A cnidarian homologue of an insect gustatory receptor functions in developmental body patterning.

Insect gustatory and odorant receptors (GRs and ORs) form a superfamily of novel transmembrane proteins, which are expressed in chemosensory neurons that detect environmental stimuli. Here we identify homologues of GRs (Gustatory receptor-like (Grl) genes) in genomes across Protostomia, Deuterostomia and non-Bilateria. Surprisingly, two Grls in the cnidarian Nematostella vectensis, NvecGrl1 and NvecGrl2, are expressed early in development, in the blastula and gastrula, but not at later stages when a putative chemosensory organ forms. NvecGrl1 transcripts are detected around the aboral pole, considered the equivalent to the head-forming region of Bilateria. Morpholino-mediated knockdown of NvecGrl1 causes developmental patterning defects of this region, leading to animals lacking the apical sensory organ. A deuterostome Grl from the sea urchin Strongylocentrotus purpuratus displays similar patterns of developmental expression. These results reveal an early evolutionary origin of the insect chemosensory receptor family and raise the possibility that their ancestral role was in embryonic development

Specific protein antigen delivery to human Langerhans cells in intact skin

Immune modulating therapies and vaccines are in high demand, not least to the recent global spread of SARS-CoV2. To achieve efficient activation of the immune system, professional antigen presenting cells have proven to be key coordinators of such responses. Especially targeted approaches, actively directing antigens to specialized dendritic cells, promise to be more effective and accompanied by reduced payload due to less off-target effects. Although antibody and glycan-based targeting of receptors on dendritic cells have been employed, these are often expensive and time-consuming to manufacture or lack sufficient specificity. Thus, we applied a small-molecule ligand that specifically binds Langerin, a hallmark receptor on Langerhans cells, conjugated to a model protein antigen. Via microneedle injection, this construct was intradermally administered into intact human skin explants, selectively loading Langerhans cells in the epidermis. The ligand-mediated cellular uptake outpaces protein degradation resulting in intact antigen delivery. Due to the pivotal role of Langerhans cells in induction of immune responses, this approach of antigen-targeting of tissue-resident immune cells offers a novel way to deliver highly effective vaccines with minimally invasive administration

First Stellar Abundances in the Dwarf Irregular Galaxy Sextans A

We present the abundance analyses of three isolated A-type supergiant stars in the dwarf irregular galaxy Sextans A from high-resolution spectra the UVES spectrograph at the VLT. Detailed model atmosphere analyses have been used to determine the stellar atmospheric parameters and the elemental abundances of the stars. The mean iron group abundance was determined from these three stars to be [(FeII,CrII)/H]=-0.99+/-0.04+/-0.06. This is the first determination of the present-day iron group abundances in Sextans A. These three stars now represent the most metal-poor massive stars for which detailed abundance analyses have been carried out. The mean stellar alpha element abundance was determined from the alpha element magnesium as [alpha(MgI)/H]=-1.09+/-0.02+/-0.19. This is in excellent agreement with the nebular alpha element abundances as determined from oxygen in the H II regions. These results are consistent from star-to-star with no significant spatial variations over a length of 0.8 kpc in Sextans A. This supports the nebular abundance studies of dwarf irregular galaxies, where homogeneous oxygen abundances are found throughout, and argues against in situ enrichment. The alpha/Fe abundance ratio is [alpha(MgI)/FeII,CrII]=-0.11+/-0.02+/-0.10, which is consistent with the solar ratio. This is consistent with the results from A-supergiant analyses in other Local Group dwarf irregular galaxies but in stark contrast with the high [alpha/Fe] results from metal-poor stars in the Galaxy, and is most clearly seen from these three stars in Sextans A because of their lower metallicities. The low [alpha/Fe] ratios are consistent with the slow chemical evolution expected for dwarf galaxies from analyses of their stellar populations.Comment: 40 pages, 8 figures, accepted for publication in A

Sub-electron Charge Relaxation via 2D Hopping Conductors

We have extended Monte Carlo simulations of hopping transport in completely disordered 2D conductors to the process of external charge relaxation. In this situation, a conductor of area $L \times W$ shunts an external capacitor $C$ with initial charge $Q_i$. At low temperatures, the charge relaxation process stops at some "residual" charge value corresponding to the effective threshold of the Coulomb blockade of hopping. We have calculated the r.m.s$.$ value $Q_R$ of the residual charge for a statistical ensemble of capacitor-shunting conductors with random distribution of localized sites in space and energy and random $Q_i$, as a function of macroscopic parameters of the system. Rather unexpectedly, $Q_{R}$ has turned out to depend only on some parameter combination: $X_0 \equiv L W \nu_0 e^2/C$ for negligible Coulomb interaction and $X_{\chi} \equiv LW \kappa^2/C^{2}$ for substantial interaction. (Here $\nu_0$ is the seed density of localized states, while $\kappa$ is the dielectric constant.) For sufficiently large conductors, both functions $Q_{R}/e =F(X)$ follow the power law $F(X)=DX^{-\beta}$, but with different exponents: $\beta = 0.41 \pm 0.01$ for negligible and $\beta = 0.28 \pm 0.01$ for significant Coulomb interaction. We have been able to derive this law analytically for the former (most practical) case, and also explain the scaling (but not the exact value of the exponent) for the latter case. In conclusion, we discuss possible applications of the sub-electron charge transfer for "grounding" random background charge in single-electron devices.Comment: 12 pages, 5 figures. In addition to fixing minor typos and updating references, the discussion has been changed and expande

