Intracellular innate immune surveillance devices in plants and animals

Multicellular eukaryotes coevolve with microbial pathogens, which exert strong selective pressure on the immune systems of their hosts. Plants and animals use intracellular proteins of the nucleotide-binding domain, leucine-rich repeat (NLR) superfamily to detect many types of microbial pathogens.The NLR domain architecture likely evolved independently and convergently in each kingdom, and the molecular mechanisms of pathogen detection by plant and animal NLRs have long been considered to be distinct. However, microbial recognition mechanisms overlap, and it is now possible to discern important key trans-kingdom principles of NLR-dependent immune function. Here, we attempt to articulate these principles.We propose that the NLR architecture has evolved for pathogen-sensing in diverse organisms because of its utility as a tightly folded "hair trigger" device into which a virtually limitless number of microbial detection platforms can be integrated. Recent findings suggest means to rationally design novel recognition capabilities to counter disease

Inclusive production of protons, anti-protons and neutrons in p+p collisions at 158 GeV/c beam momentum

New data on the production of protons, anti-protons and neutrons in p+p interactions are presented. The data come from a sample of 4.8 million inelastic events obtained with the NA49 detector at the CERN SPS at 158 GeV/c beam momentum. The charged baryons are identified by energy loss measurement in a large TPC tracking system. Neutrons are detected in a forward hadronic calorimeter. Inclusive invariant cross sections are obtained in intervals from 0 to 1.9 GeV/c (0 to 1.5 GeV/c) in transverse momentum and from -0.05 to 0.95 (-0.05 to 0.4) in Feynman x for protons (anti-protons), respectively. pT integrated neutron cross sections are given in the interval from 0.1 to 0.9 in Feynman x. The data are compared to a wide sample of existing results in the SPS and ISR energy ranges as well as to proton and neutron measurements from HERA and RHIC.Comment: 69 pages, 72 figure

Comparing proton momentum distributions in A=2A=2 and 3 nuclei via 2^2H 3^3H and 3^3He (e,e′p)(e, e'p) measurements

We report the first measurement of the $(e,e'p)$ reaction cross-section ratios for Helium-3 ($^3$He), Tritium ($^3$H), and Deuterium ($d$). The measurement covered a missing momentum range of $40 \le p_{miss} \le 550$ MeV$/c$, at large momentum transfer ($\langle Q^2 \rangle \approx 1.9$ (GeV$/c$)$^2$) and $x_B>1$, which minimized contributions from non quasi-elastic (QE) reaction mechanisms. The data is compared with plane-wave impulse approximation (PWIA) calculations using realistic spectral functions and momentum distributions. The measured and PWIA-calculated cross-section ratios for $^3$He$/d$ and $^3$H$/d$ extend to just above the typical nucleon Fermi-momentum ($k_F \approx 250$ MeV$/c$) and differ from each other by $\sim 20\%$, while for $^3$He/$^3$H they agree within the measurement accuracy of about 3\%. At momenta above $k_F$, the measured $^3$He/$^3$H ratios differ from the calculation by $20\% - 50\%$. Final state interaction (FSI) calculations using the generalized Eikonal Approximation indicate that FSI should change the $^3$He/$^3$H cross-section ratio for this measurement by less than 5\%. If these calculations are correct, then the differences at large missing momenta between the $^3$He/$^3$H experimental and calculated ratios could be due to the underlying $NN$ interaction, and thus could provide new constraints on the previously loosely-constrained short-distance parts of the $NN$ interaction.Comment: 8 pages, 3 figures (4 panels

Reproducibility in the absence of selective reporting : An illustration from large-scale brain asymmetry research

Altres ajuts: Max Planck Society (Germany).The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p-hacking. Low statistical power in individual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left-right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta-analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an "ideal publishing environment," that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% (SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically-used sample sizes

The structural basis of flagellin detection by NAIP5: A strategy to limit pathogen immune evasion

Robust innate immune detection of rapidly evolving pathogens is critical for host defense. Nucleotide-binding domain leucine-rich repeat (NLR) proteins function as cytosolic innate immune sensors in plants and animals. However, the structural basis for ligand-induced NLR activation has so far remained unknown. NAIP5 (NLR family, apoptosis inhibitory protein 5) binds the bacterial protein flagellin and assembles with NLRC4 to form a multiprotein complex called an inflammasome. Here we report the cryo–electron microscopy structure of the assembled ~1.4-megadalton flagellin-NAIP5-NLRC4 inflammasome, revealing how a ligand activates an NLR. Six distinct NAIP5 domains contact multiple conserved regions of flagellin, prying NAIP5 into an open and active conformation. We show that innate immune recognition of multiple ligand surfaces is a generalizable strategy that limits pathogen evolution and immune escape.Peer Reviewe

Resonant ionization of shallow donors in electric field

In this paper, we report on our experimental observations of the resonant ionization of a phosphorus donor in silicon in a homogeneous electric field, which is expressed in the sudden rise of the conductivity of the sample at a low temperature when the electric field approaches the critical value of ∼3.2 MV m-1. The effect is discussed in terms of the field-induced interaction of the states using a simplified model based on the effective-mass theory. The results from our model are qualitatively similar to the previously published advanced model base, which is based on the first principles; this predicts the ionization thresholds at approximate fields of 2.45 and 3.25 MV m-1, the latter being in very good agreement with our experiment. The possibility of observing more than one resonance is also discussed