UFGI Publications Round-Up Week 9/5/2016

¹Center for Safety, Simulation, and Advanced Learning Technologies, University of Florida, Gainesville, FL, USA.
²Department of Anesthesiology, University of Florida, Gainesville, FL, USA.
³Clinical & Translational Science Institute Simulation Core, University of Florida, Gainesville, FL, USA.
⁴UF Health Shands Experiential Learning Center, University of Florida, Gainesville, FL, USA.
⁵Department of Pharmaceutics, University of Florida, Gainesville, FL, USA.
⁶Computer & Information Science and Engineering, University of Florida, Gainesville, FL, USA.
⁷Department of Computer Science, University of Texas at San Antonio, San Antonio, TX, USA.

Journal: Journal of Clinical Pharmacology

Date of e-pub: March 28, 2016

Abstract: We present a race-specific model of propofol-induced loss of consciousness that is based on pharmacodynamic data collected and adapted from the peer-reviewed literature. In the proposed race-specific model that includes EC05 and EC95 concentrations, the median (EC50) (and where available 95%CI) propofol concentrations at the effect site compartment for propofol-induced loss of consciousness for whites, Chinese, blacks, and Indians are 2.8 (2.7-2.9), 2.2 (2.2-2.3), 2.0, and 1.9 μg/mL, respectively.

¹Health Informatics Institute, Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, FLkendra.vehik@epi.usf.edu.
²Health Informatics Institute, Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, FL.
³Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL.
⁴National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD.
⁵Pacific Northwest Diabetes Research Institute, Seattle, WA.
⁶Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO.
⁷Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA.
⁸Department of Pediatrics, Turku University Hospital, Turku, Finland.
⁹Institute of Diabetes Research, Helmholtz Zentrum München, and Klinikum rechts der Isar, Technische Universität München, and Forschergruppe Diabetes e.V. Neuherberg, Neuherberg, Germany.
¹⁰Department of Clinical Sciences, Lund University/CRC, Skåne University, Malmö, Sweden.
¹¹Center for Regenerative Therapies, University of Technology, Dresden, Germany Paul Langerhans Institute Dresden, German Center for Diabetes Research (DZD), Dresden, Germany.

Journal: Diabetes Care

Date of e-pub: June 16, 2016

Abstract: β-Cell autoantibodies are a feature of the preclinical phase of type 1 diabetes. Here, we asked how frequently they revert in a cohort of children at risk for type 1 diabetes and whether reversion has any effect on type 1 diabetes risk.

¹Department of Plant Pathology, University of Florida, Gainesville, FL 32611-0680, USA.
²Department of Plant Pathology, University of Florida, Gainesville, FL 32611-0680, USA. Electronic address: rollinsj@ufl.edu.

Journal: Fungal Biology

Date of e-pub: June 22 2016

Abstract: Sclerotinia sclerotiorum (Lib.) de Bary is a phytopathogenic fungus that relies on the completion of the sexual cycle to initiate aerial infections. The sexual cycle produces apothecia required for inoculum dispersal. In this study, insight into the regulation of apothecial multicellular development was pursued through functional characterization of mating-type genes. These genes are hypothesized to encode master regulatory proteins required for aspects of sexual development ranging from fertilization through fertile fruiting body development. Experimentally, loss-of-function mutants were created for the conserved core mating-type genes (MAT1-1-1, and MAT1-2-1), and the lineage-specific genes found only in S. sclerotiorum and closely related fungi (MAT1-1-5, and MAT1-2-4). The MAT1-1-1, MAT1-1-5, and MAT1-2-1 mutants are able to form ascogonia but are blocked in all aspects of apothecium development. These mutants also exhibit defects in secondary sexual characters including lower numbers of spermatia. The MAT1-2-4 mutants are delayed in carpogenic germination accompanied with altered disc morphogenesis and ascospore production. They too produce lower numbers of spermatia. All four MAT gene mutants showed alterations in the expression of putative pheromone precursor (Ppg-1) and pheromone receptor (PreA, PreB) genes. Our findings support the involvement of MAT genes in sexual fertility, gene regulation, meiosis, and morphogenesis in S. sclerotiorum.

¹Plant Molecular and Cellular Biology Program, University of Florida, Gainesville, FL 32611, USA.
²Plant Molecular and Cellular Biology Program, University of Florida, Gainesville, FL 32611, USA Horticultural Sciences Department, University of Florida, Gainesville, FL 32611, USA.
³Plant Molecular and Cellular Biology Program, University of Florida, Gainesville, FL 32611, USA Horticultural Sciences Department, University of Florida, Gainesville, FL 32611, USA drm@ufl.edu.

