TAZ Suppresses NFAT5 Activity through Tyrosine Phosphorylation

Transcriptional coactivator with PDZ-binding motif (TAZ) physically interacts with a variety of transcription factors and modulates their activities involved in cell proliferation and mesenchymal stem cell differentiation. TAZ is highly expressed in the kidney, and a deficiency of this protein results in multiple renal cysts and urinary concentration defects; however, the molecular functions of TAZ in renal cells remain largely unknown. In this study, we examined the effects of osmotic stress on TAZ expression and activity in renal cells. We found that hyperosmotic stress selectively increased protein phosphorylation at tyrosine 316 of TAZ and that this was enhanced by c-Abl activation in response to hyperosmotic stress. Interestingly, phosphorylated TAZ physically interacted with nuclear factor of activated T cells 5 (NFAT5), a major osmoregulatory transcription factor, and subsequently suppressed DNA binding and transcriptional activity of NFAT5. Furthermore, TAZ deficiency elicited an increase in NFAT5 activity in vitro and in vivo, which then reverted to basal levels following restoration of wild-type TAZ but not mutant TAZ (Y316F). Collectively, the data suggest that TAZ modulates cellular responses to hyperosmotic stress through fine-tuning of NFAT5 activity via tyrosine phosphorylation.open3

Catalytic pyrolysis of Laminaria japonica over nanoporous catalysts using Py-GC/MS

The catalytic pyrolysis of Laminaria japonica was carried out over a hierarchical meso-MFI zeolite (Meso-MFI) and nanoporous Al-MCM-48 using pyrolysis gas chromatography/mass spectrometry (Py-GC/MS). The effect of the catalyst type on the product distribution and chemical composition of the bio-oil was examined using Py-GC/MS. The Meso-MFI exhibited a higher activity in deoxygenation and aromatization during the catalytic pyrolysis of L. japonica. Meanwhile, the catalytic activity of Al-MCM-48 was lower than that of Meso-MFI due to its weak acidity

Acute Viral Myopericarditis Presenting as a Transient Effusive-Constrictive Pericarditis Caused by Coinfection with Coxsackieviruses A4 and B3

Acute myopericarditis is usually caused by viral infections, and the most common cause of viral myopericarditis is coxsackieviruses. Diagnosis of myopericarditis is made based on clinical manifestations of myocardial (such as myocardial dysfunction and elevated serum cardiac enzyme levels) and pericardial (such as inflammatory pericardial effusion) involvement. Although endomyocardial biopsy is the gold standard for the confirmation of viral infection, serologic tests can be helpful. Conservative management is the mainstay of treatment in acute myopericarditis. We report here a case of a 24-year-old man with acute myopericarditis who presented with transient effusive-constrictive pericarditis. Echocardiography showed transient pericardial effusion with constrictive physiology and global regional wall motion abnormalities of the left ventricle. The patient also had an elevated serum troponin I level. A computed tomogram of the chest showed pericardial and pleural effusion, which resolved after 2 weeks of supportive treatment. Serologic testing revealed coxsackievirus A4 and B3 coinfection. The patient received conservative medical treatment, including nonsteroidal anti-inflammatory drugs, and he recovered completely with no complications

Capric Acid Inhibits NO Production and STAT3 Activation during LPS-Induced Osteoclastogenesis

Capric acid is a second medium-chain fatty acid, and recent studies have shown that fatty acids are associated with bone density and reduce bone turnover. In this study, we investigated the effects of capric acid on lipopolysaccharide (LPS)-induced osteoclastogenesis in RAW264.7 cells. After treatment with capric acid (1 mM), the number of tartrate resistant acid phosphatase (TRAP)-positive cells decreased significantly. Capric acid reduced LPS-induced TRAP expression, an osteoclast differentiation marker, without inhibiting cell viability. LPS strongly upregulated inducible nitric oxide synthase (iNOS) mRNA levels and nitric oxide (NO) production, whereas capric acid inhibited them. Furthermore, capric acid also inhibited monocyte chemoattractant protein-1 (MCP-1) mRNA expression. Subsequently, we investigated various intracellular signaling proteins, including nuclear factor-κB (NF-κB), c-Jun-N-terminal kinase (JNK), extracellular signal regulated kinase 1/2 (ERK1/2), and signal transducer and activator of transcription 1 (STAT1) and STAT3 associated with osteoclastogenesis. Capric acid had no effects on LPS-induced activation of the NF-κB, JNK, ERK1/2, and STAT1 pathways. However, capric acid inhibited LPS-induced phosphorylation of Ser727 in STAT3. Additionally, stattic (a STAT3 inhibitor) inhibited LPS-induced iNOS and MCP-1 gene expression. In conclusion, we demonstrated that capric acid inhibited LPS-induced osteoclastogenesis by suppressing NO production via the STAT3 pathway. These results suggest that capric acid has important therapeutic implications for treating bone diseases associated with excessive osteoclastogenesis

