Ribosome binding protein GCN1 regulates the cell cycle and cell proliferation and is essential for the embryonic development of mice.

Amino acids exert many biological functions, serving as allosteric regulators and neurotransmitters, as constituents in proteins and as nutrients. GCN2-mediated phosphorylation of eukaryotic initiation factor 2 alpha (elF2α) restores homeostasis in response to amino acid starvation (AAS) through the inhibition of the general translation and upregulation of amino acid biosynthetic enzymes and transporters by activating the translation of Gcn4 and ATF4 in yeast and mammals, respectively. GCN1 is a GCN2-binding protein that possesses an RWD binding domain (RWDBD) in its C-terminus. In yeast, Gcn1 is essential for Gcn2 activation by AAS; however, the roles of GCN1 in mammals need to be established. Here, we revealed a novel role of GCN1 that does not depend on AAS by generating two Gcn1 mutant mouse lines: Gcn1-knockout mice (Gcn1 KO mice (Gcn1-/-)) and RWDBD-deleted mutant mice (Gcn1ΔRWDBD mice). Both mutant mice showed growth retardation, which was not observed in the Gcn2 KO mice, such that the Gcn1 KO mice died at the intermediate stage of embryonic development because of severe growth retardation, while the Gcn1ΔRWDBD embryos showed mild growth retardation and died soon after birth, most likely due to respiratory failure. Extension of pregnancy by 24 h through the administration of progesterone to the pregnant mothers rescued the expression of differentiation markers in the lungs and prevented lethality of the Gcn1ΔRWDBD pups, indicating that perinatal lethality of the Gcn1ΔRWDBD embryos was due to simple growth retardation. Similar to the yeast Gcn2/Gcn1 system, AAS- or UV irradiation-induced elF2α phosphorylation was diminished in the Gcn1ΔRWDBD mouse embryonic fibroblasts (MEFs), suggesting that GCN1 RWDBD is responsible for GCN2 activity. In addition, we found reduced cell proliferation and G2/M arrest accompanying a decrease in Cdk1 and Cyclin B1 in the Gcn1ΔRWDBD MEFs. Our results demonstrated, for the first time, that GCN1 is essential for both GCN2-dependent stress response and GCN2-independent cell cycle regulation

ビョウインマエ シンパイ テイシ ニオケル キュウキュウ キュウメイシ ノ キカン ソウカン ニツイテ : ホンケン ノ ゲンジョウ ト コンゴ ノ カダイ

Activities of Japanese Paramedics have increased and advanced year by year. Especially, intubation for OHCPA（out of hospital cardiopulmonary arrest） is approved since July 2004, but it is necessary to finish the training in Fire-fighter’s school and intubation practice in hospitals. In Fire-fighter’s school, Paramedics attend lectures and simulation, and in hospital, intubation practice for patients. Medical-control is the system for keeping the qualities and verification of details in the scene of pre-hospital medical care. This report discusses the states and problems of paramedic intubation, practice in hospital, airway management, from the questionnaire survey

Comparative Studies of Values of Bone Mineral Density Measured with Different Photon Absorptiometries : A Preliminary Report

In order to compare values of bone mineral density measured with various photon absorptiometries, fundamental studies, using four different types of phantoms were performed in four instruments. The QDR-1000 (dual energy X-ray absorptiometry, DEXA) and Dualomex HC-1 (dual photon absorptiometry) were employed for the determination of bone mineral of a lumbar phantom and a cylindrical phantom, and the DCS-600 (DEXA) and Bone Densitometer (single photon absorptiometry) were used for the determination of bone mineral of a rectangular phantom and a ring phantom. The results indicate that the methodology for identification of the bone edge, which is necessary to calculate bone area or bone width, and the bone mineral per unit volume, which is defined as the line bone mineral content per cross-secional area, differ with the instruments used. Furthermore, the bone mineral per unit volume depends on the bone shape of the measured objects. Therefore, it seems taht the cross calibration of bone mineral density between instruments using phantoms is limited and in vivo investigation will be required in the future

A Study of Cases with Rib Metastasis Difficult to Distinguish from Microfractures on Bone Scintigraphy

A retrospective study of about 10,000 cases at Kawasaki Medical School Hospital on whom bone scans were performed over a six year period revealed five cases in which metastasis was mistaken for a benign rib lesion. This mistake occurred because the accumulation pattern of the radionuclide in the rib region on the bone scan indicated a so-called "hot spot" observed with microfractures rather than the rod-like increased accumulation along costal bones that is coincident with the finding of bone metastasis. This experience suggests that solitary hot spots in the rib region on bone scans should be diagnosed carefully, as such an accumulation is most frequently associated with a benign etiology but rarely may be a malignant lesion

