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Goran Micevic, Durga Thakral, Meaghan McGeary, Marcus Bosenberg
The aim of this study is to determine the significance of programmed death-ligand 1 (PD-L1 or CD274) methylation in relation to PD-L1 expression and survival in melanoma. Despite the clinical importance of therapies targeting the PD-1/PD-L1 immune checkpoint in melanoma, factors regulating PD-L1 expression, including epigenetic mechanisms, are not completely understood. In this study, we examined PD-L1 promoter methylation in relation to PD-L1 expression and overall survival in melanoma patients. Our results suggest that DNA methylation regulates PD-L1 expression in melanoma, and we identify the key methylated CpG loci in the PD-L1 promoter, establish PD-L1 methylation as an independent survival prognostic factor, provide proof-of-concept for altering PD-L1 expression by hypomethylating agents, and uncover that PD-L1 methylation is associated with an interferon-signaling transcriptional phenotype...
October 21, 2018: Pigment Cell & Melanoma Research
Dixit Sharma, Ankita Sharma, Shailender Kumar Verma, Birbal Singh
Orientia tsutsugamushi (Ott) is a causative agent of chigger-borne zoonosis, scrub typhus which is life threatening and highly pervasive illness in humans. In this report, we have mined and classified the proteins involved in pathways unique to Ott by using high-throughput computational techniques. The 12 metabolic pathways were found to be unique to the pathogen. Forty-six proteins were reported to be essential for the pathogen's survival and non-homologous to the humans. The proteins were categorized into different classes, ie, enzymes, transporters, DNA-binding, secretory, and outer membrane proteins...
October 21, 2018: Journal of Molecular Recognition: JMR
Yukiko Matsuo, Tsutomu Yoshida, Kazuya Yamashita, Yukitoshi Satoh
BACKGROUND: Liquid-based cytology (LBC) is a useful cytopathological method, and LBC lung adenocarcinoma specimens may be used for genetic analysis in the near future. In the current study, the authors determined whether LBC specimens can be used for epidermal growth factor receptor (EGFR) mutation analysis in human lung adenocarcinoma cell lines. METHODS: Genomic DNA was extracted from 3 lung adenocarcinoma cell lines that were fixed in LBC preservation solution using 2 protocols (one for cultured cells and one for tissues) of a DNA extraction kit...
October 21, 2018: Cancer Cytopathology
Norio Hanafusa, Ken Tsuchiya, Kosaku Nitta
The concentration of sodium in dialysis fluid, a major determinant of extracellular fluid volume and blood pressure, plays a major role in the sodium balance in end-stage renal disease patients. A low dialysate sodium concentration (DNa) reduces interdialytic weight gain (IDWG) and blood pressure and might help ameliorate endothelial dysfunction and inflammation. However, low DNa can also increase the incidence of hypotensive episodes and muscle cramps. Sodium profiling, as typically prescribed in which the DNa is ramped up from above 140 mEq/L to nonphysiological levels, might reduce hypotension in patients with hemodynamic instability but at the cost of the consequences of hypernatremia...
October 21, 2018: Seminars in Dialysis
Preeyaporn Pornkulwat, Futoshi Kurisu, Suwat Soonglerdsongpha, Pathan Banjongproo, Papitchaya Srithep, Tawan Limpiyakorn
Ammonia-oxidizing archaea (AOA) have recently been proposed as potential players for ammonia removal in wastewater treatment plants (WWTPs). However, there is little evidence directly showing the contribution of AOA to ammonia oxidation in these engineered systems. In this study, DNA-stable isotope probing (DNA-SIP) with labeled 13 C-HCO3 - was introduced to sludge from a municipal WWTP. Quantitative PCR demonstrated that AOA amoA genes outnumbered AOB amoA genes in this WWTP sludge. AOA amoA gene sequence analysis revealed that AOA present in this WWTP were specific to one subcluster within the group 1...
October 20, 2018: Applied Microbiology and Biotechnology
Yadav Gyawali, Wei Zhang, Shiaoman Chao, Steven Xu, Xiwen Cai
We detected the deletion breakpoints of wheat ph1b mutant and the actual size of the deletion. Also, we developed ph1b deletion-specific markers useful for ph1b-mediated gene introgression and genome studies. The Ph1 (pairing homoeologous) locus has been considered a major genetic system for the diploidized meiotic behavior of the allopolyploid genome in wheat. It functions as a defense system against meiotic homoeologous pairing and recombination in polyploid wheat. A large deletion of the genomic region harboring Ph1 on the long arm of chromosome 5B (5BL) led to the ph1b mutant in hexaploid wheat 'Chinese Spring,' which has been widely used to induce meiotic homoeologous recombination for gene introgression from wild grasses into wheat...
