Polymersomes mediated intracellular delivery of antibodies: implication in anticancer therapy

Cancer is one of the leading causes of death in the developed world. Nevertheless, many pharmaceutical products available in the clinic lack of tissue specificity, and often have severe side effects. Nowadays, advances in molecular biology and biotechnology have allowed the development of biological therapeutic approaches aimed to give a step forward on cancer treatment. Biotherapy involves the use of biomolecules such as antibodies that have the potential to increase the specificity of anticancer treatments, thus limiting the side effects. Unfortunately, the effectiveness of such biomolecules is hindered by their pharmacokinetics, and their translation into patient care is heavily restricted by low solubility in water, instability / degradation in vivo and low efficiency. Besides that, such biomolecules require appropriate delivery strategies to penetrate cellular barriers, thus being able to interfere with pathways that can be involved in cancer development. This research project aims to bridge the lack of technology regarding the development of an effective and biocompatible delivery system. The pH sensitive PMPC-PDPA ((poly(2-(methacryloyloxy)ethyl phosphorylcholine) - poly(2-(diisopropylamino)ethyl methacrylate)) polymersome was employed as candidate for the intracellular delivery of functional therapeutic antibodies in live cells. The PMPC-PDPA diblock copolymer combines the ability to release the loaded cargo upon acidification within the endosomes with an overall biocompatibility. First, the antifouling proprieties of polymersomes were investigated, and then compared to micelles. Subsequently, electroporation was exploited as reliable technique to effectively encapsulate antibodies within polymersomes. The delivery of antibodies in live cells was assessed using anti γ-tubulin antibody as a model system. Finally, Ki-67 was explored as a possible target for anticancer therapy. Interestingly, relevant differences in the biological functions of this marker were revealed between cancerous and non-cancerous cells. Furthermore, antibodies against Ki-67 were delivered in live cells, and their activity was tested to explore the potential of Ki-67 as a target for anticancer therapy

Relatoría Producción Audiovisual “20 años de Radio Universidad”

El 1 de junio de 1994 Radio Universidad comenzó sus transmisiones a modo de prueba. Al cumplirse el 20º aniversario de la emisora, por pedido de la Dirección de la misma, somos convocados para elaborar un breve video institucional para ser presentado en el acto conmemorativo. A raíz de este pedido iniciamos la búsqueda de material y nos dimos cuenta que tratar de contar la esencia de la radio en menos de 7 minutos y de manera “institucional” abriría muchos caminos que no serían transitados, es por eso que optamos por trabajar en dos etapas, complementarias entre sí para poder cumplir con la demanda inicial y satisfacer nuestra demanda personal como profesionales de la comunicación. Asimismo, el fruto de esta segunda etapa, sirve también para poder presentar más acabadamente a la radio en cualquier foro en que se lo precise.Fil: Del Chierico, Lucas. Universidad Nacional de Rosario. Facultad de Ciencia Política y Relaciones Internacionales. Escuela de Comunicación Social; Argentina.Fil: Tropper, Eric. Universidad Nacional de Rosario. Facultad de Ciencia Política y Relaciones Internacionales. Escuela de Comunicación Social; Argentina

Bifidobacteria and lactobacilli in the gut microbiome of children with non-alcoholic fatty liver disease: which strains act as health players?

Introduction: Non-alcoholic fatty liver disease (NAFLD), considered the leading cause of chronic liver disease in children, can often progress from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH). It is clear that obesity is one of the main risk factors involved in NAFLD pathogenesis, even if specific mechanisms have yet to be elucidated. We investigated the distribution of intestinal bifidobacteria and lactobacilli in the stools of four groups of children: obese, obese with NAFL, obese with NASH, and healthy, age-matched controls (CTRLs). Material and methods: Sixty-one obese, NAFL and NASH children and 54 CTRLs were enrolled in the study. Anthropometric and metabolic parameters were measured for all subjects. All children with suspected NASH underwent liver biopsy. Bifidobacteria and lactobacilli were analysed in children’s faecal samples, during a broader, 16S rRNA-based pyrosequencing analysis of the gut microbiome. Results: Three Bifidobacterium spp. (Bifidobacterium longum, Bifidobacterium bifidum, and Bifidobacterium adolescentis) and five Lactobacillus spp. (L. zeae, L. vaginalis, L. brevis, L. ruminis, and L. mucosae) frequently recurred in metagenomic analyses. Lactobacillus spp. increased in NAFL, NASH, or obese children compared to CTRLs. Particularly, L. mucosae was significantly higher in obese (p = 0.02426), NAFLD (p = 0.01313) and NASH (p = 0.01079) than in CTRLs. In contrast, Bifidobacterium spp. were more abundant in CTRLs, suggesting a protective and beneficial role of these microorganisms against the aforementioned diseases. Conclusions: Bifidobacteria seem to have a protective role against the development of NAFLD and obesity, highlighting their possible use in developing novel, targeted and effective probiotics

