dMyc Functions Downstream of Yorkie to Promote the Supercompetitive Behavior of Hippo Pathway Mutant Cells

Genetic analyses in Drosophila epithelia have suggested that the phenomenon of “cell competition” could participate in organ homeostasis. It has been speculated that competition between different cell populations within a growing organ might play a role as either tumor promoter or tumor suppressor, depending on the cellular context. The evolutionarily conserved Hippo (Hpo) signaling pathway regulates organ size and prevents hyperplastic disease from flies to humans by restricting the activity of the transcriptional cofactor Yorkie (yki). Recent data indicate also that mutations in several Hpo pathway members provide cells with a competitive advantage by unknown mechanisms. Here we provide insight into the mechanism by which the Hpo pathway is linked to cell competition, by identifying dMyc as a target gene of the Hpo pathway, transcriptionally upregulated by the activity of Yki with different binding partners. We show that the cell-autonomous upregulation of dMyc is required for the supercompetitive behavior of Yki-expressing cells and Hpo pathway mutant cells, whereas the relative levels of dMyc between Hpo pathway mutant cells and wild-type neighboring cells are critical for determining whether cell competition promotes a tumor-suppressing or tumor-inducing behavior. All together, these data provide a paradigmatic example of cooperation between tumor suppressor genes and oncogenes in tumorigenesis and suggest a dual role for cell competition during tumor progression depending on the output of the genetic interactions occurring between confronted cells

dMyc Functions Downstream of Yorkie to Promote the Supercompetitive Behavior of Hippo Pathway Mutant Cells

Genetic analyses in Drosophila epithelia have suggested that the phenomenon of “cell competition” could participate in organ homeostasis. It has been speculated that competition between different cell populations within a growing organ might play a role as either tumor promoter or tumor suppressor, depending on the cellular context. The evolutionarily conserved Hippo (Hpo) signaling pathway regulates organ size and prevents hyperplastic disease from flies to humans by restricting the activity of the transcriptional cofactor Yorkie (yki). Recent data indicate also that mutations in several Hpo pathway members provide cells with a competitive advantage by unknown mechanisms. Here we provide insight into the mechanism by which the Hpo pathway is linked to cell competition, by identifying dMyc as a target gene of the Hpo pathway, transcriptionally upregulated by the activity of Yki with different binding partners. We show that the cell-autonomous upregulation of dMyc is required for the supercompetitive behavior of Yki-expressing cells and Hpo pathway mutant cells, whereas the relative levels of dMyc between Hpo pathway mutant cells and wild-type neighboring cells are critical for determining whether cell competition promotes a tumor-suppressing or tumor-inducing behavior. All together, these data provide a paradigmatic example of cooperation between tumor suppressor genes and oncogenes in tumorigenesis and suggest a dual role for cell competition during tumor progression depending on the output of the genetic interactions occurring between confronted cells

Comparative Study of SPA Mud from "Bacino Idrominerario Omogeneo dei Colli Euganei (B.I.O.C.E.)-Italy" and Industrially Optimized Mud for Skin Applications

The term "Salus per aquam (SPA) therapies" refers to therapeutic pathways that includes mud therapy. The therapeutic efficacy of a peloid depends on its chemical and mineralogical composition, as well as its technological properties. Considering the increasing use of clay-based products, it becomes essential to characterize peloids from a qualitative and quantitative point of view. Therefore, this research project aimed to develop a protocol that allows characterization of the chemical-physical composition of sludges collected from different areas of the Homogeneous Euganean Hills Hydromineral Basin (B.I.O.C.E.). The study established a comparative study both between different matrices and between the same matrices at different maturation times, including also a comparison with an industrialized product, that can be used at home, which maintains the characteristics of a natural mud. This research was developed studying the pH, grain size distribution, and chemical and mineralogical composition. Peloids are characterized by a neutral/basic pH and are divided into two categories from a granulometric point of view: The chemical composition allowed observation of numerous correlations between oxides present in the samples and to quantify the presence of heavy metals. Mineralogical analysis made it possible to identify and compare the composition of each sample, also according to the maturation time. Thanks to the methods adopted, important correlations were achieved

The lethal giant larvae tumour suppressor mutation requires dMyc oncoprotein to promote clonal malignancy

