1,910 research outputs found

    New supersymmetric Wilson loops in ABJ(M) theories

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    We present two new families of Wilson loop operators in N= 6 supersymmetric Chern-Simons theory. The first one is defined for an arbitrary contour on the three dimensional space and it resembles the Zarembo's construction in N=4 SYM. The second one involves arbitrary curves on the two dimensional sphere. In both cases one can add certain scalar and fermionic couplings to the Wilson loop so it preserves at least two supercharges. Some previously known loops, notably the 1/2 BPS circle, belong to this class, but we point out more special cases which were not known before. They could provide further tests of the gauge/gravity correspondence in the ABJ(M) case and interesting observables, exactly computable by localizationComment: 9 pages, no figure. arXiv admin note: text overlap with arXiv:0912.3006 by other author

    Capsaicin triggers autophagic cell survival which drives epithelial mesenchymal transition and chemoresistance in bladder cancer cells in an Hedgehog-dependent manner

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    Bladder cancer (BC) is a common urologic tumor characterized by high risk of recurrence and mortality. Capsaicin (CPS), used as an intravesical drug for overactive bladder, was demonstrated to induce cell death in different cancer cells including BC cells.Here we found that treatment of high-grade BC cells with high dose of CPS triggers autophagy. Infact, the CPS treatment alters the redox homeostasis by inducing production of radicals, mitochondrial depolarization, alterations of ADP/ATP ratio and activation of AMPK pathway stimulating the autophagic process in BC cells. The inhibition of autophagy, by using the specific inhibitor bafilomycin A or Beclin 1 knock-down, enhanced the CPS-induced cell death, demonstrating that CPS-induced autophagy acts as a pro-survival process in BC cells. By using PCR arrays and FACS analysis, we found that the CPS-treated BC cells displayed typical mesenchymal features of the epithelial mesenchymal transition (EMT) as elongated shape and over-expression of vimentin, α5 and β1 integrin subunits, integrin-like kinase and the anti-apoptotic Bcl-2 proteins. Moreover, we demonstrated that CPS treatment stimulates upregulation of Dhh/Ptch2/Zeb2 members of the Hedgehog signaling pathway, increases CD24, VEGFA and TIMP1 and decreases CD44 and ALCAM mRNA expression levels. By PTCH2 knock-down we found that the Hedgehog signaling pathway is involved in the CPS-induced autophagy and EMT phenotype.Finally, we also showed that the CPS-resistant EMT-positive BC cells displayed an increased drug-resistance to the cytotoxic effects of mitomycin C, gemcitabine and doxorubicine drugs commonly used in BC therapy

    Axitinib induces senescence-associated cell death and necrosis in glioma cell lines: The proteasome inhibitor, bortezomib, potentiates axitinib-induced cytotoxicity in a p21(Waf/Cip1) dependent manner.

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    Glioblastoma is associated with a poor overall survival despite new treatment advances. Antiangiogenic strategies targeting VEGF based on tyrosine kinase inhibitors (TKIs) are currently undergoing extensive research for the treatment of glioma. Herein we demonstrated that the TKI axitinib induces DNA damage response (DDR) characterized by Îł-H2AX phosphorylation and Chk1 kinase activation leading to G2/M cell cycle arrest and mitotic catastrophe in U87, T98 and U251 glioma cell lines. Moreover, we found that p21(Waf1/Cip1) increased levels correlates with induction of ROS and senescence-associated cell death in U87 and T98 cell lines, which are reverted by N-acetyl cysteine pretreatment. Conversely, U251 cell line showed a resistant phenotype in response to axitinib treatment, as evidenced by cell cycle arrest but no sign of cell death. The combinatorial use of axitinib with other therapies, with the aim of inhibiting multiple signaling pathways involved in tumor growth, can increase the efficiency of this TKI. Thus, we addressed the combined effects of axitinib with no toxic doses of the proteasome inhibitor bortezomib on the growth of U87 and T98 axitinib- sensitive and axitinib-resistant U251 cell lines. Compared to single treatments, combined exposure was more effective in inhibiting cell viability of all glioma cell lines, although with different cell death modalities. The regulation of key DDR and cell cycle proteins, including Chk1, Îł-H2AX and p21(Waf1/Cip1) was also studied in glioma cell lines. Collectively, these findings provide new perspectives for the use of axitinib in combination with Bortezomib to overcome the therapy resistance in gliomas

    MicroRNA-222 regulates muscle alternative splicing through Rbm24 during differentiation of skeletal muscle cells

