302 research outputs found

    A Comparison of Administrator and Teacher Attitudes Toward the Concept of Career Ladders for Teachers

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    Education, like any facet of the business world, has problems. Some of these problems, such as financial obligations, are major. Some, such as a lost library book, are minor. Regardless, there remains many problems. In today\u27s educational society, the common perception is that teachers are happy when best left alone. However, there is a growing feeling that teachers feel very isolated, have no way of moving up the career ladder, and fear the process of supervision and evaluation. Chapman and Lowther, in their article Teacher Satisfaction with Teaching, explained that teachers want to learn and be motivated. We must increase their job satisfaction, recognize accomplishments, and provide for change and challenge

    N-arachidonoyl glycine, an abundant endogenous lipid, potently drives directed cellular migration through GPR18, the putative abnormal cannabidiol receptor

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    Background: Microglia provide continuous immune surveillance of the CNS and upon activation rapidly change phenotype to express receptors that respond to chemoattractants during CNS damage or infection. These activated microglia undergo directed migration towards affected tissue. Importantly, the molecular species of chemoattractant encountered determines if microglia respond with pro- or anti-inflammatory behaviour, yet the signaling molecules that trigger migration remain poorly understood. The endogenous cannabinoid system regulates microglial migration via CB2 receptors and an as yet unidentified GPCR termed the 'abnormal cannabidiol' (Abn-CBD) receptor. Abn-CBD is a synthetic isomer of the phytocannabinoid cannabidiol (CBD) and is inactive at CB1 or CB2 receptors, but functions as a selective agonist at this Gi/o-coupled GPCR. N-arachidonoyl glycine (NAGly) is an endogenous metabolite of the endocannabinoid anandamide and acts as an efficacious agonist at GPR18. Here, we investigate the relationship between NAGly, Abn-CBD, the unidentified 'Abn-CBD' receptor, GPR18, and BV-2 microglial migration. Results: Using Boyden chamber migration experiments, yellow tetrazolium (MTT) conversion, In-cell Western, qPCR and immunocytochemistry we show that NAGly, at sub-nanomolar concentrations, and Abn-CBD potently drive cellular migration in both BV-2 microglia and HEK293-GPR18 transfected cells, but neither induce migration in HEKGPR55 or non-transfected HEK293 wildtype cells. Migration effects are blocked or attenuated in both systems by the 'Abn-CBD' receptor antagonist O-1918, and low efficacy agonists N-arachidonoyl-serine and cannabidiol. NAGly promotes proliferation and activation of MAP kinases in BV-2 microglia and HEK293-GPR18 cells at low nanomolar concentrations - cellular responses correlated with microglial migration. Additionally, BV-2 cells show GPR18 immunocytochemical staining and abundant GPR18 mRNA. qPCR demonstrates that primary microglia, likewise, express abundant amounts of GPR18 mRNA. Conclusions: NAGly is the most effective lipid recruiter of BV-2 microglia currently reported and its effects mimic those of Abn-CBD. The data generated from this study supports the hypothesis that GPR18 is the previously unidentified 'Abn-CBD' receptor. The marked potency of NAGly acting on GPR18 to elicit directed migration, proliferation and perhaps other MAPK-dependent phenomena advances our understanding of the lipid-based signaling mechanisms employed by the CNS to actively recruit microglia to sites of interest. It offers a novel research avenue for developing therapeutics to elicit a self-renewing population of neuroregenerative microglia, or alternatively, to prevent the accumulation of misdirected, pro-inflammatory microglia which contribute to and exacerbate neurodegenerative disease

    The Nature of the Long-Lived Excited State in a Ni^(II) Phthalocyanine Complex Investigated by X-Ray Transient Absorption Spectroscopy

