Sp1 elements in SULT2B1b promoter and 5′-untranslated region of mRNA: Sp1/Sp2 induction and augmentation by histone deacetylase inhibition

AbstractThe steroid/sterol sulfotransferase gene (SULT2B1) encodes for two isozymes of which one (SULT2B1b) sulfonates cholesterol and is selectively expressed in skin. The human SULT2B1 gene contains neither a TATAAA nor a CCAAT motif upstream of the coding region for SULT2B1b; however, this area is GC-rich. Of five Sp1 elements identified two had regulatory activity utilizing immortalized human keratinocytes: one element is located above the ostensible transcription initiation site, whereas the other is located within the 5′-untranslated region of the SULT2B1b mRNA. Sp1 and Sp2 transcription factors identified by supershift analyses induced reporter gene activity, an effect markedly augmented by histone deacetylase inhibition

Interstellar Bubbles in Two Young H II Regions

peer reviewedMassive stars are expected to produce wind-blown bubbles in the interstellar medium; however, ring nebulae, suggesting the existence of bubbles, are rarely seen around main-sequence O stars. To search for wind-blown bubbles around main-sequence O stars, we have obtained high-resolution Hubble Space Telescope WFPC2 images and high-dispersion echelle spectra of two pristine H II regions, N11B and N180B, in the Large Magellanic Cloud. These H II regions are ionized by OB associations that still contain O3 stars, suggesting that the H II regions are young and have not hosted any supernova explosions. Our observations show that wind-blown bubbles in these H II regions can be detected kinematically, but not morphologically, because their expansion velocities are comparable to or only slightly higher than the isothermal sound velocity in the H II regions. Bubbles are detected around concentrations of massive stars, individual O stars, and even an evolved red supergiant (a fossil bubble). Comparisons between the observed bubble dynamics and model predictions show a large discrepancy (1-2 orders of magnitude) between the stellar wind luminosity derived from bubble observations and models and that derived from observations of stellar winds. The number and distribution of bubbles in N11B differ from those in N180B, which can be explained by the difference in the richness of stellar content between these two H II regions. Most of the bubbles observed in N11B and N180B show a blister structure, indicating that the stars were formed on the surfaces of dense clouds. Numerous small dust clouds, similar to Bok globules or elephant trunks, are detected in these H II regions, and at least one of them hosts on-going star formation

Intellectual property rights, technical progress and the volatility of economic growth

In this note, we analyze the effects of intellectual property rights on the volatility of economic growth. Our analysis is motivated by the observation that the strengthening of patent protection and the increase in R&D in the US coincide with a reduction in growth volatility beginning in the mid 1980’s. To analyze this phenomenon, we develop an R&D-based growth model with aggregate uncertainty in the innovation process and apply the model to ask whether increasing patent strength and R&D can lead to a significant reduction in growth volatility. We find a small but non-negligible effect that explains no less than 10% of the observed reduction in growth volatility in the US

Coupled evolution of nitrogen cycling and redoxcline dynamics on the Yangtze Block across the Ediacaran-Cambrian transition

