Appointment by Archduke Ferdinand of Pilgram Marpeck as Mining Superintendent (1525)

This document is an official copy of the order appointing Pilgram Marpeck, engineer and public official, to oversee and manage for the sovereign the royal mines in the upper Inn valley of Tirol

Episodic memory encoding in middle age: effects of ageing and cognitive fatigue on brain activation

Klaassen, E., Evers, E., De Groot, R. H. M., Veltman, D., & Jolles, J. (2011, September). Episodic memory encoding in middle age: effects of ageing and cognitive fatigue on brain activation. Poster presented at the Annual meeting for the international society for neuroimaging in psychiatry, Heidelberg, Germany.Healthy cognitive aging is thought to impact most heavily on episodic memory [1]. However, changes in episodic memory prior to the age of 60 are more controversial than changes in older adults [2]. Furthermore, cognitive decline already present in middle age may not yet manifest in behavior due to the action of neural compensation processes that preserve performance at the behavioral level. Therefore, fMRI can provide valuable insights into age-related changes present in middle age [3]. It is also important to determine the extent to which middle-aged adults must compensate for the effects of cognitive aging in order to maintain performance not just in the short-term, but following sustained, fatigue inducing task performance likely, for example, to be commonly encountered during the workday. Therefore, in the current study, each participant was tested twice: once following a fatiguing condition involving the sustained performance of cognitively demanding tasks and once following a less demanding baseline condition.At baseline, activation was greater, primarily in PFC regions, in middle-aged compared to young adults. This suggests increased exertion of top-down cognitive control in middle-aged adults during successful encoding. In the fatigue condition, activation differences between the two age groups were no longer apparent. Activation in both age groups, but particularly the middle-aged group, decreased in comparison to baseline activation. Therefore, in a state of induced fatigue, middle-aged adults no longer showed greater exertion of cognitive control than young adults, and instead showed activation changes suggestive of an exhaustion of cognitive resources

Young and middle-aged schoolteachers differ in the neural correlates of memory encoding and cognitive fatigue: a functional MRI study

This investigation was inspired by growing evidence that middle-aged persons in a cognitively demanding profession might be characterized by subtle cognitive fatigue. We studied young and middle-aged male schoolteachers. They were compared in a study with functional magnetic resonance imaging to evaluate differences during successful memory encoding. The schoolteachers were additionally subjected to an induced fatigue condition involving the sustained performance of cognitively demanding tasks and to a control condition. Results showed age-related brain activation differences underlying behavioral performance including: (1) greater activation in middle-aged vs. young teachers in bilateral prefrontal cortex (PFC) areas; and (2) differential fatigue effects in the left anterior cingulate cortex (ACC) depending on age group. Middle-aged schoolteachers showed decreased ACC activation in the fatigue compared to the control condition, whereas no change in activation was found in young teachers. Findings demonstrate age effects in these middle-aged subjects that are typically found in older adults, specifically in PFC over-activation. Findings also indicate that already in middle age cognitive aging may be associated with greater resource depletion following sustained task performance. The findings underscore the notion that persons in a cognitively demanding profession can experience subtle age effects, which are evident on fMRI and which impact daily functioning. Possible practical implications for middle-aged schoolteachers are discussed

Environment, Migratory Tendency, Phylogeny and Basal Metabolic Rate in Birds

Basal metabolic rate (BMR) represents the minimum maintenance energy requirement of an endotherm and has far-reaching consequences for interactions between animals and their environments. Avian BMR exhibits considerable variation that is independent of body mass. Some long-distance migrants have been found to exhibit particularly high BMR, traditionally interpreted as being related to the energetic demands of long-distance migration. Here we use a global dataset to evaluate differences in BMR between migrants and non-migrants, and to examine the effects of environmental variables. The BMR of migrant species is significantly higher than that of non-migrants. Intriguingly, while the elevated BMR of migrants on their breeding grounds may reflect the metabolic machinery required for long-distance movements, an alternative (and statistically stronger) explanation is their occupation of predominantly cold high-latitude breeding areas. Among several environmental predictors, average annual temperature has the strongest effect on BMR, with a 50% reduction associated with a 20°C gradient. The negative effects of temperature variables on BMR hold separately for migrants and non-migrants and are not due their different climatic associations. BMR in migrants shows a much lower degree of phylogenetic inertia. Our findings indicate that migratory tendency need not necessarily be invoked to explain the higher BMR of migrants. A weaker phylogenetic signal observed in migrants supports the notion of strong phenotypic flexibility in this group which facilitates migration-related BMR adjustments that occur above and beyond environmental conditions. In contrast to the findings of previous analyses of mammalian BMR, primary productivity, aridity or precipitation variability do not appear to be important environmental correlates of avian BMR. The strong effects of temperature-related variables and varying phylogenetic effects reiterate the importance of addressing both broad-scale and individual-scale variation for understanding the determinants of BMR

Degeneration of penicillin production in ethanol-limited chemostat cultivations of Penicillium chrysogenum:A systems biology approach

