Specific inhibition of GPI-anchored protein function by homing and self-association of specific GPI anchors

The functional specificity conferred by glycophosphatidylinositol (GPI) anchors on certain membrane proteins may arise from their occupancy of specific membrane microdomains. We show that membrane proteins with noninteractive external domains attached to the same carcinoembryonic antigen (CEA) GPI anchor, but not to unrelated neural cell adhesion molecule GPI anchors, colocalize on the cell surface, confirming that the GPI anchor mediates association with specific membrane domains and providing a mechanism for specific signaling. This directed targeting was exploited by coexpressing an external domain-defective protein with a functional protein, both with the CEA GPI anchor. The result was a complete loss of signaling capabilities (through integrin–ECM interaction) and cellular effect (differentiation blockage) of the active protein, which involved an alteration of the size of the microdomains occupied by the active protein. This work clarifies how the GPI anchor can determine protein function, while offering a novel method for its modulation

Pencil-Beam Surveys for Faint Trans-Neptunian Objects

We have conducted pencil-beam searches for outer solar system objects to a limiting magnitude of R ~ 26. Five new trans-neptunian objects were detected in these searches. Our combined data set provides an estimate of ~90 trans-neptunian objects per square degree brighter than ~ 25.9. This estimate is a factor of 3 above the expected number of objects based on an extrapolation of previous surveys with brighter limits, and appears consistent with the hypothesis of a single power-law luminosity function for the entire trans-neptunian region. Maximum likelihood fits to all self-consistent published surveys with published efficiency functions predicts a cumulative sky density Sigma(<R) obeying log10(Sigma) = 0.76(R-23.4) objects per square degree brighter than a given magnitude R.Comment: Accepted by AJ, 18 pages, including 6 figure

Coexpression of rat P2X2 and P2X6 subunits in Xenopus oocytes.

Transcripts for P2X(2) and P2X(6) subunits are present in rat CNS and frequently colocalize in the same brainstem nuclei. When rat P2X(2) (rP2X(2)) and rat P2X(6) (rP2X(6)) receptors were expressed individually in Xenopus oocytes and studied under voltage-clamp conditions, only homomeric rP2X(2) receptors were fully functional and gave rise to large inward currents (2-3 microA) to extracellular ATP. Coexpression of rP2X(2) and rP2X(6) subunits in Xenopus oocytes resulted in a heteromeric rP2X(2/6) receptor, which showed a significantly different phenotype from the wild-type rP2X(2) receptor. Differences included reduction in agonist potencies and, in some cases (e.g., Ap(4)A), significant loss of agonist activity. ATP-evoked inward currents were biphasic at the heteromeric rP2X(2/6) receptor, particularly when Zn(2+) ions were present or extracellular pH was lowered. The pH range was narrower for H(+) enhancement of ATP responses at the heteromeric rP2X(2/6) receptor. Also, H(+) ions inhibited ATP responses at low pH levels (<pH 6.3). The pH-dependent blocking activity of suramin was changed at this heteromeric receptor, although the potentiating effect of Zn(2+) on ATP responses was unchanged. Thus, the rP2X(2/6) receptor is a functionally modified P2X(2)-like receptor with a distinct pattern of pH modulation of ATP activation and suramin blockade. Although homomeric P2X(6) receptors function poorly, the P2X(6) subunit can contribute to functional heteromeric P2X channels and may influence the phenotype of native P2X receptors in those cells in which it is expressed

A Brief History of Prohibition and Treatment Solutions for Substance Abusers

The predominant policy of prohibition (i.e. "War on Drugs") emerged in the early Twentieth Century. It has been expanded on since that time to become the primary thrust of drug policy in almost every nation today. We will examine how this came about and the ways in which it has contributed to the maltreatment of substance abuse disorders

