Impact of obesity on childhood kidney

Obese patients are known to have greater risks to develop hypertension, coronary vascular disease, and insulin resistance, and more attention has been recently paid to the impact of obesity on kidney. This study was conducted to investigate whether obese children have higher risk of renal injury as well as adults. Eighteen hundred and thirty school children aged 6–14 years with abnormal urinary findings on thrice occasions detected by the screening program for renal disease in Japan were enrolled. Of them, 27 children with nephritis or suspected nephritis diagnosed by persistent proteinuria with hematuria were compared to 588 without urinary abnormalities regarding their body mass index (BMI), blood pressure (BP), and serum level of total cholesterol. BMI and systolic BP (mmHg) were significantly higher in the former than in the latter. As a result, obesity may be associated with the development of renal injury even in childhood

Type D Syndrome of Inappropriate Antidiuretic Hormone Secretion in a Schizophrenia Patient with Polydipsia

A 55-year-old man with schizophrenia developed water intoxication due to primary polydipsia. His manner of antidiuretic hormone secretion was investigated by water loading and infusion of hypertonic saline to clarify the form of the syndrome of inappropriate antidiuretic hormone secretion. The plasma antidiuretic hormone level, which may be involved in the occurrence of water intoxication, was consistently low in this patient, and linked to type D syndrome of inappropriate antidiuretic hormone secretion, designated “hypovasopressinemic antidiuresis”. Although this type is not common, it should be considered as a pathophysiology for water intoxication in schizophrenia patients

Fundamental evaluation of hydrogen behavior in sodium for sodium-water reaction detection of sodium-cooled fast reactor

In a secondary cooling system of a sodium-cooled fast reactor (SFR), rapid detection of hydrogen due to sodium-water reaction (SWR) caused by water leakage from a heat exchanger tube of a steam generator (SG) is important in terms of safety and property protection of the SFR. For hydrogen detection, the hydrogen detectors using atomic transmission phenomenon of hydrogen within Ni-membrane were used in Japanese proto-type SFR “Monju”. However, during the plant operation, detection signals of water leakage were observed even in the situation without SWR concerning temperature up and down in the cooling system. For this reason, the study of a new hydrogen detector has been carried out to improve stability, accuracy and reliability. In this research, the authors focus on the difference in composition of hydrogen and the difference between the background hydrogen under normal plant operation and the one generated by SWR and theoretically estimate the hydrogen behavior in liquid sodium by using ultra-accelerated quantum chemical molecular dynamics (UA-QCMD). Based on the estimation, dissolved H or NaH, rather than molecular hydrogen (H2), is the predominant form of the background hydrogen in liquid sodium in terms of energetical stability. On the other hand, it was found that hydrogen molecules produced by the sodium-water reaction can exist stably as a form of a fine bubble concerning some confinement mechanism such as a NaH layer on their surface. At the same time, we observed experimentally that the fine H2 bubbles exist stably in the liquid sodium, longer than previously expected. This paper describes the comparison between the theoretical estimation and experimental results based on hydrogen form in sodium in the development of the new hydrogen detector in Japan

Phosphorylation of ERK5 on Thr732 is associated with ERK5 nuclear localization and ERK5-dependent transcription.

Extracellular signal-regulated kinases (ERKs) play critical roles in numerous cellular processes, including proliferation and differentiation. ERK5 contains a kinase domain at the N-terminal, and the unique extended C-terminal includes multiple autophosphorylation sites that enhance ERK5-dependent transcription. However, the impact of phosphorylation at the various sites remain unclear. In this study, we examined the role of phosphorylation at the ERK5 C-terminal. We found that a constitutively active MEK5 mutant phosphorylated ERK5 at the TEY motif, resulting in the sequential autophosphorylation of multiple C-terminal residues, including Thr732 and Ser769/773/775. However, when ERK1/2 was selectively activated by an oncogenic RAS mutant, ERK5 phosphorylation at Thr732 was induced without affecting the phosphorylation status at TEY or Ser769/773/775. The Thr732 phosphorylation was U0126-sensitive and was observed in a kinase-dead mutant of ERK5 as well, suggesting that ERK1/2 can phosphorylate ERK5 at Thr732. This phosphorylation was also promoted by epidermal growth factor and nerve growth factor in HEK293 and PC12 cells, respectively. The ERK5-T732A mutant was localized in the cytosol under basal conditions. In contrast, ERK5 phosphorylated at Thr732 via the RAS-ERK1/2 pathway and ERK5-T732E, which mimics the phosphorylated form, were localized in both the nucleus and cytosol. Finally, ER-32A and U0126 blocked ERK5-dependent MEF2C transcriptional activity. Based on these findings, we propose a novel cross-talk mechanism in which ERK1/2, following activation by growth factor stimulation, phosphorylates ERK5 at Thr732. This phosphorylation event is responsible for ERK5 nuclear localization and ERK5-dependent transcription

Endogenous ERK5 forms a complex with ERK1/2 in PC12 cells.

<p><b>(A)</b> PC12 cells were lysed, and endogenous ERK2 was immunoprecipitated using an anti-ERK2 antibody. Endogenous ERK5 and ERK2 in the immunoprecipitates or total cell lysate (TCL) were examined by Western blotting. <b>(B)</b> PC12 cells were stimulated with NGF (100 ng/ml) for 5 min, then the cells were lysed, and endogenous ERK2 was immunoprecipitated using an anti-ERK2 antibody. Endogenous ERK5 and ERK2 in the immunoprecipitates or total cell lysate (TCL) were examined by Western blotting.</p

Putative cross-talk mechanism between ERK5 and ERK1/2.

<p><b>(1)</b> Growth factors such as NGF and EGF promote phosphorylation of ERK1/2 and ERK5 at their TEY motifs through MEK1/2 and MEK5, respectively, then their kinase activity increases rapidly upon phosphorylation. (<b>2)</b> Activated ERK5 autophosphorylates its C-terminal residues including Ser769/773/775. <b>(3)</b> Activated ERK1/2 phosphorylates the C-terminal of ERK5 at Thr732; this phosphorylation event is essential for ERK5 nuclear localization and ERK5-dependent transcription via an unknown mechanism.</p

ERK1/2 phosphorylates ERK5 at Thr732 in HEK293 cells.

<p><b>(A)</b> HEK293 cells were co-transfected with mycERK5, mycERK2 and empty vector (Vec), constitutively active RAS mutant (RASV12) or constitutively active MEK5 mutant (MEK5D). The cells were incubated in the presence or absence of U0126 (20 μM) for 24 h, then ERK5 phosphorylation status at its TEY site, Thr732 and Ser769/773/775, phospho-ERK1/2 (TEY), mycERK5 and mycERK2 were examined by Western blotting. <b>(B)</b> HEK293 cells were co-transfected with RASV12, mycERK2 and mycERK5 wild-type (WT) or mycERK5 kinase-dead (KD) mutant. The cells were incubated in the presence or absence of U0126 (20 μM) for 24 h, then ERK5 phosphorylation status at its TEY site and Thr732, phospho-ERK1/2 (TEY), mycERK5 and mycERK2 were examined by Western blotting.</p