Pharmacological Preconditioning with GYKI 52466: A Prophylactic Approach to Neuroprotection.

Some toxins and drugs can trigger lasting neuroprotective mechanisms that enable neurons to resist a subsequent severe insult. This "pharmacological preconditioning" has far-reaching implications for conditions in which blood flow to the brain is interrupted. We have previously shown that in vitro preconditioning with the AMPA receptor antagonist GYKI 52466 induces tolerance to kainic acid (KA) toxicity in hippocampus. This effect persists well after washout of the drug and may be mediated via inverse agonism of G-protein coupled receptors (GPCRs). Given the amplifying nature of metabotropic modulation, we hypothesized that GYKI 52466 may be effective in reducing seizure severity at doses well below those normally associated with adverse side effects. Here we report that pharmacological preconditioning with low-dose GYKI imparts a significant protection against KA-induced seizures in vivo. GYKI (3 mg/kg, s.c.), 90-180 min prior to high-dose KA, markedly reduced seizure scores, virtually abolished all level 3 and level 4 seizures, and completely suppressed KA-induced hippocampal c-FOS expression. In addition, preconditioned animals exhibited significant reductions in high frequency/high amplitude spiking and ECoG power in the delta, theta, alpha, and beta bands during KA. Adverse behaviors often associated with higher doses of GYKI were not evident during preconditioning. The fact that GYKI is effective at doses well-below, and at pre-administration intervals well-beyond previous studies, suggests that a classical blockade of ionotropic AMPA receptors does not underlie anticonvulsant effects. Low-dose GYKI preconditioning may represent a novel, prophylactic strategy for neuroprotection in a field almost completely devoid of effective pharmaceuticals

The effects of added salt in the phase II starter pig diet

A total of 178 pigs (initially 10.5 Ib and 19 d of age) was used to compare the effects of added salt in the Phase II (d 14 to 28 postweaning) diet. Pigs were alloted by sex and inital weight and placed in pens containing either nine or 10 pigs. All pigs were fed the same Phase I diet for the first 14 d postweaning. The Phase I diet contained 20% dried whey, 7.5% spry-dried porcine plasma (SDPP), and 1.75% spray-dried blood meal (SDBM) and was formulated to contain 1.5% lysine and .42% methionine. On day 14, pigs were assigned to one of three diets that contained either 3.5 or 7 lb/ton added salt or no salt. The Phase II diet was cornsoybean meal-based, contained 10% dried whey and 2.5% SDBM, and was formulated to contain 1.25% lysine and .34% methionine. During Phase I (d 0 to 14 postweaning), average dally gain (ADG), average daily feed intake (ADFI), and feed efficiency (F/G) were .52 Ib, .63 Ib, and 1.2, respectively. During Phase II (d 14 to 28 postweaning), ADG and F/G tended to improve with increasing added salt (8 and 9 %, respectively). For the cumulative period (d 0 to 28 postweaning), numerical increases also occurred in both ADG and F/G. These results suggest that up to 7 lb/ton of added salt in a Phase II diet containing 10% dried whey improves ADG and F/G of starter pigs.; Swine Day, Manhattan, KS, November 17, 199

The Evolution of Distorted Rotating Black Holes III: Initial Data

In this paper we study a new family of black hole initial data sets corresponding to distorted ``Kerr'' black holes with moderate rotation parameters, and distorted Schwarzschild black holes with even- and odd-parity radiation. These data sets build on the earlier rotating black holes of Bowen and York and the distorted Brill wave plus black hole data sets. We describe the construction of this large family of rotating black holes. We present a systematic study of important properties of these data sets, such as the size and shape of their apparent horizons, and the maximum amount of radiation that can leave the system during evolution. These data sets should be a very useful starting point for studying the evolution of highly dynamical black holes and can easily be extended to 3D.Comment: 16 page

