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Andrea Stoccoro, Gabriele Siciliano, Lucia Migliore, Fabio Coppedè
Mitochondrial impairment is a feature of neurodegeneration and many investigators have suggested that epigenetic modifications of the mitochondrial DNA (mtDNA) might be involved in late-onset Alzheimer's disease (LOAD), but evidence in humans is limited. We assessed the methylation levels of the mtDNA D-loop region in blood DNA from 133 LOAD patients and 130 controls, observing a significant 25% reduction of DNA methylation levels in the first group (2.3 versus 3.1%). Overall, the present data indicate that there is a decreased methylation of the D-loop region in LOAD peripheral blood DNA, suggesting that mtDNA epimutations deserve further investigations in AD pathogenesis...
June 22, 2017: Journal of Alzheimer's Disease: JAD
Yang Wang, Ai-Yu Gong, Shibin Ma, Xiqiang Chen, Juliane K Strauss-Soukup, Xian-Ming Chen
Cryptosporidial infection causes dysregulated transcription of host genes key to intestinal epithelial homeostasis, but the underlying mechanisms remain obscure. Previous studies demonstrate that several C. parvum RNA transcripts are selectively delivered into epithelial cells during host cell invasion and may modulate gene transcription in infected cells. We report here that C. parvum infection suppresses the transcription of LRP5, SLC7A8, and IL33 genes in infected intestinal epithelium. Trans-suppression of these genes in infected host cells is associated with promoter enrichment of suppressive epigenetic markers (i...
June 27, 2017: Cellular Microbiology
Ping-Ying Chang, Yu-Ping Liao, Hui-Chen Wang, Yu-Chih Chen, Rui-Lan Huang, Yu-Chi Wang, Chiou-Chung Yuan, Hung-Cheng Lai
DNA methylation is a promising biomarker for cancer. The epigenetic effects of cell adhesion molecules may affect the therapeutic outcome and the present study examined their effects on survival in ovarian cancer. We integrated methylomics and genomics datasets in The Cancer Genome Atlas (n = 391) and identified 106 highly methylated adhesion-related genes in ovarian cancer tissues. Univariate analysis revealed the methylation status of eight genes related to progression-free survival. In multivariate Cox regression analysis, four highly methylated genes (CD97, CTNNA1, DLC1, HAPLN2) and three genes (LAMA4, LPP, MFAP4) with low methylation were significantly associated with poor progression-free survival...
June 16, 2017: Oncotarget
Yuan-Chao Sun, Yong-Yong Wang, Wei Ge, Shun-Feng Cheng, Paul W Dyce, Wei Shen
Gametogenesis is an essential process to ensure the transfer of genetic information from one generation to the next. It also provides a mechanism by which genetic evolution can take place. Although the genome of primordial germ cells (PGCs) is exactly the same with somatic cells within an organism, there are significant differences between their developments. For example, PGCs eventually undergo meiosis to become functional haploid gametes, and prior to that they undergo epigenetic imprinting which greatly alter their genetic regulation...
June 12, 2017: Oncotarget
Po-Hsuan Su, Yao-Wen Hsu, Rui-Lan Huang, Yu-Chun Weng, Hui-Chen Wang, Yu-Chih Chen, Yueh-Ju Tsai, Chiou-Chung Yuan, Hung-Cheng Lai
Epigenetic dysregulation is important in cervical cancer development, but the underlying mechanism is largely unknown. Increasing evidence indicates that DNA methylation is sensitive to changes in microenvironmental factors, such as nitric oxide (NO) in the chronic inflammatory cervix. However, the epigenomic effects of NO in cancer have not been investigated. In this study, we explored the methylomic effects of nitroxidative stress in HPV-immortalized precancerous cells. Chronic NO exposure promoted the acquisition of malignant phenotypes such as cell growth, migration, invasion, and anchorage-independent growth...
June 6, 2017: Oncotarget
Liyang Li, Liyun Yu, Xilin Hou
Lipid rafts are specialized lipid domains enriched in cholesterol and sphingolipid, which can be utilized in the lifecycle of numerous enveloped viruses. Bovine parainfluenza virustype3 (BPIV3) entry to cell is mediated by receptor binding and membrane fusion, but how lipid rafts in host cell membrane and BPIV3 envelope affect virus infection remains unclear. In this study, we investigated the role of lipid rafts in the different stages of BPIV3 infection. The MDBK cells were treated by methyl-β-cyclodextrin (MβCD) to disrupt cellular lipid raft, and the virus infection was determined...
May 11, 2017: Research in Veterinary Science
Chuan Yu, Xiaomin Yao, Linjie Zhao, Ping Wang, Qian Zhang, Chengjian Zhao, Shaohua Yao, Yuquan Wei
Wolf-Hirschhorn syndrome candidate 1 (WHSC1) is a histone 3 lysine 36 (H3K36) specific methyltransferase that is frequently deleted in Wolf-Hirschhorn syndrome (WHS). Whsc1 is also found mutated in a subgroup of B-cell derived malignant diseases by genomic translocation or point mutation, both of which resulted in hyperactivity of WHSC1 mediated H3K36 methylation and uncontrolled cell proliferation, suggesting that whsc1 functions as an oncogene. However, here we provided evidences to show that whsc1 also has tumor suppressor functions...
