ALBERT

Description: Activity-dependent gene transcription, including that of the brain-derived neurotrophic factor (Bdnf) gene, has been implicated in various cognitive functions. We previously demonstrated that mutant mice with selective disruption of activity-dependent BDNF expression (BDNF-KIV mice) exhibit deficits in GABA-mediated inhibition in the prefrontal cortex (PFC). Here, we show that disruption of...

Description: Two independent clinical studies have reported that fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist, has robust therapeutic effects on microvascular complications of diabetes, including diabetic retinopathy (DR) in type 2 diabetic patients. However, the expression and function of PPARα in the retina are unclear. Here, we demonstrated that PPARα...

Description: Knowledge of pressure-induced structural changes in glasses is important in various scientific fields as well as in engineering and industry. However, polyamorphism in glasses under high pressure remains poorly understood because of experimental challenges. Here we report new experimental findings of ultrahigh-pressure polyamorphism in GeO2 glass, investigated using a newly...

Description: We invert Global Positioning System (GPS) velocity data to estimate fault slip rates in California using a fault-based crustal deformation model with geologic constraints. The model assumes buried elastic dislocations across the region using Uniform California Earthquake Rupture Forecast Version 3 (UCERF3) fault geometries. New GPS velocity and geologic slip-rate data were compiled by the UCERF3 deformation working group. The result of least-squares inversion shows that the San Andreas fault slips at 19–22 mm/yr along Santa Cruz to the North Coast, 25–28 mm/yr along the central California creeping segment to the Carrizo Plain, 20–22 mm/yr along the Mojave, and 20–24 mm/yr along the Coachella to the Imperial Valley. Modeled slip rates are 7–16 mm/yr lower than the preferred geologic rates from the central California creeping section to the San Bernardino North section. For the Bartlett Springs section, fault slip rates of 7–9 mm/yr fall within the geologic bounds but are twice the preferred geologic rates. For the central and eastern Garlock, inverted slip rates of 7.5 and 4.9 mm/yr, respectively, match closely with the geologic rates. For the western Garlock, however, our result suggests a low slip rate of 1.7 mm/yr. Along the eastern California shear zone and southern Walker Lane, our model shows a cumulative slip rate of 6.2–6.9 mm/yr across its east–west transects, which is ~1 mm/yr increase of the geologic estimates. For the off-coast faults of central California, from Hosgri to San Gregorio, fault slips are modeled at 1–5 mm/yr, similar to the lower geologic bounds. For the off-fault deformation, the total moment rate amounts to 0.88 x 10 19 N·m/yr, with fast straining regions found around the Mendocino triple junction, Transverse Ranges and Garlock fault zones, Landers and Brawley seismic zones, and farther south. The overall California moment rate is 2.76 x 10 19 N·m/yr, which is a 16% increase compared with the UCERF2 model. Online Material: Table of geological slip rates.

Description: 〈p〉Meiotic resumption-coupled degradation of maternal transcripts occurs during oocyte maturation in the absence of mRNA transcription. The CCR4–NOT complex has been identified as the main eukaryotic mRNA deadenylase. 〈i〉In vivo〈/i〉 functional and mechanistic information regarding its multiple subunits remains insufficient. 〈i〉Cnot6l〈/i〉, one of four genes encoding CCR4–NOT catalytic subunits, is preferentially expressed in mouse oocytes. Genetic deletion of 〈i〉Cnot6l〈/i〉 impaired deadenylation and degradation of a subset of maternal mRNAs during oocyte maturation. Overtranslation of these undegraded mRNAs caused microtubule–chromosome organization defects, which led to activation of spindle assembly checkpoint and meiotic cell cycle arrest at prometaphase. Consequently, 〈i〉Cnot6l〈/i〉〈sup〉–/–〈/sup〉 female mice were severely subfertile. The function of CNOT6L in maturing oocytes is mediated by RNA-binding protein ZFP36L2, not maternal-to-zygotic transition licensing factor BTG4, which interacts with catalytic subunits CNOT7 and CNOT8 of CCR4–NOT. Thus, recruitment of different adaptors by different catalytic subunits ensures stage-specific degradation of maternal mRNAs by CCR4–NOT. This study provides the first direct genetic evidence that CCR4–NOT-dependent and particularly CNOT6L-dependent decay of selective maternal mRNAs is a prerequisite for meiotic maturation of oocytes.〈/p〉

