Triallelic inheritance in Bardet-Biedl syndrome, a Mendelian recessive disorder

Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder characterized by multiple clinical features that include pigmentary retinal dystrophy, polydactyly, obesity, developmental delay, and renal defects. BBS is considered an autosomal recessive disorder, and recent positional cloning efforts have identified two BBS genes (BBS2 and BBS6). We screened our cohort of 163 BBS families for mutations in both BBS2 and BBS6 and report the presence of three mutant alleles in affected individuals in four pedigrees. In addition, we detected unaffected individuals in two pedigrees who carry two BBS2 mutations but not a BBS6 mutation. We therefore propose that BBS may not be a single-gene recessive disease but a complex trait requiring three mutant alleles to manifest the phenotype. This triallelic model of disease transmission may be important in the study of both Mendelian and multifactorial disorders.     

From signals to patterns: space, time, and mathematics in developmental biology

We now have a wealth of information about the molecular signals that act on cells in embryos, but how do the control systems based on these signals generate pattern and govern the timing of developmental events? Here, I discuss four examples to show how mathematical modeling and quantitative experimentation can give some useful answers. The examples concern the Bicoid gradient in the early Drosophila embryo, the dorsoventral patterning of a frog embryo by bone morphogenetic protein signals, the auxin-mediated patterning of plant meristems, and the Notch-dependent somite segmentation clock.     

Total carbon and nitrogen abundances in lunar samples

Total carbon and nitrogen abundances were determined by using combustion-gas chromatographic techlniques. Weighited mean analyses for butlk fines were 225 and 140 ppm total carbon and 150 anid 100 ppm total nitrogen. Total carbon in fine breccia was 230 ppm; in coarse breccia, 100 ppmn; in fine-grained rock, 70 ppm; and in mediumn-grained rock, 64 ppm. The finest sieved fraction had the highest carbon content. Total nitrogen in fine breccia was 125 ppm; in coarse breccia, 100 ppm; in fine-grained rock, 115 ppm; and in medium-grained rock, 30 ppm. The total carbon and nitrogen finies appeat to be mixtuires of indigenous lunar material togetheer with meteoritic and solar wind components.     

Water Permeability of Bacterial Spores and the Concept of a Contractile Cortex

Assumption of a water-impermeable coat on bacterial spores is inconsistent with known permeabilities of organic materials. A low water content may arise through compressive contraction of the cortex during spore maturation.     

Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP

JNPL3 transgenic mice expressing a mutant tau protein, which develop neurofibrillary tangles and progressive motor disturbance, were crossed with Tg2576 transgenic mice expressing mutant beta-amyloid precursor protein (APP), thus modulating the APP-Abeta (beta-amyloid peptide) environment. The resulting double mutant (tau/APP) progeny and the Tg2576 parental strain developed Abeta deposits at the same age; however, relative to JNPL3 mice, the double mutants exhibited neurofibrillary tangle pathology that was substantially enhanced in the limbic system and olfactory cortex. These results indicate that either APP or Abeta influences the formation of neurofibrillary tangles. The interaction between Abeta and tau pathologies in these mice supports the hypothesis that a similar interaction occurs in Alzheimer's disease.