Antifungal and anti-biofilm activity of designed derivatives from kyotorphin

© 2019 British Mycological Society. Published by Elsevier Ltd. All rights reserved.Kyotorphin (KTP, l-tyrosyl-l-arginine) is an endogenous analgesic neuropeptide first isolated from bovine brain in 1979. Previous studies have shown that kyotorphins possess anti-inflammatory and antimicrobial activity. Six kyotorphins—KTP-NH2, KTP–NH2–DL, ibuprofen-conjugated KTP (IbKTP), IbKTP-NH2, N-methyl-D-Tyr-L-Arg, and N-methyl-L-Tyr-D-Arg—were designed and synthesized to improve lipophilicity and resistance to enzymatic degradation. This study assessed the antimicrobial and antibiofilm activity of these peptides. The antifungal activity of kyotorphins was determined in representative strains of Candida species, including Candida albicans ATCC 10231, Candida krusei ATCC 6258, and six clinical isolates—Candida dubliniensis 19-S, Candida glabrata 217-S, Candida lusitaniae 14-S, Candida novergensis 51-S, Candida parapsilosis 63, and Candida tropicalis 140-S—obtained from the oral cavity of HIV-positive patients. The peptides were synthesized by standard solution or solid-phase synthesis, purified by RP-HPLC (purity >95 %), and characterized by nuclear magnetic resonance. The results of the broth microdilution assay and scanning electron microscopy showed that IbKTP-NH2 presented significant antifungal activity against Candida strains and antibiofilm activity against the clinical isolates. The absence of toxic activity and survival after infection was assessed after injecting the peptide in larvae of Galleria mellonella as experimental infection model. Furthermore, IbKTP-NH2 had strong antimicrobial activity against multidrug-resistant bacteria and fungi and was not toxic to G. mellonella larvae up to a concentration of 500 mM. These results suggest that IbKTP-NH2, in addition to its known effect on cell membranes, can elicit a cellular immune response and, therefore, is promising for biomedical application.This research was supported by FAPESP (Grant No. 2017/00032-0). This article is also part of the Fungal Adaptation to Hostile Challenges special issue for the third International Symposium on Fungal Stress (ISFUS), which is supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (Grant No. 2018/20571-6) and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) (Grant No. 88881.289327/2018-01).info:eu-repo/semantics/publishedVersio

VAR2CSA Signatures of High Plasmodium falciparum Parasitemia in the Placenta

Plasmodium falciparum infected erythrocytes (IE) accumulate in the placenta through the interaction between Duffy-binding like (DBL) domains of parasite-encoded ligand VAR2CSA and chondroitin sulphate-A (CSA) receptor. Polymorphisms in these domains, including DBL2X and DBL3X, may affect their antigenicity or CSA-binding affinity, eventually increasing parasitemia and its adverse effects on pregnancy outcomes. A total of 373 DBL2X and 328 DBL3X sequences were obtained from transcripts of 20 placental isolates infecting Mozambican women, resulting in 176 DBL2X and 191 DBL3X unique sequences at the protein level. Sequence alignments were divided in segments containing combinations of correlated polymorphisms and the association of segment sequences with placental parasite density was tested using Bonferroni corrected regression models, taking into consideration the weight of each sequence in the infection. Three DBL2X and three DBL3X segments contained signatures of high parasite density (P<0.003) that were highly prevalent in the parasite population (49–91%). Identified regions included a flexible loop that contributes to DBL3X-CSA interaction and two DBL3X motifs with evidence of positive natural selection. Limited antibody responses against signatures of high parasite density among malaria-exposed pregnant women could not explain the increased placental parasitemia. These results suggest that a higher binding efficiency to CSA rather than reduced antigenicity might provide a biological advantage to parasites with high parasite density signatures in VAR2CSA. Sequences contributing to high parasitemia may be critical for the functional characterization of VAR2CSA and the development of tools against placental malaria

Women’s advancement and leadership in the biomedical research centres of Catalonia II: bringing about change

Women; Leadership; Biomedical research centresMujeres; Liderazgo; Centros de investigación biomédicaDones; Lideratge; Centres de recerca biomèdicaNew demands for biomedical research centres are related to gender balance in research teams, gender balance in decision-making, integrating gender in research, and the implementation of Gender-Equality Action Plans (GEAPs). Several approaches for the new demands andchallenges for gender equality where proposed in the Girona Summit. The approaches are related to: analysing gender equality issues, removing unconscious bias through cultural awareness, improving research by integrating a gender perspective, fostering women’s career advancement and development, ensuring gender balance and transparency in decision-making positions, modernising policies and management practices, and representing the points of view of each stakeholder (individual, research centre, funding agency and policy-maker). Although not exhaustive of all possible options, the value of these approaches is being formulated on the basis of the experiences of the delegates of the Catalan research centres. The Hypatia of Alexandria Charter was proposed, discussed, endorsed and signed by the 19 centres of health and biomedical research of Catalonia, and the policy-making and assessment responsibilities of the Health Department of the Catalan Government

VAR2CSA signatures of high Plasmodium falciparum parasitemia in the placenta.

