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Shareen H Doak, Maria Dusinska
This Mutagenesis special issue is on the topic of nanogenotoxicology. It unites a collection of reports that provide insight into: (i) the properties of engineered nanomaterials (ENMs) that contribute to genotoxicity, (ii) the genotoxic mechanisms associated with DNA damage observed in both in vitro and in vivo tests and (iii) the future test systems that will provide more accurate prediction of ENM genotoxicity to support regulatory hazard assessment frameworks. The contributions within therefore provide collective oversight of our current understanding, coupled to future perspectives aimed at overcoming technical hurdles and describing novel analytical methods to further advance the field...
January 2017: Mutagenesis
Jatin R Verma, Benjamin J Rees, Eleanor C Wilde, Catherine A Thornton, Gareth J S Jenkins, Shareen H Doak, George E Johnson
The use of manual microscopy for the scoring of chromosome damage in the in vitro micronucleus assay is often associated with user subjectivity. This level of subjectivity can be reduced by using automated platforms, which have added value of faster with high-throughput and multi-endpoint capabilities. However, there is a need to assess the reproducibility and sensitivity of these automated platforms compared with the gold standard of the manual scoring. The automated flow cytometry-based MicroFlow(®) and image analysis-based Metafer™ were used for dose response analyses in human lymphoblastoid TK6 cells exposed to the model clastogen, methyl methanesulfonate (MMS), aneugen, carbendazim, and the weak genotoxic carcinogen, ochratoxin A (OTA)...
December 10, 2016: Archives of Toxicology
Daniel J Hoffman, Maiza Campos Ponce, Carla R Taddei, Colleen M Doak
The prevalence of undernutrition has decreased in many parts of the developing world, but increased urbanization in many countries, combined with broad changes in diet, have provided a backdrop against which many challenges to human growth continue. Moreover, a number of studies now suggest that poor diet and growth in early childhood are risk factors for chronic diseases in adulthood. However, such problems appear to continue despite an improvement in food security or the delivery of nutritional supplements to children living in impoverished areas of urban centers...
December 7, 2016: Annals of Human Biology
Bradley C Doak, Jan Kihlberg
No abstract text is available yet for this article.
December 8, 2016: Expert Opinion on Drug Discovery
Stephen J Evans, Martin J D Clift, Neenu Singh, Jefferson de Oliveira Mallia, Michael Burgum, John W Wills, Thomas S Wilkinson, Gareth J S Jenkins, Shareen H Doak
With the need to understand the potential biological impact of the plethora of nanoparticles (NPs) being manufactured for a wide range of potential human applications, due to their inevitable human exposure, research activities in the field of NP toxicology has grown exponentially over the last decade. Whilst such increased research efforts have elucidated an increasingly significant knowledge base pertaining to the potential human health hazard posed by NPs, understanding regarding the possibility for NPs to elicit genotoxicity is limited...
January 2017: Mutagenesis
Biswaranjan Mohanty, Martin L Williams, Bradley C Doak, Mansha Vazirani, Olga Ilyichova, Geqing Wang, Wolfgang Bermel, Jamie S Simpson, David K Chalmers, Glenn F King, Mehdi Mobli, Martin J Scanlon
We describe a general approach to determine the binding pose of small molecules in weakly bound protein-ligand complexes by deriving distance constraints between the ligand and methyl groups from all methyl-containing residues of the protein. We demonstrate that using a single sample, which can be prepared without the use of expensive precursors, it is possible to generate high-resolution data rapidly and obtain the resonance assignments of Ile, Leu, Val, Ala and Thr methyl groups using triple resonance scalar correlation data...
October 24, 2016: Journal of Biomolecular NMR
Karen Peynshaert, Stefaan J Soenen, Bella B Manshian, Shareen H Doak, Kevin Braeckmans, Stefaan C De Smedt, Katrien Remaut
: In the last decade the interest in autophagy got an incredible boost and the phenomenon quickly turned into an extensive research field. Interestingly, dysfunction of this cytoplasmic clearance system has been proposed to lie at the root of multiple diseases including cancer. We therefore consider it crucial from a toxicological point of view to investigate if nanomaterials that are developed for biomedical applications interfere with this cellular process. Here, we study the highly promising 'gradient alloyed' Quantum Dots (QDs) that differ from conventional ones by their gradient core composition which allows for better fluorescent properties...
