Dengue Type 3 Virus, Saint Martin, 2003–2004

We describe the spread of a dengue virus during an outbreak in Saint Martin island (French West Indies) during winter 2003–2004. Dengue type 3 viruses were isolated from 6 patients exhibiting clinical symptoms. This serotype had not been detected on the island during the preceding 3 years. Genome sequence determinations and analyses showed a common origin with dengue type 3 viruses isolated in Martinique 2 years earlier

Soluzione Android-based per il Discovery e l'Accesso a Servizi fra Reti Locali Federate

Negli ultimi anni abbiamo assistito alla rapida proliferazione di dispositivi sempre più piccoli in termini di dimensioni ma con delle capacità computazionali sempre più elevate. Con il numero di questi dispositivi in continua crescita, unita alle tecnologie di comunicazione sempre più economiche è nata quella che viene chiamata Internet of Things. La caratteristica principale per far parte di Internet of Things è quella di essere in grado di comunicare con gli altri. Ad oggi le maggiore tecnologie utilizzate sono Wifi e LTE ma necessitano di una infrastruttura esistente sul territorio. Al fine di poter arginare il vincolo delle infrastrutture, sono stati implementati una serie di middleware che permettono di costruire delle particolari reti di oggetti connessi, che in letteratura vengono definite \textbf{MANET}, esempio Google Nearby. Poichè il contesto in qui vengono applicati è altamente dinamico e volatile, è fondamentale avere la possibilità di scoprire la presenza di servizi all'interno della rete, senza bisogno di nessun tipo di conoscenza. Il problema però è che non tutti i middleware offrono questa funzionalità e molte volte i normali servizi di discovery non possono essere utilizzati. Lo studio fatto in questo elaborato è mirato a cercare una soluzione a basso costo che permette di abilitare un sistema di discovery su reti federate fornendo ricerca e accesso ai servizi. La soluzione proposta è stata quella di sfruttare un servizio di discovery come DNS-SD (chiamato anche Bonjour) per scoprire i servizi in una rete locale basata su Wifi e comunicarli ad altre reti attraverso una comunicazione Wifi Direct. Come per i vari middleware, l'ipotesi alla base del funzionamento del servizio è la vicinanza geografica delle reti, in modo da poter creare un ponte tra di esse attraverso una connessione P2P

Three-Dimensional Wax Patterning of Paper Fluidic Devices

In this paper we describe a method for three-dimensional wax patterning of microfluidic paper-based analytical devices (μPADs). The method is rooted in the fundamental details of wax transport in paper and provides a simple way to fabricate complex channel architectures such as hemichannels and fully enclosed channels. We show that three-dimensional μPADs can be fabricated with half as much paper by using hemichannels rather than ordinary open channels. We also provide evidence that fully enclosed channels are efficiently isolated from the exterior environment, decreasing contamination risks, simplifying the handling of the device, and slowing evaporation of solvents

The Quantitation of 7β-Hydroxy-Epiandrosterone in the Plasma and Seminal Plasma of Men With Different Degrees of Fertility

International audience7β-hydroxy-epiandrosterone (7β-OH-EpiA) is an endogenous androgen metabolite that has been shown to exert neuroprotective, anti-inflammatory and anti-estrogenic effects. However, to the best of our knowledge no information is available about this androgen steroid in relation to sperm quality. We analyzed 7β-OH-EpiA in plasma and seminal plasma using a newly developed isotope dilution ultra-high performance liquid chromatography – mass spectrometry method. Validation met the requirements of FDA guidelines. Levels of 7β-OH-EpiA were measured in 191 men with different degrees of infertility. One-way analysis of variance followed by multiple comparison and correlation analysis adjusted for age, BMI and abstinence time were performed to evaluate the relationships between this steroid and sperm quality. Concentrations of 7β-OH-EpiA in seminal plasma were significantly higher in severely infertile men in comparison with healthy men and slightly infertile men. The same trend was found when blood plasma was evaluated. Furthermore, plasma 7β-OH-EpiA negatively correlated with sperm concentration (-0.215; p<0.01) and total count (-0.15; p<0.05). Seminal 7β-OH-EpiA was negatively associated with motility (-0.26; p<0.01), progressively motile spermatozoa (-0.233; p<0.01) and nonprogressively motile spermatozoa (-0.188; p<0.05). 7β-OH-EpiA is associated with lower sperm quality and deserves more research in that respect

