Biology subjects

Guerreiro, J. F.

Publications and source records attributed to Guerreiro, J. F..

3 recordsLinked to original sources

bioRxiv2021

Lipid Droplets and Ferritin Heavy Chain: a Devilish Liaison in Cancer Radioresistance

Although much progress has been made in cancer treatment, the molecular mechanisms underlying cancer radioresistance (RR) as well as the biological characteristic of radioresistant cancer cells still need to be clarified. In this regard, we discovered that breast, bladder, lung, neuroglioma and prostate 6 Gy X-ray resistant cells were characterized by an increase of Lipid Droplet (LD) number and that the cells containing highest LDs showed the highest clonogenic potential after irradiation. Moreover, we observed that LD content was tightly connected with the iron metabolism and in particular with the presence of the ferritin heavy chain (FTH1). In fact, breast and lung cancer cells silenced for the FTH1 gene showed a reduction in the LD numbers and, by consequence, became radiosensitive. FTH1 restoration as well as iron-chelating treatment by Deferoxamine were able to restore the LD amount and RR. Overall, these results provide evidence of a novel molecular mechanism behind RR in which LDs and FTH1 are tightly connected to each other, a synergistic effect which might be worth deeply investigating in order to make cancer cells more radiosensitive and improve the efficacy of radiation treatments.

cancer biology↗

bioRxiv2021

Analysis of coding variants in the human FTO gene from the ExAC (gnomAD) Database

Single nucleotide polymorphisms (SNPs) in the first intron of the FTO gene (alpha-ketoglutarate-dependent dioxygenase) identified by a genome-wide association study (GWAS) in 2007 continue to be the known variants with the greatest effect on adiposity in different human populations. Currently available data reveal a total of 61 different intronic SNPs associated with adiposity. Coding variants in the FTO gene, on the other hand, have been little explored, but data from complete sequencing of the exomes of various populations are available in public databases and provide an excellent opportunity to investigate potential functional variants in FTO. This study aimed to track nonsynonymous variants in the exons of the FTO gene in different population groups using the ExAC database (gnomAD) (http://exac.broadinstitute.org/) and to analyze the potential functional impact of these variants on the FTO protein. Variants were analyzed using five publicly available pathogenicity prediction programs. Of the 158 mutations identified (152 missense and 6 stop-gain), 64 (40.5%) were classified as pathogenic, 67 (42.4%) were classified as benign, and 27 (17%) were classified as inconclusive. Thirty variants were classified as pathogenic by all five predictors used in this study, and 16 mutations were classified as pathogenic by only one predictor. The largest number of mutations was found in Europeans (non-Finnish) (85/158), all with very low frequencies, and half (32/64) of the variants classified as pathogenic by the five predictors used were also found in this population. The data obtained in this analysis show that a large number of rare coding variants classified as pathogenic or potentially pathogenic by different in silico pathogenicity prediction programs are not detected by GWAS due to the low linkage disequilibrium as well as the limitations of GWAS in capturing rare variants present in less than 1.0% of the population.

molecular biology↗

bioRxiv2020

A Timescale for the Radiation of Photosynthetic Eukaryotes

Oxygenic photosynthesis is considered the most important evolutionary innovation in the history of Earth. It depends on two photosystems, responsible for the photolysis of water and the reduction of carbon dioxide. Oxygen and carbohydrates are released at the end of the reaction. Extraordinary, the oxygen released created the stratospheric ozone layer, and transformed the ocean chemistry, whereas the carbohydrates are the primary source of energy for complex cells. Several lines of evidence indicate the photosynthesis arose in the ancestors of cyanobacteria. It was spread over some eukaryotes by the acquisition of a free-living cyanobacterium, which evolved into photosynthetic plastid, the chloroplast. The timing of the chloroplast emergence is still controversy. Estimated ages range from 600 to 2100 million years ago (Mya) in accordance to previous studies. The aim of this study is to clarify several aspects of the origin and diversification of photosynthetic eukaryotes. For this purpose, we utilized a data set based on 27 protein-coding genes from genomes of cyanobacteria and photosynthetic eukaryotes, more genes than other papers that also utilized plastid genes, and performed the Bayesian analysis method to estimate the divergence times of the photosynthetic eukaryotes. Results showed photosynthetic eukaryotes emerged Late Mesoproterozoic about 1342 Mya. The Early Proterozoic oceans did not have adequate conditions for eukaryotes, because chemical elements such as zinc and molybdenum were at reduced concentrations, and they are essential to the formation of eukaryotic proteins.

evolutionary biology↗