Sleep studies in mice - open and closed loop devices for untethered recording and stimulation

Sleep is an important biological processes that has been studied extensively to date. Research in sleep typically involves mice experiments that use heavy benchtop equipment or basic neural loggers to record ECoG/EMG signals which are then processed offline in workstations. These systems limit the complexity of experiments that can be carried out to only simple open loop recordings, due to either the tethered setup used, which restricts animal movements, or the lack of devices that can offer more advanced features without compromising its portability. With rising popularity in exploring more physiological features that can affect sleep, such as temperature, whose importance has been highlighted in several papers [1][2][3] and advances in optogenetic stimulation, allowing high temporal and spatial neural control, there is now an unprecedented demand for experimental setups using new closed loop paradigms. To address this, this thesis presents compact and lightweight neural logging devices that are not only capable of measuring ECoG and EMG signals for core sleep analysis but also capable of taking high resolution temperature recordings and delivering optogenetic stimulus with fully adjustable parameters. Together with its embedded on-board automatic sleep stage scoring algorithm, the device will allow researchers for the first time to be able to quickly uncover the role a neural circuit plays in sleep regulation through selective neural stimulation when the animal is under the target sleep vigilance state. Original contributions include: the development of two novel multichannel neural logging devices, one for core sleep analysis and another for closed loop experimentation; the development and implementation of a lightweight, fast and highly accurate automatic on-line sleep stage scoring algorithm; and the development of a custom optogenetic coupler that is compatible with most current optogenetic setups for LED-Optical fibre coupling.Open Acces

The rhenium isotope composition of Atlantic Ocean seawater

The concentrations and isotopic compositions of rhenium are presented from seawater samples obtained from the primary station for the Bermuda Atlantic Time Series Study in the North Atlantic Ocean and from the 40oS UK GEOTRACES expedition in the South Atlantic Ocean. Salinity-normalized Re concentrations in both locations range between ∼6.8–7.7 ppt between 50–5000 m depth, consistent with previously published concentration data from the North Atlantic and North Pacific Oceans. Rhenium isotope values (expressed as δ187/185Re relative to NIST 3143) exhibit minimal variation around an average value of −0.17 ± 0.12‰ (n = 12, 2 S.D.), irrespective of water depth or water mass. These results confirm that the isotopic composition of perrhenate (ReO4−) in seawater is uniform. The new data establish a baseline for evaluating the isotopic mass balance of Re, and for future assessments of whether this global cycle can be disturbed by changes in seafloor redox and/or global weathering rates

Interdecadal variability and oceanic thermohaline adjustment

Changes in the strength of the thermohaline overturning circulation are associated, by geostrophy, with changes in the east-west pressure difference across an ocean basin. The tropical-polar density contrast and the east-west pressure difference are connected by an adjustment process. In flat-bottomed ocean models the adjustment is associated with viscous, baroclinic Kelvin wave propagation. Weak-high latitude stratification leads to the adjustment having an interdecadal timescale. We reexamine model interdecadal oscillations in the context of the adjustment process, for both constant flux and mixed surface boundary conditions. Under constant surface flux, interdecadal oscillations are associated with the passage of a viscous Kelvin wave around the model domain. Our results suggest the oscillations can be self-sustained by perturbations to the western boundary current arising from the southward boundary wave propagation. Mixed boundary condition oscillations are characterized by the eastward, cross-basin movement of salinity-dominated density anomalies, and the westward return of these anomalies along the northern boundary. We suggest the latter is associated with viscous Kelvin wave propagation. Under both types of boundary conditions, the strength of the thermohaline overturning and the tropical-polar density contrast vary out of phase. We show how the phase relationship is related to the boundary wave propagation. The importance of boundary regions indicates an urgent need to examine the robustness of interdecadal variability in models as the resolution is increased, and as the representation of the coastal, shelf/slope wave guide is improved. (Abriged abstract)Comment: 20 pages, AGU LaTeX, 12 figures included using epsfig, to appear in JGR, complete manuscript also available at ftp://crosby.physics.mun.ca/pub/drew/papers/gp1.ps.g

