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UFGI publication round-up week 7/10 and 7/17/17

Chilling responsive DEMETER-LIKE DNA demethylase mediates in poplar bud break.

Author information: Conde D1, Le Gac AL2, Perales M1, Dervinis C3, Kirst M3,4, Maury S2, González-Melendi P1,5, Allona I1,5.

1Centro de Biotecnología y Genómica de Plantas, Universidad Politécnica de Madrid (UPM) – Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Campus de Montegancedo UPM, Pozuelo de Alarcón, 28223, Madrid, Spain.
2LBLGC EA1207, USC 1328 INRA, University Orléans, 45067, Orléans, France.
3School of Forest Resources and Conservation, University of Florida, Gainesville, Florida, 32611, USA.
4University of Florida Genetics Institute, University of Florida, Gainesville, FL, 32611, USA.
5Departamento de Biotecnología-Biología Vegetal, Escuela Técnica Superior de Ingeniería Agronómica, Alimentaria y de Biosistemas, Universidad Politécnica de Madrid (UPM), 28040, Madrid, Spain.
Journal: Plant, Cell & Environment

Date of e-pub: July 2017

Abstract: Annual dormancy-growth cycle is a developmental and physiological process essential for the survival of deciduous trees in temperate and boreal forests. Seasonal control of shoot growth in woody perennials requires specific genetic programs responding to environmental signals. The environmental-controlled mechanisms that regulate the shift between winter dormancy and the growth promoting genetic programs are still unknown. Here, we show that dynamics in genomic DNA (gDNA) methylation levels are involved in the regulation of dormancy-growth cycle in poplar. The reactivation of growth in the apical shoot during bud break process in spring, is preceded by a progressive reduction of gDNA methylation in apex tissue. The induction in apex tissue of a chilling-dependent poplar DEMETER-LIKE 10 (PtaDML10) DNA demethylase precedes shoot growth reactivation. Transgenic poplars showing down-regulation of PtaDML8/10 caused delayed bud break. Genome wide transcriptome and methylome analysis and data mining revealed the gene targets of DML-dependent DNA demethylation are genetically associated with bud break. These data point to a chilling dependent DEMETER-like DNA demethylase mechanisms being involved in the shift from winter dormancy to a condition that precedes shoot apical vegetative growth in poplar.

 

 

Complete Genome Sequences of Three Xanthomonas citri Strains from Texas.

Author information: Munoz Bodnar A1, Santillana G2, Mavrodieva V2, Liu Z2, Nakhla M2, Gabriel DW3.

1Department of Plant Pathology, University of Florida, Gainesville, Florida, USA.
2United States Department of Agriculture, Animal and Plant Health Inspection Service, Beltsville, Maryland, USA.
3Department of Plant Pathology, University of Florida, Gainesville, Florida, USA dgabr@ufl.edu.
Journal: Genome Announcements

Date of e-pub: July 2017

Abstract: The complete genome sequences of three Xanthomonas citri strains isolated from lime trees in Texas were found to belong to the Aw group. All carried nearly identical large plasmids with similarity to those of a citrus canker strain from India and to xanthomonads from Africa and Colombia. All three strains harbored unusual pthA homologs.

 

 

Genome Sequence of Oxalobacter formigenes Strain OXCC13.

Author information: Hatch M1, Allison MJ2, Yu F3, Farmerie W3.

1Department of Pathology, Immunology and Laboratory Medicine, University of Florida, College of Medicine, Gainesville, Florida, USA hatchma@ufl.edu.
2Iowa State University, Ames, Iowa, USA.
3Interdisciplinary Center for Biotechnology Research, University of Florida, College of Medicine, Gainesville, Florida, USA.
Journal: Genome Announcements

Date of e-pub: July 2017

Abstract: The lack of Oxalobacter formigenes colonization in the human gut is generally acknowledged as a risk factor for kidney stone formation since this microorganism can play an important role in oxalate homeostasis. Here, we present the genome sequence of OXCC13, a human strain isolated from an individual residing in Germany.

 

 

Personalizing antiplatelet prescribing using genetics for patients undergoing percutaneous coronary intervention.

Author information: Cavallari LH1.

