76 results on '"MASSARELLI I"'
Search Results
2. Cytotoxic activity of polyacetylenes and polyenes isolated from roots of Echinacea pallida
- Author
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Chicca, A, Pellati, F, Adinolfi, B, Matthias, A, Massarelli, I, Benvenuti, S, Martinotti, E, Bianucci, A M, Bone, K, Lehmann, R, and Nieri, P
- Published
- 2008
- Full Text
- View/download PDF
3. Pomodoro da mensa
- Author
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Acciarri N., Ciriaci T., Pulcini L., Felicioni N., Fusari F., Sabatini E., Rotino G. L., Grillo M. S., Tucci M., Cammareri M., De Palma M., Massarelli I., Tripodi P., De Masi L., Infantino A., Pucci N., Tamietti G., Valentino D., Davino M., Davino S., Pecchioni N., Barbieri M., FRUSCIANTE, LUIGI, ERCOLANO, MARIA RAFFAELLA, BARONE, AMALIA, MONTI, LUIGI, Acciarri N., Acciarri, N., Ciriaci, T., Pulcini, L., Felicioni, N., Fusari, F., Sabatini, E., Rotino, G. L., Frusciante, Luigi, Ercolano, MARIA RAFFAELLA, Barone, Amalia, Monti, Luigi, Grillo, M. S., Tucci, M., Cammareri, M., De Palma, M., Massarelli, I., Tripodi, P., De Masi, L., Infantino, A., Pucci, N., Tamietti, G., Valentino, D., Davino, M., Davino, S., Pecchioni, N., and Barbieri, M.
- Published
- 2010
4. Proteomics for the elucidation of heat stress response mechanisms in anthers of tomato plants
- Author
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Mazzeo MF, Cacace G, Massarelli I, Grillo MS, and Siciliano RA
- Published
- 2014
5. Tomato fruit set at high temperature: linking physio-biochemical adjustaments to changes in gene expression
- Author
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GIORNO F, MASSARELLI I, R. NURCATO, GRANDILLO S, ALBA RM, GIOVANNONI JJ, LEONE A, GRILLO S., BARONE, AMALIA, MONTI, LUIGI, Giorno, F, Massarelli, I, R., Nurcato, Barone, Amalia, Grandillo, S, Alba, Rm, Giovannoni, Jj, Monti, Luigi, Leone, A, and Grillo, S.
- Published
- 2006
6. STRESS SALINO IN PATATA: COMPONENTI MOLECOLARI E MECCANISMI FISIOLOGICI ESSENZIALI PER L’ADATTAMENTO ALLO STRESS
- Author
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RAIMONDI, GIAMPAOLO, MAGGIO, ALBINO, MARTINO A., BATELLI G., MASSARELLI I., NURCATO R., LEONE A., GRILLO S., Raimondi, Giampaolo, Martino, A., Batelli, G., Massarelli, I., Nurcato, R., Leone, A., Grillo, S., and Maggio, Albino
- Published
- 2005
7. Monitoring gene expression durino tomato fruit set at high temperature
- Author
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MASSARELLI I., GIORNO F., GRANDILLO S., GIOVANNONI J. J., LEONE A., GRILLO S., BARONE, AMALIA, MONTI, LUIGI, Massarelli, I., Giorno, F., Barone, Amalia, Grandillo, S., Giovannoni, J. J., Monti, Luigi, Leone, A., and Grillo, S.
- Published
- 2005
8. Microarray analysis of tomato fruit set at high temperature
- Author
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GIORNO F., MASSARELLI I., GRANDILLO S., ALBA R. M., GIOVANNONI J. J., GRILLO S., LEONE A., BARONE, AMALIA, MONTI, LUIGI, Giorno, F., Massarelli, I., Barone, Amalia, Grandillo, S., Alba, R. M., Giovannoni, J. J., Monti, Luigi, Grillo, S., and Leone, A.
- Published
- 2005
9. Repertoire of genes expressed during tomato fruit set at high temperature
- Author
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MASSARELLI I, LANGELLA R, GIORNO F, LEONE A, GRANDILLO S, GRILLO S., BARONE, AMALIA, MONTI, LUIGI, Massarelli, I, Langella, R, Giorno, F, Barone, Amalia, Leone, A, Grandillo, S, Monti, Luigi, and Grillo, S.
- Published
- 2004
10. PROTEOMICS FOR THE ELUCIDATION OF HEAT STRESS RESPONSE
- Author
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MAZZEO MF, CACACE G, MASSARELLI I, LEONE A, GRILLO S, and SICILIANO RA
- Published
- 2010
11. Proteomics for the elucidation of heat stress response mechanisms in anthers of tomato plants
- Author
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Mazzeo M.F., Cacace G., Massarelli I., Leone A., Grillo S., and Siciliano R.A.
- Published
- 2010
12. Pomodoro da mensa
- Author
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Acciarri N, Ciriaci T, Pulcini L, Felicioni N, Fusari F, Sabatini E, Rotino GL, Frusciante L, Ercolano MF, Barone A, Monti L, Grillo MS, Grandillo S, Tucci M, Cammareri M, De Palma M, Massarelli I, Tripodi P, De Masi L, Infantino A, Pucci N, and Tamietti G
- Published
- 2010
13. Cytotoxic activity of polyacetylenes and polyenes isolated from roots of Echinacea pallida
- Author
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Chicca, A., Pellati, Federica, Adinolfi, B., Matthias, A., Massarelli, I., Benvenuti, Stefania, Martinotti, E., Bianucci, A. M., Bone, K., Lehmann, R., and Nieri, P.
- Subjects
Echinacea pallida ,cancer ,polyacetylenes ,bioavailability ,cytotoxicity ,Dose-Response Relationship, Drug ,Cell Survival ,Plant Extracts ,Biological Availability ,Polyynes ,Apoptosis ,Polyenes ,Echinacea ,acetylenes ,MIA PaCa-2 ,COLO320 ,Caco-2 ,permeability ,Research Papers ,Antineoplastic Agents, Phytogenic ,Permeability ,Pancreatic Neoplasms ,Cell Line, Tumor ,Colonic Neoplasms ,Humans ,Biological Assay ,Caco-2 Cells - Abstract
The n-hexane extracts of the roots of three medicinally used Echinacea species exhibited cytotoxic activity on human cancer cell lines, with Echinacea pallida found to be the most cytotoxic. Acetylenes are present in E. pallida lipophilic extracts but essentially absent in extracts from the other two species. In the present study, the cytotoxic effects of five compounds, two polyacetylenes (namely, 8-hydroxy-pentadeca-(9E)-ene-11,13-diyn-2-one (1) and pentadeca-(9E)-ene-11,13-diyne-2,8-dione (3)) and three polyenes (namely, 8-hydroxy-pentadeca-(9E,13Z)-dien-11-yn-2-one (2), pentadeca-(9E,13Z)-dien-11-yne-2,8-dione (4) and pentadeca-(8Z,13Z)-dien-11-yn-2-one (5)), isolated from the n-hexane extract of E. pallida roots by bioassay-guided fractionation, were investigated and the potential bioavailability of these compounds in the extract was studied.Cytotoxic effects were assessed on human pancreatic MIA PaCa-2 and colonic COLO320 cancer cell lines. Cell viability was evaluated by the WST-1 assay and apoptotic cell death by the cytosolic internucleosomal DNA enrichment and the caspase 3/7 activity tests. Caco-2 cell monolayers were used to assess the potential bioavailability of the acetylenes.The five compounds exhibited concentration-dependent cytotoxicity in both cell types, with a greater potency in the colonic cancer cells. Apoptotic cell death was found to be involved in the cytotoxic effect of the most active, compound 5. Compounds 2 and 5 were found to cross the Caco-2 monolayer with apparent permeabilities above 10 x 10(-6) cm s(-1).Compounds isolated from n-hexane extracts of E. pallida roots have a direct cytotoxicity on cancer cells and good potential for absorption in humans when taken orally.
