YPD, PombePD and WormPD: model organism volumes of the BioKnowledge library, an integrated resource for protein information.

The BioKnowledge Library is a relational database and web site (http://www.proteome.com) composed of protein-specific information collected from the scientific literature. Each Protein Report on the web site summarizes and displays published information about a single protein, including its biochemical function, role in the cell and in the whole organism, localization, mutant phenotype and genetic interactions, regulation, domains and motifs, interactions with other proteins and other relevant data. This report describes four species-specific volumes of the BioKnowledge Library, concerned with the model organisms Saccharomyces cerevisiae (YPD), Schizosaccharomyces pombe (PombePD) and Caenorhabditis elegans (WormPD), and with the fungal pathogen Candida albicans (CalPD). Protein Reports of each species are unified in format, easily searchable and extensively cross-referenced between species. The relevance of these comprehensively curated resources to analysis of proteins in other species is discussed, and is illustrated by a survey of model organism proteins that have similarity to human proteins involved in disease.

The yeast A kinases differentially regulate iron uptake and respiratory function.

Yeast has three A kinase catalytic subunits, which have greater than 75% identity and are encoded by the TPK genes (TPK1, TPK2, and TPK3) [Toda, T., Cameron, S., Sass, P., Zoller, M. & Wigler, M. (1987) Cell 50, 277-287]. Although they are redundant for viability, the three A kinases are not redundant for pseudohyphal growth [Robertson, L. S. & Fink, G. R. (1998) Proc. Natl. Acad. Sci. USA 95, 13783-13787; Pan, X. & Heitman, J. (1999) Mol. Cell. Biol. 19, 4874-4887]; Tpk2, but not Tpk1 or Tpk3, is required for pseudohyphal growth. Genome-wide transcriptional profiling has revealed unique signatures for each of the three A kinases leading to the identification of additional functional diversity among these proteins. Tpk2 negatively regulates genes involved in iron uptake and positively regulates genes involved in trehalose degradation and water homeostasis. Tpk1 is required for the derepression of branched chain amino acid biosynthesis genes that seem to have a second role in the maintenance of iron levels and DNA stability within mitochondria. The fact that TPK2 mutants grow better than wild types on nonfermentable carbon sources and on media deficient in iron supports the unique role of Tpk2 in respiratory growth and carbon source use.

Reduced fatalities related to rear seat shoulder belts.

OBJECTIVE: To determine the effect on fatality rates in crashes of installation of shoulder belts in automobile back seats. METHODS: During 1988-96, fatalities to rear outboard seat occupants of passenger cars, classified by age of occupant and vehicle curb weight were matched to data on model year in which shoulder belts became standard equipment. The same data were obtained from the same years on back seat occupants in crashes from the Crashworthiness Data System. Weighted regression was performed on death rates per occupants in crashes by belt equipment, occupant age, and vehicle weight for all occupants and occupants who claimed to be restrained. RESULTS: The risk of death is significantly lower in vehicles equipped with shoulder belts, midsized to larger cars, and among children. Claimed child restraint use is higher in cars with shoulder belts and claimed use of shoulder belts is higher among adolescents and young adults but lower among those 35 and older. However, older occupants have lower death rates in shoulder belt equipped cars. CONCLUSIONS: Shoulder belts substantially reduce risk of death relative to lap belts at prevalent use rates in each age group. Belt effectiveness when used cannot be estimated precisely because of invalid claimed use, but the lowered rates among vehicles with shoulder belts indicates that effectiveness given prevalent use is far more efficacious than lap belts without shoulder belts.

The three yeast A kinases have specific signaling functions in pseudohyphal growth.

The three yeast A kinase catalytic subunit isoforms are redundant for viability. We demonstrate that they have dramatically different roles in pseudohyphal development: Tpk2 is essential, whereas Tpk3 inhibits. Tpk1 has no discernible effect. Two-hybrid analysis identified the transcription factor Sfl1 as a protein that interacts specifically with Tpk2, but not Tpk1 or Tpk3. Deletion of SFL1 enhances pseudohyphal and invasive growth. Flo11, a cell surface flocculin required for pseudohyphal development, is transcriptionally regulated by Tpk2 and Sfl1. Genetic evidence indicates that Tpk2 acts upstream of Sfl1 in the regulation of Flo11.

Causal webs, preventive brooms, and housekeepers.

The concept of causal webs, which emphasises complex multiple causation of disease and injury, diverts attention and resources from preventive brooms that can sweep away the webs to reduce harm despite multiple causation. Epidemiologists who focus primarily on specification of causal paths in webs may overlook the modifiable necessary conditions for disease and injury. Necessary causes for disease and injury and necessary conditions for prevention are not always the same. Corporations and governments have the opportunity and means to reduce or eliminate many hazards to human health by changing products and processes that are hazardous. The arguments used to avoid doing so are often flawed and sometimes false. Public health scientists who focus on the behavior of corporations and government agencies that fail to employ preventive brooms of known effectiveness are more likely to contribute to harm reduction than those who focus on causal webs.

Motor vehicle rollover and static stability: an exposure study.

OBJECTIVES: This study examined vehicle rollovers in terms of site-specific exposure and speeds of vehicles of varying stability. METHODS: Fifty-one rollover sites in two states were visited at the same time of day and day of week as the rollover. A sample of vehicles moving in the same direction as the rollover were observed, and vehicle-specific data were obtained from identification numbers. RESULTS: Low stability, exacerbated by the addition of passengers, increased the risk of rollover. Speed was not correlated with stability and is not a confounder. CONCLUSIONS: Rollovers could be substantially reduced if motor vehicles were manufactured with a static stability of 1.2 or greater.

