Synthesis of an Amide-Based Extended Heterocyclic System Capable of Hydrogen Bonding to Both the Adenine and Uracil in dsRNA for RNA Recognition Using PNA

The majority of information known about RNA is centered around coding RNA for its role in synthesizing proteins from DNA. However, noncoding RNA is also biologically relevant, showing importance in gene expression and catalyzing reactions. Peptide Nucleic Acids, or PNAs, are a promising tool that can be used to study noncoding RNA. PNAs can bind to double-stranded RNA forming a triple helix and are highly selective for specific sequences of dsRNA. A current limitation of PNA as a ligand is that traditional nucleobases only bind with high affinity to single purine residues on the RNA, as triplex formation relies on the two hydrogen bonding sites offered by purines as opposed to only one offered by pyrimidines. More recent developments in our group and others have shown that synthetic nucleobases may be used to increase both affinity and selectivity. We have synthesized a uracil nucleobase modified to bind both the adenine and the uracil of the A-U base pair by adding a benzamide moiety to isoorotic acid. Computations suggest that this will increase the affinity of binding and make PNA relevant for use in dsRNA sequences containing both purine and pyrimidine bases

Snapping Turtle, Chelydra serpentina, Overland Movements Near the Southeastern Extent of its Range

Terrestrial movements of turtles are of interest due to the conservation implications for this imperiled group and the general lack of information on this topic, particularly in wide-ranging species. The snapping turtle, Chelydra serpentina, is one of the most broadly distributed chelonians in the world; they occur from southeastern Canada westward to Alberta and throughout the eastern half of the United States and into Central America. Most research on this species has been focused on populations in the northern portion of the range. In this study, we radio-tracked five turtles in southwestern Georgia, where published data on spatial ecology and movements are lacking. Turtles exhibited extensive overland movements which we suspect occurred in response to drought

Missing physics in stick-slip dynamics of a model for peeling of an adhesive tape

It is now known that the equations of motion for the contact point during peeling of an adhesive tape mounted on a roll introduced earlier are singular and do not support dynamical jumps across the two stable branches of the peel force function. By including the kinetic energy of the tape in the Lagrangian, we derive equations of motion that support stick-slip jumps as a natural consequence of the inherent dynamics. In the low mass limit, these equations reproduce solutions obtained using a differential-algebraic algorithm introduced for the earlier equations. Our analysis also shows that mass of the ribbon has a strong influence on the nature of the dynamics.Comment: Accepted for publication in Phys. Rev. E (Rapid Communication

Rapamycin weekly maintenance dosing and the potential efficacy of combination sorafenib plus rapamycin but not atorvastatin or doxycycline in tuberous sclerosis preclinical models

BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant tumor suppressor syndrome, characterized by hamartomatous growths in the brain, skin, kidneys, lungs, and heart, which lead to significant morbidity. TSC is caused by mutations in the TSC1 or TSC2 genes, whose products, hamartin and tuberin, form a tumor suppressor complex that regulates the PI3K/Akt/mTOR pathway. Early clinical trials show that TSC-related kidney tumors (angiomyolipomas) regress when treated with the mammalian target of rapamycin (mTOR) inhibitor, rapamycin (also known as sirolimus). Although side effects are tolerable, responses are incomplete, and tumor regrowth is common when rapamycin is stopped. Strategies for future clinical trials may include the investigation of longer treatment duration and combination therapy of other effective drug classes. RESULTS: Here, we examine the efficacy of a prolonged maintenance dose of rapamycin in Tsc2+/- mice with TSC-related kidney tumors. Cohorts were treated with rapamycin alone or in combination with interferon-gamma (IFN-g). The schedule of rapamycin included one month of daily doses before and after five months of weekly doses. We observed a 94.5% reduction in kidney tumor burden in Tsc2+/- mice treated (part one) daily with rapamycin (8 mg/kg) at 6 months ≤ age \u3c 7 months, (part 2) weekly with rapamycin (16 mg/kg) at 7 months ≤ age \u3c 12 months, and (part 3) daily with rapamycin (8 mg/kg) at 12 months ≤ age \u3c 13 months; but we did not observe any improvement with combination IFN-g plus rapamycin in this study. We also used a Tsc2-/- subcutaneous tumor model to evaluate other classes of drugs including sorafenib, atorvastatin, and doxycycline. These drugs were tested as single agents and in combination with rapamycin. Our results demonstrate that the combination of rapamycin and sorafenib increased survival and may decrease tumor volume as compared to rapamycin treatment alone while sorafenib as a single agent was no different than control. Atorvastatin and doxycycline, either as single agents or in combination with rapamycin, did not improve outcomes as compared with controls. CONCLUSION: Our results indicate that prolonged treatment with low doses of mTOR inhibitors may result in more complete and durable TSC-related tumor responses, and it would be reasonable to evaluate this strategy in a clinical trial. Targeting the Raf/Mek/Erk and/or VEGF pathways in combination with inhibiting the mTOR pathway may be another useful strategy for the treatment of TSC-related tumors

