Production of atypical measles in rhesus macaques: evidence for disease mediated by immune complex formation and eosinophils in the presence of fusion-inhibiting antibody.

The severe disease atypical measles occurred when individuals immunized with a poorly protective inactivated vaccine contracted measles, and was postulated to be due to a lack of fusion-inhibiting antibodies. Here, rhesus macaques immunized with formalin-inactivated measles vaccine developed transient neutralizing and fusion-inhibiting antibodies, but no cytotoxic T-cell response. Subsequent infection with measles virus caused an atypical rash and pneumonitis, accompanied by immune complex deposition and an increase in eosinophils. Fusion-inhibiting antibody appeared earlier in these monkeys than in non-immunized monkeys. These data indicate that atypical measles results from previous priming for a nonprotective type 2 CD4 T-cell response rather than from lack of functional antibody against the fusion protein.     

Regulation of endomembrane biogenesis in arabidopsis by phospatidic acid hydrolase

Coordination of membrane lipid biosynthesis is important for cell function during plant growth and development. Here we summarize our recent work on PHOSPHATIDIC ACID PHOSPHOHYDROLASE (PAH) which suggests that this enzyme is a key regulator of phosphaticylcholine (PC) biosynthesis in Arabidopsis thaliana. Disruption of PAH activity elevates phosphatidic acid (PA) levels and stimulates PC biosynthesis and biogenesis of the endoplasmic reticulum (ER). Furthermore, the activity of PHOSPHOCHOLINE CYTIDYLYLTRANSFERASE (CCT), which is the key enzyme controlling the rate of PC biosynthesis, is directly stimulated by PA and expression of a constitutively active version of CCT replicates the effects of PAH disruption. Hence PAH activity can control the abundance of PA, which in turn can modulate CCT activity to govern the rate of PC biosynthesis. Crucially it is not yet clear how PAH activity is regulated in Arabidopsis but there is evidence that PAH1 and PAH2 are both phosphorylated and further work will be required to investigate whether this is functionally significant.     

Total soft-tissue reconstruction of the middle and lower face with multiple simultaneous free flaps in a pediatric patient

A 2-year-old boy sustained a massive facial soft-tissue wound secondary to a dog attack. Essentially all the soft tissues of the face were absent, including innervation and intraoral lining. We describe the reconstruction of this defect with five simultaneous free tissue transfers. To our knowledge, this is the first report of five simultaneous free flaps in any patient.     

Slow Recovery from Inbreeding Depression Generated by the Complex Genetic Architecture of Segregating Deleterious Mutations

The deleterious effects of inbreeding have been of extreme importance to evolutionary biology, but it has been difficult to characterize the complex interactions between genetic constraints and selection that lead to fitness loss and recovery after inbreeding. Haploid organisms and selfing organisms like the nematode Caenorhabditis elegans are capable of rapid recovery from the fixation of novel deleterious mutation; however, the potential for recovery and genomic consequences of inbreeding in diploid, outcrossing organisms are not well understood. We sought to answer two questions: 1) Can a diploid, outcrossing population recover from inbreeding via standing genetic variation and new mutation? and 2) How does allelic diversity change during recovery? We inbred C. remanei, an outcrossing relative of C. elegans, through brother-sister mating for 30 generations followed by recovery at large population size. Inbreeding reduced fitness but, surprisingly, recovery from inbreeding at large populations sizes generated only very moderate fitness recovery after 300 generations. We found that 65% of ancestral single nucleotide polymorphisms (SNPs) were fixed in the inbred population, far fewer than the theoretical expectation of ∼99%. Under recovery, 36 SNPs across 30 genes involved in alimentary, muscular, nervous, and reproductive systems changed reproducibly across replicates, indicating that strong selection for fitness recovery does exist. Our results indicate that recovery from inbreeding depression via standing genetic variation and mutation is likely to be constrained by the large number of segregating deleterious variants present in natural populations, limiting the capacity for recovery of small populations.     

Turbine flowmeter vs. