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Single-cell multi-omics sequencing data can provide a comprehensive molecular view of cells. However, effective approaches for the integrative analysis of such data are challenging. Existing manifold alignment methods demonstrated the state-of-the-art performance on single-cell multi-omics data integration, but they are often limited by requiring that single-cell datasets be derived from the same underlying cellular structure.
In this study, we present Pamona, a partial Gromov-Wasserstein distance based manifold alignment framework that integrates heterogeneous single-cell multi-omics datasets with the aim of delineating and representing the shared and dataset-specific cellular structures across modalities. We formulate this task as a partial manifold alignment problem and develop a partial Gromov-Wasserstein optimal transport framework to solve it. Pamona identifies both shared and dataset-specific cells based on the computed probabilistic couplings of cells across datasets, and it aligns cellular modalities in a common low-dimensional space, while simultaneously preserving both shared and dataset-specific structures. Our framework can easily incorporate prior information, such as cell type annotations or cell-cell correspondence, to further improve alignment quality. We evaluated Pamona on a comprehensive set of publicly available benchmark datasets. We demonstrated that Pamona can accurately identify shared and dataset-specific cells, as well as faithfully recover and align cellular structures of heterogeneous single-cell modalities in a common space, outperforming the comparable existing methods.
Pamona software is available at https//github.com/caokai1073/Pamona.
Pamona software is available at https//github.com/caokai1073/Pamona.Diabetic foot ulcer (DFU) is a kind of common and disabling complications of Diabetes Mellitus (DM). Emerging studies have demonstrated that tendon fibroblasts play a crucial role in remodeling phase of wound healing. However, little is known about the mechanism underlying high glucose (HG)-induced decrease of tendon fibroblasts viability. In the present study the rat models of DFU were established, and collagen deposition, autophagy activation and cell apoptosis in tendon tissues were assessed using hematoxylin-eosin (HE) staining, immunohistochemistry (IHC), and TdT-Mediated dUTP Nick-End Labeling (TUNEL) assay, respectively. Tendon fibroblasts were isolated from Achilles tendon of the both limbs, and the effect of HG on autophagy activation in tendon fibroblasts was assessed using western blot analysis, Cell Counting Kit-8 (CCK-8) assay, and flow cytometry. We found that cell apoptosis was increased significantly and autophagy activation was decreased in foot tendons tissues of DFU rats compared with normal tissues. The role of HG in regulating tendon fibroblasts viability was then investigated in vitro, and data showed that HG repressed cell viability and increased cell apoptosis. Furthermore, HG treatment reduced LC3-II expression and increased p62 expression, indicating that HG repressed the activation of tendon fibroblasts. The autophagy activator rapamycin reversed the effect. More important, rapamycin alleviated the suppressive role of HG in tendon fibroblasts viability. Taken together, our data demonstrate that HG represses tendon fibroblasts proliferation by inhibiting autophagy activation in tendon injury.In this issue of JEM, Guo et al. (2021. J. Exp. Med.https//doi.org/10.1084/jem.20202350) examine the importance of tumor-derived astrocytes in SHH-medulloblastoma recurrence. They show that tumor cells transdifferentiate to tumor-derived astrocytes via bone morphogenetic proteins and Sox9, which excitingly can be targeted by BMP inhibitors.COVID-19 is a global pandemic caused by SARS-CoV-2 infection and is associated with both acute and chronic disorders affecting the nervous system. Acute neurological disorders affecting patients with COVID-19 range widely from anosmia, stroke, encephalopathy/encephalitis, and seizures to Guillain-Barre Syndrome. Chronic neurological sequelae are less well defined although exercise intolerance, dysautonomia, pain, as well as neurocognitive and psychiatric dysfunctions are commonly reported. Molecular analyses of cerebrospinal fluid and neuropathological studies highlight both vascular and immunologic perturbations. Low levels of viral RNA have been detected in the brains of few acutely ill individuals. Potential pathogenic mechanisms in the acute phase include coagulopathies with associated cerebral hypoxic-ischemic injury, blood-brain barrier abnormalities with endotheliopathy and possibly viral neuroinvasion accompanied by neuro-immune responses. Established diagnostic tools are limited by a lack of clearly defined COVID-19 specific neurological syndromes. Future interventions will require delineation of specific neurological syndromes, diagnostic algorithm development, and uncovering the underlying disease mechanisms that will guide effective therapies.
Vaccination is an efficient public health strategy for controlling infectious diseases like the COVID-19 pandemic. Therefore, this study evaluates the effect of gain-framed, loss-framed, and altruism messages on willingness to get a COVID-19 vaccine and confirms the best strategy for promoting vaccination.
