Exogenous ANP Treatment Ameliorates Myocardial Insulin Resistance and Protects against Ischemia–Reperfusion Injury in Diet-Induced Obesity

Increasing evidence suggests natriuretic peptides (NPs) coordinate interorgan metabolic crosstalk. We recently reported exogenous ANP treatment ameliorated systemic insulin resistance by inducing adipose tissue browning and attenuating hepatic steatosis in diet-induced obesity (DIO). We herein investigated whether ANP treatment also ameliorates myocardial insulin resistance, leading to cardioprotection during ischemia–reperfusion injury (IRI) in DIO. Mice fed a high-fat diet (HFD) or normal-fat diet for 13 weeks were treated with or without ANP infusion subcutaneously for another 3 weeks. Left ventricular BNP expression was substantially reduced in HFD hearts. Intraperitoneal-insulin-administration-induced Akt phosphorylation was impaired in HFD hearts, which was restored by ANP treatment, suggesting that ANP treatment ameliorated myocardial insulin resistance. After ischemia–reperfusion using the Langendorff model, HFD impaired cardiac functional recovery with a corresponding increased infarct size. However, ANP treatment improved functional recovery and reduced injury while restoring impaired IRI-induced Akt phosphorylation in HFD hearts. Myocardial ultrastructural analyses showed increased peri-mitochondrial lipid droplets with concomitantly decreased ATGL and HSL phosphorylation levels in ANP-treated HFD, suggesting that ANP protects mitochondria from lipid overload by trapping lipids. Accordingly, ANP treatment attenuated mitochondria cristae disruption after IRI in HFD hearts. In summary, exogenous ANP treatment ameliorates myocardial insulin resistance and protects against IRI associated with mitochondrial ultrastructure modifications in DIO. Replenishing biologically active NPs substantially affects HFD hearts in which endogenous NP production is impaired.     

Metabolic Remodeling with Hepatosteatosis Induced Vascular Oxidative Stress in Hepatic ERK2 Deficiency Mice with High Fat Diets

We previously demonstrated the marked hepatosteatosis and endothelial dysfunction in hepatocyte-specific ERK2 knockout mice (LE2KO) with a high-fat/high-sucrose diet (HFHSD), but detailed metabolic changes and the characteristics in insulin-sensitive organs were not tested. This study aimed to characterize metabolic remodeling with changes in insulin-sensitive organs, which could induce endothelial dysfunction in HFHSD-LE2KO. The serum glucose and fatty acid (FA) were modestly higher in HFHSD-LE2KO than HFHSD-Control. FA synthesis genes were up-regulated, which was associated with the decreased phosphorylation of AMPK and ACC, and with the up-regulation of SREBP-1 in the liver from HFHSD-LE2KO. In FA and amino acids fraction analysis, arachidonic acid/eicosapentaenoic acid ratio, L-ornithine/arginine ratio, asymmetric dimethylarginine and homocysteine levels were elevated in HFHSD-LE2KO. Insulin-induced phosphorylation of AKT was blunted in skeletal muscle. Serum leptin and IL-1β were elevated, and serum adiponectin was decreased with the enlargement of epididymal adipocytes. Finally, the enhanced superoxide levels in the aorta, which were blunted with CCCP, apocynin, and tempol, were observed in HFHSD-LE2KO. A pre-incubation of aortic rings with tempol improved endothelial dysfunction in HFHSD-LE2KO. HFHSD-LE2KO revealed an acceleration of FA synthesis in the liver leading to insulin resistance in skeletal muscle and the enlargement of visceral adipocytes. Global metabolic remodeling such as changes in arginine metabolism, ω3/ω6 ratio, and adipocytokines, could affect the vascular oxidative stress and endothelial dysfunction in HFHSD-LE2KO.     

A brush device with visual and haptic feedback for virtual painting of 3D virtual objects

We have previously developed a mixed reality (MR) painting system with which a user could take a physical object in the real world and apply virtual paint to it. However, this system could not provide the sensation of painting on virtual objects in MR space. Therefore, we subsequently proposed and developed mechanisms that simulated the effect of touch and movement when a brush device was used to paint on a virtual canvas. In this paper, we use visual and haptic feedback to provide the sensation of painting on virtual three-dimensional objects using a new brush device called the MAI Painting Brush++. We evaluate and confirm its effectiveness through several user studies.     