Journal: Journal of Experimental Botany

Date of e-pub: August 2016

Abstract: DUF177 proteins are nearly universally conserved in bacteria and plants except the Chlorophyceae algae. Thus far, duf177 mutants in bacteria have not established a function. In contrast, duf177a mutants have embryo lethal phenotypes in maize and Arabidopsis. In maize inbred W22, duf177a mutant embryos arrest at an early transition stage, whereas the block is suppressed in the B73 inbred background, conditioning an albino seedling phenotype. Background-dependent embryo lethal phenotypes are characteristic of maize plastid gene expression mutants. Consistent with the plastid gene expression hypothesis, quantitative real-time PCR revealed a significant reduction of 23S rRNA in an Escherichia coli duf177 knockout. Plastid 23S rRNA contents of duf177a mutant tissues were also markedly reduced compared with the wild-type, whereas plastid 16S, 5S, and 4.5S rRNA contents were less affected, indicating that DUF177 is specifically required for accumulation of prokaryote-type 23S rRNA. An AtDUF177A-green fluorescent protein (GFP) transgene controlled by the native AtDUF177A promoter fully complemented the Arabidopsis atduf177a mutant. Transient expression of AtDUF177A-GFP in Nicotiana benthamiana leaves showed that the protein was localized in chloroplasts. The essential role of DUF177A in chloroplast-ribosome formation is reminiscent of IOJAP, another highly conserved ribosome-associated protein, suggesting that key mechanisms controlling ribosome formation in plastids evolved from non-essential pathways for regulation of the prokaryotic ribosome.

¹Department of Physiological Sciences and Center for Environmental and Human Toxicology, and the Genetics Institute, University of Florida,Gainesville, FL 32611, USA.
²Minnesota Pollution Control Agency, Environmental Analysis and Outcomes Division, 520 Lafayette Road North, Saint Paul, MN 55155, USA.
³Mary Griggs Burke Center for Freshwater Innovation, Northland College, Ashland, WI 54806, USA. Electronic address: rlehr@northland.edu.

Journal: Comparative Biochemistry and Physiology: Part D Genomics and Proteomics

Date of e-pub: September 2016

Abstract: Perfluorinated chemicals (PFASs) stem from a wide range of sources and have been detected in aquatic ecosystems worldwide, including the upper Midwest and the state of Minnesota in the USA. This study investigated whether fish with high body burden levels of PFASs in the Twin Cities Metro Areas showed any evidence of adverse effects at the level of the transcriptome. We hypothesized that fish with higher body burden levels of PFASs would exhibit molecular responses in the liver and testis that were suggestive of oxidative and general stress, as well as impaired reproduction. Concentrations of PFASs in largemouth bass varied significantly across the sampled lakes, with the lowest concentrations of PFASs found in fish from Steiger and Upper Prior Lakes and the highest concentrations found in fish from Calhoun and Twin Lakes. Largemouth bass with high PFAS concentrations exhibited changes in the expression of genes related to lipid metabolism, energy production, RNA processing, protein production/degradation and contaminant detoxification, all of which are consistent with biomarker responses observed in other studies with PFASs. However, given the wide range of genes that were differentially expressed across the lakes and the variability observed in the mechanisms through which biological processes were affected, it is unlikely that PFASs are the only stressors affecting largemouth bass in the Twin Cities Metro Areas lakes. Indeed, Twin Lake is affected by the Joslyn superfund site which contains polycyclic aromatic hydrocarbons, pentachlorophenol, polychlorinated biphenyls, and dioxins. These compounds are also expected to drive the transcriptomics responses observed, but to what degree is difficult to ascertain at this time.

¹University of Kansas Medical Center, Kansas City, KS, USA mbutler4@kumc.edu.
²Texas Tech University, Lubbock, TX, USA.
³University of Kansas Medical Center, Kansas City, KS, USA.
⁴Loma Linda University Medical School, Loma Linda, CA, USA.
⁵University of Florida, Gainesville, FL, USA.
⁶Vanderbilt University, Nashville, TN, USA.
⁷University of California, Irvine, CA, USA.

Journal: Clinical Pediatrics

Date of e-pub: September 2016

Abstract: The purpose of the current study was to develop syndrome-specific standardized growth curves for growth hormone-treated Prader-Willi syndrome (PWS) individuals aged 0 to 18 years. Anthropometric growth-related measures were obtained on 171 subjects with PWS who were treated with growth hormone for at least 40% of their lifespan. They had no history of scoliosis. PWS standardized growth curves were developed for 7 percentile ranges using the LMS method for weight, height, head circumference, weight/length, and BMI along with normative 3rd, 50th, and 97th percentiles plotted using control data from the literature and growth databases. Percentiles were plotted on growth charts for comparison purposes. Growth hormone treatment appears to normalize stature and markedly improves weight in PWS compared with standardized curves for non-growth hormone-treated PWS individuals. Growth chart implications and recommended usage are discussed.

¹Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida Genetics Institute, University of Florida, Gainesville, FL 32611, USA. Electronic address: cmartyn@ufl.edu.
²Water Science and Technology, Environment and Climate Change Canada, Burlington, ON, Canada.

Journal: Comparative Biochemistry and Physiology: Part D Genomics and Proteomics

Date of e-pub: September 2016

Abstract: The applications for high throughput omics technologies in environmental science have increased dramatically in recent years. Transcriptomics, proteomics, and metabolomics have been used to study how chemicals in our environment affect both aquatic and terrestrial organisms, and the characterization of molecular initiating events is a significant goal in toxicology to better predict adverse responses to toxicants. This special journal edition demonstrates the scope of the science that leverages omics-based methods in both laboratory and wild populations within the context of environmental toxicology, ranging from fish to mammals. It is important to recognize that the environment comprises one axis of the One Health concept – the idea that human health is unequivocally intertwined to our environment and to the organisms that inhabit that environment. We have much to learn from a comparative approach, and studies that integrate the transcriptome, proteome, and the metabolome are expected to offer the most detailed mechanism-based adverse outcome pathways that are applicable for use in both environmental monitoring and risk assessment.

