Bosmani, A.; Guarnieri-Ibáñez, A.; Lacour, J. “Configurational Lability of Imino-Substituted Ethano Tröger Bases. Insight on the Racemization Mechanism”, Helv. Chim. Acta 2019, in press.

Polycyclic indoline‐benzodiazepines are afforded in one step by the reaction of Tröger bases with N‐sulfonyl‐1,2,3‐triazoles under Rh(II) catalysis. After α‐imino carbene formation, the process involves a cascade of [1,2]‐Stevens rearrangement, Friedel‐Crafts, Grob fragmentation and aminal formation reactions. It is highly diastereoselective (d.r.>49:1, four stereocenters incl. two bridgehead N atoms). However and in contrast with other reported carbene additions to these moieties, full racemization occurs when enantiopure Tröger Bases are used as substrates. To pinpoint the origin of this unexpected behavior, key elemental steps of the mechanism were evaluated and tested. Interestingly, it is not only the initial ring‐opening but also the latter reversible Mannich reaction of the imino‐substituted ethano Tröger base intermediate that is responsible for the loss of enantiospecificit

Goujon, A.; Colom, A.; Straková, K.; Mercier, V.; Mahecic, D.; Manley, S.; Sakai, N.; Roux, A.; Matile, S. “Mechanosensitive Fluorescent Probes to Image Membrane Tension in Mitochondria, Endoplasmic Reticulum and Lysosome”, J. Am. Chem. Soc. 2019, in press.

Measuring forces inside cells is particularly challenging. With the development of quantitative microscopy, fluorophores which allow the measurement of forces became highly desirable. We have previously introduced a mechanosensitive flipper probe, which responds to the change of plasma membrane tension by changing its fluorescence lifetime and thus allows tension imaging by FLIM. Herein, we describe the design, synthesis, and evaluation of flipper probes that selectively label intracellular organelles, i.e., lysosomes, mitochondria, and the endoplasmic reticulum. The probes respond uniformly to osmotic shocks applied extracellularly, thus confirming sensitivity toward changes in membrane tension. At rest, different lifetimes found for different organelles relate to known differences in membrane organization rather than membrane tension and allow colabeling in the same cells. At the organelle scale, lifetime heterogeneity provides unprecedented insights on ER tubules and sheets, and nuclear membranes. Examples on endosomal trafficking or increase of tension at mitochondrial constriction sites outline the potential of intracellularly targeted fluorescent tension probes to address essential questions that were previously beyond reach.

Delgado, T.; Ajoubipour, S.; Afshani, J.; Yoon, S.; Walfort, B.; Hagemann, H. “Spectroscopic properties of Dy3+- and Dy3+, B3+- doped SrAl2O4”, Opt. Mater. 2019, 89, 268-275.

The dysprosium and boron effect on the emission properties of europium-doped SrAl2O4 samples has recently attracted considerable attention due to their high brightness and long afterglow. Here, the influence of both cations, Dy3+ and B3+, on the spectroscopic properties of the europium free samples SrAl2O4:Dy3+ and SrAl2O4:Dy3+, B3+ has been investigated in order to get more insights concerning the mechanism by which they enhance the afterglow. Unique features have been observed in their excitation and emission spectra that show on one hand the lattice defects induced by the replacement of Sr2+ by Dy3+ and proves the existence of different crystallography sites for the Dy3+ ions and on the other hand, the local distortion of the energy levels of Dy3+ ions in the presence of B3+.

Soda, Y.; Citterio, D.; Bakker, E. “Equipment-Free Detection of K+ on Microfluidic Paper-based Analytical Devices Based on Exhaustive Replacement with Ionic Dye in Ion-selective Capillary Sensors”, ACS Sens. 2019, in press.

A distance-based analysis of potassium ion (K+) is introduced that is performed on a microfluidic paper-based analyti-cal device (µPAD) coupled to an ion-selective capillary sensor. The concept is based on two sequential steps, the selec-tive replacement of analyte ion with an ionic dye, and the detection of this dye in a distance-based readout on paper. To achieve the first step, the capillary sensor holds a poly (vinyl chloride) (PVC) membrane film layer plasticized by dioctyl sebacate (DOS) that contains the potassium ionophore valinomycin, a lipophilic cation-exchanger and the ion-ic indicator Thioflavin T (ThT) on its inner wall. Upon introduction of the sample, K+ in the aqueous sample solution is quantitatively extracted into the film membrane and replaced with ThT. To convert the ion exchange signal into a distance-based analysis, this solution was dropped onto the inlet area of a µPAD to flow the ThT along a channel de-fined by wax printing, resulting in the electrostatic binding of ThT to the cellulose carboxylic groups. The initial amount of K+ determines the amount ThT in the aqueous solution after ion-exchange, and consequently the distance of ThT-colored area reflects the sample K+ concentration. The ion exchange reaction was operated in a so-called “ex-haustive sensing mode” and gave a distinct response in a narrow range of K+ concentration (1~6 mM) that cannot be achieved by the classical optode sensing mode. The absence of hydrogen ions from the equilibrium competition of the capillary sensor contributed to a complete pH-independence, unlike conventional optodes that contain a pH sensitive indicator. A very high selectivity for K+ over Na+ and Ca2+ has been confirmed in separate solutions and mixed solu-tions tests. K+ measurements in pooled serum samples at concentrations between 2~6 mM are successfully demon-strated on a temperature controlled support.

