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https://www.readbyqxmd.com/read/28926604/a-novel-class-of-chemicals-that-react-with-abasic-sites-in-dna-and-specifically-kill-b-cell-cancers
#1
Shanqiao Wei, Madusha L W Perera, Ramin Sakhtemani, Ashok S Bhagwat
Most B cell cancers overexpress the enzyme activation-induced deaminase at high levels and this enzyme converts cytosines in DNA to uracil. The constitutive expression of this enzyme in these cells greatly increases the uracil content of their genomes. We show here that these genomes also contain high levels of abasic sites presumably created during the repair of uracils through base-excision repair. We further show that three alkoxyamines with an alkyne functional group covalently link to abasic sites in DNA and kill immortalized cell lines created from B cell lymphomas, but not other cancers...
2017: PloS One
https://www.readbyqxmd.com/read/28924551/identification-and-characterization-of-loop7-motif-and-its-role-in-regulating-biological-function-of-human-apobec3g-through-molecular-modeling-and-biological-assay
#2
Congjie Zhai, Ling Ma, Zhixin Zhang, Jiwei Ding, Jing Wang, Yongxin Zhang, Xiaoyu Li, Fei Guo, Liyan Yu, Jinming Zhou, Shan Cen
Human APOBEC3G (hA3G) is a cytidine deaminase which inhibits HIV-1 replication. The HIV-1 accessory protein viral infectivity factor (Vif) counteracts with hA3G by targeting it for proteasomal degradation. In this work, we constructed and optimized molecular models of the hA3G dimer and the hA3G-Vif complex. The molecular modeling study revealed that the loop7 motif of hA3G appears on the interfaces of both the hA3G-Vif complex and the hA3G dimer. Biochemical analysis provided evidence suggesting that binding of Vif to hA3G results in steric blocking of hA3G dimerization, implying that monomeric hA3G serves as a substrate for Vif-mediated degradation...
September 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28924040/a-b-z-junction-induced-by-an-a-a-mismatch-in-gac-repeats-in-the-gene-for-cartilage-oligomeric-matrix-protein-promotes-binding-with-the-hz%C3%AE-adar1-protein
#3
Narendar Kolimi, Yogeeshwar Ajjugal, Thenmalarchelvi Rathinavelan
GAC repeat expansion from five to seven in the exonic region of the gene for cartilage oligomeric matrix protein (COMP) leads to pseudoachondroplasia, a skeletal abnormality. However, the molecular mechanism by which GAC expansions in the COMP gene lead to skeletal dysplasias is poorly understood. Here, we used MD simulations which indicate that an A...A mismatch in a d(GAC)6.d(GAC)6 duplex induces negative supercoiling, leading to a local B-to-Z DNA transition. This transition facilitates the binding of d(GAC)7...
September 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28923949/cytosine-deamination-and-base-excision-repair-cause-r-loop-induced-cag-repeat-fragility-and-instability-in-saccharomyces-cerevisiae
#4
Xiaofeng A Su, Catherine H Freudenreich
CAG/CTG repeats are structure-forming repetitive DNA sequences, and expansion beyond a threshold of ∼35 CAG repeats is the cause of several human diseases. Expanded CAG repeats are prone to breakage, and repair of the breaks can cause repeat contractions and expansions. In this study, we found that cotranscriptional R-loops formed at a CAG-70 repeat inserted into a yeast chromosome. R-loops were further elevated upon deletion of yeast RNaseH genes and caused repeat fragility. A significant increase in CAG repeat contractions was also observed, consistent with previous human cell studies...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28923725/petroleum-degradation-by-endophytic-streptomyces-spp-isolated-from-plants-grown-in-contaminated-soil-of-southern-algeria
#5
Hafida Baoune, Aminata Ould El Hadj-Khelil, Graciela Pucci, Pedro Sineli, Lotfi Loucif, Marta Alejandra Polti
Petroleum hydrocarbons are well known by their high toxicity and recalcitrant properties. Their increasing utilization around worldwide led to environmental contamination. Phytoremediation using plant-associated microbe is an interesting approach for petroleum degradation and actinobacteria have a great potential for that. For this purpose, our study aimed to isolate, characterize, and assess the ability of endophytic actinobacteria to degrade crude petroleum, as well as to produce plant growth promoting traits...