Generational Shift and Drug Abuse in Older Americans

Since the problem of substance abuse by older adults began to receive serious professional attention, the focus has been almost exclusively on alcohol abuse. This reality is changing as the “baby boomers” age. We examined data from the National Household Survey on Drug Abuse (1985) and the National Survey on Drug Use and Health (2006) comparing nationwide prevalence of both legal and illicit drugs. Use of drugs by category varied over the study period; some showed little change (e.g., alcohol) while others showed marked increase (e.g., marijuana, cocaine). We found that the population of older Americans in 2006 contained greater proportions of persons who had used or continued to use illicit drugs than did older Americans in 1985. Gerontologists and geriatric services will increasingly encounter older Americans who use or abuse illicit drugs

Proximity-induced magnetism in Pt layered with rare-earth–transition-metal ferrimagnetic alloys

The proximity-induced moment (PIM) in heavy metal layers may play a significant role in heterostructured spintronic systems. In particular, the PIM of a heavy metal adjacent to a magnetic layer has been linked to interfacial spin transport behavior. Element-resolved x-ray magnetic measurements were used to investigate PIM in Pt layered with two different rare-earth (RE):3d transition-metal (TM) ferrimagnetic alloys in which the net moment was dominated by either the RE or the TM at room temperature. We observed significant PIM in Pt confined to a 2-nm interfacial region for Pt/Co77Gd23 and Pt/(Fe50Co50)77Gd23 and, in both cases, the PIM was parallel to the TM sublattice rather than the RE or the net moment. Our results highlight the prominence of the d−d mediated interactions between the Pt and the constituents of the ferrimagnetic RE:TM alloys over the net macroscopic moment

Federalism and Beyond: The Uncertain Nature of Federal/State Relationships in a Restructuring World

Federalism in the restructuring context has certainly been controversial and filled with uncertainty -- some would say perilous. Some would say the shifts in jurisdiction between federal and state governments are so serious and of such concern that we should really pause before restructuring the electric industries. Some say we have not done the right thing in the telecommunications industry either. This area is certainly filled with potential for competitors and for lawyers. To help us sort it out, we have four distinguished panelists who are going to identify some of the key state/federal jurisdictional issues in the telecommunications and electric industries - how those issues are being resolved and how they are likely to be resolved in the future. And because the telecommunications industry is further along than electricity, we are going to start with those panelists first

Evidence of Titan's Climate History from Evaporite Distribution

Water-ice-poor, 5-$\mu$m-bright material on Saturn's moon Titan has previously been geomorphologically identified as evaporitic. Here we present a global distribution of the occurrences of the 5-$\mu$m-bright spectral unit, identified with Cassini's Visual Infrared Mapping Spectrometer (VIMS) and examined with RADAR when possible. We explore the possibility that each of these occurrences are evaporite deposits. The 5-$\mu$m-bright material covers 1\% of Titan's surface and is not limited to the poles (the only regions with extensive, long-lived surface liquid). We find the greatest areal concentration to be in the equatorial basins Tui Regio and Hotei Regio. Our interpretations, based on the correlation between 5-$\mu$m-bright material and lakebeds, imply that there was enough liquid present at some time to create the observed 5-$\mu$m-bright material. We address the climate implications surrounding a lack of evaporitic material at the south polar basins: if the south pole basins were filled at some point in the past, then where is the evaporite

The Effects of Videotape Testimony in Jury Trials: Studies on Juror Decision Making, Information Retention, and Emotional Arousal

Summary of Contents I. Introduction: The Nature of the Research II. Group I : The Nugent u. Clark Studies A. Background 1. Selecting the stimulus trial 2. Editing the transcript 3. Preparing the trial a. Casting b. Equipment B. Nugent u. Clark Study 1 : live v. videotape trials 1. Questions examined 2. Procedures a. The live presentation b. The videotape presentation c. The questionnaire 3. Results and discussion a. Negligence verdicts and mean awards b. Juror perception of attorney credibility c. Juror information retention d. Juror interest and motivation 4. Conclusions from Study 1 C. Nugent u. Clark Study 2: split-screen v. full-screen videotape presentations 1. Questions examined 2. Procedure