Lo storico ignorante. Strategie dell'errore e della verità nella philosophie de l'histoire di Voltaire.

Il presente lavoro intende approfondire le procedure e le strategie di costruzione della verità storica nella filosofia della storia di Voltaire. In particolare, si è cercato di individuare il sistema di implicazioni epistemologiche sotteso alla concezione della storia come «tableau», la forma iconologica con cui Voltaire concepisce e rappresenta la sua indagine e il suo lavoro storiografico. La teoria estetica classica e le teorie sulla tragedia da un lato, il confronto con il pensiero scientifico contemporaneo e con il metodo newtoniano dall’altro costituiscono le principali fonti cui Voltaire si riferisce per inaugurare un’ originale procedura storiografica che contribuisce a consegnarlo alla posterità come “il primo storico moderno”

The role of the two splice variants and extranuclear pathway on Ki-67 regulation in non-cancer and cancer cells

Ki-67 is a nuclear protein that has been used in cancer diagnostic because of its specific cell-cycle dependent expression profile. After quantifying and characterising the expression level of Ki-67, as a function of the cell cycle, we found out that the two main splice variants of the protein (i.e. α and β) are differently regulated in non-cancerous and cancerous cells both at mRNA and protein level. We were able to correlate the presence of the α variant of the protein with the progression through the interphase of cell cycle. We also observed that the different expression profiles correspond to different degradation pathways for non-cancerous and cancerous cells. Furthermore, Ki-67 is continuously regulated and degraded via proteasome system in both cell types, suggesting an active control of the protein. However we also observed a putative extranuclear elimination pathway of Ki-67 where it is transported to the Golgi apparatus. Our evidence in the different expression of the splice variants may represent a milestone for the development of new targets for cancer diagnostic and prognostic. Additionally, the unexpected extranuclear elimination of Ki-67 strongly suggests that this protein must be looked at also outside of the "nuclear box", as thought to date

Sessismo culturale e apprendimento della lingua: Le rappresentazioni di genere nei manuali di italiano L2/LS per bambini e bambine

In Italy, several contributions have studied the presence of gender-stereotyped patterns in textbooks: many of these focused on Italian elementary school texts, and only a few on texts for teaching Italian L2/FL to young adults and adults. To this date we are not aware of any study that addresses gender stereotypes in texts for teaching Italian L2/FL to children. In the first section, this paper gives a review of the most noteworthy Italian research on the representation of gender in textbooks and Italian L2/FL coursebooks from the 1990s to present; in section two it reports, on the same topic, the findings of the quantitative and qualitative analysis of a corpus of six Italian L2/FL textbooks intended for children. The purpose of the analysis is to understand to what degree gendered content both visual and textual is purported to be neutral in language learning.In Italia diversi contributi hanno indagato sulla presenza nei libri di testo di modelli stereotipati in relazione al genere: molti di questi hanno lavorato sui testi delle scuole elementari italiane; più rari quelli sui testi per l’insegnamento dell’italiano L2/LS a ragazzi/e e a adulti. Non ci risultano studi che abbiano preso finora in esame gli stereotipi di genere nei testi per l’insegnamento dell’italiano L2/LS a bambini/e. Il contributo nella prima parte presenta una review delle ricerche italiane più significative sulla rappresentazione del genere nei libri di testo e nei testi per italiano L2/LS dagli anni Novanta a oggi; nella seconda parte offre, in merito allo stesso tema, i risultati dell’analisi quantitativa e qualitativa di un corpus di sei manuali di italiano L2/LS destinati a bambini/e. Lo scopo dell’analisi è comprendere quali contenuti di genere si fanno passare attraverso forme testuali – linguistiche e visive – spacciandole per neutre nell’apprendimento di una lingua

