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UFGI publication round-up week 02/20, 02/27 and 03/06/2017

A need to revisit clinical breakpoints of tigecycline: effect of atypical non-linear plasma protein binding.

Author information: Singh RS1, Mukker JK1, Drescher SK1, Deitchman AN1, Derendorf H2.

1Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.
2Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA. Electronic address: hartmut@cop.ufl.edu.
Journal: International Journal of Antimicrobial Agents

Date of e-pub: February 2017

Abstract: Tigecycline is highly active against various drug-resistant bacteria. The US Food and Drug Administration (FDA) recently issued a black box warning for tigecycline owing to an associated increase in all-cause mortality. Clinical breakpoints of antibiotics are vital in susceptibility testing of pathogens for the selection of antibiotic therapy; however, no consensus exists between different committees on the clinical breakpoints of tigecycline. Of note, tigecycline exhibits atypical non-linear plasma protein binding (PPB) behaviour, and the pivotal probability of target attainment (PTA) analysis for the determination of clinical breakpoints did not account for the PPB of tigecycline. In this work, the PTA analysis was performed with consideration of atypical non-linear PPB behaviour of tigecycline. A model describing atypical non-linear PPB was developed and validated. Monte Carlo simulations were performed to determine the target ratio of area under the free drug concentration-time curve to minimum inhibitory concentration (fAUC/MIC) for Escherichia coli and, subsequently, PTA analyses were performed. The target fAUC/MIC ratio for E. coli was determined as 2.05, whilst the target AUC/MIC ratio was 6.96. The PTA analyses suggest a lower clinical breakpoint of tigecycline against E. coli. This finding suggests that there is a need to revisit the current clinical breakpoints of tigecycline.

 

 

Evolutionary Conservation of ABA Signaling for Stomatal Closure in Ferns.

Author information: Cai S1, Chen G2, Wang Y2, Huang Y3, Marchant B4, Wang Y5, Yang Q2, Dai F2, Hills A5, Franks PJ6, Nevo E7, Soltis D8, Soltis P9, Sessa E10, Wolf PG11, Xue D12, Zhang G13, Pogson BJ14, Blatt MR15, Chen ZH16.

1University of Western Sydney CITY: Penrith Australia [AU].
2College of Agriculture and Biotechnology, Zhejiang University CITY: Hangzhou China [CN].
3Western Sydney University CITY: Penrith STATE: NSW Australia [AU].
4University of Puget Sound CITY: Tacoma STATE: WA United States Of America [US].
5University of Glasgow CITY: Glasgow United Kingdom [GB].
6University of Sydney CITY: Sydney POSTAL_CODE: N/A Australia [AU].
7Department of Evolutionary and Environmental Biology, Institute of Evolution, University of Haifa CITY: Haifa Israel [IL].
8University of Florida Dept Biology Univ Florida CITY: Gainesville POSTAL_CODE: 32605 United States Of America [US].
9University of Florida Florida Museum of Natural History CITY: Gainesville STATE: Florida POSTAL_CODE: 32611 United States Of America [US].
10University of Florida CITY: Gainesville United States Of America [US].
11Utah State University Dept. Biology, Utah State University, 5305 Old Main Hill CITY: Logan STATE: Utah POSTAL_CODE: 84322 United States Of America [US].
12Hangzhou Normal University CITY: Hangzhou China [CN].
13Zhejiang University Department of Agronomy, Zhejiang University, Hangzhou, CITY: China STATE: Zh POSTAL_CODE: 310058 China [CN].
14The Australian National University CITY: Canberra STATE: ACT POSTAL_CODE: 2601 Australia [AU].
15University of Glasgow CITY: Glasgow POSTAL_CODE: G12 8QQ United Kingdom [GB].
16Western Sydney University CITY: Penrith STATE: NSW POSTAL_CODE: 2751 Australia [AU] z.chen@uws.edu.au.
Journal: Plant Physiology

Date of e-pub: February 2017

Abstract: ABA-driven stomatal regulation reportedly evolved after the divergence of ferns, during the early evolution of seed plants approximately 360 Mya. This hypothesis is based on the observation that the stomata of certain fern species are unresponsive to ABA, but exhibit passive hydraulic control. However, ABA-induced stomatal closure was detected in some mosses and lycophytes. Here, we observed that a number of ABA signaling and membrane transporter protein families diversified over the evolutionary history of land plants. The aquatic ferns Azolla filiculoides and Salvinia cucullata have representatives of 23 families of proteins orthologous to those of Arabidopsis thaliana and all other land plant species studied. Phylogenetic analysis of the key ABA signaling proteins indicates an evolutionarily conserved stomatal response to ABA. Moreover, comparative transcriptomic analysis has identified a suite of ABA responsive genes that differentially expressed in a terrestrial fern species, Polystichum proliferum. These genes encode proteins associated with ABA biosynthesis, transport, reception, transcription, signaling, and ion and sugar transport, which fit the general ABA signaling pathway constructed from Arabidopsis thaliana and Hordeum vulgare. The retention of these key ABA-responsive genes could have had a profound effect on the adaptation of ferns to dry conditions. Furthermore, stomatal assays have shown the primary evidence for ABA-induced closure of stomata in two terrestrial fern species P. proliferum and Nephrolepis exaltata. In summary, we report new molecular and physiological evidence for the presence of active stomatal control in ferns.

 

 

Lack of resistance development in Bemisia tabaci to Isaria fumosorosea after multiple generations of selection.

Author information: Gao T1, Wang Z1, Huang Y1, Keyhani NO2, Huang Z1,2.

1Department of Entomology, College of Agriculture, South China Agricultural University, Guangzhou, 510642, China.
2Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Bldg. 981, Museum Rd., Gainesville, FL32611, USA.
Journal: Scientific Reports

Date of e-pub: February 2017

Abstract: The emergence of insecticide resistant insect pests is of significant concern worldwide. The whitefly, Bemisia tabaci, is an important agricultural pest and has shown incredible resilience developing resistance to a number of chemical pesticides. Entomopathogenic fungi such as Isaria fumosorosea offer an attractive alternative to chemical pesticides for insect control, and this fungus has been shown to be an effective pathogen of B. tabaci. Little is known concerning the potential for the development of resistance to I. fumosorosea by B. tabaci. Five generations of successive survivors of B. tabaci infected by I. fumosorosea were assayed with I. fumosorosea. No significant differences in susceptibility to I. fumosorosea, number of ovarioles, or ovipostioning were seen between any of the generations tested. Effects of I. fumosorosea and cell-free ethyl acetate fractions derived from the fungus on the B. tabaci fat body, ovary, and vitellogenin were also investigated. These data revealed significant deformation and degradation of ovary tissues and associated vitellogenin by the fungal mycelium as well as by cell-free ethyl acetate fungal extracts. These data indicate the lack of the emergence of resistance to I. fumosorosea under the conditions tested and demonstrate invasion of the insect reproductive tissues during fungal infection.

 

 

Probiotics (Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and Bifidobacterium longum MM-2) improve rhinoconjunctivitis-specific quality of life in individuals with seasonal allergies: a double-blind, placebo-controlled, randomized trial.

Author information: Dennis-Wall JC1, Culpepper T1, Nieves C Jr1, Rowe CC1, Burns AM1, Rusch CT1, Federico A1, Ukhanova M2, Waugh S2, Mai V2, Christman MC3, Langkamp-Henken B4.

1Food Science and Human Nutrition Department and.
2Emerging Pathogens Institute, University of Florida, Gainesville, FL; and.
3MCC Statistical Consulting LLC, Gainesville, FL.
4Food Science and Human Nutrition Department and henken@ufl.edu.
Journal: The American Journal of Clinical Nutrition

Date of e-pub: February 2017

Abstract: Rhinoconjunctivitis-specific quality of life is often reduced during seasonal allergies. The Mini Rhinoconjunctivitis Quality of Life Questionnaire (MRQLQ) is a validated tool used to measure quality of life in people experiencing allergies (0 = not troubled to 6 = extremely troubled). Probiotics may improve quality of life during allergy season by increasing the percentage of regulatory T cells (Tregs) and inducing tolerance.Objective: The objective of this study was to determine whether consuming Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and B. longum MM-2 compared with placebo would result in beneficial effects on MRQLQ scores throughout allergy season in individuals who typically experience seasonal allergies. Secondary outcomes included changes in immune markers as part of a potential mechanism for changes in MRQLQ scores.Design: In this double-blind, placebo-controlled, parallel, randomized clinical trial, 173 participants (mean ± SEM: age 27 ± 1 y) who self-identified as having seasonal allergies received either a probiotic (2 capsules/d, 1.5 billion colony-forming units/capsule) or placebo during spring allergy season for 8 wk. MRQLQ scores were collected weekly throughout the study. Fasting blood samples were taken from a subgroup (placebo, n = 37; probiotic, n = 35) at baseline and week 6 (predicted peak of pollen) to determine serum immunoglobulin (Ig) E concentrations and Treg percentages.Results: The probiotic group reported an improvement in the MRQLQ global score from baseline to pollen peak (-0.68 ± 0.13) when compared with the placebo group (-0.19 ± 0.14; P = 0.0092). Both serum total IgE and the percentage of Tregs increased from baseline to week 6, but changes were not different between groups.Conclusions: This combination probiotic improved rhinoconjunctivitis-specific quality of life during allergy season for healthy individuals with self-reported seasonal allergies; however, the associated mechanism is still unclear. This trial was registered at clinicaltrials.gov as NCT02349711.

