Generation of Organozinc Reagents from Arylsulfonium Salts Using a Nickel Catalyst and Zinc Dust

Readily available aryldimethylsulfonium triflates react with zinc powder under nickel catalysis via the selective cleavage of the sp2-hybridized carbon–sulfur bond to produce salt-free arylzinc triflates under mild conditions. This zincation displays superb chemoselectivity and thus represents a protocol that is complementary or orthogonal to existing methods. The generated arylzinc reagents show both high reactivity and chemoselectivity in palladium-catalyzed and copper-mediated cross-coupling reactions

A recyclable hydrophobic anchor-tagged asymmetric amino thiourea catalyst

A novel recyclable thiourea-based, asymmetric organocatalyst containing a hydrophobic anchor has been developed. The chemical nature of the hydrophobic anchor contributes to the desirable characteristics of the recyclable catalyst. The hydrophobic anchor-tagged thiourea catalyst is highly soluble in less polar solvents compatible to the amino thiourea catalyst-mediated asymmetric reactions, but sparingly soluble in polar solvents used for recycle process. This asymmetric catalyst delivers a catalytic performance comparable to that of a parent catalyst and can be readily recycled from reactions

A Substellar Companion to Pleiades HII 3441

We find a new substellar companion to the Pleiades member star, Pleiades HII 3441, using the Subaru telescope with adaptive optics. The discovery is made as part of the high-contrast imaging survey to search for planetary-mass and substellar companions in the Pleiades and young moving groups. The companion has a projected separation of 0".49 +/- 0".02 (66 +/- 2 AU) and a mass of 68 +/- 5 M_J based on three observations in the J-, H-, and K_S-band. The spectral type is estimated to be M7 (~2700 K), and thus no methane absorption is detected in the H band. Our Pleiades observations result in the detection of two substellar companions including one previously reported among 20 observed Pleiades stars, and indicate that the fraction of substellar companions in the Pleiades is about 10.0 +26.1/-8.8 %. This is consistent with multiplicity studies of both the Pleiades stars and other open clusters.Comment: Main text (14 pages, 4 figures, 4 tables), and Supplementary data (8 pages, 3 tables). Accepted for Publications of Astronomical Society of Japa

Efficacy and Safety of an Ultrasonically Activated Device for Sealing the Bile Ducts During Liver Resection

The use of ultrasonically activated devices (USADs) in hepatic resections may be associated with an increased rate of complications, such as postoperative bile leaks. Nonetheless, the safety of USADs for sealing bile ducts during liver surgery has not yet been established. The purpose of this study was to assess the efficacy of a USAD for sealing bile ducts. In animal experiments, the common bile duct of ten anesthetized dogs was individually occluded using a USAD. Additionally, using the prospective liver surgery database from a single institution, we identified 45 consecutive patients who underwent hepatic resection using a USAD (USAD group) and 45 similar patients who underwent hepatic resection without the use of a USAD (NUSAD group). In the occluded and harvested canine bile ducts, the mean burst pressure was 280mmHg, and the lumen of the bile duct was completely sealed morphologically. In the clinical study, there was no significant difference in postoperative mortality or complications between the two groups, and biliary leakage was observed in only one patient (0.7%) in the USAD group. These data demonstrate that the USAD is a safe, efficient, and practical instrument for use during liver surgery to achieve complete hemobiliary stasis

Change in brain plasmalogen composition by exposure to prenatal undernutrition leads to behavioral impairment of rats.

Epidemiological studies suggest that poor nutrition during pregnancy influences offspring predisposition to experience developmental and psychiatric disorders. Animal studies have shown that maternal undernutrition leads to behavioral impairment, which is linked to alterations in monoaminergic systems and inflammation in the brain. In this study, we focused on the ethanolamine plasmalogen of the brain as a possible contributor to behavioral disturbances observed in offspring exposed to maternal undernutrition. Maternal food or protein restriction between gestational day (GD) 5.5 and GD 10.5 resulted in hyperactivity of rat male adult offspring. Genes related to the phospholipid biosynthesis were found to be activated in the prefrontal cortex (PFC), but not in the nucleus accumbens or striatum, in the offspring exposed to prenatal undernutrition. Corresponding to these gene activations, increased ethanolamine plasmalogen (18:0p-22:6) was observed in the PFC using mass spectrometry imaging. A high number of crossings and the long time spent in the center area was observed in the offspring exposed to prenatal undernutrition and was mimicked in adult rats via the intravenous injection of ethanolamine plasmalogen (18:0p-22:6) incorporated into the liposome. Additionally, plasmalogen (18:0p-22:6) increased only in the PFC, and not in the nucleus accumbens or striatum. These results suggest that brain plasmalogen is one of the key molecules to control behavior and its injection using liposome is a potential therapeutic approach for cognitive impairment.Significance Statement:Maternal undernutrition correlates to developmental and psychiatric disorders. Here, we found that maternal undernutrition in early pregnancy led to hyperactivity in rat male offspring and induced gene activation of phospholipid-synthesizing enzyme and elevation of ethanolamine plasmalogen (18:0p-22:6) level in the prefrontal cortex (PFC). Intravenous injection of ethanolamine plasmalogen (18:0p-22:6) incorporated into the liposome maintained crossing activity and was circumscribed to the center area for a long time period, in prenatally undernourished offspring with aberrant behavior. Furthermore, the amount of ethanolamine plasmalogen (18:0p-22:6) increased in the PFC of the rat after injection. Our result suggests that brain plasmalogen is one of the key molecules to control behavior and that its injection using liposome is a potential therapeutic approach for cognitive impairment

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

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

Water/ice mixture- and freezing-front motion in a non-isothermal liquid bridge

We experimentally investigate the water/ice mixture- and freezing-front behavior in a water liquid bridge under isothermal and non-isothermal conditions. We find rapid propagation, temporary suspension, and regression of the water/ice mixture front, and finally, it merges with the freezing front when part of the liquid bridge is higher than the freezing temperature. However, freezing-front propagation follows dendritic ice formation, and a protrusion forms at the middle of the liquid bridge as long as the whole liquid bridge is lower than the freezing temperature. We explain those phenomena by quasi-stationary heat-transfer considerations