PexRAP inhibits PRDM16-mediated thermogenic gene expression

How the nuclear receptor PPARγ regulates the development of two functionally distinct types of adipose tissue, brown and white fat, as well as the browning of white fat, remains unclear. Our previous studies suggest that PexRAP, a peroxisomal lipid synthetic enzyme, regulates PPARγ signaling and white adipogenesis. Here, we show that PexRAP is an inhibitor of brown adipocyte gene expression. PexRAP inactivation promoted adipocyte browning, increased energy expenditure, and decreased adiposity. Identification of PexRAP-interacting proteins suggests that PexRAP function extends beyond its role as a lipid synthetic enzyme. Notably, PexRAP interacts with importin-β1, a nuclear import factor, and knockdown of PexRAP in adipocytes reduced the levels of nuclear phospholipids. PexRAP also interacts with PPARγ, as well as PRDM16, a critical transcriptional regulator of thermogenesis, and disrupts the PRDM16-PPARγ complex, providing a potential mechanism for PexRAP-mediated inhibition of adipocyte browning. These results identify PexRAP as an important regulator of adipose tissue remodeling

MED19 regulates adipogenesis and maintenance of white adipose tissue mass by mediating PPARγ-dependent gene expression

The Mediator complex relays regulatory signals from gene-specific transcription factors to the basal transcriptional machinery. However, the role of individual Mediator subunits in different tissues remains unclear. Here, we demonstrate that MED19 is essential for adipogenesis and maintenance of white adipose tissue (WAT) by mediating peroxisome proliferator-activated receptor gamma (PPARγ) transcriptional activity. MED19 knockdown blocks white adipogenesis, but not brown adipogenesis or C2C12 myoblast differentiation. Adipose-specific MED19 knockout (KO) in mice results in a striking loss of WAT, whitening of brown fat, hepatic steatosis, and insulin resistance. Inducible adipose-specific MED19 KO in adult animals also results in lipodystrophy, demonstrating its requirement for WAT maintenance. Global gene expression analysis reveals induction of genes involved in apoptosis and inflammation and impaired expression of adipose-specific genes, resulting from decreased PPARγ residency on adipocyte gene promoters and reduced association of PPARγ with RNA polymerase II. These results identify MED19 as a crucial facilitator of PPARγ-mediated gene expression in adipose tissue

Peroxisomal β-oxidation acts as a sensor for intracellular fatty acids and regulates lipolysis

To liberate fatty acids (FAs) from intracellular stores, lipolysis is regulated by the activity of the lipases adipose triglyceride lipase (ATGL), hormone-sensitive lipase and monoacylglycerol lipase. Excessive FA release as a result of uncontrolled lipolysis results in lipotoxicity, which can in turn promote the progression of metabolic disorders. However, whether cells can directly sense FAs to maintain cellular lipid homeostasis is unknown. Here we report a sensing mechanism for cellular FAs based on peroxisomal degradation of FAs and coupled with reactive oxygen species (ROS) production, which in turn regulates FA release by modulating lipolysis. Changes in ROS levels are sensed by PEX2, which modulates ATGL levels through post-translational ubiquitination. We demonstrate the importance of this pathway for non-alcoholic fatty liver disease progression using genetic and pharmacological approaches to alter ROS levels in vivo, which can be utilized to increase hepatic ATGL levels and ameliorate hepatic steatosis. The discovery of this peroxisomal β-oxidation-mediated feedback mechanism, which is conserved in multiple organs, couples the functions of peroxisomes and lipid droplets and might serve as a new way to manipulate lipolysis to treat metabolic disorders

DATF: a database of Arabidopsis transcription factors

Summary: We have developed likely the most comprehensive database of Arabidopsis transcription factors. The Database of Arabidopsis Transcription Factors (DATF) contains known and predicted Arabidopsis transcription factors (1789 genes in 49 families) with the unique information of 1177 cloned sequences and many other features including 3D structure templates, EST expression information, transcription factor binding sites and Nuclear Location Signals. Availability: DATF is freely available a

Peroxisomal β-oxidation acts as a sensor for intracellular fatty acids and regulates lipolysis

International audienceTo liberate fatty acids (FA) from intracellular stores, lipolysis is driven by the activity of the lipases ATGL, HSL and MGL. Excessive FA release as a result of uncontrolled lipolysis causes lipotoxicity, which can cause metabolic disorders. However, whether cells can sense FA directly to regulate their levels to maintain cellular homeostasis is unknown. Here we report a sensing mechanism for cellular FA content, based on peroxisomal degradation of FA and coupled ROS production, which in turn regulates FA release by modulating lipolysis. Changes in ROS levels are sensed by PEX2, which modulates ATGL levels through post-translational ubiquitination. We demonstrate the importance of this pathway for NAFLD progression using genetic and pharmacological approaches to alter ROS levels, in vivo, which can be utilized to increase hepatic ATGL levels and ameliorate hepatic steatosis. The discovery of this peroxisomal β-oxidation mediated feedback mechanism, which is conserved in multiple organs, couples the functions of peroxisomes and lipid droplets and might serve as a new way to manipulate lipolysis to treat metabolic disorders

Highly Stable Carbon Nanotube/Polyaniline Porous Network for Multifunctional Applications