1a Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics , University of Florida College of Pharmacy , Gainesville , FL , USA.
Journal: Expert Review of Cardiovascular Therapy

Date of e-pub: July 2017

Abstract: Clopidogrel is commonly prescribed with aspirin to reduce the risk for adverse cardiovascular events after percutaneous coronary intervention (PCI). However, there is significant inter-patient variability in clopidogrel response. The CYP2C19 enzyme is involved in the biotransformation of clopidogrel to its pharmacologically active form, and variation in the CYP2C19 gene contributes to clopidogrel response variability. Areas covered. This article describes the impact of CYP2C19 genotype on clopidogrel pharmacokinetics, pharmacodynamics, and effectiveness. Examples of clinical implementation of CYP2C19 genotype-guided antiplatelet therapy for patients undergoing PCI are also described as are emerging outcomes data with this treatment approach. Expert commentary. A large clinical trial evaluating outcomes with CYP2C19 genotype-guided antiplatelet therapy after PCI is on-going. In the meantime, data from pragmatic and observational studies and smaller trials support improved outcomes with genotyping after PCI and use of alternative antiplatelet therapy in patients with a CYP2C19 genotype associated with reduced clopidogrel effectiveness.

 

 

Association between age-related reductions in testosterone and risk of prostate cancer-An analysis of patients’ data with prostatic diseases.

Author information: Wang K1, Chen X1, Bird VY2, Gerke TA3, Manini TM4, Prosperi M1.

1Department of Epidemiology, University of Florida, Gainesville, FL.
2Department of Urology, University of Florida, Gainesville, FL.
3Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL.
4Department of Aging and Geriatric Research, University of Florida, Gainesville, FL.
Journal: International Journal of Cancer

Date of e-pub: July 2017

Abstract: The relationship between serum total testosterone and prostate cancer (PCa) risk is controversial. The hypothesis that faster age-related reduction in testosterone is linked with increased PCa risk remains untested. We conducted our study at a tertiary-level hospital in southeast of the USA, and derived data from the Medical Registry Database of individuals that were diagnosed of any prostate-related disease from 2001 to 2015. Cases were those diagnosed of PCa and had one or more measurements of testosterone prior to PCa diagnosis. Controls were those without PCa and had one or more testosterone measurements. Multivariable logistic regression models for PCa risk of absolute levels (one-time measure and 5-year average) and annual change in testosterone were respectively constructed. Among a total of 1,559 patients, 217 were PCa cases, and neither one-time measure nor 5-year average of testosterone was found to be significantly associated with PCa risk. Among the 379 patients with two or more testosterone measurements, 27 were PCa cases. For every 10 ng/dL increment in annual reduction of testosterone, the risk of PCa would increase by 14% [adjusted odds ratio, 1.14; 95% confidence interval (CI), 1.03-1.25]. Compared to patients with a relatively stable testosterone, patients with an annual testosterone reduction of more than 30 ng/dL had 5.03 [95% CI: 1.53, 16.55] fold increase in PCa risk. This implies a faster age-related reduction in, but not absolute level of serum total testosterone as a risk factor for PCa. Further longitudinal studies are needed to confirm this finding.

 

 

Disrupted prenatal RNA processing and myogenesis in congenital myotonic dystrophy.

Author information: Thomas JD1, Sznajder ŁJ1, Bardhi O1, Aslam FN1, Anastasiadis ZP1, Scotti MM1, Nishino I2, Nakamori M3, Wang ET1, Swanson MS1.

1Department of Molecular Genetics and Microbiology, Center for NeuroGenetics and the Genetics Institute, College of Medicine, University of Florida, Gainesville, Florida 32610, USA.
2Department of Neuromuscular Research, National Center of Neurology and Psychiatry, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
3Department of Neurology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
Journal: Genes & Development

Date of e-pub: June 2017

Abstract: Myotonic dystrophy type 1 (DM1) is a CTG microsatellite expansion (CTGexp) disorder caused by expression of CUGexp RNAs. These mutant RNAs alter the activities of RNA processing factors, including MBNL proteins, leading to re-expression of fetal isoforms in adult tissues and DM1 pathology. While this pathogenesis model accounts for adult-onset disease, the molecular basis of congenital DM (CDM) is unknown. Here, we test the hypothesis that disruption of developmentally regulated RNA alternative processing pathways contributes to CDM disease. We identify prominent alternative splicing and polyadenylation abnormalities in infant CDM muscle, and, although most are also misregulated in adult-onset DM1, dysregulation is significantly more severe in CDM. Furthermore, analysis of alternative splicing during human myogenesis reveals that CDM-relevant exons undergo prenatal RNA isoform transitions and are predicted to be disrupted by CUGexp-associated mechanisms in utero. To test this possibility and the contribution of MBNLs to CDM pathogenesis, we generated mouse Mbnl double (Mbnl1; Mbnl2) and triple (Mbnl1; Mbnl2; Mbnl3) muscle-specific knockout models that recapitulate the congenital myopathy, gene expression, and spliceopathy defects characteristic of CDM. This study demonstrates that RNA misprocessing is a major pathogenic factor in CDM and provides novel mouse models to further examine roles for cotranscriptional/post-transcriptional gene regulation during development.

