102 research outputs found
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 and 3 nuclei via H H and He measurements
We report the first measurement of the reaction cross-section
ratios for Helium-3 (He), Tritium (H), and Deuterium (). The
measurement covered a missing momentum range of
MeV, at large momentum transfer (
(GeV)) and , 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 He and H extend to just above the typical nucleon
Fermi-momentum ( MeV) and differ from each other by , while for He/H they agree within the measurement accuracy of
about 3\%. At momenta above , the measured He/H ratios differ from
the calculation by . Final state interaction (FSI) calculations
using the generalized Eikonal Approximation indicate that FSI should change the
He/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 He/H experimental and calculated ratios could be due to the
underlying interaction, and thus could provide new constraints on the
previously loosely-constrained short-distance parts of the 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
New insights into the genetic etiology of Alzheimer's disease and related dementias
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele
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
- …