- Published
- 2008
14. Flower development and fruit setting under high temperature in tomato: molecular and biochemical analysis
- Author
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Massarelli I, Giorno F., Nurcato R., Giovannoni J.J., Monti L., Leone A., and Grillo S.
- Published
- 2008
15. Regulation of desaturase gene expression, changes in membrane composition and freezing tolerance in potato plants
- Author
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DE PALMA, M, Grillo, S, Massarelli, I, Costa, A, Balogh, G, Vigh, L, and Leone, Antonietta
- Published
- 2008
16. In vitro anticancer activity of E. pallida polyacetylenes
- Author
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Adinolfi B, B., Chicca, A., Pellati, Federica, Benvenuti, Stefania, Massarelli, I., Martinotti, E., and Nieri, P.
- Subjects
Echinacea pallida ,polyacetylenes ,Anticancer activity - Published
- 2007
17. Understanding selectivity mechanism of human asialoglycoprotein receptor (ASGP-R) toward Gal- and Man-type ligands for predicting interactions with exogenous sugars
- Author
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Massarelli, I, Murgia, L, Bianucci, A. M., Chiellini, Federica, and Chiellini, Emo
- Published
- 2007
18. Changes in gene expression and physio-biochemical adjustaments caused by heat stress during tomato fruit setting
- Author
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Giorno F, Massarelli I, Nurcato R, Giovannoni JJ, Monti L, Leone A, and Grillo S
- Published
- 2007
19. Characterization and production in Escherichia coli of a dehydrin involved in cold stress response in Solanum commersonii
- Author
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Massarelli I., Costa A., De Palma M., Leone A., and Grillo S.
- Subjects
dehydrin ,fungi ,Solanum commersonii ,food and beverages ,affinity chromatography purification - Abstract
A functional screening, based on random over-expression of a plant cDNA library in Escherichia coli, was used to identify plant genes associated to salt tolerance. E. coli cells, transformed with phagemids derived from a cDNA library from Solanum commersonii plantlets, were selected on medium supplemented with 0.8 M NaCl. Sequence analysis of seven cDNAs from salt tolerant bacterial colonies revealed homology either with known plant stress-related genes (dhn2, cpn60b, epoxide hydrolase and others) or with Arabidopsis thaliana putative proteins with unknown functions. Expression of these two novel plant genes was induced by NaCl in S. commersonii and S. tuberosum cells as well as in A. thaliana seedlings, suggesting that the function of their encoded proteins in the cellular response to high salt are conserved across prokaryotes and plant kingdom. N2.1 and N2.2 transcripts were also induced by cold and water stress, but not ABA, revealing that they belong to the ABA- independent stress-responsive gene category. The two unknown cDNAs, as well as dhn2 and cpn60b, were constitutively expressed at higher level in plants of the cold tolerant potato species S. commersonii than in plants of S. tuberosum, the cold susceptible species. These findings support previous evidence that a pre-committed high constitutive transcript level of a set of stress-responsive genes is crucial for plant stress tolerance.
- Published
- 2004
20. AN IN VIVO EXPERIMENTAL METHOD TO PREDICT THE TORSADOGENIC POTENTIALITY OF DRUGS: EVALUATION OF QT PROLONGATION IN ANAESTHETISED GUINEA-PIG
- Author
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Testai, Lara, Calderone, Vincenzo, Massarelli, I, and Martinotti, E.
- Published
- 2003
21. Isolamento di un gene di Solanum commersonii che conferisce tolleranza ad alte concentrazioni saline in Escherichia Coli
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Massarelli I., Costa A., and Leone A.
- Abstract
Al fine di identificare geni che hanno un ruolo cruciale nell' adattamento/tolleranza allo stress osmotico sono stati recentemente isolati, con un approccio funzionale, dif- ferenti cloni cDNA dalla specie selvatica di patata Solanum commersonii in grado di conferire a cellule di Escherichia coli la capacita? di crescere su un terreno con elevate concentrazioni di NaCI. Uno di questi, il clone N2.1, con un ORF codificante per una proteina di 433 amminoacidi con interessanti domini funzionali, tra cui tre do- mini di membrana e un dominio di legame per l'ATP/GTP, e? stato ulteriormente ca- ratterizzato. Il gene N2.1 e? costitutivamente espresso in vari tessuti di S. commersonii ed e? indotto in risposta ad NaCI in colture cellulari. Un'analisi bioinformatica ha permesso d'iden- tificare nel database genomico di Arabidopsis thaliana, una sequenza genica che codi- fica per una proteina a funzione non nota con il 72% d'identita? aminoacidica con quello di patata. Analisi con RT-PCR, su piantine di 15 giorni di Arabidopsis thaliana hanno evidenziato che questo gene e? trascritto ad elevati livelli in risposta a sale (160 mM NaCl) e che la sua espressione e? indotta da altri ioni presenti nel mezzo di cre- scita, tra cui K+ (125 mM KCl), Li+ (25 mM LiCl), and Cs+ (18 mM CsCI). Piante transgeniche di Arabidopsis con costrutti contenenti il gene N2.1 in direzione senso ed antisenso sono state recentemente ottenute. La caratterizzazione fenotipica e molecolare, attualmente in corso, delle linee trasfor- mate e di due mutanti da inserzione (linee 'T-DNA tagged') provenienti dalla colle- zione del Salk Institute (USA), permettera? di definire il ruolo del gene N2.1 nei mec- canismi molecolari di risposta cellulare a stress salino e osmotico.
- Published
- 2003
22. Characterization of a novel plant gene that confers salt tolerance to Escherichia coli
- Author
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Massarelli I., Costa A., Grillo S., and Leone A.
- Abstract
To identily genes with crucial role in plant adaptationi tolerance to osmotic stress we have recently isolated, through a functional approach, different potato cONA clones able to conler NaCI tolerance to E coli cells. One of these, clone N2.1, has an ORF coding for a protein of 433 aminoacids with i?nteresti?nq features, including three putative intraspanning membrane domains along with a consensus motif for ATP/GTP binding. The gene is con- stitutively expressed in potato root tissues and its expression seems not to be regulated by NaCI (100mM). Homology search in the Arabidopsis genome database identified a single gene sequence which share 72% identity with the potato N2.1 clone, presently classified as unknown protein. As detected by RT-PCR, in 15 day- old Arabidopsis seedlings the gene is expressed at very low level, but it is rapidly and highly activated upon salt stress (160mM NaCI). Beside sodium, the gene is also highly induced by different ions such as K+ (125 mM KCI), Li+ (25 mM LiCI), and Cs+ (18 mM CsCI). Arabidopsis transgenic plants with sense and antisense constructs have been obtained and two different T-DNA insertion lines of the Salk collection have been identilied. Their phenotypic and molecular characterization are currently under way to deline the functional role of N2. 1 gene in the pathway of the plant celle response to salt and osmotic stress.
- Published
- 2003
23. Isolation of genes responsive to water stress in potato cell cultures
- Author
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Costa A., Di Giacomo M., Massarelli I., Leone A., and Grillo S.
