HnRNPA1 interacts with G-quadruplex in the TRA2B promoter and stimulates its transcription in human colon cancer cells

The human TRA2B gene consists of 10 exons and 9 introns and produces 5 splice isoforms (TRA2β1 to TRA2β5). TRA2B exon 2 encodes multiple premature termination codons. TRA2β1 lacks exon 2 and is translated into a functional transformer 2β (Tra2β) protein, whereas TRA2β4 contains 10 exons and works as a functional RNA. Overexpressed Tra2β and ectopic expression of TRA2β4 may be oncogenic. We found that heterogeneous nuclear ribonucleoprotein (hnRNP)A1 and hnRNPU interacted with TRA2β4 exon 2. Minigene assays revealed that hnRNPA1 facilitated inclusion of exon 2, whereas hnRNPU promoted its skipping. However, knockdown of hnRNPA1 or hnRNPU reduced both TRA2β1 and TRA2β4 levels, and overexpression of these hnRNPs increased levels of both isoforms, suggesting that hnRNPA1 and hnRNPU mainly regulate the transcription of TRA2B. In fact, hnRNPA1 and hnRNPU positively regulated the promoter activity of TRA2B. Circular dichroism analyses, electrophoretic mobility shift assays and chromatin immunoprecipitation assays demonstrated the presence of G-quadruplex (G4) formation in the promoter of TRA2B. Formation of G4 suppressed TRA2B transcription, whereas hnRNPA1, but not hnRNPU, interacted with the G4 to facilitate transcription. Our results suggest that hnRNPA1 may modulate TRA2B transcription through its regulation of G4 formation in its promoter in colon cancer cells

Ultra-high temperature Soret effect in a silicate melt: SiO2 migration to cold side

The Soret effect, temperature gradient driven diffusion, in silicate melts has been investigated intensively in the earth sciences from the 1980s. The SiO2 component is generally concentrated in the hotter region of silicate melts under a temperature gradient. Here, we report that at ultra-high temperatures above approximately 3000 K, SiO2 becomes concentrated in the colder region of the silicate melts under a temperature gradient. The interior of an aluminosilicate glass (63.3SiO2-16.3Al2O3-20.4CaO(mol%)) was irradiated with a 250 kHz femtosecond laser pulse for local heating. SiO2 migrated to the colder region during irradiation with an 800 pulse (3.2 ms irradiation). The temperature analysis indicated that migration to the colder region occurred above 3060 K. In the non-equilibrium molecular dynamics (NEMD) simulation, SiO2 migrated to the colder region under a temperature gradient, which had an average temperature of 4000 K; this result supports the experimental result. SiO2 exhibited a tendency to migrate to the colder region at 2400 K in both the NEMD and experimental study. The second-order like phase transition was observed at ~ 2000-3400 K when calculated using MD without a temperature gradient. Therefore, the second-order phase transition could be related to the migration of SiO2 to colder region. However, the detailed mechanism has not been elucidated

TRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in mice

Excess production of reactive oxygen species (ROS) caused by hyperglycemia is a major risk factor for heart failure. We previously reported that transient receptor potential canonical 3 (TRPC3) channel mediates pressure overload-induced maladaptive cardiac fibrosis by forming stably functional complex with NADPH oxidase 2 (Nox2). Although TRPC3 has been long suggested to form hetero-multimer channels with TRPC6 and function as diacylglycerol-activated cation channels coordinately, the role of TRPC6 in heart is still obscure. We here demonstrated that deletion of TRPC6 had no impact on pressure overload-induced heart failure despite inhibiting interstitial fibrosis in mice. TRPC6-deficient mouse hearts 1 week after transverse aortic constriction showed comparable increases in fibrotic gene expressions and ROS production but promoted inductions of inflammatory cytokines, compared to wild type hearts. Treatment of TRPC6-deficient mice with streptozotocin caused severe reduction of cardiac contractility with enhancing urinary and cardiac lipid peroxide levels, compared to wild type and TRPC3-deficient mice. Knockdown of TRPC6, but not TRPC3, enhanced basal expression levels of cytokines in rat cardiomyocytes. TRPC6 could interact with Nox2, but the abundance of TRPC6 was inversely correlated with that of Nox2. These results strongly suggest that Nox2 destabilization through disrupting TRPC3-Nox2 complex underlies attenuation of hyperglycemia-induced heart failure by TRPC6.Fil: Oda, Sayaka. Okazaki Institute for Integrative Bioscience; Japón. SOKENDAI; JapónFil: Numaga Tomita, Takuro. Okazaki Institute for Integrative Bioscience; Japón. SOKENDAI; JapónFil: Kitajima, Naoyuki. Okazaki Institute for Integrative Bioscience; Japón. Kyushu University; JapónFil: Tomizaki, Takashi. Okazaki Institute for Integrative Bioscience; Japón. Kyushu University; Japón. University of Tsukuba; JapónFil: Harada, Eri. Ajinomoto Co.; Japón. EA Pharma Co.; JapónFil: Shimauchi, Tsukasa. Okazaki Institute for Integrative Bioscience; Japón. Kyushu University; JapónFil: Nishimura, Akiyuki. Okazaki Institute for Integrative Bioscience; Japón. SOKENDAI; Japón. Ajinomoto Co.; JapónFil: Ishikawa, Tatsuya. Kyushu University; Japón. Ajinomoto Co.; Japón. EA Pharma Co.; JapónFil: Kumagai, Yoshito. University of Tsukuba; JapónFil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Nishida, Motohiro. Okazaki Institute for Integrative Bioscience; Japón. SOKENDAI; Japón. Kyushu University; Japón. PRESTO; Japó

The Possibility of Analyzing the "Situational Self" with Language

In this paper, we consider the "Self" constructed by the interaction between ourselves and situations. We use the term "Situational Self" in this sense. First, we briefly review some traditional theories of "Self". Most traditional theories of "Self" have regarded the "Self" as on entity. According to these theories, situations around us influence the Self from the outside. Second, we explain the "Situational Self". Contrary to traditional theories, the "Situational Self" can be regarded as the product of social construction. "Social Constructionism" also gives attention to such construction. From the aspect of this epistemology, the "Self" must depend on the individual\u27s situation. We can define our "Self" only in the social context. Potter & Wetherell (1987) suggested that this kind of Self can be grasped by analyzing the written and spoken language used by the individual. We introduce "Protocol Analysis" and "Discourse Analysis" as appropriate analytical tools. Lastly, we analyze two kinds of discourse, one is from Reicher and Potter\u27s research of the riot of St Pauls, and the other is reports which were written by three university students. Through these analyses, we can exemplify the possibility of analyzing the "Situational Self" with language

VLBI Astrometry of the Semiregular Variable RX Bootis

We present distance measurement of the semiregular variable RX Bootis (RX Boo) with its annual parallax. Using the unique dual-beam system of the VLBI Exploration of Radio Astrometry (VERA) telescope, we conducted astrometric observations of a water maser spot accompanying RX Boo referred to the quasar J1419+2706 separated by 1.69 degrees from RX Boo. We have measured the annual parallax of RX Boo to be 7.31 +/- 0.50 mas, corresponding to a distance of 136 +10/-9 pc, from the one-year monitoring observation data of one maser spot at VLSR = 3.2 km/s. The distance itself is consistent with the one obtained with Hipparcos. The distance uncertainty is reduced by a factor of two, allowing us to determine the stellar properties more accurately. Using our distance, we discuss the location of RX Boo in various sequences of Period-Luminosity (PL) relations. We found RX Boo is located in the Mira sequence of PL relation. In addition, we calculated the radius of photosphere and the mass limitation of RX Boo and discussed its evolutionary status.Comment: 8 pages, 4figure

Zinc Supplementation with Polaprezinc Protects Mouse Hepatocytes against Acetaminophen-Induced Toxicity via Induction of Heat Shock Protein 70

