Aims/hypothesis The aim of this study was to confirm a link between mitochondrial dysfunction and type 2 diabetes. Materials and methods Cellular levels of mitochondrial proteins, cellular ...mitochondrial DNA content, and mitochondrial function and morphology were assessed by MitoTracker staining and electron microscopy, in white adipose tissue of 12-week-old male wild-type, obese (ob/ob), and diabetic (db/db) mice. Results Levels of mitochondrial proteins were found to be very similar in the livers and muscles of all the mice studied. However, levels were greatly decreased in the adipocytes of db/db mice, but not in those of the wild-type and ob/ob mice. Levels of mitochondrial DNA were also found to be considerably reduced in the adipocytes of db/db mice. MitoTracker staining and under electron microscopy revealed that the number of mitochondria was reduced in adipocytes of db/db mice. Respiration and fatty acid oxidation studies indicated mitochondrial dysfunction in adipocytes of db/db mice. Interestingly, there was an increase in mitochondria and mitochondrial protein production in adipocytes of db/db mice treated with rosiglitazone, an agent that enhances insulin sensitivity. Conclusions/interpretation Taken together, these data indicate that mitochondrial loss in adipose tissue is correlated with the development of type 2 diabetes.
Manic episodes are one of the major diagnostic symptoms in a spectrum of neuropsychiatric disorders that include schizophrenia, obsessive-compulsive disorder and bipolar disorder (BD). Despite a ...possible association between BD and the gene encoding phospholipase Cγ1 (PLCG1), its etiological basis remains unclear. Here, we report that mice lacking phospholipase Cγ1 (PLCγ1) in the forebrain (Plcg1
; CaMKII) exhibit hyperactivity, decreased anxiety-like behavior, reduced depressive-related behavior, hyperhedonia, hyperphagia, impaired learning and memory and exaggerated startle responses. Inhibitory transmission in hippocampal pyramidal neurons and striatal dopamine receptor D1-expressing neurons of Plcg1-deficient mice was significantly reduced. The decrease in inhibitory transmission is likely due to a reduced number of γ-aminobutyric acid (GABA)-ergic boutons, which may result from impaired localization and/or stabilization of postsynaptic CaMKII (Ca
/calmodulin-dependent protein kinase II) at inhibitory synapses. Moreover, mutant mice display impaired brain-derived neurotrophic factor-tropomyosin receptor kinase B-dependent synaptic plasticity in the hippocampus, which could account for deficits of spatial memory. Lithium and valproate, the drugs presently used to treat mania associated with BD, rescued the hyperactive phenotypes of Plcg1
; CaMKII mice. These findings provide evidence that PLCγ1 is critical for synaptic function and plasticity and that the loss of PLCγ1 from the forebrain results in manic-like behavior.
Numerous genetic and functional studies implicate variants of Neuregulin-1 (NRG1) and its neuronal receptor ErbB4 in schizophrenia and many of its endophenotypes. Although the neurophysiological and ...behavioral phenotypes of NRG1 mutant mice have been investigated extensively, practically nothing is known about the function of NRG2, the closest NRG1 homolog. We found that NRG2 expression in the adult rodent brain does not overlap with NRG1 and is more extensive than originally reported, including expression in the striatum and medial prefrontal cortex (mPFC), and therefore generated NRG2 knockout mice (KO) to study its function. NRG2 KOs have higher extracellular dopamine levels in the dorsal striatum but lower levels in the mPFC; a pattern with similarities to dopamine dysbalance in schizophrenia. Like ErbB4 KO mice, NRG2 KOs performed abnormally in a battery of behavioral tasks relevant to psychiatric disorders. NRG2 KOs exhibit hyperactivity in a novelty-induced open field, deficits in prepulse inhibition, hypersensitivity to amphetamine, antisocial behaviors, reduced anxiety-like behavior in the elevated plus maze and deficits in the T-maze alteration reward test-a task dependent on hippocampal and mPFC function. Acute administration of clozapine rapidly increased extracellular dopamine levels in the mPFC and improved alternation T-maze performance. Similar to mice treated chronically with N-methyl-d-aspartate receptor (NMDAR) antagonists, we demonstrate that NMDAR synaptic currents in NRG2 KOs are augmented at hippocampal glutamatergic synapses and are more sensitive to ifenprodil, indicating an increased contribution of GluN2B-containing NMDARs. Our findings reveal a novel role for NRG2 in the modulation of behaviors with relevance to psychiatric disorders.
