Denervation does not induce muscle atrophy through oxidative stress

Denervation leads to the activation of the catabolic pathways, such as the ubiquitin-proteasome and autophagy, resulting in skeletal muscle atrophy and weakness. Furthermore, denervation induces oxidative stress in skeletal muscle, which is thought to contribute to the induction of skeletal muscle atrophy. Several muscle diseases are characterized by denervation, but the molecular pathways contributing to muscle atrophy have been only partially described. Our study delineates the kinetics of activation of oxidative stress response in skeletal muscle following denervation. Despite the denervation-dependent induction of oxidative stress in skeletal muscle, treatments with anti-oxidant drugs do not prevent the reduction of muscle mass. Our results indicate that, although oxidative stress may contribute to the activation of the response to denervation, it is not responsible by itself of oxidative damage or neurogenic muscle atrophy

Dimension and impact of biases in funding for species and habitat conservation

Taxonomic and aesthetic biases permeate biodiversity conservation. We used the LIFE program-the European Union's funding scheme for the environment-to explore the economic dimension of biases in species-and habitat-level conservation. Between 1992 and 2020, animal species received three times more funding than plants. Within plants, species at northern latitudes, with broader ranges, and with blue/purple flowers received more funds regardless of their extinction risk. Conversely, species online popularity was only weakly positively associated with conservation expenditure. At the habitat-level, we found no relationship between expenditure and conservation status of the habitat. Our results can inform ways forward to achieve conservation goals that are comprehensive, sustainable, and cost-effective.Peer reviewe

Design of photoactivatable metallodrugs : selective and rapid light-induced ligand dissociation from half-sandwich [Ru([9]aneS3)(N–N′)(py)]2+ complexes

The synthesis of the inert Ru(II) half-sandwich coordination compounds, [Ru([9]aneS3)(bpy)(py)][PF6]2 (1, [9]aneS3 = 1,4,7-trithiacyclononane, bpy = 2,2′-bipyridine, py = pyridine), [Ru([9]aneS3)(en)(py)][PF6]2 (2, en = 1,2-diaminoethane), and [Ru([9]aneN3)(en)(dmso-S)][PF6]2 (3, [9]aneN3 = 1,4,7-triazacyclononane), is reported along with the X-ray crystal structure of 1. We investigated whether these complexes have photochemical properties which might make them suitable for use as pro-drugs in photochemotherapy. Complexes 1 and 2 underwent rapid (minutes) aquation with dissociation of the pyridine ligand in aqueous solution when irradiated with blue light (λ = 420 or 467 nm). The photodecomposition of 3 was much slower. All complexes readily formed adducts with 9-ethylguanine (9-EtG) when this model nucleobase was present in the photolysis solution. Similarly, complex 1 formed adducts with the tripeptide glutathione (GSH), but only when photoactivated. HPLC and MS studies of 1 showed that irradiation promoted rapid formation of 1:1 (major) and 1:2 (minor) adducts of the oligonucleotide d(ATACATGCTACATA) with the fragment {Ru([9]aneS3)(bpy)}2+. Density functional theory (DFT) calculations and time-dependent DFT reproduced the major features of the absorption spectra and suggested that the lowest-lying triplet state with 3MLCT character, which is readily accessible via intersystem crossing, might be responsible for the observed dissociative behavior of the excited states. These complexes are promising for further study as potential photochemotherapeutic agents

D3.1 - Architettura dell'infrastruttura 3DLab-Sicilia e del "liquid lab"

Questo documento definisce due elementi fondamentali per il Progetto 3DLab-Sicilia sui quali si costruiscono le numerose applicazioni e i casi d’uso applicativi che sono stati discussi con ampio dettaglio nel deliverable “D4.1 – Analisi dettagliata dei requisiti dei casi d’uso“. Tali elementi sono rappresentati da: l’infrastruttura del progetto, comprensiva dei relativi elementi hardware e software; il “liquid lab”. Un ulteriore punto di contatto tra il presente rapporto e il deliverable D4.1 è rappresentato dall’adozione condivisa trasversalmente della tassonomia dell’hardware e del software relativi al progetto 3DLab-Sicilia. Per la descrizione dettagliata della tassonomia in oggetto si rimanda alla Sezione 2.1 e all’Appendice 1 del deliverable D4.1. Il presente documento è organizzato come segue. La Sezione 2 tratta, insieme ad una introduzione ai contenuti e alle finalità del presente deliverable, la descrizione dello stato dell’arte delle soluzioni oggetto di analisi in queste pagine. La Sezione 3 dettaglia ad alto livello l’architettura dell’infrastruttura del progetto per la Realtà Virtuale nelle 3 sedi selezionate in 3DLab-Sicilia: Catania, presso SWING:IT; Palermo, presso lo IEMEST; e Troina (EN), presso l’IRCCS-OASI. Nella Sezione 4 la descrizione e l’analisi tecnica dell’infrastruttura sono illustrate approfonditamente, ponendo il fuoco sui diversi elementi compresi al suo interno. Sono state analizzate le caratteristiche tecniche delle VR CAVE e dei Visori per Realtà Virtuale (VR) nonché dei dispositivi per la Realtà Aumentata (AR), i laser scanner 3D per i rilievi, i droni, il videocapillaroscopio e l’archivio digitale. La Sezione 5 dettaglia, infine, gli obiettivi, l’architettura e le caratteristiche del “liquid lab” che sarà realizzato nell’ambito del progetto

