SP-0489: HPV-transformation in the cervix and at non-cervical sites

Pla general d'un dels panells horitzontals sobre espais verds de Barcelona a l'exposició Ciutat. Barcelona projecta a l'Edifici Fòrum. Exposició sobre la planificació urbanística i arquitectònica de Barcelon

Methylglyoxal Produced by Amyloid- Peptide-Induced Nitrotyrosination of Triosephosphate Isomerase Triggers Neuronal Death in Alzheimer’s Disease

Amyloid-β peptide (Aβ) aggregates induce nitro-oxidative stress, contributing to the characteristic neurodegeneration found in Alzheimer's disease (AD). One of the most strongly nitrotyrosinated proteins in AD is the triosephosphate isomerase (TPI) enzyme which regulates glycolytic flow, and its efficiency decreased when it is nitrotyrosinated. The main aims of this study were to analyze the impact of TPI nitrotyrosination on cell viability and to identify the mechanism behind this effect. In human neuroblastoma cells (SH-SY5Y), we evaluated the effects of Aβ42 oligomers on TPI nitrotyrosination. We found an increased production of methylglyoxal (MG), a toxic byproduct of the inefficient nitro-TPI function. The proapoptotic effects of Aβ42 oligomers, such as decreasing the protective Bcl2 and increasing the proapoptotic caspase-3 and Bax, were prevented with a MG chelator. Moreover, we used a double mutant TPI (Y165F and Y209F) to mimic nitrosative modifications due to Aβ action. Neuroblastoma cells transfected with the double mutant TPI consistently triggered MG production and a decrease in cell viability due to apoptotic mechanisms. Our data show for the first time that MG is playing a key role in the neuronal death induced by Aβ oligomers. This occurs because of TPI nitrotyrosination, which affects both tyrosines associated with the catalytic center

A graph-based approach identifies dynamic H-bond communication networks in spike protein S of SARS-CoV-2

We apply graph-based approaches to identify H-bond clusters in protein complexes. Three conformations of spike protein S have distinct H-bond clusters at key sites. Hydrogen-bond clusters could govern structural plasticity of spike protein S. Protein S binds to ACE2 receptor via H-bond clusters extending deep across interface.Corona virus spike protein S is a large homo-trimeric protein anchored in the membrane of the virion particle. Protein S binds to angiotensin-converting-enzyme 2, ACE2, of the host cell, followed by proteolysis of the spike protein, drastic protein conformational change with exposure of the fusion peptide of the virus, and entry of the virion into the host cell. The structural elements that govern conformational plasticity of the spike protein are largely unknown. Here, we present a methodology that relies upon graph and centrality analyses, augmented by bioinformatics, to identify and characterize large H-bond clusters in protein structures. We apply this methodology to protein S ectodomain and find that, in the closed conformation, the three protomers of protein S bring the same contribution to an extensive central network of H-bonds, and contribute symmetrically to a relatively large H-bond cluster at the receptor binding domain, and to a cluster near a protease cleavage site. Markedly different H-bonding at these three clusters in open and pre-fusion conformations suggest dynamic H-bond clusters could facilitate structural plasticity and selection of a protein S protomer for binding to the host receptor, and proteolytic cleavage. From analyses of spike protein sequences we identify patches of histidine and carboxylate groups that could be involved in transient proton binding.PSI COVID19 Emergency Science FundSpanish Ministry of Science, Innovation and Universities RTI2018-098983-B-I00Excellence Initiative of the German Federal and State Governments via the Freie Universitat BerlinGerman Research Foundation (DFG) SFB 107

HPV distribution in cervical cancer in Portugal. A retrospective study from 1928 to 2005

Objectives To determine human papillomavirus (HPV) types in invasive cervical cancer in Portugal. Methods Cases diagnosed at the Instituto Português de Oncologia de Lisboa de Francisco Gentil from the year 1928 to 2005 were selected for HPV DNA detection and genotyping using SPF10/DEIA/LiPA25 system. Results Of the 1214 samples that were considered appropriate for HPV detection, 714 (58.8%; 95% CI: 56.0–61.6%) were positive for HPV DNA. This detection rate varied being lower in the first 3 decades (31.3%; 50.1%; 46.5%) and higher in the last decades (77.4–95.1%). This difference was due probably to the fixative used in the first three decades. The five most common types identified among HPV positive cases were HPV16 (58.2%), HPV18 (9.2%), HPV33 (6.2%), HPV45 (4.7%) and HPV31 (4.4%). Multiple infections were detected in 2.8% of the cases. HPV16 and 18 accounted for 67.4% of infections. There were no statistically significant changes of these types over the studied period. An increase at patient׳s age at diagnosis was observed in the last decades (ppublishersversionpublishe