October 17, 2016: Acta Biomaterialia
Dorothy Kammerer-Doak, Kamil Svabik, Tony Bazi
INTRODUCTION AND HYPOTHESIS: Members of the International Urogynecological Association (IUGA) come from different geographic locations and practice settings. A member survey regarding practice patterns provides valuable information for practitioners and researchers alike, and allows the IUGA to discover areas to focus on education and information dissemination. METHODS: A questionnaire was developed by the IUGA Research and Development committee and distributed electronically to IUGA surgeons...
October 17, 2016: International Urogynecology Journal
Björn Over, Pär Matsson, Christian Tyrchan, Per Artursson, Bradley C Doak, Michael A Foley, Constanze Hilgendorf, Stephen E Johnston, Maurice D Lee, Richard J Lewis, Patrick McCarren, Giovanni Muncipinto, Ulf Norinder, Matthew W D Perry, Jeremy R Duvall, Jan Kihlberg
Macrocycles are of increasing interest as chemical probes and drugs for intractable targets like protein-protein interactions, but the determinants of their cell permeability and oral absorption are poorly understood. To enable rational design of cell-permeable macrocycles, we generated an extensive data set under consistent experimental conditions for more than 200 non-peptidic, de novo-designed macrocycles from the Broad Institute's diversity-oriented screening collection. This revealed how specific functional groups, substituents and molecular properties impact cell permeability...
October 17, 2016: Nature Chemical Biology
Leanne Stannard, Shareen H Doak, Ann Doherty, Gareth J Jenkins
Human beings are exposed to carcinogens through air, water, food and tobacco smoke. Nickel chloride (NiCl2 ) is a toxic and carcinogenic environmental and occupational pollutant, which was previously classified as a non-genotoxic carcinogen and thought to not directly alter the DNA. Non-genotoxic carcinogens such as NiCl2 are difficult to detect in vitro; hence, a heavy reliance on animal studies exists. NiCl2 has previously been classified as a non-genotoxic carcinogen (NGTC); however, after studying the effect of NiCl2 on many mechanistic end-points, it has become clear that NiCl2 behaves more like a genotoxic carcinogen...
October 17, 2016: Basic & Clinical Pharmacology & Toxicology
Franziska Szokoli, Michele Castelli, Elena Sabaneyeva, Martina Schrallhammer, Sascha Krenek, Thomas G Doak, Thomas U Berendonk, Giulio Petroni
In the past 10 years, the number of endosymbionts described within the bacterial order Rickettsiales has constantly grown. Since 2006, 18 novel Rickettsiales genera inhabiting protists, such as ciliates and amoebae, have been described. In this work, we characterize two novel bacterial endosymbionts from Paramecium collected near Bloomington, IN. Both endosymbiotic species inhabit the cytoplasm of the same host. The Gram-negative bacterium "Candidatus Bealeia paramacronuclearis" occurs in clumps and is frequently associated with the host macronucleus...
December 15, 2016: Applied and Environmental Microbiology
Li Lu, William J Doak, Jeffrey W Schertzer, Paul R Chiarot
Synthetic lipid vesicles have served as important model systems to study cellular membrane biology. Research has shown that the mechanical properties of bilayer membranes significantly affects their biological behavior. The properties of a lipid bilayer are governed by lipid acyl chain length, headgroup type, and the presence of membrane proteins. However, few studies have explored how membrane architecture, in particular trans-bilayer lipid asymmetry, influences membrane mechanical properties. In this study, we investigated the effects of lipid bilayer architecture (i...
September 13, 2016: Soft Matter
Ume-Kulsoom Shah, Anna L Seager, Paul Fowler, Shareen H Doak, George E Johnson, Sharon J Scott, Andrew D Scott, Gareth J S Jenkins
Benzo[a]pyrene (B[a]P) is a known genotoxin and carcinogen, yet its genotoxic response at low level exposure has not been determined. This study was conducted to examine the interplay of dose and metabolic capacity on genotoxicity of B[a]P. Investigating and better understanding the biological significance of low level chemical exposures will help improve human health risk assessments. The genotoxic and mutagenic effects of B[a]P were investigated using human cell lines (AHH-1, MCL-5, TK6 and HepG2) with differential expression of the CYP450 enzymes CYP1A1, 1B1 and1A2 involved in B[a]P metabolism...