A numerical ocean circulation model of the Norwegian and Greenland Seas

The dynamics and thermodynamics of the Norwegian and Greenland Seas are investigated using a three-dimensional primitive equation ocean circulation model. The horizontal resolution of the model is 1° in the zonal direction and 0.5° in the meridional direction. The vertical structure is described by 15 levels. The model is driven by both annual mean and seasonally varying wind and thermohaline forcing. The connections of the Norwegian and Greenland Seas with the North Atlantic and Arctic Ocean are modelled with an open boundary condition. The simulated currents are in reasonable agreement with the observed circulation

Probing the dynamics of O-GlcNAc glycosylation in the brain using quantitative proteomics

The addition of the monosaccharide beta-N-acetyl-D-glucosamine to proteins (O-GlcNAc glycosylation) is an intracellular, post-translational modification that shares features with phosphorylation. Understanding the cellular mechanisms and signaling pathways that regulate O-GlcNAc glycosylation has been challenging because of the difficulty of detecting and quantifying the modification. Here, we describe a new strategy for monitoring the dynamics of O-GlcNAc glycosylation using quantitative mass spectrometry-based proteomics. Our method, which we have termed quantitative isotopic and chemoenzymatic tagging (QUIC-Tag), combines selective, chemoenzymatic tagging of O-GlcNAc proteins with an efficient isotopic labeling strategy. Using the method, we detect changes in O-GlcNAc glycosylation on several proteins involved in the regulation of transcription and mRNA translocation. We also provide the first evidence that O-GlcNAc glycosylation is dynamically modulated by excitatory stimulation of the brain in vivo. Finally, we use electron-transfer dissociation mass spectrometry to identify exact sites of O-GlcNAc modification. Together, our studies suggest that O-GlcNAc glycosylation occurs reversibly in neurons and, akin to phosphorylation, may have important roles in mediating the communication between neurons

What Qualities Are Most Important to Making a Point of Care Test Desirable for Clinicians and Others Offering Sexually Transmitted Infection Testing?

To investigate the possible effects of different levels of attributes of a point-of-care test (POCT) on sexually transmitted infection (STI) professionals' decisions regarding an ideal POCT for STI(s).An online survey was designed based on a large-scale in-depth focus discussion study among STI experts and professionals. The last section of the survey "build your own POCT" was designed by employing the discrete choice experiment approach. Practicing clinicians from two venues, STI-related international conference attendees and U.S. STD clinic clinicians were invited to participate in the survey. Conditional logistical regression modeling was used for data analysis.Overall, 256 subjects took the online survey with 218 (85%) completing it. Most of the participants were STD clinic clinicians who already used some POCTs in their practice. "The time frame required" was identified as a major barrier that currently made it difficult to use STI POCTs. Chlamydia trachomatis was the organism chosen as the top priority for a new POCT, followed by a test that would diagnose early seroconversion for HIV, and a syphilis POCT. Without regard to organism type selected, sensitivity of 90-99% was always the most important attribute to be considered, followed by a cost of $20. However, when the test platform was prioritized for early HIV seroconversion or syphilis, sensitivity was still ranked as most important, but specificity was rated second most important.STI professionals preferred C. trachomatis as the top priority for a new POCT with sensitivity over 90%, low cost, and a very short completion time

The XMM Cluster Survey: Forecasting cosmological and cluster scaling-relation parameter constraints

We forecast the constraints on the values of sigma_8, Omega_m, and cluster scaling relation parameters which we expect to obtain from the XMM Cluster Survey (XCS). We assume a flat Lambda-CDM Universe and perform a Monte Carlo Markov Chain analysis of the evolution of the number density of galaxy clusters that takes into account a detailed simulated selection function. Comparing our current observed number of clusters shows good agreement with predictions. We determine the expected degradation of the constraints as a result of self-calibrating the luminosity-temperature relation (with scatter), including temperature measurement errors, and relying on photometric methods for the estimation of galaxy cluster redshifts. We examine the effects of systematic errors in scaling relation and measurement error assumptions. Using only (T,z) self-calibration, we expect to measure Omega_m to +-0.03 (and Omega_Lambda to the same accuracy assuming flatness), and sigma_8 to +-0.05, also constraining the normalization and slope of the luminosity-temperature relation to +-6 and +-13 per cent (at 1sigma) respectively in the process. Self-calibration fails to jointly constrain the scatter and redshift evolution of the luminosity-temperature relation significantly. Additional archival and/or follow-up data will improve on this. We do not expect measurement errors or imperfect knowledge of their distribution to degrade constraints significantly. Scaling-relation systematics can easily lead to cosmological constraints 2sigma or more away from the fiducial model. Our treatment is the first exact treatment to this level of detail, and introduces a new `smoothed ML' estimate of expected constraints.Comment: 28 pages, 17 figures. Revised version, as accepted for publication in MNRAS. High-resolution figures available at http://xcs-home.org (under "Publications"