On the Distribution of Orbital Poles of Milky Way Satellites

In numerous studies of the outer Galactic halo some evidence for accretion has been found. If the outer halo did form in part or wholly through merger events, we might expect to find coherent streams of stars and globular clusters following similar orbits as their parent objects, which are assumed to be present or former Milky Way dwarf satellite galaxies. We present a study of this phenomenon by assessing the likelihood of potential descendant ``dynamical families'' in the outer halo. We conduct two analyses: one that involves a statistical analysis of the spatial distribution of all known Galactic dwarf satellite galaxies (DSGs) and globular clusters, and a second, more specific analysis of those globular clusters and DSGs for which full phase space dynamical data exist. In both cases our methodology is appropriate only to members of descendant dynamical families that retain nearly aligned orbital poles today. Since the Sagittarius dwarf (Sgr) is considered a paradigm for the type of merger/tidal interaction event for which we are searching, we also undertake a case study of the Sgr system and identify several globular clusters that may be members of its extended dynamical family. (ABRIDGED)Comment: accepted by ApJ, 57 pages, 13 figures, AASTeX forma

Genome-wide association study of dental caries in the Hispanic Communities Health Study/Study of Latinos (HCHS/SOL)

Dental caries is the most common chronic disease worldwide, and exhibits profound disparities in the USA with racial and ethnic minorities experiencing disproportionate disease burden. Though heritable, the specific genes influencing risk of dental caries remain largely unknown. Therefore, we performed genome-wide association scans (GWASs) for dental caries in a population-based cohort of 12 000 Hispanic/Latino participants aged 18–74 years from the HCHS/SOL. Intra-oral examinations were used to generate two common indices of dental caries experience which were tested for association with 27.7 M genotyped or imputed single-nucleotide polymorphisms separately in the six ancestry groups. A mixed-models approach was used, which adjusted for age, sex, recruitment site, five principal components of ancestry and additional features of the sampling design. Meta-analyses were used to combine GWAS results across ancestry groups. Heritability estimates ranged from 20–53% in the six ancestry groups. The most significant association observed via meta-analysis for both phenotypes was in the region of the NAMPT gene (rs190395159; P-value = 6 × 10−10), which is involved in many biological processes including periodontal healing. Another significant association was observed for rs72626594 (P-value = 3 × 10−8) downstream of BMP7, a tooth development gene. Other associations were observed in genes lacking known or plausible roles in dental caries. In conclusion, this was the largest GWAS of dental caries, to date and was the first to target Hispanic/Latino populations. Understanding the factors influencing dental caries susceptibility may lead to improvements in prediction, prevention and disease management, which may ultimately reduce the disparities in oral health across racial, ethnic and socioeconomic strata

A conceptual framework for the emerging discipline of conservation physiology

Current rates of biodiversity decline are unprecedented and largely attributed to anthropogenic influences. Given the scope and magnitude of conservation issues, policy and management interventions must maximize efficiency and efficacy. The relatively new field of conservation physiology reveals the physiological mechanisms associated with population declines, animal- environment relationships and population or species tolerance thresholds, particularly where these relate to anthropogenic factors that necessitate conservation action. We propose a framework that demonstrates an integrative approach between physiology, conservation and policy, where each can inform the design, conduct and implementation of the other. Each junction of the conservation physiology process has the capacity to foster dialogue that contributes to effective implementation, monitoring, assessment and evaluation. This approach enables effective evaluation and implementation of evidence-based conservation policy and management decisions through a process of ongoing refinement, but may require that scientists (from the disciplines of both physiology and conservation) and policy-makers bridge interdisciplinary knowledge gaps. Here, we outline a conceptual framework that can guide and lead developments in conservation physiology, as well as promote innovative research that fosters conservation-motivated policy

The Impossibility of a Perfectly Competitive Labor Market

Using the institutional theory of transaction cost, I demonstrate that the assumptions of the competitive labor market model are internally contradictory and lead to the conclusion that on purely theoretical grounds a perfectly competitive labor market is a logical impossibility. By extension, the familiar diagram of wage determination by supply and demand is also a logical impossibility and the neoclassical labor demand curve is not a well-defined construct. The reason is that the perfectly competitive market model presumes zero transaction cost and with zero transaction cost all labor is hired as independent contractors, implying multi-person firms, the employment relationship, and labor market disappear. With positive transaction cost, on the other hand, employment contracts are incomplete and the labor supply curve to the firm is upward sloping, again causing the labor demand curve to be ill-defined. As a result, theory suggests that wage rates are always and everywhere an amalgam of an administered and bargained price. Working Paper 06-0