September 15, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28921561/the-ribokinases-of-arabidopsis-thaliana-and-saccharomyces-cerevisiae-are-required-for-ribose-recycling-from-nucleotide-catabolism-which-in-plants-is-not-essential-to-survive-prolonged-dark-stress
#6
Rebekka Y Schroeder, Anting Zhu, Holger Eubel, Kathleen Dahncke, Claus-Peter Witte
Nucleotide catabolism in Arabidopsis thaliana and Saccharomyces cerevisiae leads to the release of ribose, which requires phosphorylation to ribose-5-phosphate mediated by ribokinase (RBSK). We aimed to characterize RBSK in plants and yeast, to quantify the contribution of plant nucleotide catabolism to the ribose pool, and to investigate whether ribose carbon contributes to dark stress survival of plants. We performed a phylogenetic analysis and determined the kinetic constants of plant-expressed Arabidopsis and yeast RBSKs...
September 18, 2017: New Phytologist
https://www.readbyqxmd.com/read/28919486/resveratrol-inhibits-proliferation-promotes-differentiation-and-melanogenesis-in-ht-144-melanoma-cells-through-inhibition-of-mek-erk-kinase-pathway
#7
Ming-Jun Lei, Yao Dong, Chun-Xia Sun, Xiang-Hong Zhang
The present study was aimed to investigate the effect of resveratrol on the viability of HT-144 melanoma cells and formation of melanin. MTT assay was used for analysis of cell viability and western blot for determination of phospho-Mek 1/2, phospho-Erk 1/2 (Tyr-204), Mitf, PBG-D and p-CREB-1 expression. MTT assay results showed that treatment of HT-144 cells with various doses of resveratrol led to a concentration dependent inhibition of proliferation. The antiproliferative activity was significant at 15 μM concentration of resveratrol after 24 h...
September 14, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28916770/changes-in-cd73-cd39-and-cd26-expression-on-t-lymphocytes-of-anca-associated-vasculitis-patients-suggest-impairment-in-adenosine-generation-and-turn-over
#8
Lovis Kling, Urs Benck, Annette Breedijk, Lisa Leikeim, Marianne Heitzmann, Stefan Porubsky, Bernhard K Krämer, Benito A Yard, Anna-Isabelle Kälsch
Extracellular adenosine, generated via the concerted action of CD39 and CD73, contributes to T-cell differentiation and function. Adenosine concentrations are furthermore influenced by adenosine deaminase binding protein CD26. Because aberrant T-cell phenotypes had been reported in anti-neutrophil cytoplasmic auto-antibody (ANCA)-associated vasculitis (AAV) patients, an impaired expression of these molecules on T-cells of AAV patients was hypothesized in the present study. While in AAV patients (n = 29) CD26 was increased on CD4(+) lymphocytes, CD39 and CD73 were generally reduced on patients' T-cells...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28916558/potential-of-rice-stubble-as-a-reservoir-of-bradyrhizobial-inoculum-in-rice-legume-crop-rotation
#9
Pongdet Piromyou, Teerana Greetatorn, Kamonluck Teamtisong, Panlada Tittabutr, Nantakorn Boonkerd, Neung Teaumroong
Bradyrhizobium encompasses a variety of bacteria that can live in symbiotic and endophytic associations with leguminous and non-leguminous plants such as rice. Therefore, it can be expected that rice endophytic bradyrhizobia can be applied in the rice-legume crop rotation system. Some endophytic bradyrhizobial strains were isolated from rice (Oryza sativa L.) tissues. The rice biomass could be enhanced when supplying KNO3, NH4NO3, or urea with bradyrhizobial strain inoculation, especially strain SUTN9-2. In contrast, the strains which suppressed rice growth were photosynthetic bradyrhizobia and also found to produce nitric oxide (NO) in the rice root...
September 15, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28915999/oxidative-stress-in-dairy-cows-seropositives-for-neospora-caninum
#10
Patrícia Glombowsky, Nathieli B Bottari, Vanderlei Klauck, Juscivete F Fávero, Natan M Soldá, Matheus D Baldissera, Gessica Perin, Vera M Morsch, Maria Rosa C Schetinger, Lenita M Stefani, Aleksandro S Da Silva
Bovine neosporosis is caused by the protozoan Neospora caninum and is one of the major causes of abortion in cows. Cattle are intermediate hosts of this parasite and may have asymptomatic or symptomatic infections. Therefore, the aim of this study was to evaluate oxidative stress marker reactive oxygen species (ROS), thiobarbituric reactive acid substances (TBARS) levels, glutathione S-transferase (GST), adenosine deaminase (ADA), and butyrylcholinesterase (BChE) activities in dairy cows seropositives for N...
