Overview on Molecular Biomarkers for Laryngeal Cancer: Looking for New Answers to an Old Problem

Laryngeal squamous cell cancer (LSCC) accounts for almost 25–30% of all head and neck squamous cell cancers and is clustered according to the affected districts, as this determines distinct tendency to recur and metastasize. A major role for numerous genetic alterations in driving the onset and progression of this neoplasm is emerging. However, major efforts are still required for the identification of molecular markers useful for both early diagnosis and prognostic definition of LSCC that is still characterized by significant morbidity and mortality. Non-coding RNAs appear the most promising as they circulate in all the biological fluids allowing liquid biopsy determination, as well as due to their quick and characteristic modulation useful for non-invasive detection and monitoring of cancer. Other critical aspects are related to recent progress in circulating tumor cells and DNA detection, in metastatic status and chemo-refractoriness prediction, and in the functional interaction of LSCC with chronic inflammation and innate immunity. We review all these aspects taking into account the progress of the technologies in the field of next generation sequencing

Multi-systemic alterations by chronic exposure to a low dose of bisphenol a in drinking water: Effects on inflammation and nad+-dependent deacetylase sirtuin1 in lactating and weaned rats

Bisphenol A (BPA) is largely used as a monomer in some types of plastics. It accumulates in tissues and fluids and is able to bypass the placental barrier, affecting various organs and systems. Due to huge developmental processes, children, foetuses, and neonates could be more sensitive to BPA-induced toxicity. To investigate the multi-systemic effects of chronic exposure to a low BPA dose (100 µg/L), pregnant Wistar rats were exposed to BPA in drinking water during gestation and lactation. At weaning, newborn rats received the same treatments as dams until sex maturation. Free and conjugated BPA levels were measured in plasma and adipose tissue; the size of cerebral ventricles was analysed in the brain; morpho-functional and molecular analyses were carried out in the liver with a focus on the expression of inflammatory cytokines and Sirtuin 1 (Sirt1). Higher BPA levels were found in plasma and adipose tissue from BPA treated pups (17 PND) but not in weaned animals. Lateral cerebral ventricles were significantly enlarged in lactating and weaned BPA-exposed animals. In addition, apart from microvesicular steatosis, liver morphology did not exhibit any statistically significant difference for morphological signs of inflammation, hypertrophy, or macrovesicular steatosis, but the expression of inflammatory cytokines, Sirt1, its natural antisense long non-coding RNA (Sirt1-AS LncRNA) and histone deacetylase 1 (Hdac1) were affected in exposed animals. In conclusion, chronic exposure to a low BPA dose could increase the risk for disease in adult life as a consequence of higher BPA circulating levels and accumulation in adipose tissue during the neonatal period

Chronic exposure to low dose of bisphenol A impacts on the first round of spermatogenesis via SIRT1 modulation.

Spermatogenesis depends on endocrine, autocrine and paracrine communications along the hypothalamus-pituitary-gonad axis. Bisphenol A (BPA), an estrogen-mimic endocrine disrupting chemical, is an environmental contaminant used to manufacture polycarbonate plastics and epoxy resins with toxic effects for male reproduction. Here we investigated whether the chronic exposure to low BPA doses affects spermatogenesis through the modulation of SIRT1, a NAD+-dependent deacetylase involved in the progression of spermatogenesis, with outcomes on apoptosis, oxidative stress, metabolism and energy homeostasis. BPA exposure via placenta first, and lactation and drinking water later, affected the body weight gain in male offspring at 45 postnatal days and the first round of spermatogenesis, with impairment of blood testis barrier, reactive oxygen species production, DNA damage and decreased expression of SIRT1. The analysis of SIRT1 downstream molecular pathways revealed the increase of acetyl-p53Lys370, γH2AX foci, the decrease of oxidative stress defenses and the higher apoptotic rate in the testis of treated animals, with partial rescue at sex maturation. In conclusion, SIRT1 pathways disruption after BPA exposure can have serious consequences on the first round of spermatogenesis

How to Extract Useful Randomness from Unreliable Sources

For more than 30 years, cryptographers have been looking for public sources of uniform randomness in order to use them as a set-up to run appealing cryptographic protocols without relying on trusted third parties. Unfortunately, nowadays it is fair to assess that assuming the existence of physical phenomena producing public uniform randomness is far from reality. It is known that uniform randomness cannot be extracted from a single weak source. A well-studied way to overcome this is to consider several independent weak sources. However, this means we must trust the various sampling processes of weak randomness from physical processes. Motivated by the above state of affairs, this work considers a set-up where players can access multiple potential sources of weak randomness, several of which may be jointly corrupted by a computationally unbounded adversary. We introduce SHELA (Somewhere Honest Entropic Look Ahead) sources to model this situation. We show that there is no hope of extracting uniform randomness from a SHELA source. Instead, we focus on the task of Somewhere-Extraction (i.e., outputting several candidate strings, some of which are uniformly distributed -- yet we do not know which). We give explicit constructions of Somewhere-Extractors for SHELA sources with good parameters. Then, we present applications of the above somewhere-extractor where the public uniform randomness can be replaced by the output of such extraction from corruptible sources, greatly outperforming trivial solutions. The output of somewhere-extraction is also useful in other settings, such as a suitable source of random coins for many randomized algorithms. In another front, we comprehensively study the problem of Somewhere-Extraction from a weak source, resulting in a series of bounds. Our bounds highlight the fact that, in most regimes of parameters (including those relevant for applications), SHELA sources significantly outperform weak sources of comparable parameters both when it comes to the process of Somewhere-Extraction, or in the task of amplification of success probability in randomized algorithms. Moreover, the low quality of somewhere-extraction from weak sources excludes its use in various efficient applications

