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The transverse thermoelectric effect based on the anomalous Nernst effect (ANE) has attracted attention, especially for thermoelectric and spintronic applications. Fe 3 X (X = Ga, Al) is known to exhibit a large ANE at room temperature owing to the topological electronic band structure so-called nodal web. Here, we systematically investigate ANE in the polycrystalline Fe3Ga1−xAlx and Fe3Al1−xSix. Despite significant chemical substitutions, a very robust feature of the large ANE − S y x ∼ 5.7 μ V/K is found for Fe3Ga1−xAlx (0 ≲ x ≲ 0.6), exhibiting a striking x independent nodal web contribution. Since aluminum is more low-cost and abundant than gallium, our results indicate Fe3Ga1−xAlx (x ∼ 0.6) should be suitable for large-scale thermoelectric applications. [ABSTRACT FROM AUTHOR]

Biologic function of the majority of microRNAs (miRNAs) is still unknown. Uncovering the function of miRNAs is hurdled by redundancy among different miRNAs. The deletion of Dgcr8 leads to the deficiency in producing all canonical miRNAs, therefore, overcoming the redundancy issue. Dgcr8 knockout strategy has been instrumental in understanding the function of miRNAs in a variety of cells in vitro and in vivo. In this review, we will first give a brief introduction about miRNAs, miRNA biogenesis pathway and the role of Dgcr8 in miRNA biogenesis. We will then summarize studies performed with Dgcr8 knockout cell models with a focus on embryonic stem cells. After that, we will summarize results from various in vivo Dgcr8 knockout models. Given significant phenotypic differences in various tissues between Dgcr8 and Dicer knockout, we will also briefly review current progresses on understanding miRNA-independent functions of miRNA biogenesis factors. Finally, we will discuss the potential use of a new strategy to stably express miRNAs in Dgcr8 knockout cells. In future, Dgcr8 knockout approaches coupled with innovations in miRNA rescue strategy may provide further insights into miRNA functions in vitro and in vivo. [ABSTRACT FROM AUTHOR]

For the bismuth sodium titanate (BNT)-based materials, the thermal depolarization temperature ( T d ) is always an obstacle for practical applications. Recently, BNT/ZnO composite has provided one method to resist the thermal depolarization, and however, T d values just increase to a small extent and the conclusions derive from ZnO merely. A universal selection principle for the oxides will be helpful for us to choose the suitable oxides to effectively resist the thermal depolarization, which is desperately demanded but still lacks in BNT/oxide composites. Here, we report that the deferred thermal depolarization can be also obtained in piezoelectric Bi 0.5 (Na 0.8 K 0.2 ) 0.5 TiO 3 : Al 2 O 3 (BNKT:Al 2 O 3 ) composites. T d is deferred to the higher temperatures (from 116 °C to 227 °C) with increasing Al 2 O 3 contents, as evidenced by the temperature dependence of dielectric, ferroelectric and piezoelectric properties. In addition, the piezoelectricity of BNKT:0.15Al 2 O 3 remains stable at a high temperature (∼210 °C). And, the thermal deviatoric stress from the coefficients of thermal expansion (CTE) discrepancies between Al 2 O 3 and BNKT matrix provides a stronger stabilization force than the ions diffusion-induced destabilization force, resulting in the ultimate deferred thermal depolarization and the significantly increased T d values. In particular, according to the results from the representative BNT/oxides (i.e., ZnO, Al 2 O 3 , ZrO 2 , HfO 2 ) composite, the oxide selection principle (regulating several competing factors) is given to form the appropriate thermal resistant BNT/oxide composite, which may further open the door for piezoelectric BNT-based materials from the research and application scope. [ABSTRACT FROM AUTHOR]

This study focused on eleven aspects: materials, tools, process, identity, evaluation, price, storage, packaging, beliefs, marketing, and investment and drew research results from them. The research objectives were to study the historical and cultural background of pearl raising in Hepu county, Guangxi Province, the People's Republic of China, to study the current situation and problems of pearl raising for jewelry making, medical health products, and medical cosmetics in Hepu County Guangxi Province, and to study the sustainability of pearl raising. Results found that, in the past, the local pearl products were regarded as an existing pearl treasure among the local people and were closely related to everyday life, including cultivating, processing, using, and wearing as ornaments and decorations. The behavior of local people was concerned with the local sustainability of pearl raising for jewelry making, medical health products, and medical cosmetics. The products were natural and spawned a vast treasure trove of local wisdom and local identities. Though, in recent years, the uses and aims of the pearl products were diversified, they remain essential items for local people and continue to exist at the subliminal level of society. [ABSTRACT FROM AUTHOR]

