Abstract The Berry curvature dipole (BCD) serves as a one of the fundamental contributors to emergence of the nonlinear Hall effect (NLHE). Despite intense interest due to its potential for new ...technologies reaching beyond the quantum efficiency limit, the interplay between BCD and NLHE has been barely understood yet in the absence of a systematic study on the electronic band structure. Here, we report NLHE realized in NbIrTe 4 that persists above room temperature coupled with a sign change in the Hall conductivity at 150 K. First-principles calculations combined with angle-resolved photoemission spectroscopy (ARPES) measurements show that BCD tuned by the partial occupancy of spin-orbit split bands via temperature is responsible for the temperature-dependent NLHE. Our findings highlight the correlation between BCD and the electronic band structure, providing a viable route to create and engineer the non-trivial Hall effect by tuning the geometric properties of quasiparticles in transition-metal chalcogen compounds.
Vascular endothelial growth factor and its receptors, FLK1/KDR and FLT1, are key regulators of angiogenesis. Unlike FLK1/KDR, the role of FLT1 has remained elusive. FLT1 is produced as ...soluble (sFLT1) and full-length isoforms. Here, we show that pericytes from multiple tissues produce sFLT1. To define the biologic role of sFLT1, we chose the glomerular microvasculature as a model system. Deletion of Flt1 from specialized glomerular pericytes, known as podocytes, causes reorganization of their cytoskeleton with massive proteinuria and kidney failure, characteristic features of nephrotic syndrome in humans. The kinase-deficient allele of Flt1 rescues this phenotype, demonstrating dispensability of the full-length isoform. Using cell imaging, proteomics, and lipidomics, we show that sFLT1 binds to the glycosphingolipid GM3 in lipid rafts on the surface of podocytes, promoting adhesion and rapid actin reorganization. sFLT1 also regulates pericyte function in vessels outside of the kidney. Our findings demonstrate an autocrine function for sFLT1 to control pericyte behavior.
As the performance of permanent-magnet synchronous generators improves, research on device noise is also becoming important. This study analyzes the causes of electromagnetic noise, such as the back ...electromotive force, cogging torque, torque ripple, unbalanced magnetic force, and harmonics that occur during operation for each DC and AC load. In particular, it shows that the influence of the waterfall diagram changes depending on the harmonic order of the torque ripple. By combining 2D finite element analysis and 3D mechanical analysis, electromagnetic analysis can be used to analyze the noise-generating relationship. Based on the analysis results, the electromagnetic noise generation results depending on the load are presented. The electromagnetic performance and mechanical reliability of the designed model were verified by comparing the finite element method and experimental results.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects motor neurons, leading to muscle weakness, paralysis, and eventual death. Research from the past few decades has ...appreciated that ALS is not only a disease of the motor neurons but also a disease that involves systemic metabolic dysfunction. This review will examine the foundational research of understanding metabolic dysfunction in ALS and provide an overview of past and current studies in ALS patients and animal models, spanning from full systems to various metabolic organs. While ALS-affected muscle tissue exhibits elevated energy demand and a fuel preference switch from glycolysis to fatty acid oxidation, adipose tissue in ALS undergoes increased lipolysis. Dysfunctions in the liver and pancreas contribute to impaired glucose homeostasis and insulin secretion. The central nervous system (CNS) displays abnormal glucose regulation, mitochondrial dysfunction, and increased oxidative stress. Importantly, the hypothalamus, a brain region that controls whole-body metabolism, undergoes atrophy associated with pathological aggregates of TDP-43. This review will also cover past and present treatment options that target metabolic dysfunction in ALS and provide insights into the future of metabolism research in ALS.
