Involvement of RNA-binding protein Hfq in the osmotic-response regulation of invE gene expression in Shigella sonnei

<p>Abstract</p> <p>Background</p> <p>The expression of Type III secretion system (TTSS) in <it>Shigella </it>is regulated in response to changes in environmental osmolarity and temperature. Temperature-dependent regulation of <it>virF</it>, the master regulator of TTSS synthesis, is believed to occur at the transcriptional level. We recently demonstrated, however, that TTSS synthesis also involves post-transcriptional regulation of the synthesis of InvE, a target of <it>virF </it>and key regulator of TTSS synthesis. The mRNA levels of <it>invE </it>(<it>virB</it>) are stable at 37°C, but mRNA stability markedly decreases at low temperatures where the TTSS synthesis is tightly repressed. Deletion of <it>hfq</it>, which encodes an RNA chaperone in Gram-negative bacteria, results in the restoration of expression of <it>invE </it>and other TTSS genes at low temperature due to an increase in the stability of <it>invE </it>mRNA. To date, the molecular details of the regulation of TTSS expression in response to osmotic pressure are not known. In the current study, we investigated the mechanism of regulation of TTSS by osmotic pressure.</p> <p>Results</p> <p>Transcription of <it>virF</it>, which encodes the master regulator of TTSS expression, was partially repressed under low osmotic conditions. Several lines of evidence indicated that osmolarity-dependent changes in TTSS synthesis are controlled at the post-transcriptional level, through the regulation of InvE synthesis. First, the expression InvE protein was tightly repressed under low osmotic growth conditions, even though <it>invE </it>mRNA transcripts were readily detectable. Second, under low osmotic conditions, <it>invE </it>mRNA was rapidly degraded, whereas deletion of <it>hfq</it>, which encodes an RNA chaperone, resulted in increased <it>invE </it>mRNA stability and the production of InvE protein. Third, the binding of purified Hfq <it>in vitro </it>to <it>invE </it>RNA was stronger in low-salt buffer, as assessed by gel-shift analysis and surface plasmon resonance (Biacore analysis).</p> <p>Conclusion</p> <p>Osmolarity-dependent changes in TTSS synthesis in <it>Shigella </it>involve the post-transcriptional regulation of InvE expression, in addition to partial transcriptional activation by <it>virF</it>. The stability of <it>invE </it>mRNA is reduced under low osmotic conditions, similar to the effect of temperature. Deletion of an RNA chaperone gene (<it>hfq</it>) abolished the repression of TTSS synthesis at low osmolarity through a mechanism that involved increased stability of <it>invE </it>mRNA. We propose that the expression of <it>Shigella </it>virulence genes in response to both osmolarity and temperature involves the post-transcriptional regulation of expression of InvE, a critical regulator of TTSS synthesis.</p

Seasonal and regional differences in lighting conditions and their influence on melatonin secretion

The paper presents essential results of multidisciplinary research dealing with differences in lighting conditions (natural and/or artificial) and their possible influence on melatonin secretion studied in Fukuoka (Japan) and in Warszawa (Poland). Several characteristics of lighting were considered (intensity of global 0.4-3.0 μm, visible 0.4 0.76 μm solar radiation, illuminance (lux), peak irradiance (μW∙cm−2∙nm−1), Color Corresponded Temperature (CCT, K) and peak wave length (nm)). Diurnal cycle of melatonin secretion was examined at volunteers (Poland – 15, Japan – 18), young male and female (21–33 years). Saliva samples were collected at 3h intervals, beginning at 10:00h on Thursday with subsequent sampling times at 13:00, 16:00, 19:00, 22:00 and at 01:00, 04:00 07:00h on Friday. Melatonin concentration (MC) was measured by commercials ELISA kit tests

Unusual oral mucosal microbiota after hematopoietic cell transplantation with glycopeptide antibiotics: potential association with pathophysiology of oral mucositis

Severe oral mucositis occurs frequently in patients receiving hematopoietic stem cell transplantation (HCT). Oral mucosal bacteria can be associated with progression of oral mucositis, and systemic infection may occur via ulcerative oral mucositis. However, little information is available regarding the oral microbiota after HCT. Here, PCR-denaturing gradient gel electrophoresis (DGGE) was performed to characterize the oral mucosal microbiota, which can be affected by antibiotics, before and after HCT. Sixty reduced-intensity HCT patients were enrolled. Three patients with the least antibiotic use (quinolone prophylaxis and/or β-lactam monotherapy group) and three patients with the most antibiotic use (β-lactam-glycopeptide combination therapy group) were selected. Bacterial DNA samples obtained from the oral mucosa before and after HCT were subjected to PCR-DGGE. The trajectory of oral mucositis was evaluated. The oral mucosal microbiota in the β-lactam-glycopeptide combination therapy group was different from that in the quinolone prophylaxis and/or β-lactam monotherapy group, and Staphylococcus spp. and Enterococcus spp. were identified. Lautropia mirabilis was dominant in one patient. Ulcerative oral mucositis was observed only in the β-lactam-glycopeptide combination therapy group. In conclusion, especially with the use of strong antibiotics, such as glycopeptides, the oral mucosal microbiota differed completely from that under normal conditions, and consisted of Staphylococcus spp., Enterococcus spp., and unexpectedly L. mirabilis. The normal oral microbiota consists not only of bacteria, but these unexpected bacteria could be involved in the pathophysiology as well as systemic infection via oral mucositis. Our results can be used as the basis for future studies in larger patient populations

