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https://www.readbyqxmd.com/read/29320491/cdc73-suppresses-genome-instability-by-mediating-telomere-homeostasis
#1
Rahul V Nene, Christopher D Putnam, Bin-Zhong Li, Katarina G Nguyen, Anjana Srivatsan, Christopher S Campbell, Arshad Desai, Richard D Kolodner
Defects in the genes encoding the Paf1 complex can cause increased genome instability. Loss of Paf1, Cdc73, and, Ctr9, but not Rtf1 or Leo1, caused increased accumulation of gross chromosomal rearrangements (GCRs). Combining the cdc73Δ mutation with individual deletions of 43 other genes, including TEL1 and YKU80, which are involved in telomere maintenance, resulted in synergistic increases in GCR rates. Whole genome sequence analysis of GCRs indicated that there were reduced relative rates of GCRs mediated by de novo telomere additions and increased rates of translocations and inverted duplications in cdc73Δ single and double mutants...
January 10, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29302152/spinal-mucormycosis
#2
Kunal Shah, Abhay Nene
Spinal mucormycosis is a rare and fatal condition. High degree of suspicion is required for early diagnosis and treatment.
October 2017: Journal of Global Infectious Diseases
https://www.readbyqxmd.com/read/29283561/human-p450-cyp17a1-control-of-substrate-preference-by-asparagine-202
#3
Michael C Gregory, Piotr J Mak, Yogan Khatri, James R Kincaid, Stephen G Sligar
CYP17A1 is a key steroidogenic enzyme known to conduct several distinct chemical transformations on multiple substrates. In its hydroxylase activity this enzyme adds a hydroxyl group at the 17α-position of both pregnenolone and progesterone at approximately equal rates. However, the subsequent 17,20 carbon-carbon scission reaction displays variable substrate speci-ficity in the numerous CYP17A1 isozymes operating in verte-brates, manifesting as different Kd and kcat values when presented with 17α-hydroxypregnenlone (OHPREG) versus 17α-hydroxyprogesterone (OHPROG)...
December 28, 2017: Biochemistry
https://www.readbyqxmd.com/read/29258832/characterization-of-the-theileria-parva-sporozoite-proteome
#4
James Nyagwange, Edwin Tijhaar, Nicola Ternette, Fredrick Mobegi, Kyle Tretina, Joana C Silva, Roger Pelle, Vishvanath Nene
East Coast fever is a lymphoproliferative disease caused by the tick-borne protozoan parasite Theileria parva. The sporozoite stage of this parasite, harboured and released from the salivary glands of the tick Rhipicephalus appendiculatus during feeding, invades and establishes infection in bovine lymphocytes. Blocking this initial stage of invasion presents a promising vaccine strategy for control of East Coast fever and can in part be achieved by targeting the major sporozoite surface protein p67. To support research on the biology of T...
December 16, 2017: International Journal for Parasitology
https://www.readbyqxmd.com/read/29229598/cdkn2a-p16-deletion-in-head-and-neck-cancer-cells-is-associated-with-cdk2-activation-replication-stress-and-vulnerability-to-chk1-inhibition
#5
Mayur A Gadhikar, Jiexin Zhang, Li Shen, Xiayu Rao, Jing Wang, Mei Zhao, Nene N Kalu, Faye M Johnson, Lauren A Byers, John Heymach, Walter N Hittelman, Durga Udayakumar, Raj K Pandita, Tej K Pandita, Curtis R Pickering, Abena Redwood, Helen Piwnica-Worms, Katharina Schlacher, Mitchell J Frederick, Jeffrey N Myers
Checkpoint kinase inhibitors (CHKi) exhibit striking single agent activity in certain tumors, but the mechanisms accounting for hypersensitivity are poorly understood. We screened a panel of 49 established human head and neck squamous cell carcinoma (HNSCC) cell lines and report that nearly 20% are hypersensitive to CHKi monotherapy. Hypersensitive cells underwent early S-phase arrest at drug doses sufficient to inhibit greater than 90% of Chk1 activity. Reduced rate of DNA replication fork progression and chromosomal shattering were also observed, suggesting replication stress as a root causative factor in CHKi hypersensitivity...
