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Mashup Score: 1
Current state-of-the-art tools for analyzing extracellular vesicles (EVs) offer either highly sensitive but unidimensional bulk measurements of EV components, or high-resolution multiparametric single particle analyses which lack standardization and appropriate reference materials. This limits the accuracy of assessment of marker abundance and overall marker distribution among individual EVs, and finally, the understanding of true EV heterogeneity. In this study, we aimed to define the standardized operating procedures and reference material for fluorescent characterization of EVs with two commonly used EV analytical platforms – nanoparticle tracking analysis (NTA) and nano-flow cytometry (nFCM). For the first time, we achieved quantitative fluorescence analyses on ZetaView NTA and NanoAnalyzer nFCM instruments, by utilizing yellow-green FluoSpheres (FS) with assigned ERF (equivalent reference fluorophore) values. This standardization technique allowed for fluorescent EV signal to be e
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Mashup Score: 0Downregulation of PIK3IP1/TrIP on T cells is controlled by TCR signal strength, PKC, and metalloprotease-mediated cleavage - 1 hour(s) ago
The protein known as PI3K-interacting protein (PIK3IP1), or transmembrane inhibitor of PI3K (TrIP), is highly expressed by T cells and can modulate PI3K activity in these cells. Several studies have also revealed that TrIP is rapidly downregulated following T cell activation. However, it is unclear as to how this downregulation is controlled. Using a novel monoclonal antibody that robustly stains cell-surface TrIP, we demonstrate that TrIP is lost from the surface of activated T cells in a manner dependent on the strength of signaling through the T cell receptor (TCR) and specific downstream signaling pathways. In addition, TrIP expression returns after 24 hours, suggesting that it may play a role in resetting TCR signaling at later time points. Finally, by expressing truncated forms of TrIP in cells, we identify the region in the extracellular stalk domain of TrIP that is targeted for proteolytic cleavage by metalloprotease ADAM17. ### Competing Interest Statement The authors have dec
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Mashup Score: 2Non-invasive evidence for rhythmic interactions between the human brain, spinal cord, and muscle - 2 hour(s) ago
Voluntary human movement relies on interactions between the spinal cord, brain, and sensory afferents. The integrative function of the spinal cord has proven particularly difficult to study directly and non-invasively in humans due to challenges in measuring spinal cord activity. Investigations of sensorimotor integration often rely on cortico-muscular coupling, which can capture interactions between the brain and muscle, but cannot reveal how the spinal cord mediates this communication. Here, we introduce a system for direct, non-invasive imaging of concurrent brain and cervical spinal cord activity in humans using optically-pumped magnetometers (OPMs). We used this system to study endogenous interactions between the brain, spinal cord, and muscle involved in sensorimotor control during simple maintained contraction. Participants (n=3) performed a hand contraction with real-time visual feedback while we recorded brain and spinal cord activity using OPMs and muscle activity using EMG.
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Mashup Score: 0
Proficient use of multiple fingers across both hands to manipulate objects empowers our daily interactions with the world. Gaining dexterity in performing delicate tasks with both hands can take weeks to years to master. The goal of this study is to understand if simple mechanical abstraction could improve performance on bimanual response time to visual stimuli, using index fingers and thumbs. A plate placed over the buttons was introduced to induce a new conceptualization of the task, where instead of pressing buttons, the subjects were rocking a plate over them. We observed improved performance in bimanual actions but not in unilateral actions. In the group of middle-aged individuals, synchronous bimanual responses were enhanced with the use of this mechanical augmentation. This effect remained even after removing the plate. Conversely, within a group of younger adults, there was no observed effect. We believe that highly similar afferent sensory signals from the fingers of both hand
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Mashup Score: 03-Nitropropionic acid induces histological and behavioral alterations in adult zebrafish: role of antioxidants on behavioral dysfunction - 2 hour(s) ago
Huntingtons disease (HD) is a neurodegenerative disease marked by progressive motor and non-motor symptoms such as neuropsychiatric disruption and cognitive dysfunction. It has been reported that some pathogenic mechanisms resulting in neuronal cell death in this disease involve neurodegeneration and oxidative stress. 3-Nitropropionic acid (3-NPA), a natural toxin that promotes the irreversible suppression of mitochondrial complex II, has been used to understand the HD pathogenesis. This neurotoxin mimics the biochemical, central neurodegeneration, peripheral and behavioral phenotype alterations observed in HD. Here we investigated 3-NPA (60 mg/kg) effects on histological and oxidative stress parameters on brain and muscular tissues. We also evaluated the effects of three antioxidant compounds on 3-NPA-induced behavioral phenotypes in adult zebrafish. For the evaluation of the antioxidant effects, adult zebrafish were submitted to a single acute intraperitoneal injection of vitamin C,
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Mashup Score: 0Hydrogel-embedded precision-cut lung slices support ex vivo culture of in vivo-induced premalignant lung lesions - 2 hour(s) ago