Three-dimensional carbon nanotube (CNT) networks with high porosity and electrical conductivity have many potential applications in energy and environmental areas, but the network structure is not very stable due to weak inter-CNT interactions. Here, we coat a thin polyaniline (PANI) layer on as-synthesized CNT sponge to obtain a mechanically and electrically stable network, and enable multifunctional applications. The resulting CNT/PANI network serves as stable strain sensors, highly compressible supercapacitor electrode with enhanced volume-normalized capacitance (632 F/cm³), and reinforced nanocomposites with the PANI as intermediate layer between the CNT fillers and polymeric matrix. Our results provide a simple and controllable method for achieving high-stability porous networks composed of CNTs, graphene, or other nanostructures

Overtwisted, Resolvable Carbon Nanotube Yarn Entanglement as Strain Sensors and Rotational Actuators

Introducing twists into carbon nanotube yarns could produce hierarchical architectures and extend their application areas. Here, we utilized such twists to produce elastic strain sensors over large strain (up to 500%) and rotation actuators with high energy density. We show that a helical nanotube yarn can be overtwisted into highly entangled, macroscopically random but locally organized structures, consisting of mostly double-helix segments intertwined together. Pulling the yarn ends completely resolved the entanglement in an elastic and reversible way, yielding large tensile strains with linear change in electrical resistance. Resolving an entangled yarn and releasing its twists could simultaneously rotate a heavy object (30 000 times the yarn weight) for more than 1000 cycles at high speed. The rotational actuation generated from a single entangled yarn produced energy densities up to 8.3 kJ/kg, and maintained similar capacity during repeated use. Our entangled CNT yarns represent a complex self-assembled system with applications as large-range strain sensors and robust rotational actuators

High IL2RA mRNA expression is an independent adverse prognostic biomarker in core binding factor and intermediate-risk acute myeloid leukemia

Abstract Background Elevated protein expressions of CD markers such as IL2RA/CD25, CXCR4/CD184, CD34 and CD56 are associated with adverse prognosis in acute myeloid leukemia (AML). However, the prognostic value of mRNA expressions of these CD markers in AML remains unclear. Through our pilot evaluation, IL2RA mRNA expression appeared to be the best candidate as a prognostic biomarker. Therefore, the aim of this study is to characterize the prognostic value of IL2RA mRNA expression and evaluate its potential to refine prognostification in AML. Methods In a cohort of 239 newly diagnosed AML patients, IL2RA mRNA expression were measured by TaqMan realtime quantitative PCR. Morphological, cytogenetics and mutational analyses were also performed. In an intermediate-risk AML cohort with 66 patients, the mRNA expression of prognostic biomarkers (BAALC, CDKN1B, ERG, MECOM/EVI1, FLT3, ID1, IL2RA, MN1 and WT1) were quantified by NanoString technology. A TCGA cohort was analyzed to validate the prognostic value of IL2RA. For statistical analysis, Mann–Whitney U test, Fisher exact test, logistic regression, Kaplan–Meier and Cox regression analyses were used. Results In AML cohort of 239 patients, high IL2RA mRNA expression independently predicted shorter relapse free survival (RFS, p < 0.001) and overall survival (OS, p < 0.001) irrespective of age, cytogenetics, FLT3-ITD or c-KIT D816V mutational status. In core binding factor (CBF) AML, high IL2RA mRNA expression correlated with FLT3-ITD status (p = 0.023). Multivariable analyses revealed that high IL2RA expression (p = 0.002), along with c-KIT D816V status (p = 0.013) significantly predicted shorter RFS, whereas only high IL2RA mRNA expression (p = 0.014) significantly predicted shorter OS in CBF AML. In intermediate-risk AML in which multiple gene expression markers were tested by NanoString, IL2RA significantly correlated with ID1 (p = 0.006), FLT3 (p = 0.007), CDKN1B (p = 0.033) and ERG (p = 0.030) expressions. IL2RA (p < 0.001) and FLT3 (p = 0.008) expressions remained significant in predicting shorter RFS, whereas ERG (p = 0.008) and IL2RA (p = 0.044) remained significant in predicting shorter OS. Similar analyses in TCGA intermediate-risk AML showed the independent prognostic role of IL2RA in predicting event free survival (p < 0.001) and OS (p < 0.001). Conclusions High IL2RA mRNA expression is an independent and adverse prognostic factor in AML and specifically stratifies patients to worse prognosis in both CBF and intermediate-risk AML

Pulling-Force Spinning Top for Serum Separation Combined with Paper-Based Microfluidic Devices in COVID-19 ELISA Diagnosis

The spread of Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), resulting in a global pandemic with around four million deaths. Although there are a variety of nucleic acid-based tests for detecting SARS-CoV-2, these methods have a relatively high cost and require expensive supporting equipment. To overcome these limitations and improve the efficiency of SARS-CoV-2 diagnosis, we developed a microfluidic platform that collected serum by a pulling-force spinning top and paper-based microfluidic enzyme-linked immunosorbent assay (ELISA) for quantitative IgA/IgM/IgG measurements in an instrument-free way. We further validated the paper-based microfluidic ELISA analysis of SARS-CoV-2 receptor-binding domain (RBD)-specific IgA/IgM/IgG antibodies from human blood samples as a good measurement with higher sensitivity compared with traditional IgM/IgG detection (99.7% vs 95.6%) for early illness onset patients. In conclusion, we provide an alternative solution for the diagnosis of SARS-CoV-2 in a portable manner by this smart integration of pulling-force spinning top and paper-based microfluidic immunoassay