276 research outputs found
Similarities and differences in structure, expression, and functions of VLDLR and ApoER2
Very Low Density Lipoprotein Receptor (VLDLR) and Apolipoprotein E Receptor 2 (ApoER2) are important receptors in the brain for mediating the signaling effects of the extracellular matrix protein Reelin, affecting neuronal function in development and in the adult brain. VLDLR and ApoER2 are members of the low density lipoprotein family, which also mediates the effects of numerous other extracellular ligands, including apolipoprotein E. Although VLDLR and ApoER2 are highly homologous, they differ in a number of ways, including structural differences, expression patterns, alternative splicing, and binding of extracellular and intracellular proteins. This review aims to summarize important aspects of VLDLR and ApoER2 that may account for interesting recent findings that highlight the unique functions of each receptor
Altered hippocampus synaptic function in selenoprotein P deficient mice
Selenium is an essential micronutrient that function through selenoproteins. Selenium deficiency results in lower concentrations of selenium and selenoproteins. The brain maintains it's selenium better than other tissues under low-selenium conditions. Recently, the selenium-containing protein selenoprotein P (Sepp) has been identified as a possible transporter of selenium. The targeted disruption of the selenoprotein P gene (Sepp1) results in decreased brain selenium concentration and neurological dysfunction, unless selenium intake is excessive However, the effect of selenoprotein P deficiency on the processes of memory formation and synaptic plasticity is unknown. In the present studies Sepp1(-/-) mice and wild type littermate controls (Sepp1(+/+)) fed a high-selenium diet (1 mg Se/kg) were used to characterize activity, motor coordination, and anxiety as well as hippocampus-dependent learning and memory. Normal associative learning, but disrupted spatial learning was observed in Sepp1(-/-) mice. In addition, severe alterations were observed in synaptic transmission, short-term plasticity and long-term potentiation in hippocampus area CA1 synapses of Sepp1(-/-) mice on a 1 mg Se/kg diet and Sepp1(+/+) mice fed a selenium-deficient (0 mg Se/kg) diet. Taken together, these data suggest that selenoprotein P is required for normal synaptic function, either through presence of the protein or delivery of required selenium to the CNS
The effect of word sense disambiguation accuracy on literature based discovery
Background
The volume of research published in the biomedical domain has increasingly lead to researchers focussing on specific areas of interest and connections between findings being missed. Literature based discovery (LBD) attempts to address this problem by searching for previously unnoticed connections between published information (also known as “hidden knowledge”). A common approach is to identify hidden knowledge via shared linking terms. However, biomedical documents are highly ambiguous which can lead LBD systems to over generate hidden knowledge by hypothesising connections through different meanings of linking terms. Word Sense Disambiguation (WSD) aims to resolve ambiguities in text by identifying the meaning of ambiguous terms. This study explores the effect of WSD accuracy on LBD performance.
Methods
An existing LBD system is employed and four approaches to WSD of biomedical documents integrated with it. The accuracy of each WSD approach is determined by comparing its output against a standard benchmark. Evaluation of the LBD output is carried out using timeslicing approach, where hidden knowledge is generated from articles published prior to a certain cutoff date and a gold standard extracted from publications after the cutoff date.
Results
WSD accuracy varies depending on the approach used. The connection between the performance of the LBD and WSD systems are analysed to reveal a correlation between WSD accuracy and LBD performance.
Conclusion
This study reveals that LBD performance is sensitive to WSD accuracy. It is therefore concluded that WSD has the potential to improve the output of LBD systems by reducing the amount of spurious hidden knowledge that is generated. It is also suggested that further improvements in WSD accuracy have the potential to improve LBD accuracy
Efficient unidirectional nanoslit couplers for surface plasmons
Plasmonics is based on surface plasmon polariton (SPP) modes which can be
laterally confined below the diffraction limit, thereby enabling ultracompact
optical components. In order to exploit this potential, the fundamental
bottleneck of poor light-SPP coupling must be overcome. In established SPP
sources (using prism, grating} or nanodefect coupling) incident light is a
source of noise for the SPP, unless the illumination occurs away from the
region of interest, increasing the system size and weakening the SPP intensity.