<p>Abstract</p> <p>Background</p> <p>Neoplastic overgrowth depends on the cooperation of several mutations ultimately leading to major rearrangements in cellular behaviour. Precancerous cells are often removed by cell death from normal tissues in the early steps of the tumourigenic process, but the molecules responsible for such a fundamental safeguard process remain in part elusive. With the aim to investigate the molecular crosstalk occurring between precancerous and normal cells <it>in vivo</it>, we took advantage of the clonal analysis methods that are available in <it>Drosophila </it>for studying the phenotypes due to <it>lethal giant larvae </it>(<it>lgl</it>) neoplastic mutation induced in different backgrounds and tissues.</p> <p>Results</p> <p>We observed that <it>lgl </it>mutant cells growing in wild-type imaginal wing discs show poor viability and are eliminated by Jun N-terminal Kinase (JNK)-dependent cell death. Furthermore, they express very low levels of dMyc oncoprotein compared with those found in the surrounding normal tissue. Evidence that this is a cause of <it>lgl </it>mutant cells elimination was obtained by increasing dMyc levels in <it>lgl </it>mutant clones: their overgrowth potential was indeed re-established, with mutant cells overwhelming the neighbouring tissue and forming tumourous masses displaying several cancer hallmarks. Moreover, when <it>lgl </it>mutant clones were induced in backgrounds of slow-dividing cells, they upregulated dMyc, lost apical-basal cell polarity and were able to overgrow. Those phenotypes were abolished by reducing dMyc levels in the mutant clones, thereby confirming its key role in <it>lgl</it>-induced tumourigenesis. Furthermore, we show that the <it>eiger</it>-dependent Intrinsic Tumour Suppressor pathway plays only a minor role in eliminating <it>lgl </it>mutant cells in the wing pouch; <it>lgl</it>^-/-clonal death in this region is instead driven mainly by dMyc-induced Cell Competition.</p> <p>Conclusions</p> <p>Our results provide the first evidence that dMyc oncoprotein is required in <it>lgl </it>tumour suppressor mutant tissue to promote invasive overgrowth in larval and adult epithelial tissues. Moreover, we show that dMyc abundance inside <it>versus </it>outside the mutant clones plays a key role in driving neoplastic overgrowth.</p

A Safe-by-Design Approach to "Reef Safe" Sunscreens Based on ZnO and Organic UV Filters

In recent years, the issue of coral bleaching has led to restrictions in some tropical locations (i.e., Palau, Hawaii, etc.) on the use of some organic UV sunscreen filters, such as oxybenzone and ethyl hexyl methoxycinnamate. In contrast, ZnO is considered safe for marine environments and thus is often used without considering its photocatalytic and oxidative activities related to the generation of O-2(center dot-) and HO center dot. Moreover, ZnO needs to be used in combination with other filters to reach higher protection factors. Thus, the study of its interaction with formulations and with organic filters is important in sunscreen technology for the development of safer by-design products. In this work, the photocatalytic activity of zinc oxides with different surface areas (30, 25 and 9 m(2)/g) and their interaction with selected organic sunscreen filters were investigated. In particular, the ZnO photocatalytic kinetics were studied following the photodegradation of Acid Blue 9 (AB9) observing a first-order reaction with a chemical regime. Our evaluations of the selective inhibitions by h(vb)(+) and HO center dot demonstrated a substantial predominance of the hydroxide radicals in the expression of the photocatalysis, a trend that was also confirmed by the irradiation of ZnO in an ethanolic solution. Indeed, the formulations containing both ZnO and organic filters defined as "safe" for coral reefs (i.e., Diethylamino Hydroxybenzoyl Hexyl Benzoate, DHHB, and Ethylhexyl Triazone, EHT) showed a non-negligible photocatalytic oxidation and thus the combination was underlined as safe to use

metodo non invasivo per la valutazione della capacita' antiossidante della pelle e della efficacia antiossidante in vivo di prodotti ad uso dermocosmetico

Il presente brevetto è relativo allo sviluppo di protocolli in vivo/vitro per la valutazione della capacità antiossidante della pelle utile a valutare l’efficacia di molecole o prodotti ad uso dermatologico, farmaceutico o dermo-cosmetico ad attività antiossidante. Un metodo non invasivo per misurare la capacità antiossidante della pelle e la sua variazione in seguito alla applicazione di preparazioni derrmatologiche ad attività antiossidante viene descritto. In una delle applicazioni il metodo include la raccolta di antiossidanti dalla pelle mediante un metodo non invasivo e l’analisi della relativa capacità antiossidante mediante metodologia opportuna

Determinazione della capacità antiossidanti integrale (IAC) di formulazioni cosmetiche mediante fotochemiluminescenza (PCL)

Determinazione della capacità antiossidanti integrale (IAC) di formulazioni cosmetiche mediante fotochemiluminescenza (PCL

Antiossidanti, pro-ossidanti e valutazione della capacità antiossidante

Revisione della letteratura e stato dell'arte riguardo agli antiossidanti, i pro-ossidanti e la valutazione della capacità antiossidant

Synergistic combination of multifunctional agents for cosmetic preservation

The preservation of cosmetic products has always been of special interest to the industry; microbial spoilage can lead to product degradation, and in the case of present pathogens, could contribute to a threat to the health of the consumer. In recent years the safety of many traditional preservatives has been questioned by the media and various organisations. Therefore, the cosmetics industry is looking for effective, safe, eco-friendly and sustainable, globally accepted and non-controversial solutions. Due to the current market demand, increasing efforts have been directed towards the research of ‘greener’ and milder ingredients, with favourable toxicological profiles also in the aim to reduce the irritation potential and the risk of sensitisation. To date the research is focused to the investigation of multifunctional antimicrobial agents, enabling the reduction of the number of ingredients and thus toxicological and environmental impact. In the present work, a synergistic mixture of caprylyl glycol and phenethyl alcohol, also endowed with skin emollient and fragrance properties has been investigated. This alternative preservative was found to have excellent antimicrobial activity in different cosmetic formulations whose efficacy is further increased by the addition of chelating agents

Valutazione della capacità preservante di una batteriocina in ambito cosmetico: la nisina

Valutazione della capacità preservante di una batteriocina in ambito cosmetico: la nisina