 

 

Whole-genome duplication and molecular evolution in Cornus L. (Cornaceae) – Insights from transcriptome sequences.

Author information: Yu Y1,2,3, Xiang Q1, Manos PS2, Soltis DE4,5, Soltis PS4,5, Song BH6, Cheng S7, Liu X7, Wong G8.

1Department of Plant and Microbial Biology, North Carolina State University, Raleigh, NC, United States of America.
2Key Laboratory of Bio-Resources and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, Sichuan, PR China.
3Department of Biology, Duke University, 130 Science Drive, Durham, NC, United States of America.
4Florida Natural History Museum, University of Florida, Gainesville, FL, United States of America.
5Department of Biology, University of Florida, Gainesville, FL, United States of America.
6Department of Biological Sciences, University of North Carolina at Charlotte, 9201 University City Blvd, Charlotte, NC, United States of America.
7BGI-Shenzhen, Shenzhen, China.
8Department of Biological Sciences and Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
Journal: PLoS One

Date of e-pub: February 2017

Abstract: The pattern and rate of genome evolution have profound consequences in organismal evolution. Whole-genome duplication (WGD), or polyploidy, has been recognized as an important evolutionary mechanism of plant diversification. However, in non-model plants the molecular signals of genome duplications have remained largely unexplored. High-throughput transcriptome data from next-generation sequencing have set the stage for novel investigations of genome evolution using new bioinformatic and methodological tools in a phylogenetic framework. Here we compare ten de novo-assembled transcriptomes representing the major lineages of the angiosperm genus Cornus (dogwood) and relevant outgroups using a customized pipeline for analyses. Using three distinct approaches, molecular dating of orthologous genes, analyses of the distribution of synonymous substitutions between paralogous genes, and examination of substitution rates through time, we detected a shared WGD event in the late Cretaceous across all taxa sampled. The inferred doubling event coincides temporally with the paleoclimatic changes associated with the initial divergence of the genus into three major lineages. Analyses also showed an acceleration of rates of molecular evolution after WGD. The highest rates of molecular evolution were observed in the transcriptome of the herbaceous lineage, C. canadensis, a species commonly found at higher latitudes, including the Arctic. Our study demonstrates the value of transcriptome data for understanding genome evolution in closely related species. The results suggest dramatic increase in sea surface temperature in the late Cretaceous may have contributed to the evolution and diversification of flowering plants.

 

 

Genome-wide study of resistant hypertension identified from electronic health records.

Author information: Dumitrescu L1, Ritchie MD2, Denny JC3,4, El Rouby NM5, McDonough CW5, Bradford Y2, Ramirez AH4, Bielinski SJ6, Basford MA7, Chai HS8, Peissig P9, Carrell D10, Pathak J8, Rasmussen LV11, Wang X3, Pacheco JA12, Kho AN13, Hayes MG13, Matsumoto M8, Smith ME12, Li R14, Cooper-DeHoff RM5,15, Kullo IJ16, Chute CG17, Chisholm RL12, Jarvik GP18, Larson EB10, Carey D19, McCarty CA20, Williams MS21, Roden DM4,22, Bottinger E23, Johnson JA5,24, de Andrade M8, Crawford DC15.

1Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
2Biomedical and Translational Informatics, Geisinger Health System, Danville, Pennsylvania, United States of America.
3Department of Biomedical Informatics, Vanderbilt University, Nashville, Tennessee, United States of America.
4Department of Medicine, Vanderbilt University, Nashville, Tennessee, United States of America.
5Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, Florida, United States of America.
6Division of Epidemiology, Mayo Clinic, Rochester, Minnesota, United States of America.
7Office of Research, Vanderbilt University, Nashville, Tennessee, United States of America.
8Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America.
9Biomedical Informatics Research Center, Marshfield Clinic Research Foundation, Marshfield, Wisconsin, United States of America.
10Group Health Research Institute, Seattle, Washington, United States of America.
11Department of Preventive Medicine, Division of Health and Biomedical Informatics, Northwestern University, Chicago, Illinois, United States of America.
12Center for Genetic Medicine, Northwestern University, Chicago, Illinois, United States of America.
13Department Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
14Division of Genomic Medicine, National Human Genome Research Institute, Bethesda, Maryland, United States of America.
15Epidemiology and Biostatistics, Institute for Computational Biology, Case Western Reserve University, Cleveland, Ohio, United States of America.
16Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, United States of America.
17Division of General Internal Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
18Department of Medicine, University of Washington Medical Center, Seattle, Washington, United States of America.
19Weis Center for Research, Geisinger Health System, Danville, Pennsylvania, United States of America.
20Essentia Institute of Rural Health, Duluth, Minnesota, United States of America.
21Genomic Medicine Institute, Geisinger Health System, Danville, Pennsylvania, United States of America.
22Department of Pharmacology, Vanderbilt University, Nashville, Tennessee, United States of America.
23Charles R. Bronfman Institute for Personalized Medicine, Mount Sinai, New York, New York, United States of America.
24Division of Cardiovascular Medicine, College of Medicine, University of Florida, Gainesville, Florida, United States of America.
Journal: PLoS One

Date of e-pub: February 2017

Abstract: Resistant hypertension is defined as high blood pressure that remains above treatment goals in spite of the concurrent use of three antihypertensive agents from different classes. Despite the important health consequences of resistant hypertension, few studies of resistant hypertension have been conducted. To perform a genome-wide association study for resistant hypertension, we defined and identified cases of resistant hypertension and hypertensives with treated, controlled hypertension among >47,500 adults residing in the US linked to electronic health records (EHRs) and genotyped as part of the electronic MEdical Records & GEnomics (eMERGE) Network. Electronic selection logic using billing codes, laboratory values, text queries, and medication records was used to identify resistant hypertension cases and controls at each site, and a total of 3,006 cases of resistant hypertension and 876 controlled hypertensives were identified among eMERGE Phase I and II sites. After imputation and quality control, a total of 2,530,150 SNPs were tested for an association among 2,830 multi-ethnic cases of resistant hypertension and 876 controlled hypertensives. No test of association was genome-wide significant in the full dataset or in the dataset limited to European American cases (n = 1,719) and controls (n = 708). The most significant finding was CLNK rs13144136 at p = 1.00×10-6 (odds ratio = 0.68; 95% CI = 0.58-0.80) in the full dataset with similar results in the European American only dataset. We also examined whether SNPs known to influence blood pressure or hypertension also influenced resistant hypertension. None was significant after correction for multiple testing. These data highlight both the difficulties and the potential utility of EHR-linked genomic data to study clinically-relevant traits such as resistant hypertension.

 

 

Oxidative stress-mediated NFκB phosphorylation upregulates p62/SQSTM1 and promotes retinal pigmented epithelial cell survival through increased autophagy.

Author information: Song C1, Mitter SK2, Qi X2, Beli E2, Rao HV1, Ding J3, Ip CS2, Gu H2, Akin D1, Dunn WA Jr1, Bowes Rickman C3, Lewin AS4, Grant MB2, Boulton ME2.

1Department of Anatomy and Cell Biology, University of Florida, Gainesville, Florida, United States of America.
2Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
3Departments of Ophthalmology and Cell Biology, Duke University Medical Center, Durham, North Carolina, United States of America.
4Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida, United States of America.
Journal: PLos One

Date of e-pub: February 2017

Abstract: p62 is a scaffolding adaptor implicated in the clearance of protein aggregates by autophagy. Reactive oxygen species (ROS) can either stimulate or inhibit NFκB-mediated gene expression influencing cellular fate. We studied the effect of hydrogen peroxide (H2O2)-mediated oxidative stress and NFκB signaling on p62 expression in the retinal pigment epithelium (RPE) and investigated its role in regulation of autophagy and RPE survival against oxidative damage. Cultured human RPE cell line ARPE-19 and primary human adult and fetal RPE cells were exposed to H2O2-induced oxidative stress. The human apolipoprotein E4 targeted-replacement (APOE4) mouse model of AMD was used to study expression of p62 and other autophagy proteins in the retina. p62, NFκB p65 (total, phosphorylated, nuclear and cytoplasmic) and ATG10 expression was assessed by mRNA and protein analyses. Cellular ROS and mitochondrial superoxide were measured by CM-H2DCFDA and MitoSOX staining respectively. Mitochondrial viability was determined using MTT activity. qPCR-array system was used to investigate autophagic genes affected by p62. Nuclear and cytoplasmic levels of NFκB p65 were evaluated after cellular fractionation by Western blotting. We report that p62 is up-regulated in RPE cells under H2O2-induced oxidative stress and promotes autophagic activity. Depletion of endogenous p62 reduces autophagy by downregulation of ATG10 rendering RPE more susceptible to oxidative damage. NFκB p65 phosphorylation at Ser-536 was found to be critical for p62 upregulation in response to oxidative stress. Proteasome inhibition by H2O2 causes p62-NFκB signaling as antioxidant pre-treatment reversed p62 expression and p65 phosphorylation when RPE was challenged by H2O2 but not when by Lactacystin. p62 protein but not RNA levels are elevated in APOE4-HFC AMD mouse model, suggesting reduction of autophagic flux in disease conditions. Our findings suggest that p62 is necessary for RPE cytoprotection under oxidative stress and functions, in part, by modulating ATG10 expression. NFκB p65 activity may be a critical upstream initiator of p62 expression in RPE cells under oxidative stress.

