Monochloramine inhibits ultraviolet B-induced p53 activation and DNA repair response in human fibroblasts

AbstractMonochloramine (NH2Cl) is one of the inflammation-derived oxidants, and has various effects on cell cycle, apoptosis and signal transduction. We studied the effects of NH2Cl on DNA repair response induced by ultraviolet B (UVB) irradiation in normal human diploid fibroblasts, TIG-1. TIG-1 irradiated with 20 mJ/cm2 UVB showed marked increase in thymine dimer, which decreased by about 50% after 24 h. This decrease in thymine dimer was significantly attenuated (P<0.05) by the pretreatment of NH2Cl (200 μM), which indicated DNA repair inhibition. UVB induced p53 phosphorylation at Ser15, Ser20 and Ser37, and p53 accumulation, and NH2Cl also inhibited these changes. Consequently, UVB-induced increase in the downstream effectors of p53, namely p21Cip1 and Gadd45a, were almost completely inhibited by NH2Cl. Immunoprecipitation study indicated that the association of p53 and MDM2, an E3 ubiquitin ligase for p53, did not change substantially by NH2Cl and/or UVB. The phosphorylation of p53 (Ser15 and Ser37) by UVB is catalyzed by ATR (ataxia telangiectasia mutated and Rad3 related kinase), which works as DNA damage sensor, and ATR also phosphorylates checkpoint kinase 1(Chk1) at Ser345. NH2Cl also inhibited the phosphorylation of Chk1 (Ser345). As UVB-induced DNA damage is repaired by nucleotide excision repair (NER) in human cells, these findings indicated that NH2Cl inhibited NER through the inhibition of p53 phosphorylation and accumulation, and NH2Cl probably impaired DNA damage recognition and/or ATR activation. NH2Cl may facilitate carcinogenesis through the inhibition of NER that repairs DNA damages from various carcinogens

Angiomyofibroblastoma of the vulva: a large pedunculated mass formation.

Angiomyofibroblastoma is a rare, usually small benign mesenchymal tumor that occurs in vulvar lesions of premenopausal women. A case of angiomyofibroblastoma that arose as a unique pedunculated and particularly large mass in the left vulva of a 48-year-old woman is presented herein. The patient had been aware of a gradually enlarged mass of 7 years duration without any other gynecological symptoms or signs. The maximum dimension of the tumor measured 11 cm. The resected tumor was well circumscribed with a bulging and glistening cut surface. Histological examination revealed an admixture of irregularly distributed hypercellular and hypocellular areas with spindled, plump spindled, or plasmacytoid stromal cells and abundant venular or capillary-sized vessels. Stromal cells characteristically cluster around delicate vessels within an edematous to collagenous matrix. In the present case, intralesional adipose tissue was present throughout the tumor. There was no significant nuclear atypia, and mitotic figures were very sparse. There was little stromal mucin throughout the tumor. Immunohistochemically, the stromal cells were characterized by strong reactivity for vimentin and CD34, with focal reactivity for desmin and alpha smooth muscle actin. Both estrogen and progesterone receptors were diffusely expressed in the stromal cells. These histological findings are consistent with angiomyofibroblastoma and support the hypothesis that angiomyofibroblastoma originates from perivascular stem cells with a capacity for myofibroblastic and fatty differentiation

A new device for the simultaneous recording of cerebral, cardiac, and muscular electrical activity in freely moving rodents

AbstractWe present a new technique for the simultaneous capture of bioelectrical time signals from the brain and peripheral organs of freely moving rodents. The recording system integrates all systemic signals into an electrical interface board that is mounted on an animal's head for an extended period. The interface board accommodates up to 48 channels, enabling us to analyze neuronal activity patterns in multiple brain regions by comparing a variety of physiological body states over weeks and months. This technique will advance the understanding of the neurophysiological correlate of mind–body associations in health and disease

A motor neuron disease-associated mutation produces non-glycosylated Seipin that induces ER stress and apoptosis by inactivating SERCA2b

遺伝病の原因タンパク質が小胞体ストレスを引き起こすメカニズムの解明 --神経変性疾患の新規治療戦略の確立に向けて--. 京都大学プレスリリース. 2022-12-13.A causal relationship between endoplasmic reticulum (ER) stress and the development of neurodegenerative diseases remains controversial. Here, we focused on Seipinopathy, a dominant motor neuron disease, based on the finding that its causal gene product, Seipin, is a protein that spans the ER membrane twice. Gain-of-function mutations of Seipin produce non-glycosylated Seipin (ngSeipin), which was previously shown to induce ER stress and apoptosis at both cell and mouse levels albeit with no clarified mechanism. We found that aggregation-prone ngSeipin dominantly inactivated SERCA2b, the major calcium pump in the ER, and decreased the calcium concentration in the ER, leading to ER stress and apoptosis in human colorectal carcinoma-derived cells (HCT116). This inactivation required oligomerization of ngSeipin and direct interaction of the C-terminus of ngSeipin with SERCA2b, and was observed in Seipin-deficient neuroblastoma (SH-SY5Y) cells expressing ngSeipin at an endogenous protein level. Our results thus provide a new direction to the controversy noted above

Collaborative causal inference on distributed data

The development of technologies for causal inference with the privacy preservation of distributed data has attracted considerable attention in recent years. To address this issue, we propose a data collaboration quasi-experiment (DC-QE) that enables causal inference from distributed data with privacy preservation. In our method, first, local parties construct dimensionality-reduced intermediate representations from the private data. Second, they share intermediate representations, instead of private data for privacy preservation. Third, propensity scores were estimated from the shared intermediate representations. Finally, the treatment effects were estimated from propensity scores. Our method can reduce both random errors and biases, whereas existing methods can only reduce random errors in the estimation of treatment effects. Through numerical experiments on both artificial and real-world data, we confirmed that our method can lead to better estimation results than individual analyses. Dimensionality-reduction loses some of the information in the private data and causes performance degradation. However, we observed that in the experiments, sharing intermediate representations with many parties to resolve the lack of subjects and covariates, our method improved performance enough to overcome the degradation caused by dimensionality-reduction. With the spread of our method, intermediate representations can be published as open data to help researchers find causalities and accumulated as a knowledge base.Comment: 14 pages, 4 figure

都市部女子大学生の栄養摂取状況の推移-半定量的食物摂取頻度調査票を用いた経時的栄養調査の結果-

This paper examines dietary intake over time. Subjects were 6 urban female university students aged 18-19. A diet survey was carried out 12 times between April 2008 and June 2009 at approximately monthly intervals. The subjects\u27 body weight, height were measured and their body mass index(BMI)was calculated each time they filled in Food Frequency Questionnaire Watanabe 65(FFQW65)and recorded all the food they had during the past one month. The researchers processed the data and calculated the estimated energy intakes, the amount of protein, fat and carbohydrate intakes. The estimated energy intakes were categorized and analyzed by food groups, total energy intakes per day, and the energy ingested at each meal. The data showed a significant reduction over time in average amounts of estimated total energy intake per day and estimated energy intake per meal. While the estimated energy intakes of grain, sugar, vegetables, sea food, oil and fat and miso declined significantly, estimated energy intakes of fruits and alcohol significantly increased. There was almost no change in the subjects\u27 average BMI during the entire survey. These results suggest that the trend of dietary intake during the survey was toward lower energy intake. In addition, the subjects tended to shift toward more quick-cooking cheaper materials, and yet, within these limited conditions they tried to consume a more balanced diet. For example, they ate more fruit when their intake of vegetables declined