Phospholipase D1 Mediates AMP-Activated Protein Kinase Signaling for Glucose Uptake

Glucose homeostasis is maintained by a balance between hepatic glucose production and peripheral glucose utilization. In skeletal muscle cells, glucose utilization is primarily regulated by glucose uptake. Deprivation of cellular energy induces the activation of regulatory proteins and thus glucose uptake. AMP-activated protein kinase (AMPK) is known to play a significant role in the regulation of energy balances. However, the mechanisms related to the AMPK-mediated control of glucose uptake have yet to be elucidated.Here, we found that AMPK-induced phospholipase D1 (PLD1) activation is required for (14)C-glucose uptake in muscle cells under glucose deprivation conditions. PLD1 activity rather than PLD2 activity is significantly enhanced by glucose deprivation. AMPK-wild type (WT) stimulates PLD activity, while AMPK-dominant negative (DN) inhibits it. AMPK regulates PLD1 activity through phosphorylation of the Ser-505 and this phosphorylation is increased by the presence of AMP. Furthermore, PLD1-S505Q, a phosphorylation-deficient mutant, shows no changes in activity in response to glucose deprivation and does not show a significant increase in (14)C-glucose uptake when compared to PLD1-WT. Taken together, these results suggest that phosphorylation of PLD1 is important for the regulation of (14)C-glucose uptake. In addition, extracellular signal-regulated kinase (ERK) is stimulated by AMPK-induced PLD1 activation through the formation of phosphatidic acid (PA), which is a product of PLD. An ERK pharmacological inhibitor, PD98059, and the PLD inhibitor, 1-BtOH, both attenuate (14)C-glucose uptake in muscle cells. Finally, the extracellular stresses caused by glucose deprivation or aminoimidazole carboxamide ribonucleotide (AICAR; AMPK activator) regulate (14)C-glucose uptake and cell surface glucose transport (GLUT) 4 through ERK stimulation by AMPK-mediated PLD1 activation.These results suggest that AMPK-mediated PLD1 activation is required for (14)C-glucose uptake through ERK stimulation. We propose that the AMPK-mediated PLD1 pathway may provide crucial clues to understanding the mechanisms involved in glucose uptake

Far-Ultraviolet Cooling Features of the Antlia Supernova Remnant

We present far-ultraviolet observations of the Antlia supernova remnant obtained with Far-ultraviolet IMaging Spectrograph (FIMS, also called SPEAR). The strongest lines observed are C IV 1548,1551 and C III 977. The C IV emission of this mixed-morphology supernova remnant shows a clumpy distribution, and the line intensity is nearly constant with radius. The C III 977 line, though too weak to be mapped over the whole remnant, is shown to vary radially. The line intensity peaks at about half the radius, and drops at the edge of the remnant. Both the clumpy distribution of C IV and the rise in the C IV to C III ratio towards the edge suggest that central emission is from evaporating cloudlets rather than thermal conduction in a more uniform, dense medium.Comment: 9 pages, 4 figures, will be published in ApJ December 1, 2007, v670n2 issue. see http://astro.snu.ac.kr/~jhshinn/ms.pd

Surgical Treatment of Native Valve Aspergillus Endocarditis and Fungemic Vascular Complications

Systemic infection with Aspergillus is an opportunistic disease that affects mainly immunocompromised hosts, and is associated with a high mortality rate. It typically occurs in patients with several predisposing factors, but Aspergillus endocarditis of native valves is rare and experience in diagnosis and treatment is limited. We report a case of native valve endocarditis caused by Aspergillus. A 35-yr-old male patient who underwent pericardiocentesis four months previously for pericardial effusion of unknown etiology presented with right leg pain and absence of the right femoral artery pulse. Cardiac echocardiography revealed severe mitral insufficiency with large mobile vegetations, and computed tomographic angiography showed embolic occlusion of both common iliac arteries. We performed mitral valve replacement and thromoembolectomy, and Aspergillus was identified as the vegetation. We started intravenous amphotericin B and oral itraconazole, but systemic complications developed including superior mesenteric artery aneurysm and gastrointestinal bleeding. After aggressive management, the patient was discharged 78 days post surgery on oral itraconazole. He was well at 12 months post discharge but died in a traffic accident 13 months after discharge

Unusual Bronchopulmonary Foregut Malformation Associated with Pericardial Defect: Bronchogenic Cyst Communicating with Tubular Esophageal Duplication

