quadri Roberto , Lembo Giovanni , Graziano Giulia , Di Patrizio Soldateschi Emanuele , Tagliaferri Ilario , Pinatel Eva , Sebestyén Endre , Rotta Luca , Gentile Francesco , Vaira Valentina , Lanzuolo Chiara , Ferrari Francesco 
Published: March 2024

ABSTRACTChromatin three-dimensional (3D) organization inside the cell nucleus determines the separation of euchromatin and heterochromatin domains. Their segregation results in the definition of active and inactive chromatin compartments, whereby the local concentration of associated proteins, RNA and DNA results in the formation of distinct subnuclear structures. Thus, chromatin domains spatially confined in a specific 3D nuclear compartment are expected to share similar epigenetic features and biochemical properties, in terms of accessibility and solubility.Based on this rationale, we developed the 4f-SAMMY-seq to map euchromatin and heterochromatin based on their accessibility and solubility, starting from as little as 10,000 cells. Adopting a tailored bioinformatic data analysis approach we reconstruct also their 3D segregation in active and inactive chromatin compartments and sub-compartments, thus recapitulating the characteristic properties of distinct chromatin states.A key novelty is the capability to map both the linear segmentation of open and closed chromatin domains, as well as their 3D compartmentalization in one single experiment.
Visualization of endogenous G proteins on endosomes and other organelles
Authors: Jang Wonjo , Senarath Kanishka , Feinberg Gavin , Lu Sumin , Lambert Nevin A. 
Published: March 2024

AbstractClassical G protein-coupled receptor (GPCR) signaling takes place in response to extracellular stimuli and involves receptors and heterotrimeric G proteins located at the plasma membrane. It has recently been established that GPCR signaling can also take place from intracellular membrane compartments, including endosomes that contain internalized receptors and ligands. While the mechanisms of GPCR endocytosis are well understood, it is not clear how well internalized receptors are supplied with G proteins. To address this gap we use gene editing, confocal microscopy, and bioluminescence resonance energy transfer to study the distribution and trafficking of endogenous G proteins. We show here that constitutive endocytosis is sufficient to supply newly internalized endocytic vesicles with 20-30% of the G protein density found at the plasma membrane. We find that G proteins are present on early, late, and recycling endosomes, are abundant on lysosomes, but are virtually undetectable on the endoplasmic reticulum, mitochondria, and the medial Golgi apparatus. Receptor activation does not change heterotrimer abundance on endosomes. Our findings provide a subcellular map of endogenous G protein distribution, suggest that G proteins may be partially excluded from nascent endocytic vesicles, and are likely to have implications for GPCR signaling from endosomes and other intracellular compartments.
Atypical Cell Cycle Regulation Promotes Mammary Stem Cell Expansion and Therapeutic Resistance
Authors: Fifield Bre-Anne , Vusich John , Haberfellner Erika , Andrechek Eran R. , Porter Lisa A. 
Published: March 2024

AbstractBackgroundThe cell cycle of mammary stem cells must be tightly regulated to ensure normal homeostasis of the mammary gland to prevent abnormal proliferation and susceptibility to tumorigenesis. The atypical cell cycle regulator, Spy1 can override cell cycle checkpoints, including those activated by the tumour suppressor p53 which mediates mammary stem cell homeostasis. Spy1 has also been shown to promote expansion of select stem cell populations in other developmental systems. Spy1 protein is elevated during proliferative stages of mammary gland development, is found at higher levels in human breast cancers, and promotes susceptibility to mammary tumourigenesis when combined with loss of p53. We hypothesized that Spy1 cooperates with loss of p53 to increase susceptibility to tumour initiation due to changes in susceptible mammary stem cell populations during development and drives the formation of more aggressive stem like tumours.MethodsUsing a transgenic mouse model driving expression of Spy1 within the mammary gland, mammary development and stemness were assessed. These mice were intercrossed with p53 null mice to study the tumourigenic properties of Spy1 driven p53 null tumours, as well as global changes in signaling via RNA sequencing analysis.ResultsWe show that elevated levels of Spy1 leads to expansion of mammary stem cells, even in the presence of p53, and an increase in mammary tumour formation. Spy1-driven tumours have an increased cancer stem cell population, decreased checkpoint signaling, and demonstrate an increase in therapy resistance. Loss of Spy1 decreases tumor onset and reduces the cancer stem cell population.ConclusionsThis data demonstrates the potential of Spy1 to expand mammary stem cell populations and contribute to the initiation and progression of aggressive, drug resistant breast cancers with increased cancer stem cell populations.
Frequency-specific cortico-subcortical interaction in continuous speaking and listening
Authors: Abbasi Omid , Steingräber Nadine , Chalas Nikos , Kluger Daniel S. , Gross Joachim 
Published: March 2024

AbstractSpeech production and perception involve complex neural dynamics in the human brain. Using magnetoencephalography (MEG), our study explores the interaction between cortico-cortical and cortico-subcortical connectivities during these processes. Our connectivity findings during speaking revealed a significant connection from the right cerebellum to the left temporal areas in low frequencies, which displayed an opposite trend in high frequencies. Notably, high-frequency connectivity was absent during the listening condition. These findings underscore the vital roles of cortico-cortical and cortico-subcortical connections within the speech production and perception network. The results of our new study enhance our understanding of the complex dynamics of brain connectivity during speech processes, emphasizing the distinct frequency-based interactions between various brain regions.
Frontoparietal network integrity supports cognitive function despite atrophy and hypoperfusion in pre-symptomatic frontotemporal dementia: multimodal analysis of brain function, structure and perfusion
Authors: Liu Xulin , Jones P Simon , Pasternak Maurice , Masellis Mario , Bouzigues Arabella , Russell Lucy L , Foster Phoebe H. , Ferry-Bolder Eve , van Swieten John , Jiskoot Lize , Seelaar Harro , Sanchez-Valle Raquel , Laforce Robert , Graff Caroline , Galimberti Daniela , Vandenberghe Rik , de Mendonça Alexandre , Tiraboschi Pietro , Santana Isabel , Gerhard Alexander , Levin Johannes , Sorbi Sandro , Otto Markus , Pasquier Florence , Ducharme Simon , Butler Chris , Le Ber Isabelle , Finger Elizabeth , Tartaglia Maria Carmela , Synofzik Matthis , Moreno Fermin , Borroni Barbara , Rohrer Jonathan D. , Tsvetanov Kamen A. , Rowe James B. ,   The GENFI consortium
Published: March 2024

ABSTRACTINTRODUCTIONGenetic mutation carriers of frontotemporal dementia can remain cognitively well despite neurodegeneration. A better understanding of brain structural, perfusion and functional patterns in pre-symptomatic stage could inform accurate staging and potential mechanisms.METHODSWe included 207 pre-symptomatic genetic mutation carriers and 188 relatives without mutations. The grey matter volume, cerebral perfusion, and resting-state functional network maps were co-analyzed using linked independent component analysis (LICA). Multiple regression analysis was used to investigate the relationship of LICA components to genetic status and cognition.RESULTSPre-symptomatic mutation carriers showed an age-related decrease in the left frontoparietal network integrity while non-carriers did not. Executive functions of mutation carriers became dependent on the left frontoparietal network integrity in older age.DISCUSSIONThe frontoparietal network integrity of pre-symptomatic mutation carriers showed a distinctive relationship to age and cognition compared to non-carriers, suggesting a contribution of the network integrity to brain resilience, despite atrophy and hypoperfusion.