Human VPS34 is required for internal vesicle formation within multivesicular endosomes

After internalization from the plasma membrane, activated EGF receptors (EGFRs) are delivered to multivesicular bodies (MVBs). Within MVBs, EGFRs are removed from the perimeter membrane to internal vesicles, thereby being sorted from transferrin receptors, which recycle back to the plasma membrane. The phosphatidylinositol (PI) 3′-kinase inhibitor, wortmannin, inhibits internal vesicle formation within MVBs and causes EGFRs to remain in clusters on the perimeter membrane. Microinjection of isotype-specific inhibitory antibodies demonstrates that the PI 3′-kinase required for internal vesicle formation is hVPS34. In the presence of wortmannin, EGFRs continue to be delivered to lysosomes, showing that their removal from the recycling pathway and their delivery to lysosomes does not depend on inward vesiculation. We showed previously that tyrosine kinase-negative EGFRs fail to accumulate on internal vesicles of MVBs but are recycled rather than delivered to lysosomes. Therefore, we conclude that selection of EGFRs for inclusion on internal vesicles requires tyrosine kinase but not PI 3′-kinase activity, whereas vesicle formation requires PI 3′-kinase activity. Finally, in wortmannin-treated cells there is increased EGF-stimulated tyrosine phosphorylation when EGFRs are retained on the perimeter membrane of MVBs. Therefore, we suggest that inward vesiculation is involved directly with attenuating signal transduction

Chandra Smells a RRAT: X-ray Detection of a Rotating Radio Transient

"Rotating RAdio Transients" (RRATs) are a newly discovered astronomical phenomenon, characterised by occasional brief radio bursts, with average intervals between bursts ranging from minutes to hours. The burst spacings allow identification of periodicities, which fall in the range 0.4 to 7 seconds. The RRATs thus seem to be rotating neutron stars, albeit with properties very different from the rest of the population. We here present the serendipitous detection with the Chandra X-ray Observatory of a bright point-like X-ray source coincident with one of the RRATs. We discuss the temporal and spectral properties of this X-ray emission, consider counterparts in other wavebands, and interpret these results in the context of possible explanations for the RRAT population.Comment: 5 pages, 2 b/w figures, 1 color figure. To appear in the proceedings of "Isolated Neutron Stars", Astrophysics & Space Science, in pres

Are the magnetic fields of millisecond pulsars ~ 10^8 G?

It is generally assumed that the magnetic fields of millisecond pulsars (MSPs) are $\sim 10^{8}$G. We argue that this may not be true and the fields may be appreciably greater. We present six evidences for this: (1) The $\sim 10^{8}$ G field estimate is based on magnetic dipole emission losses which is shown to be questionable; (2) The MSPs in low mass X-ray binaries (LMXBs) are claimed to have $< 10^{11}$ G on the basis of a Rayleygh-Taylor instability accretion argument. We show that the accretion argument is questionable and the upper limit $10^{11}$ G may be much higher; (3) Low magnetic field neutron stars have difficulty being produced in LMXBs; (4) MSPs may still be accreting indicating a much higher magnetic field; (5) The data that predict $\sim 10^{8}$ G for MSPs also predict ages on the order of, and greater than, ten billion years, which is much greater than normal pulsars. If the predicted ages are wrong, most likely the predicted $\sim 10^{8}$ G fields of MSPs are wrong; (6) When magnetic fields are measured directly with cyclotron lines in X-ray binaries, fields $\gg 10^{8}$ G are indicated. Other scenarios should be investigated. One such scenario is the following. Over 85% of MSPs are confirmed members of a binary. It is possible that all MSPs are in large separation binaries having magnetic fields $> 10^{8}$ G with their magnetic dipole emission being balanced by low level accretion from their companions.Comment: 16 pages, accept for publication in Astrophysics and Space Scienc

Differences in Atherosclerotic Plaque Burden and Morphology Between Type 1 and 2 Diabetes as Assessed by Multislice Computed Tomography

OBJECTIVE It is unclear whether the coronary atherosclerotic plaque burden is similar in patients with type 1 and type 2 diabetes. By using multislice computed tomography (MSCT), the presence, degree, and morphology of coronary artery disease (CAD) in patients with type 1 and type 2 diabetes were compared. RESEARCH DESIGN AND METHODS Prospectively, coronary artery calcium (CAC) scoring and MSCT coronary angiography were performed in 135 asymptomatic patients (65 patients with type 1 diabetes and 70 patients with type 2 diabetes). The presence and extent of coronary atherosclerosis as well as plaque phenotype were assessed and compared between groups. RESULTS No difference was observed in average CAC score (217 +/- 530 vs. 174 +/- 361) or in the prevalence of coronary atherosclerosis (65% vs. 71%) in patients with type 1 and type 2 diabetes. However, the prevalence of obstructive atherosclerosis was higher in patients with type 2 diabetes (n = 24; 34%) compared with that in patients with type 1 diabetes (n = 11; 17%) (P = 0.02). In addition, a higher mean number of atherosclerotic and obstructive plaques was observed in patients with type 2 diabetes. In addition, the percentage of noncalcified plaques was higher in patients with type 2 (66%) versus type 1 diabetes (27%) (P <0.001), resulting in a higher plaque burden for each CAC score compared with that in type 1 diabetic patients. CONCLUSIONS Although CAC scores and the prevalence of coronary atherosclerosis were similar between patients with type 1 and type 2 diabetes, CAD was more extensive in the latter. Also, a relatively higher proportion of noncalcified plaques was observed in patients with type 2 diabetes. These observations may be valuable in the development of targeted management strategies adapted to diabetes typ

Pulsar Timing and its Application for Navigation and Gravitational Wave Detection

Pulsars are natural cosmic clocks. On long timescales they rival the precision of terrestrial atomic clocks. Using a technique called pulsar timing, the exact measurement of pulse arrival times allows a number of applications, ranging from testing theories of gravity to detecting gravitational waves. Also an external reference system suitable for autonomous space navigation can be defined by pulsars, using them as natural navigation beacons, not unlike the use of GPS satellites for navigation on Earth. By comparing pulse arrival times measured on-board a spacecraft with predicted pulse arrivals at a reference location (e.g. the solar system barycenter), the spacecraft position can be determined autonomously and with high accuracy everywhere in the solar system and beyond. We describe the unique properties of pulsars that suggest that such a navigation system will certainly have its application in future astronautics. We also describe the on-going experiments to use the clock-like nature of pulsars to "construct" a galactic-sized gravitational wave detector for low-frequency (f_GW ~1E-9 - 1E-7 Hz) gravitational waves. We present the current status and provide an outlook for the future.Comment: 30 pages, 9 figures. To appear in Vol 63: High Performance Clocks, Springer Space Science Review