Characterization of three vasopressin receptor 2 variants: an apparent polymorphism (V266A) and two loss-of-function mutations (R181C and M311V).

Arginine vasopressin (AVP) is released from the posterior pituitary and controls water homeostasis. AVP binding to vasopressin V2 receptors (V2Rs) located on kidney collecting duct epithelial cells triggers activation of Gs proteins, leading to increased cAMP levels, trafficking of aquaporin-2 water channels, and consequent increased water permeability and antidiuresis. Typically, loss-of-function V2R mutations cause nephrogenic diabetes insipidus (NDI), whereas gain-of-function mutations cause nephrogenic syndrome of inappropriate antidiuresis (NSIAD). Here we provide further characterization of two mutant V2Rs, R181C and M311V, reported to cause complete and partial NDI respectively, together with a V266A variant, in a patient diagnosed with NSIAD. Our data in HEK293FT cells revealed that for cAMP accumulation, AVP was about 500- or 30-fold less potent at the R181C and M311V mutants than at the wild-type receptor respectively (and about 4000- and 60-fold in COS7 cells respectively). However, in contrast to wild type V2R, the R181C mutant failed to increase inositol phosphate production, while with the M311V mutant, AVP exhibited only partial agonism in addition to a 37-fold potency decrease. Similar responses were detected in a BRET assay for β-arrestin recruitment, with the R181C receptor unresponsive to AVP, and partial agonism with a 23-fold decrease in potency observed with M311V in both HEK293FT and COS7 cells. Notably, the V266A V2R appeared functionally identical to the wild-type receptor in all assays tested, including cAMP and inositol phosphate accumulation, β-arrestin interaction, and in a BRET assay of receptor ubiquitination. Each receptor was expressed at comparable levels. Hence, the M311V V2R retains greater activity than the R181C mutant, consistent with the milder phenotype of NDI associated with this mutant. Notably, the R181C mutant appears to be a Gs protein-biased receptor incapable of signaling to inositol phosphate or recruiting β-arrestin. The etiology of NSIAD in the patient with V266A V2R remains unknown

Holocene LSA archaeology from Equus Cave, Buxton-Norlim Limeworks, South Africa : an analysis of the bone tool assemblage

Abstract: Equus Cave, Buxton-Norlim Limeworks, near Taung, North West Province, South Africa, was first excavated between 1978 and 1982. While the site dates to the terminal Pleistocene and Holocene the precise age of the different layers is debated, as is the technological assignment of the deepest deposits, which are said to contain both Later or Middle Stone Age elements. While the faunal assemblage and some of the human remains have been published, the archaeology has never been fully analysed or reported. New excavations in 2012 revealed numerous artefacts including ochre, something not previously noted for this site. Comparison of total lithic artefact counts versus faunal NISPs and MNIs shows that the height of human occupation occurred during the Holocene, with preliminary analysis of the >6000 lithic assemblage indicating a dominance of notched artefacts, which, coupled with the presence of 16 bone points, is characteristic of other HoloceneWilton (Later Stone Age) sites in the region. The focus of this paper is the 16 bone points, which include projectile points and link-shafts, and how these items were manufactured and used. The results provide one of the first detailed descriptions of Later Stone Age bone tools, including rare specimens that are mostly complete or still preserve the tips, making an important contribution to our limited understanding of Later Stone Age bone tool technology