Smith, A. M.; Maroni, P.; Trefalt, G.; Borkovec, M. “Unexpectedly Large Decay Lengths of Double Layer Forces in Solutions of Symmetric, Multivalent Electrolytes”, J. Phys. Chem. B 2019, in press.

Double layer forces acting between micron-sized silica particles are measured with the atomic force microscope (AFM) in solutions of symmetric, multivalent electrolytes. In particular, the following 2:2 electrolytes, CuSO4, MgSO4, and the 3:3 electrolyte LaFe(CN)6 were investigated. For the multivalent electrolytes, the measured decay lengths are substantially larger than the ones expected on the basis of simple Debye-Hückel (DH) theory. These deviations can be explained quantitatively by the formation of neutral ion pairs. The measured surface charge density decreases in magnitude with increasing valence. Both effects are caused by ion-ion correlations, which are not included in the classical DH theory. However, this theory remains applicable provided one considers the formation of ion pairs in solution and an effective surface charge density. This effective charge is substantially smaller in magnitude than the one of the bare surface. This reduction results from adsorption of counter-ions, which becomes stronger with increasing valence. These observations reveal that DH theory is applicable even in the presence of multivalent ions, provided the effective parameters are chosen appropriately.

Kazan, R.; Müller, U.; Bürgi, T. “Doping of thiolate protected gold clusters through reaction with metal surfaces”, Nanoscale 2019, 11, 2938-2945.

A new technique is introduced for doping gold nanoclusters by using a metal surface such as Ag, Cu and Cd as a source of heteroatoms. The importance of the thiol ligand in the doping process is examined by following the reactions with MALDI-TOF mass spectrometry in the presence and the absence of the thiols on the surface. The doping reactions depend greatly on the type of the cluster and the availability of the ligand which is a crucial element for alloying. The thiol acts as a messenger exchanging the metal atoms between the cluster and the metal surface as revealed by the XPS studies performed on the metal surfaces.

Homberg, A.; Poggiali, D.; Vishe, M.; Besnard, C.; Guénée, L.; Lacour, J. “One-Step Synthesis of Diaza Macrocycles by Rh(II)-Catalyzed [3 + 6 + 3 + 6] Condensations of Morpholines and α-Diazo-β-ketoesters”, Org. Lett. 2019, 21, archive unige:113756 pdf full text [restricted access]

Selective formation of oxonium ylides from morpholines and α-diazo-β-ketoesters was achieved. This was applied to the high-concentration (0.5 M) dirhodium-catalyzed (0.1 mol %) [3 + 6 + 3 + 6] synthesis of 18-membered ring diaza macrocycles (46%–72%). Late-stage functionalization of these derivatives is demonstrated. Mechanistic evidence for a novel (undesired) diazo decomposition pathway is also reported.

Koliwer-Brandl, H.; Knobloch, P.; Barisch, C.; Welin, A.; Hanna, N.; Soldati, T.; Hilbi, H. “Distinct Mycobacterium marinum phosphatases determine pathogen vacuole phosphoinositide pattern, phagosome maturation and escape to the cytosol”, Cell. Microbiol. 2019, in press.

The causative agent of tuberculosis, Mycobacterium tuberculosis, and its close relative Mycobacterium marinum manipulate phagocytic host cells, thereby creating a replication‐permissive compartment termed the Mycobacterium‐containing vacuole (MCV). The phosphoinositide (PI) lipid pattern is a crucial determinant of MCV formation and is targeted by mycobacterial PI phosphatases. In this study, we establish an efficient phage transduction protocol to construct defined M. marinum deletion mutants lacking one or three phosphatases, PtpA, PtpB and/or SapM. These strains were defective for intracellular replication in macrophages and amoebae, and the growth defect was complemented by the corresponding plasmid‐borne genes. Fluorescence microscopy of M. marinum‐infected Dictyostelium discoideum revealed that MCVs harboring mycobacteria lacking PtpA, SapM or all three phosphatases accumulate significantly more phosphatidylinositol‐3‐phosphate (PtdIns3P) compared to MCVs containing the parental strain. Moreover, PtpA reduced MCV acidification by blocking the recruitment of the V‐ATPase, and all three phosphatases promoted bacterial escape from the pathogen vacuole to the cytoplasm. In summary, the translocated M. marinum phosphatases PtpA, PtpB and SapM determine the MCV PI pattern, compartment acidification and phagosomal escape.

