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Biomedical subjects

Thomas M Johnson

Publications and source records attributed to Thomas M Johnson.

11 recordsLinked to original sources

Denitrification in the shallow ground water of a tile-drained, agricultural watershed.

Nonpoint-source pollution of surface water by N is considered a major cause of hypoxia. Because Corn Belt watersheds have been identified as major sources of N in the Mississippi River basin, the fate and transport of N from midwestern agricultural watersheds have received considerable interest. The fate and transport of N in the shallow ground water of these watersheds still needs additional research. Our purpose was to estimate denitrification in the shallow ground water of a tile-drained, Corn Belt watershed with fine-grained soils. Over a 3-yr period, N was monitored in the surface and ground water of an agricultural watershed in central Illinois. A significant amount of N was transported past the tile drains and into shallow ground water. The ground water nitrate was isotopically heavier than tile drain nitrate, which can be explained by denitrification in the subsurface. Denitrifying bacteria were found at depths to 10 m throughout the watershed. Laboratory and push-pull tests showed that a significant fraction of nitrate could be denitrified rapidly. We estimated that the N denitrified in shallow ground water was equivalent to 0.3 to 6.4% of the applied N or 9 to 27% of N exported via surface water. These estimates varied by water year and peaked in a year of normal precipitation after 2 yr of below average precipitation. Three years of monitoring data indicate that shallow ground water in watersheds with fine-grained soils may be a significant N sink compared with N exported via surface water.

Agriculture↗

Experimentally determined uranium isotope fractionation during reduction of hexavalent U by bacteria and zero valent iron.

Variations in stable isotope ratios of redox sensitive elements are often used to understand redox processes occurring near the Earth's surface. Presented here are measurements of mass-dependent U isotope fractionation induced by U(VI) reduction by zerovalent iron (Fe0) and bacteria under controlled pH and HCO3- conditions. In abiotic experiments, Fe0 reduced U(VI), but the reaction failed to induce an analytically significant isotopic fractionation. Bacterial reduction experiments using Geobacter sulfurreducens and Anaeromyxobacter dehalogenans reduced dissolved U(VI) and caused enrichment of 238U relative to 235U in the remaining U(VI). Enrichmentfactors (epsilon) calculated using a Rayleigh distillation model are -0.31% per hundred and -0.34% per hundred for G. sulfurreducens and A. dehalogenans, respectively, under identical experimental conditions. Further studies are required to determine the range of possible values for 238U/235U fractionation factors under a variety of experimental conditions before broad application of these results is possible. However, the measurable variations in delta(5238)U show promise as indicators of reduction for future studies of groundwater contamination, geochronology, U ore deposit formation, and U biogeochemical cycling.

Bacteria↗

Genome-wide analysis of p53 under hypoxic conditions.

Hypoxia is an important nongenotoxic stress that modulates the tumor suppressor activity of p53 during malignant progression. In this study, we investigated how genotoxic and nongenotoxic stresses regulate p53 association with chromatin, p53 transcriptional activity, and p53-dependent apoptosis. We found that genotoxic and nongenotoxic stresses result in the accumulation and binding of the p53 tumor suppressor protein to the same cognate binding sites in chromatin. However, it is the stress that determines whether downstream signaling is mediated by association with transcriptional coactivators. In contrast to p53 induced by DNA-damaging agents, hypoxia-induced p53 has primarily transrepression activity. Using extensive microarray analysis, we identified families of repressed targets of p53 that are involved in cell signaling, DNA repair, cell cycle control, and differentiation. Following our previous study on the contribution of residues 25 and 26 to p53-dependent hypoxia-induced apoptosis, we found that residues 25-26 and 53-54 and the polyproline- and DNA-binding regions are also required for both gene repression and the induction of apoptosis by p53 during hypoxia. This study defines a new role for residues 53 and 54 of p53 in regulating transrepression and demonstrates that 25-26 and 53-54 work in the same pathway to induce apoptosis through gene repression.

