MicroRNA-221 silencing attenuates the degenerated phenotype of intervertebral disc cells.

The aim of this study was to investigate the role of an antichondrogenic factor, MIR221 (miR‐221), in intervertebral disc degeneration (IDD), and provide basic information for the development of a therapeutic strategy for the disc repair based on specific nucleic acid based drugs, such as miR‐221 silencing. We established a relatively quick protocol to minimize artifacts from extended in vitro culture, without selecting the different types of cells from intervertebral disc (IVD) or completely disrupting extracellular matrix (ECM), but by using the whole cell population with a part of resident ECM. During the de‐differentiation process miR‐221 expression significantly increased. We demonstrated the effectiveness of miR‐221 silencing in driving the cells towards chondrogenic lineage. AntagomiR‐221 treated cells showed in fact a significant increase of expression of typical chondrogenic markers including COL2A1, ACAN and SOX9, whose loss is associated with IDD. Moreover, antagomiR‐221 treatment restored FOXO3 expression and increased TRPS1 expression levels attenuating the severity grade of degeneration, and demonstrating in a context of tissue degeneration and inflammation not investigated before, that FOXO3 is target of miR‐221. Data of present study are promising in the definition of new molecules useful as potential intradiscal injectable biological agents

Parasympathetic nervous system dysfunction, as identified by pupil light reflex, and its possible connection to hearing impairment

Context Although the pupil light reflex has been widely used as a clinical diagnostic tool for autonomic nervous system dysfunction, there is no systematic review available to summarize the evidence that the pupil light reflex is a sensitive method to detect parasympathetic dysfunction. Meanwhile, the relationship between parasympathetic functioning and hearing impairment is relatively unknown. Objectives To 1) review the evidence for the pupil light reflex being a sensitive method to evaluate parasympathetic dysfunction, 2) review the evidence relating hearing impairment and parasympathetic activity and 3) seek evidence of possible connections between hearing impairment and the pupil light reflex. Methods Literature searches were performed in five electronic databases. All selected articles were categorized into three sections: pupil light reflex and parasympathetic dysfunction, hearing impairment and parasympathetic activity, pupil light reflex and hearing impairment. Results Thirty-eight articles were included in this review. Among them, 36 articles addressed the pupil light reflex and parasympathetic dysfunction. We summarized the information in these data according to different types of parasympathetic-related diseases. Most of the studies showed a difference on at least one pupil light reflex parameter between patients and healthy controls. Two articles discussed the relationship between hearing impairment and parasympathetic activity. Both studies reported a reduced parasympathetic activity in the hearing impaired groups. The searches identified no results for pupil light reflex and hearing impairment. Discussion and Conclusions As the first systematic review of the evidence, our findings suggest that the pupil light reflex is a sensitive tool to assess the presence of parasympathetic dysfunction. Maximum constriction velocity and relative constriction amplitude appear to be the most sensitive parameters. There are only two studies investigating the relationship between parasympathetic activity and hearing impairment, hence further research is needed. The pupil light reflex could be a candidate measurement tool to achieve this goal

Combining ability in sweet pepper for resistance to powdery mildew Capacidade de combinação em pimentão para resistência a oídio