October 20, 2018: TAG. Theoretical and Applied Genetics. Theoretische und Angewandte Genetik
Júlia Canet-Pons, Ralf Schubert, Ruth Pia Duecker, Roland Schrewe, Sandra Wölke, Matthias Kieslich, Martina Schnölzer, Andreas Chiocchetti, Georg Auburger, Stefan Zielen, Uwe Warnken
Autosomal recessive ataxia telangiectasia (A-T) is characterized by radiosensitivity, immunodeficiency, and cerebellar neurodegeneration. A-T is caused by inactivating mutations in the ataxia telangiectasiamutated (ATM) gene, a serine-threonine protein kinase involved in DNA damage response and excitatory neurotransmission. The selective vulnerability of cerebellar Purkinje neurons (PN) to A-T is not well understood. Employing global proteomic profiling of cerebrospinal fluid from patients at ages around 15 years, we detected reduced calbindin, reelin, cerebellin-1, cerebellin-3, protocadherin fat 2, sempahorin 7A, and increased apolipoprotein B and J peptides...
October 21, 2018: Neurogenetics
Lydie Debaize, Marie-Bérengère Troadec
The human Far Upstream Element (FUSE) Binding Protein 1 (FUBP1) is a multifunctional DNA- and RNA-binding protein involved in diverse cellular processes. FUBP1 is a master regulator of transcription, translation, and RNA splicing. FUBP1 has been identified as a potent pro-proliferative and anti-apoptotic factor by modulation of complex networks. FUBP1 is also described either as an oncoprotein or a tumor suppressor. Especially, FUBP1 overexpression is observed in a growing number of cancer and leads to a deregulation of targets that includes the fine-tuned MYC oncogene...
October 20, 2018: Cellular and Molecular Life Sciences: CMLS
Ke Ding, Jianyang Jiang, Liang Chen, Xiaohua Xu
BACKGROUND Non-small cell lung cancer (NSCLC) accounts for about 85% of all types of lung cancer. Methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) is involved in DNA methylation, and DNA methylation is related to tumorigenesis. The role of MTHFD1 in NSCLC was examined in our study. MATERIAL AND METHODS The correlation between the expression of MTHFD1 and the clinicopathological features of patients diagnosed with lung cancer was investigated using the chi-square test. The viability and apoptosis of NCI-H1299 cells was respectively detected using cell counting kit-8 and flow cytometry assays...
October 21, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Lene E Johannessen, Petter Brandal, Tor Åge Myklebust, Sverre Heim, Francesca Micci, Ioannis Panagopoulos
BACKGROUND: Although methylation of the O6 -methylguanine-DNA methyltransferase (MGMT) gene promoter predicts response to temozolomide in patients with glioblastoma, no consensus exists as to which assay is best for its detection. MATERIALS AND METHODS: Methylation of MGMT promoter was examined by methylation-specific polymerase chain reaction (MSP), quantitative real-time MSP, methylation-sensitive high-resolution melting analysis, and two commercial pyrosequencing (PSQ) kits...
November 2018: Cancer Genomics & Proteomics
Yonghong Wang, Ge Ning, Yaohui Wu, Shun Wu, Baiquan Zeng, Gaoqiang Liu, Xiaoxiao He, Kemin Wang
Smartly coupling exonuclease-induced target recycling signal amplifications with β-cyclodextrin host-guest recognition, a novel "signal-on" aptamer sensor for sensitive determination of ochratoxin A (OTA) was proposed for the first time. Firstly, the formation of double-strand DNA (dsDNA) was occurred by hybridizing OTA aptamer with its complementary DNA (cDNA) and as the probe DNA the cDNA at its 3' terminal was labeled with methylene blue (MB). Next, when OTA was present, the aptamer tended to form aptamer-OTA complex with conformation of G-quadruplex instead of aptamer-cDNA duplex, leading to thus the probe DNA separating from dsDNA complex...
October 11, 2018: Biosensors & Bioelectronics
Lei Wang, Tianjiao Meng, Guangshun Yu, Shasha Wu, Jingjing Sun, Huixian Jia, Huan Wang, Xinjian Yang, Yufan Zhang
An electrochemical biosensor was designed for the determination of telomerase activity using an enzyme-free, PCR-free, and convenient electrochemical strategy. In this work, the electrochemical biosensor was constructed through the functionalization of Au nanorods with a carboxylic group (AuNRs-3) and subsequent immobilization with capture DNA (cDNA) for sensing telomerase activity. Upon telomerase triggered extension, the telomerase activity is related to the amount of the adsorbed electrocatalyst, leading to the different electrochemical signals for readout...
October 9, 2018: Biosensors & Bioelectronics
C Lanier, F Bernard, S Dumez, J Leclercq-Dransart, S Lemière, F Vandenbulcke, F Nesslany, A Platel, I Devred, A Hayet, D Cuny, A Deram
Acute and long-term (3-, 10- and 56-day exposure) laboratory toxicity tests were carried out to assess the individual and combined toxic effects of cadmium (Cd) and lead (Pb) in Brassica oleracea and Trifolium repens. In addition to morphological parameters, this work also used comet assay to address endpoints in relation to genotoxicity. Bioaccumulation was measured to demonstrate the influence of the mixture on the concentrations of each metal in the plant. The statistical method reported by Ince et al. (1999) was used to evaluate the types of interaction between Cd and Pb in each treatment and concerning their combined effect...
