114 research outputs found
M. tuberculosis H37Rv comparative gene-expression analysis in synthetic medium and human macrophage.
No full textMycobacteria are intracellular pathogens that survive and grow in host macrophages. Following phagocytosis, sustained intracellular bacterial growth depends on its ability to avoid destruction by macrophage-mediated host defences such as lysosomal enzymes, reactive oxygen and the reactive nitrogen intermediates.This suggests that the interaction between host cell and microbe is delicately balanced, and can be tipped in favour of either organism. The identification of Mycobacterium tuberculosis H37Rv (MTB) genes expressed within host cells would contribute greatly to the development of new strategies to fight tuberculosis. In the present study, we compared MTB gene expression in the course of intra- (human macrophages) and extracellular growth (Sauton's medium) to ascertain whether differences might occur between gene-expression patterns in the two habitats of replication. Using reverse-transcriptase polymerase chain reaction (RT-PCR) on a group of 14 MTB-Complex-specific genes, we found that MT10Sa (a small stable RNA), 35 kDa (unknown), ahpC (alkyl hydroperoxide reductase, AhpC), sigF (alternative RNA Polymerase sigma factor), and katG (catalase-peroxidase, HPI) genes are expressed in both the environments, while Ag85B, Ag85C (members of the Antigen 85 Complex), rpoV (RNA Polymerase sigma factor) and ESAT6 (early secretory antigen, 6 kDa) are expressed only in the in vitro culture; on the other hand, Ag85A (Antigen 85 Complex), rpoB (RNA Polymerase beta sub-unit), pab (Protein antigen b), invA and invB genes (encoding proteins that show homologies with p60 of Listeria monocytogenes) are expressed only inside the macrophage. Positive RT-PCR products on cDNAs for these genomic regions were not obtained from approximately 1000-fold more bacteria grown in Laboratory Broth. Identification of M. tuberculosis genes expressed in response to phagocytosis by human macrophages increases our basic understanding of the host-pathogen interaction, and helps to identify bacterial factors necessary for in vivo survival and growth
Histoire de Piero, un designer entre deux mondes / Story of Piero. A designer between two worlds / Storia di Piero. Un designer fra due mondi
No full textIl documentario ripercorre la vita e l’opera del designer Piero Ottinetti (1927–2018) tra Milano e Chicago. Grafico, fotografo e illustratore, Ottinetti è stato una figura di spicco della cosiddetta ‘scuola milanese’ degli anni cinquanta e sessanta. Fra i suoi clienti più importanti si annoverano Montecatini, Pirelli, Philips, Salmoiraghi, OM, Busnelli, La Cimbali, Lorenz, Ceramiche Marazzi, Lebole, Cotonificio Cantoni. Piemontese, ex-partigiano, dopo la guerra Ottinetti si trasferisce a Roma per frequentare l’Accademia d’arte San Luca, più tardi a Milano frequenta corsi di grafica presso il Convitto Rinascita, una scuola professionale per ex combattenti. Debutta come assistente di Remo Muratore; quindi, dopo un breve periodo alla Rinascente, va a lavorare con Max Huber. Nel 1954 apre un proprio studio: i primi riconoscimenti arrivano grazie alla lunga collaborazione con Montecatini e Pirelli, per i quali cura annunci stampa, cataloghi e grafica per allestimenti (Fiera di Milano). Spinto dalla recessione economica e dalla crisi politica che attanaglia il paese, nel 1971 Ottinetti si trasferisce negli Stati Uniti, stabilendosi a Chicago. Dopo un’esperienza freelance, Ottinetti assume il ruolo di art director per il gruppo assicurativo Kemper, di cui rinnova marchio e identità aziendale. Lascia la professione alla metà degli anni ottanta per dedicarsi alla pittura.
