Protein kinase C gamma mutations in spinocerebellar ataxia 14 increase kinase activity and alter membrane targeting

The protein kinase C gamma (PKCgamma) gene is mutated in spinocerebellar ataxia type 14 (SCA14). In this study, we investigated the effects of two SCA14 missense mutations, G118D and C150F, on PKCgamma function. We found that these mutations increase the intrinsic activity of PKCgamma. Direct visualization of labelled PKCgamma in living cells demonstrates that the mutant protein translocates more rapidly to selected regions of the plasma membrane in response to Ca2+ influx. These results point to specific alterations in mutant PKCgamma function that could lead to the selective neuronal degeneration of SCA14

B2 attenuates polyglutamine-expanded androgen receptor toxicity in cell and fly models of spinal and bulbar muscular atrophy

Expanded polyglutamine tracts cause neurodegeneration through a toxic gain of function mechanism. Generation of inclusions is a common feature of polyglutamine diseases and other protein misfolding disorders. Inclusion formation is likely to be a defensive response of the cell to the presence of unfolded protein. Recently, the compound B2 has been shown to increase inclusion formation and decrease toxicity of polyglutamine-expanded huntingtin in cultured cells. We explored the effect of B2 on spinal and bulbar muscular atrophy (SBMA). SBMA is caused by expansion of polyglutamine in the androgen receptor (AR) and is characterized by the loss of motor neurons in the brainstem and spinal cord. We found that B2 increases the deposition of mutant AR into nuclear inclusions without altering the ligand-induced aggregation, expression, or subcellular distribution of the mutant protein. The effect of B2 on inclusions was associated with a decrease in AR transactivation function. Importantly, we show that B2 reduces mutant AR toxicity in cell and fly models of SBMA, further supporting the idea that accumulation of polyglutamine-expanded protein into inclusions is protective. Our findings suggest B2 as a novel approach to therapy for SBMA

Research Fundamentals

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71637/1/j.1553-2712.1999.tb00099.x.pd

Substituição do feno de "Coastcross" (Cynodon sp.) por casca de soja na alimentação de borregas confinadas Replacement of coastcross hay by soybean hulls in ewe lambs diets

Quarenta e oito borregas da raça Santa Inês (23,1kg de peso vivo e 124 dias de idade) foram utilizadas para avaliar os efeitos da substituição do feno de "Coastcross" por casca de soja (CS) no desempenho em confinamento. Os animais foram distribuídos em um delineamento em blocos completos casualizados com quatro tratamentos e seis repetições. As dietas experimentais foram isonitrogenadas e continham a mesma quantidade de fibra em detergente neutro (FDN). A casca de soja foi incluída nas proporções de 0; 12,5; 25 e 37,5% da matéria seca das dietas correspondendo aos tratamentos experimentais 0CS, 12,5CS, 25CS e 37,5CS, respectivamente. A FDN da CS substituiu 0; 25; 50 e 75% da FDN do feno. Houve efeito linear crescente (P<0,01) para consumo de matéria seca (0,95; 1,02; 1,08 e 1,20kg dia-1) e para ganho de peso diário (113; 137; 150 e 187g dia-1) e redução linear (P<0,01) na conversão alimentar (8,55; 7,20; 7,11 e 6,25kg de MS kg de ganho-1), com a inclusão da casca de soja. A casca de soja adicionada em dietas para borregas até 37,5% da MS melhora o desempenho, fazendo com que os animais alcancem o peso de cobrição mais rápido.<br>Forty-eight Santa Ines ewe lambs (23.1kg BW and 124 days old) were used to evaluate the replacement of coastcross hay by soybean hulls on feedlot performance. Animals were assigned to a complete randomized block design with four diets and six replicates. All diets were isonitrogenous and contained the same amount of NDF. Soybean hulls replaced hay at 0%, 12.5%, 25% or 37.5% on DM basis, corresponding to the experimental treatments OCS, 12.5CS, 25CS and 37.5CS, respectively. Soybean hulls NDF replaced hay NDF at 0, 25, 50 and 75%. There was a linear increased response (P<0.01) on dry matter intake (0.95, 1.02, 1.08 and 1.20kg day-1) and average daily gain (113, 137, 150 and 187g day-1) and a linear improvement (P<0.01) on feed conversion (8.55, 7.20, 7.11 and 6.25kg of DM kg of gain-1) when soybean hulls were added to the diet. When soybean hulls are added to the diet (up to 37.5%, DM basis) there is an improvement on animal performance and the ewe lambs attain breeding weight faster

Substituição do feno de coastcross por casca de soja na alimentação de cabras em lactação Replacement of coastcross hay by soybean hulls in diets for lactating goats

Objetivou-se com este trabalho verificar a resposta de cabras em lactação alimentadas com dietas contendo casca de soja em substituição ao feno de coastcross. Trinta e seis cabras (38±5 dias em lactação; 2,1±0,4 kg/dia) foram distribuídas em delineamento experimental de blocos completos casualizados e confinadas por oito semanas. As dietas foram compostas de 50% de volumoso e 50% de concentrado e com o mesmo teor de fibra em detergente neutro. A casca de soja substituiu o feno de coastcross em 0, 33, 67 ou 100% da matéria seca (MS). O consumo de matéria seca e a eficiência alimentar apresentaram resposta quadrática aos teores de casca de soja na dieta. A produção de leite e a variação do peso corporal não foram alteradas, porém a concentração de gordura e lactose do leite aumentou e os tempos gastos com ruminação e mastigação decresceram com a inclusão da casca de soja na dieta. A casca de soja pode substituir totalmente o feno de coastcross em dietas para cabras em lactação, pois essa substituição não prejudica a produção de leite e aumenta o teor de gordura e lactose do leite. Em comparação ao feno picado de coastcross, a casca de soja apresenta menor efetividade em estimular a ruminação e a mastigação.<br>The objective of this experiment was to verify the response of lactating goats fed diets with different levels (content) of soybean hulls replacing coastcross hay (Cynodon sp.) on performance. Thirty-six lactating Saanen goats (38±5 days of lactation; 2.1±0.4 kg/day) were assigned to a randomized complete blocks design and housed for 8 weeks. Goats were fed diets of 50% roughage and 50% concentrate, but with the same amount of neutral detergent fiber. Soybean hulls replaced hay by 0, 33, 67 or 100% of the dry matter (DM). Dry matter and NDF intake and feed efficiency showed a quadratic response to the levels of soybean hulls in the diet. Milk yield and body weight variations did not change; however, milk fat, lactose and total solids concentration increased while time spent with rumination and chewing decreased, when soybean hulls were added to the diet. Soybean hulls can replace entirely coastcross hay in diets for lactating goats, with no detrimental effect on milk yield or with an increase on milk fat and lactose concentration. Compared with chopped coastcross hay, soybean hulls show less effectiveness to stimulate rumination and chewing