Herein, we designed an online survey experiment, including a control (exposure to non-framed information) and three experimental (exposure to gain-framed, loss-framed, or altruistic messages) groups, to assess the vaccination willingness. All participants (n = 1316) were randomly assigned into one of the four groups.
The individuals exposed to gain-framed, loss-framed, or altruism messages exhibited a higher willingness to get a COVID-19 vaccine than those exposed to non-framed information. Moreover, the loss-framed information effect on vaccination willingness was more substantial than the other two messages. However, no significant difference was observed between the gain-framed and altruism messages.
This study suggests that a loss-framed information dissemination strategy could be preferable to motivate vaccination willingness against COVID-19.
This study suggests that a loss-framed information dissemination strategy could be preferable to motivate vaccination willingness against COVID-19.
The peptide-centric identification methodologies of data-independent acquisition (DIA) data mainly rely on scores for the mass spectrometric signals of targeted peptides. Among these scores, the coelution scores of peak groups constructed by the chromatograms of peptide fragment ions have a significant influence on the identification. Most of the existing coelution scores are achieved by artificially designing some functions in terms of the shape similarity, retention time shift of peak groups. However, these scores cannot characterize the coelution robustly when the peak group is in the circumstance of interference.
On the basis that the neural network is more powerful to learn the implicit features of data robustly from a large number of samples, and thus minimizing the influence of data noise, in this work, we propose Alpha-XIC, a neural network-based model to score the coelution. By learning the characteristics of the coelution of peak groups derived from the being analyzed DIA data, Alpha-XIC is capable of yielding robust coelution scores even for peak groups with interference. With this score appending to initial scores generated by the accompanying identification engine DIA-NN, the ensuing statistical validation can report the identification result and recover the misidentified peptides. In our evaluation of the HeLa dataset with gradient lengths ranging from 0.5 h to 2 h, Alpha-XIC delivered 9.4% ∼ 16.2% improvements in the number of identified precursors at 1% FDR. Furthermore, Alpha-XIC was tested on LFQbench, a mixed-species dataset with known ratios, and increased the number of peptides and proteins fell within valid ratios by up to 16.4% and 17.8%, respectively, compared to the initial identification by DIA-NN.
Source code is available at https//github.com/YuAirLab/Alpha-XIC.
Source code is available at https//github.com/YuAirLab/Alpha-XIC.Several RNA viruses can establish life-long persistent infection in mammalian hosts, but the fate of individual virus-infected cells remains undefined. Here we used Cre recombinase-encoding lymphocytic choriomeningitis virus to establish persistent infection in fluorescent cell fate reporter mice. Virus-infected hepatocytes underwent spontaneous noncytolytic viral clearance independently of type I or type II interferon signaling or adaptive immunity. Viral clearance was accompanied by persistent transcriptomic footprints related to proliferation and extracellular matrix remodeling, immune responses, and metabolism. Substantial overlap with persistent epigenetic alterations in HCV-cured patients suggested a universal RNA virus-induced transcriptomic footprint. Cell-intrinsic clearance occurred in cell culture, too, with sequential infection, reinfection cycles separated by a period of relative refractoriness to infection. Our study reveals that systemic persistence of a prototypic noncytolytic RNA virus depends on continuous spread and reinfection. Yet undefined cell-intrinsic mechanisms prevent viral persistence at the single-cell level but give way to profound transcriptomic alterations in virus-cleared cells.
As a result of low numbers of pediatric cases early in the COVID-19 pandemic, pediatric household transmission of SARS-CoV-2 remains an understudied topic.
To determine whether there are differences in the odds of household transmission by younger children compared with older children.
This population-based cohort study took place between June 1 and December 31, 2020, in Ontario, Canada. Private households in which the index case individual of laboratory-confirmed SARS-CoV-2 infection was younger than 18 years were included. SR-4370 mw Individuals were excluded if they resided in apartments missing suite information, in households with multiple index cases, or in households where the age of the index case individual was missing.
Age group of pediatric index cases categorized as 0 to 3, 4 to 8, 9 to 13, and 14 to 17 years.
Household transmission, defined as households where at least 1 secondary case occurred 1 to 14 days after the pediatric index case.
A total of 6280 households had pediatric index cases, and Differential infectivity of pediatric age groups has implications for infection prevention within households, as well as schools/childcare, to minimize risk of household secondary transmission. Additional population-based studies are required to establish the risk of transmission by younger pediatric index cases.
This study suggests that younger children may be more likely to transmit SARS-CoV-2 infection compared with older children, and the highest odds of transmission was observed for children aged 0 to 3 years. Differential infectivity of pediatric age groups has implications for infection prevention within households, as well as schools/childcare, to minimize risk of household secondary transmission. Additional population-based studies are required to establish the risk of transmission by younger pediatric index cases.
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