Bidirectional transport of cadmium across apical membrane of renal epithelial cell lines via H+-antiporter and inorganic anion exchanger

Faecal swabs obtained from a random sample of 268 cows and 90 calves on 19 Lugo (northwestern Spain) farms were examined for necrotoxigenic Escherichia coli (NTEC) producing the cytotoxic necrotizing factors type 1 (CNF1) and type 2 (CNF2). We found NTEC CNF1+ and CNF2+ on 11% and 95% of the farms, respectively, NTEC producing CNF2 were significantly more frequently isolated from calves (58%) than from cows (17%) (P < 0.001). The proportion of animals colonized with CNF2+ strains on each farm ranged from 0% to 60%. NTEC strains producing CNF2 isolated from healthy cattle belonged to 27 O serogroups; however, 64% were of one of 12 serogroups (O2, O8, O8-O75, O14, O15, O55, O86, O88, O115, O121, O147, and O168). Furthermore, the serogroups determined in CNF2+ strains isolated from cows (O2, O8, and O14) were different from those found in NTEC producing CNF2 isolated from calves (O8-O75, O15, O55, O86, O88, O115 and O147).     

Inhibitory effect of cycloartenol ferulate, a component of rice bran, on tumor promotion in two-stage carcinogenesis in mouse skin

Sentinel lymph node (SN) biopsy in primary breast cancer seems to be an alternative to complete axillary lymph node dissection for evaluation of the axillary lymph node status in selected patients. Following evaluation of the technique of SN biopsy, we applied SN biopsy clinically to 23 selected patients. A lymphoscintigraphy was performed preoperatively to evaluate lymphatic drainage. The SN was identified in the operating room by use of a hand-held gamma camera and a blue vital dye. The SN was found in all 23 patients. In 17/23 the SN was tumor free and no axillary dissection was performed; 6/23 showed a positive SN and complete axillary dissection was done. Intraoperative lymphatic mapping and SN biopsy may be the treatment of choice for evaluation of axillary node status in selected patients, for it combines accurate nodal staging and low morbidity.     

Temperature- and capsaicin-sensitive nerve fibers in brown adipose tissue attenuate thermogenesis in the rat

Different variables influence the possibility that maternal viral infection may be transmitted to the fetus, although not all fetal infections result in fetal "illness" with consequent fetopathy. As concerns the fetus, prenatal diagnosis includes invasive techniques necessary for fetal tissue sampling. These techniques carry some risks. The fetal infectious risk, as determined by maternal clinico-serological profile and according to sonographic investigation, always should be weighed against the risks and benefits of invasive diagnostic procedures. The present study re-elaborates the criteria necessary for defining fetal risk as related to the maternal serological profile. In the 26 mothers with rubeola infection, the incidence of fetal mortality was 7.7%. Fetal prognosis worsens with the precocity of eruption. In these cases the esantema is the most reliable prognostic element as an indication to perform the invasive procedure. In the 15 patients with cytomegalovirus infection, no fetal or postnatal losses occurred. Morbidity occurred in 13.3% of cases, and the two ill fetuses were classified in the same risk group. In this group of patients, the maternal serological profile is a significant predictor of fetal morbidity.     

Surgical implication of aortic dissection on long-term outcome in Marfan patients

We herein review our 17-year surgical experience for the treatment of ascending aortic aneurysm in patients with Marfan syndrome to clarify the risks of increased mortality and reoperation. The subjects consisted of 15 patients who had all undergone surgery for the aortic root and ascending aorta at Niigata University Hospital between July 1978 and January 1995. Aortic valve replacement and ascending aortic wrapping were performed in 5 patients, Bentall or Cabrol operation in 6, and combined aortic arch reconstruction and Cabrol operation in 2, as the initial surgery. Patients who had an aortic dissection (Stanford type A) at initial surgery were assigned to group I (n = 7), while those with an aortic root aneurysm were assigned to group II (n = 8). In group I, 3 patients required a second operation for the remaining aortic arch aneurysm, and 1 died due to a late rupture of the distal aneurysm. In group II, no patient needed a reoperation; however, 1 died due to an intracranial hemorrhage and another due to composite valve graft failure and distal dissection. The results thus indicate that aortic dissection seems to affect long-term outcome, and therefore the combined repair of the aortic root and transverse arch is recommended in Marfan patients with aortic dissection involving the transverse aortic arch.     

