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David P Turner

Publications and source records attributed to David P Turner.

8 recordsLinked to original sources
PubMed2024

Ovarian tumor cells gain competitive advantage by actively reducing the cellular fitness of microenvironment cells.

Cell competition and fitness comparison between cancer and tumor microenvironment (TME) cells determine oncogenic fate. Our previous study established a role for human Flower isoforms as fitness fingerprints, where the expression of Flower Win isoforms in tumor cells leads to growth advantage over TME cells expressing Lose isoforms. Here we demonstrate that the expression of Flower Lose and reduced microenvironment fitness is not a pre-existing condition but, rather, a cancer-induced phenomenon. Cancer cells actively reduce TME fitness by the exosome-mediated release of a cancer-specific long non-coding RNA, Tu-Stroma, which controls the splicing of the Flower gene in the TME cells and expression of Flower Lose isoform, which leads to reduced fitness status. This mechanism controls cancer growth, metastasis and host survival in ovarian cancer. Targeting Flower protein with humanized monoclonal antibody (mAb) in mice significantly reduces cancer growth and metastasis and improves survival. Pre-treatment with Flower mAb protects intraperitoneal organs from developing lesions despite the presence of aggressive tumor cells.

Female↗
PubMed2006

The DNA N-glycosylase MED1 exhibits preference for halogenated pyrimidines and is involved in the cytotoxicity of 5-iododeoxyuridine.

The base excision repair protein MED1 (also known as MBD4), an interactor with the mismatch repair protein MLH1, has a central role in the maintenance of genomic stability with dual functions in DNA damage response and repair. MED1 acts as a thymine and uracil DNA N-glycosylase on T:G and U:G mismatches that occur at cytosine-phosphate-guanine (CpG) methylation sites due to spontaneous deamination of 5-methylcytosine and cytosine, respectively. To elucidate the mechanisms that underlie sequence discrimination by MED1, we did single-turnover kinetics with the isolated, recombinant glycosylase domain of MED1. Quantification of MED1 substrate hierarchy confirmed MED1 preference for mismatches within a CpG context and showed preference for hemimethylated base mismatches. Furthermore, the k(st) values obtained with the uracil analogues 5-fluorouracil and 5-iodouracil were over 20- to 30-fold higher than those obtained with uracil, indicating substantially higher affinity for halogenated bases. A 5-iodouracil precursor is the halogenated nucleotide 5-iododeoxyuridine (5IdU), a cytotoxic and radiosensitizing agent. Cultures of mouse embryo fibroblasts (MEF) with different Med1 genotype derived from mice with targeted inactivation of the gene were evaluated for sensitivity to 5IdU. The results revealed that Med1-null MEFs are more sensitive to 5IdU than wild-type MEFs in both 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation assays. Furthermore, high-performance liquid chromatography analyses revealed that Med1-null cells exhibit increased levels of 5IdU in their DNA due to increased incorporation or reduced removal. These findings establish MED1 as a bona fide repair activity for the removal of halogenated bases and indicate that MED1 may play a significant role in 5IdU cytotoxicity.

Animals↗
PubMed2004

Monitoring forest carbon sequestration with remote sensing and carbon cycle modeling.

Sources and sinks of carbon associated with forests depend strongly on the management regime and spatial patterns in potential productivity. Satellite remote sensing can provide spatially explicit information on land cover, standage class, and harvesting. Carbon-cycle process models coupled to regional climate databases can provide information on potential rates of production and related rates of decomposition. The integration of remote sensing and modeling thus produces spatially explicit information on carbon storage and flux. This integrated approach was employed to compare carbon flux for the period 1992-1997 over two 165-km2 areas in western Oregon. The Coast Range study area was predominately private land managed for timber production, whereas the West Cascades study area was predominantly public land that was less productive but experienced little harvesting in the 1990s. In the Coast Range area, 17% of the land base was harvested between 1991 and 2000. Much of the area was in relatively young, productive-age classes that simulations indicate are a carbon sink. Mean annual harvest removals from the Coast Range were greater than mean annual net ecosystem production. On the West Cascades study area, a relatively small proportion (< 1%) of the land was harvested and the area as a whole was accumulating carbon. The spatially and temporally explicit nature of this approach permits identification of mechanisms underlying land base carbon flux.

Carbon↗
PubMed2004

Endurance of aneurysm clips: mechanical endurance of Yaşargil and Spetzler titanium aneurysm clips.

OBJECTIVE: To determine whether repeated use weakens titanium aneurysm clips, making them unsafe for clinical use. METHODS: Nine Yaşargil (titanium alloy) and five Spetzler (pure titanium) clips were subjected to clinically relevant maneuvers, and the effects on the closing force were assessed. Clips were considered unsafe if 1) the blades crossed, 2) the clips failed to close completely, or 3) the blood pressure could open them. RESULTS: Yaşargil and Spetzler clips significantly (P < 0.01 for both) weakened, by 18.9% and 26.1%, respectively, after 10 minutes of sustained maximal opening. After 100 open-close cycles, Spetzler clips showed no change in closing force, but the closing force of Yaşargil clips decreased significantly (P < 0.01), by a further 12.0%. CONCLUSION: Repeated use weakens Spetzler and Yaşargil clips. All Spetzler and all but one Yaşargil clips were deemed safe for clinical use at the end of the experiments.

Alloys↗
PubMed2003

Predicting leaf area index from scaling principles: corroboration and consequences.

Leaf area index (LAI) is a key biophysical variable in most process-based forest-ecosystem models. However, most such models require LAI as an input, typically obtained from empirical observations. We tested whether scaling principles based on trade-offs between single leaf and canopy properties could be effectively used to model LAI, thereby obviating the need for empirical observations. To do so, we used the process-oriented model, PnET, configured to estimate LAI from these same scaling principles. We derived biologically based LAI predictions (LAIPnET) for the Harvard Forest (Massachusetts, USA) eddy covariance tower site, a predominately mixed deciduous hardwood forest, using PnET, and compared these with a locally observed phenology record and with LAI estimates from both local (ground-based) photosynthetically active radiation transmittance (LAITRANS) and normalized difference vegetation index satellite data (LAINDVI). We generated the LAIPnET trajectory by running the PnET model with meteorological observations from the flux tower as model drivers. We derived LAITRANS from measurements of above- and below-canopy photosynthetically active radiation at the flux tower, and LAINDVI from observations from the Advanced Very High Resolution Radiometer (AVHRR) satellite-borne sensor of surface greenness for the 1 km2 cell containing the flux tower. Over a 5-year period, LAIPnET and LAITRANS values were comparable intra- and interannually, with maximum values differing by less than 0.1 to 0.2 LAI units (m2 m(-2)). Values of LAINDVI were similar to LAIPnET and LAITRANS in midsummer, but higher LAI values were predicted in the early and late portions of the growing season. In addition, we used the three alternative LAI trajectories in a modified version of the PnET model and compared the resulting outputs of gross primary production (GPP) with GPP estimates from the flux tower for 5 continuous years. The LAIPnET and LAITRANS inputs resulted in a difference of less than 3% in mean annual GPP from 1995 to 1999, and these were within 7 and 9%, respectively, of the annual eddy flux-based estimates over the same time period. The results indicate that biologically based LAI scaling approaches can closely track temporal changes in a deciduous forest and have potential for spatial and temporal scaling of LAI.

Ecosystem↗