Distinct p53 acetylation cassettes differentially influence gene-expression patterns and cell fate

The activity of the p53 gene product is regulated by a plethora of posttranslational modifications. An open question is whether such posttranslational changes act redundantly or dependently upon one another. We show that a functional interference between specific acetylated and phosphorylated residues of p53 influences cell fate. Acetylation of lysine 320 (K320) prevents phosphorylation of crucial serines in the NH(2)-terminal region of p53; only allows activation of genes containing high-affinity p53 binding sites, such as p21/WAF; and promotes cell survival after DNA damage. In contrast, acetylation of K373 leads to hyperphosphorylation of p53 NH(2)-terminal residues and enhances the interaction with promoters for which p53 possesses low DNA binding affinity, such as those contained in proapoptotic genes, leading to cell death. Further, acetylation of each of these two lysine clusters differentially regulates the interaction of p53 with coactivators and corepressors and produces distinct gene-expression profiles. By analogy with the "histone code" hypothesis, we propose that the multiple biological activities of p53 are orchestrated and deciphered by different "p53 cassettes," each containing combination patterns of posttranslational modifications and protein-protein interactions.     

Quantification of the urinary concentrations of parabens in humans by on-line solid phase extraction-high performance liquid chromatography-isotope dilution tandem mass spectrometry

Parabens (alkyl esters of p-hydroxybenzoic acid) are widely used as antimicrobial preservatives in cosmetic products, pharmaceuticals, and food processing. However, weak estrogenicity of some parabens has been revealed from several studies. Human exposure to parabens may be assessed by measuring the conjugated or free species of these compounds or their metabolites in urine. We have developed a method using on-line solid phase extraction-high performance liquid chromatography-isotope dilution tandem mass spectrometry with peak focusing to measure the urinary concentrations of methyl, ethyl, propyl, n- and iso- butyl, and benzyl parabens. This method has good reproducibility and accuracy with detection limits for all analytes below 0.2ng/mL in 100microL of urine, and permits quick and accurate analysis of a large number of samples in epidemiologic studies for assessing the prevalence of human exposure to parabens. Using this method, we detected methyl, ethyl, and propyl parabens, mostly as conjugated species, in 22 urine samples collected from anonymous adults.     

The contrasting effects of nutrient enrichment on growth,biomass allocation and decomposition of plant tissue in coastal wetlands

Background

Most studies focus on macronutrient of C, N and P and ignore other elements, which restrict our understanding on the strategy of plant nutrient adaption and nutrient cycling.

Methods

We investigated 14 element (C, N, P, S, K, Ca, Mg, Fe, Mn, Zn, Cu, Na, Al, and Ba) concentrations of green and senesced leaves in Quercus variabilis along the altitude in the Baotianman Mountains, China, and assessed their relationships with climate, soil, and plant functional traits.

Results

Leaf N,S and K increased with, C, Ca, Na, Fe, Mn, Cu and Ba decreased with, and P, Mg, Al, Zn and N:P did not change significantly with altitude. NRE and SRE increased with, and CRE decreased with altitude (p < 0.05). Among the 14 elements, nucleic acid-protein elements (N, K, S and P) were resorbed preferentially, compare to structural (Ca, Mn, and B) and enzymatic (C, Cu, Mg and Zn) that were discriminated against, and toxic (Al and Fe) elements that were totally excluded.

Conclusions

Q. variabilis can synergetically regulate green leaf multielement stoichiometry and nutrient resorption in responses to environment change. Deciduous plants may have a trade-off mechanism at the end of growing season to rebalance somatic nutrients.

     

Reproductive and recruitment dynamics of clionaid sponges on oyster reefs in North Carolina

Boring sponges belonging to the family Clionaidae have become a destructive nuisance to eastern oyster (Crassostrea virginica) aquaculture and restoration efforts in the southeastern USA. Clionaid sponges colonize the inner layers of oyster shells and remove carbonate material, compromising the quality and marketability of the oyster; however, relatively little is known about reproduction and recruitment of these sponges. Using histological techniques, reproductive activity of clionaid sponges was monitored at two sites (Cedar Island and Masonboro Sound) in coastal North Carolina. Sponge recruitment to limestone tiles (5×5 cm), oyster shells, and clam shells was monitored in 2013 and 2014; recruitment to the limestone tiles was statistically higher than recruitment to clam or oyster shells. Overall, seasonal patterns in reproduction and recruitment of clionaid sponges were generally similar at the two sites. Three species of clionaid sponge were found during field sampling (Cliona celata, C. lobata, and C. truitti), and reproductive activity (eggs and spermatocysts) of these species was observed from April to November, with peak reproduction occurring from June to September for C. lobata and from August to September for C. celata. Recruitment peaked in late summer/early fall. Additionally, the relationship between environmental conditions (temperature, salinity, dissolved oxygen, pH, and chlorophyll a) and clionaid recruitment was explored using a regression model. At Cedar Island, the best‐fit model included salinity and dissolved oxygen, while the best‐fit model at Masonboro Sound included temperature, pH, and salinity. The data from this study show that the primary reproduction and recruitment pulses occur in the fall for local clionaids, and thus mitigation strategies should be applied in the late fall or winter to minimize infestations.     

