ALBERT

Description: The North Carolina Racial Justice Act allows defendants to submit statistical studies of prosecutorial actions pertaining to their seeking the death penalty or in making peremptory challenges. These studies may consider data from four geographical regions: the state, county, judicial division or prosecutorial district. A study of the effect of race on peremptory challenges in death penalty cases demonstrating statistically significant disparities disadvantaging Black defendants has been submitted in several cases. This comment shows that a more appropriate statistical analysis yields much stronger statistical evidence that race entered into the peremptory challenge process in Randolph County than the affidavit submitted by the authors of the study. A subsequent sensitivity analysis indicates that in order for a characteristic to explain the highly statistically significant disparity, it would need to increase the odds of an individual being challenged by a factor of three and more than twice as many Black venire members would need to possess that characteristic as non-Blacks. Since the data examined excluded potential jurors who had been removed for cause, it may be difficult for the state to find a legitimate reason justifying the racial disparity.

Description: WW domain-containing oxidoreductase (WWOX) is a tumor suppressor that has been reported to lose function due to genetic alterations in several cancers. WWOX maps to the common chromosomal fragile site FRA16D and several copy number variations (CNVs) were found within this gene. In this study, we investigated the association between the CNVs of WWOX and lung cancer risk in four independent case–control studies, which are on 2942 lung cancer cases and 3074 cancer-free controls of southern, eastern and northern Chinese. A common CNV-67048 was genotyped by the Taqman real-time PCR, and its biological effect was accessed with protein expression and sequencing assays. We found that in comparison with the common 2-copy genotype, the carriers of loss variant genotypes (1-copy or 0-copy) had a significantly increased risk of lung cancer (adjusted OR = 1.39, 95% CI = 1.24–1.55, P = 9.01 x 10 –9 ) in a dose–response manner ( P trend = 1.12 x 10 –10 ), and the WWOX protein expressions in lung cancer tissues were significantly lower ( P = 0.036), accompanying a higher rate of exons absence ( P = 0.021) in subjects with loss genotypes of CNV-67048. Our data suggest that the loss genotypes of CNV-67048 in WWOX predispose their carriers to lung cancer; this might be related with altered WWOX gene expression and exons absence in them.

Description: The association of DSIF and NELF with initiated RNA Polymerase II (Pol II) is the general mechanism for inducing promoter-proximal pausing of Pol II. However, it remains largely unclear how the paused Pol II is released in response to stimulation. Here, we show that the release of the paused Pol II is cooperatively regulated by multiple P-TEFbs which are recruited by bromodomain-containing protein Brd4 and super elongation complex (SEC) via different recruitment mechanisms. Upon stimulation, Brd4 recruits P-TEFb to Spt5/DSIF via a recruitment pathway consisting of Med1, Med23 and Tat-SF1, whereas SEC recruits P-TEFb to NELF-A and NELF-E via Paf1c and Med26, respectively. P-TEFb-mediated phosphorylation of Spt5, NELF-A and NELF-E results in the dissociation of NELF from Pol II, thereby transiting transcription from pausing to elongation. Additionally, we demonstrate that P-TEFb-mediated Ser2 phosphorylation of Pol II is dispensable for pause release. Therefore, our studies reveal a co-regulatory mechanism of Brd4 and SEC in modulating the transcriptional pause release by recruiting multiple P-TEFbs via a Mediator- and Paf1c-coordinated recruitment network.

Description: Plant specific SGS3-like proteins are composed of various combinations of an RNA-binding XS domain, a zinc-finger zf-XS domain, a coil–coil domain and a domain of unknown function called XH. In addition to being involved in de novo 2 (IDN2) and SGS3, the Arabidopsis genome encodes 12 uncharacterized SGS3-like proteins. Here, we show that a group of SGS3-like proteins act redundantly in RNA-directed DNA methylation (RdDM) pathway in Arabidopsis . Transcriptome co-expression analyses reveal significantly correlated expression of two SGS3-like proteins, factor of DNA methylation 1 (FDM1) and FDM2 with known genes required for RdDM. The fdm1 and fdm2 double mutations but not the fdm1 or fdm2 single mutations significantly impair DNA methylation at RdDM loci, release transcriptional gene silencing and dramatically reduce the abundance of siRNAs originated from high copy number repeats or transposons. Like IDN2 and SGS3, FDM1 binds dsRNAs with 5' overhangs. Double mutant analyses also reveal that IDN2 and three uncharacterized SGS3-like proteins FDM3, FDM4 and FDM5 have overlapping function with FDM1 in RdDM. Five FDM proteins and IDN2 define a group of SGS3-like proteins that possess all four-signature motifs in Arabidopsis . Thus, our results demonstrate that this group of SGS3-like proteins is an important component of RdDM. This study further enhances our understanding of the SGS3 gene family and the RdDM pathway.

