Direct Optofluidic Measurement of the Lipid Permeability of Fluoroquinolones.

Quantifying drug permeability across lipid membranes is crucial for drug development. In addition, reduced membrane permeability is a leading cause of antibiotic resistance in bacteria, and hence there is a need for new technologies that can quantify antibiotic transport across biological membranes. We recently developed an optofluidic assay that directly determines the permeability coefficient of autofluorescent drug molecules across lipid membranes. Using ultraviolet fluorescence microscopy, we directly track drug accumulation in giant lipid vesicles as they traverse a microfluidic device while exposed to the drug. Importantly, our measurement does not require the knowledge of the octanol partition coefficient of the drug - we directly determine the permeability coefficient for the specific drug-lipid system. In this work, we report measurements on a range of fluoroquinolone antibiotics and find that their pH dependent lipid permeability can span over two orders of magnitude. We describe various technical improvements for our assay, and provide a new graphical user interface for data analysis to make the technology easier to use for the wider community.The work was supported by an ERC Consolidator grant “DesignerPores” awarded to UFK. JC acknowledges support from the BBSRC. MS was supported by the Friedrich Naumann Foundation for Freedom and the Swiss- European Mobility Programme. KAN was supported by the Erasmus Plus student exchange programme. SHA is supported by a Herchel Smith Postdoctoral Fellowship. SP acknowledges support from the Leverhulme Trust through an Early Career Fellowship (ECF-2013-444).This is the final version of the article. It first appeared from Nature Publishing Group at http://dx.doi.org/10.1038/srep32824

Ionic conductivity, structural deformation, and programmable anisotropy of DNA origami in electric field.

The DNA origami technique can enable functionalization of inorganic structures for single-molecule electric current recordings. Experiments have shown that several layers of DNA molecules, a DNA origami plate, placed on top of a solid-state nanopore is permeable to ions. Here, we report a comprehensive characterization of the ionic conductivity of DNA origami plates by means of all-atom molecular dynamics (MD) simulations and nanocapillary electric current recordings. Using the MD method, we characterize the ionic conductivity of several origami constructs, revealing the local distribution of ions, the distribution of the electrostatic potential and contribution of different molecular species to the current. The simulations determine the dependence of the ionic conductivity on the applied voltage, the number of DNA layers, the nucleotide content and the lattice type of the plates. We demonstrate that increasing the concentration of Mg(2+) ions makes the origami plates more compact, reducing their conductivity. The conductance of a DNA origami plate on top of a solid-state nanopore is determined by the two competing effects: bending of the DNA origami plate that reduces the current and separation of the DNA origami layers that increases the current. The latter is produced by the electro-osmotic flow and is reversible at the time scale of a hundred nanoseconds. The conductance of a DNA origami object is found to depend on its orientation, reaching maximum when the electric field aligns with the direction of the DNA helices. Our work demonstrates feasibility of programming the electrical properties of a self-assembled nanoscale object using DNA.C.Y.L., J.Y. and A.A. were supported in part by the grants from the National Science Foundation (DMR-0955959, PHY-1430124 and ECC-1227034), and the National Institutes of Health (R01- HG007406). E.A.H. acknowledges support from Schweizerische Studienstiftung (Swiss Study Foundation) and Gonville & Caius College. S.H.A. acknowledges support from a Herchel Smith postdoctoral fellowship. J.K. acknowledges support from Chinese Scholarship Council and Cambridge Overseas Trust. UFK was supported by an ERC starting grant (PassMembrane, 261101). The authors gladly acknowledge supercomputer time provided through XSEDE Allocation Grant MCA05S028 and the Blue Waters Sustained Petascale Computer System (UIUC).This is the accepted manuscript. The final version is available from ACS at pubs.acs.org/doi/abs/10.1021/nn505825z

Controlling the Reversible Assembly of Liposomes through a Multistimuli Responsive Anchored DNA.