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    The nature of the photoexcited state of octabutoxy nickel(II) phthalocyanine (NiPcOBu₈) with a 500 ps lifetime was investigated by X‐ray transient absorption (XTA) spectroscopy. Previous optical, vibrational, and computational studies have suggested that this photoexcited state has a ligand‐to‐metal charge transfer (LMCT) nature. By using XTA, which provides unambiguous information on the local electronic and nuclear configuration around the Ni center, the nature of the excited state of NiPcOBu₈ was reassessed. Using X‐ray probe pulses from a synchrotron source, the ground‐ and excited‐state X‐ray absorption spectra of NiPcOBu8 were measured. Based on the results, we identified that the excited state exhibits spectral features that are characteristic of a Ni^(1, 3)(3d_(z²), 3d_(x²-y²)) state rather than a LMCT state with a transiently reduced Ni center. This state resembles the (d,d) state of nickel(II) tetramesitylphorphyrin. The XTA features are rationalized based on the inherent cavity sizes of the macrocycles. These results may provide useful guidance for the design of photocatalysts in the future

    Older parents of people who have a learning disability : perceptions of future accomodation needs

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    The aim of this qualitative study was to provide an insight into the perceptions of older parents of learning disabled people on the future accommodation needs of their adult children. Semi-structured interviews were used to seek parental awareness of residential options available, concerns in relation to future accommodation and the preferred accommodation options for their offspring. Four couples who shared the family home with an adult who has a learning disability took part in the study and data was analysed using a step by step form of content analysis as described by Burnard (1991). Emergent themes from transcripts were then organised into main categories The results of this study suggest that older parents are dissatisfied with both statutory and private services, that they have concerns for their non-disabled children and their own ageing. Being a parent to a person who has a learning disability is seen to be a difficult task and yet parents may want to provide support at home for as long a possible. Of the parents who participated in this study, three couples wanted to maintain their adult child at home for as long as possible and the parents who were actively seeking accommodation outside the family home expected to be involved in all aspects of their daughter�s care for the long term future

    Cyclin D1 and mammary carcinoma: new insights from transgenic mouse models

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    Cyclin D1 is one of the most commonly overexpressed oncogenes in breast cancer, with 45–50% of primary ductal carcinomas overexpressing this oncoprotein. Targeted deletion of the gene encoding cyclin D1 demonstrates an essential role in normal mammary gland development while transgenic studies provide evidence that cyclin D1 is a weak oncogene in mammary epithelium. In a recent exciting development, Yu et al. demonstrate that cyclin D1-deficient mice are resistant to mammary carcinomas induced by c-neu and v-Ha-ras, but not those induced by c-myc or Wnt-1. These findings define a pivotal role for cyclin D1 in a subset of mammary cancers in mice and imply a functional role for cyclin D1 overexpression in human breast cancer

    N-Palmitoyl Glycine, a Novel Endogenous Lipid That Acts As a Modulator of Calcium Influx and Nitric Oxide Production in Sensory Neurons

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    N-arachidonoyl glycine is an endogenous arachidonoyl amide that activates the orphan G protein-coupled receptor (GPCR) GPR18 in a pertussis toxin (PTX)-sensitive manner and produces antinociceptive and antiinflammatory effects. It is produced by direct conjugation of arachidonic acid to glycine and by oxidative metabolism of the endocannabinoid anandamide. Based on the presence of enzymes that conjugate fatty acids with glycine and the high abundance of palmitic acid in the brain, we hypothesized the endogenous formation of the saturated N-acyl amide N-palmitoyl glycine (PalGly). PalGly was partially purified from rat lipid extracts and identified using nano-high-performance liquid chromatography/hybrid quadrupole time-of-flight mass spectrometry. Here, we show that PalGly is produced after cellular stimulation and that it occurs in high levels in rat skin and spinal cord. PalGly was up-regulated in fatty acid amide hydrolase knockout mice, suggesting a pathway for enzymatic regulation. PalGly potently inhibited heat-evoked firing of nociceptive neurons in rat dorsal horn. In addition, PalGly induced transient calcium influx in native adult dorsal root ganglion (DRG) cells and a DRG-like cell line (F-11). The effect of PalGly on the latter cells was characterized by strict structural requirements, PTX sensitivity, and dependence on the presence of extracellular calcium. PalGly-induced calcium influx was blocked by the nonselective calcium channel blockers ruthenium red, 1-(beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl)-1H-imidazole (SK&F96365), and La3+. Furthermore, PalGly contributed to the production of NO through calcium-sensitive nitric-oxide synthase enzymes present in F-11 cells and was inhibited by the nitric-oxide synthase inhibitor 7-nitroindazole
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