 

 

Application of the entomogenous fungus, Metarhizium anisopliae, for leafroller (Cnaphalocrocis medinalis) control and its effect on rice phyllosphere microbial diversity.

Author information: Hong M1,2,3, Peng G1,2,3, Keyhani NO1,4, Xia Y5,6,7.

1Genetic Engineering Research Center, School of Life Sciences, Chongqing University, Chongqing, 400045, People’s Republic of China.
2Chongqing Engineering Research Center for Fungal Insecticide, Chongqing, 400045, People’s Republic of China.
3Key Laboratory of Gene Function and Regulation Technologies under Chongqing Municipal Education Commission, Chongqing, 400045, People’s Republic of China.
4Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL, 32611, USA.
5Genetic Engineering Research Center, School of Life Sciences, Chongqing University, Chongqing, 400045, People’s Republic of China. yuxianxia@cqu.edu.cn.
6 Chongqing Engineering Research Center for Fungal Insecticide, Chongqing, 400045, People’s Republic of China. yuxianxia@cqu.edu.cn.
7Key Laboratory of Gene Function and Regulation Technologies under Chongqing Municipal Education Commission, Chongqing, 400045, People’s Republic of China. yuxianxia@cqu.edu.cn.
Journal: Applied Microbiology and Biotechnology

Date of e-pub: July 2017

Abstract: Microbial pesticides form critical components of integrated pest management (IPM) practices. Little, however, is known regarding the impacts of these organisms on the indigenous microbial community. We show that Metarhizium anisopliae strain CQMa421 was highly effective in controlling the rice leafroller, Cnaphalocrocis medinalis Guenee. In addition, M. anisopliae distribution and its effects on phyllosphere microbial diversity after application in field trials were investigated. Phylloplane specific distribution of the fungus was observed over time, with more rapid declines of M. anisopliae CFUs (colony-forming units) seen in the top leaf layer as compared to lower layers. Application of the fungus resulted in transient changes in the endogenous microbial diversity with variations seen in the bacterial observed species and Shannon index. Notable increases in both parameters were seen at 6-day post-application of M. anisopliae, although significant variation within sample replicates for bacteria and fungi were noted. Application of M. anisopliae increased the relative distribution of bacterial species implicated in plant growth promotion and organic pollutant degradation, e.g., Methylobacterium, Sphingobium, and Deinococcus. These data show minimal impact of M. anisopliae on endogenous microbial diversity with transient changes in bacterial abundance/diversity that may result in added benefits to crops.

 

 

International Committee on Systematics of Prokaryotes Subcommittee on the taxonomy of Mollicutes. Minutes of the closed meeting, 3rd July 2016, Brisbane, Australia.

Author information: May M1, Brown DR2.

11​Department of Biomedical Sciences, University of New England, Biddeford, Maine, USA.
22​Department of Infectious Diseases and Pathology, University of Florida, Gainesville, FL, USA.
Journal: International Journal of Systematic and Evolutionary Microbiology

Date of e-pub: July 2017

Abstract: N/A

 

 

Genomic prediction in contrast to a genome-wide association study in explaining heritable variation of complex growth traits in breeding populations of Eucalyptus.

Author information: Müller BSF1,2,3, Neves LG4, de Almeida Filho JE3, Resende MFR Jr4, Muñoz PR5, Dos Santos PET6, Filho EP6, Kirst M3, Grattapaglia D7,8.

1Cell Biology Department, Molecular Biology Program, Biological Sciences Institute, University of Brasília, Campus Darcy Ribeiro, Brasília, DF, 70910-900, Brazil.
2 EMBRAPA Genetic Resources and Biotechnology, Estação Parque Biológico, Brasília, DF, 70770-910, Brazil.
3Forest Genomics Laboratory, School of Forest Resources and Conservation, University of Florida, Gainesville, FL, 32611, USA.
4RAPiD Genomics LLC, Gainesville, FL, 32601, USA.
5Agronomy Department, University of Florida, Gainesville, FL, 32611, USA.
6EMBRAPA Forestry, Estrada da Ribeira, Km 111, Colombo, PR, 83411-000, Brazil.
7Cell Biology Department, Molecular Biology Program, Biological Sciences Institute, University of Brasília, Campus Darcy Ribeiro, Brasília, DF, 70910-900, Brazil. dario.grattapaglia@embrapa.br.
8EMBRAPA Genetic Resources and Biotechnology, Estação Parque Biológico, Brasília, DF, 70770-910, Brazil. dario.grattapaglia@embrapa.br.
Journal: BMC Genomics

