ALBERT

Description: 〈p〉Soil organisms represent the most biologically diverse community on land and govern the turnover of the largest organic matter pool in the terrestrial biosphere. The highly complex nature of these communities at local scales has traditionally obscured efforts to identify unifying patterns in global soil biodiversity and biogeochemistry. As a result, environmental covariates have generally been used as a proxy to represent the variation in soil community activity in global biogeochemical models. Yet over the past decade, broad-scale studies have begun to see past this local heterogeneity to identify unifying patterns in the biomass, diversity, and composition of certain soil groups across the globe. These unifying patterns provide new insights into the fundamental distribution and dynamics of organic matter on land.〈/p〉

Description: Cleavage stimulation factor 64 kDa (CstF64) is an essential pre-mRNA 3′ processing factor and an important regulator of alternative polyadenylation (APA). Here we characterized CstF64–RNA interactions in vivo at the transcriptome level and investigated the role of CstF64 in global APA regulation through individual nucleotide resolution UV crosslinking and immunoprecipitation...

Description: Light-controlled inhibition of malignant glioma by opsin gene transfer Cell Death and Disease 4, e893 (October 2013). doi:10.1038/cddis.2013.425 Authors: F Yang, J Tu, J-Q Pan, H-L Luo, Y-H Liu, J Wan, J Zhang, P-F Wei, T Jiang, Y-H Chen & L-P Wang

Description: Methamphetamine induces autophagy as a pro-survival response against apoptotic endothelial cell death through the Kappa opioid receptor Cell Death and Disease 5, e1099 (March 2014). doi:10.1038/cddis.2014.64 Authors: J Ma, J Wan, J Meng, S Banerjee, S Ramakrishnan & S Roy

Description: Polycomb repression complex 2 (PRC2) component EZH2 tri-methylates H3K27 and exerts epigenetic repression on target gene expression. EZH2-mediated epigenetic control of RNA polymerase II (Pol II) transcribed coding gene transcription has been well established. However, little is known about EZH2-mediated epigenetic regulation of RNA polymerase III (Pol III) transcription. Here we present a paradigm that EZH2 is involved in the repression of Pol III transcription via interaction with transcriptional factor complex IIIC (TFIIIC). EZH2 and H3K27me3 co-occupy the promoter of tRNA Tyr , 5S rRNA and 7SL RNA genes. Depletion of EZH2 or inhibition of EZH2 methyltransferase activity led to upregulation of Pol III target gene transcription. EZH2-mediated repression of Pol III transcribed gene expression requires presence of SUZ12. SUZ12 was able to interact with TFIIIC complex and knockdown of SUZ12 decreased occupancy of EZH2 and H3K27me3 at the promoter of Pol III target genes. Our findings pointed out a previously unidentified role of PRC2 complex in suppressing transcription of Pol III transcribed non-translated RNA genes, putting Pol III on a new layer of epigenetic regulation.