A seguito della sua emigrazione in America, il nome di Ottinetti è stato letteralmente rimosso da ogni successiva indagine storica. Grazie a un primo fortuito incontro nel 2011, l’autore ha più volte intervistato Ottinetti. Fin dall’inizio l’incontro ha preso la forma di una complessa ricerca di storia orale. Il formato del documentario, pur privilegiando una dimensione narrativa personale, consente un commento critico e un confronto tra il contesto culturale italiano e quello americano in cui Ottinetti si è trovato a operare dagli anni settanta. La testimonianza di Ottinetti offre inoltre un racconto senza censure della realtà quotidiana nell’ambiente del design milanese. La ricostruzione ‘giornalistica’ della sua carriera, piuttosto che ricorrere a nozioni astratte di talento o di merito, mette in evidenza il ruolo dei fattori personali e sociali nel determinare il percorso e la fortuna critica di un designer.The documentary retraces the life and works of Italian designer Piero Ottinetti (1927–2018) between Milan and Chicago. Graphic designer, photographer and illustrator, Ottinetti was a leading figure in 1960s Milan, and had a host of important clients, such as Montecatini, Pirelli, Philips, Salmoiraghi, OM, Busnelli, La Cimbali, Lorenz, Ceramiche Marazzi, Lebole, Cotonificio Cantoni. From native Piedmont, after the war Ottinetti went to Rome to attend the San Luca Art Academy, and later in Milan took courses in graphic design at the Convitto Rinascita, a professional school for ex-combatants. He made his debut as study assistant to Remo Muratore; then, after a stint at La Rinascente, went to work with Max Huber. By 1954 he opened his own studio. The first recognitions came thanks to his long-lasting collaboration with Montecatini and Pirelli, for whom over nearly two decades he produced print ads, catalogues, and exhibition graphics. Pushed by the economical recession and the political turmoil that gripped the country, in 1971 Ottinetti decided to move to the United States, settling in Chicago. Following a freelance experience, Ottinetti joined the Kemper Insurance group as art director, where he overhauled the whole corporate identity. He retired by the mid-eighties, devoting himself to painting. He lived in Waukegan, Illinois.
Following his emigration to America, Ottinetti’s name was literally removed from all subsequent historical investigations. After an happenstance discovery in 2011, the author met and interviewed Ottinetti several times. From the start the encounter took the shape of a complex oral history investigation. The documentary format, while privileging a personal narrative dimension, allows a critical commentary and a comparison between the Italian and American cultural context in which Ottinetti operated. Moreover, Ottinetti's testimony offers an uncensored, behind-the-scenes account of the everyday reality of Milan’s design circles. In particular, the journalistic-style reconstruction of his career, rather than resorting to abstract notions of talent or merit, highlights the role of personal and social factors in determining a designer's path
Targeting metabolic abnormalities in mental health prevention strategies
No full textPeople with severe mental disorders (SMI) have a shorter life expectancy of 10–20 years than the general population, mainly due to physical comorbidities, predominantly cardiovascular disease (CVD) and type 2 diabetes (T2D). Patient lifestyle-related risk factors (e.g., smoking, alcohol abuse, lack of physical activity, sedentary lifestyle, unhealthy diet) as well as the use of antipsychotics and antidepressants are likely to be involved. Furthermore, recent evidence shows that cardio-metabolic alterations are present at the beginning of psychosis and major depressive disorder, are probably related to the disease, and worsen with drugs, especially if taken for a long time. Therefore, it is of paramount importance to develop and implement strategies that can prevent and address the problem of physical comorbidity in mental disorders, and it is also essential to raise awareness among health professionals about these insidious and life-threatening conditions. The interventions that can be implemented are both pharmacological and non-pharmacological and can be applied to prevent the development of cardio-metabolic diseases or to reduce their effects in those who have already manifested alterations. The most effective interventions will be presented in the chapter. Despite the evidence that various interventions (e.g., improving physical activity) work and different editorials have required action, “lifestyle interventions” are still limited in routine clinical care
Field application of the micro biological survey method for a simple and effective assessment of the microbiological quality of water sources in developing countries
