From antimicrobial to anticancer peptides : a review

Antimicrobial peptides (AMPs) are part of the innate immune defense mechanism of many organisms. Although AMPs have been essentially studied and developed as potential alternatives for fighting infectious diseases, their use as anticancer peptides (ACPs) in cancer therapy either alone or in combination with other conventional drugs has been regarded as a therapeutic strategy to explore. As human cancer remains a cause of high morbidity and mortality worldwide, an urgent need of new, selective, and more efficient drugs is evident. Even though ACPs are expected to be selective toward tumor cells without impairing the normal body physiological functions, the development of a selective ACP has been a challenge. It is not yet possible to predict antitumor activity based on ACPs structures. ACPs are unique molecules when compared to the actual chemotherapeutic arsenal available for cancer treatment and display a variety of modes of action which in some types of cancer seem to co-exist. Regardless the debate surrounding the definition of structure-activity relationships for ACPs, great effort has been invested in ACP design and the challenge of improving effective killing of tumor cells remains. As detailed studies on ACPs mechanisms of action are crucial for optimizing drug development, in this review we provide an overview of the literature concerning peptides' structure, modes of action, selectivity, and efficacy and also summarize some of the many ACPs studied and/or developed for targeting different solid and hematologic malignancies with special emphasis on the first group. Strategies described for drug development and for increasing peptide selectivity toward specific cells while reducing toxicity are also discussed.The authors thank Fundação para a Ciência e a Tecnologia (FCT- MEC, Portugal) for funding—PTDC/QUI-BIO/112929/2009. Diana Gaspar also acknowledges FCT for fellowship SFRH/BPD/ 73500/2010 and A. Salome Veiga for funding within the FCT Investigator Programme (IF/00803/2012

Probing DNA conformational changes with high temporal resolution by Tethered Particle Motion

The Tethered Particle Motion (TPM) technique informs about conformational changes of DNA molecules, e.g. upon looping or interaction with proteins, by tracking the Brownian motion of a particle probe tethered to a surface by a single DNA molecule and detecting changes of its amplitude of movement. We discuss in this context the time resolution of TPM, which strongly depends on the particle-DNA complex relaxation time, i.e. the characteristic time it takes to explore its configuration space by diffusion. By comparing theory, simulations and experiments, we propose a calibration of TPM at the dynamical level: we analyze how the relaxation time grows with both DNA contour length (from 401 to 2080 base pairs) and particle radius (from 20 to 150~nm). Notably we demonstrate that, for a particle of radius 20~nm or less, the hydrodynamic friction induced by the particle and the surface does not significantly slow down the DNA. This enables us to determine the optimal time resolution of TPM in distinct experimental contexts which can be as short as 20~ms.Comment: Improved version, to appear in Physical Biology. 10 pages + 10 pages of supporting materia

Shifting gear in antimicrobial and anticancer peptides biophysical studies : from vesicles to cells

© 2015 European Peptide Society and John Wiley & Sons, Ltd.Despite the intensive study on the mechanism of action of membrane-activemolecules such as antimicrobial and anticancer peptides, most of the biophysical work has been performed using artificial model systems, mainly lipid vesicles. The use of these systems allows full control of the experimental parameters, and to obtain molecular-level detail on the action of peptides, the correlation with biological action is intangible. Recently, several biophysicalmethodologies have been translated to studies using bacterial and cancer cells. Here, we review biophysical studies on the mechanism of action of antimicrobial and anticancer peptides performed directly on cells. The data in these studies allow to correlate vesicle-based and cell-based studies and fill the vesicle-cell interdisciplinary gap.Projects Ciência Sem Fronteiras PVE 171/2012 (CAPES, Brazil) and MSCA-RISE-2014-Nr644167 are acknowledged. D. Gaspar and J. Freire are recipients of fellowships SFRH/BPD/73500/2010 and SFRH/BD/70423/2010 from FCT, Portugal, respectively. A.S. Veiga acknowledges FCT, Portugal, for funding within the FCT Investigator Programme (IF/00803/2012)

On the identification of Sb2Se3 using Raman scattering

Robust evidences are presented that show that the Raman mode close to 250 cm-1 in Sb2Se3 thin films does not belong to this binary compound. A study of the Raman spectrum power dependency revealed the formation of Sb2O3 for high values of power excitation when these measurements are done in normal atmospheric conditions. In order to complement this study, Sb2Se3 thin films were annealed to mimic the thermal conditions of Raman measurements and characterized by X-ray diffraction technique. These measurements showed that the compound Sb2Se3 can be replaced by Sb2O3 under those conditions and a heat-assisted chemical process explains these findings. Furthermore, it is shown what the Raman conditions that are needed for correct measurements to be performed.publishe