Melot, R.; Craveiro, M. V.; Bürgi, T.; Baudoin, O. “Divergent Enantioselective Synthesis of (Nor)illudalane Sesquiterpenes via Pd0-Catalyzed Asymmetric C(sp3)–H Activation”, Org. Lett. 2019, 21, 812-815.

A divergent enantioselective synthesis of (nor)illudalane sesquiterpenes was designed by using a Pd0-catalyzed asymmetric C(sp3)–H arylation as a key step to control the isolated, highly symmetric quaternary stereocenter of the target molecules. A matched combination of chiral substrate and catalyst proved optimal to reach good levels of stereoselectivity. This approach enabled the synthesis of three (nor)illudalanes, including (S)-deliquinone and (S)-russujaponol F, which are synthesized for the first time in enantioenriched form.

Laurent, Q.; Sakai, N.; Matile, S. “The Opening of 1,2-Dithiolanes and 1,2-Diselenolanes:  Regioselectivity, Rearrangements, and Consequences for Poly(disulfide)s, Cellular Uptake and Pyruvate Dehydrogenase Complexes”, Helv. Chim. Acta 2019, in press.

The thiol‐mediated opening of 3‐alkyl‐1,2‐dithiolanes and diselenolanes is described. The thiolate nucleophile is shown to react specifically with the secondary chalcogen atom, against steric demand, probably because the primary chalcogen atom provides a better leaving group. Once released, this primary chalcogen atom reacts with the obtained secondary dichalcogenide to produce the constitutional isomer. Thiolate migration to the primary dichalcogenide equilibrates within ca. 20 ms at room temperature at a 3 : 2 ratio in favor of the secondary dichalcogenide. The clarification of this focused question is important for the understanding of multifunctional poly(disulfide)s obtained by ring opening disulfide exchange polymerization of 3‐alkyl‐1,2‐dithiolanes, to rationalize the cellular uptake mediated by 3‐alkyl‐1,2‐diselenolanes as molecular walkers and, perhaps, also of the mode of action of pyruvate dehydrogenase complexes. The isolation of ring‐opened diselenolanes is particularly intriguing because dominant selenophilicity disfavors ring opening strongly.

Oppermann, M.; Bauer, B.; Rossi, T.; Zinna, F.; Helbing, J.; Lacour, J.; Chergui, M. “Ultrafast broadband circular dichroism in the deep ultraviolet”, Optica 2019, 6, archive unige:112702 pdf full text [free access]

The measurement of chirality and its temporal evolution are crucial for the understanding of a large range of biological functions and chemical reactions. Steady-state circular dichroism (CD) is a standard analytical tool for measuring chirality in chemistry and biology. Nevertheless, its push into the ultrafast time domain and in the deep-ultraviolet has remained a challenge, with only some isolated reports of subnanosecond CD. Here, we present a broadband time-resolved CD spectrometer in the deep ultraviolet (UV) spectral range with femtosecond time resolution. The setup employs a photoelastic modulator to achieve shot-to-shot polarization switching of a 20 kHz pulse train of broadband femtosecond deep-UV pulses (250–370 nm). The resulting sequence of alternating left- and right-circularly polarized probe pulses is employed in a pump-probe scheme with shot-to-shot dispersive detection and thus allows for the acquisition of broadband CD spectra of ground- and excited-state species. Through polarization scrambling of the probe pulses prior to detection, artifact-free static and transient CD spectra of enantiopure [Ru(bpy)3]2+ are successfully recorded with a sensitivity of <2×10−5 OD (≈0.7  mdeg). Due to its broadband deep-UV detection with unprecedented sensitivity, the measurement of ultrafast chirality changes in biological systems with amino-acid residues and peptides and of DNA oligomers is now feasible.

Lee, L. M.; Tsemperouli, M.; Poblador-Bahamonde, A. I.; Benz, S.; Sakai, N.; Sugihara, K.; Matile, S. “Anion Transport with Pnictogen Bonds in Direct Comparison with Chalcogen and Halogen Bonds”, J. Am. Chem. Soc. 2019, 141, archive unige:113057 pdf full text [restricted access]

In this Communication, we introduce transmembrane anion transport with pnictogen-bonding compounds and compare their characteristics with chalcogen- and halogen-bonding analogues. Tellurium-centered chalcogen bonds are at least as active as antimony-centered pnictogen bonds, whereas iodine-centered halogen bonds are 3 orders of magnitude less active. Irregular voltage-dependent single-channel currents, high gating charges, and efficient dye leakage support for the formation of bulky, membrane-disruptive supramolecular amphiphiles due to “too strong” binding of anions to tris(perfluorophenyl)stibanes. In contrast, the chalcogen-bonding bis(perfluorophenyl)tellanes do not cause leakage and excel as carriers with nanomolar activity, with P(Cl/Na) = 10.4 for anion/cation selectivity and P(Cl/NO3) = 4.5 for anion selectivity. The selectivities are lower with pnictogen-bonding carriers because their membrane-disturbing 3D structure also affects weaker binders (P(Cl/Na) = 2.1, P(Cl/NO3) = 2.5). Their 2D structure, directionality, hydrophobicity, and support from proximal anion−π interactions are suggested to contribute to the unique power of chalcogen bonds to transport anions across lipid bilayer membranes.

