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1. Kenaf: Opportunities for an Ancient Fiber Crop

Author: Conner C. Austin, Colleen N. Mondell, David G. Clark, and Ann C. Wilkie
Subjects: absorbent, bast fiber, biochar, biocomposites, biomass energy, fiber crops, Agriculture
Abstract: Hibiscus cannabinus (kenaf) is an annual fiber crop grown in warm seasons and known for its remarkable productivity; it has been cultivated worldwide for thousands of years as a fiber source. While every part of the plant can be utilized for some purpose, its primary significance lies in the diverse applications of its cellulosic fiber. Kenaf features a blend of long bast and short core fibers, rendering it suitable for various industrial uses. Initially utilized for cordage and livestock feed, kenaf’s applications have expanded over the last century to encompass its utilization as paper pulp, biocomposites, textiles, biomass energy, seed oil, filtration aids, industrial absorbents, and even as a component of potting medium or as a potential source of medicine. Although traditionally a niche crop, the discovery of its diverse applications positions kenaf for rapid expansion in production in the upcoming decades. This article aims to explore the manifold applications of kenaf, highlighting those with the greatest future potential and discussing those that hold promise for commercial-level application with additional research.
Published: 2024
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2. Spatial transcriptomic patterns underlying amyloid-β and tau pathology are associated with cognitive dysfunction in Alzheimer’s disease

Author: Meichen Yu, Shannon L. Risacher, Kwangsik T. Nho, Qiuting Wen, Adrian L. Oblak, Frederick W. Unverzagt, Liana G. Apostolova, Martin R. Farlow, Jared R. Brosch, David G. Clark, Sophia Wang, Rachael Deardorff, Yu-Chien Wu, Sujuan Gao, Olaf Sporns, and Andrew J. Saykin
Subjects: CP: Neuroscience, Biology (General), QH301-705.5
Abstract: Summary: Amyloid-β (Aβ) and tau proteins accumulate within distinct neuronal systems in Alzheimer’s disease (AD). Although it is not clear why certain brain regions are more vulnerable to Aβ and tau pathologies than others, gene expression may play a role. We study the association between brain-wide gene expression profiles and regional vulnerability to Aβ (gene-to-Aβ associations) and tau (gene-to-tau associations) pathologies by leveraging two large independent AD cohorts. We identify AD susceptibility genes and gene modules in a gene co-expression network with expression profiles specifically related to regional vulnerability to Aβ and tau pathologies in AD. In addition, we identify distinct biochemical pathways associated with the gene-to-Aβ and the gene-to-tau associations. These findings may explain the discordance between regional Aβ and tau pathologies. Finally, we propose an analytic framework, linking the identified gene-to-pathology associations to cognitive dysfunction in AD at the individual level, suggesting potential clinical implication of the gene-to-pathology associations.
Published: 2024
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3. nduction and Characterization of Mutations Related to Dwarf Habit in Hardy Hibiscus (Muenchhusia section)

Author: Conner C. Austin, Joshua M. Tester, James E. Webb, and David G. Clark
Subjects: branching, chemical mutagen, ethyl methanesulftonate, Plant culture, SB1-1110
Abstract: Hybrids between various species of Hibiscus in the Muenchhusia section are popular in commercial markets due to their colorful, floriferous blooms. However, many commercial cultivars are too vigorous for use in smaller garden spaces and often have only a few flowers in bloom. Stable, heritable mutants exhibiting dwarf stature and better branching architecture will be valuable to the commercial production of hardy Hibiscus. The goal of this project was to induce stable, heritable mutations using ethyl methanesulfonate that result in increased branching and a dwarf compact phenotype and introgress the compact phenotypes into lines of hardy Hibiscus to generate a series of diverse compact cultivars for use in commercial markets. Multiple mutations associated with dwarf, compact phenotypes were successfully induced. Hybridizations were made between M2 plants displaying a dwarf phenotype and hybrids developed through conventional breeding that do not possess the dwarf mutation in their background to develop diverse selections of dwarf plants. Inheritance patterns of the dwarf genes were determined through the segregation ratios of the dwarf phenotype in the F1 and F2 generations of these hybrids. Compared with wild-type progeny, dwarf progeny had shorter internode lengths and a greater number of primary branches.
Published: 2023
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4. Construction of a genome-wide genetic linkage map and identification of quantitative trait loci for powdery mildew resistance in Gerbera daisy

Author: Krishna Bhattarai, Sadikshya Sharma, Sujeet Verma, Natalia A. Peres, Shunyuan Xiao, David G. Clark, and Zhanao Deng
Subjects: Gerbera (Gerbera hybrida), powdery mildew resistance, genetic linkage map, QTL, disease resistance QTL, genotyping by sequecncing, Plant culture, SB1-1110
Abstract: Powdery mildew (PM) is a common fungal disease in many important crops. The PM caused by Podosphaera xanthii has been the most challenging problem in commercial Gerbera (Gerbera hybrida) production globally, often leading to severe losses of crop yield and quality. A small number of PM-resistant breeding lines and cultivars have been reported in Gerbera, but the underlying genetics for PM resistance in Gerbera is largely unknown. Scarcity of genomic resources such as genetic linkage maps and molecular markers has severely hindered the effort to understand the genetic basis and locate loci controlling PM resistance in Gerbera. This study aimed to construct a genome-wide genetic linkage map, identify quantitative trait loci (QTL), and molecular markers for PM resistance in Gerbera. A segregating mapping population was developed by crossing PM-resistant and -susceptible Gerbera breeding lines, genotyped by sequencing, and phenotyped for PM resistance. A genome-wide genetic linkage map constructed with 791 single polymorphic site (SNP) markers spans 1912.30 cM across 27 linkage groups (LG) and reaches a density of 1 marker per 2.42 cM. One major consistent QTL was discovered in LG16, explaining more than 16.6% of the phenotypic variance for PM resistance. The QTL was tagged with two flanking SNP markers. The availability of this genetic linkage map will be very useful for locating and tagging QTLs for other important traits in Gerbera, and the newly discovered QTL and SNP markers will enable development of molecular markers for improving Gerbera for resistance to PM.
Published: 2023
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5. Sequencing and analysis of gerbera daisy leaf transcriptomes reveal disease resistance and susceptibility genes differentially expressed and associated with powdery mildew resistance

Author: Krishna Bhattarai, Ana Conesa, Shunyuan Xiao, Natalia A. Peres, David G. Clark, Saroj Parajuli, and Zhanao Deng
Subjects: Differentially expressed genes, Disease resistance, Gerbera, Powdery mildew resistance, R-gene, Single nucleotide polymorphisms, Botany, QK1-989
Abstract: Abstract Background RNA sequencing has been widely used to profile genome-wide gene expression and identify candidate genes controlling disease resistance and other important traits in plants. Gerbera daisy is one of the most important flowers in the global floricultural trade, and powdery mildew (PM) is the most important disease of gerbera. Genetic improvement of gerbera PM resistance has become a crucial goal in gerbera breeding. A better understanding of the genetic control of gerbera resistance to PM can expedite the development of PM-resistant cultivars. Results The objectives of this study were to identify gerbera genotypes with contrasting phenotypes in PM resistance and sequence and analyze their leaf transcriptomes to identify disease resistance and susceptibility genes differentially expressed and associated with PM resistance. An additional objective was to identify SNPs and SSRs for use in future genetic studies. We identified two gerbera genotypes, UFGE 4033 and 06–245-03, that were resistant and susceptible to PM, respectively. De novo assembly of their leaf transcriptomes using four complementary pipelines resulted in 145,348 transcripts with a N50 of 1124 bp, of which 67,312 transcripts contained open reading frames and 48,268 were expressed in both genotypes. A total of 494 transcripts were likely involved in disease resistance, and 17 and 24 transcripts were up- and down-regulated, respectively, in UFGE 4033 compared to 06–245-03. These gerbera disease resistance transcripts were most similar to the NBS-LRR class of plant resistance genes conferring resistance to various pathogens in plants. Four disease susceptibility transcripts (MLO-like) were expressed only or highly expressed in 06–245-03, offering excellent candidate targets for gene editing for PM resistance in gerbera. A total of 449,897 SNPs and 19,393 SSRs were revealed in the gerbera transcriptomes, which can be a valuable resource for developing new molecular markers. Conclusion This study represents the first transcriptomic analysis of gerbera PM resistance, a highly important yet complex trait in a globally important floral crop. The differentially expressed disease resistance and susceptibility transcripts identified provide excellent targets for development of molecular markers and genetic maps, cloning of disease resistance genes, or targeted mutagenesis of disease susceptibility genes for PM resistance in gerbera.
Published: 2020
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6. Avaliação de plantas transgênicas de Petunia x hybrida contendo o gene Psag12 - ipt cultivadas sob deficiência nutricional.

Author: Francine Lorena Cuquel and David G. Clark e Keigo Minami
Subjects: Plant culture, SB1-1110
Abstract: Deficiência nutricional em plantas pode causar clorose, necrose, desfolha, redução do crescimento e da produtividade e senescência prematura. Aplicações xógenas de citocinina podem aliviar tais sintomas. Este estudo foi efetuado para avaliar os efeitos da produção auto-regulada de citocinina na tolerância de plantas de petúnia (Petunia x hybrida) à deficiência nutricional. Um gene quimérico contendo o promotor SAG12 unido ao gene ipt, o qual codifica a produção de isopentenyl transferase, uma enzima da rota metabólica da biossíntese de citocinina, foi introduzido em petúnia através de transformação mediada por Agrobacterium. Duas plantas contendo o gene ipt foram selecionadas e autopolinizadas para obtenção das linhas a serem submetidas à deficiência nutricional. Ambas as linhas PSAG12–ipt avaliadas foram mais tolerantes à deficiência nutricional que as plantas do tipo selvagem. Os resultados indicam que a produção endógena de citocinina pode aumentar a tolerância das plantas à deficiência nutricional.
Published: 2001
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7. Review of Screwtape’s Master Plan. A Satirical Take on Christianity and Culture

Author: David G. Clark
Published: 2023
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8. Review of As One Devil to Another. A Fiendish Correspondence in the Tradition of C. S. Lewis’ The Screwtape Letters

Author: David G. Clark
Published: 2023
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9. Review of The Feeling Intellect: Reading the Bible with C.S. Lewis

Author: David G. Clark
Published: 2023
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10. Review of C. S. Lewis: Views from Wake Forest. Essays on C. S. Lewis by Walter Hooper, James Como, and many others

Author: David G. Clark
Published: 2023
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11. Optimizing differential identifiability improves connectome predictive modeling of cognitive deficits from functional connectivity in Alzheimer's disease

Author: David G. Clark, Charanya Muralidharan, John D. West, Enrico Amico, Andrew J. Saykin, Mario Dzemidzic, Diana O. Svaldi, Joaquín Goñi, Liana G. Apostolova, Shannon L. Risacher, and Kausar Abbas
Subjects: cognition, Male, Computer science, Disease, 050105 experimental psychology, Functional networks, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Connectome, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, Generalizability theory, Cognitive Dysfunction, resting state, Research Articles, Aged, Aged, 80 and over, Radiological and Ultrasound Technology, Resting state fMRI, Functional connectivity, 05 social sciences, fMRI, functional connectivity, functional fingerprinting, Cognition, AD, Alzheimer's disease, Magnetic Resonance Imaging, Neurology, Identifiability, Female, Neurology (clinical), Anatomy, Nerve Net, Neuroscience, predictive modeling, 030217 neurology & neurosurgery, Research Article
Abstract: Functional connectivity, as estimated using resting state functional MRI, has shown potential in bridging the gap between pathophysiology and cognition. However, clinical use of functional connectivity biomarkers is impeded by unreliable estimates of individual functional connectomes and lack of generalizability of models predicting cognitive outcomes from connectivity. To address these issues, we combine the frameworks of connectome predictive modeling and differential identifiability. Using the combined framework, we show that enhancing the individual fingerprint of resting state functional connectomes leads to robust identification of functional networks associated to cognitive outcomes and also improves prediction of cognitive outcomes from functional connectomes. Using a comprehensive spectrum of cognitive outcomes associated to Alzheimer's disease (AD), we identify and characterize functional networks associated to specific cognitive deficits exhibited in AD. This combined framework is an important step in making individual level predictions of cognition from resting state functional connectomes and in understanding the relationship between cognition and connectivity., Using differential identifiability and connectome predictive modeling, we show that enhancing the individual fingerprint of resting state functional connectomes leads to robust identification of functional networks associated to cognitive outcomes and also improves prediction of cognitive outcomes from functional connectomes. The framework allows us to more robustly identify and characterize functional networks associated to specific cognitive outcomes exhibited in AD.
Published: 2021

12. Sequencing and analysis of gerbera daisy leaf transcriptomes reveal disease resistance and susceptibility genes differentially expressed and associated with powdery mildew resistance

Author: Natalia A. Peres, Saroj Parajuli, David G. Clark, Ana Conesa, Zhanao Deng, Krishna Bhattarai, and Shunyuan Xiao
Subjects: Gerbera, Candidate gene, Genotype, Powdery mildew resistance, Single-nucleotide polymorphism, Plant Science, Asteraceae, Plant disease resistance, Real-Time Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Susceptibility gene, Ascomycota, Simple sequence repeats, lcsh:Botany, R-gene, RNA-Seq, Gene, Plant Diseases, Genetics, Disease resistance, biology, food and beverages, R gene, Single nucleotide polymorphisms, biology.organism_classification, lcsh:QK1-989, Plant Leaves, Plant Breeding, Phenotype, Differentially expressed genes, Microsatellite, Transcriptome, Powdery mildew, Microsatellite Repeats, Research Article
Abstract: BackgroundRNA sequencing has been widely used to profile genome-wide gene expression and identify candidate genes controlling disease resistance and other important traits in plants. Gerbera daisy is one of the most important flowers in the global floricultural trade, and powdery mildew (PM) is the most important disease of gerbera. Genetic improvement of gerbera PM resistance has become a crucial goal in gerbera breeding. A better understanding of the genetic control of gerbera resistance to PM can expedite the development of PM-resistant cultivars.ResultsThe objectives of this study were to identify gerbera genotypes with contrasting phenotypes in PM resistance and sequence and analyze their leaf transcriptomes to identify disease resistance and susceptibility genes differentially expressed and associated with PM resistance. An additional objective was to identify SNPs and SSRs for use in future genetic studies. We identified two gerbera genotypes, UFGE 4033 and 06–245-03, that were resistant and susceptible to PM, respectively. De novo assembly of their leaf transcriptomes using four complementary pipelines resulted in 145,348 transcripts with a N50 of 1124 bp, of which 67,312 transcripts contained open reading frames and 48,268 were expressed in both genotypes. A total of 494 transcripts were likely involved in disease resistance, and 17 and 24 transcripts were up- and down-regulated, respectively, in UFGE 4033 compared to 06–245-03. These gerbera disease resistance transcripts were most similar to the NBS-LRR class of plant resistance genes conferring resistance to various pathogens in plants. Four disease susceptibility transcripts (MLO-like) were expressed only or highly expressed in 06–245-03, offering excellent candidate targets for gene editing for PM resistance in gerbera. A total of 449,897 SNPs and 19,393 SSRs were revealed in the gerbera transcriptomes, which can be a valuable resource for developing new molecular markers.ConclusionThis study represents the first transcriptomic analysis of gerbera PM resistance, a highly important yet complex trait in a globally important floral crop. The differentially expressed disease resistance and susceptibility transcripts identified provide excellent targets for development of molecular markers and genetic maps, cloning of disease resistance genes, or targeted mutagenesis of disease susceptibility genes for PM resistance in gerbera.
Published: 2020

13. Validated Model for Prediction of Adverse Cardiac Outcome in Patients With Fabry Disease

Author: Christopher Orsborne, Joshua Bradley, Laura J. Bonnett, Luke A. Pleva, Josephine H. Naish, David G. Clark, Nik Abidin, Peter Woolfson, Gaetano Nucifora, Matthias Schmitt, Ana Jovanovic, Christopher A. Miller, and Anna B. Reid
Subjects: Male, Predictive Value of Tests, Risk Factors, Myocardium, Fabry Disease, Humans, Female, Heart, Prospective Studies, Cardiology and Cardiovascular Medicine, Prognosis
Abstract: The cardiac manifestations of Fabry disease are the leading cause of death, but risk stratification remains inadequate. Identifying patients who are at risk of adverse cardiac outcome may facilitate more evidence-based treatment guidance. Contemporary cardiovascular cardiac magnetic resonance biomarkers have become widely adopted, but their prognostic value remains unclear.The objective of this study was to develop, internally validate, and evaluate the performance of, a prognostic model, including contemporary deep phenotyping, which can be used to generate individual risk estimates for adverse cardiac outcome in patients with Fabry disease.This longitudinal prospective cohort study consisted of 200 consecutive patients with Fabry disease undergoing clinical cardiac magnetic resonance. Median follow-up was 4.5 years (IQR: 2.7-6.3 years). Prognostic models were developed using Cox proportional hazards modeling. Outcome was a composite of adverse cardiac events. Model performance was evaluated. A risk calculator, which provides 5-year estimated risk of adverse cardiac outcome for individual patients, including men and women, was generated.The highest performing, internally validated, parsimonious multivariable model included age, native myocardial TThis study developed and internally validated a risk prediction model that accurately predicts 5-year risk of adverse cardiac outcome for individual patients with Fabry disease, including men and women, which could easily be integrated into clinical care. External validation is warranted.
Published: 2022

14. Ranking qualitative and timing‐based verbal fluency scores as predictors of incident cognitive impairment

Author: Justin Bushnell, Diana Svaldi, Matthew Ayers, Sujuan Gao, Fredrick Unverzagt, John Del Gaizo, Virginia G Wadley, Richard E Kennedy, Joaquín Goñi, and David G. Clark
Subjects: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published: 2021
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15. Randomized Controlled Trial of a Cognitive Intervention to Improve Memory in Heart Failure