September 15, 2016: Mutation Research. Genetic Toxicology and Environmental Mutagenesis
John W Wills, Nicole Hondow, Adam D Thomas, Katherine E Chapman, David Fish, Thierry G Maffeis, Mark W Penny, Richard A Brown, Gareth J S Jenkins, Andy P Brown, Paul A White, Shareen H Doak
BACKGROUND: The rapid production and incorporation of engineered nanomaterials into consumer products alongside research suggesting nanomaterials can cause cell death and DNA damage (genotoxicity) makes in vitro assays desirable for nanosafety screening. However, conflicting outcomes are often observed when in vitro and in vivo study results are compared, suggesting more physiologically representative in vitro models are required to minimise reliance on animal testing. METHOD: BASF Levasil® silica nanoparticles (16 and 85 nm) were used to adapt the 3D reconstructed skin micronucleus (RSMN) assay for nanomaterials administered topically or into the growth medium...
September 9, 2016: Particle and Fibre Toxicology
Yan Li, Shareen H Doak, Jian Yan, David H Chen, Min Zhou, Roberta A Mittelstaedt, Ying Chen, Chun Li, Tao Chen
A number of in vitro methodologies have been used to assess the genotoxicity of different nanomaterials, including titanium dioxide nanoparticles (TiO2 NPs) and silver nanoparticles (AgNPs). The in vitro micronucleus assay is one of the most commonly used test methods for genotoxicity evaluation of nanomaterials. However, due to the novel features of nanomaterials, such as high adsorption capacity and fluorescence properties, there are unexpected interactions with experimental components and detection systems...
January 2017: Mutagenesis
Bryant C Nelson, Christa W Wright, Yuko Ibuki, Maria Moreno-Villanueva, Hanna L Karlsson, Giel Hendriks, Christopher M Sims, Neenu Singh, Shareen H Doak
The rapid development of the engineered nanomaterial (ENM) manufacturing industry has accelerated the incorporation of ENMs into a wide variety of consumer products across the globe. Unintentionally or not, some of these ENMs may be introduced into the environment or come into contact with humans or other organisms resulting in unexpected biological effects. It is thus prudent to have rapid and robust analytical metrology in place that can be used to critically assess and/or predict the cytotoxicity, as well as the potential genotoxicity of these ENMs...
January 2017: Mutagenesis
Seokmin Jeon, Peter W Doak, Bobby G Sumpter, Panchapakesan Ganesh, Petro Maksymovych
Bulk molecular ionic solids exhibit fascinating electronic properties, including electron correlations, phase transitions, and superconducting ground states. In contrast, few of these phenomena have been observed in low-dimensional molecular structures, including thin films, nanoparticles, and molecular blends, not in the least because most of such structures have been composed of nearly closed-shell molecules. It is therefore desirable to develop low-dimensional ionic molecular structures that can capture potential applications...
August 23, 2016: ACS Nano
Bradley C Doak, Raymond S Norton, Martin J Scanlon
Fragment-based drug design (FBDD) has emerged as a mainstream approach for the rapid and efficient identification of building blocks that can be used to develop high-affinity ligands against protein targets. One of the strengths of FBDD is the relative ease and low cost of the primary screen to identify fragments that bind. However, the fragments that emerge from primary screens often have low affinities, with KD values in the high μM to mM range, and a significant challenge for FBDD is to develop the initial fragments into more potent ligands...
November 2016: Pharmacology & Therapeutics
Heewook Lee, Thomas G Doak, Ellen Popodi, Patricia L Foster, Haixu Tang
A majority of large-scale bacterial genome rearrangements involve mobile genetic elements such as insertion sequence (IS) elements. Here we report novel insertions and excisions of IS elements and recombination between homologous IS elements identified in a large collection of Escherichia coli mutation accumulation lines by analysis of whole genome shotgun sequencing data. Based on 857 identified events (758 IS insertions, 98 recombinations and 1 excision), we estimate that the rate of IS insertion is 3.5 × 10(-4) insertions per genome per generation and the rate of IS homologous recombination is 4...
September 6, 2016: Nucleic Acids Research
Sharif Ismail, Jonathan Duckett, Diaa Rizk, Olanrewaju Sorinola, Dorothy Kammerer-Doak, Oscar Contreras-Ortiz, Hazem Al-Mandeel, Kamil Svabik, Mitesh Parekh, Christian Phillips
INTRODUCTION AND HYPOTHESIS: This committee opinion paper summarizes available evidence about recurrent pelvic organ prolapse (POP) to provide guidance on management. METHOD: A working subcommittee from the International Urogynecological Association (IUGA) Research and Development Committee was formed. The literature regarding recurrent POP was reviewed and summarized by individual members of the subcommittee. Recommendations were graded according to the 2009 Oxford Levels of Evidence...
July 5, 2016: International Urogynecology Journal
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