Search Results (4)

I defend a diachronic constraint on justification as a necessary condition for knowledge. In my view (JTB + D), a belief is knowledge-apt only if its justification is maintainable over a context-sensitive interval Δ under ordinary avenues of evidence-accrual, including reliable memory, testimony, and communal inquiry, with no accessible undefeated defeaters arising within that interval. This temporal, process-sensitive requirement mitigates Gettier-style luck by targeting “snapshot” justification that would easily collapse under minimal further scrutiny (as in Fake Barn County), while avoiding infallibilism and over-intellectualism. I calibrate Δ by stakes and domain volatility to avoid vagueness and moving goalposts, distinguish responsive stability from mere habituation, and show how the account handles no-new-evidence scenarios without undermining ordinary memorial and testimonial knowledge. Conceptually, the proposal integrates internalist and externalist insights as it preserves reason-responsiveness over time and serves as an actual-world temporal analogue of safety, not a standalone fourth ‘dimension’. I engage canonical cases and acknowledge Zagzebski’s challenge: the view does not promise full Gettier immunity, but it raises the bar for counterexamples in ordinary environments. The result is a principled, parameterised refinement of the justification condition that better captures knowledge as an enduring, responsibly supported true belief. Full article

The identification of new genes/proteins involved in breast cancer (BC) occurrence is widely used to discover novel biomarkers and understand the molecular mechanisms of BC initiation and progression. The jumping translocation breakpoint (JTB) gene may act both as a tumor suppressor or oncogene in various types of tumors, including BC. Thus, the JTB protein could have the potential to be used as a biomarker in BC, but its neoplastic mechanisms still remain unknown or controversial. We previously analyzed the interacting partners of JTB^high protein extracted from transfected MCF7 BC cell line using SDS-PAGE complemented with in-solution digestion, respectively. The previous results suggested the JTB contributed to the development of a more aggressive phenotype and behavior for the MCF7 BC cell line through synergistic upregulation of epithelial–mesenchymal transition (EMT), mitotic spindle, and fatty acid metabolism-related pathways. In this work, we aim to complement the previously reported JTB proteomics-based experiments by investigating differentially expressed proteins (DEPs) and tumorigenic pathways associated with JTB overexpression using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Statistically different gel spots were picked for protein digestion, followed by nanoliquid chromatography–tandem mass spectrometry (nLC-MS/MS) analysis. We identified six DEPs related to the JTB^high condition vs. control that emphasize a pro-tumorigenic (PT) role. Twenty-one proteins, which are known to be usually overexpressed in cancer cells, emphasize an anti-tumorigenic (AT) role when low expression occurs. According to our previous results, proteins that have a PT role are mainly involved in the activation of the EMT process. Interestingly, JTB overexpression has been correlated here with a plethora of significant upregulated and downregulated proteins that sustain JTB tumor suppressive functions. Our present and previous results sustain the necessity of the complementary use of different proteomics-based methods (SDS-PAGE, 2D-PAGE, and in-solution digestion) followed by tandem mass spectrometry to avoid their limitations, with each method leading to the delineation of specific clusters of DEPs that may be merged for a better understanding of molecular pathways and neoplastic mechanisms related to the JTB’s role in BC initiation and progression. Full article

Human jumping translocation breakpoint (hJTB) gene is located on chromosome 1q21 and is involved in unbalanced translocation in many types of cancer. JTB protein is ubiquitously present in normal cells but it is found to be overexpressed or downregulated in various types of cancer cells, where this protein and its isoforms promote mitochondrial dysfunction, resistance to apoptosis, genomic instability, proliferation, invasion and metastasis. Hence, JTB could be a tumor biomarker for different types of cancer, such as breast cancer (BC), and could be used as a drug target for therapy. However, the functions of the protein or the pathways through which it increases cell proliferation and invasiveness of cancer cells are not well-known. Therefore, we aim to investigate the functions of JTB by using in-solution digestion-based cellular proteomics of control and upregulated and downregulated JTB protein in MCF7 breast cancer cell line, taking account that in-solution digestion-based proteomics experiments are complementary to the initial in-gel based ones. Proteomics analysis allows investigation of protein dysregulation patterns that indicate the function of the protein and its interacting partners, as well as the pathways and biological processes through which it functions. We concluded that JTB dysregulation increases the epithelial-mesenchymal transition (EMT) potential and cell proliferation, harnessing cytoskeleton organization, apical junctional complex, metabolic reprogramming, and cellular proteostasis. Deregulated JTB expression was found to be associated with several proteins involved in mitochondrial organization and function, oxidative stress (OS), apoptosis, and interferon alpha and gamma signaling. Consistent and complementary to our previous results emerged by using in-gel based proteomics of transfected MCF7 cells, JTB-related proteins that are overexpressed in this experiment suggest the development of a more aggressive phenotype and behavior for this luminal type A non-invasive/poor-invasive human BC cell line that does not usually migrate or invade compared with the highly metastatic MDA-MB-231 cells. This more aggressive phenotype of MCF7 cells related to JTB dysregulation and detected by both in-gel and in-solution proteomics could be promoted by synergistic upregulation of EMT, Mitotic spindle and Fatty acid metabolism pathways. However, in both JTB dysregulated conditions, several downregulated JTB-interacting proteins predominantly sustain antitumor activities, attenuating some of the aggressive phenotypical and behavioral traits promoted by the overexpressed JTB-related partners. Full article

Staphylococcus aureus (S. aureus) is an important zoonotic pathogen that poses a serious health concern to humans and cattle worldwide. Although it has been proven that lytic phages may successfully kill S. aureus, the interaction between the host and the phage has yet to be thoroughly investigated, which will likely limit the clinical application of phage. Here, RNA sequencing (RNA-seq) was used to examine the transcriptomics of jumbo phage SA1 and Staphylococcus JTB1-3 during a high multiplicity of infection (MOI) and RT-qPCR was used to confirm the results. The RNA-seq analysis revealed that phage SA1 took over the transcriptional resources of the host cells and that the genes were categorized as early, middle, and late, based on the expression levels during infection. A minor portion of the resources of the host was employed to enable phage replication after infection because only 35.73% (997/2790) of the host genes were identified as differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the phage infection mainly affected the nucleotide metabolism, protein metabolism, and energy-related metabolism of the host. Moreover, the expression of the host genes involved in anti-phage systems, virulence, and drug resistance significantly changed during infection. This research gives a fresh understanding of the relationship between jumbo phages and their Gram-positive bacteria hosts and provides a reference for studying phage treatment and antibiotics. Full article