RESUMO
Pattern separation (PS) has been defined as a process of reducing overlap between similar input patterns to minimize interference amongst stored representations. The present article describes this putative PS process from the "representational-hierarchical" perspective (R-H), which uses a hierarchical continuum instead of a cognitive modular processing framework to describe the organization of the ventral visual perirhinal-hippocampal processing stream. Instead of trying to map psychological constructs onto anatomical modules in the brain, the R-H model suggests that the function of brain regions depends upon what representations they contain. We begin by discussing a main principle of the R-H framework, the resolution of "ambiguity" of lower level representations via the formation of unique conjunctive representations in higher level areas, and how this process is remarkably similar to definitions of PS. Work from several species and experimental approaches suggest that this principle of resolution of ambiguity via conjunctive representations has considerable explanatory power, leads to wide possibilities for experimentation, and also supports some perhaps surprising conclusions.
Assuntos
Hipocampo/fisiologia , Memória/fisiologia , Modelos Neurológicos , Reconhecimento Fisiológico de Modelo/fisiologia , Córtex Perirrinal/fisiologia , Animais , Cognição/fisiologia , Humanos , Vias Neurais/fisiologiaRESUMO
Over recent years, accumulated evidence suggests that autophagy induction is protective in animal models of a number of neurodegenerative diseases. Intense research in the field has elucidated different pathways through which autophagy can be upregulated and it is important to establish how modulation of these pathways impacts upon disease progression in vivo and therefore which, if any, may have further therapeutic relevance. In addition, it is important to understand how alterations in these target pathways may affect normal physiology when constitutively modulated over a long time period, as would be required for treatment of neurodegenerative diseases. Here we evaluate the potential protective effect of downregulation of calpains. We demonstrate, in Drosophila, that calpain knockdown protects against the aggregation and toxicity of proteins, like mutant huntingtin, in an autophagy-dependent fashion. Furthermore, we demonstrate that, overexpression of the calpain inhibitor, calpastatin, increases autophagosome levels and is protective in a mouse model of Huntington's disease, improving motor signs and delaying the onset of tremors. Importantly, long-term inhibition of calpains did not result in any overt deleterious phenotypes in mice. Thus, calpain inhibition, or activation of autophagy pathways downstream of calpains, may be suitable therapeutic targets for diseases like Huntington's disease.
Assuntos
Autofagia/efeitos dos fármacos , Calpaína/antagonistas & inibidores , Doença de Huntington/metabolismo , Doença de Huntington/patologia , Peptídeos/metabolismo , Animais , Proteínas de Ligação ao Cálcio/biossíntese , Calpaína/genética , Calpaína/metabolismo , Modelos Animais de Doenças , Drosophila , Proteínas de Drosophila/antagonistas & inibidores , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Feminino , Técnicas de Silenciamento de Genes , Doença de Huntington/enzimologia , Doença de Huntington/terapia , Endogamia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de SinaisRESUMO
This study examined identity issues and aspects of the health behaviors of mainstreamed hard-of-hearing (HOH) students aged 11, 13, and 15 compared with their peers. A sample of 52 HOH students was matched with 470 peers of the same age, gender, and ethnicity. A survey based on the World Health Organization Health Behaviours of School Aged Children was administered and the results of the hearing and the HOH groups compared. Although there were few statistically significant differences, there were indications that the HOH students more often experienced a sense of loneliness than their hearing peers did. The majority of HOH students (55.8%) did not self-identify as having a hearing disability. When examined by the willingness to self-identify, the reported frequencies of loneliness and bullying were statistically significant. These findings support the view that the school experience of a significant number of mainstreamed HOH students is not supportive. Those students who do self-identify are physically and psychologically more at risk. The reluctance to self-identify may reflect the prevalence of negative stigma.
RESUMO
Twenty dairy cows in early lactation were assigned to one of two dietary treatment groups based on milk production and days in milk. Treatments were a total mixed ration containing 13.2% whole cottonseed on a DM basis with or without added Ca salts of long-chain fatty acids. Treatments were fed ad libitum for 11 wk. Dry matter intake and body weight were not affected by treatment. The addition of Ca salts of long-chain fatty acids had no effect on yield of actual and FCM. Percent milk fat, lactose, and SCC did not differ between treatments. Percent milk protein tended to be lower for cows fed the diet containing calcium salts of long-chain fatty acids. Milk production efficiencies and NDF and ADF digestibilities were unaffected by treatment. Results indicate that diets containing high amounts of cottonseed may mask th affects of energy provided by Ca salts of long-chain fatty acids.
Assuntos
Cálcio/farmacologia , Bovinos/fisiologia , Ácidos Graxos/farmacologia , Lactação/efeitos dos fármacos , Animais , Feminino , Leite/análise , Leite/efeitos dos fármacos , GravidezRESUMO
Twenty Holstein dairy cows in early lactation were allocated equally to one of two treatments on the basis of age, days in milk, and mean daily 2-wk pretrial milk yield. All animals were fed a total mixed ration; the ration for the treatment group was top-dressed with 90 g/d of yeast culture, Saccharomyces cerevisiae. Treatment period lasted 10 wk. Mean daily DM intake, milk production, milk composition, and BW were not significantly affected by treatment. Feed and fecal samples were collected the last 3 d of the treatment period to determine apparent total tract nutrient digestibility using ADF insoluble ash as the inert marker. No significant differences in digestibility were observed between treatment groups for CP, ADF, and NDF.