December 11, 2017: Cancer Research
https://www.readbyqxmd.com/read/29187096/survey-of-living-organ-donors-experience-and-directions-for-process-improvement
#6
Timmy Li, M Katherine Dokus, Kristin N Kelly, Nene Ugoeke, James R Rogers, George Asham, Venkatesh Abhishek Sharma, Dominic J Cirillo, Mary K Robinson, Erika K Venniro, Jeremy G Taylor, Mark S Orloff, Scott McIntosh, Randeep Kashyap
INTRODUCTION: Understanding living organ donors' experience with donation and challenges faced during the process is necessary to guide the development of effective strategies to maximize donor benefit and increase the number of living donors. METHODS: An anonymous self-administered survey, specifically designed for this population based on key informant interviews, was mailed to 426 individuals who donated a kidney or liver at our institution. Quantitative and qualitative methods including open and axial coding were used to analyze donor responses...
September 2017: Progress in Transplantation
https://www.readbyqxmd.com/read/29170444/enhanced-strength-and-ductility-in-a-friction-stir-processing-engineered-dual-phase-high-entropy-alloy
#7
S S Nene, K Liu, M Frank, R S Mishra, R E Brennan, K C Cho, Z Li, D Raabe
The potential of high-entropy alloys (HEAs) to exhibit an extraordinary combination of properties by shifting the compositional regime from the corners towards the centers of phase diagrams has led to worldwide attention by material scientists. Here we present a strong and ductile non-equiatomic HEA obtained after friction stir processing (FSP). A transformation-induced plasticity (TRIP) assisted HEA with composition Fe50Mn30Co10Cr10 (at.%) was severely deformed by FSP and evaluated for its microstructure-mechanical property relationship...
November 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29164157/inflammatory-breast-cancer-and-warm-antibody-autoimmune-hemolytic-anemia-a-rare-paraneoplastic-syndrome
#8
Nene Ugoeke, Chidinma Onweni, Jennifer Treece, Vandana Pai, Sowminya Arikapudi, Evan Kulbacki, Kailash Bajaj
Autoimmune hemolytic anemia (AIHA) is a disease process that involves the destruction of red blood cells mediated by the humoral immune system. It can be characterized as a cold agglutinin syndrome, paroxysmal cold hemoglobinuria, and warm, mixed type, and drug-induced AIHA. Although a well-established relationship exists between the presence of AIHA and lymphoproliferative malignancy, AIHA rarely presents in association with solid malignancies. An analysis of the limited number of published cases of AIHA in association with solid malignancies performed showed that AIHA may present before the diagnosis of a solid malignancy, concurrently with the presence of a solid malignancy, or even on resolution of a solid malignancy...
October 2017: Journal of Investigative Medicine High Impact Case Reports
https://www.readbyqxmd.com/read/29156801/genomic-characterization-of-human-papillomavirus-positive-and-negative-human-squamous-cell-cancer-cell-lines
#9
Nene N Kalu, Tuhina Mazumdar, Shaohua Peng, Li Shen, Vaishnavi Sambandam, Xiayu Rao, Yuanxin Xi, Lerong Li, Yuan Qi, Frederico O Gleber-Netto, Ameeta Patel, Jing Wang, Mitchell J Frederick, Jeffrey N Myers, Curtis R Pickering, Faye M Johnson
Human cancer cell lines are the most frequently used preclinical models in the study of cancer biology and the development of therapeutics. Although anatomically diverse, human papillomavirus (HPV)-driven cancers have a common etiology and similar mutations that overlap with but are distinct from those found in HPV-negative cancers. Building on prior studies that have characterized subsets of head and neck squamous cell carcinoma (HNSCC) and cervical squamous cell carcinoma (CESC) cell lines separately, we performed genomic, viral gene expression, and viral integration analyses on 74 cell lines that include all readily-available HPV-positive (9 HNSCC, 8 CESC) and CESC (8 HPV-positive, 2 HPV-negative) cell lines and 55 HPV-negative HNSCC cell lines...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29056423/effect-of-recombinant-glutathione-s-transferase-as-vaccine-antigen-against-rhipicephalus-appendiculatus-and-rhipicephalus-sanguineus-infestation
#10
Gabriela Alves Sabadin, Luís Fernando Parizi, Irene Kiio, Marina Amaral Xavier, Renata da Silva Matos, Maria Izabel Camargo-Mathias, Naftaly Wang'ombe Githaka, Vish Nene, Itabajara da Silva Vaz
The ticks Rhipicephalus appendiculatus and Rhipicephalus sanguineus are the main vectors of Theileria parva and Babesia spp. in cattle and dogs, respectively. Due to their impact in veterinary care and industry, improved methods against R. appendiculatus and R. sanguineus parasitism are under development, including vaccines. We have previously demonstrated the induction of a cross-protective humoral response against Rhipicephalus microplus following vaccination with recombinant glutathione S-transferase from Haemaphysalis longicornis tick (rGST-Hl), suggesting that this protein could control tick infestations...
