Stem-Like Adaptive Aneuploidy and Cancer Quasispecies

We analyze and reinterpret experimental evidence from the literature to argue for an ability of tumor cells to self-regulate their aneuploidy rate. We conjecture that this ability is mediated by a diversification factor that exploits molecular mechanisms common to embryo stem cells and, to a lesser extent, adult stem cells, that is eventually reactivated in tumor cells. Moreover, we propose a direct use of the quasispecies model to cancer cells based on their significant genomic instability (i.e. aneuploidy rate), by defining master sequences lengths as the sum of all copy numbers of physically distinct whole and fragmented chromosomes. We compute an approximate error threshold such that any aneuploidy rate larger than the threshold would lead to a loss of fitness of a tumor population, and we confirm that highly aneuploid cancer populations already function with aneuploidy rates close to the estimated threshold

Dismenorrea in donne lavoratrici dell'industria

La dismenorrea è una delle più comuni indisposizioni nelle donne. La frequenza varia in differenti lavori, probabilmente ciò è dovuto alla differenza nei gruppi di popolazione studiati. In alcune industrie Norvegesi, con molto personale femminile, l’inabilità periodica al lavoro dovuto ai fastidi mestruali è stato un problema di una certa importanza e la domanda è sorta nel caso in cui l’assenza è medicalmente giustificata nella visione di un moderno trattamento ormonale. Per avvicinarci al problema abbiamo pianificato di esaminare l’evento dei fastidi mestruali, particolarmente la dismenorrea, tra il personale femminile in alcune industrie Italiane in quello che appariva essere un problema. I soggetti esaminati erano impiegati di una compagnia elettrica-tecnica e di una industria tessile. Un questionario preparato da una infermiera dell’industria, è stato compilato da donne in età mestruale che erano state visitate per esami medici periodici e di pre-assunzione tra il 2002-2003. Ogni donna assistita soffriva di dolore, e quando tutti i sintomi erano considerati il 61% aveva mensilmente disturbi che ovviamente riducevano la loro capacità sul lavoro. Visto che il 9% delle donne assumevano estroprogestinici, che riducevano o eliminavano la dismenorrea, la vera prevalenza potrebbe essere leggermente superiore. Circa il 30% delle donne erano confinate a letto. Circa il 30% si assentava dal lavoro, il che illustra la grandezza del problema sia medico che economico

Involvement of pro-inflammatory cytokines and growth factors in the pathogenesis of Dupuytren's contracture: a novel target for a possible future therapeutic strategy?

Dupuytren's contracture (DC) is a benign fibro-proliferative disease of the hand causing fibrotic nodules and fascial cords which determine debilitating contracture and deformities of fingers and hands. The present study was designed to characterize pro-inflammatory cytokines and growth factors involved in the pathogenesis, progression and recurrence of this disease, in order to find novel targets for alternative therapies and strategies in controlling DC. The expression of pro-inflammatory cytokines and of growth factors was detected by immunohistochemistry in fibrotic nodules and normal palmar fascia resected respectively from patients affected by DC and carpal tunnel syndrome (CTS; as negative controls). Reverse transcription (RT)-PCR analysis and immunofluorescence were performed to quantify the expression of transforming growth factor (TGF)-β1, interleukin (IL)-1β and vascular endothelial growth factor (VEGF) by primary cultures of myofibroblasts and fibroblasts isolated from Dupuytren's nodules. Histological analysis showed high cellularity and high proliferation rate in Dupuytren's tissue, together with the presence of myofibroblastic isotypes; immunohistochemical staining for macrophages was completely negative. In addition, a strong expression of TGF-β1, IL-1β and VEGF was evident in the extracellular matrix and in the cytoplasm of fibroblasts and myofibroblasts in Dupuytren's nodular tissues, as compared with control tissues. These results were confirmed by RT-PCR and by immunofluorescence in pathological and normal primary cell cultures. These preliminary observations suggest that TGF-β1, IL-1β and VEGF may be considered potential therapeutic targets in the treatment of Dupuytren's disease (DD)

Locating the alien chromatin segment in common wheat-Aegilops longissima mildew resistant transfers

By use of the Chinese Spring ph 1b mutant, recombination was induced between the 3S1 short arm telosome of Ae. longissima and its group-3 wheat homoeologues. Transfer was thus obtained of chromosomal segments bearing the alien Pm 13 mildew resistance gene into several common wheat lines. To identify the wheat chromosome involved in each transfer, these were subjected to monosomic and C-banding analyses. Probably due to preferential 3B-3S1 pairing, irrespective of the group-3 wheat chromosome present as monosome in the critical steps of the transfer work, in 2/3 of the cases 3B turned out to be the recipient chromosome, whereas 3D was the one involved in the remaining ones. Assessment of the residual pairing ability of the recombinant chromosomes in F1's between four 3B and three 3D transfer lines and their corresponding wheat ditelosomic as well as 3S1 substitution lines, indicated about coincident values (about 40 % pairing with DT3BS) in three of the 3B recombinants, a significantly different pattern in the fourth one (10 %) and a more continuous variation among the 3D ones. An overall prevailing terminal location of the wheat-alien chromatin exchange points is tentatively hypothesized