With the increase of the production of pepper in protected environment, pathogens began to cause serious damages to producers such as Leveillula taurica (Lév.) Arn., fungus that causes powdery mildew. The systemic fungicides have not shown very satisfactory results. Thus, considering that protected cropping of pepper in Brazil is significant and growing, the incorporation of genes that confer resistance to powdery mildew is important for the maintenance of this cropping system. In this research, carried out in 2007 in Campinas, São Paulo State, Brazil, the agronomic performance and resistance to powdery mildew was determined by triple hybrids of sweet pepper through general and specific combining ability of their parents. For agronomic performance of the triple hybrid, it was evaluated the weight length and width average of the fruit, length and width ratio of the fruit and wall thickness. For severity of powdery mildew a scale of scores from 1 to 5 was used. For statistical and genetic analysis, it was adopted Griffing's method two, model I, adapted for partial diallel. The experimental design was completely randomized blocks, with 17 treatments, including ten experimental hybrids and seven parents, eight replications and four plants per plot. The additive effects were greater than the non-additive effects for all agronomic characters; 'P36-R' and 'Platero' were highlighted as good combiners; 'Quantum-R x HV-12', 'Rubia x HV-12' and 'P36-R x HV-12' presented the best specific combining ability; the mean square of the specific combining ability for the severity of the disease was significant indicating the importance of genes with dominant and epistatic effect; triple hybrids obtained by crosses with 'Quantum-R' and 'Rubia-R' had negative general combining ability and the best reactions to powdery mildew.<br>Com o aumento do cultivo protegido de pimentão, patógenos como Leveillula taurica (Lév.) Arn., fungo causador do oídio, passaram a causar sérios prejuízos aos produtores. Os fungicidas sistêmicos não têm apresentado resultados muito satisfatórios. Assim, levando-se em conta que o cultivo protegido de pimentão no Brasil é importante e crescente, a incorporação de genes que conferem resistência ao oídio é relevante para a manutenção desse sistema de cultivo. Nesse trabalho, realizado em 2007 em Campinas-SP, determinou-se o potencial agronômico e de resistência a oídio de híbridos triplos de pimentão por meio da capacidade geral e específica de combinação dos genitores. Para determinar o desempenho agronômico dos híbridos triplos, avaliaram-se o peso, comprimento e largura média do fruto, relação entre comprimento e largura do fruto e espessura da polpa. Para a avaliação da severidade da doença utilizou-se escala de notas de 1 a 5. Para as análises estatístico-genéticas, adotou-se o método dois, modelo I de Griffing, adaptado para dialelo parcial. O delineamento experimental utilizado foi o de blocos ao acaso, com 17 tratamentos, incluindo dez híbridos experimentais e sete genitores, oito repetições e quatro plantas por parcela. Os efeitos aditivos foram superiores aos efeitos nãoaditivos para todos os componentes agronômicos avaliados; 'P36-R' e 'Platero' destacaram-se como bons combinadores para os caracteres agronômicos avaliados; 'Quantum-R x HV-12', 'Rubia-R x HV-12' e 'P36-R x HV-12' apresentaram os maiores efeitos da capacidade específica de combinação para a maioria dos caracteres avaliados; o quadrado médio da capacidade específica de combinação significativo para a severidade da doença indicou a importância de genes com efeito de dominância e epistasia; híbridos triplos obtidos do cruzamento com 'Quantum-R' e 'Rubia-R' apresentaram capacidade geral de combinação negativa e as melhores reações de resistência ao oídio

Asymmetric short-term adaptation of the vertical vestibulo-ocular reflex in humans

Anatomical and electrophysiological studies have demonstrated up-down asymmetries in vertical ocular motor pathways. We investigated whether these asymmetries extend to the capacity for short-term adaptation of the vertical vestibulo-ocular reflex (VVOR) in humans. Specifically, we asked whether smooth pursuit signals are sufficient to asymmetrically adapt the VVOR. Healthy human subjects (N=8), positioned 90° left-ear-down and fixating with their eyes upon a small laser dot (diameter: 0.1°) projected on a sphere (distance: 1.4m) were trained toward low VVOR gain for 30min with symmetric and asymmetric visual VVOR cancellation paradigms, while being oscillated (0.2Hz, ±20°) on a motorized turntable about the interaural earth-vertical axis. During asymmetric VVOR cancellation, the target was head-fixed in either the pitch-up or pitch-down half-cycles of oscillation (=trained direction) and space-fixed during the other half-cycles (=untrained direction). During symmetric VVOR cancellation, the target was head-fixed throughout the oscillations. Before and after adaptation, the pitch-up and pitch-down VOR gains were assessed during turntable oscillation in complete darkness. Before adaptation, average gains of pitch-up (0.75±0.15 SD) and pitch-down (0.79±0.19 SD) VOR were not significantly different (paired t test: P>0.05). On an average, relative gain reductions induced by selective pitch-up (pitch-up VOR: 32%; pitch-down VOR: 21%) and pitch-down (pitch-up VOR: 18%; pitch-down VOR: 30%) VOR cancellation were significantly (P<0.05) larger in the trained than in the untrained direction. Symmetric visual VVOR cancellation led to a significantly (P<0.01) larger relative gain reduction of the pitch-down (41%) than the pitch-up (33%) VOR. None of the paradigms led to significant changes of phase or offset. We conclude that, in human subjects, the smooth pursuit system is capable to asymmetrically decrease the gain of the VVOR equally well in both the upward and downward direction. The unexpected asymmetric decrease of the VVOR gain after symmetric visual cancellation may be related to the directional preferences of vertical gaze-velocity sensitive Purkinje cells in the flocculus for the downward directio