No full textAccording to the World Health Organization (WHO) guidelines, “safe drinking-water must not represent any significant risk to health over a lifetime of consumption, including different sensitivities that may occur between life stages”. Traditional methods of water analysis are usually complex, time consuming and require an appropriately equipped laboratory, specialized personnel and expensive instrumentation. The aim of this work was to apply an alternative method, the Micro Biological Survey (MBS), to analyse for contaminants in drinking water. Preliminary experiments were carried out to demonstrate the linearity and accuracy of the MBS method and to verify the possibility of using the evaluation of total coliforms in 1 mL of water as a sufficient parameter to roughly though accurately determine water microbiological quality. The MBS method was then tested “on field” to assess the microbiological quality of water sources in the city of Douala (Cameroon, Central Africa). Analyses were performed on both dug and drilled wells in different periods of the year. Results confirm that the MBS method appears to be a valid and accurate method to evaluate the microbiological quality of many water sources and it can be of valuable aid in developing countries
Transcriptional profile of the immune response in the lungs of patients with active tuberculosis
No full textDespite advances in diagnosis and treatment, Mycobacterium tuberculosis causes active disease in about 8 million people worldwide annually. The study of the interplay between the host and the pathogen at the site of infection in human TB may contribute to elucidate the pathogenesis of the disease. In this work, using macroarray technology and real-time PCR, we analyzed the modulation of 847 genes encoding immune-inflammatory mediators in BALF samples of patients affected by active pulmonary TB (PTB) and control patients affected by non-TB diseases. The data show that the PTB milieu contains a complex network of gene activation. Different genes with adhesive properties and involved in tissue repair and fibrosis were modulated. In TB patients, we observed the up-regulation of cytokines, including IFN-gamma and IFN-gamma pathway genes, of several apoptotic genes, and of potent transcriptional activators. These findings can contribute to elucidate the mechanisms of MTB pathogenicity in humans. (c) 2006 Elsevier Inc. All rights reserved
Abstract 1196: Epigenetic drugs modulate long noncoding RNAs expression in BRAF inhibitor-resistant melanoma
No full textAbstract
Emergence of drug resistance is the major cause of failure of BRAF inhibitors (BRAFi) treatment in cutaneous melanoma (CM). Epigenetic modifications are known to physiologically trigger massive modifications in cellular commitment and several studies report a correlation between the drug-resistant phenotype and epigenetic alterations of tumor cells. In this setting, long noncoding RNAs (lncRNAs) represent a class of gene regulators acting at epigenetic, transcriptional and post-transcriptional level. Several studies have implicated lncRNAs in chemoresistance through their ability to impair cell cycle arrest and apoptosis, but also to induce and modulate epithelial-mesenchymal transition and cell adhesion-associated signaling pathways. LncRNAs interact with histone modifying complexes and/or DNA methyltransferases, being also targets of these epigenetic mediators. Furthermore, epigenetic drugs have been recently identified as modulators for lncRNAs function as well as their related targeting signals. Starting from these evidences, we asked the question whether epigenetic drugs could differentially affect the survival of BRAFi-resistant (VR) and -sensitive CM cells, investigating the mechanistic network involved, with a specific focus on the role of lncRNA. A panel of BRAFi-sensitive and VR CM cell lines was treated with the FDA-approved HDAC inhibitor vorinostat (SAHA). FACS analysis of annexin V-FITC/propidium iodide stained cells showed that SAHA cytotoxic activity was more pronounced on VR CM cells than on their parental counterparts. RNA-Seq analysis revealed that a large number of differentially expressed lncRNAs was modulated in VR CM cells treated with SAHA. Intriguingly, the expression of several VR up-regulated lncRNAs was decreased to levels similar to those observed in the matched parental cells. Functional analysis indicated these lncRNAs were statistically enriched in pathways involving cellular growth and proliferation, but also cellular assembly and organization. Though additional studies are required, epigenetic modulation of VR-associated lncRNAs promises to have significant therapeutic potential to restore BRAFi sensivity in CM, being concomitantly effective in killing VR cells as monotherapy. Based on our preliminary data, we could anticipate that the combined use of epigenetic and targeted drugs would increase therapeutic efficacy in CM patients relapsing to BRAFi.
