Autophagy is an intracellular degradation process for recycling macromolecules and organelles. It plays important roles in plant development and in response to nutritional demand, stress, and ...senescence. Organisms from yeast to plants contain many autophagy-associated genes (ATG). In this study, we found that a total of 33 ATG homologues exist in the rice Oryza sativa L. (Os) genome, which were classified into 13 ATG subfamilies. Six of them are alternatively spliced genes. Evolutional analysis showed that expansion of 10 OsATG homologues occurred via segmental duplication events and that the occurrence of these OsATG homologues within each subfamily was asynchronous. The Ka/Ks ratios suggested purifying selection for four duplicated OsATG homologues and positive selection for two. Calculating the dates of the duplication events indicated that all duplication events might have occurred after the origin of the grasses, from 21.43 to 66.77 million years ago. Semi-quantitative RT–PCR analysis and mining the digital expression database of rice showed that all 33 OsATG homologues could be detected in at least one cell type of the various tissues under normal or stress growth conditions, but their expression was tightly regulated. The 10 duplicated genes showed expression divergence. The expression of most OsATG homologues was regulated by at least one treatment, including hormones, abiotic and biotic stresses, and nutrient limitation. The identification of OsATG homologues showing constitutive expression or responses to environmental stimuli provides new insights for in-depth characterization of selected genes of importance in rice.
Autism is a highly heritable neurodevelopmental disorder, and known genetic variants, mostly rare, account only for a small proportion of cases. Here we report a genome-wide association study on ...autism using two Chinese cohorts as gene discovery (n=2150) and three data sets of European ancestry populations for replication analysis of top association signals. Meta-analysis identified three single-nucleotide polymorphisms, rs936938 (P=4.49 × 10(-8)), non-synonymous rs6537835 (P=3.26 × 10(-8)) and rs1877455 (P=8.70 × 10(-8)), and related haplotypes, AMPD1-NRAS-CSDE1, TRIM33 and TRIM33-BCAS2, associated with autism; all were mapped to a previously reported linkage region (1p13.2) with autism. These genetic associations were further supported by a cis-acting regulatory effect on the gene expressions of CSDE1, NRAS and TRIM33 and by differential expression of CSDE1 and TRIM33 in the human prefrontal cortex of post-mortem brains between subjects with and those without autism. Our study suggests TRIM33 and NRAS-CSDE1 as candidate genes for autism, and may provide a novel insight into the etiology of autism.
We demonstrate superresolution imaging of single rare-earth emitting centers, namely, trivalent cerium, in yttrium aluminum garnet crystals by means of stimulated emission depletion (STED) ...microscopy. The achieved all-optical resolution is ≈50 nm. Similar results were obtained on H3 color centers in diamond. In both cases, STED resolution is improving slower than the conventional inverse square-root dependence on the depletion beam intensity. In the proposed model of this effect, the anomalous behavior is caused by excited state absorption and the interaction of the emitter with nonfluorescing crystal defects in its local surrounding.
The distribution and characteristics of microstructures (microcrack and grain) of Barre granite (BG) were investigated, and three orthogonal weak planes associated with the preferred orientations of ...microcracks were identified. It has been demonstrated that both the fracture toughness and the longitudinal wave speed depend on the direction of these weak planes. In this study, disk samples cut from one BG block are prepared for split Hopkinson pressure bar (SHPB) test. The axial directions of the samples are chosen to be parallel to the preferred direction of microcracks and the samples are grouped and denoted by Y (lowest P-wave velocity), Z (highest P-wave velocity), and X (intermediate P-wave velocity). Pulse-shaper technique is adopted to achieve equilibrium of dynamic stresses on both ends of the sample and constant strain rate during the dynamic loading. For samples within the same orientation group, the maximum stress achieved shows clear strain-rate sensitivity. The effect of microcracks on the dynamic compressive response of BG depends on the strain rate for a fixed loading duration (∼230
μs). For low strain-rate loading (∼70
s
−1) and high strain-rate loading (∼130
s
−1), the maximum dynamic stress achieved is not sensitive to the microcrack orientation; for intermediate strain rate (∼100
s
−1) loading, the maximum achieved stress for Y-samples is the largest. In addition, three dynamic compressive rock failure modes are identified: quasi-elastic, cracked, and fragmented. The correlation between the failure modes and the shape of the stress–strain curves is discussed.
We report an experimental study on the onset of the large-scale coherent mean flow in Rayleigh–Bénard turbulent convection. Shadowgraph and particle image velocimetry techniques are used to visualize ...the motion of thermal plumes and measure the velocity of the plumes and of the ‘background’ flow field, as the fluid motion evolves from quiescent to steady state. The experiment reveals the dynamical origin of the initial horizontal motion required by the large-scale flow: the fluid entrainment caused by the plume's vertical motion generates vortices surrounding the plume itself. These vortices in turn generate the initial horizontal motion of the flow field. Two types of interactions have been identified: (i) direct plume–vortex interaction; and (ii) plume–plume interaction via vortices. These interactions and the interaction and merging of the vortices from neighbouring plumes lead to groupings and/or merging of plumes, which in turn generate vortices of even larger scale. As a result of these interactions, the convective flow evolves into a coherent rotatory motion consisting of mainly the plumes themselves and spanning the whole convection box. This study clearly demonstrates that it is the thermal plumes that initiate the horizontal large-scale flow across the top and bottom conducting plates.
