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Quercetin (QUER) is a natural polyphenolic compound endowed with beneficial properties for human health, with anti-aging effects. However, although this flavonoid is commercially available as a nutraceutical, target molecules/pathways underlying its pro-longevity potential have yet to be fully clarified. Here, we investigated QUER activity in yeast chronological aging, the established model for simulating the aging of postmitotic quiescent mammalian cells. We found that QUER supplementation at the onset of chronological aging, namely at the diauxic shift, significantly increases chronological lifespan (CLS). Consistent with the antioxidant properties of QUER, this extension takes place in concert with a decrease in oxidative stress. In addition, QUER triggers substantial changes in carbon metabolism. Specifically, it promotes an enhancement of a pro-longevity anabolic metabolism toward gluconeogenesis due to improved catabolism of C2 by-products of yeast fermentation and glycerol. The former is attributable to the Sir2-dependent activity of phosphoenolpyruvate carboxykinase and the latter to the L-glycerol 3-phosphate pathway. Such a combined increased supply of gluconeogenesis leads to an increase in the reserve carbohydrate trehalose, ensuring CLS extension. Moreover, QUER supplementation to chronologically aging cells in water alone amplifies their long-lived phenotype. This is associated with intracellular glycerol catabolism and trehalose increase, further indicating a QUER-specific influence on carbon metabolism that results in CLS extension.

The intensity and frequency of coral bleaching events have increased worldwide especially due to thermal stress and seawater pollution. Although it has been observed that metal concentration in seawater can affect the coral’s ability to adopt cellular defensive mechanisms to counteract bleaching, more investigations are needed to better understand the role of metals in coral physiology. In this study, we analyzed the individual and combined effects of prolonged heat stress and manganese (Mn) and iron (Fe) enrichments at the cellular level on the coral Stylophora pistillata. Thermal stress caused an up-regulation in the expression of the host Heat shock proteins (Hsps) 60 and 70, which showed a parallel pattern of modulation in all treatments, as well as an increase of lipid peroxidation (LPO) in the holobiont. Fe enrichment did not induce any change in Hsp expression or in the oxidative status of the corals both at the ambient temperature of 26°C or at increased temperature, suggesting that Fe didn’t seem to play a role in mitigating the cellular damages and the coral bleaching. Mn or MnFe enrichment at 26°C seemed to increase the oxidative stress in zooxanthellae, since high LPO and glutathione reductase (GR) levels were recorded, but it did not cause any effect on polyp Hsp expression, probably due to the antioxidant action of GR. With the temperature increase, Mn enrichments prevented any increase in Hsp levels and caused a significant decrease of LPO and GR activity, strengthening a previous hypothesis suggesting that Mn could mitigate the negative cellular effects produced by the thermal stress.

The single-celled yeast Saccharomyces cerevisiae is one of the most valuable laboratory models that has been used successfully to identify factors and pathways involved in several cellular processes, the counterparts of which are evolutionarily conserved. Furthermore, it is also a powerful tool for analyzing the effects of molecules of nutraceutical interest with the view of leading to human health benefits and improving the quality of aging. In this context, we present some of the methods that have allowed us to assess the beneficial influence of a form of vitamin B3, namely nicotinamide, on mitochondrial functionality during yeast chronological aging. Mitochondrial dysfunctions are considered to be hallmarks of aging, and of several metabolic and neurodegenerative diseases. More specifically, these methods concern the determination of the respiratory parameters in intact cells in order to evaluate the efficiency of mitochondrial respiration in concert with the risk of superoxide anion (O2−) production, which results from inefficient respiration. In addition, we describe fluorescent staining specific for O2− detection and mitochondrial membrane potential, as well as a simple clonogenic assay based on the ability of cells to grow on a carbon source that requires a functional mitochondrial metabolism.

