5,494 research outputs found

    Stronger prediction of motor recovery and outcome post-stroke by cortico-spinal tract integrity than functional connectivity

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    <div><p>Objectives</p><p>To examine longitudinal changes in structural and functional connectivity post-stroke in patients with motor impairment, and define their importance for recovery and outcome at 12 months.</p><p>Methods</p><p>First-time stroke patients (N = 31) were studied at 1–2 weeks, 3 months, and 12 months post-injury with a validated motor battery and resting-state fMRI to measure inter-hemispheric functional connectivity (FC). Fractional anisotropy (FA) of the cortico-spinal tract (CST) was derived from diffusion tensor imaging as a measure of white matter organization. ANOVAs were used to test for changes in FC, FA, and motor performance scores over time, and regression analysis related motor outcome to clinical and neuroimaging variables.</p><p>Results</p><p>FA of the ipsilesional CST improved significantly from 3 to 12 months and was strongly correlated with motor performance. FA improved even in the absence of direct damage to the CST. Inter-hemispheric FC also improved over time, but did not correlate with motor performance at 12 months. Clinical variables (early motor score, education level, and age) predicted 80.4% of the variation of motor outcome, and FA increased the predictability to 84.6%. FC did not contribute to the prediction of motor outcome.</p><p>Conclusions</p><p>Stroke causes changes to the CST microstructure that can account for behavioral variability even in the absence of demonstrable lesion. Ipsilesional CST undergoes remodeling post-stroke, even past the three-month window when most of the motor recovery happens. FA of the CST, but not inter-hemispheric FC, can improve to the prediction of motor outcome based on early motor scores.</p></div

    The MASSIVE Survey - VII. The Relationship of Angular Momentum, Stellar Mass and Environment of Early-Type Galaxies

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    We analyse the environmental properties of 370 local early-type galaxies (ETGs) in the MASSIVE and ATLAS3D surveys, two complementary volume-limited integral-field spectroscopic (IFS) galaxy surveys spanning absolute KK-band magnitude −21.5>MK>−26.6-21.5 > M_K > -26.6, or stellar mass 8×109<M∗<2×1012M⊙8 \times 10^{9} < M_* < 2 \times 10^{12} M_\odot. We find these galaxies to reside in a diverse range of environments measured by four methods: group membership (whether a galaxy is a brightest group/cluster galaxy, satellite, or isolated), halo mass, large-scale mass density (measured over a few Mpc), and local mass density (measured within the NNth neighbour). The spatially resolved IFS stellar kinematics provide robust measurements of the spin parameter λe\lambda_e and enable us to examine the relationship among λe\lambda_e, M∗M_*, and galaxy environment. We find a strong correlation between λe\lambda_e and M∗M_*, where the average λe\lambda_e decreases from ∼0.4\sim 0.4 to below 0.1 with increasing mass, and the fraction of slow rotators fslowf_{\rm slow} increases from ∼10\sim 10% to 90%. We show for the first time that at fixed M∗M_*, there are almost no trends between galaxy spin and environment; the apparent kinematic morphology-density relation for ETGs is therefore primarily driven by M∗M_* and is accounted for by the joint correlations between M∗M_* and spin, and between M∗M_* and environment. A possible exception is that the increased fslowf_{\rm slow} at high local density is slightly more than expected based only on these joint correlations. Our results suggest that the physical processes responsible for building up the present-day stellar masses of massive galaxies are also very efficient at reducing their spin, in any environment.Comment: Accepted to MNRA

    The Graphical Access Challenge for People with Visual Impairments: Positions and Pathways Forward

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    Graphical access is one of the most pressing challenges for individuals who are blind or visually impaired. This chapter discusses some of the factors underlying the graphics access challenge, reviews prior approaches to addressing this long-standing information access barrier, and describes some promising new solutions. We specifically focus on touchscreen-based smart devices, a relatively new class of information access technologies, which our group believes represent an exemplary model of user-centered, needs-based design. We highlight both the challenges and the vast potential of these technologies for alleviating the graphics accessibility gap and share the latest results in this line of research. We close with recommendations on ideological shifts in mindset about how we approach solving this vexing access problem, which will complement both technological and perceptual advancements that are rapidly being uncovered through a growing research community in this domain

    Analysis of Oligomerization Properties of Heme a Synthase Provides Insights into Its Function in Eukaryotes

