Quantitative autoradiography of [3H]muscimol binding in rat brain

A simple quantitative autoradiographic technique for the study of neurotransmitter receptors that includes the use of a tritium-sensitive film permits saturation, kinetic, and competition studies of brain samples as small as 0.01 cubic millimeter. This technique was used to study [3H]muscimol binding in rat brain. Unilateral gamma-aminobutyric acid receptor supersensitivity was observed in the substantia nigra pars reticulata after production of localized lesions of the ipsilateral corpus striatum.     

Oligoribonucleotides: improvement in chromatographic separation

The separation of mixed oligoribonucleotides obtained from enzymatic digestion of soluble RNA into fractions containing mixed oligonucleotides of identical chain length is improved by absence of terminal phosphate. Each fraction may be separated into individual components by ionexchange (Dowex) chromatography. Combination of these two chromatographic procedures yields maximum information on primary structure of the oligonucleotides.     

Carbon monoxide measurements in the troposphere

During the second flight of the space shuttle, the measurement of air pollution from satellites (MAPS) experiment in the OSTA-1 payload acquired approximately 35 hours of radiometric measurements of the carbon monoxide mixing ratio in the middle troposphere, upper troposphere, and lower stratosphere. A gas filter radiometer operating in the 4.67-micrometer band was used to acquire the data over the region from 38 degrees N to 38 degrees S during both daytime and nighttime. The performance of the measurement system was excellent. The data reduced to date indicate the presence of significant gradients in the middle tropospheric carbon monoxide mixing ratio with both latitude and longitude over the North Atlantic, the Mediterranean Sea, and the Middle East. On the basis of comparisons with directly measured values, the accuracy of the measurements is approximately 15 percent. Comparisons of data taken on successive orbits over the same geographic region indicate that the repeatability of the measurements is approximately 5 percent.     

Observation of polymer conformation hysteresis in extensional flow

Highly extensible Escherichia coli DNA molecules in planar extensional flow were visualized in dilute solution by fluorescence microscopy. For a narrow range of flow strengths, the molecules were found in either a coiled or highly extended conformation, depending on the deformation history of the polymer. This conformation hysteresis persists for many polymer relaxation times and is due to conformation-dependent hydrodynamic forces. Polymer conformational free-energy landscapes were calculated from computer simulations and show two free-energy minima for flow strengths near the coil-stretch transition. Hysteresis cycles may directly influence bulk-solution stresses and the development of stress-strain relations for dilute polymer flows.     

Refinement of an orthotopic lung cancer model in the nude rat

Over 85% of people with lung cancer eventually succumb to this disease, largely because current chemotherapies are ineffective. The testing and validation of promising new approaches generally rely on achieving responses with cell lines in vitro or in tumor xenografts in nude mice. However, quite often the results seen with these models are not recapitulated in the clinic, thus necessitating the need for better animal models of lung cancer for preclinical testing of new therapies. One promising model is that of orthotopic lung cancer, where xenografts of human lung cancer are established in lungs of immunodeficient rodents. The problems associated with this model include poor rates of engraftment, limited tumor multiplicity, and a heightened risk for surgical trauma. The purpose of our study was to develop an efficient approach to engraftment of orthotopic tumors throughout the lungs of the Rowett nude rat. Initially, we augmented immunosuppression in the rats with whole-body X-irradiation and then used orotracheal cannulas to intratracheally instill human cancer cells from the Calu-6 cell line. This protocol produced a low rate of engraftment and low tumor multiplicity. The hypothesis that slight disruption of the pulmonary epithelium or the surfactant layer would allow better tumor engraftment was tested by coadministration of either pancreatic elastase or ethylenediaminetetraacetic acid (EDTA) along with the cell instillations. Lung tumor engraftment was evaluated 8 weeks after instillation. The inclusion of elastase or EDTA with the Calu-6 cells resulted in an 80-100% engraftment rate, respectively. Coadministration of EDTA resulted in significantly larger and greater numbers of tumors/lung than those in elastase-treated animals. Temporal studies demonstrated that small nodules were scattered throughout the lung parenchyma 5 weeks after instilling Calu-6 cells and EDTA. These nodules grew to coalesce and form large masses that effaced >75% of the parenchyma at 9 weeks postinstillation. The refinements made through our studies have led to the development of an orthotopic lung cancer model that should facilitate the evaluation of novel therapies designed to treat or impede lung cancer development.     

Sensitivity of alpine stream ecosystems to climate change and human impacts

• 1 Climatic changes and water resource developments alter the relative contribution of the water sources (glacier-melt, snow-melt, rainfall run-off and springflow) to the discharge regime of alpine streams.
• 2 Likely changes in the magnitude and variability of a range of climatic determinants of glacier behaviour, as a result of an enhanced Greenhouse Effect, are shown to have important implications for the future hydrogeomorphological and thermal dynamics of alpine streams.
• 3 Zoobenthic communities typically show deterministic patterns in alpine streams due to the over-riding influence of water temperature and channel stability. These communities could act as indicators of change in the relative contribution of run-off, particularly to alterations of glacier-melt patterns.
• 4 A reduction of glacial meltwater, following diversion for HEP generation, is used as an example to illustrate the sensitivity of the zoobenthic communities to changes in temperature and flow regimes, and geomorphological dynamics.