Characterization of galactose-dependent promoters from an oleaginous fungus Mortierella alpina 1S-4.

An inducible promoter is a useful tool for the controlled expression of a given gene. In this report, we describe galactose-dependent promoters for potential use in an oleaginous fungus Mortierella alpina. We cloned the putative promoter regions of two genes encoding galactose metabolic enzymes, GAL1 and GAL10, from the genome of M. alpina 1S-4. The β-glucuronidase (GUS) reporter gene assay in M. alpina 1S-4 revealed that regulation of these promoters was dependent on the presence of galactose in the medium both with and without other sugars. With the GAL10 promoter, an approximately 50-fold increase of GUS activity was demonstrated by addition of galactose into the culture media at any cultivation phase. The 5' deletion analysis of the GAL10 promoter revealed that a promoter region of over 2, 000 bp length was required for its high-level activity and sufficient inducible response. Significantly, this is the first report of inducible promoters of zygomycetes. The GAL10 promoter will be a valuable tool for gene manipulation in M. alpina 1S-4

Selection and characterization of promoters based on genomic approach for the molecular breeding of oleaginous fungus Mortierella alpina 1S-4.

To express a foreign gene effectively, a good expression system is required. In this study, we investigated various promoters as useful tools for gene manipulation in oleaginous fungus Mortierella alpina 1S-4. We selected and cloned the promoter regions of 28 genes in M. alpina 1S-4 on the basis of expression sequence tag abundance data. The activity of each promoter was evaluated using the β-glucuronidase (GUS) reporter gene. Eight of these promoters were shown to enhance GUS expression more efficiently than a histone promoter, which is conventionally used for the gene manipulation in M. alpina. Especially, the predicted protein 3 and the predicted protein 6 promoters demonstrated approximately fivefold higher activity than the histone promoter. The activity of some promoters changed along with the cultivation phase of M. alpina 1S-4. Seven promoters with constitutive or time-dependent, high-level expression activity were selected, and deletion analysis was carried out to determine the promoter regions required to retain activity. This is the first report of comprehensive promoter analysis based on a genomic approach for M. alpina. The promoters described here will be useful tools for gene manipulation in this strain

Evodiamine Inhibits Insulin-Stimulated mTOR-S6K Activation and IRS1 Serine Phosphorylation in Adipocytes and Improves Glucose Tolerance in Obese/Diabetic Mice

Evodiamine, an alkaloid extracted from the dried unripe fruit of the tree Evodia rutaecarpa Bentham (Rutaceae), reduces obesity and insulin resistance in obese/diabetic mice; however, the mechanism underlying the effect of evodiamine on insulin resistance is unknown. This study investigated the effect of evodiamine on signal transduction relating to insulin resistance using obese/diabetic KK-Ay mice and an in vitro adipocyte culture. There is a significant decrease in the mammalian target of rapamycin (mTOR) and ribosomal S6 protein kinase (S6K) signaling in white adipose tissue (WAT) in KK-Ay mice treated with evodiamine, in which glucose tolerance is improved. In addition, reduction of insulin receptor substrate 1 (IRS1) serine phosphorylation, an indicator of insulin resistance, was detected in their WAT, suggesting suppression of the negative feedback loop from S6K to IRS1. As well as the stimulation of IRS1 and Akt serine phosphorylation, insulin-stimulated phosphorylation of mTOR and S6K is time-dependent in 3T3-L1 adipocytes, whereas evodiamine does not affect their phosphorylation except for an inhibitory effect on mTOR phosphorylation. Moreover, evodiamine inhibits the insulin-stimulated phosphorylation of mTOR and S6K, leading to down-regulation of IRS1 serine phosphorylation in the adipocytes. Evodiamine also stimulates phosphorylation of AMP-activated protein kinase (AMPK), an important regulator of energy metabolism, which may cause down-regulation of mTOR signaling in adipocytes. A similar effect on AMPK, mTOR and IRS1 phosphorylation was found in adipocytes treated with rosiglitazone. These results suggest evodiamine improves glucose tolerance and prevents the progress of insulin resistance associated with obese/diabetic states, at least in part, through inhibition of mTOR-S6K signaling and IRS1 serine phosphorylation in adipocytes

On the Travel-Times of S-Waves, Derived from the Explosion Seismic Observations

爆破地震動研究グループにおいては,現在までに,自力発破2回を含め13回の観測を行つた.グループの観測の主眼は地下構造の推定にあり,このため解析には原則として初湯の定時のみをとりあつかつていた.この論文では,Late Phaseの中で特にS波と思われるものをとりあげ,その速度を最小自乗法によつて求めた.式(1),(2)は釜石鉱山附近で得られた値,(3),(4)は東北地方,(5)は関東地方における値である.なおSnに相当するものについては遠方の観測がたりないために得られなかつた.これ等の式を用いて平行層の仮定のもとに,intercept timeから不連続面の深さをきめると,釜石附近で0.67km,東北地方で4.72kmを得るが,この値はP波よりもとめたものとそう矛盾しない

Incidence and Risk Factors of Worsened Activities of Daily Living Status Three Months after Intensive Care Unit Discharge among Critically Ill Patients: A Prospective Cohort Study

