Hard x-ray intensity autocorrelation using direct two-photon absorption

An intensity autocorrelation measurement is demonstrated to characterize a pulse duration of 9-keV x-ray free-electron laser (XFEL) pulses from a split-delay optical (SDO) system with four-bounce silicon 220 reflections in each branch. XFEL pulse replicas with variable time delays are generated by the SDO system itself. High intensity of >2×1016W/cm2 achieved in a self-seeding operation and careful data analysis allow the measurement with direct two-photon absorption. The autocorrelation trace gave a duration of 7.6±0.8fs in full width at half maximum for a Gaussian assumption. Furthermore, the trace shows good agreement with a simulation of the XFEL pulse shape propagating through the SDO system, irrespective of spectral chirps in the original XFEL pulses. Our results open the door toward direct temporal characterization of narrowband XFELs at the hard x-ray regime, such as self-seeded and future cavity-based XFELs, and indicate a solid way for temporal tailoring of ultrafast x-ray pulses with perfect crystals.Osaka T., Inoue I., Yamada J., et al. Hard x-ray intensity autocorrelation using direct two-photon absorption. Physical Review Research, 4, 1, L012035. https://doi.org/10.1103/PhysRevResearch.4.L012035

Analysis of Expressed Sequence Tags from the Fungus Aspergillus oryzae Cultured Under Different Conditions

We performed random sequencing of cDNAs from nine biologically or industrially important cultures of the industrially valuable fungus Aspergillus oryzae to obtain expressed sequence tags (ESTs). Consequently, 21 446 raw ESTs were accumulated and subsequently assembled to 7589 non-redundant consensus sequences (contigs). Among all contigs, 5491 (72.4%) were derived from only a particular culture. These included 4735 (62.4%) singletons, i.e. lone ESTs overlapping with no others. These data showed that consideration of culture grown under various conditions as cDNA sources enabled efficient collection of ESTs. BLAST searches against the public databases showed that 2953 (38.9%) of the EST contigs showed significant similarities to deposited sequences with known functions, 793 (10.5%) were similar to hypothetical proteins, and the remaining 3843 (50.6%) showed no significant similarity to sequences in the databases. Culture-specific contigs were extracted on the basis of the EST frequency normalized by the total number for each culture condition. In addition, contig sequences were compared with sequence sets in eukaryotic orthologous groups (KOGs), and classified into the KOG functional categories

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

Surface finishing method using plasma chemical vaporization machining for narrow channel walls of x-ray crystal monochromators

Channel-cut Si crystals are useful optical devices for providing monochromatic X-ray beams with extreme angular stability. Owing to difficulties in the high-precision surface finishing of narrow-channel inner walls of the crystals, typical channel-cut crystals have considerable residual subsurface crystal damage and/or roughness on their channel-wall reflection surfaces that decrease intensity and distort the wavefronts of the reflected X-rays. This paper proposes a highprecision surface finishing method for the narrowchannel inner walls based on plasma chemical vaporization machining, which is a local etching technique using atmospheric-pressure plasma. Cylinderand nozzle-shaped electrodes were designed for channel widths of more than 5 and 3 mm, respectively. We optimized process conditions for each electrode using commercial Si wafers, and obtained a removal depth of 10 μm with a surface flatness and roughness of less than 1 μm and 1 nmRMS, respectively, which should allow the damaged layers to be fully removed while maintaining the wavefront of coherent X-rays.Takashi Hirano, Yuki Morioka, Shotaro Matsumura, Yasuhisa Sano, Taito Osaka, Satoshi Matsuyama, Makina Yabashi, and Kazuto Yamauchi, “Surface Finishing Method Using Plasma Chemical Vaporization Machining for Narrow Channel Walls of X-Ray Crystal Monochromators,” Int. J. Automation Technol., Vol.13, No.2, pp. 246-253, 2019