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Hubert Li, Manbir Sandhu, Linda H Malkas, Robert J Hickey, Nagarajan Vaidehi
Proliferating cell nuclear antigen (PCNA) is a member of the family of sliding clamp proteins that serves as a clamp during DNA repair, DNA replication, cell cycle control, and multiple forms of chromatin modification. PCNA functions as a homotrimer and complexes with multiple proteins in order to carry out each of these varied functions. PCNA binds to different partner proteins in the same region of its structure, called the " interdomain connecting loop", but with different affinities. This interdomain connecting loop is an intrinsically disordered region that takes different conformations when binding to different partner proteins...
December 26, 2017: Journal of Chemical Information and Modeling
Satya Prakash Yadav, Prashant Kumar Singh, Pradeep Sharma, Naseer Iqbal, Punit Kaur, Sujata Sharma, Tej P Singh
Proliferating cell nuclear antigen (PCNA) acts as a sliding clamp to support DNA replication and repair. The structure of PCNA from Leishmania donovani (LdPCNA) has been determined at 2.73Å resolution. Structure consists of six crystallographically independent molecules which form two trimeric rings. The pore diameter of the individual trimeric ring is of the order of 37Å. The two rings are stacked through their front to front faces. In order to gain a stable packing, the rings are rotated by 42° about the pore axis and shifted by 7Å and tilted by 16° along the perpendicular direction to pore axis...
November 2017: Biochimica et Biophysica Acta
Yonghua Sang, Lin Bo, Haiyong Gu, Wengtao Yang, Yongbing Chen
BACKGROUND: Esophageal cancer has a high mortality rate, particularly in Asia, and there are obvious racial differences in regard to incidence. The purpose of our study was to assess the genetic susceptibility of functional single nucleotide polymorphisms in flap endonuclease-1 (FEN1) in esophageal squamous cell carcinoma ESCC. METHODS: Clinical blood samples of 629 ESCC cases and 686 control samples were collected. The ligation detection reaction method was used to determine FEN 1 rs174538 G>A genotypes...
May 2017: Thoracic Cancer
Yi-Chih Tsai, Yi-Hsiang Wang, Yin-Chang Liu
UVC irradiation-caused DNA lesions are repaired in mammalian cells solely by nucleotide excision repair (NER), which consists of sequential events including initial damage recognition, dual incision of damage site, gap-filling, and ligation. We have previously shown that gap-filling during the repair of UV-induced DNA lesions may be delayed by a subsequent treatment of oxidants or prooxidants such as hydrogen peroxide, flavonoids, and colcemid. We considered the delay as a result of competition for limiting protein/enzyme factor(s) during repair synthesis between NER and base excision repair (BER) induced by the oxidative chemicals...
2017: Journal of Nucleic Acids
Gaurav K Varshney, Shawn M Burgess
The search for novel ways to target and alter the genomes of living organisms accelerated rapidly this decade with the discovery of CRISPR/Cas9. Since the initial discovery, efforts to find alternative methods for altering the genome have expanded. A new study presenting an alternative approach has been demonstrated that utilizes flap endonuclease 1 (FEN-1) fused to the Fok1 endonuclease, which shows potential for DNA-guided genome targeting in vivo.
September 15, 2016: Genome Biology
Shu Xu, Shasha Cao, Bingjie Zou, Yunyun Yue, Chun Gu, Xin Chen, Pei Wang, Xiaohua Dong, Zheng Xiang, Kai Li, Minsheng Zhu, Qingshun Zhao, Guohua Zhou
Engineered endonucleases are a powerful tool for editing DNA. However, sequence preferences may limit their application. We engineer a structure-guided endonuclease (SGN) composed of flap endonuclease-1 (FEN-1), which recognizes the 3' flap structure, and the cleavage domain of Fok I (Fn1), which cleaves DNA strands. The SGN recognizes the target DNA on the basis of the 3' flap structure formed between the target and the guide DNA (gDNA) and cut the target through its Fn1 dimerization. Our results show that the SGN, guided by a pair of gDNAs, cleaves transgenic reporter gene and endogenous genes in zebrafish embryonic genome...
September 15, 2016: Genome Biology
Zhimin Peng, Zhongping Liao, Yoshihiro Matsumoto, Austin Yang, Alan E Tomkinson
The synthesis, processing, and joining of Okazaki fragments during DNA replication is complex, requiring the sequential action of a large number of proteins. Proliferating cell nuclear antigen, a DNA sliding clamp, interacts with and coordinates the activity of several DNA replication proteins, including the enzymes flap endonuclease 1 (FEN-1) and DNA ligase I that complete the processing and joining of Okazaki fragments, respectively. Although it is evident that maintaining the appropriate relative stoichiometry of FEN-1 and DNA ligase I, which compete for binding to proliferating cell nuclear antigen, is critical to prevent genomic instability, little is known about how the steady state levels of DNA replication proteins are regulated, in particular the proteolytic mechanisms involved in their turnover...
