Uniform Shapiro-Lopatinski Conditions and Boundary Value Problems on Manifolds with Bounded Geometry

Potential Analysis - We study the regularity of the solutions of second order boundary value problems on manifolds with boundary and bounded geometry. We first show that the regularity property of...     

Image-Based Morphological Profiling Identifies a Lysosomotropic,Iron-Sequestering Autophagy Inhibitor

Chemical proteomics is widely applied in small-molecule target identification. However, in general it does not identify non-protein small-molecule targets, and thus, alternative methods for target identification are in high demand. We report the discovery of the autophagy inhibitor autoquin and the identification of its molecular mode of action using image-based morphological profiling in the cell painting assay. A compound-induced fingerprint representing changes in 579 cellular parameters revealed that autoquin accumulates in lysosomes and inhibits their fusion with autophagosomes. In addition, autoquin sequesters Fe²⁺ in lysosomes, resulting in an increase of lysosomal reactive oxygen species and ultimately cell death. Such a mechanism of action would have been challenging to unravel by current methods. This work demonstrates the potential of the cell painting assay to deconvolute modes of action of small molecules, warranting wider application in chemical biology.     

New advances in the synthesis of tripyridinophane macrocycles suitable to enhance the luminescence of Ln(III) ions in aqueous solution

A series of four new 18-membered hexaaza macrocyclic ligands bearing three endocyclic pyridine units and acetate or methylenephosphonate pendant arms has been prepared. The new synthetic procedure is based on the use of amine and diamine precursors incorporating masked carboxylate or phosphonate functions and on an efficient sodium template effect which controls the crucial macrocyclization step (yields of macrocyclization reactions: 62–88%). This procedure appears as a suitable alternative compared to the classical Richman-Atkins methodology generally used for the preparation of this class of macrocycles. As demonstrated with the Eu^III and Tb^III complexes derived from two ligands, these tripyridinophane chelators form luminescent and stable mononuclear Ln^III complexes in aqueous solution at physiological pH. In such a medium, Tb^III complexes exhibit a brightness of 1700 (λ_exc?=?279?nm) and 3000 (λ_exc?=?268?nm)?M^?1?cm^?1.     

Release of nitrous oxide and dinitrogen from a transition bog under drained and rewetted conditions due to denitrification: results from a [15N]nitrate–bromide double-tracer study

Denitrification is well known being the most important nitrate-consuming process in water-logged peat soils, whereby the intermediate compound nitrous oxide (N₂O) and the end product dinitrogen (N₂) are ultimately released. The present study was aimed at evaluating the release of these gases (due to denitrification) from a nutrient-poor transition bog ecosystem under drained and three differently rewetted conditions at the field scale using a ¹⁵N-tracer approach ([¹⁵N]nitrate application, 30?kg N ha^?1) and a common closed-chamber technique. The drained site is characterized by a constant water table (WT) of –30?cm (here referred to as D30), while rewetted sites represent a constant WT of –15?cm, a constant WT of 0?cm (i.e. waterlogged), and an initial WT of 0?cm (which decreased slightly during the experiment), respectively, (here referred to as R15, R0, and R0_d, respectively). The highest N₂O emissions were observed at D30 (291?µg N₂O–N m^?2 h^?1) as well as at R0_d (665?µg N₂O–N m^?2 h^?1). At the rewetted peat sites with a constant WT (i.e. R15 and R0), considerably lower N₂O emissions were observed (maximal 37?µg N₂O–N m^?2 h^?1). Concerning N₂ only at the initially water-logged peat site R0_d considerable release rates (up to 3110?µg N₂–N m^?2 h^?1) were observed, while under drained conditions (D30) no N₂ emission and under rewetted conditions with a constant WT (R15 and R0) significantly lower N₂ release rates (maximal 668?µg N₂–N m^–2 h^?1) could be detected. In addition, it has been found that natural WT fluctuations at rewetted peat sites, in particular a rapid drop down of the WT, can induce high emission rates for both N₂O and N₂.     

Silica supported sulfated zirconia prepared by a sol-gel process: Effect of solvent evacuation procedure on the structural, textural and catalytic properties

Sol-gel process was used to prepare silica supported sulfated zirconia catalysts. The main parameter studied in this work was the gel drying method through four different ways of solvent evacuation. Textural, structural as well as the acidic properties of the four samples were studied using N₂ physisorption, X-ray diffraction, mass spectrometry, sulfur chemical analysis and adsorption-desorption of pyridine. The isomerization of n-hexane was used as a catalytic test. The surface areas and the pore distributions are highly affected by the drying mode. One of the four drying methods leads to a solid having improved textural properties and presenting both the crystalline ZrO₂ tetragonal phase and a particular type of sulfate mode bond. It seems that these three conditions are necessary for achieving high catalytic activity.     

Fluorescent Protein–photoprotein Fusions and Their Applications in Calcium Imaging

Calcium‐activated photoproteins, such as aequorin, have been used as luminescent Ca²⁺ indicators since 1967. After the cloning of aequorin in 1985, microinjection was substituted by its heterologous expression, which opened the way for a widespread use. Molecular fusion of green fluorescent protein (GFP) to aequorin recapitulated the nonradiative energy transfer process that occurs in the jellyfish Aequorea victoria, from which these two proteins were obtained, resulting in an increase of light emission and a shift to longer wavelength. The abundance and location of the chimera are seen by fluorescence, whereas its luminescence reports Ca²⁺ levels. GFP‐aequorin is broadly used in an increasing number of studies, from organelles and cells to intact organisms. By fusing other fluorescent proteins to aequorin, the available luminescence color palette has been expanded for multiplexing assays and for in vivo measurements. In this report, we will attempt to review the various photoproteins available, their reported fusions with fluorescent proteins and their biological applications to image Ca²⁺ dynamics in organelles, cells, tissue explants and in live organisms.