 

 

Stem Cell Reviews and Reports: Adult Stem Cells and Tissue Regeneration Section.

Author information: Scott EW1.

1Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL, USA. escott@ufl.edu.

Journal: Stem Cell Reviews

Date of e-pub: February 2017

Abstract: N/A

 

 

A broad-scale comparison of aerobic activity levels in vertebrates: endotherms versus ectotherms.

Author information: Gillooly JF1, Gomez JP2,3, Mavrodiev EV4.

1Department of Biology, University of Florida, Gainesville, FL 32611, USA gillooly@ufl.edu.
2Department of Biology, University of Florida, Gainesville, FL 32611, USA.
3Spatial Epidemiology and Ecology Research Laboratory, University of Florida, Gainesville, FL 32610, USA.
4Florida Museum of Natural History, University of Florida, Gainesville, FL 32611, USA.
Journal: Proceedings. Biological Sciences

Date of e-pub: February 2017

Abstract: Differences in the limits and range of aerobic activity levels between endotherms and ectotherms remain poorly understood, though such differences help explain basic differences in species’ lifestyles (e.g. movement patterns, feeding modes, and interaction rates). We compare the limits and range of aerobic activity in endotherms (birds and mammals) and ectotherms (fishes, reptiles, and amphibians) by evaluating the body mass-dependence of VO2 max, aerobic scope, and heart mass in a phylogenetic context based on a newly constructed vertebrate supertree. Contrary to previous work, results show no significant differences in the body mass scaling of minimum and maximum oxygen consumption rates with body mass within endotherms or ectotherms. For a given body mass, resting rates and maximum rates were 24-fold and 30-fold lower, respectively, in ectotherms than endotherms. Factorial aerobic scope ranged from five to eight in both groups, with scope in endotherms showing a modest body mass-dependence. Finally, maximum consumption rates and aerobic scope were positively correlated with residual heart mass. Together, these results quantify similarities and differences in the potential for aerobic activity among ectotherms and endotherms from diverse environments. They provide insights into the models and mechanisms that may underlie the body mass-dependence of oxygen consumption.

 

 

Barcoded nanoparticles for high throughput in vivo discovery of targeted therapeutics.

Author information: Dahlman JE1,2,3,4, Kauffman KJ3,5, Xing Y6,2,3, Shaw TE6,2,3, Mir FF3, Dlott CC3, Langer R6,2,3,5, Anderson DG1,2,3,5, Wang ET7,8.

1Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139; james.dahlman@bme.gatech.edu rlanger@mit.edu dgander@mit.edu eric.t.wang@ufl.edu.
2Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139.
3David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
4Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332.
5Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.
6Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139.
7David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139; james.dahlman@bme.gatech.edu rlanger@mit.edu dgander@mit.edu eric.t.wang@ufl.edu.
8Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32601.
Journal: Proceedings of the National Academy of Sciences of the United States of America

Date of e-pub: February 2017

Abstract: Nucleic acid therapeutics are limited by inefficient delivery to target tissues and cells and by an incomplete understanding of how nanoparticle structure affects biodistribution to off-target organs. Although thousands of nanoparticle formulations have been designed to deliver nucleic acids, most nanoparticles have been tested in cell culture contexts that do not recapitulate systemic in vivo delivery. To increase the number of nanoparticles that could be tested in vivo, we developed a method to simultaneously measure the biodistribution of many chemically distinct nanoparticles. We formulated nanoparticles to carry specific nucleic acid barcodes, administered the pool of particles, and quantified particle biodistribution by deep sequencing the barcodes. This method distinguished previously characterized lung- and liver- targeting nanoparticles and accurately reported relative quantities of nucleic acid delivered to tissues. Barcode sequences did not affect delivery, and no evidence of particle mixing was observed for tested particles. By measuring the biodistribution of 30 nanoparticles to eight tissues simultaneously, we identified chemical properties promoting delivery to some tissues relative to others. Finally, particles that distributed to the liver also silenced gene expression in hepatocytes when formulated with siRNA. This system can facilitate discovery of nanoparticles targeting specific tissues and cells and accelerate the study of relationships between chemical structure and delivery in vivo.

 

 

A Smart, Photocontrollable Drug Release Nanosystem for Multifunctional Synergistic Cancer Therapy.

Author information: Yi Y1, Wang H1, Wang X1, Liu Q1, Ye M1, Tan W1,2.

1Molecular Science and Biomedicine Laboratory, College of Biology, State Key Laboratory for Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering and Collaborative Research Center of Molecular Engineering for Theranostics, Hunan University , Changsha 410082, China.
2Department of Chemistry, Department of Physiology and Functional Genomics, Center for Research at Bio/Nano Interface, Shands Cancer Center, University of Florida Genetics Institute, and McKnight Brain Institute, University of Florida , Gainesville, Florida 32611-7200, United States.
Journal: ACS Applied Materials & Interfaces

Date of e-pub: February 2017

Abstract: Multifunctional synergistic therapy holds promise in biomedical studies and clinical practice. However, strategies aimed at easily integrating the components of such multimodal therapies are needed. Therefore, we herein report a smart drug release nanosystem able to perform photodynamic therapy, photothermal therapy and chemotherapy in a photocontrollable manner. Doxorubicin (DOX), a chemotherapy drug, and 5, 10, 15, 20-tetrakis (1-methylpyridinium-4-yl) porphyrin (TMPyP4), a photosensitizer, were physically intercalated into a DNA assembly immobilized on gold nanorods. The drugs were efficiently delivered to target cells and released under light irradiation, resulting in a synergism that combined phototherapy and chemotherapy for cancer treatment. This smart, photocontrollable drug release nanosystem promises precisely controlled drug release for multifunctional synergistic cancer therapy.

 

 

Molecular Elucidation of Disease Biomarkers at the Interface of Chemistry and Biology.

Author information: Zhang L1,2, Wan S2, Jiang Y1,2, Wang Y2, Fu T1, Liu Q1, Cao Z2,3, Qiu L1,2, Tan W1,2.

1Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering and College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University , Changsha 410082, China.
2Department of Chemistry and Department of Physiology and Functional Genomics, Center for Research at Bio/nano Interface, UF Health Cancer Center, UF Genetics Institute, University of Florida , Gainesville, Florida 32611, United States.
3School of Pharmacy, Fudan University, Zhangjiang Branch , No. 826 Zhangheng Rd. Pudong New District, Shanghai 201203, China.
Journal: Journal of the American Chemical Society

Date of e-pub: February 2017

Abstract: Disease-related biomarkers are objectively measurable molecular signatures of physiological status that can serve as disease indicators or drug targets in clinical diagnosis and therapy, thus acting as a tool in support of personalized medicine. For example, the prostate-specific antigen (PSA) biomarker is now widely used to screen patients for prostate cancer. However, few such biomarkers are currently available, and the process of biomarker identification and validation is prolonged and complicated by inefficient methods of discovery and few reliable analytical platforms. Therefore, in this Perspective, we look at the advanced chemistry of aptamer molecules and their significant role as molecular probes in biomarker studies. As a special class of functional nucleic acids evolved from an iterative technology termed Systematic Evolution of Ligands by Exponential Enrichment (SELEX), these single-stranded oligonucleotides can recognize their respective targets with selectivity and affinity comparable to those of protein antibodies. Because of their fast turnaround time and exceptional chemical properties, aptamer probes can serve as novel molecular tools for biomarker investigations, particularly in assisting identification of new disease-related biomarkers. More importantly, aptamers are able to recognize biomarkers from complex biological environments such as blood serum and cell surfaces, which can provide direct evidence for further clinical applications. This Perspective highlights several major advancements of aptamer-based biomarker discovery strategies and their potential contribution to the practice of precision medicine.

 

 

Pseudomonas aeruginosa Oligoribonuclease Contributes to Tolerance to Ciprofloxacin by Regulating Pyocin Biosynthesis.

Author information: Chen F1, Chen G1, Liu Y1, Jin Y1, Cheng Z1, Liu Y2,3, Yang L2,3, Jin S4,5, Wu W4.

1State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, China.
2Singapore Centre for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, Singapore, Singapore.
3School of Biological Sciences, Division of Structural Biology and Biochemistry, Nanyang Technological University, Singapore, Singapore.
4State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, China sjin@ufl.edu wuweihui@nankai.edu.cn.
5Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, Florida, USA.
Journal: Antimicrobial Agents and Chemotherapy

Date of e-pub: February 2017

Abstract: Bacterial oligoribonuclease (Orn) is a conserved 3′-to-5′ exonuclease. In Pseudomonas aeruginosa, it has been demonstrated that Orn plays a major role in the hydrolysis of pGpG, which is required for cyclic-di-GMP homeostasis. Meanwhile, Orn is involved in the degradation of nanoRNAs, which can alter global gene expression by serving as transcription initiation primers. Previously, we found that Orn is required for the type III secretion system and pathogenesis of P. aeruginosa, indicating a role of Orn in the bacterial response to environmental stimuli. Here we report that Orn is required for the tolerance of P. aeruginosa to ciprofloxacin. Transcriptome analysis of an orn mutant revealed the upregulation of pyocin biosynthesis genes. Mutation of genes involved in pyocin biosynthesis in the background of an ornmutant restored bacterial tolerance to ciprofloxacin. We further demonstrate that the upregulation of pyocin biosynthesis genes is due to RecA-mediated autoproteolysis of PrtR, which is the major negative regulator of pyocin biosynthesis genes. In addition, the SOS response genes were upregulated in the orn mutant, indicating a DNA damage stress. Therefore, our results revealed a novel role of Orn in bacterial tolerance to ciprofloxacin.

