NAIP proteins are required for cytosolic detection of specific bacterial ligands in vivo.

NLRs (nucleotide-binding domain [NBD] leucine-rich repeat [LRR]-containing proteins) exhibit diverse functions in innate and adaptive immunity. NAIPs (NLR family, apoptosis inhibitory proteins) are NLRs that appear to function as cytosolic immunoreceptors for specific bacterial proteins, including flagellin and the inner rod and needle proteins of bacterial type III secretion systems (T3SSs). Despite strong biochemical evidence implicating NAIPs in specific detection of bacterial ligands, genetic evidence has been lacking. Here we report the use of CRISPR/Cas9 to generate Naip1(-/-) and Naip2(-/-) mice, as well as Naip1-6(Δ/Δ) mice lacking all functional Naip genes. By challenging Naip1(-/-) or Naip2(-/-) mice with specific bacterial ligands in vivo, we demonstrate that Naip1 is uniquely required to detect T3SS needle protein and Naip2 is uniquely required to detect T3SS inner rod protein, but neither Naip1 nor Naip2 is required for detection of flagellin. Previously generated Naip5(-/-) mice retain some residual responsiveness to flagellin in vivo, whereas Naip1-6(Δ/Δ) mice fail to respond to cytosolic flagellin, consistent with previous biochemical data implicating NAIP6 in flagellin detection. Our results provide genetic evidence that specific NAIP proteins function to detect specific bacterial proteins in vivo

Interstellar OH+, H2O+ and H3O+ along the sight-line to G10.6-0.4

We report the detection of absorption lines by the reactive ions OH+, H2O+ and H3O+ along the line of sight to the submillimeter continuum source G10.6$-$0.4 (W31C). We used the Herschel HIFI instrument in dual beam switch mode to observe the ground state rotational transitions of OH+ at 971 GHz, H2O+ at 1115 and 607 GHz, and H3O+ at 984 GHz. The resultant spectra show deep absorption over a broad velocity range that originates in the interstellar matter along the line of sight to G10.6$-$0.4 as well as in the molecular gas directly associated with that source. The OH+ spectrum reaches saturation over most velocities corresponding to the foreground gas, while the opacity of the H2O+ lines remains lower than 1 in the same velocity range, and the H3O+ line shows only weak absorption. For LSR velocities between 7 and 50 kms$^{-1}$ we estimate total column densities of $N$(OH+) $> 2.5 \times 10^{14}$ cm$^{-2}$, $N$(H2O+) $\sim 6 \times 10^{13}$ cm$^{-2}$ and $N$(H3O+) $\sim 4.0 \times 10^{13}$ cm$^{-2}$. These detections confirm the role of O$^+$ and OH$^+$ in initiating the oxygen chemistry in diffuse molecular gas and strengthen our understanding of the gas phase production of water. The high ratio of the OH+ by the H2O+ column density implies that these species predominantly trace low-density gas with a small fraction of hydrogen in molecular form

Herschel/HIFI observations of interstellar OH+ and H2O+ towards W49N: a probe of diffuse clouds with a small molecular fraction

We report the detection of absorption by interstellar hydroxyl cations and water cations, along the sight-line to the bright continuum source W49N. We have used Herschel's HIFI instrument, in dual beam switch mode, to observe the 972 GHz N = 1 - 0 transition of OH+ and the 1115 GHz 1(11) - 0(00) transition of ortho-H2O+. The resultant spectra show absorption by ortho-H2O+, and strong absorption by OH+, in foreground material at velocities in the range 0 to 70 km/s with respect to the local standard of rest. The inferred OH+/H2O+ abundance ratio ranges from ~ 3 to ~ 15, implying that the observed OH+ arises in clouds of small molecular fraction, in the 2 - 8% range. This conclusion is confirmed by the distribution of OH+ and H2O+ in Doppler velocity space, which is similar to that of atomic hydrogen, as observed by means of 21 cm absorption measurements, and dissimilar from that typical of other molecular tracers. The observed OH+/H abundance ratio of a few E-8 suggests a cosmic ray ionization rate for atomic hydrogen of (0.6 - 2.4) E-16 s-1, in good agreement with estimates inferred previously for diffuse clouds in the Galactic disk from observations of interstellar H3+ and other species.Comment: Accepted for publication in A&A Letter

Strong absorption by interstellar hydrogen fluoride: Herschel/HIFI observations of the sight-line to G10.6-0.4 (W31C)

