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https://www.readbyqxmd.com/read/29351274/dna-polymerase-iv-primarily-operates-outside-of-dna-replication-forks-in-escherichia-coli
#1
Sarah S Henrikus, Elizabeth A Wood, John P McDonald, Michael M Cox, Roger Woodgate, Myron F Goodman, Antoine M van Oijen, Andrew Robinson
In Escherichia coli, damage to the chromosomal DNA induces the SOS response, setting in motion a series of different DNA repair and damage tolerance pathways. DNA polymerase IV (pol IV) is one of three specialised DNA polymerases called into action during the SOS response to help cells tolerate certain types of DNA damage. The canonical view in the field is that pol IV primarily acts at replisomes that have stalled on the damaged DNA template. However, the results of several studies indicate that pol IV also acts on other substrates, including single-stranded DNA gaps left behind replisomes that re-initiate replication downstream of a lesion, stalled transcription complexes and recombination intermediates...
January 19, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29345908/a-small-molecule-inhibitor-of-human-dna-polymerase-eta-potentiates-the-effects-of-cisplatin-in-tumor-cells
#2
Maroof K Zafar, Leena Maddukuri, Amit Ketkar, Narsimha Penthala, Megan R Reed, Sarah D Eddy, Peter A Crooks, Robert L Eoff
Translesion DNA synthesis (TLS) performed by human DNA polymerase eta (hpol η) allows tolerance of damage from cis-diamminedichloroplatinum(II) (CDDP or cisplatin). We have developed hpol η inhibitors derived from N-aryl-substituted indole barbituric acid (IBA), indole thiobarbituric acid (ITBA), and indole quinuclidine scaffolds and identified 5-((5-chloro-1-(naphthalen-2-ylmethyl)-1H-indol-3-yl)methylene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione (PNR-7-02), an ITBA derivative that inhibited hpol η activity with an IC50 value of 8 μM and exhibited five- to ten-fold specificity for hpol η over replicative pols...
January 18, 2018: Biochemistry
https://www.readbyqxmd.com/read/29341833/immune-modified-response-evaluation-criteria-in-solid-tumors-imrecist-refining-guidelines-to-assess-the-clinical-benefit-of-cancer-immunotherapy
#3
F Stephen Hodi, Marcus Ballinger, Benjamin Lyons, Jean-Charles Soria, Mizuki Nishino, Josep Tabernero, Thomas Powles, David Smith, Axel Hoos, Chris McKenna, Ulrich Beyer, Ina Rhee, Gregg Fine, Nathan Winslow, Daniel S Chen, Jedd D Wolchok
Purpose Treating solid tumors with cancer immunotherapy (CIT) can result in unconventional responses and overall survival (OS) benefits that are not adequately captured by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. We describe immune-modified RECIST (imRECIST) criteria, designed to better capture CIT responses. Patients and Methods Atezolizumab data from clinical trials in non-small-cell lung cancer, metastatic urothelial carcinoma, renal cell carcinoma, and melanoma were evaluated. Modifications to imRECIST versus RECIST v1...
January 17, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29337922/underdetermined-wideband-doa-estimation-for-off-grid-sources-with-coprime-array-using-sparse-bayesian-learning
#4
Yanhua Qin, Yumin Liu, Jianyi Liu, Zhongyuan Yu
Sparse Bayesian learning (SBL) is applied to the coprime array for underdetermined wideband direction of arrival (DOA) estimation. Using the augmented covariance matrix, the coprime array can achieve a higher number of degrees of freedom (DOFs) to resolve more sources than the number of physical sensors. The sparse-based DOA estimation can deteriorate the detection and estimation performance because the sources may be off the search grid no matter how fine the grid is. This dictionary mismatch problem can be well resolved by the SBL using fixed point updates...
January 16, 2018: Sensors
https://www.readbyqxmd.com/read/29335378/comparison-of-telomere-length-measurement-methods
#5
REVIEW
Tsung-Po Lai, Woodring E Wright, Jerry W Shay
The strengths and limitations of the major methods developed to measure telomere lengths (TLs) in cells and tissues are presented in this review. These include Q-PCR (Quantitative Polymerase Chain Reaction), TRF (Terminal Restriction Fragment) analysis, a variety of Q-FISH (Quantitative Fluorescence In Situ Hybridization) methods, STELA (Single TElomere Length Analysis) and TeSLA (Telomere Shortest Length Assay). For each method, we will cover information about validation studies, including reproducibility in independent laboratories, accuracy, reliability and sensitivity for measuring not only the average but also the shortest telomeres...