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    Heme a is an essential cofactor for function of cytochrome c oxidase in the mitochondrial electron transport chain. Several evolutionarily conserved enzymes have been implicated in the biosynthesis of heme a, including the heme a synthase Cox15. However, the structure of Cox15 is unknown, its enzymatic mechanism and the role of active site residues remain debated, and recent discoveries suggest additional chaperone-like roles for this enzyme. Here, we investigated Cox15 in the model eukaryote Saccharomyces cerevisiae via several approaches to examine its oligomeric states and determine the effects of active site and human pathogenic mutations. Our results indicate that Cox15 exhibits homotypic interactions, forming highly stable complexes dependent upon hydrophobic interactions. This multimerization is evolutionarily conserved and independent of heme levels and heme a synthase catalytic activity. Four conserved histidine residues are demonstrated to be critical for eukaryotic heme a synthase activity and cannot be substituted with other heme-ligating amino acids. The 20-residue linker region connecting the two conserved domains of Cox15 is also important; removal of this linker impairs both Cox15 multimerization and enzymatic activity. Mutations of COX15 causing single amino acid conversions associated with fatal infantile hypertrophic cardiomyopathy and the neurological disorder Leigh syndrome result in impaired stability (S344P) or catalytic function (R217W), and the latter mutation affects oligomeric properties of the enzyme. Structural modeling of Cox15 suggests these two mutations affect protein folding and heme binding, respectively. We conclude that Cox15 multimerization is important for heme a biosynthesis and/or transfer to maturing cytochrome c oxidase

    Analysis of Oligomerization Properties of Heme a Synthase Provides Insights into Its Function in Eukaryotes

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    Heme a is an essential cofactor for function of cytochrome c oxidase in the mitochondrial electron transport chain. Several evolutionarily conserved enzymes have been implicated in the biosynthesis of heme a, including the heme a synthase Cox15. However, the structure of Cox15 is unknown, its enzymatic mechanism and the role of active site residues remain debated, and recent discoveries suggest additional chaperone-like roles for this enzyme. Here, we investigated Cox15 in the model eukaryote Saccharomyces cerevisiae via several approaches to examine its oligomeric states and determine the effects of active site and human pathogenic mutations. Our results indicate that Cox15 exhibits homotypic interactions, forming highly stable complexes dependent upon hydrophobic interactions. This multimerization is evolutionarily conserved and independent of heme levels and heme a synthase catalytic activity. Four conserved histidine residues are demonstrated to be critical for eukaryotic heme a synthase activity and cannot be substituted with other heme-ligating amino acids. The 20-residue linker region connecting the two conserved domains of Cox15 is also important; removal of this linker impairs both Cox15 multimerization and enzymatic activity. Mutations of COX15 causing single amino acid conversions associated with fatal infantile hypertrophic cardiomyopathy and the neurological disorder Leigh syndrome result in impaired stability (S344P) or catalytic function (R217W), and the latter mutation affects oligomeric properties of the enzyme. Structural modeling of Cox15 suggests these two mutations affect protein folding and heme binding, respectively. We conclude that Cox15 multimerization is important for heme a biosynthesis and/or transfer to maturing cytochrome c oxidase

    The Assembly Factor Pet117 Couples Heme a Synthase Activity to Cytochrome Oxidase Assembly

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    Heme a is an essential metalloporphyrin cofactor of the mitochondrial respiratory enzyme cytochrome c oxidase (CcO). Its synthesis from heme b requires several enzymes, including the evolutionarily conserved heme a synthase (Cox15). Oligomerization of Cox15 appears to be important for the process of heme a biosynthesis and transfer to maturing CcO. However, the details of this process remain elusive, and the roles of any additional CcO assembly factors that may be involved remain unclear. Here we report the systematic analysis of one such uncharacterized assembly factor, Pet117, and demonstrate in Saccharomyces cerevisiae that this evolutionarily conserved protein is necessary for Cox15 oligomerization and function. Pet117 is shown to reside in the mitochondrial matrix, where it is associated with the inner membrane. Pet117 functions at the later maturation stages of the core CcO subunit Cox1 that precede Cox1 hemylation. Pet117 also physically interacts with Cox15 and specifically mediates the stability of Cox15 oligomeric complexes. This Cox15-Pet117 interaction observed by co-immunoprecipitation persists in the absence of heme a synthase activity, is dependent upon Cox1 synthesis and early maturation steps, and is further dependent upon the presence of the matrix-exposed, unstructured linker region of Cox15 needed for Cox15 oligomerization, suggesting that this region mediates the interaction or that the interaction is lost when Cox15 is unable to oligomerize. Based on these findings, it was concluded that Pet117 mediates coupling of heme a synthesis to the CcO assembly process in eukaryotes

    Functional neuroanatomy of spatial sound processing in Alzheimer's disease.

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    Deficits of auditory scene analysis accompany Alzheimer's disease (AD). However, the functional neuroanatomy of spatial sound processing has not been defined in AD. We addressed this using a "sparse" fMRI virtual auditory spatial paradigm in 14 patients with typical AD in relation to 16 healthy age-matched individuals. Sound stimulus sequences discretely varied perceived spatial location and pitch of the sound source in a factorial design. AD was associated with loss of differentiated cortical profiles of auditory location and pitch processing at the prescribed threshold, and significant group differences were identified for processing auditory spatial variation in posterior cingulate cortex (controls > AD) and the interaction of pitch and spatial variation in posterior insula (AD > controls). These findings build on emerging evidence for altered brain mechanisms of auditory scene analysis and suggest complex dysfunction of network hubs governing the interface of internal milieu and external environment in AD. Auditory spatial processing may be a sensitive probe of this interface and contribute to characterization of brain network failure in AD and other neurodegenerative syndromes
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