65 research outputs found

    Prediction by Promoter Logic in Bacterial Quorum Sensing

    Get PDF
    Quorum-sensing systems mediate chemical communication between bacterial cells, coordinating cell-density-dependent processes like biofilm formation and virulence-factor expression. In the proteobacterial LuxI/LuxR quorum sensing paradigm, a signaling molecule generated by an enzyme (LuxI) diffuses between cells and allosterically stimulates a transcriptional regulator (LuxR) to activate its cognate promoter (pR). By expressing either LuxI or LuxR in positive feedback from pR, these versatile systems can generate smooth (monostable) or abrupt (bistable) density-dependent responses to suit the ecological context. Here we combine theory and experiment to demonstrate that the promoter logic of pR – its measured activity as a function of LuxI and LuxR levels – contains all the biochemical information required to quantitatively predict the responses of such feedback loops. The interplay of promoter logic with feedback topology underlies the versatility of the LuxI/LuxR paradigm: LuxR and LuxI positive-feedback systems show dramatically different responses, while a dual positive/negative-feedback system displays synchronized oscillations. These results highlight the dual utility of promoter logic: to probe microscopic parameters and predict macroscopic phenotype

    Purinergic signalling and immune cells

    Get PDF
    This review article provides a historical perspective on the role of purinergic signalling in the regulation of various subsets of immune cells from early discoveries to current understanding. It is now recognised that adenosine 5'-triphosphate (ATP) and other nucleotides are released from cells following stress or injury. They can act on virtually all subsets of immune cells through a spectrum of P2X ligand-gated ion channels and G protein-coupled P2Y receptors. Furthermore, ATP is rapidly degraded into adenosine by ectonucleotidases such as CD39 and CD73, and adenosine exerts additional regulatory effects through its own receptors. The resulting effect ranges from stimulation to tolerance depending on the amount and time courses of nucleotides released, and the balance between ATP and adenosine. This review identifies the various receptors involved in the different subsets of immune cells and their effects on the function of these cells

    An epigenetic clock for gestational age at birth based on blood methylation data

    Get PDF

    Preparation of collagen peptide functionalized chitosan nanoparticles by ionic gelation method: An effective carrier system for encapsulation and release of doxorubicin for cancer drug delivery

    No full text
    In recent years, nanoparticles (NPs) based on biopolymers or peptides are gaining popularity for the encapsulation and release of drug molecules, especially for cancer therapy, due to their ability for targeted and controlled release. The use of collagen peptide (CP) for the preparation of chitosan (CN) NPs is especially interesting as it results in NPs that are stable under physiological conditions. In this work, mono-dispersed pH responsive CPCN NPs of about 100 nm were prepared via ionic gelation method by simple and mild co-precipitation of CN and CP. Investigation of NPs with Fourier transform infra-red (FTIR) spectroscopy and dynamic light scattering (DLS) measurements reveals that hydrogen bonding and electrostatic interactions are believed to be major driving forces for NP formation and drug encapsulation, respectively. Scanning electron microscopic (SEM) investigations show that hard and fine CPCN NPs transform to soft and bigger gel like particles as a function of collagen concentration. The unique ``polymeric gel'' structure of NPs showed high encapsulation efficiency towards doxorubicin hydrochloride (DOX) as well as pH controlled release. Anti-proliferative and cell viability analysis revealed that DOX loaded NPs showed excellent anti-proliferative characteristics against HeLa cells with favorable biocompatibility against normal cells. Such NPs have high potential for use as smart drug delivery carriers in advanced cancer therapy. (C) 2016 Elsevier B.V. All rights reserved
    corecore