 

 

Pseudomonas aeruginosa GroEL Stimulates Production of PTX3 by Activating the NF-κB Pathway and Simultaneously Downregulating MicroRNA-9.

Author information: Shin H1, Jeon J1, Lee JH1, Jin S2,3, Ha UH4.

1Department of Biotechnology and Bioinformatics, Korea University, Sejong, Republic of Korea.
2State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, China.
3Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida, USA.
4Department of Biotechnology and Bioinformatics, Korea University, Sejong, Republic of Korea haunhwan@korea.ac.kr.
Journal: Infection and Immunity

Date of e-pub: February 2017

Abstract: As one of the first lines of host defense, monocytes play important roles in clearing infected microbes. The defensive response is triggered by recognition of diverse microbial moieties, including released factors, which modulate host immune responses to establish a harsh environment for clinically important bacterial pathogens. In this study, we found that the expression of PTX3, a soluble form of pattern recognition receptor, was induced by infection with live Pseudomonas aeruginosa or treatment of cells with its supernatant. P. aeruginosa GroEL, a homolog of heat shock protein 60, was identified as one of the factors responsible for inducing the expression of PTX3 in host cells. GroEL induced PTX3 expression by activating the Toll-like receptor 4 (TLR4)-dependent pathway via nuclear factor-kappa B (NF-κB), while simultaneously inhibiting expression of microRNA-9, which targets the PTX3 transcript. Finally, by acting as an opsonin, GroEL-induced PTX3 promoted the association and phagocytosis of Staphylococcus aureus into macrophages. These data suggest that the host defensive environment is supported by the production of PTX3 in response to GroEL, which thus has therapeutic potential for clearance of bacterial infections.

 

 

Association of single nucleotide polymorphisms in candidate genes previously related to genetic variation in fertility with phenotypic measurements of reproductive function in Holstein cows.

Author information: Ortega MS1, Denicol AC1, Cole JB2, Null DJ2, Taylor JF3, Schnabel RD4, Hansen PJ5.

1Department of Animal Sciences, D.H. Barron Reproductive and Perinatal Biology Research Program and Genetics Institute, University of Florida, Gainesville 32611
2Animal Genomics and Improvement Laboratory, Agricultural Research Service, USDA, Beltsville, MD 20705
3Division of Animal Sciences, Columbia 65211
4Division of Animal Sciences, Columbia 65211; Informatics Institute, University of Missouri, Columbia 65211
5Department of Animal Sciences, D.H. Barron Reproductive and Perinatal Biology Research Program and Genetics Institute, University of Florida, Gainesville 32611. Electronic address: pjhansen@ufl.edu.
Journal: Journal of Dairy Science

Date of e-pub: March 2017

Abstract: Many genetic markers related to health or production traits are not evaluated in populations independent of the discovery population or related to phenotype. Here we evaluated 68 single nucleotide polymorphisms (SNP) in candidate genes previously associated with genetic merit for fertility and production traits for association with phenotypic measurements of fertility in a population of Holstein cows that was selected based on predicted transmitting ability (PTA) for daughter pregnancy rate (DPR; high, ≥1, n = 989; low, ≤ -1.0, n = 1,285). Cows with a high PTA for DPR had higher pregnancy rate at first service, fewer services per conception, and fewer days open than cows with a low PTA for DPR. Of the 68 SNP, 11 were associated with pregnancy rate at first service, 16 with services per conception, and 19 with days open. Single nucleotide polymorphisms in 12 genes (BDH2, BSP3, CAST, CD2, CD14, FUT1, FYB, GCNT3, HSD17B7, IBSP, OCLN, and PCCB) had significant associations with 2 fertility traits, and SNP in 4 genes (CSPP1, FCER1G, PMM2, and TBC1D24) had significant associations with each of the 3 traits. Results from this experiment were compared with results from 2 earlier studies in which the SNP were associated with genetic estimates of fertility. One study involved the same animals as used here, and the other study was of an independent population of bulls. A total of 13 SNP associated with 1 or more phenotypic estimates of fertility were directionally associated with genetic estimates of fertility in the same cow population. Moreover, 14 SNP associated with reproductive phenotype were directionally associated with genetic estimates of fertility in the bull population. Nine SNP (located in BCAS, BSP3, CAST, FUT1, HSD17B7, OCLN, PCCB, PMM2, and TBC1D24) had a directional association with fertility in all 3 studies. Examination of the function of the genes with SNP associated with reproduction in more than one study indicates the importance of steroid hormones and immune function as determinants of reproductive function. All but 1 of the 68 evaluated SNP were variable in 11 breeds besides Holstein, indicating the potential effects of these SNP on reproductive function across breeds of cattle.

 

 

Histone deacetylase 6 regulates cytokinesis and erythrocyte enucleation through deacetylation of formin protein mDia2.

Author information: Li X1, Mei Y2, Yan B1, Vitriol E1, Huang S3, Ji P2, Qiu Y4.

1Department of Anatomy and Cell Biology, College of Medicine, University of Florida, Gainesville, USA.
2Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, USA.
3Dept of Biochemistry and Molecular Biology,College of Medicine,University of Florida,Gainesville,USA.
4Division of Animal Sciences, Columbia 65211; Informatics Institute, University of Missouri, Columbia 65211
5Department of Anatomy and Cell Biology, College of Medicine, University of Florida, Gainesville, USA; qiuy@ufl.edu.
Journal: Haematologica

Date of e-pub: March 2017

Abstract: The formin mDia2 plays a critical role in a number of cellular processes through its ability to promote nucleation and elongation of actin filaments. In erythroblasts, this includes control of cytokinesis and enucleation by regulating contractile actin ring formation. Here, we report a novel mechanism of how mDia2 is regulated: through acetylation and deacetylation at lysine 970 in formin homology 2 domain. Ectopic expression of an acetyl-mimic mDia2 mutant in mouse erythroblasts is sufficient to abolish contractile actin ring formation at the cleavage furrow and subsequent erythrocyte cytokinesis and enucleation. Further, we have identified that Class II histone deacetylase 6 deacetylates and subsequently activates mDia2. Knock down or inhibition of histone deacetylase 6 impairs contractile actin ring formation, and expression of a non-acetyl-mimic mDia2 mutant restores the contractile actin ring and rescues the loss of enucleation. In addition to revealing a novel step in mDia2 regulation, this study may unveil a novel regulatory mechanism of formin mediated actin assembly, since the K970 acetylation site is conserved among Dia proteins.

 

 

Aberrant splicing in maize rough endosperm3 reveals a conserved role for U12 splicing in eukaryotic multicellular development.

Author information: Gault CM1,2, Martin F1,2, Mei W3, Bai F2, Black JB2, Barbazuk WB1,3,4, Settles AM5,2,4.

1 Plant Molecular and Cellular Biology Program, University of Florida, Gainesville, FL 32611.
2Horticultural Sciences Department, University of Florida, Gainesville, FL 32611.
3Department of Biology, University of Florida, Gainesville, FL 32611.
4Genetics Institute, University of Florida, Gainesville, FL 32611.
5Plant Molecular and Cellular Biology Program, University of Florida, Gainesville, FL 32611; settles@ufl.edu.
Journal: Proceedings of the National Academy of Sciences of the United States of America

Date of e-pub: February 2017

Abstract: RNA splicing of U12-type introns functions in human cell differentiation, but it is not known whether this class of introns has a similar role in plants. The maize ROUGH ENDOSPERM3 (RGH3) protein is orthologous to the human splicing factor, ZRSR2. ZRSR2 mutations are associated with myelodysplastic syndrome (MDS) and cause U12 splicing defects. Maize rgh3 mutants have aberrant endosperm cell differentiation and proliferation. We found that most U12-type introns are retained or misspliced in rgh3 Genes affected in rgh3 and ZRSR2 mutants identify cell cycle and protein glycosylation as common pathways disrupted. Transcripts with retained U12-type introns can be found in polysomes, suggesting that splicing efficiency can alter protein isoforms. The rgh3 mutant protein disrupts colocalization with a known ZRSR2-interacting protein, U2AF2. These results indicate conserved function for RGH3/ZRSR2 in U12 splicing and a deeply conserved role for the minor spliceosome to promote cell differentiation from stem cells to terminal fates.

 

 

Digest: Imperfect convergence in butterfly wing patterns.

Author information: Earl C1,2,3, Guralnick RP2,3, Kawahara AY2,3

1Genetics & Genomics Graduate Program, University of Florida, Gainesville, FL, USA.
2Genetics Institute, University of Florida, Gainesville, FL, USA.
3Florida Museum of Natural History, University of Florida, Gainesville, FL, USA.
Journal: Evolution

Date of e-pub: February 2017

Abstract: Butterfly wing patterns are among the most diverse morphological characteristics in nature, with many of the 18,000 or so described butterfly species readily distinguished by wing pattern alone. Wing pattern serves as one of the primary means of communication among species and is thus subject to strong natural selection for mimicry and warning color (aposematism). Convergent wing patterns are particularly evident across the butterfly genus Adelpha, suggesting this genus may be a good system to study the underlying mechanisms behind mimicry.

