High-power laser experiment forming a supercritical collisionless shock in a magnetized uniform plasma at rest.

We present an experimental method to generate quasiperpendicular supercritical magnetized collisionless shocks. In our experiment, ambient nitrogen (N) plasma is at rest and well magnetized, and it has uniform mass density. The plasma is pushed by laser-driven ablation aluminum (Al) plasma. Streaked optical pyrometry and spatially resolved laser collective Thomson scattering clarify structures of plasma density and temperatures, which are compared with one-dimensional particle-in-cell simulations. It is indicated that just after the laser irradiation, the Al plasma is magnetized by a self-generated Biermann battery field, and the plasma slaps the incident N plasma. The compressed external field in the N plasma reflects N ions, leading to counterstreaming magnetized N flows. Namely, we identify the edge of the reflected N ions. Such interacting plasmas form a magnetized collisionless shock.

Relationship Between Stress Coping Mechanisms and Depression in Kidney Transplant Recipients.

BACKGROUND: It has been reported that transplant recipients are exposed to physical and psychosocial stresses even after transplant surgery and exhibit psychological disorders such as depression. PURPOSE: In this study, we extracted trends concerning how recipients of kidney transplants cope with stress, and we also examined how they cope with depression and its countermeasures. METHOD: We administered questionnaire surveys to 109 kidney transplant recipients. These included items on personal attributes, medical information, depression, and stress-coping type scales. Statistical analysis was performed using factor analysis and multiple regression analysis. RESULTS: Fifteen out of 109 (13.8%) were found to be high-risk patients for depression based on responses to the questionnaire using the depression scale. We extracted 2 factors of stress-coping type, namely Factor 1, "Directly coping with the problem," of patients who try to directly resolve the problem in a positive manner and Factor 2, "Stress-release while avoiding the problem," for those who relieve their feelings in response to the stress without resolving the problem itself. When multiple regression analysis was conducted with the depression scale as the dependent variable and the stress-coping factor as the independent variable, Factor 1 tended to be associated with reduced depression and Factor 2 with increased depression. CONCLUSIONS: Results showed that to improve the mental health of those who receive kidney transplants, it is necessary to examine the depression and stress-coping types of such patients at an early stage and carry out education on stress-coping, focusing on resolving the actual problem.

Girdin maintains the stemness of glioblastoma stem cells.

This corrects the article DOI: 10.1038/onc.2011.466.

Low serum potassium concentration is a predictor of chronic kidney disease.

AIMS: The aim of this study was to examine whether low serum potassium concentration could be a predictor of chronic kidney disease (CKD) in a community-based cohort. MATERIALS AND METHODS: We enrolled 1001 subjects, median period of 5.7 years, and evaluated the risk factors for CKD, defined as estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m(2), and assessed whether low serum potassium concentration could predict CKD. RESULTS: Compared with the subjects without development of CKD, age, body mass index, fasting plasma glucose, uric acid (UA), creatinine and serum sodium concentration were higher, and serum potassium concentration was lower in subjects with development of CKD. Univariate Cox regression analyses demonstrated that age, body mass index, fasting plasma glucose, UA, creatinine, serum sodium concentration and serum potassium concentration were associated with progression of CKD. Multiple Cox regression analysis revealed that age, gender, creatinine and serum potassium concentration were independent predictors of CKD after adjustment for covariates. When serum potassium concentration was below 4.0 mmol/l at baseline, hazard ratio (95% confidence interval) of developing CKD was 2.65 (2.04-3.44; p < 0.0001). CONCLUSIONS: Serum potassium concentration could be a clinically relevant risk factor for the progression of CKD, defined as eGFR < 60 ml/min/1.73 m(2) , in healthy subjects.

Andropausal symptoms in men with Type 2 diabetes.

