Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production

Systems for protein degradation are essential for tight control of the inflammatory immune response. Autophagy, a bulk degradation system that delivers cytoplasmic constituents into autolysosomes, controls degradation of long-lived proteins, insoluble protein aggregates and invading microbes, and is suggested to be involved in the regulation of inflammation. However, the mechanism underlying the regulation of inflammatory response by autophagy is poorly understood. Here we show that Atg16L1 (autophagy-related 16-like 1), which is implicated in Crohn's disease, regulates endotoxin-induced inflammasome activation in mice. Atg16L1-deficiency disrupts the recruitment of the Atg12-Atg5 conjugate to the isolation membrane, resulting in a loss of microtubule-associated protein 1 light chain 3 (LC3) conjugation to phosphatidylethanolamine. Consequently, both autophagosome formation and degradation of long-lived proteins are severely impaired in Atg16L1-deficient cells. Following stimulation with lipopolysaccharide, a ligand for Toll-like receptor 4 (refs 8, 9), Atg16L1-deficient macrophages produce high amounts of the inflammatory cytokines IL-1beta and IL-18. In lipopolysaccharide-stimulated macrophages, Atg16L1-deficiency causes Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF)-dependent activation of caspase-1, leading to increased production of IL-1beta. Mice lacking Atg16L1 in haematopoietic cells are highly susceptible to dextran sulphate sodium-induced acute colitis, which is alleviated by injection of anti-IL-1beta and IL-18 antibodies, indicating the importance of Atg16L1 in the suppression of intestinal inflammation. These results demonstrate that Atg16L1 is an essential component of the autophagic machinery responsible for control of the endotoxin-induced inflammatory immune response.     

Plastid proteins crucial for symbiotic fungal and bacterial entry into plant roots

The roots of most higher plants form arbuscular mycorrhiza, an ancient, phosphate-acquiring symbiosis with fungi, whereas only four related plant orders are able to engage in the evolutionary younger nitrogen-fixing root-nodule symbiosis with bacteria. Plant symbioses with bacteria and fungi require a set of common signal transduction components that redirect root cell development. Here we present two highly homologous genes from Lotus japonicus, CASTOR and POLLUX, that are indispensable for microbial admission into plant cells and act upstream of intracellular calcium spiking, one of the earliest plant responses to symbiotic stimulation. Surprisingly, both twin proteins are localized in the plastids of root cells, indicating a previously unrecognized role of this ancient endosymbiont in controlling intracellular symbioses that evolved more recently.     

Up-grading of natural ilmenite ore by combining oxidation and acid leaching

Rutile (TiO₂) is heavily used in pigments and colorants, and the most abundant source of rutile is ilmenite. Upon oxidation of ilmenite, rutile can be formed with modest energy consumption; furthermore, after leaching, only a few byproducts are formed. Unfortunately, one drawback is the necessarily long oxidative process of typically used methods. In this study, we show that a fluidized bed reactor can be used to oxidize ilmenite ore to rapidly form rutile and pseudobrookite (Fe₂TiO₅) phases. Ilmenite was oxidized with 5vol% O₂ in Ar at temperatures of 1173 K or 1223 K and subsequently leached using a diluted H₂SO₄ solution to dissolve the pseudobrookite phase. The effects of acid concentration, temperature, and cooling rate after oxidation were investigated. We show that the ilmenite was rapidly oxidized to form rutile and pseudobrookite phases at 1173 and 1223 K in a 5vol% O₂/95vol% Ar environment within 40 min. The final maximum rutile yield was 84.2mol% after leaching in (1 + 1) H₂SO₄ solution at 393 K for 12 h.     

Effect of lower bainite/martensite/retained austenite triplex microstructure on the mechanical properties of a low-carbon steel with quenching and partitioning process

We present a study concerning Fe–0.176C–1.31Si–1.58Mn–0.26Al–0.3Cr (wt%) steel subjected to a quenching and partitioning (Q&P) process. The results of scanning electron microscopy, transmission electron microscopy, X-ray diffraction, and tensile tests demonstrate that the microstructures primarily consist of lath martensite, retained austenite, lower bainite (LB), and a small amount of tempered martensite; moreover, few twin austenite grains were observed. In the microstructure, three types of retained austenite with different sizes and morphologies were observed: blocky retained austenite (~300 nm in width), film-like retained austenite (80–120 nm in width), and ultra- fine film-like retained austenite (30–40 nm in width). Because of the effect of the retained austenite/martensite/LB triplex microstructure, the specimens prepared using different quenching temperatures exhibit high ultimate tensile strength and yield strength. Furthermore, the strength effect of LB can partially counteract the decreasing strength effect of martensite. The formation of LB substantially reduces the amount of retained austenite. Analyses of the retained austenite and the amount of blocky retained austenite indicated that the carbon content is critical to the total elongation of Q&P steel.     

