PPM1A Controls Diabetic Gene Programming through Directly Dephosphorylating PPAR?? at Ser273

Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a master regulator of adipose tissue biology. In obesity, phosphorylation of PPAR gamma at Ser273 (pSer273) by cyclin-dependent kinase 5 (CDK5)/extracellular signal-regulated kinase (ERK) orchestrates diabetic gene reprogramming via dysregulation of specific gene expression. Although many recent studies have focused on the development of non-classical agonist drugs that inhibit the phosphorylation of PPAR gamma at Ser273, the molecular mechanism of PPAR gamma dephosphorylation at Ser273 is not well characterized. Here, we report that protein phosphatase Mg2+/Mn2+-dependent 1A (PPM1A) is a novel PPAR gamma phosphatase that directly dephosphorylates Ser273 and restores diabetic gene expression which is dysregulated by pSer273. The expression of PPM1A significantly decreases in two models of insulin resistance: diet-induced obese (DIO) mice and db/db mice, in which it negatively correlates with pSer273. Transcriptomic analysis using microarray and genotype-tissue expression (GTEx) data in humans shows positive correlations between PPM1A and most of the genes that are dysregulated by pSer273. These findings suggest that PPM1A dephosphorylates PPAR gamma at Ser273 and represents a potential target for the treatment of obesity-linked metabolic disorders

Broussonetia papyrifera Root Bark Extract Exhibits Anti-inflammatory Effects on Adipose Tissue and Improves Insulin Sensitivity Potentially Via AMPK Activation

The chronic low-grade inflammation in adipose tissue plays a causal role in obesity-induced insulin resistance and its associated pathophysiological consequences. In this study, we investigated the effects of extracts of Broussonetia papyrifera root bark (PRE) and its bioactive components on inflammation and insulin sensitivity. PRE inhibited TNF-alpha-induced NF-kappa B transcriptional activity in the NF-kappa B luciferase assay and pro-inflammatory genes' expression by blocking phosphorylation of I kappa B and NF-kappa B in 3T3-L1 adipocytes, which were mediated by activating AMPK. Ten-week-high fat diet (HFD)-fed C57BL6 male mice treated with PRE had improved glucose intolerance and decreased inflammation in adipose tissue, as indicated by reductions in NF-kappa B phosphorylation and pro-inflammatory genes' expression. Furthermore, PRE activated AMP-activated protein kinase (AMPK) and reduced lipogenic genes' expression in both adipose tissue and liver. Finally, we identified broussoflavonol B (BF) and kazinol J (KJ) as bioactive constituents to suppress pro-inflammatory responses via activating AMPK in 3T3-L1 adipocytes. Taken together, these results indicate the therapeutic potential of PRE, especially BF or KJ, in metabolic diseases such as obesity and type 2 diabetes

Idiopathic severe hypermagnesemia in an extremely low birth weight infant on the first day of life

A preterm female infant born at 27 weeks of gestation with a birth weight of 990 g developed acute hypotonia, apnea, hypotension and bradycardia mimicking septic shock syndrome at 14h after birth. Laboratory tests indicated a severe hypermagnesemia of 45 mg/dL. The renal function, complete blood count and maternal blood concentrations of magnesium were normal, and the blood cultures were negative. The patient recovered with treatment including exchange transfusion. However, the etiology of the severe hypermagnesemia remains unknown

Regional outbreak of staphylococcal scalded skin syndrome in healthy children

Purpose : Staphylococcal scalded skin syndrome (SSSS) is a relatively uncommon superficial blistering skin disease that is due to Staphylococcus aureus. We had experienced a regional outbreak of SSSS over 3 years in healthy children. Methods : We retrospectively reviewed the medical records of those patients diagnosed as SSSS. Most of neonatal cases were nosocomial infections and excluded from the analysis. The clinical features, laboratory findings, the isolation and antibiotic resistance of S. aureus, the antibiotic management and other supportive treatments were analyzed. Results : Fifty-five patients with SSSS were admitted to our hospital from October 2001 to September 2004. The median age of patients was 3.0 years. Of the 55 patients, 9 were the generalized type, 13 were the intermediate type and 33 were the scarletiniform rash. All the patients were living in neighborhood of the Jinju area. S. aureus were isolated from 9 of the patients and all of the isolated S. aureus were methicillin resistant. All the patients except two were treated with intravenous flocloxacillin or nafcillin and/or cefotaxime. All the patients recovered during the follow-up period of 2 to 3 weeks. Conclusion : We experienced a regional outbreak of SSSS in previous healthy children. Further study for finding the carriers of S. aureus caused SSSS and preventing the spread of this disease is needed. Additionally, guidelines for treating SSSS due to methicillin resistant S. aureus should be established