AIMS: Serum androgen concentration is reported to be low in patients with Type 2 diabetes. There have been no studies comparing andropausal symptoms such as sleep disturbance, depression, erectile dysfunction and lower urinary tract symptoms simultaneously between men with Type 2 diabetes and subjects without diabetes. METHODS: We compared andropausal symptom scores such as the Pittsburgh Sleep Quality Index, the Self-Rating Depression Scale, the International Index of Erectile Function and the International Prostate Symptom Score in 296 men with Type 2 diabetes and in 267 subjects without diabetes. Furthermore, we evaluated relationships of andropausal symptom scores to various anthropometric factors and compared andropausal symptom scores according to diabetic complications in men with Type 2 diabetes. RESULTS: Andropausal symptom scores such as the Pittsburgh Sleep Quality Index, the Self-Rating Depression Scale, the International Index of Erectile Function and the International Prostate Symptom Score were 4.2 ± 2.6 vs. 5.0 ± 3.3, P<0.01 by unpaired Student's t-test, 34.8 ± 8.2 vs. 38.4 ± 9.3, P<0.0001, 11.5 ± 6.4 vs. 9.9 ± 6.9, P<0.01 and 7.3 ± 6.7 vs. 9.0 ± 7.1, P<0.01 in subjects without diabetes and in patients with diabetes, respectively. The Pittsburgh Sleep Quality Index was higher in patients with neuropathy than without. The Self-Rating Depression Scale was higher in patients with advanced retinopathy. The International Index of Erectile Function was lower in patients with advanced retinopathy and nephropathy. The International Index of Erectile Function was lower and the International Prostate Symptom Score was higher in patients with cardiovascular disease than without. CONCLUSIONS: Our data demonstrated that men with Type 2 diabetes have higher prevalence of andropausal symptoms, especially those with diabetic complications.

Girdin maintains the stemness of glioblastoma stem cells.

Glioblastomas (GBMs) are the most common and aggressive type of brain tumor. GBMs usually show hyperactivation of the PI3K-Akt pathway, a pro-tumorigenic signaling cascade that contributes to pathogenesis. Girdin, an actin-binding protein identified as a novel substrate of Akt, regulates the sprouting of axons and the migration of neural progenitor cells during early postnatal-stage neurogenesis in the hippocampus. Here, we show that Girdin is highly expressed in human glioblastoma (GBM). Stable Girdin knockdown in isolated GBM stem cells resulted in decreased expression of stem cell markers, including CD133, induced multilineage neural differentiation, and inhibited in vitro cell motility, ex vivo invasion, sphere-forming capacity and in vivo tumor formation. Furthermore, exogenous expression of the Akt-binding domain of Girdin, which competitively inhibits its Akt-mediated phosphorylation, diminished the expression of stem cell markers, SOX2 and nestin, and migration on the brain slice and induced the expression of neural differentiation markers glial fibrillary acidic protein/ßIII Tubulin. Our results reveal that Girdin is required for GBM-initiating stem cells to sustain the stemness and invasive properties.

Efficient delivery of liposome-mediated MGMT-siRNA reinforces the cytotoxity of temozolomide in GBM-initiating cells.

Glioblastoma multiforme (GBM) is one of the most formidable brain tumors with a mean survival period of approximately 12 months. To date, a combination of radiotherapy and chemotherapy with an oral alkylating agent, temozolomide (TMZ), has been used as first-line therapy for glioma. However, the efficacy of chemotherapy for treating GBM is very limited; this is partly because of the high activity levels of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) in tumor cells, which creates a resistant phenotype by blunting the therapeutic effect of alkylating agents. Thus, MGMT may be an important determinant of treatment failure and should be considered as a suitable target for intervention, in an effort to improve the therapeutic efficacy of TMZ. In this study, we showed that small-interfering RNA (siRNA)-based downregulation of MGMT could enhance the chemosensitivity of malignant gliomas against TMZ. Notably, TMZ-resistant glioma-initiating cells with increased DNA repair and drug efflux capabilities could be efficiently transduced with MGMT-siRNA by using a novel liposome, LipoTrust. Accordingly, such transduced glioma-initiating cells could be sensitized to TMZ in both in vitro and in vivo tumor models. Taken together, this study provides an experimental basis for the clinical use of such therapeutic combinations.

Nuclear DISC1 regulates CRE-mediated gene transcription and sleep homeostasis in the fruit fly.

Disrupted-in-schizophrenia-1 (DISC1) is one of major susceptibility factors for a wide range of mental illnesses, including schizophrenia, bipolar disorder, major depression and autism spectrum conditions. DISC1 is located in several subcellular domains, such as the centrosome and the nucleus, and interacts with various proteins, including NudE-like (NUDEL/NDEL1) and activating transcription factor 4 (ATF4)/CREB2. Nevertheless, a role for DISC1 in vivo remains to be elucidated. Therefore, we have generated a Drosophila model for examining normal functions of DISC1 in living organisms. DISC1 transgenic flies with preferential accumulation of exogenous human DISC1 in the nucleus display disturbance in sleep homeostasis, which has been reportedly associated with CREB signaling/CRE-mediated gene transcription. Thus, in mammalian cells, we characterized nuclear DISC1, and identified a subset of nuclear DISC1 that colocalizes with the promyelocytic leukemia (PML) bodies, a nuclear compartment for gene transcription. Furthermore, we identified three functional cis-elements that regulate the nuclear localization of DISC1. We also report that DISC1 interacts with ATF4/CREB2 and a corepressor N-CoR, modulating CRE-mediated gene transcription.