Nicotinamide, nicotinic acid and nicotinamide riboside are vitamin B3 precursors of NAD+ in the human diet. NAD+ has a fundamental importance for cellular biology, that derives from its essential role as a cofactor of various metabolic redox reactions, as well as an obligate co-substrate for NAD+-consuming enzymes which are involved in many fundamental cellular processes including aging/longevity. During aging, a systemic decrease in NAD+ levels takes place, exposing the organism to the risk of a progressive inefficiency of those processes in which NAD+ is required and, consequently, contributing to the age-associated physiological/functional decline. In this context, dietary supplementation with NAD+ precursors is considered a promising strategy to prevent NAD+ decrease and attenuate in such a way several metabolic defects common to the aging process. The metabolism of NAD+ precursors and its impact on cell longevity have benefited greatly from studies performed in the yeast Saccharomyces cerevisiae, which is one of the most established model systems used to study the aging processes of both proliferating (replicative aging) and non-proliferating cells (chronological aging). In this review we summarize important aspects of the role played by nicotinamide, nicotinic acid and nicotinamide riboside in NAD+ metabolism and how each of these NAD+ precursors contribute to the different aspects that influence both replicative and chronological aging. Taken as a whole, the findings provided by the studies carried out in S. cerevisiae are informative for the understanding of the complex dynamic flexibility of NAD+ metabolism, which is essential for the maintenance of cellular fitness and for the development of dietary supplements based on NAD+ precursors.

C’è una vulgata sulla “latitanza” della sintassi nello strutturalismo, in particolare europeo, e più ampiamente nei modelli europei di teoria linguistica che merita di essere vagliata nella sua attendibilità. Tra la fine dell’Ottocento e i primi del Novecento, soprattutto in ambiente germanofono, la sintassi venne infatti lungamente scrutata o avvistata come cruciale,a partire da più ambiti disciplinari, spesso fra loro irrelati e ben al di là dell’incipiente strutturalismo: dalla psicologia, dalla logica, dalla filosofia, dalla grammatica, tramille distinguo e un forte impegno di categorizzazione. Se l’obiettivo in Bühler è il monitoraggio del pensiero nel suo nascere, tra i praghesi l’intento è quello di osservare da vicino (modello del codice) le diverse risorse offerte da lingue diverse per l’organizzazione inequivoca e quanto più possibile libera dell’espressione, così come di monitorare (modello della comunicazione) l’esito compiuto dell’avvicendarsi dei pensieri nello scambio dialogico. Si lascia dunque narrare una progressione di indagini coltivate in più sedi, ma certamente spesso ambientate tra Vienna (Miklosich, Brentano, Bühler) e Praga (Marty, Zubaty, Mathesius, Funke, Carnap). Quasi si potrebbe illustrare, anche a proposito di sintassi, la sua semiosi ora propriamente simbolica di relazioni in re, ora più unilateralmente sintomatica, espressiva dell’Erlebnis dei parlanti – l’erlebte Rededi letteraria memoria, ad esempio – ora più intenzionalmente appellativa, quasi indice puntato alla volta dell’interlocutore. Quindi, sì, una semiotica della sintassi, inclusiva – ovviamente – di una semantica della stessa sintassi, che non ne teorizzi né l'estraneità alla lingua né l'autonomia dalle lingue

This study used wastewater-based epidemiology (WBE) to investigate the lifestyle of the inhabitants of Malé, the capital of the Republic of Maldives. Raw wastewater 12-h composite samples were collected from nine pumping stations serving the city area - thus representative of the whole Malé population. Samples were analysed by liquid chromatography coupled to mass spectrometry for estimating the profile of use of a large number of substances including illicit drugs, alcohol, caffeine, tobacco and pharmaceuticals. The illicit drugs most used were cannabis (THC) and heroin (700 and 18 g/day), with lower consumption of cocaine and amphetamines (0.1–1.2 g/day). It is important to note that the consumption of cannabis in Malé was comparable to that measured in other countries, while the consumption of heroin was higher. Among cathinones, mephedrone was detected at the highest levels similar to other countries. Consumption of alcohol, which is not allowed in Maldives, was found (1.3 L/day/1000 inhabitants), but at a low level compared with other countries (6–44 L/day/1000 inhabitants), while the consumption of caffeine and tobacco was generally in line with reports from other countries. Unique information on pharmaceuticals use was also provided, since no official data were available. Human lifestyle was evaluated by applying for the first time the full set of WBE methodologies available in our laboratory. Results provided valuable epidemiological information, which may be useful for national and international agencies to understand population lifestyles better, including illicit drug issues, and for planning and evaluation of drug prevention programs in Malé.