Plasmodium falciparum infected erythrocytes (IE) accumulate in the placenta through the interaction between Duffy-binding like (DBL) domains of parasite-encoded ligand VAR2CSA and chondroitin sulphate-A (CSA) receptor. Polymorphisms in these domains, including DBL2X and DBL3X, may affect their antigenicity or CSA-binding affinity, eventually increasing parasitemia and its adverse effects on pregnancy outcomes. A total of 373 DBL2X and 328 DBL3X sequences were obtained from transcripts of 20 placental isolates infecting Mozambican women, resulting in 176 DBL2X and 191 DBL3X unique sequences at the protein level. Sequence alignments were divided in segments containing combinations of correlated polymorphisms and the association of segment sequences with placental parasite density was tested using Bonferroni corrected regression models, taking into consideration the weight of each sequence in the infection. Three DBL2X and three DBL3X segments contained signatures of high parasite density (P<0.003) that were highly prevalent in the parasite population (49-91%). Identified regions included a flexible loop that contributes to DBL3X-CSA interaction and two DBL3X motifs with evidence of positive natural selection. Limited antibody responses against signatures of high parasite density among malaria-exposed pregnant women could not explain the increased placental parasitemia. These results suggest that a higher binding efficiency to CSA rather than reduced antigenicity might provide a biological advantage to parasites with high parasite density signatures in VAR2CSA. Sequences contributing to high parasitemia may be critical for the functional characterization of VAR2CSA and the development of tools against placental malaria

Temperature‐Dependent Re‐alignment of the Short Multifunctional Peptide BP100 in Membranes Revealed by Solid‐State NMR Spectroscopy and Molecular Dynamics Simulations

BP100 is a cationic undecamer peptide with antimicrobial and cell-penetrating activities. The orientation of this amphiphilic α-helix in lipid bilayers was examined under numerous conditions using solid-state 19F, 15N and 2H NMR. At high temperatures in saturated phosphatidylcholine lipids, BP100 lies flat on the membrane surface, as expected. Upon lowering the temperature towards the lipid phase transition, the helix is found to flip into an upright transmembrane orientation. In thin bilayers, this inserted state was stable at low peptide concentration, but thicker membranes required higher peptide concentrations. In the presence of lysolipids, the inserted state prevailed even at high temperature. Molecular dynamics simulations suggest that BP100 monomer insertion can be stabilized by snorkeling lysine side chains. These results demonstrate that even a very short helix like BP100 can span (and thereby penetrate through) a cellular membrane under suitable conditions

Prediction of Antibacterial Activity from Physicochemical Properties of Antimicrobial Peptides

Consensus is gathering that antimicrobial peptides that exert their antibacterial action at the membrane level must reach a local concentration threshold to become active. Studies of peptide interaction with model membranes do identify such disruptive thresholds but demonstrations of the possible correlation of these with the in vivo onset of activity have only recently been proposed. In addition, such thresholds observed in model membranes occur at local peptide concentrations close to full membrane coverage. In this work we fully develop an interaction model of antimicrobial peptides with biological membranes; by exploring the consequences of the underlying partition formalism we arrive at a relationship that provides antibacterial activity prediction from two biophysical parameters: the affinity of the peptide to the membrane and the critical bound peptide to lipid ratio. A straightforward and robust method to implement this relationship, with potential application to high-throughput screening approaches, is presented and tested. In addition, disruptive thresholds in model membranes and the onset of antibacterial peptide activity are shown to occur over the same range of locally bound peptide concentrations (10 to 100 mM), which conciliates the two types of observations

Emprenedoria : una experiència a la UdG

Presentació a càrrec del Dr. Eduard Bardagí, professor de Química de la Universitat de Girona sobre la seva experiència respecte el tema d'emprenedori

Surface density profile and AVR for Milky Way-like galaxies in TNG50

Treballs Finals de Grau de Física, Facultat de Física, Universitat de Barcelona, Curs: 2022-2023, Tutor: Chervin Fabien Pierre LaporteWe have studied the surface density profile, ΣR, and the AVR, σvz , of stars for 25 MW-like galaxies in the TNG50 simulation and compared the results with the Kordopatis et al. and Sanders et al. catalogues of Milky Way stars. ΣR of stellar disks on spiral galaxies obeys an exponential profile where younger stars are more abundant than older stars, specially so towards the end of the disk. We argue it’s because older stars were born towards the center during the formation of the galaxy and more, younger stars were born at the newly formed disk and outer regions as they were getting hotter and denser. σvz shows a decreasing trend with galactocentric radius, though for both catalogues a plateau can be seen for R >∼ 8 kpc, attributed to a more scattered sample of stars near the edge of the stellar disk. Older stars tend to show higher velocity dispersion than younger stars due to the conditions, such as gas turbulence, of when they were formed