Fracture initiation toughness, fracture energy, fracture propagation toughness, and fracture velocity are key dynamic fracture parameters. We propose a method to simultaneously measure these ...parameters for mode-I fractures in split Hopkinson pressure bar (SHPB) testing with a notched semi-circular bend (SCB) specimen. The initiation toughness is obtained from the peak load given dynamic force equilibrium. A laser gap gauge (LGG) is developed to monitor the crack surface opening displacement (CSOD) of the specimen, from which the fracture velocity and the fracture energy can be calculated. The feasibility of this methodology for coarse-grained solids is demonstrated with the SHPB-SCB experiments on Laurentian granite.
Aluminum alloy AA5083 specimens (with a nominal composition of Al-4.4Mg-0.5Mn) from the same original plate were prepared with a variation in grain size imparted by cold rolling, cryorolling, equal ...channel angular pressing and high-pressure torsion. Electron backscatter diffraction was used to determine the grain size and misorientation. The effect of grain size on the degree of sensitization for AA5083 was studied via the ASTM G67 nitric acid mass lost test, upon specimens artificially sensitized at 150 degree C for 7 d. It was revealed that the intergranular corrosion caused by sensitization in AA5083 was significantly influenced by the grain size and processing methods used for grain refinement.
Summary
Background
Disseminated superficial actinic porokeratosis (DSAP) is a rare autosomal dominant disease. In our previous research, we found that a linkage region of DSAP in a large family is ...located at 12q23·2‐q24·1. Subsequently, the mevalonate kinase gene (MVK) was shown to be pathogenic in DSAP.
Objectives
To elucidate the mechanism by which MVK mutations lead to keratinocyte apoptosis and DSAP, and to report a new missense mutation, c.566 C>T (p.A189V), in MVK in a Chinese DSAP pedigree.
Methods
The half‐life of wild‐type (WT) MVK protein and mutants was assessed using cycloheximide treatment of cells. Dimerization of MVK was analysed by coimmunoprecipitation and glutathione S transferase pull‐down assay. MVK kinase activity, production of cell cholesterol, mitochondrial complex activity and apoptosis were detected, using the corresponding commercial kits, in cells overexpressing MVK WT and mutants.
Results
Mechanically, we demonstrated that both the pathogenic p.A189V mutant and a sporadic mutation p.H312R (c.935A>G), which we reported previously, have rapid degradation, decreased kinase activity and reduced production of cell cholesterol. Also, we found the p.H312R mutation confers on the MVK protein an inability to dimerize. Further, we demonstrated that the mutants are impaired in mitochondrial function and lead to increased apoptosis.
Conclusions
Our results provide an important basis for elucidating the mechanism by which MVK missense mutations contribute to DSAP.
What's already known about this topic
The mevalonate kinase gene (MVK) has been reported as pathogenic in disseminated superficial actinic porokeratosis (DSAP) in our team's previous work but the pathogenic mechanism of MVK mutations is unclear.
What does this study add?
We report a new missense mutation in MVK in a Chinese DSAP pedigree, and show that mutants affect mitochondrial function and lead to increased apoptosis.
What is the translational message?
We have elucidated changes in molecular structure that may arise from DSAP‐associated MVK mutations; these functional structural sites may provide a target for future small‐molecule drug designs.
Linked Comment: Betz. Br J Dermatol 2019; 181:241.
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Current catalogs of brain expression quantitative trait loci (eQTL) are incomplete and the findings do not replicate well across studies. All existing cortical eQTL studies are small and emphasize ...the need for a meta-analysis. We performed a meta-analysis of 424 brain samples across five studies to identify regulatory variants influencing gene expression in human cortex. We identified 3584 genes in autosomes and chromosome X with false discovery rate q<0.05 whose expression was significantly associated with DNA sequence variation. Consistent with previous eQTL studies, local regulatory variants tended to occur symmetrically around transcription start sites and the effect was more evident in studies with large sample sizes. In contrast to random SNPs, we observed that significant eQTLs were more likely to be near 5'-untranslated regions and intersect with regulatory features. Permutation-based enrichment analysis revealed that SNPs associated with schizophrenia and bipolar disorder were enriched among brain eQTLs. Genes with significant eQTL evidence were also strongly associated with diseases from OMIM (Online Mendelian Inheritance in Man) and the NHGRI (National Human Genome Research Institute) genome-wide association study catalog. Surprisingly, we found that a large proportion (28%) of ~1000 autosomal genes encoding proteins needed for mitochondrial structure or function were eQTLs (enrichment P-value=1.3 × 10(-9)), suggesting a potential role for common genetic variation influencing the robustness of energy supply in brain and a possible role in the etiology of some psychiatric disorders. These systematically generated eQTL information should be a valuable resource in determining the functional mechanisms of brain gene expression and the underlying biology of associations with psychiatric disorders.
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