Snail protein inhibition by drug repositioning for recurrent breast cancer: an in-silico study

Objective: Snail is a transcription factor that promotes epithelial-mesenchymal transition (EMT) and facilitates tumor progression and metastasis in breast cancer. Therefore, it is a promising target for the development of anticancer agents. The objective of this study was to identify FDA-approved drugs that can be repurposed as Snail inhibitors. Materials and Methods: Using a virtual screening strategy, three molecules were selected among 1615 (Stivarga, Paritaprevir and Sorafenib). Molecular docking and molecular dynamics simulation were performed to examine Snail-drugs interactions. Results: Our docking analysis identified Stivarga and Sorafenib, two antineoplastic drugs, as potential repositioning drugs to treat recurrent breast cancer due to their low free binding energy values. Additional molecular dynamics simulations of the Snail-drug systems revealed that Sorafenib was the most stable, lasting from 30 to 120 ns and forming 2-4 hydrogen bonds. Conclusions: The antineoplastic drugs Stivarga and Sorafenib have better affinity and inhibition of Snail and could be a simple drug therapy for recurrent breast cancer

Reversible stimulus-responsive Cu(i) iodide pyridine coordination polymer

We present a structurally flexible copper–iodide–pyridine-based coordination polymer showing drastic variations in its electrical conductivity driven by temperature and sorption of acetic acid molecules. The dramatic effect on the electrical conductivity enables the fabrication of a simple and robust device for gas detection. X-ray diffraction studies and DFT calculations allow the rationalisation of these observations.We are thankful for support from MICINN (MAT2013-46753-C2-1-P, MAT2013-46502-C2-1/2-P and CTQ2011-26507), Eusko Jaurlaritza (S-PE13UN016) and Generalitat Valenciana PrometeoII/2014/076

Production, characterization, and antigen specificity of recombinant 62-71-3, a candidate monoclonal antibody for rabies prophylaxis in humans

Rabies kills many people throughout the developing world every year. The murine monoclonal antibody (mAb) 62-71-3 was recently identified for its potential application in rabies postexposure prophylaxis (PEP). The purpose here was to establish a plant-based production system for a chimeric mouse-human version of mAb 62-71-3, to characterize the recombinant antibody and investigate at a molecular level its interaction with rabies virus glycoprotein. Chimeric 62-71-3 was successfully expressed in Nicotiana benthamiana. Glycosylation was analyzed by mass spectroscopy; functionality was confirmed by antigen ELISA, as well as rabies and pseudotype virus neutralization. Epitope characterization was performed using pseudotype virus expressing mutagenized rabies glycoproteins. Purified mAb demonstrated potent viral neutralization at 500 IU/mg. A critical role for antigenic site I of the glycoprotein, as well as for two specific amino acid residues (K226 and G229) within site I, was identified with regard to mAb 62-71-3 neutralization. Pseudotype viruses expressing glycoprotein from lyssaviruses known not to be neutralized by this antibody were the controls. The results provide the molecular rationale for developing 62-71-3 mAb for rabies PEP; they also establish the basis for developing an inexpensive plant-based antibody product to benefit low-income families in developing countries.—Both, L., van Dolleweerd, C., Wright, E., Banyard, A. C., Bulmer-Thomas, B., Selden, D., Altmann, F., Fooks, A. R., Ma, J. K.-C. Production, characterization, and antigen specificity of recombinant 62-71-3, a candidate monoclonal antibody for rabies prophylaxis in humans

Toward a multiscale modeling framework for understanding serotonergic function

Despite its importance in regulating emotion and mental wellbeing, the complex structure and function of the serotonergic system present formidable challenges toward understanding its mechanisms. In this paper, we review studies investigating the interactions between serotonergic and related brain systems and their behavior at multiple scales, with a focus on biologically-based computational modeling. We first discuss serotonergic intracellular signaling and neuronal excitability, followed by neuronal circuit and systems levels. At each level of organization, we will discuss the experimental work accompanied by related computational modeling work. We then suggest that a multiscale modeling approach that integrates the various levels of neurobiological organization could potentially transform the way we understand the complex functions associated with serotonin

Public–Private Partnership in Tunisia: Enfidha Airport Assessment of an Infrastructure Achievement

One of the largest recent private-sector investments and the first airport private-sector concession in the Maghreb is Enfidha Airport, a key factor in the success of the Tunisian Government’s public– private partnership (PPP) strategy. However, since Tunisia’s Jasmine Revolution, political and social turmoil is sweeping the country and worsening the economic indicators. This article aims to assess this PPP infrastructure, allowing us to determine if it is profitable in the long term and contributes therefore to the economic growth. The case study reveals the key role of the economic, social, and political environment in Tunisia, the dawn of the Arab Spring

A formal classification of the Lygeum spartum vegetation of the Mediterranean Region

Aims We examined local and regional contribution on the grasslands dominated by Lygeum spartum from Southern Europe and North Africa to produce a formalised classification of this vegetation and to identify main factors driving its plant species composition. Location Mediterranean Basin and Iberian Peninsula. Methods We used a dataset of 728 relevés, which were resampled to reduce unbalanced sampling effort, resulting in a dataset of 568 relevés and 846 taxa. We classified the plots by TWINSPAN, interpreted the resulting pools, and used them to develop formal definitions of phytosociological alliances characterised by L. spartum vegetation. The definitions were included in an expert system to assist automatic vegetation classification. We related the alliances to climatic factors and described their biogeographical features and ecological preferences. The floristic relationships between these alliances were analysed and visualised using distance‐based redundancy analysis. Results We defined eleven alliances of L. spartum vegetation, including the newly described Launaeo laniferae‐Lygeion sparti from SW Morocco and the Noaeo mucronatae‐Lygeion sparti from the Algerian highlands and NE Morocco. Biogeographical, climatic, and edaphic factors were revealed as putatively driving the differentiation between the alliances. The vegetation of clayey slopes and inland salt basins displayed higher variability in comparison with those of coastal salt marshes. Main conclusions The most comprehensive formal classification, accompanied by an expert system, of the L. spartum vegetation was formulated. The expert system, containing the formal definitions of the phytosociological alliances, will assist in identification of syntaxonomic position of new datasets

First direct detection constraints on planck-scale mass dark matter with multiple-scatter signatures using the DEAP-3600 detector

Dark matter with Planck-scale mass (?1019 GeV/c2) arises in well-motivated theories and could be produced by several cosmological mechanisms. A search for multiscatter signals from supermassive dark matter was performed with a blind analysis of data collected over a 813 d live time with DEAP-3600, a 3.3 t single-phase liquid argon-based detector at SNOLAB. No candidate signals were observed, leading to the first direct detection constraints on Planck-scale mass dark matter. Leading limits constrain dark matter masses between 8.3×106 and 1.2×1019 GeV/c2, and Ar40-scattering cross sections between 1.0×10-23 and 2.4×10-18 cm2. These results are interpreted as constraints on composite dark matter models with two different nucleon-to-nuclear cross section scalings