Serial Cerebral Perfusion Imaging in a Case with Herpes Simplex Encephalitis

To evaluate cerebral blood flow, single photon emission computed tomographies (SPECTs) were serially performed in a case with herpes simplex encephalitis (HSE). Increased accumulation of N-ispropyl-I-123-p-iodoamphetamine (I-123-IMP) and Tc - 99m - hexamethylpropyleneamine oxime (Tc - 99m - HM - PAO) were noticed in the acute phase, and continued for seven weeks after the onset of the disease. In the third week, regional cerebral blood flow (rCBF) was estimated with I-123-IMP SPECT, and rCBF showed a high value in the affected temporal and occipital lobes of 60 to 70 ml/100 g/min (normal value; 40-50 ml/100 g/min), reflecting high accumulation of the tracer. After the twelfth week, when chinical symptoms and laboratory data had improved, the increased accumulation of these tracers was converted to a decreased accumulation

Abnormal axon guidance signals and reduced interhemispheric connection via anterior commissure in neonates of marmoset ASD model

In autism spectrum disorder (ASD), disrupted functional and structural connectivity in the social brain has been suggested as the core biological mechanism underlying the social recognition deficits of this neurodevelopmental disorder. In this study, we aimed to identify genetic and neurostructural abnormalities at birth in a non-human primate model of ASD, the common marmoset with maternal exposure to valproic acid (VPA), which has been reported to display social recognition deficit in adulthood. Using a comprehensive gene expression analysis, we found that 20 genes were significantly downregulated in VPA-exposed neonates. Of these, Frizzled3 (FZD3) and PIK3CA were identified in an axon guidance signaling pathway. FZD3 is essential for the normal development of the anterior commissure (AC) and corpus callosum (CC); hence, we performed diffusion tensor magnetic resonance imaging with a 7-Tesla scanner to measure the midsagittal sizes of these structures. We found that the AC size in VPA-exposed neonates was significantly smaller than that in age-matched controls, while the CC size did not differ. These results suggest that downregulation of the genes related to axon guidance and decreased AC size in neonatal primates may be linked to social brain dysfunctions that can happen later in life

Successful cricothyrotomy for emergency airway management : a case report

A ６０ year-old male was brought to our emergency department by ambulance due to sudden onset of dyspnea. On examination, he was in coma since his level of consciousness decreased during transport, blood pressure was １９９／１１１mmHg, heart rate was１００ beats per minute, respirations were １０ per minute, blood oxygen saturation level（SpO２）was１００％ via assisted ventilation with Bag-Valve-Mask, and stridor was heard on auscultation. Those findings indicated airway emergency and endotracheal intubation was required. However, attempts at intubation were unsuccessful due to restriction of mouth opening. Muscle relaxant was then given to perform rapid sequence intubation, which caused vomiting. Failure to ventilation and intubation resulted in cardiopulmonary arrest. Chest compression was started immediately and decision for cricothyrotomy was made. １０ minute after cricothyrotomy, he revived. Subsequently, systemic management including therapeutic normothermia was performed at intensive care unit, then he regained consciousness. He was discharged １ month after admission

Conduction-band electronic states of YbInCu4 studied by photoemission and soft x-ray absorption spectroscopies

We have studied conduction-band (CB) electronic states of a typical valence-transition compound YbInCu4 by means of temperature-dependent hard x-ray photoemission spectroscopy (HX-PES) of the Cu 2p3/2 and In 3d5/2 core states taken at hν=5.95 keV, soft x-ray absorption spectroscopy (XAS) of the Cu 2p3/2 core absorption region around hν∼935 eV, and soft x-ray photoemission spectroscopy (SX-PES) of the valence band at the Cu 2p3/2 absorption edge of hν=933.0 eV. With decreasing temperature below the valence transition at TV=42 K, we have found that (1) the Cu 2p3/2 and In 3d5/2 peaks in the HX-PES spectra exhibit the energy shift toward the lower binding-energy side by ∼40 and ∼30 meV, respectively, (2) an energy position of the Cu 2p3/2 main absorption peak in the XAS spectrum is shifted toward higher photon-energy side by ∼100 meV, with an appearance of a shoulder structure below the Cu 2p3/2 main absorption peak, and (3) an intensity of the Cu L3VV Auger spectrum is abruptly enhanced. These experimental results suggest that the Fermi level of the CB-derived density of states is shifted toward the lower binding-energy side. We have described the valence transition in YbInCu4 in terms of the charge transfer from the CB to Yb 4f states