Author: David G. Clark, Heather Burney, Marita G. Titler, Susan J. Pressler, Susan G. Dorsey, Irmina Gradus-Pizlo, Bruno Giordani, Sujuan Gao, Kelly L. Wierenga, Kittie Reid Lake, Miyeon Jung, and Dean G. Smith
Subjects: Comparative Effectiveness Research, medicine.medical_specialty, Activities of daily living, Clinical Trials and Supportive Activities, Clinical Sciences, Nursing, Cardiorespiratory Medicine and Haematology, Cardiovascular, computerized cognitive training, Article, law.invention, Quality of life (healthcare), Cognition, Randomized controlled trial, cognitive dysfunction, Clinical Research, law, Behavioral and Social Science, Activities of Daily Living, Medicine, Humans, nurse-enhancement intervention, Heart Failure, Cognitive Intervention, Recall, business.industry, Working memory, Prevention, Brain-Derived Neurotrophic Factor, Rehabilitation, Cognitive training, Cardiovascular System & Hematology, Physical therapy, Quality of Life, Cardiology and Cardiovascular Medicine, business
Abstract: Background The objective of this 3-arm randomized controlled trial was to evaluate efficacy of computerized cognitive training (CCT) to improve primary outcomes of delayed recall memory and serum brain-derived neurotrophic factor (BDNF) levels and secondary outcomes of working memory, instrumental activities of daily living (IADL), and health-related quality of life (HRQL) among patients with heart failure (HF). Methods and Results Patients (N = 256) were randomly assigned to 8 weeks of CCT using BrainHQ, computerized crossword puzzles active control intervention, and usual care. All patients received weekly nurse enhancement interventions. Data were collected at enrollment and baseline visits and at 10 weeks and 4 and 8 months. In mixed effects models, there were no statistically significant group or group by time differences in outcomes. There were statistically significant differences over time in all outcomes in all groups. Patients improved over time on measures of delayed recall memory, working memory, IADL, and HRQL and had decreased serum BDNF. Conclusions CCT did not improve outcomes compared with the active control intervention and usual care. Nurse enhancement interventions may have led to improved outcomes over time. Future studies are needed to test nurse enhancement interventions in combination with other cognitive interventions to improve memory in HF. LaySummary In 256 patients with heart failure, 8 weeks of computerized cognitive training, computerized crossword puzzles, or usual care were studied for effects on (1st) recall memory and serum brain-derived neurotrophic factor (BDNF) and (2nd) working memory, instrumental activities of daily living (IADL), and health-related quality of life (HRQL). Measurements were at baseline, 10 weeks, 4- and 8-months. Nurse enhancement interventions (e.g., support, assessment) were provided. Recall memory, working memory, IADL, and HRQL improved over time. There were no statistically significant differences among treatment groups over time. BDNF unexpectedly decreased. Nurse enhancement interventions may explain improved outcomes. Future studies are needed.
Published: 2021

16. Effects of Melatonin and AVG on Plant Growth of Three Pilea Species in Darkness

Author: Chi Dinh Nguyen, Diying Xiang, Heqiang Huo, David G. Clark, and Jayson Opgenorth
Subjects: Melatonin, Chlorophyll content, Plant growth, Darkness, Botany, medicine, Plant Science, Horticulture, Biology, Pilea, biology.organism_classification, medicine.drug
Published: 2020
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17. Identifying Breeding Priorities for Blueberry Flavor Using Biochemical, Sensory, and Genotype by Environment Analyses.

Author: Jessica L Gilbert, Matthew J Guthart, Salvador A Gezan, Melissa Pisaroglo de Carvalho, Michael L Schwieterman, Thomas A Colquhoun, Linda M Bartoshuk, Charles A Sims, David G Clark, and James W Olmstead
Subjects: Medicine, Science
Abstract: Breeding for a subjective goal such as flavor is challenging, as many blueberry cultivars are grown worldwide, and identifying breeding targets relating to blueberry flavor biochemistry that have a high degree of genetic control and low environmental variability are priorities. A variety of biochemical compounds and physical characters induce the sensory responses of taste, olfaction, and somatosensation, all of which interact to create what is perceived flavor. The goal of this study was to identify the flavor compounds with a larger genetic versus environmental component regulating their expression over an array of cultivars, locations, and years. Over the course of three years, consumer panelists rated overall liking, texture, sweetness, sourness, and flavor intensity of 19 southern highbush blueberry (Vaccinium corymbosum hybrids) genotypes in 30 sensory panels. Significant positive correlations to overall liking of blueberry fruit (P
Published: 2015
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18. Strong Fluorescence Expression of ZsGreen1 in Petunia Flowers by Agrobacterium tumefaciens–mediated Transformation

Author: David G. Clark, Maria I. Alvarez, Joshua M. Tester, Thomas A. Colquhoun, Keun H. Cho, Jooyoung Kim, Veronica Y. Laux, and Lauren K. Valad
Subjects: biology, Chemistry, fungi, Stamen, Agrobacterium tumefaciens, Genetically modified crops, Horticulture, biology.organism_classification, Petunia, Molecular biology, Hypocotyl, Transformation (genetics), Inflorescence, Gene expression, Genetics
Abstract: Fluorescent proteins (FT) have become essential, biological research tools. Many novel genes have been cloned from a variety of species and modified for effective, stable, and strong expression in transgenic organisms. Although there are many applications, FT expression has been employed most commonly at the cellular level in plants. To investigate FT expression at the whole-plant level, particularly in flowers, petunia ‘Mitchell Diploid’ [MD (Petunia ×hybrida)] was genetically transformed with seven genes encoding FTs: DsRed2, E2Crimson, TurboRFP, ZsGreen1, ZsYellow1, rpulFKz1, or aeCP597. Each gene was cloned into a pHK-DEST-OE vector harboring constitutive figwort mosaic virus 35S promoter and NOS-terminator. These plasmids were individually introduced into the genome of MD by Agrobacterium tumefaciens–mediated transformation. Shoot regeneration efficiency from the cocultured explants ranged from 8.3% to 20.3%. Various intensities of red, green, and yellow fluorescence were detected from TurboRFP, ZsGreen1, and ZsYellow1-transgenic flowers, respectively, under ultraviolet light for specific excitation and emission filters. More than 70% of plants established from the regenerated shoots were confirmed as transgenic plants. Transgenic ZsGreen1 petunia generated strong, green fluorescence in all flower organs of T0 plants including petals, stigmas, styles, anthers, and filaments. Most of the chromophores were localized to the cytoplasm but also went into the nuclei of petal cells. There was a positive linear relationship (R2 = 0.88) between the transgene expression levels and the relative fluorescent intensities of the ZsGreen1-transgenic flowers. No fluorescence was detected from the flowers of DsRed2-, E2Crimson-, rpulFKz1-, or aeCP597-transgenic petunias even though their gene transcripts were confirmed through semiquantitative reverse transcriptase-polymerase chain reaction. T1 generation ZsGreen1 plants showed green fluorescence emission from the cotyledons, hypocotyls, and radicles, which indicated stable FT expression was heritable. Four homozygous T2 inbred lines were finally selected. Throughout this study, we demonstrated that ZsGreen1 was most suitable for generating visible fluorescence in MD flowers among the seven genes tested. Thus, ZsGreen1 may have excellent potential for better utility as a sensitive selectable marker.
Published: 2019
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19. Down regulation of p-coumarate 3-hydroxylase in petunia uniquely alters the profile of emitted floral volatiles

Author: David G. Clark, Timothy S. Johnson, Jooyoung Kim, Robert T. Swanson, Keun H. Cho, Maria I. Alvarez, and Thomas A. Colquhoun
Subjects: 0301 basic medicine, Coumaric Acids, Plant physiology, Down-Regulation, lcsh:Medicine, Phenylalanine, Flowers, Esterase, Petunia, Article, Cinnamic acid, Mixed Function Oxygenases, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Biosynthesis, Metabolomics, lcsh:Science, Volatile Organic Compounds, Multidisciplinary, Phenylpropanoid, biology, fungi, lcsh:R, food and beverages, Metabolism, biology.organism_classification, Isoeugenol, 030104 developmental biology, chemistry, Biochemistry, lcsh:Q, Propionates, Volatilization, Carboxylic Ester Hydrolases, Acyltransferases, 030217 neurology & neurosurgery
Abstract: Petunia × hybrida cv ‘Mitchell Diploid’ floral volatile benzenoid/phenylpropanoid (FVBP) biosynthesis ultimately produces floral volatiles derived sequentially from phenylalanine, cinnamic acid, and p-coumaric acid. In an attempt to better understand biochemical steps after p-coumaric acid production, we cloned and characterized three petunia transcripts with high similarity to p-coumarate 3-hydroxylase (C3H), hydroxycinnamoyl-CoA:shikimate/quinate hydroxycinnamoyl transferase (HCT), and caffeoyl shikimate esterase (CSE). Transcript accumulation of PhC3H and PhHCT was highest in flower limb tissue during open flower stages. PhCSE transcript accumulation was also highest in flower limb tissue, but it was detected earlier at initial flower opening with a bell-shaped distribution pattern. Down regulation of endogenous PhC3H transcript resulted in altered transcript accumulation of many other FVBP network transcripts, a reduction in floral volatiles, and the emission of a novel floral volatile. Down regulation of PhHCT transcript did not have as large of an effect on floral volatiles as was observed for PhC3H down regulation, but eugenol and isoeugenol emissions were significantly reduced on the downstream floral volatiles. Together these results indicate that PhC3H is involved in FVBP biosynthesis and the reduction of PhC3H transcript influences FVBP metabolism at the network level. Additional research is required to illustrate PhHCT and PhCSE functions of petunia.
Published: 2019
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20. Effects of Light Quality on Vegetative Cutting and In Vitro Propagation of Coleus (Plectranthus scutellarioides)

Author: Nathan Wallace-Springer, David G. Clark, Veronica Y. Laux, Keun H. Cho, Thomas A. Colquhoun, and Kevin M. Folta
Subjects: Horticulture, food.ingredient, food, biology, Plectranthus scutellarioides, Coleus, biology.organism_classification
Abstract: Coleus (Plectranthus scutellarioides) is an attractive and popular ornamental plant with propagation mainly achieved through vegetative cuttings. For commercial purposes, it is of interest to enhance the speed of establishment while maintaining high quality. Light quality has been shown to influence adventitious root development, so these experiments examined the effect of narrow-bandwidth light treatments on root growth and overall plant quality for seven coleus cultivars with vegetative cuttings in potting soil and one cultivar with shoot tip in vitro cultures onto Murashige and Skoog (MS) agar medium. During the 28 days of the propagation period, the cuttings grown under narrow-bandwidth red light (R; 663.4 nm at peak) more than doubled in the adventitious root number compared with those under blue light (B; 445.7 nm at peak) and green light (G; 530.0 nm at peak) in five cultivars. R light also increased fresh weight of the cuttings by 55.6% more than G light. In comparison, the cuttings grown under G light yielded significantly lower root and shoot dry mass than other light treatments. R light cuttings showed more dry mass content (9.63%) than those under white light (W; 437.4 nm and 559.5 nm at peak) and G light (7.85% and 5.86%, respectively). A positive correlation (R2 = 0.598, P < 0.001) was found between the formation of adventitious roots and gained fresh weight of cuttings. R light made the reddish color of leaves significantly stronger in most cultivars, whereas the cuttings exposed to G light became less vivid compared with other light conditions. When the shoot tips were propagated in vitro onto MS medium, R light treatment initiated the root development more rapidly than other lights, with significantly greater rooting rate (20.0% and 63.6%, respectively) at day 5 and 10. The shoot tips under R light also formed significantly more roots (12.3 per cutting) than those grown under narrow-bandwidth B light (5.8 per cutting). The shoot tips showed browning at an early stage and newly emerged leaves grew very compactly under B light. The combination of red and green light (R+G) increased more than twice as much roots and dry mass compared with W light. In addition, the R+G light led to morphological changes, including larger leaves and longer petioles and internodes than those in other light treatments. The exposure to R+G+B and B light made the shoots very compact for the 28 days of in vitro culture period and significantly increased the chlorophyll contents resulting in dark green leaves.
Published: 2019
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21. Strawberry flavor: diverse chemical compositions, a seasonal influence, and effects on sensory perception.

Author: Michael L Schwieterman, Thomas A Colquhoun, Elizabeth A Jaworski, Linda M Bartoshuk, Jessica L Gilbert, Denise M Tieman, Asli Z Odabasi, Howard R Moskowitz, Kevin M Folta, Harry J Klee, Charles A Sims, Vance M Whitaker, and David G Clark
Subjects: Medicine, Science
Abstract: Fresh strawberries (Fragaria x ananassa) are valued for their characteristic red color, juicy texture, distinct aroma, and sweet fruity flavor. In this study, genetic and environmentally induced variation is exploited to capture biochemically diverse strawberry fruit for metabolite profiling and consumer rating. Analyses identify fruit attributes influencing hedonics and sensory perception of strawberry fruit using a psychophysics approach. Sweetness intensity, flavor intensity, and texture liking are dependent on sugar concentrations, specific volatile compounds, and fruit firmness, respectively. Overall liking is most greatly influenced by sweetness and strawberry flavor intensity, which are undermined by environmental pressures that reduce sucrose and total volatile content. The volatile profiles among commercial strawberry varieties are complex and distinct, but a list of perceptually impactful compounds from the larger mixture is better defined. Particular esters, terpenes, and furans have the most significant fits to strawberry flavor intensity. In total, thirty-one volatile compounds are found to be significantly correlated to strawberry flavor intensity, only one of them negatively. Further analysis identifies individual volatile compounds that have an enhancing effect on perceived sweetness intensity of fruit independent of sugar content. These findings allow for consumer influence in the breeding of more desirable fruits and vegetables. Also, this approach garners insights into fruit metabolomics, flavor chemistry, and a paradigm for enhancing liking of natural or processed products.
Published: 2014
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22. Effects of Maternal Environment on Seed Germination and Seedling Vigor of Petunia × hybrida under Different Abiotic Stresses

Author: Chi Dinh Nguyen, Heqiang Alfred Huo, David G. Clark, Hector E. Pérez, and Jianjun Chen
Subjects: 0106 biological sciences, 0301 basic medicine, maternal effect, Plant Science, drought, 01 natural sciences, Petunia, Article, salinity, 03 medical and health sciences, chemistry.chemical_compound, Ornamental plant, petunia, Abscisic acid, Ecology, Evolution, Behavior and Systematics, Abiotic component, Ecology, biology, fungi, Maternal effect, Botany, food and beverages, biology.organism_classification, Salinity, Horticulture, 030104 developmental biology, chemistry, ABA, Germination, Seedling, QK1-989, heat, 010606 plant biology & botany
Abstract: Seed germination and seedling vigor can be affected by environmental cues experienced by the mother plant. However, information about how the maternal environment affects seed quality is scarce in ornamental plants. This study aimed to investigate the effects of two different maternal environments on the seed germination and seedling vigor of Petunia × hybrida under a variety of abiotic stresses. Petunia mother plants were grown in either a greenhouse during the summer months or an indoor controlled-temperature-and-light environment. Collected seeds were subjected to external stressors, including polyethylene glycol (PEG), sodium chloride (NaCl), high temperature, and abscisic acid (ABA), to determine seed germination percentage and seedling vigor. Results indicated that seeds harvested from the mother plants grown in a controlled environment germinated better than seeds harvested from the mother plants grown in the greenhouse when suboptimal germination conditions were applied. Additionally, the seedlings from the controlled maternal environment performed better in both ABA and salinity stress tests than the greenhouse seedlings. Interestingly, the greenhouse seedlings displayed less reactive oxygen species (ROS) damage and lower electrolyte leakage than the controlled environment seedlings under dehydration stress. The difference in germination and seedling vigor of seeds from the two different maternal environments might be due to the epigenetic memory inherited from the mother plants. This study highlighted the strong impact of the maternal environment on seed germination and seedling vigor in Petunia and may assist in high-quality seed production in ornamental plants.
Published: 2021

23. Quantitative dissection of color patterning in the foliar ornamental Coleus reveals underlying features driving aesthetic value

Author: Margaret H. Frank, David G. Clark, Mao Li, Viktoriya Coneva, and Daniel H. Chitwood
Subjects: Aesthetic value, food.ingredient, food, Evolutionary biology, Ornamental plant, Trait, Color analysis, Coleus, Biology, Plant biology
Abstract: SummaryColeus is a popular ornamental plant that exhibits a diverse array of foliar color patterns. New cultivars are currently hand selected by both amateur and experienced plant breeders. In this study, we reimagine coleus breeding using a quantitative color analysis framework.Despite impressive advances in high-throughput data collection and processing, complex color patterns remain challenging to extract from image datasets. Using a new phenotyping approach called “ColourQuant,” we extract and analyze pigmentation patterns from one of the largest coleus breeding populations in the world.Working with this massive dataset, we are able to analyze quantitative relationships between maternal plants and their progeny, identify features that underlie breeder-selections, and collect and compare consumer input on trait preferences.This study is one of the most comprehensive explorations into complex color patterning in plant biology and provides new insights and tools for exploring the color pallet of the plant kingdom.
Published: 2021
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24. Olfactory Landmarks and Path Integration Converge to Form a Cognitive Spatial Map

Author: Mark J. Schnitzer, Walter Fischler-Ruiz, Narendra R. Joshi, Lacey J. Kitch, Larry F. Abbott, David G. Clark, Virginia Devi-Chou, and Richard Axel
Subjects: Iterative and incremental development, Landmark, Computer science, business.industry, musculoskeletal, neural, and ocular physiology, Place cell, Cognition, Sensory system, Odor, Path integration, Computer vision, Spatial maps, Artificial intelligence, business, psychological phenomena and processes
Abstract: The convergence of internal path integration and external sensory landmarks generates a cognitive spatial map in the hippocampus. We studied how spatially localized odor cues are recognized as landmarks to guide navigation by recording the activity of neurons in CA1 during a virtual navigation task. We found that odor cues enriched place cell representations and dramatically improving navigation. Presentation of the same odor at different locations generated distinct place cell representations. An odor cue at a proximal location not only enhanced the local place cell density but also led to the formation of place cells beyond the cue. This resulted in the recognition of a second, more distal odor cue as a distinct landmark, suggesting an iterative mechanism for extending spatial representations into unknown territory. Our results establish that odors can serve as landmarks to guide navigation, and they motivated a model in which path integration and odor landmarks interact in a sequential, iterative process to generate cognitive spatial maps over long distances.
Published: 2021
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25. Duration of verbal fluency inter‐word intervals and risk of cognitive impairment

