Intrachromosomal Looping Is Required for Activation of Endogenous Pluripotency Genes during Reprogramming

SummaryGeneration of induced pluripotent stem cells (iPSCs) by defined factors is an extremely inefficient process, because there is a strong epigenetic block preventing cells from achieving pluripotency. Here we report that virally expressed factors bound to the promoters of their target genes to the same extent in both iPSCs and unreprogrammed cells (URCs). However, expression of endogenous pluripotentcy genes was observed only in iPSCs. Comparison of local chromatin structure of the OCT4 locus revealed that there was a cohesin-complex-mediated intrachromosomal loop that juxtaposes a downstream enhancer to the gene’s promoter, enabling activation of endogenous stemness genes. None of these long-range interactions were observed in URCs. Knockdown of the cohesin-complex gene SMC1 by RNAi abolished the intrachromosomal interaction and affected pluripotency. These findings highlight the importance of the SMC1-orchestrated intrachromosomal loop as a critical epigenetic barrier to the induction of pluripotency

CD180 Ligation Inhibits TLR7- and TLR9-Mediated Activation of Macrophages and Dendritic Cells Through the Lyn-SHP-1/2 Axis in Murine Lupus

Activation of TLR7 and TLR9 by endogenous RNA- or DNA-containing ligands, respectively, can lead to hyper-activation of immune cells, including macrophages and DCs, subsequently contributes to the pathogenesis of SLE. CD180, a TLR-like protein, is specifically involved in the development and activation of immune cells. Our previous study and others have reported that CD180-negative B cells are dramatically increased in SLE patients and responsible for the production of auto-antibodies. However, the mode of CD180 expression on macrophages and DCs in SLE remains unclear and the role of CD180 on regulating TLR7- and TLR9-mediated activation of macrophages and DCs are largely unknown. In the present study, we found that the percentages of CD180-negative macrophages and DCs were both increased in SLE patients and lupus-prone MRL/lpr mice compared with healthy donors and wild-type mice, respectively. Notably, ligation of CD180 significantly inhibited the activation of TLR7 and TLR9 signaling pathways in macrophages and DCs through the Lyn-SHP-1/2 axis. What's more, injection of anti-CD180 Ab could markedly ameliorate the lupus-symptoms of imiquimod-treated mice and lupus-prone MRL/lpr mice through inhibiting the activation of macrophages and DCs. Collectively, our results highlight a critical role of CD180 in regulating TLR7- and TLR9-mediated activation of macrophages and DCs, hinting that CD180 can be regarded as a potential therapeutic target for SLE treatment

Molecular Cloning, Characterization and Expression Analysis of Two Members of the Pht1 Family of Phosphate Transporters in Glycine max

BACKGROUND: Phosphorus is one of the macronutrients essential for plant growth and development. The acquisition and translocation of phosphate are pivotal processes of plant growth. In a large number of plants, phosphate uptake by roots and translocation within the plant are presumed to occur via a phosphate/proton cotransport mechanism. PRINCIPAL FINDINGS: We cloned two cDNAs from soybean (Glycine max), GmPT1 and GmPT2, which show homology to the phosphate/proton cotransporter PHO84 from the budding yeast Saccharomyces cerevisiae. The amino acid sequence of the products predicted from GmPT1 and GmPT2 share 61% and 63% identity, respectively, with the PHO84 in amino acid sequence. The deduced structure of the encoded proteins revealed 12 membrane-spanning domains with a central hydrophilic region. The molecular mass values are ∼58.7 kDa for GmPT1 and ∼58.6 kDa for GmPT2. Transiently expressed GFP-protein fusions provide direct evidence that the two Pi transporters are located in the plasma membrane. Uptake of radioactive orthophosphate by the yeast mutant MB192 showed that GmPT1 and GmPT2 are dependent on pH and uptake is reduced by the addition of uncouplers of oxidative phosphorylation. The K(m) for phosphate uptake by GmPT1 and GmPT2 is 6.65 mM and 6.63 mM, respectively. A quantitative real time RT-PCR assay indicated that these two genes are expressed in the roots and shoots of seedlings whether they are phosphate-deficient or not. Deficiency of phosphorus caused a slight change of the expression levels of GmPT1 and GmPT2. CONCLUSIONS: The results of our experiments show that the two phosphate transporters have low affinity and the corresponding genes are constitutively expressed. Thereby, the two phosphate transporters can perform translocation of phosphate within the plant

