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Nanobiotechnology: “Design and engineering of tumor-targeted, dual-acting cytotoxic nanoparticles”

Nanobiotechnology: “Design and engineering of tumor-targeted, dual-acting cytotoxic nanoparticles”

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Acta Biomaterialia DOI:https://doi.org/10.3390/pharmaceutics12111004 Abstract The possibility to conjugate tumor-targeted cytotoxic nanoparticles and conventional antitumoral drugs in single pharmacological entities would open a wide spectrum of opportunities in nanomedical oncology. This principle has been explored here by using CXCR4-targeted self-assembling protein nanoparticles based on two potent microbial toxins, the exotoxin A from Pseudomonas aeruginosa and the diphtheria toxin from Corynebacterium diphtheriae, to which oligo-floxuridine and monomethyl auristatin E respectively have been chemically coupled. The resulting multifunctional hybrid nanoconjugates, with a hydrodynamic size of around 50 nm, are stable and internalize target cells with a biological impact. Althoug
La Nit Europea de la Recerca

La Nit Europea de la Recerca

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La Nit Europea de la Recerca és un esdeveniment dedicat a la divulgació de la ciència i se celebra cada any en més de 300 ciutats de 30 països d’Europa al mateix temps. A causa de les circumstàncies derivades del COVID19, enguany se celebrarà el 27 i 28 de novembre, tot i que hi haurà diferents activitats, tallers, xerrades, etc. durant tota la setmana. L’objectiu d’aquesta iniciativa és apropar el món de la recerca al públic general de forma amena. Des de l’IBB, ens sumem a aquesta gran iniciativa i participarem activament per compartir amb la societat la recerca que fem al centre. Així doncs, les activitats promogudes per investigadors i investigadores de l’IBB són les següents: Xerrada divulgativa impartida per Salvador Ventura, titulada “Desmuntant el LEGO: A la cerca d’una cura p
Nanobiotechnology: “Fluorescent Dye Labeling Changes the Biodistribution of Tumor-Targeted Nanoparticles”

Nanobiotechnology: “Fluorescent Dye Labeling Changes the Biodistribution of Tumor-Targeted Nanoparticles”

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Pharmaceutics 2020, 12(11), 1004 DOI:https://doi.org/10.3390/pharmaceutics12111004   Abstract Fluorescent dye labeling is a common strategy to analyze the fate of administered nanoparticles in living organisms. However, to which extent the labeling processes can alter the original nanoparticle biodistribution has been so far neglected. In this work, two widely used fluorescent dye molecules, namely, ATTO488 (ATTO) and Sulfo-Cy5 (S-Cy5), have been covalently attached to a well-characterized CXCR4-targeted self-assembling protein nanoparticle (known as T22-GFP-H6). The biodistribution of labeled T22-GFP-H6-ATTO and T22-GFP-H6-S-Cy5 nanoparticles has been then compared to that of the non-labeled nanoparticle in different CXCR4+ tumor mouse models. We observed that while parent
Protein Folding and Conformational Diseases. “Atomistic fibrillar architectures of polar prion-inspired heptapeptides”

Protein Folding and Conformational Diseases. “Atomistic fibrillar architectures of polar prion-inspired heptapeptides”

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  https://doi.org/10.1039/D0SC05638C https://pubs.rsc.org/en/content/articlelanding/2020/sc/d0sc05638c#!divAbstract Abstract This article provides the computational prediction of the atomistic architectures resulting from self-assembly of the polar heptapeptide sequences NYNYNYN, SYSYSYS and GYGYGYG. Using a combination of molecular dynamics and a newly developed tool for non-covalent interaction analysis, we uncover the properties of a new class of bionanomaterials, including hydrogen-bonded polar zippers, and the relationship between peptide composition, fibril geometry and weak interaction networks. Our results, corroborated by experimental observations, provide the basis for the rational design of prion-inspired nanomaterials.
Formulacions precises i més eficaces per administrar proteïnes

Formulacions precises i més eficaces per administrar proteïnes

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Les proteïnes recombinants, molècules biològiques amb potencial terapèutic, representen un avenç en la salut humana i animal com és el cas de la insulina. Aquestes, però, un cop administrades són degradades ràpidament. En aquest sentit i en el cas de les malalties infeccioses, el grup de Nanobiotecnologia de la UAB estudia unes nanopartícules que contenen la proteïna interferó-gamma (IFN-γ) i que activen les defenses de les vaques lleteres. Fins i tot, en milloren el rendiment biològic. Les proteïnes recombinants tenen un gran impacte socioeconòmic, principalment en els sectors industrial i biofarmacèutic. La possibilitat d’accedir a grans quantitats de proteïnes d’elevada puresa ha contribuït a la millora de vida de molts pacients que necessiten una aportació extra d’aquest tipus de bi
Protein Folding and Conformational Diseases. “SolupHred: A Server to Predict the pH-dependent Aggregation of Intrinsically Disordered Proteins”