- Subjects
water stress ,food and beverages ,potato ,cDNA-AFLP ,gene isolation - Abstract
Drought is one of major stress limiting factors for crop productivity. This stress condition affects almost all plant functions, including growth and development. Plants respond to osmotic stresses by activating mechanisms of repair and protection of cellular metabolism as a result of the action of different genes that operate in a complex and coordinate network. In order to identify key genes involved in response to drought, we studied the differential expression of potato cells upon PEG-mediated osmotic stress of different intensity (5-20% PEG) and duration (15min, 1h, 24h). The systematic comparison, by cDNA-AFLP, of changes in gene expression during gradual adaptation to low water potential with those induced by abrupt exposure to water stress, allowed to identify cDNA fragments specific for each response. As first screening, about 60 cDNAs fragments were identified as to be differentially expressed. Fourteen cDNA clones were isolated and their pattern of expression confirmed a clear up-regulation upon stress as determined by RT-PCR. Many of these AFLP tags match typical stress responsive genes belonging to different functional classes, i.e. protein synthesis (elongation factor 1a, ribosomal proteins), chaperone activity and protein degradation (hsp20, RER), ROS scavenging pathway (phenylalanine ammonia-lyase, peroxidase). Sequence homology search revealed that the remaining six cDNA clones encode hypothetical or unknown proteins, never described as to be stress- inducible before. Three cDNAs are highly homologous to potato or tomato EST, one homologous to a cDNA expressed during arabidopsis seed development. When potato cDNA sequences were converted into arabidopsis hortologs, conserved domains were identified, such as plant DNA binding homodomain (clone #96) or transmembrane domains (clones #102 and 103). No hits were found in current databases for fragments #114 and 131. Further characterization of the most interesting clones is in progress for the isolation of the corresponding full-length cDNAs and the functional analysis of the genes in arabidopsis mutants.
- Published
- 2002
24. Differential expression of potato calmodulin genes by cold, heat and salt stress
- Author
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Massarelli I., Grillo S., Costa A., and Leone A.
- Subjects
potato cells ,Calmodulin ,gene expression ,temperature and salt stress - Abstract
Calmodulin (CaM) is a protein modulated by calcium, an important component of signal transduction of plant response to external stimuli. Three different CaM cDNAs were isolated from a Solanum commersonii library by screening with a RT-PCR fragment amplified from a conserved region of the S. tuberosum CaM1 gene. The three cDNAs (ScCaM1, ScCaM3 and ScCaM5), sharing 85% identity inside the coding region, have a predicted amino acid sequence of 149 residues, highly homologous to other known plant calmodulins (90% identity). The 3'-untranslated regions (UTR) are highly divergent (only 47% homology) and were used as probes to monitor changes in gene expression in potato cells exposed to temperature stress (cold and heat) and NaCl treatment. Transcripts corresponding to ScCaM1 and ScCaM5 were rapidly induced in response to cold, heat and salt stress. However, when the 3' UTR region of each gene was used as probe, differences in the kinetics of induction and the amount of transcripts were revealed. The expression of ScCaM3 genes was only induced in potato leaves after cold treatment but not in the stress condition tested on cells culture. The same stress treatments applied to potato cells pre-exposed to gradual osmotic stress did not affect the steady-state level of CaM mRNAs, suggesting that one or more components involved in the perception and intracellular transduction of temperature stress signal might have been altered under persistent osmotic stress.
- Published
- 2002
25. Isolation of genes involved in response to osmotic stress
- Author
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Costa A., Massarelli I., Dragonetti E., Leone A., and Grillo S.
- Subjects
food and beverages - Abstract
Two different approaches were used to identify genes involved in the cellular response to water and salinity stress in potato. 1) Differential Display of mRNAs (DDRT-PCR), was used to isolate and distinguish genes whose expression is modulated during short and/or long-term water stress. 2) Functional analysis of potato cDNA clones by over-expression in E. coli cells, to fish out genes that provide salinity tolerance. The isolation and partial characterization of 17 different potato cDNA clones whose expression is modulated in response to abiotic stresses is reported.
- Published
- 1999
26. Drought-tolerance or shock-induced genes: how to discriminate?
- Author
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Grillo S., Consiglio F., Costa A., Massarelli I., and Leone A.
- Subjects
food and beverages - Abstract
Cells of many glycophyte crop plants are able to respond to a graduaI water deficit by a set of biochemical and metabolic adjustments to cope with the new cellular water balance. However, when a change in the cellular water content is sudden, it may cause cellular damage and ultimately to cell death. In either case, sets of genes are inhibited or activated. In acclimated cells, the function of the activated gene products is associated with the recovery of a normal cellular metabolism, but it is rather aimed at repairing cellular damage in water-shocked cells. To identify genes associated with the plant ability to acclimate to drought, our laboratory has characterized a potato cell population exposed to increasing concentrations of PEG 8000, to mimic graduaI water deficit. DDRT-PCR has been used extensively for cloning genes differentially expressed in response to graduaI water deficit. mRNA populations of acclimated cells were compared with those of PEG- shocked cells. The comparison was also made with mRNAs of ABA- treated cells, based on the findings that ABA accumulates in shocked cells but not in acclimated cells. A set of cDNAs specific for each mechanism was identified and cloned. Genes under study include genes involved in the maintenance of membrane stability and physical state under water stress (desaturases), as well as in Ca2+ mediated signal transduction pathway (calmodulins).
- Published
- 1998
27. Cloning, characterization and expression of three calmodulin genes of Solanum commersonii
- Author
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Massarelli I., Costa A., Leone A., and Grillo S.
- Abstract
Calmodulin (CaM) is modulated by calcium, which is an important factor of plant signal transduction. Three different CaM cDNAs were isolated from a cDNA library of the cold tolerant potato wild species S. commersonii, by screennig with a RT-PCR fragment (350bp) from S. tuberosum gene CaM1. Clones ScCaM1, ScCaM3, ScCaM5 are 918, 899, 881 bp long respectively and contain a complete ORF coding for 149 amino acid residues. While nucleotide identity inside the coding region of three clones is high (81%), the 3' untranslated regions are divergent (only 47 % identity) and different also in lenght (330bp ScCaM1, 290bp ScCaM3, 416bp ScCaM5). The three clones share 93% identity and are highly homologus to other cloned plant and animal calmodulin genes (80-90%). Highly conserved motives were identified in the coding region, including four Ca2+-binding motives (EF-hands), one N-glycosylation site, two N-myristoylation sites, 7 protein C kinase and 1 casein kinase II putative phosphorylation sites. To ascertain whether or not the three CaM clones were differentially induced by specific environmental stresses, the 3' untraslated divergent regions were used as probes in Northern blot analysis. Though transcripts corresponding to the three clones were rapidly induced (within 30 min) by NaCl, high and low temperature and water deficit, differences in the kinetics of induction and the amount of transcript were uncovered by each probe. Interestingly, the same stress treatments did not affect the steady-state level of CaM mRNAs in a potato cell population, adapted to growth in a medium containing 20%PEG. This finding suggests that one or more components involved in the perception and intracellular transduction of the stress signal might have been altered during the adaptation process.
