Dynamin 1 is important for microtubule organization and stabilization in glomerular podocytes

Dynamin 1 is a neuronal endocytic protein that participates in vesicle formation by scission of invaginated membranes. Dynamin 1 is also expressed in the kidney; however, its physiological significance to this organ remains unknown. Here, we show that dynamin 1 is crucial for microtubule organization and stabilization in glomerular podocytes. By immunofluorescence and immunoelectron microscopy, dynamin 1 was concentrated at microtubules at primary processes in rat podocytes. By immunofluorescence of differentiated mouse podocytes (MPCs), dynamin 1 was often colocalized with microtubule bundles, which radially arranged toward periphery of expanded podocyte. In dynamin 1-depleted MPCs by RNAi, alpha-tubulin showed a dispersed linear filament-like localization, and microtubule bundles were rarely observed. Furthermore, dynamin 1 depletion resulted in the formation of discontinuous, short acetylated alpha-tubulin fragments, and the decrease of microtubule-rich protrusions. Dynamins 1 and 2 double-knockout podocytes showed dispersed acetylated alpha-tubulin and rare protrusions. In vitro, dynamin 1 polymerized around microtubules and cross-linked them into bundles, and increased their resistance to the disassembly-inducing reagents Ca(2+)and podophyllotoxin. In addition, overexpression and depletion of dynamin 1 in MPCs increased and decreased the nocodazole resistance of microtubules, respectively. These results suggest that dynamin 1 supports the microtubule bundle formation and participates in the stabilization of microtubules

Generation of electromagnetic waves from 0.3 to 1.6 terahertz with a high-T-c superconducting Bi2Sr2CaCu2O8+delta intrinsic Josephson junction emitter

To obtain higher power P and frequency f emissions from the intrinsic Josephson junctions in a high-T-c superconducting Bi2Sr2CaCu2O8+delta single crystal, we embedded a rectangular stand-alone mesa of that material in a sandwich structure to allow for efficient heat exhaust. By varying the current-voltage (I-V) bias conditions and the bath temperature T-b, f is tunable from 0.3 to 1.6 THz. The maximum P of a few tens of mu W, an order of magnitude greater than from previous devices, was found at T-b similar to 55K on an inner I-V branch at the TM(1,0) cavity resonance mode frequency. The highest f of 1.6 THz was found at T-b = 10K on an inner I-V branch, but away from cavity resonance frequencies. A possible explanation is presented

Factors associated with hypoglycemia unawareness and severe hypoglycemia in type 1 diabetes mellitus patients

Abstract Aims/Introduction Several factors are associated with hypoglycemia unawareness and severe hypoglycemia, but few large studies have analyzed Japanese patients with type 1 diabetes. The aim of this study was to analyze the risk factors for hypoglycemia unawareness and severe hypoglycemia in Japanese type 1 diabetes patients. Materials and Methods A self‐administered questionnaire investigated events, complications and treatments associated with hypoglycemia in patients with type 1 diabetes. Multiple logistic regression analysis of factors associated with hypoglycemia unawareness and severe hypoglycemia requiring medical treatment was carried out. The coefficient of variation (CV) of blood glucose levels was determined using blood samples collected at six outpatient visits. Results Of the 1,619 participants, 44.2% and 10.4% experienced hypoglycemia unawareness and severe hypoglycemia, respectively. Mean HbA1c levels in patients with hypoglycemia unawareness were lower than those in patients without hypoglycemia unawareness. The type 1 diabetes subtype, glycated hemoglobin (HbA1c) level, CV of blood glucose levels and history of severe hypoglycemia requiring medical treatment were significant independent variables predicting the presence of hypoglycemia unawareness. The glucose CV and a history of hypoglycemia unawareness were significant independent variables predicting severe hypoglycemia requiring medical treatment. In stratified analyses of patients divided into four groups according to glucose CV and HbA1c levels, the high‐glucose‐CV/low‐HbA1c group had the highest odds ratios for hypoglycemia unawareness (2.60) and severe hypoglycemia requiring medical treatment (2.55). Conclusions The ambulant glucose CV correlated with both hypoglycemia unawareness and severe hypoglycemia. Patients with high glucose CV and low HbA1c are at high risk of such adverse events, and their treatment strategies should be reviewed

