Adiponectin and AMP kinase activator stimulate proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells

<p>Abstract</p> <p>Background</p> <p>Adiponectin is a key mediator of the metabolic syndrome that is caused by visceral fat accumulation. Adiponectin and its receptors are known to be expressed in osteoblasts, but their actions with regard to bone metabolism are still unclear. In this study, we investigated the effects of adiponectin on the proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells.</p> <p>Results</p> <p>Adiponectin receptor type 1 (AdipoR1) mRNA was detected in the cells by RT-PCR. The adenosine monophosphate-activated protein kinase (AMP kinase) was phosphorylated by both adiponectin and a pharmacological AMP kinase activator, 5-amino-imidazole-4-carboxamide-riboside (AICAR), in the cells. AdipoR1 small interfering RNA (siRNA) transfection potently knocked down the receptor mRNA, and the effect of this knockdown persisted for as long as 10 days after the transfection. The transfected cells showed decreased expressions of type I collagen and osteocalcin mRNA, as determined by real-time PCR, and reduced ALP activity and mineralization, as determined by von Kossa and Alizarin red stainings. In contrast, AMP kinase activation by AICAR (0.01–0.5 mM) in wild-type MC3T3-E1 cells augmented their proliferation, differentiation, and mineralization. BrdU assay showed that the addition of adiponectin (0.01–1.0 μg/ml) also promoted their proliferation. Osterix, but not Runx-2, appeared to be involved in these processes because AdipoR1 siRNA transfection and AICAR treatments suppressed and enhanced osterix mRNA expression, respectively.</p> <p>Conclusion</p> <p>Taken together, this study suggests that adiponectin stimulates the proliferation, differentiation, and mineralization of osteoblasts via the AdipoR1 and AMP kinase signaling pathways in autocrine and/or paracrine fashions.</p

Antenna System Composed of T-Shaped Elements Coupled to an Open Radial Waveguide

An antenna system composed of an activated open radial waveguide (RadWG) and parasitic T-shaped elements is proposed as a high-gain antenna, where the radiation beam is steerable around the system axis. The T-shaped elements are proximity-coupled to the RadWG. It is found that the upper round plate for the RadWG contributes to forming a desirable beam and increasing the gain. The beam steering with a gain of greater than targeted 9 dBi in 16 azimuthal directions is obtained by changing the location of open-state T-shaped elements whose height is 0.18 wavelength. Effects on the radiation characteristics of the system parameters, including the RadWG height, upper round plate diameter, ground plane diameter, and number of open-state T-shaped elements, are also analyzed and discussed

Quantitative Estimation of Urate Transport in Nephrons in Relation to Urinary Excretion Employing Benzbromarone-Loading Urate Clearance Tests in Cases of Hyperuricemia

Background: A four-component system for urate transport in nephrons has been proposed and widely investigated by various investigators studying the mechanisms underlying urinary urate excretion. However, quantitative determinations of urate transport have not been clearly elucidated yet. Methods: The equation Cua = {Ccr(1 – R1) + TSR}(1 – R2) was designed to approximate mathematically urate transport in nephrons, where R1 = urate reabsorption ratio; R2 = urate postsecretory reabsorption ratio; TSR = tubular secretion rate; Cua = urate clearance, and Ccr = creatinine clearance . To investigate relationships between the three unknown variables (R1, R2, and TSR), this equation was expressed as contour lines of one unknown on a graph of the other two unknowns. Points at regular intervals on each contour line for the equation were projected onto a coordinate axis and the high-density regions corresponding to high-density intervals of a coordinate were investigated for three graph types. For benzbromarone (BBR)-loading Cua tests, Cua was determined before and after oral administration of 100 mg of BBR and CuaBBR(∞) was calculated from the ratio of CuaBBR(100)/Cua. Results: Before BBR administration, points satisfying the equation on the contour line for R1 = 0.99 were highly dense in the region R2 = 0.87–0.92 on all three graphs, corresponding to a TSR of 40–60 ml/min in hyperuricemia cases (HU). After BBR administration, the dense region was shifted in the direction of reductions in both R1 and R2, but TSR was unchanged. Under the condition that R1 = 1 and R2 = 0, urate tubular secretion (UTS) was considered equivalent to calculated urinary urate excretion (Uex) in a model of intratubular urate flow with excess BBR; CuaBBR(∞) = TSR was deduced from the equation at R1 = 1 and R2 = 0. In addition, TSR of the point under the condition that R1 = 1 and R2 = 0 on the graph agreed with TSR for the dense region at excess BBR. TSR was thus considered approximately equivalent to CuaBBR(∞), which could be determined from a BBR-loading Cua test. Approximate values for urate glomerular filtration, urate reabsorption, UTS, urate postsecretory reabsorption (UR2), and Uex were calculated as 9,610; 9,510; 4,490; 4,150, and 440 µg/min for HU and 6,890; 6,820; 4,060; 3,610, and 520 µg/min for normal controls (NC), respectively. The most marked change in HU was the decrease in TSR (32.0%) compared to that in NC, but UTS did not decrease. Calculated intratubular urate contents were reduced more by higher UR2 in HU than in NC. This enhanced difference resulted in a 15.4% decrease in Uex for HU. Conclusion: Increased UR2 may represent the main cause of urate underexcretion in HU