- Published
- 1998
28. Isolation, characterization and expression of an elongation factor 1α gene in potato (Solanum tuberosum) cell cultures
- Author
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Costa, A., primary, Di Giacomo, M., additional, Massarelli, I., additional, De Palma, M., additional, Leone, A., additional, and Grillo, M. S., additional
- Published
- 2010
- Full Text
- View/download PDF
29. Functional screening of plant stress-related cDNAs by random over-expression in Escherichia coli
- Author
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Massarelli, I., primary, Cioffi, R., additional, Batelli, G., additional, De Palma, M., additional, Costa, A., additional, Grillo, S., additional, and Leone, A., additional
- Published
- 2006
- Full Text
- View/download PDF
30. Torsadogenic Cardiotoxicity of Antipsychotic Drugs: a Structural Feature, Potentially Involved in the Interaction with Cardiac HERG Potassium Channels
- Author
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Testai, L., primary, Bianucci, A. M., additional, Massarelli, I., additional, Breschi, M. C., additional, Martinotti, E., additional, and Calderone, V., additional
- Published
- 2004
- Full Text
- View/download PDF
31. Enhanced and feedback-resistant γ-glutamyl kinase activity of an Escherichia coli transformant carrying a mutated proB gene of Streptococcus thermophilus
- Author
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Massarelli, I, primary
- Published
- 2000
- Full Text
- View/download PDF
32. Enhanced and feedback-resistant gamma-glutamyl kinase activity of an Escherichia coli transformant carrying a mutated proBA gene of Streptococcus thermophilus
- Author
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Giuseppe Forlani, Immacolata Massarelli, Maurilio De Felice, Ezio Ricca, Massarelli, I, Forlani, G, Ricca, Ezio, DE FELICE, M., Massarelli, I., Forlani, G., Ricca, E., and DE FELICE, Maurilio
- Subjects
3-4-dehydroproline ,Streptococcus thermophilus ,Proline ,Molecular Sequence Data ,medicine.disease_cause ,Polymerase Chain Reaction ,Microbiology ,Feedback ,chemistry.chemical_compound ,Biosynthesis ,Aspartic acid ,Escherichia coli ,Genetics ,medicine ,Point Mutation ,Amino Acid Sequence ,Kinase activity ,glutamyl kinase ,proB ,proline biosynthesis ,azetidine-2-carboxylate ,Molecular Biology ,Amino acid synthesis ,chemistry.chemical_classification ,Base Sequence ,biology ,Point mutation ,Streptococcus ,Phosphotransferases (Carboxyl Group Acceptor) ,biology.organism_classification ,Amino acid ,Amino Acid Substitution ,chemistry ,Biochemistry ,Transformation, Bacterial ,Azetidinecarboxylic Acid - Abstract
We used a PCR-based method to generate a single base pair mutation in the proB gene of Streptococcus thermophilus, which replaced an aspartic acid with a glycine residue at position 192 of the first proline biosynthetic enzyme gamma-glutamyl kinase. This was the first identified mutation in amino acid biosynthesis in S. thermophilus to our knowledge. The mutation caused an enhanced, feedback-resistant gamma-glutamyl kinase activity and conferred an analogue-resistant phenotype to an Escherichia coli transformant containing the mutated gene.
- Published
- 2000
33. Early prenatal use of a multivitamin diminishes the risk for inadequate vitamin D status in pregnant women: results from the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort study.
- Author
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Weiler HA, Brooks SPJ, Sarafin K, Fisher M, Massarelli I, Luong TM, Johnson M, Morisset AS, Dodds L, Taback S, Helewa M, von Dadelszen P, Smith G, Lanphear BP, Fraser WD, and Arbuckle TE
- Subjects
- Adult, Cohort Studies, Diet, Female, Humans, Longitudinal Studies, Pregnancy, Prenatal Nutritional Physiological Phenomena, Vitamin D Deficiency prevention & control, Vitamins administration & dosage, Vitamins pharmacology
- Abstract
Background: Reports on the adequacy of vitamin D status of pregnant women are not available in Canada., Objectives: The objectives of this study were to examine vitamin D status across pregnancy and identify the correlates of vitamin D status of pregnant women in Canada., Methods: Pregnant women (≥18 years) from 6 provinces (2008-2011) participating in a longitudinal cohort were studied. Sociodemographic data, obstetrical histories, and dietary and supplemental vitamin D intakes were surveyed. Plasma 25-hydroxyvitamin D (25OHD) was measured using an immunoassay standardized to LC-MS/MS from samples collected during the first (n = 1905) and third trimesters (n = 1649) and at delivery (n = 1543). The proportion of women with ≥40 nmol/L of plasma 25OHD (adequate status) was estimated at each time point, and factors related to achieving this cut point were identified using repeated-measures logistic regression. Differences in 25OHD concentrations across trimesters and at delivery were tested a using repeated-measures ANOVA with a post hoc Tukey's test., Results: In the first trimester, 93.4% (95% CI: 92.3%-94.5%) of participants had 25OHD ≥40 nmol/L. The mean plasma 25OHD concentration increased from the first to the third trimester and then declined by delivery (69.8 ± 0.5 nmol/L, 78.6 ± 0.7 nmol/L, and 75.7 ± 0.7 nmol/L, respectively; P < 0.0001). A lack of multivitamin use early in pregnancy reduced the odds of achieving 25OHD ≥40 nmol/L (ORadj = 0.33; 95% CI: 0.25-0.42) across all time points. Factors associated with not using a prenatal multivitamin included multiparity (ORadj = 2.08; 95% CI: 1.42-3.02) and a below-median income (ORadj = 1.39; 95% CI: 1.02-1.89)., Conclusions: The results from this cohort demonstrate the importance of early multivitamin supplement use to achieve an adequate vitamin D status in pregnant women., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)
- Published
- 2021
- Full Text
- View/download PDF
34. Association between gestational urinary bisphenol a concentrations and adiposity in young children: The MIREC study.
- Author
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Braun JM, Li N, Arbuckle TE, Dodds L, Massarelli I, Fraser WD, Lanphear BP, and Muckle G
- Subjects
- Canada, Child, Preschool, Cohort Studies, Dietary Exposure adverse effects, Dietary Exposure statistics & numerical data, Female, Humans, Male, Maternal Exposure adverse effects, Maternal Exposure statistics & numerical data, Pregnancy, Prospective Studies, Adiposity, Benzhydryl Compounds urine, Phenols urine
- Abstract
Background: Bisphenol A (BPA) is a high production volume chemical and because of its use in many consumer products, exposure is ubiquitous. Gestational BPA exposure has been associated with excess adiposity in rodent studies, but not consistently in human studies. We investigated the relation between gestational BPA exposure and early childhood adiposity in a prospective cohort study of 719 mother-child pairs., Methods: We used data from the MIREC Study, a prospective Pan-Canadian pregnancy and birth cohort study. We measured BPA in urine samples collected at an average of 12.1 weeks (range: 6.3-15 weeks) gestation and measured children's weight, height, waist/hip circumference, and subscapular/triceps skinfold thickness at an average age of 3.5 years (range: 1.9-6.2). We estimated covariate-adjusted associations of log
2 -transformed BPA concentrations with child adiposity measures and examined whether these associations differed in boys and girls., Results: Median BPA concentrations were 0.8 ng/mL (IQR: 0.5-1.4). Among both boys and girls, each 2-fold increase in BPA concentrations was associated with higher waist-to-hip ratio (β: 0.003; 95% CI: 0.001, 0.005). The association of BPA with waist circumference and subscapular skinfold thickness was modified by sex (sex x BPA interaction p-values<0.2). In girls, each 2-fold increase in BPA concentrations was associated with a 0.2 cm (95% CI: 0.0, 0.5) and 0.15 mm (95% CI: 0.01, 0.30) increase in waist circumference and subscapular skinfolds, respectively. Associations were generally null or slightly inverse in boys., Conclusions: In this cohort, gestational urinary BPA concentrations were associated with subtle increases in girl's central adiposity during early childhood., (Copyright © 2019 Elsevier Inc. All rights reserved.)- Published
- 2019
- Full Text
- View/download PDF
35. Low 25-hydroxyvitamin D levels are more prevalent in Canadians of South Asian than European ancestry inhabiting the National Capital Region of Canada.