Synthesis of brookite-typed titania from titanium chloride solution

The brookite-phase TiO2 was prepared by a hydrothermal synthesis of titanium chloride solution.The thermolysis time and the pH value of the solution were controlled during the synthesis.X-ray diffraction experiments showed that TiO2 powders partially containing the brookite-phase were successfully obtained.A great amount of OH -in the reaction solution was found to be important to obtain the brookite phase because the intermediate complex leading to the brookite phase consumes more OH-than other phases like...     

Loss of autophagy in the central nervous system causes neurodegeneration in mice

Protein quality-control, especially the removal of proteins with aberrant structures, has an important role in maintaining the homeostasis of non-dividing neural cells. In addition to the ubiquitin-proteasome system, emerging evidence points to the importance of autophagy--the bulk protein degradation pathway involved in starvation-induced and constitutive protein turnover--in the protein quality-control process. However, little is known about the precise roles of autophagy in neurons. Here we report that loss of Atg7 (autophagy-related 7), a gene essential for autophagy, leads to neurodegeneration. We found that mice lacking Atg7 specifically in the central nervous system showed behavioural defects, including abnormal limb-clasping reflexes and a reduction in coordinated movement, and died within 28 weeks of birth. Atg7 deficiency caused massive neuronal loss in the cerebral and cerebellar cortices. Notably, polyubiquitinated proteins accumulated in autophagy-deficient neurons as inclusion bodies, which increased in size and number with ageing. There was, however, no obvious alteration in proteasome function. Our results indicate that autophagy is essential for the survival of neural cells, and that impairment of autophagy is implicated in the pathogenesis of neurodegenerative disorders involving ubiquitin-containing inclusion bodies.     

Stepwise radial complexation of imine groups in phenylazomethine dendrimers

Dendrimers are highly branched organic macromolecules with successive layers or 'generations' of branch units surrounding a central core. Organic-inorganic hybrid versions have also been produced, by trapping metal ions or metal clusters within the voids of the dendrimers. The unusual, tree-like topology endows these nanometre-sized macromolecules with a gradient in branch density from the interior to the exterior, which can give rise to an energy gradient that directs the transfer of charge and energy from the dendrimer periphery to its core. Here we show that tin ions, Sn(2+), complex to the imine groups of a spherical polyphenylazomethine dendrimer in a stepwise fashion. This behaviour reflects a gradient in the electron density associated with the imine groups, with complexation in a more peripheral generation proceeding only after complexation in generations closer to the core has been completed. By attaching an electron-withdrawing group to the dendrimer core, we are able to change the complexation pattern, so that the core imines are complexed last. By further extending this strategy, it should be possible to control the number and location of metal ions incorporated into dendrimer structures, which might find uses as tailored catalysts or building blocks for advanced materials.     

Mobilization of a transposon in the rice genome

Rice (Oryza sativa L.) is an important crop worldwide and, with the availability of the draft sequence, a useful model for analysing the genome structure of grasses. To practice efficient rice breeding through genetic engineering techniques, it is important to identify the economically important genes in this crop. The use of mobile transposons as gene tags in intact plants is a powerful tool for functional analysis because transposon insertions often inactivate genes. Here we identify an active rice transposon named miniature Ping (mPing) through analysis of the mutability of a slender mutation of the glume-the seed structure that encloses and determines the shape of the grain. The mPing transposon is inserted in the slender glume (slg) mutant allele but not in the wild-type allele. Search of the O. sativa variety Nipponbare genome identified 34 sequences with high nucleotide similarity to mPing, indicating that mPing constitutes a family of transposon elements. Excision of mPing from slg plants results in reversion to a wild-type phenotype. The mobility of the transposon mPing in intact rice plants represents a useful alternative tool for the functional analysis of rice genes.