A Keck/DEIMOS Spectroscopy of Lyman Alpha Blobs at Redshift z=3.1

We present the results of an intermediate resolution (~2 angstrom) spectroscopy of a sample of 37 candidate Lyman alpha blobs and emitters at redshift z=3.1 using the DEIMOS spectrograph on the 10 m Keck telescope. The emission lines are detected for all the 37 objects and have variety in their line profiles. The Lyman alpha velocity widths (FWHM) of the 28 objects with higher quality spectra, measured by fitting a single Gaussian profile, are in the range of 150 - 1700 km/s and correlate with the Lyman alpha spatial extents. All the 12 Lyman alpha blobs (>16 arcsec^2) have large velocity widths of > 500 km/s. While there are several possible physical interpretations of the Lyman alpha velocity widths (motion of gravitationally-bound gas clouds, inflows, merging of clumps, or outflows from superwinds), the large velocity widths of the Lyman alpha blobs suggest that they are the sites of massive galaxy formation. If we assume gravitationally-bound gas clouds, the dynamical masses of the Lyman alpha blobs are estimated to be ~10^12 - 10^13 Msun. Even for the case of outflows, the outflow velocities are likely to be the same order of the rotation velocities as inferred from the observational evidence for local starburst galaxies.Comment: Accepted for publication in ApJ

Charge Transfer Cross Sections for Multiply Charged Slow Ne, Ar, Kr and Xe Ions on Various Gas Targets : II. Molecular Gas Targets

Observed charge transfer cross sections are compiled, similarly to Part I, for multiply charged Ne, Ar, Kr and Xe ions on several molecular targets in an energy region from a few to tens keV. The projectiles are recoil ions produced by using our “ion-impact ion source” (IIIS). The values are compared with the results of other research workers

Large-scale Filamentary Structure around the Protocluster at Redshift z=3.1

We report the discovery of a large-scale coherent filamentary structure of Lyman alpha emitters in a redshift space at z=3.1. We carried out spectroscopic observations to map the three dimensional structure of the belt-like feature of the Lyman alpha emitters discovered by our previous narrow-band imaging observations centered on the protocluster at z=3.1. The feature was found to consist of at least three physical filaments connecting with each other. The result is in qualitative agreement with the prediction of the 'biased' galaxy-formation theories that galaxies preferentially formed in large-scale filamentary or sheet-like mass overdensities in the early Universe. We also found that the two known giant Lyman alpha emission-line nebulae showing high star-formation activities are located near the intersection of these filaments, which presumably evolves into a massive cluster of galaxies in the local Universe. This may suggest that massive galaxy formation occurs at the characteristic place in the surrounding large-scale structure at high redshift.Comment: 11 pages, 3 figures, accepted for publication in ApJ Letter

Seizure and Profound Hypokalemia: Unusual Presentation of Primary Hyperparathyroidism

A 68-year-old man was admitted because of tonic–clonic convulsion. He had been receiving 200 mg itraconazole for 10 days. He had hypokalaemia (2.2 mEq/l), hypercalcaemia (Cacorr 11.0 mg/dl) and elevated serum parathyroid hormone (PTH, 95 pg/ml). Ultrasound examination of the neck revealed a low echoic tumour. Cessation of itraconazole and fluid supplementation eradicated clinical symptoms and profound hypokalaemia, but serum potassium remained low normal (3.4 mEq/l) and the mild hypercalcaemia and elevated PTH were unchanged. To conclude, a small amount of itraconazole (200 mg) precipitated profound hypokalaemia and seizure in a patient with mild hyperparathyroidism and low normal serum potassium