Polaprezinc, a chelate compound consisting of zinc and l-carnosine, is clinically used as a medicine for gastric ulcers. It has been shown that induction of heat shock protein (HSP) is involved in protective effects of polaprezinc against gastric mucosal injury. In the present study, we investigated whether polaprezinc and its components could induce HSP70 and prevent acetaminophen (APAP) toxicity in mouse primary cultured hepatocytes. Hepatocytes were treated with polaprezinc, zinc sulfate or l-carnosine at the concentration of 100 µM for 9 h, and then exposed to 10 mM APAP. Polaprezinc or zinc sulfate increased cellular HSP70 expression. However, l-carnosine had no influence on it. Pretreatment of the cells with polaprezinc or zinc sulfate significantly suppressed cell death as well as cellular lipid peroxidation after APAP treatment. In contrast, pretreatment with polaprezinc did not affect decrease in intracellular glutathione after APAP. Furthermore, treatment with KNK437, an HSP inhibitor, attenuated increase in HSP70 expression induced by polaprezinc, and abolished protective effect of polaprezinc on cell death after APAP. These results suggested that polaprezinc, in particular its zinc component, induces HSP70 expression in mouse primary cultured hepatocytes, and inhibits lipid peroxidation after APAP treatment, resulting in protection against APAP toxicity

Protection by Exogenously Added Coenzyme Q9 against Free Radical-Induced Injuries in Human Liver Cells

Reduced coenzyme Q10 (CoQ10H2) is known as a potent antioxidant in biological systems. However, it is not yet known whether CoQ9H2 could act as an antioxidant in human cells. The aim of this study is to assess whether exogenously added CoQ9 can protect human liver cells against injuries induced by a water-soluble radical initiator, 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) and a lipid-soluble radical initiator, 2,2'-azobis(2,4-dimethylvaleronitrile) (AMVN). CoQ9-enriched cells were obtained by treatment of HepG2 cells with 10 µM CoQ9 liposomes for 24 h. CoQ9-enriched cells were exposed to 10 mM AAPH and 500 µM AMVN over 4 h and 24 h, respectively. The loss of viability after treatment with AAPH or AMVN was much less in CoQ9-enriched cells than in naive HepG2 cells. The decrease in glutathione and the increase in thiobarbituric acid-reactive substance after treatment with AAPH or AMVN were also suppressed in CoQ9-enriched cells. The incubation of CoQ9-enriched cells with AAPH or AMVN led to a decrease in cellular CoQ9H2 and reciprocal increase in cellular CoQ9 resulting from its antioxidant function. Taken together, it was demonstrated for the first time that exogenously added CoQ9 could prevent oxidative stress-mediated damage to human cells by virtue of its antioxidant activity

RNA Binding Proteins and Genome Integrity

Genome integrity can be threatened by various endogenous or exogenous events. To counteract these stressors, the DNA damage response network contributes to the prevention and/or repair of genomic DNA damage and serves an essential function in cellular survival. DNA binding proteins are involved in this network. Recently, several RNA-binding proteins (RBPs) that are recruited to DNA damage sites have been shown to be direct players in the prevention or repair of DNA damage. In addition, non-coding RNAs, themselves, are involved in the RNA-mediated DNA repair system. Furthermore, RNA modification such as m6A methylation might also contribute to the ultraviolet-responsive DNA damage response. Accumulating evidence suggests that RNA metabolism is more deeply involved in diverse cellular functions than previously expected, and is also intricately associated with the maintenance of genome integrity. In this review, we highlight the roles of RBPs in the maintenance of genome integrity

GGA and leptin secretion

Geranylgeranylacetone (GGA) is a chaperon inducer that protects various types of cell and tissue against stress. We examined whether GGA modulated energy intake and expenditure under stressful conditions. After mice were untreated or treated orally with GGA (0.16 g per kg body weight per day) for 10 days, they were subjected to 2-h restraint stress once or once a day for 5 consecutive days. GGA administration did not affect corticosterone response to the stress. Restraint stress rapidly decreased plasma leptin levels in control mice. GGA significantly increased circulating leptin levels without changing food intake and prevented the stress-induced decline of circulating leptin. However GGA-treated mice significantly reduced food intake during the repeated stress, compared with control mice. GGA prevented the stress-induced decline of leptin mRNA and its protein levels in epidydimal adipose tissues. We also found that GGA decreased ghrelin mRNA expression in gastric mucosa before the stress, whereas GGA-treated mice recovered the ghrelin mRNA expression to the baseline level after the repeated stress. Leptin and ghrelin are now recognized as regulators of anxiety and depressive mood. Our results suggest that GGA may regulate food intake and relief stress-induced mood disturbance through regulating leptin and ghrelin secretions