Fibroblast Growth Factor-2 and the HIV-1 Tat Protein Synergize in Promoting Bcl-2 Expression and Preventing Endothelial Cell Apoptosis: Implications for the Pathogenesis of AIDS-Associated Kaposi's Sarcoma

Kaposi's sarcoma (KS) is a vascular tumor frequently occurring in Human Immunodeficiency Virus- (HIV-) 1-infected individuals. Our previous work indicated that the angiogenic fibroblast growth factor (FGF)-2 and the Tat protein of HIV-1, both expressed in KS lesions of HIV-infected patients, synergize at inducing angioproliferative, KS-like lesions in mice. Here we show that the development of angioproliferative lesions promoted in mice by combined Tat and FGF-2 associates with an increase in the levels of expression of the antiapoptotic Bcl-2 protein. Upregulation of Bcl-2 expression by combined FGF-2 and Tat occurs also in vitro, and this protects human primary endothelial cells from programmed cell death. As Bcl-2 is expressed in human KS lesions in a fashion paralleling the progression of the disease, these findings suggest a molecular mechanism by which Tat and FGF-2 cooperate in KS maintenance and progression in HIV-infected individuals

Traditional farmers’ varieties: a valuable source of genetic variability for biofortification programs

Several studies underlined the superiority from a nutritional point of view of ancient varieties. In the last years the interest for landraces has been growing, for this reason preservation and valorisation of these genetic sources is very important. In particular these varieties are source of precious genetic variability interesting from a scientific point of view to preserve biodiversity but also for biofortification programs aimed to support small rural communities, where the particular maize germplasm has been developed. In this work we characterized from the nutritional point of view 13 ancient Italian varieties and one coming from Spain (Millo Corvo). In this pre-breeding work we demonstrate the nutritional superiority of ancient varieties if compared with modern hybrids. In particular Spinato di Gandino is the best variety for milling properties and for oil, protein, and total phosphorus content; Storo is the best variety for calorific value and for carotenoids and free phosphorus content. Using these varieties in the next future we will start a bio-fortification program aimed to obtain new populations with improved yields and high nutritional value

3D Microfluidic model for evaluating immunotherapy efficacy by tracking dendritic cell behaviour toward tumor cells

Immunotherapy efficacy relies on the crosstalk within the tumor microenvironment between cancer and dendritic cells (DCs) resulting in the induction of a potent and effective antitumor response. DCs have the specific role of recognizing cancer cells, taking up tumor antigens (Ags) and then migrating to lymph nodes for Ag (cross)-presentation to naïve T cells. Interferon-α-conditioned DCs (IFN-DCs) exhibit marked phagocytic activity and the special ability of inducing Ag-specific T-cell response. Here, we have developed a novel microfluidic platform recreating tightly interconnected cancer and immune systems with specific 3D environmental properties, for tracking human DC behaviour toward tumor cells. By combining our microfluidic platform with advanced microscopy and a revised cell tracking analysis algorithm, it was possible to evaluate the guided efficient motion of IFN-DCs toward drug-treated cancer cells and the succeeding phagocytosis events. Overall, this platform allowed the dissection of IFN-DC-cancer cell interactions within 3D tumor spaces, with the discovery of major underlying factors such as CXCR4 involvement and underscored its potential as an innovative tool to assess the efficacy of immunotherapeutic approaches

Phenol-Rich Food Acceptability: The Influence of Variations in Sweetness Optima and Sensory-Liking Patterns

