Concentrations of metronidazole in human plasma and saliva after tablet or gel administration

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Non-specific immune parameters and physiological response of Nile tilapia fed beta-glucan and vitamin C for different periods and submitted to stress and bacterial challenge

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Proteomic Analysis of Gastrocnemius Muscle in Rats with Streptozotocin-Induced Diabetes and Chronically Exposed to Fluoride

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Imunomodulação por Actigen® em tilápia-do-nilo (Oreochromis niloticus): Respostas fisiológicas e desempenho produtivo após desafio com LPS

Pós-graduação em Ciência e Tecnologia Animal - FEIS

Dietary patterns are associated with general and central obesity in elderly living in a Brazilian city

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Dietary intake association with IFG and responses of a lifestyle changing protocol in a community-b based adult cohort

Objective: Investigate the association of diet on Impaired Fasting Glucose (IFG) and response of a lifestyle changing protocol (LISC) on a community sample of adults. Methods: A cross sectional study of LISC was conducted with 1004 subjects. From those, 264 adults individuals participated in a 20-week intervention based on physical exercises and dietary counseling and were divided in three groups, normoglycemic, IFG, and T2DM. Evaluations were done at baseline (M0) and after a 20-week intervention (M1). The analyses were performed by using SAS, version 9.2., and results were discussed based on the level of significance of p<0.05. Results: At baseline, the three groups differed for plasma triglycerides, and number of altered metabolic syndrome (MetS) components. T2DM differed from normoglicemic by presenting higher intake of meat, lower of sugar, and less dietary variety, along with higher plasma levels of uric acid. After 20-week intervention, normoglicemics, IFG and T2DM responded similarly to LISC. Both genders increased body fatness. Men increased fasting plasma insulin, saturated fatty acid intake, along with a decrease of vegetable oil intake while women showed a significant increase in HEI and dietary fiber intake and a trend to higher sugar and protein intake and lower vegetable oil intake. Overall T2DM decreased 68% from M0 (9.5%) to M1 (6.4%) of LISC. Conclusion: Our data showed a significant difference in food composition on altered plasma glucose, and its further normalization with lifestyle intervention was independent of significant body weight and body fat changes.

Talent Management in Higher Education: Developing Emerging Leaders Within the Administration at Private Colleges and Universities

This research focused on identifying a series of successful practices relating to administrative talent management within the higher education setting. The field study included a thorough examination of seven small to mid-size private colleges and universities that have incorporated employee development strategies. These strategies were aimed at growing future leaders from within the organization in order to achieve continuity and support institutional priorities. Specifically, several focus areas were investigated including presidential vision, leadership commitment, talent management’s place among institutional priorities, program characteristics, and program evaluation. Among the commonalities that were gathered included support at the senior officer level who serve as advocates, mentors, and program facilitators, a strong connection between talent management and the institutions’ strategic plans, and a holistic approach to developing talent at all levels of the organizations. In addition, both coaching and opportunities for growth in the work environment were evident within several of the institutions. Also, academic leadership development was considered to be a part of the talent management strategy within three of the colleges and universities. The key differentiators included the incorporation of organizational and leadership competencies to provide focus toward the performance development process at two institutions, the implementation of a succession planning model at another institution, and the location of human resource generalists in departments across two of the institutions to identify learning opportunities for both individuals and work teams. Based on both the findings from the field study and the literature review, a comprehensive procedural model is introduced that serves to support human resource departments and higher education professionals, in general, who are looking to either begin or broaden their own talent management approach. However, despite the progress that has been made across several institutions noted throughout the research study, much more must be learned in terms of how the time and resources invested in talent management translates to institutional success. Advisor: James O‘Hanlon

Selection for Increased Starvation Resistance Using Drosophila melanogaster: Investigating Physiological and Life History Trait Responses to Starvation and Dietary Supplementation in the Context of an Obese Phenotype

