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single cell methylation

Sema Sevimli, Frances C Knight, Pavlo Gilchuk, Sebastian Joyce, John T Wilson
Vaccine design has undergone a shift towards the use of purified protein subunit vaccines, which offer increased safety and greater control over antigen specificity, but at the expense of immunogenicity. Here we report the development of a new polymer-based vaccine delivery platform engineered to enhance immunity through the co-delivery of protein antigens and the Toll-like receptor 7 (TLR7) agonist imiquimod (IMQ). Owing to the preferential solubility of IMQ in fatty acids, a series of block copolymer micelles with a fatty acid-mimetic core comprising lauryl methacrylate (LMA) and methacrylic acid (MAA), and a poly(ethylene glycol) methyl ether methacrylate (PEGMA) corona decorated with pyridyl disulfide ethyl methacrylate (PDSM) moieties for antigen conjugation were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization...
February 13, 2017: ACS Biomaterials Science & Engineering
Haotian Wu, Molly S Estill, Alexander Shershebnev, Alexander Suvorov, Stephen A Krawetz, Brian W Whitcomb, Holly Dinnie, Tayyab Rahil, Cynthia K Sites, J Richard Pilsner
STUDY QUESTION: Are preconception phthalate and phthalate replacements associated with sperm differentially methylated regions (DMRs) among men undergoing IVF? SUMMARY ANSWER: Ten phthalate metabolites were associated with 131 sperm DMRs that were enriched in genes related to growth and development, cell movement and cytoskeleton structure. WHAT IS KNOWN ALREADY: Several phthalate compounds and their metabolites are known endocrine disrupting compounds and are pervasive environmental contaminants...
September 12, 2017: Human Reproduction
Lei Yin, Chong Su, Tianming Ren, Xiangjun Meng, Meiyun Shi, J Paul Fawcett, Mengliang Zhang, Wei Hu, Jingkai Gu
The covalent attachment of polyethylene glycol (PEG) to therapeutic compounds (known as PEGylation) is one of the most promising techniques to improve the biological efficacy of small molecular weight drugs. After administration, PEGylated prodrugs can be metabolized into pharmacologically active compounds so that PEGylated drug, free drug and released PEG are present simultaneously in the body. Understanding the pharmacokinetic behavior of these three compounds is needed to guide the development of pegylated theranostic agents...
October 12, 2017: Analyst
Michael R Blaisse, Hongjun Dong, Beverly Fu, Michelle C Y Chang
Cell-based synthesis offers many opportunities for preparing small molecules from simple renewable carbon sources by telescoping multiple reactions into a single fermentation step. One challenge in this area is the development of enzymatic carbon-carbon bond forming cycles that enable a modular disconnection of a target structure into cellular building blocks. In this regard, synthetic pathways based on thiolase enzymes to catalyze the initial carbon-carbon bond forming step between acyl coenzyme A (CoA) substrates offer a versatile route for biological synthesis, but the substrate diversity of such pathways is currently limited...
October 9, 2017: Journal of the American Chemical Society
Jingtao Guo, Edward J Grow, Chongil Yi, Hana Mlcochova, Geoffrey J Maher, Cecilia Lindskog, Patrick J Murphy, Candice L Wike, Douglas T Carrell, Anne Goriely, James M Hotaling, Bradley R Cairns
Human adult spermatogonial stem cells (hSSCs) must balance self-renewal and differentiation. To understand how this is achieved, we profiled DNA methylation and open chromatin (ATAC-seq) in SSEA4(+) hSSCs, analyzed bulk and single-cell RNA transcriptomes (RNA-seq) in SSEA4(+) hSSCs and differentiating c-KIT(+) spermatogonia, and performed validation studies via immunofluorescence. First, DNA hypomethylation at embryonic developmental genes supports their epigenetic "poising" in hSSCs for future/embryonic expression, while core pluripotency genes (OCT4 and NANOG) were transcriptionally and epigenetically repressed...
October 5, 2017: Cell Stem Cell
Gavin Kelsey, Oliver Stegle, Wolf Reik
Single-cell multi-omics has recently emerged as a powerful technology by which different layers of genomic output-and hence cell identity and function-can be recorded simultaneously. Integrating various components of the epigenome into multi-omics measurements allows for studying cellular heterogeneity at different time scales and for discovering new layers of molecular connectivity between the genome and its functional output. Measurements that are increasingly available range from those that identify transcription factor occupancy and initiation of transcription to long-lasting and heritable epigenetic marks such as DNA methylation...
October 6, 2017: Science
Micaela D Garcia, Karina Formoso, Gabriela I Aparicio, Alberto C C Frasch, Camila Scorticati
Single point mutations or variations in the expression of the gene encoding the neuronal glycoprotein M6a have been associated with psychiatric disorders such as Alzheimer's disease, depression and schizophrenia. In cultured neurons, M6a positively contributes to neurite extension, axon guidance, filopodia/spine outgrowth, and synapse formation. The endocytic processes of neuronal membrane proteins are linked to the differentiation, growth, signaling and plasticity of neurons. However, the roles of M6a and the precise mechanisms through which M6a internalizes and recycles back to the neuronal membrane are unknown...
