The effects of codon context on in vivo translation speed

pre-printWe developed a bacterial genetic system based on translation of the his operon leader peptide gene to determine the relative speed at which the ribosome reads single or multiple codons in vivo. Low frequency effects of so-called ‘‘silent'' codon changes and codon neighbor (context) effects could be measured using this assay. An advantage of this system is that translation speed is unaffected by the primary sequence of the His leader peptide. We show that the apparent speed at which ribosomes translate synonymous codons can vary substantially even for synonymous codons read by the same tRNA species. Assaying translation through codon pairs for the 59- and 39- side positioning of the 64 codons relative to a specific codon revealed that the codon-pair orientation significantly affected in vivo translation speed. Codon pairs with rare arginine codons and successive proline codons were among the slowest codon pairs translated in vivo. This system allowed us to determine the effects of different factors on in vivo translation speed including Shine-Dalgarno sequence, rate of dipeptide bond formation, codon context, and charged tRNA levels

The Advertisement Value of Transformational & Informational Appeal on Company Facebook Pages

The advertisement value of Facebook is an under-developed area of social media research. Transformational and informational advertising appeal has yet to be studied as it relates to social media. This paper utilizes established classification and measurement scales from marketing literature to classify companies and their Facebook posts and measures the advertisement value of these posts. The study uses a sample of 100 companies from the 2015 Fortune 500 list. Results indicate that posts with transformational appeal are more engaging to the consumer than informational appeal; however, posts with informational appeal have greater advertisement value for the company. The results also indicate there is no relationship between type of company and type of appeal used by companies

Phase 1 study of sirolimus in combination with oral cyclophosphamide and topotecan in children and young adults with relapsed and refractory solid tumors.

PurposeTo determine the maximum tolerated dose (MTD), toxicities, and pharmacodynamics effects of sirolimus combined with oral metronomic topotecan and cyclophosphamide in a pediatric population.Materials and methodsPatients who were 1 to 30 years of age with relapsed/refractory solid tumors (including CNS) were eligible. Patients received daily oral sirolimus and cyclophosphamide (25-50 mg/m2/dose) on days 1-21 and oral topotecan (0.8 mg/m2/dose) on days 1-14 in 28-day cycles. Sirolimus steady-state plasma trough concentrations of 3-7.9 ng/mL and 8-12.0 ng/mL were evaluated, with dose escalation based on a 3+3 phase 1 design. Biomarkers of angiogenesis were also evaluated.ResultsTwenty-one patients were treated (median age 18 years; range 9-30). Dose-limiting toxicities included myelosuppression, ALT elevation, stomatitis, and hypertriglyceridemia. The MTD was sirolimus with trough goal of 8-12.0 ng/mL; cyclophosphamide 25 mg/m2/dose; and topotecan 0.8 mg/m2/dose. No objective responses were observed. Four patients had prolonged stable disease > 4 cycles (range 4-12). Correlative biomarker analyses demonstrated reductions in thrombospondin-1 (p=0.043) and soluble vascular endothelial growth factor receptor-2 plasma concentrations at 21 days compared to baseline.ConclusionsThe combination of oral sirolimus, topotecan, and cyclophosphamide was well tolerated and biomarker studies demonstrated modulation of angiogenic pathways with this regimen

Discovery of a Transiting Planet Near the Snow-Line

In most theories of planet formation, the snow-line represents a boundary between the emergence of the interior rocky planets and the exterior ice giants. The wide separation of the snow-line makes the discovery of transiting worlds challenging, yet transits would allow for detailed subsequent characterization. We present the discovery of Kepler-421b, a Uranus-sized exoplanet transiting a G9/K0 dwarf once every 704.2 days in a near-circular orbit. Using public Kepler photometry, we demonstrate that the two observed transits can be uniquely attributed to the 704.2 day period. Detailed light curve analysis with BLENDER validates the planetary nature of Kepler-421b to >4 sigmas confidence. Kepler-421b receives the same insolation as a body at ~2AU in the Solar System and for a Uranian albedo would have an effective temperature of ~180K. Using a time-dependent model for the protoplanetary disk, we estimate that Kepler-421b's present semi-major axis was beyond the snow-line after ~3Myr, indicating that Kepler-421b may have formed at its observed location.Comment: 14 pages, 10 figures, 3 tables. Accepted in Ap

