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An unfolded protein-induced conformational switch activates mammalian IRE1.
The unfolded protein response (UPR) adjusts the cell's protein folding capacity in the endoplasmic reticulum (ER) according to need. IRE1 is the most conserved UPR sensor in eukaryotic cells. It has remained controversial, however, whether mammalian and yeast IRE1 use a common mechanism for ER stress sensing. Here, we show that similar to yeast, human IRE1α's ER-lumenal domain (hIRE1α LD) binds peptides with a characteristic amino acid bias. Peptides and unfolded proteins bind to hIRE1α LD's MHC-like groove and induce allosteric changes that lead to its oligomerization. Mutation of a hydrophobic patch at the oligomerization interface decoupled peptide binding to hIRE1α LD from its oligomerization, yet retained peptide-induced allosteric coupling within the domain. Importantly, impairing oligomerization of hIRE1α LD abolished IRE1's activity in living cells. Our results provide evidence for a unifying mechanism of IRE1 activation that relies on unfolded protein binding-induced oligomerization
New Physics at the LHC. A Les Houches Report: Physics at TeV Colliders 2009 - New Physics Working Group
We present a collection of signatures for physics beyond the standard model
that need to be explored at the LHC. First, are presented various tools
developed to measure new particle masses in scenarios where all decays include
an unobservable particle. Second, various aspects of supersymmetric models are
discussed. Third, some signatures of models of strong electroweak symmetry are
discussed. In the fourth part, a special attention is devoted to high mass
resonances, as the ones appearing in models with warped extra dimensions.
Finally, prospects for models with a hidden sector/valley are presented. Our
report, which includes brief experimental and theoretical reviews as well as
original results, summarizes the activities of the "New Physics" working group
for the "Physics at TeV Colliders" workshop (Les Houches, France, 8-26 June,
2009).Comment: 189 page
Mapping interactions with the chaperone network reveals factors that protect against tau aggregation.
A network of molecular chaperones is known to bind proteins ('clients') and balance their folding, function and turnover. However, it is often unclear which chaperones are critical for selective recognition of individual clients. It is also not clear why these key chaperones might fail in protein-aggregation diseases. Here, we utilized human microtubule-associated protein tau (MAPT or tau) as a model client to survey interactions between ~30 purified chaperones and ~20 disease-associated tau variants (~600 combinations). From this large-scale analysis, we identified human DnaJA2 as an unexpected, but potent, inhibitor of tau aggregation. DnaJA2 levels were correlated with tau pathology in human brains, supporting the idea that it is an important regulator of tau homeostasis. Of note, we found that some disease-associated tau variants were relatively immune to interactions with chaperones, suggesting a model in which avoiding physical recognition by chaperone networks may contribute to disease
New Physics at the LHC. A Les Houches Report: Physics at TeV Colliders 2009 - New Physics Working Group
We present a collection of signatures for physics beyond the standard model that need to be explored at the LHC. First, are presented various tools developed to measure new particle masses in scenarios where all decays include an unobservable particle. Second, various aspects of supersymmetric models are discussed. Third, some signatures of models of strong electroweak symmetry are discussed. In the fourth part, a special attention is devoted to high mass resonances, as the ones appearing in models with warped extra dimensions. Finally, prospects for models with a hidden sector/valley are presented. Our report, which includes brief experimental and theoretical reviews as well as original results, summarizes the activities of the "New Physics" working group for the "Physics at TeV Colliders" workshop (Les Houches, France, 8-26 June, 2009)
Component fractionation of wood-tar by column chromatography with the packing material of silica gel
Combining functional weed ecology and crop stable isotope ratios to identify cultivation intensity: a comparison of cereal production regimes in Haute Provence, France and Asturias, Spain
This investigation combines two independent
methods of identifying crop growing conditions and husbandry
practices—functional weed ecology and crop stable
carbon and nitrogen isotope analysis—in order to assess
their potential for inferring the intensity of past cereal
production systems using archaeobotanical assemblages.
Present-day organic cereal farming in Haute Provence,
France features crop varieties adapted to low-nutrient soils
managed through crop rotation, with little to no manuring.
Weed quadrat survey of 60 crop field transects in this region
revealed that floristic variation primarily reflects
geographical differences. Functional ecological weed data
clearly distinguish the Provence fields from those surveyed
in a previous study of intensively managed spelt wheat in
Asturias, north-western Spain: as expected, weed ecological
data reflect higher soil fertility and disturbance in
Asturias. Similarly, crop stable nitrogen isotope values
distinguish between intensive manuring in Asturias and
long-term cultivation with minimal manuring in Haute
Provence. The new model of cereal cultivation intensity
based on weed ecology and crop isotope values in Haute
Provence and Asturias was tested through application to
two other present-day regimes, successfully identifying a
high-intensity regime in the Sighisoara region, Romania,
and low-intensity production in Kastamonu, Turkey. Application
of this new model to Neolithic archaeobotanical
assemblages in central Europe suggests that early farming
tended to be intensive, and likely incorporated manuring,
but also exhibited considerable variation, providing a finer
grained understanding of cultivation intensity than previously
available
Shuffled ATG8 interacting motifs form an ancestral bridge between UFMylation and autophagy
UFMylation involves the covalent modification of substrate proteins with UFM1 (Ubiquitin‐fold modifier 1) and is important for maintaining ER homeostasis. Stalled translation triggers the UFMylation of ER‐bound ribosomes and activates C53‐mediated autophagy to clear toxic polypeptides. C53 contains noncanonical shuffled ATG8‐interacting motifs (sAIMs) that are essential for ATG8 interaction and autophagy initiation. However, the mechanistic basis of sAIM‐mediated ATG8 interaction remains unknown. Here, we show that C53 and sAIMs are conserved across eukaryotes but secondarily lost in fungi and various algal lineages. Biochemical assays showed that the unicellular alga Chlamydomonas reinhardtii has a functional UFMylation pathway, refuting the assumption that UFMylation is linked to multicellularity. Comparative structural analyses revealed that both UFM1 and ATG8 bind sAIMs in C53, but in a distinct way. Conversion of sAIMs into canonical AIMs impaired binding of C53 to UFM1, while strengthening ATG8 binding. Increased ATG8 binding led to the autoactivation of the C53 pathway and sensitization of Arabidopsis thaliana to ER stress. Altogether, our findings reveal an ancestral role of sAIMs in UFMylation‐dependent fine‐tuning of C53‐mediated autophagy activation
Collider aspects of flavour physics at high Q
This review presents flavour related issues in the production and decays of
heavy states at LHC, both from the experimental side and from the theoretical
side. We review top quark physics and discuss flavour aspects of several
extensions of the Standard Model, such as supersymmetry, little Higgs model or
models with extra dimensions. This includes discovery aspects as well as
measurement of several properties of these heavy states. We also present public
available computational tools related to this topic.Comment: Report of Working Group 1 of the CERN Workshop ``Flavour in the era
of the LHC'', Geneva, Switzerland, November 2005 -- March 200
Abstracts of presentations on plant protection issues at the fifth international Mango Symposium Abstracts of presentations on plant protection issues at the Xth international congress of Virology: September 1-6, 1996 Dan Panorama Hotel, Tel Aviv, Israel August 11-16, 1996 Binyanei haoma, Jerusalem, Israel
Root and canal symmetry in the mandibular anterior teeth of patients attending a dental clinic: CBCT study
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