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Staphylococcus aureus is an important pathogen implicated in various diseases, including staphylococcal food poisoning. Bacteriocins are considered safe and effective antimicrobial substances for the prevention of the growth of pathogenic bacteria. In this article, we describe the purification and characterization of pasteuricin, a novel bacteriocin produced by Staphylococcus pasteuri RSP-1. A cell-free supernatant of S. pasteuri RSP-1 exerted strong antimicrobial activity against staphylococci, including methicillin-resistant S. aureus (MRSA), and gram-positive bacteria. The loss of antimicrobial activity upon treatment with proteolytic enzymes confirmed the proteinaceous nature of pasteuricin. A rapid and pronounced bactericidal effect of pasteuricin was confirmed by a live-dead bacterial viability assay. To our knowledge, pasteuricin is the first reported S. pasteuri bacteriocin that inhibits S. aureus. Because pasteuricin is characterized by strong antimicrobial activity and high stability, it has potential as an alternative antimicrobial agent to antibiotics. [ABSTRACT FROM AUTHOR]

Pointwise intensity-based algorithms are the most popular algorithms in dynamic laser speckle measurement of physical or biological activity. The output of this measurement is a two-dimensional map which qualitatively separates regions of higher or lower activity. In the paper, we have proposed filtering of activity maps to enhance visualization and to enable quantitative determination of activity time scales. As a first step, we have proved that the severe spatial fluctuations within the map resemble a signal-dependent noise. As a second step, we have illustrated implementation of the proposed idea by applying filters to non-normalized and normalized activity estimates derived from synthetic and experimental data. Statistical behavior of the estimates has been analyzed to choose the filter parameters, and substantial narrowing of the probability density functions of the estimates has been achieved after the filtering. The filtered maps exhibit an improved contrast and allowed for quantitative description of activity. [ABSTRACT FROM AUTHOR]

The evolutionary trajectory of glioblastoma (GBM) is a multifaceted biological process that extends beyond genetic alterations alone. Here, we perform an integrative proteogenomic analysis of 123 longitudinal glioblastoma pairs and identify a highly proliferative cellular state at diagnosis and replacement by activation of neuronal transition and synaptogenic pathways in recurrent tumors. Proteomic and phosphoproteomic analyses reveal that the molecular transition to neuronal state at recurrence is marked by post-translational activation of the wingless-related integration site (WNT)/ planar cell polarity (PCP) signaling pathway and BRAF protein kinase. Consistently, multi-omic analysis of patient-derived xenograft (PDX) models mirror similar patterns of evolutionary trajectory. Inhibition of B-raf proto-oncogene (BRAF) kinase impairs both neuronal transition and migration capability of recurrent tumor cells, phenotypic hallmarks of post-therapy progression. Combinatorial treatment of temozolomide (TMZ) with BRAF inhibitor, vemurafenib, significantly extends the survival of PDX models. This study provides comprehensive insights into the biological mechanisms of glioblastoma evolution and treatment resistance, highlighting promising therapeutic strategies for clinical intervention. [Display omitted] • Longitudinal proteogenomic analysis reveals increased neuronal state at recurrence • Neuronal transition associates with activation of WNT/PCP pathway and BRAF kinase • Resistance to therapy via neuronal transition is recapitulated in GBM PDX models • BRAF kinase inhibition impairs the neuronal transition of GBM at recurrence Kim et al. reveal that glioblastoma develops therapeutic resistance through a neuronal transition caused by changes in the WNT/PCP pathway and BRAF kinase, as shown by extensive proteogenomic analysis. Notably, inhibiting BRAF kinase disrupts this lethal transformation, offering potential therapeutic avenues. [ABSTRACT FROM AUTHOR]