Drosophila comes of age as a model system for understanding the function of cytoskeletal proteins in cells, tissues, and organisms

available in PMC 2016 June 30For the last 100 years, Drosophila melanogaster has been a powerhouse genetic system for understanding mechanisms of inheritance, development, and behavior in animals. In recent years, advances in imaging and genetic tools have led to Drosophila becoming one of the most effective systems for unlocking the subcellular functions of proteins (and particularly cytoskeletal proteins) in complex developmental settings. In this review, written for non-Drosophila experts, we will discuss critical technical advances that have enabled these cell biological insights, highlighting three examples of cytoskeletal discoveries that have arisen as a result: (1) regulation of Arp2/3 complex in myoblast fusion, (2) cooperation of the actin filament nucleators Spire and Cappuccino in establishment of oocyte polarity, and (3) coordination of supracellular myosin cables. These specific examples illustrate the unique power of Drosophila both to uncover new cytoskeletal structures and functions, and to place these discoveries in a broader in vivo context, providing insights that would have been impossible in a cell culture model or in vitro. Many of the cellular structures identified in Drosophila have clear counterparts in mammalian cells and tissues, and therefore elucidating cytoskeletal functions in Drosophila will be broadly applicable to other organisms.National Institutes of Health (U.S.) (NIH/NINDS (DP2 NS082127))Pew Scholars Program in the Biomedical SciencesNational Institutes of Health (U.S.) (NIH/NIGMS (R01-GM084947))American Cancer Society (Research Scholar Award

Editorial: Advanced Strategies to Reduce the Nitrate Content in Vegetables

Editorial on the Research Topic Advanced Strategies to Reduce the Nitrate Content in Vegetable

Oligodendroglial Process Formation is Differentially Affected by Modulating the Intra- and Extracellular Cholesterol Content

Cholesterol is an essential component of eukaryotic plasma membranes and plays an important role in membrane organization and signaling processes. It is the major lipid component of detergent resistant caveolin-1 containing rafts which previously had been reported as a platform for nerve growth factor (NGF) signaling in oligodendrocytes (OL). Surprisingly, a knockdown of caveolin-1 attenuated the process formation of OL (Schmitz et al. J Neurosci Res 88:572–588, 2010), for which a loss of cholesterol could be responsible. In the present report, we could show that a caveolin-1 knockdown resulted in an elevation of cellular cholesterol level; it may indicate an important role of caveolin-1 in cholesterol trafficking to the plasma membrane. Treatment with exogenous PEG cholesterol, which was incorporated to the plasma membrane, supported oligodendroglial process formation, in particular when OL were stimulated by NGF. In this context we have found that OL express NPC1L1 (Niemann–Pick disease type C1-Like 1) which could modulate cholesterol uptake. In contrast, depletion of membrane-bound cholesterol diminished NGF-induced process formation concomitant with a reduced activity of p42/44 mitogen-activated protein kinases

Red Light Is Effective in Reducing Nitrate Concentration in Rocket by Increasing Nitrate Reductase Activity, and Contributes to Increased Total Glucosinolates Content

Rocket cultivation is increasing to supply the expanding ready-to-eat market because of its unique taste, but crops are often over fertilized to avoid nitrogen deficiencies. This leads to nitrate accumulation in leaves, and the products of their degradation (nitrites and nitrosamines) have been related to several health problems. Nitrate concentrations in rocket and other leafy vegetables are subject to limits by the EU legislation, yet rocket holds a great nutritional value. Degradation products of glucosinolates (isothiocyanates) have been consistently linked with benefits to human health. We investigated the influence of nitrogen application (1 and 8 mM), species [Eruca sativa (L.) Cav. and Diplotaxis tenuifolia (L.) DC.] and light spectrum (full spectrum, red, blue and red + blue) on the nitrate concentration, nitrate reductase activity and glucosinolate content of rocket grown in a soil-less system. Red light decreased the nitrate concentration with respect to the blue spectrum (4,270 vs. 7,100 mg⋅kg–1 of fresh weight, respectively), but such reduction was influenced by the species and the nitrogen level (significantly higher in D. tenuifolia and with the higher concentration of N). The nitrate reductase activity increased under red light in D. tenuifolia, with the lower N concentration. Rocket is known to contain several health-promoting compounds mainly antioxidants and glucosinolates, as secondary metabolites that act as part of plant defense mechanisms. The total content of glucosinolates was mainly affected by the species (D. tenuifolia showed the highest concentrations). Our results will help growers to tailor light spectra with the aim of reducing nitrate concentration and to remain within EU legislative limits, without any detrimental influence on other qualitative parameters in rocket

Comparison between tensile properties and indentation properties measured with various shapes indenters of Copper-Chromium-Zirconium alloy at macroscale level

In this paper the experimental results of tensile properties and indentationproperties, as a function of pyramidal and spherical indenters, of Copper-Chromium-Zirconium alloy, in the macro-scale range at room temperature, are presented and compared. Measurements are performed on three Cu-Cr-Zr samples in order to evaluate different heat treatments: two samples areaged for 2 hours in a vacuum furnace at 480 °C, 550 °C and one sample is kept as received. The experimental procedures for the measurement of indentation modulus, by using the primary hardness standard machine at INRiM, and tensile modulus, by means of engineering tensile tests at CIRA, aredescribed