Author: Matthew Ayers, Sujuan Gao, Justin Bushnell, Fred Unverzagt, Viriginia G. Wadley, and David G. Clark
Subjects: medicine.medical_specialty, Epidemiology, Health Policy, Early disease, Audiology, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Duration (music), medicine, Verbal fluency test, Neurology (clinical), Geriatrics and Gerontology, Psychology, Cognitive impairment, Word (computer architecture)
Published: 2020
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26. Secondary tauopathy in a genetic synucleinopathy, mitochondrial protein–associated neurodegeneration (MPAN)

Author: Randall L. Woltjer, Naly Setthavongsack, Penelope Hogarth, Susan J. Hayflick, Alison Freed, David G. Clark, Marlous van der Weijden, Dolly Zhen, Kristen Shirley, Daphne Garcia, Victoria Krajbich, Suh Young Jeong, Vy Nguyen, Allison Gregory, and Katrina Wakeman
Subjects: Alpha-synuclein, Epidemiology, Health Policy, Neurodegeneration, Neuropathology, Biology, medicine.disease, Cell biology, Psychiatry and Mental health, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Developmental Neuroscience, chemistry, medicine, Neurology (clinical), Tauopathy, Geriatrics and Gerontology, Mitochondrial protein
Published: 2020
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27. Understanding the Browning Reactions in Sweet Basil

Author: Samantha Burrell, Keun H. Cho, David G. Clark, and Annelise E. Vieira
Subjects: Ocimum americanum, Transformation (genetics), food, biology, Biochemistry, RNA interference, Sweet Basil, Molecular cloning, biology.organism_classification, Ocimum, Gene, Polyphenol oxidase, food.food
Abstract: Polyphenol oxidase (PPO) is a well-characterized enzyme that is conserved across plant species and is responsible for catalyzing the rapid polymerization of o-quinones that results in tissue browning. As these oxidation reactions result in significant reductions in food crop commercial viability, nutritional content, and general desirability, an opportunity exists to improve a variety of crops via genetic regulation of PPO expression. The main objective of this project was to clone the DNA sequence of genes encoding PPO. Using mRNA as a template to synthesize DNA, two putative PPO sequences were cloned from Ocimum basilicum and Ocimum americanum, two basil species of commercial relevance. A secondary objective of this project was to insert a cloned PPO sequence into an RNAi vector for the purpose of making transgenic basil plants with reduced PPO expression. A hairpin RNAi construct was successfully developed to reduce the expression of both PPO genes as their DNA sequences were highly homologous. The next step for this project will depend on the development of transformation and regeneration protocols for these species, which have proven to be difficult. Once the RNAi PPO constructs are introduced into basil cells and successfully regenerated into plants, reduced browning of basil leaf tissue when it is wounded or cut is expected.
Published: 2020
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28. Parts-Prospecting for a High-Efficiency Thiamin Thiazole Biosynthesis Pathway

Author: Guillaume A.W. Beaudoin, Thomas A. Colquhoun, Jiayi Sun, Jesse F. Gregory, Keun H. Cho, Maria Ralat, Andrew D. Hanson, Cindy L. Sigler, Jaya Joshi, Jenelle A. Patterson, Zhanao Deng, and David G. Clark
Subjects: 0106 biological sciences, Physiology, Methanococcus, Research Articles - Focus Issue, Plant Science, medicine.disease_cause, 01 natural sciences, chemistry.chemical_compound, Bacterial Proteins, Escherichia coli, Genetics, medicine, Araceae, Thiamine, Thiazole, chemistry.chemical_classification, Bacteria, food and beverages, Plants, Directed evolution, Plant cell, Biosynthetic Pathways, Complementation, Thiazoles, Enzyme, Metabolic Engineering, Biochemistry, chemistry, Alternative complement pathway, Function (biology), 010606 plant biology & botany
Abstract: Plants synthesize the thiazole precursor of thiamin (cThz-P) via THIAMIN4 (THI4), a suicide enzyme that mediates one reaction cycle and must then be degraded and resynthesized. It has been estimated that this THI4 turnover consumes 2% to 12% of the maintenance energy budget and that installing an energy-efficient alternative pathway could substantially increase crop yield potential. Available data point to two natural alternatives to the suicidal THI4 pathway: (i) nonsuicidal prokaryotic THI4s that lack the active-site Cys residue on which suicide activity depends, and (ii) an uncharacterized thiazole synthesis pathway in flowers of the tropical arum lily Caladium bicolor that enables production and emission of large amounts of the cThz-P analog 4-methyl-5-vinylthiazole (MVT). We used functional complementation of an Escherichia coli ΔthiG strain to identify a nonsuicidal bacterial THI4 (from Thermovibrio ammonificans) that can function in conditions like those in plant cells. We explored whether C. bicolor synthesizes MVT de novo via a novel route, via a suicidal or a nonsuicidal THI4, or by catabolizing thiamin. Analysis of developmental changes in MVT emission, extractable MVT, thiamin level, and THI4 expression indicated that C. bicolor flowers make MVT de novo via a massively expressed THI4 and that thiamin is not involved. Functional complementation tests indicated that C. bicolor THI4, which has the active-site Cys needed to operate suicidally, may be capable of suicidal and – in hypoxic conditions – nonsuicidal operation. T. ammonificans and C. bicolor THI4s are thus candidate parts for rational redesign or directed evolution of efficient, nonsuicidal THI4s for use in crop improvement.
Published: 2018
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29. Differential Impact of Index Stroke on Dementia Risk in African-Americans Compared to Whites

Author: E.J. Amella, Catrina Sims-Robinson, Robert J. Adams, Andrea D. Boan, A. Benitez, Daniel T. Lackland, Bruce Ovbiagele, and David G. Clark
Subjects: Male, medicine.medical_specialty, Time Factors, Index (economics), Databases, Factual, South Carolina, 030204 cardiovascular system & hematology, Risk Assessment, White People, Article, 03 medical and health sciences, Sex Factors, 0302 clinical medicine, Risk Factors, Internal medicine, Prevalence, medicine, Humans, Dementia, Dementia diagnosis, Cognitive impairment, Stroke, Aged, Proportional Hazards Models, Differential impact, Aged, 80 and over, Proportional hazards model, business.industry, Incidence, Rehabilitation, Age Factors, Health Status Disparities, Middle Aged, Prognosis, medicine.disease, Black or African American, Female, Surgery, Neurology (clinical), Diagnosis code, Cognition Disorders, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery
Abstract: OBJECTIVE: To compare whites and African-Americans in terms of dementia risk following index stroke. METHODS: The data consisted of billing and International Classification of Diseases, Ninth Revision diagnosis codes from the South Carolina Revenue and Fiscal Affairs office on all hospital discharges within the state between 2000 and 2012. The sample consisted of 68,758 individuals with a diagnosis of ischemic stroke prior to 2010 (49,262 white [71.65%] and 19,496 African-Americans [28.35%]). We identified individuals in the dataset who were subsequently diagnosed with any of 5 categories of dementia and evaluated time to dementia diagnosis in Cox Proportional Hazards models. We plotted cumulative hazard curves to illustrate the effect of race on dementia risk after controlling for age, sex, and occurrence of intervening stroke. RESULTS: Age at index stroke was significantly different between the 2 groups, with African-Americans being younger on average (70.0 [SD 12.5] in whites versus 64.5 [SD 14.1] in African-Americans, P
Published: 2018
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30. Patient and Caregiver Assessment of the Benefits From the Clinical Use of Amyloid PET Imaging

Author: Keith N. Fargo, Sujuan Gao, Bradford C. Dickerson, Jared R. Brosch, Susan De Santi, David G. Clark, Gil D. Rabinovici, Mary Guerriero Austrom, Rafid Mustafa, Bradley S. Glazier, Liana G. Apostolova, Maria C. Carrillo, and Martha Tierney
Subjects: Male, medicine.medical_specialty, MEDLINE, Amyloid pet, Article, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Surveys and Questionnaires, Life insurance, Health care, medicine, Humans, Cognitive Dysfunction, 030212 general & internal medicine, Cognitive decline, Psychiatry, Amyloid beta-Peptides, business.industry, Middle Aged, Clinical Practice, Psychiatry and Mental health, Clinical Psychology, Early Diagnosis, Positive response, Caregivers, Positron-Emission Tomography, Family medicine, Female, Geriatrics and Gerontology, business, Gerontology, Disability insurance, 030217 neurology & neurosurgery
Abstract: Introduction Few studies to date have explored patient and caregiver views on the clinical use of amyloid positron emission tomography (PET). Methods A 7-item questionnaire assessing patient and caregiver views (510 total respondents) toward amyloid PET imaging was advertised broadly through alz.org/trialmatch. Results We received 510 unique responses from 48 US states, 2 Canadian provinces, the Dominican Republic, and Greece. Both patients and caregivers indicated that they would want to receive amyloid imaging if offered the opportunity. Over 88% of respondents had a positive response (∼10% with neutral and 2% with negative responses) to whether amyloid PET should be offered routinely and be reimbursed. Such information was felt to be useful for long-term legal, financial, and health care planning. Respondents identifying with early age cognitive decline (younger than 65 y) were more likely to explore options for disability insurance (P=0.03). Responders from the Midwest were more likely to utilize information from amyloid imaging for legal planning (P=0.02), disability insurance (P=0.02), and life insurance (P=0.04) than other US regions. Discussion Patients and caregivers supported the use of amyloid PET imaging in clinical practice and felt that the information would provide significant benefits particularly in terms of future planning.
Published: 2018
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31. Cascaded Multi-view Canonical Correlation (CaMCCo) for Early Diagnosis of Alzheimer’s Disease via Fusion of Clinical, Imaging and Omic Features

Author: Sterling C. Johnson, Paul Malloy, Joy L. Taylor, Alan J. Lerner, Pradeep Garg, Pierre N. Tariot, David G. Clark, Steven G. Potkin, Franklin Watkins, Howard Bergman, Dana M. Pogorelec, Charles D. Smith, Pradeep Varma, Stephen Pasternack, Betty Lind, Saba Wolday, Douglas W. Scharre, Donna Munic, Marwan N. Sabbagh, Adam S. Fleisher, Joanne S. Allard, Cynthia Hunt, Lidia Glodzik, Charles Bernick, Daniel D'Agostino, Owen T. Carmichael, Geoffrey Tremont, Christopher H. van Dyck, Maria Carroll, Po Lu, Leslie Gordineer, Catherine Mc-Adams-Ortiz, Irina Rachisky, Antero Sarrael, Clifford R. Jack, David Bachman, Dick Trost, Scott Herring, Arthur W. Toga, Evan Fletcher, Christina A. Michel, Lon S. Schneider, Francine Parfitt, Kelly M. Makino, Anahita Adeli, Daniel Varon, Christine M. Belden, Nunzio Pomara, Thomas O. Obisesan, Howard Feldman, Howard Chertkow, Sandra W. Jacobson, Haibo Wang, Greg Jicha, Laura A. Flashman, George Bartzokis, Beau M. Ances, Stacy Schneider, Earl A. Zimmerman, Munir Chowdhury, Bruce L. Miller, Javier Villanueva-Meyer, Kristin Fargher, Michael W. Weiner, Dana Nguyen, Ranjan Duara, T. Y. Lee, Lisa C. Silbert, Benita Mudge, Marilyn S. Albert, James J. Lah, Janet S. Cellar, Gad A. Marshall, Michael Lin, Marc Seltzer, Leslie Shaw, Bojana Stefanovic, Daniel C. Marson, Kyle B. Womack, Liberty Teodoro, Connie Brand, Nadira Trncic, Maria Kataki, Russell H. Swerdlow, Paul S. Aisen, Brigid Reynolds, Mony J. de Leon, Sandra E. Black, Rachelle S. Doody, Paula Ogrocki, Andrew J. Saykin, Raymundo Hernando, Leyla deToledo-Morrell, Anna Burke, Sherye A. Sirrel, Henry W. Querfurth, Jeffrey R. Petrella, Norman R. Relkin, Judith L. Heidebrink, Vernice Bates, Mary L. Creech, David C. Perry, Curtis Caldwell, Sara Dolen, Anton P. Porsteinsson, Patricia Lynn Johnson, Erik D. Roberson, Effie M. Mitsis, Kathleen Johnson, John Q. Trojanowki, Raina Carter, James E. Galvin, Karen Blank, John C. Morris, Bryan M. Spann, Keith A. Johnson, Jared R. Tinklenberg, Stephen Salloway, Ronald J. Killiany, Mimi Dang, Smita Kittur, Mary Quiceno, Kaycee M. Sink, Helen Vanderswag, Erin E. Franklin, Robbartha, Kim Martin, Gaby Thai, Allyson C. Rosen, Karen L. Bell, Tracy Kendall, P. M. Doraiswamy, Kathleen Tingus, Angela Oliver, Adrian Preda, Mary L. Hynes, Laurel A. Beckett, William J. Jagust, Jeffrey M. Burns, Ronald C. Petersen, Allan I. Levey, Balebail Ashok Raj, Lawrence S. Honig, Martin R. Farlow, Richard E. Carson, Dana Mathews, David S. Knopman, Robert C. Green, Jerome A. Yesavage, Elizabeth Finger, Ann Marie Hake, David S. Geldmacher, Yaakov Stern, Raj C. Shah, M.-Marsel Mesulam, Ruth A. Mulnard, Jacobo Mintzer, Howard J. Rosen, Peggy Roberts, Joseph F. Quinn, Raymond Scott Turner, Maria T. Greig, Salvador Borges-Neto, Jeffrey Kaye, Randall Griffith, Diana R. Kerwin, Neill R. Graff-Radford, James B. Brewer, John C. Brockington, Ging-Yuek Robin Hsiung, Anant Madabhushi, Andrew E. Budson, Martha G. MacAvoy, Stephen Correia, Terence Z. Wong, Michelle Rainka, Elizabeth Oates, Alexander Norbash, Chiadi U. Onyike, Gloria Chaing, Kris Johnson, Hillel Grossman, Gary R. Conrad, Nancy Johnson, Lisa D. Ravdin, Mauricio Beccera, Reisa A. Sperling, Heather Johnson, Kristine Lipowski, Charles DeCarli, Barton Lane, Joanne L. Lord, Carl H. Sadowsky, Chris Hosein, Marissa Natelson Love, M. Ismail, Liana G. Apostolova, Dzintra Celmins, Brian R. Ott, Brittany Cerbone, Sanjay Asthana, Alice D. Brown, Neil W. Kowall, Peter A. Hardy, Andrew Kertesz, Sara S. Mason, Horacio Capote, Pauline Maillard, Stephanie Kielb, Henry Rusinek, Ellen Woo, Jeff D. Williamson, Susan De Santi, Amanda Smith, John M Olichney, Michele Assaly, Karen S. Anderson, Parianne Fatica, Brandy R. Matthews, Michael Borrie, Susan Rountree, Chuang Kuo Wu, Curtis Tatsuoka, Teresa Villena, Asha Singanamalli, Borna Bonakdarpour, Colleen S. Albers, Cynthia M. Carlsson, Bonnie S. Goldstein, Sonia Pawluczyk, Edward Coleman, Kenneth M. Spicer, Jared R. Brosch, William Brooks, Partha Sinha, Stephanie Reeder, Daniel Silverman, Robert B. Santulli, Godfrey D. Pearlson, Mark A. Mintun, and Sandra Weintraub
Subjects: 0301 basic medicine, Male, Proteomics, Science, Neuroimaging, Disease, Sensitivity and Specificity, Article, 03 medical and health sciences, 0302 clinical medicine, Text mining, Alzheimer Disease, medicine, Humans, Cognitive Dysfunction, Set (psychology), Aged, Aged, 80 and over, Multidisciplinary, Modalities, business.industry, Pattern recognition, Alzheimer’s Disease Neuroimaging Initiative, Genomics, Models, Theoretical, medicine.disease, 030104 developmental biology, Categorization, Case-Control Studies, Medicine, Female, Artificial intelligence, Alzheimer's disease, business, Canonical correlation, 030217 neurology & neurosurgery, Algorithms, Biomarkers
Abstract: The introduction of mild cognitive impairment (MCI) as a diagnostic category adds to the challenges of diagnosing Alzheimer’s Disease (AD). No single marker has been proven to accurately categorize patients into their respective diagnostic groups. Thus, previous studies have attempted to develop fused predictors of AD and MCI. These studies have two main limitations. Most do not simultaneously consider all diagnostic categories and provide suboptimal fused representations using the same set of modalities for prediction of all classes. In this work, we present a combined framework, cascaded multiview canonical correlation (CaMCCo), for fusion and cascaded classification that incorporates all diagnostic categories and optimizes classification by selectively combining a subset of modalities at each level of the cascade. CaMCCo is evaluated on a data cohort comprising 149 patients for whom neurophysiological, neuroimaging, proteomic and genomic data were available. Results suggest that fusion of select modalities for each classification task outperforms (mean AUC = 0.92) fusion of all modalities (mean AUC = 0.54) and individual modalities (mean AUC = 0.90, 0.53, 0.71, 0.73, 0.62, 0.68). In addition, CaMCCo outperforms all other multi-class classification methods for MCI prediction (PPV: 0.80 vs. 0.67, 0.63).
Published: 2017
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32. Sphingosine-1-phosphate receptor-1 (S1P1) is expressed by lymphocytes, dendritic cells, and endothelium and modulated during inflammatory bowel disease