Corals show spatial acclimatisation to local environment conditions. However, the various cellular mechanisms involved in local acclimatisation and variable bleaching patterns in corals remain to be thoroughly understood. In this study, the modulation of a protein implicated in cellular heat stress tolerance, the heat shock protein 70, was compared at both gene (hsp70) and protein (Hsp70) expression level in bleaching tolerant near-coast Acropora muricata colonies and bleaching susceptible reef colonies, in the lagoon of Belle Mare (Mauritius). The relative Hsp70 levels varied significantly between colonies from the two different locations, colonies having different health conditions and the year of collection. Before the bleaching event of 2016, near-coast colonies had higher basal levels of both Hsp70 gene and protein compared to reef colonies. During the bleaching event, the near-coast colonies did not bleach and had significantly higher relative levels of both Hsp70 gene and protein compared to bleached reef colonies. No significant genetic differentiation between the two studied coral populations was observed and all the colonies analysed were associated with Symbiodiniaceae of the genus Symbiodinium (Clade A) irrespective of location and sampling period. These findings provide further evidence of the involvement of Hsp70 in conferring bleaching tolerance to corals. Moreover, the consistent expression differences of Hsp70 gene and protein between the near-coast and reef coral populations in a natural setting indicate that the modulation of this Hsp is involved in local acclimatisation of corals to their environments.

The microbial communities associated with plant's compartments and the expression of the chloroplast chaperonin Hsp60 have been simultaneously analyzed during the diel cycle in the marine seagrass Thalassia hemprichii from the lagoon of Magoodhoo island (Maldives), characterized by remarkable daily shifts in temperature and light. Plants showed a significant up-regulation of Hsp60 expression from 8.00 a.m. to 2.00 p.m., in correspondence with the increase in temperature and light, confirming their role as defense mechanism against photoinhibition and oxidative damage. However, a further significant increase of the Hsp60 level was also observed when irradiance and temperature dropped, suggesting that the cellular stress was still in progress. The plant-associated microbial communities showed differences by plant compartment and sampling time, with the aboveground compartment (leaves) being much more dynamic than the belowground one (roots/rhizomes). In the phyllosphere, a progressive shift during the day from the absolute dominance of the Gammaproteobacteria class, mainly constituted of Enterobacteraceae family, to the increase of the biodiversity due to the rise of Alphaproteobacteria was observed. Belowground, the microbial diversity was much lower than aboveground, being Gammaproteobacteria the most represented class throughout all sampling times. Vibrionaceae family was the most abundant at 8:00 a.m. and 6.00 p.m. decreasing slightly at 2.00 p.m., partially replaced by Halomonadaceae. The combined biochemical and microbial markers allows to assess the plant stress response and to deepen the knowledge on the seagrasses adaptation to harsh and changing environmental conditions, resulting useful to detect early signs of change in an organism's physiological state. Furthermore, the variation of Hsp60 expression and associated bacterial communities in response to light and temperature fluctuations support the ‘holobiont’ theory, which considers the plant/microorganism

Coral bleaching represents the most serious threat to contemporary coral reefs. In response, focus is being laid on understanding the cellular processes involved in the response of corals to the environmental stresses and the molecular mechanisms that determine the bleaching patterns. In the present study, a component of the cellular stress response such as the expression of the heat shock proteins (Hsps) was analyzed following the coral bleaching event which occurred in the central Red Sea (Saudi Arabia) in 2015. During this event, corals of different species, growth forms and sites showed variable bleaching susceptibility. In particular, we investigated the expression of Hsp70, Hsp60 and Hsp32 in both healthy and bleached colonies belonging to four different coral species (Goniopora lobata, Porites lobata, Seriatopora hystrix and Stylophora pistillata), in order to explore the intra- and inter-specific modulation of these biomarkers as well as the existence of spatial patterns of Hsp expression. In healthy colonies, the level of all the biomarkers was significantly different among the different species, although within each species it remained similar regardless of the distance from the shore. All the coral species showed a significant modulation of the Hsp expression in response to bleaching, whose typology and amplitude were species-specific. In all the species, Hsp70 and Hsp60 showed a coordinated dual expression, which, in response to bleaching resulted in an up-regulation in G. lobata and P. lobata and in a down-regulation in S. hystrix and S. pistillata. Hsp32 was up-regulated in all four species following bleaching, indicative of elevated oxidative stress. Overall, the protein expression profiles of each species contribute to assess the role of Hsps in regulating the susceptibility to thermal stresses of the various coral taxa of the Red Sea.

