Humans appear no more sensitive than laboratory animals to the inhibition of red blood cell cholinesterase by dichlorvos

Inhibition of red blood cell (RBC) cholinesterase is a consistent and sensitive indicator of exposure to dichlorvos (DDVP). Absent human data, default 10-fold adjustment factors for potential interspecies and intraspecies sensitivity differences would be used in developing a reference dose from the no observed effect levels for this endpoint obtained in toxicological assessments of laboratory animals. However, many studies of the cholinesterase-inhibiting effects associated with DDVP exposure have been conducted in humans, including healthy male volunteers, other healthy subpopulations, and diverse clinical subpopulations. Indeed, ample human data exist to permit a data-based assessment of potential interspecies sensitivity differences in RBC cholinesterase inhibition associated with DDVP exposure. In aggregate, these data demonstrate that the DDVP doses producing inhibition in humans are virtually identical to those eliciting the same levels of inhibition in laboratory rats, mice, monkeys, and dogs. Thus, healthy humans appear to be no more sensitive than laboratory animals to DDVP's effects on RBC cholinesterase, and an interspecies uncertainty factor of 1 is appropriate and scientifically warranted for use in DDVP risk assessments.     

Performance of the log-linear approach to case-parent triad data for assessing maternal genetic associations with offspring disease: type I error, power, and bias

Maternal genetic variation may serve as a biomarker in studies aimed at clarifying fetal determinants of infant or adult disease. The log-linear approach to case-parent triad data (LCPT) can be used to investigate maternal genetic polymorphisms in relation to offspring disease risk, but LCPT operating characteristics have been reported for only a limited range of situations. The authors performed a simulation study to investigate the performance of the LCPT for assessing maternal associations with offspring disease risk over a wide range of scenarios with varying sample sizes (n), high-risk allele frequencies (f ), and modes of inheritance, all of which greatly affect the expected number of triads in informative categories. For most f values less than 0.5, the LCPT approach with 200 triads allowed for approximately 80% power to detect valid, unbiased maternal relative risks of 2 when inheritance was log-additive or dominant. When inheritance was recessive, this was true for most f 's greater than 0.35. Outside of this range, however, power and bias depended greatly on the mode of inheritance, f, and n. On the basis of these findings, epidemiologists may consider the LCPT a useful approach for assessing maternal relative risks unless one expects a very rare or fairly common maternal allele to increase offspring disease risk.     

Chemoattraction of male gametes by a pheromone produced by female gametes of Chlamydomonas

In isogamous species of Chlamydomonas, such as Chlamydomonas reinhardtii and Chlamydomonas eugametos, the sexual process involves the use of flagella agglutinins by which the gametes of compatible strains adhere through chance encounter and ultimately pair and fuse to form zygotes. In a newly described heterogamous species, Chlamydomonas allensworthii, the sexual process is initiated by the chemoattraction of small sperm to a sexually competent female gamete, which continues to secrete the pheromone until it has fused with one of the sperm so attracted. From bacteria-free female strains of C. allensworthii, the chemoat-tractant has been isolated and identified as a pentosylated hydroquinone (Mr = 532) whose spectral, chemical, and physical properties are in accord with the structure of a 2,3-dimethyl-5-(triprenylcarboxymethyl)-1,4-benzohydroquinone-1-(beta-xyloside). A rapid bioassay of the pheromone uses DEAE-Toyopearl 650M beads to which the pheromone adsorbs. When such activated beads are placed in a suspension of sperm, they act as surrogate females and attract the small motile sperm. The purified pheromone shows activity at a concentration as low as 1 pM.     

Is retaining the youthful functional anatomy underlying speed of information processing a signature of successful cognitive ageing? An event-related fMRI study of inspection time performance

It has been hypothesized that individual differences in cognitive ageing might in part be based on the relative preservation of speed of information processing. However, the biological foundations of processing speed are not understood. Here we compared two groups of non-demented older people who had relatively similar IQs at age 11 but differed markedly in non-verbal reasoning ability at age 70: 'cognitive sustainers' (n=25), and 'cognitive decliners' (n=15). Using an event-related fMRI design, we studied the BOLD response while they performed an inspection time task. Inspection time is a two-alternative forced choice, backward masking test of the speed of the early stages of visual information processing. Inspection time has a well-established, significant association with higher cognitive abilities. The group of cognitive sustainers showed a pattern of BOLD activation-deactivation in response to inspection time stimulus duration differences that was similar to a healthy young sample [Deary, I.J., Simonotto, E., Meyer, M., Marshall, A., Marshall, I., Goddard, N., Watdlaw, J.M., 2004a. The functional anatomy of inspection time: an event-related fMRI study. NeuroImage 22, 1466-1479]. The group of cognitive decliners lacked these clear neural networks. The relative preservation of complex reasoning skills in old age may be associated with the preservation of the neural networks that underpin fundamental information processing in youth.