October 19, 2017: Vaccine
https://www.readbyqxmd.com/read/28958783/evaluating-genetic-drift-in-time-series-evolutionary-analysis
#11
Nuno R Nené, Ville Mustonen, Christopher J R Illingworth
The Wright-Fisher model is the most popular population model for describing the behaviour of evolutionary systems with a finite population size. Approximations have commonly been used but the model itself has rarely been tested against time-resolved genomic data. Here, we evaluate the extent to which it can be inferred as the correct model under a likelihood framework. Given genome-wide data from an evolutionary experiment, we validate the Wright-Fisher drift model as the better option for describing evolutionary trajectories in a finite population...
September 25, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28945760/appraising-the-relevance-of-dna-copy-number-loss-and-gain-in-prostate-cancer-using-whole-genome-dna-sequence-data
#12
Niedzica Camacho, Peter Van Loo, Sandra Edwards, Jonathan D Kay, Lucy Matthews, Kerstin Haase, Jeremy Clark, Nening Dennis, Sarah Thomas, Barbara Kremeyer, Jorge Zamora, Adam P Butler, Gunes Gundem, Sue Merson, Hayley Luxton, Steve Hawkins, Mohammed Ghori, Luke Marsden, Adam Lambert, Katalin Karaszi, Gill Pelvender, Charlie E Massie, Zsofia Kote-Jarai, Keiran Raine, David Jones, William J Howat, Steven Hazell, Naomi Livni, Cyril Fisher, Christopher Ogden, Pardeep Kumar, Alan Thompson, David Nicol, Erik Mayer, Tim Dudderidge, Yongwei Yu, Hongwei Zhang, Nimish C Shah, Vincent J Gnanapragasam, William Isaacs, Tapio Visakorpi, Freddie Hamdy, Dan Berney, Clare Verrill, Anne Y Warren, David C Wedge, Andrew G Lynch, Christopher S Foster, Yong Jie Lu, G Steven Bova, Hayley C Whitaker, Ultan McDermott, David E Neal, Rosalind Eeles, Colin S Cooper, Daniel S Brewer
A variety of models have been proposed to explain regions of recurrent somatic copy number alteration (SCNA) in human cancer. Our study employs Whole Genome DNA Sequence (WGS) data from tumor samples (n = 103) to comprehensively assess the role of the Knudson two hit genetic model in SCNA generation in prostate cancer. 64 recurrent regions of loss and gain were detected, of which 28 were novel, including regions of loss with more than 15% frequency at Chr4p15.2-p15.1 (15.53%), Chr6q27 (16.50%) and Chr18q12...