Author: Thangaraj Karuppuchamy, Robert Peach, David G. Clark, Hugh Rosen, Pedro J. Gonzalez-Cabrera, Paul Jedlicka, Giorgos Bamias, Gor Sarkisyan, En-hui Behrens, Jesus Rivera-Nieves, Fiona Scott, Joshua D. Boyer, Lauren Gima, and Marisol Veny
Subjects: 0301 basic medicine, Ozanimod, Endothelium, Lymphocyte, Immunology, Mice, Transgenic, Inflammation, Inflammatory bowel disease, Article, Mice, 03 medical and health sciences, chemistry.chemical_compound, Cell Movement, medicine, Animals, Humans, Immunologic Factors, Immunology and Allergy, Ileitis, Lymphocytes, Colitis, Receptor, Cells, Cultured, Oxadiazoles, Fingolimod Hydrochloride, business.industry, Dextran Sulfate, Dendritic Cells, Inflammatory Bowel Diseases, medicine.disease, Intestines, Mice, Inbred C57BL, Disease Models, Animal, Receptors, Lysosphingolipid, 030104 developmental biology, medicine.anatomical_structure, chemistry, Indans, Cancer research, medicine.symptom, business, Immunologic Memory
Abstract: The sphingosine-1-phosphate receptor-1 (S1P1) agonist ozanimod ameliorates ulcerative colitis, yet its mechanism of action is unknown. Here, we examine the cell subsets that express S1P1 in intestine using S1P1-eGFP mice, the regulation of S1P1 expression in lymphocytes after administration of dextran sulfate sodium (DSS), after colitis induced by transfer of CD4+CD45RBhi cells, and by crossing a mouse with TNF-driven ileitis with S1P1-eGFP mice. We then assayed the expression of enzymes that regulate intestinal S1P levels, and the effect of FTY720 on lymphocyte behavior and S1P1 expression. We found that not only T and B cells express S1P1, but also dendritic (DC) and endothelial cells. Furthermore, chronic but not acute inflammatory signals increased S1P1 expression, while the enzymes that control tissue S1P levels in mice and humans with inflammatory bowel disease (IBD) were uniformly dysregulated, favoring synthesis over degradation. Finally, we observed that FTY720 reduced T-cell velocity and induced S1P1 degradation and retention of Naïve but not effector T cells. Our data demonstrate that chronic inflammation modulates S1P1 expression and tissue S1P levels and suggests that the anti-inflammatory properties of S1PR agonists might not be solely due to their lymphopenic effects, but also due to potential effects on DC migration and vascular barrier function.
Published: 2017
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33. P1-449: AUTOMATIC TRANSCRIPTION OF VERBAL FLUENCY RECORDINGS

Author: Justin Bushnell, Viriginia G. Wadley, David G. Clark, and Fredrick Unverzagt
Subjects: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Transcription (biology), Health Policy, Verbal fluency test, Neurology (clinical), Geriatrics and Gerontology, Psychology, Neuroscience
Published: 2019
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34. In Pursuit of the Perfect Peach: Consumer-assisted Selection of Peach Fruit Traits

Author: Robert Kluson, Thomas A. Colquhoun, Mercy A. Olmstead, Howard R. Moskowitz, Jessica L. Gilbert, and David G. Clark
Subjects: Computer science, business.industry, Horticulture, business, Selection (genetic algorithm), Biotechnology
Abstract: Despite production of the first domestically produced peach of the calendar year in the United States, the subtropical peach industry faces marketing challenges, particularly with small fruit size. Although important, size is only one aspect of fruit quality, and not inclusive of all possible fruit quality attributes. Thus, this research asked consumers to identify an “ideal” peach given a combination of possible peach fruit quality attributes to help determine their influence on consumer purchase. These attributes were verified with farmers’ market intercept studies. The top attributes that fostered purchase likelihood included flavor, texture, size, and firmness. Psychophysics studies showed that consumers preferred peaches that were sweet, juicy, round, with freestone or semifreestone characteristics, whereas consumers were less likely to purchase peaches with mealy, dry, or meaty textures. Young consumers (ages 18–24) preferred crisp, firm peaches with good flavor, whereas older consumers (ages 51–65) preferred sweet, melting-texture peaches. Farmers’ market intercept studies found consumers (ages 45–65) preferred melting-texture peaches with good flavor that led to increased overall liking. In addition, in the farmers’ market studies, aroma and flavor were important attributes and were highly correlated with overall liking. Objective measurements of total soluble solids (TSS) were not correlated with overall liking, indicating that although the nationwide experiment found consumers desired sweet peaches, other attributes may contribute more favorably to overall liking.
Published: 2015
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35. Brain multiplexes reveal morphological connectional biomarkers fingerprinting late brain dementia states

Author: Jerome A. Yesavage, Thomas O. Obisesan, Ann Marie Hake, Yaakov Stern, Betty Lind, Daniel D'Agostino, Daniel Varon, Christine M. Belden, Evan Fletcher, Jef Williamson, Howard Feldman, Pauline Maillard, Stephanie Kielb, Dana Mathews, Henry Rusinek, Sonia Pawluczyk, Donna Munic, Michele Assaly, Ines Mahjoub, Barton Lane, Andrew J. Saykin, Raymundo Hernando, Randall Grifth, Paul S. Aisen, Brittany Cerbone, Saba Wolday, Douglas W. Scharre, Karen S. Anderson, Sara S. Mason, Marwan N. Sabbagh, Geofrey Tremont, Stacy Schneider, Marilyn S. Albert, Tracy Kendall, P. M. Doraiswamy, Antero Sarrael, Kenneth M. Spicer, George Bartzokis, Parianne Fatica, Christopher H. van Dyck, Maria Carroll, Benita Mudge, Beau M. Ances, Brandy R. Matthews, Allyson C. Rosen, Chiadi U. Onyike, Gloria Chaing, Helen Vanderswag, Javier Villanueva-Meyer, Stephanie Reeder, Erin E. Franklin, Sandra Weintraub, Liberty Teodoro, Connie Brand, Arthur W. Toga, Mony J. de Leon, Sandra E. Black, Robert C. Green, Russell H. Swerdlow, Leyla deToledo-Morrell, Bryan M. Spann, Judith L. Heidebrink, Leslie Shaw, Ruth A. Mulnard, Rob Bartha, Sterling C. Johnson, Kristin Fargher, Susan De Santi, Curtis Caldwell, Rachelle S. Doody, Erik D. Roberson, Norman R. Relkin, Kathleen Johnson, Raj C. Shah, Kris Johnson, Diana Kerwin, M.-Marsel Mesulam, Howard J. Rosen, Peggy Roberts, Michael Borrie, Martin R. Farlow, Steven G. Potkin, Reisa A. Sperling, John Q. Trojanowki, Amanda Smith, James J. Lah, Mary L. Creech, Janet S. Cellar, Michael Lin, Terence Z. Wong, Howard Bergman, Dana M. Pogorelec, Gaby Thai, Jacobo Mintzer, Raina Carter, Heather Johnson, Francine Parftt, Karen Blank, Daniel C. Marson, Nancy Johnson, Susan Rountree, Michelle Rainka, Elizabeth Oates, Stephen Correia, John C. Morris, Alan J. Lerner, Pradeep Garg, Mauricio Beccera, Mary L. Hynes, Chuang Kuo Wu, Curtis Tatsuoka, Brian R. Ott, Joy L. Taylor, Mohamed Ali Mahjoub, Adrian Preda, Islem Rekik, Ronald C. Petersen, Kathleen Tingus, Vernice Bates, Irina Rachisky, Neill Graf-Radford, Alexander Norbash, Teresa Villena, Paul Malloy, Cliford Jack, Pierre N. Tariot, Anton P. Porsteinsson, Jefrey Burns, Owen Carmichael, Maria T. Greig, Marc Seltzer, Pradeep Varma, Jefrey Petrella, James E. Galvin, Joseph F. Quinn, Franklin Watkins, John M Olichney, Joanne L. Lord, Raymond Scott Turner, Adam S. Fleisher, Salvador Borges-Neto, James B. Brewer, Carl H. Sadowsky, Andrew E. Budson, Martha G. MacAvoy, Joanne S. Allard, L. Schneider, Stephen Salloway, Kim Martin, Mary Quiceno, Kaycee M. Sink, Sanjay Asthana, Laurel A. Beckett, Alice D. Brown, David S. Knopman, Neil W. Kowall, Efe Mitsis, Elizabeth Finger, David C. Perry, Bojana Stefanovic, David S. Geldmacher, Andrew Kertesz, Cynthia M. Carlsson, Charles Bernick, Earl A. Zimmerman, Bonnie S. Goldstein, Dzintra Celmins, Paula Ogrocki, Daniel H.S. Silverman, David G. Clark, Charles D. Smith, Nunzio Pomara, Stephen Pasternack, Howard Chertkow, Christina A. Michel, Sandra W. Jacobson, Po Lu, Peter A. Hardy, Greg Jicha, David Bachman, Laura A. Flashman, Munir Chowdhury, Bruce L. Miller, Ging Yuek Robin Hsiung, Horacio Capote, Gad A. Marshall, Brigid Reynolds, Jefrey Kaye, Patricia Lynn Johnson, Ronald J. Killiany, Mimi Dang, Smita Kittur, Lawrence S. Honig, Ranjan Duara, T. Y. Lee, Keith A. Johnson, Karen L. Bell, Allan I. Levey, Scott Herring, Michael W. Weiner, Ellen Woo, Dana Nguyen, Robert B. Santulli, Godfrey D. Pearlson, Mark A. Mintun, Sara Dolen, Jared R. Tinklenberg, Edward Coleman, Jared R. Brosch, John C. Brockington, William Brooks, Partha Sinha, M. Ismail, Balebail Ashok Raj, Lisa D. Ravdin, Kristine Lipowski, Charles DeCarli, Borna Bonakdarpour, Colleen S. Albers, Chris Hosein, Marissa Natelson Love, Kyle B. Womack, Maria Kataki, Nadira Trncic, Anna Burke, Sherye A. Sirrel, Henry W. Querfurth, Liana G. Apostolova, Angela Oliver, William J. Jagust, Richard E. Carson, Cynthia Hunt, Lidia Glodzik, Hillel Grossman, Gary R. Conrad, Leslie Gordineer, Catherine Mc-Adams-Ortiz, Dick Trost, Kelly M. Makino, Anahita Adeli, and Lisa C. Silbert
Subjects: Right entorhinal cortex, Models, Neurological, lcsh:Medicine, Biology, Article, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, medicine, Humans, Middle frontal gyrus, Dementia, Patient treatment, lcsh:Science, Cognitive impairment, Multidisciplinary, Extramural, lcsh:R, Brain, Diagnostic marker, Alzheimer’s Disease Neuroimaging Initiative, medicine.disease, Magnetic Resonance Imaging, Brain region, lcsh:Q, Cognition Disorders, Neuroscience, Biomarkers, 030217 neurology & neurosurgery
Abstract: Accurate diagnosis of mild cognitive impairment (MCI) before conversion to Alzheimer’s disease (AD) is invaluable for patient treatment. Many works showed that MCI and AD affect functional and structural connections between brain regions as well as the shape of cortical regions. However, ‘shape connections’ between brain regions are rarely investigated -e.g., how morphological attributes such as cortical thickness and sulcal depth of a specific brain region change in relation to morphological attributes in other regions. To fill this gap, we unprecedentedly design morphological brain multiplexes for late MCI/AD classification. Specifically, we use structural T1-w MRI to define morphological brain networks, each quantifying similarity in morphology between different cortical regions for a specific cortical attribute. Then, we define a brain multiplex where each intra-layer represents the morphological connectivity network of a specific cortical attribute, and each inter-layer encodes the similarity between two consecutive intra-layers. A significant performance gain is achieved when using the multiplex architecture in comparison to other conventional network analysis architectures. We also leverage this architecture to discover morphological connectional biomarkers fingerprinting the difference between late MCI and AD stages, which included the right entorhinal cortex and right caudal middle frontal gyrus.
Published: 2018
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36. Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

