Stimuli-Responsive Polyguanidino-Oxanorbornene Membrane Transporters as Multicomponent Sensors in Complex Matrices

We introduce guanidinium-containing synthetic polymers based on polyguanidino-oxanorbornenes (PGONs) as anion transporters in lipid bilayers that can be activated and inactivated by chemical stimulation. According to fluorogenic anion export experiments with vesicles, PGON transporters are most active in neutral bilayers near their phase transition, with EC50's in the nanomolar range. Six times higher effective transporter concentrations were measured with aminonaphthalene-1,3,6-trisulfonate than with 5(6)-carboxyfluorescein, demonstrating the importance of anion binding for transport and excluding nonspecific efflux. Negative surface potentials efficiently annihilate transport activity, while inside-negative membrane potentials slightly increase it. These trends demonstrate the functional importance of counterions to hinder the binding of hydrophilic counterions and to minimize the global positive charge of the transporter-counterion complexes. Strong, nonlinear increases in activity with polymer length reveal a significant polymer effect. Overall, the characteristics of PGONs do not match those of similar systems (for example, polyarginine) and hint toward an interesting mode of action, clearly different from nonspecific leakage caused by detergents. The activity of PGONs increases in the presence of amphiphilic anions such as pyrenebutyrate (EC50 = 70 microM), while several other amphiphilic anions tested were inactive. PGONs are efficiently inactivated by numerous hydrophilic anions including ATP (IC 50 = 150 microM), ADP (IC50 = 460 microM), heparin (IC50 = 1.0 microM), phytate (IC50 = 0.4 microM), and CB hydrazide (IC50 = 26 microM). The compatibility of this broad responsiveness with multicomponent sensing in complex matrices is discussed and illustrated with lactate sensing in sour milk. The PGON lactate sensor operates together with lactate oxidase as a specific signal generator and CB hydrazide as an amplifier for covalent capture of the pyruvate product as CB hydrazone (IC50 = 1.5 microM)

USE OF INHALANT ANESTHETICS IN THREE SNAKE SPECIES

Different snake species respond differently to various anesthetic agents. Hence, an anesthetic procedure developed for one species cannot necessarily be safely transferred to another species. The goal of this paper is to summarize our experience using inhalant anesthetics on three snake species, including both procedures that were successful and those we found to be less satisfactory. We found isoflurane delivered with a precision vaporizer to be the best agent to anesthetize black rat snakes (Elaphe o. obsoleta). Sex and mass did not seem to affect induction times in black rat snakes, but larger female rat snakes recovered faster from anesthesia than smaller females. Halothane delivered in the open method provided consistent anesthesia in northern water snakes (Nerodia s. sipedon), although it caused some mortality and should not be used on debilitated patients. Halothane delivered with a precision vaporizer may be used to anesthetize eastern massasauga rattlesnakes (Sistrurus c. catenatus). However, care must be taken to prevent mortality resulting from anesthetic overdose. Sex and mass had no effect on induction and recovery times in the rattlesnakes, but stressed animals require longer induction and recovery times

Stanniocalcin-1 Regulates Extracellular ATP-Induced Calcium Waves in Human Epithelial Cancer Cells by Stimulating ATP Release from Bystander Cells

Background: The epithelial cell response to stress involves the transmission of signals between contiguous cells that can be visualized as a calcium wave. In some cell types, this wave is dependent on the release of extracellular trinucleotides from injured cells. In particular, extracellular ATP has been reported to be critical for the epithelial cell response to stress and has recently been shown to be upregulated in tumors in vivo. Methodology/Principal Findings: Here, we identify stanniocalcin-1 (STC1), a secreted pleiotrophic protein, as a critical mediator of calcium wave propagation in monolayers of pulmonary (A549) and prostate (PC3) epithelial cells. Addition of STC1 enhanced and blocking STC1 decreased the distance traveled by an extracellular ATP-dependent calcium wave. The same effects were observed when calcium was stimulated by the addition of exogenous ATP. We uncover a positive feedback loop in which STC1 promotes the release of ATP from cells in vitro and in vivo. Conclusions/Significance: The results indicated that STC1 plays an important role in the early response to mechanical injury by epithelial cells by modulating signaling of extracellular ATP. This is the first report to describe STC1 as a modulator o

Cas9+ conditionally-immortalized macrophages as a tool for bacterial pathogenesis and beyond.

