牛山英治が編纂した山岡鉄舟の伝記について

Table S8. Comparison of GD in different studies. MICN is an abbreviation of Modified introduction in China; TS is an abbreviation of Tropical/Subtropical; SS is an abbreviation of Stiff Stalk; NSS is an abbreviation of non-Stiff Stalk; HZS is an abbreviation of Huangzaosi. (XLSX 11 kb

Combining Ultrarapid Mixing with Photochemical Oxidation to Probe Protein Folding

We demonstrate a new method to study protein folding by combining fast photochemical oxidation of proteins (FPOP) with ultrarapid microfluidic mixing to observe kinetics on the microsecond time scale. Folding proteins pass through a focused UV laser beam, creating OH radicals that label the select protein side chains and are analyzed with mass spectrometry. As a proof of principle, we demonstrate this method with hen egg lysozyme that shows at least two kinetic phases before 1 ms, which are compared with those observed by Trp fluorescence. This method provides another, complementary probe of the early, complex steps of protein folding

Olive Component Oleuropein Promotes β‑Cell Insulin Secretion and Protects β‑Cells from Amylin Amyloid-Induced Cytotoxicity

Oleuropein, a natural product derived from olive leaves, has reported anti-diabetic functions. However, detailed molecular mechanisms for how it affects β-cell functions remain poorly understood. Here, we present evidence that oleuropein promotes glucose-stimulated insulin secretion (GSIS) in β-cells. The effect is dose-dependent and stimulates the ERK/MAPK signaling pathway. We further demonstrated that oleuropein inhibits the cytotoxicity induced by amylin amyloids, a hallmark feature of type 2 diabetes. We demonstrated that these dual functions are structure-specific: we identified the 3-hydroxytyrosol moiety of oleuropein as the main functional entity responsible for amyloid inhibition, but the novel GSIS function requires the entire structure scaffold of the molecule

Effect of Hydrophobic Interactions on the Folding Mechanism of β‑Hairpins

Hydrophobic interactions are essential in stabilizing protein structures. How they affect the folding pathway and kinetics, however, is less clear. We used time-resolved infrared spectroscopy to study the dynamics of hydrophobic interactions of β-hairpin variants of the sequence Trpzip2 (SWTW­ENGKW­TWK-NH2) that is stabilized by two cross-strand Trp–Trp pairs. The hydrophobicity strength was varied by substituting the tryptophans pairwise by either tyrosines or valines. Relaxation dynamics were induced by a laser-excited temperature jump, which separately probed for the loss of the cross-strand β-hairpin interaction and the rise of the disordered structure. All substitutions tested result in reduced thermal stability, lower transition temperatures, and faster dynamics compared to Trpzip2. However, the changes in folding dynamics depend on the amino acid substituted for Trp. The aromatic substitution of Tyr for Trp results in the same kinetics for the unfolding of sheet and growth of disorder, with similar activation energies, independent of the substitution position. Substitution of Trp with a solely hydrophobic Val results in even faster kinetics than substitution with Tyr but is additionally site-dependent. If the hairpin has a Val pair close to its termini, the rate constants for loss of sheet and gain of disorder are the same, but if the pair is close to the turn, the sheet and disorder components show different relaxation kinetics. The Trp → Val substitutions reveal that hydrophobic interactions alone weakly stabilize the hairpin structure, but adding edge-to-face aromatic interaction strengthens it, and both modify the complex folding process

A Clean and General Strategy To Decorate a Titanium Metal–Organic Framework with Noble-Metal Nanoparticles for Versatile Photocatalytic Applications

We demonstrate a facile and general approach for the fabrication of highly dispersed Au, Pd, and Pt nanoparticles (NPs) on MIL-125­(Ti) without using extra reducing and capping agents. Noble-metal NP formation is directed by an in situ redox reaction between the reductive MIL-125­(Ti) with Ti³⁺ and oxidative metal salt precursors. The resulting composites function as efficient photocatalysts

Preparation of MIL-53(Fe)-Reduced Graphene Oxide Nanocomposites by a Simple Self-Assembly Strategy for Increasing Interfacial Contact: Efficient Visible-Light Photocatalysts

In this work, MIL-53­(Fe)-reduced graphene oxide (M53-RGO) nanocomposites have been successfully fabricated by a facile and efficient electrostatic self-assembly strategy for improving the interfacial contact between RGO and the MIL-53­(Fe). Compared with D-M53-RGO (direct synthesis of MIL-53­(Fe)-reduced graphene oxide nanocomposites via one-pot solvothermal approach), M53-RGO nanocomposites exhibit improved photocatalytic activity compared with the D-M53-RGO under identical experimental conditions. After 80 min of visible light illumination (λ ≥ 420 nm), the reduction ratio of Cr­(VI) is rapidly increased to 100%, which is also higher than that of reference sample (N-doped TiO₂). More significantly, the M53-RGO nanocomposites are proven to perform as bifunctional photocatalysts with considerable activity in the mixed systems (Cr­(VI)/dyes) under visible light, which made it a potential candidate for industrial wastewater treatment. Combining with photoelectrochemical analyses, it could be revealed that the introduction of RGO would minimize the recombination of photogenerated electron–hole pairs. Additionally, the effective interfacial contact between MIL-53­(Fe) and RGO surface would further accelerate the transfer of photogenerated electrons, leading to the enhancement of photocatalytic activity of M53-RGO toward photocatalytic reactions. Finally, a possible photocatalytic reaction mechanism is also investigated in detail