Dalla fondazione dell’Università Cattolica (1921) e sino alla fine degli anni ‘50 del XX secolo, la figura di Agostino Gemelli si distingue nel panorama scientifico-culturale italiano, in particolare quello cattolico - complessivamente povero e di livello modesto - per la sua forte statura internazionale e per la sua precocità intuitiva ed interpretativa. Aspetti di originalità sono la sua formazione in Germania, l’impegno civico e scientifico in due discipline giovani (la psicologia e la fonetica, oggi lontane per settori disciplinari). Instancabile e combattivo agitatore di idee innovanti, aperto al confronto e al dibattito, fu sentinella vigile e attenta alla formazione degli studiosi e dei giovani e ricoprì prestigiose cariche educative e culturali. Il Laboratorio di Psicologia al quale si aggiunse nel 1929 una sezione di fonetica dotata di una strumentazione all’avanguardia, è al centro di una fitta rete di scambi, meta di visite di studiosi da tutto il mondo. Lunghissimi elenchi di nomi prestigiosi sono stati stilati: psicologi, linguisti, fisiatri, filosofi, medici, logopedisti, fisiologi, fonetisti si incontravano nel laboratorio. Le ricerche in ambito fonetico, condotte dagli anni 1920, hanno proiettato e imposto Gemelli sulla scena internazionale per il loro carattere tecnologicamente avanzato, per l’approccio pluridisciplinare, per il carisma dello studioso, per le sue vaste conoscenze, la sicurezza di metodo e la forza persuasiva. I suoi studi sulla voce furono forse i più celebri - e oggi i meno noti - alla fine degli anni ’30 e fino alla seconda guerra mondiale. Su questi studi soffermeremo il nostro sguardo approfondendo alcune significative presenze di fonetisti/linguisti stranieri a Milano; nonché alcuni tra gli innumerevoli carteggi e viaggi scientifici di Gemelli.

Nicotinamide adenine dinucleotide (NAD+) represents an essential cofactor in sustaining cellular bioenergetics and maintaining cellular fitness, and has emerged as a therapeutic target to counteract aging and age-related diseases. Besides NAD+ involvement in multiple redox reactions, it is also required as co-substrate for the activity of Sirtuins, a family of evolutionary conserved NAD+-dependent deacetylases that regulate both metabolism and aging. The founding member of this family is Sir2 of Saccharomyces cerevisiae, a well-established model system for studying aging of post-mitotic mammalian cells. In this context, it refers to chronological aging, in which the chronological lifespan (CLS) is measured. In this paper, we investigated the effects of changes in the cellular content of NAD+ on CLS by altering the expression of mitochondrial NAD+ carriers, namely Ndt1 and Ndt2. We found that the deletion or overexpression of these carriers alters the intracellular levels of NAD+ with opposite outcomes on CLS. In particular, lack of both carriers decreases NAD+ content and extends CLS, whereas NDT1 overexpression increases NAD+ content and reduces CLS. This correlates with opposite cytosolic and mitochondrial metabolic assets shown by the two types of mutants. In the former, an increase in the efficiency of oxidative phosphorylation is observed together with an enhancement of a pro-longevity anabolic metabolism toward gluconeogenesis and trehalose storage. On the contrary, NDT1 overexpression brings about on the one hand, a decrease in the respiratory efficiency generating harmful superoxide anions, and on the other, a decrease in gluconeogenesis and trehalose stores: all this is reflected into a time-dependent loss of mitochondrial functionality during chronological aging.

The skin is an extremely extended organ of the body and, due to this large surface, it is continuously exposed to microorganisms. Skin damage can easily lead to infections in the dermis which can, in turn, result in the dissemination of pathogens into the bloodstream. Understanding how the immune system fights infections at the very early stage and how the host can eliminate the pathogens is an important step to set the base for future therapeutic interventions. Here we describe a model of Candida albicans infection that can visualize the processes that occur early during an infection, including when the pathogen has passed the epithelial barrier, as well as the immune response elicited by the C. albicans invasion. We used this infection model to perform histological analyses that show the immune cells that infiltrate the skin as well as the presence and localization of the pathogen. Samples collected after the infection can be processed for RNA extraction.

