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Macrophages play an important role in the pathogenesis of systemic lupus erythematosus-associated diffuse alveolar hemorrhage (DAH). The immunomodulation of macrophage responses might be a potential approach for the prevention and treatment of DAH. Erythropoietin (EPO) could regulate macrophage bioactivities by binding to the EPO receptor expressing on macrophages. This study assessed the effects of EPO on DAH protection using an immune-mediated DAH murine model with macrophages as the major contributor. A DAH murine model was established in female C57BL/6 mice by an i.p. injection of pristane. We found that EPO administration alleviates DAH by reducing pulmonary macrophages recruitment and promoting phenotype switch toward M2 macrophages in vivo. EPO drove macrophages to the anti-inflammatory phenotype in the primary murine bone marrow-derived macrophages and macrophages cell line RAW 264.7 with LPS, IFN-γ, and IL-4 in vitro. Moreover, EPO treatment increases the expression of EPOR and decreases the expression of miR-494-3p, resulting in increased phosphorylation of JAK2 and STAT3. In conclusion, EPO can be a potential therapeutic agent in DAH by reducing cell apoptosis and regulating macrophage polarization through the EPOR/JAK2/STAT3 axis. Further studies are also needed to validate the direct target of miR-494-3p in regulating JAK2/STAT3 signaling transduction. [ABSTRACT FROM AUTHOR]

Background: Sporopollenin is a major component of the pollen exine pattern. In Arabidopsis, acyl-CoA synthetase5 (ACOS5) is involved in sporopollenin precursor biosynthesis. In this study, we identified its orthologue, OsACOS12, in rice (Oryza sativa) and compared the functional conservation of ACOS in rice to Arabidopsis. Results: Sequence analysis showed that OsACOS12 shares 63.9 % amino acid sequence identity with ACOS5. The osacos12 mutation caused by a pre-mature stop codon in LOC_Os04g24530 exhibits defective sexine resulting in a male sterile phenotype in rice. In situ hybridization shows that OsACOS12 is expressed in tapetal cells and microspores at the transcript level. The localization of OsACOS12-GFP demonstrated that OsACOS12 protein is accumulated in tapetal cells and anther locules. OsACOS12 driven by the ACOS5 promoter could partially restore the male fertility of the acos5 mutant in Arabidopsis. Conclusions: OsACOS12 is an orthologue of ACOS5 that is essential for sporopollenin synthesis in rice. ACOS5 and OsACOS12 are conserved for pollen wall formation in monocot and dicot species. [ABSTRACT FROM AUTHOR]

The endoplasmic reticulum quality control protein activating transcription factor 6 (ATF6) has emerged as a novel metabolic regulator. Here, we show that adenovirus-mediated overexpression of the dominant-negative form of ATF6 (dnATF6) increases susceptibility to develop hepatic steatosis in diet-induced insulin-resistant mice and fasted mice. Overexpression of dnATF6 or small interfering RNA-mediated knockdown of ATF6 decreases the transcriptional activity of peroxisome proliferator-activated receptor α (PPARα)/retinoid X receptor complex, and inhibits oxygen consumption rates in hepatocytes, possibly through inhibition of the binding of PPARα to the promoter of its target gene. Intriguingly, ATF6 physically interacts with PPARα, enhances the transcriptional activity of PPARα, and triggers activation of PPARα downstream targets, such as CPT1α and MCAD, in hepatocytes. Furthermore, hepatic overexpression of the active form of ATF6 promotes hepatic fatty acid oxidation and protects against hepatic steatosis in diet-induced insulin-resistant mice. These data delineate the mechanism by which ATF6 controls the activity of PPARα and hepatic mitochondria fatty acid oxidation. Therefore, strategies to activate ATF6 could be used as an alternative avenue to improve liver function and treat hepatic steatosis in obesity. [ABSTRACT FROM AUTHOR]

Anther development in Arabidopsis, a popular model plant for plant biology and genetics, is controlled by a complex gene network. Despite the extensive use of this genus for genetic research, little is known about its regulatory network. In this paper, the direct transcriptional regulatory relationships between genes expressed in Arabidopsis anther development were predicted with an integrated bioinformatic method that combines mining of microarray data with promoter analysis. A total of 7710 transcription factor-gene pairs were obtained. The 80 direct regulatory relationships demonstrating the highest confidence were screened from the initial 7710 pairs; three of the 80 were validated by previous experiments. The results indicate that our predicted results were reliable. The regulatory relationships revealed by this research and described in this paper may facilitate further investigation of the molecular mechanisms of anther development. The bioinformatic method used in this work can also be applied to the prediction of gene regulatory relationships in other organisms. [ABSTRACT FROM AUTHOR]

With the goal of identifying an improved delivery scheme for intracellular tracking and anticancer therapy, we explored a novel double functionalization of a carbon nanotube delivery system containing antisense oligodeoxynucleotides (ASODNs) as a therapeutic gene and CdTe quantum dots as fluorescent labeling probes via electrostatically layer-by-layer assembling. This is the first time that we used mercaptoacetic acid-capped CdTe quantum dots as fluorescent labeling probes for clearly tracking the intracellular transport and evaluating delivery efficiency of ASODNs by functionalized multiwalled carbon nanotubes (MWNTs). [ABSTRACT FROM AUTHOR]

The Arabidopsis thaliana ASYMMETRIC LEAVES1 (AS1) and AS2 genes are important for repressing class I KNOTTED1-like homeobox (KNOX) genes and specifying leaf adaxial identity in leaf development. RNA-dependent RNA polymerases (RdRPs) are critical for posttranscriptional and transcriptional gene silencing in eukaryotes; however, very little is known about their functions in plant development. Here, we show that the Arabidopsis RDR6 gene (also called SDE1 and SGS2) that encodes a putative RdRP, together with AS1 and AS2, regulates leaf development, rdr6 single mutant plants displayed only minor phenotypes, whereas rdr6 as1 and rdr6 as2 double mutants showed dramatically enhanced as1 and as2 phenotypes, with severe defects in the leaf adaxial-abaxial polarity and vascular development. In addition, the double mutant plants produced more lobed leaves than the as1 and as2 single mutants and showed leaf-like structures associated on a proportion of leaf blades. The abnormal leaf morphology of the double mutants was accompanied by an extended ectopic expression of a class I KNOX gene BREVIPEDICELLUS (BP) and high levels of microRNA165/166 that may lead to mRNA degradation of genes in the class III HD-ZIP family. Taken together, our data suggest that the Arabidopsis RDR6-associated epigenetic pathway and the AS1-AS2 pathway synergistically repress BP and MIR165/166 for proper plant development. [ABSTRACT FROM AUTHOR]