Lyotropic liquid crystallinity of amylose tris(alkylcarbamates): Cholesteric and smectic phase formation in different solvents

Oyamada K., Terao K., Suwa M., et al. Lyotropic liquid crystallinity of amylose tris(alkylcarbamates): Cholesteric and smectic phase formation in different solvents. Macromolecules, 46(11), 4589-4595, May 20, 2013. Copyright © 2013, American Chemical Society. https://doi.org/10.1021/ma400787c

Solution properties of a cyclic chain having tunable chain stiffness: Cyclic amylose tris(n-butylcarbamate) in theta and good solvents

Terao K., Shigeuchi K., Oyamada K., et al. Solution properties of a cyclic chain having tunable chain stiffness: Cyclic amylose tris(n-butylcarbamate) in Θ and good solvents. Macromolecules, 46, 13, 5355. https://doi.org/10.1021/ma400774r

Side-chain-dependent helical conformation of amylose alkylcarbamates: Amylose tris(ethylcarbamate) and amylose tris(n-hexylcarbamate)

Eight amylose tris(ethylcarbamate) (ATEC) samples ranging in the weight-average molar mass Mw from 1.0 - 104 to 1.1 - 106 g mol-1 and five amylose tris(n-hexylcarbamate) (ATHC) samples of which Mw varies from 4.9 - 104 to 2.2 - 106 g mol-1 have been prepared from enzymatically synthesized amylose samples having narrow dispersity indices and no branching. Small-angle angle X-ray scattering (SAXS), light scattering, viscometry, and infrared (IR) absorption measurements were carried out for their dilute solutions, that is, ATEC in tetrahydrofuran (THF), 2-methoxyethanol (2ME), methanol (MeOH), and ATHC in THF and 1-propanol (1PrOH) to determine M w, particle scattering functions, intrinsic viscosities, and IR spectra. SAXS and viscosity measurements were also made on ATEC in d- and l-ethyl lactates. The data were analyzed in terms of the wormlike cylinder model to estimate the helix pitch (or contour length) per residue h and the Kuhn segment length λ-1 (stiffness parameter, twice the persistence length). Both ATEC and ATHC have large λ-1 in THF, that is, 33 and 75 nm, respectively, and smaller λ-1 were obtained in alcohols, indicating that they have rigid helical conformation stabilized by intramolecular hydrogen bonds in THF. On the contrary, the helical structure estimated from the h value significantly depends on the alkyl side groups in a complex fashion, that is, h = 0.36 nm for ATEC, h = 0.29 nm for ATHC, and h = 0.26 nm for amylose tris(n-butylcarbamate) (ATBC). This is likely related to the bulkiness of side groups packed inside the amylosic helices. The solvent dependence of h, λ-1, and the fraction fhyd of intramolecular hydrogen bonds for ATEC can be explained by a current model as is the case with ATBC [ Terao, K.; Macromolecules 2010, 43, 1061 ], in which each contour point along the chain takes loose helical and rigid helical sequences independently. © 2012 American Chemical Society.Terao K., Maeda F., Oyamada K., et al. Side-chain-dependent helical conformation of amylose alkylcarbamates: Amylose tris(ethylcarbamate) and amylose tris(n-hexylcarbamate). Journal of Physical Chemistry B, 116(42), 12714-12720, October 5, 2012. Copyright © 2012, American Chemical Society. https://doi.org/10.1021/jp307998t

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Solution Properties of a Cyclic Chain Having Tunable Chain Stiffness: Cyclic Amylose Tris(<i>n</i>‑butylcarbamate) in Θ and Good Solvents

Small-angle X-ray scattering measurements were made for nine cyclic amylose tris­(<i>n</i>-butylcarbamate) (cATBC) samples ranging in the weight-average molar mass <i>M</i>_w from 1.6 × 10⁴ to 1.1 × 10⁵ to determine the <i>z</i>-average mean-square radius of gyration ⟨<i>S</i>²⟩_<i>z</i> and the particle scattering function <i>P</i>(<i>q</i>) in two good solvents, tetrahydrofuran (THF) and methanol (MeOH) at 25 °C and in a Θ solvent, 2-propanol (2PrOH) at the Θ temperature (35 °C). Static and dynamic light scattering measurements were carried out for cATBC in 2PrOH to determine <i>M</i>_w, the second virial coefficient <i>A</i>₂, and the hydrodynamic radius <i>R</i>_H. The dimensional and hydrodynamic properties are consistently explained by the current theories for wormlike ring having substantially the same model parameters obtained for linear analogues, that is, the Kuhn segment length λ^–1 of THF, 2PrOH, and MeOH are 75, 20, and 11 nm, respectively. Furthermore, number of hydrogen bonds decreases with the order of THF, 2PrOH, and MeOH, as is the case with linear ATBC. These results indicate that cATBC has rigid helical backbone stabilized by intramolecular hydrogen bonds in THF and it loosens with increasing solvent polarity. Indeed, lyotropic liquid crystallinity was found for cATBC in THF. In the Θ condition, 2PrOH at 35 °C, cATBC has large positive <i>A</i>₂ values, (1.3–1.4) × 10^–4 mol g^–2 cm³. It is successfully explained by the simulation results considering intermolecular topological interaction

Lyotropic Liquid Crystallinity of Amylose Tris(alkylcarbamates): Cholesteric and Smectic Phase Formation in Different Solvents

Lyotropic liquid crystallinity was investigated for amylose tris­(<i>n</i>-butylcarbamate) (ATBC), amylose tris­(ethylcarabamate) (ATEC), and amylose tris­(<i>n</i>-hexylcarbamate) (ATHC) in tetrahydrofuran (THF) and ethyl lactates (ELs) by using phase separation experiments, polarized microscopic observation, small-angle X-ray diffraction, and circular dichroism measurements. Concentrated THF solution of ATBC has selective reflection at visible light wavelength, indicating the formation of cholesteric phase. A current theory well explains the phase diagram of ATBC, ATEC, and ATHC in THF. On the other hand, ELs solution forms smectic phase and it has significantly different phase diagram, that is, the biphasic range is much wider than that in THF. In other words, highly concentrated smectic phase can be obtained from semidilute and rather low viscosity ELs solution. This is likely because amylose alkylcarbamate chains may have significant anisotropic intermolecular attractive interaction in between polymer chains in ELs or intermolecular interactions between the chain ends are much more different from those in THF