October 14, 2016: Journal of Biological Chemistry
J Haumann, J W Geurts, S M J van Kuijk, B Kremer, E A Joosten, M H J van den Beuken-van Everdingen
BACKGROUND: Cancer pain is still inadequately treated in up to 60% of cancer patients. Based on the additional effect on the N-Methyl-d-Aspartate receptor, we expected that methadone (Met) could provide better pain relief than fentanyl (Fen) in cancer pain with a neuropathic pain component. METHODS: A randomised controlled trial was performed with 52 strong opioids naive patients with head-and-neck cancer with substantial pain (pain Numerical Rating Scale [NRS] > 4) and a neuropathic pain component (Douleur Neuropathique [DN4] > 4)...
September 2016: European Journal of Cancer
A L Oropesa, A M Floro, P Palma
In the present study, the endocrine activity of the antiepileptic pharmaceutical carbamazepine (CBZ) in the crustacean Daphnia magna was assessed. To assess the hormonal activity of the drug, we exposed maternal daphnids and embryos to environmental relevant concentrations of CBZ (ranging from 10 to 200 μg/L) and to mixtures of CBZ with fenoxycarb (FEN; 1 μg/L). Chronic exposure to CBZ significantly decreased the reproductive output and the number of molts of D. magna at 200 μg/L. This compound induced the production of male offspring (12 ± 1...
September 2016: Environmental Science and Pollution Research International
Ayman Al-Hendy, Michael P Diamond, Thomas G Boyer, Sunil K Halder
CONTEXT: Somatic mutations in the Med12 gene are known to activate Wnt/β-catenin signaling in human uterine fibroids (UFs). OBJECTIVE: The objective of the study was to examine the role of vitamin D3 in the modulation of Wnt/β-catenin and mammalian target of rapamycin (mTOR) signaling in human UF cells. DESIGN: Immortalized human UF cells (HuLM) and human primary UF (PUF) cells were treated with increasing concentrations of vitamin D3 and thereafter analyzed using Western blots and immunocytochemistry...
April 2016: Journal of Clinical Endocrinology and Metabolism
Rashmirekha Pati, Ishani Das, Ranjit Kumar Mehta, Rojalin Sahu, Avinash Sonawane
Zinc oxide nanoparticles (ZnO-NPs) have wide biological applications, which have raised serious concerns about their impact on the health and environment. Although, various studies have shown ZnO-NP toxicity on different cells underin vitroconditions, sufficient information is lacking regarding toxicity and underlying mechanisms underin vivoconditions. In this work, we investigated genotoxic, clastogenic, and cytotoxic effects of ZnO-NPs on macrophages and in adult mice. ZnO-NP-treated mice showed signs of toxicity such as loss in body weight, passive behavior and reduced survival...
April 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
Pankaj Wadhwa, Priti Jain, Hemant R Jadhav
Flap endonuclease-I (FEN-1) is involved in DNA repair and considered to be a novel target for the development of anticancer agents. N-hydroxy urea derivatives have been reported as FEN-1 inhibitors. To derive in vitro and in silico correlation, we have performed 2D-quantitative structure activity relationship (QSAR) analysis and docking studies on these compounds. 2D-QSAR models were developed using multiple linear regression (MLR) analysis and cross-validation using leave one out (LOO) method. The best model displayed R(2) of 0...
2015: Current Computer-aided Drug Design
Amy Hubert, Jordana M Henderson, Martis W Cowles, Kelly G Ross, Matthew Hagen, Christa Anderson, Claudia J Szeterlak, Ricardo M Zayas
BACKGROUND: Planarians are renowned for their regenerative capacity and are an attractive model for the study of adult stem cells and tissue regeneration. In an effort to better understand the molecular mechanisms underlying planarian regeneration, we performed a functional genomics screen aimed at identifying genes involved in this process in Schmidtea mediterranea. METHODS: We used microarrays to detect changes in gene expression in regenerating and non-regenerating tissues in planarians regenerating one side of the head and followed this with high-throughput screening by in situ hybridization and RNAi to characterize the expression patterns and function of the differentially expressed genes...
October 12, 2015: BMC Genomics
Shakti Ranjan Satapathy, Sumit Siddharth, Dipon Das, Anmada Nayak, Chanakya Nath Kundu
A poly(lactic-co-glycolic acid) (PLGA)-based uniform (50-100 nm) hybrid nanoparticle (QAgNP) with positive zeta potential (0.52 ± 0.09 mV) was prepared by single emulsion solvent evaporation method with bioactive small molecule quinacrine (QC) in organic phase and silver (Ag) in aqueous phase. Physiochemical properties established it as a true hybrid nanoparticle and not a mixture of QC and Ag. Antitumor activity of QAgNP was evaluated by using various cancer cell lines including H-357 oral cancer cells and OSCC-cancer stem cell in an in vitro model system...
