20 research outputs found

    Ontogeny of serotonin and serotonin2A receptors in rat auditory cortex

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    Maturation of the mammalian cerebral cortex is, in part, dependent upon multiple coordinated afferent neurotransmitter systems and receptor-mediated cellular linkages during early postnatal development. Given that serotonin (5-HT) is one such system, the present study was designed to specifically evaluate 5-HT tissue content as well as 5-HT2A receptor protein levels within the developing auditory cortex (AC). Using high performance liquid chromatography (HPLC), 5-HT and the metabolite, 5-hydroxyindoleacetic acid (5-HIAA), was measured in isolated AC, which demonstrated a developmental dynamic, reaching young adult levels early during the second week of postnatal development. Radioligand binding of 5-HT2A receptors with the 5-HT2A/2C receptor agonist, 125I-DOI ((+/−)-1-(2,5- dimethoxy-4-iodophenyl)-2-aminopropane HCl; in the presence of SB206553, a selective 5-HT2C receptor antagonist, also demonstrated a developmental trend, whereby receptor protein levels reached young adult levels at the end of the first postnatal week (P8), significantly increased at P10 and at P17, and decreased back to levels not significantly different from P8 thereafter. Immunocytochemical labeling of 5-HT2A receptors and confocal microscopy revealed that 5-HT2A receptors are largely localized on layer II/III pyramidal cell bodies and apical dendrites within AC. When considered together, the results of the present study suggest that 5-HT, likely through 5-HT2A receptors, may play an important role in early postnatal AC development

    The relationship of employment to self-perception and well-being in women: A cognitive analysis

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    We investigated the relationship of employment to self-perception and well-being in women who held two different cognitive orientations toward paid work (career oriented and not career oriented) and who also varied in the degree to which their current employment status realized their view of paid work. The data were taken from a 1977 survey of a large sample of women and included responses to questions about self-esteem, life satisfaction, and self-perception. The results indicated that career-oriented women who were employed full time were happier with themselves and their lives than those employed part time or not employed. In contrast, for women who were not career oriented, being employed was not associated with greater self-esteem or well-being. In addition, career-oriented women who were employed were the most likely to emphasize job-related characteristics in their self-descriptions. These findings suggest that the psychological benefits of employment that have been identified repeatedly in previous research are likely to be accrued only by women who regard paid work as a meaningful self-fulfilling activity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45581/1/11199_2004_Article_BF00288148.pd

    Do assisted living facilities that offer a dementia care program differ from those that do not? A population-level cross-sectional study in Ontario, Canada

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    Abstract Background Many residents of assisted living facilities live with dementia, but little is known about the characteristics of assisted living facilities that provide specialized care for older adults who live with dementia. In this study, we identify the characteristics of assisted living facilities that offer a dementia care program, compared to those that do not offer such a program. Methods We conducted a population-level cross-sectional study on all licensed assisted living facilities in Ontario, Canada in 2018 (n = 738). Facility-level characteristics (e.g., resident and suite capacities, etc.) and the provision of the other 12 provincially regulated care services (e.g., pharmacist and medical services, skin and wound care, etc.) attributed to assisted living facilities were examined. Multivariable Poisson regression with robust standard errors was used to model the characteristics of assisted living facilities associated with the provision of a dementia care program. Results There were 123 assisted living facilities that offered a dementia care program (16.7% versus 83.3% no dementia care). Nearly half of these facilities had a resident capacity exceeding 140 older adults (44.7% versus 21.6% no dementia care) and more than 115 suites (46.3% versus 20.8% no dementia care). All assisted living facilities that offered a dementia care program also offered nursing services, meals, assistance with bathing and hygiene, and administered medications. After adjustment for facility characteristics and other provincially regulated care services, the prevalence of a dementia care program was nearly three times greater in assisted living facilities that offered assistance with feeding (Prevalence Ratio [PR] 2.91, 95% Confidence Interval [CI] 1.98 to 4.29), and almost twice as great among assisted living facilities that offered medical services (PR 1.78, 95% CI 1.00 to 3.17), compared to those that did not. Conclusions A dementia care program was more prevalent in assisted living facilities that housed many older adults, had many suites, and offered at least five of the other 12 regulated care services. Our findings deepen the understanding of specialized care for dementia in assisted living facilities

    A regulatory role for the cohesin loader NIPBL in nonhomologous end joining during immunoglobulin class switch recombination.

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    DNA double strand breaks (DSBs) are mainly repaired via homologous recombination (HR) or nonhomologous end joining (NHEJ). These breaks pose severe threats to genome integrity but can also be necessary intermediates of normal cellular processes such as immunoglobulin class switch recombination (CSR). During CSR, DSBs are produced in the G1 phase of the cell cycle and are repaired by the classical NHEJ machinery. By studying B lymphocytes derived from patients with Cornelia de Lange Syndrome, we observed a strong correlation between heterozygous loss-of-function mutations in the gene encoding the cohesin loading protein NIPBL and a shift toward the use of an alternative, microhomology-based end joining during CSR. Furthermore, the early recruitment of 53BP1 to DSBs was reduced in the NIPBL-deficient patient cells. Association of NIPBL deficiency and impaired NHEJ was also observed in a plasmid-based end-joining assay and a yeast model system. Our results suggest that NIPBL plays an important and evolutionarily conserved role in NHEJ, in addition to its canonical function in sister chromatid cohesion and its recently suggested function in HR

    A novel mutation in the POLE2 gene causing combined immunodeficiency

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    16sinonenoneFrugoni, Francesco; Dobbs, Kerry; Felgentreff, Kerstin; Aldhekri, Hasan; Al Saud, Bandar K.; Arnaout, Rand; Ali, Afshan Ashraf; Abhyankar, Avinash; Alroqi, Fayhan; Giliani, Silvia; Ojeda, Mayra Martinez; Tsitsikov, Erdyni; Pai, Sung-Yun; Casanova, Jean Laurent; Notarangelo, Luigi D.; Manis, John P.Frugoni, Francesco; Dobbs, Kerry; Felgentreff, Kerstin; Aldhekri, Hasan; Al Saud, Bandar K.; Arnaout, Rand; Ali, Afshan Ashraf; Abhyankar, Avinash; Alroqi, Fayhan; Giliani, Silvia Clara; Ojeda, Mayra Martinez; Tsitsikov, Erdyni; Pai, Sung Yun; Casanova, Jean Laurent; Notarangelo, Luigi D.; Manis, John P
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