Search results for "Eino"
showing 10 items of 282 documents
Neurodegeneration in tauopathies and synucleinopathies.
2016
International audience; While increasing life expectancy is a major achievement, the global aging of societies raises a number of medical issues, such as the development of age-related disorders, including neurodegenerative diseases. The three main disease groups constituting the majority of neurodegenerative diseases are tauopathies, alpha-synucleinopathies and diseases due to repetitions of glutamine (including Huntington's disease). In each neurodegenerative disease, the accumulation of one or more aggregated proteins has been identified as the molecular signature of the disease (as seen, for example, in Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, amyotrophic lat…
On the (un)coupling of the chromophore, tongue interactions, and overall conformation in a bacterial phytochrome
2018
Phytochromes are photoreceptors in plants, fungi, and various microorganisms and cycle between metastable red light-absorbing (Pr) and far-red light-absorbing (Pfr) states. Their light responses are thought to follow a conserved structural mechanism that is triggered by isomerization of the chromophore. Downstream structural changes involve refolding of the so-called tongue extension of the phytochrome-specific GAF-related (PHY) domain of the photoreceptor. The tongue is connected to the chromophore by conserved DIP and PRXSF motifs and a conserved tyrosine, but the role of these residues in signal transduction is not clear. Here, we examine the tongue interactions and their interplay with …
Coordination of the biliverdin D-ring in bacteriophytochromes.
2018
Phytochrome proteins translate light into biochemical signals in plants, fungi and microorganisms. Light cues are absorbed by a bilin chromophore, leading to an isomerization and a rotation of the D-ring. This relays the signal to the protein matrix. A set of amino acids, which is conserved across the phytochrome superfamily, holds the chromophore in the binding pocket. However, the functional role of many of these amino acids is not yet understood. Here, we investigate the hydrogen bonding network which surrounds the D-ring of the chromophore in the resting (Pr) state. We use UV/vis spectroscopy, infrared absorption spectroscopy and X-ray crystallography to compare the photosensory domains…
The Pharmacology of Visual Hallucinations in Synucleinopathies
2019
Visual hallucinations (VH) are commonly found in the course of synucleinopathies like Parkinson's disease and dementia with Lewy bodies. The incidence of VH in these conditions is so high that the absence of VH in the course of the disease should raise questions about the diagnosis. VH may take the form of early and simple phenomena or appear with late and complex presentations that include hallucinatory production and delusions. VH are an unmet treatment need. The review analyzes the past and recent hypotheses that are related to the underlying mechanisms of VH and then discusses their pharmacological modulation. Recent models for VH have been centered on the role played by the decoupling …
p27Kip1 regulates alpha-synuclein expression
2018
Alpha-synuclein (α-SYN) is the main component of anomalous protein aggregates (Lewy bodies) that play a crucial role in several neurodegenerative diseases (synucleinopathies) like Parkinson’s disease and multiple system atrophy. However, the mechanisms involved in its transcriptional regulation are poorly understood. We investigated here the role of the cyclin-dependent kinase (Cdk) inhibitor and transcriptional regulator p27Kip1 (p27) in the regulation of α-SYN expression. We observed that selective deletion of p27 by CRISPR/Cas9 technology in neural cells resulted in increased levels of α-SYN. Knock-down of the member of the same family p21Cip1 (p21) also led to increased α-SYN levels, in…
Illuminating a Phytochrome Paradigm – a Light-Activated Phosphatase in Two-Component Signaling Uncovered
2020
ABSTRACTBacterial phytochrome photoreceptors usually belong to two-component signaling systems which transmit environmental stimuli to a response regulator through a histidine kinase domain. Phytochromes switch between red light-absorbing and far-red light-absorbing states. Despite exhibiting extensive structural responses during this transition, the model bacteriophytochrome fromDeinococcus radiodurans(DrBphP) lacks detectable kinase activity. Here, we resolve this long-standing conundrum by comparatively analyzing the interactions and output activities of DrBphP and a bacteriophytochrome fromAgrobacterium fabrum(AgP1). Whereas AgP1 acts as a conventional histidine kinase, we identify DrBp…
Varieties of State Aid and Technological Development: Government Support to the Pulp and Paper Industry, the 1970s to the 1990s
2018
Countries promote the development of pulp and paper industry through industrial, technology and innovation policy measures. Direct interventions and regional and environmental policies, together with more general governmental measures on trade negotiations, taxation, labour policies, and infrastructure development (e.g. roads, energy) have also had an impact on shaping the geographical location of and investments in the pulp and paper industry. This chapter presents an historical overview of government support on pulp and paper industry in the Organisation for Economic Co-operation and Development (OECD) countries from roughly the 1970s to the 1990s. As the earlier literature suggests, in c…
La fortificación del Reino de Valencia en la década de1640 a la luz de la revolución militar
2019
This article proposes a study of the traditions in defensive architecture that concurred in the projects designed by Spanish military engineers for the fortification of the Valencian frontier in 1648 and 1649, in the context of the War of Catalonia (1640-1652). For this it is essential to follow the route of the Valencian adaptations to the military revolution in the matter of fortifications throughout the sixteenth century and compare them with those brought to Valencia in 1641 by the Marquis of Leganes and his engineers from the school of Milan.
Taide kulttuurien välisenä siltana : kansainvälinen lasten ja nuorten taidekilpailu ja -näyttely kansainvälisyyskasvattajana 1970-1990
2015
Miten taide ja taidekasvatus voi edistää kansainvälisyyskasvatusta? Mikä taiteessa ja taidekasvatuksessa mahdollistaa tämän kaltaisen toiminnan? Miten kansainvälisyyskasvatus on näkynyt vuonna 1971 perustetun Hyvinkään Kansainvälisen lasten ja nuorten taidekilpailun ja –näyttelyn taustalla vaikuttaneissa tavoitteissa? Miten kansainvälinen taidekilpailu ja -näyttely on toiminut kansainvälisyyskasvattajana? Näihin kysymyksiin etsin vastauksia tässä pro-gradu-tutkielmassani. Kansainvälisyyskasvatus tuli yleiseksi tavoitteeksi toisen maailmansodan jälkeen muodostetun YK:n ja sen kasvatus-, tiede- ja kulttuurijärjestön Unescon kehotuksissa. Etenkin Unescon vuoden 1974 suositus kehotti kasvattama…
The UK needs a sustainable strategy for COVID-19
2020
The UK is well into the second wave of COVID-19, with 60 051 lives lost to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to date, according to provisional data from the Office for National Statistics. Official UK Government data show that cases have been rising exponentially since late August, 2020, with increases across all regions in England in recent weeks.As of Nov 4, 2020, the UK had 25 177 confirmed daily cases. These are almost certainly underestimates as between Oct 17 and Oct 23, 2020, England alone had 52 000 estimated daily cases.Estimates of the effective reproduction number in England vary between 1.1 and 1.6.Daily deaths have doubled every fortnight si…