- Author
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Nagasaka R, Swist E, Sarafin K, Gagnon C, Rondeau I, Massarelli I, Cheung W, Laffey P, Brooks SP, and Ratnayake WMN
- Subjects
- Adult, Aged, Asian People, Canada epidemiology, Dietary Supplements, Female, Humans, Male, Middle Aged, Prevalence, Seasons, Skin Pigmentation, Surveys and Questionnaires, Vitamin D blood, Vitamin D Deficiency epidemiology, White People, Young Adult, Vitamin D analogs & derivatives, Vitamin D Deficiency diagnosis
- Abstract
The US Institute of Medicine defined serum 25-hydroxyvitamin D (25OHD) cut point values of 30 nmol/L and 40 nmol/L were used to assess the vitamin D status of South Asian and European Canadians of self-identified ancestry living in the National Capital Region of Canada. Serum 25OHD values were measured in the spring and fall of 2012 to represent status during the winter and summer months, respectively. A total of 1238 measurements were obtained from 669 participants (49% South Asian ancestry): some participants were measured only once (spring or fall). Median 25OHD values were significantly higher in participants of European ancestry: 70.8 nmol/L (68.1, 73.5; 95% CI) versus South Asian ancestry: 42.7 nmol/L (40.5, 45.0; P<0.001). Spring vs. fall differences were small for each ethnic group and significant only for those of European ancestry (2.9, CI: 1.0-4.9 nmol/L; P = 0.01). Among participants of South Asian ancestry, 27.3% (fall) and 29.1% (spring) of females had values <40 nmol/L while the percentages for males were considerably higher (36.5% and 44.2%, respectively). The corresponding values for participants of European ancestry were ≤10%, showing that the South Asian participants were less likely to achieve the 25OHD concentrations established by the IOM for optimum bone health. Investigation of the factors related to serum 25OHD levels showed that supplement intake and ethnic background were associated with the biggest differences. Skin color was not a major factor, suggesting that genetic factors are responsible for the observed differences between participants of different ethnic backgrounds., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2018
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36. Response mechanisms induced by exposure to high temperature in anthers from thermo-tolerant and thermo-sensitive tomato plants: A proteomic perspective.
- Author
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Mazzeo MF, Cacace G, Iovieno P, Massarelli I, Grillo S, and Siciliano RA
- Subjects
- Flowers growth & development, Flowers metabolism, Solanum lycopersicum growth & development, Pollen growth & development, Pollen metabolism, Heat-Shock Response physiology, Hot Temperature, Solanum lycopersicum metabolism, Plant Proteins metabolism, Proteome metabolism, Proteomics methods
- Abstract
Constant global warming is one of the most detrimental environmental factors for agriculture causing significant losses in productivity as heat stress (HS) conditions damage plant growth and reproduction. In flowering plants such as tomato, HS has drastic repercussions on development and functionality of male reproductive organs and pollen. Response mechanisms to HS in tomato anthers and pollen have been widely investigated by transcriptomics; on the contrary, exhaustive proteomic evidences are still lacking. In this context, a differential proteomic study was performed on tomato anthers collected from two genotypes (thermo-tolerant and thermo-sensitive) to explore stress response mechanisms and identify proteins possibly associated to thermo-tolerance. Results showed that HS mainly affected energy and amino acid metabolism and nitrogen assimilation and modulated the expression of proteins involved in assuring protein quality and ROS detoxification. Moreover, proteins potentially associated to thermo-tolerant features, such as glutamine synthetase, S-adenosylmethionine synthase and polyphenol oxidase, were identified., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2018
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37. Addition of food group equivalents to the Canadian Diet History Questionnaire II for the estimation of the Canadian Healthy Eating Index-2005.
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McInerney M, Ho V, Koushik A, Massarelli I, Rondeau I, McCormack GR, and Csizmadi I
- Subjects
- Adult, Aged, Aged, 80 and over, Canada, Databases, Factual, Educational Status, Female, Guidelines as Topic, Humans, Male, Middle Aged, Recommended Dietary Allowances, Sex Factors, Smoking, Young Adult, Diet Surveys, Diet, Healthy, Food
- Abstract
Introduction: Poor diet quality has been shown to increase the risk of common chronic diseases that can negatively impact quality of life and burden the healthcare system. Canada's Food Guide evidence-based recommendations provide dietary guidance aimed at increasing diet quality. Compliance with Canada's Food Guide can be assessed with the Canadian Healthy Eating Index (C-HEI), a diet quality score. The recently designed Canadian Diet History Questionnaire II (C-DHQ II), a comprehensive food frequency questionnaire could be used to estimate the C-HEI in Canadian populations with the addition of food group equivalents (representing Canada's Food Guide servings) to the C-DHQ II nutrient database. We describe methods developed to augment the C-DHQ II nutrient database to estimate the C-HEI., Methods: Food group equivalents were created using food and nutrient data from existing published food and nutrient databases (e.g. the Canadian Community Health Survey - Cycle 2.2 Nutrition [2004]). The variables were then added to the C-DHQ II companion nutrient database. C-HEI scores were determined and descriptive analyses conducted for participants who completed the C-DHQ II in a cross-sectional Canadian study., Results: The mean (standard deviation) C-HEI score in this sample of 446 adults aged 20 to 83 was 64.4 (10.8). Women, non-smokers, and those with more than high school education had statistically significant higher C-HEI scores than men, smokers and those with high school diplomas or less., Conclusion: The ability to assess C-HEI using the C-DHQ II facilitates the study of diet quality and health outcomes in Canada., Competing Interests: The authors have no conflicts of interest to disclose.
- Published
- 2018
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38. Self-Report Dietary Assessment Tools Used in Canadian Research: A Scoping Review.
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Kirkpatrick SI, Vanderlee L, Raffoul A, Stapleton J, Csizmadi I, Boucher BA, Massarelli I, Rondeau I, and Robson PJ
- Subjects
- Canada, Diet, Feasibility Studies, Humans, Mental Recall, Meta-Analysis as Topic, Randomized Controlled Trials as Topic, Nutrition Assessment, Nutrition Surveys methods, Self Report
- Abstract
Choosing the most appropriate dietary assessment tool for a study can be a challenge. Through a scoping review, we characterized self-report tools used to assess diet in Canada to identify patterns in tool use and to inform strategies to strengthen nutrition research. The research databases Medline, PubMed, PsycINFO, and CINAHL were used to identify Canadian studies published from 2009 to 2014 that included a self-report assessment of dietary intake. The search elicited 2358 records that were screened to identify those that reported on self-report dietary intake among nonclinical, non-Aboriginal adult populations. A pool of 189 articles (reflecting 92 studies) was examined in-depth to assess the dietary assessment tools used. Food-frequency questionnaires (FFQs) and screeners were used in 64% of studies, whereas food records and 24-h recalls were used in 18% and 14% of studies, respectively. Three studies (3%) used a single question to assess diet, and for 3 studies the tool used was not clear. A variety of distinct FFQs and screeners, including those developed and/or adapted for use in Canada and those developed elsewhere, were used. Some tools were reported to have been evaluated previously in terms of validity or reliability, but details of psychometric testing were often lacking. Energy and fat were the most commonly studied, reported by 42% and 39% of studies, respectively. For ∼20% of studies, dietary data were used to assess dietary quality or patterns, whereas close to half assessed ≤5 dietary components. A variety of dietary assessment tools are used in Canadian research. Strategies to improve the application of current evidence on best practices in dietary assessment have the potential to support a stronger and more cohesive literature on diet and health. Such strategies could benefit from national and global collaboration., (© 2017 American Society for Nutrition.)
