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M Campos Ponce, K Polman, N Roos, F T Wieringa, J Berger, C M Doak
Introduction Even though micronutrient deficiency is still a major public health problem, it is still unclear which interventions are most effective in improving micronutrient status. This review therefore aims to summarize the evidence published in systematic reviews on intervention strategies that aim at improving micronutrient status in children under the age of five. Methods We searched the literature and included systematic reviews that reported on micronutrient status as a primary outcome for children of 0-5 years old, had a focus on low or middle income countries...
June 4, 2018: Maternal and Child Health Journal
Geneva R Doak, Kathryn L Schwertfeger, David K Wood
Tumor-associated macrophages are known contributors of tumor progression in the primary tumor via multiple mechanisms. However, recent studies have demonstrated the ability of macrophages to promote secondary tumor development by inhibiting tumoricidal immune response, initiating angiogenesis, remodeling the local matrix, and directly communicating with cancer cells. In this review, we discuss macrophage functions in establishing distant metastases including formation of the premetastatic niche, extravasation of circulating cancer cells, and colonization of secondary metastases...
June 2018: Trends in Cancer
Vasanthanathan Poongavanam, Bradley C Doak, Jan Kihlberg
Recent years have seen a dramatic increase in the number of drugs approved in chemical space outside of Lipinski's rule of 5, that is in what has been termed beyond rule of 5 (bRo5) space. The development of three major classes of oral drugs that treat HIV and HCV infections and the growing evidence that novel, difficult targets can be accessed has prompted research into understanding design of drugs displaying cell permeability, solubility and ultimately oral bioavailability in bRo5 space. Studies have found a consistent outer property limit for a reasonable chance of de novo designing oral bioavailability...
May 24, 2018: Current Opinion in Chemical Biology
Hongan Long, Thomas G Doak, Michael Lynch
Mutation is one of the most fundamental evolutionary forces. Studying variation in the mutation rate within and among closely-related species can help reveal mechanisms of genome divergence, but such variation is unstudied in the vast majority of organisms. Previous studies on ciliated protozoa have found extremely low mutation rates. In this study, using mutation-accumulation techniques combined with deep whole-genome sequencing, we explore the germline base-substitution mutation-rate variation of three cryptic species in the Paramecium aurelia species complex- P...
May 24, 2018: G3: Genes—Genomes—Genetics
Megan G Behringer, Brian I Choi, Samuel F Miller, Thomas G Doak, Jonathan A Karty, Wanfeng Guo, Michael Lynch
How genetic variation is generated and maintained remains a central question in evolutionary biology. When presented with a complex environment, microbes can take advantage of genetic variation to exploit new niches. Here we present a massively parallel experiment where WT and repair-deficient ( ∆mutL ) Escherichia coli populations have evolved over 3 y in a spatially heterogeneous and nutritionally complex environment. Metagenomic sequencing revealed that these initially isogenic populations evolved and maintained stable subpopulation structure in just 10 mL of medium for up to 10,000 generations, consisting of up to five major haplotypes with many minor haplotypes...
April 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
Rosalie Elespuru, Stefan Pfuhler, Marilyn Aardema, Tao Chen, Shareen H Doak, Ann Doherty, Christopher S Farabaugh, Julia Kenny, Mugimane Manjanatha, Brinda Mahadevan, Martha M Moore, Gladys Ouédraogo, Leon F Stankowski, Jennifer Y Tanir
Nanomaterials (NMs) present unique challenges in safety evaluation. An international working group, the Genetic Toxicology Technical Committee of the International Life Sciences Institute's Health and Environmental Sciences Institute, has addressed issues related to the genotoxicity assessment of NMs. A critical review of published data has been followed by recommendations on methods alterations and best practices for the standard genotoxicity assays: bacterial reverse mutation (Ames); in vitro mammalian assays for mutations, chromosomal aberrations, micronucleus induction, or DNA strand breaks (comet); and in vivo assays for genetic damage (micronucleus, comet and transgenic mutation assays)...
April 26, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Stephanie E A Burnell, Samantha Spencer-Harty, Suzie Howarth, Owen Bodger, Howard Kynaston, Claire Morgan, Shareen H Doak
Six-transmembrane epithelial antigen of the prostate-2 (STEAP2) expression is increased in prostate cancer when compared to normal prostate, suggesting STEAP2 may drive prostate cancer progression. This study aimed to establish the functional role of STEAP2 in prostate tumourigenesis and evaluate if its knockdown resulted in reduced invasive potential of prostate cancer cells. PC3 and LNCaP cells were transfected with STEAP2 siRNA and proliferation, migration, invasion and gene expression analyses were performed...