Assuntos
Fenômenos Fisiológicos da Nutrição Animal , Bovinos/fisiologia , Digestão , Lactação , Saccharomyces cerevisiae/fisiologia , Ração Animal , Animais , Peso Corporal , Bovinos/metabolismo , Ingestão de Alimentos , FemininoRESUMO
Six ruminally and duodenally fistulated Holstein cows 60 d postpartum were assigned randomly to each of two treatments in a single reversal design. Treatments consisted of placebo or 25 mg of sometribove (bST) injected daily. Treatments were initiated at 60 d +/- 7 postpartum and maintained for 6 wk with a 3-wk adjustment between treatment periods. All cows received a TMR consisting of 16% CP and 1.67 Mcal of NE I/kg of DM. Influence of bST on rumen fermentation characteristics, digesta rate of passage, apparent nutrient digestibility, and milk production was evaluated. Milk yield of treated animals was 4.0 kg/d higher than controls. The 3.5% FCM and milk production efficiency (3.5% FCM/DMI) were significantly higher in treated animals than in controls (29.0 vs. 25.4 kg/d and 1.38 vs. 1.21 kg/kg, respectively). Percentage of rumen cellulolytic bacteria (of total viable bacteria) was not significantly different for bST-treated animals (6.4 vs. 3.4%). Total number of rumen protozoa tended to be higher (7.25 vs. 6.55 x 10(3)/ml) in bST-treated animals. Ruminal percentages of CP, NH3 N, alpha-amino N, VFA, and pH were unaffected by treatment. Sometribove treatment did not significantly affect liquid dilution or solids turnover rates. Percentages of CP, alpha-amino N, and NH3 N content in duodenal samples were unaffected by treatment. Total tract apparent digestibility of nutrients and mean daily DMI were unaffected by treatment.
Assuntos
Bovinos/fisiologia , Digestão/efeitos dos fármacos , Hormônio do Crescimento/análogos & derivados , Lactação/efeitos dos fármacos , Rúmen/metabolismo , Animais , Bactérias/efeitos dos fármacos , Feminino , Fermentação/efeitos dos fármacos , Hormônio do Crescimento/administração & dosagem , Hormônio do Crescimento/farmacologia , Hormônios/administração & dosagem , Hormônios/farmacologia , Hormônio do Crescimento Humano , Injeções Subcutâneas/veterinária , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologia , Rúmen/efeitos dos fármacos , Rúmen/microbiologiaRESUMO
Third-cutting alfalfa hay harvested at bud stage and wilted to approximately 65% moisture was treated with a live bacterial inoculant at the rate of 300,000 cfu/g fresh alfalfa. Treated alfalfa was packed in polyethylene bags. Samples were taken at time of ensiling and d 1, 2, 3, 4, 7, and 28 postensiling. Mean pH was lower in the treated haylage (5.09 and 5.71 for treatment and control, respectively). Mean temperatures were higher in the treated haylage (30.0 and 28.0 degrees C for treatment and control, respectively). Mold count, water-soluble carbohydrate, alpha amino nitrogen, CP, and ADF were not affected by treatment. Regardless of treatment, pH, mold counts, and water-soluble carbohydrates declined with time. There was no significant difference between treatments for DM intake, milk production, and milk composition.
Assuntos
Ração Animal , Bactérias/metabolismo , Bovinos/fisiologia , Lactação/metabolismo , Medicago sativa , Silagem , Análise de Variância , Animais , Contagem de Colônia Microbiana , Feminino , Fungos/crescimento & desenvolvimento , Concentração de Íons de Hidrogênio , Lactobacillus/metabolismo , Análise dos Mínimos Quadrados , Pediococcus/metabolismo , Gravidez , TemperaturaRESUMO
Concentrated separator by-product was fed to cattle to determine TDN, milk production, and feed preference. The TDN content of concentrated separator by-product was determined using a substitution method involving a basal diet of alfalfa and grass hay and a treatment diet of alfalfa and grass hay plus 10% added concentrated separator by-product. Four ruminally cannulated cows in a replicated 2 x 2 Latin square design were used. The estimated TDN content of concentrated separator by-product was 59.3%. Twenty midlactation dairy cows were fed either a control ration containing 20% molasses dried beet pulp or a treatment ration containing 20% concentrated separator by-product dried beet pulp. Cows in the treatment group produced significantly less daily milk and 3.5% FCM than the control group. Percentages of milk fat, protein, lactose, and SNF were not different between treatments. Eight Holstein heifers were used to determine feed preference. Heifers were given a choice among 20% molasses dried beet pulp (control) or 10, 15, or 30% concentrated separator by-product dried beet pulp. Heifers showed no preference between 10 or 15% concentrated separator by-product dried beet pulp and control, but preferred the control over the 30% concentrated separator by-product dried beet pulp.