Electronic Chart of the Future: The Hampton Roads Project

ECDIS is evolving from a two-dimensional static display of chart-related data to a decision support system capable of providing real-time or forecast information. While there may not be consensus on how this will occur, it is clear that to do this, ENC data and the shipboard display environment must incorporate both depth and time in an intuitively understandable way. Currently, we have the ability to conduct high-density hydrographic surveys capable of producing ENCs with decimeter contour intervals or depth areas. Yet, our existing systems and specifications do not provide for a full utilization of this capability. Ideally, a mariner should be able to benefit from detailed hydrographic data, coupled with both forecast and real-time water levels, and presented in a variety of perspectives. With this information mariners will be able to plan and carry out transits with the benefit of precisely determined and easily perceived underkeel, overhead, and lateral clearances. This paper describes a Hampton Roads Demonstration Project to investigate the challenges and opportunities of developing the “Electronic Chart of the Future.” In particular, a three-phase demonstration project is being planned: 1. Compile test datasets from existing and new hydrographic surveys using advanced data processing and compilation procedures developed at the University of New Hampshire’s Center for Coastal and Ocean Mapping/Joint Hydrographic Center (CCOM/JHC); 2. Investigate innovative approaches being developed at the CCOM/JHC to produce an interactive time- and tide-aware navigation display, and to evaluate such a display on commercial and/or government vessels; 3. Integrate real-time/forecast water depth information and port information services transmitted via an AIS communications broadcast

Use of stormwater impoundments near airports by birds recognizedas hazardous to aviation safety

Design of privately-owned stormwater impoundments within or near airport siting criteria has received little attention with regard to potential hazards posed to aviation safety. In particular, minimizing use of these impoundments by bird species recognized as hazardous to aviation poses an important challenge. Emergent vegetation, shoreline irregularity, and proximity of other water resources are linked to avian richness and diversity within wetlands, as well as bird use of stormwater impoundments on airports. We predicted also that impoundments with bank slope \u3e20% and those functioning as detention facilities, where water is periodically drawn down, would negatively influence use by birds; and that shoreline-vegetation diversity and local land-use diversity would be positively correlated with use. Over 104 weeks(March 2008 to March 2010), we surveyed bird use of 40 stormwater impoundments in the Auburn-Opelika Metropolitan area, Lee County, AL, USA, typical of privately-owned facilities located within or near airport siting criteria. We quantified local-scale and site-specific parameters possibly affecting bird use and evaluated fit for 17 a priori models relative to detection of 10 individual avian foraging guilds recognized as hazardous to aviation safety. Relative likelihoods of best-approximating models (Akaike weights) ranged from approximately 0.42 to 0.92. Based on best-approximating models for at least five of the 10 guilds, we suggest that broad reduction in use of stormwater impoundments, located within or near airport siting criteria, by bird species hazardous to aviation can be achieved via designs which minimize perimeter, surface area, and the ratio of open water to emergent vegetation

A Comparison of Male and Female Title I ADA Discrimination Allegations in Relation to Employer Characteristics

This investigation determined if there is a difference in the proportion of Title I workplace discrimination allegations filed by females in comparison to males under the Americans with Disabilities Act (ADA) in relation to the employer characteristics. Findings are reported and implications for future research and vocational rehabilitation practice

Rapid Oscillations in Cataclysmic Variables. XVI. DW Cancri

We report photometry and spectroscopy of the novalike variable DW Cancri. The spectra show the usual broad H and He emission lines, with an excitation and continuum slope characteristic of a moderately high accretion rate. A radial-velocity search yields strong detections at two periods, 86.1015(3) min and 38.58377(6) min. We interpret these as respectively the orbital period P_orb of the binary, and the spin period P_spin of a magnetic white dwarf. The light curve also shows the spin period, plus an additional strong signal at 69.9133(10) min, which coincides with the difference frequency 1/P_spin-1/P_orb. These periods are stable over the 1 year baseline of measurement. This triply-periodic structure mimics the behavior of several well-credentialed members of the "DQ Herculis" (intermediate polar) class of cataclysmic variables. DQ Her membership is also suggested by the mysteriously strong sideband signal (at nu_spin-nu_orb), attesting to a strong pulsed flux at X-ray/EUV/UV wavelengths. DW Cnc is a new member of this class, and would be an excellent target for extended observation at these wavelengths.Comment: PDF, 28 pages, 6 tables, 9 figures; accepted, in press, to appear June 2004, PASP; more info at http://cba.phys.columbia.edu