A Continual Trials Approach to Recognition Memory in Mice

This thesis sought to address and improve resolve some issues surrounding tests of recognition memory in animals. Since these spontaneous object recognition memory tasks are widely used, especially in mice, there is a need to develop a recognition task that would reduce the variability, extend and translate the task to potential areas of neuroscience research. Study 1 sought to validate the continual trials approach that was originally designed for rats to mice and replicate the findings of Ameen-Ali et al., (2012) in the spontaneous object recognition and object-location task. Study 1 found that performance of mice was comparable to previous studies of object recognition and object location memory, and statistically meaningful results were obtained with approximately 30 – 50 % fewer mice than typically used in the standard one trial a day version of the spontaneous object recognition tasks. Study 2 sought to extend the continual trials apparatus to establish the age-related changes of object recognition and object-location memory in normal ageing mice; and found that ageing mice showed no age-related decline of recognition memory. Study 3 found no evidence of age-related changes of object recognition and object-location memory in a transgenic mouse model of Alzheimer’s Disease, TASTPM mice. In study 4, the continual trials apparatus was adapted to incorporate variable retention delays (by blocking the sample and test phases) and found no evidence of delay-dependent effect on object recognition memory. Study 5 provided novel evidence that NMDA blockade using the MK-801 drug had no effect on object recognition memory in mice when controlled for state-dependency of memory. The key findings of this thesis include the successful validation of the continual trials apparatus in mice and the evidence that studies using reduced number of mice can nonetheless provide valid results in object recognition memory tasks

TLR ligand-induced podosome disassembly in dendritic cells is ADAM17 dependent

Toll-like receptor (TLR) signaling induces a rapid reorganization of the actin cytoskeleton in cultured mouse dendritic cells (DC), leading to enhanced antigen endocytosis and a concomitant loss of filamentous actin–rich podosomes. We show that as podosomes are lost, TLR signaling induces prominent focal contacts and a transient reduction in DC migratory capacity in vitro. We further show that podosomes in mouse DC are foci of pronounced gelatinase activity, dependent on the enzyme membrane type I matrix metalloprotease (MT1-MMP), and that DC transiently lose the ability to degrade the extracellular matrix after TLR signaling. Surprisingly, MMP inhibitors block TLR signaling–induced podosome disassembly, although stimulated endocytosis is unaffected, which demonstrates that the two phenomena are not obligatorily coupled. Podosome disassembly caused by TLR signaling occurs normally in DC lacking MT1-MMP, and instead requires the tumor necrosis factor α–converting enzyme ADAM17 (a disintegrin and metalloprotease 17), which demonstrates a novel role for this “sheddase” in regulating an actin-based structure

A meta-analysis of rates of return to agricultural R & D: ex pede Herculem?

IFPRI has long argued that spending on agricultural research constitutes a sound investment in poverty reduction and agricultural and economic growth, through improvements in productivity. This argument is based partly on the reported evidence of high rates of return to agricultural research, typically believed to be in the range of 40–60 percent per year. Yet there continues to be controversy over whether these figures are to be believed, and over what they actually indicate. This study represents the first attempt to take a comprehensive look at all the available evidence on rates of return to investments in agricultural R&D since 1953, and the only attempt to do so in a formal statistical fashion. This report has compiled and documented the literature in ways that make it more accessible and more useful to other researchers and policymakers, as well as others interested in the evidence. The analysis reveals some systematic patterns and some sources of biases that make it easier to interpret the evidence and draw meaningful conclusions. (Excerpted from Summary by Per Pinstrup-Andersen)Development projects Evaluation., Agricultural research, Statistics., Agricultural economics and policies,

Continual trials spontaneous recognition tasks in mice: reducing animal numbers and improving our understanding of the mechanisms underlying memory

