DNA Damage Triggers a New Phase in Neurodegeneration.

Subcellular compartmentalization contributes to the organization of a plethora of molecular events occurring within cells. This can be achieved in membraneless organelles generated through liquid-liquid phase separation (LLPS), a demixing process that separates and concentrates cellular reactions. RNA is often a critical factor in mediating LLPS. Recent evidence indicates that DNA damage response foci are membraneless structures formed via LLPS and modulated by noncoding transcripts synthesized at DNA damage sites. Neurodegeneration is often associated with DNA damage, and dysfunctional LLPS events can lead to the formation of toxic aggregates. In this review, we discuss those gene products involved in neurodegeneration that undergo LLPS and their involvement in the DNA damage response

SARS-CoV-2 infection induces DNA damage, through CHK1 degradation and impaired 53BP1 recruitment, and cellular senescence

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the RNA virus responsible for the coronavirus disease 2019 (COVID-19) pandemic. Although SARS-CoV-2 was reported to alter several cellular pathways, its impact on DNA integrity and the mechanisms involved remain unknown. Here we show that SARS-CoV-2 causes DNA damage and elicits an altered DNA damage response. Mechanistically, SARS-CoV-2 proteins ORF6 and NSP13 cause degradation of the DNA damage response kinase CHK1 through proteasome and autophagy, respectively. CHK1 loss leads to deoxynucleoside triphosphate (dNTP) shortage, causing impaired S-phase progression, DNA damage, pro-inflammatory pathways activation and cellular senescence. Supplementation of deoxynucleosides reduces that. Furthermore, SARS-CoV-2 N-protein impairs 53BP1 focal recruitment by interfering with damage-induced long non-coding RNAs, thus reducing DNA repair. Key observations are recapitulated in SARS-CoV-2-infected mice and patients with COVID-19. We propose that SARS-CoV-2, by boosting ribonucleoside triphosphate levels to promote its replication at the expense of dNTPs and by hijacking damage-induced long non-coding RNAs' biology, threatens genome integrity and causes altered DNA damage response activation, induction of inflammation and cellular senescence.Gioia, Tavella et al. show that severe acute respiratory syndrome coronavirus 2 causes DNA damage through CHK1 degradation and impairs 53BP1 recruitment to DNA lesions. The induced DNA damage is associated with expression of pro-inflammatory cytokines and senescence markers

WOOD-UP

The fundamental vision of the WOOD-UP project was to develop existing wood gasification plants in South Tyrol towards a polygenerative use in order to be able to produce not only energy but also high-quality charcoal (biochar) for the improvement of soil fertility and for climate protection. The project, funded by the European Regional Development Fund ERDF 2014–2020, was implemented by the Free University of Bolzano together with the Laimburg Research Centre. Based on the life cycle analysis (LCA) or scenario analysis of the entire production chain of wood gasification, strengths and weaknesses of the existing systems were identified with regard to their impact on the environment. Thanks to the results obtained, a number of suggestions for improvement could be formulated.; Il miglioramento verso un assetto poligenerativo degli attuali impianti altoatesini di gassificazione della biomassa legnosa, dove oltre all’energia si possa produrre biochar di qualità da impiegare in agricoltura come ammendante con effetti positivi sulla fertilità dei suoli e sulla mitigazione dei cambiamenti climatici è la visione che ha sostenuto il progetto WOOD-UP. Il progetto, finanziato con fondi FESR 2014-2020, ha visto la collaborazione tra la Libera Università di Bolzano e il Centro di Sperimentazione Laimburg. L’analisi del ciclo di vita e di scenario dell’intera filiera di gassificazione ha evidenziato elementi di forza e di debolezza dell’attuale filiera in termini di impatti ambientali e ha permesso di avanzare proposte di miglioramento sulla base dei risultati ottenuti dalla sperimentazione. ; Grundlegende Vision des Projektes WOOD-UP war die Entwicklung der bestehenden Holzvergasungsanlagen in Südtirol hin zu einer polygenerativen Nutzung, um neben Energie auch hochwertige Holzkohle (Biochar) zur Verbesserung der Bodenfruchtbarkeit und zum Klimaschutz erzeugen zu können. Das mit Mitteln aus dem Europäischen Fonds für regionale Entwicklung EFRE 2014–2020 finanzierte Projekt wurde von der Freien Universität Bozen gemeinsam mit dem Versuchszentrum Laimburg umgesetzt. Anhand der Lebenszyklusanalyse (LCA) bzw. der Szenarioanalyse der gesamten Produktionskette der Holzvergasung wurden Stärken und Schwächen der bestehenden Systeme hinsichtlich ihrer Auswirkungen auf die Umwelt aufgezeigt. Dank der erzielten Versuchsergebnisse konnte eine Reihe von Verbesserungsvorschlägen formuliert werden