We report a case of unusual bronchopulmonary foregut malformation composed of a mediastinal bronchogenic cyst with sequestrated lung tissue and communicating tubular esophageal duplication associated with complete pericardial defect. A 18-yr-old man, who had suffered from dry cough and mild dyspnea, was admitted because of an incidentally detected chest mass. A computed tomography scan demonstrated a cystic mass with an air fluid level connected with esophagus in the middle mediastinum. The surgically resected mass was a pleural invested accessory lobe of the lung (8.0×7.0×4.5 cm) connected with the esophageal wall by a tubular structure (3.0 cm in length and 2.0 cm in diameter). A complete left pericardial defect was also identified. Histologically, the cystic wall was composed of fibrovascular connective tissue with a smooth muscle layer, mixed seromucous glands and cartilage, and the inner surface of the cyst was lined by ciliated pseudostratified columnar epithelium. The inner surface of the tubular structure was lined by non-keratinizing or keratinizing squamous epithelium, and the wall contained submucosal mucous glands, muscularis mucosa, and duplicated muscularis propria. This case is important in understanding the embryological pathogenesis of the variable spectrum of the bronchopulmonary foregut malformation

Properties of Central Caustics in Planetary Microlensing

To maximize the number of planet detections, current microlensing follow-up observations are focusing on high-magnification events which have a higher chance of being perturbed by central caustics. In this paper, we investigate the properties of central caustics and the perturbations induced by them. We derive analytic expressions of the location, size, and shape of the central caustic as a function of the star-planet separation, $s$, and the planet/star mass ratio, $q$, under the planetary perturbative approximation and compare the results with those based on numerical computations. While it has been known that the size of the planetary caustic is \propto \sqrt{q}, we find from this work that the dependence of the size of the central caustic on $q$ is linear, i.e., \propto q, implying that the central caustic shrinks much more rapidly with the decrease of $q$ compared to the planetary caustic. The central-caustic size depends also on the star-planet separation. If the size of the caustic is defined as the separation between the two cusps on the star-planet axis (horizontal width), we find that the dependence of the central-caustic size on the separation is \propto (s+1/s). While the size of the central caustic depends both on $s$ and q, its shape defined as the vertical/horizontal width ratio, R_c, is solely dependent on the planetary separation and we derive an analytic relation between R_c and s. Due to the smaller size of the central caustic combined with much more rapid decrease of its size with the decrease of q, the effect of finite source size on the perturbation induced by the central caustic is much more severe than the effect on the perturbation induced by the planetary caustic. Abridged.Comment: 5 pages, 4 figures, ApJ accepte

Gravitational Microlensing: A Tool for Detecting and Characterizing Free-Floating Planets

Various methods have been proposed to search for extrasolar planets. Compared to the other methods, microlensing has unique applicabilities to the detections of Earth-mass and free-floating planets. However, the microlensing method is seriously flawed by the fact that the masses of the detected planets cannot be uniquely determined. Recently, Gould, Gaudi, & Han introduced an observational setup that enables one to resolve the mass degeneracy of the Earth-mass planets. The setup requires a modest adjustment to the orbit of an already proposed Microlensing planet-finder satellite combined with ground-based observations. In this paper, we show that a similar observational setup can also be used for the mass determinations of free-floating planets with masses ranging from ~0.1 M_J to several Jupiter masses. If the proposed observational setup is realized, the future lensing surveys will play important roles in the studies of Earth-mass and free-floating planets, which are the populations of planets that have not been previously probed.Comment: total 8 pages, including 3 figures, ApJ, in press (Mar 1, 2004

Microporation is a valuable transfection method for efficient gene delivery into human umbilical cord blood-derived mesenchymal stem cells

<p>Abstract</p> <p>Background</p> <p>Mesenchymal stem cells (MSCs) are an attractive source of adult stem cells for therapeutic application in clinical study. Genetic modification of MSCs with beneficial genes makes them more effective for therapeutic use. However, it is difficult to transduce genes into MSCs by common transfection methods, especially nonviral methods. In this study, we applied microporation technology as a novel electroporation technique to introduce enhanced green fluorescent protein (EGFP) and brain-derived neurotropfic factor (BDNF) plasmid DNA into human umbilical cord blood-derived MSCs (hUCB-MSCs) with significant efficiency, and investigated the stem cell potentiality of engineered MSCs through their phenotypes, proliferative capacity, ability to differentiate into multiple lineages, and migration ability towards malignant glioma cells.</p> <p>Results</p> <p>Using microporation with EGFP as a reporter gene, hUCB-MSCs were transfected with higher efficiency (83%) and only minimal cell damage than when conventional liposome-based reagent (<20%) or established electroporation methods were used (30-40%). More importantly, microporation did not affect the immunophenotype of hUCB-MSCs, their proliferation activity, ability to differentiate into mesodermal and ectodermal lineages, or migration ability towards cancer cells. In addition, the BDNF gene could be successfully transfected into hUCB-MSCs, and BDNF expression remained fairly constant for the first 2 weeks <it>in vitro </it>and <it>in vivo</it>. Moreover, microporation of BDNF gene into hUCB-MSCs promoted their <it>in vitro </it>differentiation into neural cells.</p> <p>Conclusion</p> <p>Taken together, the present data demonstrates the value of microporation as an efficient means of transfection of MSCs without changing their multiple properties. Gene delivery by microporation may enhance the feasibility of transgenic stem cell therapy.</p