Presynaptic CRF1 Receptors Mediate the Ethanol Enhancement of GABAergic Transmission in the Mouse Central Amygdala

Corticotropin-releasing factor (CRF) is a 41-amino-acid neuropeptide involved in stress responses initiated from several brain areas, including the amygdala formation. Research shows a strong relationship between stress, brain CRF, and excessive alcohol consumption. Behavioral studies suggest that the central amygdala (CeA) is significantly involved in alcohol reward and dependence. We recently reported that the ethanol augmentation of GABAergic synaptic transmission in rat CeA involves CRF1 receptors, because both CRF and ethanol significantly enhanced the amplitude of evoked GABAergic inhibitory postsynaptic currents (IPSCs) in CeA neurons from wild-type (WT) and CRF2 knockout (KO) mice, but not in neurons of CRF1 KO mice. The present study extends these findings using selective CRF receptor ligands, gene KO models, and miniature IPSC (mIPSC) analysis to assess further a presynaptic role for the CRF receptors in mediating ethanol effects in the CeA. In whole-cell patch recordings of pharmacologically isolated GABAAergic IPSCs from slices of mouse CeA, both CRF and ethanol augmented evoked IPSCs in a concentration-dependent manner, with low EC50s. A CRF1 (but not CRF2) KO construct and the CRF1-selective nonpeptide antagonist NIH-3 (LWH-63) blocked the augmenting effect of both CRF and ethanol on evoked IPSCs. Furthermore, the new selective CRF1 agonist stressin1, but not the CRF2 agonist urocortin 3, also increased evoked IPSC amplitudes. Both CRF and ethanol decreased paired-pulse facilitation (PPF) of evoked IPSCs and significantly enhanced the frequency, but not the amplitude, of spontaneous miniature GABAergic mIPSCs in CeA neurons of WT mice, suggesting a presynaptic site of action. The PPF effect of ethanol was abolished in CeA neurons of CRF1 KO mice. The CRF1 antagonist NIH-3 blocked the CRF- and ethanol-induced enhancement of mIPSC frequency in CeA neurons. These data indicate that presynaptic CRF1 receptors play a critical role in permitting or mediating ethanol enhancement of GABAergic synaptic transmission in CeA, via increased vesicular GABA release, and thus may be a rational target for the treatment of alcohol abuse and alcoholism

Pervasive Genetic Hitchhiking and Clonal Interference in 40 Evolving Yeast Populations

The dynamics of adaptation determines which mutations fix in a population, and hence how reproducible evolution will be. This is central to understanding the spectra of mutations recovered in evolution of antibiotic resistance1, the response of pathogens to immune selection2,3, and the dynamics of cancer progression4,5. In laboratory evolution experiments, demonstrably beneficial mutations are found repeatedly6–8, but are often accompanied by other mutations with no obvious benefit. Here we use whole-genome whole-population sequencing to examine the dynamics of genome sequence evolution at high temporal resolution in 40 replicate Saccharomyces cerevisiae populations growing in rich medium for 1,000 generations. We find pervasive genetic hitchhiking: multiple mutations arise and move synchronously through the population as mutational “cohorts.” Multiple clonal cohorts are often present simultaneously, competing with each other in the same population. Our results show that patterns of sequence evolution are driven by a balance between these chance effects of hitchhiking and interference, which increase stochastic variation in evolutionary outcomes, and the deterministic action of selection on individual mutations, which favors parallel evolutionary solutions in replicate populations

Beef production from feedstuffs conserved using new technologies to reduce negative environmental impacts

