Potent inhibition of microRNA in vivo without degradation

Chemically modified antisense oligonucleotides (ASOs) are widely used as a tool to functionalize microRNAs (miRNAs). Reduction of miRNA level after ASO inhibition is commonly reported to show efficacy. Whether this is the most relevant endpoint for measuring miRNA inhibition has not been adequately addressed in the field although it has important implications for evaluating miRNA targeting studies. Using a novel approach to quantitate miRNA levels in the presence of excess ASO, we have discovered that the outcome of miRNA inhibition can vary depending on the chemical modification of the ASO. Although some miRNA inhibitors cause a decrease in mature miRNA levels, we have identified a novel 2′-fluoro/2′-methoxyethyl modified ASO motif with dramatically improved in vivo potency which does not. These studies show there are multiple mechanisms of miRNA inhibition by ASOs and that evaluation of secondary endpoints is crucial for interpreting miRNA inhibition studies

Identificaçao da Via Lenta na Reentrada Nodal Atrioventricular Usando o Intervalo Atrioventricular Mais Curto

Em 10 pacientes consecutivos, realizou-se o mapeamento da parede septal do átrio direito durante taquicardia supraventricular por reentrada nodal AV, para comprovar a hipótese de que o intervalo AV mais curto identificava a área de conduçao da via lenta. O septo atrial foi dividido em quatro zonas distintas. Em sete dos pacientes o intervalo AV anterógrado mais curto foi encontrado na zona 3; em dois, na zona 4; no último, na zona 2. A modificaçao por radiofreqüência da via lenta foi obtida com sucesso, em todos os pacientes, na área de conduçao AV mais curta. O intervalo AV durante ritmo sinusal permaneceu inalterado antes e após a ablaçao. Após um seguimento de 21 ±4 meses, nenhum deles teve recorrência dos sintomas

Identificaçao da Via Lenta na Reentrada Nodal Atrioventricular Usando o Intervalo Atrioventricular Mais Curto

Em 10 pacientes consecutivos, realizou-se o mapeamento da parede septal do átrio direito durante taquicardia supraventricular por reentrada nodal AV, para comprovar a hipótese de que o intervalo AV mais curto identificava a área de conduçao da via lenta. O septo atrial foi dividido em quatro zonas distintas. Em sete dos pacientes o intervalo AV anterógrado mais curto foi encontrado na zona 3; em dois, na zona 4; no último, na zona 2. A modificaçao por radiofreqüência da via lenta foi obtida com sucesso, em todos os pacientes, na área de conduçao AV mais curta. O intervalo AV durante ritmo sinusal permaneceu inalterado antes e após a ablaçao. Após um seguimento de 21 ±4 meses, nenhum deles teve recorrência dos sintomas

Gibberellin A1 Metabolism Contributes to the Control of Photoperiod-Mediated Tuberization in Potato

Some potato species require a short-day (SD) photoperiod for tuberization, a process that is negatively affected by gibberellins (GAs). Here we report the isolation of StGA3ox2, a gene encoding a GA 3-oxidase, whose expression is increased in the aerial parts and is repressed in the stolons after transfer of photoperiod-dependent potato plants to SD conditions. Over-expression of StGA3ox2 under control of constitutive or leaf-specific promoters results in taller plants which, in contrast to StGA20ox1 over-expressers previously reported, tuberize earlier under SD conditions than the controls. By contrast, StGA3ox2 tuber-specific over-expression results in non-elongated plants with slightly delayed tuber induction. Together, our experiments support that StGA3ox2 expression and gibberellin metabolism significantly contribute to the tuberization time in strictly photoperiod-dependent potato plants

Additive QTLs on three chromosomes control flowering time in woodland strawberry (Fragaria vesca L.)

Flowering time is an important trait that affects survival, reproduction and yield in both wild and cultivated plants. Therefore, many studies have focused on the identification of flowering time quantitative trait locus (QTLs) in different crops, and molecular control of this trait has been extensively investigated in model species. Here we report the mapping of QTLs for flowering time and vegetative traits in a large woodland strawberry mapping population that was phenotyped both under field conditions and in a greenhouse after flower induction in the field. The greenhouse experiment revealed additive QTLs in three linkage groups (LG), two on both LG4 and LG7, and one on LG6 that explain about half of the flowering time variance in the population. Three of the QTLs were newly identified in this study, and one co-localized with the previously characterized FvTFL1 gene. An additional strong QTL corresponding to previously mapped PFRU was detected in both field and greenhouse experiments indicating that gene(s) in this locus can control the timing of flowering in different environments in addition to the duration of flowering and axillary bud differentiation to runners and branch crowns. Several putative flowering time genes were identified in these QTL regions that await functional validation. Our results indicate that a few major QTLs may control flowering time and axillary bud differentiation in strawberries. We suggest that the identification of causal genes in the diploid strawberry may enable fine tuning of flowering time and vegetative growth in the closely related octoploid cultivated strawberry.Peer reviewe