Stimulatory action of protein kinase C(epsilon) isoform on the slow component of delayed rectifier K+ current in guinea-pig atrial myocytes.

BACKGROUND AND PURPOSE: Protein kinase C (PKC) comprises at least twelve isoforms and has an isoform-specific action on cardiac electrical activity. The slow component of delayed rectifier K(+) current (I (Ks)) is one of the major repolarizing currents in the hearts of many species and is also potentiated by PKC activation. Little is known, however, about PKC isoform(s) functionally involved in the potentiation of I (Ks) in native cardiac myocytes. EXPERIMENTAL APPROACH: I (Ks) was recorded from guinea-pig atrial myocytes, using the whole-cell configuration of patch-clamp method. KEY RESULTS: Bath application of phenylephrine enhanced I (Ks) concentration-dependently with EC(50) of 5.4 microM and the maximal response (97.1+/-11.9% increase, n=16) was obtained at 30 microM. Prazosin (1 microM) almost totally abolished the potentiation of I (Ks) by phenylephrine, supporting the involvement of alpha(1)-adrenoceptors. The stimulatory action of phenylephrine was significantly, if not entirely, inhibited by the general PKC inhibitor bisindolylmaleimide I but was little affected by Gö-6976, Gö-6983 and rottlerin. Furthermore, this stimulatory effect was significantly reduced by dialyzing atrial myocytes with PKCepsilon-selective inhibitory peptide epsilonV1-2 but was not significantly affected by conventional PKC isoform-selective inhibitory peptide betaC2-4. Phorbol 12-myristate 13-acetate (PMA) at 100 nM substantially increased I (Ks) by 64.2+/-1.3% (n=6), which was also significantly attenuated by an internal dialysis with epsilonV1-2 but not with betaC2-4. CONCLUSIONS AND IMPLICATIONS: The present study provides experimental evidence to suggest that, in native guinea-pig cardiac myocytes, activation of PKC contributes to alpha(1)-adrenoceptor-mediated potentiation of I (Ks) and that epsilon is the isoform predominantly involved in this PKC action.

High-speed gas sensor for chemosensory event-related potentials or magnetic fields.

The observation of odor and air exchange with high temporal accuracy is necessary to obtain strict chemosensory event-related potentials (CSERPs) or magnetic fields, as proposed by Evans et al. [Evans W, Kobal G, Lorig T, Prah J. Suggestions for collection and reporting of chemosensory (olfactory) event-related potentials. Chem Senses, 1993; 18: 751- 6]. No suitable method for real time observation of gas stimuli, however, has been available until now. We have developed a technique to measure accurately gas molecule concentrations with a high temporal resolution. We determined that attenuation of sound amplitude varies in a manner dependent on the average molecular weight through which the sound wave passes. Based on this principle, we have designed a high-speed gas concentration sensor utilizing ultrasound. We investigated the practical potential of this sensor using a chemosensory stimulator (olfactometer); we succeeded in observing rapid gas exchange between air and nitrogen with a 2 kHz sampling rate. The signal/noise ratio of the stimulus was greater than 42 dB. In a 20 min experiment we determined that, for this olfactometer, the gas onset latency was 79 ms and the rise time was 16 ms. No significant artifact to magnetic fields was observed, even when the sensor was situated near a whole head magnetoencephalography (MEG) system. These results indicate that this sensor could be used for the observation of odor and air exchange, as well as, for real time monitoring of odor stimuli during actual experiments with a participant.

The comparative effects of propofol versus thiopentone on left ventricular function during electroconvulsive therapy.

The purpose of this study was to compare the effect of propofol versus thiopentone on haemodynamics during electroconvulsive therapy (ECT), as estimated by echocardiography. Twenty-eight ASA 1 or 2 patients scheduled for ECT were randomly divided into two groups, to receive propofol 1 mg/kg (propofol group, n = 14) or thiopentone 2 mg/kg (thiopentone group, n = 14). Bilateral ECT was performed after the administration of propofol or thiopentone, succinylcholine and following assisted mask ventilation with 100% oxygen. Cardiac function was examined by transthoracic echocardiography, prior to induction of anaesthesia and throughout ECT until ten minutes after the seizure. In the propofol group, increased end-systolic area (ESA) and decreased fractional area change (FAC) were observed at one minute after the electrical shock compared with the awake condition. In the thiopentone group, increased ESA and decreased FAC were observed from one to three minutes after the electrical shock compared with the awake condition. There was no statistically significant change in afterload in the propofol group during the study. In contrast, increased afterload was observed from one to three minutes after the electrical shock in the thiopentone group (awake condition, 26 +/- 7 mmHg/cm2 [mean +/- SD]; one minute after ECT, 42 +/- 7*; two minutes after ECT, 44 +/- 6*; three minutes after ECT; 40 +/- 5*, respectively) (*P < 0.05). We concluded that a lesser haemodynamic change occurs after propofol anaesthesia (1 mg/kg) compared with thiopentone anaesthesia (2 mg/kg) during ECT.