Processing of gas in cosmological filaments around Virgo cluster

Galaxies have different morphology, gas content, and star formation rate (SFR) in dense environments like galaxy clusters. The impact of environmental density extends to several virial radii, and galaxies are pre-processed in filaments and groups, before falling into the cluster. Our goal is to quantify this pre-processing, in terms of gas content and SFR, as a function of density in cosmic filaments. We have observed the two first CO transitions in 163 galaxies with the IRAM-30m telescope, and added 82 measurements from the literature, for a sample of 245 galaxies in the filaments around Virgo. We gathered HI-21cm measurements from the literature, and observed 69 galaxies with the Nan\c{c}ay telescope, to complete our sample. We compare our filament galaxies with comparable samples from the Virgo cluster and with the isolated galaxies of the AMIGA sample. We find a clear progression from field, to filament, and cluster galaxies for decreasing SFR, increasing fraction of galaxies in the quenching phase, increasing proportion of early-type galaxies and decreasing gas content. Galaxies in the quenching phase, defined as having SFR below 1/3 of the main sequence rate, are between 0-20\% in the isolated sample, while they are 20-60\% in the filaments and 30-80\% in the Virgo cluster. Processes that lead to star formation quenching are already at play in filaments. They depend mostly on the local galaxy density, while the distance to filament spine is a secondary parameter. While the HI to stellar mass ratio decreases with local density by ~1 dex in the filaments, and ~2 dex in the Virgo cluster with respect to the field, the decrease is much less for the H$_2$ to stellar mass ratio. As the environmental density increases, the gas depletion time decreases, since the gas content decreases faster than the SFR. This suggests that gas depletion significantly precedes star formation quenching.Comment: 24 pages, plus 98 pages of supplementary material, submitted to A&

A massive multiphase plume of gas in Abell 2390’s brightest cluster galaxy

We present new ALMA CO(2-1) observations tracing 2.2 × 1010 M. of molecular gas in Abell 2390’s brightest cluster galaxy, where half the gas is located in a one-sided plume extending 15 kpc out from the galaxy centre. This molecular gas has a smooth and positive velocity gradient, and is receding 250 km s−1 faster at its farthest point than at the galaxy centre. To constrain the plume’s origin, we analyse our new observations alongside existing X-ray, optical, and radio data. We consider the possibility that the plume is a jet-driven outflow with lifting aided by jet-inflated X-ray bubbles, is a trail of gas stripped from the main galaxy by ram pressure, or is formed of more recently cooled and infalling gas. The galaxy’s star formation and gas cooling rate suggest the lifespan of its molecular gas may be low compared with the plume’s age – which would favour a recently cooled plume. Molecular gas in close proximity to the active galactic nucleus is also indicated by 250 km s−1 wide CO(2-1) absorption against the radio core, as well as previously detected CO(1-0) and H I absorption. This absorption is optically thick and has a line-of-sight velocity towards the galaxy centre of 200 km s−1. We discuss simple models to explain its origin

Voids in kesterites and the influence of lamellae preparation by focused ion beam for transmission electron microscopy analyses

Kesterite solar cells based in Cu2ZnSnS4 and Cu2ZnSnSe4 are potential future candidates to be used in thin film solar cells. The technology still has to be developed to a great extent and for this to happen, high levels of confidence in the characterization methods are required so that improvements can be made on solid interpretations. In this study we show that the interpretations of one of the most used characterization techniques in kesterites, scanning transmission electron microscopy (STEM), might be affected by its specimen preparation when using focused ion beam (FIB). Using complementary measurements based on scanning electron microscopy and Raman scattering spectroscopy, compelling evidences show that secondary phases of ZnSe mixed in the bulk of Cu2ZnSnSe4 are the likely cause of the appearance of voids in the STEM lamellae. Sputtering simulations support this interpretation by showing that Zn in a ZnSe matrix is preferentially sputtered compared with any metal atom in a Cu2ZnSnSe4 matrix.publishe

Guar gum as a new antimicrobial peptide delivery system against diabetic foot ulcers Staphylococcus aureus isolates

© 2016 The AuthorsDiabetic patients frequently develop diabetic foot ulcers (DFUs), particularly those patients vulnerable to Staphylococcus aureus opportunistic infections. It is urgent to find new treatments for bacterial infections. The antimicrobial peptide (AMP) nisin is a potential candidate, mainly due to its broad spectrum of action against pathogens. Considering that AMP can be degraded or inactivated before reaching its target at therapeutic concentrations, it is mandatory to establish effective AMP delivery systems, with the natural polysaccharide guar gum being one of the most promising. We analysed the antimicrobial potential of nisin against 23 S. aureus DFU biofilm-producing isolates. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), minimum biofilm inhibitory concentration (MBIC) and minimum biofilm eradication concentration (MBEC) were determined for nisin diluted in HCl and incorporated in guar gum gel. Statistical analysis was performed using the Wilcoxon matched-pair test. Nisin was effective against all isolates, including some multidrug-resistant clinical isolates, independent of whether it is incorporated in guar gum. While differences among MIC, MBC and MBIC values were observed for HCl- and guar gum- nisin, no significant differences were found between MBEC values. Inhibitory activity of both systems seems to differ only twofold, which does not compromise guar gum gel efficiency as a delivery system. Our results highlight the potential of nisin as a substitute for or complementary therapy to current antibiotics used for treating DFU infections, which is extremely relevant considering the increase in multidrug-resistant bacteria dissemination. The guar gum gel represents an alternative, practical and safe delivery system for AMPs, allowing the development of novel topical therapies as treatments for bacterial skin infections.The authors would like to acknowledge the Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa [Project UID/CVT/00276/2013, funded by Fundação para a Ciência e Tecnologia (FCT), Portugal]. This study was also conducted with the financial support of the project PTDC/SAU-MIC/122816/2010: ‘Biofilms in diabetic foot: microbial virulence characterization and cross-talk of major isolates’, funded by the FCT, Portugal. Raquel Santos, Diogo Barros and Ana Salomé Veiga acknowledge the FCT, Portugal, respectively, for two PhD fellowships (SFRH/BD/100571/2014 and PD/BD/113457/2015) and fellowship IF/00803/2012 under the FCT Investigator Programme.info:eu-repo/semantics/publishedVersio