905 research outputs found
Glial D-Serine Gates NMDA Receptors at Excitatory Synapses in Prefrontal Cortex.
N-methyl-D-aspartate receptors (NMDARs) subserve numerous neurophysiological and neuropathological processes in the cerebral cortex. Their activation requires the binding of glutamate and also of a coagonist. Whereas glycine and D-serine (D-ser) are candidates for such a role at central synapses, the nature of the coagonist in cerebral cortex remains unknown. We first show that the glycine-binding site of NMDARs is not saturated in acute slices preparations of medial prefrontal cortex (mPFC). Using enzymes that selectively degrade either D-ser or glycine, we demonstrate that under the present conditions, D-ser is the principle endogenous coagonist of synaptic NMDARs at mature excitatory synapses in layers V/VI of mPFC where it is essential for long-term potentiation (LTP) induction. Furthermore, blocking the activity of glia with the metabolic inhibitor, fluoroacetate, impairs NMDAR-mediated synaptic transmission and prevents LTP induction by reducing the extracellular levels of D-serine. Such deficits can be restored by exogenous D-ser, indicating that the D-amino acid mainly originates from glia in the mPFC, as further confirmed by double-immunostaining studies for D-ser and anti-glial fibrillary acidic protein. Our findings suggest that D-ser modulates neuronal networks in the cerebral cortex by gating the activity of NMDARs and that altering its levels is relevant to the induction and potentially treatment of psychiatric and neurological disorders
Contribution of the d-Serine-Dependent Pathway to the Cellular Mechanisms Underlying Cognitive Aging
An association between age-related memory impairments and changes in functional plasticity in the aging brain has been under intense study within the last decade. In this article, we show that an impaired activation of the strychnine-insensitive glycine site of N-methyl-d-aspartate receptors (NMDA-R) by its agonist d-serine contributes to deficits of synaptic plasticity in the hippocampus of memory-impaired aged rats. Supplementation with exogenous d-serine prevents the age-related deficits of isolated NMDA-R-dependent synaptic potentials as well as those of theta-burst-induced long-term potentiation and synaptic depotentiation. Endogenous levels of d-serine are reduced in the hippocampus with aging, that correlates with a weaker expression of serine racemase synthesizing the amino acid. On the contrary, the affinity of d-serine binding to NMDA-R is not affected by aging. These results point to a critical role for the d-serine-dependent pathway in the functional alterations of the brain underlying memory impairment and provide key information in the search for new therapeutic strategies for the treatment of memory deficits in the elderly
Collaboration Towards a More Inclusive Society: The Case of South African ICT4D Researchers
In this study, research collaboration in the context of South African
Information and Communication for Development (ICT4D) researchers was
investigated using a mixed methods approach. South Africa, a country with stark
development challenges and on the other hand a well-established ICT infrastructure,
provides an appropriate context for ICT4D research. Firstly, a quantitative
analysis of South African research collaboration between 2003 and 2016
was conducted to determine the existing research collaboration patterns of South
African ICT4D researchers. This is based on the publications in three top ICT4D
journals namely the Electronic Journal of Information Systems in Developing
Countries (EJISDC), Information Technologies & International Development
(ITID), and Information Technology for Development (ITD). The results show
that most co-authored papers were intra-institutional collaborations, with limited
inter-institutional collaboration between South African authors or between
South African and other African authors. Secondly, interviews were conducted
with South African researchers who emerged as inter- and intra-institutional
collaborators to gain insight into the technology, drivers and barriers affecting
South African research collaboration. We report our findings and discuss the
implications for employing research collaboration as a mechanism for
addressing inequality and supporting inclusion.School of Computin
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A Comparison between the Compass Fundus Perimeter and the Humphrey Field Analyzer
Purpose: To evaluate relative diagnostic precision and testâretest variability of 2 devices, the Compass (CMP, CenterVue, Padova, Italy) fundus perimeter and the Humphrey Field Analyzer (HFA, Zeiss, Dublin, CA), in detecting glaucomatous optic neuropathy (GON).