End of project reportMost (ca. 86%) Irish farms make some silage. Besides directly providing feed for livestock, the provision of grass silage within integrated grassland systems makes an important positive contribution to effective grazing management and improved forage utilisation by grazing animals, and to effective feed budgeting by farmers. It can also contribute to maintaining the content of desirable species in pastures, and to livestock not succumbing to parasites at sensitive times of the year. Furthermore, the optimal recycling of nutrients collected from housed livestock can often be best achieved by spreading the manures on the land used for producing the conserved feed. On most Irish farms, grass silage will remain the main conserved forage for feeding to livestock during winter for the foreseeable future. However, on some farms high yields of whole-crop (i.e. grain + straw) cereals such as wheat, barley and triticale, and of forage maize, will be an alternative option provided that losses during harvesting, storage and feedout are minimised and that input costs are restrained. These alternative forages have the potential to reliably support high levels of animal performance while avoiding the production of effluent. Their production and use however will need to advantageously integrate into ruminant production systems. A range of technologies can be employed for crop production and conservation, and for beef production, and the optimal options need to be identified. Beef cattle being finished indoors are offered concentrate feedstuffs at rates that range from modest inputs through to ad libitum access. Such concentrates frequently contain high levels of cereals such as barley or wheat. These cereals are generally between 14% to 18% moisture content and tend to be rolled shortly before being included in coarse rations or are more finely processed prior to pelleting. Farmers thinking of using ‘high-moisture grain’ techniques for preserving and processing cereal grains destined for feeding to beef cattle need to know how the yield, conservation efficiency and feeding value of such grains compares with grains conserved using more conventional techniques. European Union policy strongly encourages a sustainable and multifunctional agriculture. Therefore, in addition to providing European consumers with quality food produced within approved systems, agriculture must also contribute positively to the conservation of natural resources and the upkeep of the rural landscape. Plastics are widely used in agriculture and their post-use fate on farms must not harm the environment - they must be managed to support the enduring sustainability of farming systems. There is an absence of information on the efficacy of some new options for covering and sealing silage with plastic sheeting and tyres, and an absence of an inventory of the use, re-use and post-use fate of plastic film on farms. Irish cattle farmers operate a large number of beef production systems, half of which use dairy bred calves. In the current, continuously changing production and market conditions, new beef systems must be considered. A computer package is required that will allow the rapid, repeatable simulation and assessment of alternate beef production systems using appropriate, standardised procedures. There is thus a need to construct, evaluate and utilise computer models of components of beef production systems and to develop mathematical relationships to link system components into a network that would support their integration into an optimal system model. This will provide a framework to integrate physical and financial on-farm conditions with models for estimating feed supply and animal growth patterns. Cash flow and profit/loss results will be developed. This will help identify optimal systems, indicate the cause of failure of imperfect systems and identify areas where applied research data are currently lacking, or more basic research is required

Optical properties of the vibrations in charged C60_{60} molecules

The transition strengths for the four infrared-active vibrations of charged C$_{60}$ molecules are evaluated in self-consistent density functional theory using the local density approximation. The oscillator strengths for the second and fourth modes are strongly enhanced relative to the neutral C$_{60}$ molecule, in good agreement with the experimental observation of ``giant resonances'' for those two modes. Previous theory, based on a ``charged phonon'' model, predicted a quadratic dependence of the oscillator strength on doping, but this is not borne out in our calculations.Comment: 10 pages, RevTeX3.

Analytic Detection Thresholds for Measurements of Linearly Polarized Intensity Using Rotation Measure Synthesis

A fully analytic statistical formalism does not yet exist to describe radio-wavelength measurements of linearly polarized intensity that are produced using rotation measure synthesis. In this work we extend the analytic formalism for standard linear polarization, namely that describing measurements of the quadrature sum of Stokes Q and U intensities, to the rotation measure synthesis environment. We derive the probability density function and expectation value for Faraday-space polarization measurements for both the case where true underlying polarized emission is present within unresolved Faraday components, and for the limiting case where no such emission is present. We then derive relationships to quantify the statistical significance of linear polarization measurements in terms of standard Gaussian statistics. The formalism developed in this work will be useful for setting signal-to-noise ratio detection thresholds for measurements of linear polarization, for the analysis of polarized sources potentially exhibiting multiple Faraday components, and for the development of polarization debiasing schemes.Comment: 14 pages, 6 figures, accepted for publication in MNRA

English in Wartime: A Symposium by College Teachers

After the declaration of war upon us by the Axis nations, it seemed the editors of College English that the members of the College should, as soon as possible, co-operate in determining how best to fulfil our special responsibility throughout World War II. As a first step, we invited twenty-five teachers of English in colleges and universities to suggest how we should meet this professional emergency. The Planning Commission of the N.C.T.E., at their meeting in Chicago during the Christmas holidays, and the College Section, at their meeting in Indianapolis with the M.L.A., considered general and basic wartime policies for the National Council. The result of these deliberations will be presented in the March College English. To assemble a preliminary survey of opinion on the teaching of English in World War II, we had to act quickly in order to meet the deadline for the February issue. Nine letters from college men and women came back in time to be included in the symposium. The weakness of the small number, however, is overcome by the strength of the unified and obviously representative character of the responses. Teachers of English believe in the permanent value of the work they are doing. In peace or in war the discipline of the humanities is a way to decency in human relations. Those who have written for the symposium agree that our time of emergency requires of us, as teachers of English, a more vigorous concentration than ever upon clear expression and broad, permanently vital reading. We will need to make curriculum changes, and individually we will perform special wartime duties; but the initial message from outstanding college teachers is that we must do the job for which we are trained: help others to realize the power which emanates from great literature to live humanely in the midst of conflict

