629 research outputs found
Human neutrophil peptide 1 variants bearing arginine modified cationic side chains: Effects on membrane partitioning
No full textα-Defensins (e.g. human neutrophil peptides, HNPs) have a broad spectrum bactericidal activity contributing to human innate immunity. The positive charge of amino acid side chains is responsible for the first interaction of cationic antimicrobial peptides with negatively charged bacterial membranes. α-Defensins contain a high content of Arg residues compared to Lys. In this paper, different peptide analogs including substitution of Arg-14 respectively with NG-NG′-asymmetric dimethyl-l-arginine (ADMA), NG-NG′-symmetric dimethyl-l-arginine (SDMA) and Lys (R14K and R15KR14KR15K) variants have been studied to test the role of Arg guanidino group and the localized cationic charge of Lys for interaction with lipid membranes. Our findings show that all the variants have a decreased disruptive activity against the bilayer. The methylated analogs show a reduction in membrane partitioning due to the lack of their ability to form hydrogen bonds. Comparison with the native HNP-1 peptide has been discussed. © 2014 Elsevier B.V. All rights reserved
The defensin–lipid interaction: Insights on the binding states of the human antimicrobial peptide HNP-1 to model bacterial membranes
No full textAntimicrobial peptides are an important component of innate immunity and have generated considerable interest as a new potential class of natural antibiotics. The biological activity of antimicrobial peptides is strongly influenced by peptide-membrane interactions. Human Neutrophil Peptide 1 (HNP-1) is a 30 aminoacid peptide, belonging to the class of α-defensins. Many biophysical studies have been performed on this peptide to define its mechanism of action. Combining spectroscopic and thermodynamic analysis, insights on the interaction of the α-defensin with POPE:POPG:CL negative charged bilayers are given. The binding states of the peptide below and above the threshold concentration have been analyzed showing that the interaction with lipid bilayers is dependent by peptide concentration. These novel results that indicate how affinity and biological activities of natural antibiotics are depending by their concentration, might open new way of investigation of the antimicrobial mode of action
ARGININE-LYSINE SWAPS SELECTIVELY ENHANCE ANTIMICROBIAL ACTIVITY OVER CYTOTOXIC ACTIVITY OF LL-37
No full textLL-37 is the only cationic peptide belonging to the cathelicidin family expressed in humans. LL-37 has bactericidal activity and exerts immunomodulatory functions forming, together with other peptides, the first line of defense against infections. The formation of LL-37 aggregates in the presence of neutral membranes promotes lack of specificity for microbial cells, which could explain why LL-37 becomes cytotoxic towards eukaryotic cells at high concentrations. Cationic amino-acids such arginine (Arg) and lysine (Lys) are known determinants for bacterial killing, however little is known about how Lys-Arg exchange can influence LL-37 biological activities. Since antimicrobial peptides are promising candidates for the development of novel anti-infective agents, we have compared the bactericidal and cytotoxic effects of five LL-37 variants with wild type peptide. The bactericidal activity was tested against Escherichia coli and Streptococcus agalactiae, while cytotoxicity was measured against A549, a human bronchoepithelial cell line. We found clear differences in bacterial killing kinetics towards both pathogens when central Arg were mutated in Lys, with Arg more efficient than Lys in bacterial membrane permeation. Of interest, the Arg at position 34 can compensate for the absence of the Arg at position 19 and 23 and the presence of Lys at the other positions resulted in a diminished toxicity for eukaryotic cells. Our study sheds new light on key amino-acid residues of LL-37 and should be considered when novel cationic amphipathic peptides derived from LL-37 are designed
A Spectroscopic Study of the Aggregation State of the Human Antimicrobial Peptide LL-37 in Bacterial versus Host Cell Model Membranes
No full textThe LL-37 antimicrobial peptide is the only cathelicidin peptide found in
humans that has antimicrobial and immunomodulatory properties. Because it exerts also
chemotactic and angiogenetic activity, LL-37 is involved in promoting wound healing,
reducing inflammation, and strengthening the host immune response. The key to the
effectiveness of antimicrobial peptides (AMPs) lies in the different compositions of bacterial
versus host cell membranes. In this context, antimicrobial peptide LL-37 and two variants
were studied in the presence of model membranes with different lipid compositions and
charges. The investigation was performed using an experimental strategy that combines the
site-directed spin labeling−electron paramagnetic resonance technique with circular
dichroism and fluorescence emission spectroscopies. LL-37 interacts with negatively charged
membranes forming a stable aggregate, which can likely produce toroidal pores until the