Heat Stress Enhances the Accumulation of Polyadenylated Mitochondrial Transcripts in Arabidopsis thaliana

Background: Polyadenylation of RNA has a decisive influence on RNA stability. Depending on the organisms or subcellular compartment, it either enhances transcript stability or targets RNAs for degradation. In plant mitochondria, polyadenylation promotes RNA degradation, and polyadenylated mitochondrial transcripts are therefore widely considered to be rare and unstable. We followed up a surprising observation that a large number of mitochondrial transcripts are detectable in microarray experiments that used poly(A)-specific RNA probes, and that these transcript levels are significantly enhanced after heat treatment. Methodology/Principal Findings: As the Columbia genome contains a complete set of mitochondrial genes, we had to identify polymorphisms to differentiate between nuclear and mitochondrial copies of a mitochondrial transcript. We found that the affected transcripts were uncapped transcripts of mitochondrial origin, which were polyadenylated at multiple sites within their 39region. Heat-induced enhancement of these transcripts was quickly restored during a short recovery period. Conclusions/Significance: Our results show that polyadenylated transcripts of mitochondrial origin are more stable than previously suggested, and that their steady-state levels can even be significantly enhanced under certain conditions. As many microarrays contain mitochondrial probes, due to the frequent transfer of mitochondrial genes into the genome

Anxiety and depression in keratotic oral lichen planus: a multicentric study from the SIPMO

Objectives: Oral lichen planus with exclusive keratotic reticular, papular, and/or plaque-like lesions (K-OLP) is a clinical pattern of OLP that may be associated with a complex symptomatology and psychological alteration. The aim of the study was to evaluate the prevalence of anxiety (A) and depression (D) in patients with K-OLP, analyzing the potential predictors which can affect mental health status. Methods: Three hundred K-OLP patients versus 300 healthy controls (HC) were recruited in 15 Italian universities. The Numeric Rating Scale (NRS), Total Pain Rating Index (T-PRI), and Hamilton Rating Scales for Depression and for Anxiety (HAM-D and HAM-A) were administered. Results: The K-OLP patients showed statistically higher scores in the NRS, T-PRI, HAM-D, and HAM-A compared with the HC (p-value < 0.001**). A and D were found in 158 (52.7%) and 148 (49.3%) K-OLP patients. Strong linear correlations were identified between HAM-A, HAM-D, NRS, T-PRI, and employment status and between HAM-D, HAM-A, NRS, T-PRI, employment status, and female gender. Multivariate logistic regression revealed that HAM-D and HAM-A showed the greatest increase in the R2 value for A and D in the K-OLP patients, respectively (DR2 = 55.5% p-value < 0.001**; DR2 = 56.5% p-value < 0.001**). Conclusions: The prevalence of A and D is higher in the K-OLP patients compared with the HC, also found in K-OLP subjects without pain, suggesting that the processing of pain may be in a certain way independent of the processing of mood. Clinical relevance: Mood disorders and pain assessment should be carefully performed in relation to K-OLP to obtain a complete analysis of the patients

High familial burden of cancer correlates with improved outcome from immunotherapy in patients with NSCLC independent of somatic DNA damage response gene status

