Environmental concerns surrounding drilling for gas are intense due to expansion of shale gas drilling operations. Controversy surrounding the impact of drilling on air and water quality has pitted industry and lease-holders against individuals and groups concerned with environmental protection and public health. Because animals often are exposed continually to air, soil, and groundwater and have more frequent reproductive cycles, animals can be used as sentinels to monitor impacts to human health. This study involved interviews with animal owners who live near gas drilling operations. The findings illustrate which aspects of the drilling process may lead to health problems and suggest modifications that would lessen but not eliminate impacts. Complete evidence regarding health impacts of gas drilling cannot be obtained due to incomplete testing and disclosure of chemicals, and nondisclosure agreements. Without rigorous scientific studies, the gas drilling boom sweeping the world will remain an uncontrolled health experiment on an enormous scale.

The recent demonstrations that thrombolytic therapy with plasminogen activators can result in substantial reductions in mortality from coronary thrombosis have generated considerable interest in the properties of fibrinolytic enzymes. Examination of the primary sequence of these proteins (which include tissue plasminogen activator, plasminogen, and urokinase) reveals that each is composed of a mosaic of domains which appear to be spatially distinct and connected by short peptide linkers. There is, however, little experimental information about the three-dimensional structure of any of the proteins, although several X-ray diffraction and NMR studies of isolated domains have been reported. Here we report two-dimensional NMR spectra of intact urokinase which are remarkably well resolved for a protein of this molecular weight. This effect is a consequence of substantial independent motion between individual domains of the protein, which overcomes the broadening effects anticipated for the slow overall tumbling rate of the intact molecule. As well as having significance for the physiological role of the protein, these results provide a direct means for the comparison of structural features determined for the isolated domains with those of the intact protein and may provide a basis for proposing or evaluating models for the overall structure of fibrinolytic proteins. Preliminary results with other proteins indicate that this approach may be generally applicable to other multidomain proteins of the fibrinolytic family.

The solution structure of neuronal bungarotoxin (nBgt) has been studied by using two-dimensional 1H NMR spectroscopy. Sequence-specific assignments for over 95% of the backbone resonances and 85% of the side-chain resonances have been made by using a series of two-dimensional spectra at four temperatures. From these assignments over 75% of the NOESY spectrum has been assigned, which has in turn provided 582 distance constraints. Twenty-seven coupling constants (NH-alpha CH) were determined from the COSY spectra, which have provided dihedral angle constraints. In addition, hydrogen exchange experiments have suggested the probable position of hydrogen bonds. The NOE constraints, dihedral angle constraints, and the rates of amide proton exchange suggest that a triple-stranded antiparallel beta sheet is the major component of secondary structure, which includes 25% of the amino acid residues. A number of NOE peaks were observed that were inconsistent with the antiparallel beta-sheet structure. Because we have confirmed by sedimentation equilibrium that nBgt exists as a dimer, we have reinterpreted these NOE constraints as intermolecular interactions. These constraints suggest that the dimer consists of a six-stranded antiparallel beta sheet (three from each monomer), with residues 55-59 forming the dimer interface.

Public health concerns related to the expansion of unconventional oil and gas drilling have sparked intense debate. In 2012, we published case reports of animals and humans affected by nearby drilling operations. Because of the potential for long-term effects of even low doses of environmental toxicants and the cumulative impact of exposures of multiple chemicals by multiple routes of exposure, a longitudinal study of these cases is necessary. Twenty-one cases from five states were followed longitudinally; the followup period averaged 25 months. In addition to humans, cases involved food animals, companion animals and wildlife. More than half of all exposures were related to drilling and hydraulic fracturing operations; these decreased slightly over time. More than a third of all exposures were associated with wastewater, processing and production operations; these exposures increased slightly over time. Health impacts decreased for families and animals moving from intensively drilled areas or remaining in areas where drilling activity decreased. In cases of families remaining in the same area and for which drilling activity either remained the same or increased, no change in health impacts was observed. Over the course of the study, the distribution of symptoms was unchanged for humans and companion animals, but in food animals, reproductive problems decreased and both respiratory and growth problems increased. This longitudinal case study illustrates the importance of obtaining detailed epidemiological data on the long-term health effects of multiple chemical exposures and multiple routes of exposure that are characteristic of the environmental impacts of unconventional drilling operations.