- Published
- 2017
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39. The Comparative Reliability and Feasibility of the Past-Year Canadian Diet History Questionnaire II: Comparison of the Paper and Web Versions.
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Lo Siou G, Csizmadi I, Boucher BA, Akawung AK, Whelan HK, Sharma M, Al Rajabi A, Vena JE, Kirkpatrick SI, Koushik A, Massarelli I, Rondeau I, and Robson PJ
- Subjects
- Adult, Aged, Aged, 80 and over, Body Mass Index, Canada, Diet, Dietary Carbohydrates administration & dosage, Dietary Fats administration & dosage, Dietary Fiber administration & dosage, Dietary Proteins administration & dosage, Feasibility Studies, Female, Humans, Male, Middle Aged, Nutrition Assessment, Reproducibility of Results, Socioeconomic Factors, Waist Circumference, Internet, Nutrition Surveys, Surveys and Questionnaires
- Abstract
Advances in technology-enabled dietary assessment include the advent of web-based food frequency questionnaires, which may reduce costs and researcher burden but may introduce new challenges related to internet connectivity and computer literacy. The purpose of this study was to evaluate the intra- and inter-version reliability, feasibility and acceptability of the paper and web Canadian Diet History Questionnaire II (CDHQ-II) in a sub-sample of 648 adults (aged 39-81 years) recruited from Alberta's Tomorrow Project. Participants were randomly assigned to one of two groups: (1) paper, web, paper; or (2) web, paper, web over a six-week period. With few exceptions, no statistically significant differences in mean nutrient intake were found in the intra- and inter-version reliability analyses. The majority of participants indicated future willingness to complete the CDHQ-II online, and 59% indicated a preference for the web over the paper version. Findings indicate that, in this population of adults drawn from an existing cohort, the CDHQ-II may be administered in paper or web modalities (increasing flexibility for questionnaire delivery), and the nutrient estimates obtained with either version are comparable. We recommend that other studies explore the feasibility and reliability of different modes of administration of dietary assessment instruments prior to widespread implementation.
- Published
- 2017
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40. Using national dietary intake data to evaluate and adapt the US Diet History Questionnaire: the stepwise tailoring of an FFQ for Canadian use.
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Csizmadi I, Boucher BA, Lo Siou G, Massarelli I, Rondeau I, Garriguet D, Koushik A, Elenko J, and Subar AF
- Subjects
- Canada, Female, Humans, Male, United States, Diet, Diet Surveys, Nutrition Policy
- Abstract
Objective: To evaluate the Canadian Diet History Questionnaire I (C-DHQ I) food list and to adapt the US DHQ II for Canada using Canadian dietary survey data., Design: Twenty-four-hour dietary recalls reported by adults in a national Canadian survey were analysed to create a food list corresponding to C-DHQ I food questions. The percentage contribution of the food list to the total survey intake of seventeen nutrients was used as the criterion to evaluate the suitability of the C-DHQ I to capture food intake in Canadian populations. The data were also analysed to identify foods and to modify portion sizes for the C-DHQ II., Setting: The Canadian Community Health Survey (CCHS) - Cycle 2.2 Nutrition (2004)., Subjects: Adults (n 20 159) who completed 24 h dietary recalls during in-person interviews., Results: Four thousand five hundred and thirty-three foods and recipes were grouped into 268 Food Groups, of which 212 corresponded to questions on the C-DHQ I. Nutrient intakes captured by the C-DHQ I ranged from 79 % for fat to 100 % for alcohol. For the new C-DHQ II, some food questions were retained from the original US DHQ II while others were added based on foods reported in CCHS and foods available on the Canadian market since 2004. Of 153 questions, 143 were associated with portion sizes of which fifty-three were modified from US values. Sex-specific nutrient profiles for the C-DHQ II nutrient database were derived using CCHS data., Conclusions: The C-DHQ I and II are designed to optimize the capture of foods consumed by Canadian populations.
- Published
- 2016
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41. Dietary assessment is a critical element of health research - Perspective from the Partnership for Advancing Nutritional and Dietary Assessment in Canada.
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Labonté MÈ, Kirkpatrick SI, Bell RC, Boucher BA, Csizmadi I, Koushik A, L'Abbé MR, Massarelli I, Robson PJ, Rondeau I, Shatenstein B, Subar AF, and Lamarche B
- Abstract
Challenges and complexities associated with assessing dietary intakes are numerous, but not insurmountable. This opinion paper from Canadian researchers draws attention to the importance of building capacity and providing funding opportunities for research in dietary assessment methods in Canada and elsewhere. Such strategies would contribute to a better understanding of the roles played by diet in human health and better translation of this information into the most meaningful and effective dietary guidelines, policies, and interventions.
- Published
- 2016
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42. Rankings of iron, vitamin D, and calcium intakes in relation to maternal characteristics of pregnant Canadian women.
- Author
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Morisset AS, Weiler HA, Dubois L, Ashley-Martin J, Shapiro GD, Dodds L, Massarelli I, Vigneault M, Arbuckle TE, and Fraser WD
- Subjects
- Adult, Body Weight, Canada, Cohort Studies, Diet, Dietary Supplements, Female, Humans, Logistic Models, Micronutrients administration & dosage, Micronutrients blood, Multivariate Analysis, Nutritional Requirements, Reproducibility of Results, Socioeconomic Factors, Surveys and Questionnaires, Young Adult, Calcium, Dietary administration & dosage, Iron, Dietary administration & dosage, Maternal Nutritional Physiological Phenomena, Pregnancy, Vitamin D administration & dosage
- Abstract
Iron, vitamin D, and calcium intakes in the prenatal period are important determinants of maternal and fetal health. The objective of this study was to examine iron, vitamin D, and calcium intakes from diet and supplements in relation to maternal characteristics. Data were collected in a subsample of 1186 pregnant women from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a cohort study including pregnant women recruited from 10 Canadian sites between 2008 and 2011. A food frequency questionnaire was administered to obtain rankings of iron, calcium, and vitamin D intake (16-21 weeks of pregnancy). Intakes from supplements were obtained from a separate questionnaire (6-13 weeks of pregnancy). Women were divided into 2 groups according to the median total intake of each nutrient. Supplement intake was an important contributor to total iron intake (median 74%, interquartile range (IQR) 0%-81%) and total vitamin D intake (median 60%, IQR 0%-73%), while the opposite was observed for calcium (median 18%, IQR 0%-27%). Being born outside of Canada was significantly associated with lower total intakes of iron, vitamin D, and calcium (p ≤ 0.01 for all). Consistent positive indicators of supplement use (iron, vitamin D, and calcium) were maternal age over 30 years and holding a university degree. In conclusion, among Canadian women, the probability of having lower iron, vitamin D, and calcium intakes is higher among those born outside Canada; supplement intake is a major contributor to total iron and vitamin D intakes; and higher education level and age over 30 years are associated with supplement intake.
- Published
- 2016
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43. A Methylene Group on C-2 of 24,24-Difluoro-19-nor-1α,25-dihydroxyvitamin D3 Markedly Increases Bone Calcium Mobilization in Vivo.