Background: In microbial production of non-catabolic products such as antibiotics a loss of production capacity upon long-term cultivation (for example chemostat), a phenomenon called strain degeneration, is often observed. In this study a systems biology approach, monitoring changes from gene to produced flux, was used to study degeneration of penicillin production in a high producing Penicillium chrysogenum strain during prolonged ethanol-limited chemostat cultivations. Results: During these cultivations, the biomass specific penicillin production rate decreased more than 10-fold in less than 22 generations. No evidence was obtained for a decrease of the copy number of the penicillin gene cluster, nor a significant down regulation of the expression of the penicillin biosynthesis genes. However, a strong down regulation of the biosynthesis pathway of cysteine, one of the precursors of penicillin, was observed. Furthermore the protein levels of the penicillin pathway enzymes L-alpha-(d-aminoadipyl)-L-alpha-cystenyl-D-alpha-valine synthetase (ACVS) and isopenicillin-N synthase (IPNS), decreased significantly. Re-cultivation of fully degenerated cells in unlimited batch culture and subsequent C-limited chemostats did only result in a slight recovery of penicillin production. Conclusions: Our findings indicate that the observed degeneration is attributed to a significant decrease of the levels of the first two enzymes of the penicillin biosynthesis pathway, ACVS and IPNS. This decrease is not caused by genetic instability of the penicillin amplicon, neither by down regulation of the penicillin biosynthesis pathway. Furthermore no indications were obtained for degradation of these enzymes as a result of autophagy. Possible causes for the decreased enzyme levels could be a decrease of the translation efficiency of ACVS and IPNS during degeneration, or the presence of a culture variant impaired in the biosynthesis of functional proteins of these enzymes, which outcompeted the high producing part of the population

The case for a 'sub-millimeter SDSS' : a 3D map of galaxy evolution to z~10

Science White paper submitted to the Astro2020 Decadal SurveyThe Sloan Digital Sky Survey (SDSS) was revolutionary because of the extraordinary breadth and ambition of its optical imaging and spectroscopy. We argue that a 'sub-millimeter SDSS' - a sensitive large-area imaging+spectroscopic survey in the sub-mm window - will revolutionize our understanding of galaxy evolution in the early Universe. By detecting the thermal dust continuum emission and atomic and molecular line emission of galaxies out to z~10 it will be possible to measure the redshifts, star formation rates, dust and gas content of hundreds of thousands of high-z galaxies down to ~L*. Many of these galaxies will have counterparts visible in the deep optical imaging of the Large Synoptic Survey Telescope. This 3D map of galaxy evolution will span the peak epoch of galaxy formation all the way back to cosmic dawn, measuring the co-evolution of the star formation rate density and molecular gas content of galaxies, tracking the production of metals and charting the growth of large-scale structure.Non peer reviewe

ELOF1 is a transcription-coupled DNA repair factor that directs RNA polymerase II ubiquitylation

Two side-by-side papers report that the transcription elongation factor ELOF1 drives transcription-coupled repair and prevents replication stress.Cells employ transcription-coupled repair (TCR) to eliminate transcription-blocking DNA lesions. DNA damage-induced binding of the TCR-specific repair factor CSB to RNA polymerase II (RNAPII) triggers RNAPII ubiquitylation of a single lysine (K1268) by the CRL4(CSA) ubiquitin ligase. How CRL4(CSA) is specifically directed towards K1268 is unknown. Here, we identify ELOF1 as the missing link that facilitates RNAPII ubiquitylation, a key signal for the assembly of downstream repair factors. This function requires its constitutive interaction with RNAPII close to K1268, revealing ELOF1 as a specificity factor that binds and positions CRL4(CSA) for optimal RNAPII ubiquitylation. Drug-genetic interaction screening also revealed a CSB-independent pathway in which ELOF1 prevents R-loops in active genes and protects cells against DNA replication stress. Our study offers key insights into the molecular mechanisms of TCR and provides a genetic framework of the interplay between transcriptional stress responses and DNA replication.Cancer Signaling networks and Molecular Therapeutic

The 2018 European heatwave led to stem dehydration but not to consistent growth reductions in forests

Heatwaves exert disproportionately strong and sometimes irreversible impacts on forest ecosystems. These impacts remain poorly understood at the tree and species level and across large spatial scales. Here, we investigate the effects of the record-breaking 2018 European heatwave on tree growth and tree water status using a collection of high-temporal resolution dendrometer data from 21 species across 53 sites. Relative to the two preceding years, annual stem growth was not consistently reduced by the 2018 heatwave but stems experienced twice the temporary shrinkage due to depletion of water reserves. Conifer species were less capable of rehydrating overnight than broadleaves across gradients of soil and atmospheric drought, suggesting less resilience toward transient stress. In particular, Norway spruce and Scots pine experienced extensive stem dehydration. Our high-resolution dendrometer network was suitable to disentangle the effects of a severe heatwave on tree growth and desiccation at large-spatial scales in situ, and provided insights on which species may be more vulnerable to climate extremes

The 2018 European heatwave led to stem dehydration but not to consistent growth reductions in forests

Publisher Copyright: © 2022, The Author(s).Heatwaves exert disproportionately strong and sometimes irreversible impacts on forest ecosystems. These impacts remain poorly understood at the tree and species level and across large spatial scales. Here, we investigate the effects of the record-breaking 2018 European heatwave on tree growth and tree water status using a collection of high-temporal resolution dendrometer data from 21 species across 53 sites. Relative to the two preceding years, annual stem growth was not consistently reduced by the 2018 heatwave but stems experienced twice the temporary shrinkage due to depletion of water reserves. Conifer species were less capable of rehydrating overnight than broadleaves across gradients of soil and atmospheric drought, suggesting less resilience toward transient stress. In particular, Norway spruce and Scots pine experienced extensive stem dehydration. Our high-resolution dendrometer network was suitable to disentangle the effects of a severe heatwave on tree growth and desiccation at large-spatial scales in situ, and provided insights on which species may be more vulnerable to climate extremes.Peer reviewe