Mitochondrial functionality is one of the main factors involved in cell survival, and mitochondrial dysfunctions have been identified as an aging hallmark. In particular, the insurgence of mitochondrial dysfunctions is tightly connected to mitochondrial metabolism. During aging, both mitochondrial oxidative and biosynthetic metabolisms are progressively altered, with the development of malfunctions, in turn affecting mitochondrial functionality. In this context, the relation between mitochondrial pathways and aging is evolutionarily conserved from single-celled organisms, such as yeasts, to complex multicellular organisms, such as humans. Useful information has been provided by the yeast Saccharomyces cerevisiae, which is being increasingly acknowledged as a valuable model system to uncover mechanisms underlying cellular longevity in humans. On this basis, we review the impact of specific aspects of mitochondrial metabolism on aging supported by the contributions brought by numerous studies performed employing yeast. Initially, we will focus on the tricarboxylic acid cycle and oxidative phosphorylation, describing how their modulation has consequences on cellular longevity. Afterward, we will report information regarding the importance of nicotinamide adenine dinucleotide (NAD) metabolism during aging, highlighting its relation with mitochondrial functionality. The comprehension of these key points regarding mitochondrial metabolism and their physiological importance is an essential first step for the development of therapeutic interventions that point to increase life quality during aging, therefore promoting "healthy aging," as well as lifespan itself

In corals, different biological processes are associated with the daily variation of temperature and light, which in shallow reefs can vary widely and regularly reach extreme levels. The expression of cellular defense mechanisms such as the heat shock proteins Hsp70 and Hsp60 was analyzed in coral colonies adapted to live in a shallow lagoon, during three consecutive days characterized by the same temperature/light trend. Each of the three species investigated showed a significant diel modulation of both Hsps, which also displayed a coordinated expression. However, the diel modulations of both Hsps were species specific and only that of the branching Acropora tenuis appeared correlated with the temperature. All the species displayed high Hsp levels at 13.00 and 16.00, probably as protection for the cellular stress produced by the elevated temperature and light. Taken together, the results may provide useful information about the cellular mechanisms involved in the corals adaptation to extreme conditions.

Le incomprensioni del grammatico istriano Giovanni Moise nei confronti della grammatica storica mostrano il cambio di paradigma introdotto dalla nuova scienza linguistica alla fine dell'Ottocento. D'altra parte un'opera grammaticale come la sua può ancora riuscire utile, come mostra la documentazione reperibile in Moise a proposito della storia delle frasi scisse in italiano.

La nozione di cultura linguistica riceve nel Circolo Linguistico di Praga un’attenzione programmatica. Compare nelle Tesi del ’29, del ’32 e nell’Introduzione della rivista del Circolo, Slovo a Slovesnost (1935). (Havránek, Jakobson, Mathesius, Mukařovský, Trnka 1935: 2-3). Spicca l’impegno costruttivo e di innovazione, ben comprensibile nel quadro progettuale di un’autonomia nazionale acquisita di recente (1918) e nel fervore teorico di una prospettiva linguistica, strutturale e funzionale, promossa e recepita su scala europea e non solo. Al confronto, la situazione italiana appare notevolmente diversa, sia in termini politici, sia culturali: a una tradizione letteraria di altissimo profilo non si affianca, nel primo Novecento, un impegno linguistico-teorico vivace. L’intervento ne cerca le ragioni, mettendo a confronto alcune tesi di Benedetto Croce e di Antonio Gramsci. «La conoscenza umana ha due forme: o è conoscenza intuitiva o conoscenza logica; conoscenza per la fantasia o conoscenza per l’intelletto; conoscenza dell’individuale o conoscenza dell’universale; delle cose singole ovvero delle loro relazioni: è, insomma, o produttrice d’immagini o produttrice di concetti. [...] La scienza dell’arte e quella del linguaggio, l’Estetica e la Linguistica, in quanto vere scienze, sono, non già due scienze distinte, ma una scienza sola. Non che vi sia una Linguistica speciale; ma la ricercata scienza linguistica, Linguistica generale, in ciò che ha di riducibile a filosofia, non è se non Estetica. [...] Filosofia del linguaggio e filosofia dell’arte sono la stessa cosa. Agli aut-aut della premessa segue una reductio ad unum che premia la compiutezza dell’opera d’arte, la creatività poetica in particolare, rispetto alla tecnica delle regole grammaticali. Alla riforma Gentile (1923) che propone che l'apprendimento della lingua nazionale nelle classi elementari si basi sull'espressione viva o parlata, si opporrà la rivendicazione gramsciana del carattere classi