Description: We applied multiple geochemical tracers ( 87 Sr/ 86 Sr, [Sr], 13 C, and 18 O) to waters and carbonates of the lower Colorado River system to evaluate its paleohydrology over the past 12 Ma. Modern springs in Grand Canyon reflect mixing of deeply derived (endogenic) fluids with meteoric (epigenic) recharge. Travertine (〈1 Ma) and speleothems (2–4 Ma) yield 87 Sr/ 86 Sr and 13 C and 18 O values that overlap with associated water values, providing justification for use of carbonates as a proxy for the waters from which they were deposited. The Hualapai Limestone (12–6 Ma) and Bouse Formation (5.6–4.8 Ma) record paleohydrology immediately prior to and during integration of the Colorado River. The Hualapai Limestone was deposited from 12 Ma (new ash age) to 6 Ma; carbonates thicken eastward to ~210 m toward the Grand Wash fault, suggesting that deposition was synchronous with fault slip. A fanning-dip geometry is suggested by correlation of ashes between subbasins using tephrochronology. New detrital-zircon ages are consistent with the "Muddy Creek constraint," which posits that Grand Wash Trough was internally drained prior to 6 Ma, with limited or no Colorado Plateau detritus, and that Grand Wash basin was sedimentologically distinct from Gregg and Temple basins until after 6 Ma. New isotopic data from Hualapai Limestone of Grand Wash basin show values and ranges of 87 Sr/ 86 Sr, 13 C, and 18 O that are similar to Grand Canyon springs and travertines, suggesting a long-lived spring-fed lake/marsh system sourced from western Colorado Plateau groundwater. Progressive up-section decrease in 87 Sr/ 86 Sr and 13 C and increase in 18 O in the uppermost 50 m of the Hualapai Limestone indicate an increase in meteoric water relative to endogenic inputs, which we interpret to record progressively increased input of high-elevation Colorado Plateau groundwater from ca. 8 to 6 Ma. Grand Wash, Hualapai, Gregg, and Temple basins, although potentially connected by groundwater, were hydrochemically distinct basins before ca. 6 Ma. The 87 Sr/ 86 Sr, 13 C, and 18 O chemostratigraphic trends are compatible with a model for downward integration of Hualapai basins by groundwater sapping and lake spillover. The Bouse Limestone (5.6–4.8 Ma) was also deposited in several hydrochemically distinct basins separated by bedrock divides. Northern Bouse basins (Cottonwood, Mojave, Havasu) have carbonate chemistry that is nonmarine. The 87 Sr/ 86 Sr data suggest that water in these basins was derived from mixing of high- 87 Sr/ 86 Sr Lake Hualapai waters with lower- 87 Sr/ 86 Sr, first-arriving "Colorado River" waters. Covariation trends of 13 C and 18 O suggest that newly integrated Grand Wash, Gregg, and Temple basin waters were integrated downward to the Cottonwood and Mojave basins at ca. 5–6 Ma. Southern, potentially younger Bouse basins are distinct hydrochemically from each other, which suggests incomplete mixing during continued downward integration of internally drained basins. Bouse carbonates display a southward trend toward less radiogenic 87 Sr/ 86 Sr values, higher [Sr], and heavier 18 O that we attribute to an increased proportion of Colorado River water through time plus increased evaporation from north to south. The 13 C and 18 O trends suggest alternating closed and open systems in progressively lower (southern) basins. We interpret existing data to permit the interpretation that the southernmost Blythe basin may have had intermittent mixing with marine water based on 13 C and 18 O covariation trends, sedimentology, and paleontology. [Sr] versus 87 Sr/ 86 Sr modeling suggests that southern Blythe basin 87 Sr/ 86 Sr values of ~0.710–0.711 could be produced by 25%–75% seawater mixed with river water (depending on [Sr] assumptions) in a delta–marine estuary system. We suggest several refinements to the "lake fill-and-spill" downward integration model for the Colorado River: (1) Lake Hualapai was fed by western Colorado Plateau groundwater from 12 to 8 Ma; (2) high-elevation Colorado Plateau groundwater was progressively introduced to Lake Hualapai from ca. 8 to 6 Ma; (3) Colorado River water arrived at ca. 5–6 Ma; and (4) the combined inputs led to downward integration by a combination of groundwater sapping and sequential lake spillover that first delivered Colorado Plateau water and detritus to the Salton Trough at ca. 5.3 Ma. We propose that the groundwater sapping mechanism strongly influenced lake evolution of the Hualapai and Bouse Limestones and that groundwater flow from the Colorado Plateau to Grand Wash Trough led to Colorado River integration.

Description: SLX4 assembles a toolkit of endonucleases SLX1, MUS81 and XPF, which is recruited to telomeres via direct interaction of SLX4 with TRF2. Telomeres present an inherent obstacle for DNA replication and repair due to their high propensity to form branched DNA intermediates. Here we provide novel insight into the mechanism and regulation of the SLX4 complex in telomere preservation. SLX4 associates with telomeres throughout the cell cycle, peaking in late S phase and under genotoxic stress. Disruption of SLX4's interaction with TRF2 or SLX1 and SLX1's nuclease activity independently causes telomere fragility, suggesting a requirement of the SLX4 complex for nucleolytic resolution of branched intermediates during telomere replication. Indeed, the SLX1–SLX4 complex processes a variety of telomeric joint molecules in vitro . The nucleolytic activity of SLX1-SLX4 is negatively regulated by telomeric DNA-binding proteins TRF1 and TRF2 and is suppressed by the RecQ helicase BLM in vitro . In vivo , in the presence of functional BLM, telomeric circle formation and telomere sister chromatid exchange, both arising out of nucleolytic processing of telomeric homologous recombination intermediates, are suppressed. We propose that the SLX4-toolkit is a telomere accessory complex that, in conjunction with other telomere maintenance proteins, ensures unhindered, but regulated telomere maintenance.

