105 research outputs found
Utopia e distopia na produção artística e teórica de Witkacy
The purpose of this article is to investigate the utopian and dystopic frontiers present in the artistic and theoretical production of the Polish artist Stanislaw Ignacy Witkiewicz, known by the pseudonym Witkacy (1885-1939). The hypothesis raised here is that there is a certain contradiction between theory and practice performed by the artist. Even considering that creativity was threatened with extinction in this new society subjugated by mechanization, Witkacy had a utopian view of art, believing that this was the only mechanism capable of give the individual the opportunity of experience the Mystery of Existence. However, in his literary productions, especially in the novel, the artist reveals an antagonistic vision, creating frighteningly dystopian images of the society. What moves this study is the conflict generated by these opposing views. While, on the one hand, the artist manifested an idealization, a utopian vision of art, on the other hand there is a deep pessimism, a dystopian view of man and society. This article will confine itself to analyzing two literary works, Insatiability (1930) and the play The Mother (written in 1924 and published in 1962) as well as the theoretical production of the artist ”“ New Forms in Painting and the Misunderstandings Arising Therefrom (1919) and Pure form in the Theater (1921).O objetivo deste artigo é investigar as fronteiras do utópico e do distópico presentes na produção artística e teórica do artista polonês Stanislaw Ignacy Witkiewicz, conhecido pelo pseudônimo Witkacy (1885-1939). A hipótese aqui levantada é a de que haja uma certa contraditoriedade entre teoria e prática realizada pelo artista. Mesmo considerando que a criatividade estava ameaçada de extinção nessa nova sociedade subjugada pela mecanização, Witkacy possuía uma visão utópica acerca da arte, pois acreditava ser este o único mecanismo capaz de fazer o indivíduo experimentar o Mistério da Existência. Já em suas produções literárias, especialmente no romance, o artista revela uma visão antagônica, criando imagens assustadoramente distópicas da sociedade. O que move esse estudo é o conflito gerado por estas visões opostas. Enquanto, por um lado, o artista manifestou uma idealização, uma visão utópica da arte, por outro lado há um profundo pessimismo, uma visão distópica do homem e da sociedade. Este artigo se limitará a analisar duas obras literárias, Insaciabilidade (1930) e a peça A Mãe (escrita em 1924 e publicada em 1962), bem como a produção teórica do artista ”“ New Forms in Painting and the Misunderstandings Arising Therefrom (1919) e Pure Form in the Theater (1921)
Chemical communication between synthetic and natural cells: a possible experimental design
The bottom-up construction of synthetic cells is one of the most intriguing
and interesting research arenas in synthetic biology. Synthetic cells are built
by encapsulating biomolecules inside lipid vesicles (liposomes), allowing the
synthesis of one or more functional proteins. Thanks to the in situ synthesized
proteins, synthetic cells become able to perform several biomolecular
functions, which can be exploited for a large variety of applications. This
paves the way to several advanced uses of synthetic cells in basic science and
biotechnology, thanks to their versatility, modularity, biocompatibility, and
programmability. In the previous WIVACE (2012) we presented the
state-of-the-art of semi-synthetic minimal cell (SSMC) technology and
introduced, for the first time, the idea of chemical communication between
synthetic cells and natural cells. The development of a proper synthetic
communication protocol should be seen as a tool for the nascent field of
bio/chemical-based Information and Communication Technologies (bio-chem-ICTs)
and ultimately aimed at building soft-wet-micro-robots. In this contribution
(WIVACE, 2013) we present a blueprint for realizing this project, and show some
preliminary experimental results. We firstly discuss how our research goal
(based on the natural capabilities of biological systems to manipulate chemical
signals) finds a proper place in the current scientific and technological
contexts. Then, we shortly comment on the experimental approaches from the
viewpoints of (i) synthetic cell construction, and (ii) bioengineering of