Previous experiments have identified numerous RNA ligase deoxyribozymes, each of which can synthesize either 2',5'-branched RNA, linear 2'-5'-linked RNA, or linear 3'-5'-linked RNA. These products may be formed by reaction of a 2'-hydroxyl or 3'-hydroxyl of one RNA substrate with the 5'-triphosphate of a second RNA substrate. Here the inherent propensities for nucleophilic reactivity of specific hydroxyl groups were assessed using RNA substrates related to the natural sequences of spliceosome substrates and group II introns. With the spliceosome substrates, nearly half of the selected deoxyribozymes mediate a ligation reaction involving the natural branch-point adenosine as the nucleophile. In contrast, mostly linear RNA is obtained with the group II intron substrates. Because the two sets of substrates differ at only three nucleotides, we conclude that the location of the newly created ligation junction in DNA-catalyzed branch formation depends sensitively on the RNA substrate sequences. During the experiment that led primarily to branched RNA, we abruptly altered the selection strategy to demand that the deoxyribozymes create linear 3'-5' linkages by introducing an additional selection step involving the 3'-5'-selective 8-17 deoxyribozyme. Although no 3'-5' linkages (⩽ 1%) were detectable in the pool products at the point that the 3'-5' selection pressure was applied, deoxyribozymes that specifically create 3'-5' linkages quickly emerged within a few selection rounds. Our success in obtaining 3'-5' linkages via this approach shows that the outcome of deoxyribozyme selection experiments can be dramatically redirected by strategic changes in the selection procedure, even at a late stage. These results relate to natural selection, in which abrupt environmental variation can provide a rapid change in selection pressure. Linear 3'-5' RNA linkages are an important practical objective because the native backbone is desirable in site-specifically modified ribozymes assembled by ligation. Therefore, this new approach to obtain 3'-5'-selective RNA ligase deoxyribozymes is particularly important for ongoing selection efforts. [ABSTRACT FROM AUTHOR]

Virtual synchronous generator control is considered as an effective solution to optimize the frequency response characteristics of doubly fed induction generator. However, due to the insufficient control bandwidth of the original virtual synchronous generator, it has little control effect over the oscillating components of the power caused by the unbalanced grid voltage. Therefore, long-term unbalanced voltage will cause a series of problems, such as distortion of stator and rotor currents, as well as oscillations of power and electromagnetic torque, which seriously affect the power quality and the operating performance of the doubly fed induction generator. To solve these problems, the concept of extended power is introduced, and the second-order generalized integrator-based resonant controller is used to control the extended power and traditional power. Control targets of the extended power method are discussed and extended, so that the doubly fed induction generator system using extended power resonant control-based virtual synchronous generator control can realize three different control targets under the unbalanced grid condition. The three control targets are: balanced and sinusoidal stator current, sinusoidal stator current and constant active power, and sinusoidal stator current and constant reactive power and electromagnetic torque. The three control targets can also be flexibly switched according to the real-time requirements of the grid with unbalanced voltage. The simulation results verify the effectiveness of the control method. [ABSTRACT FROM AUTHOR]

Oxygen sensor is an important technique in various applications including industrial process control, medical equipment, biological fabrication, etc. The reported optical fiber‐based configurations so far, using gas‐sensitive coating do not meet the stringent performance targets, such as fast response time and low limit of detection (LOD). Tin‐based halide perovskites are sensitive to oxygen with potential use for sensor applications. Here, the halide perovskite‐based oxygen optical fiber sensor by combining phenylethylammonium tin iodide (PEA2SnI4) and tilted fiber Bragg grating (TFBG) is demonstrated. The PEA2SnI4‐based oxygen optical fiber sensor is reversible at room temperature with a response time of about 10 s, and the experimental LOD approaches to an extremely low oxygen concentration of about 50 ppm. The as‐fabricated oxygen sensor shows a relative response change of 0.6 dB for an oxygen concentration increase from 50 ppm to 5% with good gas selection against NO2, CO, CO2, H2. This work extends the sensor applications of halide perovskites, providing a novel technique for rapid and repeatable oxygen gas detection at a low level. [ABSTRACT FROM AUTHOR]

The section: "miRNA‑independent functions of DICER" was missed between the section "miRNA‑independent functions of DROSHA and DGCR8" and the section "The Dgcr8 knockout strategy to study miRNA functions" in the original publications. [ABSTRACT FROM AUTHOR]

