Involvement of proteasome activation

Alzheimer's disease (AD) is the most common form of dementia worldwide, characterized by a progressive decline in a variety of cognitive and non-cognitive functions. The amyloid beta protein cascade hypothesis places the formation of amyloid beta protein aggregates on the first position in the complex pathological cascade leading to neurodegeneration, and therefore AD might be considered to be a protein-misfolding disease. The Ubiquitin Proteasome System (UPS), being the primary protein degradation mechanism with a fundamental role in the maintenance of proteostasis, has been identified as a putative therapeutic target to delay and/or to decelerate the progression of neurodegenerative disorders that are characterized by accumulated/aggregated proteins. The purpose of this study was to test if the activation of proteasome in vivo can alleviate AD pathology. Specifically by using two compounds with complementary modes of proteasome activation and documented antioxidant and redox regulating properties in the 5xFAD transgenic mice model of AD, we ameliorated a number of AD related deficits. Shortly after proteasome activation we detected significantly reduced amyloid-beta load correlated with improved motor functions, reduced anxiety and frailty level. Essentially, to our knowledge this is the first report to demonstrate a dual activation of the proteasome and its downstream effects. In conclusion, these findings open up new directions for future therapeutic potential of proteasome-mediated proteolysis enhancement.publishersversionpublishe

Μουσικοθεατρικά έργα του Λουί Άντριεσσεν: η συνεργασία με τους Πήτερ Γκρίναγουεϊ και Χαλ Χάρτλεϊ

Η εργασία αυτή εστιάζει στα έργα του σύγχρονου Ολλανδού συνθέτη Λουί Άντριεσσεν που δημιούργησε καθώς συνεργάστηκε με τους πρωτοποριακούς σκηνοθέτες Πήτερ Γκρίναγουεϊ και Χαλ Χάρτλεϊ. Στα έργα αυτά επιχειρούνται, μεταξύ άλλων, νέοι συσχετισμοί μεταξύ της μουσικής και των άλλων τεχνών, σκηνική χρήση πολυμέσων και αλληλεπιδράσεις της σκηνικής αναπαράστασης τόσο με τις κινηματογραφικές προβολές όσο και με βιντεοπροβολές. Στη δεκαετία του 1990 ο συνθέτης συνεργάστηκε τρεις φορές με τον Πήτερ Γκρίναγουεϊ: αρχικά στην τηλεταινία μικρού μήκους M is for Man, Music, Mozart (1991) και στη συνέχεια στις όπερες Rosa. A Horse Drama (1994) και Writing to Vermeer (1999). Με τον Χαλ Χάρτλεϊ συνεργάστηκε στην πολυμεσική όπερα La Commedia (2008), η οποία αποτελεί μεταφορά της Θείας Κωμωδίας του Δάντη. Και οι τρεις αυτές όπερες είναι μη συμβατικές οπερατικές παραγωγές της Εθνικής Ολλανδικής Όπερας και έχουν ως κοινό γνώρισμα τον συνδυασμό του κινηματογράφου με τη μουσική και το θέατρο.This paper focuses on the works of the contemporary Dutch composer Louis Adriessen that he created while collaborating with the pioneering filmmakers Peter Greenaway and Hal Hartley. These music theatre works attempt, among other things, new correlations between music and other arts, stage use of multimedia and interactions of stage representation with both film and video projections. In the 1990s the composer collaborated three times with Peter Grinaway: first in the short film "M is for Man, Music, Mozart" (1991) and then in the operas "Rosa. A Horse Drama" (1994) and "Writing to Vermeer" (1999). With Hal Hartley he collaborated on the multimedia opera "La Commedia" (2008), which is an adaptation of Dante's "Divine Comedy". All three of these operas are unconventional operatic productions of the Dutch National Opera and share the common feature of combining film with music and theatre

Greek renal nurses' attitudes towards death

This study aims to assess how Greek renal nurses feel about death and examine any relationships between their attitudes and demographic factors. Design: Descriptive quantitative study. The sample comprised of 49 nurses. Methodology: Voluntary and anonymous completion of the Death Attitude Profile-Revised and a demographic questionnaire. Results: 44 respondents were female and 5 were male with a mean age of 25.80 years. The mean nursing experience was 10.9 years. Nursing experience and age were the variables most likely to predict nurses' attitudes towards death. Nurses with specific education on palliative care had less difficulty talking about death and dying and did not have a fear of death. The Hospital-based teams (known as palliative care teams, supportive care teams or symptom assessment teams) had statistically significant different relationships with fear of death and neutral acceptance scores. Conclusions: It is recommended to include education on death and care of the dying in the nursing degree course in order for nurses who are giving terminal phase patient care to be better able deal with issues that death evolves