Author: John Hardy, Nick C. Fox, Lena Lilius, Christine Van Broeckhoven, Mindy J. Katz, Carlos Cruchaga, Joshua W. Miller, Carol Brayne, Letizia Concari, Christopher Shaw, Minerva M. Carrasquillo, Richard Mayeux, Anne Boland, Charles DeCarli, Helena C. Chui, Laura B. Cantwell, Yoland Aladro Benito, Chuang Kuo Wu, Elaine R. Peskind, Andrew McDavid, M. Ilyas Kamboh, Amanda Smith, Pascual Sánchez-Juan, Jean-François Deleuze, Jayanadra J. Himali, Thomas H. Mosley, Thomas J. Montine, Chuanhai Cao, Andreas J. Forstner, Thomas G. Beach, Robert Barber, Miquel Aguilar, Liming Qu, Jerome I. Rotter, Matthew J. Huentelman, Christiane Reitz, Christopher J. O'Donnell, Steven G. Younkin, Bradley T. Hyman, Bruce L. Miller, Rachelle S. Doody, Eric B. Larson, Ronald L. Hamilton, Todd E. Golde, Steven E. Arnold, Melissa E. Garcia, Rachel Raybould, Lena Kilander, Mark A. Sager, Kevin Morgan, Kathryn L. Lunetta, William Perry, Joseph D. Buxbaum, Craig S. Atwood, Thomas D. Bird, Michael Conlon O'Donovan, Robert Olaso, Juan Fortea, Susanne Moebus, Lisa L. Barnes, Rachel Marshall, Huntington Potter, Mercè Boada, Shahzad Ahmad, Paolo Caffarra, Daniel C. Marson, Jonathan L. Haines, Perrie M. Adams, John M Olichney, Lars Lannfelt, Stefanie Heilmann-Heimbach, Markus M. Nöthen, Shubhabrata Mukherjee, John Malamon, Xue Wang, Christopher S. Carlson, Karen Ritchie, Roger N. Rosenberg, Paul K. Crane, Alexa S. Beiser, Céline Bellenguez, Robert C. Green, Maria Urbano, Petra Proitsi, John Powell, Elisa Majounie, Ammar Al-Chalabi, Hakon Hakonarson, Yogen Patel, Martin Scherer, Julie Williams, Richard B. Lipton, Vincent Dermecourt, Adam L. Boxer, Gerard D. Schellenberg, David G. Clark, Anita L. DeStefano, Joel H. Kramer, Victoria Alvarez, Nandini Badarinarayan, Oscar L. Lopez, Chris Corcoran, Ubaldo Bonuccelli, Donald R. Royall, James Bowen, Monica Diez Fairen, Tricia A. Thornton-Wells, Nilufer Ertekin-Taner, Florence Pasquier, Martin Ingelsson, Yi Zhao, John R. Gilbert, Valentina Escott-Price, Amanda B. Kuzma, Fabienne Garzia, Reinhard Heun, Otto Valladares, Andrew J. Saykin, Sara Ortega-Cubero, Liana G. Apostolova, Henry L. Paulson, John K Kauwe, Imelda Barber, Carolina Ceballos Diaz, Douglas Galasko, M. Arfan Ikram, Lluís Tárraga, Carlo Caltagirone, Joan S. Reisch, Wolfgang Maier, Bruno Vellas, Rebecca Sims, Angela Hodges, Matthew P. Frosch, Isabel Henández, Annakaisa Haapasalo, Thor Aspelund, Håkan Thonberg, Aimee Pierce, Roger L. Albin, Wayne W. Poon, Rebecca Sussams, Amy Braddel, Ranjan Duara, Albert V. Smith, Kirk C. Wilhelmsen, Gianfranco Spalletta, Simon Lovestone, Peter Passmore, Ana Frank-García, Cynthia M. Carlsson, Jade Chapman, Nathan D. Price, Philip L. De Jager, John M. Ringman, Seung Hoan Choi, Nicola Denning, Michael John Owen, Clinton T. Baldwin, Amalia C. Bruni, Denis A. Evans, Rudolph E. Tanzi, Dominique Campion, Laura Fratiglioni, Alberto Lleó, Per Hoffmann, Carole Dufouil, Charlotte Forsell, Alun Meggy, Charlene Thomas, Robert S. Stern, James B. Leverenz, Tatiana Foroud, William W. Seeley, James J. Lah, Brian A. Lawlor, Kenneth B. Fallon, Matthias Riemenschneider, Ryan M. Huebinger, Regina M. Carney, Clinton B. Wright, Didier Hannequin, Deborah Blacker, Anne Kinhult-Ståhlbom, Ekaterina Rogaeva, Andrew P. Lieberman, Bernardino Ghetti, Linda J. Van Eldik, Bernadette McGuinness, Thomas Fairchild, Margaret A. Pericak-Vance, Ashok Raj, Reinhold Schmidt, Ronald C. Petersen, Harald Hampel, María J. Bullido, Steven L. Carroll, Maria Candida Deniz Naranjo, Kathleen A. Welsh-Bohmer, Myriam Fornage, Joseph F. Quinn, Caroline Graff, Claudia L. Satizabal, Patrice L. Whitehead, David Wallon, Christopher Medway, Lindsay A. Farrer, Vilmundur Gudnason, Peter St George-Hyslop, Pau Pastor, Frank Jessen, Erin L. Abner, Johanna Jakobsdottir, Hieab H.H. Adams, Roberta Cecchetti, Walter A. Kukull, Thomas S. Wingo, Michelle K. Lupton, Valur Emilsson, Susan M. McCurry, Simon Mead, Hilkka Soininen, Sandra Weintraub, Amy Gerrish, Lindy E. Harrell, Lina Keller, Jean-Charles Lambert, Denise Harold, Stephen Todd, Wei Gu, Maura Gallo, Najaf Amin, Lenore J. Launer, Eleonora Sacchinelli, Mikko Hiltunen, Cécile Dulary, Eliecer Coto, Xueqiu Jian, Nathalie Fievet, Patrizia Mecocci, Sarah Taylor, Eric Boerwinkle, Maria Serpente, Ronald G. Munger, Ina Giegling, Carlo Masullo, Aoibhinn Lynch, Eliezer Masliah, Anne M. Koivisto, Chang En Yu, Qiong Yang, Benedetta Nacmias, Wayne C. McCormick, Kristelle Brown, Alessio Squassina, Deborah C. Mash, Brian W. Kunkle, Makrina Daniilidou, Alison Goate, David Carrell, Kara L. Hamilton-Nelson, Sandra Barral, Vincent Chouraki, Kristel Sleegers, Frank J. Wolters, Joseph E. Parisi, Iwona Kłoszewska, Ronald C. Kim, Sonia Moreno-Grau, Marina Arcaro, Carmen Muñoz Fernadez, Vernon S. Pankratz, Duane Beekly, Sabrina Pichler, Gislain Septier, Delphine Bacq, Amanda J. Myers, Adam C. Naj, Frank Martiniuk, Sudha Seshadri, Badri N. Vardarajan, Joshua A. Sonnen, M.-Marsel Mesulam, Howard J. Rosen, James T. Becker, Chiara Fenoglio, Ge Li, Alberto Pilotto, Mary Sano, Olivier Hanon, Honghuang Lin, Jean Paul G. Vonsattel, W. T. Longstreth, Daniela Galimberti, David C. Rubinsztein, RoseMarie Brundin, Vilmantas Giedraitis, Christine M. Hulette, Peter Holmans, Martin Dichgans, Maria Vronskaya, Céline Derbois, Michelangelo Mancuso, Constantine G. Lyketsos, Christophe Tzourio, Jacques Epelbaum, Raffaele Maletta, Mariet Allen, Hong-Dong Li, James R. Burke, Rik Vandenberghe, David G. Mann, Bruce M. Psaty, Lawrence S. Honig, Beth A. Dombroski, Erik D. Roberson, Cornelia M. van Duijn, Benjamin Grenier-Boley, Seppo Helisalmi, Jean-François Dartigues, Russell H. Swerdlow, Paola Bossù, Ashley R. Winslow, Elio Scarpini, Lesley Jones, Sebastien Engelborghs, John Q. Trojanowski, Jeffrey Kaye, Jenny Lord, Chiara Cupidi, Janet A. Johnston, Dan Rujescu, Feroze Golamaully, Anne Braae, Rafael Blesa, L. Adrienne Cupples, Dennis W. Dickson, Gail P. Jarvik, David W. Fardo, David H. Cribbs, Michael Gill, Jose Bras, Allan I. Levey, Jennifer Williamson, Rhodri Thomas, John C. Morris, Lei Yu, Debby W. Tsuang, Annette M. Hartmann, John H. Growdon, John Collinge, Claudine Berr, Fernando Rivadeneira, Oliver Peters, Albert Hofman, Frank M. LaFerla, Vivianna M. Van Deerlin, James Uphill, David A. Bennett, Onofre Combarros, Gudny Eiriksdottir, Jeremy D. Burgess, Melanie L. Dunstan, Elizabeth Crocco, Keeley J. Brookes, Robert R. Graham, Lon S. Schneider, Eden R. Martin, Matt Hill, Neill R. Graff-Radford, Joseph T. Hughes, Vincenzo Solfrizzi, Taniesha Morgan, Antonio Ciaramella, Bruno Dubois, Juan C. Troncoso, Paolo Bosco, Jordi Clarimón, Daniel H. Geschwind, Virginia Boccardi, Barry Reisberg, Timothy W. Behrens, Annette L. Fitzpatrick, Salvatore Spina, Alexis Brice, Eileen H. Bigio, Marla Gearing, Jeffrey M. Burns, Carol A. Miller, Marilyn S. Albert, Sven J. van der Lee, Sandro Sorbi, C. Dirk Keene, Daniel Levy, Antonio Daniele, Eric M. Reiman, Paramita Chakrabarty, Oscar Sotolongo-Grau, Helena Schmidt, Francesco Panza, Murray A. Raskind, Rita Guerreiro, Gyungah Jun, Anna Karydas, Markus Leber, Harry V. Vinters, Cory C. Funk, Charles C. White, Jill R. Murrell, Sid E. O'Bryant, Nigel J. Cairns, Josée Dupuis, Ann C. McKee, Julie A. Schneider, Megan L. Grove, Malcolm B. Dick, Bradley F. Boeve, Jennifer A. Brody, Sanjay Asthana, Agustín Ruiz, Stefan Herms, Yuning Chen, David Craig, Neil W. Kowall, Maria Donata Orfei, JoAnn T. Tschanz, Florentino Sanchez Garcia, Manuel Mayhaus, Alfredo Ramirez, James Turton, André G. Uitterlinden, Davide Seripa, Lee-Way Jin, Kelley Faber, Maria C. Norton, Shuo Li, Steven H. Ferris, Steffi G. Riedel-Heller, Joshua C. Bis, Li-San Wang, Johannes Kornhuber, Peter Paul De Deyn, Martin R. Farlow, Randall L. Woltjer, Gary W. Beecham, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Hospital of the University of Pennsylvania (HUP), Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Icelandic Heart Association [Kopavogur, Iceland] (IHA), John P. Hussman Institute for Human Genomics [Miami, FL, USA], University of Miami [Coral Gables], Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Department of Medicine, University of Washington [Seattle], Dr. John T. Macdonald Foundation [Miami, FL, USA] (Department of Human Genetics), Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Department of Genomics [Bonn, Germany] (Institute of Human Genetics), University of Bonn-Institute of Human Genetics [Bonn, Germany], Department of Molecular Genetics, Institut Català de Neurociències Aplicades [Barcelona, Spain], Well Advanced Solutions, Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], The University of Texas Health Science Center at Houston (UTHealth), Columbia University [New York], University of Eastern Finland, Life & Brain Center - Department of Genomics, Rheinische Friedrich-Wilhelms-Universität Bonn, Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), John P. Hussman Institute for Human Genomics, Neurobiologie de la Croissance et de la Senescence, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Emmy Noether Project (SFB 833), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Boston University [Boston] (BU), Department of Genomics, Institute for Systems Biology [Seattle, WA, USA], Universitätsklinikum Bonn (UKB), Centre of Excellence for Robotic Vision [Canberra], Australian Research Council [Canberra] (ARC), Neuroscience and Mental Health Research Institute [Cardiff, UK] (School of Medicine), Boston University School of Medicine (BUSM), Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, University of Pennsylvania [Philadelphia], Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Department of Epidemiology and Biostatistics, ERASMUS, Hospital Universitario Doctor Negrín [Las Palmas de Gran Canaria, Spain], Department of Neurodegenerative Diseases, University of Mississippi Medical Center (UMMC), Pathology and Laboratory Medicine [Philadelphia, PA, USA] (Penn Neurodegeneration Genomics Center), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bioinformatics, GlaxoSmithKline, Aging Research Center [Karolinska Institutet] (ARC ), Stockholm University-Karolinska Institutet [Stockholm], University of Nottingham, UK (UON), University of Texas Health Science Center, Department of Neurobiology, Caring Sciences and Society (NVS), University of Bari Aldo Moro (UNIBA), Ageing Group, Centre for Public Health, Queen's University [Belfast] (QUB), Mayo Clinic [Jacksonville], Maurice Wohl Clinical Neuroscience Institut, King‘s College London, Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Casa Sollievo della Sofferenza [San Giovanni Rotondo] (IRCCS), Università degli Studi di Perugia (UNIPG), Framingham Heart Study, Boston University [Boston] (BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), CHU Rouen, Normandie Université (NU), Universidad Autonoma de Madrid (UAM), Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), University of Florida [Gainesville] (UF), University of Parma = Università degli studi di Parma [Parme, Italie], Center for Cognitive Disorders AUSL [Parma, Italy], School of Public Health [Boston], Uppsala University, Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC), National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Xi'an Jiaotong University (Xjtu), Department of Public health and Caring Sciences, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden, Institute of Gerontology and Geriatrics, Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Geriatric Medicine and Metabolic Diseases, Departments of Nuclear Medicine, University Medical Centre Hamburg-Eppendorf [Hamburg, Germany], University of Texas Southwestern Medical Center [Dallas], University of Cologne, Laboratoire d'Etudes et de Recherche en Informatique d'Angers (LERIA), Université d'Angers (UA), Johns Hopkins University (JHU), Universität Leipzig [Leipzig], University of Iceland [Reykjavik], Metacohorts Consortium, Harvard School of Public Health, Catholic University of Rome, Medical University Graz, Baylor College of Medicine (BCM), Baylor University, University of North Texas Health Science Center [Fort Worth], Santa Lucia Foundation (IRCCS), Nextel S.A. [Bilbao], Massachusetts General Hospital [Boston], Department of Pathology and Laboratory Medicine and Indiana Alzheimer disease Center, Indiana University School of Medicine, Indiana University System-Indiana University System, Joint Institute for the Study of the Atmosphere and Ocean (JISAO), Beijing University of Technology, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Saul B. Korey Department of Neurology, Albert Einstein College of Medicine [New York]-Yeshiva University, Utah State University (USU), Fundació per la Recerca Biomèdica i Social Mútua Terrassa [Barcelona, Spain], Hospital Universitario Mutua de Terrassa, Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Department of neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland, Department of neurology, University of Eastern Finland-University Hospital of Kuopio-University of Eastern Finland-University Hospital of Kuopio, Medical University of Łódź (MUL), University of Leicester, MRC Prion Unit, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University of Milan, Fondazione Istituto di Ricerca e Cura Carattere Scientifico [Rome], Università degli Studi di Roma Tor Vergata [Roma], Saarland University Hospital, Universitat Autònoma de Barcelona (UAB), Regional Neurogenetic Centre [Lamezia Terme, Italy] (CRN - ASP Catanzaro), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, Universidade do Porto, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Experimental and Clinical Pharmacology, St. James Hospital and Trinity College [Dublin, Ireland], School of Medicine [Dublin], Trinity College Dublin, University of Sheffield [Sheffield], Lancaster University, University of Michigan [Ann Arbor], University of Michigan System, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, University of Wisconsin-Madison, Rush Alzheimer Disease Center [Chicago, IL, États-Unis], Rush University Medical Center [Chicago], Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), School of Engineering [Cardiff], Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Northwestern University Feinberg School of Medicine, Mayo Clinic [Rochester], Swedish Medical Center [Seattle, WA, USA], University of California [San Francisco] (UCSF), University of California, Duke University [Durham], University of Kansas Medical Center [Lawrence], Laboratory of Molecular Neuropsychiatry, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Washington University in Saint Louis (WUSTL), University of South Florida [Tampa] (USF), Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Medical University of South Carolina [Charleston] (MUSC), University of Southern California (USC), Los Alamos National Laboratory (LANL), Centre de biologie du développement (CBD), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Neurology Department, University of California, Davis (UCDavis-Neuro), University of California [Davis] (UC Davis), University of California [Irvine] (UCI), Mount Sinai Medical Center, Indiana State University, University of Alabama at Birmingham [ Birmingham] (UAB), University of Kentucky, New York University [New York] (NYU), NYU System (NYU), Department of Medical and Molecular Genetics, Department of Epidemiology and biostatistics, VU University Medical Center [Amsterdam], Emory University [Atlanta, GA], Department of Neurology, University of California-University of California-David Geffen School of Medicine [Los Angeles], Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Department of Medical Genetics, HMNC Brain Health, Alzheimer Disease Research Laboratory, Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Oregon Health and Science University [Portland] (OHSU), Cleveland Clinic, Laboratoire d'Informatique, Systèmes, Traitement de l'Information et de la Connaissance (LISTIC), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Department of Psychiatry, School of Medicine-Johns Hopkins University and Johns Hopkins Bayview Medical Center, Douglas Mental Health University Institute [Montréal], McGill University = Université McGill [Montréal, Canada], Department of neurosciences, University of California [San Diego] (UC San Diego), Department of Physics and Astronomy [Fort Worth], Texas Christian University (TCU), Department of Computer Science [University of California, Davis], Indiana University System, Institute for Aging and Alzheimer’s Disease Research [Fort Worth] (IAADR), Department of Laboratory Medicine and Pathology, Mayo Clinic, Institute for Memory Impairments and Neurological Disorders [Irvine], University of Colorado Anschutz [Aurora], Tanz Center Research in Neurodegenerative Diseases [Toronto], University of Toronto, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Keck School of Medicine [Los Angeles], Indiana University [South Bend], Massachusetts General Hospital, Novartis Institutes for Biomedical Research [Cambridge, MA, USA], Departments of Pathology and Laboratory Medicine (Neuropathology) and Neurology, UCLA Medical Center-David Geffen School of Medicine [Los Angeles], University of California-University of California-University of California [Los Angeles] (UCLA), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Institut de Génomique d'Evry (IG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, University of Antwerp (UA), Institute Born-Bunge, Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], University of Kuopio, Centre Mémoire de Ressources et de Recherche [Lille-Bailleul] (CMRR), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Hôpital Roger Salengro [Lille], Laboratoire d'Analyse Génomique, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Inserm-U1167, Dpt Gériatrie [CHU Broca], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neuroépidémiologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 AMP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department of Epidemiology, University of Washington, School of Medicine [Los Angeles], Albert Einstein College of Medicine [New York], IdiPAZ - Instituto de Investigación La Paz [Madrid, Spain], Instituto de Física Teórica UAM/CSIC (IFT), Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Department of Internal Medicine, University of Central Asturias [Oviedo, Spain], Human Genome Sequencing Center, Baylor College of Medicine, Baylor University-Baylor University, Department of Epidemiology, Erasmus Medical Centre, Translational Genomics Research Institute [Phoenix, AZ, USA], University of Arizona, Banner Alzheimer's Institute [Phoenix, AZ, États-Unis], University of Texas Health Science Center at San Antonio [San Antonio], Mount Sinai School of Medicine, Department of Psychiatry-Icahn School of Medicine at Mount Sinai [New York] (MSSM), Department. of Neurological Sciences, University of Milan, IRCCS Ospedale Maggiore Policlinico, Centre for Research in Neurodegenerative Diseases, VA Puget Sound Health Care System/GRECC [Seattle, WA, USA], University of Pisa - Università di Pisa, Pfizer Worldwide Research and Development [Cambridge, MA, USA], Università cattolica del Sacro Cuore [Piacenza e Cremona] (Unicatt), Texas Tech University Health Sciences Center, Texas Tech University [Lubbock] (TTU), Saarland University [Saarbrücken], University of Bonn, Department of Public Health and Primary Care, University of Cambridge [UK] (CAM), Cambridge Institute for Medical Research (CIMR), Department of Molecular Neurosciences, Institute of Neurology, UCL, Institute of Psychiatry, Institute of psychiatry, University of British Columbia (UBC), the Clinical Neuroscience Research Group, University of Manchester [Manchester]-Greater Manchester Neurosciences Centre, Aristotle University of Thessaloniki, Memory and Dementia Centre, 3rd Department of Neurology, G. Pa, University of Barcelona, University of Southampton, Department of Psychiatry [Oxford] (POWIC), University of Oxford [Oxford]-The Warneford Hospital, School of Psychology [Cardiff University], Department of Medical Sciences, UCL, Institute of Neurology [London], Washington University School of Medicine, Netherlands Genomics Initiative, Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), School of Medecine, Center for Translational and Computational Neuroimmunology [New York, NY, États-Unis] (CTCN), Department of Neurology [New York, NY, États-Unis], Columbia University Medical Center (CUMC), Columbia University [New York]-Columbia University [New York]-Columbia University Medical Center (CUMC), Columbia University [New York]-Columbia University [New York], School of Life Sciences, Department of Neuroscience, Mayo Clinic Jacksonville, Icelandic Heart Association, Heart Preventive Clinic and Research Institute, Klinik für Psychiatrie, Martin-Luther-University Halle-Wittenberg, Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Clínica Universidad de Navarra [Pamplona], Neurodegenerative Brain Diseases Group, VIB, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University-Medical Research Council, Brigham Young University (BYU), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, The Gertrude H Sergivesky Center, Columbia University College of Physicians and Surgeons, Genetic Epidemiology Unit, Section of Clinical and Molecular Neurogenetics, Universität zu Lübeck [Lübeck], University of Pennsylvania - Department of Pathology & Laboratory Medecine, Framingham Heart Study [Framingham, MA, USA], ANR-10-IAHU-0006,IHU-A-ICM,Institut de Neurosciences Translationnelles de Paris(2010), European Project: 29845,LSH-ACC-MENTOR, University of Pennsylvania-University of Pennsylvania, Universität Bonn = University of Bonn-Institute of Human Genetics [Bonn, Germany], Universität Leipzig-Universität Leipzig, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), University of Pennsylvania, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Università degli Studi di Perugia = University of Perugia (UNIPG), Universidad Autónoma de Madrid (UAM), Università degli studi di Parma = University of Parma (UNIPR), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Universität Leipzig, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Yeshiva University- Albert Einstein College of Medicine [New York], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Università degli Studi di Milano = University of Milan (UNIMI), Saarland University Hospital (UKS), Università degli Studi di Firenze = University of Florence (UniFI), Universidade do Porto = University of Porto, University of California (UC)-University of California (UC), University of California [San Francisco] (UC San Francisco), University of California (UC), University of Kansas Medical Center [Kansas City, KS, USA], Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), University of California [Irvine] (UC Irvine), University of Kentucky (UK), University of California (UC)-University of California (UC)-David Geffen School of Medicine [Los Angeles], Department of Computer Science [Univ California Davis] (CS - UC Davis), University of California (UC)-University of California (UC)-University of California [Los Angeles] (UCLA), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Groupe de recherche clinique Alzheimer Precision Medicine (GRC 21 - APM), Sorbonne Université (SU), Universidad Autónoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), University of Texas Health Science Center at San Antonio [San Antonio, Tx, USA], Universität Bonn = University of Bonn, University of Oxford-The Warneford Hospital, Medical Research Council-Cardiff University, Universität zu Lübeck = University of Lübeck [Lübeck], Epidemiology, Neurology, Gastroenterology & Hepatology, Internal Medicine, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement (Inserm U1167 - RID-AGE - Institut Pasteur), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Eberhard Karls Universität Tübingen, IRCCS 'Casa Sollievo della Sofferenza', Centro de Investigación Biomédica en Red para Enfermedades Neurodegenerativas (Ciberned), University of Florida [Gainesville], University of Parma, Troubles cognitifs dégénératifs et vasculaires (U1171), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-INSERM, Yeshiva University- Albert Einstein College of Medicine, Institut d’Électronique, de Microélectronique et de Nanotechnologie (IEMN) - UMR 8520 (IEMN), Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Université Polytechnique Hauts-de-France (UPHF)-Ecole Centrale de Lille-Université Polytechnique Hauts-de-France (UPHF)-Institut supérieur de l'électronique et du numérique (ISEN), Autonomous University of Barcelona (UAB), Università degli Studi di Firenze [Firenze], Universidade do Porto [Porto], Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Washington University in St Louis, University of South Florida (USF), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, McGill University, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique (CNRS), Neuropsychiatrie : recherche épidémiologique et clinique, Alzheimer Precision Medicine GRC n°21 (APM), CHU Pitié-Salpêtrière [APHP], Albert Einstein College of Medicine, Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Spain] (CSIC), Università Cattolica del S. Cuore - Catholic University of the Sacred Hearth, University of Florence (UNIFI), CIBER de Enfermedades Neurodegenerativas (CIBERNED), Universität zu Lübeck [Lübeck] - University of Lübeck [Lübeck], [ANR-10-IAIHU-06],« Investissements d'avenir » ,Agence nationale de la recherche (ANR), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Icahn School of Medicine at Mount Sinai [New York] (MSSM)-Department of Psychiatry, van der Lee, Sven J [0000-0003-1606-8643], Naj, Adam C [0000-0002-9621-2942], Badarinarayan, Nandini [0000-0002-6944-748X], Chouraki, Vincent [0000-0002-4698-1794], Graham, Robert R [0000-0001-7151-4277], Hoffmann, Per [0000-0002-6573-983X], Smith, Albert V [0000-0003-1942-5845], Satizabal, Claudia L [0000-0002-1115-4430], Brody, Jennifer A [0000-0001-8509-148X], Wolters, Frank J [0000-0003-2226-4050], Lupton, Michelle K [0000-0002-7274-7299], Lin, Honghuang [0000-0003-3043-3942], Adams, Hieab H [0000-0003-3687-2508], Giedraitis, Vilmantas [0000-0003-3423-2021], Pasquier, Florence [0000-0001-9880-9788], Chen, Yuning [0000-0002-7358-7055], Bossù, Paola [0000-0002-1432-0078], Ghetti, Bernardino [0000-0002-1842-8019], Yang, Qiong [0000-0002-3658-1375], Aspelund, Thor [0000-0002-7998-5433], Bullido, María J [0000-0002-6477-1117], Rivadeneira, Fernando [0000-0001-9435-9441], Rubinsztein, David C [0000-0001-5002-5263], Al-Chalabi, Ammar [0000-0002-4924-7712], Tsolaki, Magda [0000-0002-2072-8010], De Jager, Philip L [0000-0002-8057-2505], Dickson, Dennis W [0000-0001-7189-7917], Van Broeckhoven, Christine [0000-0003-0183-7665], Ikram, M Arfan [0000-0003-0372-8585], Amouyel, Philippe [0000-0001-9088-234X], Lambert, Jean-Charles [0000-0003-0829-7817], Apollo - University of Cambridge Repository, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 APM), Berr, Claudine, Institut de Neurosciences Translationnelles de Paris - - IHU-A-ICM2010 - ANR-10-IAHU-0006 - IAHU - VALID, and Mentoring of LifeSciHealth-Multipliers in the Accession Candidate Countries - LSH-ACC-MENTOR - 29845 - OLD
Subjects: 0301 basic medicine, Linkage disequilibrium, [SDV]Life Sciences [q-bio], Medizin, Sequence Homology, Genome-wide association study, genetics [Alzheimer Disease], metabolism [Microglia], Linkage Disequilibrium, 0302 clinical medicine, genetics [Protein Interaction Maps], genetics [Membrane Glycoproteins], Gene Frequency, Immunologic, genetics [Adaptor Proteins, Signal Transducing], Receptors, genetics [Exome], Odds Ratio, Innate, genetics [Receptors, Immunologic], Exome, Protein Interaction Maps, genetics [Genetic Predisposition to Disease], Receptors, Immunologic, ABI3 protein, human, Genetics, Adaptor Proteins, Signal Transducing, Alzheimer Disease, Amino Acid Sequence, Case-Control Studies, Gene Expression Profiling, Genetic Predisposition to Disease, Genotype, Humans, Immunity, Innate, Membrane Glycoproteins, Microglia, Phospholipase C gamma, Sequence Homology, Amino Acid, Polymorphism, Single Nucleotide, Adaptor Proteins, Single Nucleotide, 3. Good health, [SDV] Life Sciences [q-bio], Amino Acid, Settore MED/26 - NEUROLOGIA, genetics [Phospholipase C gamma], [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Alzheimer's disease, Common disease-common variant, Biology, Article, 03 medical and health sciences, ddc:570, medicine, Journal Article, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Polymorphism, Allele frequency, TREM2 protein, human, TREM2, Case-control study, Signal Transducing, Immunity, medicine.disease, R1, Minor allele frequency, genetics [Immunity, Innate], 030104 developmental biology, Human medicine, 030217 neurology & neurosurgery
Abstract: International audience; We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10-8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10-10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10-10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10-14, OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.
Published: 2017
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37. [P4–327]: PATIENT AND CAREGIVER ASSESSMENT OF THE BENEFITS FROM THE CLINICAL USE OF AMYLOID‐PET IMAGING

