Biology subjects

Almeida, G.

Publications and source records attributed to Almeida, G..

3 recordsLinked to original sources

bioRxiv2025

THE HUMAN NEUROBLASTOMA SH-SY5Y CELL LINE AS A MODEL TO ASSESS β-AMYLOID NEUROTOXICITY: A SYSTEMATIC REVIEW AND META-ANALYSIS

The SH-SY5Y human neuroblastoma cell line is widely used as an in vitro model of {beta}-amyloid (A{beta}) neurotoxicity in Alzheimers disease (AD). However, the lack of standardized protocols for assessing A{beta} toxicity - including differentiation strategies for SH-SY5Y cells - limits the comparability of results across studies. To address these issues, we conducted a systematic review and meta-analysis to evaluate how methodological factors influence A{beta}-induced toxicity in SH-SY5Y cells. We included 359 eligible studies encompassing 1,192 MTT-based comparisons of cell viability between A{beta}-treated and control SH-SY5Y cells. A three-level meta-analysis estimated mean cell viability after A{beta} exposure at 63% of control levels (95% CI [61.6; 64.3]), with very high heterogeneity (I{superscript 2}=99.6%). Meta-regression identified significant associations between increased toxicity and higher A{beta} concentrations, longer exposure durations, and the use of peptide preparations described as fibrils. Conversely, differentiation protocols, duration, and cell density did not significantly influence toxicity outcomes. Reporting quality was often poor, with frequent omissions regarding cell line origin, authentication, contamination testing, A{beta} preparation details and nature of the experimental unit. Overall, our findings show robust A{beta} toxicity in SH-SY5Y cells, primarily driven by dose, exposure time, and A{beta} aggregation state, but not cell differentiation status. Our conclusions highlight the critical need for better reporting of A{beta} exposure parameters to enhance reproducibility and translational potential in AD research.

neuroscience↗

bioRxiv2021

Neutralizing antibody-independent immunity to SARS-CoV-2 in hamsters and hACE-2 transgenic mice immunized with a RBD/Nucleocapsid fusion protein

The nucleocapsid (N) and the receptor binding domain (RBD) of the Spike (S) proteins elicit robust antibody and T cell responses either in vaccinated or COVID-19 convalescent individuals. We generated a chimeric protein that comprises the sequences of RBD from S and N antigens (SpiN). SpiN was highly immunogenic and elicited a strong IFN{gamma} response from T cells and high levels of antibodies to the inactivated virus, but no neutralizing antibodies. Importantly, hamsters and the human Angiotensin Convertase Enzyme-2-transgenic mice immunized with SpiN were highly resistant to challenge with the wild type SARS-CoV-2, as indicated by viral load, clinical outcome, lung inflammation and lethality. Thus, the N protein should be considered to induce T-cell-based immunity to improve SARS-CoV-2 vaccines, and eventually to circumvent the immune scape by variants.

immunology↗

bioRxiv2021

CALANGO: an annotation-based, phylogeny-aware comparative genomics framework for exploring and interpreting complex genotypes and phenotypes

The increasing availability of genomic, annotation, evolutionary and phenotypic data for species contrasts with the lack of studies that adequately integrate these heterogeneous data sources to produce biologically meaningful knowledge. Here, we present CALANGO, a phylogeny-aware comparative genomics tool that uncovers functional molecular convergences and homologous regions associated with quantitative genotypes and phenotypes across species, enabling the fast discovery of novel statistically sound, biologically relevant phenotype-genotype associations. We demonstrate the usefulness of CALANGO in two case studies. The first one unveils potential causal links between prophage density and the pathogenicity phenotype in Escherichia coli, and confidently demonstrates how CALANGO supports the investigation of basic causal relationships by enabling a level of counterfactual investigation of observed associations in the data. As a second case study, we used our tool to search for homologous regions associated with a complex phenotypic trait in a major group of eukaryotes: the evolution of maximum height in angiosperms. We confidently identify a previously unknown association between maximum plant height and the expansion of the self-incompatibility system, a molecular mechanism that prevents inbreeding and increases genetic diversity. Taller species also have lower rates of molecular evolution due to their longer generation times, a critical concern for their long-term viability. The new mechanism we report could counterbalance this fact, and have far-reaching consequences for fields as diverse as conservation biology and agriculture. CALANGO is provided as a fully operational R package that can be freely installed from CRAN.

bioinformatics↗