Photocontrol of Solvent Responsiveness of Structural Colored Balloons

The structural colored balloons (SCBs) composed of poly­(vinyl cinnamate) (PVCi) showed solvent responsiveness of structural color by the change of shell thickness along with the size change by osmotic pressure, and the gradual color change could be stopped by UV irradiation. The rate of size change was decreased by the increase of the molecular weight upon photo-cross-linking reaction of PVCi

Solvent-Responsive Structural Colored Balloons

The structural colored balloons (SCBs) consisting of polymer microcapsules showed several structural colors developed by optical thin-layer interference. The SCBs were prepared using a mixture of low- and high-molecular-weight polystyrene to give solvent responsiveness. When the surrounding solvent was transferred from water to the acetone/water mixture using a flow cell, the SCBs swelled at first and shrunk subsequently. The gradual color change of the SCBs was observed along with the size change. The color change accompanying the size change was successfully reproduced by assuming that the total amount of polymer in the thin film does not change. The swelling rate was rationalized by the diffusion of solvent through the shell polystyrene film to the inside of the balloons

Charge-Pairing Mechanism of Phosphorylation Effect upon Amyloid Fibrillation of Human Tau Core Peptide

Phosphorylation of a fibrillogenic protein, human tau, is believed to play crucial roles in the pathogenesis of Alzheimer’s disease. For elucidating molecular mechanisms of the phosphorylation effect on tau fibrillation, we synthesized a peptide, VQIVY310K (PHF6) and its phosphorylated derivative (PHF6pY). PHF6 is a partial peptide surrounding a plausible in vivo phosphorylation site Tyr310 and forms amyloid-type fibrils similar to those generated by full-length tau. Fibrillation of PHF6 and PHF6pY were studied by spectroscopic and microscopic methods, and the critical concentration of the fibrillation was determined for comparing the fibril stability. The results showed that the phosphorylation strongly influenced the fibrillation propensity of PHF6 by changing its dependency on pH and ionic strength. On the basis of the observations, we suggested that charged sites on the phosphate group and its electrostatic pairing with the neighboring charged residues were physical origins of the phosphorylation effect. To verify this charge-pairing mechanism, we conducted experiments using a series of PHF6 derivatives with non-native charge distributions. The electrostatic interaction in an intermolecular mode was also demonstrated by the system composed of two different peptide species, which found that fibrillation of nonphosphorylated PHF6 was drastically enhanced when a trace amount of phosphorylated PHF6 molecules coexisted. A simulation analysis utilizing crystal coordinates of the PHF6 fibril was also performed for interpreting the experimental results in a molecular level. The present study using the model peptide system gave us a microscopically insightful view on the roles of tau phosphorylation in amyloid-related diseases

Positional Effects of Phosphorylation on the Stability and Morphology of Tau-Related Amyloid Fibrils

Hyperphosphorylated forms of tau protein are the main component of paired helical filaments (PHFs) of neurofibrillary tangles in the brain of Alzheimer’s disease patients. To understand the effect of phosphorylation on the fibrillation of tau, we utilized tau-derived phosphorylated peptides. The V₃₀₆QIVYK₃₁₁ sequence (PHF6) in the microtubule-binding domain is known to play a key role in the fibrillation of tau, and the short peptide corresponding to the PHF6 sequence forms amyloid-type fibrils similar to those generated by full-length tau. We focused on the amino acid residue located at the N-terminus of the PHF6 sequence, serine or lysine in the native isoform of tau, and synthesized the PHF6 derivative peptides with serine or lysine at the N-terminus of PHF6. Peptides phosphorylated at serine and/or tyrosine were synthesized to mimic the possible phosphorylation at these positions. The critical concentrations of the fibrillation of peptides were determined to quantitatively assess fibril stability. The peptide with the net charge of near zero tended to form stable fibrils. Interestingly, the peptide phosphorylated at the N-terminal serine residue exhibited remarkably low fibrillation propensity as compared to the peptide possessing the same net charge. Transmission electron microscopy measurements of the fibrils visualized the paired helical or straight fibers and segregated masses of the fibers or heterogeneous rodlike fibers depending on the phosphorylation status. Further analyses of the fibrils by the X-ray fiber diffraction method and Fourier transform infrared spectroscopic measurements indicated that all the peptides shared a common cross-β structure. In addition, the phosphoserine-containing peptides showed the characteristics of β-sandwiches that could interact with both faces of the β-sheet. On the basis of these observations, possible protofilament models with four β-sheets were constructed to consider the positional effects of the serine and/or tyrosine phosphorylations. The electrostatic intersheet interaction between phosphate groups and the amino group of lysine enhanced the lateral association between β-sheets to compensate for the excess charge. In addition to the previously postulated net charge of the peptide, the position of the charged residue plays a critical role in the amyloid fibrillation of tau