Post-wet chemical treatments using sulfuric acid and hydrogen peroxide mixture (SPM) or tetramethyl ammonium hydroxide (TMAH) solutions were performed to reduce dry etch-induced surface damage of ...β-Ga2O3 caused by the inductively coupled plasma-reactive ion etching (ICP-RIE) process using the Cl2/BCl3 gas mixture. The addition of BCl3 to the Cl2/BCl3 gas mixture resulted in a significant enhancement of the etch rate of β-Ga2O3. However, it increased the surface roughness with the formation of the nonvolatile etch by-product B2O3 as a result of the BCl3/β-Ga2O3 reaction. The post-SPM treatment led to the reduction of dry etch-induced surface damage of β-Ga2O3 to a certain extent with the removal of B2O3. On the other hand, the post-TMAH treatment significantly improved the surface morphology of the dry etched β-Ga2O3 surface. During the post-TMAH treatment, the chemical reaction between the damaged β-Ga2O3 layer caused by ICP-RIE process and OH− in the TMAH solution led to the formation of the Ga oxide, followed by the simultaneous dissolution of the Ga oxide and the B2O3. Thus, the post-TMAH treatment effectively recovered the surface damage of β-Ga2O3 induced by the ICP-RIE process using the Cl2/BCl3 gas mixture.
Multiple alterations of cellular metabolism have been documented in experimental studies of autosomal dominant polycystic kidney disease (ADPKD) and are thought to contribute to its pathogenesis. To ...elucidate the molecular pathways and transcriptional regulators associated with the metabolic changes of renal cysts in ADPKD, we compared global gene expression data from human PKD1 renal cysts, minimally cystic tissues (MCT) from the same patients, and healthy human kidney cortical tissue samples. We found gene expression profiles of PKD1 renal cysts were consistent with the Warburg effect with gene pathway changes favoring increased cellular glucose uptake and lactate production, instead of pyruvate oxidation. Additionally, mitochondrial energy metabolism was globally depressed, associated with downregulation of gene pathways related to fatty acid oxidation (FAO), branched-chain amino acid (BCAA) degradation, the Krebs cycle, and oxidative phosphorylation (OXPHOS) in renal cysts. Activation of mTORC1 and its two target proto-oncogenes, HIF-1α and MYC, was predicted to drive the expression of multiple genes involved in the observed metabolic reprogramming (e.g., GLUT3, HK1/HK2, ALDOA, ENO2, PKM, LDHA/LDHB, MCT4, PDHA1, PDK1/3, MPC1/2, CPT2, BCAT1, NAMPT); indeed, their predicted expression patterns were confirmed by our data. Conversely, we found AMPK inhibition was predicted in renal cysts. AMPK inhibition was associated with decreased expression of PGC-1α, a transcriptional coactivator for transcription factors PPARα, ERRα, and ERRγ, all of which play a critical role in regulating oxidative metabolism and mitochondrial biogenesis. These data provide a comprehensive map of metabolic pathway reprogramming in ADPKD and highlight nodes of regulation that may serve as targets for therapeutic intervention.
Cellular senescence, an irreversible state of growth arrest, underlies organismal aging and age‐related diseases. Recent evidence suggests that aging intervention based on inhibition of cellular ...senescence might be a promising strategy for treatment of aging and age‐related diseases. Embryonic stem cells (ESCs) and ESC conditioned medium (CM) have been suggested as a desirable source for regenerative medicine. However, effects of ESC‐CM on cellular senescence remain to be determined. We found that treatment of senescent human dermal fibroblasts with CM from mouse ESCs (mESCs) decreases senescence phenotypes. We found that platelet‐derived growth factor BB in mESC‐CM plays a critical role in antisenescence effect of mESC‐CM through upregulation of fibroblast growth factor 2. We confirmed that mESC‐CM treatment accelerates the wound‐healing process by down‐regulating senescence‐associated p53 expression in in vivo models. Taken together, our results suggest that mESC‐CM has the ability to suppress cellular senescence and maintain proliferative capacity. Therefore, this strategy might emerge as a novel therapeutic strategy for aging and age‐related diseases.—Bae, Y.‐U., Choi, J.‐H., Nagy, A., Sung, H.‐K., Kim, J.‐R. Antisenescence effect of mouse embryonic stem cell conditioned medium through a PDGF/FGF pathway. FASEB J. 30, 1276–1286 (2016). www.fasebj.org
Purpose of Review
Obesity is a major risk factor for the development of hypertension (HTN), a leading cause of cardiovascular morbidity and mortality. Growing body of research suggests that adipose ...tissue function is directly associated with the pathogenesis of obesity-related HTN. In this review, we will discuss recent research on the role of adipose tissue in blood pressure (BP) regulation and activation of brown adipose tissue (BAT) as a potentially new therapeutic means for obesity-related HTN.
