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.     

Shear-induced molecular precession in a hexatic Langmuir monolayer

Liquid crystalline behaviour is generally limited to a select group of specially designed bulk substances. By contrast, it is a common feature of simple molecular monolayers and other quasi-two-dimensional systems, which often possess a type of in-plane ordering that results from unbinding of dislocations-a 'hexatic' liquid crystalline phase. The flow of monolayers is closely related to molecular transport in biological membranes, affects foam and emulsion stability and is relevant to microfluidics research. For liquid crystalline phases, it is important to understand the coupling of the molecular orientation to the flow. Orientationally ordered (nematic) phases in bulk liquid crystals exhibit 'shear aligning' or 'tumbling' behaviour under shear, and are described quantitatively by Leslie-Ericksen theory. For hexatic monolayers, the effects of flow have been inferred from textures of Langmuir-Blodgett films and directly observed at the macroscopic level. However, there is no accepted model of hexatic flow at the molecular level. Here we report observations of a hexatic Langmuir monolayer that reveal continuous, shear-induced molecular precession, interrupted by occasional jump discontinuities. Although superficially similar to tumbling in a bulk nematic phase, the kinematic details are quite different and provide a possible mechanism for domain coarsening and eventual molecular alignment in monolayers. We explain the precession and jumps within a quantitative framework that involves coupling of molecular orientation to the local molecular hexatic 'lattice', which is continuously deformed by shear.     

The alcohol syndromes: the intrarecombigenic effect of acetaldehyde

Sister chromatid exchange was studied in lymphocyte and fibroblast cultures. Alcohol caused no disturbance under normal conditions but an acetaldehyde level above 40 muM inhibited cell multiplication and elevated SCE considerably. A high acetaldehyde level is thought to elicit the fetal alcohol syndrome, a view supported by clinical and experimental observations.     

The Shwachman-Bodian-Diamond syndrome protein mediates translational activation of ribosomes in yeast

The autosomal recessive disorder Shwachman-Diamond syndrome, characterized by bone marrow failure and leukemia predisposition, is caused by deficiency of the highly conserved Shwachman-Bodian-Diamond syndrome (SBDS) protein. Here, we identify the function of the yeast SBDS ortholog Sdo1, showing that it is critical for the release and recycling of the nucleolar shuttling factor Tif6 from pre-60S ribosomes, a key step in 60S maturation and translational activation of ribosomes. Using genome-wide synthetic genetic array mapping, we identified multiple TIF6 gain-of-function alleles that suppressed the pre-60S nuclear export defects and cytoplasmic mislocalization of Tif6 observed in sdo1Delta cells. Sdo1 appears to function within a pathway containing elongation factor-like 1, and together they control translational activation of ribosomes. Thus, our data link defective late 60S ribosomal subunit maturation to an inherited bone marrow failure syndrome associated with leukemia predisposition.     

Influence of oxidative phosphorylation inhibitors on the histamine release in the anaphylactic reactionin vitro

Résumé Des expériences ont été faites pour étudier l'influence des inhibiteurs de la phosphorylation oxydative sur la libération d'histamine pendant la réaction anaphylactique.Une inhibition de la libération d'histamine a été observée, suggérant que des composés phosphorylés riches en énergie sont liés au mécanisme de libération.

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Fellow from the Conselho Nacional de Pesquisas.     

Alteration of enzyme activities in detached leaves and their counteraction by kinetin

Zusammenfassung In abgetrennten Blättern werden verschiedene Enzyme, besonders aber die Pentosephosphatcyclus-Dehydrogenasen aktiviert. Gleichzeitig steigt die Atmungsintensität an. Die Malonatsensitivität der O₂-Aufnahme nimmt ab. Die Ausbildung der obigen Stoffwechsellage kann durch Kinetin gehemmt werden.     

Promises of Presence

My review of Ike Kamphof’s “Webcams to Save Nature: Online Space as Affective and Ethical Space” focuses on the question how the engagement of the spectator of the described websites is temporally structured and how the discrepancy between the instantaneity of affective response and the duration of moral engagement is solved. I propose to draw on Alexander Nehamas’ philosophy of beauty as an in-between, bringing affect and ethics closer together.     

Glutamate stimulates inositol phosphate formation in striatal neurones

The major excitatory amino acids, glutamate (Glu) and aspartate (Asp), are thought to act at three receptor subtypes in the mammalian central nervous system (CNS). These are termed quisqualate (QA), N-methyl-D-aspartate (NMDA) and kainate (KA) receptors according to the specific agonist properties of these compounds revealed by electrophysiological studies. Although Glu has been shown to stimulate cyclic GMP formation in brain slices, direct regulation of second messenger systems (cyclic AMP, Ca2+ or inositol phosphates) subsequent to activation of excitatory amino-acid receptors, has not been extensively studied. Here we demonstrate that in striatal neurones, excitatory amino acids, but not inhibitory or non-neuroactive amino acids, induce a three- to fourfold increase in inositol mono-, di- and triphosphate (IP, IP, IP) formation with the relative potency QA greater than Glu greater than NMDA, KA. The Glu-evoked formation of inositol phosphates appears to result principally from actions at QA as well as NMDA receptors on striatal neurones. Our results suggest that excitatory amino acids stimulate inositol phosphate formation directly, rather than indirectly by the evoked release and subsequent actions of adenosine or acetylcholine.