Date of e-pub: July 2017

Abstract: The advent of high-throughput genotyping technologies coupled to genomic prediction methods established a new paradigm to integrate genomics and breeding. We carried out whole-genome prediction and contrasted it to a genome-wide association study (GWAS) for growth traits in breeding populations of Eucalyptus benthamii (n =505) and Eucalyptus pellita (n =732). Both species are of increasing commercial interest for the development of germplasm adapted to environmental stresses.

Predictive ability reached 0.16 in E. benthamii and 0.44 in E. pellita for diameter growth. Predictive abilities using either Genomic BLUP or different Bayesian methods were similar, suggesting that growth adequately fits the infinitesimal model. Genomic prediction models using ~5000-10,000 SNPs provided predictive abilities equivalent to using all 13,787 and 19,506 SNPs genotyped in the E. benthamii and E. pellita populations, respectively. No difference was detected in predictive ability when different sets of SNPs were utilized, based on position (equidistantly genome-wide, inside genes, linkage disequilibrium pruned or on single chromosomes), as long as the total number of SNPs used was above ~5000. Predictive abilities obtained by removing relatedness between training and validation sets fell near zero for E. benthamii and were halved for E. pellita. These results corroborate the current view that relatedness is the main driver of genomic prediction, although some short-range historical linkage disequilibrium (LD) was likely captured for E. pellita. A GWAS identified only one significant association for volume growth in E. pellita, illustrating the fact that while genome-wide regression is able to account for large proportions of the heritability, very little or none of it is captured into significant associations using GWAS in breeding populations of the size evaluated in this study.

This study provides further experimental data supporting positive prospects of using genome-wide data to capture large proportions of trait heritability and predict growth traits in trees with accuracies equal or better than those attainable by phenotypic selection. Additionally, our results document the superiority of the whole-genome regression approach in accounting for large proportions of the heritability of complex traits such as growth in contrast to the limited value of the local GWAS approach toward breeding applications in forest trees.

 

 

Role of Genetic Testing in Patients undergoing Percutaneous Coronary Intervention.

Author information: Moon JY1, Franchi F1, Rollini F1, Rivas Rios JR1, Kureti M1, Cavallari LH2,3,4, Angiolillo DJ1.

1a Division of Cardiology , University of Florida College of Medicine , Jacksonville , FL , USA.
2 b Department of Pharmacotherapy and Translational Research, College of Pharmacy , University of Florida , Gainesville , FL , USA.
3c Center for Pharmacogenomics , University of Florida , Gainesville , FL , USA.
4d Clinical & Translational Science Institute , University of Florida , Gainesville , FL , USA.
Journal: Expert Review of Clinical Pharmacology

Date of e-pub: July 2017

Abstract: Variability in individual response profiles to antiplatelet therapy, in particular clopidogrel, is a well-established phenomenon. Genetic variations of the cytochrome P450 (CYP) 2C19 enzyme, a key determinant in clopidogrel metabolism, have been associated with clopidogrel response profiles. Moreover, the presence of a CYP2C19 loss-of-function allele is associated with an increased risk of atherothrombotic events among clopidogrel-treated patients undergoing percutaneous coronary interventions (PCI), prompting studies evaluating the use of genetic tests to identify patients who may be potential candidates for alternative platelet P2Y12 receptor inhibiting therapies (prasugrel or ticagrelor). Areas covered: The present manuscript provides an overview of genetic factors associated with response profiles to platelet P2Y12 receptor inhibitors and their clinical implications, as well as the most recent developments and future considerations on the role of genetic testing in patients undergoing PCI. Expert Commentary: The availability of more user-friendly genetic tests has contributed towards the development of many ongoing clinical trials and personalized medicine programs for patients undergoing PCI. Results of pilot investigations have shown promising results, which however need to be confirmed in larger-scale studies to support the routine use of genetic testing as a strategy to personalize antiplatelet therapy and improve clinical outcomes.

 

 

Estrogen Signaling through both Membrane and Nuclear Receptors in the Liver of Fathead Minnow.

Author information: Garcia-Reyero N1, Jayasinghe BS2, Kroll KJ3, Sabo-Attwood T2, Denslow ND2.