Lung cancer is the leading cause of global cancer death and prevention strategies are key to reducing mortality. Medical prevention may have a larger impact than treatment on mortality by targeting high-risk populations and reducing their lung cancer risk. Premalignant lesions (PMLs) that can be intercepted by prevention agents are difficult to study in humans but easily accessible in murine preclinical carcinogenesis studies. Precision-cut lung slices (PCLS) are underutilized as an ex vivo model for lung cancer studies due to limited culture time. Embedding PCLS within bioengineered hydrogels extends PCLS viability and functionality for up to six weeks. Here, we embedded PCLS generated from urethane-induced murine PMLs in cell-degradable and non-degradable hydrogels to study viability and activity of the tissues over six weeks. PMLs in hydrogel-embedded PCLS maintained viability, gene expression, and proliferation. Treatment of hydrogel-embedded PCLS containing urethane-induced PMLs w
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Mashup Score: 0Deep Quantitative Proteomics Identifies Conserved Proteome Alterations in Low and High-Grade Serous Ovarian Cancers - 2 hour(s) ago
Low-grade serous ovarian carcinoma (LGSOC) is a rare and largely chemoresistant subtype of epithelial ovarian cancer. Unlike treatment for high-grade serous ovarian cancer (HGSOC), management options for LGSOC patients are limited, in part, due to a lack of deep molecular characterization of this disease. To address this limitation, we performed quantitative mass spectrometry-based proteomic analyses of whole tissue collections of tumors harvested from LGSOC (n=12) and HGSOC (n=24) patients or normal fallopian tube tissues (n=12) from women with benign disease. We quantified 7,043 proteins across all patient samples and unsupervised analyses revealed proteome alterations distinctly stratify fallopian tube tissue, LGSOC, and HGSOC tumors. Proteins elevated in LGSOC compared to HGSOC tumors (LIMMA adjusted p < 0.05) were enriched for pathways regulating cilium assembly and included a pathway regulating activation of FAK1 by MET, a therapeutic target in LGSOC. Using data from an independe
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Mashup Score: 0High Refractive Index Imaging Buffer for Dual Color 3D SMLM Imaging of Thick Samples - 2 hour(s) ago
The current limitations of single-molecule localization microscopy (SMLM) in deep tissue imaging, primarily due to depth-dependent aberrations caused by refractive index (RI) mismatch, present a significant challenge in achieving high-resolution images at greater depths. To extend the imaging depth, we optimized the imaging buffer of SMLM with RI matched to the objective immersion medium, and systematically evaluated five different RI matched buffers, focusing on their impact on the blinking behavior of red-absorbing dyes and the quality of reconstructed super-resolution images. Particularly, we found clear unobstructed brain imaging cocktails (CUBIC) based imaging buffer could match the RI of oil and was able to clear the tissue samples. With the help of RI matched imaging buffer, we showed high quality dual color 3D SMLM images with imaging depth ranging from few microns to tens of microns in both cultured cells and sectioned tissue samples. This advancement offers a practical and ac
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Mashup Score: 0SMC complex unidirectionally translocates DNA by coupling segment capture with an asymmetric kleisin path - 2 hour(s) ago
SMC (structural maintenance of chromosomes) protein complexes are ring-shaped molecular motors essential for genome folding. Despite recent progress, the detailed molecular mechanism of DNA translocation in concert with the ATP-driven conformational changes of the complex remains to be clarified. In this study, we elucidated the mechanisms of SMC action on DNA using multiscale molecular dynamics simulations. We first created a near-atomic full-length model of prokaryotic SMC-kleisin complex that implemented protein-DNA hydrogen bond interactions derived from fully atomistic simulations and emulated ATP-dependent conformational changes. Extensive simulations of the SMC complex with 800 base pairs of duplex DNA over the ATP cycle revealed unidirectional DNA translocation via the DNA segment capture mechanism. The process exhibited a step size of ~200 base pairs, wherein the complex captured a DNA segment of about the same size within the SMC ring in the engaged state, followed by its pum
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Mashup Score: 0RegulaTome: a corpus of typed, directed, and signed relations between biomedical entities in the scientific literature - 2 hour(s) ago
Motivation: In the field of biomedical text mining, the ability to extract relations from literature is crucial for advancing both theoretical research and practical applications. There is a notable shortage of corpora designed to enhance the extraction of multiple types of relations, particularly focusing on proteins and protein-containing entities such as complexes and families, as well as chemicals. Results: In this work, we present RegulaTome, a corpus that overcomes the limitations of several existing biomedical relation extraction (RE) corpora, many of which concentrate on single-type relations at the sentence level. RegulaTome stands out by offering 16,962 relations annotated in over 2,500 documents, making it the most extensive dataset of its kind to date. This corpus is specifically designed to cover a broader spectrum of over 40 relation types beyond those traditionally explored, setting a new benchmark in the complexity and depth of biomedical RE tasks. Our corpus both broad
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Quantitative fluorescent nanoparticle tracking analysis and nano-flow cytometry enable advanced characterization of single extracellular vesicles https://t.co/UmoIKNQ631 #bioRxiv