ALBERT

Description: Article The transfer of spin polarization from electrons to nuclei is important for nuclear spin-based techniques such as nuclear magnetic resonance. Here Wang and colleagues achieve sensitive magnetic control of the hyperpolarization of nuclei near optically polarized nitrogen-vacancy centres in diamond. Nature Communications 4 doi: 10.1038/ncomms2930

Description: Mammalian splicing regulatory protein RNA-binding motif protein 4 (RBM4) has an alanine repeat-containing C-terminal domain (CAD) that confers both nuclear- and splicing speckle-targeting activities. Alanine-repeat expansion has pathological potential. Here we show that the alanine-repeat tracts influence the subnuclear targeting properties of the RBM4 CAD in cultured human cells. Notably, truncation of the alanine tracts redistributed a portion of RBM4 to paraspeckles. The alanine-deficient CAD was sufficient for paraspeckle targeting. On the other hand, alanine-repeat expansion reduced the mobility of RBM4 and impaired its splicing activity. We further took advantage of the putative coactivator activator (CoAA)-RBM4 conjoined splicing factor, CoAZ, to investigate the function of the CAD in subnuclear targeting. Transiently expressed CoAZ formed discrete nuclear foci that emerged and subsequently separated—fully or partially—from paraspeckles. Alanine-repeat expansion appeared to prevent CoAZ separation from paraspeckles, resulting in their complete colocalization. CoAZ foci were dynamic but, unlike paraspeckles, were resistant to RNase treatment. Our results indicate that the alanine-rich CAD, in conjunction with its conjoined RNA-binding domain(s), differentially influences the subnuclear localization and biogenesis of RBM4 and CoAZ.

Description: AMP-activated protein kinase-α1 as an activating kinase of TGF-β-activated kinase 1 has a key role in inflammatory signals Cell Death and Disease 3, e357 (July 2012). doi:10.1038/cddis.2012.95 Authors: S Y Kim, S Jeong, E Jung, K-H Baik, M H Chang, S A Kim, J-H Shim, E Chun & K-Y Lee

Description: Mutations in GATA4 and TBX5 are associated with congenital heart defects in humans. Interaction between GATA4 and TBX5 is important for normal cardiac septation, but the underlying molecular mechanisms are not well understood. Here, we show that Gata4 and Tbx5 are co-expressed in the embryonic atria and ventricle, but after E15.5, ventricular expression of Tbx5 decreases. Co-localization and co-immunoprecipitation studies demonstrate an interaction of Gata4 and Tbx5 in the developing atria and ventricles, but the ventricular interaction declines after E14.5. Gata4 +/– ;Tbx5 +/– mouse embryos display decreased atrial and ventricular myocardial thickness at E11.5, prior to cardiac septation. To determine the cell lineage in which the interaction was functionally significant in vivo , mice heterozygous for Gata4 in the myocardium or endocardium and heterozygous for Tbx5 ( Gata4 MyoDel/wt ;Tbx5 +/– and Gata4 EndoDel/wt ;Tbx5 +/– , respectively) were generated. Gata4 MyoDel/wt ;Tbx5 +/– mice displayed embryonic lethality, thin myocardium with reduced cell proliferation, and atrioventricular septation defects similar to Gata4;Tbx5 compound heterozygotes while Gata4 EndoDel/wt ;Tbx5 +/– embryos were normal. Cdk4 and Cdk2 , cyclin-dependent kinases required for myocardial development and septation were reduced in Gata4 +/– ;Tbx5 +/– hearts. Cdk4 is a known direct target of Gata4 and the regulation of Cdk2 in the developing heart has not been studied. Chromatin immunoprecipitation and transactivation studies demonstrate that Gata4 and Tbx5 directly regulate Cdk4 while only Tbx5 activates Cdk2 expression. These findings highlight the mechanisms by which disruption of the Gata4 and Tbx5 interaction in the myocardium contributes to cardiac septation defects in humans.