We report the detection of strong absorption by interstellar hydrogen fluoride along the sight-line to the submillimeter continuum source G10.6-0.4 (W31C). We have used Herschel's HIFI instrument, in dual beam switch mode, to observe the 1232.4763 GHz J=1-0 HF transition in the upper sideband of the Band 5a receiver. The resultant spectrum shows weak HF emission from G10.6-0.4 at LSR velocities in the range -10 to -3 km/s, accompanied by strong absorption by foreground material at LSR velocities in the range 15 to 50 km/s. The spectrum is similar to that of the 1113.3430 GHz 1(11)-0(00) transition of para-water, although at some frequencies the HF (hydrogen fluoride) optical depth clearly exceeds that of para-H2O. The optically-thick HF absorption that we have observed places a conservative lower limit of 1.6E+14 cm-2 on the HF column density along the sight-line to G10.6-0.4. Our lower limit on the HF abundance, 6E-9 relative to hydrogen nuclei, implies that hydrogen fluoride accounts for between ~ 30 and 100% of the fluorine nuclei in the gas phase along this sight-line. This observation corroborates theoretical predictions that - because the unique thermochemistry of fluorine permits the exothermic reaction of F atoms with molecular hydrogen - HF will be the dominant reservoir of interstellar fluorine under a wide range of conditions.Comment: Accepted for publication in Astronomy and Astrophysics (Herschel special issue). This revised version corrects a typographic error in the HTML abstract, in which the lower limit on the HF abundance (should be 6E-9) was previously misstated. The abstract in the PDF version is correct and the latter has not been modifie

Self-selection biases in psychological studies: Personality and affective disorders are prevalent among participants

Respondents select the type of psychological studies that they want to participate in consistence with their needs and individual characteristics, which creates an unintentional self-selection bias. The question remains whether participants attracted by psychological studies may have more psychological dysfunctions related to personality and affective disorders compared to the general population. We investigated (N = 947; 62% women) whether the type of the invitation (to talk about recent critical or regular life events) or the source of the data (either face-to-face or online) attracts people with different psychopathology. Most importantly, participants who alone applied to take part in paid psychological studies had more symptoms of personality disorders than those who had never before applied to take part in psychological studies. The current results strongly translate into a recommendation for either the modification of recruitment strategies or much greater caution when generalizing results for this methodological reason

Microhabitats of benthic foraminifera - a static concept or a dynamic adaption to optimize food aquisition?

In situ observations of microhabitat preferences of living benthic foraminifera are presented from sediments of the Norwegian-Greenland Sea, the upwelling area off northwestern Africa and the shallow-water Kiel Bight (Baltic Sea). Certain foraminiferal species (e.g.Cibicidoides wuellerstorfi andRupertina stabilis) can be regarded as strictly epibenthic species, colonizing elevated habitats that are strongly affected by bottom water hydrodynamics. Large epibenthic foraminifera (e.g.Rhabdammina abyssorum andHyperammina crassatina) colonize the sediment surface in areas where strong bottom currents occur and might have by virtue of their own size an impact on the small-scale circulation patterns of the bottom water. Motile species changing from epifaunal to infaunal habitats (e.g.Pyrgo rotalaria, Melonis barleeanum, Elphidium excavatum clavatum, Elphidium incertum, Ammotium cassis andSphaeroidina bulloides) are regarded here as highly adaptable to changes in food availability and/or changing environmental conditions. This flexible behaviour is regarded as a dynamic adaptation to optimize food acquisition, rather than a static concept leading to habitat classification of these ubiquitous rhizopods

Mechanical Properties of Glassy Polyethylene Nanofibers via Molecular Dynamics Simulations

The extent to which the intrinsic mechanical properties of polymer fibers depend on physical size has been a matter of dispute that is relevant to most nanofiber applications. Here, we report the elastic and plastic properties determined from molecular dynamics simulations of amorphous, glassy polymer nanofibers with diameter ranging from 3.7 to 17.7 nm. We find that, for a given temperature, the Young’s elastic modulus E decreases with fiber radius and can be as much as 52% lower than that of the corresponding bulk material. Poisson’s ratio ν of the polymer comprising these nanofibers was found to decrease from a value of 0.3 to 0.1 with decreasing fiber radius. Our findings also indicate that a small but finite stress exists on the simulated nanofibers prior to elongation, attributable to surface tension. When strained uniaxially up to a tensile strain of ε = 0.2 over the range of strain rates and temperatures considered, the nanofibers exhibit a yield stress σy between 40 and 72 MPa, which is not strongly dependent on fiber radius; this yield stress is approximately half that of the same polyethylene simulated in the amorphous bulk.DuPont MIT AllianceDuPont (Firm) (Young Professor Award

Square wave adsorptive stripping voltammetric determination of famotidine in urine

Electrochemical studies of famotidine were carried out using voltammetric techniques: cyclic voltammetry, linear sweep and square wave adsorptive stripping voltammetry. The dependence of the current on pH, buffer concentration, nature of the buffer, and scan rate was investigated. The best results for the determination of famotidine were obtained in MOPS buffer solution at pH 6.7. This electroanalytical procedure enabled to determine famotidine in the concentration range 1 x 10(-9)-4 x 10(-8) mol L-1 by linear sweep adsorptive stripping voltammetry (LS AdSV) and 5 x 10(-10)-6 x 10(-8) mol L-1 by square wave adsorptive stripping voltammetry (SW AdSV). Repeatability, precision and accuracy of the developed methods were checked. The detection and quantification limits were found to be 1.8 x 10(-10) and 6.2 x 10(-10) mol L-1 for LS AdSV and 4.9 x 10(-11) and 1.6 x 10(-10) mol L-1 for SW AdSV, respectively. The method was applied for the determination of famotidine in urine. (c) 2005 Elsevier B.V. All rights reserved