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UFGI publication round-up week 2/19

Sci Rep. 2018 Feb 21;8(1):3430. doi: 10.1038/s41598-018-21653-x.

Proteome analysis of Aspergillus flavus isolate-specific responses to oxidative stress in relationship to aflatoxin production capability.

Author information

1
Department of Plant Pathology, University of Georgia, Tifton, GA, USA.
2
USDA-ARS Crop Protection and Management Research Unit, Tifton, GA, USA.
3
Center of Excellence in Genomics & Systems Biology, International Crop Research Institute for the Semi-Arid Tropics (ICRISAT), Patancheru, Telangana, India.
4
Department of Biology, Genetics Institute, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, FL, USA.
5
College of Biology and Environmental Science, Nanjing Forestry University, Nanjing, China.
6
College of Plant Protection, Fujian Agriculture and Forestry University, Fuzhou, Fujian, China.
7
Department of Plant Pathology and Crop Physiology, Louisiana State University, Baton Rouge, LA, USA.
8
Department of Crop and Soil Sciences, University of Georgia, Tifton, GA, USA.
9
USDA-ARS Crop Protection and Management Research Unit, Tifton, GA, USA. baozhu.guo@ars.usda.gov.

Abstract

Aspergillus flavus is an opportunistic pathogen of plants such as maize and peanut under conducive conditions such as drought stress resulting in significant aflatoxin production. Drought-associated oxidative stress also exacerbates aflatoxin production by A. flavus. The objectives of this study were to use proteomics to provide insights into the pathogen responses to H2O2-derived oxidative stress, and to identify potential biomarkers and targets for host resistance breeding. Three isolates, AF13, NRRL3357, and K54A with high, moderate, and no aflatoxin production, were cultured in medium supplemented with varying levels of H2O2, and examined using an iTRAQ (Isobaric Tags for Relative and Absolute Quantification) approach. Overall, 1,173 proteins were identified and 220 were differentially expressed (DEPs). Observed DEPs encompassed metabolic pathways including antioxidants, carbohydrates, pathogenicity, and secondary metabolism. Increased lytic enzyme, secondary metabolite, and developmental pathway expression in AF13 was correlated with oxidative stress tolerance, likely assisting in plant infection and microbial competition. Elevated expression of energy and cellular component production in NRRL3357 and K54A implies a focus on oxidative damage remediation. These trends explain isolate-to-isolate variation in oxidative stress tolerance and provide insights into mechanisms relevant to host plant interactions under drought stress allowing for more targeted efforts in host resistance research.

 
 

Adv Biochem Eng Biotechnol. 2018 Feb 21. doi: 10.1007/10_2017_53. [Epub ahead of print]

Nanotechnology in Plants.

Author information

1
Department of Analytical Chemistry, Faculty of Pharmacy, Erciyes University, Kayseri, Turkey. ismailocsoy66@gmail.com.
2
Department of Analytical Chemistry, Faculty of Pharmacy, Erciyes University, Kayseri, Turkey.
3
Department of Chemistry and Shands Cancer Center, University of Florida, Gainesville, FL, USA. tan@chem.ufl.edu.

Abstract

The integration of nanotechnology in medicine has had a tremendous impact in the past few decades. The discovery of synthesis of nanomaterials (NMs) and their functions as versatile tools promoted various applications in nano-biotechnology and nanomedicine. Although the physical and chemical methods are still considered as commonly used methods, they introduce several drawbacks such as the use of toxic chemicals (solvent, reducing, and capping agents) and poor control of size, size distribution, and morphology, respectively. Additionally, the NMs synthesized in organic solvents and hydrophobic surfactants rapidly aggregate in aqueous solutions or under physiologic conditions, limiting their applications in medicine. Many of the phase-transfer strategies were developed and applied for the transfer of NMs into aqueous solutions. Although great efforts have been put into phase transfers, they mostly include expensive, time-consuming, intensive labor work, multi steps, and complicated procedures.Use of plant extracts in the biological synthesis method offers stark advantages over other biomolecules (protein, enzyme, peptide, and DNA). Plant extracts have been commonly used for food, medicine, NM synthesis, and biosensing. There are many viable techniques developed for the production of plant extracts with various contents based on their simplicity, cost, and the type of extract content. In this chapter, we conduct a comparative study for extract preparation techniques, the use of extracts for metallic single and hybrid nanoparticle (NP) synthesis, and their antimicrobial properties against pathogenic and plant-based bacteria. Graphical Abstract.