- Author
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Flores A, Massarelli I, Thoden JB, Plum LA, and DeLuca HF
- Subjects
- Animals, Bone and Bones metabolism, Calcitriol chemical synthesis, Calcitriol chemistry, Calcitriol pharmacology, Cell Differentiation drug effects, Cell Line, Tumor, Crystallography, X-Ray, Humans, Male, Molecular Conformation, Molecular Docking Simulation, Rats, Rats, Sprague-Dawley, Receptors, Calcitriol metabolism, Stereoisomerism, Structure-Activity Relationship, Transcription, Genetic, Vitamin D3 24-Hydroxylase genetics, Vitamin D3 24-Hydroxylase metabolism, Bone and Bones drug effects, Calcitriol analogs & derivatives, Calcium metabolism
- Abstract
Four side chain fluorinated analogues of 1α,25-dihydroxy-19-norvitamin D have been prepared in convergent syntheses using the Wittig-Horner reaction as a key step. Structures and absolute configurations of analogues 3 and 5 were confirmed by X-ray crystallography. All analogues showed high potency in HL-60 cell differentiation and vitamin D-24-hydroxylase (24-OHase) transcription as compared to 1α,25-dihydroxyvitamin D3 (1). Most important is that all of the 20S-configured derivatives (4 and 6) had high bone mobilizing activity in vivo. However, in the 20R series, a 2-methylene group was required for high bone mobilizing activity. A change in positioning of the 20R molecule in the vitamin D receptor when the 2-methylene group is present may provide new insight into the molecular basis of bone calcium mobilization induced by vitamin D.
- Published
- 2015
- Full Text
- View/download PDF
44. EPA and DHA status of South Asian and white Canadians living in the National Capital Region of Canada.
- Author
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Nagasaka R, Gagnon C, Swist E, Rondeau I, Massarelli I, Cheung W, and Ratnayake WM
- Subjects
- Adult, Aged, Animals, Asian People, Biomarkers blood, Cardiovascular Diseases blood, Cardiovascular Diseases prevention & control, Diet, Erythrocytes metabolism, Female, Fishes, Humans, Male, Middle Aged, Nutritional Requirements, Ontario, Risk Factors, White People, Young Adult, Docosahexaenoic Acids administration & dosage, Eicosapentaenoic Acid administration & dosage, Fatty Acids, Omega-3 blood
- Abstract
To minimize the risk of cardiovascular disease (CVD), most dietary guidelines have recommended consuming 500 mg/day of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) or two servings of oily fish/week. The sum of percent EPA and DHA in red blood cell (RBC) total fatty acids-termed the omega-3 index-has been proposed as a biomarker for assessing the risk of death from CVD. The omega-3 indices of ≤4, >4 to <8 and ≥8 % have been proposed to be associated with high, intermediate and low CVD risks, respectively. In this study, we determined the EPA + DHA intake level and the omega-3 index of South Asian Canadians (SAC; n = 308) and white Canadians (WC; n = 341) age 20-79 years living in the National Capital Region of Canada. The mean EPA + DHA intake levels were 569 ± 571 mg/day for SAC and 684 ± 865 mg/day for WC and 46 % of SAC and 43 % of WC met the recommended EPA + DHA intake level of 500 mg/day. The mean omega-3 indices were 6.6 and 5.9 % for SAC and WC respectively. The suggested cardio-protective target level for the omega-3 index of ≥8 % was observed only in 19.8 % of SAC and in 9.4 % of WC subjects. The majority of the participants (74.4 % of SAC and 82.7 % of WC) were in the >4 to <8 % range. These results suggest that although study participants' dietary intake of EPA + DHA is adequate, this intake was not sufficient to provide an omega-3 index that is considered cardio-protective.
- Published
- 2014
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45. Selection of a human butyrylcholinesterase-like antibody single-chain variable fragment resistant to AChE inhibitors from a phage library expressed in E. coli.
- Author
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Podestà A, Rossi S, Massarelli I, Carpi S, Adinolfi B, Fogli S, Bianucci AM, and Nieri P
- Subjects
- Butyrylcholinesterase genetics, Butyrylcholinesterase immunology, Humans, Recombinant Proteins biosynthesis, Recombinant Proteins chemistry, Recombinant Proteins genetics, Recombinant Proteins immunology, Butyrylcholinesterase chemistry, Cholinesterase Inhibitors chemistry, Escherichia coli, Gene Expression, Gene Library, Single-Chain Antibodies biosynthesis, Single-Chain Antibodies chemistry, Single-Chain Antibodies genetics, Single-Chain Antibodies immunology
- Abstract
Organophosphates are potent poisoning agents that cause severe cholinergic toxicity. Current treatment has been reported to be unsatisfactory and novel antidotes are needed. In this study, we used a single-chain variable fragment (scFv) library to select a recombinant antibody fragment (WZ1-14.2.1) with butyrylcholinesterase-like catalytic activity by using an innovative method integrating genetic selection and the bait-and-switch strategy. Ellman assay demonstrated that WZ1-14.2.1 has Michaelis-Menten kinetics in the hydrolysis of all the three substrates used, acetylthiocholine, propionylthiocholine and butyrylthiocholine. Notably, the catalytic activity was resistant to the following acetylcholinesterase inhibitors: neostigmine, iso-OMPA, chlorpyrifos oxon, dichlorvos, and paraoxon ethyl. Otherwise, the enzymatic activity of WZ1-14.2.1 was inhibited by the selective butyrylcholinesterase inhibitor, ethopropazine, and by the Ser-blocking agent phenylmethanesuphonyl fluoride. A hypothetical 3D structure of the WZ1-14.2.1 catalytic site, compatible with functional results, is proposed on the basis of a molecular modeling analysis.
- Published
- 2014
- Full Text
- View/download PDF
46. Asg1 is a stress-inducible gene which increases stomatal resistance in salt stressed potato.
- Author
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Batelli G, Massarelli I, Van Oosten M, Nurcato R, Vannini C, Raimondi G, Leone A, Zhu JK, Maggio A, and Grillo S
- Subjects
- Abscisic Acid pharmacology, Adaptation, Physiological, Arabidopsis genetics, Arabidopsis physiology, Carbohydrates pharmacology, Gene Knockout Techniques, Germination, Mutation, Onions genetics, Onions physiology, Organ Specificity, Osmotic Pressure, Plant Growth Regulators pharmacology, Plant Leaves cytology, Plant Leaves drug effects, Plant Leaves genetics, Plant Leaves physiology, Plant Proteins genetics, Plants, Genetically Modified, Recombinant Fusion Proteins, Seeds cytology, Seeds drug effects, Seeds genetics, Seeds physiology, Signal Transduction, Sodium Chloride pharmacology, Solanum tuberosum cytology, Solanum tuberosum drug effects, Solanum tuberosum physiology, Stress, Physiological, Gene Expression Regulation, Plant physiology, Plant Proteins metabolism, Plant Stomata physiology, Solanum tuberosum genetics
- Abstract
The identification of critical components in plant salt stress adaptation has greatly benefitted, in the last two decades, from fundamental discoveries in Arabidopsis and close model systems. Nevertheless, this approach has also highlighted a non-complete overlap between stress tolerance mechanisms in Arabidopsis and agricultural crops. Within a long-running research program aimed at identifying salt stress genetic determinants in potato by functional screening in Escherichia coli, we isolated Asg1, a stress-related gene with an unknown function. Asg1 is induced by salt stress in both potato and Arabidopsis and by abscisic acid in Arabidopsis. Asg1 is actively transcribed in all plant tissues. Furthermore, Asg1 promoter analysis confirmed its ubiquitous expression, which was remarkable in pollen, a plant tissue that undergoes drastic dehydration/hydration processes. Fusion of Asg1 with green fluorescent protein showed that the encoded protein is localized close to the plasma membrane with a non-continuous pattern of distribution. In addition, Arabidopsis knockout asg1 mutants were insensitive to both NaCl and sugar hyperosmotic environments during seed germination. Transgenic potato plants over-expressing the Asg1 gene revealed a stomatal hypersensitivity to NaCl stress which, however, did not result in a significantly improved tuber yield in stress conditions. Altogether, these data suggest that Asg1 might interfere with components of the stress signaling pathway by promoting stomatal closure and participating in stress adaptation., (Copyright © 2012 Elsevier GmbH. All rights reserved.)
