Effects of Intoxicating Free-Choice Alcohol Consumption During Adolescence on Drinking and Impulsivity During Adulthood in Selectively Bred High Alcohol Preferring Mice

Background— Abuse of alcohol during adolescence continues to be a problem, and it has been shown that earlier onset of drinking predicts increased alcohol abuse problems later in life. High levels of impulsivity have been demonstrated to be characteristic of alcoholics, and impulsivity has also been shown to predict later alcohol use in teenage subjects, showing that impulsivity may precede the development of alcohol use disorders. These experiments examined adolescent drinking in a high-drinking, relatively impulsive mouse population, and assessed its effects on adult drinking and adult impulsivity. Methods— Experiment 1: Selectively bred High-Alcohol Preferring (HAPII) mice were given either alcohol (free choice access) or water only for two weeks during middle adolescence or adulthood. All mice were given free choice access to alcohol 30 days later, in adulthood. Experiment 2: Adolescent HAPII mice drank alcohol and water, or water alone, for two weeks, and were then trained to perform a delay discounting task as adults to measure impulsivity. In each experiment, effects of volitional ethanol consumption on later behavior were assessed. We expected adolescent alcohol exposure to increase subsequent drinking and impulsivity. Results— Mice consumed significant quantities of ethanol, reaching average blood ethanol concentrations (BECs) of 142 mg/dl (adolescent) or 154 mg/dl (adult) in Experiment 1. Adolescent mice in experiment 2 reached an average of 108 mg/dl. Mice exposed to alcohol in either adolescence or adulthood showed a transient increase in ethanol consumption, but we observed no differences in impulsivity in adult mice as a function of whether mice drank alcohol during adolescence. Conclusions— These findings indicate that HAPII mice drink intoxicating levels of alcohol during both adolescence and adulthood, and that this volitional intake has long-term effects on subsequent drinking behavior. Nonetheless, this profound exposure to alcohol during adolescence does not increase impulsivity in adulthood, indicating that long-term changes in drinking are mediated by mechanisms other than impulsivity

Loss of receptor activity-modifying protein 2 in mice causes placental dysfunction and alters PTH1R regulation

Receptor activity-modifying protein 2 (Ramp2) is a single-pass transmembrane protein that heterodimerizes with several family B G-protein coupled receptors to alter their function. Ramp2 has been primarily characterized in association with calcitonin receptor-like receptor (Calcrl, CLR), forming the canonical receptor complex for the endocrine peptide adrenomedullin (Adm, AM). However, we previously demonstrated that Ramp2+/- female mice display a constellation of endocrine-related phenotypes that are distinct from those of Adm+/- and Calcrl+/- mice, implying that RAMP2 has physiological functions beyond its canonical complex. Here, we localize Ramp2 expression in the mouse placenta, finding that Ramp2 is robustly expressed in the fetal labyrinth layer, and then characterize the effects of loss of Ramp2 on placental development. Consistent with the expression pattern of Ramp2 in the placenta, Ramp2-/- placentas have a thinner labyrinth layer with significantly fewer trophoblast cells secondary to a reduction in trophoblast proliferation. We also find that absence of Ramp2 leads to failed spiral artery remodeling unaccompanied by changes in the uterine natural killer cell population. Furthermore, we assess changes in gene expression of other RAMP2-associated G-protein coupled receptors (GPCRs), concluding that Ramp2 loss decreases parathyroid hormone 1 receptor (Pthr1) expression and causes a blunted response to systemic parathyroid hormone (PTH) administration in mice. Ultimately, these studies provide in vivo evidence of a role for RAMP2 in placental development distinct from the RAMP2-CLR/AM signaling paradigm and identify additional pathways underlying the endocrine and fertility defects of the previously characterized Ramp2 heterozygous adult females