 
 

Mol Plant Pathol. 2018 Feb 20. doi: 10.1111/mpp.12667. [Epub ahead of print]

Functional characterization of the citrus canker susceptibility gene CsLOB1.

Author information

1
Citrus Research and Education Center, Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences (IFAS), University of Florida, Lake Alfred, Fl, U.S.A.
2
Citrus Research Institute Center, Southwest University, Chongqing, China.
3
Department of Plant Pathology, IFAS, University of Florida, Gainesville, FL, U. S. A.

Abstract

Xanthomonas citri ssp. citri (Xcc) is an important plant pathogenic bacterium that causes citrus canker disease worldwide. PthA, a transcriptional activator-like (TAL) effector, directs the expression of canker susceptibility gene CsLOB1. Here, we report our recent progress in functional characterization of CsLOB1. Subcellular localization analysis of CsLOB1 protein in citrus protoplast revealed that CsLOB1 is primarily localized in the nucleus. We showed that CsLOB1 expression driven by the dexamethasone (DEX) in the CsLOB1-GR transgenic plants is associated with pustule formation following treatment with DEX. Pustule formation was not observed in DEX-treated wild-type plants and in non-treated CsLOB1-GR transgenic plants. Water soaking is typically associated with symptoms of citrus canker. Weaker water soaking was observed with pustule formation in the CsLOB1-GR transgenic plants following DEX treatment. When CsLOB1-GR-transgenic Duncan grapefruit leaves were inoculated with Xcc306ΔpthA4 and treated with DEX, typical canker symptoms including hypertrophy, hyperplasia and water soaking symptoms were observed on DEX-treated transgenic plant leaves, but not on mock-treated plants. Twelve citrus genes that are induced by PthA4 are also stimulated by the DEX-induced expression of CsLOB1. Since CsLOB1 acts as a transcriptional factor, we identified putative targets of CsLOB1 via bioinformatic and electrophoretic mobility shift assays. Cs2g20600, which encodes a zinc finger CsHC4 type ring finger protein, has been identified to be a direct target of CsLOB1. This study advances our understanding of the function of CsLOB1 and the molecular mechanism of how Xcc causes canker symptoms via CsLOB1. This article is protected by copyright. All rights reserved.

 
 

Clin Pharmacol Ther. 2018 Feb 20. doi: 10.1002/cpt.1048. [Epub ahead of print]

Research directions in the clinical implementation of pharmacogenomics – An Overview of US programs and projects.

Author information

1
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892.
2
The Jackson Laboratory for Mammalian Genetics, Bar Harbor, ME, 04609.
3
Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago IL, 60611.
4
American Institutes for Research, Washington, DC 20007.
5
Duke Center for Applied Genomic and Precision Medicine, Duke University, Durham, NC 27708.
6
HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806.
7
DeBartolo Family Personalized Medicine Institute, Moffitt Cancer Center, Tampa, FL 33612.
8
Department of Medicine, Pharmacology, and Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN 37203.
9
Genomic Medicine Institute, Geisinger, Danville PA, 17822.
10
Partners Healthcare, Cambridge, MA 02139.
11
Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, Gainesville, FL 32610.
12
Departments of Biomedical Informatics and Medicine, Vanderbilt University, Nashville, TN 37203.
13
Mission Health, Personalized Medicine Program, Asheville, NC -28801.
14
Department of Biomedical Data Science, Stanford University, Stanford, CA 94305.
15
Division of Clinical Pharmacology, Toxicology and Therapeutic Innovation, Children’s Mercy Hospital, Kansas City, MO 64108.
16
Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada, M5S3M2.
17
Pharmacology Department, Northwestern University, Chicago, IL 60611.
18
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611.
19
Department of Pathology, Brigham & Women’s Hospital and Harvard Medical School, Boston, MA 02115.
20
Biomedical and Translational Informatics Institute, Geisinger Health System, Danville, PA 17822.
21
Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN 46202.
22
Dana-Farber Cancer Institute, Boston, MA 02215.
23
Center for Individualized Medicine, Mayo Clinic Rochester, MN 55905.
24
Department of Pharmacotherapy & Translational Research, University of Florida College of Pharmacy, Gainesville, FL 32610.
25
Departments of Pathology, Laboratory Medicine, and Pediatrics, University of Vermont Medical Center, Burlington, VT 05401.
26
Optum, Eden Prairie, MN 55344.
27
Pharmaceutical Sciences Department, St. Jude Children’s Research Hospital, Memphis, TN 38105.

