66 research outputs found

    RGD-conjugated gold nanorods induce radiosensitization in melanoma cancer cells by downregulating αvβ3 expression

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    Background: Melanoma is known to be radioresistant and traditional treatments have been intractable. Therefore, novel approaches are required to improve the therapeutic efficacy of melanoma treatment. In our study, gold nanorods conjugated with Arg-Gly-Asp peptides (RGD-GNRs) were used as a sensitizer to enhance the response of melanoma cells to 6 mV radiation. Methods and materials: A375 melanoma cells were treated by gold nanorods or RGD-GNRs with or without irradiation. The antiproliferative impact of the treatments was measured by MTT assay. Radiosensitizing effects were determined by colony formation assay. Apoptosis and cell cycle data were measured by flow cytometry. Integrin alpha(v)beta(3) expression was also investigated by flow cytometry. Results: Addition of RGD-GNRs enhanced the radiosensitivity of A375 cells with a dose-modifying factor of 1.35, and enhanced radiation-induced apoptosis. DNA flow cytometric analysis indicated that RGD-GNRs plus irradiation induced significant G2/M phase arrest in A375 cells. Both spontaneous and radiation-induced expressions of integrin alpha(v)beta(3) were downregulated by RGD-GNRs. Conclusion: Our study indicated that RGD-GNRs could sensitize melanoma A375 cells to irradiation. It was hypothesized that this was mainly through downregulation of radiation-induced alpha(v)beta(3), in addition to induction of a higher proportion of cells within the G2/M phase. The combination of RGD-GNRs and radiation needs further investigation.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000302718200001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Nanoscience & NanotechnologyPharmacology & PharmacySCI(E)22ARTICLE915-924

    Genome-wide association and interaction studies of CSF T-tau/Aβ42 ratio in ADNI cohort

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    The pathogenic relevance in Alzheimer’s disease (AD) presents a decrease of cerebrospinal fluid (CSF) amyloid-ß42 (Aß42) burden and an increase in CSF total-tau (T-tau) levels. In this work, we performed genome-wide association study (GWAS) and genome-wide interaction study (GWIS) of T-tau/Aß42 ratio as an AD imaging quantitative trait (QT) on 843 subjects and 563,980 single nucleotide polymorphisms (SNPs) in ADNI cohort. We aim to identify not only SNPs with significant main effects but also SNPs with interaction effects to help explain “missing heritability”. Linear regression method was used to detect SNP-SNP interactions among SNPs with uncorrected p-value≤0.01 from the GWAS. Age, gender and diagnosis were considered as covariates in both studies. The GWAS results replicated the previously reported AD-related genes APOE, APOC1 and TOMM40, as well as identified 14 novel genes, which showed genome-wide statistical significance. GWIS revealed 7 pairs of SNPs meeting the cell-size criteria and with bonferroni-corrected p-value≤0.05. As we expect, these interaction pairs all had marginal main effects but explained a relatively high-level variance of T-tau/Aß42, demonstrating their potential association with AD pathology

    In situ Observation of Sodium Dendrite Growth and Concurrent Mechanical Property Measurements Using an Environmental Transmission Electron Microscopy–Atomic Force Microscopy (ETEM-AFM) Platform

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    Akin to Li, Na deposits in a dendritic form to cause a short circuit in Na metal batteries. However, the growth mechanisms and related mechanical properties of Na dendrites remain largely unknown. Here we report real-time characterizations of Na dendrite growth with concurrent mechanical property measurements using an environmental transmission electron microscopy–atomic force microscopy (ETEM-AFM) platform. In situ electrochemical plating produces Na deposits stabilized with a thin Na2CO3 surface layer (referred to as Na dendrites). These Na dendrites have characteristic dimensions of a few hundred nanometers and exhibit different morphologies, including nanorods, polyhedral nanocrystals, and nanospheres. In situ mechanical measurements show that the compressive and tensile strengths of Na dendrites with a Na2CO3 surface layer vary from 36 to >203 MPa, which are much larger than those of bulk Na. In situ growth of Na dendrites under the combined overpotential and mechanical confinement can generate high stress in these Na deposits. These results provide new baseline data on the electrochemical and mechanical behavior of Na dendrites, which have implications for the development of Na metal batteries toward practical energy-storage applications

