Biochemical Properties of a Decoy Oligodeoxynucleotide Inhibitor of STAT3 Transcription Factor.

Cyclic STAT3 decoy (CS3D) is a second-generation, double-stranded oligodeoxynucleotide (ODN) that mimics a genomic response element for signal transducer and activator of transcription 3 (STAT3), an oncogenic transcription factor. CS3D competitively inhibits STAT3 binding to target gene promoters, resulting in decreased expression of proteins that promote cellular proliferation and survival. Previous studies have demonstrated antitumor activity of CS3D in preclinical models of solid tumors. However, prior to entering human clinical trials, the efficiency of generating the CS3D molecule and its stability in biological fluids should be determined. CS3D is synthesized as a single-stranded ODN and must have its free ends ligated to generate the final cyclic form. In this study, we report a ligation efficiency of nearly 95 percent. The ligated CS3D demonstrated a half-life of 7.9 h in human serum, indicating adequate stability for intravenous delivery. These results provide requisite biochemical characterization of CS3D that will inform upcoming clinical trials

The use of complementary and alternative medicine among california adults with and without cancer.

This article examines the extent and correlates of complementary and alternative medicine (CAM) use among a population-based sample of California adults that is highly diverse in terms of sociodemographic characteristics and health status. As a follow-up to a state-wide health survey of 55,428 people, 9187 respondents were interviewed by phone regarding their use of 11 different types of CAM providers, special diets, dietary supplements, mind-body interventions, self-prayer and support groups. The sample included all participants in the initial survey who reported a diagnosis of cancer, all the non-white respondents, as well as a random sample of all the white respondents. The relation of CAM use to the respondents' demographic characteristics and health status is assessed. CAM use among Californians is generally high, and the demographic factors associated with high rates of CAM use are the same in California as have been found in other studies. Those reporting a diagnosis of cancer and those who report other chronic health problems indicate a similar level of visits to CAM providers. However, those with cancer are less likely to report using special diets, and more likely to report using support groups and prayer. Health status, gender, ethnicity and education have an independent impact upon CAM use among those who are healthy as well as those who report suffering from chronic health problems, although the precise relation varies by the type of CAM used

Tuning oxo formation energies using spectator ligands in the MIL-100 metal organic framework

https://tigerprints.clemson.edu/csrp/1008/thumbnail.jp

Regulatory Circuit of Human MicroRNA Biogenesis

miRNAs (microRNAs) are a class of endogenous small RNAs that are thought to negatively regulate protein production. Aberrant expression of many miRNAs is linked to cancer and other diseases. Little is known about the factors that regulate the expression of miRNAs. We have identified numerous regulatory elements upstream of miRNA genes that are likely to be essential to the transcriptional and posttranscriptional regulation of miRNAs. Newly identified regulatory motifs occur frequently and in multiple copies upstream of miRNAs. The motifs are highly enriched in G and C nucleotides, in comparison with the nucleotide composition of miRNA upstream sequences. Although the motifs were predicted using sequences that are upstream of miRNAs, we find that 99% of the top-predicted motifs preferentially occur within the first 500 nucleotides upstream of the transcription start sites of protein-coding genes; the observed preference in location underscores the validity and importance of the motifs identified in this study. Our study also raises the possibility that a considerable number of well-characterized, disease-associated transcription factors (TFs) of protein-coding genes contribute to the abnormal miRNA expression in diseases such as cancer. Further analysis of predicted miRNA–protein interactions lead us to hypothesize that TFs that include c-Myb, NF-Y, Sp-1, MTF-1, and AP-2α are master-regulators of miRNA expression. Our predictions are a solid starting point for the systematic elucidation of the causative basis for aberrant expression patterns of disease-related (e.g., cancer) miRNAs. Thus, we point out that focused studies of the TFs that regulate miRNAs will be paramount in developing cures for miRNA-related diseases. The identification of the miRNA regulatory motifs was facilitated by a new computational method, K-Factor. K-Factor predicts regulatory motifs in a set of functionally related sequences, without relying on evolutionary conservation

An ANGPTL4-ceramide-protein kinase Cζ axis mediates chronic glucocorticoid exposure-induced hepatic steatosis and hypertriglyceridemia in mice.

Chronic or excess glucocorticoid exposure causes lipid disorders such as hypertriglyceridemia and hepatic steatosis. Angptl4 (angiopoietin-like 4), a primary target gene of the glucocorticoid receptor in hepatocytes and adipocytes, is required for hypertriglyceridemia and hepatic steatosis induced by the synthetic glucocorticoid dexamethasone. Angptl4 has also been shown to be required for dexamethasone-induced hepatic ceramide production. Here, we further examined the role of ceramide-mediated signaling in hepatic dyslipidemia caused by chronic glucocorticoid exposure. Using a stable isotope-labeling technique, we found that dexamethasone treatment induced the rate of hepatic de novo lipogenesis and triglyceride synthesis. These dexamethasone responses were compromised in Angptl4-null mice (Angptl4-/-). Treating mice with myriocin, an inhibitor of the rate-controlling enzyme of de novo ceramide synthesis, serine palmitoyltransferase long-chain base subunit 1 (SPTLC1)/SPTLC2, decreased dexamethasone-induced plasma and liver triglyceride levels in WT but not Angptl4-/- mice. We noted similar results in mice infected with adeno-associated virus-expressing small hairpin RNAs targeting Sptlc2. Protein phosphatase 2 phosphatase activator (PP2A) and protein kinase Cζ (PKCζ) are two known downstream effectors of ceramides. We found here that mice treated with an inhibitor of PKCζ, 2-acetyl-1,3-cyclopentanedione (ACPD), had lower levels of dexamethasone-induced triglyceride accumulation in plasma and liver. However, small hairpin RNA-mediated targeting of the catalytic PP2A subunit (Ppp2ca) had no effect on dexamethasone responses on plasma and liver triglyceride levels. Overall, our results indicate that chronic dexamethasone treatment induces an ANGPTL4-ceramide-PKCζ axis that activates hepatic de novo lipogenesis and triglyceride synthesis, resulting in lipid disorders