Abstract

Response to a drug often differs widely among individual patients. This variability is frequently observed not only with respect to effective responses but also with adverse drug reactions. Matching patients to the drugs that are most likely to be effective and least likely to cause harm is the goal of effective therapeutics. Pharmacogenomics (PGx) holds the promise of precision medicine through elucidating the genetic determinants responsible for pharmacological outcomes and using them to guide drug selection and dosing. Here, we survey the US landscape of research programs in PGx implementation, review current advances and clinical applications of PGx, summarize the obstacles that have hindered PGx implementation, and identify the critical knowledge gaps and possible studies needed to help to address them. This article is protected by copyright. All rights reserved.

 
 

Nat Plants. 2018 Feb 19. doi: 10.1038/s41477-018-0114-0. [Epub ahead of print]

One effector at a time.

Author information

1
Department of Plant Pathology, University of Florida, Gainesville, FL, USA. ffwhite@ufl.edu.
2
Department of Plant Pathology, University of Florida, Gainesville, FL, USA.

 
 

Proc Natl Acad Sci U S A. 2018 Feb 20;115(8):E1749-E1758. doi: 10.1073/pnas.1721191115. Epub 2018 Feb 5.

Uterine influences on conceptus development in fertility-classified animals.

Author information

1
Division of Animal Sciences, University of Missouri, Columbia, MO 65211.
2
Fort Keogh Livestock and Range Research Laboratory, United States Department of Agriculture Agricultural Research Service, Miles City, MT 59301.
3
Department of Animal Sciences, University of Florida, Gainesville, FL 32611.
4
Department of Animal Sciences, Washington State University, Pullman, WA 99164.
5
Center for Reproductive Biology, Washington State University, Pullman, WA 99164.
6
Division of Animal Sciences, University of Missouri, Columbia, MO 65211; spencerte@missouri.edu.

Abstract

A major unresolved issue is how the uterus influences infertility and subfertility in cattle. Serial embryo transfer was previously used to classify heifers as high-fertile (HF), subfertile (SF), or infertile (IF). To assess pregnancy loss, two in vivo-produced embryos were transferred into HF, SF, and IF heifers on day 7, and pregnancy outcome was assessed on day 17. Pregnancy rate was substantially higher in HF (71%) and SF (90%) than IF (20%) heifers. Elongating conceptuses were about twofold longer in HF than SF heifers. Transcriptional profiling detected relatively few differences in the endometrium of nonpregnant HF, SF, and IF heifers. In contrast, there was a substantial difference in the transcriptome response of the endometrium to pregnancy between HF and SF heifers. Considerable deficiencies in pregnancy-dependent biological pathways associated with extracellular matrix structure and organization as well as cell adhesion were found in the endometrium of SF animals. Distinct gene expression differences were also observed in conceptuses from HF and SF animals, with many of the genes decreased in SF conceptuses known to be embryonic lethal in mice due to defects in embryo and/or placental development. Analyses of biological pathways, key players, and ligand-receptor interactions based on transcriptome data divulged substantial evidence for dysregulation of conceptus-endometrial interactions in SF animals. These results support the ideas that the uterus impacts conceptus survival and programs conceptus development, and ripple effects of dysregulated conceptus-endometrial interactions elicit loss of the postelongation conceptus in SF cattle during the implantation period of pregnancy.

 
 

Proc Natl Acad Sci U S A. 2018 Feb 20;115(8):E1906-E1915. doi: 10.1073/pnas.1712251115. Epub 2018 Feb 5.

Regulation of Arabidopsis brassinosteroid receptor BRI1 endocytosis and degradation by plant U-box PUB12/PUB13-mediated ubiquitination.

Zhou J1,2,3Liu D4,5Wang P2,6Ma X1,2Lin W2,6Chen S7,8,9Mishev K4,5Lu D1,2Kumar R4,5Vanhoutte I4,5Meng X3He P1,2Russinova E10,5Shan L11,6.