Selective serotonin reuptake inhibitors and nutraceutical combination in major depression disorder: A case-control study

6noreservedIntroduction: Major depressive disorder (MDD) is a primary cause of disability in adults, affecting daily functioning and decreasing quality of life. The focus on the role of nutraceuticals as adjunctive treatments to improve antidepressant response is paying growing interest. The study aims to compare the antidepressants response in the utilization of selective serotonin reuptake inhibitors (SSRIs) versus a combination of SSRIs and nutraceutical supplements based on S-Adenosyl methionine (SAMe), N-acetylcysteine (NAC) and folate in terms of efficacy and tolerability. Methods: A casecontrol study was carried out between March 2018 and September 2019. Cases and controls were evaluated through the following scales: Hospital Anxiety Depression Scale (HADS); Clinical Global Impression (CGI); Patient Global Impression of Improvement (PGI-I); Antidepressant Adverse Events checklist (AES). Results: A significant difference between the two groups of patients emerged at T1 in the HADS-A (p = 0.004) score and in the CGI score (p = 0.01), due to a major improvement in patients with a nutraceutical co-prescription. At T3 a significant statistical difference emerged, showing a greater improvement at HADS-D in the case group (p = 0.006), confirmed by a higher remission rate in patients taking a nutraceutical co-prescription. No differences in terms of adverse events emerged. Conclusion: This study shows promising data about the role of nutraceuticals as adjunctive treatment in major depressive disorder to improve SSRIs efficacy, with good tolerability. More data are needed to confirm these results, particularly about the role of nutraceuticals to decrease the latency of SSRIs response. Psychopharmacology Bulletin. 2021;51(4):31–39. OT FOR REPR.mixedIelmini M.; Caselli I.; Ceccon F.; Diurni M.; Poloni N.; Callegari C.Ielmini, M.; Caselli, I.; Ceccon, F.; Diurni, M.; Poloni, N.; Callegari, C

Medically unexplained physical symptoms in hospitalized patients: A 9-year retrospective observational study

Introduction: \u201cMedically Unexplained Physical Symptoms\u201d (MUPS) defines a subgroup of patients presenting physical symptoms of unclear origin. The study aims to profile clinical and socio-demographic characteristics of patients with MUPS. Materials and Methods: This 9-years observational retrospective study assesses all patients admitted between 2008 and 2016 in the divisions of neurology and gastroenterology. Socio-demographic and clinical variables were evaluated: gender, age, diagnosis or diagnostic hypothesis, presence of psychiatric comorbidities, psychiatric evaluation, pharmacological treatment, number of admissions/visits. Results: Among 2,479 neurological patients 10.1% presented MUPS. Patients were more frequently women (63.5%), with a mean age of about 50 years. Reported symptoms were headache (22.6%), seizures (8.7%), vertigo (5.9%), fibromyalgia (5.5%), paresthesia (5.1%), visual disturbances (5.1%), amnesia (3.9%). The diagnosis was somatoform disorder in 6.3% of cases, conversion disorder in 2.7%, and somatic symptom disorder in 1.5% only. 2,560 outpatients were evaluated in gastroenterology division. 9.6% (n = 248) of patients had MUPS; 62.1% of them were women. The most affected age group ranged between 15 and 45 years. The most frequent diagnoses were functional abdominal pain (50%), dysmotility-like dyspepsia (26.6%), irritable bowel syndrome (10.4%), meteorism of unknown cause (2.4%), hiccup (1.6%), burning mouth syndrome (1.2%). No patients received a diagnosis of somatic symptom disorder. Discussion: Patients with MUPS are more often women, of middle age, with self-referred specific symptomatology. While neurological patients received a diagnostic-therapeutic approach in line with the literature, gastroenterological patients mainly received antipsychotics. A more comprehensive assessment and a development of psychoeducational interventions are needed to improve patients' quality and quantity of life