On the Star Class Group of a Pullback

For the domain $R$ arising from the construction $T, M,D$, we relate the star class groups of $R$ to those of $T$ and $D$. More precisely, let $T$ be an integral domain, $M$ a nonzero maximal ideal of $T$, $D$ a proper subring of $k:=T/M$, $\phi: T\to k$ the natural projection, and let $R={\phi}^{-1}(D)$. For each star operation $\ast$ on $R$, we define the star operation $\ast_\phi$ on $D$, i.e., the ``projection'' of $\ast$ under $\phi$, and the star operation ${(\ast)}_{_{T}}$ on $T$, i.e., the ``extension'' of $\ast$ to $T$. Then we show that, under a mild hypothesis on the group of units of $T$, if $\ast$ is a star operation of finite type, 0\to \Cl^{\ast_{\phi}}(D) \to \Cl^\ast(R) \to \Cl^{{(\ast)}_{_{T}}}(T)\to 0 is split exact. In particular, when $\ast = t_{R}$, we deduce that the sequence 0\to \Cl^{t_{D}}(D) {\to} \Cl^{t_{R}}(R) {\to}\Cl^{(t_{R})_{_{T}}}(T) \to 0 is split exact. The relation between ${(t_{R})_{_{T}}}$ and $t_{T}$ (and between \Cl^{(t_{R})_{_{T}}}(T) and \Cl^{t_{T}}(T)) is also investigated.Comment: J. Algebra (to appear

Polynomial extensions of semistar operations

We provide a complete solution to the problem of extending arbitrary semistar operations of an integral domain $D$ to semistar operations of the polynomial ring $D[X]$. As an application, we show that one can reobtain the main results of some previous papers concerning the problem in the special cases of stable semistar operations of finite type or semistar operations defined by families of overrings. Finally, we investigate the behavior of the polynomial extensions of the most important and classical operations such as $d_D$, $v_D$, $t_D$, $w_D$ and $b_D$ operations

Susceptibility to Oxidative Stress is Greater in Korean Patients with Coronary Artery Disease than Healthy Subjects

There are some evidences that the increased oxidative stress and thus increased oxidizability of lipoproteins and DNA can contribute to the development of certain human diseases, such as cardiovascular disease. To confirm the association of DNA damage with cardiovascular disease, we investigated susceptibility of DNA to oxidation in lymphocytes and oxidative stress related parameters in blood of patients with coronary artery disease (CAD). Subjects were consisted of 42 patients (27 men, 15 women) with documented CAD and 49 apparently healthy subjects (33 men, 16 women) as controls. Cellular DNA damage induced by 100 µM H2O2 was measured using Comet assay and quantified by TL. There were no differences in age (61.4 ± 1.7 years vs 62.0 ± 2.2 years) between the two groups. All the findings were shown to be independent of either sex or smoking habit. The patients showed significantly higher TL (87.3 ± 1.6 µm) compared to the control (79.3 ± 1.7 µm, p<0.01). Plasma TRAP, vitamin C, γ-tocopherol, and α-carotene levels in patients group were lower than those of control groups, while erythrocytic catalase activity increased in patients group. In conclusion, we observed that reduced overall antioxidant status was closely connected to higher susceptibility of DNA damage in CAD patients

Sargassum fulvellum

Ultraviolet (UV) radiation has been reported to induce cutaneous inflammation such as erythema and edema via induction of proinflammatory enzymes and mediators. Sargassum fulvellum is a brown alga of Sargassaceae family which has been demonstrated to exhibit antipyretic, analgesic, antiedema, antioxidant, antitumor, fibrinolytic, and hepatoprotective activities. The purpose of this study is to investigate anti-inflammatory effects of ethylacetate fraction of ethanol extract of Sargassum fulvellum (SFE-EtOAc) in HaCaT keratinocytes and BALB/c mice. In HaCaT cells, SFE-EtOAc effectively inhibited UVB-induced cytotoxicity (60 mJ/cm2) and the expression of proinflammatory proteins such as cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS). Furthermore, SFE-EtOAc significantly reduced UVB-induced production of proinflammatory mediators including prostaglandin E2 (PGE2) and nitric oxide (NO). In BALB/c mice, topical application of SFE-EtOAc prior to UVB irradiation (200 mJ/cm2) effectively suppressed the UVB-induced protein expression of COX-2, iNOS, and TNF-α and subsequently attenuated generation of PGE2 and NO as well. In another experiment, SFE-EtOAc pretreatment suppressed UVB-induced reactive oxygen species production and exhibited an antioxidant potential by upregulation of antioxidant enzymes such as catalase and Cu/Zn-superoxide dismutase in HaCaT cells. These results suggest that SFE-EtOAc could be an effective anti-inflammatory agent protecting against UVB irradiation-induced skin damages

