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Acer rubrum is difficult to root during cutting propagation. Auxin/indole-acetic acids (Aux/IAA) proteins, which are encoded by the early response genes of auxin, are transcriptional repressors that play important roles in auxin-mediated root growth and development. In this study, ArAux/IAA13 and ArAux/IAA16, which were significantly differentially expressed after 300 mg/L indole butyric acid treatment, were cloned. Heatmap analysis revealed that they might be associated with the process of adventitious root (AR) growth and development mediated by auxin. Subcellular localization analysis showed that they performed their function in the nucleus. Bimolecular fluorescence complementation assays revealed the interactions between them and two auxin response factor (ARF) proteins, ArARF10 and ArARF18, confirming their relevance to AR growth and development. Overexpression of transgenic plants confirmed that the overexpression of ArAux/IAA13 and ArAux/IAA16 inhibited AR development. These results help elucidate the mechanisms of auxin-mediated AR growth and development during the propagation of A. rubrum and provide a molecular basis for the rooting of cuttings. [ABSTRACT FROM AUTHOR]

Dysregulated lipid droplet accumulation has been identified as one of the main contributors to liver steatosis during nonalcoholic fatty liver disease (NAFLD). However, the underlying molecular mechanisms for excessive lipid droplet formation in the liver remain largely unknown. In the current study, hepatic E4 promoter–binding protein 4 (E4BP4) plays a critical role in promoting lipid droplet formation and liver steatosis in a high-fat diet (HFD)–induced NAFLD mouse model. Hepatic E4bp4 deficiency (E4bp4-LKO) protects mice from HFD-induced liver steatosis independently of obesity and insulin resistance. Our microarray study showed a markedly reduced expression of lipid droplet binding genes, such as Fsp27, in the liver of E4bp4-LKO mice. E4BP4 is both necessary and sufficient to activate Fsp27 expression and lipid droplet formation in primary mouse hepatocytes. Overexpression of Fsp27 increased lipid droplets and triglycerides in E4bp4-LKO primary mouse hepatocytes and restored hepatic steatosis in HFD-fed E4bp4-LKO mice. Mechanistically, E4BP4 enhances the transactivation of Fsp27 by CREBH in hepatocytes. Furthermore, E4BP4 is modified by SUMOylation, and HFD feeding induces deSUMOylation of hepatic E4BP4. SUMOylation of five lysine residues of E4BP4 is critical for the downregulation of Fsp27 and lipid droplets by cAMP signaling in hepatocytes. Taken together, this study revealed that E4BP4 drives liver steatosis in HFD-fed mice through its regulation of lipid droplet binding proteins. Our study also highlights the critical role of deSUMOylation of hepatic E4BP4 in promoting NAFLD. [ABSTRACT FROM AUTHOR]

The purpose of this study is to test the effects of whole-body animal exposure to airborne particulate matter (PM) with an aerodynamic diameter of <10 μm (PM10) in the mouse cornea and in vitro. C57BL/6 mice were exposed to control or 500 µg/m3 PM10 for 2 weeks. In vivo, reduced glutathione (GSH) and malondialdehyde (MDA) were analyzed. RT-PCR and ELISA evaluated levels of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling and inflammatory markers. SKQ1, a novel mitochondrial antioxidant, was applied topically and GSH, MDA and Nrf2 levels were tested. In vitro, cells were treated with PM10 ± SKQ1 and cell viability, MDA, mitochondrial ROS, ATP and Nrf2 protein were tested. In vivo, PM10 vs. control exposure significantly reduced GSH, corneal thickness and increased MDA levels. PM10-exposed corneas showed significantly higher mRNA levels for downstream targets, pro-inflammatory molecules and reduced Nrf2 protein. In PM10-exposed corneas, SKQ1 restored GSH and Nrf2 levels and lowered MDA. In vitro, PM10 reduced cell viability, Nrf2 protein, and ATP, and increased MDA, and mitochondrial ROS; while SKQ1 reversed these effects. Whole-body PM10 exposure triggers oxidative stress, disrupting the Nrf2 pathway. SKQ1 reverses these deleterious effects in vivo and in vitro, suggesting applicability to humans. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to clarify the dynamic neural activity of levodopa‐induced dyskinesia (LID) in Parkinson's disease (PD). Methods: Using dynamic functional network connectivity (dFNC) analysis, we evaluated 41 PD patients with LID (LID group) and 34 PD patients without LID (No‐LID group). Group spatial independent component analysis and sliding‐window approach were employed. Moreover, we applied a k‐means clustering algorithm on windowed functional connectivity (FC) matrices to identify reoccurring FC patterns (i.e., states). Results: The optimal number of states was determined to be five, the so‐called State 1, 2, 3, 4, and 5. In ON phase, compared with No‐LID group, LID group occurred more frequently and dwelled longer in strongly connected State 1, characterized by strong positive connections between visual network (VIS) and sensorimotor network (SMN). When switching from OFF to ON phase, LID group occurred less frequently in State 3 and State 4. Meanwhile, LID group dwelled longer in State 2 and shorter in State 3. No‐LID group occurred more frequently in State 5 and less frequently in State 3. Additionally, correlation analysis demonstrated that dyskinesia's severity was associated with frequency of occurrence and dwell time in State 2, dominated by inferior frontal cortex in cognitive executive network (CEN). Conclusion: Using dFNC analysis, we found that dyskinesia may be related to the dysfunctional inhibition of CEN on motor loops and excessive excitation of VIS and SMN, which provided evidence of the changes in brain dynamics associated with the occurrence of dyskinesia. [ABSTRACT FROM AUTHOR]

Recent studies have suggested a link between inhaled particulate matter (PM) exposure and increased mortality and morbidity associated with pulmonary and cardiovascular diseases. However, a precise understanding of the biological mechanism underlying PM-associated toxicity and pathogenesis remains elusive. Here, we investigated the impact of PM exposure in intracellular stress signaling pathways with animal models and cultured cells. Inhalation exposure of the mice to environmentally relevant fine particulate matter (aerodynamic diameter < 2.5 [micro]m, [PM.sub.2.5]) induces endoplasmic reticulum (ER) stress and activation of unfolded protein response (UPR) in the lung and liver tissues as well as in the mouse macrophage cell line RAW264.7. Ambient [PM.sub.2.5] exposure activates double-strand RNA-activated protein kinase-like ER kinase (PERK), leading to phosphorylation of translation initiation factor eIF2[alpha] and induction of C/EBP homologous transcription factor CHOP/GADD153. Activation of PERK-mediated UPR pathway relies on the production of reactive oxygen species (ROS) and is critical for [PM.sub.2.5]-induced apoptosis. Furthermore, [PM.sub.2.5] exposure can activate ER stress sensor IRE1[alpha], but it decreases the activity of IRE1[alpha] in splicing the mRNA encoding the UPR trans-activator X-box binding protein 1 (XBP1). Together, our study suggests that [PM.sub.2.5] exposure differentially activates the UPR branches, leading to ER stress-induced apoptosis through the PERK-eIF2[alpha]-CHOP UPR branch. This work provides novel insights into the cellular and molecular basis by which ambient [PM.sub.2.5] exposure elicits its cytotoxic effects that may be related to air pollution-associated pathogenesis. air pollution; unfolded protein response doi: 10.1152/ajpcell.00529.2009.