October 2017: Comparative Immunology, Microbiology and Infectious Diseases
https://www.readbyqxmd.com/read/28912488/gene-expression-and-methylation-analyses-suggest-dctd-as-a-prognostic-factor-in-malignant-glioma
#11
Huimin Hu, Zheng Wang, Mingyang Li, Fan Zeng, Kuanyu Wang, Ruoyu Huang, Haoyuan Wang, Fan Yang, Tingyu Liang, Hua Huang, Tao Jiang
Malignant glioma is the most common brain cancer with dismal outcomes. Individual variation of the patients' survival times is remarkable. Here, we investigated the transcriptome and promoter methylation differences between patients of malignant glioma with short (less than one year) and the patients with long (more than three years) survival in CGGA (Chinese Glioma Genome Atlas), and validated the differences in TCGA (The Cancer Genome Atlas) to identify the genes whose expression levels showed high concordance with prognosis of glioma patients, as well as played an important role in malignant progression...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28912244/potential-role-of-intratumor-bacteria-in-mediating-tumor-resistance-to-the-chemotherapeutic-drug-gemcitabine
#12
Leore T Geller, Michal Barzily-Rokni, Tal Danino, Oliver H Jonas, Noam Shental, Deborah Nejman, Nancy Gavert, Yaara Zwang, Zachary A Cooper, Kevin Shee, Christoph A Thaiss, Alexandre Reuben, Jonathan Livny, Roi Avraham, Dennie T Frederick, Matteo Ligorio, Kelly Chatman, Stephen E Johnston, Carrie M Mosher, Alexander Brandis, Garold Fuks, Candice Gurbatri, Vancheswaran Gopalakrishnan, Michael Kim, Mark W Hurd, Matthew Katz, Jason Fleming, Anirban Maitra, David A Smith, Matt Skalak, Jeffrey Bu, Monia Michaud, Sunia A Trauger, Iris Barshack, Talia Golan, Judith Sandbank, Keith T Flaherty, Anna Mandinova, Wendy S Garrett, Sarah P Thayer, Cristina R Ferrone, Curtis Huttenhower, Sangeeta N Bhatia, Dirk Gevers, Jennifer A Wargo, Todd R Golub, Ravid Straussman
Growing evidence suggests that microbes can influence the efficacy of cancer therapies. By studying colon cancer models, we found that bacteria can metabolize the chemotherapeutic drug gemcitabine (2',2'-difluorodeoxycytidine) into its inactive form, 2',2'-difluorodeoxyuridine. Metabolism was dependent on the expression of a long isoform of the bacterial enzyme cytidine deaminase (CDDL), seen primarily in Gammaproteobacteria. In a colon cancer mouse model, gemcitabine resistance was induced by intratumor Gammaproteobacteria, dependent on bacterial CDDL expression, and abrogated by cotreatment with the antibiotic ciprofloxacin...
September 15, 2017: Science
https://www.readbyqxmd.com/read/28912080/induced-prodrug-activation-by-conditional-protein-degradation
#13
Andrew S Gaynor, Wilfred Chen
Enzyme prodrug therapies hold potential as a targeted treatment option for cancer patients. However, off-target effects can be detrimental to patient health and represent a safety concern. This concern can be alleviated by including a failsafe mechanism that can abort the therapy in healthy cells. This feature can be included in enzyme prodrug therapies by use of conditional degradation tags, which degrade the protein unless stabilized. We call this process Degradation-Directed Enzyme Prodrug Therapy (DDEPT)...
September 11, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28911688/curcumin-inhibits-adenosine-deaminase-and-arginase-activities-in-cadmium-induced-renal-toxicity-in-rat-kidney
#14
Ayodele Jacob Akinyemi, Nora Onyebueke, Opeyemi Ayodeji Faboya, Sunday Amos Onikanni, Adewale Fadaka, Israel Olayide
In this study, the effect of enzymes involved in degradation of renal adenosine and l-arginine was investigated in rats exposed to cadmium (Cd) and treated with curcumin, the principal active phytochemical in turmeric rhizome. Animals were divided into six groups (n = 6): saline/vehicle, saline/curcumin 12.5 mg/kg, saline/curcumin 25 mg/kg, Cd/vehicle, Cd/curcumin 12.5 mg/kg, and Cd/curcumin 25 mg/kg. The results of this study revealed that the activities of renal adenosine deaminase and arginase were significantly increased in Cd-treated rats when compared with the control (p < 0...
April 2017: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/28905055/the-c-terminal-cytidine-deaminase-domain-of-apobec3g-itself-undergoes-intersegmental-transfer-for-a-target-search-as-revealed-by-real-time-nmr-monitoring
#15
Keisuke Kamba, Takashi Nagata, Masato Katahira
APOBEC3G (A3G), an anti-human immunodeficiency virus 1 factor, deaminates cytidines. We examined deamination of two cytidines located separately on substrate ssDNA by the C-terminal domain (CTD) of A3G using real-time NMR monitoring. The deamination preference between the two cytidines was lost when either the substrate or non-substrate ssDNA concentration increased. When the non-substrate ssDNA concentration increased, the deamination activity first increased, but then decreased. This indicates that even a single domain, A3G-CTD, undergoes intersegmental transfer for a target search...