Country of origin, culture, self-esteem and intimate partner violence among community dwelling Hispanic women

The purpose of this study was to explore variations in demographics, culture, self-esteem and intimate partner violence among Hispanic women according to country of origin, and to identify factors that are associated with differences in intimate partner violence. Baseline data from a randomized control trial testing the efficacy of an HIV prevention program was used. Path analyses were conducted to describe relationships between variables and identify potential mediators. Differences between Colombian women and women from other Central/South American countries were noted for intimate partner violence. Self-esteem was the only factor that was associated with these differences. Interventions that address the unique needs of Hispanic sub-groups and promote self-esteem are needed

Enhancing the Structure of the WRF-Hydro Hydrologic Model for Semiarid Environments

In August 2016, the National Weather Service Office of Water Prediction (NWS/OWP) of the National Oceanic and Atmospheric Administration (NOAA) implemented the operational National Water Model (NWM) to simulate and forecast streamflow, soil moisture, and other model states throughout the contiguous United States. Based on the architecture of the WRF-Hydro hydrologic model, the NWM does not currently resolve channel infiltration, an important component of the water balance of the semiarid western United States. Here, we demonstrate the benefit of implementing a conceptual channel infiltration function (from the KINEROS2 semidistributed hydrologic model) into the WRF-Hydro model architecture, configured as NWM v1.1. After calibration, the updated WRF-Hydro model exhibits reduced streamflow errors for the Walnut Gulch Experimental Watershed (WGEW) and the Babocomari River in southeast Arizona. Model calibration was performed using NLDAS-2 atmospheric forcing, available from the NOAA National Centers for Environmental Prediction (NCEP), paired with precipitation forcing from NLDAS-2, NCEP Stage IV, or local gauge precipitation. Including channel infiltration within WRF-Hydro results in a physically realistic hydrologic response in the WGEW, when the model is forced with high-resolution, gauge-based precipitation in lieu of a national product. The value of accounting for channel loss is also demonstrated in the Babocomari basin, where the drainage area is greater and the cumulative effect of channel infiltration is more important. Accounting for channel infiltration loss thus improves the streamflow behavior simulated by the calibrated model and reduces evapotranspiration bias when gauge precipitation is used as forcing. However, calibration also results in increased high soil moisture bias, which is likely due to underlying limitations of the NWM structure and calibration methodology.University Corporation for Atmospheric Science (UCAR) COMET Cooperative Project; NOAA Joint Technology Transfer Initiative (JTTI) Federal Grant [NA17OAR4590183]6 month embargo; published online 22 April 2019This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Maternal Responses in the Face of Infection Risk

When animals are sick, their physiology and behavior change in ways that can impact their offspring. Research is emerging showing that infection risk alone can also modify the physiology and behavior of healthy animals. If physiological responses to environments with high infection risk take place during reproduction, it is possible that they lead to maternal effects. Understanding whether and how high infection risk triggers maternal effects is important to elucidate how the impacts of infectious agents extend beyond infected individuals and how, in this way, they are even stronger evolutionary forces than already considered. Here, to evaluate the effects of infection risk on maternal responses, we exposed healthy female Japanese quail to either an immune-challenged (lipopolysaccharide [LPS] treated) mate or to a healthy (control) mate. We first assessed how females responded behaviorally to these treatments. Exposure to an immune-challenged or control male was immediately followed by exposure to a healthy male, to determine whether treatment affected paternity allocation. We predicted that females paired with immune-challenged males would avoid and show aggression towards those males, and that paternity would be skewed towards the healthy male. After mating, we collected eggs over a 5-day period. As an additional control, we collected eggs from immune-challenged females mated to healthy males. We tested eggs for fertilization status, embryo sex ratio, as well as albumen corticosterone, lysozyme activity, and ovotransferrin, and yolk antioxidant capacity. We predicted that immune-challenged females would show the strongest changes in the egg and embryo metrics, and that females exposed to immune-challenged males would show intermediate responses. Contrary to our predictions, we found no avoidance of immune-challenged males and no differences in terms of paternity allocation. Immune-challenged females laid fewer eggs, with an almost bimodal distribution of sex ratio for embryos. In this group, albumen ovotransferrin was the lowest, and yolk antioxidant capacity decreased over time, while it increased in the other treatments. No differences in albumen lysozyme were found. Both females that were immune-challenged and those exposed to immune-challenged males deposited progressively more corticosterone in their eggs over time, a pattern opposed to that shown by females exposed to control males. Our results suggest that egg-laying Japanese quail may be able to respond to infection risk, but that additional or prolonged sickness symptoms may be needed for more extensive maternal responses