Description: An increased knowledge of the genetic regulation of expression in Arabidopsis thaliana is likely to provide important insights about the basis of the plant’s extensive phenotypic variation. Here, we reanalyzed two publicly available datasets with genome-wide data on genetic and transcript variation in large collections of natural A. thaliana accessions. Transcripts from more than half of all genes were detected in the leaves of all accessions, and from nearly all annotated genes in at least one accession. Thousands of genes had high transcript levels in some accessions, but no transcripts at all in others, and this pattern was correlated with the genome-wide genotype. In total, 2669 eQTL were mapped in the largest population, and 717 of them were replicated in the other population. A total of 646 cis -eQTL-regulated genes that lacked detectable transcripts in some accessions was found, and for 159 of these we identified one, or several, common structural variants in the populations that were shown to be likely contributors to the lack of detectable RNA transcripts for these genes. This study thus provides new insights into the overall genetic regulation of global gene expression diversity in the leaf of natural A. thaliana accessions. Further, it also shows that strong cis -acting polymorphisms, many of which are likely to be structural variations, make important contributions to the transcriptional variation in the worldwide A. thaliana population.

Description: T cell activation is a well-established model for studying cellular responses to exogenous stimulation. Using strand-specific RNA-seq, we observed that intron retention is prevalent in polyadenylated transcripts in resting CD4 + T cells and is significantly reduced upon T cell activation. Several lines of evidence suggest that intron-retained transcripts are less stable than fully spliced transcripts. Strikingly, the decrease in intron retention (IR) levels correlate with the increase in steady-state mRNA levels. Further, the majority of the genes upregulated in activated T cells are accompanied by a significant reduction in IR. Of these 1583 genes, 185 genes are predominantly regulated at the IR level, and highly enriched in the proteasome pathway, which is essential for proper T cell proliferation and cytokine release. These observations were corroborated in both human and mouse CD4 + T cells. Our study revealed a novel post-transcriptional regulatory mechanism that may potentially contribute to coordinated and/or quick cellular responses to extracellular stimuli such as an acute infection.

Description: Protein turnover can be achieved via the lysosome/vacuole and the autophagic degradation pathways. Evidence has accumulated revealing that efficient autophagic degradation requires functional endosomal sorting complex required for transport (ESCRT) machinery. However, the interplay between the ESCRT machinery and the autophagy regulator remains unclear. Here, we show that FYVE domain...

Description: SBF-1 exerts strong anticervical cancer effect through inducing endoplasmic reticulum stress-associated cell death via targeting sarco/endoplasmic reticulum Ca2+-ATPase 2 Cell Death and Disease 5, e1581 (December 2014). doi:10.1038/cddis.2014.538 Authors: W Li, Z Ouyang, Q Zhang, L Wang, Y Shen, X Wu, Y Gu, Y Shu, B Yu, X Wu, Y Sun & Q Xu

Description: Aims Although stem CO 2 efflux is critical to ecosystem carbon and energy balance and its feedback to future climate change, little information is available on stem CO 2 efflux and its responses to temperature, especially in subtropical China. This study aims to (i) evaluate the temporal and spatial variations of stem CO 2 efflux of three species, including oak ( Quercus acutissima Carr.), masson pine ( Pinus massoniana Lamb.) and loblolly pine ( Pinus taeda Linn.) in subtropical China and (ii) analyze the temperature sensitivity of stem CO 2 efflux in the three species based on 2-year field measurements. Methods We measured stem CO 2 efflux and stem temperature (at 3 cm depth) of the three species using the horizontally oriented soil chamber technique from September 2008 to August 2010. We also conducted a 24-h measurement to examine the diurnal variation of stem CO 2 efflux in three consecutive days in April 2009. Important findings The temporal dynamics of stem CO 2 efflux followed the change of the stem temperature in a 3-cm depth with a bell-shaped curve in the three species. Stem temperature explained 77–85% of the seasonal variations of stem CO 2 efflux over the entire study period in the three species. The temperature sensitivity ( Q 10 ) of stem CO 2 efflux was obviously different among the three species with higher Q 10 value found in oak (2.24) and lower values in the coniferous species (1.76 and 1.63). Our results also showed that the Q 10 values of stem CO 2 efflux in all the three species were lower in the growing season than that in the non-growing season, indicating that the growth and maintenance respiration had different temperature responses. Moreover, we found that the temperature-normalized stem CO 2 efflux ( R 10 ) changed greatly between the growing and non-growing seasons in oak and masson pine, but not in loblolly pine. Additionally, we also found that in the non-growing season, the principal factor responsible for the spatial variation of stem CO 2 efflux among the 15 sampling trees was sapwood volume, whereas in the growing season, stem CO 2 efflux was closely related to annual dry-matter production in the three subtropical species.