September 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28935864/high-levels-of-ammonia-do-not-raise-fine-particle-ph-sufficiently-to-yield-nitrogen-oxide-dominated-sulfate-production
#13
Hongyu Guo, Rodney J Weber, Athanasios Nenes
High levels of ammonia (NH3) have been suggested to elevate ambient particle pH levels to near neutral acidity (pH = 7), a condition that promotes rapid SO2 oxidation by NO2 to form aerosol sulfate concentration consistent with "London fog" levels. This postulation is tested using aerosol data from representative sites around the world to conduct a thorough thermodynamic analysis of aerosol pH and its sensitivity to NH3 levels. We find that particle pH, regardless of ammonia levels, is always acidic even for the unusually high NH3 levels found in Beijing (pH = 4...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28873442/use-of-a-novel-antigen-expressing-system-to-study-the-salmonella-enterica-serovar-typhi-protein-recognition-by-t-cells
#14
Rosângela Salerno-Gonçalves, Hervé Tettelin, David Lou, Stephanie Steiner, Tasmia Rezwanul, Qin Guo, William D Picking, Vishvanath Nene, Marcelo B Sztein
Salmonella enterica serovar Typhi (S. Typhi), the causative agent of the typhoid fever, is a pathogen of great public health importance. Typhoid vaccines have the potential to be cost-effective measures towards combating this disease, yet the antigens triggering host protective immune responses are largely unknown. Given the key role of cellular-mediated immunity in S. Typhi protection, it is crucial to identify S. Typhi proteins involved in T-cell responses. Here, cells from individuals immunized with Ty21a typhoid vaccine were collected before and after immunization and used as effectors...
September 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28790110/replication-stress-leading-to-apoptosis-within-the-s-phase-contributes-to-synergism-between-vorinostat-and-azd1775-in-hnscc-harboring-high-risk-tp53-mutation
#15
Noriaki Tanaka, Ameeta A Patel, Lin Tang, Natalie L Silver, Antje Lindemann, Hideaki Takahashi, Roman Jaksik, Xiayu Rao, Nene N Kalu, Tseng-Cheng Chen, Jiping Wang, Mitchell J Frederick, Faye Johnson, Frederico O Gleber-Netto, Siqing Fu, Marek Kimmel, Jing Wang, Walter N Hittelman, Curtis R Pickering, Jeffrey N Myers, Abdullah A Osman
Purpose: The cure rate for patients with advanced head and neck squamous cell carcinoma (HNSCC) remains poor due to resistance to standard therapy primarily consisting of chemoradiation. As mutation of TP53 in HNSCC occurs in 60% to 80% of non-HPV-associated cases and is in turn associated with resistance to these treatments, more effective therapies are needed. In this study, we evaluated the efficacy of a regimen combining vorinostat and AZD1775 in HNSCC cells with a variety of p53 mutations.Experimental Design: Clonogenic survival assays and an orthotopic mouse model of oral cancer were used to examine the in vitro and in vivo sensitivity of high-risk mutant p53 HNSCC cell lines to vorinostat in combination with AZD1775...
August 8, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28781391/microphysical-explanation-of-the-rh-dependent-water-affinity-of-biogenic-organic-aerosol-and-its-importance-for-climate
#16
N Rastak, A Pajunoja, J C Acosta Navarro, J Ma, M Song, D G Partridge, A Kirkevåg, Y Leong, W W Hu, N F Taylor, A Lambe, K Cerully, A Bougiatioti, P Liu, R Krejci, T Petäjä, C Percival, P Davidovits, D R Worsnop, A M L Ekman, A Nenes, S Martin, J L Jimenez, D R Collins, D O Topping, A K Bertram, A Zuend, A Virtanen, I Riipinen
A large fraction of atmospheric organic aerosol (OA) originates from natural emissions that are oxidized in the atmosphere to form secondary organic aerosol (SOA). Isoprene (IP) and monoterpenes (MT) are the most important precursors of SOA originating from forests. The climate impacts from OA are currently estimated through parameterizations of water uptake that drastically simplify the complexity of OA. We combine laboratory experiments, thermodynamic modeling, field observations, and climate modeling to (1) explain the molecular mechanisms behind RH-dependent SOA water-uptake with solubility and phase separation; (2) show that laboratory data on IP- and MT-SOA hygroscopicity are representative of ambient data with corresponding OA source profiles; and (3) demonstrate the sensitivity of the modeled aerosol climate effect to assumed OA water affinity...