Sm–Nd chronometers use
146
Sm and
147
Sm to determine the ages of major events in the early Solar System. Their half-lives are the most important nuclear parameters determining the accuracy of ...chronometry. However, the
146
Sm half-life is not well-established: the published values differ by
∼
30%, which results in significant uncertainties in the Solar System timeline. We are re-measuring the half-lives of
146
Sm and
147
Sm using decay energy spectroscopy and metallic magnetic calorimeters to improve the accuracy of the Sm–Nd chronometers. We report recent experimental results from our first measurement of a
147
Sm source, as well as status and plans for experiments on
146
Sm.
To identify the prevalence, clinical characteristics, risk factors of hepatic complications after a Fontan operation.
This was a cross-sectional study of 139 Fontan patients who underwent cardiac CT ...scans out of a total of 204 patients who had undergone the Fontan procedure between 1986 and 2003. Mean age was 19.0 ± 6.3 years and mean elapsed time since the initial Fontan operation was 11.5 ± 4.7 years. Subjects' clinical features, echocardiograms, radiological features and biochemical test results were reviewed. Various non-invasive hepatic fibrosis blood markers were also evaluated.
Fifty-seven patients had hepatic complications, including radiological features of liver cirrhosis (25.9%), thrombocytopenia (7.2%), hyperbilirubinaemia (20.9%) and hepatic masses (2.9%). Hepatic complications were also significantly associated with ventricular dysfunction (p=0.020), absence of fenestration (p=0.004), thrombus in the Fontan tract (p=0.027), sinus node dysfunction (p=0.034) and tachyarrhythmia (p<0.001). In a multivariate analysis, the elapsed time since the initial Fontan operation was the only measure that was correlated with hepatic complications; the odds ratio of the post-Fontan duration of 16-20 years to that of 0-5 years was 9.00 (CI 2.24 to 36.17). The non-invasive hepatic fibrosis blood marker (Forns index) was also correlated with the elapsed time since the initial Fontan operation (r=0.718, p<0.001).
Late hepatic dysfunction and cirrhotic change were often seen in Fontan patients. Moreover, hepatic complications were correlated with the duration of Fontan circulation. Therefore, after a Fontan operation, regular evaluation of the hepatic condition is required--for which some non-invasive hepatic fibrosis markers can be effectively used.
Ocean–atmosphere interaction over the Northern Hemisphere western boundary current (WBC) regions (i.e., the Gulf Stream, Kuroshio, Oyashio, and their extensions) is reviewed with an emphasis on their ...role in basin-scale climate variability. SST anomalies exhibit considerable variance on interannual to decadal time scales in these regions. Low-frequency SST variability is primarily driven by basin-scale wind stress curl variability via the oceanic Rossby wave adjustment of the gyre-scale circulation that modulates the latitude and strength of the WBC-related oceanic fronts. Rectification of the variability by mesoscale eddies, reemergence of the anomalies from the preceding winter, and tropical remote forcing also play important roles in driving and maintaining the low-frequency variability in these regions. In the Gulf Stream region, interaction with the deep western boundary current also likely influences the low-frequency variability. Surface heat fluxes damp the low-frequency SST anomalies over the WBC regions; thus, heat fluxes originate with heat anomalies in the ocean and have the potential to drive the overlying atmospheric circulation. While recent observational studies demonstrate a local atmospheric boundary layer response to WBC changes, the latter’s influence on the large-scale atmospheric circulation is still unclear. Nevertheless, heat and moisture fluxes from the WBCs into the atmosphere influence the mean state of the atmospheric circulation, including anchoring the latitude of the storm tracks to the WBCs. Furthermore, many climate models suggest that the large-scale atmospheric response to SST anomalies driven by ocean dynamics in WBCregions can be important in generating decadal climate variability. As a step toward bridging climate model results and observations, the degree of realism of the WBC in current climate model simulations is assessed. Finally, outstanding issues concerning ocean–atmosphere interaction in WBC regions and its impact on climate variability are discussed.
