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.     

序线性拓扑空间中非凸多目标规划成立弱鞍点准则的几个条件

在序线性拓扑空间中，我们讨论了一类非凸多目标规划问题，得到了与弱有效解相关联的弱鞍点存在性（即成立弱鞍点准则）的几个必要且充分条件和充分条件。我们所获得的结果推广了已知的一些结果。     

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.     

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.     

Gamma globulins in the mice vaginal fluids: Cyclic and experimental variations

Summary The study of the gamma globulins in the vaginal fluids reveals that the lowest values were found in mice at estrus and in castrated mice 8 days after the estrogen treatment. We suggest that the variation of gamma globulins in the vaginal fluids is influenced both under physiological and experimental conditions by estrogens.This work was supported by a grant of the Conicet No. 4973 b/74.Fellow of Scientific Investigator Career. Consejo Nacional de Investigaciones Cientificas y Técnicas.Member of Scientific Investigator Career. Consejo Nacional de Investigaciones Científicas y Técnicas.     

Gamma globulins in the mice vaginal fluids: cyclic and experimental variations.

The study of the gamma globulins in the vaginal fluids reveals that the lowest values were found in mice at estrus and in castrated mice 8 days after the estrogen treatment. We suggest that the variation of gamma globulins in the vaginal fluids is influenced both under physiological and experimental conditions by estrogens.     

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.     

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.