35 research outputs found
Multigenerational memory and adaptive adhesion in early bacterial biofilm communities
Using multigenerational, single-cell tracking we explore the earliest events of biofilm formation by Pseudomonas aeruginosa. During initial stages of surface engagement (â€20 h), the surface cell population of this microbe comprises overwhelmingly cells that attach poorly (~95 stay <30 s, well below the âŒ1-h division time) with little increase in surface population. If we harvest cells previously exposed to a surface and direct them to a virgin surface, we find that these surface-exposed cells and their descendants attach strongly and then rapidly increase the surface cell population. This âadaptive,â time-delayed adhesion requires determinants we showed previously are critical for surface sensing: type IV pili (TFP) and cAMP signaling via the Pil-Chp-TFP system. We show that these surface-adapted cells exhibit damped, coupled out-of-phase oscillations of intracellular cAMP levels and associated TFP activity that persist for multiple generations, whereas surface-naĂŻve cells show uncorrelated cAMP and TFP activity. These correlated cAMPâTFP oscillations, which effectively impart intergenerational memory to cells in a lineage, can be understood in terms of a Turing stochastic model based on the Pil-Chp-TFP framework. Importantly, these cAMPâTFP oscillations create a state characterized by a suppression of TFP motility coordinated across entire lineages and lead to a drastic increase in the number of surface-associated cells with near-zero translational motion. The appearance of this surface-adapted state, which can serve to define the historical classification of âirreversibly attachedâ cells, correlates with family tree architectures that facilitate exponential increases in surface cell populations necessary for biofilm formation. © 2018 National Academy of Sciences. All Rights Reserved
MTA1, a Novel ATP Synthase Complex Modulator, Enhances Colon Cancer Liver Metastasis by Driving Mitochondrial Metabolism Reprogramming
Abstract Liver metastasis is the most fatal event of colon cancer patients. Warburg effect has been long challenged by the fact of upregulated oxidative phosphorylation (OXPHOS), while its mechanism remains unclear. Here, metastasisâassociated antigen 1 (MTA1) is identified as a newly identified adenosine triphosphate (ATP) synthase modulator by interacting with ATP synthase F1 subunit alpha (ATP5A), facilitates colon cancer liver metastasis by driving mitochondrial bioenergetic metabolism reprogramming, enhancing OXPHOS; therefore, modulating ATP synthase activity and downstream mTOR pathways. Highâthroughput screening of an anticancer drug shows MTA1 knockout increases the sensitivity of colon cancer to mitochondrial bioenergetic metabolismâtargeted drugs and mTOR inhibitors. Inhibiting ATP5A enhances the sensitivity of liverâmetastasized colon cancer to sirolimus in an MTA1âdependent manner. The therapeutic effects are verified in xenograft models and clinical cases. This research identifies a new modulator of mitochondrial bioenergetic reprogramming in cancer metastasis and reveals a new mechanism on upregulating mitochondrial OXPHOS as the reversal of Warburg effect in cancer metastasis is orchestrated
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Multigenerational memory and adaptive adhesion in early bacterial biofilm communities
Using multigenerational, single-cell tracking we explore the earliest events of biofilm formation by Pseudomonas aeruginosa During initial stages of surface engagement (â€20 h), the surface cell population of this microbe comprises overwhelmingly cells that attach poorly (âŒ95% stay <30 s, well below the âŒ1-h division time) with little increase in surface population. If we harvest cells previously exposed to a surface and direct them to a virgin surface, we find that these surface-exposed cells and their descendants attach strongly and then rapidly increase the surface cell population. This "adaptive," time-delayed adhesion requires determinants we showed previously are critical for surface sensing: type IV pili (TFP) and cAMP signaling via the Pil-Chp-TFP system. We show that these surface-adapted cells exhibit damped, coupled out-of-phase oscillations of intracellular cAMP levels and associated TFP activity that persist for multiple generations, whereas surface-naĂŻve cells show uncorrelated cAMP and TFP activity. These correlated cAMP-TFP oscillations, which effectively impart intergenerational memory to cells in a lineage, can be understood in terms of a Turing stochastic model based on the Pil-Chp-TFP framework. Importantly, these cAMP-TFP oscillations create a state characterized by a suppression of TFP motility coordinated across entire lineages and lead to a drastic increase in the number of surface-associated cells with near-zero translational motion. The appearance of this surface-adapted state, which can serve to define the historical classification of "irreversibly attached" cells, correlates with family tree architectures that facilitate exponential increases in surface cell populations necessary for biofilm formation
How useful are geochemical and mineralogical indicators in assessing trace metal contamination and bioavailability in a post-restoration Mediterranean lagoon?
Determination of histamine H2 receptor antagonists in pharmaceutical formulations by CE-MS
Nutrient exchange and oxygen demand at the sedimentâwater interface during dry and wet seasons off the Medjerda River Delta (Tunis Gulf, Tunisia)
Reactivity of transition metal atoms supported or not on TiO2(110) toward CO and H adsorption
Trace Metal Concentrations in the Seston of the Gulf of Ä°skenderun (Turkey, North-Eastern Mediterranean)
Electrochemical biosensors - sensor principles and architectures
Quantification of biological or biochemical processes are of utmost importancefor medical, biological and biotechnological applications. However, converting the biologicalinformation to an easily processed electronic signal is challenging due to the complexity ofconnecting an electronic device directly to a biological environment. Electrochemical biosensorsprovide an attractive means to analyze the content of a biological sample due to thedirect conversion of a biological event to an electronic signal. Over the past decades severalsensing concepts and related devices have been developed. In this review, the most commontraditional techniques, such as cyclic voltammetry, chronoamperometry, chronopotentiometry,impedance spectroscopy, and various field-effect transistor based methods are presented alongwith selected promising novel approaches, such as nanowire or magnetic nanoparticle-basedbiosensing. Additional measurement techniques, which have been shown useful in combinationwith electrochemical detection, are also summarized, such as the electrochemical versionsof surface plasmon resonance, optical waveguide lightmode spectroscopy, ellipsometry,quartz crystal microbalance, and scanning probe microscopy.The signal transduction and the general performance of electrochemical sensors are often determinedby the surface architectures that connect the sensing element to the biological sampleat the nanometer scale. The most common surface modification techniques, the various electrochemicaltransduction mechanisms, and the choice of the recognition receptor moleculesall influence the ultimate sensitivity of the sensor. New nanotechnology-based approaches,such as the use of engineered ion-channels in lipid bilayers, the encapsulation of enzymesinto vesicles, polymersomes, or polyelectrolyte capsules provide additional possibilities forsignal amplification.In particular, this review highlights the importance of the precise control over the delicateinterplay between surface nano-architectures, surface functionalization and the chosen sensortransducer principle, as well as the usefulness of complementary characterization tools tointerpret and to optimize the sensor response