Paved with Good Intentions: The Failure of Passive Disability Policy in Canada

It is common in the disability community to speak of unfulfilled aspirations for full citizenship and participation in the mainstream of Canadian society. In Canada, as in much of the developed world, many adults with disabilities remain outside the mainstream, especially in regard to economic opportunities. Unfortunately, many of the disability policies currently pursued by Canadian governments are unlikely to improve this situation, and may in fact make it worse. This paper offers a critical analysis of a common instrument of current disability policy, the passive cash benefit. I will focus, in particular, on the effects of passive transfers on prospects for adults with disabilities to reach their full income potential through employment. I will attempt to establish that passive income support strategies – for adults with disabilities and for low-income people in general – force their intended beneficiaries to sacrifice employment prospects for help with short-term income needs, a trade-off that reinforces poverty and dependency over the longer term

Novel Candidate Genes Associated with Hippocampal Oscillations

The hippocampus is critical for a wide range of emotional and cognitive behaviors. Here, we performed the first genome-wide search for genes influencing hippocampal oscillations. We measured local field potentials (LFPs) using 64-channel multi-electrode arrays in acute hippocampal slices of 29 BXD recombinant inbred mouse strains. Spontaneous activity and carbachol-induced fast network oscillations were analyzed with spectral and cross-correlation methods and the resulting traits were used for mapping quantitative trait loci (QTLs), i.e., regions on the genome that may influence hippocampal function. Using genome-wide hippocampal gene expression data, we narrowed the QTLs to eight candidate genes, including Plcb1, a phospholipase that is known to influence hippocampal oscillations. We also identified two genes coding for calcium channels, Cacna1b and Cacna1e, which mediate presynaptic transmitter release and have not been shown to regulate hippocampal network activity previously. Furthermore, we showed that the amplitude of the hippocampal oscillations is genetically correlated with hippocampal volume and several measures of novel environment exploration

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Oligodendroglial myelination requires astrocyte-derived lipids.

In the vertebrate nervous system, myelination of axons for rapid impulse propagation requires the synthesis of large amounts of lipids and proteins by oligodendrocytes and Schwann cells. Myelin membranes are thought to be cell-autonomously assembled by these axon-associated glial cells. Here, we report the surprising finding that in normal brain development, a substantial fraction of the lipids incorporated into central nervous system (CNS) myelin are contributed by astrocytes. The oligodendrocyte-specific inactivation of sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP), an essential coactivator of the transcription factor SREBP and thus of lipid biosynthesis, resulted in significantly retarded CNS myelination; however, myelin appeared normal at 3 months of age. Importantly, embryonic deletion of the same gene in astrocytes, or in astrocytes and oligodendrocytes, caused a persistent hypomyelination, as did deletion from astrocytes during postnatal development. Moreover, when astroglial lipid synthesis was inhibited, oligodendrocytes began incorporating circulating lipids into myelin membranes. Indeed, a lipid-enriched diet was sufficient to rescue hypomyelination in these conditional mouse mutants. We conclude that lipid synthesis by oligodendrocytes is heavily supplemented by astrocytes in vivo and that horizontal lipid flux is a major feature of normal brain development and myelination

Effects of a high-fat diet (HFD) on myelination, myelin protein levels, and white matter conduction velocity.

<p><b>A)</b> Electron microscopy (EM) analysis of optic nerve (ON) and corpus callosum (CC) myelination in cross-sections of glial fibrillary acidic protein (GFAP)-SREBP cleavage-activating protein (SCAP) mice (P120) on either a standard diet (SD) or HFD. See <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002605#pbio.1002605.g005" target="_blank">Fig 5A and 5C</a> for representative EM images of wild-type (WT) animals (P120) on SD or HFD. Scale bar, 2 μm. Bar graphs, percentage of axons that are myelinated (left). Morphometric analysis of myelinated axons showing g-ratio (middle and right). For ON of GFAP-SCAP mice, the relation between axon diameter (x) and g-ratio (y) was y = 3E − 05x + 0.825 for SD and y = 6E − 05x + 0.7687 for HFD, with coefficients of determination R² = 0.06062 (SD) and R² = 0.23735 (HFD). For CC of GFAP-SCAP mice, the relation between axon diameter (x) and g-ratio (y) was y = 7E − 05x + 0.8008 for SD and y = 0.0001x + 0.701 for HFD, with coefficients of determination R² = 0.11285 (SD) and R² = 0.26559 (HFD). <i>t</i> test, ** <i>p</i> < 0.01, * <i>p</i> < 0.05, # <i>p</i> = 0.07, <i>n</i> = 3–4. <b>B)</b> Immunoblot against depicted myelin proteins and coomassie staining of protein levels of total brain extracts of GFAP-SCAP mutant and WT mice (P120) fed with SD or HFD. Right panel: quantification of immunoblot for depicted myelin proteins for GFAP-SCAP and WT mice fed with SD or HFD (<i>n</i> = 3). Coomassie staining was used for normalization. Data are presented as mean ± SEM, in which WT-SD levels were set to 100%. <i>t</i> test * <i>p</i> < 0.05; ** <i>p</i> < 0.01). <b>C)</b> Example of compound action potential waveforms in the CC for a WT mouse on a standard diet (WT-SD), and a GFAP-SCAP mutant mouse on a standard diet (GFAP-SCAP-SD) or high fat diet (GFAP-SCAP-HFD). Right panel: individual plots of conduction velocity measurements in the CC of GFAP-SCAP mutant and WT fed with SD or HFD. Chi-square test, <i>n</i> = 12–17, * <i>p</i> < 0.05, *** < 0.001. The numeric data can be found in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002605#pbio.1002605.s006" target="_blank">S1 Data</a>.</p