Feng, S.; Harayama, T.; Chang, D.; Hannich, J. T.; Winssinger, N.; Riezman, H. “Lysosome-targeted photoactivation reveals local sphingosine metabolism signatures”, Chem. Sci. 2019, in press.

Lipids are essential components of eukaryotic cell membranes and play crucial roles in cellular signaling and metabolism. While increasing evidence shows that the activities of lipids are dependent upon subcellular localization, tools to study local lipid metabolism and signaling are limited. Herein, we report an approach that enabled us to selectively deliver photo-caged lipids into lysosomes and thereafter to quickly release the lipid molecules by illumination. On combining this method with genetic techniques and lipidomics, we were able to investigate the localization-dependent metabolism of an important intermediate of sphingolipid metabolism, sphingosine. Our data reveal a distinct metabolic pattern of lysosomal sphingosine. In general, this method has the potential to serve as a platform to study lysosomal metabolism and signaling of various lipids and metabolites in living cells.

Maechler, F. A.; Allier, C.; Roux, A.; Tomba, C. “Curvature Dependent constraints drive remodeling of epithelia”, J. Cell Sci. 2019, 132, cs222372.

Epithelial tissues function as barriers that separate the organism from the environment. They usually have highly curved shapes, such as tubules or cysts. However, the processes by which the geometry of the environment and the cell's mechanical properties set the epithelium shape are not yet known. In this study, we encapsulated two epithelial cell lines, MDCK and J3B1A, into hollow alginate tubes and grew them under cylindrical confinement forming a complete monolayer. MDCK monolayers detached from the alginate shell at a constant rate, whereas J3B1A monolayers detached at a low rate unless the tube radius was reduced. We showed that this detachment is driven by contractile stresses in the epithelium and can be enhanced by local curvature. This allows us to conclude that J3B1A cells exhibit smaller contractility than MDCK cells. Monolayers inside curved tubes detach at a higher rate on the outside of a curve, confirming that detachment is driven by contraction.

Babič, A.; Vorobiev, V.; Trefalt, G.; Crowe, L. A.; Helm, L.; Vallée, J.-P.; Allémann, E. “MRI micelles self-assembled from synthetic gadolinium-based nano building blocks”, Chem. Commun. 2019, 55, 945-948.

A synthetic nano building block endowed with amphiphilic properties and chelated gadolinium is presented. Spontaneous self-assembly into small 12 nm corona-core stealth Gd-micelles with inherently high gadolinium loading occurs in water. Gd-Micelles are a new blood pool contrast agent with high relaxivity for magnetic resonance imaging.

McAlpine, J. B.; Chen, S.-N.; Kutateladze, A.; MacMillan, J. B.; Appendino, G.; Barison, A.; Beniddir, M. A.; Biavatti, M. W.; Bluml, S.; Boufridi, A.; Butler, M. S.; Capon, R. J.; Choi, Y. H.; Coppage, D.; Crews, P.; Crimmins, M. T.; Csete, M.; Dewapriya, P.; Egan, J. M.; Garson, M. J.; Genta-Jouve, G.; Gerwick, W. H.; Gross, H.; Harper, M. K.; Hermanto, P.; Hook, J. M.; Hunter, L.; Jeannerat, D.; Ji, N.-Y.; Johnson, T. A.; Kingston, D. G. I.; Koshino, H.; Lee, H.-W.; Lewin, G.; Li, J.; Linington, R. G.; Liu, M.; McPhail, K. L.; Molinski, T. F.; Moore, B. S.; Nam, J.-W.; Neupane, R. P.; Niemitz, M.; Nuzillard, J.-M.; Oberlies, N. H.; Ocampos, F. M. M.; Pan, G.; Quinn, R. J.; Reddy, D. S.; Renault, J.-H.; Rivera-Chávez, J.; Robien, W.; Saunders, C. M.; Schmidt, T. J.; Seger, C.; Shen, B.; Steinbeck, C.; Stuppner, H.; Sturm, S.; Taglialatela-Scafati, O.; Tantillo, D. J.; Verpoorte, R.; Wang, B.-G.; Williams, C. M.; Williams, P. G.; Wist, J.; Yue, J.-M.; Zhang, C.; Xu, Z.; Simmler, C.; Lankin, D. C.; Bisson, J.; Pauli, G. F. “Correction: The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research”, Nat. Prod. Rep. 2019, 36, archive unige:113449 pdf full text [free access]

Correction for ‘The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research’ by James B. McAlpine et al., Nat. Prod. Rep., 2019, DOI: 10.1039/c7np00064b.