Design: Multicenter, cross-sectional, case-control study.
Participants: We sequentially enrolled 499 patients with glaucoma and 444 normal subjects to analyze relative precision. A separate group of 44 patients with glaucoma and 54 normal subjects was analyzed to assess testâretest variability.
Methods: One eye of recruited subjects was tested with the index tests: HFA (Swedish interactive thresholding algorithm [SITA] standard strategy) and CMP (Zippy Estimation by Sequential Testing [ZEST] strategy), 24-2 grid. The reference test for GON was specialist evaluation of fundus photographs or OCT, independent of the visual field (VF). For both devices, linear regression was used to calculate the sensitivity decrease with age in the normal group to compute pointwise total deviation (TD) values and mean deviation (MD). We derived 5% and 1% pointwise normative limits. The MD and the total number of TD values below 5% (TD 5%) or 1% (TD 1%) limits per field were used as classifiers.
Main Outcome Measures: We used partial receiver operating characteristic (pROC) curves and partial area under the curve (pAUC) to compare the diagnostic precision of the devices. Pointwise mean absolute deviation and BlandâAltman plots for the mean sensitivity (MS) were computed to assess testâretest variability.
Results: Retinal sensitivity was generally lower with CMP, with an average mean difference of 1.85±0.06 decibels (dB) (mean ± standard error, P < 0.001) in healthy subjects and 1.46±0.05 dB (mean ± standard error, P < 0.001) in patients with glaucoma. Both devices showed similar discriminative power. The MD metric had marginally better discrimination with CMP (pAUC difference ± standard error, 0.019±0.009, P = 0.035). The 95% limits of agreement for the MS were reduced by 13% in CMP compared with HFA in participants with glaucoma and by 49% in normal participants. Mean absolute deviation was similar, with no significant differences.
Conclusions: Relative diagnostic precision of the 2 devices is equivalent. Testâretest variability of MS for CMP was better than for HFA
Molecular excitation in the Interstellar Medium: recent advances in collisional, radiative and chemical processes
We review the different excitation processes in the interstellar mediumComment: Accepted in Chem. Re
The Einstein effect provides global evidence for scientific source credibility effects and the influence of religiosity
All-sky Search for High-Energy Neutrinos from Gravitational Wave Event GW170104 with the ANTARES Neutrino Telescope
Advanced LIGO detected a significant gravitational wave signal (GW170104)
originating from the coalescence of two black holes during the second
observation run on January 4, 2017. An all-sky high-energy
neutrino follow-up search has been made using data from the ANTARES neutrino
telescope, including both upgoing and downgoing events in two separate
analyses. No neutrino candidates were found within s around the GW
event time nor any time clustering of events over an extended time window of
months. The non-detection is used to constrain isotropic-equivalent
high-energy neutrino emission from GW170104 to less than
erg for a spectrum
The ANTARES Collaboration: Contributions to ICRC 2017 Part I: Neutrino astronomy (diffuse fluxes and point sources)
Papers on neutrino astronomy (diffuse fluxes and point sources, prepared for
the 35th International Cosmic Ray Conference (ICRC 2017, Busan, South Korea) by
the ANTARES Collaboratio
The ANTARES Collaboration: Contributions to ICRC 2017 Part II: The multi-messenger program
Papers on the ANTARES multi-messenger program, prepared for the 35th
International Cosmic Ray Conference (ICRC 2017, Busan, South Korea) by the
ANTARES Collaboratio
The ANTARES Collaboration: Contributions to ICRC 2017 Part III: Searches for dark matter and exotics, neutrino oscillations and detector calibration
Papers on the searches for dark matter and exotics, neutrino oscillations and
detector calibration, prepared for the 35th International Cosmic Ray Conference
(ICRC 2017, Busan, South Korea) by the ANTARES Collaboratio
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