Ionic Coulomb blockade and anomalous mole fraction effect in NaChBac bacterial ion channels

We report an experimental study of the influences of the fixed charge and bulk ionic concentrations on the conduction of biological ion channels, and we consider the results within the framework of the ionic Coulomb blockade model of permeation and selectivity. Voltage clamp recordings were used to investigate the Na$^+$/Ca$^{2+}$ anomalous mole fraction effect (AMFE) exhibited by the bacterial sodium channel NaChBac and its mutants. Site-directed mutagenesis was used to study the effect of either increasing or decreasing the fixed charge in their selectivity filters for comparison with the predictions of the Coulomb blockade model. The model was found to describe well some aspects of the experimental (divalent blockade and AMFE) and simulated (discrete multi-ion conduction and occupancy band) phenomena, including a concentration-dependent shift of the Coulomb staircase. These results substantially extend the understanding of ion channel selectivity and may also be applicable to biomimetic nanopores with charged walls

Theory and Experiments on Multi-Ion Permeation and Selectivity in the NaChBac Ion Channel

The highly selective permeation of ions through biological ion channels is an unsolved problem of noise and fluctuations. In this paper, we motivate and introduce a non-equilibrium and self-consistent multi-species kinetic model, with the express aims of comparing with experimental recordings of current versus voltage and concentration and extracting important permeation parameters. For self-consistency, the behavior of the model at the two-state, i.e., selective limit in linear response, must agree with recent results derived from an equilibrium statistical theory. The kinetic model provides a good fit to data, including the key result of an anomalous mole fraction effect

Inventory and review of the Mio–Pleistocene São Jorge flora (Madeira Island, Portugal): palaeoecological and biogeographical implications

The occurrence of plant fossils on Madeira Island has been known since the mid-nineteenth century. Charles Lyell and George Hartung discovered a leaf bed rich in Lauraceae and fern fossils at S~ao Jorge in 1854. The determinations were controversial but a full review was never performed. Here we propose possible geological settings for the fossiliferous outcrop, and present an inventory and a systematic review of the surviving specimens of the S~ao Jorge macroflora. The S~ao Jorge leaf bed no longer outcrops due to a landslide in 1865. It was possible to establish the two alternative volcano stratigraphical settings in the sedimentary intercalations from the Middle Volcanic Complex, ranging in age from 7 to 1.8 Ma. The descriptions of Heer (1857), Bunbury (1859) and Hartung & Mayer (1864) are reviewed based on 82 surviving specimens. From the initial 37 taxa, we recognize only 20: Osmunda sp., Pteridium aquilinum, Asplenium cf. onopteris, aff. Asplenium, cf. Polystichum, cf. Davallia, Woodwardia radicans, Filicopsida gen. et sp. indet. 1 and 2, Ocotea foetens, Salix sp., Erica arborea, cf. Vaccinium, Rubus sp, cf. Myrtus, Magnoliopsida gen. et sp. indet. 1 to 3, Liliopsida gen. et sp. indet. 1. Magnoliopsida gen. et sp. indet. 4 is based on one previously undescribed flower or fruit. The floristic composition of the S~ao Jorge fossils resembles the current floristic association of temperate stink laurel (Ocotea foetens) forest, suggesting a warm and humid palaeoclimate and indicating that laurel forests were present in Macaronesia at least since the Gelasian, a time when the palaeotropical geofloral elements were almost extinct in Europe.info:eu-repo/semantics/publishedVersio

Fermi observations of high-energy gamma-ray emission from GRB 080825C

The Fermi Gamma-ray Space Telescope (FGST) has opened a new high-energy window in the study of Gamma-Ray Bursts (GRBs). Here we present a thorough analysis of GRB 080825C, which triggered the Fermi Gamma-ray Burst Monitor (GBM), and was the first firm detection of a GRB by the Fermi Large Area Telescope (LAT). We discuss the LAT event selections, background estimation, significance calculations, and localization for Fermi GRBs in general and GRB 080825C in particular. We show the results of temporal and time-resolved spectral analysis of the GBM and LAT data. We also present some theoretical interpretation of GRB 080825C observations as well as some common features observed in other LAT GRBs.Comment: 18 pages, 7 figures. Accepted for publication in ApJ. Corresponding authors: A. Bouvier, J. Granot, A.J. van der Hors

SEARCHING the GAMMA-RAY SKY for COUNTERPARTS to GRAVITATIONAL WAVE SOURCES: FERMI GAMMA-RAY BURST MONITO R and LARGE AREA TELESCOPE OBSERVATIONS of LVT151012 and GW151226