A Pathophysiological Role of Plasma Indoxyl Sulfate in Patients with Heart Failure

Background: One of uremic toxins, indoxyl sulfate (IS), is associated with cardiovascular events. This study aimed to measure the plasma IS levels in patients with and without chronic heart failure (CHF). Methods: We measured plasma IS levels in 49 patients with CHF and an estimated glomerular filtration rate (eGFR) of 40–60 ml/min/1.73 m2 from our institute. These were compared with 31 healthy subjects without CHF (a control), but with comparable eGFR levels, from our resident cohort study. We also test the effect of AST-120 (the oral adsorbent) in 16 CHF patients. Results: The plasma IS levels in 49 CHF patients increased (1.38 ± 0.84 (SD) vs 0.12 ± 0.07 μg/ml (a control), p < 0.001), and fractional shortening (FS) levels were correlated with the plasma IS levels in these subjects. Second, in our database of the hospitalized CHF patients, we retrospectively reviewed the data for eight CHF patients with stage 3–5 chronic kidney disease (CKD) who received treatment with AST-120, before and one year after treatment, and compared these patients with eight sex-matched CHF patients with stage 3–5 CKD without AST-120. AST-120 decreased plasma IS levels and improved cardiac function. Conclusions: Plasma IS levels increased in patients with CHF along with cardiac systolic dysfunction compared with those in healthy subjects, and AST-120 improved cardiac dysfunction in patients with CHF. Oral adsorbents may represent a novel treatment for CHF

ALDH1-high ovarian cancer stem-like cells can be isolated from serous and clear cell adenocarcinoma cells, and ALDH1 high expression is associated with poor prognosis.

Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined as a small population of cancer cells that have high tumorigenicity. Furthermore, CSCs/CICs are resistant to several cancer therapies, and CSCs/CICs are therefore thought to be responsible for cancer recurrence after treatment and distant metastasis. In epithelial ovarian cancer (EOC) cases, disease recurrence after chemotherapy is frequently observed, suggesting ovarian CSCs/CICs are involved. There are four major histological subtypes in EOC, and serous adenocarcinoma and clear cell adenocarcinoma are high-grade malignancies. We therefore analyzed ovarian CSCs/CICs from ovarian carcinoma cell lines (serous adenocarcinoma and clear cell adenocarcinoma) and primary ovarian cancer cells in this study. We isolated ovarian CSCs/CICs as an aldehyde dehydrogenase 1 high (ALDH1(high)) population from 6 EOC cell lines (3 serous adenocarcinomas and 3 clear cell adenocarcinomas) by the ALDEFLUOR assay. ALDH1(high) cells showed greater sphere-forming ability, higher tumorigenicity and greater invasive capability, indicating that ovarian CSCs/CICs are enriched in ALDH1(high) cells. ALDH1(high) cells could also be isolated from 8 of 11 primary ovarian carcinoma samples. Immunohistochemical staining revealed that higher ALDH1 expression levels in ovary cancer cases are related to poorer prognosis in both serous adenocarcinoma cases and clear cell adenocarcinoma cases. Taken together, the results indicate that ALDH1 is a marker for ovarian CSCs/CICs and that the expression level of ALDH1 might be a novel biomarker for prediction of poor prognosis

Drought-induced root plasticity of two upland NERICA varieties under conditions with contrasting soil depth characteristics