Artificial selection for starvation resistance provided insight into the relationships between evolved physiological and life history trait responses following exposure to biologically induced stress. Investigations of alterations to body composition, metabolic rate, movement, and life history traits including development time, female egg production, and longevity in response to brief periods of starvation were conducted on genetically based starvation-resistant and control lines of Drosophila melanogaster. Analysis of the starvation-resistant lines indicated increased energy storage with increased triglyceride deposition and conversion of carbohydrates to lipid, as identified by respiratory quotient values. Correlations between reductions in metabolic rates and movement in the starvation-resistant lines, suggested the presence of an evolved physiological response resulting in energy conservation. Investigations of life history traits in the starvation-resistant lines indicated no significant differences in development time or reproduction between the selected and control lines. Measurements of longevity, however, indicated a significant reduction in starvation-resistant D. melanogaster lifespan. These results suggested that elevated lipid concentrations, similar to that observed with obesity, were correlated with premature mortality. Exposure of the starvation-resistant and control lines to diets supplemented with glucose, palmitic acid, and a 2:1 mixture of casein to albumin were used to investigate alterations in body composition, movement, and life history traits. Results obtained from this study indicated that increased sugar in the diet led to increased carbohydrate, glycogen, total sugar, trehalose, and triglyceride concentrations, while increased fat and protein in the diet resulted in increased soluble protein, carbohydrate, glycogen, total sugar, and trehalose concentrations. Examination of life history trait responses indicated reduced fecundity in females exposed to increased glucose concentrations. Increased supplementations of palmitic acid was consistently correlated with an overall reduction in lifespan in both the starvation-resistant and control Drosophila lines, while measurements of movement indicated increased female activity levels in flies exposed to diets supplemented with fat and protein. Analyses of the physiological and life history trait responses to starvation and dietary supplementation on Drosophila melanogaster used in the present study has implications for investigating the mechanisms underlying the development and persistence of human obesity and associated metabolic disorders.

A CURRENT EXAMINATION OF DIETARY INTAKES OF FIBER, CALCIUM, IRON, AND ZINC AND THEIR RELATIONSHIP TO BLOOD LEAD LEVELS IN U.S. CHILDREN AGED 1-5 YEARS

A CURRENT EXAMINATION OF DIETARY INTAKES OF FIBER, CALCIUM, IRON, AND ZINC AND THEIR RELATIONSHIP TO BLOOD LEAD LEVELS IN U.S. CHILDREN AGED 1-5 YEARS Stephanie Ann Melchert, M.S. University of Nebraska, 2010 Adviser: Kaye Stanek Krogstrand The effect of lead on the health and well-being of those exposed has been well documented and many efforts have been made to reduce exposure of lead to the United States population. Despite these efforts, many studies have documented cognitive impairments and behavioral problems in children with even low levels of lead in their blood. Previous studies have suggested that a proper diet may have a role in the prevention of elevated blood lead levels in children. The objective of this study was to determine if there was an inverse correlation of blood lead levels (BLL) in children to their dietary intakes of fiber, calcium, iron, and zinc considering low levels of lead exposure. This study examined 1019 children in the National Health and Nutrition Examination Survey (NHANES) conducted from 2005-2006. Data were analyzed using Spearman’s rank correlations to correlate continuous variables to BLL in children and independent samples t-tests were used to compare mean blood lead levels of categorical variables. Results indicate that BLL in children is significantly correlated with and weight, recumbent length/standing height, dietary fiber intake and continine, a marker of cigarette smoke exposure. BLL was not significantly correlated with calcium, iron, zinc, or vitamin C. A significant difference was found in the mean BLL of children who took supplements, lived in smoking homes, as well as those who lived in homes built before 1978. Overall, this study shows that children living in homes built before 1978 remain at greater risk for lead exposure, and adequate dietary fiber intake may provide benefits to children who are exposed to lead.

