Impacts of Waste from Concentrated Animal Feeding Operations on Water Quality

Waste from agricultural livestock operations has been a long-standing concern with respect to contamination of water resources, particularly in terms of nutrient pollution. However, the recent growth of concentrated animal feeding operations (CAFOs) presents a greater risk to water quality because of both the increased volume of waste and to contaminants that may be present (e.g., antibiotics and other veterinary drugs) that may have both environmental and public health importance. Based on available data, generally accepted livestock waste management practices do not adequately or effectively protect water resources from contamination with excessive nutrients, microbial pathogens, and pharmaceuticals present in the waste. Impacts on surface water sources and wildlife have been documented in many agricultural areas in the United States. Potential impacts on human and environmental health from long-term inadvertent exposure to water contaminated with pharmaceuticals and other compounds are a growing public concern. This work-group, which is part of the Conference on Environmental Health Impacts of Concentrated Animal Feeding Operations: Anticipating Hazards—Searching for Solutions, identified needs for rigorous ecosystem monitoring in the vicinity of CAFOs and for improved characterization of major toxicants affecting the environment and human health. Last, there is a need to promote and enforce best practices to minimize inputs of nutrients and toxicants from CAFOs into freshwater and marine ecosystems

Nonidentifiability of the Source of Intrinsic Noise in Gene Expression from Single-Burst Data

Over the last few years, experimental data on the fluctuations in gene activity between individual cells and within the same cell over time have confirmed that gene expression is a “noisy” process. This variation is in part due to the small number of molecules taking part in some of the key reactions that are involved in gene expression. One of the consequences of this is that protein production often occurs in bursts, each due to a single promoter or transcription factor binding event. Recently, the distribution of the number of proteins produced in such bursts has been experimentally measured, offering a unique opportunity to study the relative importance of different sources of noise in gene expression. Here, we provide a derivation of the theoretical probability distribution of these bursts for a wide variety of different models of gene expression. We show that there is a good fit between our theoretical distribution and that obtained from two different published experimental datasets. We then prove that, irrespective of the details of the model, the burst size distribution is always geometric and hence determined by a single parameter. Many different combinations of the biochemical rates for the constituent reactions of both transcription and translation will therefore lead to the same experimentally observed burst size distribution. It is thus impossible to identify different sources of fluctuations purely from protein burst size data or to use such data to estimate all of the model parameters. We explore methods of inferring these values when additional types of experimental data are available

Minimization and management of wastes from biomedical research.

Several committees were established by the National Association of Physicians for the Environment to investigate and report on various topics at the National Leadership Conference on Biomedical Research and the Environment held at the 1--2 November 1999 at the National Institutes of Health in Bethesda, Maryland. This is the report of the Committee on Minimization and Management of Wastes from Biomedical Research. Biomedical research facilities contribute a small fraction of the total amount of wastes generated in the United States, and the rate of generation appears to be decreasing. Significant reductions in generation of hazardous, radioactive, and mixed wastes have recently been reported, even at facilities with rapidly expanding research programs. Changes in the focus of research, improvements in laboratory techniques, and greater emphasis on waste minimization (volume and toxicity reduction) explain the declining trend in generation. The potential for uncontrolled releases of wastes from biomedical research facilities and adverse impacts on the general environment from these wastes appears to be low. Wastes are subject to numerous regulatory requirements and are contained and managed in a manner protective of the environment. Most biohazardous agents, chemicals, and radionuclides that find significant use in research are not likely to be persistent, bioaccumulative, or toxic if they are released. Today, the primary motivations for the ongoing efforts by facilities to improve minimization and management of wastes are regulatory compliance and avoidance of the high disposal costs and liabilities associated with generation of regulated wastes. The committee concluded that there was no evidence suggesting that the anticipated increases in biomedical research will significantly increase generation of hazardous wastes or have adverse impacts on the general environment. This conclusion assumes the positive, countervailing trends of enhanced pollution prevention efforts by facilities and reductions in waste generation resulting from improvements in research methods will continue

Thiolutin is a zinc chelator that inhibits the Rpn11 and other JAMM metalloproteases

Thiolutin is a disulfide-containing antibiotic and anti-angiogenic compound produced by Streptomyces. Its biological targets are not known. We show that reduced thiolutin is a zinc chelator that inhibits the JAB1/MPN/Mov34 (JAMM) domain–containing metalloprotease Rpn11, a deubiquitinating enzyme of the 19S proteasome. Thiolutin also inhibits the JAMM metalloproteases Csn5, the deneddylase of the COP9 signalosome; AMSH, which regulates ubiquitin-dependent sorting of cell-surface receptors; and BRCC36, a K63-specific deubiquitinase of the BRCC36-containing isopeptidase complex and the BRCA1–BRCA2-containing complex. We provide evidence that other dithiolopyrrolones also function as inhibitors of JAMM metalloproteases