1Environmental Laboratory, US Army Engineer Research & Development Center, Vicksburg, MS 39180, USA; Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611, USA; Department of Environmental and Global Health, University of Florida, Gainesville, FL, 32611, USA. Electronic address: natalia@icnanotox.org.
2Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611, USA; Department of Environmental and Global Health, University of Florida, Gainesville, FL, 32611, USA.
3Environmental Laboratory, US Army Engineer Research & Development Center, Vicksburg, MS 39180, USA.
Journal: General and Comparative Endocrinology

Date of e-pub: July 2017

Abstract: Estradiol is a potent sex steroid hormone that controls reproduction and other cellular pathways in fish. It is known to regulate important proteins such as vitellogenin, the egg yolk precursor protein, and zona radiata proteins that form the eggshell for fish eggs. These proteins are made in the liver and transported out into the blood from where they are taken up into the ovary during oogenesis. Estradiol can exert its influence directly through soluble nuclear receptors (there are three in fish) or indirectly through membrane receptors and a phosphorylation cascade. Often there is coordination through both genomic and non-genomic pathways. We have used a toxicogenomics approach to determine the contribution of genomic and non-genomic regulation in the liver of fathead minnows exposed to 5 ng ethinylestradiol per liter or to a mixture of 5 ng ethinylestradiol and 100 ng ZM189,154 (ZM) per liter. ZM has previously been shown to be a “perfect” antagonist for the fish nuclear estrogen receptors but has displayed agonistic activities for membrane receptors. We find that both nuclear and membrane receptors contribute to the biosynthesis of vitellogenin 1 and estrogen receptor one (Esr1), among others. In addition, lipid metabolism pathways appear to require both activities.

 

 

A strictly monofunctional bacterial hydroxymethylpyrimidine phosphate kinase precludes damaging errors in thiamin biosynthesis.

Author information: Thamm AM1, Li G2, Taja-Moreno M1, Gerdes SY3, de Crécy-Lagard V4, Bruner SD2, Hanson AD5.

1Horticultural Sciences, University of Florida, Gainesville, Florida, FL 32611-0690, United States.
2Chemistry, University of Florida, Gainesville, Florida, FL 32611-7200, United States.
3Fellowship for Interpretation of Genomes, Burr Ridge, Illinois, Afghanistan.
4Microbiology and Cell Science Department, University of Florida, Gainesville, Florida, FL 32611-0690, United States.
5Horticultural Sciences, University of Florida, Gainesville, Florida, FL 32611-0690, United States adha@ufl.edu.
Journal: The Biochemical Journal

Date of e-pub: July 2017

Abstract: The canonical kinase (ThiD) that converts the thiamin biosynthesis intermediate hydroxymethylpyrimidine (HMP) monophosphate to the diphosphate can also very efficiently convert free HMP to the monophosphate in prokaryotes, plants, and fungi. This HMP kinase activity enables salvage of HMP, but it is not substrate-specific and so allows toxic HMP analogs and damage products to infiltrate the thiamin biosynthesis pathway. Comparative analysis of bacterial genomes uncovered a gene, thiD2 , that is often fused to the thiamin synthesis gene thiE and could potentially encode a replacement for ThiD. Standalone ThiD2 proteins and ThiD2 fusion domains are small (~130-residues) and do not belong to any previously known protein family. Genetic and biochemical analyses showed that representative standalone and fused ThiD2 proteins catalyze phosphorylation of HMP monophosphate, but not of HMP or its toxic analogs and damage products such as bacimethrin and 5-(hydroxymethyl)-2-methylpyrimidin-4-ol. As strictly monofunctional HMP monophosphate kinases, ThiD2 proteins eliminate a potentially fatal vulnerability of canonical ThiD, at the cost of the ability to reclaim HMP formed by thiamin turnover.

 

 

Undergraduate Minor in Health Disparities in Society: a Magnet for Under-represented Pre-professional Students.

Author information: Guyer LK1,2,3, Wayne ML4,5, Hardt NS6.