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    A number of microRNAs have been shown to regulate skeletal muscle development and differentiation. MicroRNA-222 is downregulated during myogenic differentiation and its overexpression leads to alteration of muscle differentiation process and specialized structures. By using RNA-induced silencing complex (RISC) pulldown followed by RNA sequencing, combined with in silico microRNA target prediction, we have identified two new targets of microRNA-222 involved in the regulation of myogenic differentiation, Ahnak and Rbm24. Specifically, the RNA-binding protein Rbm24 is a major regulator of muscle-specific alternative splicing and its downregulation by microRNA-222 results in defective exon inclusion impairing the production of muscle-specific isoforms of Coro6, Fxr1 and NACA transcripts. Reconstitution of normal levels of Rbm24 in cells overexpressing microRNA-222 rescues muscle-specific splicing. In conclusion, we have identified a new function of microRNA-222 leading to alteration of myogenic differentiation at the level of alternative splicing, and we provide evidence that this effect is mediated by Rbm24 protei

    Safety performance assessment of food industry facilities using a fuzzy approach

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    The latest EU policies focus on the issue of food safety with a view to assuring adequate and standard quality levels for the food produced and/or consumed within the EC. To that purpose, the environment where agricultural products are manufactured and processed plays a crucial role in achieving food hygiene. As a consequence, it is of the utmost importance to adopt proper building solutions which meet health and hygiene requirements and to use suitable tools to measure the levels achieved. Similarly, it is necessary to verify and evaluate the level of safety and welfare of the workers in their working environment. The safety of the workers has not only an ethical and social value but also an economic implication, since possible accidents or environmental stressors are the major causes of the lower efficiency and productivity of workers. However, the technical solutions adopted in the manufacturing facilities in order to achieve adequate levels of safety and welfare of the workers are not always consistent with the solutions aimed at achieving adequate levels of food hygiene, even if both of them comply with sectoral rules which are often unconnected with each other. Therefore, it is fundamental to design suitable models of analysis that allow assessing buildings as a whole, taking into account both health and hygiene safety as well as the safety and welfare of workers. Hence, this paper proposes an evaluation model that, based on an established study protocol and on the application of a fuzzy logic procedure, allows evaluating the global safety level of a building. The proposed model allows to obtain a synthetic and global value of the building performance in terms of food hygiene and safety and welfare of the workers as well as to highlight possible weaknesses. Though the model may be applied in either the design or the operational phase of a building, this paper focuses on its application to certain buildings already operational in a specific productive context

    Effect of LPS-induced inflammatory state on some aspects of reproductive function of rabbit does

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    Effetto dell\u2019infiammazione indotta con LPS su alcuni aspetti della funzione riproduttiva nelle coniglie. Scopo della ricerca \ue8 stato quello di studiare un modello d\u2019induzione sperimentale di infiammazione con lipopolisaccaridi (LPS) microbici nella coniglia fattrice e l'eventuale effetto sulla risalita degli spermatozoi. Due gruppi di 6 coniglie fattrici sono state inoculate per via intra-peritoneale rispettivamente con LPS di E. coli 0127:B8 (100 \ub5g/kg peso vivo), o con soluzione fisiologica (controllo). Sono stati rilevati per 72 ore temperatura rettale e il numero dei leucociti; dopo inseminazione artificiale \ue8 stata valutata la risalita degli spermatozoi nel tratto riproduttivo femminile e la situazione ovarica. L\u2019infiammazione sperimentale ha indotto un rilevante incremento della temperatura rettale e sostanziali modifiche a livello di leucociti che sono comunque scomparse entro 72 ore. Anche il numero di spermatozoi risaliti \ue8 stato significativamente pi\uf9 basso a livello di corna uterine e addirittura nullo a livello dell\u2019ovidutto. In conclusione si pu\uf2 affermare che \ue8 possibile costruire un modello d\u2019induzione dello stato infiammatorio nella coniglia mediante inoculazione intra-peritoneale di 100 \ub5g LPS/kg di peso vivo.The efficiency of the cycled production system in rabbit farms is greatly conditioned by the fertility rate of does. Nulliparous does generally exhibit high fertility rate (Castellini et al., 1998), whereas the reproductive performances of multiparous does goes down. One reason of this reduction is related to the use of intensive reproductive rhythms which implies an overlapping between lactation and insemination which often produces a severe energy deficit. As in other mammals, lactation shows a strong hormonal antagonism with the reproductive activity. An other cause of hypo-fertility depends on the sanitary condition of does. Genital tract inflammation and/or infection is one of the major causes of infertility (Gram et al., 2002) and often determined by incorrect practices of artificial insemination (AI). It has been demonstrated that uterine infection negatively affects fertility (Facchin et al., 1999) and prolongs the life span of corpora lutea (Boiti et al., 1999) due to uterine leukocytes infiltration, reduced prostaglandins synthesis and increased spermatozoa reabsorption. Lipopolysaccarides (LPS), constituents of the Gram-negative germ wall, are potent stimulators of prostaglandins synthesis and are widely used to simulate inflammation in several district and organs. The aim of the paper was to verify the effect of an LPS-induced inflammatory state on some aspects of reproductive function of non-lactating rabbit does
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