Author: Maria C. Carrillo, Gil D. Rabinovici, Martha Tierney, David G. Clark, Bradley S. Glazier, Sujuan Gao, Jared R. Brosch, Liana G. Apostolova, Susan De Santi, Mary Guerriero Austrom, Rafid Mustafa, Bradford C. Dickerson, and Keith N. Fargo
Subjects: medicine.medical_specialty, medicine.diagnostic_test, Epidemiology, business.industry, Health Policy, Amyloid pet, Clinical Practice, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Positive response, Developmental Neuroscience, Positron emission tomography, Family medicine, Life insurance, Health care, medicine, Neurology (clinical), Geriatrics and Gerontology, Cognitive decline, business, Disability insurance
Abstract: Introduction Few studies to date have explored patient and caregiver views on the clinical use of amyloid positron emission tomography (PET). Methods A 7-item questionnaire assessing patient and caregiver views (510 total respondents) toward amyloid PET imaging was advertised broadly through alz.org/trialmatch. Results We received 510 unique responses from 48 US states, 2 Canadian provinces, the Dominican Republic, and Greece. Both patients and caregivers indicated that they would want to receive amyloid imaging if offered the opportunity. Over 88% of respondents had a positive response (∼10% with neutral and 2% with negative responses) to whether amyloid PET should be offered routinely and be reimbursed. Such information was felt to be useful for long-term legal, financial, and health care planning. Respondents identifying with early age cognitive decline (younger than 65 y) were more likely to explore options for disability insurance (P=0.03). Responders from the Midwest were more likely to utilize information from amyloid imaging for legal planning (P=0.02), disability insurance (P=0.02), and life insurance (P=0.04) than other US regions. Discussion Patients and caregivers supported the use of amyloid PET imaging in clinical practice and felt that the information would provide significant benefits particularly in terms of future planning.
Published: 2017
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38. Pattern Discovery in Brain Imaging Genetics via SCCA Modeling with a Generic Non-convex Penalty

Author: Arthur W. Toga, Leslie M. Shaw, Kristin Fargher, Mary L. Creech, Richard Frank, Po H. Lu, Daniel C. Marson, Karen Blank, Kristine Lipowski, Charles DeCarli, Vernice Bates, Marc Seltzer, Norm Foster, Matt A. Bernstein, Janet S. Cellar, David G. Clark, Sonia Pawluczyk, David A. Wolk, Charles D. Smith, Neill R. Graff-Radford, Stephen Pasternack, Warren Barker, Paul Malloy, Chris Hosein, Steven E. Arnold, Paul S. Aisen, Adam Schwartz, Kenneth M. Spicer, Marissa Natelson Love, Iris Sim, Brendan J Kelly, Danielle J Harvey, Howard Feldman, David Bachman, Clifford R. Jack, Scott Herring, David C. Perry, Pierre N. Tariot, Chiadi U. Onyike, Paul M. Thompson, Gloria Chaing, Stephanie Reeder, David T.W. Jones, Anton P. Porsteinsson, Joanne L. Lord, Pauline Maillard, Lori A. Daiello, Kris Johnson, Steven G. Potkin, Reisa A. Sperling, Carl H. Sadowsky, Stephanie Kielb, Mohammed O. Sheikh, Jason Karlawish, Kim Martin, Allyson C. Rosen, Susan M. Landau, Dana Nguyen, Oscar L. Lopez, Kejal Kantarci, Neil Buckholtz, Christopher M. Clark, Laurel A. Beckett, Jingwen Yan, Michael Borrie, Greg Sorensen, Amanda Smith, Chad Ward, Bret J. Borowski, Stephen Salloway, Mary Quiceno, Kwangsik Nho, Marilyn S. Albert, Ann Marie Hake, Kaycee M. Sink, Howard Bergman, Lei Guo, Terence Z. Wong, Michael W. Weiner, William Z. Potter, David S. Knopman, M. Saleem Ismail, Alan J. Lerner, Pradeep Garg, Susan Rountree, Michal J. Figurski, Michelle Rainka, Kim Poki-Walker, Irina Rachisky, Chet Mathis, Elizabeth Finger, Jeff D. Williamson, Jeffrey R. Petrella, Prashanthi Vemuri, Gus Jiminez, Keith A. Johnson, Sara Dolen, Curtis Tatsuoka, Nadira Trncic, Pradeep Varma, Raj C. Shah, Karen L. Bell, Elizabeth Oates, Robert A. Koeppe, Adam S. Fleisher, Daniel D'Agostino, Joanne S. Allard, Jeffrey Kaye, Jared R. Tinklenberg, Saba Wolday, Leon J. Thal, Allan I. Levey, Douglas W. Scharre, James B. Brewer, Randall Griffith, Cynthia M. Carlsson, Nunzio Pomara, Howard Chertkow, Charles Bernick, Kefei Liu, Howard J. Rosen, Ranjan Duara, Howard Fillit, T. Y. Lee, Alexander Norbash, Bonnie S. Goldstein, Benita Mudge, John A. Rogers, John M Olichney, Leyla deToledo-Morrell, John C. Brockington, Nick C. Fox, Greg Jicha, Lei Du, Erik D. Roberson, Effie M. Mitsis, Kathleen Johnson, Vesna Sossi, Munir Chowdhury, Bruce L. Miller, Dana Mathews, Jeffrey M. Burns, Steven M. Paul, Balebail Ashok Raj, Chuang Kuo Wu, Karen Ekstam Smith, Xiaohui Yao, Hyungsub Shim, Ging-Yuek Robin Hsiung, Anna Burke, Sherye A. Sirrel, Teresa Villena, Geoffrey Tremont, Susan K. Schultz, Barton Lane, Sandra Jacobson, Tatiana Foroud, Michele Assaly, Sara S. Mason, Zaven S. Khachaturian, Archana B. Balasubramanian, James J. Lah, George Bartzokis, Parianne Fatica, Michael Lin, Laura A. Flashman, M. Marcel Mesulam, Dzintra Celmins, Brandy R. Matthews, Brian R. Ott, Gad A. Marshall, Lisa D. Ravdin, Sandra Weintraub, Sterling C. Johnson, Liberty Teodoro, Lisa Taylor-Reinwald, Karen Crawford, Christine M. Belden, Connie Brand, Bryan M. Spann, Marc Raichle, Ki Won Nam, Joy L. Taylor, Virginia M.-Y. Lee, Victoria Shibley, Franklin Watkins, T. J. Montine, Russell H. Swerdlow, Martin J. Sadowski, Hristina Koleva, Peter A. Hardy, Judith L. Heidebrink, Diana R. Kerwin, Antero Sarrael, Curtis Caldwell, Beau M. Ances, John K. Hsiao, Javier Villanueva-Meyer, Sandra E. Black, Horacio Capote, Eric M. Reiman, Jacobo Mintzer, Richard E. Carson, Stephen Correia, Valory N. Pavlik, Jeff Gunter, Anaztasia Ulysse, Lon S. Schneider, Brigid Reynolds, Patricia Lynn Johnson, Bojana Stefanovic, Kathleen Tingus, John Q. Trojanowki, Ronald J. Killiany, Mimi Dang, Raina Carter, Franz Hefti, Andrew E. Budson, Martha G. MacAvoy, Daniel H.S. Silverman, Smita Kittur, John C. Morris, Donna M. Simpson, Norbert Schuff, Peter Davies, Lawrence S. Honig, Joseph F. Quinn, Ronald G. Thomas, Raymond Scott Turner, Salvador Borges-Neto, Kyle B. Womack, Maria Kataki, Emily Rogalski, Angela Oliver, Maria C. Carrillo, Betty Lind, Lew Kuller, P. Murali Doraiswamy, William J. Jagust, Mary Ann Oakley, Donna Munic, Liana G. Apostolova, David M. Holtzman, Adrian Preda, Robert B. Santulli, Marwan N. Sabbagh, Godfrey D. Pearlson, Mark A. Mintun, Mary L. Hynes, Borna Bonakdarpour, Colleen S. Albers, Ronald C. Petersen, Devon Gessert, Scott C. Neu, Hillel Grossman, Gary R. Conrad, Kelley Faber, Edward Coleman, Karen E. Anderson, Owen Carmichael, Jared R. Brosch, William Brooks, Partha Sinha, Leslie Gordineer, Martin R. Farlow, Thomas O. Obisesan, Jennifer Mason, Kelly M. Makino, Li Shen, Shannon L. Risacher, Sungeun Kim, Lisa C. Silbert, Junwei Han, Ellen Woo, Dick Trost, Francine Parfitt, Michael C. Donohue, Sanjay Asthana, Alice D. Brown, Neil W. Kowall, Andrew Kertesz, Earl A. Zimmerman, Paula Ogrocki, Kewei Chen, Magdalena Korecka, Mrunalini Gaikwad, Nigel J. Cairns, Peter J. Snyder, Norman R. Relkin, Nancy Johnson, Mauricio Beccera, M. L. Senjem, Helen Vanderswag, Erin E. Franklin, Robert C. Green, Jerome A. Yesavage, Ann Marie Milliken, Maria T. Greig-Custo, David S. Geldmacher, Yaakov Stern, Tamie Sather, Evan Fletcher, Sarah Walter, Stacy Schneider, Rob Bartha, Rachelle S. Doody, Andrew J. Saykin, Raymundo Hernando, Christopher H. van Dyck, and Maria Carroll
Subjects: 0301 basic medicine, Male, lcsh:Medicine, Feature selection, Neuroimaging, Biology, Polymorphism, Single Nucleotide, Article, Pattern Recognition, Automated, Correlation, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Feature (machine learning), Image Processing, Computer-Assisted, Humans, lcsh:Science, Aged, Genetics, Computational model, Multidisciplinary, Models, Statistical, lcsh:R, Alzheimer’s Disease Neuroimaging Initiative, Regression, body regions, 030104 developmental biology, Phenotype, Pattern recognition (psychology), Multivariate Analysis, lcsh:Q, Female, Canonical correlation, 030217 neurology & neurosurgery, Algorithms, Alzheimer's Disease Neuroimaging Initiative
Abstract: Brain imaging genetics intends to uncover associations between genetic markers and neuroimaging quantitative traits. Sparse canonical correlation analysis (SCCA) can discover bi-multivariate associations and select relevant features, and is becoming popular in imaging genetic studies. The L1-norm function is not only convex, but also singular at the origin, which is a necessary condition for sparsity. Thus most SCCA methods impose $${\ell }_{{\bf{1}}}$$ ℓ 1 -norm onto the individual feature or the structure level of features to pursuit corresponding sparsity. However, the $${\ell }_{{\bf{1}}}$$ ℓ 1 -norm penalty over-penalizes large coefficients and may incurs estimation bias. A number of non-convex penalties are proposed to reduce the estimation bias in regression tasks. But using them in SCCA remains largely unexplored. In this paper, we design a unified non-convex SCCA model, based on seven non-convex functions, for unbiased estimation and stable feature selection simultaneously. We also propose an efficient optimization algorithm. The proposed method obtains both higher correlation coefficients and better canonical loading patterns. Specifically, these SCCA methods with non-convex penalties discover a strong association between the APOE e4 rs429358 SNP and the hippocampus region of the brain. They both are Alzheimer’s disease related biomarkers, indicating the potential and power of the non-convex methods in brain imaging genetics.
Published: 2017
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39. Ploidy Levels and Pollen Stainability of Lantana camara Cultivars and Breeding Lines

Author: Carol D. Robacker, David G. Clark, David M. Czarnecki, Zhanao Deng, and Amanda J. Hershberger
Subjects: Chromosome number, biology, Pollen, Botany, Lantana camara, medicine, Cultivar, Horticulture, Ploidy, medicine.disease_cause, biology.organism_classification, Medicinal plants, Invasive species
Abstract: Lantana camara L., a popular nursery and landscape plant, is categorized as an invasive species in Florida, because it produces viable pollen and cross-pollinates with the native species Lantana depressa Small. The invasive potential of L. camara is a challenging issue for the nursery and landscape industry, so sterile non-invasive cultivars are needed to replace fertile invasive ones. This study aimed to determine the ploidy level and male fertility of both commercial L. camara cultivars and breeding lines to identify male-sterile cultivars and assess the effectiveness of sterile triploid production in L. camara. A polyploid series was identified among 32 L. camara cultivars and breeding lines. Male fertility, based on pollen stainability, varied widely among the cultivars/breeding lines. Ploidy level was the most important factor determining L. camara pollen stainability/male sterility. On average, diploids exhibited the highest pollen stainability (64.6%) followed by tetraploids (45.1%), pentaploids (34.6%), and hexaploids (18.0%). Triploids showed the lowest pollen stainability (9.3%), suggesting that generating triploids would be an effective genetic approach to producing sterile L. camara and reducing its pollen-mediated invasiveness. Pollen stainability of triploid cultivars, Balandpawn (LandmarkTM Pink Dawn PP15,516), Lemon Drop, Miss Huff, New Gold, New Red Lantana, Red Butler, Red Spread Lantana, Samson Lantana, and Sunset Lantana was consistently below 10%. A number of triploid cultivars had pollen stainability approaching 20% to 30%, indicating a necessity for careful examination and screening of newly produced triploids to ensure high sterility in selected triploids. Pollen stainability variation was observed within ploidy levels, implying the existence of other genetic and environmental factors that influence the pollen stainability/male fertility of L. camara. Results from this study suggest that there is excellent potential to develop genetically sterile cultivars in L. camara for the U.S. nursery and landscape industry.
Published: 2014
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40. Consumer-assisted Selection of Blueberry Fruit Quality Traits

