The speaking vocabulary of kindergarten, grade I, grade II, and grade III

Thesis (Ed.M.)--Boston Universit

Inhibition of synaptic transmission and G protein modulation by synthetic CaV2.2 Ca2+ channel peptides

Abstract: Modulation of presynaptic voltage-dependent Ca+ channels is a major means of controlling neurotransmitter release. The CaV 2.2 Ca2+ channel subunit contains several inhibitory interaction sites for Gβγ subunits, including the amino terminal (NT) and I–II loop. The NT and I–II loop have also been proposed to undergo a G protein-gated inhibitory interaction, whilst the NT itself has also been proposed to suppress CaV 2 channel activity. Here, we investigate the effects of an amino terminal (CaV 2.2[45–55]) ‘NT peptide’ and a I–II loop alpha interaction domain (CaV 2.2[377–393]) ‘AID peptide’ on synaptic transmission, Ca2+ channel activity and G protein modulation in superior cervical ganglion neurones (SCGNs). Presynaptic injection of NT or AID peptide into SCGN synapses inhibited synaptic transmission and also attenuated noradrenaline-induced G protein modulation. In isolated SCGNs, NT and AID peptides reduced whole-cell Ca2+ current amplitude, modified voltage dependence of Ca2+ channel activation and attenuated noradrenaline-induced G protein modulation. Co-application of NT and AID peptide negated inhibitory actions. Together, these data favour direct peptide interaction with presynaptic Ca2+ channels, with effects on current amplitude and gating representing likely mechanisms responsible for inhibition of synaptic transmission. Mutations to residues reported as determinants of Ca2+ channel function within the NT peptide negated inhibitory effects on synaptic transmission, Ca2+ current amplitude and gating and G protein modulation. A mutation within the proposed QXXER motif for G protein modulation did not abolish inhibitory effects of the AID peptide. This study suggests that the CaV 2.2 amino terminal and I–II loop contribute molecular determinants for Ca2+ channel function; the data favour a direct interaction of peptides with Ca2+ channels to inhibit synaptic transmission and attenuate G protein modulation. Non-technical summary: Nerve cells (neurones) in the body communicate with each other by releasing chemicals (neurotransmitters) which act on proteins called receptors. An important group of receptors (called G protein coupled receptors, GPCRs) regulate the release of neurotransmitters by an action on the ion channels that let calcium into the cell. Here, we show for the first time that small peptides based on specific regions of calcium ion channels involved in GPCR signalling can themselves inhibit nerve cell communication. We show that these peptides act directly on calcium channels to make them more difficult to open and thus reduce calcium influx into native neurones. These peptides also reduce GPCR-mediated signalling. This work is important in increasing our knowledge about modulation of the calcium ion channel protein; such knowledge may help in the development of drugs to prevent signalling in pathways such as those involved in pain perception

An Observational Determination of the Bolometric Quasar Luminosity Function

We combine a large set of quasar luminosity function (QLF) measurements from the rest-frame optical, soft and hard X-ray, and near- and mid-infrared bands to determine the bolometric QLF in the redshift interval z=0-6. Accounting for the observed distributions of quasar column densities and variation of spectral energy distribution (SED) shapes, and their dependence on luminosity, makes it possible to integrate the observations in a reliable manner and provides a baseline in redshift and luminosity larger than that of any individual survey. We infer the QLF break luminosity and faint-end slope out to z~4.5 and confirm at high significance (>10sigma) previous claims of a flattening in both the faint- and bright-end slopes with redshift. With the best-fit estimates of the column density distribution and quasar SED, which both depend on luminosity, a single bolometric QLF self-consistently reproduces the observed QLFs in all bands and at all redshifts for which we compile measurements. Ignoring this luminosity dependence does not yield a self-consistent bolometric QLF and there is no evidence for any additional dependence on redshift. We calculate the expected relic black hole mass function and mass density, cosmic X-ray background, and ionization rate as a function of redshift and find they are consistent with existing measurements. The peak in the total quasar luminosity density is well-constrained at z=2.15+/-0.05. We provide a number of fitting functions to the bolometric QLF and its manifestations in various bands, and a script to return the QLF at arbitrary frequency and redshift from these fits, as the most simple inferences from the QLF measured in a single band can be misleading.Comment: 24 pages, 11 figures. Submitted to ApJ. A routine to return the QLF from the fits herein is available at http://www.cfa.harvard.edu/~phopkins/Site/qlf.htm

A Community Narration Assessment of Master's Level Psychology Students at Antioch University Los Angeles

Applied Community Psychology (ACP) is a specialty field of study in the Master’s of Arts in Clinical Psychology (MAP) at Antioch University Los Angeles (AULA).  Students participate in classes and workshops that present theory along with opportunities for real life application.  In the Spring 2019 quarter, eight students were enrolled in a Community Narration (CN) approach workshop to learn the theory and practice of facilitating the CN.  The students used CN to discover commonalities and differences in their experiences as students of AULA.  They created a community narrative which expressed the culture of students at AULA.  In addition, the students learned how to conduct CN in the community with application in program evaluation and consultation.  A discussion of the results of the community narrative that emerged is described, and implications for faculty and administrators are presented

