Raft-derived tau-associated vesicles

Aims: Neurofibrillary tangles (NFTs), a cardinal pathological feature of neurodegenerative disorders, such as Alzheimer's disease (AD) are primarily composed of hyper‐phosphorylated tau protein. Recently, several other molecules, including flotillin‐1, phosphatidylinositol‐4,5‐bisphosphate [PtdIns(4,5)P2] and cyclin‐dependent kinase 5 (CDK5), have also been revealed as constituents of NFTs. Flotillin‐1 and PtdIns(4,5)P2 are considered markers of raft microdomains, whereas CDK5 is a tau kinase. Therefore, we hypothesized that NFTs have a relationship with raft domains and the tau phosphorylation that occurs within NFTs. Methods: We investigated six cases of AD, six cases of other neurodegenerative diseases with NFTs and three control cases. We analysed the PtdIns(4,5)P2‐immunopositive material in detail, using super‐resolution microscopy and electron microscopy to elucidate its pattern of expression. We also investigated the spatial relationship between the PtdIns(4,5)P2‐immunopositive material and tau kinases through double immunofluorescence analysis. Results: Pretangles contained either paired helical filaments (PHFs) or PtdIns(4,5)P2‐immunopositive small vesicles (approximately 1 μm in diameter) with nearly identical topology to granulovacuolar degeneration (GVD) bodies. Various combinations of these vesicles and GVD bodies, the latter of which are pathological hallmarks observed within the neurons of AD patients, were found concurrently in neurons. These vesicles and GVD bodies were both immunopositive not only for PtdIns(4,5)P2, but also for several tau kinases such as glycogen synthase kinase‐3β and spleen tyrosine kinase. Conclusions: These observations suggest that clusters of raft‐derived vesicles that resemble GVD bodies are substructures of pretangles other than PHFs. These tau kinase‐bearing vesicles are likely involved in the modification of tau protein and in NFT formation

Observation of Spin-Dependent Charge Symmetry Breaking in ΛN\Lambda N Interaction: Gamma-Ray Spectroscopy of Λ4^4_{\Lambda }He

The energy spacing between the ground-state spin doublet of $^4_\Lambda$He(1$^+$,0$^+$) was determined to be $1406 \pm 2 \pm 2$ keV, by measuring $\gamma$ rays for the $1^+ \to 0^+$ transition with a high efficiency germanium detector array in coincidence with the $^4$He$(K^-,\pi^-)$ $^4_\Lambda$He reaction at J-PARC. In comparison to the corresponding energy spacing in the mirror hypernucleus $^4_\Lambda$H, the present result clearly indicates the existence of charge symmetry breaking (CSB) in $\Lambda N$ interaction. It is also found that the CSB effect is large in the $0^+$ ground state but is by one order of magnitude smaller in the $1^+$ excited state, demonstrating that the $\Lambda N$ CSB interaction has spin dependence

Search for the Θ+\Theta^{+} pentaquark via the π−p→K−X\pi^-p\to K^-X reaction at 1.92 GeV/cc

The $\Theta^+$ pentaquark baryon was searched for via the $\pi^-p\to K^-X$ reaction in a missing-mass resolution of 1.4 MeV/$c^2$(FWHM) at J-PARC. $\pi^-$ meson beams were incident on the liquid hydrogen target with the beam momentum of 1.92 GeV/$c$. No peak structure corresponding to the $\Theta^+$ mass was observed. The upper limit of the production cross section averaged over the scattering angle of 2$^{\circ}$ to 15$^{\circ}$ in the laboratory frame was obtained to be 0.26 $\mu$b/sr in the mass region of 1.51$-$1.55 GeV/$c^2$.The upper limit of the $\Theta^+$ decay width using the effective Lagrangian approach was obtained to be 0.72 MeV/$c^2$ and 3.1 MeV/$c^2$ for $J^P_{\Theta}=1/2^+$ and $J^P_{\Theta}=1/2^-$, respectively.Comment: 5 pages, 3 figures, 1 tabl

Search for Λ6^6_\LambdaH hypernucleus by the 6^6Li(π−,K+)(\pi^-,K^+) reaction at pπ−p_{\pi^-} = 1.2 GeV/cc

We have carried out an experiment to search for a neutron-rich hypernucleus, $^6_{\Lambda}$H, by the $^6$Li($\pi^-,K^+$) reaction at $p_{\pi^-}$ =1.2 GeV/$c$. The obtained missing mass spectrum with an estimated energy resolution of 3.2 MeV (FWHM) showed no peak structure corresponding to the $^6_{\Lambda}$H hypernucleus neither below nor above the $^4_{\Lambda}$H$+2n$ particle decay threshold. An upper limit of the production cross section for the bound $^6_{\Lambda}$H hypernucleus was estimated to be 1.2 nb/sr at 90% confidence level.Comment: 6 pages, 5 figures, published versio

Dietary soy and meat proteins induce distinct physiological and gene expression changes in rats

This study reports on a comprehensive comparison of the effects of soy and meat proteins given at the recommended level on physiological markers of metabolic syndrome and the hepatic transcriptome. Male rats were fed semi-synthetic diets for 1 wk that differed only regarding protein source, with casein serving as reference. Body weight gain and adipose tissue mass were significantly reduced by soy but not meat proteins. The insulin resistance index was improved by soy, and to a lesser extent by meat proteins. Liver triacylglycerol contents were reduced by both protein sources, which coincided with increased plasma triacylglycerol concentrations. Both soy and meat proteins changed plasma amino acid patterns. The expression of 1571 and 1369 genes were altered by soy and meat proteins respectively. Functional classification revealed that lipid, energy and amino acid metabolic pathways, as well as insulin signaling pathways were regulated differently by soy and meat proteins. Several transcriptional regulators, including NFE2L2, ATF4, Srebf1 and Rictor were identified as potential key upstream regulators. These results suggest that soy and meat proteins induce distinct physiological and gene expression responses in rats and provide novel evidence and suggestions for the health effects of different protein sources in human diets

Lipopolysaccharide from Gut-Associated Lymphoid-Tissue-Resident Alcaligenes faecalis: Complete Structure Determination and Chemical Synthesis of Its Lipid A

Alcaligenes faecalis is the predominant Gram-negative bacterium inhabiting gut-associated lymphoid tissues, Peyer's patches. We previously reported that an A. faecalis lipopolysaccharide (LPS) acted as a weak agonist for Toll-like receptor 4 (TLR4)/myeloid differentiation factor-2 (MD-2) receptor as well as a potent inducer of IgA without excessive inflammation, thus suggesting that A. faecalis LPS might be used as a safe adjuvant. In this study, we characterized the structure of both the lipooligosaccharide (LOS) and LPS from A. faecalis. We synthesized three lipid A molecules with different degrees of acylation by an efficient route involving the simultaneous introduction of 1- and 4′-phosphates. Hexaacylated A. faecalis lipid A showed moderate agonistic activity towards TLR4-mediated signaling and the ability to elicit a discrete interleukin-6 release in human cell lines and mice. It was thus found to be the active principle of the LOS/LPS and a promising vaccine adjuvant candidate