[Display omitted] TRIM71 is an RNA-binding protein with ubiquitin ligase activity. Numerous functions of mammalian TRIM71, including cell cycle regulation, embryonic stem cell (ESC) self-renewal, and reprogramming of pluripotent stem cells, are related to its RNA-binding property. We previously reported that a long noncoding RNA (lncRNA) Trincr1 interacts with mouse TRIM71 (mTRIM71) to repress FGF/ERK pathway in mouse ESCs (mESCs). Herein, we identify an RNA motif specifically recognized by mTRIM71 from Trincr1 RNA, and solve the crystal structure of the NHL domain of mTRIM71 complexed with the RNA motif. Similar to the zebrafish TRIM71, mTRIM71 binds to a stem-loop structured RNA fragment of Trincr1, and an adenosine base at the loop region is crucial for the mTRIM71 interaction. We map similar hairpin RNAs preferably bound by TRIM71 in the mRNA UTRs of the cell-cycle related genes regulated by TRIM71. Furthermore, we identify key residues of mTRIM71, conserved among mammalian TRIM71 proteins, required for the RNA-binding property. Single-site mutations of these residues significantly impair the binding of TRIM71 to hairpin RNAs in vitro and to mRNAs of Cdkn1a/p21 and Rbl2/p130 in mESCs. Furthermore, congenital hydrocephalus (CH) specific mutation of mTRIM71 impair its binding to the RNA targets as well. These results reveal molecular mechanism behind the recognition of RNA by mammalian TRIM71 and provide insights into TRIM71 related diseases. [ABSTRACT FROM AUTHOR]

Global dosage control is an underlying miRNA regulatory strategy to achieve accurate post-transcriptional regulation. miRNA dosage control regulates embryonic development, stem cell fate decisions, neurodevelopment and immune responses. miRNA dosage control occurs at different steps of miRNA biogenesis in various physiological contexts. Dysregulation of global miRNA dosage contributes to cancer, embryo death, and neurological diseases. Artificial manipulation of global miRNA dosage provides a novel approach to treat human diseases. In mammals, miRNAs recognize target mRNAs via base pairing, which leads to a complex 'multiple-to-multiple' regulatory network. Previous studies have focused on the regulatory mechanisms and functions of individual miRNAs, but alterations of many individual miRNAs do not strongly disturb the miRNA regulatory network. Recent studies revealed the important roles of global miRNA dosage control events in physiological processes and pathogenesis, suggesting that miRNAs can be considered as a 'cellular buffer' that controls cell fate. Here, we review the current state of research on how global miRNA dosage is tightly controlled to regulate development, tumorigenesis, neurophysiology, and immunity. We propose that methods of controlling global miRNA dosage may serve as effective therapeutic tools to cure human diseases. [ABSTRACT FROM AUTHOR]

SUMMARY: The regulated biosynthesis of chlorophyll is important because of its effects on plant photosynthesis and dry biomass production. In this study, a map‐based cloning approach was used to isolate the cytochrome P450‐like gene BnaC08g34840D (BnCDE1) from a chlorophyll‐deficient mutant (cde1) of Brassica napus obtained by ethyl methanesulfonate (EMS) mutagenization. Sequence analyses revealed that BnaC08g34840D in the cde1 mutant (BnCDE1I320T) encodes a substitution at amino acid 320 (Ile320Thr) in the conserved region. The over‐expression of BnCDE1I320T in ZS11 (i.e., gene‐mapping parent with green leaves) recapitulated a yellow‐green leaf phenotype. The CRISPR/Cas9 genome‐editing system was used to design two single‐guide RNAs (sgRNAs) targeting BnCDE1I320T in the cde1 mutant. The knockout of BnCDE1I320T in the cde1 mutant via a gene‐editing method restored normal leaf coloration (i.e., green leaves). These results indicate that the substitution in BnaC08g34840D alters the leaf color. Physiological analyses showed that the over‐expression of BnCDE1I320T leads to decreases in the number of chloroplasts per mesophyll cell and in the contents of the intermediates of the chlorophyll biosynthesis pathway in leaves, while it increases heme biosynthesis, thereby lowering the photosynthetic efficiency of the cde1 mutant. The Ile320Thr mutation in the highly conserved region of BnaC08g34840D inhibited chlorophyll biosynthesis and disrupted the balance between heme and chlorophyll biosynthesis. Our findings may further reveal how the proper balance between the chlorophyll and heme biosynthesis pathways is maintained. Significance Statement: Genetic changes in the chlorophyll biosynthesis pathway may affect plant photosynthesis and dry biomass production, and the genetic and molecular mechanisms of leaf‐color variations are complex. We found a novel CYP705 family gene (BnCDE1I320T) of cytochrome P450 superfamily affected the contents of chlorophyll intermediates and heme to control the leaf color by map‐based cloning and genetic transformation experiments in Brassica napus. [ABSTRACT FROM AUTHOR]