定年退職半年前の公務員の生活習慣

本研究の目的は、定年退職半年前の公務員の食生活、運動習慣、休養、喫煙、飲酒などの健康に関わる生活習慣の実態を明らかにし、定年退職前後の生活習慣の支援のための基礎資料を得ることである。自治体職員向け定年退職準備セミナー受講者で、定年退職までの期間が約半年かつ58～60歳の男女176人を分析対象とした。生活習慣については項目別に単純集計し、男女別、職業別にx^2検定を行った。その結果80.7%は男性であり平均年齢は59.2歳だった。職業は専門的・技術的職業が46.0%で最も多かった。健康度自己評価は「非常に健康」「まあまあ健康」を合わせると83.3%だった。生活習慣については以下の結果を得た。1)食生活:朝食、野菜を毎日食べる人は70～80%、「食事の時間を決めて食べる」(62.1%)が多く、「ゆっくり時間をかけて食べる」(13.4%)「よく噛んで食べる」(17.9%)は低い割合だった。2)運動習慣:運動している人は64.8%で中でも「ウォーキング」(46.5%)が最も多かった。3)喫煙・飲酒:喫煙する人は全体の31%で1日の喫煙本数は11～20本が55.6%と最も多かった。お酒を飲む人は全体の75.6%であり「毎日飲む」(42.9%)が最も多かった。4)睡眠:1日の睡眠時間が「6～8時間未満」(68.9%)が最も多かった。5)基本属性と生活習慣との関連:男性は睡眠時間を十分に確保しており、女性は食事に気をつけていることが明らかになった。さらに職業別では、専門的・技術的職業の人は食事の内容に心がけていることが多かった

Combined Influences of Gradual Changes in Room Temperature and Light around Dusk and Dawn on Circadian Rhythms of Core Temperature, Urinary 6-Hydroxymelatonin Sulfate and Waking Sensation Just after Rising

The present experiment aimed at knowing how a gradual changes of room temperature (Ta) and light in the evening and early morning could influence circadian rhythms of core temperature (Tcore), skin temperatures, urinary 6-hydroxymelatonin sulfate and waking sensation just after rising in humans. Two kinds of room environment were provided for each participant: 1) Constant room temperature (Ta) of 27 °C over the 24 h and LD-rectangular light change with abrupt decreasing from 3,000 lx to100 lx at 1800,abrupt increasing from 0 lx to 3,000 lx at 0700. 2) Cyclic changes of Ta and with gradual decrease from 3,000 lx to 100 lx onset at 1700 (twilight period about 2 h), with gradual increasing from 0 lx to 3,000 lx onset at 0500 (about 2 h). Main results are summarized as follows: 1) Circadian rhythms of nadir in the core temperature (Tcore) significantly advanced earlier under the influence of gradual changes of Ta and light than no gradual changes of Ta and light. 2) Nocturnal fall of Tcore and morning rise of Tcore were greater and quicker, respectively, under the influence of gradual changes of Ta and light than no gradual changes of Ta and light. 3) Urinary 6-hydroxymelatonin sulfate during nocturnal sleep was significantly greater under the influence of gradual changes of Ta and light. 4) Waking sensation just after rising was significantly better under the influence of gradual changes of Ta and light. We discussed these findings in terms of circadian and thermoregulatory physiology

Reciprocal Effects of Oxidative Stress on Heme Oxygenase Expression and Activity Contributes to Reno-Vascular Abnormalities in EC-SOD Knockout Mice