Amino Acid Sequence↗

p53QS: an old mutant teaches us new tricks.

The p53 protein functions as a tumor suppressor, preventing aberrant cellular proliferation in response to various genotoxic and non-genotoxic stress signals. Although p53's ability to induce apoptosis is critical to its capacity to suppress tumorigenesis, the role of transcriptional activation in p53's apoptotic function has been highly controversial. To address this issue, our laboratory generated a p53 mutant knock-in mouse strain in which residues 25 and 26, previously shown to be critical for p53's transactivation function, were mutated from leucine and tryptophan to glutamine and serine, respectively. Our analysis of cells derived from these mice provided significant insight into p53 activity at both the molecular and cellular level. In particular, our data suggest that p53 utilizes discrete mechanisms to transactivate different target genes, and that p53 employs distinct mechanisms to induce apoptosis in response to different stresses. This p53QS mutant mouse strain represents a powerful means to dissect p53 function in vivo.

Animals↗

The p53QS transactivation-deficient mutant shows stress-specific apoptotic activity and induces embryonic lethality.

The role of transcriptional activation in p53 function is highly controversial. To define this role in vivo, we generated a Trp53 knock-in construct encoding a protein carrying mutations of two residues that are crucial for transactivation (L25Q,W26S). Here we show that these mutations have selective effects on the biological functions of p53. Although its ability to activate various p53 target genes is largely compromised, the p53(QS) protein retains the ability to transactivate the gene Bax. The ability of the p53(QS) mutant protein to elicit a DNA damage-induced G1 cell cycle-arrest response is also partially impaired. p53(QS) has selective defects in its ability to induce apoptosis: it is completely unable to activate apoptosis in response to DNA damage, is partially unable to do so when subjected to serum deprivation and retains substantial apoptotic activity upon exposure to hypoxia. These findings suggest that p53 acts through distinct, stimulus-specific pathways to induce apoptosis. The importance of the biological activity of p53(QS) in vivo is underscored by our finding that expression of p53(QS), which cannot bind mdm2, induces embryonic lethality. Taken together, these results suggest that p53 has different mechanisms of action depending on specific contextual cues, which may help to clarify the function of p53 in preventing cancer.

Animals↗

Using chromium stable isotope ratios to quantify Cr(VI) reduction: lack of sorption effects.

Chromium stable isotope values can be effectively used to monitor reduction of Cr(VI) in natural waters. We investigate effects of sorption during transport of Cr(VI) which may also shift Cr isotopes values, complicating efforts to quantify reduction. This study shows that Cr stable isotope fractionation caused by sorption is negligible. Equilibrium fractionation of Cr stable isotopes between dissolved Cr(VI) and Cr(VI) adsorbed onto gamma-Al2O3 and goethite is less than 0.04 per thousand (53Cr/52Cr) under environmentally relevant pH conditions. Batch experiments at pH 4.0 and pH 6.0 were conducted in series to sequentially magnify small isotope fractionations. A simple transport model suggests that adsorption may cause amplification of a small isotope fractionation along extreme fringes of a plume, leading to shifts in 53Cr/52Cr values. We therefore suggest that isotope values at extreme fringes of Cr plumes be critically evaluated for sorption effects. A kinetic effect was observed in experiments with goethite at pH 4 where apparently lighter isotopes diffuse into goethite clumps at a faster rate before eventually reaching equilibrium. This observed kinetic effect may be important in a natural system that has not attained equilibrium and is in need of further study. Cr isotope fractionation caused by speciation of Cr(VI) between HCrO4- and CrO4(2-) was also examined, and we conclude that it is not measurable. In the absence of isotope fractionation caused by equilibrium speciation and sorption, most of the variation in delta53Cr values may be attributed to reduction, and reliable estimates of Cr reduction can be made.

Absorption↗

The Wisconsin Research Network Firearm Safety Survey.

