A highly selective, sensitive caffeic acid (CA) detection based on calcium oxide nanoparticles (CaO NPs) derived from extract of Moringa oleifera leaves decorated graphitic carbon nitride covalently grafted poly vinyl alcohol (CaO/g-CN/PVA) nanocomposite modified glassy carbon electrode (GCE) was studied. A facile sonochemical method was adapted to synthesis nanomaterials and characterized by HR-TEM (High resolution transmission electron microscopy), FT-IR (Fourier transform infrared spectroscopy), XRD (X-ray diffraction), FE-SEM (Field emission scanning electron microscopy), EDX (Energy dispersive X-ray analysis), Mapping and BET (Brunauer-Emmett-Teller) analysis, and electrochemical techniques. The nanocomposite modified GCE exhibited an excellent catalytic performance to the oxidation of CA under optimized conditions owing to better electron transfer efficiency, conductivity and high surface area of the electrode material.
View Article and Find Full Text PDFNovel visible-light-driven Ag ()-doped BiZrO (BZO) nanocomposites in pudina (P) extract ( L.), -1, 3, 5, 7, and 9 mol %, were synthesized by the one-pot greener solution combustion method. The as-synthesized nanocomposite materials were characterized by using various spectral [X-ray diffraction (XRD), Fourier transform infrared, UV-visible, UV- diffuse reflectance spectra, X-ray photoelectron spectroscopy], electrochemical (cyclic voltammetry, electrochemical impedance spectroscopy), and analytical (scanning electron microscopy-energy-dispersive X-ray spectroscopy, transmission electron microscopy, Brunauer-Emmett-Teller) techniques.
View Article and Find Full Text PDFVα24-invariant natural killer T cells (NKTs) have anti-tumor properties that can be enhanced by chimeric antigen receptors (CARs). Here we report updated interim results from the first-in-human phase 1 evaluation of autologous NKTs co-expressing a GD2-specific CAR with interleukin 15 (IL15) (GD2-CAR.15) in 12 children with neuroblastoma (NB).
View Article and Find Full Text PDFIn this rapid growing eco-friendly research world, synthesis of non-toxic, highly effective photocatalyst for potential applications is necessary. Herein, a strong ability BiZrO nanoparticle (BZO NP) with pyrochlore structure was fabricated by solution combustion synthesis using green (Mentha spicata) and chemical (Glycine) fuels. The X-ray diffraction analysis confirms the formation of pure phase for synthesized BZO NP using pudina extract (BZOP NP) compared to BZO NP using Glycine fuel (BZOG NP).
View Article and Find Full Text PDFSystemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease. Knowledge of circulating immune cell types and states associated with SLE remains incomplete. We profiled more than 1.
View Article and Find Full Text PDFSingle-cell RNA sequencing (scRNA-seq) has the potential to provide powerful, high-resolution signatures to inform disease prognosis and precision medicine. This paper takes an important first step towards this goal by developing an interpretable machine learning algorithm, CloudPred, to predict individuals' disease phenotypes from their scRNA-seq data. Predicting phenotype from scRNA-seq is challenging for standard machine learning methods-the number of cells measured can vary by orders of magnitude across individuals and the cell populations are also highly heterogeneous.
View Article and Find Full Text PDFSingle-cell RNA-sequencing (scRNA-Seq) is a compelling approach to directly and simultaneously measure cellular composition and state, which can otherwise only be estimated by applying deconvolution methods to bulk RNA-Seq estimates. However, it has not yet become a widely used tool in population-scale analyses, due to its prohibitively high cost. Here we show that given the same budget, the statistical power of cell-type-specific expression quantitative trait loci (eQTL) mapping can be increased through low-coverage per-cell sequencing of more samples rather than high-coverage sequencing of fewer samples.
View Article and Find Full Text PDFAn amendment to this paper has been published and can be accessed via a link at the top of the paper.
View Article and Find Full Text PDFThe observation that disease-associated genetic variants typically reside outside of exons has inspired widespread investigation into the genetic basis of transcriptional regulation. While associations between the mRNA abundance of a gene and its proximal SNPs (cis-eQTLs) are now readily identified, identification of high-quality distal associations (trans-eQTLs) has been limited by a heavy multiple testing burden and the proneness to false-positive signals. To address these issues, we develop GBAT, a powerful gene-based pipeline that allows robust detection of high-quality trans-gene regulation signal.