Heme oxygenase (HO) system is one of the key regulators of cellular redox homeostasis which responds to oxidative stress (ROS) via HO-1 induction. However, recent reports have suggested an inhibitory effect of ROS on HO activity. In light of these conflicting reports, this study was designed to evaluate effects of chronic oxidative stress on HO system and its role in contributing towards patho-physiological abnormalities observed in extracellular superoxide dismutase (EC-SOD, SOD3) KO animals. Experiments were performed in WT and EC-SOD(−/−) mice treated with and without HO inducer, cobalt protoporphyrin (CoPP). EC-SOD(−/−) mice exhibited oxidative stress, renal histopathological abnormalities, elevated blood pressure, impaired endothelial function, reduced p-eNOS, p-AKT and increased HO-1 expression; although, HO activity was significantly (P \u3c 0.05) attenuated along with attenuation of serum adiponectin and vascular epoxide levels (P \u3c 0.05). CoPP, in EC-SOD(−/−) mice, enhanced HO activity (P \u3c 0.05) and reversed aforementioned pathophysiological abnormalities along with restoration of vascular EET, p-eNOS, p-AKT and serum adiponectin levels in these animals. Taken together our results implicate a causative role of insufficient activation of heme-HO-adiponectin system in pathophysiological abnormalities observed in animal models of chronic oxidative stress such as EC-SOD(−/−) mice

乳癌術前化学療法において腋窩リンパ節転移が陰性化するための効果予測因子の検討

Purpose: We investigated the role of tumor-infiltrating lymphocytes (TILs) in pretreatment primary breast cancer to predict pathological response to neoadjuvant chemotherapy (NAC) in patients with clinical node-positive disease (cN +). Methods: The subjects of this study were 60 patients with cN + , who received NAC followed by breast surgery with axillary lymph node dissection (ALND). We conducted a semi-quantitative assessment of TILs in pretreatment primary tumors and their association with clinicopathological factors and axillary lymph node metastasis. Results: We observed a higher number of TILs in tumors with negative hormone receptors, positive human epidermal growth factor receptor 2, or high Ki67. TILs were associated with a favorable response to NAC in primary tumors. The rate of axillary pathologic complete response (Ax-pCR) was significantly higher in patients with a high number of TILs than in patients with a low number of TILs (72.0% versus 17.1%, p < 0.001). In multivariable analysis, a high number of TILs was a significant predictor of Ax-pCR as well as of pCR of the primary tumor after NAC. Importantly, all patients with HER2-positive tumors in the high TILs group showed Ax-pCR on ALND. Conclusion: TILs in pretreatment primary breast cancer had the potential to predict therapeutic efficacy of NAC in patients with clinical node-positive disease.博士（医学）・乙第1498号・令和3年3月15日© Springer Nature Singapore Pte Ltd. 2020This is a post-peer-review, pre-copyedit version of an article published in Surgery today. The final authenticated version is available online at: https://doi.org/10.1007/s00595-020-02157-6

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In July, 1973,We measured the healthy bodies of three-hundred and eighty-two children (9～12years old) of T elementary school in Kagoshima by means of the type II silhouetter. This time we chose the best three-hundred and sixteen examples of side-silhouettes and examined their bust angle, posterior waist angle, and hip angle respectively, taking into account the distinction of the sex and age. The general results of the examination are as follows : (1) The order of the average degrees of angle of a child (from the first to the sixth grade) is (1) bust angle, " (2) posterior waist angle, (3) hip angle. But the individual variation is great in each angle. (2) The somatotype of a boy, when he reaches the age of 12,and his shoulder blades grow, making the posterior waist angle wide, comes to be like that of an adult. (3) In the case of the somatotype of a girl, the growth of her bust and hips with the onset of her adolescence is observed plainly on the side-silhouette. (4) The side-silhouette of a nine or ten-year-old child (whether a boy or a girl) shows greater individual unevenness of trunk-level than that of an eleven or twelve-year-old child

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In order to examine the somatotypes of the human flank, in May in 1974,we measured the three-hundred healthy bodies of the boys and girls of \u27I\u27 City Junior High School in Kagoshima ranging in age from 13 to 15 by means of the Type II silhouetter, The results of the examination are as follows : (This paper is continued from the preceding one and the way we took of measuring and the number of the items of the results are the same as in the preceding paper.) 1. The order of the average degree of the angles of the 13 and 15-year-old boys is : (1) posterior waist angle, (2) bust angle, (3) hip angle. But in the case of the 14-year-old boys and the 13 to 15-year-old girls, the order is : (1) bust angle, (2) posterior waist angle, (3) hip angle. In the case of the girls, they all without distinction of age show great difference in the degree of each angle, but the 14 and 15-year-old boys show nearly similar bust angle and posterior waist angle. 2. In regard to the side-silhouettes from the waist up, the girls, on the average, show greater convexity than the boys. And in regard to the average degree of the 14 and 15-year-old pupils\u27 bust angle, and in regard to that of the 15-year-old pupils\u27 hip angle, the girls show higher degree-than the boys with one percent of level of significance. 3. In regard to the posterior waist angle, the boys show greater convexity than the girls with one percent of significance. And the 13-year-old pupils of both sexes show the highest average degree and the degree of the angle becomes lower as they grow older. 4. In the case of the girls, they all seem to show the beginning of the womanly growth of the bust, when they reach the age of thirteen