Protein Folding and Conformational Diseases. “SolupHred: A Server to Predict the pH-dependent Aggregation of Intrinsically Disordered Proteins”

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    Bioinformatics, btaa909, https://doi.org/10.1093/bioinformatics/btaa909 Abstract Summary: Polypeptides are exposed to changing environmental conditions that modulate their intrinsic aggregation propensities. Intrinsically disordered proteins (IDPs) constitutively expose their aggregation determinants to the solvent, thus being especially sensitive to its fluctuations. However, solvent conditions are often disregarded in computational aggregation predictors. We recently developed a phenomenological model to predict IDPs' solubility as a function of the solution pH, which is based on the assumption that both protein lipophilicity and charge depend on this parameter. The model anticipated solubility changes in different IDPs accurately. In this application note, we p
Protein Folding and Conformational Diseases. “Functional Amyloids Germinate in Plants”

Protein Folding and Conformational Diseases. “Functional Amyloids Germinate in Plants”

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https://doi.org/10.1016/j.tplants.2020.10.001 https://www.sciencedirect.com/science/article/pii/S1360138520303253#f0005 First identified in human disorders, amyloids serve biological functions in bacteria, archaea, fungi, and animals; however, their role in plants has remained unexplored. Recently, Antonets et al. identified a functional amyloid in plants, with a crucial role in seed longevity, confirming that amyloids are universally exploited for organisms’ adaptation. Keywords functional amyloids plants garden pea seed storage vicilin seed longevity
Protein Folding and Conformational Diseases. “Inhibition of α-Synuclein Aggregation and Mature Fibril Disassembling With a Minimalistic Compound, ZPDm”

Protein Folding and Conformational Diseases. “Inhibition of α-Synuclein Aggregation and Mature Fibril Disassembling With a Minimalistic Compound, ZPDm”

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Front. Bioeng. Biotechnol., 16 October 2020 | https://doi.org/10.3389/fbioe.2020.588947 Synucleinopathies are a group of disorders characterized by the accumulation of α-Synuclein amyloid inclusions in the brain. Preventing α-Synuclein aggregation is challenging because of the disordered nature of the protein and the stochastic nature of fibrillogenesis, but, at the same time, it is a promising approach for therapeutic intervention in these pathologies. A high-throughput screening initiative allowed us to discover ZPDm, the smallest active molecule in a library of more than 14.000 compounds. Although the ZPDm structure is highly related to that of the previously described ZPD-2 aggregation inhibitor, we show here that their mechanisms of action are entirely different. ZPDm inhibits the
Molecular Biology: “Immunodominant proteins P1 and P40/P90 from human pathogen Mycoplasma pneumoniae”

Molecular Biology: “Immunodominant proteins P1 and P40/P90 from human pathogen Mycoplasma pneumoniae”

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https://www.nature.com/articles/s41467-020-18777-y Vizarraga, D., Kawamoto, A., Matsumoto, U. et al. Immunodominant proteins P1 and P40/P90 from human pathogen Mycoplasma pneumoniae. Nat Commun 11, 5188 (2020). https://doi.org/10.1038/s41467-020-18777-y Abstract Mycoplasma pneumoniae is a bacterial human pathogen that causes primary atypical pneumonia. M. pneumoniae motility and infectivity are mediated by the immunodominant proteins P1 and P40/P90, which form a transmembrane adhesion complex. Here we report the structure of P1, determined by X-ray crystallography and cryo-electron microscopy, and the X-ray structure of P40/P90. Contrary to what had been suggested, the binding site for sialic acid was found in P40/P90 and not in P1. Genetic and clinical variability concentrates on
Evolutive Immunology. “Epigenetic differences in the innate response after immune stimulation during zebrafish sex differentiation”

Evolutive Immunology. “Epigenetic differences in the innate response after immune stimulation during zebrafish sex differentiation”

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 https://doi.org/10.1016/j.dci.2020.103848 Abstract Infections are able to trigger epigenetic modifications; however, epigenetic-mediating infections in the immune system in fish is currently unavailable. Within this purpose, zebrafish were immune-stimulated with three lipopolysaccharides (LPS) during sex differentiation. Methylation patterns of three immune genes were studied by a candidate gene approach together with gene expression analysis, and in adulthood, sex ratios were determined. It was shown that the entrance of LPS was through the gills and accumulated in the pronephros. Significant hypomethylation levels of CASP9 and a significant CpG site for IL1β after Pseudomonas aeruginosa LPS exposure were found. No methylation difference was observed for TNFα. Gene expression a