Alzheimer's disease: molecular concepts and therapeutic targets

The beta amyloid peptide is the major component of the neuritic plaques, the characteristic lesions in Alzheimer's disease. Mutations in three genes (APP, PS-1, and PS-2) cause familial Alzheimer's disease by alteration of the rate of generation of amyloid peptide or the length of this peptide. However, in the 90% non-familial cases, other factors play a major pathogenetic role. These include the apolipoprotein E genotype, the "plaque-associated" proteins promoting the formation of toxic fibrillar aggregates or the chronic inflammatory responses. The aim of this review is to explain the steps in the complex cascade leading to Alzheimer's disease and, based on this, to report the current efforts to intervene in these different pathophysiological events in order to prevent progression of Alzheimer's disease. Whereas acetylcholine substitution is currently used in clinical practice, future therapeutical strategies to combat Alzheimer's disease may include anti-inflammatory treatments, vaccination against beta amyloid peptide, or treatment with cholesterol-lowering drugs.     

Comparison of indoor and outdoor residential levels of volatile organic chemicals in five U.S. geographical areas

Matched pairs of indoor and outdoor air samples from residences in Greensboro, NC; Baton Rouge/ Geismar, LA; Deer Park/Pasadena, TX; Elizabeth/Bayonne, NJ: Antioch/W. Pittsburg, CA; and several small communities in the Los Angeles area were collected and analyzed for over 20 volatile organic compounds during the period from 1981 to 1984. Indoor (I) medians and maximum levels were higher than the corresponding outdoor (O) concentrations over the large majority of chemicals studied. In some cases, e.g., chloroform, dichlorobenzenes, and tetrachloroethylene, the median ratios (I/O) were greater than 10.     

Vibrations in the orbwebs of Nuctenea sclopetaria (Araneidae)

Summary Orbweaving spiders obtain much information from web-borne vibrations. One of their major problems is to distinguish relevant vibrations, particularly prey-produced signals, from irrelevant vibrations, particularly wind noise. This problem was studied by measuring the spectral characteristics of prey-and wind-induced web vibrations, and the spider's responsiveness to sinusoidal stimuli. In wind-generated vibration (Fig. 1) signal amplitude is large below 10 Hz and decreases by 30 to 40 dB/decade above the lowest resonance frequency for each type of web vibration. The lowest resonance for transverse vibration is 3 Hz with a 200 mg spider, and 10 Hz for longitudinal and lateral vibration. Below 10 Hz transverse vibration is much larger than the other two types, but this difference decreases at higher frequencies. Most of the amplitude in prey signals is below 50 Hz (Fig. 2), except for buzzing insects such as flies, bees and mosquitoes, whose high wing beats generate significant motion above 100 Hz. The spider's response threshold for sinusoidal stimuli in the prey-catching region of the web (Fig. 3) declines at 20 dB/decade over the range that could be measured (10 to 3,200 Hz for longitudinal, 18 to 560 Hz for transverse and 18 to 320 Hz for lateral vibration). The threshold curve for longitudinal vibration is 10 to 20 dB lower than for the other two types and has a minimum of 7 m RMS near 300 Hz. This difference appears to have a mechanical rather than a sensory basis, due to the better transmission of longitudinal vibration through the web (Fig. 4A). If the effect of the spider on web vibration is also considered, the resulting adjusted threshold curve (Fig. 4B: data available for longitudinal vibration only), shows a continuous decline of approximately 30 dB/decade. A possible mechanism for recognizing prey signals based on spectral information is discussed.     

Optimal pricing,use, and exploration of uncertain natural resource stocks

Units of natural resources, to be called “mines,” are assumed distributed over an unexplored territory according to a Poisson process in space. At any moment, total reserves and unexplored land are given. Society can determine the rate of consumption and the rate of exploration. Reserves are drawn down by consumption and increased by discoveries made during exploration; the amount of unexplored land is decreased by exploration. At any moment, the payoff of society is a concave function of consumption less a linear function of exploration with future payoffs discounted. Optimal policies are considered and, in particular, it is shown for a large amount of unexplored land the shadow prices of reserves and of unexplored land move in random cycles but show only a slight upward tread, thereby casting some light on the failure of mineral prices to rise at the market rate of interest.     