April 19, 2018: Scientific Reports
Andrew J Parnell, James E Bradford, Emma V Curran, Adam L Washington, Gracie Adams, Melanie N Brien, Stephanie L Burg, Carlos Morochz, J Patrick A Fairclough, Pete Vukusic, Simon J Martin, Scott Doak, Nicola J Nadeau
Iridescence is an optical phenomenon whereby colour changes with the illumination and viewing angle. It can be produced by thin film interference or diffraction. Iridescent optical structures are fairly common in nature, but relatively little is known about their production or evolution. Here we describe the structures responsible for producing blue-green iridescent colour in Heliconius butterflies. Overall the wing scale structures of iridescent and non-iridescent Heliconius species are very similar, both having longitudinal ridges joined by cross-ribs...
April 2018: Journal of the Royal Society, Interface
Marie-Elena Brett, Heather E Bomberger, Geneva R Doak, Matthew A Price, James B McCarthy, David K Wood
Numerous studies have demonstrated the importance of altered hyaluronan metabolism to malignant progression of multiple tumor types, including breast carcinomas. Increased hyaluronan (HA) metabolism in the stroma of primary tumors promotes activation of oncogenic signaling pathways that impact tumor initiation, growth, and invasion. Carcinoma cell synthesis and assembly of HA-rich pericellular matrices induces a stromal-independent phenotype, which is associated with cancer progression. Although the pro-tumorigenic role of stromal HA is well established, a novel but unexplored hypothesis is that carcinoma cell-associated HA pericellular matrices promote metastasis of circulating tumor cells...
April 23, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Marie Luise Grünbein, Robert L Shoeman, R Bruce Doak
To conduct X-ray Free-Electron Laser (XFEL) measurements at megahertz (MHz) repetition rates, sample solution must be delivered in a micron-sized liquid free-jet moving at up to 100 m/s. This exceeds by over a factor of two the jet speeds measurable with current high-speed camera techniques. Accordingly we have developed and describe herein an alternative jet velocimetry based on dual-pulse nanosecond laser illumination. Three separate implementations are described, including a small laser-diode system that is inexpensive and highly portable...
March 19, 2018: Optics Express
Weibo Zheng, Chundi Wang, Ying Yan, Feng Gao, Thomas G Doak, Weibo Song
Ciliated protists are a large group of single-celled eukaryotes with separate germline and somatic nuclei in each cell. The somatic genome is developed from the zygotic nucleus through a series of chromosomal rearrangements, including fragmentation, DNA elimination, de novo telomere addition, and DNA amplification. This unique feature makes them perfect models for research in genome biology and evolution. However, genomic research of ciliates has been limited to a few species, owing to problems with DNA contamination and obstacles in cultivation...
March 1, 2018: Genome Biology and Evolution
Matteo Rossi Sebastiano, Bradley C Doak, Maria Backlund, Vasanthanathan Poongavanam, Björn Over, Giuseppe Ermondi, Giulia Caron, Pär Matsson, Jan Kihlberg
Conformational flexibility has been proposed to significantly affect drug properties outside rule-of-5 (Ro5) chemical space. Here, we investigated the influence of dynamically exposed polarity on cell permeability and aqueous solubility for a structurally diverse set of drugs and clinical candidates far beyond the Ro5, all of which populated multiple distinct conformations as revealed by X-ray crystallography. Efflux-inhibited (passive) Caco-2 cell permeability correlated strongly with the compounds' minimum solvent-accessible 3D polar surface areas (PSA), whereas aqueous solubility depended less on the specific 3D conformation...
May 10, 2018: Journal of Medicinal Chemistry
I Montero-Serra, C Linares, D F Doak, J B Ledoux, J Garrabou
Understanding the role of the environment in shaping the evolution of life histories remains a major challenge in ecology and evolution. We synthesize longevity patterns of marine sessile species and find strong positive relationships between depth and maximum lifespan across multiple sessile marine taxa, including corals, bivalves, sponges and macroalgae. Using long-term demographic data on marine sessile and terrestrial plant species, we show that extreme longevity leads to strongly dampened population dynamics...