Radiation-induced cerebral aneurysm successfully treated with endovascular coil embolization.

In a 30-year-old male, multiple cerebral aneurysms developed 19 years after receiving 60 Gy of irradiation for craniophariginoma. Angiogram revealed right IC-PC and upper basilar trunk aneurysms in addition to atherosclerotic change. The right IC-PC aneurysm was wrapped and the basilar trunk aneurysm located between the origins of SCA and AICA was treated by endovascular coil embolization. The packing of the aneurysm was complete, but stenosis of the basilar artery appeared. The patient was discharged uneventfully and follow-up angiogram 6 months later demonstrated that the aneurysm had disappeared and the patency of the basilary artery had been preserved. Radiation-induced intracranial vasculopathy is a well-recognized phenomenon, but aneurysm formation is less common than arterial occlusive lesion. However, the mortality rate after bleeding is so high that immediate diagnosis and treatment by direct surgery or coil embolization are necessary.

Use of nitrogen stable isotope ratio of periphyton for monitoring nitrogen sources in a river system.

In order to confirm the usefulness of the N stable isotope ratio of periphyton (mainly composed of attached algae) as an indicator for monitoring the N sources in river watersheds, we measured the isotope ratio of periphyton along the Chikuma River. In the river, both the concentrations of dissolved total nitrogen (DTN) and the delta15N values of periphyton increased downstream. Specific nitrogen loading rates (SNLR) calculated from administrative data also showed an increase downstream from 7 to 11 kg N ha(-1) yr(-1), with the increasing contribution by sewage and livestock waste from 6 to 40% to total N loading. There are significant positive relationships between the DTN concentration and the SNLR (r2=0.54, P<0.05), and the delta15N values of periphyton and the SNLR (r2=0.78, P<0.05). The increase in DTN concentration reflected the increase in input of N loading. The increase in delta15N of periphyton might reflect the increase in relative contribution by sewage and livestock waste down the river, especially the increase in sewage. The present study indicates the usefulness of the N stable isotope ratio of periphyton as an indicator for monitoring N sources in a river system.

Grafting neural stem cells improved the impaired spatial recognition in ischemic rats.

To determine the possible therapeutic potential of neural stem cells (NSCs) introduced into the damaged central nervous system, we grafted adult hippocampus-derived NSCs into the hippocampus of rats with transient global ischemia. Transient four-vessel occlusion yielded 90-95% losses of pyramidal neurons in the hippocampal CA1 region. In this region, 1-3% of the grafted cells survived; and 3-9% of them expressed NeuN, a neuronal marker. Rats with more than 120 NeuN-positive cells showed partial improvement of impaired spatial learning in a water maze test. These results suggest that NSCs grafted in the ischemic brain are able to differentiate into neurons and to improve spatial recognition.

Thiopental enhances human platelet aggregation by increasing arachidonic acid release.

Conflicting results have been reported regarding the effect of thiopental on aggregation and cytosolic calcium levels in platelets. The present study attempted to clarify these phenomena. Using platelet-rich plasma or washed suspensions, platelet aggregation, thromboxane (TX) B2 formation, arachidonic acid (AA) release, and cytosolic free calcium concentrations ([Ca2+]i) were measured in the presence or absence of thiopental (30-300 microM). Platelet activation was induced by adenosine diphosphate (ADP, 0.5-15 microM), epinephrine (0.1-20 microM) arachidonic acid (0.5-1.5 mM), or (+)-9,11-epithia-11,12-methano-TXA2 (STA2, 30-500 nM). Measurements of primary aggregation were performed in the presence of indomethacin (10 microM). Low concentrations of ADP and epinephrine, which did not induce secondary aggregation in a control study, induced strong secondary aggregation in the presence of thiopental (> or = 100 microM). Thiopental (> or = 100 microM) also increased the TXB2 formation induced by ADP and epinephrine. Thiopental (300 microM) increased ADP- and epinephrine-induced 3H-AA release. Thiopental (300 microM) also augmented the ADP- and epinephrine-induced increases in [Ca2+]i in the presence of indomethacin. Thiopental appears to enhance ADP- and epinephrine-induced secondary platelet aggregation by increasing AA release during primary aggregation, possibly by the activation of phospholipase A2.