Family history of cancer (FHC) is a hallmark of cancer risk and an independent predictor of outcome, albeit with uncertain biologic foundations. We previously showed that FHC-high patients experienced prolonged overall (OS) and progression-free survival (PFS) following PD-1/PD-L1 checkpoint inhibitors. To validate our findings in patients with NSCLC, we evaluated two multicenter cohorts of patients with metastatic NSCLC receiving either first-line pembrolizumab or chemotherapy. From each cohort, 607 patients were randomly case-control matched accounting for FHC, age, performance status, and disease burden. Compared to FHC-low/negative, FHC-high patients experienced longer OS (HR 0.67 [95% CI 0.46-0.95], p\u2009=\u20090.0281), PFS (HR 0.65 [95% CI 0.48-0.89]; p\u2009=\u20090.0074) and higher disease control rates (DCR, 86.4% vs 67.5%, p\u2009=\u20090.0096), within the pembrolizumab cohort. No significant associations were found between FHC and OS/PFS/DCR within the chemotherapy cohort. We explored the association between FHC and somatic DNA damage response (DDR) gene alterations as underlying mechanism to our findings in a parallel cohort of 118 NSCLC, 16.9% of whom were FHC-high. The prevalence of\u2009 65\u20091 somatic DDR gene mutation was 20% and 24.5% (p\u2009=\u20090.6684) in FHC-high vs. FHC-low/negative, with no differences in tumor mutational burden (6.0 vs. 7.6 Mut/Mb, p\u2009=\u20090.6018) and tumor cell PD-L1 expression. FHC-high status identifies NSCLC patients with improved outcomes from pembrolizumab but not chemotherapy, independent of somatic DDR gene status. Prospective studies evaluating FHC alongside germline genetic testing are warranted

Characterisation of unusual transcript classes in Arabidopsis thaliana

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Periodic Tables: an interdisciplinary proposal between chemistry and literature

This paper presents an example of interdisciplinary teaching between chemistry and literature. Our starting point was the analysis of Mendeleev’s periodic table and the collection of short stories “Il sistema periodico”, by Primo Levi, a chemist himself before becoming a writer. The main aim of the paper is to propose a dialogue between two different views of the world, trying to highlight the questions that both disciplines arise. i.e. in how many ways can we read and represent the world around us? How do we respond to our need for order? Faced with questions like these, chemistry and literature do not appear far from each other. Trying to work in this interdisciplinary perspective, the teaching proposal is organised in four steps: a thematic approach to Levi’s text; a presentation of the founding principles of Mendeleev’s table; a a digital processing in line with the methods of digital humanities; some final observations that can be shared with students who must be able to consider and tackle them.L’articolo presenta una proposta didattica interdisciplinare tra chimica e letteratura. Parte da due punti di riferimento: la tavola periodica di Mendeleev e la raccolta di racconti “Il sistema periodico”, di Primo Levi, chimico lui stesso prima ancora di diventare scrittore. L’obiettivo principale è quello provare a far dialogare due diverse visioni del mondo, cercando di evidenziare le domande che entrambe le discipline pongono: in quanti modi possiamo leggere e rappresentare il mondo che ci circonda? Come rispondiamo al nostro bisogno di dargli un ordine? Di fronte a domande come queste, la chimica e la letteratura non sembrano così distanti tra loro. Cercando di lavorare in questo spazio interdisciplinare, la proposta didattica è organizzata in quattro fasi: una lettura tematica del testo di Levi; una presentazione dei principi fondanti della tavola di Mendeleev; un’elaborazione digitale in ambito di Digital Humanities; alcune considerazioni finali con cui vorremmo che gli studenti e le studentesse si confrontassero

Models of molecular photocatalysts for water oxidation: Strategies for conjugating the Ru(bda) fragment (bda\ua0=\ua02,2\u2032-bipyridine-6,6\u2032-dicarboxylate) to porphyrin photosensitizers

Model dyads, in which the Ru(bda) water oxidation catalyst (WOC) is connected to a porphyrin, were prepared following two different modular strategies: i) the direct linkage approach, in which porphyrins bearing peripheral pyridyl rings are bound to the {Ru(bda)} fragment as axial ligands, and ii) the metal-containing ligand approach, in which symmetrical trans-[Ru(bda)(L)2] or unsymmetrical trans-[Ru(bda)(L)(pic)] compounds (L = bifunctional pyridyl linker), are axially bound to metalloporphyrins. Both synthetic strategies are modular and thus rather flexible in nature. As proofs of principle, the following Ru(bda) \u2013 porphyrin dyads are described: trans-[Ru(bda)(4\u2032 -MPyP)2] (2, 4\u2032 -MPyP = 5-(4\u2032 -pyridyl)-10,15,20-phenylporphyrin), and the sandwich compounds [trans-Ru(bda)(4,4\u2032 -bpy)2{Ru(CO)(TPP)}2] (5) and [trans-Ru(bda)(4,4\u2032 -bpy)2(6Zn)]2 (7), where 6Zn is the porphyrin metallacycle [trans,cis,cis-RuCl2(CO)2(Zn c54\u2032 -cisDPyP)]2 (4\u2032 -cisDPyP = 5,10-(4\u2032 -pyridyl)-15,20- (phenyl)-porphyrin