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Search Results: 1 - 10 of 144390 matches for " Carlito B. Lebrilla "
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Glycan Biomarkers in Cancer Diagnosis
Carlito B. Lebrilla
Journal of Analytical Science & Technology , 2011,
Abstract: Glycosylation is a post-translational modification that is found on about 70% of all human proteins. It is sensitive to the biochemical envirnonment and has been shown to vary between contral and cancer patients. Glycans represent a new paradigm for biomarker discovery, but is faced with considerable challenges. Glycans are difficult to analyze in terms of their structure and their position in the proteins. In this presentation, the methods for glycan analysis are described in context of biomarker discovery. Glycosylation holds considerable promise potentially increasing the sensitivity and specificity
Analysis and role of oligosaccharides in milk
L. Renee Ruhaak* & Carlito B. Lebrilla*
BMB Reports , 2012,
Abstract: Milk is an important fluid in glycobiology because it contains anumber of short carbohydrate chains either free or asglycoconjugates. These compounds as a class are the mostabundant component and benefit the infant by developing andmaintaining the infant’s gut flora. New and emerging methodsfor oligosaccharide analysis have been developed to study milk.These methods allow for the rapid profiling of oligosaccharidemixtures with quantitation. With these tools, the role ofoligosaccharide in milk is being understood. They further pointto how oligosaccharide analysis can be performed, which untilnow has been very difficult and have lagged significantly thoseof other biopolymers.
On the analysis of glycomics mass spectrometry data via the regularized area under the ROC curve
Jingjing Ye, Hao Liu, Crystal Kirmiz, Carlito B Lebrilla, David M Rocke
BMC Bioinformatics , 2007, DOI: 10.1186/1471-2105-8-477
Abstract: Maximizing the empirical AUC of glycomics MS data is a large-dimensional optimization problem. The technical difficulty is that the empirical AUC function is not continuous. Instead, it is in fact an empirical 0–1 loss function with a large number of linear predictors. An approach was investigated that regularizes the area under the ROC curve while replacing the 0–1 loss function with a smooth surrogate function. The constrained threshold gradient descent regularization algorithm was applied, where the regularization parameters were chosen by the cross-validation method, and the confidence intervals of the regression parameters were estimated by the bootstrap method. The method is called TGDR-AUC algorithm. The properties of the approach were studied through a numerical simulation study, which incorporates the positive values of mass spectrometry data with the correlations between measurements within person. The simulation proved asymptotic properties that estimated AUC approaches the true AUC. Finally, mass spectrometry data of serum glycan for ovarian cancer diagnosis was analyzed. The optimal combination based on TGDR-AUC algorithm yields plausible result and the detected biomarkers are confirmed based on biological evidence.The TGDR-AUC algorithm relaxes the normality and independence assumptions from previous literatures. In addition to its flexibility and easy interpretability, the algorithm yields good performance in combining potential biomarkers and is computationally feasible. Thus, the approach of TGDR-AUC is a plausible algorithm to classify disease status on the basis of multiple biomarkers.With rapidly developing biotechnology, the use of high-throughput clinical laboratory data to detect disease conditions and predict patients' outcomes is becoming a reality for medical practice. These technologies include microarray, mass spectrometry applied to proteomics, and new imaging modalities, which have been engaged in research on detecting clinical disease,
Novel High-Molecular Weight Fucosylated Milk Oligosaccharides Identified in Dairy Streams
Raj Mehra, Daniela Barile, Mariarosaria Marotta, Carlito B. Lebrilla, Caroline Chu, J. Bruce German
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0096040
Abstract: Oligosaccharides are the third largest component in human milk. This abundance is remarkable because oligosaccharides are not digestible by the newborn, and yet they have been conserved and amplified during evolution. In addition to encouraging the growth of a protective microbiota dominated by bifidobacteria, oligosaccharides have anti-infective activity, preventing pathogens from binding to intestinal cells. Although it would be advantageous adding these valuable molecules to infant milk formula, the technologies to reproduce the variety and complexity of human milk oligosaccharides by enzymatic/organic synthesis are not yet mature. Consequently, there is an enormous interest in alternative sources of these valuable oligosaccharides. Recent research has demonstrated that bovine milk and whey permeate also contain oligosaccharides. Thus, a thorough characterization of oligosaccharides in bovine dairy streams is an important step towards fully assessing their specific functionalities. In this study, bovine milk oligosaccharides (BMOs) were concentrated by membrane filtration from a readily available dairy stream called “mother liquor”, and analyzed by high accuracy MALDI FT-ICR mass spectrometry. The combination of HPLC and accurate mass spectrometry allowed the identification of ideal processing conditions leading to the production of Kg amount of BMO enriched powders. Among the BMOs identified, 18 have high-molecular weight and corresponded in size to the most abundant oligosaccharides present in human milk. Notably 6 oligosaccharides contained fucose, a sugar monomer that is highly abundant in human milk, but is rarely observed in bovine milk. This work shows that dairy streams represent a potential source of complex milk oligosaccharides for commercial development of unique dairy ingredients in functional foods that reproduce the benefits of human milk.
