RESUMO
Background and Objectives: In stroke rehabilitation, the use of either implicit or explicit learning as a motor learning approach during dual tasks is common, but it is unclear which strategy is more beneficial. This study aims to determine the benefits of implicit versus explicit motor learning approaches in patients with stroke. Materials and Methods: Seventeen patients with stroke and 21 control participants were included. Motor learning was evaluated using the Serial Reaction Time Task (SRTT) in the context of dual-task conditions. The SRTT was conducted on two separate days: one day for implicit learning conditions and the other day for explicit learning conditions. Under the explicit learning conditions, a task rule was given to the participants before they started the task, but not under the implicit learning conditions. Learning scores were calculated for both implicit and explicit learning, and these scores were then compared within groups for patients with stroke and controls. We calculated the difference in learning scores between implicit and explicit learning and conducted a correlation analysis with the Trail Making Test (TMT) Parts A and B. Results: Learning scores on the SRTT were not different between implicit and explicit learning in controls but were significantly greater in patients with stroke for implicit learning than for explicit learning. The difference in learning scores between implicit and explicit learning in patients with stroke was correlated with TMT-A and showed a correlation trend with TMT-B. Conclusions: Implicit learning approaches may be effective in the acquisition of motor skills with dual-task demands in post-stroke patients with deficits in attention and working memory.
Assuntos
Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Análise e Desempenho de Tarefas , Aprendizagem , Acidente Vascular Cerebral/complicações , Memória de Curto PrazoRESUMO
Spemann's organizer plays a key role in dorsal-ventral (DV) patterning in the amphibian embryo by secreting diffusible proteins such as Chordin, an antagonist to ventralizing bone morphogenetic proteins (BMPs). The DV patterning is so robust that an amphibian embryo with its ventral half surgically removed can develop into a smaller but proportionally patterned larva. Here, we show that this robust patterning depends on facilitated Chordin degradation and requires the expression of the Chordin-proteinase inhibitor Sizzled on the opposite side. Sizzled, which is stable and diffuses widely along the DV axis, stabilizes Chordin and expands its distribution in the ventral direction. This expanded Chordin distribution, in turn, limits BMP-dependent Sizzled production, forming an axis-wide feedback loop for shaping Chordin's activity. Using bisection assays, we demonstrate that Chordin degradation is dynamically controlled by embryo-size-coupled Sizzled accumulation. We propose a scaling model that enables the DV pattern to adjust proportionally to embryonic axis size.
Assuntos
Padronização Corporal , Embrião não Mamífero/metabolismo , Glicoproteínas/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas de Xenopus/metabolismo , Xenopus laevis/embriologia , Animais , Tamanho Corporal , Técnicas de Silenciamento de Genes , Glicoproteínas/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Organizadores Embrionários/metabolismo , Proteínas de Xenopus/genéticaRESUMO
Dorsal axial formation during vertebrate embryogenesis exhibits robust resistance to perturbations in patterning signals. However, how such stability is supported at the molecular level remains largely elusive. Here we show that Xenopus ONT1, an Olfactomedin-class secreted protein, stabilizes axial formation by restricting Chordin activity on the dorsal side. When ONT1 function is attenuated, the embryo becomes hyperdorsalized by a normally subeffective dose of Chordin. ONT1 binds Chordin and BMP1/Tolloid-class proteinases (B1TP) via distinct domains and acts as a secreted scaffold that enhances B1TP-mediated Chordin degradation by facilitating enzyme-substrate association. ONT1 is indispensable for fine-tuning BMP signaling in the axial tissue, and a similar role has been suggested for dorsally expressed BMPs such as ADMP. Simultaneous inhibition of ONT1 and dorsally expressed BMPs (ADMP and BMP2) synergistically caused drastic dorsalization. These results indicate that stable axial formation depends on two compensatory regulatory pathways involving ONT1/B1TP and dorsally expressed BMPs.
Assuntos
Padronização Corporal , Proteínas da Matriz Extracelular/metabolismo , Glicoproteínas/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas de Xenopus/metabolismo , Xenopus laevis/embriologia , Animais , Proteína Morfogenética Óssea 1 , Proteínas Morfogenéticas Ósseas/metabolismo , Linhagem Celular , Galinhas , Embrião não Mamífero/metabolismo , Proteínas da Matriz Extracelular/química , Glicoproteínas/química , Humanos , Metaloendopeptidases/metabolismo , Metaloproteases/metabolismo , Estrutura Terciária de Proteína , Metaloproteases Semelhantes a Toloide , Proteínas de Xenopus/químicaRESUMO
We report directed differentiaion of retinal precursors in vitro from mouse ES cells. Six3+ rostral brain progenitors are generated by culturing ES cells under serum-free suspension conditions (SFEB culture) in the presence of Wnt and Nodal antagonists (Dkk1 and LeftyA), and subsequently steered to differentiate into Rx+ cells (16%) by treatment with activin and serum. Consistent with the characteristics of early neural retinal precursors, the induced Rx+ cells coexpress Pax6 and the mitotic marker Ki67, but not Nestin. The ES cell-derived precursors efficiently generate cells with the photoreceptor phenotype (rhodopsin+, recoverin+) when cocultured with embryonic retinal cells. Furthermore, organotypic culture studies demonstrate the selective integration and survival of ES cell-derived cells with the photoreceptor phenotype (marker expression and morphology) in the outer nuclear layer of the retina. Taken together, ES cells treated with SFEB/Dkk1/LeftyA/serum/activin generate neural retinal precursors, which have the competence of photoreceptor differentiation.