¹Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611, USA. Electronic address: cmartyn@ufl.edu.
²Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611, USA.
³St. Johns River Water Management District, Palatka, FL 32177, USA.
⁴Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611, USA. Electronic address: ndenslow@ufl.edu.

Journal: Comparative Biochemistry and Physiology: Part D Genomics and Proteomics

Date of e-pub: September 2016

Abstract: Lake Apopka (FL, USA) has elevated levels of some organochlorine pesticides in its sediments and a portion of its watershed has been designated a US Environmental Protection Agency Superfund site. This study assessed reproductive endpoints in Florida largemouth bass (LMB) (Micropterus salmoides floridanus) after placement into experimental ponds adjacent to Lake Apopka. LMB collected from a clean reference site (DeLeon Springs) were stocked at two periods of time into ponds constructed in former farm fields on the north shore of the lake. LMB were stocked during early and late oogenesis to determine if there were different effects of contamination on LMB that may be attributed to their reproductive stage. LMB inhabiting the ponds for ~4months had anywhere from 2 to 800 times higher contaminant load for a number of organochlorine pesticides (e.g. p, p’-DDE, methoxychlor) compared to control animals. Gonadosomatic index and plasma vitellogenin were not different between reproductively-stage matched LMB collected at reference sites compared to those inhabiting the ponds. However, plasma 17β-estradiol was lower in LMB inhabiting the Apopka ponds compared to ovary stage-matched LMB from the St. Johns River, a site used as a reference site. Sub-network enrichment analysis revealed that genes related to reproduction (granulosa function, oocyte development), endocrine function (steroid metabolism, hormone biosynthesis), and immune function (T cell suppression, leukocyte accumulation) were differentially expressed in the ovaries of LMB placed into the ponds. These data suggest that (1) LMB inhabiting the Apopka ponds showed disrupted reproduction and immune responses and that (2) gene expression profiles provided site-specific information by discriminating LMB from different macro-habitats.

¹Center for Environmental and Human Toxicology, Department of Physiological Sciences, College of Veterinary Medicine, UF Genetics Institute, University of Florida, Gainesville, FL 32611, USA.
²Department of Biology and Canadian Rivers Institute, University of New Brunswick, Saint John, New Brunswick E2L 4L5, Canada.
³Center for Environmental and Human Toxicology, Department of Physiological Sciences, College of Veterinary Medicine, UF Genetics Institute, University of Florida, Gainesville, FL 32611, USA; Department of Biology and Canadian Rivers Institute, University of New Brunswick, Saint John, New Brunswick E2L 4L5, Canada. Electronic address: cmartyn@ufl.edu.

Journal: Comparative Biochemistry and Physiology: Part D Genomics and Proteomics

Date of e-pub: September 2016

Abstract: Characterizing factors that contribute to transcript variability is necessary before molecular endpoints are widely adopted as biomarkers for environmental monitoring programs and risk assessment. Here, we employed a meta-analysis approach to understand how reproductive stage, breeding strategy, and tissue type influence transcript variability in multiple fish species. Transcript abundance from the scientific literature was examined by method of quantification (qPCR or microarray), and the extracted data were used to calculate the coefficient of variation (CoV) for each transcript. Based on qPCR data, variability in the abundance of estrogen receptor 1 and hydroxysteroid dehydrogenase 3b was dependent upon reproductive stage and/or breeding strategy in the female ovaries. The variability of other transcripts in the steroid biosynthesis pathway as well as other steroid receptors did not depend upon sex, breeding strategy, or reproductive stage. Variability estimates were used to determine sample size requirements for detecting specific critical effects in molecular endpoints. It was estimated that only 37.8% of published studies used in the qPCR meta-analysis had sufficient experimental power (0.8) to detect a 2-fold expression difference in a transcript. To build upon these analyses, microarray data were used to measure overall variability of the transcriptome, and it was determined that the vitellogenic reproductive stage had the lowest transcriptomic variability compared to other reproductive stages. This variability was lower in a single-spawning species (largemouth bass) compared to a multiple-spawner (fathead minnow). Following this, a meta-analysis of 777 microarrays for multiple fish species was performed to determine the influence of breeding strategy and tissue type on transcriptomic variability. In this analysis, single-spawning fish showed lower gonadal and hepatic transcriptome variability compared to multiple-spawning species. Thus, these species may be more appropriate for sampling molecular endpoints in monitoring programs. Transcript variability was lowest in the brain, followed by the gonads and liver, which may reflect fewer morphological changes relative to these tissues. The results of this study should be used in conjunction with other experimental and sampling recommendations to optimize the use of molecular endpoints in regulatory ecotoxicology and environmental monitoring programs.