Potent and Stable Attenuation of Live-HIV-1 by Gain of a Proteolysis-resistant Inhibitor of NF-κB (IκB-αS32/36A) and the Implications for Vaccine Development *

Live-attenuated human immunodeficiency viruses (HIVs) are candidates for Acquired Immunodeficiency Syndrome (AIDS) vaccine. Based on the simian immunodeficiency virus (SIV) model for AIDS, loss-of-function (e.g. deletion of accessory genes such as nef) has been forwarded as a primary approach for creating enfeebled, but replication-competent, HIV-1/SIV. Regrettably, recent evidence suggests that loss-of-function alone is not always sufficient to prevent the emergence of virulent mutants. New strategies that attenuate via mechanisms distinct from loss-of-function are needed for enhancing the safety phenotype of viral genome. Here, we propose gain-of-function to be used simultaneously with loss-of-function as a novel approach for attenuating HIV-1. We have constructed an HIV-1 genome carrying the cDNA of a proteolysis-resistant nuclear factor-kappaB inhibitor (IkappaB-alphaS32/36A) in the nef region. HIV-1 expressing IkappaB-alphaS32/36A down-regulates viral expression and is highly attenuated in both Jurkat and peripheral blood mononuclear cells. We provide formal proof that the phenotypic and attenuating characteristics of IkappaB-alphaS32/36A permit its stable maintenance in a live, replicating HIV-1 despite 180 days of forced ex vivo passaging in tissue culture. As compared with other open-reading frames embedded into HIV/SIV genome, this degree of stability is unprecedented. Thus, IkappaB-alphaS32/36A offers proof-of-principle that artifactually gained functions, when used to attenuate the replication of live HIV-1, can be stable. These findings illustrate gain-of-function as a feasible strategy for developing safer live-attenuated HIVs to be tested as candidates for AIDS vaccine

THE ADVENT OF INDUSTRY 4.0 IN MANUFACTURING INDUSTRY: LITERATURE REVIEW AND GROWTH OPPORTUNITIES

Nowadays, the value creation process is based on management of a large amount of data, the Big Data, which are able to connect businesses and customers from all over the world (Xie et al., 2016). Considering the managerial and industrial points of view, Industry 4.0 is a new economic model for the industrial world (Peressotti, 2016), based on the evolution of production paradigm, technological change and process logic adoption: companies should change their business models, invest in staff training, adopting new managerial tools. As a result, the change of the market (from standardized to diversified) with the production of customized products. Machines and robots are able to communicate each other, to take decisions and to self-update. The production lines are automated: control and maintenance tasks can be performed remotely. As a consequence, the creation of the agile value chain: it allows you to monitor large amounts of data in real time, to track status and location of goods, to control the production process distantly. To study the level of adoption of 4.0 industrialization plans, two global indicators have been analyzed: they identify the placement of the largest industrial powers as a result of their industrialization policies adoption. Since the literature review shows few academic contributions and the subject is studied from engineering, computer and industrial design points of view, the objective of the work is to provide a theoretical contribution to managerial and industrial studies: the adoption of innovation in economic policy represents an opportunity to improve the country identity and the competitiveness level. So it is essential to encourage companies to adopt innovative tools, making the production automated. The methodology used is the content analysis technique: literature analysis, reports, conference proceedings, publications and websites are consulted. The originality of the work is to investigate a topic developed recently in Italy

Sub-nanomolar detection of biogenic amines by SERS effect induced by hairy Janus silver nanoparticles

Surface enhanced Raman scattering (SERS) is largely used as a transduction method for analytes detection in liquid and vapor phase. In particular, SERS effect was promoted by a plethora of different metal and semiconducting nanoparticles (NPs) and silver and gold nanoparticles appear particularly suitable for this application. Nevertheless, silver nanoparticles intrinsic propensity to aggregate in large clusters reduces the possibility to use naked nanoparticles in SERS applications, for this reason they are usually functionalized with organic molecules. This approach inhibits the aggregation process but, on the other hand, reduces the surficial area of the NPs able to interact with the analyte molecules. In the present work, we propose a simple method to obtain surficial anisotropic Janus silver nanoparticles: octadecylamine was used to stabilize the nanoparticles and to promote the deposition of the silver nanoparticles on a solid substrate. The AgNPs/octadecylamine nanostructures showed the typical “hairy” Janus morphology and a strong SERS effect was observed when two biogenic amines, i. e. 2-phenylethylamine and tyramine, were fluxed on the solid film. SERS phenomenon was studied as a function both of the chemical structure of the fluxed amine and of the distance between the aromatic moiety and the nanoparticle allowing to propose the AgNPs/octadecylamine Janus nanoparticles as an active layer for the detection of phenylethylamine and tyramine in picomolar concentration

Do the Fastest Open-Water Swimmers have A Higher Speed in Middle- and Long-Distance Pool Swimming Events?