March 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29330301/genetic-control-of-predominantly-error-free-replication-through-an-acrolein-derived-minor-groove-dna-adduct
#6
Jung-Hoon Yoon, Richard P Hodge, Linda C Hackfeld, Jeseong Park, Jayati Roy Choudhury, Satya Prakash, Louise Prakash
Acrolein, an α, β unsaturated aldehyde, is generated in vivo as the end product of lipid peroxidation and from metabolic oxidation of polyamines, and it is an ubiquitous environmental pollutant. The reaction of acrolein with the N2 of guanine in DNA leads to the formation of γ-hydroxy-1-N2-propano-2' deoxyguanosine (γ-HOPdG) which can exist in DNA in a ring-closed or a ring-opened form. Here we identify the translesion synthesis (TLS) DNA polymerases (Pols) which conduct replication through the permanently ring-opened reduced form of γ-HOPdG [(r) γ-HOPdG] and show that replication through this adduct is mediated via Rev1/Polη, Polι/Polκ, and Polθ dependent pathways, respectively...
January 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29322223/is-the-timed-loaded-standing-test-a-valid-measure-of-back-muscle-endurance-in-people-with-vertebral-osteoporosis
#7
M Newman, R Newman, T Hughes, K Vadher, K L Barker
Timed loaded standing (TLS) is a suggested measure of back muscle endurance for people with vertebral osteoporosis. Surface electromyography revealed back muscles work harder and fatigue during TLS. The test end-point and total time were associated with back fatigue. The findings help demonstrate the concurrent validity of the TLS test. INTRODUCTION: The TLS test is suggested as a measure of back muscle endurance for patients with vertebral osteoporosis. However, to date, no study has demonstrated that TLS does measure back extensor or erector spinae (ES) muscle endurance...
January 10, 2018: Osteoporosis International
https://www.readbyqxmd.com/read/29321870/contrasting-genetic-metrics-and-patterns-among-naturalized-rainbow-trout-oncorhynchus-mykiss-in-two-patagonian-lakes-differentially-impacted-by-trout-aquaculture
#8
Cristian B Canales-Aguirre, Lisa W Seeb, James E Seeb, María I Cádiz, Selim S Musleh, Ivan Arismendi, Gonzalo Gajardo, Ricardo Galleguillos, Daniel Gomez-Uchida
Different pathways of propagation and dispersal of non-native species into new environments may have contrasting demographic and genetic impacts on established populations. Repeated introductions of rainbow trout (Oncorhynchus mykiss) to Chile in South America, initially through stocking and later through aquaculture escapes, provide a unique setting to contrast these two pathways. Using a panel of single nucleotide polymorphisms, we found contrasting genetic metrics and patterns among naturalized trout in Lake Llanquihue, Chile's largest producer of salmonid smolts for nearly 50 years, and Lake Todos Los Santos (TLS), a reference lake where aquaculture has been prohibited by law...
January 2018: Ecology and Evolution
https://www.readbyqxmd.com/read/29311385/immune-cell-infiltration-and-tertiary-lymphoid-structures-as-determinants-of-antitumor-immunity
#9
REVIEW
Victor H Engelhard, Anthony B Rodriguez, Ileana S Mauldin, Amber N Woods, J David Peske, Craig L Slingluff
Limited representation of intratumoral immune cells is a major barrier to tumor control. However, simply enhancing immune responses in tumor-draining lymph nodes or through adoptive transfer may not overcome the limited ability of tumor vasculature to support effector infiltration. An alternative is to promote a sustained immune response intratumorally. This idea has gained traction with the observation that many tumors are associated with tertiary lymphoid structures (TLS), which organizationally resemble lymph nodes...
January 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29306013/rad18-promotes-the-migration-and-invasion-of-esophageal-squamous-cell-cancer-via-the-jnk-mmps-pathway
#10
Shitao Zou, Jianlong Yang, Jiaming Guo, Ye Su, Chao He, Jinchang Wu, Lan Yu, Wei-Qun Ding, Jundong Zhou
As a key regulator of DNA translesion synthesis (TLS) pathway, RAD18 is error-prone and contributes to the accumulation of DNA mutations. We have recently shown that RAD18 is overexpressed in human esophageal squamous cell cancer (ESCC) and acts to promote ESCC progression. The current study aims to understand the molecular mechanism by which RAD18 enhances the invasiveness and metastasis of ESCC cells. We found that RAD18 expression is markedly higher in high T stage ESCCs compared to low T stage groups. Kaplan-Meier analysis showed an inverse correlation between RAD18 expression and patient prognosis...