Resveratrol (RSV) is a naturally occurring polyphenolic compound endowed with interesting biological properties/functions amongst which are its activity as an antioxidant and as Sirtuin activating compound towards SIRT1 in mammals. Sirtuins comprise a family of NAD+-dependent protein deacetylases that are involved in many physiological and pathological processes including aging and age-related diseases. These enzymes are conserved across species and SIRT1 is the closest mammalian orthologue of Sir2 of Saccharomyces cerevisiae. In the field of aging researches, it is well known that Sir2 is a positive regulator of replicative lifespan and, in this context, the RSV effects have been already examined. Here, we analyzed RSV effects during chronological aging, in which Sir2 acts as a negative regulator of chronological lifespan (CLS). Chronological aging refers to quiescent cells in stationary phase; these cells display a survival-based metabolism characterized by an increase in oxidative stress. We found that RSV supplementation at the onset of chronological aging, namely at the diauxic shift, increases oxidative stress and significantly reduces CLS. CLS reduction is dependent on Sir2 presence both in expired medium and in extreme Calorie Restriction. In addition, all data point to an enhancement of Sir2 activity, in particular Sir2-mediated deacetylation of the key gluconeogenic enzyme phosphoenolpyruvate carboxykinase (Pck1). This leads to a reduction in the amount of the acetylated active form of Pck1, whose enzymatic activity is essential for gluconeogenesis and CLS extension.

Black band disease (BBD) is a widespread coral pathology caused by a microbial consortium dominated by cyanobacteria, which is significantly contributing to the loss of coral cover and diversity worldwide. Since the effects of the BBD pathogens on the physiology and cellular stress response of coral polyps appear almost unknown, the expression of some molecular biomarkers, such as Hsp70, Hsp60, HO-1, and MnSOD, was analyzed in the apparently healthy tissues of Goniopora columna located at different distances from the infection and during two disease development stages. All the biomarkers displayed different levels of expression between healthy and diseased colonies. In the healthy corals, low basal levels were found stable over time in different parts of the same colony. On the contrary, in the diseased colonies, a strong up-regulation of all the biomarkers was observed in all the tissues surrounding the infection, which suffered an oxidative stress probably generated by the alternation, at the progression front of the disease, of conditions of oxygen supersaturation and hypoxia/anoxia, and by the production of the cyanotoxin microcystin by the BBD cyanobacteria. Furthermore, in the infected colonies, the expression of all the biomarkers appeared significantly affected by the development stage of the disease. In conclusion, our approach may constitute a useful diagnostic tool, since the cellular stress response of corals is activated before the pathogens colonize the tissues, and expands the current knowledge of the mechanisms controlling the host responses to infection in corals

Climate changes have increased the intensity/frequency of extreme thermal events, which represent serious threats to the health of reef-building corals. Since the vulnerability of corals exposed to thermal stresses are related to their ability to regulate Heat shock proteins (Hsps), we have analyzed together the time related expression profiles of the mitochondrial Hsp60 and the associated changes in tissue pigmentation in Seriatopora caliendrum subjected to 48 h of heat and cold treatments characterized by moderate (±2 °C) and severe (±6 °C) shocks. For the first time, an Hsp60 response was observed in a scleractinian coral exposed to cold stresses. Furthermore, the Hsp60 modulations and the changes in the tissue coloration were found to be specific for each treatment. A strong down-regulation at the end of the treatments was observed following both the severe shocks, but only the severe heat stress led to bleaching in concert with the lowest levels of Hsp60, suggesting that a severe heat shock can be more deleterious than an exposure to a severe cold temperature. On the contrary, a moderate cold stress seems to be more harmful than a moderate temperature increase, which could allow coral acclimation. Our results can provide a potential framework for understanding the physiological tolerance of corals under possible future climate changes.