The influence of human activity patterns on personal PM exposure: a comparative analysis of filter-based and continuous particle measurements

Particulate matter (PM) exposure data from the U.S. Environmental Protection Agency (EPA)-sponsored 1998 Baltimore and 1999 Fresno PM exposure studies were analyzed to identify important microenvironments and activities that may lead to increased particle exposure for select elderly (>65 years old) subjects. Integrated 24-hr filter-based PM2.5 or PM10 mass measurements [using Personal Environmental Monitors (PEMs)] included personal measurements, indoor and outdoor residential measurements, and measurements at a central indoor site and a community monitoring site. A subset of the participants in each study wore passive nephelometers that continuously measured (1-min averaging time) particles ranging in size from 0.1 to approximately 10 microm. Significant activities and locations were identified by a statistical mixed model (p < 0.01) for each study population based on the measured PM2.5 or PM10 mass and time activity data. Elevated PM concentrations were associated with traveling (car or bus), commercial locations (store, office, mall, etc.), restaurants, and working. The modeled results were compared to continuous PM concentrations determined by the nephelometers while participants were in these locations. Overall, the nephelometer data agreed within 6% of the modeled PM2.5 results for the Baltimore participants and within approximately 20% for the Fresno participants (variability was due to zero drift associated with the nephelometer). The nephelometer did not agree as well with the PM10 mass measurements, most likely because the nephelometer optimally responds to fine particles (0.3-2 microm). Approximately one-half (54 +/- 31%; mean +/- standard deviation from both studies) of the average daily PM2.5 exposure occurred inside residences, where the participants spent an average of 83 +/- 10% of their time. These data also showed that a significant portion of PM2.5 exposure occurred in locations where participants spent only 4-13% of their time.     

Copulation behavior and paternity in the chaffinch

Summary We investigated two aspects of sperm competition in a wild population of chaffinches Fringilla coelebs: copulation behavior and genetic parentage determined by DNA fingerprinting. Pairs copulated at a high rate before laying, peaking at 4.4 copulation attempts per hour on day –3 relative to laying, with an average of 207 copulation attempts (83 behaviorally successful) per clutch. Extra-pair copulation attempts (n = 20) made up 7.8% of all copulation attempts that females were involved in. The rate at which pairs copulated was lower during egg-laying, but there was no evidence that this was due to the male of the pair timing copulations to coincide with an insemination window; it was more likely due to the fact that females solicited copulations at a lower rate. Both sexes solicited copulations but males solicited mainly extra-pair copulations. DNA fingerprinting showed that 17.0% of chicks (n = 47) in 23% of broods (n = 13) were fathered by a male other than the one paired to their mother. There was no evidence of intraspecific brood parasitism. In three cases where we were able to identify the father of extra-pair offspring it proved to be a neighboring male.Correspondence to: B.C. Sheldon     

Risk communication in the internet age: The rise of disorganized skepticism

Communicating risks has become a core ingredient in the regulatory functions of government, interest group advocacy, public health, and corporate relations. The channels of risk communication have grown in complexity along with the development and expansion of the Internet and the birth of personalized blogging. This paper discusses three stages in the development of risk communication as an area of study and research. It examines the way risk is framed in three channels of communication, newsprint, the Expanded Academic Index, and Google using the example of the controversial chemical perfluorooctanoic acid (PFOA). The paper concludes that the Internet, as illustrated by the Google search engine, has created more opportunities for citizen learning and expanded the breadth and channels of risk communication, while also providing new opportunities for stakeholders to influence the message. Democritization of information does not necessarily create greater concordance between the cultural and technical assessment of risk.