Phosphorylation of Chk1 by ATM- and Rad3-related (ATR) in Xenopus Egg Extracts Requires Binding of ATRIP to ATR but Not the Stable DNA-binding or Coiled-coil Domains of ATRIP

ATR, a critical regulator of DNA replication and damage checkpoint responses, possesses a binding partner called ATRIP. We have studied the functional properties of Xenopus ATR and ATRIP in incubations with purified components and in frog egg extracts. In purified systems, ATRIP associates with DNA in both RPA-dependent and RPA-independent manners, depending on the composition of the template. However, in egg extracts, only the RPA-dependent mode of binding to DNA can be detected. ATRIP adopts an oligomeric state in egg extracts that depends upon binding to ATR. In addition, ATR and ATRIP are mutually dependent on one another for stable binding to DNA in egg extracts. The ATR-dependent oligomerization of ATRIP does not require an intact coiled-coil domain in ATRIP and does not change in the presence of checkpoint-inducing DNA templates. Egg extracts containing a mutant of ATRIP that cannot bind to ATR are defective in the phosphorylation of Chk1. However, extracts containing mutants of ATRIP lacking stable DNA-binding and coiled-coil domains show no reduction in the phosphorylation of Chk1 in response to defined DNA templates. Furthermore, activation of Chk1 does not depend upon RPA under these conditions. These results suggest that ATRIP must associate with ATR in order for ATR to carry out the phosphorylation of Chk1 effectively. However, this function of ATRIP does not involve its ability to mediate the stable binding of ATR to defined checkpoint-inducing DNA templates in egg extracts, does not require an intact coiled-coil domain, and does not depend on RPA

Notch1 intracellular domain suppresses APP intracellular domain—Tip60–Fe65 complex mediated signaling through physical interaction

AbstractThe amyloid beta-precursor protein (APP) and the Notch receptor are both type 1 integral transmembrane proteins, and both are cleaved by presenilin-dependent gamma-secretase activity. In this study, we have demonstrated that the Notch intracellular domain (Notch1-IC) suppresses APP-intracellular domain (AICD)-mediated ROS generation and cell death after being processed by gamma secretase. Notch1-IC physically interacts with AICD, Fe65, and Tip60, thereby disrupting the association of the AICD–Fe65–Tip60 trimeric transcription activator complex in AICD signaling. AICD–Fe65–Tip60 mediated reactive oxygen species generation was found to be suppressed by Notch1-IC. Furthermore, AICD–Fe65–Tip60 was shown to mediate cell death in human neuroblastoma cells, and the overexpression of Notch1-IC inhibited cell death induced by AICD–Fe65–Tip60. Collectively, our findings indicate that Notch1-IC plays the role of a negative regulator in AICD signaling via the disruption of the AICD–Fe65–Tip60 trimeric complex

Endoplasmic Reticulum Stress and Insulin Biosynthesis: A Review

Insulin resistance and pancreatic beta cell dysfunction are major contributors to the pathogenesis of diabetes. Various conditions play a role in the pathogenesis of pancreatic beta cell dysfunction and are correlated with endoplasmic reticulum (ER) stress. Pancreatic beta cells are susceptible to ER stress. Many studies have shown that increased ER stress induces pancreatic beta cell dysfunction and diabetes mellitus using genetic models of ER stress and by various stimuli. There are many reports indicating that ER stress plays an important role in the impairment of insulin biosynthesis, suggesting that reduction of ER stress could be a therapeutic target for diabetes. In this paper, we reviewed the relationship between ER stress and diabetes and how ER stress controls insulin biosynthesis

Gene Expression Profiles are Altered in Human Papillomavirus-16 E6 D25E-Expressing Cell Lines

Previously, we have reported that the human papillomavirus (HPV) type 16 E6 D25E is the most prevalent variant in Korean women at high risk for cervical cancers. Several studies have identified an association between the increased frequency of this variant and the elevated risk of cervical intraepithelial neoplasia and invasive cervical carcinoma. To investigate whether the HPV-16 E6 D25E variant might influence cervical cancer progression, we used an oligonucleotide microarray approach to identify transcriptionally altered gene expression patterns in recombinant wild-type E6 or E6 D25E variant-expressing HPV-negative cancer cells. We found that 211 genes were significantly up- or down-regulated (at least 1.5-fold, p < 0.05). We identified 14 genes, nine down-regulated and five up-regulated upon E6 D25E expression, compared with wild-type E6 expression. These results further emphasize the unique biological activity of the HPV-16 E6 D25E variant