Spontaneous recognition tasks are widely used as a laboratory measure of memory in animals but give rise to high levels of behavioural noise leading to a lack of reliability. Previous work has shown that a modification of the procedure to allow continual trials testing (in which many trials are run concurrently in a single session) decreases behavioural noise and thus significantly reduces the numbers of rats required to retain statistical power. Here we demonstrate for the first time that this improved method of testing extends to mice, increasing the overall power of the approach. Moreover, our results show that the new continual trials approach provides the additional benefits of heightened sensitivity and thus provides greater insight into the mechanisms at play. Standard (c57) and transgenic Alzheimer model (TASTPM) mice were tested both at 7 and 10 months of age in both object recognition (OR) and object location (OL) spontaneous recognition tasks using the continual trials methodology. Both c57 and TASTPM mice showed age-dependent changes in performance in OR. While c57 mice also showed age-related changes in performance of OL, TASTPM mice were unable to perform OL at either age. Significantly, we demonstrate that differences in OL performance in c57s and TASTPM animals is a result of proactive interference rather than an absolute inability to recognise object-location combinations. We argue that these continual trials approaches provide overall improved reliability and better interpretation of the memory ability of mice, as well as providing a significant reduction in overall animal use

Spectral Energy Distributions of Local Luminous And Ultraluminous Infrared Galaxies

Luminous and ultraluminous infrared galaxies ((U)LIRGs) are the most extreme star forming galaxies in the universe. The local (U)LIRGs provide a unique opportunity to study their multi-wavelength properties in detail for comparison to their more numerous counterparts at high redshifts. We present common large aperture photometry at radio through X-ray wavelengths, and spectral energy distributions (SEDs) for a sample of 53 nearby LIRGs and 11 ULIRGs spanning log (LIR/Lsun) = 11.14-12.57 from the flux-limited Great Observatories All-sky LIRG Survey (GOALS). The SEDs for all objects are similar in that they show a broad, thermal stellar peak and a dominant FIR thermal dust peak, where nuLnu(60um) / nuLnu(V) increases from ~2-30 with increasing LIR. When normalized at IRAS-60um, the largest range in the luminosity ratio, R(lambda)=log[nuLnu(lambda)/nuLnu(60um)] observed over the full sample is seen in the Hard X-rays (HX=2-10 keV). A small range is found in the Radio (1.4GHz), where the mean ratio is largest. Total infrared luminosities, LIR(8-1000um), dust temperatures, and dust masses were computed from fitting thermal dust emission modified blackbodies to the mid-infrared (MIR) through submillimeter SEDs. The new results reflect an overall ~0.02 dex lower luminosity than the original IRAS values. Total stellar masses were computed by fitting stellar population synthesis models to the observed near-infrared (NIR) through ultraviolet (UV) SEDs. Mean stellar masses are found to be log(M/Msun) = 10.79+/-0.40. Star formation rates have been determined from the infrared (SFR_IR~45Msun/yr) and from the monochromatic UV luminosities (SFR_UV~1.3Msun/yr), respectively. Multiwavelength AGN indicators have be used to select putative AGN: about 60% of the ULIRGs would have been classified as an AGN by at least one of the selection criteria.Comment: 39 pages, including 12 figures and 11 tables; accepted for publication in ApJ

Statistical Properties of Contact Maps

A contact map is a simple representation of the structure of proteins and other chain-like macromolecules. This representation is quite amenable to numerical studies of folding. We show that the number of contact maps corresponding to the possible configurations of a polypeptide chain of N amino acids, represented by (N-1)-step self avoiding walks on a lattice, grows exponentially with N for all dimensions D>1. We carry out exact enumerations in D=2 on the square and triangular lattices for walks of up to 20 steps and investigate various statistical properties of contact maps corresponding to such walks. We also study the exact statistics of contact maps generated by walks on a ladder.Comment: Latex file, 15 pages, 12 eps figures. To appear on Phys. Rev.

Lived experiences of ‘peak water’ in the high mountains of Nepal and Peru

Peak water describes the hydrological response of glacier-fed rivers to climate change, indicating that warming first drives increasing discharge until a glacier mass loss threshold is surpassed and discharge falls below values observed prior to contemporary climate warming. Although the physical principles of peak water are well understood and accepted, there remains little empirical work evaluating how hydrological dynamics associated with peak water are experienced by residents of high mountain communities at the frontlines of glacial change. In response, this study—drawing on 160 household interviews, 34 key informant interviews, and 4 focus groups—uses a contextual vulnerability approach to characterize lived experiences of peak water in communities of the upper Manaslu region of the Nepal Himalaya and the Cordillera Huayhuash region of the Peruvian Andes. It problematizes characteristics of vulnerability postulated in the glacio-hydrological modelling literature by revealing unanticipated experiences of peak water dynamics on both the rising and falling limb of the peak water profile. The study complements existing glacio-hydrology literature, demonstrates the importance of social theoretical perspectives in the evaluation of human vulnerability to peak water, and provides insights that can help appropriately target scarce adaptation resources