microorganisms, providing up-to-date results from our laboratory. Finally, we
shortly discuss how autopoiesis can be used as a theoretical framework for
defining synthetic minimal life, minimal cognition, and as bridge between
synthetic biology and artificial intelligence.Comment: In Proceedings Wivace 2013, arXiv:1309.712
Phenotyping spontaneous locomotor activity in inbred and outbred mouse strains by using Digital Ventilated Cages
Mouse strains differ markedly in all behaviors, independently of their genetic background. We undertook this study to disentangle the diurnal activity and feature key aspects of three non-genetically altered mouse strains widely used in research, C57BL/6NCrl (inbred), BALB/cAnNCrl (inbred) and CRL:CD1(ICR) (outbred). With this aim, we conducted a longitudinal analysis of the spontaneous locomotor activity of the mice during a 24-h period for 2 months, in two different periods of the year to reduce the seasonality effect. Mice (males and females) were group-housed in Digital Ventilated Cages (Tecniplast), mimicking standard housing conditions in research settings and avoiding the potential bias provided in terms of locomotor activity by single housing. The recorded locomotor activity was analyzed by relying on different and commonly used circadian metrics (i.e., day and night activity, diurnal activity, responses to lights-on and lights-off phases, acrophase and activity onset and regularity disruption index) to capture key behavioral responses for each strain. Our results clearly demonstrate significant differences in the circadian activity of the three selected strains, when comparing inbred versus outbred as well as inbred strains (C57BL/6NCrl versus BALB/cAnNCrl). Conversely, males and females of the same strain displayed similar motor phenotypes; significant differences were recorded only for C57BL/6NCrl and CRL:CD1(ICR) females, which displayed higher average locomotor activity from prepuberty to adulthood. All strain-specific differences were further confirmed by an unsupervised machine learning approach. Altogether, our data corroborate the concept that each strain behaves under characteristic patterns, which needs to be taken into consideration in the study design to ensure experimental reproducibility and comply with essential animal welfare principles
Age-related central regulation of orexin and NPY in the short-lived African killifish Nothobranchius furzeri
Orexin A (OXA) and neuropeptide Y (NPY) are two hypothalamic neuropeptides involved in the regulation of feeding behavior and food intake in all vertebrates. Accumulating evidences document that they undergo age-related modifications, with consequences on metabolism, sleep/wake disorders and progression of neurodegenerations. The present study addressed the age related changes in expression and distribution of orexin A (its precursor is also known as hypocretin\u2014HCRT) and NPY, and their regulation by food intake in the short-lived vertebrate model Nothobranchius furzeri. Our experiments, conducted on male specimens, show that: (a) HCRT and OXA and NPY mRNA and protein are localized in neurons of diencephalon and optic tectum, as well as in numerous fibers projecting through the entire neuroaxis, and are colocalized in specific nuclei; (b) in course of aging, HCRT and NPY expressing neurons are localized also in telencephalon and rhombencephalon; (c) HCRT expressing neurons increased slightly in the diencephalic area of old animals and in fasted animals, whereas NPY increased sharply; (d) central HCRT levels are not regulated neither in course of aging nor by food intake; and (e) central NPY levels are augmented in course of aging, and regulated by food intake only in young. These findings represent a great novelty in the study of central orexinergic and NPY-ergic systems in vertebrates', demonstrating an uncommon and unprecedented described regulation of these two orexigenic neuropeptides
Identification of FDA-Approved Drugs as Antivirulence Agents Targeting the pqs Quorum-Sensing System of Pseudomonas aeruginosa