 

 

Regulatory cascade and biological activity of Beauveria bassiana oosporein that limits bacterial growth after host death.

Author information: Fan Y1, Liu X2, Keyhani NO3, Tang G2, Pei Y2, Zhang W2, Tong S2.

1Biotechnology Research Center, Southwest University, Chongqing 400715, China; fyh@swu.edu.cn.
2Biotechnology Research Center, Southwest University, Chongqing 400715, China.
3Department of Microbiology and Cell Science, University of Florida, Gainesville, FL 32611.
Journal: Proceedings of the National Academy of Sciences of the United States of America

Date of e-pub: February 2017

Abstract: The regulatory network and biological functions of the fungal secondary metabolite oosporein have remained obscure. Beauveria bassiana has evolved the ability to parasitize insects and outcompete microbial challengers for assimilation of host nutrients. A novel zinc finger transcription factor, BbSmr1 (B. bassiana secondary metabolite regulator 1), was identified in a screen for oosporein overproduction. Deletion of Bbsmr1 resulted in up-regulation of the oosporein biosynthetic gene cluster (OpS genes) and constitutive oosporein production. Oosporein production was abolished in double mutants of Bbsmr1 and a second transcription factor, OpS3, within the oosporein gene cluster (ΔBbsmr1ΔOpS3), indicating that BbSmr1 acts as a negative regulator of OpS3 expression. Real-time quantitative PCR and a GFP promoter fusion construct of OpS1, the oosporein polyketide synthase, indicated that OpS1 is expressed mainly in insect cadavers at 24-48 h after death. Bacterial colony analysis in B. bassiana-infected insect hosts revealed increasing counts until host death, with a dramatic decrease (∼90%) after death that correlated with oosporein production. In vitro studies verified the inhibitory activity of oosporein against bacteria derived from insect cadavers. These results suggest that oosporein acts as an antimicrobial compound to limit microbial competition on B. bassiana-killed hosts, allowing the fungus to maximally use host nutrients to grow and sporulate on infected cadavers.

 

 

Genome Editing for Sickle Cell Disease: A Little BCL11A Goes a Long Way.

Author information: Hossain MA1, Bungert J2

1Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USA; UF Health Cancer Center, Center for Epigenetics, Genetics Institute, University of Florida, Gainesville, FL 32610, USA.
2Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USA; UF Health Cancer Center, Center for Epigenetics, Genetics Institute, University of Florida, Gainesville, FL 32610, USA. Electronic address: jbungert@ufl.edu.
Journal: Molecular Therapy : The Journal of the American Society of Gene Therapy

Date of e-pub: March 2017

Abstract: N/A

 

 

Electroacupuncture relieves depression-like symptoms in rats exposed to chronic unpredictable mild stress by activating ERK signaling pathway.

Author information: Li W1, Zhu Y2, Saud SM3, Guo Q4, Xi S5, Jia B6, Jiao S7, Yang X8, Lu J8, Song S9, Tu Y10.

1Department of Scientific Research Management, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China. Electronic address: lwddoctor@hotmail.com.
2Xi’an XD Group Hospital, Xi’an 710077, China.
3Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Newark, NJ 07103, USA.
4Oncology Department, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.
5Department of Traditional Chinese Medicine, Medical College of the Xiamen University, Xiamen 361102, China.
6Department of Acupuncture, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.
7Editorial department, Journal of Traditional Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.
8School of Acupuncture-Moxibustion and Tui Na, Beijing University of Chinese Medicine, Beijing 100029, China.
9Department of Pharmaceutics, University of Florida, Gainesville, FL 32610, USA.
10School of Acupuncture-Moxibustion and Tui Na, Beijing University of Chinese Medicine, Beijing 100029, China. Electronic address: tuyab@263.net.
Journal: Neuroscience Letters

Date of e-pub: March 2017

Abstract: Electroacupuncture (EA) has been shown to alleviate the symptoms associated with major depressive disorder; however, the underlying mechanisms remain unclear. While the mainstay treatment for depression are pharmacological agents that modulate serotonergic and/or noradrenergic activity of the brain, recent data suggest that, neurotrophins may play a larger role in the pathogenesis of depression and may offer better therapeutic potential in alleviating symptoms associated with depression. One downstream target of neurotrophins is the extracellular signal-regulated kinase (ERK)/Mitogen-activated protein kinase (MAPK) cascade, a major mediator of cellular stress often associated with clinical depression. In this study, we assessed whether the efficacy of EA is due to regulation of these novel pathways using an animal model of depression induced by chronic unpredictable mild stress (CUMS). We found that EA stimulation at specific locations, Baihui (GV20), and Yintang (GV29) ameliorated the behavioral responses of CUMS, which included reduced locomotion, decreased sucrose intake and weight loss. Furthermore, EA increased the activation of ERK and ribosomal s6 kinase (RSK) levels under stress. Both the behavioral and biochemical responses to EA were attenuated with administration of ERK inhibitor, suggesting that EA improves depression-like symptoms in stressed rats, in part, by activation of ERK signaling.

 

 

SHH Protein Variance in the Limb Bud Is Constrained by Feedback Regulation and Correlates with Altered Digit Patterning.

Author information: Zhang R1,2, Lee C1,2, Lawson LY1,2, Svete LJ1,2, McIntyre LM1,2, Harfe BD3,2.

1Department of Molecular Genetics & Microbiology, College of Medicine, University of Florida, Gainesville, Florida 32610.
2Genetics Institute, University of Florida, Gainesville, Florida 32610.
3Department of Molecular Genetics & Microbiology, College of Medicine, University of Florida, Gainesville, Florida 32610 bharfe@ufl.edu.
Journal: G3 (Bethesda, Md.)

Date of e-pub: March 2017

Abstract: mRNA variance has been proposed to play key roles in normal development, population fitness, adaptability, and disease. While variance in gene expression levels may be beneficial for certain cellular processes, for example in a cell’s ability to respond to external stimuli, variance may be detrimental for the development of some organs. In the bilaterally symmetric vertebrate limb buds, the amount of Sonic Hedgehog (SHH) protein present at specific stages of development is essential to ensure proper patterning of this structure. To our surprise, we found that SHH protein variance is present during the first 10 hr of limb development. The variance is virtually eliminated after the first 10 hr of limb development. By examining mutant animals, we determined that the ability of the limb bud apical ectodermal ridge (AER) to respond to SHH protein was required for reducing SHH variance during limb formation. One consequence of the failure to eliminate variance in SHH protein was the presence of polydactyly and an increase in digit length. These data suggest a potential novel mechanism in which alterations in SHH variance during evolution may have driven changes in limb patterning and digit length.

 

 

Pseudouridine Modification Inhibits Muscleblind-like 1 (MBNL1) Binding to CCUG Repeats and Minimally Structured RNA through Reduced RNA Flexibility.

Author information: deLorimier E1, Hinman MN1, Copperman J1, Datta K2, Guenza M1, Berglund J3,2.

1From the Institute of Molecular Biology, Department of Chemistry and Biochemistry, University of Oregon, Eugene, Oregon 97403 and.
2the Center for NeuroGenetics, Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, Florida 32610-3010.
3From the Institute of Molecular Biology, Department of Chemistry and Biochemistry, University of Oregon, Eugene, Oregon 97403 and aberglund@ufl.edu.
Journal: The Journal of Biological Chemistry

Date of e-pub: March 2017

Abstract: Myotonic dystrophy type 2 is a genetic neuromuscular disease caused by the expression of expanded CCUG repeat RNAs from the non-coding region of the CCHC-type zinc finger nucleic acid-binding protein (CNBP) gene. These CCUG repeats bind and sequester a family of RNA-binding proteins known as Muscleblind-like 1, 2, and 3 (MBNL1, MBNL2, and MBNL3), and sequestration plays a significant role in pathogenicity. MBNL proteins are alternative splicing regulators that bind to the consensus RNA sequence YGCY (Y = pyrimidine). This consensus sequence is found in the toxic RNAs (CCUG repeats) and in cellular RNA substrates that MBNL proteins have been shown to bind. Replacing the uridine in CCUG repeats with pseudouridine (Ψ) resulted in a modest reduction of MBNL1 binding. Interestingly, Ψ modification of a minimally structured RNA containing YGCY motifs resulted in more robust inhibition of MBNL1 binding. The different levels of inhibition between CCUG repeat and minimally structured RNA binding appear to be due to the ability to modify both pyrimidines in the YGCY motif, which is not possible in the CCUG repeats. Molecular dynamic studies of unmodified and pseudouridylated minimally structured RNAs suggest that reducing the flexibility of the minimally structured RNA leads to reduced binding by MBNL1.

 

 

Luminescent iridium(iii) complexes as COX-2-specific imaging agents in cancer cells.

Author information: Liu C1, Yang C2, Lu L3, Wang W1, Tan W4, Leung CH2, Ma DL1.

1Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China. edmondma@hkbu.edu.hk.
2State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China. duncanleung@umac.mo.
3Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China. edmondma@hkbu.edu.hk and College of Chemistry and Pharmaceutical Sciences, Qingdao Agricultural University, Qingdao 266109, China.
4Department of Chemistry and Department of Physiology and Functional Genomics, Center for Research at the Bio/Nano Interface, Shands Cancer Center, UF Genetics Institute, McKnight Brain Institute, University of Florida, Gainesville, USA. tan@chem.ufl.edu and Molecular Sciences and Biomedicine Laboratory, State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering and College of Biology, Collaborative Innovation Center for Molecular Engineering and Theranostics, Hunan University, Changsha, China.
Journal: Chemical Communications (Cambridge, England)

Date of e-pub: March 2017

Abstract: Two luminescent iridium(iii) complexes, 1 and 2, were synthesized and evaluated for their ability to probe COX-2 in human cancer cells. This is the first application of iridium(iii) complexes as imaging agents for COX-2. We demonstrate that complex 1 differentiates cancer cells from normal cells with high stability and low cytotoxicity.