Description: Article In nanoscale magnetic resonance, the coupling with negatively charged nitrogen-vacancy centres in diamond—used as optical transducers—broadens the spectrum of the spin to detect. Wang et al. present a detection technique that resolves the spin spectra through optically detected cross-relaxation. Nature Communications doi: 10.1038/ncomms5135 Authors: Hai-Jing Wang, Chang S. Shin, Scott J. Seltzer, Claudia E. Avalos, Alexander Pines, Vikram S. Bajaj

Description: Scaling relationships among twig size, leaf size and leafing intensity fundamentally influence the twig–leaf deployment pattern, a property that affects the architecture and functioning of plants. However, our understanding of how these relationships change within a species or between species as a function of forest succession is unclear. We determined log–log scaling relationships between twig cross-sectional area (twig size) and each of total and individual leaf area, and leafing intensity (the number of leaves per twig volume) for 78 woody species along a successional series in subtropical evergreen forests in eastern China. The series included four stages: secondary shrub (S1), young (S2), sub-climax (S3) and climax evergreen broadleaved forests (S4). The scaling slopes in each of the three relationships did not differ among the four stages. The y -intercept did not shift among the successional stages in the relationship between twig cross-sectional area and total leaf area; however, the y -intercept was greatest in S4, intermediate in S3 and lowest in S2 and S1 for the relationship between twig size and individual leaf area, while the opposite pattern was found for the twig size-leafing intensity relationship. This indicates that late successional trees have few but large leaves while early successional trees have more small leaves per unit twig size. For the relationship between twig cross-sectional area and total leaf area, there was no difference in the regression slope between recurrent (appear in more than one stages) and non-recurrent species (appear in only one stage) for each of the S1–S2, S2–S3 and S3–S4 pairs. A significant difference in the y -intercept was found in the S2–S3 pair only. In the relationship between twig cross-sectional area and individual leaf area, the regression slope between recurrent and non-recurrent species was homogeneous in the S1–S2 and S3–S4 pairs, but heterogeneous in the S2–S3 pair. We conclude that forest succession caused the shift in the intercept, but did not affect scaling slopes for relationships among twig size, leaf size and leaf intensity. For recurrent species, the invariant scaling slope in the twig–leaf size relationship between adjacent pairs of successional stages may be related to their phenotypic plasticity by adjusting their twig and leaf deployment strategy to similar to what the non-recurrent species display.

Description: MicroRNAs (miRNAs) are small RNAs ~22 nt in length that are involved in the regulation of a variety of physiological and pathological processes. Advances in high-throughput small RNA sequencing (smRNA-seq), one of the next-generation sequencing applications, have reshaped the miRNA research landscape. In this study, we established an integrative database, the YM500 ( http://ngs.ym.edu.tw/ym500/ ), containing analysis pipelines and analysis results for 609 human and mice smRNA-seq results, including public data from the Gene Expression Omnibus (GEO) and some private sources. YM500 collects analysis results for miRNA quantification, for isomiR identification (incl. RNA editing), for arm switching discovery, and, more importantly, for novel miRNA predictions. Wetlab validation on 〉100 miRNAs confirmed high correlation between miRNA profiling and RT-qPCR results ( R = 0.84). This database allows researchers to search these four different types of analysis results via our interactive web interface. YM500 allows researchers to define the criteria of isomiRs, and also integrates the information of dbSNP to help researchers distinguish isomiRs from SNPs. A user-friendly interface is provided to integrate miRNA-related information and existing evidence from hundreds of sequencing datasets. The identified novel miRNAs and isomiRs hold the potential for both basic research and biotech applications.

Description: Insulin concentration is critical in culturing human neural stem cells and neurons Cell Death and Disease 4, e766 (August 2013). doi:10.1038/cddis.2013.295 Authors: Y-H Rhee, M Choi, H-S Lee, C-H Park, S-M Kim, S-H Yi, S-M Oh, H-J Cha, M-Y Chang & S-H Lee

Description: In recent years, human regulatory SNPs (rSNPs) have been widely studied. Here, we present database rSNPBase, freely available at http://rsnp.psych.ac.cn/ , to provide curated rSNPs that analyses the regulatory features of all SNPs in the human genome with reference to experimentally supported regulatory elements. In contrast with previous SNP functional annotation databases, rSNPBase is characterized by several unique features. (i) To improve reliability, all SNPs in rSNPBase are annotated with reference to experimentally supported regulatory elements. (ii) rSNPBase focuses on rSNPs involved in a wide range of regulation types, including proximal and distal transcriptional regulation and post-transcriptional regulation, and identifies their potentially regulated genes. (iii) Linkage disequilibrium (LD) correlations between SNPs were analysed so that the regulatory feature is annotated to SNP-set rather than a single SNP. (iv) rSNPBase provides the spatio-temporal labels and experimental eQTL labels for SNPs. In summary, rSNPBase provides more reliable, comprehensive and user-friendly regulatory annotations on rSNPs and will assist researchers in selecting candidate SNPs for further genetic studies and in exploring causal SNPs for in-depth molecular mechanisms of complex phenotypes.