Author: James W. Olmstead, Howard R. Moskowitz, Thomas A. Colquhoun, Jessica L. Gilbert, Laura A. Levin, and David G. Clark
Subjects: Index (economics), business.industry, End user, media_common.quotation_subject, Supply chain, Survey sampling, Horticulture, Product (business), Agricultural science, New product development, Production (economics), Quality (business), Business, media_common
Abstract: Additional index words. blueberry breeding, ﬂavor, fruit quality, Vaccinium corymbosumAbstract.Blueberriesareahigh-valuefruitthathasexperiencedextraordinarygrowthinconsumption in the past decade. Maintaining this growing market requires an un-derstandingofthecurrentmarketanditspotentialforexpansion.Toassaytheimpactof36 speciﬁc blueberry sensory and psychological traits on consumer interest, a blueberryfruitqualitystudywasconstructedusingtechniquesthatallowmanyfeaturestobetestedin an analysis by combining speciﬁcs from different categories that describe a product.Individual traits that most impact the likelihood of fruit purchase were identiﬁed. Sweetand intense blueberry ﬂavor yielded the most positive purchase interest, whereas badtexture attributes such as seediness were the most detrimental to interest. It was alsopossible to deﬁne two interest segments within the survey population that shared similarresponses to particular experimentally assayed traits. The larger segment of the samplepopulation (61%) was most interested in the aspects of blueberry ﬂavor, whereas thesecond segment of respondents (39%) was most inﬂuenced by health aspects commonlyassociatedwithblueberryfruitconsumption.Bothsegmentsrespondednegativelytobadtexture. This study suggests that breeders and producers should exploit genetic andenvironmental variables that contribute to improved blueberry ﬂavor and that market-ing strategies to sell blueberry cultivars of superior ﬂavor may be appropriate.Blueberries [northernhighbush( Vacciniumcorymbosum), southern highbush (V. corym-bosum hybrids), rabbiteye (V. virgatum), andlowbush (V. angustifolium)] are an economi-cally important small fruit crop in the UnitedStates with 277 million pounds harvestedfor fresh production valued at $850.8 millionU.S. in 2012 (USDA, 2013). Blueberry acre-age continues to increase worldwide in ac-cordance with growing demand for theseantioxidant-rich fruit. Although native toNorth America, breeding programs have de-veloped blueberry cultivars that grow in awider array of climates, allowing productionto ﬂourish in South America, Europe, Asia,and Australia. Global highbush blueberry pro-duction passed the one billion pound mark in2012 and continues to accelerate (Brazelton,2013). Historically, many traits have beenselected for in blueberry breeding programswith producers in mind, including climaticadaptation, yield, mechanical harvest poten-tial, and disease resistance. Conversely, thefruit quality traits of interest to the consumerarewhatshouldultimatelyfuelproductionandproﬁtability. In recent surveys, only 48% ofU.S. consumers had bought blueberries in thepast 12 months compared with 88% of con-sumers who had bought the highest sellingfruit, bananas (Fresh Trends, 2013). Of the48% of U.S. consumers who purchased blue-berries in the past year, 15% of these con-sumers were reportedly regular buyers ofblueberries (Brazelton, 2013; Fresh Trends,2013). Converting seldom purchasers intofrequent purchasers through product satisfac-tion could have a beneﬁcial impact on theblueberry market. To provide this level ofproduct satisfaction, it is critical to assess theexpectations and desires of the current blue-berry consumer to make sure these parametersare being met. Increasing market penetrationfor the 50% of consumers who did notpurchase blueberries in the past 3 years willbeimportantto drive continuedexpansionofblueberryproductionaswell(Brazelton,2013;Fresh Trends, 2013).Developing a new blueberry cultivar withimproved traits for the producer or consumeris a long-termprocess.From thetimeaninitialcross between two blueberry parents is made,the earliest a resulting progeny is typical-ly considered for release is 10 years. Thisplant must then be marketed to nurseries orfarmerswhomasspropagatetheclones,whichmeansthattheblueberrybreederdesigningtheparental crosses is catering to an industrynearly two decades in the future. Breedersoften work closely with the producers and aretherefore aware of the changing needs offarmers. However, consumer satisfaction withthe end product is inﬂuencing new directionsin research and development of horticul-tural crops, encouraging breeder focus ontraits such as improved strawberry (Fragaria·ananassa) ﬂavor (Colquhoun et al., 2012)andﬂowerfragrance(Levinetal.,2012).Withlengthy breeding cycles, it is critical to em-pirically assay the psychological inﬂuences ofconsumer blueberry purchases before com-mitting to years of manipulating traits thatmay not actually affect marketability. Addi-tionally, this information could be used totailor messages directed to the consumerthrough commercial marketing, in advertise-ments, and on packaging.When a consumer encounters a product,multiple attributes of the product may in-ﬂuence their purchase decision. The con-sumer may not necessarily be rational orconsciously aware of the reasoning for thisdecision, and outright asking of the consumerto identify their desires may introduce cog-nitive bias (DellaVigna, 2009; Price and Riis,2012; Redelmeier and Dickinson, 2011).Additionally, attempting to test a high num-ber of variables for psychological impact cancause subject frustration and cognitive bur-den (Park and Lessig, 1981). Both of theseissues can be tackled using modiﬁed conjointanalysis and rule-developing experimenta-tion. In this approach, the consumer is pre-sented with sets of three to four individualdescriptive phrases or elements at a time,which reduces the variable load on the re-spondent. Byposingmanyscenarios inwhicha product has a few attributes in differentcombinations, it is then possible to pull outindividually impactful elements from thescheme (Behe, 2006; Behe et al., 1999,2013; Jaeger et al., 2011; Moskowitz, 2012;Moskowitz et al., 2006; Moskowitz andGofman, 2007). This method has been pre-viously implemented to analyze favorablecharacteristics of fresh strawberries andﬂowers as a tool to guide breeding efforts inthese horticultural crops (Colquhoun et al.,2012; Levin et al., 2012). The strawberrystudy identiﬁed sweetness and complex ﬂa-vors as the most important traits to con-sumers, resulting in a large amount of effortand resources that have been devoted tobiochemically characterizing strawberry ﬂa-vor for identiﬁcation of enhanced qualitycultivars (Schwieterman et al., 2014).This study was conducted as part of anongoing effort to implement consumer-assisted selection in horticultural breedingprograms. Consumer-assisted selection is anapproach to product development that seeksto identify which features are of most impor-tance to the end user, an ambition that can besometimes be diluted along a complex supplychain. We sought to identify which blueberrytraits are of most importance to consumersand may motivate purchase likelihood. Weconducted two consumer-assisted marketing
Published: 2014
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41. Lower Hippocampal Volume Predicts Decrements in Lane Control Among Drivers With Amnestic Mild Cognitive Impairment

Author: Cynthia Owsley, Jan A. den Hollander, Virginia G. Wadley, Lindy E. Harrell, Daniel C. Marson, John C. Brockington, Ozioma C. Okonkwo, Luke E. Stoeckel, Karlene Ball, Jennifer Elgin, David G. Clark, H. Randall Griffith, and Christopher C. Stewart
Subjects: Gerontology, medicine.medical_specialty, medicine.diagnostic_test, Case-control study, Poison control, Magnetic resonance imaging, Odds ratio, medicine.disease, Psychiatry and Mental health, Atrophy, Internal medicine, medicine, Cardiology, Dementia, Biomarker (medicine), Neurology (clinical), Geriatrics and Gerontology, Alzheimer's disease, Psychology
Abstract: Objectives: There are few methods to discern driving risks in patients with early dementia and mild cognitive impairment (MCI). We aimed to determine whether structural magnetic resonance imaging (MRI) of the hippocampus—a biomarker of probable Alzheimer pathology and a measure of disease severity in those affected—is linked to objective ratings of on-road driving performance in older adults with and without amnestic MCI. Methods: In all, 49 consensus-diagnosed participants from an Alzheimer’s Disease Research Center (15 diagnosed with amnestic MCI and 34 demographically similar controls) underwent structural MRI and on-road driving assessments. Results: Mild atrophy of the left hippocampus was associated with less-than-optimal ratings in lane control but not with other discrete driving skills. Decrements in left hippocampal volume conferred higher risk for less-than-optimal lane control ratings in the patients with MCI (B = −1.63, standard error [SE] = .74, Wald = 4.85, P = .028), but not in controls (B = 0.13, SE = .415, Wald = 0.10, P = .752). The odds ratio and 95% confidence interval for below-optimal lane control in the MCI group was 4.41 (1.18-16.36), which was attenuated to 3.46 (0.88-13.60) after accounting for the contribution of left hippocampal volume. Conclusion: These findings suggest that there may be a link between hippocampal atrophy and difficulties with lane control in persons with amnestic MCI. Further study appears warranted to better discern patterns of brain atrophy in MCI and Alzheimer disease and whether these could be early markers of clinically meaningful driving risk.
Published: 2013
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42. Potential for Increasing Southern Highbush Blueberry Flavor Acceptance by Breeding for Major Volatile Components

Author: Michael L. Schwieterman, Thomas A. Colquhoun, Jessica L. Gilbert, James W. Olmstead, and David G. Clark
Subjects: Flavour, food and beverages, Titratable acid, Horticulture, Biology, chemistry.chemical_compound, Linalool, chemistry, Soluble solids, Cultivar, Food science, Gene–environment interaction, Chemical composition, Flavor
Abstract: Previously, when selecting for flavor in the University of Florida southern highbush blueberry (SHB, Vaccinium corymbosum L. hybrids) breeding program, sugar/acid ratios and breeder preference were the only factors considered. A more precise method of evaluating flavor would include volatile compounds that may also contribute to the flavor experience. Therefore, volatile profiles of five SHB cultivars (Farthing, FL01-173, Scintilla, Star, and Sweetcrisp) were compared using gas chromatography–mass spectrometry. All cultivars were harvested on four separate dates within the harvest season, and fruit from each cultivar were also harvested at four developmental stages on the first harvest date. Among the cultivars, soluble solids content and volatile production tended to increase with fruit maturity, whereas titratable acidity decreased. All volatile components were more variable than measures of sugars and acids during the harvest season. Many of the volatiles present varied significantly between harvest dates, resulting in significant genotype × environment interactions during the harvest season. A closer examination of linalool, trans-2-hexenol, trans-2-hexenal, hexanal, and 1-penten-3-ol, five volatile compounds commonly associated with blueberry flavor, showed cultivar, developmental stage, and harvest date differences for each volatile. ‘Star’ experienced the least variation through the harvest period.
Published: 2013
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43. Longitudinal measurement and hierarchical classification framework for the prediction of Alzheimer's disease

Author: Mary L. Hynes, Liberty Teodoro, John C. Brockington, Connie Brand, Paul Malloy, Russell H. Swerdlow, Ronald C. Petersen, Judith L. Heidebrink, Pierre N. Tariot, Curtis Caldwell, Clifford R. Jack, David G. Clark, Neill R. Graff-Radford, Charles D. Smith, Geoffrey Tremont, Ranjan Duara, Stephen Pasternack, T. Y. Lee, Owen Carmichael, Nadira Trncic, Irina Rachisky, Daniel D'Agostino, James J. Lah, Steven G. Potkin, Howard Bergman, Dana M. Pogorelec, Lon S. Schneider, Anna Burke, Sherye A. Sirrel, Henry W. Querfurth, Michael Lin, David Bachman, Edward Coleman, Michele Assaly, Allyson C. Rosen, Jeffrey M. Burns, Balebail Ashok Raj, Jared R. Brosch, Joanne L. Lord, William Brooks, Brigid Reynolds, Karen S. Anderson, Sandra Jacobson, Nunzio Pomara, Patricia Lynn Johnson, George Bartzokis, Parianne Fatica, Benita Mudge, Dana Nguyen, Carl H. Sadowsky, Michael Borrie, Qianjin Feng, Chiadi U. Onyike, Partha Sinha, Gloria Chaing, Howard Chertkow, Leyla deToledo-Morrell, Bojana Stefanovic, Richard E. Carson, Wufan Chen, Ronald J. Killiany, Mimi Dang, Thomas O. Obisesan, Christopher H. van Dyck, Maria Carroll, Gaby Thai, Arthur W. Toga, Chuang Kuo Wu, Erik D. Roberson, Effie M. Mitsis, Smita Kittur, Keith A. Johnson, Dana Mathews, Sara Dolen, Raj C. Shah, M.-Marsel Mesulam, Howard J. Rosen, Karen L. Bell, Ging-Yuek Robin Hsiung, Teresa Villena, Kris Johnson, Saba Wolday, Douglas W. Scharre, Kyle B. Womack, Maria Kataki, Barton Lane, Angela Oliver, Greg Jicha, Reisa A. Sperling, Wei Yang, David S. Geldmacher, Lawrence S. Honig, Sanjay Asthana, Janet S. Cellar, William J. Jagust, Dzintra Celmins, Susan Rountree, Christina A. Michel, Allan I. Levey, Tracy Kendall, Lisa D. Ravdin, Jared R. Tinklenberg, Brittany Cerbone, Alice D. Brown, Marilyn S. Albert, Andrew J. Saykin, Raymundo Hernando, Sandra Weintraub, John Q. Trojanowki, Raina Carter, Betty Lind, Kristin Fargher, Sterling C. Johnson, P. Murali Doraiswamy, Jeffrey R. Petrella, Neil W. Kowall, Sara S. Mason, Heather Johnson, Mary L. Creech, Stacy Schneider, Donna Munic, Liana G. Apostolova, Peter A. Hardy, Munir Chowdhury, Bruce L. Miller, Ruth A. Mulnard, Curtis Tatsuoka, Po H. Lu, Daniel C. Marson, Pauline Maillard, John C. Morris, Marwan N. Sabbagh, Jeffrey Kaye, Hillel Grossman, Gary R. Conrad, Karen Blank, Meiyan Huang, Stephanie Kielb, Andrew Kertesz, Jerome A. Yesavage, Leslie Shaw, Martin R. Farlow, Maria T. Greig, Jacobo Mintzer, Susan De Santi, David S. Knopman, Marc Seltzer, Scott Herring, Joy L. Taylor, Vernice Bates, Rob Bartha, Cynthia Hunt, Henry Rusinek, Randall Griffith, Cynthia M. Carlsson, Charles Bernick, Bonnie S. Goldstein, Rachelle S. Doody, Leslie Gordineer, Catherine Mc-Adams-Ortiz, Kim Martin, Howard Feldman, David C. Perry, Horacio Capote, Lidia Glodzik, Stephen Correia, James B. Brewer, Elizabeth Finger, Jeff D. Williamson, Franklin Watkins, Borna Bonakdarpour, Colleen S. Albers, M. Saleem Ismail, Alan J. Lerner, Daniel Varon, Christine M. Belden, Sonia Pawluczyk, Paul S. Aisen, Pradeep Garg, Kelly M. Makino, Laurel A. Beckett, Peggy Roberts, Nancy Johnson, Anahita Adeli, Terence Z. Wong, Michelle Rainka, Elizabeth Oates, Amanda Smith, Kenneth M. Spicer, Laura A. Flashman, Kristine Lipowski, Charles DeCarli, Stephanie Reeder, Mauricio Beccera, Dick Trost, Alexander Norbash, Lisa C. Silbert, Michael W. Weiner, Gad A. Marshall, Ann Marie Hake, Pradeep Varma, Francine Parfitt, Chris Hosein, Adam S. Fleisher, Marissa Natelson Love, Joanne S. Allard, Earl A. Zimmerman, Kathleen Tingus, Brian R. Ott, Joseph F. Quinn, Anton P. Porsteinsson, Paula Ogrocki, Raymond Scott Turner, Salvador Borges-Neto, James E. Galvin, Yaakov Stern, Andrew E. Budson, Martha G. MacAvoy, Daniel H.S. Silverman, Robert B. Santulli, Adrian Preda, Godfrey D. Pearlson, Mark A. Mintun, Stephen Salloway, Mary Quiceno, Kaycee M. Sink, John M Olichney, Antero Sarrael, Beau M. Ances, Javier Villanueva-Meyer, Mony J. de Leon, Sandra E. Black, Bryan M. Spann, Diana R. Kerwin, Ellen Woo, Helen Vanderswag, Erin E. Franklin, Robert C. Green, and Norman R. Relkin
Subjects: Male, Computer science, Neuroimaging, Disease, computer.software_genre, Sensitivity and Specificity, Article, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Predictive Value of Tests, mental disorders, medicine, Dementia, Humans, Cognitive Dysfunction, Longitudinal Studies, Cognitive impairment, Aged, Aged, 80 and over, Multidisciplinary, medicine.diagnostic_test, business.industry, Brain, Pattern recognition, Magnetic resonance imaging, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Early Diagnosis, Disease Progression, Female, Data mining, Artificial intelligence, business, computer, 030217 neurology & neurosurgery, Alzheimer's Disease Neuroimaging Initiative, Follow-Up Studies
Abstract: Accurate prediction of Alzheimer’s disease (AD) is important for the early diagnosis and treatment of this condition. Mild cognitive impairment (MCI) is an early stage of AD. Therefore, patients with MCI who are at high risk of fully developing AD should be identified to accurately predict AD. However, the relationship between brain images and AD is difficult to construct because of the complex characteristics of neuroimaging data. To address this problem, we present a longitudinal measurement of MCI brain images and a hierarchical classification method for AD prediction. Longitudinal images obtained from individuals with MCI were investigated to acquire important information on the longitudinal changes, which can be used to classify MCI subjects as either MCI conversion (MCIc) or MCI non-conversion (MCInc) individuals. Moreover, a hierarchical framework was introduced to the classifier to manage high feature dimensionality issues and incorporate spatial information for improving the prediction accuracy. The proposed method was evaluated using 131 patients with MCI (70 MCIc and 61 MCInc) based on MRI scans taken at different time points. Results showed that the proposed method achieved 79.4% accuracy for the classification of MCIc versus MCInc, thereby demonstrating very promising performance for AD prediction.
Published: 2017