amount of bound peptide exceeds a critical concentration. At the same time, we have clearly detected an aggregate with a higher
oligomeric degree for interaction of LL-37 with neutral membranes. These data confirm the absence of cell selectivity of the
peptide and a more complex role in stimulating host cells
Anti-oxidant and anti-inflammatory activity of ketogenic diet. New perspectives for neuroprotection in alzheimer’s disease
No full textThe ketogenic diet, originally developed for the treatment of epilepsy in non-responder children, is spreading to be used in the treatment of many diseases, including Alzheimer’s disease. The main activity of the ketogenic diet has been related to improved mitochondrial function and decreased oxidative stress. B-Hydroxybutyrate, the most studied ketone body, has been shown to reduce the production of reactive oxygen species (ROS), improving mitochondrial respiration: it stimulates the cellular endogenous antioxidant system with the activation of nuclear factor erythroid-derived 2-related factor 2 (Nrf2), it modulates the ratio between the oxidized and reduced forms of nicotinamide adenine dinucleotide (NAD+/NADH) and it increases the efficiency of electron transport chain through the expression of uncoupling proteins. Furthermore, the ketogenic diet performs anti-inflammatory activity by inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) activation and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome as well as inhibiting histone deacetylases (HDACs), improving memory encoding. The underlying mechanisms and the perspectives for the treatment of Alzheimer’s disease are discussed
The Pottesman Collection in the British Museum. Early Dynastic and Sargonic administrative texts. With an Appendix on a Palmyrene Inscription
No full textEdizione, trascrizione, traduzione e commento di un frammento di iscrizione palmirena inedita presente nella collezione Pottesman del British Museum (Appendice Agostini).The British Museum houses a small collection of six cuneiform tablets and a Palmyrene dedicatory inscription purchased in 1987 from the private collection of Solomon Pottesman. The aim of the present contribution is to provide a catalog of this lot and an edition of the so far unpublished cuneiform texts. In the appendix, Alessio Agostini added the edition of the Palmyrene inscription, which would have otherwise gone beyond the capabilities of the present author
Recensione di Cecilia Falchini (2023). Ruperto di deutz - Un’intima familiarità. Antologia, Edizioni Qiqajon (Comunità di Bose), Magnano (Bi), 281 pp.
No full textReview of Cecilia Falchini (2023). Ruperto di deutz - Un’intima familiarità. Antologia, Edizioni Qiqajon (Comunità di Bose), Magnano (Bi), 281 pp.
Author: Alessio MagogaRecensione di Cecilia Falchini (2023). Ruperto di deutz - Un’intima familiarità. Antologia, Edizioni Qiqajon (Comunità di Bose), Magnano (Bi), 281 pp.
Autor: Alessio Magog
Conformational characterization of full-length X-chromosome-linked inhibitor of apoptosis protein (XIAP) through an integrated approach
No full textThe X-chromosome-linked inhibitor of apoptosis protein (XIAP) is a multidomain protein whose main function is to block apoptosis by caspase inhibition. XIAP is also involved in other signalling pathways, including NF-κB activation and copper homeostasis. XIAP is overexpressed in tumours, potentiating cell survival and resistance to chemotherapeutics, and has therefore become an important target for the treatment of malignancy. Despite the fact that the structure of each single domain is known, the conformation of the full-length protein has never been determined. Here, the first structural model of the full-length XIAP dimer, determined by an integrated approach using nuclear magnetic resonance, small-angle X-ray scattering and electron paramagnetic resonance data, is presented. It is shown that XIAP adopts a compact and relatively rigid conformation, implying that the spatial arrangement of its domains must be taken into account when studying the interactions with its physiological partners and in developing effective inhibitors
Handheld-Impedance-Measurement System with seven-decade capability and potentiostatic function
No full textThis paper describes design and test of a new impedance-measurement system for nonlinear devices that exhibits a seven-decade range and works down to a frequency of 0.01 Hz. The system is specifically designed for electrochemical measurements, but the proposed architecture can be employed in many other fields where flexible signal generation and analysis are required. The system employs an unconventional signal generator based on two pulsewidth modulation (PWM) oscillators and an autocalibration system that allows uncertainties of less than 3% to be obtained over a range of 1 kΩ to 100 GΩ. A synchronous demodulation processing allows the noise superimposed to the low-amplitude input signals to be made negligibl
El Tlacuache Núm. 16 (2001). 16 Año 1 (2001) octubre. El Tlacuache
No full text- ¿Entre la Guerra Santa y la Cruzada? por Aníbal Quijano. - Nuestro patrimonio desconocido por Teresita Loera y Anaite Monterforte. - El Yahutli por Margarita Avilés y Macrina Fuentes. - Haciendas por Carlos Fernando Alessio Robles
- …
