Inicialmente, foram analisados dados peso-idade do nascimento até 100 meses de idade, de vacas de quatro grupos genéticos (G): Nelore (NEL), ½Canchim + ½Nelore (CN), ½Angus + ½Nelore (AN) e ½Simental + ½Nelore (SN), pertencentes a Embrapa Pecuária Sudeste, São Carlos. Os animais considerados neste estudo nasceram de 1998 a 2001 (Ano), na primavera e outono (EP), e foram criados em sistema de produção intensiva, recebendo três níveis de suplementação pós-desmama (M): 0, 1,5; 3,0 kg/animal/dia de concentrado. O objetivo neste estudo foi comparar diferentes modelos não-lineares para estimar o crescimento, e avaliar a influência de efeitos de ambiente e grupo genético sobre os parâmetros estimados. Os modelos não-lineares: Brody, Gompertz, Logístico, Von Bertalanffy e Richards foram ajustados por mínimos quadrados ordinários e ponderados, considerando a variância normal e ponderada pelo inverso dos pesos em diferentes períodos. Foi usado o procedimento NLIN do SAS. Os modelos Brody e Von Bertalanffy convergiram para todos os G, havendo, entretanto, leve superioridade do Brody ponderado. Na comparação do ajuste dos modelos considerando o uso do inverso da variância os modelos mostraram-se mais adequado. As estimativas dos parâmetros peso assintótico (A) e taxa de maturidade (k) do modelo de Brody ponderado foram analisadas por meio de modelo que, além do efeito médio global, incluiu os efeitos de G, M, EP e as interações entre estes efeitos. Houve diferenças significativas das curvas de crescimento médias para os G. Na análise individual dos parâmetros A e k estimados através do modelo Brody ponderado, verificou-se que A foi influenciado (P<0,05) por G e EP e k foi influenciado (P<0,05) por M, fornecidos aos animais durante quatro meses após desmama. Melhorias no manejo alimentar resultaram em menor variação na forma das curvas de crescimentos e em altas taxas de maturidade. Na segunda parte, verificou-se a qualidade do modelo Brody, ponderado pelo inverso das variâncias dos pesos, quanto ao ajuste peso-idade como também a influência das estimativas do peso à maturidade (A) e da taxa de maturidade (k) sobre características produtivas das vacas NEL, CN, AN e SN. Foram organizados 10 grupos contemporâneos (GC), com concatenação dos efeitos Ano-EP-M para cada G. Utilizando-se um modelo misto com efeitos de G e GC, foi incluído, alternadamente covariáveis linear e quadrática de A e k, na análise das características produtivas: peso à desmama dos bezerros (PD); número (ND8) e kg (KD8) de bezerros desmamados em até 8 anos de permanência da vaca no rebanho; relação PD/peso da vaca ao parto (PD_PVP); relação PD/peso da vaca à desmama do bezerro (PD_PVD); relação PD/unidade metabólica da vaca (PV0,75) à desmama do bezerro (PDW). Houve diferença significativa (P<0,05) da curva de crescimento entre os grupos genéticos (G) e também entre os grupos de contemporâneos (GC) dentro de G. Verificou-se que estas características foram, em geral, influenciadas (P<0,01) tanto pelos efeitos linear e quadrático de A quanto pelos efeitos linear e quadrático de k. / Initially, were analyzed weight-age data from birth to 100 months of age from cows of four genetic groups (G): Nellore (NEL), ½Nellore + ½Canchim (CN), ½Angus +½Nellore (AN) and ½Simmental + ½Nellore (SN), of a experiment carried out at Embrapa Southeast Cattle Research Center, State of São Paulo, Brazil. The animals considered in this study were born from 1998 to 2001 (Year) in spring and fall (EP), and were managed in intensive production system and submitted to three of levels of supplementation post-weaning (M): 0, 1.5 and 3.0 kg/animal/day of concentrate. The objective of this study was to compare different nonlinear models to fitted growth curves, of beef cattle females, and to evaluate of environmental and genetic group effects on the estimated parameters. The nonlinear models: Brody, Gompertz, Logistic, Von Bertalanffy and Richards were fitted by ordinary least squares and weighted by the inverse