June 24, 2017: Neoplasia: An International Journal for Oncology Research
Xiwen Liu, Jialiang Wu, Yujie Sun, Wei Xie
Anserine (β-alanyl-N(Pi) -methyl-L-histidine) is a natural metabolite present in skeletal muscle and the central nervous system of vertebrates, and plays important physiological roles in living organisms. The production of anserine is catalyzed by carnosine N-methyltransferases, which transfer a methyl group to carnosine (β-alanyl-L-histidine). However, the structural basis of the substrate recognition for the enzymes is unknown. We present the crystal structure of the putative carnosine N-methyltransferase from yeast named YNL092W in complex with SAH, solved by the single-wavelength anomalous dispersion (SAD) method...
June 27, 2017: ACS Chemical Biology
Moon-Jin Cho, Soo-Young Park
Carbon dots (CDs) are covalently coupled to the polyacrylic acid (PAA) block of polystyrene-b-polyacrylic acid (PS-b-PAA). The produced amphiphilic PS-b-PAA-CD shows excellent solubility and micellar formation in selective solvents. Transmission electron microscopy study shows that the micelle of PS-b-PAA-CD in water (a PAA-selective solvent) has a strawberry-like shape with the CDs as patches on the PAA corona surface although that in toluene (a PS-selective solvent) has a reversed shape with the CDs in the core...
June 27, 2017: ACS Applied Materials & Interfaces
Daniel B Werz, Alexander Lücht, Lukas J Patalag, Peter G Jones, André U Augustin
Reactions of 2-aryl cyclopropane dicarboxylates with naphthoquinones are reported. The key feature was the use of catalytic amounts of SnCl2, which acts as both electron donor and Lewis acid. By an in-situ umpolung of naphthoquinone the formerly electrophilic species is converted into a nucleophile that is able to trigger the ring-opening of the three-membered ring with formation of a new C-C bond. Treatment of these products with base under oxidative conditions resulted - by losing methyl formate - in cyclopentannulated products with fully conjugated π systems exhibiting intensive absorptions in the visible range...
June 27, 2017: Angewandte Chemie
Min Guan, Xiwei Wu, Peiguo Chu, Warren A Chow
SK-UT-1 uterine leiomyosarcomas (Ut-LMS) cells were transduced with a fatty acid synthase (FASN)-containing retroviral vector to recapitulate the "lipogenic phenotype of cancer." Consistent with this model, forced expression of FASN enhanced SK-UT-1 proliferation, migration, and cellular motion. Further investigation showed FASN promotes trimethylation of H3K9 (H3K9me3) and acetylation of H3K27 (H3K27ac) in SK-UT-1 cells. In contrast, siRNA targeting of FASN in high endogenous FASN expressing SK-LMS-1 Ut-LMS cells inhibits trimethylation of H3K9 and acetylation of H3K27...
2017: PloS One
Kai R Laukamp, Florian Lindemann, Matthias Weckesser, Volker Hesselmann, Sandra Ligges, Johannes Wölfer, Astrid Jeibmann, Bastian Zinnhardt, Thomas Viel, Michael Schäfers, Werner Paulus, Walter Stummer, Otmar Schober, Andreas H Jacobs
The value of combined L-( methyl-[(11)C]) methionine positron-emitting tomography (MET-PET) and magnetic resonance imaging (MRI) with regard to tumor extent, entity prediction, and therapy effects in clinical routine in patients with suspicion of a brain tumor was investigated. In n = 65 patients with histologically verified brain lesions n = 70 MET-PET and MRI (T1-weighted gadolinium-enhanced [T1w-Gd] and fluid-attenuated inversion recovery or T2-weighted [FLAIR/T2w]) examinations were performed. The computer software "visualization and analysis framework volume rendering engine (Voreen)" was used for analysis of extent and intersection of tumor compartments...
January 1, 2017: Molecular Imaging
Emre Demirci, Rafay Ahmed, Meltem Ocak, Joseph Latoche, April Radelet, Nicole DeBlasio, N Scott Mason, Carolyn J Anderson, James M Mountz
PURPOSE: We investigated 2-(5-fluoro-pentyl)-2-methyl-malonic acid ((18)F-ML-10) positron emission tomography (PET) imaging of apoptosis posttherapy to determine optimal timing for predicting chemotherapy response in a mouse head/neck xenograft cancer model. PROCEDURES: BALB/c nude mice (4-8 weeks old) were implanted with UM-SCC-22B tumors. The treatment group received 2 doses of doxorubicin (10 mg/kg, days 0, 2). Small animal (18)F-ML-10 PET/computed tomography was performed before and on days 1, 3, and 7 postchemotherapy...