1Center for Gender, Sexualities and Women’s Studies Research, University of Florida, Gainesville, FL, 32611, USA. lkguyer@ufl.edu.
2Department of Biology, College of Liberal Arts and Sciences, University of Florida, Gainesville, FL, 32611, USA. lkguyer@ufl.edu.
3College of Public Health and Health Professions, University of Florida, Gainesville, FL, 32610, USA. lkguyer@ufl.edu.
4Center for Gender, Sexualities and Women’s Studies Research, University of Florida, Gainesville, FL, 32611, USA.
5Department of Biology, College of Liberal Arts and Sciences, University of Florida, Gainesville, FL, 32611, USA.
6College of Medicine, University of Florida, Gainesville, FL, 32610, USA.
Journal: Journal of Racial and Ethnic Health Disparities

Date of e-pub: July 2017

Abstract: Increasing the diversity of tomorrow’s healthcare work force remains a challenge despite many thoughtful published reports and recommendations. As part of an effort to grow a more diverse pre-professional health population, we created an undergraduate minor, Health Disparities in Society, at the University of Florida. Most courses for the minor were identified from existing offerings, and we created only two new courses, an introduction course and a capstone service-learning course. The new minor quickly became the most popular in the College of Liberal Arts and Sciences (which has approximately 12,000 total undergraduate students), and importantly, students selecting the minor were more likely to be under-represented minorities than would be expected given undergraduate demographics. Pre-professional students choosing this minor reflect the desired diversity of the healthcare workforce of tomorrow.

 

 

Hormone receptor status of a first primary breast cancer predicts contralateral breast cancer risk in the WECARE study population.

Author information: Reiner AS1,2, Lynch CF3, Sisti JS4, John EM5,6, Brooks JD7, Bernstein L8, Knight JA7,9, Hsu L10, Concannon P11, Mellemkjær L12, Tischkowitz M13, Haile RW6, Shen R4, Malone KE10, Woods M4, Liang X4, Morrow M4, Bernstein JL4; WECARE Study Collaborative Group.

1Memorial Sloan Kettering Cancer Center, New York, NY, USA. reinera@mskcc.org.
2MPH, 485 Lexington Avenue, 2nd Floor, New York, NY, 10017, USA. reinera@mskcc.org.
3University of Iowa, Iowa City, IA, USA.
4Memorial Sloan Kettering Cancer Center, New York, NY, USA.
5Cancer Prevention Institute of California, Fremont, CA, USA.
6Stanford Department of Medicine, Division of Oncology, and the Stanford Cancer Institute, Stanford, CA, USA.
7University of Toronto, Dalla Lana School of Public Health Sciences, Toronto, Canada.
8Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA.
9Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada.
10Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
11Genetics Institute and Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, USA.
12Danish Cancer Society Research Center, Copenhagen, Denmark.
13Department of Medical Genetics, University of Cambridge, Cambridge, UK.
Journal: Breast Cancer Research : BCR

Date of e-pub: July 2017

Abstract: Previous population-based studies have described first primary breast cancer tumor characteristics and their association with contralateral breast cancer (CBC) risk. However, information on influential covariates such as treatment, family history of breast cancer, and BRCA1/2 mutation carrier status was not available. In a large, population-based, case-control study, we evaluated whether tumor characteristics of the first primary breast cancer are associated with risk of developing second primary asynchronous CBC, overall and in subgroups of interest, including among BRCA1/2 mutation non-carriers, women who are not treated with tamoxifen, and women without a breast cancer family history.

The Women’s Environmental Cancer and Radiation Epidemiology Study is a population-based case-control study of 1521 CBC cases and 2212 individually-matched controls with unilateral breast cancer. Detailed information about breast cancer risk factors, treatment for and characteristics of first tumors, including estrogen receptor (ER) and progesterone receptor (PR) status, was obtained by telephone interview and medical record abstraction. Multivariable risk ratios (RRs) and 95% confidence intervals (CIs) were estimated in conditional logistic regression models, adjusting for demographics, treatment, and personal medical and family history. A subset of women was screened for BRCA1/2 mutations.

Lobular histology of the first tumor was associated with a 30% increase in CBC risk (95% CI 1.0-1.6). Compared to women with ER+/PR+ first tumors, those with ER-/PR- tumors had increased risk of CBC (RR = 1.4, 95% CI 1.1-1.7). Notably, women with ER-/PR- first tumors were more likely to develop CBC with the ER-/PR- phenotype (RR = 5.4, 95% CI 3.0-9.5), and risk remained elevated in multiple subgroups: BRCA1/2 mutation non-carriers, women younger than 45 years of age, women without a breast cancer family history, and women who were not treated with tamoxifen.

Having a hormone receptor negative first primary breast cancer is associated with increased risk of CBC. Women with ER-/PR- primary tumors were more likely to develop ER-/PR- CBC, even after excluding BRCA1/2 mutation carriers. Hormone receptor status, which is routinely evaluated in breast tumors, may be used clinically to determine treatment protocols and identify patients who may benefit from increased surveillance for CBC.

