Emotional and emotive language: modal particles and tags in unified Berlin

This paper endeavours to show the relationship between emotion and language, in particular with respect to the use of modal particles in German. Modal particles have long been considered insignificant fillers without a specific function and as such, not worthy of linguistic investigation. This is clearly a view which cannot be sustained. Modal particles have been found to illustrate the speaker’s opinion of what is being said; in addition, they may add emphasis. Certain German modal particles (especially halt and eben) are examined as they occur in a corpus of utterances containing accounts of highly emotional events, related to East and West Berliners’ experiences after the fall of the Berlin Wall and German unification. By reviewing spoken accounts of events which were life-changing for one side, but only nominal for the other, thereby producing different emotions, the article demonstrates the use of these modal particles. The analysis suggests that there is a direct link between emotion and the way these speakers of German use their language

The gene coding for PGC-1α modifies age at onset in Huntington's Disease

Huntington's disease (HD) is one of the most common autosomal dominant inherited, neurodegenerative disorders. It is characterized by progressive motor, emotional and cognitive dysfunction. In addition metabolic abnormalities such as wasting and altered energy expenditure are increasingly recognized as clinical hallmarks of the disease. HD is caused by an unstable CAG repeat expansion in the HD gene (HTT), localized on chromosome 4p16.3. The number of CAG repeats in the HD gene is the main predictor of disease-onset, but the remaining variation is strongly heritable. Transcriptional dysregulation, mitochondrial dysfunction and enhanced oxidative stress have been implicated in the pathogenesis. Recent studies suggest that PGC-1α, a transcriptional master regulator of mitochondrial biogenesis and metabolism, is defective in HD. A genome wide search for modifier genes of HD age-of-onset had suggested linkage at chromosomal region 4p16-4p15, near the locus of PPARGC1A, the gene coding for PGC-1α. We now present data of 2-loci PPARGC1A block 2 haplotypes, showing an effect upon age-at-onset in 447 unrelated HD patients after statistical consideration of CAG repeat lengths in both HTT alleles. Block 1 haplotypes were not associated with the age-at-onset. Homozygosity for the 'protective' block 2 haplotype was associated with a significant delay in disease onset. To our knowledge this is the first study to show clinically relevant effects of the PGC-1α system on the course of Huntington's disease in humans

Mutations in valosin-containing protein (VCP) decrease ADP/ATP translocation across the mitochondrial membrane and impair energy metabolism in human neurons

Mutations in the gene encoding valosin-containing protein (VCP) lead to multisystem proteinopathies including frontotemporal dementia. We have previously shown that patient-derived VCP mutant fibroblasts exhibit lower mitochondrial membrane potential, uncoupled respiration, and reduced ATP levels. This study addresses the underlying basis for mitochondrial uncoupling using VCP knockdown neuroblastoma cell lines, induced pluripotent stem cells (iPSCs), and iPSC-derived cortical neurons from patients with pathogenic mutations in VCP. Using fluorescent live cell imaging and respiration analysis we demonstrate a VCP mutation/knockdown-induced dysregulation in the adenine nucleotide translocase, which results in a slower rate of ADP or ATP translocation across the mitochondrial membranes. This deregulation can explain the mitochondrial uncoupling and lower ATP levels in VCP mutation-bearing neurons via reduced ADP availability for ATP synthesis. This study provides evidence for a role of adenine nucleotide translocase in the mechanism underlying altered mitochondrial function in VCP-related degeneration, and this new insight may inform efforts to better understand and manage neurodegenerative disease and other proteinopathies

Outcrop analogue study to determine reservoir properties of the Los Humeros and Acoculco geothermal fields, Mexico

The Los Humeros geothermal system is steam dominated and currently under exploration with 65 wells (23 producing). Having temperatures above 380 ∘C, the system is characterized as a super hot geothermal system (SHGS). The development of such systems is still challenging due to the high temperatures and aggressive reservoir fluids which lead to corrosion and scaling problems. The geothermal system in Acoculco (Puebla, Mexico; so far only explored via two exploration wells) is characterized by temperatures of approximately 300 ∘C at a depth of about 2 km. In both wells no geothermal fluids were found, even though a well-developed fracture network exists. Therefore, it is planned to develop an enhanced geothermal system (EGS). For better reservoir understanding and prospective modeling, extensive geological, geochemical, geophysical and technical investigations are performed within the scope of the GEMex project. Outcrop analogue studies have been carried out in order to identify the main fracture pattern, geometry and distribution of geological units in the area and to characterize all key units from the basement to the cap rock regarding petro- and thermo-physical rock properties and mineralogy. Ongoing investigations aim to identify geological and structural heterogeneities on different scales to enable a more reliable prediction of reservoir properties. Beside geological investigations, physical properties of the reservoir fluids are determined to improve the understanding of the hydrochemical processes in the reservoir and the fluid-rock interactions, which affect the reservoir rock properties

Sustained expression of PGC-1α in the rat nigrostriatal system selectively impairs dopaminergic function

Mitochondrial dysfunction and oxidative stress have been implicated in the etiology of Parkinson's disease. Therefore, pathways controlling mitochondrial activity rapidly emerge as potential therapeutic targets. Here, we explore the neuronal response to prolonged overexpression of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), a transcriptional regulator of mitochondrial function, both in vitro and in vivo. In neuronal primary cultures from the ventral midbrain, PGC-1α induces mitochondrial biogenesis and increases basal respiration. Over time, we observe an increasing proportion of the oxygen consumed by neurons which are dedicated to adenosine triphosphate production. In parallel to enhanced oxidative phosphorylation, PGC-1α progressively leads to a decrease in mitochondrial polarization. In the adult rat nigrostriatal system, adeno-associated virus (AAV)-mediated overexpression of PGC-1α induces the selective loss of dopaminergic markers and increases dopamine (DA) catabolism, leading to a reduction in striatal DA content. In addition, PGC-1α prevents the labeling of nigral neurons following striatal injection of the fluorogold retrograde tracer. When PGC-1α is expressed at higher levels following intranigral AAV injection, it leads to overt degeneration of dopaminergic neurons. Finally, PGC-1α overexpression does not prevent nigrostriatal degeneration in pathologic conditions induced by α-synuclein overexpression. Overall, we find that lasting overexpression of PGC-1α leads to major alterations in the metabolic activity of neuronal cells which dramatically impair dopaminergic function in vivo. These results highlight the central role of PGC-1α in the function and survival of dopaminergic neurons and the critical need for maintaining physiological levels of PGC-1α activity