Making Progress Toward The Degree

Introduction Students\u27 ability to complete degrees in a timely manner has become one of the key new issues in higher education. Enrollment increases along with resource cuts have created increasing problems for student progress, which Western has been confronting through curricular changes, enrollment management policy changes, and higher workload for faculty and staff. At the same time, increases in tuition have highlighted students\u27 felt need for efficient progress. Two recent findings illustrate the impact of these pressures on the university. First, nearly half (44.9%) of students who entered Western in Fall, 1994, said at least one course they wanted to take was unavailable; one-fourth (25.6%) said more than one was unavailable. These figures would be much higher were it not for extensive recent efforts by the university to increase course access. Second, one-third (33.3%) of new students entering Fall, 1994 said a major reason influencing their choice of major field would be their ability to complete the major within an acceptable time. The great majority (81.1%) said this consideration is at least a minor reason for choosing their major field. The United States Congress recognized the issue of degree completion in 1991 when it passed the Student Right-To-Know and Campus Security Act. This act states that each college, receiving federal funds, must disclose a graduation rate for full-time, degree seeking Freshmen. National studies on time to complete baccalaureate degree show that 43.0% of graduates do so within 4 years, 70.8% graduate within 5 years, and 81% graduate within 6 years--19% take longer than 6 years to complete their degree (National Center for Education Statistics; 1993). On a more local level, one that is more comparable to Western Washington University, a study of California State University, a public university with moderately selective admission requirements, showed that 81.0% of transfer students graduate in 4 years (average = 3.5 years), and 80.0% of Freshmen students graduate in 6 years (average = 5.6 years) (Garcia; 1994). Is the length of time necessary to complete a baccalaureate degree increasing

Pulsed-Addition Ring-Opening Metathesis Polymerization: Catalyst-Economical Syntheses of Homopolymers and Block Copolymers

Poly(tert-butyl ester norbornene imide) homopolymers and poly(tert-butyl ester norbornene imide-b-N-methyloxanorbornene imide) copolymers were prepared by pulsed-addition ring-opening metathesis polymerization (PA-ROMP). PA-ROMP is a unique polymerization method that employs a symmetrical cis-olefin chain transfer agent (CTA) to simultaneously cap a living polymer chain and regenerate the ROMP initiator with high fidelity. Unlike traditional ROMP with chain transfer, the CTA reacts only with the living chain end, resulting in narrowly dispersed products. The regenerated initiator can then initiate polymerization of a subsequent batch of monomer, allowing for multiple polymer chains with controlled molecular weight and low polydispersity to be generated from one metal initiator. Using the fast-initiating ruthenium metathesis catalyst (H_2IMes)(Cl)_2(pyr)_2RuCHPh and cis-4-octene as a CTA, the capabilities of PA-ROMP were investigated with a Symyx robotic system, which allowed for increased control and precision of injection volumes. The results from a detailed study of the time required to carry out the end-capping/initiator-regeneration step were used to design several experiments in which PA-ROMP was performed from one to ten cycles. After determination of the rate of catalyst death, a single, low polydispersity polymer was prepared by adjusting the amount of monomer injected in each cycle, maintaining a constant monomer/catalyst ratio. Additionally, PA-ROMP was used to prepare nearly perfect block copolymers by quickly injecting a second monomer at a specific time interval after the first monomer injection, such that chain transfer had not yet occurred. Polymers were characterized by gel permeation chromatography with multiangle laser light scattering

Self-assembly of the cyclic lipopeptide daptomycin: spherical micelle formation does not depend on the presence of calcium chloride

The cyclic lipopeptide Daptomycin, used as a treatment for infections where antimicrobial resistance is observed, is shown to self-assemble into spherical micelles above a critical aggregation concentration. Micelles are observed either in the absence or presence of CaCl2, in contrast to claims in the literature that CaCl2 is required for micellization

Strong genetic influences on the stability of autistic traits in childhood

Objective: Disorders on the autism spectrum, as well as autistic traits in the general population, have been found to be both highly stable across age and highly heritable at individual ages. However, little is known about the overlap in genetic and environmental influences on autistic traits across age and the contribution of such influences to trait stability itself. The present study investigated these questions in a general population sample of twins. Method: More than 6,000 twin pairs were rated on an established scale of autistic traits by their parents at 8, 9, and 12 years of age and by their teachers at 9 and 12 years of age. Data were analyzed using structural equation modeling. Results: The results indicated that, consistently across raters, not only were autistic traits stable, and moderately to highly heritable at individual ages, there was also a high degree of overlap in genetic influences across age. Furthermore, autistic trait stability could largely be accounted for by genetic factors, with the environment unique to each twin playing a minor role. The environment shared by twins had virtually no effect on the longitudinal stability in autistic traits. Conclusions: Autistic traits are highly stable across middle childhood and this stability is caused primarily by genetic factors