We present a novel approach to reversibly control the assembly of liposomes through an anchored multistimuli responsive DNA oligonucleotide decorated with an azobenzene moiety (AZO-ON1). We show that liposomes assembly can be simultaneously controlled by three external stimuli: light, Mg(2+), and temperature. (i) Light alters the interaction of AZO-ON1 with liposomes, which influences DNA coating and consequently liposomes assembly. (ii) Mg(2+) induces the assembly, hence variation in its concentration enables for reversibility. (iii) Double-stranded AZO-ON1 is more efficient than single-stranded AZO-ON1 in triggering the assembly of liposomes and temperature has been used for controllable assembly through DNA thermal denaturation. Our multiresponsive AZO-ON1 represents a unique example in which multiple stimuli can be simultaneously applied to regulate the reversible assembly of liposomes.S.H.A. acknowledges support from a Herchel Smith postdoctoral fellowship. M. R. acknowledges support from an Early Postdoc Mobility fellowship of Swiss National Science Foundation. A. A and R. E. acknowledge support from MINECO, Spain, CTQ2014-52588-R. U.F.K. acknowledges support from an ERC Starting Grant Passmembrane 261101.This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by ACS

Proses Pengolahan dan Kualitas Air Minum di Kompleks Perumahan Karyawan PT. Chevron Pacific Indonesia (PT. CPI) Duri-Riau Tahun 2014

Water is one of the important matter after the air, nobody can life without drinking until 4-5 days. Drinking water which is not qualified, can resulting disease or even death. Water treatment can prevents disease and resulting qualified drinking water. PT. Chevron Pacific Indonesia (PT. CPI) is one of the companies which has a water treating plant to makes drinking water from raw water The purpose of this research is to know the process of water treatment, the quality of raw water after treatment and quality of distributed drinking water to employees housing PT. Chevron Pacific Indonesia Duri. This research was descriptive survey using simple random sampling technique with 1102 populations and 30 samples. Data were analyzed descriptively in tabulation and narration. The result of the research showed that the water treatment was using coagulation, floculation, sedimentation and desinfectan process. Based on the analysis of obtaained data, the quality of raw water was qualified, whereas the quality of water which was finish the treatment and the quality of distributed drinking water to employees housing on Maret 2014 were not qualified in one parameter. Most of the respondents have been using water as drinking water. The conclusion of this research is the water treatmen process in PT. Chevron Pacific Indonesia was conventional water treatment (complete water treatment). Overall water quality is good, it is recommended to improve adsorption using activated carbon, renew and re-examine the tools used and provision of information about water quality to water users

Is every female equal? Caste biasing in tropical paper wasps

Item does not contain fulltextDiseases caused by nontuberculous mycobacteria are emerging in many settings. With an increased number of patients needing treatment, the role of drug susceptibility testing is again in the spotlight. This articles covers the history and methodology of drug susceptibility tests for nontuberculous mycobacteria, but focuses on the correlations between in vitro drug susceptibility, pharmacokinetics and in vivo outcomes of treatment. Among slow-growing nontuberculous mycobacteria, clear correlations have been established for macrolides and amikacin (Mycobacterium avium complex) and for rifampicin (Mycobacterium kansasii). Among rapid-growing mycobacteria, correlations have been established in extrapulmonary disease for aminoglycosides, cefoxitin and co-trimoxazole. In pulmonary disease, correlations are less clear and outcomes of treatment are generally poor, especially for Mycobacterium abscessus. The clinical significance of inducible resistance to macrolides among rapid growers is an important topic. The true role of drug susceptibility testing for nontuberculous mycobacteria still needs to be addressed, preferably within clinical trials

Multiplexed ionic current sensing with glass nanopores

We report a method for simultaneous ionic current measurements of single molecules across up to 16 solid state nanopore channels. Each device, costing less than $20, contains 16 glass nanopores made by laser assisted capillary pulling. We demonstrate simultaneous multichannel detection of double stranded DNA and trapping of DNA origami nanostructures to form hybrid nanopores

The indole pulse: a new perspective on indole signalling in Escherichia coli.

Indole has diverse signalling roles, including modulation of biofilm formation, virulence and stress responses. Changes are induced by indole concentrations of 0.5-1.0 mM, similar to those found in the supernatant of Escherichia coli stationary phase culture. Here we describe an alternative mode of indole signalling that promotes the survival of E. coli cells during long-term stationary phase. A mutant that has lost the ability to produce indole demonstrates reduced survival under these conditions. Significantly, the addition of 1 mM indole to the culture supernatant is insufficient to restore long-term survival to the mutant. We provide evidence that the pertinent signal in this case is not 1 mM indole in the culture supernatant but a transient pulse of intra-cellular indole at the transition from exponential growth to stationary phase. During this pulse the cell-associated indole reaches a maximum of approximately 60 mM. We argue that this is sufficient to inhibit growth and division by an ionophore-based mechanism and causes the cells to enter stationary phase before resources are exhausted. The unused resources are used to repair and maintain cells during the extended period of starvation