Evidence for the Involvement of a Src-Related Tyrosine Kinase inXenopusEgg Activation

AbstractRecently, we have purified a Src-related tyrosine kinase, namedXenopustyrosine kinase (Xyk), from oocytes ofXenopus laevisand found that the enzyme is activated within 1 min following fertilization [Satoet al.(1996)J. Biol. Chem.271, 13250–13257]. A concomitant translocation of a part of the activated enzyme from the membrane fraction to the cytosolic fraction was also observed. In the present study, we show that parthenogenetic egg activation by a synthetic RGDS peptide [Y. Iwao and T. Fujimura, T. (1996)Dev. Biol.177, 558–567], an integrin-interacting peptide, but not by electrical shock or the calcium ionophore A23187 causes the kinase activation, tyrosine phosphorylation, and translocation of Xyk. A synthetic tyrosine kinase-specific inhibitor peptide was employed to analyze the importance of the Xyk activity in egg activation. We found that the peptide inhibits the kinase activity of purified Xyk at IC50of 8 μM. Further, egg activation induced by sperm or RGDS peptide but not by A23187 was inhibited by microinjection of the peptide. In the peptide-microinjected eggs, penetration of the sperm nucleus into the egg cytoplasm and meiotic resumption in the egg were blocked. Indirect immunofluorescence study demonstrates that Xyk is exclusively localized to the cortex ofXenopuseggs, indicating that Xyk can function in close proximity to the sperm–egg or RGDS peptide–egg interaction site. Taken together, these data suggest that the tyrosine kinase Xyk plays an important role in the early events ofXenopusegg activation in a manner independent or upstream of calcium signaling

Renal tubular Sirt1 attenuates diabetic albuminuria by epigenetically suppressing Claudin-1 overexpression in podocytes

Sirtuin 1 (Sirt1), a NAD[superscript +]-regulated deacetylase with numerous known positive effects on cellular and whole-body metabolism, is expressed in the renal cortex and medulla. It is known to have protective effects against age-related disease, including diabetes. Here we investigated the protective role of Sirt1 in diabetic renal damage. We found that Sirt1 in proximal tubules (PTs) was downregulated before albuminuria occurred in streptozotocin-induced or obese (db/db) diabetic mice. PT-specific SIRT1 transgenic and Sirt1 knockout mice showed prevention and aggravation of the glomerular changes that occur in diabetes, respectively, and nondiabetic knockout mice exhibited albuminuria, suggesting that Sirt1 in PTs affects glomerular function. Downregulation of Sirt1 and upregulation of the tight junction protein Claudin-1 by SIRT1-mediated epigenetic regulation in podocytes contributed to albuminuria. We did not observe these phenomena in 5/6 nephrectomized mice. We also demonstrated retrograde interplay from PTs to glomeruli using nicotinamide mononucleotide (NMN) from conditioned medium, measurement of the autofluorescence of photoactivatable NMN and injection of fluorescence-labeled NMN. In human subjects with diabetes, the levels of SIRT1 and Claudin-1 were correlated with proteinuria levels. These results suggest that Sirt1 in PTs protects against albuminuria in diabetes by maintaining NMN concentrations around glomeruli, thus influencing podocyte function.Japan. Ministry of Education, Culture, Sports, Science and Technology (Grant 22790800

実習における介護計画記録と毎日の計画実践記録の様式と記載方法の試案

介護の質を向上させるために必要不可欠な介護過程であるが,介護においてはまだ十分に普及し活用されていないのが現状で,介護過程をどのように学ばせるかといった教材はまだまだ不足しているように思われる。2年間という限られた時間に効果的に介護過程教育を行うために介護計画記録と毎日の実践記録の様式と記載方法を試案したのでその内容を報告する

側頭筋を貫通する顎動脈の一例

We found a case of the right maxillary artery piercing the temporal muscle in a 71-year-old Japanese male cadaver during an anatomical dissection carried out at Iwate Medical University in 2005. The main route of the maxillary artery in this case was running near the infratemporal ridge which was the extreme inferior origin of the temporal muscle. The origin of the pierced muscle bundle by this artery was from the infratemporal ridge to the infratemporal fossa. At the mastication, the route of the maxillary artery piercing the temporal muscle was thought productive of a disturbance in the bloodstream. We alerted the surgeon about the route in this case when the operation area reached the pterygopalatine fossa

An autopsy case of familial amyotrophic lateral sclerosis and dementia with p.R487H VCP gene mutation

We described an autopsied case of amyotrophic lateral sclerosis (ALS)-dementia with p.R487H mutation in the VCP gene. TDP-43-positive neuronal cytoplasmic inclusions (NCI), neuronal intranuclear inclusions (NII) and glial cytoplasmic inclusions were observed in the brain. The frequency of NCI was small but equal to that of NII, an atypical finding for VCP-related disorders. In contrast, the findings in the spinal cord and brainstem closely resembled those of sporadic ALS