Transcriptome Profiling of Bovine Milk Oligosaccharide Metabolism Genes Using RNA-Sequencing
Saumya Wickramasinghe,Serenus Hua,Gonzalo Rincon,Alma Islas-Trejo,J. Bruce German,Carlito B. Lebrilla,Juan F. Medrano
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0018895
Abstract: This study examines the genes coding for enzymes involved in bovine milk oligosaccharide metabolism by comparing the oligosaccharide profiles with the expressions of glycosylation-related genes. Fresh milk samples (n = 32) were collected from four Holstein and Jersey cows at days 1, 15, 90 and 250 of lactation and free milk oligosaccharide profiles were analyzed. RNA was extracted from milk somatic cells at days 15 and 250 of lactation (n = 12) and gene expression analysis was conducted by RNA-Sequencing. A list was created of 121 glycosylation-related genes involved in oligosaccharide metabolism pathways in bovine by analyzing the oligosaccharide profiles and performing an extensive literature search. No significant differences were observed in either oligosaccharide profiles or expressions of glycosylation-related genes between Holstein and Jersey cows. The highest concentrations of free oligosaccharides were observed in the colostrum samples and a sharp decrease was observed in the concentration of free oligosaccharides on day 15, followed by progressive decrease on days 90 and 250. Ninety-two glycosylation-related genes were expressed in milk somatic cells. Most of these genes exhibited higher expression in day 250 samples indicating increases in net glycosylation-related metabolism in spite of decreases in free milk oligosaccharides in late lactation milk. Even though fucosylated free oligosaccharides were not identified, gene expression indicated the likely presence of fucosylated oligosaccharides in bovine milk. Fucosidase genes were expressed in milk and a possible explanation for not detecting fucosylated free oligosaccharides is the degradation of large fucosylated free oligosaccharides by the fucosidases. Detailed characterization of enzymes encoded by the 92 glycosylation-related genes identified in this study will provide the basic knowledge for metabolic network analysis of oligosaccharides in mammalian milk. These candidate genes will guide the design of a targeted breeding strategy to optimize the content of beneficial oligosaccharides in bovine milk.
Proteomic Analysis of Bifidobacterium longum subsp. infantis Reveals the Metabolic Insight on Consumption of Prebiotics and Host Glycans
Jae-Han Kim, Hyun Joo An, Daniel Garrido, J. Bruce German, Carlito B. Lebrilla, David A. Mills
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0057535
Abstract: Bifidobacterium longum subsp. infantis is a common member of the intestinal microbiota in breast-fed infants and capable of metabolizing human milk oligosaccharides (HMO). To investigate the bacterial response to different prebiotics, we analyzed both cell wall associated and whole cell proteins in B. infantis. Proteins were identified by LC-MS/MS followed by comparative proteomics to deduce the protein localization within the cell. Enzymes involved in the metabolism of lactose, glucose, galactooligosaccharides, fructooligosaccharides and HMO were constitutively expressed exhibiting less than two-fold change regardless of the sugar used. In contrast, enzymes in N-Acetylglucosamine and sucrose catabolism were induced by HMO and fructans, respectively. Galactose-metabolizing enzymes phosphoglucomutase, UDP-glucose 4-epimerase and UTP glucose-1-P uridylytransferase were expressed constitutively, while galactokinase and galactose-1-phosphate uridylyltransferase, increased their expression three fold when HMO and lactose were used as substrates for cell growth. Cell wall-associated proteomics also revealed ATP-dependent sugar transport systems associated with consumption of different prebiotics. In addition, the expression of 16 glycosyl hydrolases revealed the complete metabolic route for each substrate. Mucin, which possesses O-glycans that are structurally similar to HMO did not induced the expression of transport proteins, hydrolysis or sugar metabolic pathway indicating B. infantis do not utilize these glycoconjugates.