Le produzioni ceramiche di Fratte

A Fratte documenti di attività finalizzate alla produzione di ceramiche si riferiscono alla fase di vita di età sannitica e provengono soprattutto dall’area sud-orientale (Zona 2) della cosiddetta Acropoli. Qui sono stati rinvenuti resti di una fornace, mentre documenti significativi vengono anche dai livelli superiori di un pozzo posto all’interno di un edificio di forma rettangolare, sul versante occidentale dell’area, a poca distanza dalla fornace. Si tratta verosimilmente di scarti di produzione relativi a tipi vascolari ampiamente attestati durante le fasi finali dell’insediamento; tali evidenze indicano con certezza che a cavallo tra IV e III sec. a.C. sono prodotte localmente ceramiche d’uso quotidiano sia in argilla acroma e grezza sia a vernice nera

Publicly Verifiable Zero Knowledge from (Collapsing) Blockchains

Publicly Verifiable Zero-Knowledge proofs are known to exist only from setup assumptions such as a trusted common reference string or a random oracle. Unfortunately, the former requires a trusted party while the latter does not exist. Blockchains are distributed systems that already exist and provide certain security properties (under some honest majority assumption), hence, a natural recent research direction has been to use a blockchain as an alternative setup assumption. In TCC 2017 Goyal and Goyal proposed a construction of a publicly verifiable zero-knowledge (pvZK) proof system for some proof-of-stake blockchains. The zero-knowledge property of their construction however relies on some additional and not fully specified assumptions about the current and future behavior of honest blockchain players. In this paper we provide several contributions. First, we show that when using a blockchain to design a provably secure protocol, it is dangerous to rely on demanding additional requirements on behaviors of the blockchain players. We do so by showing an “attack of the clones” whereby a malicious verifier can use a smart contract to slyly (not through bribing) clone capabilities of honest stakeholders and use those to invalidate the zero-knowledge property of the proof system by Goyal and Goyal. Second, we propose a new publicly verifiable zero-knowledge proof system that relies on non-interactive commitments and on an assumption on the min-entropy of some blocks appearing on the blockchain. Third, motivated by the fact that blockchains are a recent innovation and their resilience in the long run is still controversial, we introduce the concept of collapsing blockchain, and we prove that the zero-knowledge property of our scheme holds even if the blockchain eventually becomes insecure and all blockchain players eventually become dishonest

SIRT1 Activation by Natural Phytochemicals: An Overview

Sirtuins are class III histone deacetylases, whose enzymatic activity is dependent on NAD+ as a cofactor. Sirtuins are reported to modulate numerous activities by controlling gene expression, DNA repair, metabolism, oxidative stress response, mitochondrial function, and biogenesis. Deregulation of their expression and/or action may lead to tissue-specific degenerative events involved in the development of several human pathologies, including cancer, neurodegeneration, and cardiovascular disease. The most studied member of this class of enzymes is sirtuin 1 (SIRT1), whose expression is associated with increasing insulin sensitivity. SIRT1 has been implicated in both tumorigenic and anticancer processes, and is reported to regulate essential metabolic pathways, suggesting that its activation might be beneficial against disorders of the metabolism. Via regulation of p53 deacetylation and modulation of autophagy, SIRT1 is implicated in cellular response to caloric restriction and lifespan extension. In recent years, scientific interest focusing on the identification of SIRT1 modulators has led to the discovery of novel small molecules targeting SIRT1 activity. This review will examine compounds of natural origin recently found to upregulate SIRT1 activity, such as polyphenolic products in fruits, vegetables, and plants including resveratrol, fisetin, quercetin, and curcumin. We will also discuss the potential therapeutic effects of these natural compounds in the prevention and treatment of human disorders, with particular emphasis on their metabolic impact

Testimonianze da Poseidonia e da Fratte

L’Università degli Studi di Salerno svolge da tempo ricerche sistematiche a Paestum e Fratte sia attraverso indagini sul terreno sia attraverso la revisione e la rilettura di vecchi contesti di scavo; la messa in sistema dei dati così ottenuti consente oggi alcune brevi riflessioni sulla produzione nell’ambito di contesti sacri