Sequence-specific cleavage of RNA by a hybrid ribonuclease H

AbstractSite-specific cleavage of the 22-, 132- and 534-base RNAs by the DNA/protein hybrid R Nase H were examined. The 22-base RNA was chemically synthesized, and 132- and 534-base RNAs were prepared by run-off transcription. The hybrid enzyme cleaves these RNAs, which contain a single target sequence, primarily at the unique phosphodiester bond within the target sequence. The hybrid enzyme performs multiple turnovers, and at a substrate/enzyme ratio of 10:1 the RNAs are almost completely cleaved by the hybrid enzyme at 37°C within 1 h. We propose that hybrid RNase H molecules with various oligodeoxyribonucleotides function as RNA restriction enzymes and are useful for structural and functional studies of RNA

Chlortetracycline and Demeclocycline Inhibit Calpains and Protect Mouse Neurons against Glutamate Toxicity and Cerebral Ischemia

Minocycline is a potent neuroprotective tetracycline in animal models of cerebral ischemia. We examined the protective properties of chlortetracycline (CTC) and demeclocycline (DMC) and showed that these two tetracyclines were also potent neuroprotective against glutamate-induced neuronal death in vitro and cerebral ischemia in vivo. However, CTC and DMC appeared to confer neuroprotection through a unique mechanism compared with minocycline. Rather than inhibiting microglial activation and caspase, CTC and DMC suppressed calpain activities. In addition, CTC and DMC only weakly antagonized N-methyl-D-aspartate (NMDA) receptor activities causing 16 and 14%, respectively, inhibition of NMDA-induced whole cell currents and partially blocked NMDA-induced Ca2+ influx, commonly regarded as the major trigger of neuronal death. In vitro and in vivo experiments demonstrated that the two compounds selectively inhibited the activities of calpain I and II activated following glutamate treatment and cerebral ischemia. In contrast, minocycline did not significantly inhibit calpain activity. Taken together, these results suggested that CTC and DMC provide neuroprotection through suppression of a rise in intracellular Ca2+ and inhibition of calpains

Optimal Robust PID control for first- and second-order plus dead-time processes

The present study proposes a new design method for a proportional-integral-derivative (PID) control system for first-order plus dead-time (FOPDT) and over-damped second-order plus dead-time (SOPDT) systems. What is presented is an optimal PID tuning constrained to robust stability. The optimal tuning is defined for each one of the two operation modes the control system may operate in: servo (reference tracking) and regulation (disturbance rejection). The optimization problem is stated for a normalized second-order plant that unifies FOPDT and SOPDT process models. Different robustness levels are considered and for each one of them, the set of optimal controller parameters is obtained. In a second step, suitable formulas are found that provide continuous values for the controller parameters. Finally, the effectiveness of the proposed method is confirmed through numerical examples

ナンキョク カンソクセン シラセ デ エラレタ センジョウ ジュウリョク データ ノ セイビ

砕氷船「しらせ」船不での重力測定は,第27次南極地域観測隊以来,継続実施されており,およそ17年分のデータが蓄積されている.この内,第27次隊から第33次隊のデータについては,すでに処理されたMGD77フォーマットのデータが提供されていたが,第34次隊以降のデータについては,統一的なデータ処理がされないままの状態であった.そこで,今回,第34次隊から第46次隊の間に得られたデータについて新たにデータ処理を実施し,重力異常データを作成した.この際,特に長波長域での重力データの精度向不のため,第27次隊以降のすべてのデータについて衛星高度計による海域重力異常を基準としたドリフト補正を行った.ここでは,これらの処理の概要ならびに得られたデータセットの状況について報告する.A ship-borne gravity survey on board the icebreaker Shirase has been continuously conducted since JARE-27 (the 27th Japanese Antarctic Research Expedition); about 17 years of gravity data have been accumulated. Although data obtained from JARE-27 to JARE-33 have already been processed and stored in MGD77 format, data starting with JARE-34 have remained unprocessed. We newly processed the data from JARE-34 to JARE-46 to obtain free-air gravity anomalies. To attain better quality, especially in the long wavelength gravity signals, we also applied drift corrections for all the data sets since JARE-27 by employing satellite derived gravity anomalies as a reference gravity field. This report summarizes the data processing and the status of the surface ship gravity data

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