To identify differences in root plasticity patterns of two upland New Rice for Africa (NERICA) varieties, NERICA 1 and 4, in response to drought under conditions with contrasting soil profile characteristics, soil moisture gradients were imposed using a sloping bed system with depths ranging 30–65 cm and a line-source sprinkler system with a uniformly shallow soil layer of 20 cm depth. Varietal differences in shoot and root growths were identified only under moderate drought conditions, 11–18% v/v soil moisture content. Further, under moderate drought soil conditions where roots could penetrate into the deep soil layer, deep root development was greater in NERICA 4 than in NERICA 1, which contributed to maintaining dry matter production. However, under soil conditions with underground impediment to deep root development, higher shoot dry weight was noted for NERICA 1 than for NERICA 4 at 11–18% v/v soil moisture content, which was attributed to increased lateral root development in the shallow soil layer in NERICA 1. Enhanced lateral root development in the 0–20-cm soil layer was identified in NERICA 1 even under soil conditions without an impediment to deep root development; however, this did not contribute to maintaining dry matter production in upland rice. Thus, we show different root developmental traits associated with drought avoidance in the two NERICA varieties, and that desirable root traits for upland rice cultivation vary depending on the target soil environment, such as the distribution of soil moisture and root penetration resistance

Drought-induced root plasticity of two upland NERICA varieties under conditions with contrasting soil depth characteristics

To identify differences in root plasticity patterns of two upland New Rice for Africa (NERICA) varieties, NERICA 1 and 4, in response to drought under conditions with contrasting soil profile characteristics, soil moisture gradients were imposed using a sloping bed system with depths ranging 30–65 cm and a line-source sprinkler system with a uniformly shallow soil layer of 20 cm depth. Varietal differences in shoot and root growths were identified only under moderate drought conditions, 11–18% v/v soil moisture content. Further, under moderate drought soil conditions where roots could penetrate into the deep soil layer, deep root development was greater in NERICA 4 than in NERICA 1, which contributed to maintaining dry matter production. However, under soil conditions with underground impediment to deep root development, higher shoot dry weight was noted for NERICA 1 than for NERICA 4 at 11–18% v/v soil moisture content, which was attributed to increased lateral root development in the shallow soil layer in NERICA 1. Enhanced lateral root development in the 0–20-cm soil layer was identified in NERICA 1 even under soil conditions without an impediment to deep root development; however, this did not contribute to maintaining dry matter production in upland rice. Thus, we show different root developmental traits associated with drought avoidance in the two NERICA varieties, and that desirable root traits for upland rice cultivation vary depending on the target soil environment, such as the distribution of soil moisture and root penetration resistance

Generation of electromagnetic waves from 0.3 to 1.6 terahertz with a high- T_c superconducting Bi₂Sr₂CaCu₂O_8+δ intrinsic Josephson junction emitter

To obtain higher power P and frequency f emissions from the intrinsic Josephson junctions in a high-Tc superconducting Bi2Sr2CaCu2O8+δ single crystal, we embedded a rectangular stand-alone mesa of that material in a sandwich structure to allow for efficient heat exhaust. By varying the current-voltage (I-V) bias conditions and the bath temperature Tb, f is tunable from 0.3 to 1.6THz. The maximum P of a few tens of µW, an order of magnitude greater than from previous devices, was found at Tb ~55K on an inner I-V branch at the TM(1,0) cavity resonance mode frequency. The highest f of 1.6THz was found at Tb=10K on an inner I-V branch, but away from cavity resonance frequencies. A possible explanation is presented

ALDEFLUOR assay for 6 epithelial ovarian cancer cell lines.

<p>ALDH1^high cells were detected in 3 serous adenocarcinoma cell lines (AMOC-2, HUOA and OVCAR-3) and in 3 clear cell adenocarcinoma cell lines (ES-2, RMG-1 and TOV-21G). SSC-A: single strand conformation analysis. BAAA: boron-dipyrromethene- aminoacetaldehyde. FITC-A: fluorescein isothiocyanate analysis. Percentages in boxes indicate ALDH1^high cell ratios. Diethylaminobenzaldehyde (DEAB), an ALDH-specific inhibitor, was used as a negative control.</p