Citation Format: Barbara Montico, Giorgio Giurato, Katy Mastorci, Aurora Rizzo, Maria Ravo, Francesca Rizzo, Alessandro Weisz, Riccardo Dolcetti, Francesca Colizzi, Luca Sigalotti, Elisabetta Fratta. Epigenetic drugs modulate long noncoding RNAs expression in BRAF inhibitor-resistant melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1196. doi:10.1158/1538-7445.AM2017-1196</jats:p
Postural control in childhood: investigating the neurodevelopmental gradient hypothesis
No full textNeurodevelopmental disorders (NDDs) have been suggested to lie on a gradient continuum, all resulting from common brain disturbances, but with different degrees of impairment severity. This case-control study aimed to assess postural stability against such hypothesis in 104 children/adolescents aged 5-17, of whom 81 had NDDs and 23 were healthy controls. Compared to healthy controls, Autism Spectrum Disorder (ASD) resulted in the most severely impaired neurodevelopmental condition, followed by Attention Deficit Hyperactive Disorder (ADHD) and Tourette Syndrome (TS). In particular, while ASD children/adolescents performed worse than healthy controls in a number of sensory conditions across all parameters, ADHD children/adolescents performed worse than healthy controls only in the sway area for the most complex sensory conditions, when their vision and somatosensory functions were both compromised, and performance in Tourette Syndrome (TS) was roughly indistinguishable from that of healthy controls. Finally, differences were also observed between clinical groups, with ASD children/adolescents, and to a much lesser extent ADHD children/adolescents, performing worse than TS children/adolescents, especially when sensory systems were not operationally accurate. Evidence from this study indicates that poor postural control may be a useful biomarker for risk assessment during neurodevelopment, in line with predictions from the gradient hypothesis
Autophagy in BRAF-mutant cutaneous melanoma: recent advances and therapeutic perspective
No full text: Macroautophagy, hereafter referred to as autophagy, represents a highly conserved catabolic process that maintains cellular homeostasis. At present, the role of autophagy in cutaneous melanoma (CM) is still controversial, since it appears to be tumor-suppressive at early stages of malignant transformation and cancer-promoting during disease progression. Interestingly, autophagy has been found to be often increased in CM harboring BRAF mutation and to impair the response to targeted therapy. In addition to autophagy, numerous studies have recently conducted in cancer to elucidate the molecular mechanisms of mitophagy, a selective form of mitochondria autophagy, and secretory autophagy, a process that facilitates unconventional cellular secretion. Although several aspects of mitophagy and secretory autophagy have been investigated in depth, their involvement in BRAF-mutant CM biology has only recently emerged. In this review, we aim to overview autophagy dysregulation in BRAF-mutant CM, along with the therapeutic advantages that may arise from combining autophagy inhibitors with targeted therapy. In addition, the recent advances on mitophagy and secretory autophagy involvement in BRAF-mutant CM will be also discussed. Finally, since a number of autophagy-related non-coding RNAs (ncRNAs) have been identified so far, we will briefly discussed recent advances linking ncRNAs to autophagy regulation in BRAF-mutant CM
Technology and design of innovative flexible electrode for biomedical applications
No full textThe electrochemotherapy is an effective treatment that requires the application of an intense electric field to the tumoral tissue to open the cellular membrane and deliver drugs. This work will present the results of the ongoing research project, showing a new technology and design geometry that allows to realize flexible electrodes able to wrap biological tissues bringing the necessary electric field intensity for the electroporation of cells to reach a unique penetration depth to the centimeter range. The flexible electrode is realized by conversion of porous silicon into nano-porous metals (copper and/or gold) filled by a biocompatible thermoplastic polymer. © 2011 IEEE
Design, synthesis, and biological evaluation of substituted 2,3-dihydro-1H-cyclopenta[b]quinolin-9-ylamine related compounds as fructose-1,6-bisphosphatase inhibitors
No full text8 pages, 4 figures, 1 tableIn a search for structurally new inhibitors of fructose-1,6-bisphosphatase (F16BPase), substituted 2,3-dihydro-1H-cyclopenta[b]quinoline derivatives were synthesized. It has been shown that the 2,3-dihydro-1H-cyclopenta[b]quinoline moiety may represent a suitable scaffold for the synthesis of potent F16BPase inhibitors endowed with significantly lower EGFR tyrosine kinase inhibitory activityPeer reviewe
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