View Article and Find Full Text PDFWe present Vision, a tool for annotating the sources of variation in single cell RNA-seq data in an automated and scalable manner. Vision operates directly on the manifold of cell-cell similarity and employs a flexible annotation approach that can operate either with or without preconceived stratification of the cells into groups or along a continuum. We demonstrate the utility of Vision in several case studies and show that it can derive important sources of cellular variation and link them to experimental meta-data even with relatively homogeneous sets of cells.
View Article and Find Full Text PDFUnlabelled: Correlation among traits is a fundamental feature of biological systems that remains difficult to study. To address this problem, we developed a flexible approach that allows us to identify factors associated with inter-individual variation in correlation. We use data from three human cohorts to study the effects of genetic and environmental variation on correlations among mRNA transcripts and among NMR metabolites.
View Article and Find Full Text PDFWhile genetic variants are known to be associated with overall gene abundance in stimulated immune cells, less is known about their effects on alternative isoform usage. By analyzing RNA-seq profiles of monocyte-derived dendritic cells from 243 individuals, we uncovered thousands of unannotated isoforms synthesized in response to influenza infection and type 1 interferon stimulation. We identified more than a thousand quantitative trait loci (QTLs) associated with alternate isoform usage (isoQTLs), many of which are independent of expression QTLs (eQTLs) for the same gene.
View Article and Find Full Text PDFOrganogenesis requires the complex interactions of multiple cell lineages that coordinate their expansion, differentiation, and maturation over time. Here, we profile the cell types within the epithelial and mesenchymal compartments of the murine pancreas across developmental time using a combination of single-cell RNA sequencing, immunofluorescence, in situ hybridization, and genetic lineage tracing. We identify previously underappreciated cellular heterogeneity of the developing mesenchyme and reconstruct potential lineage relationships among the pancreatic mesothelium and mesenchymal cell types.
View Article and Find Full Text PDFOver 90% of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. One possible mechanism is that genetic variants affect the activity of one or more cis-regulatory elements leading to gene expression variation in specific cell types. To identify such cases, we analyzed ATAC-seq and RNA-seq profiles from stimulated primary CD4 T cells in up to 105 healthy donors.
View Article and Find Full Text PDFIn this Letter, analysis of steady-state regulatory T (Treg) cell percentages from Il2ra enhancer deletion (EDEL) and wild-type (WT) mice revealed no differences between them (Extended Data Fig. 9d). This analysis included two mice whose genotypes were incorrectly assigned.
View Article and Find Full Text PDFDroplet single-cell RNA-sequencing (dscRNA-seq) has enabled rapid, massively parallel profiling of transcriptomes. However, assessing differential expression across multiple individuals has been hampered by inefficient sample processing and technical batch effects. Here we describe a computational tool, demuxlet, that harnesses natural genetic variation to determine the sample identity of each droplet containing a single cell (singlet) and detect droplets containing two cells (doublets).
View Article and Find Full Text PDFThe majority of genetic variants associated with common human diseases map to enhancers, non-coding elements that shape cell-type-specific transcriptional programs and responses to extracellular cues. Systematic mapping of functional enhancers and their biological contexts is required to understand the mechanisms by which variation in non-coding genetic sequences contributes to disease. Functional enhancers can be mapped by genomic sequence disruption, but this approach is limited to the subset of enhancers that are necessary in the particular cellular context being studied.
View Article and Find Full Text PDFUbiquitin is essential for eukaryotic life and varies in only 3 amino acid positions between yeast and humans. However, recent deep sequencing studies indicate that ubiquitin is highly tolerant to single mutations. We hypothesized that this tolerance would be reduced by chemically induced physiologic perturbations.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
August 2015
T-cell genome engineering holds great promise for cell-based therapies for cancer, HIV, primary immune deficiencies, and autoimmune diseases, but genetic manipulation of human T cells has been challenging. Improved tools are needed to efficiently "knock out" genes and "knock in" targeted genome modifications to modulate T-cell function and correct disease-associated mutations. CRISPR/Cas9 technology is facilitating genome engineering in many cell types, but in human T cells its efficiency has been limited and it has not yet proven useful for targeted nucleotide replacements.
View Article and Find Full Text PDFGenomic imprinting is an important regulatory mechanism that silences one of the parental copies of a gene. To systematically characterize this phenomenon, we analyze tissue specificity of imprinting from allelic expression data in 1582 primary tissue samples from 178 individuals from the Genotype-Tissue Expression (GTEx) project. We characterize imprinting in 42 genes, including both novel and previously identified genes.
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