Anzola, M.; Winssinger, N. “Turn On of a Ruthenium(II) Photocatalyst by DNA-Templated Ligation”, Chem. Eur. J. 2019, 25, archive unige:112587 pdf full text [restricted access]

Here, the synthesis of a RuII photocatalyst by light‐directed oligonucleotide‐templated ligation reaction is described. The photocatalyst was found to have tremendous potential for signal amplification with >15000 turnovers measured in 9 hours. A templated reaction was used to turn on the activity of this ruthenium(II) photocatalyst in response to a specific DNA sequence. The photocatalysis of the ruthenium(II) complex was harnessed to uncage a new precipitating dye that is highly fluorescent and photostable in the solid state. This reaction was used to discriminate between different DNA analytes based on localization of the precipitate as well as for in cellulo miRNA detection. Finally, a bipyridine ligand functionalized with two different peptide nucleic acid (PNA) sequences was shown to enable template‐mediated ligation (turn on of the ruthenium(II) photocatalysis) and recruitment of substrate for templated photocatalysis.

Wasnik, V. H.; Lipp, P.; Kruse, K. “Positional information readout in Ca2+ signaling”,, e-Print Arch., Quant. Biol. 2019, in press.

Living cells respond to spatial signals. Signal transmission to the cell interior often involves the release of second messengers like Ca2+ . They will eventually trigger a physiological response by activating kinases that in turn activate target proteins through phosphorylation. Here, we investigate theoretically how positional information can be accurately read out by protein phosphorylation in spite of rapid second messenger diffusion. We find that accuracy is increased by binding of the kinases to the cell membrane prior to phosphorylation and by increasing the rate of Ca2+ loss from the cell interior. These findings could explain some salient features of conventional protein kinases C.

Bonner, R.; Hopfgartner, G. “SWATH data independent acquisition mass spectrometry for metabolomics”, TrAC, Trends Anal. Chem. 2019, in press.

Systems Biology and ‘Omics’ require reproducible identification and quantitation of many compounds, preferably in large sample cohorts. Liquid chromatography-mass spectrometry is important since data generated can be used for structure elucidation and highly specific targeted quantitation. Despite great success, the technique has limitations such as: compound coverage in one analysis, method development time and single sample analysis time which determines throughput. New instrument capabilities have led to improved methods, including ‘Data Independent Acquisition’ so-called because acquisition is not changed by acquired data. SWATH-MS is a specific example that has quickly become prominent in proteomics because of increased peptide coverage, high quantitation accuracy, excellent reproducibility and the generation of a ‘digital map’. These capabilities are important in small molecules analyses although uptake in these applications has been slower. We describe the SWATH-MS technique, review its use in applications such as metabolomics and forensics, and summarize on-going improvements and future prospects.

Zdrachek, E.; Bakker, E. “Potentiometric Sensing”, Anal. Chem. 2019, 91, 2-26.

This review describes, with 186 references, progress in the field of potentiometric sensing in the period between January 2016 and August 2018. January 2016 was when the last fundamental review covering the topic of potentiometric sensors appeared in the special issue of Analytical Chemistry and was set as start date. This review starts with a description of progress in the development and improve-ment of reference electrodes, which represent an indispensable part of any electro-chemical cell and has a particularly important influence on the accuracy of potentiometric measurements. It continues with an overview of recent achievements and discoveries in the domain of solid-contact ion-selective electrodes. This section was structured mainly by the type of ion-to-electron transducing material dis-cussed. Next, insights into modern theory of potentiometry is given, describing the use of numerical simulation to predict time dependent potential changes at ion-selective membranes as well as new protocols for determining selectivity coefficient. Subsequently, new and non-classical readout principles for ion-selective electrodes are presented. It is followed by a section dedicated to new materials ex-ploited for ion-selective electrodes (ISEs), including membrane materials, ion-exchange nanopores, room temperature ionic liquids, molecular imprinted polymers and new ionophores. Recent developments in the area of miniaturized ISEs, including paper-based devices, wearable sensors, miniaturized pH sensors, ion-selective microelectrodes and ion-selective field effect transistors (ISFET), are discussed in the next section. The review ends with a discussion of some analytical applications for potentiometric sensors, including polyion detection and environmental, clinical and surfactant analysis.

Goujon, A.; Straková, K.; Sakai, N.; Matile, S. “Streptavidin Interfacing as a General Strategy to Localize Fluorescent Membrane Tension Probes in Cells”, Chem. Sci. 2019, 10, archive unige:112559 pdf full text [free access]

To image the mechanical properties of biological membranes, twisted push–pull mechanophores that respond to membrane tension by planarization in the ground state have been introduced recently. For their application in biological systems, these so-called fluorescent flippers will have to be localized to specific environments of cellular membranes. In this report, we explore streptavidin as a versatile connector between biotinylated flipper probes and biotinylated targets. Fluorescence spectroscopy and microscopy with LUVs and GUVs reveal the specific conditions needed for desthiobiotin-loaded streptavidin to deliver biotinylated flippers selectively to biotinylated membranes. Selectivity for biotinylated plasma membranes is also observed in HeLa cells, confirming the compatibility of this strategy with biological systems. Streptavidin interfacing does not affect the mechanosensitivity of the flipper probes, red shift in the excitation maximum and fluorescence lifetime increase with membrane order and tension, as demonstrated, inter alia, using FLIM.