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

A lab-on-a-disc platform enables serial monitoring of individual CTCs associated with tumor progression during EGFR-targeted therapy for patients with NSCLC

Rationale: Unlike traditional biopsy, liquid biopsy, which is a largely non-invasive diagnostic and monitoring tool, can be performed more frequently to better track tumors and mutations over time and to validate the efficiency of a cancer treatment. Circulating tumor cells (CTCs) are considered promising liquid biopsy biomarkers; however, their use in clinical settings is limited by high costs and a low throughput of standard platforms for CTC enumeration and analysis. In this study, we used a label-free, high-throughput method for CTC isolation directly from whole blood of patients using a standalone, clinical setting-friendly platform. Methods: A CTC-based liquid biopsy approach was used to examine the efficacy of therapy and emergent drug resistance via longitudinal monitoring of CTC counts, DNA mutations, and single-cell-level gene expression in a prospective cohort of 40 patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. Results: The change ratio of the CTC counts was associated with tumor response, detected by CT scan, while the baseline CTC counts did not show association with progression-free survival or overall survival. We achieved a 100% concordance rate for the detection of EGFR mutation, including emergence of T790M, between tumor tissue and CTCs. More importantly, our data revealed the importance of the analysis of the epithelial/mesenchymal signature of individual pretreatment CTCs to predict drug responsiveness in patients. Conclusion: The fluid-assisted separation technology disc platform enables serial monitoring of CTC counts, DNA mutations, as well as unbiased molecular characterization of individual CTCs associated with tumor progression during targeted therapy

Characterization of Fabry mice treated with recombinant adeno-associated virus 2/8-mediated gene transfer

<p>Abstract</p> <p>Background</p> <p>Enzyme replacement therapy (ERT) with α-galactosidase A (α-Gal A) is currently the most effective therapeutic strategy for patients with Fabry disease, a lysosomal storage disease. However, ERT has limitations of a short half-life, requirement for frequent administration, and limited efficacy for patients with renal failure. Therefore, we investigated the efficacy of recombinant adeno-associated virus (rAAV) vector-mediated gene therapy for a Fabry disease mouse model and compared it with that of ERT.</p> <p>Methods</p> <p>A pseudotyped rAAV2/8 vector encoding α-Gal A cDNA (rAAV2/8-hAGA) was prepared and injected into 18-week-old male Fabry mice through the tail vein. The α-Gal A expression level and globotriaosylceramide (Gb3) levels in the Fabry mice were examined and compared with Fabry mice with ERT. Immunohistochemical and ultrastructural studies were conducted.</p> <p>Results</p> <p>Treatment of Fabry mice with rAAV2/8-hAGA resulted in the clearance of accumulated Gb3 in tissues such as liver, spleen, kidney, heart, and brain with concomitant elevation of α-Gal A enzyme activity. Enzyme activity was elevated for up to 60 weeks. In addition, expression of the α-Gal A protein was identified in the presence of rAAV2/8-hAGA at 6, 12, and 24 weeks after treatment. α-Gal A activity was significantly higher in the mice treated with rAAV2/8-hAGA than in Fabry mice that received ERT. Along with higher α-Gal A activity in the kidney of the Fabry mice treated with gene therapy, immunohistochemical studies showed more α-Gal A expression in the proximal tubules and glomerulus, and less Gb3 deposition in Fabry mice treated with this gene therapy than in mice given ERT. The α-gal A gene transfer significantly reduced the accumulation of Gb3 in the tubules and podocytes of the kidney. Electron microscopic analysis of the kidneys of Fabry mice also showed that gene therapy was more effective than ERT.</p> <p>Conclusions</p> <p>The rAAV2/8-hAGA mediated α-Gal A gene therapy provided improved efficiency over ERT in the Fabry disease mouse model. Furthermore, rAAV2/8-hAGA-mediated expression showed a greater effect in the kidney than ERT.</p