May 28, 2017: Geophysical Research Letters
https://www.readbyqxmd.com/read/28761521/safety-and-efficacy-of-spinal-loop-rectangle-and-sublaminar-wires-for-osteoporotic-vertebral-compression-fracture-fixation
#17
Sanganagouda Shivanagouda Patil, Shekhar Yashwant Bhojaraj, Abhay Madhusudan Nene
BACKGROUND: Natural history of osteoporotic vertebral compression fractures (OVCFs), that is, collapse, loads the rigid pedicle screw rod construct in the absence of anterior column reconstruction, often leading to implant back outs. Semi rigid spinal loop rectangle and sublaminar wire construct allows controlled axial collapse and does not require anterior column reconstruction. MATERIALS AND METHODS: This is a retrospective study of 50 consecutive patients of OVCFs...
July 2017: Asian Journal of Neurosurgery
https://www.readbyqxmd.com/read/28760483/preliminary-efficacy-investigations-of-oral-fipronil-against-anopheles-arabiensis-when-administered-to-zebu-cattle-bos-indicus-under-field-conditions
#18
Richard M Poché, Naftaly Githaka, Frans van Gool, Rebekah C Kading, Daniel Hartman, Larisa Polyakova, Edward Okoth Abworo, Vishvanath Nene, Saul Lozano-Fuentes
Globally, malaria remains one of the most important vector-borne diseases despite the extensive use of vector control, including indoor residual spraying (IRS) and insecticide-treated nets (ITNs). These control methods target endophagic vectors, whereas some malaria vectors, such as Anopheles arabiensis, preferentially feed outdoors on cattle, making it a complicated vector to control using conventional strategies. Our study evaluated whether treating cattle with a capsule containing the active ingredient (AI) fipronil could reduce vector density and sporozoite rates, and alter blood feeding behavior, when applied in a small-scale field study...
December 2017: Acta Tropica
https://www.readbyqxmd.com/read/28753852/desnt-a-poor-prognosis-category-of-human-prostate-cancer
#19
Bogdan-Alexandru Luca, Daniel S Brewer, Dylan R Edwards, Sandra Edwards, Hayley C Whitaker, Sue Merson, Nening Dennis, Rosalin A Cooper, Steven Hazell, Anne Y Warren, Rosalind Eeles, Andy G Lynch, Helen Ross-Adams, Alastair D Lamb, David E Neal, Krishna Sethia, Robert D Mills, Richard Y Ball, Helen Curley, Jeremy Clark, Vincent Moulton, Colin S Cooper
BACKGROUND: A critical problem in the clinical management of prostate cancer is that it is highly heterogeneous. Accurate prediction of individual cancer behaviour is therefore not achievable at the time of diagnosis leading to substantial overtreatment. It remains an enigma that, in contrast to breast cancer, unsupervised analyses of global expression profiles have not currently defined robust categories of prostate cancer with distinct clinical outcomes. OBJECTIVE: To devise a novel classification framework for human prostate cancer based on unsupervised mathematical approaches...
March 6, 2017: European Urology Focus
https://www.readbyqxmd.com/read/28730066/-these-are-not-luxuries-it-is-essential-for-access-to-life-disability-related-out-of-pocket-costs-as-a-driver-of-economic-vulnerability-in-south-africa
#20
Jill Hanass-Hancock, Siphumelele Nene, Nicola Deghaye, Simmi Pillay
BACKGROUND: With the dawn of the new sustainable development goals, we face not only a world that has seen great successes in alleviating poverty but also a world that has left some groups, such as persons with disabilities, behind. Middle-income countries (MICs) are home to a growing number of persons with disabilities. As these countries strive to achieve the new goals, we have ample opportunity to include persons with disabilities in the emerging poverty alleviation strategies. However, a lack of data and research on the linkages between economic vulnerability and disability in MICs hampers our understanding of the factors increasing economic vulnerability in people with disabilities...
2017: African Journal of Disability
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