Synergistic Uric Acid-Lowering Effects of the Combination of Chrysanthemum indicum

Chrysanthemum indicum Linne flower (CF) and Cinnamomum cassia (L.) J. Persl bark (CB) extracts have served as the main ingredients in several prescriptions designed to treat hyperuricemia and gout in traditional Chinese and Korean medicine. However, little is known about the combination effects of a CF and CB (CC) mixture on hyperuricemia. In our study, we investigated the antihyperuricemic effects of CC mixture and the mechanisms underlying these effects in normal and potassium oxonate- (PO-) induced hyperuricemic rats. The CC mixture significantly decreased uric acid levels in normal and PO-induced hyperuricemic rats and showed the enhanced hypouricemic effect compared to CF or CB alone. Furthermore, the CC mixture increased renal uric acid excretion in PO-induced hyperuricemic rat. We found that CC mixture and its major components, chlorogenic acid, 3,4-dicaffeoylquinic acid (isochlorogenic acid), coumarin, cinnamaldehyde, trans-cinnamic acid, and o-methoxycinnamaldehyde, inhibit the activity of xanthine oxidase (XOD) in vitro. The CC mixture exerts antihyperuricemic effects accompanied partially by XOD activity inhibition. Therefore, the CC mixture may have potential as a treatment for hyperuricemia and gout

A Study on Apparel Design for Chiropractic Training

In severe cases of spinal misalignment due to wrong back posture during adolescence or focusing on work, modern people can have back pain. Such a symptom is commonly referred to as scoliosis and it already became one of the lifestyle diseases. Hence, the purpose of the present study was to develop a functional musculoskeletal correction wear that can help with maintaining a correct posture by relaxing tonic muscles and maximizing the tension of the relaxed muscle using the principle of sports taping. Market research for design development was conducted at department stores and specialty road shops separately. Department stores were visited on weekdays when the store is not crowded, and specialty road shops were visited at around three o’clock on weekdays after checking their opening, lunch, and closing times. Since the apparel should not interfere with exercise movements while maintaining the body shape, the survey was carried out mostly on yoga and lifestyle training apparel focusing on elasticity and percentage of blending fiber. A camera and audio recorder were prepared and took pictures of clothing tags that show the ratio of polyester and spandex while trying on and checking products at the stores. Data were collected by asking the staff at road specialty shops who has more professional knowledge about the advantages and functions of the existing products and recording their answers. Point color schemes in black color family in which body shapes can look beautiful were mostly checked. Due to the design characteristics that have to maintain the spine, the designs of all-in-one products that can maintain the upper and lower torsos were checked at underwear stores. The existing products were evaluated for their designs to be adopted including the material, integrated into the new design, and then modified and supplemented, and the following chiropractic apparel design was drawn (Table 1). An all-in-one design that wraps around the hips and upper thighs for easy counterbalancing between the upper and lower body was chosen. A design with an accent line that makes body shape looks beautiful and Used compression wear material that is comfortable for activities and presses tight against the skin. Activates the muscle activities of latissimus dorsi muscle using taping method, and provides tension to maintain correct posture of round back and shoulders. In conclusion, prevention, exercise, and stretching are important for scoliosis and sound posture for the loin should be constantly maintained. To that end, not only the proper use of chairs but also apparel that is worn all the time can be helpful

anti-9,10-Di(1-naphth­yl)anthracene pyridine disolvate

In the title compound, C34H22·2C5H5N, there is a crystallographic inversion center in the middle of the anthracene ring system. The dihedral angle between the mean planes of the anthracene and naphthalene ring systems is 83.96 (4)°. The crystal structure is stabilized by weak inter­molecular C—H⋯N and C—H⋯π inter­actions