An epidemiological study of roadway fatalities related to farm vehicles: United States, 1988 to 1993.

Compared with the estimated injury fatality rate for workers in all occupations (nine in 100,000 in 1988) the farm fatality rate (48 in 100,000) was among the highest in the nation; in 1993, these rates were eight and 35 in 100,000, respectively. On-road farm-vehicle fatalities have been identified as a significant problem, yet these events apparently have not been investigated in a comprehensive manner. The purpose of this study was to investigate the circumstances surrounding all on-road, non-truck, farm-vehicle crash fatalities in the United States form 1988 through 1993. The National Highway Traffic Safety Administration's Fatal Accident Reporting System, which includes data for all US fatal on-road motor vehicle crashes, was the source of data. Driver-related variables were compared among farm vehicles, vehicles in collisions with farm vehicles, and all other vehicles in rural, fatal crashes; environmental variables were compared between rural farm-vehicle and non-farm-vehicle crashes. During 1988 to 1993, in rural areas, 444 farm-vehicle occupants were killed; in addition, 238 occupants of other vehicles or pedestrians were killed in collisions with the farm vehicles. The farm vehicles were disproportionately involved in overturns, rear-end collisions, and incidents in which the injured person fell from the vehicle, when compared with all other non-farm vehicles involved in rural-area fatal crashes. Of the farm vehicles involved in fatal crashes at night, dawn, or dusk, 65% were struck in the rear, compared with 4% of vehicles involved in fatal non-farm-vehicle crashes. Compared with drivers in all other rural crashes, farm-vehicle operators were more likely to be male, have a greater proportion of convictions for driving while intoxicated, and a lower proportion of previous speeding convictions. From this initial investigation, it appears that the fatal-crash involvement of farm vehicles are related to vehicle and environmental factors that are changeable. Given the proportion of overturns associated with farm-vehicle crashes (21%) compared with non-farm vehicles (9%), there is a need to investigate design characteristics of the farm vehicles. The large proportion of farm vehicles struck in the rear during daylight (24%) as well as night, dawn, or dusk hours (65%), compared with non-farm vehicles (4% and 4%, respectively), suggest factors related to visibility and perception of the farm vehicles' speed that provide a basis for further study.

Reducing death on the road: the effects of minimum safety standards, publicized crash tests, seat belts, and alcohol.

OBJECTIVES: Two phases of attempts to improve passenger car crash worthiness have occurred: minimum safety standards and publicized crash tests. This study evaluated these attempts, as well as changes in seat belt and alcohol use, in terms of their effect on occupant death and fatal crash rates. METHODS: Data on passenger car occupant fatalities and total involvement in fatal crashes, for 1975 through 1991, were obtained from the Fatal Accident Reporting System. Rates per mile were calculated through published sources on vehicle use by vehicle age. Regression estimates of effects of regulation, publicized crash tests, seat belt use and alcohol involvement were obtained. RESULTS: Substantial reductions in fatalities occurred in the vehicle model years from the late 1960s through most of the 1970s, when federal standards were applied. Some additional increments in reduced death rates, attributable to additional improved vehicle crashworthiness, occurred during the period of publicized crash tests. Increased seat belt use and reduced alcohol use also contributed significantly to reduced deaths. CONCLUSIONS: Minimum safety standards, crashworthiness improvements, seat belt use laws, and reduced alcohol use each contributed to a large reduction in passenger car occupant deaths.

Child injury control: surveillance and research questions.

Injury is the leading cause of death for every year but the first of a child's life and, additionally, generates enormous costs in health care, disability, pain, and suffering. Research and programmatic efforts for injury control continue to have low priority relative to their modest costs and potential to reduce health-care and other costs to society. Modest improvements in data systems would lead to more effective targeting of injury control efforts that are useful in preventing injuries. Analytic studies of changeable risk factors and effectiveness of interventions would widen the range of available interventions and their cost-effectiveness.

Highway deaths: false PR on the effects of PR.

In June, 1988, the Department of Public Safety (DPS) in South Carolina launched a media campaign, called "Highways or Dieways?", in an attempt to reduce motor vehicle fatalities. Deaths per vehicle mile declined during the succeeding years and the DPS attributed all of the reduction to the campaign, gleaning some 62 awards in the process. This research indicates that the DPS took credit for a decline in fatalities that resulted from other factors. Fatality rates in South Carolina were actually higher during the campaign than would have been expected from the historic association of South Carolina's rates with the national rate or those of other states in the region. The campaign actually illustrates the principle that ad campaigns alone are often ineffective in changing public health.

Fatal car fires from rear-end crashes: the effects of fuel tank placement before and after regulation.

A federal standard for fuel tank integrity in cars was applied to 1977 and subsequent models. National data indicate that fatalities per 10,000 occupants in rear-end crashes of small cars, where fire was the most harmful event, were reduced by approximately 57% if the fuel tank was located behind the rear axle and 77% if the tank was situated directly above or in front of the rear axle.

Study of road-rail crashes in Claremore, OK, and allocation of resources for preventive measures.

Road-rail crossings where a train and motor vehicle crashed were compared with the next crossing in the direction from which the train traveled at the same time of day and day of week of the crash. The odds of a crash were much lower at crossings with automatically lowered gates (odds ratio = 0.11). Average road traffic was much higher at crash sites; the presence of automatic gates was unrelated to the volume of road traffic. Federally funded modifications of road-rail crossings have substantially reduced deaths at such sites. The program would be more cost effective, however, if criteria for highest risk sites were applied more systematically, and funds were apportioned among the States according to their relative proportions of the problem.