Background: It has been shown that the fastest open-water swimmers (OW-swimmers) increase significantly the speed in the last split of the open-water events. The aim of the present work was to determine if the fastest OW-swimmers have a higher speed in the middle- and long-distance pool swimming events, and to develop a multivariate model that can predict the medalist group in the 10-km competition. Methods: A total of 484 athletes (252-males and 232-females) were included in the analysis. Swimmers were divided into four groups based on their finishing position in the competition. For each swimmer, the absolute best performance (PB) of 200, 400, 800 and 1500-meter in long course, the seasonal best performance (SPB) obtained before the open-water events and critical velocity (CV) were analyzed. Multivariate analysis of variance (MANOVA) was used to detect significant differences between groups and discriminant analysis was used to predict a grouping variable. Results: All the variables analyzed were significantly different between groups (p < 0.001). The first discriminant function correctly classified 50% of the overall female and male swimmers. Conclusion: Fastest OW-swimmers have a higher speed in middle- and long-distance pool swimming events. Further studies should include different anthropometric and physiological variables to increase the accuracy of classification

The impact of a 14-day altitude training camp on olympic-level open-water swimmers' sleep

Despite the common belief that sleep quality at altitude is poor, the scientific evidence to support this notion is still modest. Therefore, the purpose of the present study was to evaluate possible changes of actigraphy-based and subjective sleep parameters in a group of elite open-water swimmers during a 14-day altitude training camp (ATC) at 1500 m. The study subjects were five Olympic-level open-water swimmers (mean age: 25.0 ± 3.2 years; 3 females and 2 males). All subjects wore a wrist activity monitor and filled a sleep diary for 18 consecutive nights, 4 nights before and 14 nights during ATC. The data were then analyzed at four different time points: before ATC (PRE), the first two days of ATC (T1), and after one (T2) and two weeks of ATC (T3). Training load, assessed as the covered distance (km), session rating of perceived exertion (sRPE), and heart rate (HR), was monitored during the week before and the first and second week of ATC. No significant differences in objective and subjective scores of sleep quality were detected, whereas the sleep onset time (p = 0.018; η2p = 0.83, large) and sleep offset time (p &lt; 0.001; η2p = 0.95, large) significantly differed among PRE, T1, T2, and T3: elite athletes started to sleep and woke up ≃ 1 h earlier the first two days of ATC compared to PRE (sleep onset time: p = 0.049; sleep offset time: p = 0.016). Further, an increase in the training volume during the two weeks of the ATC was observed, with the most time spent in a low-intensity regime and an increase in time spent in a high-intensity regime compared to PRE. Sleep quality was not negatively influenced by a 14-day altitude training camp at 1500 m in a group of Olympic-level elite swimmers despite an increase in perceived exertion during training sessions. Nonetheless, early sleep onset and sleep offset times were observed for the first two nights of ATC: elite athletes started to sleep and woke up ≃ 1 h earlier compared to the baseline nights

Enhanced Bioactivity of Pomegranate Peel Extract following Controlled Release from CaCO3 Nanocrystals

none9Pomegranate peel extract is rich of interesting bioactive chemicals, principally phenolic compounds, which have shown antimicrobial, anticancer, and antioxidative properties. The aim of this work was to improve extract’ bioactivity through the adsorption on calcium carbonate nanocrystals. Nanocrystals revealed as efficient tools for extract adsorption reaching 50% of loading efficiency. Controlled release of the contained metabolites under acidic pH has been found, as it was confirmed by quantitative assay and qualitative study through NMR analysis. Specific functionality of inorganic nanocarriers could be also tuned by biopolymeric coating. The resulting coated nanoformulations showed a great antimicrobial activity against B. cinerea fungus preventing strawberries disease better than a commercial fungicide. Furthermore, nanoformulations demonstrated a good antiproliferative activity in neuroblastoma and breast cancer cells carrying out a higher cytotoxic effect respect to free extract, confirming a crucial role of nanocarriers. Finally, pomegranate peel extract showed a very high radical scavenging ability, equal to ascorbic acid. Antioxidant activity, measured also in intracellular environment, highlighted a protective action of extract-adsorbed nanocrystals twice than free extract, providing a possible application for new nutraceutical formulations.Regione Puglia, Project Research for Innovation (REFIN) “Sintesi di un sistema teranostico a base di nano-cellulosa per la detection e la cura dei tumori” Ministero dello Sviluppo Economico, bando “AGRIFOOD” D.M. 5 marzo 2018 Capo III. Prog. N. F/200060/01-03/X45 PERSEFONE - Punica granatum e Nanotecnologie: una value chain per la valorizzazione degli scarti e sottoprodotti finalizzata alla produzione di integratori alimentari e compost. PON Ricerca e Innovazione 2014-2020 - Avviso per la presentazione di progetti dei Ricerca Industriale e Sviluppo Sperimentale nelle 12 aree di specializzazione individuate dal PNR 2015 – 2020, di cui al Decreto Direttoriale MIUR del 13 luglio 2017, n. 1735 NanotEcnologie chiMiche green per la protEzione Sostenibile delle pIante (NEMESI) ARS01_01002 Area di Specializzazione “Chimica Verde” CUP: F36C18000180005, Ministero dell'Università e Ricerca. “Olivicoltura e difesa da Xylella fastidiosa e da insetti vettori in Italia - (Oli.Di.X.I.It)”, prot. Mipaaf n.0011485 del 05/04/2017 Ministry of Agricultural, Food and Forestry Policies.openFrancesca Baldassarre; Viviana Vergaro; Federica De Castro; Francesca Biondo; Gian Paolo Suranna; Paride Papadia; Francesco P. Fanizzi; Domenico Rongai; Giuseppe CiccarellaBaldassarre, Francesca; Vergaro, Viviana; DE CASTRO, Federica; Biondo, Francesca; Suranna, Gian Paolo; Papadia, Paride; Fanizzi, Francesco P.; Rongai, Domenico; Ciccarella, Giusepp