of the variances of the weights in different periods. It was used the NLIN procedure of SAS. The parameters asymptotic weight (A) and maturing rate (k) obtained from model of Brody were analyzed by a mixed linear model that, besides the overall mean effect, included the effects of G, M, EP, and the interactions among these effects. The Brody and Von Bertalanffy models converged for all genetic groups, although slight superiority of the weighted Brody. Comparing the goodness of fit of these models, the use of the inverse of variances showed more efficient than the adjust of the models considering normal variances. Individual analysis of A and k estimated the model weighted Brody, the A parameter was influenced (P <0.05) by genetic group and season of birth and k was influenced (P <0 05) for levels of supplementation to the animals. Improvements in feeding supplementation resulted in less variation in the shape of growth curves and rates of maturity. In the second part of the work, it was evaluated the goodness of the Brody model, weighted by the inverse variance weights, in the adjust of weight-age data, and also analyzed the influence of the maturity weight (A) and maturing rate (k) estimates for traits cows productivity. Were organized 10 contemporary groups (CG) with concatenation of effects Year- EP-M for each G. Considering a mixed model with effects of G and CG (10 contemporaneous groups organized by concatenation Year-EP-M effects), linear and quadratic covariate effects of A and k, were added, alternately, for the analysis of the following traits: weaning weight of calve (WW), number (NW8) and kg (KW8) of calves weaned over 8 years of the cow in the herd; WW/weight of the cow at calving (WW_WC); WW/cow weight at weaning of calf (WW_WWC); and WW/metabolic unit of the cow (PV0,75) at weaning of the calf (MW). There was significant difference (P<0.05) of the growth curve among the genetic groups and also among contemporary groups within G. It was found that the production traits were, in general, influenced (P<0.01) by both linear and quadratic effects of A and k.

Poultry provide affordable animal protein products compared to other animal products in agricultural industry. The demand of organic food by world health organisation and call for discard of conventional laying cage production method led to this research study. The aim of the study was to determine how (4 x 4) full diallel crossbreeding of the Potchefstroom Koekoek (PK), Naked neck (NN), Lohmann Brown (LB) and White Leghorn (WL) had an effect on production performance, egg parameters, genetic and phenotypic characteristics of F1 crossbreed offspring. The study was conducted at the Agricultural Research Council (ARC), Livestock Production Improvement at the Irene Campus, which is situated about 25 km south of Pretoria. The (4 x 4) full diallel crossbreeding design used on four chicken breeds to produce four pure breeds, six crossbreeds and six reciprocal crosses. The total number of 352 chickens with16 treatments (2 cocks and 20 hens) used in phase 1 and 384 chickens 16 F1-treatments (3 cocks + 21 hens) used in phase 2. Data was analysed by full factorial analysis of variance (ANOVA), General Linear Model procedures and Scheffe post-hoc for multiple comparison of the means of different variable data. The outcome had shown that crossbreeding had an effect on the production performance, genetic and phenotypic characteristics. The performed F1 crossbreeds emerge from crossbreeding between the local dual-purpose PK and commercial LB chicken breeds. PKLB dominated on growth and production performance traits compared to other crossbreeds. All set null hypothesis differ significantly at (p < 0.05), the outcome of all five hypothesis of this study were rejected. In conclusion PKLB was the best performing F1 crossbreed, based on its best performance on growth, FCR, cost of rearing, productive, high quality safe eggshell, economic efficiency and consumer preference (brown