 

 

The peopling of the Americas and the origin of the Beringian occupation model.

Author information: Mulligan CJ1, Szathmáry EJ2.

1Department of Anthropology, Genetics Institute, University of Florida, Gainesville, Florida, 32610-3610.
2Department of Anthropology, University of Manitoba, Winnipeg, Manitoba, Canada, R3T 2M6.
Journal: American Journal of Physical Anthropology

Date of e-pub: March 2017

Abstract: The current model for peopling of the Americas involves divergence from an ancestral Asian population followed by a period of population isolation and genetic diversification in Beringia, and finally, a rapid expansion into and throughout the Americas. Studies in the 1970s sought to characterize the biological relationships between different indigenous populations and first proposed an occupation of Beringia. More recent studies using molecular genetic markers often neglect to reference early works that laid the groundwork for current colonization models. We address this matter, and briefly summarize the literature and technological advances that contributed to our current understanding of the peopling of the Americas. Furthermore, we argue that describing the process of peopling of the Americas as “migrations from Asia” minimizes the significant genetic diversification that occurred outside of Asia, and offends indigenous Americans by discounting their origin narratives and land rights. Rather than referring to the indigenous peoples of the Americas as “migrants” or “immigrants,” we recommend consistency in the language used to describe all post-glacial expansions of people into Asia, Europe and the Americas.

 

 

Concise Review: Induced Pluripotent Stem Cell Research in the Era of Precision Medicine.

Author information: Hamazaki T1, El Rouby N2, Fredette NC3, Santostefano KE3, Terada N3.

1Department of Pediatrics, Osaka City University Graduate School of Medicine, Osaka, Japan.
2Department of Pharmacotherapy and Translational Research, College of Pharmacy, and Center for Pharmacogenomics, Gainesville, Florida, USA.
3Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, and Center for Cellular Reprogramming, University of Florida, Gainesville, Florida, USA.
Journal: Stem Cells

Date of e-pub: March 2017

Abstract: Recent advances in DNA sequencing technologies are revealing how human genetic variations associate with differential health risks, disease susceptibilities, and drug responses. Such information is now expected to help evaluate individual health risks, design personalized health plans and treat patients with precision. It is still challenging, however, to understand how such genetic variations cause the phenotypic alterations in pathobiologies and treatment response. Human induced pluripotent stem cell (iPSC) technologies are emerging as a promising strategy to fill the knowledge gaps between genetic association studies and underlying molecular mechanisms. Breakthroughs in genome editing technologies and continuous improvement in iPSC differentiation techniques are particularly making this research direction more realistic and practical. Pioneering studies have shown that iPSCs derived from a variety of monogenic diseases can faithfully recapitulate disease phenotypes in vitro when differentiated into disease-relevant cell types. It has been shown possible to partially recapitulate disease phenotypes, even with late onset and polygenic diseases. More recently, iPSCs have been shown to validate effects of disease and treatment-related single nucleotide polymorphisms identified through genome wide association analysis. In this review, we will discuss how iPSC research will further contribute to human health in the coming era of precision medicine. Stem Cells 2017;35:545-550.

 

 

A method for obtaining simian immunodeficiency virus RNA sequences from laser capture microdissected and immune captured CD68+ and CD163+ macrophages from frozen tissue sections of bone marrow and brain.

Author information: Mallard J1, Papazian E1, Soulas C2, Nolan DJ3, Salemi M3, Williams KC4.

1Department of Biology, Boston College, Chestnut Hill, MA, USA.
2Department of Biology, Boston College, Chestnut Hill, MA, USA; Department of Research and Development, Innate Pharma, Marseille, France.
3Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA; Department of Pathology Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL, USA.
4Department of Biology, Boston College, Chestnut Hill, MA, USA. Electronic address: kenneth.williams.3@bc.edu.
Journal: Journal of Immunological Methods

Date of e-pub: March 2017

Abstract: Laser capture microdissection (LCM) is used to extract cells or tissue regions for analysis of RNA, DNA or protein. Several methods of LCM are established for different applications, but a protocol for consistently obtaining lentiviral RNA from LCM captured immune cell populations is not described. Obtaining optimal viral RNA for analysis of viral genes from immune-captured cells using immunohistochemistry (IHC) and LCM is challenging. IHC protocols have long antibody incubation times that increase risk of RNA degradation. But, immune capture of specific cell populations like macrophages without staining for virus cannot result in obtaining only a fraction of cells which are productively lentivirally infected. In this study we sought to obtain simian immunodeficiency virus (SIV) RNA from SIV gp120+ and CD68+ monocyte/macrophages in bone marrow (BM) and CD163+ perivascular macrophages in brain of SIV-infected rhesus macaques. Here, we report an IHC protocol with RNase inhibitors that consistently results in optimal quantity and yield of lentiviral RNA from LCM-captured immune cells.

 

 

In planta production and characterization of a hyperthermostable GH10 xylanase in transgenic sugarcane.

Author information: Kim JY1,2, Nong G3, Rice JD3, Gallo M1,4, Preston JF3, Altpeter F5.

1Plant Molecular and Cellular Biology Program, Agronomy Department, Genetics Institute, University of Florida – IFAS, Gainesville, FL, USA.
2Division of Biotechnology, Korea University, Seongbuk-Gu, Seoul, 02841, Republic of Korea.
3Department of Microbiology and Cell Science, University of Florida – IFAS, Gainesville, FL, USA.
4Delaware Valley University, Doylestown, PA, USA.
5Plant Molecular and Cellular Biology Program, Agronomy Department, Genetics Institute, University of Florida – IFAS, Gainesville, FL, USA. altpeter@ufl.edu.
Journal: Plant Molecular Biology

Date of e-pub: March 2017

Abstract: Sugarcane (Saccharum sp. hybrids) is one of the most efficient and sustainable feedstocks for commercial production of fuel ethanol. Recent efforts focus on the integration of first and second generation bioethanol conversion technologies for sugarcane to increase biofuel yields. This integrated process will utilize both the cell wall bound sugars of the abundant lignocellulosic sugarcane residues in addition to the sucrose from stem internodes. Enzymatic hydrolysis of lignocellulosic biomass into its component sugars requires significant amounts of cell wall degrading enzymes. In planta production of xylanases has the potential to reduce costs associated with enzymatic hydrolysis but has been reported to compromise plant growth and development. To address this problem, we expressed a hyperthermostable GH10 xylanase, xyl10B in transgenic sugarcane which displays optimal catalytic activity at 105 °C and only residual catalytic activity at temperatures below 70 °C. Transgene integration and expression in sugarcane were confirmed by Southern blot, RT-PCR, ELISA and western blot following biolistic co-transfer of minimal expression cassettes of xyl10B and the selectable neomycin phosphotransferase II. Xylanase activity was detected in 17 transgenic lines with a fluorogenic xylanase activity assay. Up to 1.2% of the total soluble protein fraction of vegetative progenies with integration of chloroplast targeted expression represented the recombinant Xyl10B protein. Xyl10B activity was stable in vegetative progenies. Tissues retained 75% of the xylanase activity after drying of leaves at 35 °C and a 2 month storage period. Transgenic sugarcane plants producing Xyl10B did not differ from non-transgenic sugarcane in growth and development under greenhouse conditions. Sugarcane xylan and bagasse were used as substrate for enzymatic hydrolysis with the in planta produced Xyl10B. TLC and HPLC analysis of hydrolysis products confirmed the superior catalytic activity and stability of the in planta produced Xyl10B with xylobiose as a prominent degradation product. These findings will contribute to advancing consolidated processing of lignocellulosic sugarcane biomass.

 

 

Utility of Microdialysis in Infectious Disease Drug Development and Dose Optimization.

Author information: Deitchman AN1, Heinrichs MT1, Khaowroongrueng V1, Jadhav SB1, Derendorf H2.

1Department of Pharmaceutics, University of Florida, 1345 Center Drive, PO Box 100494, Gainesville, Florida, 32610, USA.
2Department of Pharmaceutics, University of Florida, 1345 Center Drive, PO Box 100494, Gainesville, Florida, 32610, USA. hartmut@ufl.edu.
Journal: The AAPS Journal

Date of e-pub: March 2017

Abstract: Adequate drug penetration to a site of infection is absolutely imperative to ensure sufficient antimicrobial treatment. Microdialysis is a minimally invasive, versatile technique, which can be used to study the penetration of an antiinfective agent in virtually any tissue of interest. It has been used to investigate drug distribution and pharmacokinetics in variable patient populations, as a tool in dose optimization, a potential utility in therapeutic drug management, and in the study of biomarkers of disease progression. While all of these applications have not been fully explored in the field of antiinfectives, this review provides an overview of how microdialysis has been applied in various phases of drug development, a focus on the specific applications in the subspecialties of infectious disease (treatment of bacterial, fungal, viral, parasitic, and mycobacterial infections), and developing applications (biomarkers and therapeutic drug management).

