Syntaxin 16 and syntaxin 5 are required for efficient retrograde transport of several exogenous and endogenous cargo proteins

Retrograde transport allows proteins and lipids to leave the endocytic pathway to reach other intracellular compartments, such as trans-Golgi network (TGN)/Golgi membranes, the endoplasmic reticulum and, in some instances, the cytosol. Here, we have used RNA interference against the SNARE proteins syntaxin 5 and syntaxin 16, combined with recently developed quantitative trafficking assays, morphological approaches and cell intoxication analysis to show that these SNARE proteins are not only required for efficient retrograde transport of Shiga toxin, but also for that of an endogenous cargo protein - the mannose 6-phosphate receptor - and for the productive trafficking into cells of cholera toxin and ricin. We have found that the function of syntaxin 16 was specifically required for, and restricted to, the retrograde pathway. Strikingly, syntaxin 5 RNA interference protected cells particularly strongly against Shiga toxin. Since our trafficking analysis showed that apart from inhibiting retrograde endosome-to-TGN transport, the silencing of syntaxin 5 had no additional effect on Shiga toxin endocytosis or trafficking from TGN/Golgi membranes to the endoplasmic reticulum, we hypothesize that syntaxin 5 also has trafficking-independent functions. In summary, our data demonstrate that several cellular and exogenous cargo proteins use elements of the same SNARE machinery for efficient retrograde transport between early/recycling endosomes and TGN/Golgi membranes

Reactions of azoalkenes derived from hydrazones of ethyl bromopyruvate with electron rich alkenes and heterocycles

Three hydrazones of ethyl bromopyruvate, the dinitrophenylhydrazone 2a, the toluene-4-sulphonylhydrazone 2b and the t-butoxycarbonylhydrazone 2c, have been reacted with a series of nucleophilic alkenes and heterocycles in the presence of sodium carbonate. Azoalkenes 3 are presumed as intermediates and adducts have been isolated. The azoalkenes derived from hydrazones 2a and 2c are found to be useful electrophiles and electrophilic dienes

Effect of Light-Cure Initiation Time on Polymerization Efficiency and Orthodontic Bond Strength with a Resin-Modified Glass-Ionomer

Objectives –  The polymerization and acid–base reactions in resin-modified glass-ionomers (RMGI) are thought to compete with and inhibit one another. To examine the effect of visible light-cure (VLC) delay on the polymerization efficiency and orthodontic bond strength of a dual-cured RMGI. Setting and Sample Population –  The Orthodontics Graduate Program at Marquette University. An in vitro study utilizing 72 freshly extracted human bicuspid teeth. Materials and Methods –  A RMGI light-cured immediately, 2.5, 5, or 10 min after mixing comprised the experimental groups. Isothermal and dynamic temperature scan differential scanning calorimetry (DSC) analysis of the RMGI was performed to determine extents of VLC polymerization and acid–base reaction exotherms. Human premolars (n = 18/group) were bonded with the RMGI. Shear bond strength and adhesive remnant index (ARI) scores were determined. Results –  Differential scanning calorimetry results showed the 10-min-delay RMGI group experienced significantly (p \u3c 0.05) lower VLC polymerization compared with the other groups. Acid–base reaction exotherms were undetected in all groups except the 10-min delay group. No significant differences (p \u3e 0.05) were noted among the groups for mean shear bond strength. A chi-square test showed no significant difference (p = 0.428) in ARI scores between groups. Conclusions –  Delay in light-curing may reduce polymerization efficiency and alter the structure of the RMGI, but orthodontic shear bond strength does not appear to be compromised

Astrophysics datamining in the classroom: Exploring real data with new software tools and robotic telescopes

Within the efforts to bring frontline interactive astrophysics and astronomy to the classroom, the Hands on Universe (HOU) developed a set of exercises and platform using real data obtained by some of the most advanced ground and space observatories. The backbone of this endeavour is a new free software Web tool - Such a Lovely Software for Astronomy based on Image J (Salsa J). It is student-friendly and developed specifically for the HOU project and targets middle and high schools. It allows students to display, analyze, and explore professionally obtained astronomical images, while learning concepts on gravitational dynamics, kinematics, nuclear fusion, electromagnetism. The continuous evolving set of exercises and tutorials is being completed with real (professionally obtained) data to download and detailed tutorials. The flexibility of the Salsa J platform tool enables students and teachers to extend the exercises with their own observations. The software developed for the HOU program has been designed to be a multi-platform, multi-lingual experience for image manipulation and analysis in the classroom. Its design enables easy implementation of new facilities (extensions and plugins), minimal in-situ maintenance and flexibility for exercise plugin. Here, we describe some of the most advanced exercises about astrophysics in the classroom, addressing particular examples on gravitational dynamics, concepts currently introduced in most sciences curricula in middle and high schools.Comment: 10 pages, 12 images, submitted to the special theme issue Using Astronomy and Space Science Research in Physics Courses of the American Journal of Physic