January 3, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29301327/family-a-and-b-dna-polymerases-in-cancer-opportunities-for-therapeutic-interventions
#11
REVIEW
Vinit Shanbhag, Shrikesh Sachdev, Jacqueline A Flores, Mukund J Modak, Kamalendra Singh
DNA polymerases are essential for genome replication, DNA repair and translesion DNA synthesis (TLS). Broadly, these enzymes belong to two groups: replicative and non-replicative DNA polymerases. A considerable body of data suggests that both groups of DNA polymerases are associated with cancer. Many mutations in cancer cells are either the result of error-prone DNA synthesis by non-replicative polymerases, or the inability of replicative DNA polymerases to proofread mismatched nucleotides due to mutations in 3'-5' exonuclease activity...
January 2, 2018: Biology
https://www.readbyqxmd.com/read/29290749/rasburicase-induced-hemolytic-anemia-in-an-adolescent-with-unknown-glucose-6-phosphate-dehydrogenase-deficiency
#12
Manzilat Akande, Anthony N Audino, Joseph D Tobias
Rasburicase, used in the prevention and treatment of tumor lysis syndrome (TLS), may cause hemolytic anemia and methemoglobinemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Although routine screening for G6PD deficiency has been recommended, given the turnaround time for test results and the urgency to treat TLS, such screening may not be feasible. We report a case of rasburicase-induced hemolytic anemia without methemoglobinemia in an adolescent with T-cell lymphoblastic lymphoma, TLS, and previously unrecognized G6PD deficiency...
November 2017: Journal of Pediatric Pharmacology and Therapeutics: JPPT: the Official Journal of PPAG
https://www.readbyqxmd.com/read/29281621/the-translesion-dna-polymerases-pol-%C3%AE-and-rev1-are-activated-independently-of-pcna-ubiquitination-upon-uv-radiation-in-mutants-of-dna-polymerase-%C3%AE
#13
Carine Tellier-Lebegue, Eléa Dizet, Emilie Ma, Xavier Veaute, Eric Coïc, Jean-Baptiste Charbonnier, Laurent Maloisel
Replicative DNA polymerases cannot insert efficiently nucleotides at sites of base lesions. This function is taken over by specialized translesion DNA synthesis (TLS) polymerases to allow DNA replication completion in the presence of DNA damage. In eukaryotes, Rad6- and Rad18-mediated PCNA ubiquitination at lysine 164 promotes recruitment of TLS polymerases, allowing cells to efficiently cope with DNA damage. However, several studies showed that TLS polymerases can be recruited also in the absence of PCNA ubiquitination...
December 27, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29279354/germinal-centers-determine-the-prognostic-relevance-of-tertiary-lymphoid-structures-and-are-impaired-by-corticosteroids-in-lung-squamous-cell-carcinoma
#14
Karina Silina, Alex Soltermann, Farkhondeh Movahedian Attar, Ruben Casanova, Zina M Uckeley, Helen Thut, Muriel Wandres, Sergejs Isajevs, Phil F Cheng, Alessandra Curioni Fontecedro, Periklis Foukas, Mitchell P Levesque, Holger Moch, Aija Linē, Maries van den Broek
In solid tumors, the presence of lymph node-like structures called tertiary lymphoid structures (TLS) is associated with improved patient survival. However, little is known about how TLS form in cancer, how their function affects survival, and whether they are affected by cancer therapy. In this study, we used multi-spectral microscopy, quantitative pathology and gene expression profiling to analyze TLS formation in human lung squamous cell carcinoma (LSCC) and in an experimental model of lung TLS induction...
December 26, 2017: Cancer Research
https://www.readbyqxmd.com/read/29273933/neck-contouring-without-rhytidectomy-in-the-presence-of-excess-skin
#15
Ji H Son, Christina Pindar, Kristopher Katira, Bahman Guyuron
BACKGROUND: Patients with severe neck skin laxity due to excess submental adipose tissue have required either standard rhytidectomy or direct excision of neck skin with Z-plasty and submental lipectomy. Our recent experiences with four patients who declined cervicofacial rhytidectomy demonstrate that submental lipectomy and platysmarrhaphy appear to obtain sufficient improvement. METHODS: The submental area, submandibular area, and lateral neck are injected with local anesthetic...