Reaction of acyclic enaminones with methoxymethylene meldrum's acid: synthetic and structural implications
Cunha, Silvio;Silva, Viviane C. da;Napolitano, Hamilton B.;Lariucci, Carlito;Vencato, Ivo;
Journal of the Brazilian Chemical Society , 2003, DOI: 10.1590/S0103-50532003000100017
Abstract: the reaction of acyclic enaminones with methoxymethylene meldrum's acid afforded n-adduct and/or c-adduct of enaminones in moderate to good yields. the regiochemistry of this reaction depends on the n-amino substituent of the enaminone. the c-adduct is a precursor to 2-pyridones. x-ray analysis of two n-adducts were investigated and the z-s-z configuration assigned.
Reaction of acyclic enaminones with methoxymethylene meldrum's acid: synthetic and structural implications
Cunha Silvio,Silva Viviane C. da,Napolitano Hamilton B.,Lariucci Carlito
Journal of the Brazilian Chemical Society , 2003,
Abstract: The reaction of acyclic enaminones with methoxymethylene Meldrum's acid afforded N-adduct and/or C-adduct of enaminones in moderate to good yields. The regiochemistry of this reaction depends on the N-amino substituent of the enaminone. The C-adduct is a precursor to 2-pyridones. X-ray analysis of two N-adducts were investigated and the Z-s-Z configuration assigned.
Biological and structure-activity evaluation of chalcone derivatives against bacteria and fungi
Silva, Wender A.;Andrade, Carlos Kleber Z.;Napolitano, Hamilton B.;Vencato, Ivo;Lariucci, Carlito;Castro, Miriam. R. C. de;Camargo, Ademir J.;
Journal of the Brazilian Chemical Society , 2013, DOI: 10.1590/S0103-50532013000100018
Abstract: the present work describes the antibacterial and antifungal activities of several chalcones obtained by a straight claisen-schmidt aldol condensation determined by the minimal inhibitory concentration against different microorganisms (gram-positive and gram-negative bacteria and fungi). solid state crystal structures of seven chalcones were determined by x-ray diffraction (xrd) analysis. chemometric studies were carried out in order to identify a potential structure-activity relationship.
Afastamento por doen?a entre trabalhadores de saúde em um hospital público do estado da Bahia
Martins, Patrícia Freitas;Sobrinho, Carlito Lopes Nascimento;Silva, Marina Vieira;Pereira, Nara Bernardes;Gon?alves, Cicília Marques;Rebou?as, Bárbara Santana;Cartaxo, Luana de Assis;
Revista Brasileira de Saúde Ocupacional , 2009, DOI: 10.1590/S0303-76572009000200008
Abstract: this work describes the socio-demographic characteristics of health care workers, their work, and the incidence of sick leave in a public hospital in the state of bahia, brazil during the period between july 1, 2005 and june 30, 2006. data was collected from the personnel department register, from doctors' statements for the leave, and from a document issued by the bahia state health department. the results showed an average of 2.31 doctors' statements per worker. among 837 workers, 31.9% were absent at least once due to illness, during the mentioned period. of these, 91.0% were women; 60.7% ≥ 40 years old; 60% had been working at the institution for ≥ 12.5 years; 70% were permanent civil servants covered by a specific pay system; 59.5% worked 40 hours a week. most of the absentees belonged to the nursing staff and worked either in the emergency ward or in the icu. we expect that this study will encourage new discussions on the characteristics of hospital work, will incite the implementation of workers' health services in the hospital studied and new research on the issue.
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