Inappropriate antidiuretic hormone syndrome presenting as ectopic antidiuretic hormone-secreting gastric adenocarcinoma: a case report

INTRODUCTION: Although the syndrome of inappropriate antidiuretic hormone has connection with various malignant tumors, there are few reports associated with advanced gastric cancer. CASE PRESENTATION: We describe the case of a 63-year-old Korean male with inappropriate antidiuretic hormone syndrome due to an ectopic antidiuretic hormone-producing advanced gastric adenocarcinoma manifested with overt serum hypo-osmolar hyponatremia and high urinary sodium concentrations. His adrenal, thyroidal, and renal functioning were normal, and the hyponatremia improved following removal of the tumor. The cancer cells were immunostained and found to be positive for the antidiuretic hormone. To our knowledge, this is the first report of an antidiuretic hormone-secreting advanced gastric adenocarcinoma associated with the syndrome of inappropriate antidiuretic hormone, showing cancer cells immunostained for the antidiuretic hormone. CONCLUSIONS: Although a strong relationship between gastric cancer and the syndrome of inappropriate antidiuretic hormone remains to be established, we suggest that gastric cancer could be included as a differential diagnosis of cancer that is associated with the syndrome of antidiuretic hormone

Dependence of GCRs influx on the Solar North-South Asymmetry

We investigate the dependence of the amount of the observed galactic cosmic ray (GCR) influx on the solar North-South asymmetry using the neutron count rates obtained from four stations and sunspot data in archives spanning six solar cycles from 1953 to 2008. We find that the observed GCR influxes at Moscow, Kiel, Climax and Huancayo stations are more suppressed when the solar activity in the southern hemisphere is dominant compared with when the solar activity in the northern hemisphere is dominant. Its reduction rates at four stations are all larger than those of the suppression due to other factors including the solar polarity effect on the GCR influx. We perform the student's t-test to see how significant these suppressions are. It is found that suppressions due to the solar North-South asymmetry as well as the solar polarity are significant and yet the suppressions associated with the former are larger and more significant.Comment: 17 pages, 3figures, accepted to JAST

Satellite radiance data assimilation for binary tropical cyclone cases over the western North Pacific

A total of three binary tropical cyclone (TC) cases over the Western North Pacific are selected to investigate the effects of satellite radiance data assimilation on analyses and forecasts of binary TCs. Two parallel cycling experiments with a 6 h interval are performed for each binary TC case, and the difference between the two experiments is whether satellite radiance observations are assimilated. Satellite radiance observations are assimilated using the Weather Research and Forecasting Data Assimilation (WRFDA)'s three-dimensional variational (3D-Var) system, which includes the observation operator, quality control procedures, and bias correction algorithm for radiance observations. On average, radiance assimilation results in slight improvements of environmental fields and track forecasts of binary TC cases, but the detailed effects vary with the case. When there is no direct interaction between binary TCs, radiance assimilation leads to better depictions of environmental fields, and finally it results in improved track forecasts. However, positive effects of radiance assimilation on track forecasts can be reduced when there exists a direct interaction between binary TCs and intensities/structures of binary TCs are not represented well. An initialization method (e.g., dynamic initialization) combined with radiance assimilation and/or more advanced DA techniques (e.g., hybrid method) can be considered to overcome these limitations

A Case of Non-Hodgkin's Lymphoma in Patient with Coombs' Negative Hemolytic Anemia and Idiopathic Thrombocytopenic Purpura

Coombs' negative autoimmune hemolytic anemia (AIHA) is a rare disease which shares similar clinical and hematological features with Coombs' positive AIHA, but its exact frequency remains unknown. There have been few reports of idiopathic thrombocytopenic purpura (ITP) and Coombs' negative AIHA associated with other lymphoproliferative disorders (LPDs). Since there is a well known association between LPDs and autoimmune phenomena, it is important to investigate the possibility of an underlying malignancy. We report a case of ITP and Coombs' negative AIHA associated with diffuse large B-cell lymphoma