Properties of Nanocrystals-formulated Aluminosilicate Bricks

In the present work, seven different types of nanocrystals were studied as additives in the formulation of aluminosilicate bricks. The considered nanocrystals consisted of anatase titanium dioxide (two differently shaped types), boron modified anatase, calcium carbonate (in calcite phase), aluminium hydroxide and silicon carbide (of two diverse sizes), which were prepared using different methods. Syntheses aim to give a good control over a particle’s size and shape. Anatase titania nanocrystals, together with the nano-aluminium hydroxide ones, were synthesized via microwave-assisted procedures, with the use of different additives and without the final calcination steps. The silicon carbide nanoparticles were prepared via laser pyrolysis. The nano-calcium carbonate was prepared via a spray drying technique. All of the nanocrystals were tested as fillers (in 0.5, 1 and 2 wt. % amounts) in a commercial aluminosilicate refractory (55 % Al2O3, 42 % SiO2). They were used to prepare bricks that were thermally treated at 1300 °C for 24 hours, according to the international norms. The differently synthesized nanocrystals were added for the preparation of the bricks, with the aim to improve their heat-insulating and/or mechanical properties. The nanocrystals-modified refractories showed variations in properties, with respect to the untreated aluminosilicate reference in heat-insulating performances (thermal diffusivities were measured by the “hot disk” technique). In general, they also showed improvements in mechanical compression resistance for all of the samples at 2 wt. %. The best heat insulation was obtained with the addition of nano-aluminium hydroxide at 2 wt. %, while the highest mechanical compression breaking resistance was found with nano-CaCO3 at 2 wt. %. These outcomes were investigated with complementary techniques, like mercury porosimetry for porosity, and Archimedes methods to measure physical properties like the bulk and apparent densities, apparent porosities and water absorption. The results show that the nano-aluminium hydroxide modified bricks were the most porous, which could explain the best heat-insulating performances. There is a less straightforward explanation for the mechanical resistance results, as they may have relations with the characteristics of the pores. Furthermore, the nanoparticles may have possible reactions with the matrix during the heat treatments

Non-Aβ-dependent factors associated with global cognitive and physical function in alzheimer's disease: a pilot multivariate analysis

Recent literature highlights the importance of identifying factors associated with mild cognitive impairment (MCI) and Alzheimer's Disease (AD). Actual validated biomarkers include neuroimaging and cerebrospinal fluid assessments; however, we investigated non-Aβ-dependent factors associated with dementia in 12 MCI and 30 AD patients. Patients were assessed for global cognitive function (Mini-Mental state examination-MMSE), physical function (Physical Performance Test-PPT), exercise capacity (6-min walking test-6MWT), maximal oxygen uptake (VO₂max), brain volume, vascular function (flow-mediated dilation-FMD), inflammatory status (tumor necrosis factor-α ,TNF- α, interleukin-6, -10 and -15) and neurotrophin receptors (p75NTR and Tropomyosin receptor kinase A -TrkA). Baseline multifactorial information was submitted to two separate backward stepwise regression analyses to identify the variables associated with cognitive and physical decline in demented patients. A multivariate regression was then applied to verify the stepwise regression. The results indicated that the combination of 6MWT and VO₂max was associated with both global cognitive and physical function (MMSE = 11.384 + (0.00599 × 6MWT) - (0.235 × VO₂max)); (PPT = 1.848 + (0.0264 × 6MWT) + (19.693 × VO₂max)). These results may offer important information that might help to identify specific targets for therapeutic strategies (NIH Clinical trial identification number NCT03034746)