Biology subjects

Manca, A.

Publications and source records attributed to Manca, A..

3 recordsLinked to original sources

bioRxiv2024

Simulated microgravity accelerates alpha-synuclein aggregation and induces oxidative stress in an in vitro Parkinson disease model

Parkinsons disease (PD) is a neurodegenerative disorder characterized by the accumulation of alpha-synuclein aggregates and progressive neuronal loss in the substantia nigra, with aging being its primary risk factor. The current available models to study PD mechanisms are largely relying on genetic mutations to recapitulate PD typical hallmarks, such as increased alpha-synuclein aggregation. However, they do not model the aging features associated with the disease. Microgravity, a condition experience by astronauts during space missions, is known to induce ageing-like modifications on both systemic and cellular physiology. To replicate the aging-related stress observed in PD patients, we exposed SH-SY5Y and 3K-SNCA mutant cell lines to simulated microgravity. Our findings revealed that simulated microgravity enhanced PD alterations, with a significant increase in misfolded and phosphorylated a-syn. This was accompanied by heightened oxidative stress, as evidenced by increased levels of reactive oxygen species, without a sufficient antioxidant response. These results suggest that simulated microgravity effectively mimics and accelerate the stress associated with aging in PD cell models, regardless of the presence of PD mutation. This study highlights the potential of simulated microgravity as a tool for investigating aging processes in neurodegenerative diseases.

neuroscience↗

bioRxiv2022

Landscape of immune-related signatures induced by targeting of different epigenetic regulators in melanoma: implications for immunotherapy

BackgroundInnovative cancer immunotherapy approaches aim at combining immune checkpoint inhibitors with other immunomodulatory agents. Epigenetic regulators can control immune-related genes, therefore targeting them with specific inhibitors may be a potential way forward. Here we identified immune-related signatures induced by four classes of epigenetic drugs in human melanoma cells to define the most promising agent and to understand its biological activity in-vitro, in-vivo and in clinical samples. MethodsHuman melanoma cell lines were characterized for mutational and differentiation profile and treated with inhibitors of DNA methyltransferases (guadecitabine), histone deacetylases (givinostat), bromodomain and extraterminal domain proteins (JQ1 and OTX-015) and enhancer of zeste homolog 2 (GSK126). Drug-specific gene signatures were identified by Clariom S and Nanostring platforms. Modulation of 14 proteins was determined by quantitative western blot. Ingenuity Pathway Analysis (IPA) identified Upstream Regulator (UR) molecules explaining changes in gene expression and biological activity of drugs. Gene set enrichment and IPA were used to test modulation of guadecitabine-specific gene and UR signatures, respectively, in on-treatment tumor biopsies from melanoma patients enrolled in the Phase Ib NIBIT-M4 Guadecitabine + Ipilimumab Trial. ResultsDrug-specific gene and UR signatures were identified for each of the four inhibitors. Immune-related genes were frequently upregulated by guadecitabine, to a lesser extent by givinostat, but downregulated by JQ1 and OTX-015. GSK126 was the least active drug. Treatment of melanoma cells with combination of two epigenetic drugs revealed a dominant effect of guadecitabine and JQ1 on immune-related gene modulation. Drug-specific modulatory profiles were confirmed at the protein level. The guadecitabine-specific UR signature was characterized by activated molecules of the TLR, NF-kB, and IFN innate immunity pathways and was induced in drug-treated melanoma, mesothelioma, hepatocarcinoma cell lines and human melanoma xenografts. Most of the guadecitabine-specific signature genes (n>160) were upregulated in on-treatment tumor biopsies from NIBIT-M4 trial. Progressive activation of guadecitabine UR signature molecules was observed in on-treatment tumor biopsies from responding compared to non-responding patients. ConclusionsGuadecitabine was the most promising immunomodulatory agent among those investigated. This DNA methyltransferases inhibitor emerged as a strong inducer of innate immunity pathways, supporting the rationale for its use in combinatorial immunotherapy approaches.

immunology↗

bioRxiv2020

Inflated citations and metrics of journals discontinued from Scopus for publication concerns: the GhoS(t)copus Project

Background Scopus is considered a leading bibliometric database. It contains the largest number of abstracts and articles cited in peer reviewed publications. The journals included in Scopus are periodically re-evaluated to ensure they meet indexing criteria. Afterwards, some journals might be discontinued for publication concerns. Despite their discontinuation, previously published articles remain indexed and continue to be cited. The metrics and characteristics of journals discontinued for publication concerns have yet to be studied. This study aimed (1) to evaluate the main features and citation metrics of journals discontinued from Scopus for publication concerns, before and after discontinuation, and (2) to determine the extent of predatory journals among the discontinued journals.Materials and Methods Eight authors surveyed a list of discontinued journals from Scopus (version July 2019). Data regarding metrics, citations and indexing were extracted from Scopus or other scientific databases, for the journals discontinued for publication concerns.Results A total of 317 journals were evaluated. The mean number of citations per year after discontinuation was significantly higher than before (median of difference 64 citations, p<0.0001), and so was the number of citations per document (median of difference 0.4 citations, p<0.0001). The total number of citations after discontinuation was 607,261, with a median of 713 citations (IQR 254-2056, range 0-19468) per journal. The open access publishing model was declared for 93% (294/317) of the journals, but only nine of these are currently indexed in the Directory of Open Access Journals (DOAJ). Twenty-two percent (72/317) of the journals were included in the Cabell blacklist.Conclusions The citation count of journals discontinued for publication concerns, increases despite discontinuation. Countermeasures should be taken to ensure the validity and reliability of Scopus metrics both at journal- and author-level for the purpose of scientific assessment of publishing.View Full Text

scientific communication and education↗