2017: Frontiers in Molecular Neuroscience
Seongyeol Lee, Jieon Lee, Sehyun Chae, Yunwon Moon, Ho-Youl Lee, Bongju Park, Eun Gyeong Yang, Daehee Hwang, Hyunsung Park
Hypoxia increases both active and repressive histone methylation levels via decreased activity of histone demethylases. However, how such increases coordinately regulate induction or repression of hypoxia-responsive genes is largely unknown. Here, we profiled active and repressive histone tri-methylations (H3K4me3, H3K9me3, and H3K27me3) and analyzed gene expression profiles in human adipocyte-derived stem cells under hypoxia. We identified differentially expressed genes (DEGs) and differentially methylated genes (DMGs) by hypoxia and clustered the DEGs and DMGs into four major groups...
August 25, 2017: Nucleic Acids Research
Baptiste Pierman, Frederic Toussaint, Aurelie Bertin, Daniel Levy, Nicolas Smargiasso, Ewin De Pauw, Marc Boutry
Within the plant ABC transporter family, pleiotropic drug resistance (PDR) transporters play essential functions, such as in hormone transport or defense against biotic and abiotic stresses. NtPDR1 from Nicotiana tabacum has been shown to be involved in the constitutive defense against pathogens through the secretion of toxic cyclic diterpenes such as the antimicrobial substrates cembrene and sclareol from the leaf hairs (trichomes). However, direct evidence of an interaction between NtPDR1 and terpenes is lacking...
September 29, 2017: Journal of Biological Chemistry
Linda J W Bosch, Geert Trooskens, Petur Snaebjornsson, Veerle M H Coupé, Sandra Mongera, Josien C Haan, Susan D Richman, Miriam Koopman, Jolien Tol, Tim de Meyer, Joost Louwagie, Luc Dehaspe, Nicole C T van Grieken, Bauke Ylstra, Henk M W Verheul, Manon van Engeland, Iris D Nagtegaal, James G Herman, Philip Quirke, Matthew T Seymour, Cornelis J A Punt, Wim van Criekinge, Beatriz Carvalho, Gerrit A Meijer
Diversity in colorectal cancer biology is associated with variable responses to standard chemotherapy. We aimed to identify and validate DNA hypermethylated genes as predictive biomarkers for irinotecan treatment of metastatic CRC patients. Candidate genes were selected from 389 genes involved in DNA Damage Repair by correlation analyses between gene methylation status and drug response in 32 cell lines. A large series of samples (n=818) from two phase III clinical trials was used to evaluate these candidate genes by correlating methylation status to progression-free survival after treatment with first-line single-agent fluorouracil (Capecitabine or 5-fluorouracil) or combination chemotherapy (Capecitabine or 5-fluorouracil plus irinotecan (CAPIRI/FOLFIRI))...
September 8, 2017: Oncotarget
Weilong Guo, Ping Zhu, Matteo Pellegrini, Michael Zhang, Xiangfeng Wang, Zhongfu Ni
Motivation: DNA methylation is important for gene silencing and imprinting in both plants and animals. Recent advances in bisulfite sequencing allow detection of single nucleotide variations (SNVs) achieving high sensitivity, but accurately identifying heterozygous SNVs from partially C-to-T converted sequences remains challenging. Results: We designed two methods, BayesWC and BinomWC, that substantially improved the precision of heterozygous SNV calls from ∼80% to 99% while retaining comparable recalls...
September 18, 2017: Bioinformatics
Jens Langstein, Michael D Milsom, Daniel B Lipka
Epigenome regulation is a critical mechanism that governs cell identity, lineage specification and developmental cell fates. With the advent of low-input and single-cell technologies as well as sophisticated cell labeling techniques, our understanding of transcriptional and epigenetic regulation of hematopoiesis is currently undergoing dramatic changes. Increasingly, evidence suggests that the epigenome conformation acts as a critical decision-making mechanism that instructs self-renewal, differentiation and developmental fates of hematopoietic progenitor cells...
September 27, 2017: Seminars in Cancer Biology
Rosemary K Le, Parthapratim Das, Kristina M Mahan, Seth A Anderson, Tyrone Wells, Joshua S Yuan, Arthur J Ragauskas
Use of oleaginous microorganisms as "micro-factories" for accumulation of single cell oils for biofuel production has increased significantly to mitigate growing energy demands, resulting in efforts to upgrade industrial waste, such as second-generation lignocellulosic residues, into potential feedstocks. Dilute-acid pretreatment (DAP) is commonly used to alter the physicochemical properties of lignocellulosic materials and is typically coupled with simultaneous saccharification and fermentation (SSF) for conversion of sugars into ethanol...