Post-transcriptional and translational regulations play essential roles during cellular reprogramming and in the maintenance and differentiation of pluripotent stem cells (PSCs). MicroRNAs (miRNAs) control cell cycle, glycolysis, chromatin state, survival and pluripotency of ESCs. Likewise, many miRNAs assist or act as a barrier for the generation of induced pluripotent stem cells (iPSCs). Recent studies also reveal exciting new directions on miRNA functions in regulating the switch between naive and primed pluripotent states as well as the establishment of totipotent-like state. Furthermore, the biogenesis and function of pluripotency related miRNAs are regulated by various RNA binding proteins (RBPs) at different levels. Revealing the interplay between RBPs and miRNAs will advance our understanding of molecular mechanisms controlling pluripotency and provide better means to manipulate PSCs for clinical applications. In this review, we summarize recent findings on the function of miRNAs in ESCs and during reprogramming. In addition, we also discuss new directions on miRNA functions in regulating the switch between different pluripotent states and RBP-mediated regulation of miRNA biogenesis and function in pluripotency control. [ABSTRACT FROM AUTHOR]

Thermophilic nucleic acid polymerases, isolated from organisms that thrive in extremely hot environments, possess great DNA/RNA synthesis activities under high temperatures. These enzymes play indispensable roles in central life activities involved in DNA replication and repair, as well as RNA transcription, and have already been widely used in bioengineering, biotechnology, and biomedicine. Xeno nucleic acids (XNAs), which are analogs of DNA/RNA with unnatural moieties, have been developed as new carriers of genetic information in the past decades, which contributed to the fast development of a field called xenobiology. The broad application of these XNA molecules in the production of novel drugs, materials, and catalysts greatly relies on the capability of enzymatic synthesis, reverse transcription, and amplification of them, which have been partially achieved with natural or artificially tailored thermophilic nucleic acid polymerases. In this review, we first systematically summarize representative thermophilic and hyperthermophilic polymerases that have been extensively studied and utilized, followed by the introduction of methods and approaches in the engineering of these polymerases for the efficient synthesis, reverse transcription, and amplification of XNAs. The application of XNAs facilitated by these polymerases and their mutants is then discussed. In the end, a perspective for the future direction of further development and application of unnatural nucleic acid polymerases is provided. [ABSTRACT FROM AUTHOR]

The impact of modification in molecules or deacetylation of konjac glucomannan (KGM) on the stress resistance in vivo has rarely been studied systematically. This research studied the effects of KGM with different molecular weights and degrees of deacetylation on the stress resistance and physical fitness of Caenorhabditis elegans. After the nematodes were incubated with modified KGM, the survival rate of nematodes under oxidative and heat stress, as well as the fertility and locomotion were measured. KGM(2-5) with molecular weight of 212, 124, 94 and 67 kDa can significantly prolong the mean and maximum lifespan of nematodes in the presence of paraquat. Under heat stress, all partially degraded konjac glucomannan (PDKGM) showed the significant extension of survival rates. Da(1-3) with deacetylation of 7%, 32% and 46% improved the survival rates of nematodes under oxidative stress. Furthermore, genes expression showed that KGM(2-5) and Da(1-3) upregulated the expression of sod-3, hsp-16.2, and atf-7. Taken together, molecular weight reduction or deacetylation of KGM have a significant impact on the stress resistance in vivo. PDKGM applied in stress resistance will be suggested not to exceed 200 kDa and deacylation of KGM will be suggested to be below 50%. Diagram illustrating impacts of konjac glucomannan with degradation (PDKGM) and with deacetylation (Da-KGM) on stress resistance of Caenorhabditis elegans as well as underlying mechanisms. [Display omitted] • Partially degraded KGM improved stress resistances, fertilities and locomotion. • Moderate deacetylation enhanced worm resistance, fecundity and motility. • Degradation of KGM applied in stress resistance was suggested not to exceed 200 ku. • Deacetylation of KGM applied in stress resistance was suggested to be below 50%. [ABSTRACT FROM AUTHOR]