Improved Surgical Technique for Heterotopic Aortic Transplantation in Mice

Transplant arteriosclerosis is the main limitation for long-term survival of solid organ transplant recipients. Animal models would provide invaluable tools to investigate the cellular and molecular mechanisms underlying the pathogenesis of transplant arteriosclerosis, as well as for studies with novel drugs and other reagents for the prevention of the disease. We have therefore developed a modified technique for aortic transplantation in mice. The central suture ligation of the recipient abdominal aorta allowed a simpler end-to-side anastomosis of a segment of the donor thoracic aorta into the infrarenal portion of the recipient abdominal aorta. Using this technique, the overall survival rate was 94%. We also observed typical aspects of chronic rejection of the aortic allografts not observed with isografts. Our new technique is relatively easy to perform and has a low incidence of thrombosis, thus being useful for studying various aspects of transplant arteriosclerosis

Clinical Efficacy of Primary Tumor Volume Measurements: Comparison of Different Primary Sites

ObjectivesThe purpose of study was to determine the clinical efficacy of primary tumor volume measurements of different primary sites in the oropharynx compared to the oral cavity.MethodsA retrospective analysis of 85 patients with oral cavity or oropharynx cancer. The tumor area was manually outlined from axial magnetic resonance (MR) series. The software calculated the tumor volumes, automatically. The values of the primary tumor volumes were then subdivided into separate groups (≤3,500 mm3, >3,500 mm3).ResultsThe prognostic indicators were the cT and cN (oral cavity); age, primary site, cT, cN, and primary tumor volume (oropharynx) on the univariate analysis. There was no significant prognostic factor for oral cavity cancer on the multivariate analysis. Primary site, cN, and primary tumor volume were independent prognostic indicators for oropharynx cancer by multivariate analysis.ConclusionPrimary tumor volume measurement is a reliable way to stratify outcome, and make up for the weak points in the American Joint Committee on Cancer staging system with oropharynx cancer

Precessing Jet and Large Dust Grains in the V380 Ori NE Star-forming Region

The V380 Ori NE bipolar outflow was imaged in the SiO and CO J = 1 - 0 lines, and dense cores in L1641 were observed in the 2.0-0.89 mm continuum. The highly collimated SiO jet shows point-symmetric oscillation patterns in both position and velocity, which suggests that the jet axis is precessing and the driving source may belong to a non-coplanar binary system. By considering the position and velocity variabilities together, accurate jet parameters were derived. The protostellar system is viewed nearly edge-on, and the jet has a flow speed of 35 km/s and a precession period of 1600 years. The CO outflow length gives a dynamical timescale of 6300 years, and the protostar must be extremely young. The inferred binary separation of 6-70 au implies that this protobinary system may have been formed through the disk instability process. The continuum spectra of L1641 dense cores indicate that the emission comes from dust, and the fits with modified blackbody functions give emissivity power indices of beta = 0.3-2.2. The emissivity index shows a positive correlation with the molecular line width, but no strong correlation with bolometric luminosity or temperature. V380 Ori NE has a particularly low value of beta = 0.3, which tentatively suggests the presence of millimeter-sized dust grains. Because the dust growth takes millions of years, much longer than the protostellar age, this core may have produced large grains in the starless core stage. HH 34 MMS and HH 147 MMS also have low emissivity indices.Comment: To appear in the Astrophysical Journal Supplement Serie