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Diferenciação Celular/efeitos dos fármacos , Proteínas do Olho/metabolismo , Proteínas de Homeodomínio/metabolismo , Fatores de Transcrição Box Pareados/metabolismo , Proteínas Repressoras/metabolismo , Retina/citologia , Células-Tronco/citologia , Ativinas/farmacologia , Animais , Células Cultivadas , Meios de Cultura Livres de Soro/farmacologia , Vetores Genéticos , Imuno-Histoquímica , Hibridização In Situ , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Fatores de Determinação Direita-Esquerda , Lentivirus , Camundongos , Proteínas do Tecido Nervoso/metabolismo , Fator de Transcrição PAX6 , Retina/metabolismo , Rodopsina/metabolismo , Soro , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Proteína Homeobox SIX3RESUMO
Early spherical Xenopus laevis embryos are transformed into a streamlined shape through convergent extension movements. Here we report that a p75(NTR)-related transmembrane protein, NRH1, has an essential function in the regulation of these movements. NRH1 was expressed in marginal zone tissues of the gastrula and in the posterior ectoderm of the neurula. Attenuation of the NRH1 function inhibited convergent extension movements in the embryo and in activin-treated animal caps. NRH1 activated downstream effectors of the Wnt/planar cell polarity pathway: small GTPases and the cascade of MKK7-JNK. Furthermore, gain- and loss-of-function phenotypes of NRH1 were rescued by co-injection of dominant-negative and constitutively active forms of these downstream effectors, respectively, suggesting that NRH1 functions as a positive modulator of planar cell polarity signalling. Interestingly, NRH1 does not require Dishevelled (Xdsh) for the activation of these downstream effectors or translocation of Xdsh to the membrane, suggesting that NRH1 signalling interacts with planar cell polarity signalling downstream of Xdsh. This demonstrates an essential role for p75(NTR)-related signalling in early embryonic morphogenesis.
Assuntos
Movimento Celular/fisiologia , Receptores de Fator de Crescimento Neural/fisiologia , Proteínas de Xenopus/fisiologia , Animais , Western Blotting , Padronização Corporal/genética , Movimento Celular/genética , Polaridade Celular/genética , Ativação Enzimática , GTP Fosfo-Hidrolases/metabolismo , Gástrula , Regulação da Expressão Gênica no Desenvolvimento , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Receptores de Fator de Crescimento Neural/genética , Transdução de Sinais , Proteínas de Xenopus/genética , Xenopus laevis/embriologiaRESUMO
We have recently demonstrated that serotonin (5-HT) increases the production of type 4 collagen by cultured human mesangial cells. Here we examined the clinical effects of a 5-HT(A2) receptor antagonist whether it would prevent the development or progression of diabetic nephropathy. We compared the levels of 5-hydroxyindole-3-acetic acid (5-HIAA), the major metabolite of 5-HT, in 24-h urine samples of patients with type 2 diabetes (n=110) and normal subjects (n=40). We then investigated the effects of 24-month treatment with sarpogrelate hydrochloride, a 5-HT(A2) receptor antagonist, on urinary albumin level in 10 type 2 diabetics with microalbuminuria, compared with not treated control group. Urinary 5-HIAA in diabetic patients was significantly higher (3.44+/-1.43 mg/day) than in normal subjects (1.62+/-0.50 mg/day, P<0.001), and correlated significantly with hemoglobin A1c (r=0.56, P<0.001) and with fasting blood glucose (r=0.37, P<0.001). Sarpogrelate significantly reduced urinary albumin excretion level within 3 months of commencement of treatment (24.3+/-8.58 mg/g Cr, P<0.05), which was persistently seen during the treatment, while no such change was noted in the control group (32.2+/-13.4 mg/g Cr). Our study indicate that high levels of 5-HT in type 2 diabetics may be one of the underlying mechanisms of diabetic nephropathy, and that treatment with 5-HT(A2) receptor antagonists may reduce or inhibit the development of nephropathy.