Background: Plant height is an important architecture trait which is a fundamental yield-determining trait in crops. Variety with dwarf or semi-dwarf phenotype is a major objective in the breeding because dwarfing architecture can help to increase harvest index, increase planting density, enhance lodging resistance, and thus be suitable for mechanization harvest. Although some germplasm or genes associated with dwarfing plant type have been carried out. The molecular mechanisms underlying dwarfism in oilseed rape (Brassica napus L.) are poorly understood, restricting the progress of breeding dwarf varieties in this species. Here, we report a new dwarf mutant Bndwarf2 from our B. napus germplasm. We studied its inheritance and mapped the dwarf locus BnDWARF2. Results: The inheritance analysis showed that the dwarfism phenotype was controlled by one semi-dominant gene, which was mapped in an interval of 787.88 kb on the C04 chromosome of B. napus by Illumina Brassica 60 K Bead Chip Array. To fine-map BnDWARF2, 318 simple sequence repeat (SSR) primers were designed to uniformly cover the mapping interval. Among them, 15 polymorphic primers that narrowed down the BnDWARF2 locus to 34.62 kb were detected using a F2:3 family population with 889 individuals. Protein sequence analysis showed that only BnaC04.BIL1 (BnaC04g41660D) had two amino acid residues substitutions (Thr187Ser and Gln399His) between ZS11 and Bndwarf2, which encoding a GLYCOGEN SYNTHASE KINASE 3 (GSK3-like). The quantitative real-time PCR (qRT-PCR) analysis showed that the BnaC04.BIL1 gene expressed in all tissues of oilseed rape. Subcellular localization experiment showed that BnaC04.BIL1 was localized in the nucleus in tobacco leaf cells. Genetic transformation experiments confirmed that the BnaC04.BIL1 is responsible for the plant dwarf phenotype in the Bndwarf2 mutants. Overexpression of BnaC04.BIL1 reduced plant height, but also resulted in compact plant architecture. Conclusions: A dominant dwarfing gene, BnaC04.BIL1, encodes an GSK3-like that negatively regulates plant height, was mapped and isolated. Our identification of a distinct gene locus may help to improve lodging resistance in oilseed rape. [ABSTRACT FROM AUTHOR]

[Display omitted] Enhanced glycolysis is a distinct feature associated with numerous stem cells and cancer cells. However, little is known about its regulatory roles in gene expression and cell fate determination. Here, we confirm that glycolytic metabolism and lactate production decrease during the differentiation of mouse embryonic stem cells (mESCs). Importantly, acidic pH due to lactate accumulation can transiently prevent the silencing of mESC self-renewal in differentiation conditions. Furthermore, acidic pH partially blocks the differentiation of human ESCs (hESCs). Mechanistically, acidic pH downregulates AGO1 protein and de-represses a subset of mRNA targets of miR-290/302 family of microRNAs which facilitate the exit of naive pluripotency state in mESCs. Interestingly, AGO1 protein is also downregulated by acidic pH in cancer cells. Altogether, this study provides insights into the potential function and underlying mechanism of acidic pH in pluripotent stem cells (PSCs). [ABSTRACT FROM AUTHOR]

Objectives: Mouse embryonic stem cell (mESC) culture contains various heterogeneous populations, which serve as excellent models to study gene regulation in early embryo development. The heterogeneity is typically defined by transcriptional activities, for example, the expression of Nanog or Rex1 mRNA. Our objectives were to identify mESC heterogeneity that are caused by mechanisms other than transcriptional control. Materials and methods: Klf3 mRNA and protein were analysed by RT‐qPCR, Western blotting or immunofluorescence in mESCs, C2C12 cells, early mouse embryos and various mouse tissues. An ESC reporter line expressing KLF3‐GFP fusion protein was made to study heterogeneity of KLF3 protein expression in ESCs. GFP‐positive mESCs were sorted for further analysis including RT‐qPCR and RNA‐seq. Results: In the majority of mESCs, KLF3 protein is actively degraded due to its proline‐rich sequence and highly disordered structure. Interestingly, KLF3 protein is stabilized in a small subset of mESCs. Transcriptome analysis indicates that KLF3‐positive mESCs upregulate genes that are initially activated in 8‐cell embryos. Consistently, KLF3 protein but not mRNA is dramatically increased in 8‐cell embryos. Forced expression of KLF3 protein in mESCs promotes the expression of 8‐cell‐embryo activated genes. Conclusions: Our study identifies previously unrecognized heterogeneity due to KLF3 protein expression in mESCs. [ABSTRACT FROM AUTHOR]

This paper develops the impedance models of grid-connected converters under the virtual synchronous generator (VSG) strategy with a cascaded inner control loop and analyzes the system stability of VSG controlled converters with different kinds of weak grid. Different from existing small-signal models with high dimensions, a single-in-single-out (SISO) impedance model with simple mathematical expression is obtained in this paper, which is applied to identify the influence of the cascaded control loop on impedance characteristics and system stability. It is found that the impedance characteristics of VSG controlled converters can become capacitive below the fundamental frequency, and it is mainly caused by the voltage controller in the cascaded control loop of the VSG strategy. Impedance-based stability analysis shows that the capacitive impedance characteristics can benefit the compatibility of converters operated with the series-compensated weak grid, but may deteriorate the system stability with the inductive weak grid, which can be avoided by increasing the proportional coefficients of the cascaded voltage and current controllers or applying a larger virtual resistor to reduce the negative resistance in the capacitive frequency range. Experiments based on the control-hardware-in-loop (CHIL) platform were carried out to verify the developed analytical models and possible system instable cases. [ABSTRACT FROM AUTHOR]