 

 

A lectin receptor kinase as a potential sensor for extracellular nicotinamide adenine dinucleotide in Arabidopsis thaliana.

Author information: Wang C1, Zhou M1, Zhang X1, Yao J2, Zhang Y3, Mou Z1.

1Department of Microbiology and Cell Science, University of Florida, Gainesville, United States.
2Target Sciences, GlaxoSmithKline, King of Prussia, United States.
3Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States.
Journal: ELife

Date of e-pub: July 2017

Abstract: Nicotinamide adenine dinucleotide (NAD+) participates in intracellular and extracellular signaling events unrelated to metabolism. In animals, purinergic receptors are required for extracellular NAD+ (eNAD+) to evoke biological responses, indicating that eNAD+ may be sensed by cell-surface receptors. However, the identity of eNAD+-binding receptors still remains elusive. Here, we identify a lectin receptor kinase (LecRK), LecRK-I.8, as a potential eNAD+ receptor in Arabidopsis. The extracellular lectin domain of LecRK-I.8 binds NAD+ with a dissociation constant of 436.5 104.8 nM, although much higher concentrations are needed to trigger in vivo responses. Mutations in LecRK-I.8 inhibit NAD+-induced immune responses, whereas overexpression of LecRK-I.8 enhances the Arabidopsis response to NAD+. Furthermore, LecRK-I.8 is required for basal resistance against bacterial pathogens, substantiating a role for eNAD+ in plant immunity. Our results demonstrate that lectin receptors can potentially function as eNAD+-binding receptors and provide direct evidence for eNAD+ being an endogenous signaling molecule in plants.

 

 

Developmental mechanisms of intervertebral disc and vertebral column formation.

Author information: Lawson LY1, Harfe BD1.

1Department of Molecular Genetics and Microbiology, Genetics Institute University of Florida, College of Medicine, Gainesville, FL, USA.
Journal: Wiley Interdisciplinary Reviews. Developmental Biology

Date of e-pub: July 2017

Abstract: The vertebral column consists of repeating units of ossified vertebrae that are adjoined by fibrocartilagenous intervertebral discs. These structures form from the embryonic notochord and somitic mesoderm. In humans, congenital malformations of the vertebral column include scoliosis, kyphosis, spina bifida, and Klippel Feil syndrome. In adulthood, a common malady affecting the vertebral column includes disc degeneration and associated back pain. Indeed, recent reports estimate that low back pain is the number one cause of disability worldwide. Our review provides an overview of the molecular mechanisms underlying vertebral column morphogenesis and intervertebral disc development and maintenance, with an emphasis on what has been gleaned from recent genetic studies in mice. The aim of this review is to provide a developmental framework through which vertebral column formation can be understood so that ultimately, research scientists and clinicians alike can restore disc health with appropriately designed gene and cell-based therapies. For further resources related to this article, please visit the WIREs website.

 

 

microRNA dependent and independent deregulation of long non-coding RNAs by an oncogenic herpesvirus.

Author information: Sethuraman S1, Gay LA1, Jain V1, Haecker I1, Renne R1,2,3.

1Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida, United States of America.
2UF Health Cancer Center, University of Florida, Gainesville, Florida, United States of America.
3UF Genetics Institute, University of Florida, Gainesville, Florida, United States of America.
Journal: PLoS Pathogens

Date of e-pub: July 2017

Abstract: Kaposi’s sarcoma (KS) is a highly prevalent cancer in AIDS patients, especially in sub-Saharan Africa. Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent of KS and other cancers like Primary Effusion Lymphoma (PEL). In KS and PEL, all tumors harbor latent KSHV episomes and express latency-associated viral proteins and microRNAs (miRNAs). The exact molecular mechanisms by which latent KSHV drives tumorigenesis are not completely understood. Recent developments have highlighted the importance of aberrant long non-coding RNA (lncRNA) expression in cancer. Deregulation of lncRNAs by miRNAs is a newly described phenomenon. We hypothesized that KSHV-encoded miRNAs deregulate human lncRNAs to drive tumorigenesis. We performed lncRNA expression profiling of endothelial cells infected with wt and miRNA-deleted KSHV and identified 126 lncRNAs as putative viral miRNA targets. Here we show that KSHV deregulates host lncRNAs in both a miRNA-dependent fashion by direct interaction and in a miRNA-independent fashion through latency-associated proteins. Several lncRNAs that were previously implicated in cancer, including MEG3, ANRIL and UCA1, are deregulated by KSHV. Our results also demonstrate that KSHV-mediated UCA1 deregulation contributes to increased proliferation and migration of endothelial cells.