Positive effects of zinc supplementation on growth, GH, IGF1, and IGFBP3 in eutrophic children

Zinc is an essential micronutrient for growth and development. Its deficiency causes growth retardation in children and adolescents. The present study analyzes the effect of zinc on growth hormone (GH) secretion, insulin-like growth factor 1 (IGF1), and insulin-like growth factor-binding protein 3 (IGFBP3) in normal children before puberty. Thirty normal children were studied, 15 boys and 15 girls, aged 6-9 years. They were orally supplemented with 5 mg Zn/day for 3 months and 0.06537 mg Zn/kg body weight was injected before and after oral supplementation. Dietary intake and anthropometric measurements were assessed at baseline and end of study. Plasma GH levels increased during intravenous zinc administration and IGF1 and IGFBP3 increased after oral zinc supplementation. There was a positive correlation between the areas under the curves of GH and zinc after oral supplementation. Zinc supplementation was possibly effective in improving the body zinc status of the children, secretory levels of IGF1 and IGFBP3, GH potentialization, and height.

Dynamic complex formation between HD-GYP, GGDEF and PilZ domain proteins regulates motility in Xanthomonas campestris

RpfG is a member of a class of wide spread bacterial two-component regulators with an HD-GYP cyclic di-GMP phosphodiesterase domain. In the plant pathogen Xanthomonas campestris, RpfG together with the sensor kinase RpfC regulates multiple factors as a response to the cell-to-cell Diffusible Signalling Factor (DSF). A dynamic physical interaction of RpfG with two diguanylate cyclase (GGDEF) domain proteins controls motility. Here we show that, contrary to expectation, regulation of motility by the GGDEF domain proteins does not depend upon their cyclic di-GMP synthetic activity. Furthermore we show that the complex of RpfG and GGDEF domain proteins recruits a specific PilZ domain adaptor protein, and this complex then interacts with the pilus motor proteins PilU and PiIT. The results support a model in which DSF signalling influences motility through the highly regulated dynamic interaction of proteins that affect pilus action. A specific motif that we identify to be required for HD-GYP domain interaction is conserved in a number of GGDEF domain proteins, suggesting that regulation via interdomain interactions is of broad relevance.

Theoretical studies of Membrane Proteins : Properties, Prediction Methods and Genome-wide analysis

Membrane proteins are a large and important class of proteins. They are responsible for several of the key functions in a living cell, e.g. transport of nutrients and ions, cell-cell signaling, and cell-cell adhesion. Despite their importance it has not been possible to study their structure and organization in much detail because of the difficulty to obtain 3D structures. In this thesis theoretical studies of membrane protein sequences and structures have been carried out by analyzing existing experimental data. The data comes from several sources including sequence databases, genome sequencing projects, and 3D structures. Prediction of the membrane spanning regions by hydrophobicity analysis is a key technique used in several of the studies. A novel method for this is also presented and compared to other methods. The primary questions addressed in the thesis are: What properties are common to all membrane proteins? What is the overall architecture of a membrane protein? What properties govern the integration into the membrane? How many membrane proteins are there and how are they distributed in different organisms? Several of the findings have now been backed up by experiments. An analysis of the large family of G-protein coupled receptors pinpoints differences in length and amino acid composition of loops between proteins with and without a signal peptide and also differences between extra- and intracellular loops. Known 3D structures of membrane proteins have been studied in terms of hydrophobicity, distribution of secondary structure and amino acid types, position specific residue variability, and differences between loops and membrane spanning regions. An analysis of several fully and partially sequenced genomes from eukaryotes, prokaryotes, and archaea has been carried out. Several differences in the membrane protein content between organisms were found, the most important being the total number of membrane proteins and the distribution of membrane proteins with a given number of transmembrane segments. Of the properties that were found to be similar in all organisms, the most obvious is the bias in the distribution of positive charges between the extra- and intracellular loops. Finally, an analysis of homologues to membrane proteins with known topology uncovered two related, multi-spanning proteins with opposite predicted orientations. The predicted topologies were verified experimentally, providing a first example of "divergent topology evolution".