Background: We aimed to determine risk factors associated with worsened activity of daily living (ADL) status three months after intensive care unit (ICU) discharge. Methods: In this prospective, observational study, we enrolled critically ill adult patients that were emergently admitted to an ICU. We assessed ADL status by Barthel index score prior to ICU admission and three months after ICU discharge. The primary outcome was worsened ADL status, defined as a ≥10 decrease in Barthel index score. Results: We enrolled 102 patients (median age was 72 years old, 55% were male, and 87% received mechanical ventilation during ICU stay), and 42 patients (41%) had worsened ADL status three months after discharge from ICU. Multivariate analysis revealed that older age (>70 years old; adjusted odds ratio (aOR) 3.68; 95% confidence interval (95%CI) 1.33–10.19), high burden of chronic illness (aOR 4.11; 95%CI 1.43–11.81), and longer duration of mechanical ventilation (≥4 days; aOR 2.83; 95%CI 1.04–7.69) were independent risk factors for worsened ADL status at three months. Conclusions: Almost half of the critically ill adult patients in this cohort had worsened ADL status after ICU discharge. Older age, high burden of chronic illness, and longer duration of mechanical ventilation were risk factors for worsened ADL status

Incidence and Risk Factors of Worsened Activities of Daily Living Status Three Months after Intensive Care Unit Discharge among Critically Ill Patients: A Prospective Cohort Study

Background: We aimed to determine risk factors associated with worsened activity of daily living (ADL) status three months after intensive care unit (ICU) discharge. Methods: In this prospective, observational study, we enrolled critically ill adult patients that were emergently admitted to an ICU. We assessed ADL status by Barthel index score prior to ICU admission and three months after ICU discharge. The primary outcome was worsened ADL status, defined as a ≥10 decrease in Barthel index score. Results: We enrolled 102 patients (median age was 72 years old, 55% were male, and 87% received mechanical ventilation during ICU stay), and 42 patients (41%) had worsened ADL status three months after discharge from ICU. Multivariate analysis revealed that older age (>70 years old; adjusted odds ratio (aOR) 3.68; 95% confidence interval (95%CI) 1.33–10.19), high burden of chronic illness (aOR 4.11; 95%CI 1.43–11.81), and longer duration of mechanical ventilation (≥4 days; aOR 2.83; 95%CI 1.04–7.69) were independent risk factors for worsened ADL status at three months. Conclusions: Almost half of the critically ill adult patients in this cohort had worsened ADL status after ICU discharge. Older age, high burden of chronic illness, and longer duration of mechanical ventilation were risk factors for worsened ADL status

Permissive untreated pseudoaneurysm concept in damage control interventional radiology for traumatic pancreaticoduodenal artery injury

Background Angioembolization for traumatic pancreaticoduodenal artery injury with unstable circulation, which characteristically requires a prolonged procedure time, does not yet have a standardized strategy for damage control interventional radiology. Case Presentation We encountered two cases of rare traumatic pancreaticoduodenal artery injury wherein the patients were saved by a multidisciplinary team with a shared goal of clinical success, rather than the procedural success of angioembolization. Both patients treated with angioembolization had residual pseudoaneurysm or faint extravasation in the pancreaticoduodenal artery arcade. We prioritized critical care with preemptive plasma transfusion and aggressive blood pressure control, and planned repeat angiography. The patients showed no clinical signs of rebleeding or pseudoaneurysm based on computed tomography during follow‐up. Conclusion Our findings suggest that the permissive untreated pseudoaneurysm concept can be useful in developing damage control interventional radiology strategies for trauma cases with challenging time limitations, such as traumatic pancreaticoduodenal artery injury with circulatory collapse

Comparative Efficacy of Tocilizumab and Baricitinib Administration in COVID-19 Treatment : A Retrospective Cohort Study

Background and Objectives: Tocilizumab and baricitinib have been observed to improve the outcomes of patients with coronavirus disease 2019 (COVID-19). However, a comparative evaluation of these drugs has not been performed. Materials and Methods: A retrospective, single-center study was conducted using the data of COVID-19 patients admitted to Hokkaido University hospital between April 2020 and September 2021, who were treated with tocilizumab or baricitinib. The clinical characteristics of the patients who received tocilizumab were compared to those of patients who received baricitinib. Univariate and multivariate logistic regression analyses of the outcomes of all-cause mortality and improvement in respiratory status were performed. The development of secondary infection events was analyzed using the Kaplan-Meier method and the log-rank test. Results: Of the 459 patients hospitalized with COVID-19 during the study, 64 received tocilizumab treatment and 34 baricitinib treatment, and those 98 patients were included in the study. Most patients were treated with concomitant steroids and exhibited the same severity level at the initiation of drug treatment. When compared to each other, neither tocilizumab nor baricitinib use were associated with all-cause mortality or improvement in respiratory status within 28 days from drug administration. Conclusions: Age, chronic renal disease and early administration of TCZ or BRT from the onset of COVID-19 were independent prognostic factors for all-cause mortality, whereas anti-viral drug use and the severity of COVID-19 at baseline were associated with an improvement in respiratory status. Secondary infection-free survival rates of patients treated with tocilizumab and those treated with baricitinib did not significantly differ. The results suggest that both tocilizumab and baricitinib could be clinically equivalent agents of choice in treatment of COVID-19

爆破地震動観測によつて得られたS波の走時について

爆破地震動研究グループにおいては,現在までに,自力発破2回を含め13回の観測を行つた.グループの観測の主眼は地下構造の推定にあり,このため解析には原則として初湯の定時のみをとりあつかつていた.この論文では,Late Phaseの中で特にS波と思われるものをとりあげ,その速度を最小自乗法によつて求めた.式(1),(2)は釜石鉱山附近で得られた値,(3),(4)は東北地方,(5)は関東地方における値である.なおSnに相当するものについては遠方の観測がたりないために得られなかつた.これ等の式を用いて平行層の仮定のもとに,intercept timeから不連続面の深さをきめると,釜石附近で0.67km,東北地方で4.72kmを得るが,この値はP波よりもとめたものとそう矛盾しない