January 1, 2017: Molecular Imaging
Mckenna Schroeder, Qiuming Wang, Somayesadat Badieyan, Zhan Chen, E Neil G Marsh
Using an engineered enzyme (nitro-reductase) that is covalently tethered to a self-assembled monolayer (SAM) surface through a unique surface cysteine residue, results in a well-defined protein monolayer that is amenable to detailed kinetic and spectroscopic analysis. Here we investigate two surface properties that are generally thought to have an important influence of enzyme activity and stability: surface hydrophobicity and surface crowding. Two nitro-reductase variants were covalently tethered to orient the protein's pseudo-2-fold symmetry axis either parallel or perpendicular to the surface...
June 27, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
Michael Tüchler, Stefan Holler, Jörg A Schachner, Ferdinand Belaj, Nadia C Mösch-Zanetti
The reaction of iron(II) triflate with 6-tert-butyl-3-thiopyridazine (PnH) and 4-methyl-6-tert-butyl-3-thiopyridazine ((Me)PnH) respectively led to iron bis(diorganotrisulfide) complexes [Fe((R)PnS3Pn(R))2](OTf)2 [R = H (1a) and Me (2a)]. The corresponding perchlorate complexes were prepared by using the iron(II) chloride precursor and the subsequent addition of 2 equiv of NaClO4, giving [Fe((R)PnS3Pn(R))2](ClO4)2 [R = H (1b) and Me (2b)]. The compounds were fully characterized including single-crystal X-ray diffraction analysis...
June 27, 2017: Inorganic Chemistry
Ying Wang, Suchada Rajca, Andrzej Rajca
We report the synthesis and kinetic study of PEGylated, water soluble aminyl radical 2. The radical possesses four mPEG-3 groups replacing four methyl groups in the tert-butyl groups at the 3- and 6-positions of 1,3,6,8-Tetra-tert-butyl carbazyl (TTBC). This structure is designed to mitigate the rapid decomposition of the radical via intramolecular 1,5-hydrogen atom transfer (1,5-HAT) that was observed in its constitutional isomer 1-H with four mPEG-3 groups in the vicinity of the nitrogen-centered radical (1- and 8-positions of TTBC)...
June 27, 2017: Journal of Organic Chemistry
Luca C Gobbi, Henner Knust, Matthias Körner, Michael Honer, Christian Czech, Sara Belli, Dieter Muri, Martin R Edelmann, Thomas Hartung, Isabella Erbsmehl, Sandra Grall-Ulsemer, Andreas Koblet, Marianne Rueher, Sandra Steiner, Hayden T Ravert, William B Mathews, Daniel P Holt, Hiroto Kuwabara, Heather Valentine, Robert F Dannals, Dean F Wong, Edilio Borroni
Aggregates of tau and beta amyloid (Aβ) plaques constitute the histopathological hallmarks of Alzheimer's disease and are prominent targets for novel therapeutics as well as for biomarkers for diagnostic in vivo imaging. In recent years much attention has been devoted to the discovery and development of new PET tracers to image tau aggregates in the living human brain. Access to a selective PET tracer to image and quantify tau aggregates represents a unique tool to support the development of any novel therapeutic agent targeting pathological forms of tau...
June 27, 2017: Journal of Medicinal Chemistry
Ashley S Johns, Colin D Bain
Ink-jet printing of high-molecular-weight polymers is inhibited by the extensional elasticity of the polymer chains. This article describes how emulsions can be used to print high-molecular-weight polymers at much higher concentrations than is possible in a binary solution. The polymers are dissolved in the dispersed phase of an oil-in-water emulsion. The surface tension of the oil-water interface opposes deformation of the oil droplets during ejection from the nozzle and leads to the extensional strain occurring in the polymer-free continuous phase...
June 27, 2017: ACS Applied Materials & Interfaces
M Taskova, M C Barducci, K Astakhova
There is currently an unmet need for reliable tools that allow for direct detection and quantification of modifications in genomic DNA. For example, in cancer research and clinical diagnostics, target DNA has to be amplified and sequenced in order to reveal mutations. For 5-methylcytosine detection, bisulfite treatment of DNA is applied for the analysis, which often leads to poor specificity and reproducibility of the results. Herein we describe a simple approach that specifically detects clinically significant modifications in the human oncogenes BRAF and KRAS...
June 27, 2017: Organic & Biomolecular Chemistry
Baiyan Li, Xinglong Dong, Hao Wang, Dingxuan Ma, Kui Tan, Zhan Shi, Yves J Chabal, Yu Han, Jing Li
Highly efficient capture of radioactive organic iodides (ROIs) from off-gas mixtures remains a substantial challenge for nuclear waste treatment. Current materials utilized for ROI sequestration suffer from low capacity, high cost (e.g. use of noble metals), and poor recyclability. Recently, we have developed a new strategy to tackle this challenge by functionalizing MOF materials with tertiary amines to create molecular traps for the effective capture and removal of ROIs (e.g. radioactive methyl iodide) from nuclear wastes...
June 27, 2017: Faraday Discussions
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