Intravenous Neuromyelitis Optica Autoantibody in Mice Targets Aquaporin-4 in Peripheral Organs and Area Postrema

The pathogenesis of neuromyelitis optica (NMO) involves binding of IgG autoantibodies (NMO-IgG) to aquaporin-4 (AQP4) on astrocytes in the central nervous system (CNS). We studied the in vivo processing in mice of a recombinant monoclonal human NMO-IgG that binds strongly to mouse AQP4. Following intravenous administration, serum [NMO-IgG] decreased with t1/2 ∼18 hours in wildtype mice and ∼41 hours in AQP4 knockout mice. NMO-IgG was localized to AQP4-expressing cell membranes in kidney (collecting duct), skeletal muscle, trachea (epithelial cells) and stomach (parietal cells). NMO-IgG was seen on astrocytes in the area postrema in brain, but not elsewhere in brain, spinal cord, optic nerve or retina. Intravenously administered NMO-IgG was also seen in brain following mechanical disruption of the blood-brain barrier. Selective cellular localization was not found for control (non-NMO) IgG, or for NMO-IgG in AQP4 knockout mice. NMO-IgG injected directly into brain parenchyma diffused over an area of ∼5 mm2 over 24 hours and targeted astrocyte foot-processes. Our data establish NMO-IgG pharmacokinetics and tissue distribution in mice. The rapid access of serum NMO-IgG to AQP4 in peripheral organs but not the CNS indicates that restricted antibody access cannot account for the absence of NMO pathology in peripheral organs

Using a Body-Fixed Sensor to Identify Subclinical Gait Difficulties in Older Adults with IADL Disability: Maximizing the Output of the Timed Up and Go

Objective: The identification and documentation of subclinical gait impairments in older adults may facilitate the appropriate use of interventions for preventing or delaying mobility disability. We tested whether measures derived from a single body-fixed sensor worn during traditional Timed Up and Go (TUG) testing could identify subclinical gait impairments in community dwelling older adults without mobility disability. Methods: We used data from 432 older adults without dementia (mean age 83.30±7.04 yrs, 76.62% female) participating in the Rush Memory and Aging Project. The traditional TUG was conducted while subjects wore a body-fixed sensor. We derived measures of overall TUG performance and different subtasks including transitions (sit-to-stand, stand-to-sit), walking, and turning. Multivariate analysis was used to compare persons with and without mobility disability and to compare individuals with and without Instrumental Activities of Daily Living disability (IADL-disability), all of whom did not have mobility disability. Results: As expected, individuals with mobility disability performed worse on all TUG subtasks (p<0.03), compared to those who had no mobility disability. Individuals without mobility disability but with IADL disability had difficulties with turns, had lower yaw amplitude (p<0.004) during turns, were slower (p<0.001), and had less consistent gait (p<0.02). Conclusions: A single body-worn sensor can be employed in the community-setting to complement conventional gait testing. It provides a wide range of quantitative gait measures that appear to help to identify subclinical gait impairments in older adults

Spatiotemporal dynamics of the postnatal developing primate brain transcriptome.

Developmental changes in the temporal and spatial regulation of gene expression drive the emergence of normal mature brain function, while disruptions in these processes underlie many neurodevelopmental abnormalities. To solidify our foundational knowledge of such changes in a primate brain with an extended period of postnatal maturation like in human, we investigated the whole-genome transcriptional profiles of rhesus monkey brains from birth to adulthood. We found that gene expression dynamics are largest from birth through infancy, after which gene expression profiles transition to a relatively stable state by young adulthood. Biological pathway enrichment analysis revealed that genes more highly expressed at birth are associated with cell adhesion and neuron differentiation, while genes more highly expressed in juveniles and adults are associated with cell death. Neocortex showed significantly greater differential expression over time than subcortical structures, and this trend likely reflects the protracted postnatal development of the cortex. Using network analysis, we identified 27 co-expression modules containing genes with highly correlated expression patterns that are associated with specific brain regions, ages or both. In particular, one module with high expression in neonatal cortex and striatum that decreases during infancy and juvenile development was significantly enriched for autism spectrum disorder (ASD)-related genes. This network was enriched for genes associated with axon guidance and interneuron differentiation, consistent with a disruption in the formation of functional cortical circuitry in ASD

Quantum search by measurement

We propose a quantum algorithm for solving combinatorial search problems that uses only a sequence of measurements. The algorithm is similar in spirit to quantum computation by adiabatic evolution, in that the goal is to remain in the ground state of a time-varying Hamiltonian. Indeed, we show that the running times of the two algorithms are closely related. We also show how to achieve the quadratic speedup for Grover's unstructured search problem with only two measurements. Finally, we discuss some similarities and differences between the adiabatic and measurement algorithms.Comment: 8 pages, 2 figure