Comparative analysis of the transcriptome across distant species

The transcriptome is the readout of the genome. Identifying common features in it across distant species can reveal fundamental principles. To this end, the ENCODE and modENCODE consortia have generated large amounts of matched RNA-sequencing data for human, worm and fly. Uniform processing and comprehensive annotation of these data allow comparison across metazoan phyla, extending beyond earlier within-phylum transcriptome comparisons and revealing ancient, conserved features. Specifically, we discover co-expression modules shared across animals, many of which are enriched in developmental genes. Moreover, we use expression patterns to align the stages in worm and fly development and find a novel pairing between worm embryo and fly pupae, in addition to the embryo-to-embryo and larvae-to-larvae pairings. Furthermore, we find that the extent of non-canonical, non-coding transcription is similar in each organism, per base pair. Finally, we find in all three organisms that the gene-expression levels, both coding and non-coding, can be quantitatively predicted from chromatin features at the promoter using a 'universal model' based on a single set of organism-independent parameters

Figure Of Merit For Optimizing The Performance Of Uniform Lying Helix Cholesteric Liquid Crystals

The figure of merit (FoM) is defined to evaluate the performance of ULH devices. The trade-offs between operation voltage, transmittance, and response time in uniform lying helix (ULH) cholesteric liquid crystals (CLC) are investigated. Excellent agreement between theory and experiment is achieved. The viewing angle of ULH displays is also studied. Our results give first quantitative demonstration that ULH exhibits a similar viewing angle to IPS. After phase compensation, the isocontrast ratio of ULH can reach \u3e100:1 over 85° viewing cone

Energy Storage System Controller Design for Suppressing Electromechanical Oscillation of Power Systems

Through the feedback of the rotor speed and/or the grid frequency, an energy storage system (ESS) can effectively suppress the electromechanical oscillation of a power system. This paper proposes a novel control strategy and controller parameter design method for ESSs to achieve the desired performance of oscillation suppression, including smaller frequency and rate of change of frequency (ROCOF) deviation than their threshold values. Firstly, a dynamic model of the electromechanical time scale of a synchronous generator dominated power system with ESS was established. Then, based on the dynamic model and the electric torque analysis method, the mechanism of an ESS with the feedback signal of the rotor speed to suppress the electromechanical oscillation was investigated. Finally, the controller parameter design method for the ESS was developed to achieve the desired performance of oscillation suppression. With the help of the well-designed ESS, the electromechanical oscillation of a synchronous generator dominated power system can be effectively suppressed in shorter transient response times, and the grid frequency deviation and the ROCOF can be limited to below their threshold values. The simulation results also verify the effectiveness of the proposed control strategy and the controller parameter design method

Circulating Coxsackievirus A16 Identified as Recombinant Type A Human Enterovirus, China

To determine the relationship of coxsackievirus A16 (CA16) to prototype CA16-G10, we conducted a phylogenetic analysis of circulating CA16 strains in China. Complex recombinant forms of CA16-related viruses involving multiple human enteroviruses, subgroup A (CA4, CA16, and enterovirus 71), are prevalent among patients with hand, foot, and mouth disease

Macroscopic Model For Analyzing The Electro-Optics Of Uniform Lying Helix Cholesteric Liquid Crystals

A macroscopic model is developed for analyzing the electro-optics of short-pitch uniform lying helix (ULH) cholesteric liquid crystals (CLCs). Both flexoelectric effect and dielectric effect make important contributions to the maximum transmittance and operation voltage of the ULH devices. Based on the proposed macroscopic approximation, we derive an analytical expression to quantitatively evaluate the relative strength of these two effects. Very good agreement between theory and experiment is achieved. We also investigate the viewing angle of ULH CLC displays and find that their viewing angle characteristics are similar to those of conventional in-plane switching liquid crystal displays