Recent Findings
Adipose tissue provides mechanical protection of the blood vessels and plays a role in regulation of vascular tone. Exercise and fasting activate BAT and induce browning of white adipose tissue (WAT). BAT-secreted FGF21 lowers BP and protects against HTN. Browning of perivascular WAT improves HTN.
Summary
New insights on WAT browning and BAT activation can open new avenues of potential therapeutic interventions to treat obesity-related HTN.
Glaucoma is a leading cause of blindness, afflicting more than 60 million people worldwide. Increased intraocular pressure (IOP) due to impaired aqueous humor drainage is a major risk factor for the ...development of glaucoma. Here, we demonstrated that genetic disruption of the angiopoietin/TIE2 (ANGPT/TIE2) signaling pathway results in high IOP, buphthalmos, and classic features of glaucoma, including retinal ganglion degeneration and vision loss. Eyes from mice with induced deletion of Angpt1 and Angpt2 (A1A2Flox(WB) mice) lacked drainage pathways in the corneal limbus, including Schlemm's canal and lymphatic capillaries, which share expression of the PROX1, VEGFR3, and FOXC family of transcription factors. VEGFR3 and FOXCs have been linked to lymphatic disorders in patients, and FOXC1 has been linked to glaucoma. In contrast to blood endothelium, in which ANGPT2 is an antagonist of ANGPT1, we have shown that both ligands cooperate to regulate TIE2 in the lymphatic network of the eye. While A1A2Flox(WB) mice developed high IOP and glaucoma, expression of ANGPT1 or ANGPT2 alone was sufficient for ocular drainage. Furthermore, we demonstrated that loss of FOXC2 from lymphatics results in TIE2 downregulation, suggesting a mechanism for ocular defects in patients with FOXC mutations. These data reveal a pathogenetic and molecular basis for glaucoma and demonstrate the importance of angiopoietin ligand cooperation in the lymphatic endothelium.
Abstract
Prominin-1 (PROM1), also known as CD133, is expressed in hepatic progenitor cells (HPCs) and cholangiocytes of the fibrotic liver. In this study, we show that PROM1 is upregulated in the ...plasma membrane of fibrotic hepatocytes. Hepatocellular expression of PROM1 was also demonstrated in mice (
Prom1
CreER
; R26
TdTom
) in which cells expressed TdTom under control of the
Prom1
promoter. To understand the role of hepatocellular PROM1 in liver fibrosis, global and liver-specific
Prom1
-deficient mice were analyzed after bile duct ligation (BDL). BDL-induced liver fibrosis was aggravated with increased phosphorylation of SMAD2/3 and decreased levels of SMAD7 by global or liver-specific
Prom1
deficiency but not by cholangiocyte-specific
Prom1
deficiency. Indeed, PROM1 prevented SMURF2-induced SMAD7 ubiquitination and degradation by interfering with the molecular association of SMAD7 with SMURF2. We also demonstrated that hepatocyte-specific overexpression of SMAD7 ameliorated BDL-induced liver fibrosis in liver-specific
Prom1-
deficient mice. Thus, we conclude that PROM1 is necessary for the negative regulation of TGFβ signaling during liver fibrosis.
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