Ding, J.; Cherubini, T.; Yuan, D.; Bakker, E. “Paper-supported thin-layer ion transfer voltammetry for ion detection”, Sens. Actuators, B 2019, 280, 69-76.

We report here on paper-supported thin sample layer voltammetry for the determination of ions. To achieve this goal, a simple setup for the coupling of a commercially available electrode to a silver rod electrode was designed and evaluated for paper-supported thin-layer voltammetry. Linear scan ion transfer voltammetry was explored here for ion-selective membranes doped with an ionophore. The ion-transfer processes and electrochemical behaviors of the system are here evaluated and confirmed by numerical simulation. In the proof-of-concept experiments described, the ions tetrabutylammonium chloride (TBA+) and potassium (K+) were studied as model analytes at membranes without and with ionophore, respectively. A linear relationship from 0.1 mM to 1.0 mM K+ was obtained between the charge and ion concentration. The coexistence of background sodium ions did not give appreciable interference, but the background wave was not completely isolated from the analyte wave, as also confirmed by the model. The methodology was successfully demonstrated for determination of K+ in mineral water. It is anticipated that this paper-supported thin-layer detection approach may provide an attractive readout protocol for disposable paper-based analytical devices as the methodology does not place strict demands on reference electrode performance.

Adriouach, S.; Vorobiev, V.; Trefalt, G.; Allémann, E.; Lange, N.; Babič, A. “Squalene-PEG: Pyropheophorbide–a nanoconstruct for tumor theranostics”, Nanomedicine 2019, 15, 243-251.

Novel nanoscale drug delivery biomaterials are of great importance for the diagnosis and treatment of different cancers. We have developed a new pegylated squalene (SQ-PEG) derivative with self-assembly properties. Supramolecular assembly with a lipophilic photosensitizer pyropheophorbide-a (Ppa) by nanoprecipitation gave nanoconstructs SQ-PEG:Ppa with an average size of 200 nm in diameter and a drug loading of 18% (w/w). The composite material demonstrates nanoscale optical properties by tight packing of Ppa within Sq-PEG:Ppa resulting in 99.99% fluorescence self-quenching. The biocompatibility of the nanomaterial and cell phototoxicity under light irradiation were investigated on PC3 prostate tumor cells in vitro. SQ-PEG:Ppa showed excellent phototoxic effect at low light dose of 5.0 J/cm2 as a consequence of efficient cell internalization of Ppa by the nanodelivery system. The diagnostic potential of SQ-PEG:Ppa nanoconstructs to deliver Ppa to tumors in vivo was demonstrated in chick embryo model implanted with U87MG glioblastoma micro tumors.

Lombardot, T.; Morgat, A.; Axelsen, K. B.; Aimo, L.; Hyka-Nouspikel, N.; Niknejad, A.; Ignatchenko, A.; Xenarios, I.; Coudert, E.; Redaschi, N.; Bridge, A. “Updates in Rhea: SPARQLing biochemical reaction data”, Nucleic Acids Res. 2019, 47, D596-D600.

Rhea ( is a comprehensive and non-redundant resource of over 11 000 expert-curated biochemical reactions that uses chemical entities from the ChEBI ontology to represent reaction participants. Originally designed as an annotation vocabulary for the UniProt Knowledgebase (UniProtKB), Rhea also provides reaction data for a range of other core knowledgebases and data repositories including ChEBI and MetaboLights. Here we describe recent developments in Rhea, focusing on a new resource description framework representation of Rhea reaction data and an SPARQL endpoint ( that provides access to it. We demonstrate how federated queries that combine the Rhea SPARQL endpoint and other SPARQL endpoints such as that of UniProt can provide improved metabolite annotation and support integrative analyses that link the metabolome through the proteome to the transcriptome and genome. These developments will significantly boost the utility of Rhea as a means to link chemistry and biology for a more holistic understanding of biological systems and their function in health and disease.

Palermo, G.; Guglielmelli, A.; Pezzi, L.; Cataldi, U.; De Sio, L.; Caputo, R.; De Luca, A.; Bürgi, T.; Tabiryan, N.; Umeton, C. “A command layer for anisotropic plasmonic photo-thermal effects in liquid crystal”, Liq. Cryst. 2019, 45, 2214-2220.

