The apolipoprotein E (APOE) ε4 allele constitutes the major genetic risk for the development of late onset Alzheimer's disease (AD). However, its influence on the neurodegeneration that occurs in early AD remains unresolved. In this study, the resting state magnetoencephalography(MEG) recordings were obtained from 27 aged healthy controls and 36 mild cognitive impairment (MCI) patients. All participants were divided into carriers and non-carriers of the ε4 allele. We have calculated the functional connectivity (FC) in the source space along brain regions estimated using the Harvard-Oxford atlas and in the classical bands. Then, a two way ANOVA analysis (diagnosis and APOE) was performed in each frequency band. The diagnosis effect consisted of a diminished FC within the high frequency bands in the MCI patients, affecting medial temporal and parietal regions. The APOE effect produced a decreased long range FC in delta band in ε4 carriers. Finally, the interaction effect showed that the FC pattern of the right frontal-temporal region could be reflecting a compensatory/disruption process within the ε4 allele carriers. Several of these results correlated with cognitive decline and neuropsychological performance. The present study characterizes how the APOE ε4 allele and MCI status affect the brain's functional organization by analyzing the FC patterns in MEG resting state in the sources space. Therefore a combination of genetic, neuropsychological, and neurophysiological information might help to detect MCI patients at higher risk of conversion to AD and asymptomatic subjects at higher risk of developing a manifest cognitive deterioration.
A label-free DNA and single nucleotide polymorphism (SNP) sensing method is described. It is based on the use of the pseudodielectric function of gallium plasmonic nanoparticles (GaNPs) deposited on Si (100) substrates under reversal of the polarization handedness condition. Under this condition, the pseudodielectric function is extremely sensitive to changes in the surrounding medium of the nanoparticle surface providing an excellent sensing platform competitive to conventional surface plasmon resonance. DNA sensing has been carried out by immobilizing a thiolated capture probe sequence from Helicobacter pylori onto GaNP/Si substrates; complementary target sequences of Helicobacter pylori can be quantified over the range of 10 pM to 3.0 nM with a detection limit of 6.0 pM and a linear correlation coefficient of R(2) = 0.990. The selectivity of the device allows the detection of a single nucleotide polymorphism (SNP) in a specific sequence of Helicobacter pylori, without the need for a hybridization suppressor in solution such as formamide. Furthermore, it also allows the detection of this sequence in the presence of other pathogens, such as Escherichia coli in the sample. The broad applicability of the system was demonstrated by the detection of a specific gene mutation directly associated with cystic fibrosis in large genomic DNA isolated from blood cells.
ZnO nanowires (NWs) with different radii (rNW) have been aligned between pre-patterned electrodes using dielectrophoresis (DEP) for the fabrication of high gain UV sensors. The DEP conditions (voltage amplitude and frequency) and electrode material, geometry and size were optimized to enhance the efficiency during the DEP process. To understand the alignment mechanism of the ZnO NWs, the dielectrophoretic force (FDEP) was analyzed as a function of the DEP conditions and NW dimensions. These studies showed that the DEP alignment process tends to trap NWs with a smaller radius. The effects of NW size on device performance were analyzed by means of I-V measurements in darkness and under illumination (200 nm < λ < 600 nm). In darkness, the NW resistance increases as rNW decreases due to the reduction of the conduction volume, until saturation is reached for rNW < 65 nm. On the other hand, the NW spectral photoresponse shows high values around 10(8) A W(-1) (measured at 5 V and λ < 370 nm) and follows a linear trend as a function of the NW cross section. In addition, the cut-off wavelength depends on rNW, presenting a clear blue-shift for NWs with a lower radius (rNW < 50 nm). Transient photoresponse studies show that NWs with lower radii have longer rise times and shorter decay times mainly due to surface trapping effects. Regardless of NW size, passivation of the surface using a dielectric capping layer of SiO2 reduces the dynamic range of the photoresponse due to a strong increase of the dark current.
Esta es la versión de autor del artículo publicado en: This is an author produced version of a paper published in:Biosensors and Bioelectronics 74 (2015)
Microtubules are cytoskeletal polymers of tubulin dimers assembled into protofilaments that constitute nanotubes undergoing periods of assembly and disassembly. Static electron micrographs suggest a structural transition of straight protofilaments into curved ones occurring at the tips of disassembling microtubules. However, these structural transitions have never been observed and the process of microtubule disassembly thus remains unclear. Here, label‐free optical microscopy capable of selective imaging of the transient structural changes of protofilaments at the tip of a disassembling microtubule is introduced. Upon induced disassembly, the transition of ordered protofilaments into a disordered conformation is resolved at the tip of the microtubule. Imaging the unbinding of individual tubulin oligomers from the microtubule tip reveals transient pauses and relapses in the disassembly, concurrent with increased organization of protofilament segments at the microtubule tip. These findings show that microtubule disassembly is a discrete process and suggest a stochastic mechanism of switching from the disassembly to the assembly phase.
An immunosensor to detect small molecules, such as glutathione (GSH), has been developed by combination of ellipsometry and Kretschmann surface plasmon resonance (SPR). The Au thin film used for surface plasmon polariton (SPP) excitation is functionalized with anti-GSH to specifically bind GSH. At low concentrations, the small refractive index changes caused by the low molecular weight of GSH induced only negligible shifts in the plasmon resonant energy during GSH binding. To improve sensitivity, gold nanoparticles (AuNPs) are functionalized with glutathione acting as amplifiers of the antigen-antibody interaction. Changes induced by the AuNP adsorption are monitored using Ψ and Δ ellipsometric functions. After performing competitive assays using solutions containing different concentrations of free GSH and a constant amount of functionalized AuNPs, it was concluded that the resonant energy linearly shifts as the relative concentration of free GSH increases. A detection limit for free GSH in the nanomolar range is found, demonstrating the effectiveness of AuNPs to enhance the sensitivity to immunoreactions in total internal reflection ellipsometry.
Ga nanoparticles (GaNPs) produced by thermal evaporation or epitaxial methods on graphene sheets present strong plasmonic effects that can couple to graphene phonons. In this work, GaNPs are deposited on graphene monolayers supported on Cu, quartz, and SiO2/Si substrates. The use of graphene increases the interparticle distance and improves the size uniformity. The enhancement of G and 2D graphene Raman lines is analyzed for the different substrates under excitation at 633 and 532 nm. The plasmonic effects are investigated using spectroscopic ellipsometry, finding a strong resonant mode at energies between 1.7 and 2.0 eV and an incidence angle of 55.6°. Finally, the heterogeneous surfaces are functionalized for the preparation of optical biosensors exposing the surface to 3,3′‐dithiodipropionic acid di(N‐succinimidyl ester) (DTSP). A significant energy shift of the ellipsometric signal on the Ga/graphene surfaces is observed in comparison to Ga/Si surfaces.
Sketch of GaNPs atop graphene and biofunctionalizing agent (DTSP). Dip in the Psi ellipsometric function, and associated step in the Delta function, found around the GaNPs–graphene coupling resonance at an incident angle of 55.6°.
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