Using Global Positioning System Technology to Manage Human-Black Bear Incidents at Yosemite National Park

Managing human–bear (Ursus spp.) incidents is a top management priority in national parks inhabited by bears. Yosemite National Park (Yosemite), located in the Sierra Nevada in California, USA, receives up to 5 million visitors annually. It is also home to 300–500 black bears (U. americanus). Yosemite has an extensive history of black bear research, educational programs, and innovative solutions for reducing human–bear incidents. Despite this, human–bear incidents peaked in 1998 at 1,584. The resulting political fallout led to Yosemite receiving funds to expand its bear management program, including increasing its staffing and garbage pick-up, and improving the park’s bear-resistant infrastructure. In 2011, Yosemite reached a milestone when it recorded only 114 human–bear incidents—a 93% decrease from the 1998 high. To sustain this lower level of incidents while facing shrinking budgets and increasing visitation, bear managers turned to more modern technology. From 2014–2018, we evaluated the effectiveness of using global positioning system (GPS) collars to manage bears more proactively, increase staff and public engagement with bears, and gain insight into the bears’ spatial and temporal movements. The GPS collars were effective in achieving these goals, while also improving both our time management and our communication with park management. By the end of November 2018, Yosemite had recorded only 22 human–bear incidents—a 99% decrease from the 1998 high. The GPS collars are now an integral part of the Yosemite bear management program. We provide recommendations on how GPS technology may help other parks reduce human–bear incidents

Light-Element Abundance Variations at Low Metallicity: the Globular Cluster NGC 5466

We present low-resolution (R~850) spectra for 67 asymptotic giant branch (AGB), horizontal branch and red giant branch (RGB) stars in the low-metallicity globular cluster NGC 5466, taken with the VIRUS-P integral-field spectrograph at the 2.7-m Harlan J. Smith telescope at McDonald Observatory. Sixty-six stars are confirmed, and one rejected, as cluster members based on radial velocity, which we measure to an accuracy of 16 km s-1 via template-matching techniques. CN and CH band strengths have been measured for 29 RGB and AGB stars in NGC 5466, and the band strength indices measured from VIRUS-P data show close agreement with those measured from Keck/LRIS spectra previously taken of five of our target stars. We also determine carbon abundances from comparisons with synthetic spectra. The RGB stars in our data set cover a range in absolute V magnitude from +2 to -3, which permits us to study the rate of carbon depletion on the giant branch as well as the point of its onset. The data show a clear decline in carbon abundance with rising luminosity above the luminosity function "bump" on the giant branch, and also a subdued range in CN band strength, suggesting ongoing internal mixing in individual stars but minor or no primordial star-to-star variation in light-element abundances.Comment: 10 pages, emulateapj format, AJ accepte

The Large-scale and Small-scale Clustering of Lyman-Break Galaxies at 3.5 < z< 5.5 from the GOODS survey

We report on the angular correlation function of Lyman-break galaxies (LBGs) at z~4 and 5 from deep samples obtained from the Great Observatories Deep Origins Survey (GOODS). Similar to LBGs at z~3, the shape of w(theta) of the GOODS LBGs is well approximated by a power-law with slope beta~0.6 at angular separation theta > 10 arcsec. The clustering strength of z~4, 5 LBGs also depends on the rest-frame UV luminosity, with brighter galaxies more strongly clustered than fainter ones, implying a general correlation between halos' mass and LBGs' star-formation rate. At smaller separations, w(theta) of deep samples significantly exceeds the extrapolation of the large-scale power-law fit, implying enhanced spatial clustering at scales r < 1 Mpc. We also find that bright LBGs statistically have more faint companions on scales theta < 20 arcsec than fainter ones, showing that the enhanced small-scale clustering is very likely due to sub-structure, namely the fact that massive halos can host multiple galaxies. A simple model for the halo occupation distribution and the CDM halo mass function reproduce well the observed w(theta). The scaling relationship of the clustering strength with volume density and with redshift is quantitatively consistent with that of CDM halos. A comparison of the clustering strength of three samples of equal luminosity limit at z ~ 3, 4 and 5 shows that the LBGs at z~5 are hosted in halos about one order of magnitude less massive than those in the lower redshift bins, suggesting that star-formation was more efficient at higher-redshift.Comment: replaced with the version accepted for publication in ApJ. 46 pages, 10 figures; minor changes to text, one subsection adde

Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: prospective cohort analysis

Objective To investigate whether angiotensin receptor blockers protect against Alzheimer’s disease and dementia or reduce the progression of both diseases