December 22, 2017: Aesthetic Plastic Surgery
https://www.readbyqxmd.com/read/29247828/hypersensitivity-of-mouse-embryonic-fibroblast-cells-defective-for-dna-polymerases-%C3%AE-%C3%AE-and-%C3%AE%C2%BA-to-various-genotoxic-compounds-its-potential-for-application-in-chemical-genotoxic-screening
#16
Jun-Ichi Akagi, Masayuki Yokoi, Young-Man Cho, Takeshi Toyoda, Haruo Ohmori, Fumio Hanaoka, Kumiko Ogawa
Genotoxic agents cause modifications of genomic DNA, such as alkylation, oxidation, bulky adduct formation, and strand breaks, which potentially induce mutations and changes to the structure or number of genes. Majority of point mutations are generated during error-prone bypass of modified nucleotides (translesion DNA synthesis, TLS); however, when TLS fails, replication forks stalled at lesions eventually result in more lethal effects, formation of double-stranded breaks (DSBs). Here we compared sensitivities to various compounds among mouse embryonic fibroblasts derived from wild-type and knock-out mice lacking one of the three Y-family TLS DNA polymerases (Polη, Polι, and Polκ) or all of them (TKO)...
November 26, 2017: DNA Repair
https://www.readbyqxmd.com/read/29246407/can-ct-imaging-of-the-chest-abdomen-and-pelvis-identify-all-vertebral-injuries-of-the-thoracolumbar-spine-without-dedicated-reformatting
#17
Jonathan B Imran, Tarik D Madni, Jeffrey H Pruitt, Canon Cornelius, Madhu Subramanian, Audra T Clark, Ali A Mokdad, Paul Rizk, Joseph P Minei, Michael W Cripps, Alexander L Eastman
BACKGROUND: The main objective of this study was to compare detection rates of clinically significant thoracolumbar spine (TLS) fracture between computed tomography (CT) imaging of the chest, abdomen, and spine (CT CAP) and CT for the thoracolumbar spine (CT TL). METHODS: We retrospectively identified patients at our institution with a TLS fracture over a two-year period that had both CT CAP and reformatted CT TL imaging. The sensitivity of CT CAP to identify fracture was calculated for each fracture type...
December 5, 2017: American Journal of Surgery
https://www.readbyqxmd.com/read/29230244/tumor-lysis-syndrome-in-patients-with-hematological-malignancies
#18
REVIEW
Yohannes Belay, Ketsela Yirdaw, Bamlaku Enawgaw
Tumor lysis syndrome is a metabolic complication that may follow the initiation of cancer therapy. It commonly occurs in hematological malignant patients particularly non-Hodgkin's lymphoma and acute leukemia due to chemotherapy or spontaneously. It is characterized by a biochemical abnormality such as hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia and its clinical outcome is directly related to these biochemical abnormalities. Prevention and treatment of tumor lysis syndrome depend on immediate recognition of patients at risk...
2017: Journal of Oncology
https://www.readbyqxmd.com/read/29225880/tumor-lysis-syndrome-with-massive-hyperphosphatemia-and-hyperuricemia
#19
Abhilash Koratala
Tumor lysis syndrome (TLS) occurs when tumor cells release their contents into the bloodstream, typically in response to chemotherapy, leading to the characteristic findings of hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia, and acute kidney injury. Twinkle artifacts on renal ultrasound may indicate calcium phosphate deposits in such patients.
December 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/29208956/pol%C3%AE-o-glcnacylation-governs-genome-integrity-during-translesion-dna-synthesis
#20
Xiaolu Ma, Hongmei Liu, Jing Li, Yihao Wang, Yue-He Ding, Hongyan Shen, Yeran Yang, Chenyi Sun, Min Huang, Yingfeng Tu, Yang Liu, Yongliang Zhao, Meng-Qiu Dong, Ping Xu, Tie-Shan Tang, Caixia Guo
DNA polymerase η (Polη) facilitates translesion DNA synthesis (TLS) across ultraviolet (UV) irradiation- and cisplatin-induced DNA lesions implicated in skin carcinogenesis and chemoresistant phenotype formation, respectively. However, whether post-translational modifications of Polη are involved in these processes remains largely unknown. Here, we reported that human Polη undergoes O-GlcNAcylation at threonine 457 by O-GlcNAc transferase upon DNA damage. Abrogation of this modification results in a reduced level of CRL4CDT2-dependent Polη polyubiquitination at lysine 462, a delayed p97-dependent removal of Polη from replication forks, and significantly enhanced UV-induced mutagenesis even though Polη focus formation and its efficacy to bypass across cyclobutane pyrimidine dimers after UV irradiation are not affected...
December 5, 2017: Nature Communications
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