The effect of nutrient availability and temperature on chain length of the diatom, Skeletonema costatum

We determined the effects of temperature and nutrients on thechain length of a diatom, Skeletonema costatum, in batch cultureand enclosure experiments with estuarine water from San FranciscoBay, USA, using the recently developed CytoBuoy flow cytometer.Determination of the number of cells per diatom chain by CytoBuoyflow cytometer and associated software correlated well withbut was much more precise and time efficient than microscopicquantification. Increasing temperatures (from 6, 8 to 17°C)and nutrient concentrations induced high growth rates and dominanceby longer chains in a cultured S. costatum strain that was originallyacclimatized to a temperature range of 11–30°C. Similarly,a positive correlation between growth rate and chain lengthwas observed in S. costatum in batch culture and natural communitiesin enclosure experiments. Maximal chain lengths of S. costatumwere greater in natural populations than in the batch culture.Longer chains affect sinking rates and thus likely help thediatom remain suspended in the upper part of the water columnwhere physical and chemical parameters are more favorable forgrowth.     

Hybrid chickadees are deficient in learning and memory

Identifying the phenotypes underlying postzygotic reproductive isolation is crucial for fully understanding the evolution and maintenance of species. One potential postzygotic isolating barrier that has rarely been examined is learning and memory ability in hybrids. Learning and memory are important fitness‐related traits, especially in scatter‐hoarding species, where accurate retrieval of hoarded food is vital for winter survival. Here, we test the hypothesis that learning and memory ability can act as a postzygotic isolating barrier by comparing these traits among two scatter‐hoarding songbird species, black‐capped (Poecile atricapillus) and Carolina chickadees (Poecile carolinensis), and their naturally occurring hybrids. In an outdoor aviary setting, we find that hybrid chickadees perform significantly worse on an associative learning spatial task and are worse at solving a novel problem compared to both parental species. Deficiencies in learning and memory abilities could therefore contribute to postzygotic reproductive isolation between chickadee species. Given the importance of learning and memory for fitness, our results suggest that these traits may play an important, but as yet overlooked, role in postzygotic reproductive isolation.     

Synthesis and PGE2 inhibitory activity of novel diarylheptanoids

Prostaglandin E₂ (PGE₂) is a lipid mediator of inflammation and its inhibition has become a popular drug target due to its harmful physiological roles. Diarylheptanoids are one class of compounds that have shown successful inhibition of PGE₂. This paper reports the synthesis and PGE₂ inhibitory activity of a series of analogues of a naturally occurring diarylheptanoid. The most efficacious compounds were examined for dose-dependent PGE₂ inhibition. Among several promising compounds, the lead candidate exhibited an IC₅₀ value of 0.56?ng/µL or 1.7?µM with no detectable toxicity at the highest dose of 10?ng/µL.     

PEGylation of Vesicular Stomatitis Virus Extends Virus Persistence in Blood Circulation of Passively Immunized Mice

We are developing oncolytic vesicular stomatitis viruses (VSVs) for systemic treatment of multiple myeloma, an incurable malignancy of antibody-secreting plasma cells that are specifically localized in the bone marrow. One of the presumed advantages for using VSV as an oncolytic virus is that human infections are rare and preexisting anti-VSV immunity is typically lacking in cancer patients, which is very important for clinical success. However, our studies show that nonimmune human and mouse serum can neutralize clinical-grade VSV, reducing the titer by up to 4 log units in 60 min. In addition, we show that neutralizing anti-VSV antibodies negate the antitumor efficacy of VSV, a concern for repeat VSV administration. We have investigated the potential use of covalent modification of VSV with polyethylene glycol (PEG) or a function-spacer-lipid (FSL)–PEG construct to inhibit serum neutralization and to limit hepatosplenic sequestration of systemically delivered VSV. We report that in mice passively immunized with neutralizing anti-VSV antibodies, PEGylation of VSV improved the persistence of VSV in the blood circulation, maintaining a more than 1-log-unit increase in VSV genome copies for up to 1 h compared to the genome copy numbers for the non-PEGylated virus, which was mostly cleared within 10 min after intravenous injection. We are currently investigating if this increase in PEGylated VSV circulating half-life can translate to increased virus delivery and better efficacy in mouse models of multiple myeloma.