Host defence peptides (HDPs) are evolutionarily conserved components of innate immunity. Human HDPs, produced by a variety of immune cells of hematopoietic and epithelial origin, are generally ...grouped into two families: beta structured defensins and variably-structured cathelicidins. We report the characterization of a very promising cryptic human HDP, here called GVF27, identified in 11-hydroxysteroid dehydrogenase-1 β-like protein.
Conformational analysis of GVF27 and its propensity to bind endotoxins were performed by NMR, Circular Dichroism, Fluorescence and Dynamic Light Scattering experiments. Crystal violet and WST-1 assays, ATP leakage measurement and colony counting procedures were used to investigate antimicrobial, anti-biofilm, cytotoxicity and hemolytic activities. Anti-inflammatory properties were evaluated by ELISA.
GVF27 possesses significant antibacterial properties on planktonic cells and sessile bacteria forming biofilm, as well as promising dose dependent abilities to inhibit attachment or eradicate existing mature biofilm. It is unstructured in aqueous buffer, whereas it tends to assume a helical conformation in mimic membrane environments as well as it is able to bind lipopolysaccharide (LPS) and lipoteichoic acid (LTA). Notably it is not toxic towards human and murine cell lines and triggers a significant innate immune response by attenuating expression levels of pro-inflammatory interleukins and release of nitric oxide in LPS induced macrophages.
Human GVF27 may offer significant advantages as leads for the design of human-specific therapeutics.
Human cryptic host defence peptides are naturally no immunogenic and for this they are a real alternative for solving the lack of effective antibiotics to control bacterial infections.
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•A new human cryptic peptide, named GVF27, has been identified in 11-hydroxysteroid dehydrogenase-1 β-like.•GVF27 is unstructured in aqueous buffer but assumes a well defined conformation in mimic membrane environments.•GVF27 exerts anti-biofilm actions and broad spectrum antimicrobial activities.•GVF27 binds bacterial endotoxins as LPS and LTA.•GVF27 induces mitigation of pro-inflammatory mediators production in LPS induced murine macrophages.
Abstract
PANDORE is the environmental box that is going to be used for the quality control of loaded local supports of the ATLAS ITk Pixel Outer Barrel at LAPP (Annecy, France). First PANDORE, its ...interlock system, diphasic CO
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cooling station, and data acquisition system are described. Subsequently, the results of the qualification tests are shown. Given the complexity of the ITk Pixel Outer Barrel system, several loading sites are going to be needed. By documenting the state-of-the-art of PANDORE, this note aims to help the wide ITk Pixel community in the discussion for standardizing the quality control procedure and equipment of the loaded local supports.
The application of Micromegas for sampling calorimetry puts specific constraints on the design and performance of this gaseous detector. In particular, uniform and linear response, low noise and ...stability against high ionisation density deposits are prerequisites for achieving good energy resolution. A Micromegas-based hadronic calorimeter was proposed for an application at a future linear collider experiment and three technologically advanced prototypes of 1×1m2 were constructed. Their merits relative to the above-mentioned criteria are discussed on the basis of measurements performed at the CERN SPS test-beam facility.
Sampling calorimeters can be finely segmented and used to detect showers with high spatial resolution. This imaging power can be exploited at future linear collider experiments where the measurement ...of jet energy by a Particle flow method requires optimal use of tracking and calorimeter information. Gaseous detectors can achieve high granularity and a hadron sampling calorimeter using Micromegas chambers as active elements is considered in this paper. Compared to traditional detectors using wires or resistive plates, Micromegas is free of space charge effects and could therefore show superior calorimetric performance. To test this concept, a prototype of 1×1m2 equipped with 9216 readout pads of 1×1cm2 has been built. Its technical and basic operational characteristics are reported.
MICRO MEsh GAseous Structure (MICROMEGAS) and Gas Electron Multipliers (GEM) detectors are two candidates for the active medium of a Digital Hadronic CALorimeter (DHCAL) as part of a high energy ...physics experiment at a future linear collider (ILC/CLIC). Physics requirements lead to a highly granular hadronic calorimeter with up to thirty million channels with probably only hit information (digital readout calorimeter). To validate the concept of digital hadronic calorimetry with such small cell size, the construction and test of a cubic meter technological prototype, made of 40 planes of one square meter each, is necessary. This technological prototype would contain about 400 000 electronic channels, thus requiring the development of front-end ASIC. Based on the experience gained with previous ASIC that were mounted on detectors and tested in particle beams, a new ASIC called MICROROC has been developped. This paper summarizes the caracterisation campaign that was conducted on this new chip as well as its integration into a large area Micromegas chamber of one square meter.
The peptide VLL-28, identified in the sequence of an archaeal protein, the transcription factor Stf76 from Sulfolobus islandicus, was previously identified and characterized as an antimicrobial ...peptide, possessing a broad-spectrum antibacterial activity.
Through a combined approach of NMR and Circular Dichroism spectroscopy, Dynamic Light Scattering, confocal microscopy and cell viability assays, the interaction of VLL-28 with the membranes of both parental and malignant cell lines has been characterized and peptide mechanism of action has been studied.
It is here demonstrated that VLL-28 selectively exerts cytotoxic activity against murine and human tumor cells. By means of structural methodologies, VLL-28 interaction with the membranes has been proven and the binding residues have been identified. Confocal microscopy data show that VLL-28 is internalized only into tumor cells. Finally, it is shown that cell death is mainly caused by a time-dependent activation of apoptotic pathways.
VLL-28, deriving from the archaeal kingdom, is here found to be endowed with selective cytotoxic activity towards both murine and human cancer cells and consequently can be classified as an ACP.
VLL-28 represents the first ACP identified in an archaeal microorganism, exerting a trans-kingdom activity.
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•VLL-28 is the first ACP identified in the archaeal kingdom.•VLL-28 exerts a selective cytotoxic action towards cancer cells.•Residues involved in the interaction between VLL-28 and cell membranes have been identified.•Cell death occurs upon a time-dependent activation of apoptotic cell pathway.
The recent progress in R&D of the Micromegas detectors for hadronic calorimetry including new engineering-technical solutions, electronics development, and accompanying simulation studies with ...emphasis on the comparison of the physics performance of the analog and digital readout is described. The developed prototypes are with 2 bit digital readout to exploit the Micromegas proportional mode and thus improve the calorimeter linearity. In addition, measurements of detection efficiency, hit multiplicity, and energy shower profiles obtained during the exposure of small size prototypes to radioactive source quanta, cosmic particles and accelerator beams are reported. Eventually, the status of a large scale chamber (1 × 1 m2) are also presented with prospective towards the construction of a 1 m3 digital calorimeter consisting of 40 such chambers.
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