Structural Aspects for the Recognition of ATP by Ribonucleopeptide Receptors

A modular structure of ribonucleopeptide (RNP) affords a framework to construct macromolecular receptors and fluorescent sensors. We have isolated ATP-binding RNP with the minimum of nucleotides for ATP binding, in which the RNA consensus sequence is different from those reported for RNA aptamers against the ATP analogues. The three-dimensional structure of the substrate-binding complex of RNP was studied to understand the ATP-binding mechanism of RNP. A combination of NMR measurements, enzymatic and chemical mapping, and nucleotide mutation studies of the RNP-adenosine complex show that RNP interacts with the adenine ring of adenosine by forming a U:A:U triple with two invariant U nucleotides. The observed recognition mode for the adenine ring is different from those of RNA aptamers for ATP derivatives reported previously. The RNP-adenosine complex is folded into a particular structure by formation of the U:A:U triple and a Hoogsteen type A:U base pair. This recognition mechanism was successfully utilized to convert the substrate-binding specificity of RNP from ATP- to GTP-binding with a C+:G:C triple recognition mode

Structural Insight into an Alzheimer’s Brain-Derived Spherical Assembly of Amyloid β by Solid-State NMR

Accumulating evidence suggests that various neuro­degenerative diseases, including Alzheimer’s disease (AD), are linked to cytotoxic diffusible aggregates of amyloid proteins, which are metastable intermediate species in protein misfolding. This study presents the first site-specific structural study on an intermediate called amylo­spheroid (ASPD), an AD-derived neurotoxin composed of oligomeric amyloid-β (Aβ). Electron microscopy and immunological analyses using ASPD-specific “conformational” antibodies established synthetic ASPD for the 42-residue Aβ(1–42) as an excellent structural/morphological analogue of native ASPD extracted from AD patients, the level of which correlates with the severity of AD. ¹³C solid-state NMR analyses of approximately 20 residues and interstrand distances demonstrated that the synthetic ASPD is made of a homogeneous single conformer containing parallel β-sheets. These results provide profound insight into the native ASPD, indicating that Aβ is likely to self-assemble into the toxic intermediate with β-sheet structures in AD brains. This approach can be applied to various intermediates relevant to amyloid diseases

Guest-to-Host Transmission of Structural Changes for Stimuli-Responsive Adsorption Property

We show that structural changes of a guest molecule can trigger structural transformations of a crystalline host framework. Azobenzene was introduced into a flexible porous coordination polymer (PCP), and cis/trans isomerizations of the guest azobenzene by light or heat successfully induced structural transformations of the host PCP in a reversible fashion. This guest-to-host structural transmission resulted in drastic changes in the gas adsorption property of the host–guest composite, displaying a new strategy for creating stimuli-responsive porous materials

Association of epidemiological factors with clustered strains.

<p>Association of epidemiological factors with clustered strains.</p

Maximum Likelihood phylogenetic tree of 1518 global genomes and 34 concatenated genomes of pH1N1/09 viruses.

NUS sequences are in circles (red represent clusters and yellow others) and non-NUS Singaporean sequences are in blue triangles. Clusters were identified with strong bootstrap support (>70%). Trees were generated in RAxML using the GTR substitution matrix and GAMMA model of rate heterogeneity with 1000 bootstrap replicates. The best scoring tree was visualized in MEGA 6.</p

Results of phylogeny trait association for pH1N1/09 viruses.

<p>Results of phylogeny trait association for pH1N1/09 viruses.</p