 

 

Age-Specific Prevalence of Hoarding and Obsessive Compulsive Disorder: A Population-Based Study.

Author information: Cath DC1, Nizar K2, Boomsma D3, Mathews CA4.

1Department of Clinical Psychology, Utrecht University, Utrecht, The Netherlands; Department of Psychiatry, University Medical Center Groningen, Rob Giel Onderzoekscentrum, Groningen, The Netherlands.
2Department of Psychiatry, University of California, San Francisco, San Francisco, CA.
3Department of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands.
4Department of Psychiatry, University of Florida, Gainesville, FL. Electronic address: carolmathews@ufl.edu.
Journal: The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry

Date of e-pub: March 2017

Abstract: Little is known about the age-specific prevalence of hoarding and obsessive compulsive symptoms (OCS), particularly in older age groups. The objectives of this study were to estimate the age-specific prevalence, severity, and relationships between hoarding and OCS in males and females using a large population-based sample.

We assessed the age-specific prevalence rates of hoarding disorder (HD) and OC disorder (OCD) in males and females (at various age ranges between 15 and 97 years) from the Netherlands Twins Register (N = 15,194). Provisional HD and OCD diagnoses were made according to Diagnostic and Statistical Manual of Mental Health Disorders, 5th Edition, criteria using self-report measures. We also assessed hoarding and OCS severity in the various age groups and explored specific hoarding and OCS patterns (e.g., difficulty discarding, excessive acquisition, clutter, checking, washing, perfectionism, and obsessions) with age.

Prevalence of provisional HD diagnoses (2.12%) increased linearly by 20% with every 5 years of age (z = 13.8, p < 0.0001) and did not differ between males and females. Provisional OCD diagnoses were most common in younger individuals and in individuals over age 65. Co-occurring OCD increased hoarding symptom severity (coefficient: 4.5; SE: 0.2; 95% CI: 4.1-4.9; t = 22.0, p < 0.0001). Difficulty discarding for HD and checking behaviors for OCD appeared to drive most increases in these diagnoses in older ages.

Increased prevalence and severity of HD with age appears to be primarily driven by difficulties with discarding. Increases in OCD prevalence with older age were unexpected and of potential clinical relevance.

 

 

Islet-Derived CD4 T Cells Targeting Proinsulin in Human Autoimmune Diabetes.

Author information: Michels AW1, Landry LG1, McDaniel KA1, Yu L1, Campbell-Thompson M2, Kwok WW3,4, Jones KL5, Gottlieb PA1, Kappler JW1,6,7,8,9, Tang Q10,11, Roep BO12,13, Atkinson MA2, Mathews CE2, Nakayama M14,6.

1Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO.
2Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL.
3Benaroya Research Institute at Virginia Mason, Seattle, WA.
4Department of Medicine, University of Washington, Seattle, WA.
5Department of Pediatrics, Section of Hematology, Oncology, and Bone Marrow Transplant, University of Colorado School of Medicine, Aurora, CO.
6Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO.
7Howard Hughes Medical Institute, Denver, CO.
8Department of Biomedical Research, National Jewish Health, Denver, CO.
9Program in Structural Biology and Biochemistry, University of Colorado School of Medicine, Aurora, CO.
10Department of Surgery, University of California, San Francisco, San Francisco, CA.
11Diabetes Center, University of California, San Francisco, San Francisco, CA.
12Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
13Department of Diabetes Immunology, Diabetes & Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, CA.
14Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO maki.nakayama@ucdenver.edu.
Journal: Diabetes

Date of e-pub: March 2017

Abstract: Type 1 diabetes results from chronic autoimmune destruction of insulin-producing β-cells within pancreatic islets. Although insulin is a critical self-antigen in animal models of autoimmune diabetes, due to extremely limited access to pancreas samples, little is known about human antigenic targets for islet-infiltrating T cells. Here we show that proinsulin peptides are targeted by islet-infiltrating T cells from patients with type 1 diabetes. We identified hundreds of T cells from inflamed pancreatic islets of three young organ donors with type 1 diabetes with a short disease duration with high-risk HLA genes using a direct T-cell receptor (TCR) sequencing approach without long-term cell culture. Among 85 selected CD4 TCRs tested for reactivity to preproinsulin peptides presented by diabetes-susceptible HLA-DQ and HLA-DR molecules, one T cell recognized C-peptide amino acids 19-35, and two clones from separate donors responded to insulin B-chain amino acids 9-23 (B:9-23), which are known to be a critical self-antigen-driving disease progress in animal models of autoimmune diabetes. These B:9-23-specific T cells from islets responded to whole proinsulin and islets, whereas previously identified B:9-23 responsive clones from peripheral blood did not, highlighting the importance of proinsulin-specific T cells in the islet microenvironment.

 

 

Polymorphism at expressed DQ and DR loci in five common equine MHC haplotypes.

Author information: Miller D1, Tallmadge RL1, Binns M2, Zhu B3, Mohamoud YA4, Ahmed A4, Brooks SA5, Antczak DF6.

1Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA.
2Equine Analysis Systems, 5472 Leestown Road, Lexington, KY, 40511, USA.
3Children’s Hospital of Oakland Research Institute, Oakland, CA, 94609, USA.
4Weill Cornell Medicine-Qatar, Doha, Qatar.
5University of Florida, Gainesville, FL, 32611, USA.
6Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA. dfa1@cornell.edu.
Journal: Immunogenetics

Date of e-pub: March 2017

Abstract: The polymorphism of major histocompatibility complex (MHC) class II DQ and DR genes in five common equine leukocyte antigen (ELA) haplotypes was determined through sequencing of mRNA transcripts isolated from lymphocytes of eight ELA homozygous horses. Ten expressed MHC class II genes were detected in horses of the ELA-A3 haplotype carried by the donor horses of the equine bacterial artificial chromosome (BAC) library and the reference genome sequence: four DR genes and six DQ genes. The other four ELA haplotypes contained at least eight expressed polymorphic MHC class II loci. Next generation sequencing (NGS) of genomic DNA of these four MHC haplotypes revealed stop codons in the DQA3 gene in the ELA-A2, ELA-A5, and ELA-A9 haplotypes. Few NGS reads were obtained for the other MHC class II genes that were not amplified in these horses. The amino acid sequences across haplotypes contained locus-specific residues, and the locus clusters produced by phylogenetic analysis were well supported. The MHC class II alleles within the five tested haplotypes were largely non-overlapping between haplotypes. The complement of equine MHC class II DQ and DR genes appears to be well conserved between haplotypes, in contrast to the recently described variation in class I gene loci between equine MHC haplotypes. The identification of allelic series of equine MHC class II loci will aid comparative studies of mammalian MHC conservation and evolution and may also help to interpret associations between the equine MHC class II region and diseases of the horse.

 

 

Animal models of RLS phenotypes.

Author information: Allen RP1, Donelson NC2, Jones BC3, Li Y4, Manconi M5, Rye DB6, Sanyal S2, Winkelmann J7.

1Johns Hopkins Research Institute, Asthma& Allergy Bldg 1B76b, 5501 Hopkins Bayview Blvd, Baltimore, MD 21224, USA.
2Neurology Research, 115 Broadway, Bio 6, Biogen, Cambridge, MA 02142, USA.
3Department of Genetics, Genomics and Informatics, University of Tennessee, Memphis, TN, USA. Electronic address: bjone129@uthsc.edu.
4Department of Neurology, College of Medicine, University of Florida, Gainesville, Florida 32610, USA.
5Sleep Center, Neurocenter of Southern Switzerland, Civic Hospital of Lugano, Lugano, Switzerland.
6Program in Sleep, Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA.
7Institute of Neurogenomics, Helmholtz Zentrum München, Munich, Germany.
Journal: Sleep Medicine

Date of e-pub: March 2017

Abstract: Restless legs syndrome (RLS) is a complex disorder that involves sensory and motor systems. The major pathophysiology of RLS is low iron concentration in the substantia nigra containing the cell bodies of dopamine neurons that project to the striatum, an area that is crucial for modulating movement. People who have RLS often present with normal iron values outside the brain; recent studies implicate several genes are involved in the syndrome. Like most complex diseases, animal models usually do not faithfully capture the full phenotypic spectrum of “disease,” which is a uniquely human construct. Nonetheless, animal models have proven useful in helping to unravel the complex pathophysiology of diseases such as RLS and suggesting novel treatment paradigms. For example, hypothesis-independent genome-wide association studies (GWAS) have identified several genes as increasing the risk for RLS, including BTBD9. Independently, the murine homolog Btbd9 was identified as a candidate gene for iron regulation in the midbrain in mice. The relevance of the phenotype of another of the GWAS identified genes, MEIS1, has also been explored. The role of Btbd9 in iron regulation and RLS-like behaviors has been further evaluated in mice carrying a null mutation of the gene and in fruit flies when the BTBD9 protein is degraded. The BTBD9 and MEIS1 stories originate from human GWAS research, supported by work in a genetic reference population of mice (forward genetics) and further verified in mice, fish flies, and worms. Finally, the role of genetics is further supported by an inbred mouse strain that displays many of the phenotypic characteristics of RLS. The role of animal models of RLS phenotypes is also extended to include periodic limb movements.

 

 

Effect-based tools for monitoring estrogenic mixtures: Evaluation of five in vitro bioassays.