November 2, 2015: Molecular Pharmaceutics
Ying-Chen Kuo, Lin-Fen Hsieh, Hong-Jen Chiou
Postherpetic neuralgia is a common and challenging complication of herpes zoster infection, particularly in older people. In recent decades, first-line treatments, including oral or topical medication, have become well established. However, few studies have reported the efficacy of interventional procedures for the treatment of postherpetic neuralgia. Here, the authors present a case of intractable postherpetic neuralgia treated with musculocutaneous peripheral nerve block under ultrasound guidance. Symptoms remained controlled at 1 mo follow-up...
January 2016: American Journal of Physical Medicine & Rehabilitation
Nai-Yu Liu, Hsiao-Hui Lee, Zee-Fen Chang, Yeou-Guang Tsay
It has been observed that a modified peptide and its non-modified counterpart, when analyzed with reverse phase liquid chromatography, usually share a very similar elution property [1-3]. Inasmuch as this property is common to many different types of protein modifications, we propose an informatics-based approach, featuring the generation of segmental average mass spectra ((sa)MS), that is capable of locating different types of modified peptides in two-dimensional liquid chromatography-mass spectrometric (LC-MS) data collected for regular protease digests from proteins in gels or solutions...
September 10, 2015: Analytica Chimica Acta
Rong-Liang Liang, Xu-Ping Xu, Tian-Cai Liu, Jian-Wei Zhou, Xian-Guo Wang, Zhi-Qi Ren, Fen Hao, Ying-Song Wu
Alpha-fetoprotein (AFP), a primary marker for many diseases including various cancers, is important in clinical tumor diagnosis and antenatal screening. Most immunoassays provide high sensitivity and accuracy for determining AFP, but they are expensive, often complex, time-consuming procedures. A simple and rapid point-of-care system that integrates Eu (III) chelate microparticles with lateral flow immunoassay (LFIA) has been developed to determine AFP in serum with an assay time of 15 min. The approach is based on a sandwich immunoassay performed on lateral flow test strips...
September 3, 2015: Analytica Chimica Acta
Geng Fen Han, Zi Ming Wang, Gang Chen, Kui Jun Chen, Si Yu Wu, Sen Zhang, Xi Nan Lai, Ai Min Wang
BACKGROUND: The characteristics of explosion in water are different from those in air and vary in different water depths. It is important to investigate the characteristics and mechanisms of extremity injuries caused by mine blasts in shoals. METHODS: A total of ninety New Zealand rabbits were randomly divided into four groups put in different depths of water (land group, midpoint of the thigh in the shoal 1 group, the xiphoid process in the shoal 2 group, and control group)...
September 2015: Ulusal Travma Ve Acil Cerrahi Dergisi, Turkish Journal of Trauma & Emergency Surgery: TJTES
Hock-Kean Liew, Hung-Yu Cheng, Li-Chuan Huang, Kuo-Wei Li, Hsiao-Fen Peng, Hui-I Yang, Peter Bor-Chian Lin, Jon-Son Kuo, Cheng-Yoong Pang
OBJECTIVE: Alcohol intoxication is associated with worse intracerebral hemorrhage (ICH) outcome, indicating the important role of alcohol in ICH pathogenesis. We intended to investigate the effects of ethanol pretreatment on the severity of ICH-induced brain injury in rats. METHODS: At 1 hour after intraperitoneal injection of ethanol (3 g/kg), 0.2 U bacterial collagenase was infused into the striatum of male Sprague-Dawley rats to induce ICH. Accumulative mortality rate, body weight changes, and motorsensory and neurological abnormalities were evaluated...
January 2016: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
Yanmin Zhang, Zhaoxiao Du, Zirong Zhuang, Yanjun Wang, Fen Wang, Shuai Liu, Han Wang, Hairong Feng, Haoyuan Li, Liyan Wang, Xianghong Zhang, Aijun Hao
Glioblastoma, the most common type of primary malignant brain tumor, is a devastating disease associated with a median survival of approximately 12 months. Here, we have tested E804, the commercially available indirubin derivatives, against U251 and U87 glioblastoma cells. Treatment with E804 significantly inhibits the growth of human glioblastoma cells lines via induction of differentiation and apoptosis. Differentiation induction is coupled with increased expression of glial fibriliary acidic protein, a marker for mature astrocytes...
November 2015: Journal of Neuro-oncology
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