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Biomedical subjects

Charles Harris

Publications and source records attributed to Charles Harris.

5 recordsLinked to original sources

Twenty-five-year study of radionuclides in the Susquehanna river via periphyton biomonitors.

This 25-y study monitored aquatic and terrestrial gamma-ray-emitting radionuclide levels near a nuclear power plant. It is the only known, long-term environmental survey of its kind. It was conducted neither by a utility owner, nor by a government agency, but rather by a private, environmental research institution. Compared to dozens of other flora and fauna, periphyton was found to be the best indicator to biomonitor the Susquehanna River, which runs near PPL Susquehanna's nuclear plant. Sampling began in 1979 before the first plant start-up and continued for the next 24 years. Monitoring began two months after the Three Mile Island accident of 28 March 1979 and includes Three Mile Island area measurements. Ongoing measurements detected fallout from Chernobyl in 1986, as well as I not released from PPL Susquehanna. Although this paper concentrates on radionuclides found in periphyton, the scope of the entire environmental program includes a wide variety of aquatic and land-based plants, animals, and inorganic matter. Other species and matter studied were fish, mussels, snails, crayfish, insects, humus, mushrooms, lichens, squirrels, deer, cabbage, tomatoes, coarse and flocculated sediment, and more. Results show periphyton works well for detection of radionuclide activity, even in concentrations less than 100 Bq kg (picocuries per gram amounts). Data indicate that PPL Susquehanna's radionuclide releases have had no known environmental or human health impact.

Biological Assay↗

Genomic segmental polymorphisms in inbred mouse strains.

By analyzing genomic copy-number differences using high-resolution mouse whole-genome BAC arrays, we uncover substantial differences in regional DNA content between inbred strains of mice. The identification of these apparently common segmental polymorphisms suggests that these differences can contribute to genetic variability and pathologic susceptibility.

Animals↗

Identification of JNK-dependent and -independent components of cerebellar granule neuron apoptosis.

Cerebellar granule neurons grown in high potassium undergo rapid apoptosis when switched to medium containing 5 mm potassium, a stimulus mimicking deafferentation. This cell death can be blocked by genetic deletion of Bax, a member of the pro-apoptotic Bcl-2 family, cycloheximide an inhibitor of macromolecular synthesis or expression of dominant-negative c-jun. These observations suggest that Bax activation is the result of c-jun target gene(s) up-regulation following trophic withdrawal. Candidate genes include the BH3-only Bcl-2 family members Dp5 and Bim. The molecular mechanisms underlying granule cell neuronal apoptosis in response to low potassium were investigated using CEP-1347 (KT7515), an inhibitor of the MLK family of JNKKK. CEP-1347 provided protection of potassium-serum-deprived granule cells, but such neuroprotection was not long term. The incomplete protection was not due to incomplete blockade of the JNK signaling pathway because c-jun phosphorylation as well as induction of c-jun RNA and protein were completely blocked by CEP-1347. Following potassium-serum deprivation the JNKK MKK4 becomes phosphorylated, an event blocked by CEP-1347. Cells that die in the presence of CEP-1347 activate caspases; and dual inhibition of caspases and MLKs has additive, not synergistic, effects on survival. A lack of synergism was also seen with the p38 inhibitor SB203580, indicating that the neuroprotective effect of the JNK pathway inhibitor cannot be explained by p38 activation. Activation of the JNK signaling pathway seems to be a key event in granule cell apoptosis, but these neurons cannot survive long term in the absence of sustained PI3 kinase signaling.

Animals↗