Photo-anisotropic properties of a particular command layer for Liquid Crystals (LCs), based on azo-benzene material, are exploited to control the photo-thermal response of a single layer of homogeneously and uniformly distributed Au nanoparticles, immobilised on a glass substrate. Experiments demonstrate that the intrinsic anisotropy of materials can influence the photo-thermal response of plasmonic systems. Indeed, the resonant absorption of radiation by plasmonic subunits is followed by a noticeable increase of their temperature. However, the thermal response observed in presence of a homogeneous and random array of AuNPs directly exposed to air or embedded in ice is typically isotropic; on the contrary, a homogenous, yet thin, coating made of a particular command layer for LCs, deposited on a large-area carpet of AuNPs, influences their thermal response in an anisotropic way. In particular, the temperature increase, induced by pumping with a laser source of resonant wavelength with the plasmonic AuNPs, strongly depends on the alignment direction of the command layer. This effect makes the command layer of particular interest for its capability to drive intriguing optically induced ‘thermal-reorientational’ effects in a liquid crystal film.

Klinkert, K.; Levernier, N.; Gross, P.; Gentili, C.; von Tobel, L.; Pierron, M.; Busso, C.; Herrman, S.; Grill, S. W.; Kruse, K.; Gonczy, P. “Aurora A depletion reveals centrosome-independent polarization mechanism in C. elegans”, bioRxiv, Cell Biol. 2019, in press.

How living systems break symmetry in an organized manner is an important question in biology. In C. elegans zygotes, symmetry breaking normally occurs in the vicinity of centrosomes, resulting in anterior-directed cortical flows and establishment of a single posterior PAR-2 domain. Here, we report that zygotes depleted of the Aurora A kinase AIR-1 or of centrosomes establish two posterior domains, one at each pole. Using transgenic animals and microfabricated triangular chambers, we establish that such bipolarity occurs in a PAR-2- and curvature-dependent manner. Furthermore, we develop an integrated physical model of symmetry breaking, establishing that local PAR-dependent weakening of the actin cortex, together with mutual inhibition of anterior and posterior PAR proteins, provides a mechanism for self-organized PAR polarization without functional centrosomes in C. elegans.

Saad, M. M.; Michalet, S.; Fossou, R. K.; Putnik-Delić, M.; Crèvecoeur, M.; Meyer, J.; De Malézieux, C.; Hopfgartner, G.; Maksimovic, I.; Perret, X. “Loss of NifQ leads to accumulation of porphyrins and altered metal-homeostasis in nitrogen-fixing symbioses”, Mol. Plant-Microbe Interact. 2019, 32, 208-216.

Symbiotic nitrogen fixation between legumes and rhizobia involves a coordinated expression of many plant and bacterial genes as well as finely tuned metabolic activities of micro- and macro-symbionts. In spite of such complex interactions, symbiotic proficiency remains a resilient process with host plants apparently capable of compensating for some deficiencies in rhizobia. What controls nodule homeostasis is still poorly understood and probably varies between plant species. In this respect, the promiscuous Sinorhizobium (Ensifer) fredii strain NGR234 has become a model to assess the relative contribution of single gene products to many symbioses. Here, we describe how a deletion in nifQ of NGR234 (strain NGRΔnifQ) makes nodules of Vigna unguiculata, Vigna radiata and Macroptilium atropurpureum but not of the mimisoid tree Leucaena leucocephala, purple red. This peculiar dark-nodule phenotype did not necessarily correlate with a decreased proficiency of NGRΔnifQ, but coincided with a twenty-fold or more accumulation of coproporphyrin III and uroporphyrin III in V. unguiculata nodules. Porphyrin accumulation was not restricted to plant cells infected with bacteroids but also extended to nodule cortex. Nodule metal-homeostasis was altered but not sufficiently to prevent assembly and functioning of nitrogenase. Although NifQ role in donating molybdenum during assembly of nitrogenase cofactor FeMo-co makes it essential in free-living diazotrophs, our results highlight NifQ dispensability in many legume species.

Banafsheh, M.; Wesolowski, T. A. “ERRATUM: Nonadditive kinetic potentials from inverted Kohn-Sham problem”, Int. J. Quantum Chem. 2019, in press.

The following article “Nonadditive kinetic potentials from inverted Kohn–Sham problem” by M Banafsheh and TA Wesolowski has been published in the Int. J. Quantum Chem. 2018;118:e25410, The publisher of the International Journal of Quantum Chemistry, Wiley, has been contacted by the lead author of this article to inform us that his laboratory has found a bug in the code used in the work that affects the reported potential near nuclei in Fig. 3 of this paper. No other data presented in the article is affected by this error. The International Journal of Quantum Chemistry is publishing this note in order to alert readers of the potential errors affecting the data displayed in Fig. 3. The lead author's lab is investigating the bug and reassessing the data presented in Fig 3, and this notice will be updated when a final outcome of the debugging process has been reached.

Buckley, C. M.; Heath, V. L.; Gueho, A.; Bosmani, C.; Knobloch, P.; Sikakana, P.; Personnic, N.; Dove, S. K.; Michell, R. H.; Meier, R.; Hilbi, H.; Soldati, T.; Insall, R. H.; King, J. “PIKfyve/Fab1 is required for efficient V-ATPase and hydrolase delivery to phagosomes, phagosomal killing, and restriction of Legionella infection”, bioRxiv, Cell Biol. 2019, in press.