October 18, 2018: Ecotoxicology and Environmental Safety
Lei Wang, Munish Kumar, Qipan Deng, Xu Wang, Ming Liu, Zhaojian Gong, Shanshan Zhang, Xiaodong Ma, Zijun Y Xu-Monette, Min Xiao, Qing Yi, Ken H Young, Kenneth S Ramos, Yong Li
Although epidemiologic studies have suggested a possible association between occupational exposures to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the risk of development of multiple myeloma, definitive evidence in support of this association is lacking. In the present study, we employed the Vk*Myc mouse model of multiple myeloma to assess the impact of TCDD exposure on multiple myeloma pathogenesis. TCDD induced splenomegaly and multiple peripheral blood abnormalities, including anemia and high serum IgG levels...
October 18, 2018: Cancer Letters
Fang Wang, Dongbo Zhao, Ling Jiang, Jun Song, Yunfei Liu
Fourier infrared spectrometer and X-ray diffractometer were used to detect the spectra of lab-made U:A (uracil and adenine hydrate dried at room temperature), lab-made C:G (cytosine and guanine hydrate dried at room temperature), U + A (mixture of uracil and adenine), and C + G (mixture of cytosine and guanine). The results of our testing showed that U:A did not form a eutectic, but C:G did. In order to further characterize the vibrational modes of RNA base pair crystals, the absorption spectra of 1‑methyl‑5‑bromouracil‑9‑methyladenine (abbreviated as 1M5BU:9MA) and 1‑methylcytosine‑9‑ethylguanine (abbreviated as 1MC:9EG) were calculated based on the PBC-GEBF (generalized energy-based fragmentation approach under periodic boundary conditions) method...
October 16, 2018: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
Parham Jabbarzadeh Kaboli, Melody Pui-Yee Leong, Patimah Ismail, King-Hwa Ling
BACKGROUND: Berberine is an alkaloid plant-based DNA intercalator that affects gene regulation, particularly expression of oncogenic and tumor suppressor proteins. The effects of berberine on different signaling proteins remains to be elucidated. The present study aimed to identify the effects of berberine against key oncogenic proteins in breast cancer cells. METHODS: Molecular docking and molecular dynamics simulations were used for EGFR, p38, ERK1/2, and AKT...
August 1, 2018: Pharmacological Reports: PR
Ignacio Sánchez, Fay Betsou, William Mathieson
Vacuum centrifugal (SpeedVac) concentration is commonly applied to nucleic acids extracted from formalin-fixed paraffin-embedded (FFPE) sections, but with an unknown impact. We concentrated DNA and RNA from FFPE biospecimens using different time/temperature SpeedVac combinations of up to 30 min concentration at 45 °C, then used spectrophotometry, spectrofluorometry, RIN, PERM, DV200, qRT-PCR, DIN and the Illumina FFPE QC Assay to assess the changes in quantity, purity and integrity induced by the concentration process...
October 18, 2018: Analytical Biochemistry
M Shanmugavadivu, Bharath Kumar Velmurugan
Antrodia camphorata is an expensive mushroom that grows on the inner cavity of an endangered native tree of Taiwan namely Cinnamomum kanehirai Hayata. It is used as a traditional medicine in Taiwan and has several health benefits including free radical scavenging, anti-inflammatory, antimicrobial, hepatoprotective, neuroprotective, antidiabetic, and free radical-induced DNA damage protecting activities. Antroquinonol is a tetrahydro ubiquinone derivative found predominately in the mycelium of Antrodia camphorata, and is characterized by numerous biological and pharmacological activities...
October 18, 2018: Chemico-biological Interactions
Yimin Hu, Fang Nan, Sarah Wanjiku Maina, Jia Guo, Shenglu Wu, Zhihong Xin
Plipastatin, a cyclic lipopeptide, exhibits inhibitory activity toward filamentous fungi and plays an important role in the prevention of plant diseases, and post-harvest preservation of fruits and vegetables. However, the application of plipastatin has been hampered by low yields in natural strains, while chemical synthesis is not feasible because of its complex chemical structure. In this study, a scarless genetic modification method was applied to construct a heterologous expression host (Bacillus subtilis 1A751 Δpps) by knocking out the natural plipastatin genes from B...
October 18, 2018: Journal of Biotechnology
David Guenat, Véronique Dalstein, Frédéric Mauny, Maëlle Saunier, Jenny Briolat, Christine Clavel, Didier Riethmuller, Christiane Mougin, Jean-Luc Prétet
High risk HPV infection is the necessary cause for the development of precancerous and cancerous lesions of the cervix. Among HPV, HPV16 represents the most carcinogenic type. Since the determination of HPV16 DNA load could be clinically useful, we assessed quantitative real-time PCR targeting E6HPV16 and albumin genes on two different platforms. Series of SiHa cells diluted in PreservCyt were used to assess repeatability and reproducibility of two in-house real-time PCR techniques run in two different laboratories to determine HPV16 load...
October 18, 2018: Papillomavirus Research
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