We present the Fermi Gamma-ray Burst Monitor (GBM) and Large Area Telescope (LAT) observations of the LIGO binary black hole merger event GW151226 and candidate LVT151012. At the time of the LIGO triggers on LVT151012 and GW151226, GBM was observing 68% and 83% of the localization regions, and LAT was observing 47% and 32%, respectively. No candidate electromagnetic counterparts were detected by either the GBM or LAT. We present a detailed analysis of the GBM and LAT data over a range of timescales from seconds to years, using automated pipelines and new techniques for characterizing the flux upper bounds across large areas of the sky. Due to the partial GBM and LAT coverage of the large LIGO localization regions at the trigger times for both events, differences in source distances and masses, as well as the uncertain degree to which emission from these sources could be beamed, these non-detections cannot be used to constrain the variety of theoretical models recently applied to explain the candidate GBM counterpart to GW150914

Effect of Plasmodium falciparum sulfadoxine-pyrimethamine resistance on the effectiveness of intermittent preventive therapy for malaria in pregnancy in Africa: a systematic review and meta-analysis.

BACKGROUND: Resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine threatens the antimalarial effectiveness of intermittent preventive treatment during pregnancy (IPTp) in sub-Saharan Africa. We aimed to assess the associations between markers of sulfadoxine-pyrimethamine resistance in P falciparum and the effectiveness of sulfadoxine-pyrimethamine IPTp for malaria-associated outcomes. METHODS: For this systematic review and meta-analysis, we searched databases (from Jan 1, 1990 to March 1, 2018) for clinical studies (aggregated data) or surveys (individual participant data) that reported data on low birthweight (primary outcome) and malaria by sulfadoxine-pyrimethamine IPTp dose, and for studies that reported on molecular markers of sulfadoxine-pyrimethamine resistance. Studies that involved only HIV-infected women or combined interventions were excluded. We did a random-effects meta-analysis (clinical studies) or multivariate log-binomial regression (surveys) to obtain summarised dose-response data (relative risk reduction [RRR]) and multivariate meta-regression to explore the modifying effects of sulfadoxine-pyrimethamine resistance (as indicated by Ala437Gly, Lys540Glu, and Ala581Gly substitutions in the dhps gene). This study is registered with PROSPERO, number 42016035540. FINDINGS: Of 1097 records screened, 57 studies were included in the aggregated-data meta-analysis (including 59 457 births). The RRR for low birthweight declined with increasing prevalence of dhps Lys540Glu (ptrend=0·0060) but not Ala437Gly (ptrend=0·35). The RRR was 7% (95% CI 0 to 13) in areas of high resistance to sulfadoxine-pyrimethamine (Lys540Glu ≥90% in east and southern Africa; n=11), 21% (14 to 29) in moderate-resistance areas (Ala437Gly ≥90% [central and west Africa], or Lys540Glu ≥30% to <90% [east and southern Africa]; n=16), and 27% (21 to 33) in low-resistance areas (Ala437Gly <90% [central and west Africa], or Lys540Glu <30% [east and southern Africa]; n=30; ptrend=0·0054 [univariate], I2=69·5%). The overall RRR in all resistance strata was 21% (17 to 25). In the analysis of individual participant data from 13 surveys (42 394 births), sulfadoxine-pyrimethamine IPTp was associated with reduced prevalence of low birthweight in areas with a Lys540Glu prevalence of more than 90% and Ala581Gly prevalence of less than 10% (RRR 10% [7 to 12]), but not in those with an Ala581Gly prevalence of 10% or higher (pooled Ala581Gly prevalence 37% [range 29 to 46]; RRR 0·5% [-16 to 14]; 2326 births). INTERPRETATION: The effectiveness of sulfadoxine-pyrimethamine IPTp is reduced in areas with high resistance to sulfadoxine-pyrimethamine among P falciparum parasites, but remains associated with reductions in low birthweight even in areas where dhps Lys540Glu prevalence exceeds 90% but where the sextuple-mutant parasite (harbouring the additional dhps Ala581Gly mutation) is uncommon. Therapeutic alternatives to sulfadoxine-pyrimethamine IPTp are needed in areas where the prevalence of the sextuple-mutant parasite exceeds 37%. FUNDING: US Centers for Disease Control and Prevention, the Malaria in Pregnancy Consortium (funded through a grant from the Bill & Melinda Gates Foundation to the Liverpool School of Tropical Medicine), Worldwide Antimalarial Resistance Network, European and Developing Countries Clinical Trials Partnership