Productive performance and milk protein fraction composition of dairy cows supplemented with sodium monensin Desempenho produtivo e composição da fração protéica do leite em vacas sob suplementação com monensina sódica

The objective of this work was to evaluate the levels of sodium monensin on lactating cows and their effects on productive performance and milk protein fraction composition. It was used 12 Holstein cows, distributed in four balanced 3 &#215; 3 Latin squares, and fed three diets: one control without monensin, and two diets with monensin at the levels of 24 or 48 mg/kg DM added to the concentrate. Milk production was daily measured throughout the entire experimental period. The samples used for analysis of milk composition were collected on two alternated days from the two daily milking. Non-protein nitrogen, total nitrogen and non-casein nitrogen contents were directly evaluated in the milk, and casein, whey protein and true protein contents were indirectly determined. The use of monensin in the rations reduced dry matter and nutrient intake, especially when diet with 48 mg/kg of dry matter was given. The ration with 24 mg/kg of DM increased milk production, with or without correction, and also fat and lactose yield, and it improved productive efficiency. The levels of monensin in the ratios did not influence contents of milk crude protein, non-protein nitrogen, non-casein nitrogen, true protein, casein, casein/true protein ratio, whey protein, and of all those fractions expressed as percentage of crude protein. The utilization of monensin in the ratio at the dose of 24 mg/kg of DM influences positively the productive performance of lactating cows, and it does not influence the composition of milk protein fractions.<br>Objetivou-se avaliar níveis de monensina sódica para vacas em lactação e seus efeitos no desempenho produtivo e na composição da fração protéica do leite. Foram utilizadas 12 vacas da raça Holandesa, distribuídas em quatro quadrados latinos 3 &#215; 3 balanceados e alimentadas com três rações: uma controle sem monensina, e duas com monensima nos níveis de 24 mg/kg de matéria seca ou 48 mg/kg MS adicionada ao concentrado. A produção de leite foi mensurada diariamente durante todo o período experimental. As amostras utilizadas para análise da composição do leite foram coletadas em dois dias alternados e provenientes das duas ordenhas diárias. Foram analisados no leite os teores de nitrogênio não-protéico, nitrogênio total e nitrogênio não-caseinoso e indiretamente os teores de caseína, proteína do soro e proteína verdadeira. A utilização de monensina nas rações ocasionou redução do consumo de MS e de nutrientes, especialmente quando fornecida a ração com 48 mg/kg de MS. A ração com 24 mg/kg de MS promoveu aumento da produção de leite, sem e com correção, e da produção de gordura e lactose e aumento da eficiência produtiva. Os níveis de monensina nas rações não influenciaram os teores de proteína bruta, nitrogênio não-protéico, nitrogênio não-caseinoso, proteína verdadeira, caseína, relação caseína/proteína verdadeira, proteína do soro do leite e de todas essas frações expressas em porcentagem da proteína bruta. A utilização de monensina na ração na dose de 24 mg/kg de MS influencia positivamente o desempenho produtivo de vacas em lactação e não afeta a composição das frações protéicas do leite

The Biology of the Presenilin Complexes

APP proteolytic processing Alzheimer's Disease (AD) is characterized by the deposition of two kinds of abnormal protein aggregates, senile plaques and neurofibrillary tangles, and by neuronal dysfunction and cell loss in the brain. Senile plaques are primarily composed of extracellular deposits of hydrophobic 37-43 amino acid Aβ peptides. Aβ peptides are derived by successive enzymatic cleavages of the type I membrane protein, β-amyloid precursor protein (APP) (Haass and Selkoe 1993). APP is first cleaved close to the membrane in the extracellular domain by either α-or β-secretase, resulting in a release of soluble APP ectodomains, and residual membrane-tethered C-terminal protein stubs, termed C83 or C99, respectively (The numbers indicate the length of each carboxylterminal fragment). C83 and C99 are substrates for γ-secretase, an activity that generates p3 and Aβ peptides, respectively. γ-Secretase processes substrates at different positions within the membrane domain and thus, both Aβ and p3 have "ragged" termini. Aβ has been best studied in this regard and species between 37 and 43 amino acid residues have been identified. γ-Secretase cleavage of APP also releases the intracellular carboxy-terminal "APP intracellular domain" or "AICD". The function of both Aβ and AICD is the subject of intense investigations. Because Aβ42 is the primary constituent of the amyloid fibrils deposited in the AD brains, and mutations in APP and presenilin enhance the production of this peptide, γ-secretase cleavage of APP is a pivotal step in AD pathogenesis. It is striking that this proteolytic reaction occurs within the highly hydrophobic environment of the membrane. Identification of presenilin Genetic studies in familial AD (FAD) cases have identified disease-linked mutations in three genes that contribute to AD. The first pathogenic mutations in early-onset FAD families were found in the APP gene on chromosome 21 (Chartier-Harlin et al. 1991; Goate et al. 1991; Murrell et al. 1991). However, subsequent studies indicated that mutations in APP account only for a small fraction of FAD cases. Several genetic studies indicated a major locus for FAD on chromosome 14 in early onset autosomal dominant AD, and in 1995, the Presenilin1 (PS1) gene on chromosome 14 (14q24.3) was identified by positional cloning (Sherrington et al. 1995). Shortly thereafter, it was shown that mutations in the closely related PS2 gene on chromosome 1 (1q42.2) could cause FAD as well (Levy-Lahad et al. 1995; Rogaev et al. 1995). Studies in transgenic mice (Borchelt et al. 1996; Duff et al. 1996) and cultured cells (Citron et al. 1997; Scheuner et al. 1996; Tomita et al. 1997) have revealed that expression of FAD-linked PS variants elevates Aβ42/Aβ40 ratios. Moreover, transgenic mice that co-express FAD-mutant PS1 and APP develop amyloid plaques much earlier than age-matched mutant APP mice (Borchelt et al. 1997). Therefore, PS mutations cause a change in the Aβ42/40 ratio, but whether PS is directly involved in γ-secretase processing of APP was unclear. However, in PS-deficient neurons and fibroblasts, APP processing was greatly impaired, leading to the accumulation of the C83 and C99 APP fragments, the direct substrates of γ-secretase, and inhibition of Aβ (and p3) generation (De Strooper et al. 1998; Xia et al. 1998). Thus, PS are directly required for γ-secretase cleavage of APP. Overall, the findings imply that mutations in the substrate (APP) or in the proteolytic machinery (PS) result in similar changes in Aβ42 generation (Scheuner et al. 1996). This provides very strong support for the "amyloid cascade hypothesis". © 2007 Springer Science+Business Media, LLC. All rights reserved