By engulfing potentially harmful microbes, professional phagocytes are continually at risk from intracellular pathogens. To avoid becoming infected, the host must kill pathogens in the phagosome before they can escape or establish a survival niche. Here, we analyse the role of the phosphoinositide (PI) 5-kinase PIKfyve in phagosome maturation and killing, using the amoeba and model phagocyte Dictyostelium discoideum. PIKfyve plays important but poorly understood roles in vesicular trafficking by catalysing formation of the lipids phosphatidylinositol (3,5)-bisphosphate (PI(3,5)2) and phosphatidylinositol-5-phosphate (PI(5)P). Here we show that its activity is essential during early phagosome maturation in Dictyostelium. Disruption of PIKfyve inhibited delivery of both the vacuolar V-ATPase and proteases, dramatically reducing the ability of cells to acidify newly formed phagosomes and digest their contents. Consequently, PIKfyve- cells were unable to generate an effective antimicrobial environment and efficiently kill captured bacteria. Moreover, we demonstrate that cells lacking PIKfyve are more susceptible to infection by the intracellular pathogen Legionella pneumophila. We conclude that PIKfyve-catalysed phosphoinositide production plays a crucial and general role in ensuring early phagosomal maturation, protecting host cells from diverse pathogenic microbes.

McAlpine, J. B.; Chen, S.-N.; Kutateladze, A.; MacMillan, J. B.; Appendino, G.; Barison, A.; Beniddir, M. A.; Biavatti, M. W.; Bluml, S.; Boufridi, A.; Butler, M. S.; Capon, R. J.; Choi, Y. H.; Coppage, D.; Crews, P.; Crimmins, M. T.; Csete, M.; Dewapriya, P.; Egan, J. M.; Garson, M. J.; Genta-Jouve, G.; Gerwick, W. H.; Gross, H.; Harper, M. K.; Hermanto, P.; Hook, J. M.; Hunter, L.; Jeannerat, D.; Ji, N.-Y.; Johnson, T. A.; Kingston, D. G. I.; Koshino, H.; Lee, H.-W.; Lewin, G.; Li, J.; Linington, R. G.; Liu, M.; McPhail, K. L.; Molinski, T. F.; Moore, B. S.; Nam, J.-W.; Neupane, R. P.; Niemitz, M.; Nuzillard, J.-M.; Oberlies, N. H.; Ocampos, F. M. M.; Pan, G.; Quinn, R. J.; Reddy, D. S.; Renault, J.-H.; Rivera-Chávez, J.; Robien, W.; Saunders, C. M.; Schmidt, T. J.; Seger, C.; Shen, B.; Steinbeck, C.; Stuppner, H.; Sturm, S.; Taglialatela-Scafati, O.; Tantillo, D. J.; Verpoorte, R.; Wang, B.-G.; Williams, C. M.; Williams, P. G.; Wist, J.; Yue, J.-M.; Zhang, C.; Xu, Z.; Simmler, C.; Lankin, D. C.; Bisson, J.; Pauli, G. F. “The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research”, Nat. Prod. Rep. 2019, 36, archive unige:113449 pdf full text [free access]

With contributions from the global natural product (NP) research community, and continuing the Raw Data Initiative, this review collects a comprehensive demonstration of the immense scientific value of disseminating raw nuclear magnetic resonance (NMR) data, independently of, and in parallel with, classical publishing outlets. A comprehensive compilation of historic to present-day cases as well as contemporary and future applications show that addressing the urgent need for a repository of publicly accessible raw NMR data has the potential to transform natural products (NPs) and associated fields of chemical and biomedical research. The call for advancing open sharing mechanisms for raw data is intended to enhance the transparency of experimental protocols, augment the reproducibility of reported outcomes, including biological studies, become a regular component of responsible research, and thereby enrich the integrity of NP research and related fields.

Carlini, L.; Mahecic, D.; Kleele, T.; Roux, A.; Manley, S. “Membrane bending energy and tension govern mitochondrial division”, bioRxiv, Biophys. 2019, in press.

Mitochondria rely on cellular machinery for their division, which is an essential component of metabolic response of the cell. Many division factors have been identified; however, a framework accounting for the energetic requirements of the mitochondrial fission process is lacking. We report that the presence of an active constriction does not ensure fission. Instead, by measuring constrictions down to ~100 nm with time-lapse super-resolution microscopy, we found that 34% of constrictions failed to divide and 'reversed' to an unconstricted state. Higher local curvatures - reflecting an increased bending energy - made constriction sites more likely to divide, but often with a significant residual energy barrier to fission. Our data suggest that membrane tension, largely arising from pulling forces, could account for this missing energy. These results lead us to propose that mitochondrial fission is probabilistic, and can be modeled as arising from bending energy complemented by a fluctuating membrane tension.