Colorectal anticancer activity of a novel class of triazolic triarylmethane derivatives

peer reviewedTriarylmethanes and triazoles constitute privileged structures extensively used in drug discovery programs. In this work, 12 novel triarylmethanes linked to a triazole ring were designed, synthesized, and chemically characterized aiming to target colorectal cancer. The synthetic strategy for triarylmethanes mono- and bi-substituted by a functionalized triazole ring involved a 1,3-dipolar cycloaddition. A preliminary screening in human colorectal cancer cells (HT-29 and HCT116) and murine primary fibroblasts (L929) allowed the selection of the best candidate 9b based on its high inhibition of cancer cell proliferation with an IC50 of 11 μM on HT-29 and 14 μM on HCT116 and its non-cytotoxic effects on murine fibroblasts (<100 μM). A deep mechanistic study on various pathways showed that compound 9b induces caspase-3 cleavage, and its inhibitory effect on PARP activity is correlated with the increase of DNA fragmentation in cancer cells. Moreover, 9b induced apoptosis promoted by the inhibition of anti-apoptotic cell survival signaling pathways demonstrated via the downregulation of phosphorylated Akt and ERK proteins. Finally, the predicted binding modes of compounds 8c and 9b to five potential biological targets (i.e., AKT, ERK-1 and ERK-2, PARP and caspase-3) was evaluated using molecular modeling, and the predictions of the SuperPred webserver identified ERK2 as the most remarkable target. Also predicted in silico, 9b displayed appropriate drug-likeness and good absorption, distribution, metabolism and excretion (ADME) profiles

Pegylated triarylmethanes: Synthesis, antimicrobial activity, anti-proliferative behavior and in silico studies

We describe herein the synthesis, characterization and biological studies of novel PEGylated triarylmethanes. Non-symmetrical and symmetrical triarylmethanes series have been synthesized by Friedel-Crafts hydroxyalkylation or directly from bisacodyl respectively followed by a functionalization with PEG fragments in order to increase bioavailability and biological effectiveness. The antimicrobial activity was investigated against Gram-positive and Gram-negative foodborne pathogens and against Candida albicans, an opportunistic pathogenic yeast. The biocidal activity was also studied using Staphylococcus aureus as a reference bacterium. Almost all PEGylated molecules displayed an antifungal activity comparable with fusidic acid with MIC values ranging from 6.25 to 50 μg/mL. Compounds also revealed a promising anti-biofilm activity with biofilm eradication percentages values above 80% for the best molecules (compounds 4d and 7). Compounds 7 and 8b showed a modest antiproliferative activity against human colorectal cancer cell lines HT-29. Finally, in silico predictions suggested adequate ADME and drug-likeness profiles for the synthetized triarylmethanes.Peer reviewe

The NF-κB RelA Transcription Factor Is Critical for Regulatory T Cell Activation and Stability

International audienceRegulatory T cells (Tregs) play a major role in immune homeostasis and in the prevention of autoimmune diseases. It has been shown that c-Rel is critical in Treg thymic differentiation, but little is known on the role of NF-κB on mature Treg biology. We thus generated mice with a specific knockout of RelA, a key member of NF-κB, in Tregs. These mice developed a severe autoimmune syndrome with multi-organ immune infiltration and high activation of lymphoid and myeloid cells. Phenotypic and transcriptomic analyses showed that RelA is critical in the acquisition of the effector Treg state independently of surrounding inflammatory environment. Unexpectedly, RelA-deficient Tregs also displayed reduced stability and cells that had lost Foxp3 produced inflammatory cytokines. Overall, we show that RelA is critical for Treg biology as it promotes both the generation of their effector phenotype and the maintenance of their identity