September 14, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28895850/gene-therapy-approaches-to-immunodeficiency
#16
REVIEW
Sujal Ghosh, H Bobby Gaspar
Transfer of gene-corrected autologous hematopoietic stem cells in patients with primary immunodeficiencies has emerged as a new therapeutic approach. Patients with various conditions lacking a suitable donor have been treated with retroviral vectors and a gene-addition strategy. Initial promising results were shadowed by the occurrence of malignancies in some of these patients. Current trials, developed in the last decade, use safer viral vectors to overcome the risk of genotoxicity and have led to improved clinical outcomes...
October 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/28895046/characterization-of-cadmium-resistant-klebsiella-pneumoniae-mcc-3091-promoted-rice-seedling-growth-by-alleviating-phytotoxicity-of-cadmium
#17
Krishnendu Pramanik, Soumik Mitra, Anumita Sarkar, Tithi Soren, Tushar Kanti Maiti
Cadmium (Cd) phytotoxicity in agricultural land is a major global concern now-a-days resulting in very poor yield. Plant growth-promoting rhizobacteria (PGPR)-mediated bioremediation is one of the convenient strategies for detoxification of Cd from the soil and for plant growth promotion under Cd stress. The selected strain K5 was identified as Klebsiella pneumoniae based on MALDI-TOF MS ribosomal protein and 16S rDNA sequence-based homology. The strain possessed several PGP traits viz. IAA production (3413 μg/mL), phosphate solubilization (80...
September 11, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28893659/a-halotolerant-enterobacter-sp-displaying-acc-deaminase-activity-promotes-rice-seedling-growth-under-salt-stress
#18
Anumita Sarkar, Pallab Kumar Ghosh, Krishnendu Pramanik, Soumik Mitra, Tithi Soren, Sanjeev Pandey, Monohar Hossain Mondal, Tushar Kanti Maiti
Agricultural productivity is proven to be hampered by the synthesis of reactive oxygen species (ROS) and production of stress-induced ethylene under salinity stress. One-aminocyclopropane-1-carboxylic acid (ACC) is the direct precursor of ethylene synthesized by plants. Bacteria possessing ACC deaminase activity can use ACC as a nitrogen source preventing ethylene production. Several salt-tolerant bacterial strains displaying ACC deaminase activity were isolated from rice fields, and their plant growth-promoting (PGP) properties were determined...
September 9, 2017: Research in Microbiology
https://www.readbyqxmd.com/read/28888888/sepsis-induced-by-cecal-ligation-and-perforation-clp-alters-nucleotidase-activities-in-platelets-of-rats
#19
Renata S Pereira, Claudia M Bertoncheli, Stephen A Adefegha, Lívia G Castilhos, Karine L Silveira, João Felipe P Rezer, Pedro H Doleski, Fátima H Abdalla, Karen F Santos, Claudio A M Leal, Roberto C V Santos, Emerson A Casali, Cesar E J Moritz, Daniel R Stainki, Daniela B R Leal
Sepsis is a potentially lethal condition, and it is associated with platelet alterations. The present study sought to investigate the activity of ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase), E-5'-nucleotidase, and ecto-adenosine deaminase (E-ADA) in the platelets of rats that were induced with sepsis. Male Wistar rats were divided into three groups of ten animals each: a negative control group (normal; NC); a group that underwent surgical procedures (sham); and a group that underwent cecal ligation and perforation (CLP)...
September 6, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28887583/mir-608-regulating-the-expression-of-ribonucleotide-reductase-m1-and-cytidine-deaminase-is-repressed-through-induced-gemcitabine-chemoresistance-in-pancreatic-cancer-cells
#20
Azam Rajabpour, Ali Afgar, Habibollah Mahmoodzadeh, Jalal-E-Din Radfar, Farzad Rajaei, Ladan Teimoori-Toolabi
PURPOSE: Gemcitabine resistance is the main problem in pancreatic adenocarcinoma patients. Hence, we aimed to identify the correlation between expression of RRM1 and CDA as the resistance genes and their predicted targeting miR-608 in the resistant pancreatic cancer cell lines to gemcitabine. METHODS: Dual luciferase assay was performed to determine whether both RRM1 and CDA are targeted by miR-608 in 293T and pancreatic cancer cell lines. AsPC-1 and MIA PaCa-2 cell lines became gradually resistant to gemcitabine by exposing to the increasing doses of gemcitabine...
September 8, 2017: Cancer Chemotherapy and Pharmacology
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