National surveys have reported information on firearm ownership and storage practices, but primary care physicians question whether such information can be generalized to their communities and the patient populations they serve. In this study, an anonymous survey was distributed to 100 consecutive patients in 11 primary care clinics throughout Wisconsin. Demographic information and information on the patient's willingness to have firearm safety discussed as part of their routine care, firearm ownership in the household, firearm storage practices, and the patient's purpose for owning firearms were collected. The study found that patients were willing to answer anonymous survey questions about firearm ownership and storage in their homes. The most effective screening question on gun safety was whether firearms were kept in the home for personal protection. Patients at rural clinics were more likely to own firearms than patients in urban clinics. Keeping firearms for recreational purposes was more common than keeping them for personal protection, which was associated with unsafe storage practices. A majority of patients reported not wanting to receive information on firearm safety from their physician. Overall, the study found that it was not possible to generalize national information on firearm ownership and storage to surveyed patients of primary care clinics in Wisconsin.

Adult↗

Chromium isotopes and the fate of hexavalent chromium in the environment.

Measurements of chromium (Cr) stable-isotope fractionation in laboratory experiments and natural waters show that lighter isotopes reacted preferentially during Cr(VI) reduction by magnetite and sediments. The 53Cr/52Cr ratio of the product was 3.4 +/- 0.1 per mil less than that of the reactant. 53Cr/52Cr shifts in water samples indicate the extent of reduction, a critical process that renders toxic Cr(VI) in the environment immobile and less toxic.

California↗

A term extraction tool for expanding content in the domain of functioning, disability, and health: proof of concept.

Among the challenges in developing terminology systems is providing complete content coverage of specialized subject fields. This paper reports on a term extraction tool designed for the development and expansion of terminology systems concerned with functioning, disability, and health. Content relevant to this domain is the emphasis of the foci and targets of many nursing terminologies. We extend previously published term extraction algorithms by applying two filters. The first filter is based on the raw frequency of the content words in the lexical string under consideration. The second filter applies the notion of a complete syntactic node to discover relevant noun or verb phrases. While we report on a limited corpus (30,607 words comprising 4103 terms from 60 dismissal note summaries), the recall, precision, and F-measures we observed are encouraging and suggest continued development and testing of the tool is merited.

Algorithms↗

Ground water age.

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Models, Theoretical↗

Selenium stable isotope ratios in California agricultural drainage water management systems.

Selenium stable isotope ratios are known to shift in predictable ways during various microbial, chemical, and biological processes, and can be used to better understand Se cycling in contaminated environments. In this study we used Se stable isotopes to discern the mechanisms controlling the transformation of oxidized, aqueous forms of Se to reduced, insoluble forms in sediments of Se-affected environments. We measured 80Se/76Se in surface waters, shallow ground waters, evaporites, digested plants and sediments, and sequential extracts from several sites where agricultural drainage water is processed in the San Joaquin Valley of California. Selenium isotope analyses of samples obtained from the Tulare Lake Drainage District flow-through wetland reveal small isotopic contrasts (mean difference 0.7%) between surface water and reduced Se species in the underlying sediments. Selenium in aquatic macrophytes was very similar isotopically to the NaOH and Na2SO3 sediment extracts designed to recover soluble organic Se and Se(0), respectively. For the integrated on-farm drainage management sites, evaporite salts were slightly (approximately 0.6%) enriched in the heavier isotope relative to the inferred parent waters, whereas surface soils were slightly (approximately 1.4%) depleted. Bacterial or chemical reduction of Se(VI) or Se(IV) may be occurring at these sites, but the small isotopic contrasts suggest that other, less isotopically fractionating mechanisms are responsible for accumulation of reduced forms in the sediments. These findings provide evidence that Se assimilation by plants and algae followed by deposition and mineralization is the dominant transformation pathway responsible for accumulation of reduced forms of Se in the wetland sediments.

Agriculture↗