Copyright © 2018 American Society for Microbiology. All Rights Reserved. The long-term use of antibiotics has led to the emergence of multidrug-resistant bacteria. A promising strategy to combat bacterial infections aims at hampering their adaptability to the host environment without affecting growth. In this context, the intercellular communication system quorum sensing (QS), which controls virulence factor production and biofilm formation in diverse human pathogens, is considered an ideal target. Here, we describe the identification of new inhibitors of the pqs QS system of the human pathogen Pseudomonas aeruginosa by screening a library of 1,600 U.S. Food and Drug Administration-approved drugs. Phenotypic characterization of ad hoc engineered strains and in silico molecular docking demonstrated that the antifungal drugs clotrimazole and miconazole, as well as an antibacterial compound active against Gram-positive pathogens, clofoctol, inhibit the pqs system, probably by targeting the transcriptional regulator PqsR. The most active inhibitor, clofoctol, specifically inhibited the expression of pqs-controlled virulence traits in P. aeruginosa, such as pyocyanin production, swarming motility, biofilm formation, and expression of genes involved in siderophore production. Moreover, clofoctol protected Galleria mellonella larvae from P. aeruginosa infection and inhibited the pqs QS system in P. aeruginosa isolates from cystic fibrosis patients. Notably, clofoctol is already approved for clinical treatment of pulmonary infections caused by Gram-positive bacterial pathogens; hence, this drug has considerable clinical potential as an antivirulence agent for the treatment of P. aeruginosa lung infections
SMO Inhibition Modulates Cellular Plasticity and Invasiveness in Colorectal Cancer
Colon Cancer (CC) is the fourth most frequently diagnosed tumor and the second leading cause of death in the USA. Abnormalities of Hedgehog pathway have been demonstrated in several types of human cancers, however the role of Hedgehog (Hh) in CC remain controversial. In this study, we analyzed the association between increased mRNA expression of GLI1 and GLI2, two Hh target genes, and CC survival and recurrence by gene expression microarray from a cohort of 382 CC patients. We found that patients with increased expression of GLI1 showed a statistically significant reduction in survival. In order to demonstrate a causal role of Hh pathway activation in the pathogenesis of CC, we treated HCT 116, SW480 and SW620 CC cells lines with GDC-0449, a pharmacological inhibitor of Smoothened (SMO). Treatment with GDC-0449 markedly reduced expression of Hh target genes GLI1, PTCH1, HIP1, MUC5AC, thus indicating that this pathway is constitutively active in CC cell lines. Moreover, GDC-0449 partially reduced cell proliferation, which was associated with upregulation of p21 and downregulation of CycD1. Finally, treatment with the same drug reduced migration and three-dimensional invasion, which were associated with downregulation of Snail1, the EMT master gene, and with induction of the epithelial markers Cytokeratin-18 and E-cadherin. These results were confirmed by SMO genetic silencing. Notably, treatment with 5E1, a Sonic Hedgehog-specific mAb, markedly reduced the expression of Hedgehog target genes, as well as inhibited cell proliferation and mediated reversion toward an epithelial phenotype. This suggests the existence of a Hedgehog autocrine signaling loop affecting cell plasticity and fostering cell proliferation andmigration/invasion in CC cell lines. These discoveries encourage future investigations to better characterize the role of Hedgehog in cellular plasticity and invasion during the different steps of CC pathogenesis.Peer reviewe
A Morphological and Ultrastructural Study of the Anterior Digestive Tract of Adult Nile Tilapia Oreochromis niloticus
Among the most-used fish species in aquaculture is the Nile tilapia, due to its rapid
growth rate and its adaptation to a wide range of farming conditions. A careful description of
the morphology of the digestive tract, particularly the esophagus and stomach, allows a better
understanding of the relationship between structure and function. Combining scanning and light
microscopy we highlighted the presence of five different zones in the stomach (1: esophagus-gastric
lumen passage; 2: descending glandular portion; 3: fundic portion; 4: ascending glandular portion; 5:
gastric-pyloric transition portion). Histochemical investigation showed a secretion of carboxylates
mucopolysaccharides along the esophagus and sulphated complex carbohydrates in the stomach.