To address the lack of awareness on environmental values, this study estimates the environmental value of mountain ranges (Jeongmaek) connected to the Baekdudaegan mountain system in South Korea. ...Seven Jeongmaek are studied during 2011–2016 using a questionnaire survey and the contingent valuation method. Based on willingness to pay (WTP) for biodiversity, this study finds that the lowest estimated WTP was KRW 5813 for Geumbuk and Hannam-Geumbuk Jeongmaek, and the highest value was KRW 120,471 for Hanbuk Jeongmaek. These differences in WTP appear to be significantly determined by education level and number of visits of respondents.
The stabilizer of a YBCO coated conductor (CC) plays a very important role in bypassing the over-current and transferring the heat generated at the moment of a fault. Therefore, one of big issues is ...to determine the best material for the stabilizer and its dimensions for high performance in a HTS power application system. In the case of a superconducting fault current limiter (SFCL), which requires it to react immediately to any fault, the characteristics of the stabilizer are decisive in limiting the fault current and recovering the superconducting properties during and after quenching. This study examined the electrical and thermal behavior of YBCO CCs with various stabilizer thicknesses in fault mode to determine the effects of the stabilizer thickness on the quench/recovery characteristics of YBCO CCs. In particular, the electric field intensity (E) of YBCO CCs in fault mode were calculated and compared with the experimental results.
Background
The safety and effectiveness of radiofrequency catheter ablation (RFCA) for supraventricular tachycardia (SVT) in young children was investigated.
Methods
Ninety‐five children who ...underwent RFCA procedures were stratified according to age (group 1, 0–4 years, n = 24; group 2, 5–9 years, n = 71) and were evaluated retrospectively.
Results
Among the 95 patients, atrioventricular reentrant tachycardia was 78.9%, atrioventricular nodal reentrant tachycardia was 10.5%, and ectopic atrial tachycardia was 8.4%. The acute success rate of RFCA was 97.9% and the recurrence rate was 11.6%. RFCA was performed for different main reasons in each group, including drug‐resistant tachycardia (37.5% in group 1 vs 7% in group 2; P = 0.001) and symptomatic tachycardia (4.2% in group 1 vs 57.7% in group 2; P < 0.001). There was no significant difference in success rate, recurrence rate, and procedure and fluoroscopy duration between the two groups. The acute success rates did not differ significantly between patients with a single accessory pathway (AP) and those with multiple APs; however, failure or recurrence was more common in the patients with multiple APs (38.5% vs 11.5%; P = 0.01). The multiple APs were found frequently on the right side (P = 0.005). Septal dyskinesia with left ventricular dysfunction in Wolff‐Parkinson‐White syndrome and tachycardia‐induced cardiomyopathy improved after RFCA.
Conclusions
RFCA was found to be effective and safe for SVT in young children.
Web services are currently one of the trends in network-based business services, which intuitively will be applied to build a semantic web-based decision support system (DSS). Since web services are ...self-contained, modular business process applications, based on open standards, enable integration models for facilitating program-to-program interactions. Decision modules in a semantic web-based DSS can be viewed as a web service. However, according to the current features, web services know only about themselves, they are neither autonomous, nor are they designed to use ontologies; they are passive until invoked, and they do not provide for composing functionalities. These lead to the motivation on building a sophisticated web service to contain these features and to utilize web services on behalf of the user. This paper aims to propose a new concept of Meta Web Service, a web service-based DSS. The meta web service understands the user's problem statement with ontology, performs web service discovery, web service composition, and automatically generates codes for composite web service execution. Case-based reasoning is applied to quickly find past histories of successful service compositions. A prototype of research web service has been developed to show the feasibility of the proposed idea.
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