117 research outputs found

    Implementing guidelines for the prescribing of vancomycin and teicoplanin

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    The Goldbeter-Koshland switch in the first-order region and its response to dynamic disorder

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    In their classical work (Proc. Natl. Acad. Sci. USA, 1981, 78:6840-6844), Goldbeter and Koshland mathematically analyzed a reversible covalent modification system which is highly sensitive to the concentration of effectors. Its signal-response curve appears sigmoidal, constituting a biochemical switch. However, the switch behavior only emerges in the "zero-order region", i.e. when the signal molecule concentration is much lower than that of the substrate it modifies. In this work we showed that the switching behavior can also occur under comparable concentrations of signals and substrates, provided that the signal molecules catalyze the modification reaction in cooperation. We also studied the effect of dynamic disorders on the proposed biochemical switch, in which the enzymatic reaction rates, instead of constant, appear as stochastic functions of time. We showed that the system is robust to dynamic disorder at bulk concentration. But if the dynamic disorder is quasi-static, large fluctuations of the switch response behavior may be observed at low concentrations. Such fluctuation is relevant to many biological functions. It can be reduced by either increasing the conformation interconversion rate of the protein, or correlating the enzymatic reaction rates in the network.Comment: 23 pages, 4 figures, accepted by PLOS ON

    Ancient origins determine global biogeography of hot and cold desert cyanobacteria

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    Factors governing large-scale spatio-temporal distribution of microorganisms remain unresolved, yet are pivotal to understanding ecosystem value and function. Molecular genetic analyses have focused on the influence of niche and neutral processes in determining spatial patterns without considering the temporal scale. Here, we use temporal phylogenetic analysis calibrated using microfossil data for a globally sampled desert cyanobacterium, Chroococcidiopsis, to investigate spatio-temporal patterns in microbial biogeography and evolution. Multilocus phylogenetic associations were dependent on contemporary climate with no evidence for distance-related patterns. Massively parallel pyrosequencing of environmental samples confirmed that Chroococcidiopsis variants were specific to either hot or cold deserts. Temporally scaled phylogenetic analyses showed no evidence of recent inter-regional gene flow, indicating populations have not shared common ancestry since before the formation of modern continents. These results indicate that global distribution of desert cyanobacteria has not resulted from widespread contemporary dispersal but is an ancient evolutionary legacy. This highlights the importance of considering temporal scales in microbial biogeography

    Broad Antiviral Activity of Carbohydrate-Binding Agents against the Four Serotypes of Dengue Virus in Monocyte-Derived Dendritic Cells

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    BACKGROUND: Dendritic cells (DC), present in the skin, are the first target cells of dengue virus (DENV). Dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) is present on DC and recognizes N-glycosylation sites on the E-glycoprotein of DENV. Thus, the DC-SIGN/E-glycoprotein interaction can be considered as an important target for inhibitors of viral replication. We evaluated various carbohydrate-binding agents (CBAs) against all four described serotypes of DENV replication in Raji/DC-SIGN(+) cells and in monocyte-derived DC (MDDC). METHODOLOGY/PRINCIPAL FINDINGS: A dose-dependent anti-DENV activity of the CBAs Hippeastrum hybrid (HHA), Galanthus nivalis (GNA) and Urtica dioica (UDA), but not actinohivin (AH) was observed against all four DENV serotypes as analyzed by flow cytometry making use of anti-DENV antibodies. Remarkably, the potency of the CBAs against DENV in MDDC cultures was significantly higher (up to 100-fold) than in Raji/DC-SIGN(+) cells. Pradimicin-S (PRM-S), a small-size non-peptidic CBA, exerted antiviral activity in MDDC but not in Raji/DC-SIGN(+) cells. The CBAs act at an early step of DENV infection as they bind to the viral envelope of DENV and subsequently prevent virus attachment. Only weak antiviral activity of the CBAs was detected when administered after the virus attachment step. The CBAs were also able to completely prevent the cellular activation and differentiation process of MDDC induced upon DENV infection. CONCLUSIONS/SIGNIFICANCE: The CBAs exerted broad spectrum antiviral activity against the four DENV serotypes, laboratory-adapted viruses and low passage clinical isolates, evaluated in Raji/DC-SIGN(+) cells and in primary MDDC

    Perioperative echocardiography-guided hemodynamic therapy in high-risk patients:a practical expert approach of hemodynamically focused echocardiography

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    The number of high-risk patients undergoing surgery is growing. To maintain adequate hemodynamic functioning as well as oxygen delivery to the vital organs (DO2) amongst this patient population, a rapid assessment of cardiac functioning is essential for the anesthesiologist. Pinpointing any underlying cardiovascular pathophysiology can be decisive to guide interventions in the intraoperative setting. Various techniques are available to monitor the hemodynamic status of the patient, however due to intrinsic limitations, many of these methods may not be able to directly identify the underlying cause of cardiovascular impairment. Hemodynamic focused echocardiography, as a rapid diagnostic method, offers an excellent opportunity to examine signs of filling impairment, cardiac preload, myocardial contractility and the function of the heart valves. We thus propose a 6-step-echocardiographic approach to assess high-risk patients in order to improve and maintain perioperative DO2. The summary of all echocardiographic based findings allows a differentiated assessment of the patient's cardiovascular function and can thus help guide a (patho)physiological-orientated and individualized hemodynamic therapy

    Status and Prospects of ZnO-Based Resistive Switching Memory Devices

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    In the advancement of the semiconductor device technology, ZnO could be a prospective alternative than the other metal oxides for its versatility and huge applications in different aspects. In this review, a thorough overview on ZnO for the application of resistive switching memory (RRAM) devices has been conducted. Various efforts that have been made to investigate and modulate the switching characteristics of ZnO-based switching memory devices are discussed. The use of ZnO layer in different structure, the different types of filament formation, and the different types of switching including complementary switching are reported. By considering the huge interest of transparent devices, this review gives the concrete overview of the present status and prospects of transparent RRAM devices based on ZnO. ZnO-based RRAM can be used for flexible memory devices, which is also covered here. Another challenge in ZnO-based RRAM is that the realization of ultra-thin and low power devices. Nevertheless, ZnO not only offers decent memory properties but also has a unique potential to be used as multifunctional nonvolatile memory devices. The impact of electrode materials, metal doping, stack structures, transparency, and flexibility on resistive switching properties and switching parameters of ZnO-based resistive switching memory devices are briefly compared. This review also covers the different nanostructured-based emerging resistive switching memory devices for low power scalable devices. It may give a valuable insight on developing ZnO-based RRAM and also should encourage researchers to overcome the challenges

    Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

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    In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field
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