12openInternationalItalian coauthor/editorThe consumption of phenol-rich foods is limited by their prominent bitterness and astringency. This issue has been addressed by adding sweet tastes, which suppress bitterness, but this is not a complete solution since individuals also differ in their preference for sweetness. In this study, we aimed at identifying groups of consumers differing in sweetness optima and sensory-liking patterns. To this end, increasing concentrations of sucrose were added to a chocolate pudding base. This allowed us to (1) investigate if individual differences in sensory responses are associated with different sweet liking optima in a product context, (2) define the psychological and oro-sensory profile of sweet liker phenotypes derived using a product context, and (3) assess if individuals differing in sweet liking optima differ also in consumption and liking of phenol-rich foods and beverages as a function of their sensory properties (e.g., sweeter vs. more bitter and astringent products). Individuals (1208; 58.4% women, 18–69 years) were characterised for demographics, responsiveness to 6-n-propylthiouracil (PROP), personality traits and attitudes toward foods. Three clusters were identified based on correlations between sensory responses (sweetness, bitterness and astringency) and liking of the samples: liking was positively related to sweetness and negatively to bitterness and astringency in High and Moderate Sweet Likers, and the opposite in Inverted U-Shaped. Differences between clusters were found in age, gender and personality. Furthermore, the Inverted-U Shaped cluster was found to have overall healthier food behaviours and preferences, with higher liking and consumption of phenol-rich vegetables and beverages without added sugar. These findings point out the importance of identifying the individual sensory-liking patterns in order to develop more effective strategies to promote the acceptability of healthy phenol-rich foods.openSpinelli, Sara; Prescott, John; Pierguidi, Lapo; Dinnella, Caterina; Arena, Elena; Braghieri, Ada; Di Monaco, Rossella; Gallina Toschi, Tullia; Endrizzi, Isabella; Proserpio, Cristina; Torri, Luisa; Monteleone, ErminioSpinelli, S.; Prescott, J.; Pierguidi, L.; Dinnella, C.; Arena, E.; Braghieri, A.; Di Monaco, R.; Gallina Toschi, T.; Endrizzi, I.; Proserpio, C.; Torri, L.; Monteleone, E

1H–NMR fingerprinting and supervised pattern recognition to evaluate the stability of virgin olive oil during storage

Metabolomic fingerprinting of virgin olive oil (VOO) by 1H NMR spectroscopy was used to study its stability during storage simulating normal shelf life conditions during its commercialization. A representative set of VOOs covering the full range of possible chemical compositions were exposed to light (500 lux for 12 h/day) at 25 °C for 12 months or stored in the dark at 25 °C, 30 °C and 35 °C for 24 months. Multivariate data analysis of the 1H NMR spectra of the oil samples provided classification models to evaluate VOO freshness and to verify the light exposure of the VOO during storage, as well as regression models to determine VOO storage time and tentatively the best before date of a fresh VOO. These predictive models disclosed the chemical compounds responsible for the compositional changes in VOO due to hydrolytic and oxidative degradation taking place during its storage, and confirmed that light and increasing temperature enhance these processes. The presence of characteristic resonances of hydroperoxides (primary oxidation products) and the decrease of 1H signals assigned to phenolic compounds, mainly secoiridoid derivatives, and other minor compounds such as fatty acids, squalene and native (E)-2-hexenal present in fresh VOO revealed its oxidative degradation. Further, the emergence of low intensity 1H signals of saturated aldehydes meant that the secondary oxidation process has started at a low rate and yield. Moreover, the decrease of the 1H signals of triacylglycerides and sn-1,2-diacylglycerides, and the increase of sn-1,3-diacylglycerides indicated that hydrolytic degradation of VOO and diacylglyceride isomerisation was occurring. 1H NMR fingerprint of VOO together with pattern recognition techniques afford relevant information to assess the quality of VOOs taking into consideration legal, sensory and health-promoting aspects.Fil: Alonso Salces, Rosa Maria. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; ArgentinaFil: Gallo, Blanca. Universidad del País Vasco; EspañaFil: Collado, María Isabel. Universidad del País Vasco; EspañaFil: Sasía Arriba, Andrea. Universidad del País Vasco; EspañaFil: Viacava, Gabriela Elena. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Departamento de Ingeniería Química. Grupo de Investigación en Ingeniería en Alimentos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; ArgentinaFil: García González, Diego Luis. Universidad Pablo de Olavide; EspañaFil: Gallina Toschi, Tullia. Universidad de Bologna; ItaliaFil: Servili, Maurizio. Università di Perugia; ItaliaFil: Berrueta, Luis Ángel. Universidad del País Vasco; Españ

Progression of brain atrophy in spinocerebellar ataxia type 2: A longitudinal tensor-based morphometry study