Strong iron demand during hypoxia-induced erythropoiesis is associated with down-regulation of iron-related proteins and myoglobin in human skeletal muscle

[EN] Iron is essential for oxygen transport because it is incorporated in the heme of the oxygen-binding proteins hemoglobin and myoglobin. An interaction between iron homeostasis and oxygen regulation is further suggested during hypoxia, in which hemoglobin and myoglobin syntheses have been reported to increase. This study gives new insights into the changes in iron content and iron-oxygen interactions during enhanced erythropoiesis by simultaneously analyzing blood and muscle samples in humans exposed to 7 to 9 days of high altitude hypoxia (HA). HA up-regulates iron acquisition by erythroid cells, mobilizes body iron, and increases hemoglobin concentration. However, contrary to our hypothesis that muscle iron proteins and myoglobin would also be up-regulated during HA, this study shows that HA lowers myoglobin expression by 35% and down-regulates iron-related proteins in skeletal muscle, as evidenced by decreases in L-ferritin (43%), transferrin receptor (TfR; 50%), and total iron content (37%). This parallel decrease in L-ferritin and TfR in HA occurs independently of increased hypoxia-inducible factor 1 (HIF-1) mRNA levels and unchanged binding activity of iron regulatory proteins, but concurrently with increased ferroportin mRNA levels, suggesting enhanced iron export. Thus, in HA, the elevated iron requirement associated with enhanced erythropoiesis presumably elicits iron mobilization and myoglobin down-modulation, suggesting an altered muscle oxygen homeostasis.

Evidence of prognostic relevant expression profiles of heat-shock proteins and glucose-regulated proteins in oesophageal adenocarcinomas

A high percentage of oesophageal adenocarcinomas show an aggressive clinical behaviour with a significant resistance to chemotherapy. Heat-shock proteins (HSPs) and glucose-regulated proteins (GRPs) are molecular chaperones that play an important role in tumour biology. Recently, novel therapeutic approaches targeting HSP90/GRP94 have been introduced for treating cancer. We performed a comprehensive investigation of HSP and GRP expression including HSP27, phosphorylated (p)-HSP27((Ser15)), p-HSP27((Ser78)), p-HSP27((Ser82)), HSP60, HSP70, HSP90, GRP78 and GRP94 in 92 primary resected oesophageal adenocarcinomas by using reverse phase protein arrays (RPPA), immunohistochemistry (IHC) and real-time quantitative RT-PCR (qPCR). Results were correlated with pathologic features and survival. HSP/GRP protein and mRNA expression was detected in all tumours at various levels. Unsupervised hierarchical clustering showed two distinct groups of tumours with specific protein expression patterns: The hallmark of the first group was a high expression of p-HSP27((Ser15, Ser78, Ser82)) and low expression of GRP78, GRP94 and HSP60. The second group showed the inverse pattern with low p-HSP27 and high GRP78, GRP94 and HSP60 expression. The clinical outcome for patients from the first group was significantly improved compared to patients from the second group, both in univariate analysis (p = 0.015) and multivariate analysis (p = 0.029). Interestingly, these two groups could not be distinguished by immunohistochemistry or qPCR analysis. In summary, two distinct and prognostic relevant HSP/GRP protein expression patterns in adenocarcinomas of the oesophagus were detected by RPPA. Our approach may be helpful for identifying candidates for specific HSP/GRP-targeted therapies.

Snake C-type lectin-like proteins and platelet receptors

Snake venoms are complex mixtures of biologically active proteins and peptides. Many affect haemostasis by activating or inhibiting coagulant factors or platelets, or by disrupting endothelium. Snake venom components are classified into various families, such as serine proteases, metalloproteinases, C-type lectin-like proteins, disintegrins and phospholipases. Snake venom C-type lectin-like proteins have a typical fold resembling that in classic C-type lectins such as the selectins and mannose-binding proteins. Many snake venom C-type lectin-like proteins have now been characterized, as heterodimeric structures with alpha and beta subunits that often form large molecules by multimerization. They activate platelets by binding to VWF or specific receptors such as GPIb, alpha2beta1 and GPVI. Simple heterodimeric GPIb-binding molecules mainly inhibit platelet functions, whereas multimeric ones activate platelets. A series of tetrameric snake venom C-type lectin-like proteins activates platelets by binding to GPVI while another series affects platelet function via integrin alpha2beta1. Some act by inducing VWF to bind to GPIb. Many structures of these proteins, often complexed with their ligands, have been determined. Structure-activity studies show that these proteins are quite complex despite similar backbone folding. Snake C-type lectin-like proteins often interact with more than one platelet receptor and have complex mechanisms of action.