Macrophages play critical roles in immunity, development, tissue repair, and cancer, but studies of their function have been hampered by poorly-differentiated tumor cell lines and genetically-intractable primary cells. Here we report a facile system for genome editing in non-transformed macrophages by differentiating ER-Hoxb8 myeloid progenitors from Cas9-expressing transgenic mice. These conditionally immortalized macrophages (CIMs) retain characteristics of primary macrophages derived from the bone marrow yet allow for easy genetic manipulation and a virtually unlimited supply of cells. We demonstrate the utility of this system for dissection of host genetics during intracellular bacterial infection using two important human pathogens: Listeria monocytogenes and Mycobacterium tuberculosis

Experimental limits of ghost diffraction: Popper’s thought experiment

Quantum ghost diffraction harnesses quantum correlations to record diffraction or interference features using photons that have never interacted with the diffractive element. By designing an optical system in which the diffraction pattern can be produced by double slits of variable width either through a conventional diffraction scheme or a ghost diffraction scheme, we can explore the transition between the case where ghost diffraction behaves as conventional diffraction and the case where it does not. For conventional diffraction the angular extent increases as the scale of the diffracting object is reduced. By contrast, we show that no matter how small the scale of the diffracting object, the angular extent of the ghost diffraction is limited (by the transverse extent of the spatial correlations between beams). Our study is an experimental realisation of Popper’s thought experiment on the validity of the Copenhagen interpretation of quantum mechanics. We discuss the implication of our results in this context and explain that it is compatible with, but not proof of, the Copenhagen interpretation

The fundamental pro-groupoid of an affine 2-scheme

A natural question in the theory of Tannakian categories is: What if you don't remember \Forget? Working over an arbitrary commutative ring $R$, we prove that an answer to this question is given by the functor represented by the \'etale fundamental groupoid \pi_1(\spec(R)), i.e.\ the separable absolute Galois group of $R$ when it is a field. This gives a new definition for \'etale \pi_1(\spec(R)) in terms of the category of $R$-modules rather than the category of \'etale covers. More generally, we introduce a new notion of "commutative 2-ring" that includes both Grothendieck topoi and symmetric monoidal categories of modules, and define a notion of $\pi_1$ for the corresponding "affine 2-schemes." These results help to simplify and clarify some of the peculiarities of the \'etale fundamental group. For example, \'etale fundamental groups are not "true" groups but only profinite groups, and one cannot hope to recover more: the "Tannakian" functor represented by the \'etale fundamental group of a scheme preserves finite products but not all products.Comment: 46 pages + bibliography. Diagrams drawn in Tik

Complete IRAC mapping of the CFHTLS-DEEP, MUSYC AND NMBS-II FIELDS

The IRAC mapping of the NMBS-II fields program is an imaging survey at 3.6 and 4.5$\mu$m with the Spitzer Infrared Array Camera (IRAC). The observations cover three Canada-France-Hawaii Telescope Legacy Survey Deep (CFHTLS-D) fields, including one also imaged by AEGIS, and two MUSYC fields. These are then combined with archival data from all previous programs into deep mosaics. The resulting imaging covers a combined area of about 3 $deg^2$, with at least $\sim$2 hr integration time for each field. In this work, we present our data reduction techniques and document the resulting coverage maps at 3.6 and 4.5$\mu$m. All of the images are W-registered to the reference image, which is either the z-band stack image of the 25\% best seeing images from the CFHTLS-D for CFHTLS-D1, CFHTLS-D3, and CFHTLS-D4, or the K-band images obtained at the Blanco 4-m telescope at CTIO for MUSYC1030 and MUSYC1255. We make all images and coverage maps described herein publicly available via the Spitzer Science Center.Comment: Accepted in PASP; released IRAC mosaics available upon publication of the pape

Phylogeny and biogeography of the Canarian Solanum vespertilio and S. lidii (Solanaceae)