These results suggest that mucins play a protective role of the epithelial lining, which is essential for a
correct digestive process. Finally, the characterization of the main cellular structures may be inspiring
for more advanced studies aiming to decipher the role of specific molecules, such as neuropeptides,
involved in the physiological digestive process
Orexin-A Prevents Lipopolysaccharide-Induced Neuroinflammation at the Level of the Intestinal Barrier
In states of intestinal dysbiosis, a perturbation of the normal microbiome composition, the intestinal epithelial barrier (IEB) permeability is increased as a result of the disruption of the epithelial tight junction protein network, in which occludin is mostly affected. The loss of IEB integrity promotes endotoxemia, that is, bacterial lipopolysaccharide (LPS) translocation from the intestinal lumen to the circulatory system. This condition induces an enhancement of pro-inflammatory cytokines, which leads to neuroinflammation through the gut-brain axis. Orexin-A (OX-A), a neuropeptide implicated in many physiological functions and produced mainly in the brain lateral hypothalamic area, is expressed also in several peripheral tissues. Orexin-producing neurons have been found in the myenteric plexus to project to orexin receptor 1 (OX-1R)-expressing enterocytes of the intestinal villi. In the present study we investigated the protective role of OX-A against LPS-induced increase of IEB permeability and microglia activation in both an in vivo and in vitro model of the gut-brain axis. By exploiting biochemical, immunocytochemical, immunohistochemical, and functional approaches, we demonstrate that OX-A preserves the IEB and occludin expression, thus preventing endotoxemia and subsequent neuroinflammation
Expression and distribution of leptin and its receptors in the digestive tract of DIO (diet-induced obese) zebrafish.
The expression and localization of leptin (A and B) and its receptor family in control and diet-induced obese (DIO) adult male zebrafish gut, after 5-weeks overfeeding, administering Artemia nauplii, as fat-rich food, were investigated. Recently, the obese adult zebrafish was considered an experimental model with pathophysiological pathways similar to mammalian obesity. Currently, there are no reports about leptin in fish obesity, or in a state of altered energy balance. By qRT-PCR, leptin A and leptin B expression levels were significantly higher in DIO zebrafish gut than in the control group (CTRL), and the lowest levels of leptin receptor mRNA appeared in DIO zebrafish gut. The presence of leptin and its receptor proteins in the intestinal tract was detected by western blot analysis in both control and DIO zebrafish. By single immunohistochemical staining, leptin and leptin receptor immunoreactive endocrine cells were identified in the intestinal tract either in DIO or control zebrafish. Moreover, leptin immunopositive enteric nervous system elements were observed in both groups. By double immunohistochemical staining, leptin and its receptor were colocalized especially in DIO zebrafish. Thus, our study represents a starting point in the investigation of a possible involvement of leptin in control of energy homeostasis in control and DIO zebrafish
Orexins and receptor OX2R in the gastroenteric apparatus of two teleostean species: Dicentrarchus labrax and Carassius auratus
Orexin A and B peptides and the receptor OX2R were studied in sea bass and goldfish gastroenteric tract by immunoblotting combined with densitometric analysis using NIH Image J software and immunohistochemical techniques. These teleost species present a different gut organization and diverse feeding habits. Immunoblotting experiments showed one band of 16 kDa corresponding to prepro-orexin, and one band of 38 kDa corresponding to the OX2R receptor. Immunohistochemical localization of OXA and OXB was observed in the enteric nervous system throughout the gastroenteric tract of both species. OXA and OXB immunoreactive cells were found in the gastric and intestinal regions of sea bass, and were mainly found in the basal region of folds in intestinal bulb, and in the midgut and hindgut of goldfish. The distribution of OX2R was mainly detected in the mucosa of the gastroenteric tract of sea bass and goldfish. This distribution suggests an endocrine action of OXA and OXB in the gastrointestinal tract as well as involvement in the peripheral control of food intake and digestive processes in both species. This study might also serve to determine the productive factors in breeding and as a baseline for future experimental studies on the regulation of the gastroenteric functions in non-mammalian vertebrates
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