Abundance analysis of two late A-type stars HD 32115 and HD 37594

We have performed abundance analysis of two slowly rotating, late A-type stars, HD 32115 (HR 1613) and HD 37594 (HR 1940), based on obtained echelle spectra covering the spectral range 4000-9850 AAngstrom. These spectra allowed us to identify an extensive line list for 31 chemical elements, the most complete to date for A-type stars. Two approaches to abundance analysis were used, namely a ``manual'' (interactive) and a semi-automatic procedure for comparison of synthetic and observed spectra and equivalent widths. For some elements non-LTE (NLTE) calculations were carried out and the corresponding corrections have been applied. The abundance pattern of HD 32115 was found to be very close to the solar abundance pattern, and thus may be used as an abundance standard for chemical composition studies in middle and late A stars. Further, its H-alpha line profile shows no core-to-wing anomaly like that found for cool Ap stars and therefore also may be used as a standard in comparative studies of the atmospheric structures of cool, slowly rotating Ap stars. HD 37594 shows a metal deficiency at the level of -0.3 dex for most elements and triangle-like cores of spectral lines. This star most probably belongs to the Delta Scuti group.Comment: 10 pages, 4 figure

A Numerical Study of Transport and Shot Noise at 2D Hopping

We have used modern supercomputer facilities to carry out extensive Monte Carlo simulations of 2D hopping (at negligible Coulomb interaction) in conductors with the completely random distribution of localized sites in both space and energy, within a broad range of the applied electric field $E$ and temperature $T$, both within and beyond the variable-range hopping region. The calculated properties include not only dc current and statistics of localized site occupation and hop lengths, but also the current fluctuation spectrum. Within the calculation accuracy, the model does not exhibit $1/f$ noise, so that the low-frequency noise at low temperatures may be characterized by the Fano factor $F$. For sufficiently large samples, $F$ scales with conductor length $L$ as $(L_c/L)^{\alpha}$, where $\alpha=0.76\pm 0.08 < 1$, and parameter $L_c$ is interpreted as the average percolation cluster length. At relatively low $E$, the electric field dependence of parameter $L_c$ is compatible with the law $L_c\propto E^{-0.911}$ which follows from directed percolation theory arguments.Comment: 17 pages, 8 figures; Fixed minor typos and updated reference

A Numerical Study of Coulomb Interaction Effects on 2D Hopping Transport

We have extended our supercomputer-enabled Monte Carlo simulations of hopping transport in completely disordered 2D conductors to the case of substantial electron-electron Coulomb interaction. Such interaction may not only suppress the average value of hopping current, but also affect its fluctuations rather substantially. In particular, the spectral density $S_I (f)$ of current fluctuations exhibits, at sufficiently low frequencies, a $1/f$-like increase which approximately follows the Hooge scaling, even at vanishing temperature. At higher $f$, there is a crossover to a broad range of frequencies in which $S_I (f)$ is nearly constant, hence allowing characterization of the current noise by the effective Fano factor F\equiv S_I(f)/2e \left. For sufficiently large conductor samples and low temperatures, the Fano factor is suppressed below the Schottky value (F=1), scaling with the length $L$ of the conductor as $F = (L_c / L)^{\alpha}$. The exponent $\alpha$ is significantly affected by the Coulomb interaction effects, changing from $\alpha = 0.76 \pm 0.08$ when such effects are negligible to virtually unity when they are substantial. The scaling parameter $L_c$, interpreted as the average percolation cluster length along the electric field direction, scales as $L_c \propto E^{-(0.98 \pm 0.08)}$ when Coulomb interaction effects are negligible and $L_c \propto E^{-(1.26 \pm 0.15)}$ when such effects are substantial, in good agreement with estimates based on the theory of directed percolation.Comment: 19 pages, 7 figures. Fixed minor typos and updated reference

Electronic correlation effects and the Coulomb gap at finite temperature

We have investigated the effect of the long-range Coulomb interaction on the one-particle excitation spectrum of n-type Germanium, using tunneling spectroscopy on mechanically controllable break junctions. The tunnel conductance was measured as a function of energy and temperature. At low temperatures, the spectra reveal a minimum at zero bias voltage due to the Coulomb gap. In the temperature range above 1 K the Coulomb gap is filled by thermal excitations. This behavior is reflected in the temperature dependence of the variable-range hopping resitivity measured on the same samples: Up to a few degrees Kelvin the Efros-Shkovskii ln$R \propto T^{-1/2}$ law is obeyed, whereas at higher temperatures deviations from this law are observed, indicating a cross-over to Mott's ln$R \propto T^{-1/4}$ law. The mechanism of this cross-over is different from that considered previously in the literature.Comment: 3 pages, 3 figure

A remote secondary binding pocket promotes heteromultivalent targeting of DC-SIGN

Dendritic cells (DC) are antigen-presenting cells coordinating the interplay of the innate and the adaptive immune response. The endocytic C-type lectin receptors DC-SIGN and Langerin display expression profiles restricted to distinct DC subtypes and have emerged as prime targets for next-generation immunotherapies and anti-infectives. Using heteromultivalent liposomes copresenting mannosides bearing aromatic aglycones with natural glycan ligands, we serendipitously discovered striking cooperativity effects for DC-SIGN+ but not for Langerin+ cell lines. Mechanistic investigations combining NMR spectroscopy with molecular docking and molecular dynamics simulations led to the identification of a secondary binding pocket for the glycomimetics. This pocket, located remotely of DC-SIGN’s carbohydrate bindings site, can be leveraged by heteromultivalent avidity enhancement. We further present preliminary evidence that the aglycone allosterically activates glycan recognition and thereby contributes to DC-SIGN-specific cell targeting. Our findings have important implications for both translational and basic glycoscience, showcasing heteromultivalent targeting of DCs to improve specificity and supporting potential allosteric regulation of DC-SIGN and CLRs in general