Nitric Oxide Synthase Neurons in the Preoptic Hypothalamus Are NREM and REM Sleep-Active and Lower Body Temperature.

When mice are exposed to external warmth, nitric oxide synthase (NOS1) neurons in the median and medial preoptic (MnPO/MPO) hypothalamus induce sleep and concomitant body cooling. However, how these neurons regulate baseline sleep and body temperature is unknown. Using calcium photometry, we show that NOS1 neurons in MnPO/MPO are predominantly NREM and REM active, especially at the boundary of wake to NREM transitions, and in the later parts of REM bouts, with lower activity during wakefulness. In addition to releasing nitric oxide, NOS1 neurons in MnPO/MPO can release GABA, glutamate and peptides. We expressed tetanus-toxin light-chain in MnPO/MPO NOS1 cells to reduce vesicular release of transmitters. This induced changes in sleep structure: over 24 h, mice had less NREM sleep in their dark (active) phase, and more NREM sleep in their light (sleep) phase. REM sleep episodes in the dark phase were longer, and there were fewer REM transitions between other vigilance states. REM sleep had less theta power. Mice with synaptically blocked MnPO/MPO NOS1 neurons were also warmer than control mice at the dark-light transition (ZT0), as well as during the dark phase siesta (ZT16-20), where there is usually a body temperature dip. Also, at this siesta point of cooled body temperature, mice usually have more NREM, but mice with synaptically blocked MnPO/MPO NOS1 cells showed reduced NREM sleep at this time. Overall, MnPO/MPO NOS1 neurons promote both NREM and REM sleep and contribute to chronically lowering body temperature, particularly at transitions where the mice normally enter NREM sleep

How coastal strategic planning reflects interrelationships between ecosystem services: a four-step method

Explicit and integrated inclusion of ecosystem services (ESs) and their interrelationships can improve the quality of strategic plans and decision-making processes. However, there is little systematic analysis of how ES interrelationships are framed in policy language, particularly in coastal planning discourse. The objective of this paper is therefore to present a four-step method, based on content analysis, to assess ES interrelationships in coastal strategic planning documents. The method consists of: 1) selecting strategic plans; 2) identifying ESs; 3) identifying drivers, ESs and their effects; and 4) constructing relational diagrams. The four-step method is applied to a case of Jiaozhou Bay in China, demonstrating its capacity of identifying which drivers and ES trade-offs and synergies are formulated in coastal strategic plans. The method is helpful to identify overlooked ES interrelationships, inform temporal and spatial issues, and assess the continuity of plans' attention to interrelationships. The main methodological contributions are discussed by emphasizing its broad scope of drivers and ESs and an explicit distinction among the cause of relationships. The developed method also has the potential of cross-fertilizing other kinds of approaches and facilitating practical planning processes

Dynamic sea level changes following changes in the thermohaline circulation

Using the coupled climate model CLIMBER-3a, we investigate changes in sea surface elevation due to a weakening of the thermohaline circulation (THC). In addition to a global sea level rise due to a warming of the deep sea, this leads to a regional dynamic sea level change which follows quasi-instantaneously any change in the ocean circulation. We show that the magnitude of this dynamic effect can locally reach up to ~1m, depending on the initial THC strength. In some regions the rate of change can be up to 20-25 mm/yr. The emerging patterns are discussed with respect to the oceanic circulation changes. Most prominent is a south-north gradient reflecting the changes in geostrophic surface currents. Our results suggest that an analysis of observed sea level change patterns could be useful for monitoring the THC strength.Comment: Climate Dynamics (2004), submitted. See also http://www.pik-potsdam.de/~ander