50 research outputs found
Mecamylamine, dihydro-β-erythroidine, and dextromethorphan block conditioned responding evoked by the conditional stimulus effects of nicotine
Current smokers express the desire to quit. However, the majority find it difficult to remain abstinent. As such, research efforts continually seek to develop more effective treatment. One such area of research involves the interoceptive stimulus effects of nicotine as either a discriminative stimulus in an operant drug discrimination task, or more recently as a conditional stimulus (CS) in a discriminated goal-tracking task. The present work investigated the potential role nicotinic acetylcholine receptors in the CS effects of nicotine (0.4 mg/kg) using antagonists with differential selectivity for β2*, α7*, α6β2*, and α3β4* receptors. Methyllycaconitine (MLA) had no effect on nicotine-evoked conditioned responding. Mecamylamine and dihydro-β-erythroidine (DHβE) dose dependently blocked responding evoked by the nicotine CS. In a time-course assessment of mecamylamine and DHβE, each blocked conditioned responding when given 5 min before testing and still blocked conditioned responding when administered 200 min before testing. Two novel bis-picolinium analogs (N, N’-(3, 3′-(dodecan-1,12-diyl)-bis-picolinium dibromide [bPiDDB], and N, N’- (decan-1,10-diyl)-bis-picolinium diiodide [bPiDI]) did not block nicotine-evoked conditioned responding. Finally, pretreatment with low dose combinations of mecamylamine, dextromethorphan, and/or bupropion were used to target α3β4* receptors. No combination blocked conditioned responding evoked by the training dose of nicotine. However, a combination of mecamylamine and dextromethorphan partially blocked nicotine-evoked conditioned responding to a lower dose of nicotine (0.1 mg/kg). These results indicate that β2* and potentially α3β4* nicotinic acetylcholine receptors play a role in the CS effects of nicotine and are potential targets for the development of nicotine cessation aids
Mecamylamine, dihydro-β-erythroidine, and dextromethorphan block conditioned responding evoked by the conditional stimulus effects of nicotine
Current smokers express the desire to quit. However, the majority find it difficult to remain abstinent. As such, research efforts continually seek to develop more effective treatment. One such area of research involves the interoceptive stimulus effects of nicotine as either a discriminative stimulus in an operant drug discrimination task, or more recently as a conditional stimulus (CS) in a discriminated goal-tracking task. The present work investigated the potential role nicotinic acetylcholine receptors in the CS effects of nicotine (0.4 mg/kg) using antagonists with differential selectivity for β2*, α7*, α6β2*, and α3β4* receptors. Methyllycaconitine (MLA) had no effect on nicotine-evoked conditioned responding. Mecamylamine and dihydro-β-erythroidine (DHβE) dose dependently blocked responding evoked by the nicotine CS. In a time-course assessment of mecamylamine and DHβE, each blocked conditioned responding when given 5 min before testing and still blocked conditioned responding when administered 200 min before testing. Two novel bis-picolinium analogs (N, N’-(3, 3′-(dodecan-1,12-diyl)-bis-picolinium dibromide [bPiDDB], and N, N’- (decan-1,10-diyl)-bis-picolinium diiodide [bPiDI]) did not block nicotine-evoked conditioned responding. Finally, pretreatment with low dose combinations of mecamylamine, dextromethorphan, and/or bupropion were used to target α3β4* receptors. No combination blocked conditioned responding evoked by the training dose of nicotine. However, a combination of mecamylamine and dextromethorphan partially blocked nicotine-evoked conditioned responding to a lower dose of nicotine (0.1 mg/kg). These results indicate that β2* and potentially α3β4* nicotinic acetylcholine receptors play a role in the CS effects of nicotine and are potential targets for the development of nicotine cessation aids
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The evolution of Home Economics as a subject in Irish primary and post-primary education from the 1800s to the twenty-first century
This paper is a historical review, documenting the evolution of Home Economics as a subject in Irish primary and post-primary education from the 1800s to the twenty-first century. In the 1800s and early twentieth-century domestic subjects, including cookery, was widely taught to females in both primary and post-primary schools. The philosophical underpinning of the subject was to enhance the quality of life for families. The subject remained a popular choice for young women up until the establishment of the Irish Free State which, thereafter, witnessed many changes in the teaching of cookery and domestic science in primary and post-primary schools. The core ideology of the subject has remained relevant and it aims to provide students with knowledge, practical skills, understanding and attitudes for everyday life as individuals and as family members. This reflects the richness of the subject from the past and the relevance of the subject in addressing issues of a twenty-first century society
Precise Quantitation of the Latent HIV-1 Reservoir: Implications for Eradication Strategies
The quantitative viral outgrowth assay (QVOA) provides a precise minimal estimate of the reservoir of resting CD4+ T-cell infection (resting cell infection [RCI]). However, the variability of RCI over time during antiretroviral therapy (ART), relevant to assess potential effects of latency-reversing agents or other interventions, has not been fully described. We performed QVOA on resting CD4+ T cells obtained via leukapheresis from 37 human immunodeficiency virus (HIV)–infected patients receiving stable suppressive ART for a period of 6 years. Patients who started ART during acute (n = 17) or chronic (n = 20) HIV infection were studied once HIV RNA levels were 6-fold were rare. We suggest that a 6-fold decline is a relevant threshold to reliably identify effects of antilatency interventions on RCI
Incident Sexually Transmitted Infection as a Biomarker for High-Risk Sexual Behavior After Diagnosis of Acute HIV