Background: Studies of leaf shape development and plant stature have made important contributions to the fields of plant breeding and developmental biology. The optimization of leaf morphology and plant height to improve lodging resistance and photosynthetic efficiency, increase planting density and yield, and facilitate mechanized harvesting is a desirable goal in Brassica napus. Results: Here, we investigated a B. napus germplasm resource exhibiting up-curled leaves and a semi-dwarf stature. In progeny populations derived from NJAU5737 and Zhongshuang 11 (ZS11), we found that the up-curled leaf trait was controlled by a dominant locus, BnUC2. We then fine mapped the BnUC2 locus onto an 83.19-kb interval on chromosome A05 using single nucleotide polymorphism (SNP) and simple sequence repeat (SSR) markers. We further determined that BnUC2 was a major plant height QTL that explained approximately 70% of the phenotypic variation in two BC5F3 family populations derived from NJAU5737 and ZS11. This result implies that BnUC2 was also responsible for the observed semi-dwarf stature. The fine mapping interval of BnUC2 contained five genes, two of which, BnaA05g16700D (BnaA05.IAA2) and BnaA05g16720D, were revealed by comparative sequencing to be mutated in NJAU5737. This result suggests that the candidate gene mutation (BnaA05g16700D, encoding Aux/IAA2 proteins) in the conserved Degron motif GWPPV (P63S) was responsible for the BnUC2 locus. In addition, investigation of agronomic traits in a segregated population indicated that plant height, main inflorescence length, and branching height were significantly reduced by BnUC2, whereas yield was not significantly altered. The determination of the photosynthetic efficiency showed that the BnUC2 locus was beneficial to improve the photosynthetic efficiency. Our findings may provide an effective foundation for plant type breeding in B. napus. Conclusions: Using SNP and SSR markers, a dominant locus (BnUC2) related to up-curled leaves and semi-dwarf stature in B. napus has been fine mapped onto an 83.19-kb interval of chromosome A05 containing five genes. The BnaA05.IAA2 is inferred to be the candidate gene responsible for the BnUC2 locus. [ABSTRACT FROM AUTHOR]

The first author's name is spelled incorrectly. The correct name is: Yuelong Yan. The correct citation is: Yan Y, Zhang C, Hao J, Wang X-L, Ming J, Mi L, et al. (2019) DPPA2/4 and SUMO E3 ligase PIAS4 opposingly regulate zygotic transcriptional program. PLoS Biol 17(6): e3000324. https://doi.org/10.1371/journal.pbio.3000324By Yuelong Yan; Chao Zhang; Jing Hao; Xue-Lian Wang; Jia Ming; Li Mi; Jie Na; Xinli Hu and Yangming WangReported by Author; Author; Author; Author; Author; Author; Author; Author; Author [Extracted from the article]

The molecular mechanism controlling the zygotic genome activation (ZGA) in mammals remains poorly understood. The 2-cell (2C)-like cells spontaneously emerging from cultures of mouse embryonic stem cells (ESCs) share some key transcriptional and epigenetic programs with 2C-stage embryos. By studying the transition of ESCs into 2C-like cells, we identified developmental pluripotency associated 2 and 4 (Dppa2/4) as important regulators controlling zygotic transcriptional program through directly up-regulating the expression of double homeobox (Dux). In addition, we found that DPPA2 protein is sumoylated and its activity is negatively regulated by small ubiquitin-like modifier (Sumo) E3 ligase protein inhibitor of activated STAT 4 (PIAS4). PIAS4 is down-regulated during ZGA process and during transitioning of ESCs into 2C-like cells. Depleting Pias4 or overexpressing Dppa2/4 is sufficient to activate 2C-like transcriptional program, whereas depleting Dppa2/4 or forced expression of Pias4 or Sumo2–Dppa2 inhibits 2C-like transcriptional program. Furthermore, ectopic expression of Pias4 or Sumo2–Dppa2 impairs early mouse embryo development. In summary, our study identifies key molecular rivals consisting of transcription factors and a Sumo2 E3 ligase that regulate zygotic transcriptional program upstream of Dux. [ABSTRACT FROM AUTHOR]

Myocardial ischemia-reperfusion (I/R) injury is unavoidable during cardioplegic arrest and open-heart surgery. Danshen is one of the most popular traditional herbal medicines in China, which has entered the Food and Drug Administration-approved phase III clinical trial. This study was aimed to develop a human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) model to mimic I/R injury and evaluate the cardioprotective effect of regular cardioplegic solution with Danshen. hiPSC-CMs were cultured with the crystalloid cardioplegic solution (Thomas group) and Thomas solution with 2 or 10 µg/mL Danshen (Thomas plus Danshen groups). The cells under normoxic culture condition served as baseline group. Then, the cells were placed in a modular incubator chamber. After 45 min hypoxia and 3 h reoxygenation, hiPSC-CMs subjected to hypoxia/reoxygenation resulted in a sharp increase of reactive oxygen species (ROS) content in Thomas group versus baseline group. Compared with the Thomas group, ROS accumulation was significant suppressed in Thomas plus Danshen groups, which might result from elevating the content of glutathione and enhanced activities of superoxide dismutase and glutathione peroxidase. The enhanced L-type Ca2+ current in hiPSC-CMs after I/R injury was also significantly decreased by Danshen, and meanwhile intracellular Ca2+ level was reduced and calcium overload was suppressed. Thomas plus Danshen groups also presented less irregular transients and lower apoptosis rates. As a result, Danshen could improve antioxidant and calcium handling in cardiomyocytes during I/R and lead to reduced arrhythmia events and apoptosis rates. hiPSC-CMs model offered a platform for the future translational study of the cardioplegia. [ABSTRACT FROM AUTHOR]