eggshell and yolk colour). / Dikgogo di neelana ka dikumo tsa poroteine ya diphologolo go tshwantshanngwa le dikumo tsa diphologolo tse dingwe mo intasetering ya temo. Tlhokego ya dijo tse di bolang mo mekgatlhong ya boitekanelo ya lefatshe le pitso ya go latlha mekgwa ya kumo ya dikgetshe tsa go beela tsa tlwaelo di ne tsa isa kwa thutong ya patlisiso eno. Maikaelelo a thuto eno ke go tlhomamisa gore tsadiso ya kgabaganyo ya dilo tse pedi kgotsa go feta go tshwantshanya kgolagano ya mofuta wa dijene le tikologo tse di tletseng tsa (4 x 4) tsa Potchefstroom Koekoek (PK), Naked Neck (NN), Lohmann Brown (LB) le White Leghorn (WL) di na le ponalo mo tiragatsong ya kumo, diparametera tsa mae, le dijene le diponagalo tsa kgolagano ya mofuta wa dijene le tikologo tsa ditsadiso tsa kgabaganyo tsa ngwana wa F1. Thuto e ne ya diragadiwa kwa Agricultural Research Council (ARC) le Tokafatso ya Kumo ya Diruiwa kwa khempaseng ya Irene, e e agilweng bokana ka 25 km jwa borwa jwa Pretoria. Ditsadiso tsa kgabaganyo tsa dilo tse pedi kgotsa go feta go tshwantshanya kgolagano ya mofuta wa dijene le tikologo tse di tletseng tsa (4 x 4) di ne tsa dirisiwa mo mefuteng ya ditsadiso tsa dikgogo go ntsha mefuta ya ditsadiso e e tletseng e mene, ditsadiso tsa kgabaganyo tse thataro le dikgabaganyo tse di tshwanang tse thataro. Palo e e tletseng ya dikgogo tse di 352 ka ditiragatso di le 16 (mekoko e le 2 le dithole di le 20) di ne tsa dirisiwa mo letlhakoreng la 1 le dikgogo di le 384 ka ditiragatso tsa F1 di le 16 (mekoko e le 3 + dithole di le 21) di ne tsa dirisiwa mo letlhakoreng la 2. Data e ne ya tshetshereganngwa ka tshetshereganyo ya dintlha tse di tletseng tsa pharologantsho (ANOVA), dikgato tsa General Linear Model le tshwantshanyo ya bontsintsi ya morago (ANOVA), dikgato tsa General Linear Model le tshwantshanyo ya bontsintsi ya morago ga tiragalo ya Scheffe ka mekgwa ya data ya pharologantsho e e farologaneng. Ditlamorago di ne tsa bontsha gore ditsadiso tsa kgabaganyo di na le ponalo mo tiragatsong ya kumo, ga mmogo le diponagalo tsa dijene le setlhopha sa kgolagano ya mofuta wa dijene le tikologo. Go ne ga diriswa mefuta ya ditsadiso tsa kgabaganyo ya F1 tse di tlhagelelang go tswa mo ditsadisong tsa kgabaganyo magareng ga mefuta ya ditsadiso tsa dikgogo tsa PK tsa lebaka la gabedi la selegae le LB ya kgwebo. PKLB e ne ya fekeetsa metlhala ya tiragatso ya kgolo le kumo go tshwantshanngwa le mefuta ya ditsadiso tsa kgabaganyo tse dingwe. Setlhopha sotlhe sa dikakanyo tsa lefela se x farologana mo go bonagalang ka (p < 0.05) le ditlamorago tsa dikakanyo tse tlhano tse tsotlhe tsa thuto eno di ne tsa kganediwa. Kwa bokhutlong, PKLB e ne ya nna mofuta wa ditsadiso tsa F1 o o diragatsang go gaisa, go ikaegilwe ka tiragatso mabapi le kgolo, FCR, tshenyegelo ya go tsadisa, kumo, boleng jo bo kwa godimo jwa dikgapetla tsa mae tse di babalesegileng, bokgoni jwa ikonomi le boikgethelo jwa modirisi (dikgapetla tsa mae tse di tshetlha le mmala wa tlhae). / Agriculture and  Animal Health / Ph. D. (Agriculture)

Glycosphingolipid (GSL) metabolism is a complex process involving proteins and enzymes at distinct locations within the cell. Mammalian GSLs are typically based on glucose or galactose, forming glucosylceramide (GlcCer) and galactosylceramide (GalCer). Most GSLs are derived from GlcCer, which is synthesized on the cytosolic leaflet of the Golgi, while all subsequent GSLs are synthesized on the lumenal side. We have utilized both pharamacological and genetic manipulation approaches to selectively regulate GSL metabolism and better understand its mechanistic details. We have developed analogues of GlcCer and GalCer by substituting the fatty acid moiety with an adamanatane frame. The resulting adamantylGSLs are more water-soluble than their natural counterparts. These analogues selectively interfere with GSL metabolism at particular points within the metabolic pathway. At 40 µM, adaGlcCer prevents synthesis of all GSLs downstream of GlcCer, while also