The authors acknowledge funding support from the NSF FESD and Earth-Life Transitions programs (T.L.), the NASA Astrobiology Institute under Cooperative Agreement No. NNA15BB03A issued through the Science Mission Directorate (T.L.), the key project of the Natural Science Foundation of China (C.-F.C.) (No. 41730424), and the program of China Scholarships Council (Y.C.) (No. 201504910582). Nitrogen and carbon isotope analyses were funded by startup funds from Virginia Tech to B.C.G.The Ediacaran-Cambrian transition is characterized by the evolution of complex eukaryotes and rapid diversification of metazoans. However, linkages between environmental triggers and evolutionary patterns remain unclear. Here, we present high-resolution records of carbon and nitrogen isotopic data (δ13C, δ15N) for a drill core extending from the early Ediacaran Doushantuo Formation to the early Cambrian Jiumenchong Formation, located on the slope of the Yangtze Block. Our data show that sedimentary bulk nitrogen isotope values (δ15Nbulk) decrease progressively from the early Ediacaran to the early Cambrian, broadly concurrent with nitrogen isotope data from other sections throughout the Yangtze Block. During the early Ediacaran, however, δ15Nbulk values from our study are higher (maximum 11.2‰) compared to those from more restricted coeval sections, suggesting a higher degree of denitrification in our slope section. The early Ediacaran δ15Nbulk data from the Yangtze Block may thus provide indirect evidence for an upwelling system that led to a shallower redoxcline in slope environments of the Upper Yangtze region. Widespread light δ15Nbulk values from the early Cambrian (minimum −7.5‰) paired with excess silicate-bound nitrogen throughout much of the Yangtze Block are most parsimoniously interpreted as non-quantitative assimilation of ammonium (NH4+) with relatively high concentrations of NH4+ accumulating in the deep basin. Overall, the spatial and temporal trends in nitrogen cycling across the Yangtze Block suggest that fixed nitrogen was more bioavailable in the Ediacaran-Cambrian Yangtze Basin compared to previously studied Mesoproterozoic sections, although nitrogen speciation in the photic zone may have varied with time. Environmental factors such as oxygen levels and nitrogen bioavailability may have shaped the evolutionary trajectory of life on the Yangtze Block and potentially elsewhere across the Ediacaran-Cambrian transition.PostprintPeer reviewe

Investigating the uses of corporate reputation and its effects on brand segmentation, brand differentiation and brand positioning: evidence from the Taiwanese pharmaceutical industry

This study advances current knowledge on building a brand strategy that includes corporate reputation. It employs three theories – value creation, strategic resources and corporate communication – to study the uses of corporate reputation and its effect on brand segmentation, brand differentiation and brand positioning. In the context of the Taiwanese pharmaceutical industry, a sequential mixed method approach is applied and data are analyzed using PLS SEM. Findings demonstrate the relative impacts of three uses of corporate reputation (value creation, strategic resources and corporate communication) on brand image strategy (brand segmentation, brand differentiation and brand positioning) and the implications are evaluated. This study discovers that the inclusion of medicine prices is necessary and that it negatively moderates the impact of the overall uses of corporate reputation on overall brand image strategy. This research contributes empirically as one of the few that tests reputation-and-branding-building models outside the USA and Europe

Docetaxel-Loaded PLGA Nanoparticles Improve Efficacy in Taxane-Resistant Triple-Negative Breast Cancer

Novel treatment strategies, including nanomedicine, are needed for improving management of triple-negative breast cancer. Patients with triple-negative breast cancer, when considered as a group, have a worse outcome after chemotherapy than patients with breast cancers of other subtypes, a finding that reflects the intrinsically adverse prognosis associated with the disease. The aim of this study was to improve the efficacy of docetaxel by incorporation into a novel nanoparticle platform for the treatment of taxane-resistant triple-negative breast cancer. Rod-shaped nanoparticles encapsulating docetaxel were fabricated using an imprint lithography based technique referred to as Particle Replication in Nonwetting Templates (PRINT). These rod-shaped PLGA-docetaxel nanoparticles were tested in the C3(1)-T-antigen (C3Tag) genetically engineered mouse model (GEMM) of breast cancer that represents the basal-like subtype of triple-negative breast cancer and is resistant to therapeutics from the taxane family. Thi..

The Reproducibility of Lists of Differentially Expressed Genes in Microarray Studies

Reproducibility is a fundamental requirement in scientific experiments and clinical contexts. Recent publications raise concerns about the reliability of microarray technology because of the apparent lack of agreement between lists of differentially expressed genes (DEGs). In this study we demonstrate that (1) such discordance may stem from ranking and selecting DEGs solely by statistical significance (P) derived from widely used simple t-tests; (2) when fold change (FC) is used as the ranking criterion, the lists become much more reproducible, especially when fewer genes are selected; and (3) the instability of short DEG lists based on P cutoffs is an expected mathematical consequence of the high variability of the t-values. We recommend the use of FC ranking plus a non-stringent P cutoff as a baseline practice in order to generate more reproducible DEG lists. The FC criterion enhances reproducibility while the P criterion balances sensitivity and specificity