Sexually transmitted infection (STI) diagnosis following diagnosis of acute HIV infection (AHI) indicates ongoing high-risk sexual behavior and possible risk of HIV transmission. We assessed predictors of STI acquisition and the effect of time since care entry on STI incidence in AHI patients in care and receiving consistent risk-reduction messaging
Removing the invisibility cloak: Using space design to influence patron behavior and increase service desk usage
In small branch libraries, patrons seeking assistance from library staff outside of the
dedicated single-service desk often results in large staffing inefficiencies. This paper
presents a case study in which the authors applied behavioral psychology models to a
branch library’s space arrangement to identify possible factors influencing patron service
point choices. A subsequent full space rearrangement was instituted which utilized human
behavior research, service desk design principles, and low-cost methods to create a space
that reduced barriers and influenced patrons back to the main service desk. The paper
reports on the 11-month study that followed and the impact the rearrangement had on
patron behavior. Results indicate that simple rearrangement of existing furniture and
equipment into new configurations have direct influence on service desk usage and can
encourage new patron behaviors. Space and human behavior are inherently connected and
library managers should establish goals for how they envision their spaces to be used and
arrange them in ways that encourage wanted behaviors.Ye
Relic neutrino masses and the highest energy cosmic rays
We consider the possibility that a large fraction of the ultrahigh energy
cosmic rays are decay products of Z bosons which were produced in the
scattering of ultrahigh energy cosmic neutrinos on cosmological relic
neutrinos. We compare the observed ultrahigh energy cosmic ray spectrum with
the one predicted in the above Z-burst scenario and determine the required mass
of the heaviest relic neutrino as well as the necessary ultrahigh energy cosmic
neutrino flux via a maximum likelihood analysis. We show that the value of the
neutrino mass obtained in this way is fairly robust against variations in
presently unknown quantities, like the amount of neutrino clustering, the
universal radio background, and the extragalactic magnetic field, within their
anticipated uncertainties. Much stronger systematics arises from different
possible assumptions about the diffuse background of ordinary cosmic rays from
unresolved astrophysical sources. In the most plausible case that these
ordinary cosmic rays are protons of extragalactic origin, one is lead to a
required neutrino mass in the range 0.08 eV - 1.3 eV at the 68 % confidence
level. This range narrows down considerably if a particular universal radio
background is assumed, e.g. to 0.08 eV - 0.40 eV for a large one. The required
flux of ultrahigh energy cosmic neutrinos near the resonant energy should be
detected in the near future by AMANDA, RICE, and the Pierre Auger Observatory,
otherwise the Z-burst scenario will be ruled out.Comment: 19 pages, 22 figures, REVTeX
Fixed-dose combination emtricitabine/tenofovir/efavirenz initiated during acute HIV infection; 96-week efficacy and durability
Demonstrate rapid initiation of co-formulated treatment during acute HIV infection (AHI) is feasible and efficacious
Integrating social science into conservation planning
A growing body of literature has highlighted the value of social science for conservation, yet the diverse approaches of the social sciences are still inconsistently incorporated in conservation initiatives. Building greater capacity for social science integration in conservation requires frameworks and case studies that provide concrete guidance and specific examples. To address this need, we have developed a framework aimed at expanding the role for social science in formal conservation planning processes. Our framework illustrates multiple ways in which social science research can contribute to four stages of such processes: 1) defining the problem and project team; 2) defining goals; 3) identifying impact pathways and designing interventions; and 4) developing and evaluating indicators of success (or failure). We then present a timely case study of wolf reintroduction in Colorado, U.S.A., to demonstrate the opportunities, challenges, and complexities of applying our framework in practice
Genomic Targets of Brachyury (T) in Differentiating Mouse Embryonic Stem Cells
The T-box transcription factor Brachyury (T) is essential for formation of the posterior mesoderm and the notochord in vertebrate embryos. Work in the frog and the zebrafish has identified some direct genomic targets of Brachyury, but little is known about Brachyury targets in the mouse.Here we use chromatin immunoprecipitation and mouse promoter microarrays to identify targets of Brachyury in embryoid bodies formed from differentiating mouse ES cells. The targets we identify are enriched for sequence-specific DNA binding proteins and include components of signal transduction pathways that direct cell fate in the primitive streak and tailbud of the early embryo. Expression of some of these targets, such as Axin2, Fgf8 and Wnt3a, is down regulated in Brachyury mutant embryos and we demonstrate that they are also Brachyury targets in the human. Surprisingly, we do not observe enrichment of the canonical T-domain DNA binding sequence 5'-TCACACCT-3' in the vicinity of most Brachyury target genes. Rather, we have identified an (AC)(n) repeat sequence, which is conserved in the rat but not in human, zebrafish or Xenopus. We do not understand the significance of this sequence, but speculate that it enhances transcription factor binding in the regulatory regions of Brachyury target genes in rodents.Our work identifies the genomic targets of a key regulator of mesoderm formation in the early mouse embryo, thereby providing insights into the Brachyury-driven genetic regulatory network and allowing us to compare the function of Brachyury in different species