Associations between Quantitative Mobility Measures Derived from Components of Conventional Mobility Testing and Parkinsonian Gait in Older Adults

Objective: To provide objective measures which characterize mobility in older adults assessed in the community setting and to examine the extent to which these measures are associated with parkinsonian gait. Methods: During conventional mobility testing in the community-setting, 351 ambulatory non-demented Memory and Aging Project participants wore a belt with a whole body sensor that recorded both acceleration and angular velocity in 3 directions. We used measures derived from these recordings to quantify 5 subtasks including a) walking, b) transition from sit to stand, c) transition from stand to sit, d) turning and e) standing posture. Parkinsonian gait and other mild parkinsonian signs were assessed with a modified version of the original Unified Parkinson’s Disease Rating Scale (mUPDRS). Results: In a series of separate regression models which adjusted for age and sex, all 5 mobility subtask measures were associated with parkinsonian gait and accounted for 2% to 32% of its variance. When all 5 subtask measures were considered in a single model, backward elimination showed that measures of walking sit to stand and turning showed independent associations with parkinsonian gait and together accounted for more than 35% of its variance. Cross-validation using data from a 2nd group of 258 older adults showed similar results. In similar analyses, only walking was associated with bradykinesia and sway with tremor. Interpretation Quantitative mobility subtask measures vary in their associations with parkinsonian gait scores and other parkinsonian signs in older adults. Quantifying the different facets of mobility has the potential to facilitate the clinical characterization and understanding the biologic basis for impaired mobility in older adults

A high-flux source of polarization-entangled photons from a periodically-poled KTP parametric downconverter

We have demonstrated a high-flux source of polarization-entangled photons using a type-II phase-matched periodically-poled KTP parametric downconverter in a collinearly propagating configuration. We have observed quantum interference between the single-beam downconverted photons with a visibility of 99% and a measured coincidence flux of 300/s/mW of pump. The Clauser-Horne-Shimony-Holt version of Bell's inequality was violated with a value of 2.711 +/- 0.017.Comment: 7 pages submitted to Physical Review

Hypolocomotion, asymmetrically directed behaviors (licking, lifting, flinching, and shaking) and dynamic weight bearing (gait) changes are not measures of neuropathic pain in mice

<p>Abstract</p> <p>Background</p> <p>Spontaneous (non-evoked) pain is a major clinical symptom of neuropathic syndromes, one that is understudied in basic pain research for practical reasons and because of a lack of consensus over precisely which behaviors reflect spontaneous pain in laboratory animals. It is commonly asserted that rodents experiencing pain in a hind limb exhibit hypolocomotion and decreased rearing, engage in both reflexive and organized limb directed behaviors, and avoid supporting their body weight on the affected side. Furthermore, it is assumed that the extent of these positive or negative behaviors can be used as a dependent measure of spontaneous chronic pain severity in such animals. In the present study, we tested these assumptions via blinded, systematic observation of digital video of mice with nerve injuries (chronic constriction or spared nerve injury), and automated assessment of locomotor behavior using photocell detection and dynamic weight bearing (i.e., gait) using the CatWalk^®system.</p> <p>Results</p> <p>We found no deficits in locomotor activity or rearing associated with neuropathic injury. The frequency of asymmetric (ipsilaterally directed) behaviors were too rare to be seriously considered as representing spontaneous pain, and in any case did not statistically exceed what was blindly observed on the contralateral hind paw and in control (sham operated and unoperated) mice. Changes in dynamic weight bearing, on the other hand, were robust and ipsilateral after spared nerve injury (but not chronic constriction injury). However, we observed timing, pharmacological, and genetic dissociation of mechanical allodynia and gait alterations.</p> <p>Conclusions</p> <p>We conclude that spontaneous neuropathic pain in mice cannot be assessed using any of these measures, and thus caution is warranted in making such assertions.</p

Experimental realization of a low-noise heralded single photon source

We present a heralded single-photon source with a much lower level of unwanted background photons in the output channel by using the herald photon to control a shutter in the heralded channel. The shutter is implemented using a simple field programable gate array controlled optical switch.Comment: 4 pages, 5 figure

A conditional-phase switch at the single-photon level

We present an experimental realization of a two-photon conditional-phase switch, related to the ``$c$-$\phi$'' gate of quantum computation. This gate relies on quantum interference between photon pairs, generating entanglement between two optical modes through the process of spontaneous parametric down-conversion (SPDC). The interference effect serves to enhance the effective nonlinearity by many orders of magnitude, so it is significant at the quantum (single-photon) level. By adjusting the relative optical phase between the classical pump for SPDC and the pair of input modes, one can impress a large phase shift on one beam which depends on the presence or absence of a single photon in a control mode.Comment: 8 pages, 4 figure