Back-side illumination of subwavelength apertures in optically thick metal
films eliminates this problem but does not ensure a unique propagation
direction for the SPP. We propose a novel back-side slit-illumination method
based on drilling a periodic array of indentations at one side of the slit. We
demonstrate that the SPP running in the array direction can be suppressed, and
the one propagating in the opposite direction enhanced, providing localized
unidirectional SPP launching.Comment: 13 pages, 4 figure
4DXpress: a database for cross-species expression pattern comparisons
In the major animal model species like mouse, fish or fly, detailed spatial information on gene expression over time can be acquired through whole mount in situ hybridization experiments. In these species, expression patterns of many genes have been studied and data has been integrated into dedicated model organism databases like ZFIN for zebrafish, MEPD for medaka, BDGP for Drosophila or GXD for mouse. However, a central repository that allows users to query and compare gene expression patterns across different species has not yet been established. Therefore, we have integrated expression patterns for zebrafish, Drosophila, medaka and mouse into a central public repository called 4DXpress (expression database in four dimensions). Users can query anatomy ontology-based expression annotations across species and quickly jump from one gene to the orthologues in other species. Genes are linked to public microarray data in ArrayExpress. We have mapped developmental stages between the species to be able to compare developmental time phases. We store the largest collection of gene expression patterns available to date in an individual resource, reflecting 16 505 annotated genes. 4DXpress will be an invaluable tool for developmental as well as for computational biologists interested in gene regulation and evolution. 4DXpress is available at http://ani.embl.de/4DXpress
Phenothiazine-mediated rescue of cognition in tau transgenic mice requires neuroprotection and reduced soluble tau burden
Abstract Background It has traditionally been thought that the pathological accumulation of tau in Alzheimer's disease and other tauopathies facilitates neurodegeneration, which in turn leads to cognitive impairment. However, recent evidence suggests that tau tangles are not the entity responsible for memory loss, rather it is an intermediate tau species that disrupts neuronal function. Thus, efforts to discover therapeutics for tauopathies emphasize soluble tau reductions as well as neuroprotection. Results Here, we found that neuroprotection alone caused by methylene blue (MB), the parent compound of the anti-tau phenothiaziazine drug, Rember™, was insufficient to rescue cognition in a mouse model of the human tauopathy, progressive supranuclear palsy (PSP) and fronto-temporal dementia with parkinsonism linked to chromosome 17 (FTDP17): Only when levels of soluble tau protein were concomitantly reduced by a very high concentration of MB, was cognitive improvement observed. Thus, neurodegeneration can be decoupled from tau accumulation, but phenotypic improvement is only possible when soluble tau levels are also reduced. Conclusions Neuroprotection alone is not sufficient to rescue tau-induced memory loss in a transgenic mouse model. Development of neuroprotective agents is an area of intense investigation in the tauopathy drug discovery field. This may ultimately be an unsuccessful approach if soluble toxic tau intermediates are not also reduced. Thus, MB and related compounds, despite their pleiotropic nature, may be the proverbial "magic bullet" because they not only are neuroprotective, but are also able to facilitate soluble tau clearance. Moreover, this shows that neuroprotection is possible without reducing tau levels. This indicates that there is a definitive molecular link between tau and cell death cascades that can be disrupted.http://deepblue.lib.umich.edu/bitstream/2027.42/78314/1/1750-1326-5-45.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78314/2/1750-1326-5-45.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78314/3/1750-1326-5-45-S1.PDFPeer Reviewe
Modulation of surface plasmon coupling-in by one-dimensional surface corrugation
Surface plasmon-polaritons have recently attracted renewed interest in the
scientific community for their potential in sub-wavelength optics, light
generation and non-destructive sensing. Given that they cannot be directly
excited by freely propagating light due to their intrinsical binding to the
metal surface, the light-plasmon coupling efficiency becomes of crucial
importance for the success of any plasmonic device. Here we present a
comprehensive study on the modulation (enhancement or suppression) of such
coupling efficiency by means of one-dimensional surface corrugation. Our
approach is based on simple wave interference and enables us to make
quantitative predictions which have been experimentally confirmed at both the
near infra-red and telecom ranges.Comment: 20 pages, 13 figures, submitted to New Journal of Physics, revised
tex
Plasmonic nanoparticle monomers and dimers: From nano-antennas to chiral metamaterials
We review the basic physics behind light interaction with plasmonic
nanoparticles. The theoretical foundations of light scattering on one metallic
particle (a plasmonic monomer) and two interacting particles (a plasmonic
dimer) are systematically investigated. Expressions for effective particle
susceptibility (polarizability) are derived, and applications of these results
to plasmonic nanoantennas are outlined. In the long-wavelength limit, the
effective macroscopic parameters of an array of plasmonic dimers are
calculated. These parameters are attributable to an effective medium
corresponding to a dilute arrangement of nanoparticles, i.e., a metamaterial
where plasmonic monomers or dimers have the function of "meta-atoms". It is
shown that planar dimers consisting of rod-like particles generally possess
elliptical dichroism and function as atoms for planar chiral metamaterials. The
fabricational simplicity of the proposed rod-dimer geometry can be used in the
design of more cost-effective chiral metamaterials in the optical domain.Comment: submitted to Appl. Phys.
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