elevating GlcCer levels, by inhibiting lactosylceramide (LacCer) synthase and glucocerebrosidase, respectively. AdaGalCer specifically reduces synthesis of globotriaosylceramide (Gb3) and downstream globo-series GSLs. AdaGalCer also increases Gaucher disease N370S glucocerebrosidase expression, lysosomal localization and activity. AdaGSLs, therefore, have potential as novel therapeutic agents in diseases characterized by GSL anomalies and as tools to study the effects of GSL modulation. Two predominant theories have been developed to explain how GlcCer accesses the Golgi lumen: one involving direct translocation from the cytosolic-to-lumenal leaflet of the Golgi by the ABC transporter P-glycoprotein (P-gp, ABCB1, MDR1), and the other involving retrograde transport of GlcCer by FAPP2 to the ER, followed by entry into the vesicular transport system for Golgi lumenal access. To examine the in vivo involvement of P-gp in GSL metabolism, we generated a knockout model by crossbreeding the Fabry disease mouse with the P-gp knockout mouse. HPLC analyses of tissue Gb3 levels revealed a tissue-specific reduction in MDR1/Fabry mice. TLC analyses, however, did not show such reduction. In addition, we performed a gene knockdown study using siRNA against P-gp and FAPP2. Results show these siRNA to have distinct effects on GSL levels that are cell-type specific. These results give rise to the prospect of unique therapeutic approaches by targeting P-gp or FAPP2 for synthesis inhibition of particular GSL pathways.

Glycosphingolipid (GSL) metabolism is a complex process involving proteins and enzymes at distinct locations within the cell. Mammalian GSLs are typically based on glucose or galactose, forming glucosylceramide (GlcCer) and galactosylceramide (GalCer). Most GSLs are derived from GlcCer, which is synthesized on the cytosolic leaflet of the Golgi, while all subsequent GSLs are synthesized on the lumenal side. We have utilized both pharamacological and genetic manipulation approaches to selectively regulate GSL metabolism and better understand its mechanistic details. We have developed analogues of GlcCer and GalCer by substituting the fatty acid moiety with an adamanatane frame. The resulting adamantylGSLs are more water-soluble than their natural counterparts. These analogues selectively interfere with GSL metabolism at particular points within the metabolic pathway. At 40 µM, adaGlcCer prevents synthesis of all GSLs downstream of GlcCer, while also elevating GlcCer levels, by inhibiting lactosylceramide (LacCer) synthase and glucocerebrosidase, respectively. AdaGalCer specifically reduces synthesis of globotriaosylceramide (Gb3) and downstream globo-series GSLs. AdaGalCer also increases Gaucher disease N370S glucocerebrosidase expression, lysosomal localization and activity. AdaGSLs, therefore, have potential as novel therapeutic agents in diseases characterized by GSL anomalies and as tools to study the effects of GSL modulation. Two predominant theories have been developed to explain how GlcCer accesses the Golgi lumen: one involving direct translocation from the cytosolic-to-lumenal leaflet of the Golgi by the ABC transporter P-glycoprotein (P-gp, ABCB1, MDR1), and the other involving retrograde transport of GlcCer by FAPP2 to the ER, followed by entry into the vesicular transport system for Golgi lumenal access. To examine the in vivo involvement of P-gp in GSL metabolism, we generated a knockout model by crossbreeding the Fabry disease mouse with the P-gp knockout mouse. HPLC analyses of tissue Gb3 levels revealed a tissue-specific reduction in MDR1/Fabry mice. TLC analyses, however, did not show such reduction. In addition, we performed a gene knockdown study using siRNA against P-gp and FAPP2. Results show these siRNA to have distinct effects on GSL levels that are cell-type specific. These results give rise to the prospect of unique therapeutic approaches by targeting P-gp or FAPP2 for synthesis inhibition of particular GSL pathways.