R2d2 drives selfish sweeps in the house mouse

A selective sweep is the result of strong positive selection driving newly occurring or standing genetic variants to fixation, and can dramatically alter the pattern and distribution of allelic diversity in a population. Population-level sequencing data have enabled discoveries of selective sweeps associated with genes involved in recent adaptations in many species. In contrast, much debate but little evidence addresses whether "selfish" genes are capable of fixation - thereby leaving signatures identical to classical selective sweeps - despite being neutral or deleterious to organismal fitness. We previously described R2d2, a large copy-number variant that causes nonrandom segregation of mouse Chromosome 2 in females due to meiotic drive. Here we show population-genetic data consistent with a selfish sweep driven by alleles of R2d2 with high copy number (R2d2) in natural populations. We replicate this finding in multiple closed breeding populations from six outbred backgrounds segregating for R2d2 alleles. We find that R2d2 rapidly increases in frequency, and in most cases becomes fixed in significantly fewer generations than can be explained by genetic drift. R2d2 is also associated with significantly reduced litter sizes in heterozygous mothers, making it a true selfish allele. Our data provide direct evidence of populations actively undergoing selfish sweeps, and demonstrate that meiotic drive can rapidly alter the genomic landscape in favor of mutations with neutral or even negative effects on overall Darwinian fitness. Further study will reveal the incidence of selfish sweeps, and will elucidate the relative contributions of selfish genes, adaptation and genetic drift to evolution

Patients Hospitalized for COVID-19 in the Periods of Delta and Omicron Variant Dominance in Greece: Determinants of Severity and Mortality

Background: Coronavirus disease 2019 (COVID-19) has been a pandemic since 2020, and depending on the SARS-CoV-2 mutation, different pandemic waves have been observed. The aim of this study was to compare the baseline characteristics of patients in two phases of the pandemic and evaluate possible predictors of mortality. Methods: This is a retrospective multicenter observational study that included patients with COVID-19 in 4 different centers in Greece. Patients were divided into two groups depending on the period during which they were infected during the Delta and Omicron variant predominance. Results: A total of 979 patients (433 Delta, 546 Omicron) were included in the study (median age 67 years (54, 81); 452 [46.2%] female). Compared to the Omicron period, the patients during the Delta period were younger (median age [IQR] 65 [51, 77] vs. 70 [55, 83] years, p p = 0.001), had higher procalcitonin levels (ng/mL): 0.08 [0.05, 0.17] vs. 0.06 [0.02, 0.16], p = 0.005, ferritin levels (ng/mL): 301 [159, 644] vs. 239 [128, 473], p = 0.002, C- reactive protein levels (mg/L): 40.4 [16.7, 98.5] vs. 31.8 [11.9, 81.7], p = 0.003, and lactate dehydrogenase levels (U/L): 277 [221, 375] vs. 255 [205, 329], p p p 2/FiO2 ratio on admission were identified as independent predictors of mortality for patients in the Omicron period. Conclusions: In the Omicron wave, patients were older with a higher number of comorbidities, but patients with the Delta variant had more severe disease and a longer duration of hospitalization

Trusts. A Comparative Study.

International audienceA selective sweep is the result of strong positive selection driving newly occurring or standing genetic variants to fixation, and can dramatically alter the pattern and distribution of allelic diversity in a population. Population-level sequencing data have enabled discoveries of selective sweeps associated with genes involved in recent adaptations in many species. In contrast, much debate but little evidence addresses whether "selfish" genes are capable of fixation-thereby leaving signatures identical to classical selective sweeps-despite being neutral or deleterious to organismal fitness. We previously described R2d2, a large copy-number variant that causes nonrandom segregation of mouse Chromosome 2 in females due to meiotic drive. Here we show population-genetic data consistent with a selfish sweep driven by alleles of R2d2 with high copy number (R2d2(HC)) in natural populations. We replicate this finding in multiple closed breeding populations from six outbred backgrounds segregating for R2d2 alleles. We find that R2d2(HC) rapidly increases in frequency, and in most cases becomes fixed in significantly fewer generations than can be explained by genetic drift. R2d2(HC) is also associated with significantly reduced litter sizes in heterozygous mothers, making it a true selfish allele. Our data provide direct evidence of populations actively undergoing selfish sweeps, and demonstrate that meiotic drive can rapidly alter the genomic landscape in favor of mutations with neutral or even negative effects on overall Darwinian fitness. Further study will reveal the incidence of selfish sweeps, and will elucidate the relative contributions of selfish genes, adaptation and genetic drift to evolution