Description: Riparian plants in arid areas are subject to frequent hydrological fluctuations induced through natural flow variation and water use by humans. Although many studies have focused on the success of Tamarix ramosissima Ledeb. in its invaded ranges, its major competitor in its home range, Populus euphratica Oliv., historically has dominated riparian forests where both species occur naturally. Thus, identifying ecophysiological differences between T. ramosissima and its co-evolved competitor under varying hydrological conditions may help us understand how flow regimes affect dominance in its home range and promote invasion in new ranges. We examined ecophysiological responses of T. ramosissima and P. euphratica , which are both native to the Tarim River Basin, northwest China, to experimental alterations in groundwater. Seedlings of both species were grown in lysimeters, first under well-watered conditions and then exposed to different groundwater treatments: inundation, drought, and relatively shallow, moderate and deep groundwater. Under inundation, T. ramosissima showed little growth whereas P. euphratica died after ~45 days. Droughted seedlings of both species suffered from considerable water stress evidenced by slow growth, decreased total leaf area and specific leaf area, and decreased xylem water potential (), maximum photosynthetic rate and carboxylation efficiency. Both species had better ecophysiological performances under shallow and moderate groundwater conditions. When groundwater declined below rooting depth, seedlings of both species initially experienced decreased , but of T. ramosissima recovered late in the experiment whereas P. euphratica maintained decreased . This ability of T. ramosissima to recover from water deficit might result from its rapid root elongation and subsequent ability to acquire groundwater, which in turn likely provides ecophysiological advantages over P. euphratica . Our results suggest that recent groundwater declines along the Tarim River could facilitate T. ramosissima more due to its rapid response to changed groundwater availability. This trait may also help the success of T. ramosissima as it invaded riparian ecosystems in southwestern USA.

Description: The regulation of Schwann cell (SC) responses to injury stimuli by microRNAs (miRNAs) remains to be explored. Here, we identified 17 miRNAs that showed dynamic expression alterations at five early time points following rat sciatic nerve resection. Then we analyzed the expression pattern of 17 miRNAs, and integrated their putative targets with differentially expressed mRNAs. The resulting 222 potential targets were mainly involved in cell phenotype modulation, including immune response, cell death and cell locomotion. Among 17 miRNAs, miR-182 expression was up-regulated. The enhanced expression of miR-182 was correlated with nerve injury-induced phenotype modulation of SCs. Further investigation revealed that fibroblast growth factor 9 (FGF9) and neurotrimin (NTM) were two direct targets of miR-182 in SCs, with miR-182 binding to the 3'-untranslated region of FGF9 and NTM. Silencing of FGF9 and NTM recapitulated the inhibiting effect of miR-182 mimics on SC proliferation and migration, respectively, whereas enforced knockdown of FGF9 and NTM reversed the promoting effect of miR-182 inhibitor on SC proliferation and migration, respectively. Our data indicate that nerve injury inhibits SC proliferation and migration through rapid regulation of miR-182 by targeting FGF9 and NTM, providing novel insights into the roles of miRNAs in nerve injury and repair.

Description: PubChem ( https://pubchem.ncbi.nlm.nih.gov ) is a public repository for information on chemical substances and their biological activities, launched in 2004 as a component of the Molecular Libraries Roadmap Initiatives of the US National Institutes of Health (NIH). For the past 11 years, PubChem has grown to a sizable system, serving as a chemical information resource for the scientific research community. PubChem consists of three inter-linked databases, Substance, Compound and BioAssay. The Substance database contains chemical information deposited by individual data contributors to PubChem, and the Compound database stores unique chemical structures extracted from the Substance database. Biological activity data of chemical substances tested in assay experiments are contained in the BioAssay database. This paper provides an overview of the PubChem Substance and Compound databases, including data sources and contents, data organization, data submission using PubChem Upload, chemical structure standardization, web-based interfaces for textual and non-textual searches, and programmatic access. It also gives a brief description of PubChem3D, a resource derived from theoretical three-dimensional structures of compounds in PubChem, as well as PubChemRDF, Resource Description Framework (RDF)-formatted PubChem data for data sharing, analysis and integration with information contained in other databases.