A Community Narration Assessment of Master's Level Psychology Students at Antioch University Los Angeles

Applied Community Psychology (ACP) is a specialty field of study in the Master’s of Arts in Clinical Psychology (MAP) at Antioch University Los Angeles (AULA).  Students participate in classes and workshops that present theory along with opportunities for real life application.  In the Spring 2019 quarter, eight students were enrolled in a Community Narration (CN) approach workshop to learn the theory and practice of facilitating the CN.  The students used CN to discover commonalities and differences in their experiences as students of AULA.  They created a community narrative which expressed the culture of students at AULA.  In addition, the students learned how to conduct CN in the community with application in program evaluation and consultation.  A discussion of the results of the community narrative that emerged is described, and implications for faculty and administrators are presented

A Population of X-ray Weak Quasars: PHL 1811 Analogs at High Redshift

We report the results from Chandra and XMM-Newton observations of a sample of 10 type 1 quasars selected to have unusual UV emission-line properties (weak and blueshifted high-ionization lines; strong UV Fe emission) similar to those of PHL 1811, a confirmed intrinsically X-ray weak quasar. These quasars were identified by the Sloan Digital Sky Survey at high redshift (z~2.2); eight are radio quiet while two are radio intermediate. All of the radio-quiet PHL 1811 analogs are notably X-ray weak by a mean factor of ~13. These sources lack broad absorption lines and have blue UV/optical continua, suggesting they are intrinsically X-ray weak. However, their average X-ray spectrum appears to be harder than those of typical quasars, which may indicate the presence of heavy intrinsic X-ray absorption. Our radio-quiet PHL 1811 analogs support a connection between an X-ray weak spectral energy distribution and PHL 1811-like UV emission lines; this connection provides an economical way to identify X-ray weak type 1 quasars. The fraction of radio-quiet PHL 1811 analogs in the radio-quiet quasar population is estimated to be < 1.2%. We have investigated correlations between relative X-ray brightness and UV emission-line properties for a sample combining radio-quiet PHL 1811 analogs, PHL 1811, and typical type 1 quasars. These correlation analyses suggest that PHL 1811 analogs may have extreme wind-dominated broad emission-line regions. Observationally, radio-quiet PHL 1811 analogs appear to be a subset (~30%) of radio-quiet weak-line quasars. The existence of a subset of quasars in which high-ionization "shielding gas" covers most of the BELR, but little more than the BELR, could potentially unify the PHL 1811 analogs and WLQs. The two radio-intermediate PHL 1811 analogs are X-ray bright. One of them appears to have jet-dominated X-ray emission, while the nature of the other remains unclear.Comment: ApJ accepted; 25 pages, 11 figures and 8 table

Determinants of the voltage dependence of G protein modulation within calcium channel β subunits

CaVβ subunits of voltage-gated calcium channels contain two conserved domains, a src-homology-3 (SH3) domain and a guanylate kinase-like (GK) domain with an intervening HOOK domain. We have shown in a previous study that, although Gβγ-mediated inhibitory modulation of CaV2.2 channels did not require the interaction of a CaVβ subunit with the CaVα1 subunit, when such interaction was prevented by a mutation in the α1 subunit, G protein modulation could not be removed by a large depolarization and showed voltage-independent properties (Leroy et al., J Neurosci 25:6984–6996, 2005). In this study, we have investigated the ability of mutant and truncated CaVβ subunits to support voltage-dependent G protein modulation in order to determine the minimal domain of the CaVβ subunit that is required for this process. We have coexpressed the CaVβ subunit constructs with CaV2.2 and α2δ-2, studied modulation by the activation of the dopamine D2 receptor, and also examined basal tonic modulation. Our main finding is that the CaVβ subunit GK domains, from either β1b or β2, are sufficient to restore voltage dependence to G protein modulation. We also found that the removal of the variable HOOK region from β2a promotes tonic voltage-dependent G protein modulation. We propose that the absence of the HOOK region enhances Gβγ binding affinity, leading to greater tonic modulation by basal levels of Gβγ. This tonic modulation requires the presence of an SH3 domain, as tonic modulation is not supported by any of the CaVβ subunit GK domains alone

How effective is stretching in maintaining range of movement for children with cerebral palsy?

YesBackground: Cerebral Palsy (CP) is the most common childhood disorder affecting four percent of children born in the UK. It is common for children with CP to have reduced range of movement (ROM) due to spasticity and contractures. Stretching is commonly used in physiotherapy programmes to manage this. Aim: This critical review aims to evaluate the evidence base behind the use of stretching for children with CP. Methods: A systematic literature search of AMED, CINAHL, MEDLINE and Cochrane Library Trials was conducted. Returned searches were assessed against strict criteria according to a predefined PICOS (Population, Intervention, Comparison, Outcome, Study). These studies were then critically appraised to assess the validity, reliability and clinical relevance. Findings: There is evidence supporting the use of stretching in children with CP. However there is also some evidence to suggest very little or no positive change. All of the included studies have methodological limitations, which questions the validity of the results. Conclusions/Recommendations: The research suggests some positive outcomes for the use of stretching in CP, studies that did not find positive outcomes found no adverse effects; however further research in the area is required to validate the effectiveness of stretching to maintain ROM in children with CP