Progression of myopathology in Kearns-Sayre syndrome

We report on the progression of myopathology by comparing two biopsies from a patient with a Kearns-Sayre-Syndrome. The first biopsy was taken in 1979 and showed 10% ragged-red fibers. Myopathic changes were slight including internal nuclei and fiber splitting in 10% of the fibers. Electron microscopy revealed typical mitochondrial abnormalities with regard to number and shape. In 1989 a second biopsy was performed for an extended analysis of mitochondrial DNA. This time less than 5% of all fibers were ragged-red. Severe myopathic changes could be detected which so far has rarely been reported in mitochondrial cytopathy

Circadian Programs of Transcriptional Activation, Signaling, and Protein Turnover Revealed by Microarray Analysis of Mammalian Cells

Many aspects of physiology and behavior are temporally organized into daily 24 hr rhythms, driven by an endogenous circadian clock. Studies in eukaryotes have identified a network of interacting genes forming interlocked autoregulatory feedback loops which underlie overt circadian organization in single cells [1, 2]. While in mammals the master oscillator resides in the suprachiasmatic nuclei of the hypothalamus [2], semiautonomous circadian oscillators also exist in peripheral tissues [3–5] and in immortalized fibroblasts, where rhythmicity is induced following a serum shock [6, 7]. We used this model system in combination with high-density cDNA microarrays to examine the magnitude and quality of clock control of gene expression in mammalian cells. Supported by application of novel bioinformatics tools, we find ∼2% of genes, including expected canonical clock genes, to show consistent rhythmic circadian expression across five independent experiments. Rhythmicity in most of these genes is novel, and they fall into diverse functional groups, highlighted by a predominance of transcription factors, ubiquitin-associated factors, proteasome components, and Ras/MAPK signaling pathway components. When grouped according to phase, 68% of the genes were found to peak during estimated subjective day, 32% during estimated subjective night, with a tendency to peak at a phase corresponding to anticipation of dawn or dusk

Editorial note for the Geodesy and Geodynamics journal special issue Contemporary Research in Geodynamics and Earth Tides : An account of the 18th Geodynamics and Earth Tides Symposium 2016, Trieste, Italy

This volume aims at conveying the rich and interdisciplinary topics discussed at the 18th Geodynamics and Earth Tides Symposium, Trieste, 2016. For seventeen times the gathering was named the Earth Tides Symposium, when giving tribute to the evolution of the observed signals, the term geodynamics was added to the title.The present volume aims at a full coverage of the Symposium by including the entire list of abstracts that were presented either as oral or poster presentation

A first Alps - dedicated gravity data set - introduction and status of the AlpArray gravity field activities

In this contribution, activities of the AlpArray Gravity Research Group (AAGRG) are introduced. Since 2018, this group in the frame of the AlpArray project (http://www.alparray.ethz.ch/en/home/) prepares gravity and other data sets to support multidisciplinary goals of the project. It is focused on the mantle, plate and surface processes in the Alps-Apennines-Carpathians-Dinarides orogenic system. In 2018, the AAGRG set up its own methodology guidelines and assembled available land-gravity data and digital elevation model (DEM) data from all the participating countries. Our presentation targets especially three goals: 1) to introduce AAGRG activities as an integral part of the AlpArray project for studying Alpine orogeny \u2013 a goal that by definition requires international cooperation, 2) to review the input data and the works accomplished so far, and, 3) to discuss the steps to be taken to produce detailed gravity maps of the region \u2013 the first Alps-dedicated gravity field data set. We plan to prepare gravity grids in a homogeneous processing approach of either 2x2 km or 4x4 km resolution, depending on the coverage and data quality. The final data sets will be made public in late 2019. A special emphasis is put on the calculation of the Bouguer anomaly using ellipsoidal rather tha normal heights. For calculating topographic effects the preference is given to local DEMs, where available, as they often provide higher quality and spatial resolutions. The public gravity data sets are evaluated with the high-resolution geopotential models like EIGEN-6C4 or EGM2008 \u2013 a useful means for identifying biases in the data coming from various countries and campaigns

Neuronal hemoglobin affects dopaminergic cells' response to stress

Hemoglobin (Hb) is the major protein in erythrocytes and carries oxygen (O2) throughout the body. Recently, Hb has been found synthesized in atypical sites, including the brain. Hb is highly expressed in A9 dopaminergic (DA) neurons of the substantia nigra (SN), whose selective degeneration leads to Parkinson's disease (PD). Here we show that Hb confers DA cells' susceptibility to 1-methyl-4-phenylpyridinium (MPP(+)) and rotenone, neurochemical cellular models of PD. The toxic property of Hb does not depend on O2 binding and is associated with insoluble aggregate formation in the nucleolus. Neurochemical stress induces epigenetic modifications, nucleolar alterations and autophagy inhibition that depend on Hb expression. When adeno-associated viruses carrying \u3b1- and \u3b2-chains of Hb are stereotaxically injected into mouse SN, Hb forms aggregates and causes motor learning impairment. These results position Hb as a potential player in DA cells' homeostasis and dysfunction in PD. Copyright The Author(s) 201

Methamphetamine-Induced Dopamine-Independent Alterations in Striatal Gene Expression in the 6-Hydroxydopamine Hemiparkinsonian Rats

Unilateral injections of 6-hydroxydopamine into the medial forebrain bundle are used extensively as a model of Parkinson's disease. The present experiments sought to identify genes that were affected in the dopamine (DA)–denervated striatum after 6-hydroxydopamine-induced destruction of the nigrostriatal dopaminergic pathway in the rat. We also examined whether a single injection of methamphetamine (METH) (2.5 mg/kg) known to cause changes in gene expression in the normally DA-innervated striatum could still influence striatal gene expression in the absence of DA. Unilateral injections of 6-hydroxydopamine into the medial forebrain bundle resulted in METH-induced rotational behaviors ipsilateral to the lesioned side and total striatal DA depletion on the lesioned side. This injection also caused decrease in striatal serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels. DA depletion was associated with increases in 5-HIAA/5-HT ratios that were potentiated by the METH injection. Microarray analyses revealed changes (± 1.7-fold, p<0.025) in the expression of 67 genes on the lesioned side in comparison to the intact side of the saline-treated hemiparkinsonian animals. These include follistatin, neuromedin U, and tachykinin 2 which were up-regulated. METH administration caused increases in the expression of c-fos, Egr1, and Nor-1 on the intact side. On the DA-depleted side, METH administration also increased the expression of 61 genes including Pdgf-d and Cox-2. There were METH-induced changes in 16 genes that were common in the DA-innervated and DA-depleted sides. These include c-fos and Nor-1 which show greater changes on the normal DA side. Thus, the present study documents, for the first time, that METH mediated DA-independent changes in the levels of transcripts of several genes in the DA-denervated striatum. Our results also implicate 5-HT as a potential player in these METH-induced alterations in gene expression because the METH injection also caused significant increases in 5-HIAA/5-HT ratios on the DA-depleted side