Enhanced glycolysis is a main feature of pluripotent stem cells ( PSCs) and is proposed to be important for the maintenance and induction of pluripotency. The molecular mechanism underlying enhanced glycolysis in PSCs is not clear. Using Dgcr8−/− mouse embryonic stem cells ( ESCs) that lack mature mi RNAs, we found that miR-290 cluster of mi RNAs stimulates glycolysis by upregulating glycolytic enzymes Pkm2 and Ldha, which are also essential for the induction of pluripotency during reprogramming. Mechanistically, we identified Mbd2, a reader for methylated CpGs, as the target of miR-290 cluster that represses glycolysis and reprogramming. Furthermore, we discovered Myc as a key target of Mbd2 that controls metabolic switch in ESCs. Importantly, we demonstrated that miR-371 cluster, a human homolog of miR-290 cluster, stimulates glycolysis to promote the reprogramming of human fibroblasts. Hence, we identified a previously unappreciated mechanism by which miR-290/371 mi RNAs orchestrate epigenetic, transcriptional and metabolic networks to promote pluripotency in PSCs and during reprogramming. [ABSTRACT FROM AUTHOR]

Micro RNAs play important roles in controlling the embryonic stem cell ( ESC) state. Although much is known about micro RNAs maintaining ESC state, micro RNAs that are responsible for promoting ESC differentiation are less reported. Here, by screening 40 micro RNAs pre-selected by their expression patterns and predicted targets in Dgcr8-null ESCs, we identify 14 novel differentiation-associated micro RNAs. Among them, miR-27a and miR-24, restrained by c-Myc in ESC, exert their roles of silencing self-renewal through directly targeting several important pluripotency-associated factors, such as Oct4, Foxo1 and Smads. CRISPR/Cas9-mediated knockout of all miR-27/24 in ESCs leads to serious deficiency in ESC differentiation in vitro and in vivo. Moreover, depleting of them in mouse embryonic fibroblasts can evidently promote somatic cell reprogramming. Altogether, our findings uncover the essential role of miR-27 and miR-24 in ESC differentiation and also demonstrate novel micro RNAs responsible for ESC differentiation. [ABSTRACT FROM AUTHOR]

Leaf trait is an important target trait in crop breeding programs. Moderate leaf curling may be a help for improving crop yield by minimizing the shadowing by leaves. Mining locus for leaf curling trait is of significance for plant genetics and breeding researches. The present study identified a novel rapeseed accession with up-curling leaf, analyzed the up-curling leaf trait inheritance, and fine mapped the locus for up-curling leaf property (Bnuc3) in Brassica napus. Genetic analysis revealed that the up-curling leaf trait is controlled by a single dominant locus, named BnUC3. We performed an association study of BnUC3 with single nucleotide polymorphism (SNP) markers using a backcross population derived from the homozygous up-curling leaf line NJAU-M1295 and the canola variety 'zhongshuang11' with typical flat leaves, and mapped the BnUC3 locus in a 1.92 Mb interval of chromosome A02 of B. napus. To further map BnUC3, 232 simple sequence repeat (SSR) primers and four pairs of Insertion/Deletion (InDel) primers were developed for the mapping interval. Among them, five SSR markers and two InDel markers were polymorphic. By these markers, the mapping interval was narrowed to 92.0 kb using another F2 population. This fine mapping interval has 11 annotated genes among which BnaA02T0157000ZS were inferred to be candidate casual genes for up-curling leaf based on the cloned sequence analysis, gene functionality, and gene expression analysis. The current study laid a foundational basis for further elucidating the mechanism of BnUC3 and breeding of variety with up-curling leaf. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) evolve more rapidly than mRNAs. Whether conserved lncRNAs undergo conserved processing, localization, and function remains unexplored. We report differing subcellular localization of lncRNAs in human and mouse embryonic stem cells (ESCs). A significantly higher fraction of lncRNAs is localized in the cytoplasm of hESCs than in mESCs. This turns out to be important for hESC pluripotency. FAST is a positionally conserved lncRNA but is not conserved in its processing and localization. In hESCs, cytoplasm-localized h FAST binds to the WD40 domain of the E3 ubiquitin ligase β-TrCP and blocks its interaction with phosphorylated β-catenin to prevent degradation, leading to activated WNT signaling, required for pluripotency. In contrast, m Fast is nuclear retained in mESCs, and its processing is suppressed by the splicing factor PPIE, which is highly expressed in mESCs but not hESCs. These findings reveal that lncRNA processing and localization are previously under-appreciated contributors to the rapid evolution of function. • Subcellular localization of conserved lncRNAs is different in hESCs and mESCs • Cytoplasmic h FAST but not nuclear m Fast promotes WNT signaling in hESC pluripotency • PPIE regulates distinct FAST processing in hESCs and mESCs • RNA processing and localization contribute to lncRNA functional evolution A pair of lncRNA orthologs exhibits different subcellular localization in human and murine ESCs because of differential RNA processing, which, in turn, leads to their functional divergence in the context of pluripotency regulation. The findings highlight how conserved lncRNAs may achieve functional evolution through non-conserved RNA processing. [ABSTRACT FROM AUTHOR]