February 28, 2018: Proceedings. Biological Sciences
Brechje de Gier, Gisela M Pita-Rodríguez, Maiza Campos-Ponce, Margot van de Bor, Chhoun Chamnan, Raquel Junco-Díaz, Colleen M Doak, Marion Fiorentino, Khov Kuong, Fidel Angel-Núñez, Megan E Parker, Marlene Perignon, Lázara Rojas-Rivero, Jacques Berger, Katja Polman, Frank T Wieringa
No abstract text is available yet for this article.
June 2018: Acta Tropica
Alan M Magee, Michelle Breathnach, Stephen Doak, Fiona Thornton, Conor Noone, Louise G McKenna
During an investigation, the question of interest might be whether or not a person has worn a given garment. Wearer DNA studies have contributed to our knowledge and understanding of DNA transfer and persistence on items of worn clothing. However, there is currently no extensive dataset on DNA profiling outcomes from a variety of upper garments. Therefore we investigated the DNA profiling outcomes from the collars and/or cuffs of forty-four upper garments of worn clothing and determined the quantity of wearer and non-wearer DNA recovered...
May 2018: Forensic Science International. Genetics
Jared L Wilmoth, Peter W Doak, Andrea Timm, Michelle Halsted, John D Anderson, Marta Ginovart, Clara Prats, Xavier Portell, Scott T Retterer, Miguel Fuentes-Cabrera
The factors leading to changes in the organization of microbial assemblages at fine spatial scales are not well characterized or understood. However, they are expected to guide the succession of community development and function toward specific outcomes that could impact human health and the environment. In this study, we put forward a combined experimental and agent-based modeling framework and use it to interpret unique spatial organization patterns of H1-Type VI secretion system (T6SS) mutants of P . aeruginosa under spatial confinement...
2018: Frontiers in Microbiology
G A Zavala, O P García, M Camacho, D Ronquillo, M Campos-Ponce, C Doak, K Polman, J L Rosado
The aim of the present study was to evaluate associations between intestinal parasitic infection with intestinal and systemic inflammatory markers in school-aged children with high rates of obesity. Plasma concentrations of C-Reactive Protein (CRP), leptin, TNF-α, IL-6 and IL-10 were measured as systemic inflammation markers and count of stool leukocytes as marker of intestinal inflammation in 291 children (6-10 years). Intestinal parasitic infection was measured by stool examination. Logistic regression analyses were performed to determine the odds of having high inflammatory markers for each parasite or group of parasites as compared to parasite-free children while adjusting for sex, age, mother's educational level and percentage of body fat...
April 2018: Parasite Immunology
Ume-Kulsoom Shah, Jefferson de Oliveira Mallia, Neenu Singh, Katherine E Chapman, Shareen H Doak, Gareth J S Jenkins
The liver's role in metabolism of chemicals makes it an appropriate tissue for toxicity testing. Current testing protocols, such as animal testing and two-dimensional liver cell systems, offer limited resemblance to in vivo liver cell behaviour, in terms of gene expression profiles and metabolic competence; thus, they do not always accurately predict human toxicology. In vitro three-dimensional liver cell models offer an attractive alternative. This study reports on the development of a 3D liver model, using HepG2 cells, by a hanging-drop technique, with a focus on evaluating spheroid growth characteristics and suitability for genotoxicity testing...
January 2018: Mutation Research
Sam P Tarassoli, Zita M Jessop, Ayesha Al-Sabah, Neng Gao, Sairan Whitaker, Shareen Doak, Iain S Whitaker
BACKGROUND: Commercially available tissue engineered skin remains elusive despite extensive research because the multi-stratified anisotropic structure is difficult to replicate in vitro using traditional tissue engineering techniques. Bioprinting, involving computer-controlled deposition of cells and scaffolds into spatially controlled patterns, is able to control not only the macro but also micro and nanoarchitecture and could offer the potential to more faithfully replicate native skin...
May 2018: Journal of Plastic, Reconstructive & Aesthetic Surgery: JPRAS
Allison M Louthan, Robert M Pringle, Jacob R Goheen, Todd M Palmer, William F Morris, Daniel F Doak
Predicting how species' abundances and ranges will shift in response to climate change requires a mechanistic understanding of how multiple factors interact to limit population growth. Both abiotic stress and species interactions can limit populations and potentially set range boundaries, but we have a poor understanding of when and where each is most critical. A commonly cited hypothesis, first proposed by Darwin, posits that abiotic factors (e.g., temperature, precipitation) are stronger determinants of range boundaries in apparently abiotically stressful areas ("stress" indicates abiotic factors that reduce population growth), including desert, polar, or high-elevation environments, whereas species interactions (e...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
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