44. MRI volume of the medial frontal cortex predicts financial capacity in patients with mild Alzheimer’s disease

Author: Katherine Belue, Roy C. Martin, John C. Brockington, H. Randall Griffith, Kristen L. Triebel, David G. Clark, Luke E. Stoeckel, Daniel C. Marson, Lindy E. Harrell, Ozioma C. Okonkwo, Jan A. den Hollander, Jacquelynn N. Copeland, and Christopher C. Stewart
Subjects: Male, Financing, Personal, Cognitive Neuroscience, Decision Making, Statistics as Topic, Precuneus, Sensitivity and Specificity, behavioral disciplines and activities, Article, Angular gyrus, Behavioral Neuroscience, Cellular and Molecular Neuroscience, Atrophy, Cognitive Reserve, Alzheimer Disease, medicine, Humans, Cognitive Dysfunction, Radiology, Nuclear Medicine and imaging, Aged, Cognitive reserve, Finance, medicine.diagnostic_test, business.industry, Neuropsychology, Reproducibility of Results, Magnetic resonance imaging, Organ Size, medicine.disease, Magnetic Resonance Imaging, Frontal Lobe, Psychiatry and Mental health, medicine.anatomical_structure, Neurology, Frontal lobe, Female, Neurology (clinical), Alzheimer's disease, Psychology, business
Abstract: Persons with mild Alzheimer's disease (AD) have significant deficits in financial abilities. This study examined the relationship between brain structure volumes, cognition, and financial capacity in patients with mild AD. Sixteen mild AD patients and 16 older adult comparisons completed the Financial Capacity Instrument (FCI), a psychometric measure of financial abilities, and also underwent magnetic resonance imaging (MRI) to obtain volumes of the bilateral hippocampi, angular gyri, precunei, and medial and dorsolateral frontal cortices. Mild AD patients performed significantly below comparisons on the FCI and had significantly smaller hippocampi. Among mild AD patients, FCI performance was moderately correlated with frontal (medial and dorsolateral frontal cortex) and posterior (angular gyri and precunei) cortical volumes. Stepwise regression demonstrated that medial frontal cortex volume predicted FCI score. The relationship between medial frontal cortex volume and overall FCI score was partially mediated by two measures of simple attention (DRS Attention, DRS Construction). The findings suggest that medial frontal cortex atrophy and associated declines in simple attention play an increasingly important role in declining financial skills in patients with mild AD.
Published: 2013
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45. Using machine learning to classify temporal lobe epilepsy based on diffusion MRI

Author: Neda Mofrad, Joseph A. Helpern, John Del Gaizo, Russell Glenn, David G. Clark, Jens H. Jensen, and Leonardo Bonilha
Subjects: Adult, Male, diffusion kurtosis imaging, Support Vector Machine, Magnetic Resonance Imaging (MRI), computer.software_genre, Machine learning, behavioral disciplines and activities, support vector machines, 030218 nuclear medicine & medical imaging, Temporal lobe, Machine Learning, 03 medical and health sciences, Behavioral Neuroscience, 0302 clinical medicine, Voxel, Fractional anisotropy, Humans, Diffusion Kurtosis Imaging, Original Research, business.industry, Bayes Theorem, Middle Aged, Temporal Lobe, Support vector machine, Diffusion Magnetic Resonance Imaging, Diffusion Tensor Imaging, Epilepsy, Temporal Lobe, Test set, Kurtosis, Anisotropy, epilepsy, Female, Artificial intelligence, Psychology, business, computer, 030217 neurology & neurosurgery, Diffusion MRI
Abstract: Background It is common for patients diagnosed with medial temporal lobe epilepsy (TLE) to have extrahippocampal damage. However, it is unclear whether microstructural extrahippocampal abnormalities are consistent enough to enable classification using diffusion MRI imaging. Therefore, we implemented a support vector machine (SVM)-based method to predict TLE from three different imaging modalities: mean kurtosis (MK), mean diffusivity (MD), and fractional anisotropy (FA). While MD and FA can be calculated from traditional diffusion tensor imaging (DTI), MK requires diffusion kurtosis imaging (DKI). Methods Thirty-two TLE patients and 36 healthy controls underwent DKI imaging. To measure predictive capability, a fivefold cross-validation (CV) was repeated for 1000 iterations. An ensemble of SVM models, each with a different regularization value, was trained with the subject images in the training set, and had performance assessed on the test set. The different regularization values were determined using a Bayesian-based method. Results Mean kurtosis achieved higher accuracy than both FA and MD on every iteration, and had far superior average accuracy: 0.82 (MK), 0.68 (FA), and 0.51 (MD). Finally, the MK voxels with the highest coefficients in the predictive models were distributed within the inferior medial aspect of the temporal lobes. Conclusion These results corroborate our earlier publications which indicated that DKI shows more promise in identifying TLE-associated pathological features than DTI. Also, the locations of the contributory MK voxels were in areas with high fiber crossing and complex fiber anatomy. These traits result in non-Gaussian water diffusion, and hence render DTI less likely to detect abnormalities. If the location of consistent microstructural abnormalities can be better understood, then it may be possible in the future to identify the various phenotypes of TLE. This is important since treatment outcome varies dependent on type of TLE.
Published: 2016

46. Clinical, Imaging, Pathological, and Biochemical Characterization of a Novel Presenilin 1 Mutation (N135Y) Causing Alzheimer's Disease

Author: David G. Clark, Kyle A. Den Beste, Randall J. Bateman, Tammie L.S. Benzinger, J. Nicholas Cochran, Erik D. Roberson, John C. Morris, David S. Geldmacher, Marissa Natelson Love, and Brian A. Gordon
Subjects: 0301 basic medicine, Proband, Adult, Aging, Pathology, medicine.medical_specialty, Spastic gait, Neuroimaging, Neuropsychological Tests, Presenilin, Article, 03 medical and health sciences, 0302 clinical medicine, Atrophy, Alzheimer Disease, medicine, PSEN1, Presenilin-1, Missense mutation, Humans, Genetic Testing, Genetic Association Studies, Amyloid beta-Peptides, General Neuroscience, Brain, Electroencephalography, Middle Aged, medicine.disease, Magnetic Resonance Imaging, 030104 developmental biology, Positron-Emission Tomography, Mutation (genetic algorithm), Mutation, Female, Neurology (clinical), Geriatrics and Gerontology, Psychology, 030217 neurology & neurosurgery, Developmental Biology, Executive dysfunction
Abstract: We present two cases of early-onset Alzheimer's disease due to a novel N135Y mutation in PSEN1. The proband presented with memory and other cognitive symptoms at age 32. Detailed clinical characterization revealed initial deficits in memory with associated dysarthria, progressing to involve executive dysfunction, spastic gait, and episodic confusion with polyspike discharges on long-term electroencephalography. Amyloid- and FDG-PET scans showed typical results of Alzheimer's disease. By history, the proband's father had developed cognitive symptoms at age 42 and died at age 48. Neuropathological evaluation confirmed Alzheimer's disease, with moderate to severe amyloid angiopathy. Skeletal muscle showed type 2 fiber– predominant atrophy with pale central clearing. Genetic testing of the proband revealed an N135Y missense mutation in PSEN1. This mutation was predicted to be pathogenic by in silico analysis. Biochemical analysis confirmed that the mutation caused an increased Aβ42/Aβ40 ratio, consistent with other PSEN1 mutations and with a loss of presenilin function.
Published: 2016

47. Petuniaflowers solve the defence/apparency dilemma of pollinator attraction by deploying complex floral blends

Author: Thomas A. Colquhoun, Danny Kessler, David G. Clark, Ian T. Baldwin, and Celia Diezel
Subjects: Volatile Organic Compounds, Herbivore, Pollination, biology, Ecology, Host (biology), Flowers, Generalist and specialist species, biology.organism_classification, Biological Evolution, Petunia, Attraction, Pollinator, Odorants, Botany, Animals, RNA Interference, Oecanthus fultoni, Herbivory, Selection, Genetic, Ecology, Evolution, Behavior and Systematics
Abstract: Flowers recruit floral visitors for pollination services by emitting fragrances. These scent signals can be intercepted by antagonists such as florivores to locate host plants. Hence, as a consequence of interactions with both mutualists and antagonists, floral bouquets likely consist of both attractive and defensive components. While the attractive functions of floral bouquets have been studied, their defensive function has not, and field-based evidence for the deterrence of floral-scent constituents is lacking. In field and glasshouse experiments with five lines of transgenic Petunia x hybrida plants specifically silenced in their ability to release particular components of their floral volatile bouquet, we demonstrate that the emission of single floral-scent compounds can dramatically decrease damage from generalist florivores. While some compounds are used in host location, others prevent florivory. We conclude that the complex blends that comprise floral scents are likely sculpted by the selective pressures of both pollinators and herbivores.
Published: 2012
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48. Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis

Author: Marla Gearing, David G. Clark, Steven L. Carroll, Marianne Johnstone, Darwin L. Conwell, Gregory A. Cote, Sandra Weintraub, Matthew P. Frosch, Stuart Sherman, Badri N. Vardarajan, Joshua A. Sonnen, Lindy E. Harrell, Peter B. Cotton, Lisa L. Barnes, Lawrence S. Honig, Carol A. Miller, Adam Slivka, Michelle A. Anderson, Nadine M. Melhem, David A. Bennett, Joel H. Kramer, Jill P. Smith, Michele D. Lewis, Mary Ganguli, Jean Paul Vonsatte, Thomas J. Montine, Lee-Way Jin, Kenneth B. Fallon, Marilyn S. Albert, Eliezer Masliah, John H. Growdon, Barry Reisberg, Chuanhai Cao, Patricia L. Kramer, Douglas J. Hartman, Allan I. Levey, Jennifer Williamson, Vivianna M. Van Deerlin, Wayne W. Poon, Alison Goate, Vijay P. Singh, Bernie Devlin, Christiane Reitz, Ann C. McKee, Amanda Smith, Neill R. Graff-Radford, Walter A. Kukul, John Baillie, Andres Gelrud, Ranjan Duara, Thomas D. Bird, Clinton B. Wright, Deborah Blacker, Chiao-Feng Lin, Ge Li, Ronald C. Kim, Deborah C. Mash, Debby W. Tsuang, John P. Neoptolemos, Timothy B. Gardner, Kathryn L. Lunetta, Steven G. Younkin, Kara L. Hamilton-Nelson, Ronald L. Hamilton, F. Yesim Demirci, Eric M. Reiman, Charles DeCarli, John M Olichney, Richard Mayeux, Gregory A. Jicha, Michael R. O'Connell, Matt Tector, Eileen H. Bigio, Jonathan D. Glass, M. Ilyas Kamboh, Randall E. Brand, Christopher Lawrence, Steven E. Arnold, Jessica LaRusch, Elaine R. Peskind, David H. Cribbs, M.-Marsel Mesulam, Constantine G. Lyketsos, Michelle L. Kienholz, Frank M. LaFerla, Duane Beekly, Kelley Faber, Salvatore Spina, Gyungah Jun, Thiruvengadam Muniraj, Erik D. Roberson, Anna Karydas, Steven H. Ferris, Bruce L. Miller, Randall L. Woltjer, Li-San Wang, Lon S. Schneider, John C. Morris, John Q. Trojanowski, Jeffrey Kaye, Joseph E. Parisi, Nilufer Ertekin-Taner, Harry V. Vinters, Lidiya Orlichenko, Robert Barber, Chris E. Forsmark, Mary Sano, Bimaljit S. Sandhu, Peter A. Banks, Martin R. Farlow, Bradley T. Hyman, Joseph F. Quinn, Gary W. Beecham, James A. DiSario, Hakon Hakonarson, Daniel C. Marson, Adam C. Naj, Frank Martiniuk, Oscar L. Lopez, Mary E. Money, Julia Mayerle, William Greenhalf, Kathryn Roeder, Adam L. Boxer, Christine M. Hulette, Gerard D. Schellenberg, Georgios I. Papachristou, Douglas Galasko, James R. Burke, Donna B. Stolz, Murray A. Raskind, Peter Simon, Linda J. Van Eldik, Robert A. Hawes, Chang En Yu, Tatiana Foroud, Jonathan L. Haines, Stephen R. Wisniewski, William W. Seeley, Dhiraj Yadav, James J. Lah, C. Mel Wilcox, Sid Gilman, Liana G. Apostolova, Howard J. Rosen, Clinton T. Baldwin, Robert S. Stern, Narcis O. Zarnescu, Dennis W. Dickson, Margaret A. Pericak-Vance, Ashok Raj, Stephen T. Amann, Joseph D. Buxbaum, Ronald C. Petersen, Robert C. Green, David C. Whitcomb, Rudolph E. Tanzi, Lindsay A. Farrer, Helena C. Chui, Laura B. Cantwell, Wendy J. Mack, Samer Alkaade, Nigel J. Cairns, Thomas G. Beach, Frank Ulrich Weiss, Alyssa M. Krasinskas, Elizabeth Head, Nalini M. Guda, Julie A. Schneider, Malcolm B. Dick, Roger N. Rosenberg, Jill R. Murrel, Otto Valladares, Andrew J. Saykin, Huntington Potter, John R. Gilbert, Neil W. Kowall, Joseph Romagnuolo, Markus M. Lerch, Aimee Pierce, Roger L. Albin, John M. Ringman, James B. Leverenz, Carlos Cruchaga, Joshua W. Miller, Lei Yu, M. Michael Barmada, Lambertus Klei, Andrew P. Lieberman, Bernardino Ghetti, Robert Sutton, Kathleen A. Welsh-Bohmer, Juan C. Troncoso, Edward H. Koo, Elizabeth Crocco, Eden R. Martin, Daniel H. Geschwind, and Regina M. Carney
Subjects: Male, Pancreatic disease, Pancreatitis, Alcoholic, Genome-wide association study, Biology, Article, 03 medical and health sciences, 0302 clinical medicine, Sex Factors, Gene Frequency, Genotype, Genetics, medicine, PRSS2, Humans, Genetic Predisposition to Disease, Trypsin, Allele, Allele frequency, Homozygote, Genetic Variation, medicine.disease, 3. Good health, Hemizygote, 030220 oncology & carcinogenesis, Immunology, Claudins, Mutation, Trypsinogen, Pancreatitis, 030211 gastroenterology & hepatology, Female, Genome-Wide Association Study
Abstract: Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR and SPINK1 variants were associated with pancreatitis risk. We now report two associations at genome-wide significance identified and replicated at PRSS1-PRSS2 (P < 1 × 10(-12)) and X-linked CLDN2 (P < 1 × 10(-21)) through a two-stage genome-wide study (stage 1: 676 cases and 4,507 controls; stage 2: 910 cases and 4,170 controls). The PRSS1 variant likely affects disease susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous in males) CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men (male hemizygote frequency is 0.26, whereas female homozygote frequency is 0.07).
Published: 2012

49. Using Mind Genomics® to Identify Essential Elements of a Flower Product

Author: Jeri L. Callaway, Howard R. Moskowitz, Laura A. Levin, Thomas A. Colquhoun, Kelly M. Langer, and David G. Clark
Subjects: education.field_of_study, Demographics, media_common.quotation_subject, Applied psychology, Consumer health, Population, Horticulture, Consumer satisfaction, Research participant, Perception, Botany, Product (category theory), Psychology, education, Female students, media_common
Abstract: The IdeaMap® software suite and the concept of Mind Genomics® were used to analyze which features of a flower product are influential to consumer perception. By presenting online human subjects with combinations of elements that describe a flower product, a database was created to define how individuals perceive distinct components of an overall flower product. This study was conducted with two separate groups of participants, the first provided by a panelist fielding house and the second administered to an undergraduate introduction to plants and gardening class. The fielding house participants represented various demographic groups throughout the United States and the majority was 40 years of age and older. The undergraduate class participants consisted primarily of white, female students between the ages of 18 and 24 years. Each study participant was exposed to a permutation of flower-based elements derived from six categories: flower color, flower shape, consumer health and wellness, flower fragrance, flower purchase location, and flower use. The results of the two studies illustrated which elements of each flower category appealed to different demographics of the population and were used to identify segments of the population that possessed similar mindsets toward elements of interest and disinterest in regard to a flower product. In both the fielding house and student IdeaMap® studies, the highest and lowest interest values were for elements from the flower fragrance category, indicating that floral fragrance is an important aspect of flowers with respect to current and future consumer satisfaction. Three distinct segments were identified in each study with the segments being primarily concerned with elements involving olfaction, visual, and other attributes of a flower product.
Published: 2012
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50. The Chemical Interactions Underlying Tomato Flavor Preferences

Author: Dawn Bies, Thomas A. Colquhoun, Lauren M. McIntyre, Derek J. Snyder, Howard R. Moskowitz, Adilia Blandon-Ubeda, David G. Clark, Charles Goulet, Denise M. Tieman, Esther van der Knaap, Gustavo Rubén Rodríguez, Linda M. Bartoshuk, Mark G. Taylor, Harry J. Klee, Peter Bliss, Charles A. Sims, Asli Z. Odabasi, and Melissa H. Mageroy
Subjects: 0106 biological sciences, Taste, media_common.quotation_subject, Olfaction, Biology, 01 natural sciences, General Biochemistry, Genetics and Molecular Biology, Food Preferences, 03 medical and health sciences, Solanum lycopersicum, Perception, Humans, Food science, Sugar, Aroma, Flavor, 030304 developmental biology, media_common, 2. Zero hunger, Volatile Organic Compounds, 0303 health sciences, Agricultural and Biological Sciences(all), Biochemistry, Genetics and Molecular Biology(all), business.industry, Taste Perception, Sweetness, Plants, Genetically Modified, biology.organism_classification, Biotechnology, Models, Chemical, Odor, Fruit, General Agricultural and Biological Sciences, business, 010606 plant biology & botany
Abstract: Summary Although human perception of food flavors involves integration of multiple sensory inputs, the most salient sensations are taste and olfaction [1]. Ortho- and retronasal olfaction are particularly crucial to flavor because they provide the qualitative diversity so important to identify safe versus dangerous foods [2]. Historically, flavor research has prioritized aroma volatiles present at levels exceeding the orthonasally measured odor threshold [3], ignoring the variation in the rate at which odor intensities grow above threshold. Furthermore, the chemical composition of a food in itself tells us very little about whether or not that food will be liked. Clearly, alternative approaches are needed to elucidate flavor chemistry. Here we use targeted metabolomics and natural variation in flavor-associated sugars, acids, and aroma volatiles to evaluate the chemistry of tomato fruits, creating a predictive and testable model of liking. This nontraditional approach provides novel insights into flavor chemistry, the interactions between taste and retronasal olfaction, and a paradigm for enhancing liking of natural products. Some of the most abundant volatiles do not contribute to consumer liking, whereas other less abundant ones do. Aroma volatiles make contributions to perceived sweetness independent of sugar concentration, suggesting a novel way to increase perception of sweetness without adding sugar.
Published: 2012
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