Author information: Kunz PY1, Simon E1, Creusot N2, Jayasinghe BS3, Kienle C1, Maletz S4, Schifferli A1., Schönlau C4, Aït-Aïssa S2, Denslow ND3, Hollert H4, Werner I1, Vermeirssen EL5.

1Swiss Centre for Applied Ecotoxicology Eawag-EPFL, 8600 Dübendorf, Switzerland.
2INERIS, Institut National de l’Environnement Industriel et des Risques, Unité ECOT, Verneuil en Halatte, France.
3University of Florida, Center for Environmental and Human Toxicology, Gainesville, FL, USA.
4RWTH Aachen University, Institute for Environmental Research, Aachen, Germany.
5Swiss Centre for Applied Ecotoxicology Eawag-EPFL, 8600 Dübendorf, Switzerland. Electronic address: etienne.vermeirssen@oekotoxzentrum.ch.
Journal: Water Research

Date of e-pub: March 2017

Abstract: In vitro estrogen receptor transactivation assays (ERTAs) are increasingly used to measure the overall estrogenic activity of environmental water samples, which may serve as an indicator of exposure of fish or other aquatic organisms to (xeno)estrogens. Another potential area of application of ERTAs is to assist the monitoring of the potent steroids 17β-estradiol (E2) and 17α-ethinylestradiol (EE2) under the Water Framework Directive (WFD) watch-list mechanism. Chemical analysis of E2 and EE2 is currently hampered by limits of quantification being mostly above the proposed annual average Environmental Quality Standards (AA-EQS) of 0.4 and 0.035 ng/L, respectively. Sensitive ERTAs could circumvent current detection challenges by measuring total estrogenic activity expressed as E2-equivalent (EEQ) concentrations. However, the use of different ERTAs results in different EEQ concentrations for the same sample. Reasons for these differences are known, but it remains unclear how to use and interpret bioassay results in a harmonised way. The aim of this study was to compare the intra- and inter-day variability of EEQ measurements using five different ERTAs (YES, ERα-CALUX, MELN, T47D-KBluc and GeneBLAzer-ERα) with regard to their applicability as effect-based tools in environmental monitoring. Environmentally relevant artificial mixtures of (xeno)estrogens were prepared to represent samples with higher (i.e. multiple times the AA-EQS for E2) or lower pollution levels (i.e. around the AA-EQS for E2). Mixtures were tested either directly or following solid phase extraction (SPE). The SPE step was included, as environmental samples typically require enrichment before analysis. Samples were analysed repeatedly to test intra-day and inter-day variability. Estrogenicity was quantified using the 10% effect level (PC10) of the positive control (E2) and expressed as EEQ concentrations. The average coefficient of variation (CV) of EEQ concentrations for the five ERTAs and all samples was 32%. CV was lower for intra-day experiments (30%) compared to inter-day experiments (37%). Sample extraction using SPE did not lead to additional variability; the intra-day CV for SPE extracted samples was 28%. Of the five ERTAs, ERα-CALUX had the best precision and repeatability (overall CV of 13%).

 

 

Current limitations and recommendations to improve testing for the environmental assessment of endocrine active substances.

Author information: Coady KK1, Biever RC2, Denslow ND3, Gross M4, Guiney PD5, Holbech H6, Karouna-Renier NK7, Katsiadaki I8, Krueger H9, Levine SL10, Maack G11, Williams M12, Wolf JC13, Ankley GT14.

1The Dow Chemical Company, Toxicology and Environmental Research and Consulting, Midland, Michigan, USA.
2Smithers Viscient Laboratories, Wareham, Massachusetts, USA.
3Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, Florida, USA.
4wca, Faringdon, United Kingdom.
5Molecular and Environmental Toxicology Center, University of Wisconsin, Madison, Madison, Wisconsin, USA.
6Department of Biology, University of Southern Denmark, Odense M, Denmark.
7USGS Patuxent Wildlife Research Center, Beltsville, Maryland.
8Centre for Environment Fisheries and Aquaculture Science, Dorset, United Kingdom.
9Wildlife International, Division of EAG Laboratories, Easton, Maryland, USA.
10Global Regulatory Sciences, Monsanto Company, St Louis, Missouri, USA.
11German Environment Agency, Dessau-Roßlau, Germany.
12CSIRO Land and Water, South Australia, Australia.
13Experimental Pathology Laboratories, Sterling, Virginia, USA.
14US Environmental Protection Agency, Duluth, Minnesota.
Journal: Integrated Environmental Assessment and Management

Date of e-pub: March 2017

Abstract: In the present study, existing regulatory frameworks and test systems for assessing potential endocrine active chemicals are described, and associated challenges are discussed, along with proposed approaches to address these challenges. Regulatory frameworks vary somewhat across geographies, but all basically evaluate whether a chemical possesses endocrine activity and whether this activity can result in adverse outcomes either to humans or to the environment. Current test systems include in silico, in vitro, and in vivo techniques focused on detecting potential endocrine activity, and in vivo tests that collect apical data to detect possible adverse effects. These test systems are currently designed to robustly assess endocrine activity and/or adverse effects in the estrogen, androgen, and thyroid hormone signaling pathways; however, there are some limitations of current test systems for evaluating endocrine hazard and risk. These limitations include a lack of certainty regarding: 1) adequately sensitive species and life stages; 2) mechanistic endpoints that are diagnostic for endocrine pathways of concern; and 3) the linkage between mechanistic responses and apical, adverse outcomes. Furthermore, some existing test methods are resource intensive with regard to time, cost, and use of animals. However, based on recent experiences, there are opportunities to improve approaches to and guidance for existing test methods and to reduce uncertainty. For example, in vitro high-throughput screening could be used to prioritize chemicals for testing and provide insights as to the most appropriate assays for characterizing hazard and risk. Other recommendations include adding endpoints for elucidating connections between mechanistic effects and adverse outcomes, identifying potentially sensitive taxa for which test methods currently do not exist, and addressing key endocrine pathways of possible concern in addition to those associated with estrogen, androgen, and thyroid signaling. Integr Environ Assess Manag 2017;13:302-316. © 2016 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

 

 

Effects of four commercial fungal formulations on mortality and sporulation in house flies (Musca domestica) and stable flies (Stomoxys calcitrans).

Author information: Weeks EN1, Machtinger ET2, Gezan SA3, Kaufman PE1, Geden CJ4.

1Department of Entomology and Nematology, University of Florida, Gainesville, FL, U.S.A.
2Invasive Insect Biocontrol and Behaviour Laboratory, U.S. Department of Agriculture-Agricultural Research Service (USDA-ARS), Beltsville, MD, U.S.A.
3School of Forest Resources and Conservation, University of Florida, Gainesville, FL, U.S.A.
4Center for Medical, Agricultural and Veterinary Entomology, USDA-ARS, Gainesville, FL, U.S.A.
Journal: Medical and Veterinary Entomology

Date of e-pub: March 2017

Abstract: The house fly Musca domestica L. (Diptera: Muscidae) and stable fly Stomoxys calcitrans (L.) (Diptera: Muscidae) are major pests of livestock. Biological control is an important tool in an integrated control framework. Increased mortality in filth flies has been documented with entomopathogenic fungi, several strains of which are commercially available. Three strains of Beauveria bassiana (Balsamo-Crivelli) Vuillemin (Hypocreales: Cordycipitaceae) and one strain of Metarhizium brunneum (Petch) (Hypocreales: Clavicipitaceae) were tested in commercial formulations for pathogenicity against house flies and stable flies. There was a significant increase in mortality of house flies with three of the formulations, BotaniGard® ES, Mycotrol® O, and Met52® EC, during days 4-9 in comparison with balEnce™ and the control. In stable flies, mortality rates were highest with Met52® EC, followed by Mycotrol® O, BotaniGard® ES and, finally, balEnce™. There was a significant fungal effect on sporulation in both house flies and stable flies. Product formulation, species differences and fungal strains may be responsible for some of the differences observed. Future testing in field situations is necessary. These commercial biopesticides may represent important tools in integrated fly management programmes.

 

 

Plant-Derived Terpenes: A Feedstock for Specialty Biofuels.

Author information: Mewalal R1, Rai DK2, Kainer D3, Chen F4, Külheim C3, Peter GF5, Tuskan GA6.

1Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA.
2Biology and Soft Matter Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA.
3Research School of Biology, The Australian National University, Canberra, ACT 2601, Australia.
4Department of Plant Sciences, University of Tennessee, Knoxville, TN 37996, USA.
5School of Forest Resources and Conservation, University of Florida, Gainesville, FL 32611, USA.
6Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA. Electronic address: tuskanga@ornl.gov.
Journal: Trends in Biotechnology

Date of e-pub: March 2017

Abstract: Research toward renewable and sustainable energy has identified specific terpenes capable of supplementing or replacing current petroleum-derived fuels. Despite being naturally produced and stored by many plants, there are few examples of commercial recovery of terpenes from plants because of low yields. Plant terpene biosynthesis is regulated at multiple levels, leading to wide variability in terpene content and chemistry. Advances in the plant molecular toolkit, including annotated genomes, high-throughput omics profiling, and genome editing, have begun to elucidate plant terpene metabolism, and such information is useful for bioengineering metabolic pathways for specific terpenes. We review here the status of terpenes as a specialty biofuel and discuss the potential of plants as a viable agronomic solution for future terpene-derived biofuels.

 
NOTE: These abstracts were retrieved from the U.S. National Library of Medicine website managed in collaboration with the U.S. National Library of Medicine

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