Hair cortisol concentrations in bovine neonates born to healthy and ill cows

The goal of this study was to investigate the hair cortisol concentration (HCC) in healthy and ill cows and their newborn calves. A total of 40 cows and their 42 newborn calves were divided into two groups: group 1 consisted of 19 clinically healthy cows and their 20 newborn calves, and group 2 comprised 21 cows that had had a chronic illness in the third trimester of gestation and their 22 newborn calves. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) system was used to measure the HCC in hair samples that were collected from the cows and calves on the day the calves were born. In both groups, the mean HCCs of the calves was significantly higher than that of the cows (group 1, 31,0 vs. 0,6 pg/mg; group 2, 19,4 vs. 0,8 pg/mg; P

Evaluating portable air cleaner effectiveness in residential settings to reduce exposures to biomass smoke resulting from prescribed burns

AIM: Prescribed burning is the most common method employed to reduce fuel loads in flammable landscapes. This practice is designed to reduce the hazard associated with uncontrolled bushfires. Prescribed burns are frequently conducted close to residential areas, and the associated smoke impacts can adversely affect community health. Particulate matter is the predominant pollutant within the smoke and is strongly and consistently linked with adverse health effects. Outdoor smoke readily infiltrates buildings and reduces the quality of indoor air. Portable air cleaners containing high-efficiency particulate air (HEPA) filters are a promising indoor air quality intervention for reducing outdoor smoke exposure.METHODS: We provided 10 homes from semirural regions of Victoria, Australia, with HEPA cleaners and conducted continuous monitoring of indoor and outdoor fine particulate matter (PM2.5) for 2-4 weeks during prescribed burning periods. We calculated the potential improvements to indoor air quality when operating a HEPA cleaner during a smoke episode. Ventilation measures were conducted to identify points of smoke ingress and housing characteristics that could lead to higher infiltration rates.RESULTS: Depending on the house, the use of HEPA cleaners resulted in a reduction in indoor PM2.5 concentrations of 30-74%.CONCLUSIONS: HEPA cleaners have the potential to substantially improve indoor air quality during episodic smoke episodes.</p

Retired A Stars and Their Companions VIII: 15 New Planetary Signals Around Subgiants and Transit Parameters for California Planet Search Planets with Subgiant Hosts

We present the discovery of seven new planets and eight planet candidates around subgiant stars, as additions to the known sample of planets around "retired A stars." Among these are the possible first three-planet systems around subgiant stars, HD 163607 and HD 4917. Additionally, we present calculations of possible transit times, durations, depths, and probabilities for all known planets around subgiant (3 9%

miR-27a and miR-27b regulate autophagic clearance of damaged mitochondria by targeting PTEN-induced putative kinase 1 (PINK1)

Computational prediction of miRNA candidates for human PINK1. a Computation prediction of miRNAs expressed in human midbrain with putative binding sites in the 3′UTR of human PINK1 mRNA. We first searched miRNAs that have putative binding sites in the 3′UTR of human PINK1 mRNA by utilizing several miRNA-target prediction algorithms, such as miRanda [67], miRWalk [68], RNAhybrid [37], and Targetscan [69]. Among 49 miRNAs commonly predicted by different algorithms, 7 miRNAs were known to be expressed in human midbrain [34]. miR-27a/b are predicted to have 2 putative binding sites in the 3′UTR of human PINK1 mRNA, while all other miRNAs are predicted to have 1 putative binding site. b Computational binding prediction of miR-27a/b and their binding sites in the 3′UTR of human PINK1 mRNA. The binding free energies were determined by the RNAhybrid algorithm. (PDF 68 kb