The endemic and rare Solanum vespertilio and S. lidii from the Canary Islands are notable in being andromonoecious, self compatible, highly heterandrous (with short >reward= anthers and one very long >pollination= anther), and bearing strongly zygomorphic corollas. Solanum vespertilio flowers are also tetramerous, and some display enantiostyly. Given their island distribution, uncommon for solanums, and many distinctive reproductive features, the phylogenetic position is of interest. With new molecular data from the chloroplast trnT-F region and the nuclear granule-bound starch synthase gene (GBSSI or waxy), we confirm the hypothesis that these two species are phylogenetically associated with Solanum lineages from Africa, rather than with previously suggested Mexican species. The phylogeny facilitates understanding the evolution of the unique suite of reproductive characteristics in these island endemics.Las endémicas y raras especies Solanum vespertilio y S. lidii de las Islas Canarias son notables por ser andromonoicas, autocompatibles, altamente heterándricas (con anteras cortas para recompensa y una muy larga para polinización) y por tener corolas fuertemente zigomórficas. Las flores de Solanum vespertilio son, además, tetrámeras y muestran enantiostilia. Dada su distribución insular, poco común para Solanum, y sus distintivas características reproductivas, su posición filogenética es de interés. Con nuevos datos moleculares de la región trnT-F del ADN del cloroplasto y del gen nuclear de la enzima almidón sintasa unida al gránulo (GBSSI o waxy), confirmamos la hipótesis de que estas dos especies están filogenéticamente asociadas con los linajes geográficamente próximos de Solanum africanos, más que con especies mexicanas previamente sugeridas. La filogenia facilita la comprensión de la evolución del conjunto singular de características reproductivas de estas especies endémicas de islas

Falcon Neuro: an event-based sensor on the International Space Station

We report on the Falcon neuro event-based sensor (EBS) instrument that is designed to acquire data from lightning and sprite phenomena and is currently operating on the International Space Station. The instrument consists of two independent, identical EBS cameras pointing in two fixed directions, toward the nominal forward direction of flight and toward the nominal Nadir direction. The payload employs stock DAVIS 240C focal plane arrays along with custom-built control and readout electronics to remotely interface with the cameras. To predict the sensor’s ability to effectively record sprites and lightning, we explore temporal response characteristics of the DAVIS 240C and use lab measurements along with reported limitations to model the expected response to a characteristic sprite illumination time-series. These simulations indicate that with appropriate camera settings the instrument will be capable of capturing these transient luminous events when they occur. Finally, we include initial results from the instrument, representing the first reported EBS recordings successfully collected aboard a space-based platform and demonstrating proof of concept that a neuromorphic camera is capable of operating in the space environment

No More Active Galactic Nuclei in Clumpy Disks Than in Smooth Galaxies at z~2 in CANDELS / 3D-HST

We use CANDELS imaging, 3D-HST spectroscopy, and Chandra X-ray data to investigate if active galactic nuclei (AGNs) are preferentially fueled by violent disk instabilities funneling gas into galaxy centers at 1.3<z<2.4. We select galaxies undergoing gravitational instabilities using the number of clumps and degree of patchiness as proxies. The CANDELS visual classification system is used to identify 44 clumpy disk galaxies, along with mass-matched comparison samples of smooth and intermediate morphology galaxies. We note that, despite being being mass-matched and having similar star formation rates, the smoother galaxies tend to be smaller disks with more prominent bulges compared to the clumpy galaxies. The lack of smooth extended disks is probably a general feature of the z~2 galaxy population, and means we cannot directly compare with the clumpy and smooth extended disks observed at lower redshift. We find that z~2 clumpy galaxies have slightly enhanced AGN fractions selected by integrated line ratios (in the mass-excitation method), but the spatially resolved line ratios indicate this is likely due to extended phenomena rather than nuclear AGNs. Meanwhile the X-ray data show that clumpy, smooth, and intermediate galaxies have nearly indistinguishable AGN fractions derived from both individual detections and stacked non-detections. The data demonstrate that AGN fueling modes at z~1.85 - whether violent disk instabilities or secular processes - are as efficient in smooth galaxies as they are in clumpy galaxies.Comment: ApJ accepted. 17 pages, 17 figure