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MicroRNAs (miRNAs) play an important role in the development of the brain and also implicated in the pathogenesis of neurological diseases such as Alzheimer's disease (AD). Recent studies implied that dysregulation of miRNAs is involved in neuropsychiatric disorders such as anxiety disorder in AD.In this study, behavioral experiments such as open field test, elevated plus maze test and light-dark box test were performed to evaluate anxiety-like behaviors in a triple transgenic mouse model of AD (3xTg-AD mice), and Q-PCR was used to measure the change of miR-34a expression.Behavioral tests revealed anxiety-like behaviors in 3xTg-AD mice. Q-PCR assay showed significantly elevated expression of miR-34a in the hippocampus of 3xTg-AD mice compared with the age- and gender-matched wild-type mice. Western-blot analysis showed that the expression of metabotropic glutamate receptor 7 (GRM7) but not fibroblast growth factor-2 (FGF2), two anxiety disorder-related target genes of miR-34a, was significantly decreased in hippocampus of 3xTg-AD mice compared with the wild-type mice.We concluded that anxiety-like behavior occurred in 3xTg-AD mice with an involvement of miR-34a/GRM7.

Aims CLARITY is a novel technique which enables three-dimensional visualization of immunostained tissue for the study of circuitry and spatial interactions between cells and molecules in the brain. In this study, we aimed to compare methodological differences in the application of CLARITY between rodent and large human post mortem brain samples. In addition, we aimed to investigate if this technique could be used to visualize Lewy pathology in a post mortem Parkinson's brain. Methods Rodent and human brain samples were clarified and immunostained using the passive version of the CLARITY technique. Samples were then immersed in different refractive index matching media before mounting and visualizing under a confocal microscope. Results We found that tissue clearing speed using passive CLARITY differs according to species (human vs. rodents), brain region and degree of fixation (fresh vs. formalin-fixed tissues). Furthermore, there were advantages to using specific refractive index matching media. We have applied this technique and have successfully visualized Lewy body inclusions in three dimensions within the nucleus basalis of Meynert, and the spatial relationship between monoaminergic fibres and Lewy pathologies among nigrostriatal fibres in the midbrain without the need for physical serial sectioning of brain tissue. Conclusions The effective use of CLARITY on large samples of human tissue opens up many potential avenues for detailed pathological and morphological studies.

1. Minocycline, memantine,and glycoconjugate were assessed for their ability to protect cultured primary cortical neurons against double-stranded RNA-induced neurotoxicity. 2. Minocycline but not memantine or glycoconjugate protected cultured cells and warrants further investigation.

Excitation profiles of depolarized modes (blg, b2g) in Ni etioporphyrin I exhibit marked 0–0 resonance Raman intensity upon Q‐band excitation. By contrast, inversely polarized Raman scattering (a2g) is stronger with 0–1 excitation. Within the crude Born–Oppenheimer approximation, a theoretical model is presented which explains the 0–0 enhancements of depolarized modes as arising from interference of intermanifold (Q –B) and intramanifold (Q –Q) vibronic coupling. Comparison of computed and observed excitation profiles shows that a weak Jahn–Teller distortion is present in the Q state. The vibronic model predicts behavior of Raman intensity in the B (Soret) electronic state. Evidence of increased vibronic coupling of both 400 and 1365 cm−1 polarized vibrations (a1g) is found in chromium tetraphenylporphyrin with the appearance of a supernumerary peak at 1400 cm−1 in the excitation profile of the 400 cm−1 vibration. Excitation profiles of a2g modes in the chromium complex exhibit an apparent decrease in exc...

This paper treats the responses of a controlled system to step and pulse disturbances where the rate of change of the controlling variable is bounded. Optimum transients in the sense of minimizing the maximum error, response duration, and other variables are derived for step and pulse disturbances whose parameters, i.e., magnitude, sense of change, instant of occurrence and pulse duration, are either completely known in advance, or known at the instant the disturbance starts, or not known in advance at all. It is shown that the more that is known about the disturbance beforehand, the better the response that can be obtained. The improvement may be very great. The optimum control function for a pulse disturbance known at the initiation of the pulse contains disturbance parameters. A practical control function can be derived by eliminating these parameters so that no advance information about the disturbance is required. The resulting control function will yield optimum transients and will depend entirely on the system error and its derivatives. This practical control function yields improved response over classical theory to a train of pulse-load disturbances.