Activation of ataxia telangiectasia muted under experimental models and human Parkinson’s disease

In the present study we demonstrated that neurotoxin MPP⁺-induced DNA damage is followed by ataxia telangiectasia muted (ATM) activation either in cerebellar granule cells (CGC) or in B65 cell line. In CGC, the selective ATM inhibitor KU-55933 showed neuroprotective effects against MPP⁺-induced neuronal cell loss and apoptosis, lending support to the key role of ATM in experimental models of Parkinson’s disease. Likewise, we showed that knockdown of ATM levels in neuroblastoma B65 cells using an ATM-specific siRNA attenuates the phosphorylation of retinoblastoma protein without affecting other cell-cycle proteins involved in the G₀/G₁ cell-cycle phase. Moreover, we demonstrated DNA damage, in human brain samples of PD patients. These findings support a model in which MPP⁺ leads to ATM activation with a subsequent DNA damage response and activation of pRb. Therefore, this study demonstrates a new link between DNA damage by MPP⁺ and cell-cycle re-entry through retinoblastoma protein phosphorylation.     

Approach to a quantitative differentiation between the respiratory effects evoked from the lung stretch and the lung deflation receptors during thoracic compression

Zusammenfassung Die beiden Annahmen, dass sich bei Thoraxkompression die Verminderung der Impulssequenz der Lungendehnungsrezeptoren analog zum Lungenentdehnungsreflex auswirke, und dass sich dessen inspiratorische Atmungseffekte zu jenen des Lungenkollapsreflexes addieren, erscheinen gerechtfertigt. Diese Annahmen ermöglichen eine quantitative Differenzierung zwischen dem respiratorischen Einfluss der Lungendehnungs-und Lungenkollapsrezeptoren bei Thoraxkompression. Damit können die auf die Erregung der Lungenkollapsrezeptoren zu beziehenden Atmungsveränderungen (f,I/E) erstmals isoliert und quantitativ dargestellt werden.

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Presented at the 2nd Meeting of the Swiss Physiological Society, Zürich, 8 November 1969.     

Neurogenic effects of β-amyloid in the choroid plexus epithelial cells in Alzheimer’s disease

β-amyloid (Aβ) can promote neurogenesis, both in vitro and in vivo, by inducing neural progenitor cells to differentiate into neurons. The choroid plexus in Alzheimer’s disease (AD) is burdened with amyloid deposits and hosts neuronal progenitor cells. However, neurogenesis in this brain tissue is not firmly established. To investigate this issue further, we examined the effect of Aβ on the neuronal differentiation of choroid plexus epithelial cells in several experimental models of AD. Here we show that Aβ regulates neurogenesis in vitro in cultured choroid plexus epithelial cells as well as in vivo in the choroid plexus of APP/Ps1 mice. Treatment with oligomeric Aβ increased proliferation and differentiation of neuronal progenitor cells in cultured choroid plexus epithelial cells, but decreased survival of newly born neurons. These Aβ-induced neurogenic effects were also observed in choroid plexus of APP/PS1 mice, and detected also in autopsy tissue from AD patients. Analysis of signaling pathways revealed that pre-treating the choroid plexus epithelial cells with specific inhibitors of TyrK or MAPK diminished Aβ-induced neuronal proliferation. Taken together, our results support a role of Aβ in proliferation and differentiation in the choroid plexus epithelial cells in Alzheimer’s disease.     

Predicting Recessions with Factor Linear Dynamic Harmonic Regressions

We propose a new framework for building composite leading indicators for the Spanish economy using monthly targeted predictors and small‐scale dynamic factor models. Our leading indicator index, based on the low‐frequency components of four monthly economic variables, is able to predict the onset of the Spanish recessions as well as the gross domestic product (GDP) growth cycles and classical industrial production cycles, both historically and in real time. Also, our leading indicator provides substantial aid in forecasting annual and quarterly GDP growth rates. Using only real data available at the beginning of each forecast period, our indicator one‐step‐ahead forecasts shows substantial improvements over other alternatives. Copyright © 2013 John Wiley & Sons, Ltd.     

Autoradiographic study of the penetration of non-histone chromatin proteins into differentiating cells.

Attention has previously been drawn to a specific effect of NHCP on embryonic Pleurodeles cell differentiation. With a modified NHCP labelling technique, autoradiography has revealed a cytoplasmic concentration of labelled NHCP and has not revealed any difference between homospecific and heterospecific NHCP penetration.     

Mutations in dynamin 2 cause dominant centronuclear myopathy

Autosomal dominant centronuclear myopathy is a rare congenital myopathy characterized by delayed motor milestones and muscular weakness. In 11 families affected by centronuclear myopathy, we identified recurrent and de novo missense mutations in the gene dynamin 2 (DNM2, 19p13.2), which encodes a protein involved in endocytosis and membrane trafficking, actin assembly and centrosome cohesion. The transfected mutants showed reduced labeling in the centrosome, suggesting that DNM2 mutations might cause centronuclear myopathy by interfering with centrosome function.     

Has the Earth's sixth mass extinction already arrived?

Palaeontologists characterize mass extinctions as times when the Earth loses more than three-quarters of its species in a geologically short interval, as has happened only five times in the past 540?million years or so. Biologists now suggest that a sixth mass extinction may be under way, given the known species losses over the past few centuries and millennia. Here we review how differences between fossil and modern data and the addition of recently available palaeontological information influence our understanding of the current extinction crisis. Our results confirm that current extinction rates are higher than would be expected from the fossil record, highlighting the need for effective conservation measures.     

Forecasting European GNP data through common factor models and other procedures

In this paper we present an extensive study of annual GNP data for five European countries. We look for intercountry dependence and analyse how the different economies interact, using several univariate ARIMA and unobserved components models and a multivariate model for the GNP incorporating all the common information among the variables. We use a dynamic factor model to take account of the common dynamic structure of the variables. This common dynamic structure can be non‐stationary (i.e. common trends) or stationary (i.e. common cycles). Comparisons of the models are made in terms of the root mean square error (RMSE) for one‐step‐ahead forecasts. For this particular group of European countries, the factor model outperforms the remaining ones. Copyright © 2002 John Wiley & Sons, Ltd.     

The Effects of Disaggregation on Forecasting Nonstationary Time Series

This paper focuses on the effects of disaggregation on forecast accuracy for nonstationary time series using dynamic factor models. We compare the forecasts obtained directly from the aggregated series based on its univariate model with the aggregation of the forecasts obtained for each component of the aggregate. Within this framework (first obtain the forecasts for the component series and then aggregate the forecasts), we try two different approaches: (i) generate forecasts from the multivariate dynamic factor model and (ii) generate the forecasts from univariate models for each component of the aggregate. In this regard, we provide analytical conditions for the equality of forecasts. The results are applied to quarterly gross domestic product (GDP) data of several European countries of the euro area and to their aggregated GDP. This will be compared to the prediction obtained directly from modeling and forecasting the aggregate GDP of these European countries. In particular, we would like to check whether long‐run relationships between the levels of the components are useful for improving the forecasting accuracy of the aggregate growth rate. We will make forecasts at the country level and then pool them to obtain the forecast of the aggregate. The empirical analysis suggests that forecasts built by aggregating the country‐specific models are more accurate than forecasts constructed using the aggregated data. Copyright © 2014 John Wiley & Sons, Ltd.