Description: Motivation: Researchers worldwide have generated a huge volume of genomic data, including thousands of genome-wide association studies (GWAS) and massive amounts of gene expression data from different tissues. How to perform a joint analysis of these data to gain new biological insights has become a critical step in understanding the etiology of complex diseases. Due to the polygenic architecture of complex diseases, the identification of risk genes remains challenging. Motivated by the shared risk genes found in complex diseases and tissue-specific gene expression patterns, we propose as an E mpirical Bayes approach to integrating P leiotropy and Tissue- S pecific information (EPS) for prioritizing risk genes. Results: As demonstrated by extensive simulation studies, EPS greatly improves the power of identification for disease-risk genes. EPS enables rigorous hypothesis testing of pleiotropy and tissue-specific risk gene expression patterns. All of the model parameters can be adaptively estimated from the developed expectation–maximization (EM) algorithm. We applied EPS to the bipolar disorder and schizophrenia GWAS from the Psychiatric Genomics Consortium, along with the gene expression data for multiple tissues from the Genotype-Tissue Expression project. The results of the real data analysis demonstrate many advantages of EPS. Availability and implementation : The EPS software is available on https://sites.google.com/site/liujin810822 . Contact: eeyang@hkbu.edu.hk Supplementary information : Supplementary data are available at Bioinformatics online.

Description: The Fanconi anemia protein SLX4 assembles a genome and telomere maintenance toolkit, consisting of the nucleases SLX1, MUS81 and XPF. Although it is known that SLX4 acts as a scaffold for building this complex, the molecular basis underlying this function of SLX4 remains unclear. Here, we report that functioning of SLX4 is dependent on its dimerization via an oligomerization motif called the BTB domain. We solved the crystal structure of the SLX4 BTB dimer, identifying key contacts (F681 and F708) that mediate dimerization. Disruption of BTB dimerization abrogates nuclear foci formation and telomeric localization of not only SLX4 but also of its associated nucleases. Furthermore, dimerization-deficient SLX4 mutants cause defective cellular response to DNA interstrand crosslinking agent and telomere maintenance, underscoring the contribution of BTB domain-mediated dimerization of SLX4 in genome and telomere maintenance.

Description: Gamma-ray burst (GRB) optical and X-ray afterglow luminosity is expected to correlate with the GRB isotropic equivalent kinetic energy of the outflow in the standard synchrotron model for GRB afterglows. Previous studies, using prompt GRB isotropic equivalent energy ( E iso ) as a proxy for isotropic equivalent kinetic energy, have generally confirmed a correlation between X-ray and optical afterglow luminosities. Assuming that GRB afterglow luminosity does not evolve strongly with redshift, we identify a strong Malmquist bias in GRB optical and X-ray afterglow luminosity data. We show that selection effects dominate the observed E iso – L opt, X correlations, and have likely been underestimated in other studies. The bias is strongest for a subset of optically faint bursts m  〉 24 at 24 h with z  〉 2. After removing this optical selection bias, the E iso – L opt, X correlation for long GRBs is not statistically significant, but combining both long and short GRB luminosity data the correlation is significant. Using the median of the E iso and L opt, X distributions, we apply the synchrotron model assuming the same power-law index for short and long GRBs, but different microphysical parameter distributions. Comparing the ratio of optical and X-ray luminosities, we find tentative evidence that the fraction of post-shock energy in magnetic fields, B , could be systematically higher in short GRBs compared to long GRBs.