The DiGeorge syndrome critical region gene 8 (Dgcr8) knockout strategy has been widely used to study the function of canonical microRNAs (miRNAs) in vitro and in vivo. However, primary miRNA (pri-miRNA) transcripts are accumulated in Dgcr8 knockout cells due to interrupted processing. Whether abnormally accumulated pri-miRNAs have any function is unknown. Here, using clustered regularly interspaced short palindromic repeats system/CRISPR-associated protein 9 (CRISPR/Cas9), we successfully knocked out the primary microRNA-290~295 (pri-miR-290~295) cluster, the most highly expressed miRNA cluster in mouse embryonic stem cells (ESCs), in Dgcr8 knockout background. We found that the major defects associated with Dgcr8 knockout in mouse ESCs, including higher expression of epithelial-to-mesenchymal transition (EMT) markers, slower proliferation, G1 accumulation, and defects in silencing self-renewal, were not affected by the deletion of pri-miR-290~290 cluster. Interestingly, the transcription of neighboring gene nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing 12(Nlrp12) was upregulated upon the deletion of the pri-miR-290~295 cluster. Together, our results suggested that the major defects in Dgcr8 knockout ESCs were not due to the accumulation of pri-miR-290~295, and the deletion of miRNA genes could affect the transcription of neighboring DNA elements. [ABSTRACT FROM AUTHOR]

Background: Leaf shape development research is important because leaf shapes such as moderate curling can help to improve light energy utilization efficiency. Leaf growth and development includes initiation of the leaf primordia and polar differentiation of the proximal-distal, adaxial-abaxial, and centrolateral axes. Changes in leaf adaxial-abaxial polarity formation, auxin synthesis and signaling pathways, and development of sclerenchyma and cuticle can cause abnormal leaf shapes such as up-curling leaf. Although many genes related to leaf shape development have been reported, the detailed mechanism of leaf development is still unclear. Here, we report an up-curling leaf mutant plant from our Brassica napus germplasm. We studied its inheritance, mapped the up-curling leaf locus BnUC1, built near-isogenic lines for the Bnuc1 mutant, and evaluated the effect of the dominant leaf curl locus on leaf photosynthetic efficiency and agronomic traits. Results: The up-curling trait was controlled by one dominant locus in a progeny population derived from NJAU5734 and Zhongshuang 11 (ZS11). This BnUC1 locus was mapped in an interval of 2732.549 kb on the A05 chromosome of B. napus using Illumina Brassica 60 K Bead Chip Array. To fine map BnUC1, we designed 201 simple sequence repeat (SSR) primers covering the mapping interval. Among them, 16 polymorphic primers that narrowed the mapping interval to 54.8 kb were detected using a BC6F2 family population with 654 individuals. We found six annotated genes in the mapping interval using the B. napus reference genome, including BnaA05g18250D and BnaA05g18290D, which bioinformatics and gene expression analyses predicted may be responsible for leaf up-curling. The up-curling leaf trait had negative effects on the agronomic traits of 30 randomly selected individuals from the BC6F2 population. The near-isogenic line of the up-curling leaf (ZS11-UC1) was constructed to evaluate the effect of BnUC1 on photosynthetic efficiency. The results indicated that the up-curling leaf trait locus was beneficial to improve the photosynthetic efficiency. Conclusions: An up-curling leaf mutant Bnuc1 was controlled by one dominant locus BnUC1. This locus had positive effects on photosynthetic efficiency, negative effects on some agronomic traits, and may help to increase planting density in B. napus. [ABSTRACT FROM AUTHOR]