Polarization signals in mantis shrimps

While color signals are well known as a form of animal communication, a number of animals communicate using signals based on patterns of polarized light reflected from specialized body parts or structures. Mantis shrimps, a group of marine crustaceans, have evolved a great diversity of such signals, several of which are based on photonic structures. These include resonant scattering devices, structures based on layered dichroic molecules, and structures that use birefringent layers to produce circular polarization. Such biological polarizers operate in different spectral regions ranging from the near-UV to medium wavelengths of visible light. In addition to the structures that are specialized for signal production, the eyes of many species of mantis shrimp are adapted to detect linearly polarized light in the ultraviolet and in the green, using specialized sets of photoreceptors with oriented, dichroic visual pigments. Finally, a few mantis shrimp species produce biophotonic retarders within their photoreceptors that permit the detection of circularly polarized light and are thus the only animals known to sense this form of polarization. Mantis shrimps use polarized light in species-specific signals related to mating and territorial defense, and their means of manipulating light's polarization can inspire designs for artificial polarizers and achromatic retarders

On the evaluation of some three-body variational integrals

Stable recursive relations are presented for the numerical computation of the integrals $$\int d{\bf r}_1 d{\bf r}_2 r_1^{l-1} r_2^{m-1} r_{12}^{n-1} \exp{\{-\alpha r_1 -\beta r_2 -\gamma r_{12}\}}$$ ($l$, $m$ and $n$ integer, $\alpha$, $\beta$ and $\gamma$ real) when the indices $l$, $m$ or $n$ are negative. Useful formulas are given for particular values of the parameters $\alpha$, $\beta$ and $\gamma$.Comment: 12 pages, 1 figure (PS) and 3 tables. Old figures 2 and 3 replaced by Tables I and III. A further table added. Paper enlarged giving some tips on the convergence of quadrature

In vivo microdialysis to determine subcutaneous interstitial fluid penetration and pharmacokinetics of fluconazole in intensive care unit patients with sepsis

The objective of the study was to describe the subcutaneous interstitial fluid (ISF) pharmacokinetics of fluconazole in critically ill patients with sepsis. This prospective observational study was conducted at two tertiary intensive care units in Australia. Serial fluconazole concentrations were measured over 24 h in plasma and subcutaneous ISF using microdialysis. The concentrations in plasma and microdialysate were measured using a validated high-performance liquid chromatography system with electrospray mass spectrometer detector method. Noncompartmental pharmacokinetic analysis was performed. Twelve critically ill patients with sepsis were enrolled. The mean in vivo fluconazole recovery rates +/- standard deviation (SD) for microdialysis were 51.4% +/- 16.1% with a mean (+/- SD) fluconazole ISF penetration ratio of 0.52 +/- 0.30 (coefficient of variation, 58%). The median free plasma area under the concentration-time curve from 0 to 24 h (AUC(0-24)) was significantly higher than the median ISF AUC(0-24) (340.4 versus 141.1 mg . h/liter; P = 0.004). There was no statistical difference in median fluconazole ISF penetration between patients receiving and not receiving vasopressors (median, 0.28 versus 0.78; P = 0.106). Both minimum and the maximum concentrations of drug in serum (C-max and C-min) showed a significant correlation with the fluconazole plasma exposure (Cmax, R-2 = 0.86, P < 0.0001; Cmin, R-2 = 0.75, P < 0.001). Our data suggest that fluconazole was distributed variably, but incompletely, from plasma into subcutaneous interstitial fluid in this cohort of critically ill patients with sepsis. Given the variability of fluconazole interstitial fluid exposures and lack of clinically identifiable factors by which to recognize patients with reduced distribution/exposure, we suggest higher than standard doses to ensure that drug exposure is adequate at the site of infection

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