49 research outputs found
Supporting active learning in an undergraduate geotechnical engineering course using group-based audience response systems quizzes
Computational Bacterial Genome-Wide Analysis of Phylogenetic Profiles Reveals Potential Virulence Genes of Streptococcus agalactiae
The phylogenetic profile of a gene is a reflection of its evolutionary history
and can be defined as the differential presence or absence of a gene in a set of
reference genomes. It has been employed to facilitate the prediction of gene
functions. However, the hypothesis that the application of this concept can also
facilitate the discovery of bacterial virulence factors has not been fully
examined. In this paper, we test this hypothesis and report a computational
pipeline designed to identify previously unknown bacterial virulence genes using
group B streptococcus (GBS) as an example. Phylogenetic profiles of all GBS
genes across 467 bacterial reference genomes were determined by
candidate-against-all BLAST searches,which were then used to identify candidate
virulence genes by machine learning models. Evaluation experiments with known
GBS virulence genes suggested good functional and model consistency in
cross-validation analyses (areas under ROC curve, 0.80 and 0.98 respectively).
Inspection of the top-10 genes in each of the 15 virulence functional groups
revealed at least 15 (of 119) homologous genes implicated in virulence in other
human pathogens but previously unrecognized as potential virulence genes in GBS.
Among these highly-ranked genes, many encode hypothetical proteins with possible
roles in GBS virulence. Thus, our approach has led to the identification of a
set of genes potentially affecting the virulence potential of GBS, which are
potential candidates for further in vitro and in
vivo investigations. This computational pipeline can also be
extended to in silico analysis of virulence determinants of
other bacterial pathogens
Adaptive response and apoptosis in HCT116 cells upon endoplasmic reticulum stress
Trabajo presentaod en el XVIII Congreso de la Sociedad Española de BiologÃa Celular, celebrado en Badajoz (España), del 15 al 18 de octubre de 2019Objective: To investigate the interconnection between adaptive and apoptotic responses in tumor cells undergoing ER stress, a situation frequently observed during tumor growth.
Material and Methods: the human tumor colorectal HCT116 cell line was used as model system. Knockdown of FLIPL, TRAF2 and RIPK1 were accomplished using small-interference RNA. Cells overexpressing FLIPL were generated by retrovirus infection and selection with puromycin. Multicellular tumor spheroids were prepared by the hanging drop method and grown in 96 well plates coated with agarose until treatment.
Results: we have identified FLIPL as an important regulator in the balance between apoptosis and survival in conventional 2D cultures of HCT116 cells. FLIPL downregulation or overexpression provokes sensitization or protection to ER stress, respectively. We have also demonstrated that RIPK1 and TRAF2, two negative modulators of TRAIL-induced apoptosis, have a protective role against ER stress-induced apoptosis. In addition, we show that HCT116 3D spheroids, whose architecture resemble solid tumours, are more resistant to ER stress-induced UPR signalling and apoptosis although more experiments are needed to decipher the molecular and cellular basis of this resistance.
Conclusions: (1) FLIPL, TRAF2 and RIPK1 play an adaptive role to delay ER stress-induced apoptosis in HCT116 cells and (2) HCT116-derived spheroids are more resistant to ER stress than standard 2D cultures