Need-based resource allocation: different need indicators, different results?

<p>Abstract</p> <p>Background</p> <p>A key policy objective in most publicly financed health care systems is to allocate resources according to need. Many jurisdictions implement this policy objective through need-based allocation models. To date, no gold standard exists for selecting need indicators. In the absence of a gold standard, sensitivity of the choice of need indicators is of concern. The primary objective of this study was to assess the consistency and plausibility of estimates of per capita relative need for health services across Canadian provinces based on different need indicators.</p> <p>Methods</p> <p>Using the 2000/2001 Canadian Community Health Survey, we estimated relative per capita need for general practitioner, specialist, and hospital services by province using two approaches that incorporated a different set of need indicators: (1) demographics (age and sex), and (2) demographics, socioeconomic status, and health status. For both approaches, we first fitted regression models to estimate standard utilization of each of three types of health services by indicators of need. We defined the standard as average levels of utilization by needs indicators in the national sample. Subsequently, we estimated expected per capita utilization of each type of health services in each province. We compared these estimates of per capita relative need with premature mortality in each province to check their face validity.</p> <p>Results</p> <p>Both approaches suggested that expected relative per capita need for three services vary across provinces. Different approaches, however, yielded different and inconsistent results. Moreover, provincial per capita relative need for the three health services did not always indicate the same direction of need suggested by premature mortality in each province. In particular, the two approaches suggested Newfoundland had less need than the Canadian average for all three services, but it had the highest premature mortality in Canada.</p> <p>Conclusion</p> <p>Substantial differences in need for health care may exist across Canadian provinces, but the direction and magnitude of differences depend on the need indicators used. Allocations from models using survey data lacked face validity for some provinces. These results call for the need to better understand the biases that may result from the use of survey data for resource allocation.</p

Ursinus College Alumni Journal, March 1961

The President writes • Who gets into college? • Mr. Dolman comments • Search for certainty • Two foreign students sponsored • Dr. Miller on TV • Announcing an alumni seminar • The thousand and second night\u27s tale • Student European tour • Two students attend white house conference • Greetings from Philadelphia • Spring Festival replaces May Day • Dr. Shilling speaks • Final Forum of the semester • Dr. Miller to teach in India • Ursinus Women\u27s Club • Attention, alumni: Constitution change • Portrait of a pioneer • Jacobs promoted to Captain • Henschel takes over new post • Nominees for Alumni Association offices • Alumni regionals announce meetings • January 1961 mid year report of the Loyalty Fund campaign • Wrestling results • Basketball review • Ursinus girls dominate U.S. hockey team • Track prospects • Happy retirement • John Shuttleworth, \u2745 • Class notes • Births • Weddings • Necrologyhttps://digitalcommons.ursinus.edu/alumnijournal/1070/thumbnail.jp

Ursinus College Alumni Journal, August 1967

Exposure \u2767 Ursinus • Viewpoint at commencement time: Means to an end; Toward freedom; Liberal morality; Open-minded attitude; Quality vs. quantity • From the President • What makes Suzy a language dud? • The paradox of urbia: an interview • Negro voices of the city • Springtime was alumni time • Dr. Myers wins alumni award • Dr. Wessel speaks on urbia • Alumni giving climbs in 1967 • Campus clippings: Collegeville area grows; Staigers tour world; Color film; Miss congeniality; New Board members; Placement service; Schultze promoted; Humble gift; Include Ursinus in your will • Sporting scene: Tennis; Baseball; Track • Anatomy of medical school life • Class notebook • Faculty members speak at spring regional meetings • Weddings • Births • In memoriam • Physicians Club meets •https://digitalcommons.ursinus.edu/alumnijournal/1089/thumbnail.jp