Prev Chronic Dis

Improving population health is not simple. Many instruments are available for changing behavior and consequent outcomes. However, the following basic principles should guide development of any incentive arrangement: 1) identify the desired outcome, 2) identify the behavior change that will lead to this outcome, 3) determine the potential effectiveness of the incentive in achieving the behavior change, 4) link a financial incentive directly to this outcome or behavior, 5) identify the possible adverse effects of the incentive, and 6) evaluate and report changes in the behavior or outcome in response to the incentive. A wide range of financial and nonfinancial incentives is available to encourage efficient behaviors and discourage costly and unproductive ones. Evidence for the beneficial effects of incentive programs has been slow to emerge, partly because such evidence must show how behaviors have changed because of the incentive. Nevertheless, the potential for incentive programs in health care seems large, and research should support their design and assess their effect

Gut microbiota markers in obese adolescent and adult patients: Age-dependent differential patterns

Obesity levels, especially in children, have dramatically increased over the last few decades. Recently, several studies highlighted the involvement of gut microbiota in the pathophysiology of obesity. We investigated the composition of gut microbiota in obese adolescents and adults compared to age-matched normal weight (NW) volunteers in order to assemble age- and obesity-related microbiota profiles. The composition of gut microbiota was analyzed by 16S rRNA-based metagenomics. Ecological representations of microbial communities were computed, and univariate, multivariate, and correlation analyses performed on bacterial profiles. The prediction of metagenome functional content from 16S rRNA gene surveys was carried out. Ecological analyses revealed a dissimilarity among the subgroups, and resultant microbiota profiles differed between obese adolescents and adults. Using statistical analyses, we assigned, as microbial markers, Faecalibacterium prausnitzii and Actinomyces to the microbiota of obese adolescents, and Parabacteroides, Rikenellaceae, Bacteroides caccae, Barnesiellaceae, and Oscillospira to the microbiota of NW adolescents. The predicted metabolic profiles resulted different in adolescent groups. Particularly, biosynthesis of primary bile acid and steroid acids, metabolism of fructose, mannose, galactose, butanoate, and pentose phosphate and glycolysis/gluconeogenesis were for the majority associated to obese, while biosynthesis and metabolism of glycan, biosynthesis of secondary bile acid, metabolism of steroid hormone and lipoic acid were associated to NW adolescents. Our study revealed unique features of gut microbiota in terms of ecological patterns, microbial composition and metabolism in obese patients. The assignment of novel obesity bacterial markers may open avenues for the development of patient-tailored treatments dependent on age-related microbiota profiles

Pathophysiology of Type 1 Diabetes and Gut Microbiota Role

Type 1 diabetes (T1D) is a multifactorial autoimmune disease driven by T-cells against the insulin-producing islet beta-cells, resulting in a marked loss of beta-cell mass and function. Although a genetic predisposal increases susceptibility, the role of epigenetic and environmental factors seems to be much more significant. A dysbiotic gut microbial profile has been associated with T1D patients. Moreover, new evidence propose that perturbation in gut microbiota may influence the T1D onset and progression. One of the prominent features in clinically silent phase before the onset of T1D is the presence of a microbiota characterized by low numbers of commensals butyrate producers, thus negatively influencing the gut permeability. The loss of gut permeability leads to the translocation of microbes and microbial metabolites and could lead to the activation of immune cells. Moreover, microbiota-based therapies to slow down disease progression or reverse T1D have shown promising results. Starting from this evidence, the correction of dysbiosis in early life of genetically susceptible individuals could help in promoting immune tolerance and thus in reducing the autoantibodies production. This review summarizes the associations between gut microbiota and T1D for future therapeutic perspectives and other exciting areas of research

Live cell imaging of membrane / cytoskeleton interactions and membrane topology

We elucidate the interaction between actin and specific membrane components, using real time live cell imaging, by delivering probes that enable access to components, that cannot be accessed genetically. We initially investigated the close interplay between Phosphatidylinositol 4,5-bisphosphate (PIP2) and the F-actin network. We show that, during the early stage of cell adhesion, PIP2 forms domains within the filopodia membrane. We studied these domains alongside cell spreading and observed that these very closely follow the actin tread-milling. We show that this mechanism is associated with an active transport of PIP2 rich organelles from the cell perinuclear area to the edge, along actin fibers. Finally, mapping other phospholipids and membrane components we observed that the PIP2 domains formation is correlated with sphingosine and cholesterol rafts