Hematopoietic Stem/Progenitor Cells Express Functional Mitochondrial Energy-Dependent Cystic Fibrosis Transmembrane Conductance Regulator

Bone marrow-derived hematopoietic stem/progenitor cells (HSPCs) encompass a wide array of cell subsets with different capacities of engraftment and injured tissue-regenerating potential. The characterization/isolation of the stem cell subpopulations represents a major challenge to improve the efficacy of transplantation protocols used in regenerative medicine. Cystic fibrosis (CF) is one of the diseases whose hope of cure relies on the successful application of cell-based gene therapy. This study was aimed at characterizing murine HSPCs on the basis of their bioenergetic competence and CF transmembrane conductance regulator (CFTR) expression. Positively immunoselected Sca-1(+) HSPCs encompassed 2 populations distinguished by their different size, Sca-1 expression and mitochondrial content. The smaller were the cells, the higher was Sca-1 expression and the lower was the intracellular density of functional mitochondria. Reverse transcription-polymerase chain reaction and western blotting revealed that HSPCs expressed CFTR mRNA and protein, which was also functional, as assessed by spectrofluorimetric and patch-clamp techniques. Inhibition of mitochondrial oxidative phosphorylation by oligomycin resulted in a 70% decrease of both the intracelluar adenosine triphosphate content and CFTR-mediated channel activity. Finally, HSPCs with lower Sca-1 expression and higher mitochondrial content displayed higher CFTR levels. Our findings identify 2 subpopulations in HSPCs and unveil a so-far unappreciated relationship between bioenergetic metabolism and CFTR in HSPC biology

Molecular epidemiology of meticillin-resistant Staphylococcus aureus in Italian cystic fibrosis patients: A national overview

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On the stability of standing waves of Klein-Gordon equations in a semiclassical regime

We investigate the orbital stability and instability of standing waves for two classes of Klein-Gordon equations in the semi-classical regime.Comment: 9 page

Clobetasol promotes neuromuscular plasticity in mice after motoneuronal loss via sonic hedgehog signaling, immunomodulation and metabolic rebalancing

Motoneuronal loss is the main feature of amyotrophic lateral sclerosis, although pathogenesis is extremely complex involving both neural and muscle cells. In order to translationally engage the sonic hedgehog pathway, which is a promising target for neural regeneration, recent studies have reported on the neuroprotective effects of clobetasol, an FDA-approved glucocorticoid, able to activate this pathway via smoothened. Herein we sought to examine functional, cellular, and metabolic effects of clobetasol in a neurotoxic mouse model of spinal motoneuronal loss. We found that clobetasol reduces muscle denervation and motor impairments in part by restoring sonic hedgehog signaling and supporting spinal plasticity. These effects were coupled with reduced pro-inflammatory microglia and reactive astrogliosis, reduced muscle atrophy, and support of mitochondrial integrity and metabolism. Our results suggest that clobetasol stimulates a series of compensatory processes and therefore represents a translational approach for intractable denervating and neurodegenerative disorders

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Didattica come metodo. Progettare la conservazione tra conoscenza e innovazione

La didattica del restauro è affrontata in questa sede riflettendo, in particolare, sul progetto e le modalità della sua trasmissione. Se ne analizzano gli apparati di metodo e, segnatamente, i contenuti esegetici ed ermeneutici, ricostruendone il ruolo assunto nella formazione dell’architetto ‘generalista’ e del laureato in Design e Comunicazione. Ai fini di una valutazione epistemologica, atta a definirne anche i caratteri e le implicazioni didattiche, i temi indicati sono ricostruiti, in primis, alla luce dell’evoluzione che il progetto di restauro e il competente impianto di metodo hanno registrato dagli anni Ottanta all’attualità. Rilevandone le proprietà che ne sostanziano oggi natura, logiche e finalità ne sono, segnatamente, investigati i rapporti, ontologicamente, intrecciati con la conoscenza nelle sue varie fasi e i riflessi della loro trasmissione. Attraverso il rilievo riconosciuto all’esercizio esegetico e ai suoi strumenti nel quadro dell’iter formativo descritto, anche in forza della collaborazione con le altre discipline si evidenziano, inoltre, le ricadute sviluppate nei futuri architetti dall’acquisizione di simili competenze, soprattutto, in quanto driver delle responsabilità etiche, culturali e sociali implicite nella professione. Nella seconda parte gli argomenti citati sono inquadrati nella prospettiva della funzione che l’esperienza del progetto di conservazione assolve per gli studenti di Design e Comunicazione. Partendo dalle affinità che le culture del restauro e del design manifestano, specie, nella comune attenzione per la materia e per le regole che ne sovraintendono la modifica, si esplora il valore che l’esegesi e la restituzione della realtà architettonica in quanto “materia” - in primis, la lettura diretta – esprimono nell’indicato contesto. Constatata la durevole distanza tra le acquisizioni teoriche e la concreta applicazione di procedure finalizzate alla comprensione del dato reale, l’esercizio del progetto di conservazione invera, difatti, per questi studenti un’occasione preziosa per imparare a riconoscere e interpretare i processi di produzione, cioè, i contenuti fondanti di una figura professionale così orientata. La connotazione analitica e critica del restauro, la propensione all’ascolto paziente, anche mediante le sinergie sviluppate con altri settori scientifici, l’approccio al progetto ‘umile’ e ‘aperto’, capace di esprimere i legami di continuità tra memoria e innovazione governando la complessità e il cambiamento sostanziano, infine, i fondamentali ingredienti di metodo che, gli autori, riconoscono alla didattica di settore. Più che nozioni di un sapere specialistico, destinato poi alla dispersione se non adeguatamente coltivato e aggiornato, tali acquisizioni esprimono, infatti, le basi culturali ed etiche del rispetto per il patrimonio e l’ambiente, dunque, le attitudini che, sempre, dovrebbero orientare l’operatività di architetti e designer

"Conservazione e valorizzazione dei beni culturali: il caso della Comunità Montana Alento-Montestella (SA"),

Pubblicazione realizzata nell'ambito del progetto ITACA (Interventi di Trasferimento di Abilità e Competenze Ambientali), cofinanziato dal Fonso Sociale Europeo - P.O.R. Sardegna 2000-2006 Asse III, Misura 3.9 - Formazione specialistica sulla tutela del paesaggio e adeguamento delle competenze della pubblica amministrazione, promosso dalla Regione Sardegna e coordinato dalle Università di Sassari e Cagliari

Compositions comprising aqueous dispersions of crosslinkable polyurethanes having perfluoropolyether structures

Dispersione di polimeri fluorurati per trattamenti idro-oleorepellenti di tessut