 

 

Cell fate specification in the lingual epithelium is controlled by antagonistic activities of Sonic hedgehog and retinoic acid.

Author information: El Shahawy M1, Reibring CG1, Neben CL2, Hallberg K1, Marangoni P2, Harfe BD3, Klein OD2,4, Linde A1, Gritli-Linde A1.

1Department of Oral Biochemistry, Institute of Odontology, Sahlgrenska Academy at the University of Gothenburg, SE, Göteborg, Sweden.
2Program in Craniofacial Biology and Department of Orofacial Sciences, University of California San Francisco, CA, United States of America.
3Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL, United States of America.
4Department of Pediatrics and Institute for Human Genetics, University of California San Francisco, CA, United States of America.
Journal: PLoS Genetics

Date of e-pub: July 2017

Abstract: The interaction between signaling pathways is a central question in the study of organogenesis. Using the developing murine tongue as a model, we uncovered unknown relationships between Sonic hedgehog (SHH) and retinoic acid (RA) signaling. Genetic loss of SHH signaling leads to enhanced RA activity subsequent to loss of SHH-dependent expression of Cyp26a1 and Cyp26c1. This causes a cell identity switch, prompting the epithelium of the tongue to form heterotopic minor salivary glands and to overproduce oversized taste buds. At developmental stages during which Wnt10b expression normally ceases and Shh becomes confined to taste bud cells, loss of SHH inputs causes the lingual epithelium to undergo an ectopic and anachronic expression of Shh and Wnt10b in the basal layer, specifying de novo taste placode induction. Surprisingly, in the absence of SHH signaling, lingual epithelial cells adopted a Merkel cell fate, but this was not caused by enhanced RA signaling. We show that RA promotes, whereas SHH, acting strictly within the lingual epithelium, inhibits taste placode and lingual gland formation by thwarting RA activity. These findings reveal key functions for SHH and RA in cell fate specification in the lingual epithelium and aid in deciphering the molecular mechanisms that assign cell identity.

 

 

Redox regulation of a guard cell SNF1-related protein kinase in Brassica napus, an oilseed crop.

Author information: Zhu M1, Zhang T1, Ji W1,2, Silva-Sanchez C3, Song WY4,5, Assmann SM6, Harmon AC1,4, Chen S7,3,4.

1Department of Biology, Genetics Institute, University of Florida, Gainesville, FL 32610, U.S.A.
2Plant Bioengineering Laboratory, College of Life Sciences, Northeast Agricultural University, Harbin 150030, China.
3Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, FL 32610, U.S.A.
4Plant Molecular and Cellular Biology Program, University of Florida, Gainesville, FL 32610, U.S.A.
5Department of Plant Pathology, University of Florida, Gainesville, FL 32610, U.S.A.
6Department of Biology, Pennsylvania State University, University Park, PA 16802, U.S.A.
7Department of Biology, Genetics Institute, University of Florida, Gainesville, FL 32610, U.S.A. schen@ufl.edu.
Journal: The Biochemical Journal

Date of e-pub: July 2017

Abstract: Kinase-mediated phosphorylation is a pivotal regulatory process in stomatal responses to stresses. Through a redox proteomics study, a sucrose non-fermenting 1-related protein kinase (SnRK2.4) was identified to be redox-regulated in Brassica napus guard cells upon abscisic acid treatment. There are six genes encoding SnRK2.4 paralogs in B. napus Here, we show that recombinant BnSnRK2.4-1C exhibited autophosphorylation activity and preferentially phosphorylated the N-terminal region of B. napus slow anion channel (BnSLAC1-NT) over generic substrates. The in vitro activity of BnSnRK2.4-1C requires the presence of manganese (Mn2+). Phosphorylation sites of autophosphorylated BnSnRK2.4-1C were mapped, including serine and threonine residues in the activation loop. In vitro BnSnRK2.4-1C autophosphorylation activity was inhibited by oxidants such as H2O2 and recovered by active thioredoxin isoforms, indicating redox regulation of BnSnRK2.4-1C. Thiol-specific isotope tagging followed by mass spectrometry analysis revealed specific cysteine residues responsive to oxidant treatments. The in vivo activity of BnSnRK2.4-1C is inhibited by 15 min of H2O2 treatment. Taken together, these data indicate that BnSnRK2.4-1C, an SnRK preferentially expressed in guard cells, is redox-regulated with potential roles in guard cell signal transduction.

 

 

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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