Spinocerebellar ataxia type 2 (SCA2) is the second most frequent autosomal dominant inherited ataxia worldwide. We investigated the capability of magnetic resonance imaging (MRI) to track in vivo progression of brain atrophy in SCA2 by examining twice 10 SCA2 patients (mean interval 3.6 years) and 16 age- and gender-matched healthy controls (mean interval 3.3 years) on the same 1.5 T MRI scanner. We used T1-weighted images and tensor-based morphometry (TBM) to investigate volume changes and the Inherited Ataxia Clinical Rating Scale to assess the clinical deficit. With respect to controls, SCA2 patients showed significant higher atrophy rates in the midbrain, including substantia nigra, basis pontis, middle cerebellar peduncles and posterior medulla corresponding to the gracilis and cuneatus tracts and nuclei, cerebellar white matter (WM) and cortical gray matter (GM) in the inferior portions of the cerebellar hemisphers. No differences in WM or GM volume loss were observed in the supratentorial compartment. TBM findings did not correlate with modifications of the neurological deficit. In conclusion, MRI volumetry using TBM is capable of demonstrating the progression of pontocerebellar atrophy in SCA2, supporting a possible role of MRI as biomarker in future trials

Transdifferentiation of pancreatic ductal cells to endocrine β-cells,”

Abstract The regenerative process in the pancreas is of particular interest, since diabetes, whether Type 1 or Type 2, results from an inadequate amount of insulin-producing β-cells. Islet neogenesis, or the formation of new islets, seen as budding of hormone-positive cells from the ductal epithelium, has long been considered to be one of the mechanisms of normal islet growth after birth and in regeneration, and suggested the presence of pancreatic stem cells. Results from the rat regeneration model of partial pancreatectomy led us to hypothesize that differentiated pancreatic ductal cells were the pancreatic progenitors after birth, and that with replication they regressed to a less differentiated phenotype and then could differentiate to form new acini and islets. There are numerous supportive results for this hypothesis of neogenesis, including the ability of purified primary human ducts to form insulin-positive cells budding from ducts. However, to rigorously test this hypothesis, we took a direct approach of genetically marking ductal cells using CAII (carbonic anhydrase II) as a duct-cell-specific promoter to drive Cre recombinase in lineage-tracing experiments using the Cre-Lox system. We show that CAII-expressing pancreatic cells act as progenitors that give rise to both new islets and acini after birth and after injury (ductal ligation). This identification of a differentiated pancreatic cell type as an in vivo progenitor for all differentiated pancreatic cell types has implications for a potential expandable source for new islets for replenishment therapy for diabetes either in vivo or ex vivo

Quantitative dopamine transporter imaging assessment in Parkinson’s disease (PD) patients carrying GBA gene mutations compared with Idiopathic PD patients: A case-control study

Background: Genetic risk factors impact around 15% of Parkinson’s disease (PD) patients and at least 23 variants have been identified including Glucocerebrosidase (GBA) gene variants. Using different clinical and instrumental qualitative-based data, various studies have been published on GBA-PD cohorts which suggested possible differences in dopaminergic nigrostriatal denervation pattern, particularly in caudate and putamen nuclei. Methods: This retrospective study included two consecutive homogenous cohorts of GBA-PD and idiopathic (I-PD) patients. Each consecutive GBA-PD patient has been matched with a 1:1 pairing method with a consecutive I-PD subject according to age, age at disease onset, sex, Hoehn & Yahr (H&Y) staging scale and comorbidity level (CCI). Semiquantitative volumetric data by the DaTQUANTTM software integrated in the DaTSCAN exam performed at time of the diagnosis (SPECT imaging performed according to current guidelines of I-123 FPCIT SPECT imaging) were extrapolated. Bilateral specific binding ratios (SBR) at putamen and caudate levels were calculated, using the occipital lobes uptake. The Mann–Whitney test was performed to compare the two cohorts while the Spearman’s test was used to find correlations between motor and volumetric data in each group. Bonferroni correction was used to account for multiple comparisons. Results: Two cohorts of 25 patients each (GBA-PD and I-PD), were included. By comparing GBA-PD and I-PD patients, lower SBR values were found in the most affected anterior putamen and left caudate of the GBA-PD cohort. Furthermore, in the GBA-PD cohort the SBR of the most affected posterior putamen negatively correlated with the H&Y scale. However, none of these differences or correlations remained significant after Bonferroni correction for multiple comparisons. Conclusions: We observed differences in SBR values in GBA-PD patients compared with I-PD. However, these differences were no longer significant after Bonferroni multiple comparisons correction highlighting the need for larger, longitudinal studies