Super-chiral vibrational spectroscopy with metasurfaces for high-sensitive identification of alanine enantiomers

Chiral nature of an enantiomer can be characterized by circular dichroism (CD) spectroscopy, but such a technique usually suffers from weak signal even with a sophisticated optical instrument. Recent demonstrations of plasmonic metasurfaces showed that chiroptical interaction of molecules can be engineered, thereby greatly simplifying a measurement system with high sensing capability. Here, by exploiting super-chiral field in a metasurface, we experimentally demonstrate high-sensitive vibrational CD spectroscopy of alanine enantiomers, the smallest chiral amino acid. Under linearly polarized excitation, the metasurface consisting of an array of staggered Au nano-rods selectively produces the left- and right-handed super-chiral fields at 1600 cm−1, which spectrally overlaps with the functional group vibrations of alanine. In the Fourier-transform infrared spectrometer measurements, the mirror symmetric CD spectra of D- and L-alanine are clearly observed depending on the handedness of the metasurface, realizing the reliable identification of small chiral molecules. The corresponding numerical simulations reveal the underlying resonant chiroptical interaction of plasmonic modes of the metasurface and vibrational modes of alanine. Our approach demonstrates a high-sensitive vibrational CD spectroscopic technique, opening up a reliable chiral sensing platform for advanced infrared inspection technologies

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

Fusion of Photochromic Reaction and Synthetic Reaction: Photoassisted Cyclization to Highly Strained Chiral Azobenzenophanes

A method for synthesizing highly strained cyclic structures by combining photochromic and synthetic reactions is described. Tightly linked azobenzene–binaphthyl dyads (<i>R</i>)-<b>4</b> and (<i>R</i>)-<b>6</b> could not be obtained by conventional cyclization, but continuous application of photoirradiation, which induced (<i>E</i>)→(<i>Z</i>) isomerization of the azobenzene moiety, allowed the cyclization reaction to proceed, affording the desired chiral azobenzenophanes

Photoinversion of <i>Cisoid</i>/<i>Transoid</i> Binaphthyls

Axially chiral binaphthyl-azobenzene cyclic dyads in which the two moieties are connected by two linkers of different lengths were synthesized. In the case of benzylated-binaphthyl analogue <b>2b</b>, photoirradiation resulted in a dramatic change of the CD spectrum and optical rotation. Experimental and theoretical analyses indicated that the dihedral angle of the two naphthalene rings is strongly coupled to the azobenzene photoisomerization; <i>cis</i>-azobenzene induces a <i>transoid</i>-binaphthyl structure, while <i>trans</i>-azobenzene induces a <i>cisoid</i>-binaphthyl structure

Fusion of Photochromic Reaction and Synthetic Reaction: Photoassisted Cyclization to Highly Strained Chiral Azobenzenophanes

A method for synthesizing highly strained cyclic structures by combining photochromic and synthetic reactions is described. Tightly linked azobenzene–binaphthyl dyads (<i>R</i>)-<b>4</b> and (<i>R</i>)-<b>6</b> could not be obtained by conventional cyclization, but continuous application of photoirradiation, which induced (<i>E</i>)→(<i>Z</i>) isomerization of the azobenzene moiety, allowed the cyclization reaction to proceed, affording the desired chiral azobenzenophanes