September 29, 2017: AMB Express
Lijiao Geng, Wei Liu, Yong Chen
Ample evidence has demonstrated the involvement of microRNAs in Parkinson's disease pathogenesis. miR-124-3p was reported to be able to improve neural functional recovery. However, the underlying mechanism of miR-124-3p in Parkinson's disease progression was not well established. This study was designed to investigate the role of miR-124-3p in methyl phenyl pyridinium iodide (MPP)(+)-induced SH-SY5Y cells, an in vitro Parkinson's disease model. It is observed that miR-124-3p expression was decreased, and STAT3 expression was increased in MPP(+)-induced SH-SY5Y cells...
January 1, 2017: Experimental Biology and Medicine
Qin Gu, Tiantian Ji, Xiao Sun, Hai Huang, Hao Zhang, Xi Lu, Liming Wu, Rong Huo, Huijun Wu, Xuewen Gao
Histone methylation plays important biological roles in eukaryotic cells. Methylation of lysine 9 at histone H3 (H3K9me) is critical for regulating chromatin structure and gene transcription. Dim5 is a lysine histone methyltransferase (KHMTase) enzyme, which is responsible for the methylation of H3K9 in eukaryotes. In the current study, we identified a single ortholog of Neurospora crassa Dim5 in Fusarium verticillioides. In this study, we report that FvDim5 regulates the trimethylation of H3K9 (H3K9me3). The FvDIM5 deletion mutant (ΔFvDim5) showed significant defects in conidiation, perithecium production and fungal virulence...
October 16, 2017: FEMS Microbiology Letters
Nicole White, Miles Benton, Daniel Kennedy, Andrew Fox, Lyn Griffiths, Rodney Lea, Kerrie Mengersen
Cell- and sex-specific differences in DNA methylation are major sources of epigenetic variation in whole blood. Heterogeneity attributable to cell type has motivated the identification of cell-specific methylation at the CpG level, however statistical methods for this purpose have been limited to pairwise comparisons between cell types or between the cell type of interest and whole blood. We developed a Bayesian model selection algorithm for the identification of cell-specific methylation profiles that incorporates knowledge of shared cell lineage and allows for the identification of differential methylation profiles in one or more cell types simultaneously...
2017: PloS One
Annie Liu, Nathaniel N Urban
Early sensory experience shapes the anatomy and function of sensory circuits. In the mouse olfactory bulb (OB), prenatal and early postnatal odorant exposure through odorized food (food/odorant pairing) not only increases the volume of activated glomeruli but also increases the number of mitral and tufted cells (M/TCs) connected to activated glomeruli. Given the importance of M/TCs in OB output and in mediating lateral inhibitory networks, increasing the number of M/TCs connected to a single glomerulus may significantly change odorant representation by increasing the total output of that glomerulus and/or by increasing the strength of lateral inhibition mediated by cells connected to the affected glomerulus...
September 2017: ENeuro
Long Jin, So-Ra Ko, Chang Soo Lee, Chi-Yong Ahn, Hee-Mock Oh, Hyung-Gwan Lee
A novel Gram-negative bacterium strain, DRW22-8(T), was isolated from fresh water taken at a depth of 22 m at Daechung Reservoir, Republic of Korea. The cells of strain DRW22-8(T) were aerobic and motile with a single polar flagellum or non-motile (stalked), and formed creamy-white colonies on R2A agar. The phylogenetic analysis based on 16S rRNA gene sequencing indicated that the strain formed a separate lineage within the order Rhodobacterales, showing similarity values under 91.8 % with its closest phylogenetic neighbours, Hirschia litorea, Hirschia baltica and Hirschia maritima...
September 28, 2017: International Journal of Systematic and Evolutionary Microbiology
Lianbin Yao, Nurulhuda Mustafa, Eng Chong Tan, Anders Poulsen, Prachi Singh, Minh-Dao Duong-Thi, Jeannie X T Lee, Pondy Murugappan Ramanujulu, Wee Joo Chng, Jeffrey J Y Yen, Sten Ohlson, Brian W Dymock
Concomitant inhibition of multiple oncogenic pathways is a desirable goal in cancer therapy. To achieve such an outcome with a single molecule would simplify treatment regimes. Herein the core features of ruxolitinib (1), a marketed JAK1/2 inhibitor, have been merged with the HDAC inhibitor vorinostat (2), leading to new molecules which are bispecific targeted JAK/HDAC inhibitors. A preferred pyrazole substituted pyrrolopyrimidine, 24, inhibits JAK1 and HDACs 1,2,3,6 and 10 with IC50s of less than 20 nM, is <100 nM potent against JAK2 and HDAC11 and is selective for the JAK family against a panel of 97 kinases...
September 27, 2017: Journal of Medicinal Chemistry
Sabine A G Cuijpers, Edwin Willemstein, Alfred C O Vertegaal
Post translational protein modifications (PTMs) including small chemical groups and small proteins, belonging to the ubiquitin family, are essential for virtually all cellular processes. In addition to modification by a single PTM, proteins can be modified by a combination of different modifiers, which are able to influence each other. Since little is known about crosstalk between different ubiquitin family members, we developed an improved method enabling identification of co-modified proteins on a system-wide level using mass spectrometry...
September 26, 2017: Molecular & Cellular Proteomics: MCP
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