    Helical Luttinger liquid on the edge of a 2-dimensional topological antiferromagnet

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    Boundary helical Luttinger liquid (HLL) with broken bulk time-reversal symmetry belongs to a unique topological class which may occur in antiferromagnets (AFM). Here, we search for signatures of HLL on the edge of a recently discovered topological AFM, MnBi2Te4 even-layer. Using scanning superconducting quantum interference device, we directly image helical edge current in the AFM ground state appearing at its charge neutral point. Such helical edge state accompanies an insulating bulk which is topologically distinct from the ferromagnetic Chern insulator phase as revealed in a magnetic field driven quantum phase transition. The edge conductance of the AFM order follows a power-law as a function of temperature and source-drain bias which serves as strong evidence for HLL. Such HLL scaling is robust at finite fields below the quantum critical point. The observed HLL in a layered AFM semiconductor represents a highly tunable topological matter compatible with future spintronics and quantum computation

    Genome-wide Network-assisted Association and Enrichment Study of Amyloid Imaging Phenotype in Alzheimer's Disease

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    Background: The etiology of Alzheimer's disease remains poorly understood at the mechanistic level, and genome-wide network-based genetics have the potential to provide new insights into the disease mechanisms. Objective: The study aimed to explore the collective effects of multiple genetic association signals on an AV-45 PET measure, which is a well-known Alzheimer's disease biomarker, by employing a network assisted strategy. Methods: First, we took advantage of a dense module search algorithm to identify modules enriched by genetic association signals in a protein-protein interaction network. Next, we performed statistical evaluation to the modules identified by dense module search, including a normalization process to adjust the topological bias in the network, a replication test to ensure the modules were not found randomly , and a permutation test to evaluate unbiased associations between the modules and amyloid imaging phenotype. Finally, topological analysis, module similarity tests and functional enrichment analysis were performed for the identified modules. Results: We identified 24 consensus modules enriched by robust genetic signals in a genome-wide association analysis. The results not only validated several previously reported AD genes (APOE, APP, TOMM40, DDAH1, PARK2, ATP5C1, PVRL2, ELAVL1, ACTN1 and NRF1), but also nominated a few novel genes (ABL1, ABLIM2) that have not been studied in Alzheimer's disease but have shown associations with other neurodegenerative diseases. Conclusion: The identified genes, consensus modules and enriched pathways may provide important clues to future research on the neurobiology of Alzheimer's disease and suggest potential therapeutic targets

    Multivariate genome wide association and network analysis of subcortical imaging phenotypes in Alzheimer's disease

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    Background: Genome-wide association studies (GWAS) have identified many individual genes associated with brain imaging quantitative traits (QTs) in Alzheimer's disease (AD). However single marker level association discovery may not be able to address the underlying biological interactions with disease mechanism. Results: In this paper, we used the MGAS (Multivariate Gene-based Association test by extended Simes procedure) tool to perform multivariate GWAS on eight AD-relevant subcortical imaging measures. We conducted multiple iPINBPA (integrative Protein-Interaction-Network-Based Pathway Analysis) network analyses on MGAS findings using protein-protein interaction (PPI) data, and identified five Consensus Modules (CMs) from the PPI network. Functional annotation and network analysis were performed on the identified CMs. The MGAS yielded significant hits within APOE, TOMM40 and APOC1 genes, which were known AD risk factors, as well as a few new genes such as LAMA1, XYLB, HSD17B7P2, and NPEPL1. The identified five CMs were enriched by biological processes related to disorders such as Alzheimer's disease, Legionellosis, Pertussis, and Serotonergic synapse. Conclusions: The statistical power of coupling MGAS with iPINBPA was higher than traditional GWAS method, and yielded new findings that were missed by GWAS. This study provides novel insights into the molecular mechanism of Alzheimer's Disease and will be of value to novel gene discovery and functional genomic studies
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