- Published
- 2012
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47. Synthesis and biological activities of vitamin D-like inhibitors of CYP24 hydroxylase.
- Author
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Chiellini G, Rapposelli S, Zhu J, Massarelli I, Saraceno M, Bianucci AM, Plum LA, Clagett-Dame M, and DeLuca HF
- Subjects
- 25-Hydroxyvitamin D3 1-alpha-Hydroxylase antagonists & inhibitors, Amino Acid Sequence, Animals, Calcifediol analogs & derivatives, Calcifediol chemical synthesis, Calcifediol chemistry, Calcium chemistry, Cell Differentiation, Cyclopropanes chemical synthesis, Cyclopropanes chemistry, Enzyme Activation, Enzyme Inhibitors chemistry, Enzyme Inhibitors pharmacology, HL-60 Cells, Half-Life, Humans, Hydroxycholecalciferols chemistry, Magnetic Resonance Spectroscopy, Mice, Molecular Sequence Data, Osteoblasts drug effects, Rats, Sequence Homology, Amino Acid, Transcriptional Activation, Vitamin D chemistry, Vitamin D3 24-Hydroxylase, Enzyme Inhibitors chemical synthesis, Steroid Hydroxylases antagonists & inhibitors, Vitamin D analogs & derivatives
- Abstract
Selective inhibitors of CYP24A1 represent an important synthetic target in a search for novel vitamin D compounds of therapeutic value. In the present work, we show the synthesis and biological properties of two novel side chain modified 2-methylene-19-nor-1,25(OH)(2)D(3) analogs, the 22-imidazole-1-yl derivative 2 (VIMI) and the 25-N-cyclopropylamine compound 3 (CPA1), which were efficiently prepared in convergent syntheses utilizing the Lythgoe type Horner-Wittig olefination reaction. When tested in a cell-free assay, both compounds were found to be potent competitive inhibitors of CYP24A1, with the cyclopropylamine analog 3 exhibiting an 80-1 selective inhibition of CYP24A1 over CYP27B1. Addition of 3 to a mouse osteoblast culture sustained the level of 1,25(OH)(2)D(3), further demonstrating its effectiveness in CYP24A1 inhibition. Importantly, the in vitro effects on human promyeloid leukemia (HL-60) cell differentiation by 3 were nearly identical to those of 1,25(OH)(2)D(3) and in vivo the compound showed low calcemic activity. Finally, the results of preliminary theoretical studies provide useful insights to rationalize the ability of analog 3 to selectively inhibit the cytochrome P450 isoform CYP24A1., (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF
48. Identification of selective ligands for human fibrin recognition using high-throughput docking.
- Author
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Massarelli I, Imbriani M, Chiellini F, Chiellini E, and Bianucci AM
- Subjects
- Databases, Factual, Fluorometry, Humans, Molecular Structure, Protein Binding, Epitopes chemistry, Epitopes metabolism, Fibrin chemistry, Fibrin metabolism
- Abstract
The ultimate aim of this study is to identify new molecules that are able to recognize polymerized fibrin, which is the main component of a thrombus. These selective ligands can be exposed on the surface of particular nanoparticles used for the targeted delivery of fibrinolytic drugs. The targeted delivery of these drugs is expected to help to keep under control the severe side effects which can occur if the drugs are administered systemically. The study focuses on the application of high-throughput docking methods used to screen a library of thousands of commercial compounds. The aim was to identify molecules that are potentially capable of interacting with the human fibrin γ(312-324) epitope. The best scoring compounds were purchased and tested through fluorimetric assays in order to estimate their affinity toward fibrin. The results show that the protocol proposed here for identifying new compounds of interest may provide a valuable contribution to the discovery of lead molecules for human fibrin recognition., (Copyright © 2011 John Wiley & Sons, Ltd.)
- Published
- 2011
- Full Text
- View/download PDF
49. Optimizing QSAR models for predicting ligand binding to the drug-metabolizing cytochrome P450 isoenzyme CYP2D6.
- Author
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Saraceno M, Massarelli I, Imbriani M, James TL, and Bianucci AM
- Subjects
- Cytochrome P-450 CYP2D6 chemistry, Cytochrome P-450 CYP2D6 Inhibitors, Enzyme Inhibitors chemistry, Enzyme Inhibitors pharmacology, Humans, Inhibitory Concentration 50, Models, Biological, Protein Binding, Quantitative Structure-Activity Relationship, Small Molecule Libraries chemistry, Small Molecule Libraries pharmacology, Cytochrome P-450 CYP2D6 metabolism, Ligands, Models, Molecular
- Abstract
The cytochrome P450 isozyme CYP2D6 binds a large variety of drugs, oxidizing many of them, and plays a crucial role in establishing in vivo drug levels, especially in multidrug regimens. The current study aimed to develop reliable predictive models for estimating the CYP2D6 inhibition properties of drug candidates. Quantitative structure-activity relationship (QSAR) studies utilizing 51 known CYP2D6 inhibitors were carried out. Performance achieved using models based on two-dimensional (2D) molecular descriptors was compared with performance using models entailing additional molecular descriptors that depend upon the three-dimensional (3D) structure of ligands. To properly compute the descriptors, all the 3D inhibitor structures were optimized such that induced-fit binding of the ligand to the active site was accommodated. CODESSA software was used to obtain equations for correlating the structural features of the ligands to their pharmacological effects on CYP2D6 (inhibition). The predictive power of all the QSAR models obtained was estimated by applying rigorous statistical criteria. To assess the robustness and predictability of the models, predictions were carried out on an additional set of known molecules (prediction set). The results showed that only models incorporating 3D descriptors in addition to 2D molecular descriptors possessed the requisite high predictive power for CYP2D6 inhibition., (© 2011 John Wiley & Sons A/S.)
- Published
- 2011
- Full Text
- View/download PDF
50. Three-dimensional models of the oligomeric human asialoglycoprotein receptor (ASGP-R).
- Author
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Massarelli I, Chiellini F, Chiellini E, and Bianucci AM
- Subjects
- Amino Acid Sequence, Binding Sites, Humans, Molecular Sequence Data, Protein Binding, Protein Multimerization, Protein Structure, Tertiary, Asialoglycoprotein Receptor chemistry, Molecular Docking Simulation
- Abstract
The work presented here is aimed at suggesting plausible hypotheses for functional oligomeric forms of the human asialoglycoprotein receptor (ASGP-R), by applying a combination of different computational techniques. The functional ASGP-R is a hetero-oligomer, that comprises of several subunits of two different kinds (H1 and H2), which are highly homologous. Its stoichiometry is still unknown. An articulated step-wise modeling protocol was used in order to build the receptor model in a minimal oligomeric form, necessary for it to bind multi-antennary carbohydrate ligands. The ultimate target of the study is to contribute to increasing the knowledge of interactions between the human ASGP-R and carbohydrate ligands, at the molecular level, pertinent to applications in the field of hepatic tissue engineering.
- Published
- 2010
- Full Text
- View/download PDF
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