Additional file 1 of Empowerment for behaviour change through social connections: a qualitative exploration of women’s preferences in preconception health promotion in the state of Victoria, Australia

Additional file 1: Supplementary file 1. The development of themes and sub-themes from codes

Data_Sheet_1_Differential diagnosis of mild cognitive impairment of Alzheimer’s disease by Simoa p-tau181 measurements with matching plasma and CSF.docx

Alzheimer’s disease (AD) is characterized by a long preclinical phase. Although late-stage AD/dementia may be robustly differentiated from cognitively normal individuals by means of a clinical evaluation, PET imaging, and established biofluid biomarkers, disease differentiation between cognitively normal and various subtypes of mild cognitive impairment (MCI) remains a challenging task. Differential biomarkers for early-stage AD diagnosis with accessible biofluid samples are urgently needed. Misfolded phosphorylated tau aggregates (p-tau) are present in multiple neurodegenerative diseases known as “tauopathies”, with the most common being AD. P-tau181 is a well-established p-tau biomarker to differentiate AD dementia from non-AD pathology. However, it is unclear if p-tau181 is capable of diagnosing MCI, an early AD stage, from cognitively normal subjects, or if it can discriminate MCI subtypes amnestic MCI (aMCI) from non-amnestic MCI (naMCI). Here we evaluated the capability of p-tau181 in diagnosing MCI from cognitively normal subjects and discriminating aMCI from naMCI subtypes. We collected matching plasma and CSF samples of a clinically diagnosed cohort of 35 cognitively normal, 34 aMCI, 17 naMCI, and 31 AD dementia cases (total 117 participants) with supplemental CSF Aβ42 and total tau AD biomarker levels and performed Simoa p-tau181 assays. The diagnostic capabilities of Simoa p-tau181 assays to differentiate these cohorts were evaluated. We found (i) p-tau181 can robustly differentiate MCI or aMCI from cognitively normal cohorts with matching plasma and CSF samples, but such differentiation is weaker in diagnosing naMCI from cognitively normal groups, (ii) p-tau181 is not capable of differentiating aMCI from naMCI cohorts, and (iii) either factor of Aβ or total tau burden markedly improved differentiation power to diagnose aMCI from cognitively normal group. Plasma and CSF p-tau181 levels may serve as a promising biomarker for diagnosing aMCI from normal controls in the preclinical phase. But more robust new biomarkers are needed to differentiate naMCI from cognitively normal cases or to discriminate between MCI subtypes, aMCI from naMCI.</p

Developmental Gene Expression Profiling along the Tonotopic Axis of the Mouse Cochlea

<div><p>The mammalian cochlear duct is tonotopically organized such that the basal cochlea is tuned to high frequency sounds and the apical cochlea to low frequency sounds. In an effort to understand how this tonotopic organization is established, we searched for genes that are differentially expressed along the tonotopic axis during neonatal development. Cochlear tissues dissected from P0 and P8 mice were divided into three equal pieces, representing the base, middle and apex, and gene expression profiles were determined using the microarray technique. The gene expression profiles were grouped according to changes in expression levels along the tonotopic axis as well as changes during neonatal development. The classified groups were further analyzed by functional annotation clustering analysis to determine whether genes associated with specific biological function or processes are particularly enriched in each group. These analyses identified several candidate genes that may be involved in cochlear development and acquisition of tonotopy. We examined the expression domains for a few candidate genes in the developing mouse cochlea. <em>Tnc</em> (<em>tenacin C)</em> and <em>Nov (nephroblastoma overexpressed gene)</em> are expressed in the basilar membrane, with increased expression toward the apex, which may contribute to graded changes in the structure of the basilar membrane along the tonotopic axis. In addition, <em>Fst</em> (<em>Follistatin)</em>, an antagonist of TGF-β/BMP signaling, is expressed in the lesser epithelial ridge and at gradually higher levels towards the apex. The graded expression pattern of <em>Fst</em> is established at the time of cochlear specification and maintained throughout embryonic and postnatal development, suggesting its possible role in the organization of tonotopy. Our data will provide a good resource for investigating the developmental mechanisms of the mammalian cochlea including the acquisition of tonotopy.</p> </div

Amylin Amyloid Inhibition by Flavonoid Baicalein: Key Roles of Its Vicinal Dihydroxyl Groups of the Catechol Moiety

Amyloid formation of the 37-residue amylin is involved in the pathogenesis of type 2 diabetes and, potentially, diabetes-induced neurological deficits. Numerous flavonoids exhibit inhibitory effects against amylin amyloidosis, but the mechanisms of inhibition remain unclear. Screening a library of natural compounds uncovered a potent lead compound, the flavone baicalein. Baicalein inhibits amylin amyloid formation and reduces amylin-induced cytotoxicity. Analogue analyses demonstrated, for the first time, key roles of the vicinal hydroxyl groups on the A-ring. We provided mass spectrometric evidence that incubating baicalein and amylin leads to their conjugation, consistent with a Schiff base mechanism