SMA observations of C2H in High-Mass Star Forming Regions

C$_2$H is a representative hydrocarbon that is abundant and ubiquitous in the interstellar medium (ISM). To study its chemical properties, we present Submillimeter Array (SMA) observations of the C$_2$H $N=3-2$ and HC$_3$N $J=30-29$ transitions and the 1.1 mm continuum emission toward four OB cluster-forming regions, AFGL 490, ON 1, W33 Main, and G10.6-0.4, which cover a bolometric luminosity range of $\sim$10$^3$--10$^6$ $L_{\odot}$. We found that on large scales, the C$_2$H emission traces the dense molecular envelope. However, for all observed sources, the peaks of C$_2$H emission are offset by several times times 10$^4$ AU from the peaks of 1.1 mm continuum emission, where the most luminous stars are located. By comparing the distribution and profiles of C$_2$H hyperfine lines and the 1.1 mm continuum emission, we find that the C$_2$H column density (and abundance) around the 1.1 mm continuum peaks is lower than those in the ambient gas envelope. Chemical models suggest that C$_2$H might be transformed to other species owing to increased temperature and density; thus, its reduced abundance could be the signpost of the heated molecular gas in the $\sim$10$^4$ AU vicinity around the embedded high-mass stars. Our results support such theoretical prediction for centrally embedded $\sim10^3$--$10^6L_{\odot}$ OB star-forming cores, while future higher-resolution observations are required to examine the C$_2$H transformation around the localized sites of high-mass star formation.Comment: 10 pages, 6 figures. ApJ accepted. Comments welcom

Cofilin Activation in Peripheral CD4 T Cells of HIV-1 Infected Patients: A Pilot Study

Cofilin is an actin-depolymerizing factor that regulates actin dynamics critical for T cell migration and T cell activation. In unstimulated resting CD4 T cells, cofilin exists largely as a phosphorylated inactive form. Previously, we demonstrated that during HIV-1 infection of resting CD4 T cells, the viral envelope-CXCR4 signaling activates cofilin to overcome the static cortical actin restriction. In this pilot study, we have extended this in vitro observation and examined cofilin phosphorylation in resting CD4 T cells purified from the peripheral blood of HIV-1-infected patients. Here, we report that the resting T cells from infected patients carry significantly higher levels of active cofilin, suggesting that these resting cells have been primed in vivo in cofilin activity to facilitate HIV-1 infection. HIV-1-mediated aberrant activation of cofilin may also lead to abnormalities in T cell migration and activation that could contribute to viral pathogenesis.Department of Defense (National Defense Science and Engineering Fellowship); National Institute of Allergy and Infectious Diseases (AI069981

Comparison of capecitabine and tegafur/gimeracil/oteracil (S-1) in the treatment of advanced breast carcinoma in the elderly

Purpose: To analyse and compare the clinical effects and safety of capecitabine and tegafur/gimeracil/oteracil (S-1) in the treatment of advanced breast carcinoma.Methods: Eighty-four metastatic breast cancer elderly patients for whom first or second-line treatment had failed, were selected from among those admitted to the oncology ward of Binjiang People’s Hospital, China between January 2014 and June 2015. They were randomly divided into S-1 group (n =41) and capecitabine group (n = 41) and received varying doses of those drugs  according to body surface area. Clinical effects, progression-free survival, and incidence of adverse reactions were compared for the two groups following treatment.Results: Disease control rate (CR) in S-1 group was 55.6 %, much higher than 35.1 % observed for capecitabine group (p < 0.05). The disease control rate for the S-1 group was 93.7 %, also much higher than the 70.6 % found in capecitabine group. Survival analysis showed that the median survival times of the two groups did not differ significantly (p > 0.05). Furthermore, some adverse reactions such as myelosuppression and lack of strength, did not differ significantly between the two groups (p > 0.05), whereas others, including leukopenia, nausea and vomiting and hand-foot syndrome were more serious and frequent in capecitabine group than in S-1 group (p < 0.05).Conclusion: Monotherapy with S-1 is more effective than that with capecitabine. Adverse reactions are minimal for both drugs.Keywords: Breast carcinoma, Capecitabine, S-1, Adverse reactions,  Myelosuppression, Leukopenia, Hand-foot syndrom

AZI23'UTR Is a New SLC6A3 Downregulator Associated with an Epistatic Protection Against Substance Use Disorders

Regulated activity of SLC6A3, which encodes the human dopamine transporter (DAT), contributes to diseases such as substance abuse disorders (SUDs); however, the exact transcription mechanism remains poorly understood. Here, we used a common genetic variant of the gene, intron 1 DNP1B sequence, as bait to screen and clone a new transcriptional activity, AZI23'UTR, for SLC6A3. AZI23'UTR is a 3' untranslated region (3'UTR) of the human 5-Azacytidine Induced 2 gene (AZI2) but appeared to be transcribed independently of AZI2. Found to be present in both human cell nuclei and dopamine neurons, this RNA was shown to downregulate promoter activity through a variant-dependent mechanism in vitro. Both reduced RNA density ratio of AZI23'UTR/AZI2 and increased DAT mRNA levels were found in ethanol-naive alcohol-preferring rats. Secondary analysis of dbGaP GWAS datasets (Genome-Wide Association Studies based on the database of Genotypes and Phenotypes) revealed significant interactions between regions upstream of AZI23'UTR and SLC6A3 in SUDs. Jointly, our data suggest that AZI23'UTR confers variant-dependent transcriptional regulation of SLC6A3, a potential risk factor for SUDs

Effect of deletion of the rgpA gene on selected virulence of Porphyromonas gingivalis

AbstractBackground/purposeThe most potent virulence factors of the periodontal pathogen Porphyromonas gingivalis are gingipains, three cysteine proteases (RgpA, RgpB, and Kgp) that bind and cleave a wide range of host proteins. Considerable proof indicates that RgpA contributes to the entire virulence of the organism and increases the risk of periodontal disease by disrupting the host immune defense and destroying the host tissue. However, the functional significance of this proteinase is incompletely understood. It is important to analyze the effect of arginine-specific gingipain A gene (rgpA) on selected virulence and physiological properties of P. gingivalis.Materials and methodsElectroporation and homologous recombination were used to construct an rgpA mutant of P. gingivalis ATCC33277. The mutant was verified by polymerase chain reaction and sodium dodecyl sulfate–polyacrylamide gel electrophoresis. Cell structures of the mutant were examined by transmission electron microscopy and homotypic biofilm formation was examined by confocal laser scanning microscopy.ResultsGene analysis revealed that the rgpA gene was deleted and replaced by a drug resistance gene marker. The defect of the gene resulted in a complete loss of RgpA proteinase, a reduction of out membrane vesicles and hemagglutination, and an increase in homotypic biofilm formation.ConclusionOur data indicate that an rgpA gene deficient strain of P. gingivalis is successfully isolated. RgpA may have a variety of physiological and pathological roles in P. gingivalis