Virtually no myelin membrane synthesis in CNP-SREBP cleavage-activating protein (SCAP)/glial fibrillary acidic protein (GFAP)-SCAP brains.

<p><b>A)</b> Electron microscopy (EM) analysis of the corpus callosum (CC) and optic nerve (ON) in P20-old wild-type (WT) mice or mice carrying a deletion in both astrocytes and oligodendrocytes (CNP-SCAP/GFAP-SCAP). Bar graphs show the percentage of axons that are myelinated. <b>B)</b> Enlarged view on part of the electron micrograph of CNP-SCAP/GFAP-SCAP ON in A. <b>C)</b> morphometric analysis of myelinated axons in the ON of WT, CNP-SCAP, GFAP-SCAP, and CNP-SCAP/GFAP-SCAP mice at p20, showing myelin membrane thickness. <i>n</i> = at least 3 animals. Membrane thickness for each CNP-SCAP/GFAP-SCAP animal was determined for at least 22 axons that were wrapped by oligodendrocyte membrane, as depicted in 10B and D. <b>D)</b> Electron microscopic analysis of myelin membranes in the ON of WT, CNP-SCAP, GFAP-SCAP, and CNP-SCAP/GFAP-SCAP mice. Data are presented as mean ± SEM. <i>t</i> test * <i>p</i> < 0.05, *** <i>p</i> < 0.001, <i>n</i> ≥ 3. Scale bar, (A) 2 μm, (B) 0.75 μm, (C) 0.1 μm. The numeric data underlying Fig 10A and C can be found in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002605#pbio.1002605.s006" target="_blank">S1 Data</a>.</p

Persistent hypomyelination in glial fibrillary acidic protein (GFAP)- SREBP cleavage-activating protein (SCAP) mutant brains.

<p><b>A)</b> Electron microscopy (EM) analysis of corpus callosum myelination in cross-sections of either wild-type (WT) or GFAP-SCAP mice at P120. Bar graph shows the percentage of axons that is myelinated. <b>B)</b> Morphometric analysis of axons on corpus callosum of WT and GFAP-SCAP mice, showing g-ratio (myelinated axons) and axonal size distribution (both myelinated and non-myelinated axons) at P120. The relation between axon diameter (x) and g-ratio (y) was y = 9E − 05x + 0.7287 for WT and y = 7E − 05x + 0.8008 for GFAP-SCAP, with coefficients of determination R² = 0.25384 (WT) and 0.11285 (GFAP-SCAP). <b>C)</b> EM analysis of optic nerve myelination in cross-sections of either WT or GFAP-SCAP mice at depicted time points. Bar graph shows the percentage of axons that is myelinated. <b>D)</b> Morphometric analysis of axons on optic nerves of WT and GFAP-SCAP mice, showing g-ratio (myelinated axons), axonal size distribution (both myelinated and nonmyelinated axons), and myelin membrane thickness at P20 and P120. At P20, the relation between axon diameter (x) and g-ratio (y) was y = 8E − 05x + 0.7262 for WT and y = 5E − 05x + 0.8003 for GFAP-SCAP, with coefficients of determination R² = 0.31108 (WT) and 0.11441 (GFAP-SCAP). At P120: y = 9E − 05x + 0.7079 (WT); y = 3E − 05x + 0.825 (GFAP-SCAP), R² = 0.3288 (WT) and R² = 0.06062 (GFAP-SCAP). Scale bars, 2 μm. <i>t</i> test # <i>p</i> = 0.079, * <i>p</i> < 0.05, ** <i>p</i> < 0.01, <i>n</i> = 3. The numeric data can be found in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002605#pbio.1002605.s006" target="_blank">S1 Data</a>.</p