Neocognitron with improved bend-extractors: Recognition of handwritten digits in the real world

We have reported previously that the performance of a neocognitron can be improved by a built-in bend-extracting layer. The conventional bend-extracting layer can detect bend points and end points of lines correctly, but not always crossing points of lines. This paper shows that an introduction of a mechanism of disinhibition can make the bend-extracting layer detect not only bend points and end points, but also crossing points of lines correctly. This paper also demonstrates that a neocognitron with this improved bend-extracting layer can recognise handwritten digits in the real world with a recognition rate of about 98%. We use the technique of dual thresholds for feature-extracting S-cells, and higher threshold values are used in the learning than in the recognition phase. We discuss how the threshold values affect the recognition rate.     

An experimental investigation on thermal striping: Mixing phenomena of a vertical non-buoyant jet with two adjacent buoyant jets as measured by ultrasound Doppler velocimetry

An experimental investigation on the thermal mixing phenomena of three quasi-planar vertical jets, with the central jet at a lower relative temperature than the two adjacent jets, was conducted. The central jet was unheated (‘cold’), while the two adjacent jets were heated (‘hot’). The temperature difference and velocity ratio between the heated (h) and unheated (c) jets were, ΔT_hc=5°C, 10°C and r=V_cold,exit/V_hot,exit=1.0 (isovelocity), 0.7, 0.5 (non-isovelocity) respectively. The typical Reynolds number was Re_D=1.8×10⁴, where D is the hydraulic diameter of the exit nozzle. Velocity measurement of a reference single-jet and triple-jet arrangement were taken by ultrasound Doppler velocimetry (UDV) while temperature data were taken by a vertically traversed thermocouple array. Our UDV data revealed that, beyond the exit region, our single-jet data behaved in the classic manner. In contrast, the triple-jet exhibited, for example, up to 20 times the root-mean-square velocity values of the single-jet, especially in the regions in-between the cold and hot jets. In particular, for the isovelocity case (V_exit=0.5 m/s) with ΔT_hc=5°C, we found that the convective mixing predominantly takes place at axial distances, z/D=2.0–4.5, over a spanwise width, x/D|2.25|, centered about the cold jet. An estimate of the turbulent heat flux distribution semi-quantitatively substantiated our results. As for the non-isovelocity case, temperature data showed a localized asymmetry that subsequently delayed the onset of mixing. Convective mixing however, did occur and yielded higher post-mixing temperatures in comparison to the isovelocity case.     

Nuclear localization of the delta subunit of Ca2+/calmodulin-dependent protein kinase II in rat cerebellar granule cells

To examine the physiological roles of the delta subunit of Ca2+/calmodulin-dependent protein kinase II (CaM kinase IIdelta) in brain, we examined the localization of CaM kinase IIdelta in the rat brain. A specific antibody to CaM kinase IIdelta1-delta4 isoforms was prepared by immunizing rabbits with a synthesized peptide corresponding to the unique carboxyl-terminal end of these isoforms. The prepared antibody did not recognize the alpha, beta, and gamma subunits, which were each overexpressed in NG108-15 cells. Immunoblot analysis on various regions and the nuclear fractions from rat brains suggested that some isoforms of CaM kinase IIdelta1-delta4 were abundant in the nucleus in the cerebellum. Total RNA from the cerebellum was analyzed by RT-PCR with a primer pair from variable domain 1 to variable domain 2. We detected the three PCR products delta3.1, delta3.4, and delta3 that contained the nuclear localization signal. These CaM kinase IIdelta3 isoforms were localized in the nuclei in transfected NG108-15 cells. Immunohistochemical study suggested the existence of these isoforms in the nuclei in cerebellar granule cells. These results suggest that CaM kinase IIdelta3 isoforms are involved in nuclear Ca2+ signaling in cerebellar granule cells.