Author information

1
Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843.
2
Institute for Plant Genomics and Biotechnology, Texas A&M University, College Station, TX 77843.
3
Shanghai Key Laboratory of Bio-Energy Crops, School of Life Sciences, Shanghai University, Shanghai 200444, China.
4
Department of Plant Biotechnology and Bioinformatics, Ghent University, 9052 Ghent, Belgium.
5
Center for Plant Systems Biology, VIB, 9052 Ghent, Belgium.
6
Department of Plant Pathology and Microbiology, Texas A&M University, College Station, TX 77843.
7
Department of Biology, University of Florida, Gainesville, FL 32610.
8
Genetics Institute, University of Florida, Gainesville, FL 32610.
9
Plant Molecular and Cellular Biology Program, University of Florida, Gainesville, FL 32610.
10
Department of Plant Biotechnology and Bioinformatics, Ghent University, 9052 Ghent, Belgium; eurus@psb.vib-ugent.be lshan@tamu.edu.
11
Institute for Plant Genomics and Biotechnology, Texas A&M University, College Station, TX 77843; eurus@psb.vib-ugent.be lshan@tamu.edu.

Abstract

Plants largely rely on plasma membrane (PM)-resident receptor-like kinases (RLKs) to sense extracellular and intracellular stimuli and coordinate cell differentiation, growth, and immunity. Several RLKs have been shown to undergo internalization through the endocytic pathway with a poorly understood mechanism. Here, we show that endocytosis and protein abundance of the Arabidopsis brassinosteroid (BR) receptor, BR INSENSITIVE1 (BRI1), are regulated by plant U-box (PUB) E3 ubiquitin ligase PUB12- and PUB13-mediated ubiquitination. BR perception promotes BRI1 ubiquitination and association with PUB12 and PUB13 through phosphorylation at serine 344 residue. Loss of PUB12 and PUB13 results in reduced BRI1 ubiquitination and internalization accompanied with a prolonged BRI1 PM-residence time, indicating that ubiquitination of BRI1 by PUB12 and PUB13 is a key step in BRI1 endocytosis. Our studies provide a molecular link between BRI1 ubiquitination and internalization and reveal a unique mechanism of E3 ligase-substrate association regulated by phosphorylation.

 
 

Antimicrob Agents Chemother. 2018 Feb 23;62(3). pii: e02099-17. doi: 10.1128/AAC.02099-17. Print 2018 Mar.

Effect of Genetic Variation of NAT2 on Isoniazid and SLCO1B1 and CES2 on Rifampin Pharmacokinetics in Ghanaian Children with Tuberculosis.

Author information

1
Department of Microbiology, Komfo Anokye Teaching Hospital, Kumasi, Ghana.
2
Department of Medicine, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA.
3
College of Life Sciences, Hunan Normal University, Changsha, China.
4
Department of Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
5
Department of Medicine, The Miriam Hospital, Providence, Rhode Island, USA.
6
Department of Child Health, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
7
Directorate of Child Health, Komfo Anokye Teaching Hospital, Kumasi, Ghana.
8
College of Pharmacy, University of Florida, Gainesville, Florida, USA.
9
College of Veterinary Medicine, Washington State University, Pullman, Washington, USA.
10
College of Medicine and Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA awewura.kwara@medicine.ufl.edu.

Abstract

Isoniazid and rifampin are essential components of first-line antituberculosis (anti-TB) therapy. Understanding the relationship between genetic factors and the pharmacokinetics of these drugs could be useful in optimizing treatment outcomes, but this is understudied in children. We investigated the relationship between N-acetyltransferase type 2 (NAT2) genotypes and isoniazid pharmacokinetics, as well as that between the solute carrier organic anion transporter family member 1B1 (encoded by SLCO1B1) and carboxylesterase 2 (CES2) single nucleotide polymorphisms (SNPs) and rifampin pharmacokinetics in Ghanaian children. Blood samples were collected at times 0, 1, 2, 4, and 8 h postdose in children with tuberculosis on standard first-line therapy for at least 4 weeks. Isoniazid and rifampin concentrations were determined by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, and pharmacokinetic parameters were calculated using noncompartmental analysis. Genotyping of NAT2SLCO1B1, and CES2 SNPs were performed using validated TaqMan genotyping assays. The Kruskal-Wallis test was used to compare pharmacokinetic parameters among the three genotypic groups and was followed by the Wilcoxon rank sum test for pairwise group comparisons. Genotype status inferred by the NAT2 4-SNP and 7-SNP genotyping panels identified children with a slow acetylator phenotype but not the rapid genotype. For rifampin, only the rare SLCO1B1*1b homozygous variant was associated with rifampin pharmacokinetics. Our findings suggest that NAT2 and SCLCO1B1*1b genotyping may have minimal clinical utility in dosing decisions at the population level in Ghanaian children, but it could be useful at the individual level or in populations that have a high frequency of implicated genotypes. Further studies in other populations are warranted.

 

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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