Improving Heart Failure Self-Management Support by Actively Engaging Out-of-Home Caregivers: Results of a Feasibility Study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72336/1/j.1751-7133.2008.07474.x.pd

A randomized trial of aspirin on the risk of embolic events in patients with infective endocarditis

AbstractObjectivesThis study examined the effect of aspirin on the risk of embolic events in infective endocarditis (IE).BackgroundEmbolism is a major complication of IE, and studies in animal models have shown that platelet inhibition with aspirin can lead to more rapid vegetation resolution and a lower rate of embolic events.MethodsWe conducted a randomized, double-blinded, placebo-controlled trial of aspirin treatment (325 mg/day) for four weeks in patients with IE to test the hypothesis that the addition of aspirin would reduce the incidence of clinical systemic embolic events. Patients with perivalvular abscess were excluded. Serial cerebral computed tomograms and transesophageal echocardiograms were obtained in a subset of patients.ResultsDuring the four-year study period, 115 patients were enrolled: 60 assigned to aspirin and 55 assigned to placebo. Embolic events occurred in 17 patients (28.3%) on aspirin and 11 patients (20.0%) on placebo, with an odds ratio (OR) of 1.62 (95% confidence interval [CI] 0.68 to 3.86, p = 0.29). There was a trend toward a higher incidence of bleeding in the patients taking aspirin versus placebo (OR 1.92, 95% CI 0.76 to 4.86, p = 0.075). Development of new intracranial lesions was similar in both groups. Aspirin had no effect on vegetation resolution and valvular dysfunction.ConclusionsIn endocarditis patients already receiving antibiotic treatment, the addition of aspirin does not appear to reduce the risk of embolic events and is likely associated with an increased risk of bleeding. Aspirin is not indicated in the early management of patients with IE

Derivation of Improved Surface and TOA Broadband Fluxes Using CERES-derived Narrowband-to-Broadband Coefficients

Satellites can provide global coverage of a number of climatically important radiative parameters, including broadband (BB) shortwave (SW) and longwave (LW) fluxes at the top of the atmosphere (TOA) and surface. These parameters can be estimated from narrowband (NB) Geostationary Operational Environmental Satellite (GOES) data, but their accuracy is highly dependent on the validity of the narrowband-to-broadband (NB-BB) conversion formulas that are used to convert the NB fluxes to broadband values. The formula coefficients have historically been derived by regressing matched polarorbiting satellite BB fluxes or radiances with their NB counterparts from GOES (e.g., Minnis et al., 1984). More recently, the coefficients have been based on matched Earth Radiation Budget Experiment (ERBE) and GOES-6 data (Minnis and Smith, 1998). The Clouds and the Earth's Radiant Energy Budget (CERES see Wielicki et al. 1998)) project has recently developed much improved Angular Distribution Models (ADM; Loeb et al., 2003) and has higher resolution data compared to ERBE. A limited set of coefficients was also derived from matched GOES-8 and CERES data taken on Topical Rainfall Measuring Mission (TRMM) satellite (Chakrapani et al., 2003; Doelling et al., 2003). The NB-BB coefficients derived from CERES and the GOES suite should yield more accurate BB fluxes than from ERBE, but are limited spatially and seasonally. With CERES data taken from Terra and Aqua, it is now possible to derive more reliable NB-BB coefficients for any given area. Better TOA fluxes should translate to improved surface radiation fluxes derived using various algorithms. As part of an ongoing effort to provide accurate BB flux estimates for the Atmospheric Radiation Measurement (ARM) Program, this paper documents the derivation of new NB-BB coefficients for the ARM Southern Great Plains (SGP) domain and for the Darwin region of the Tropical Western Pacific (DTWP) domain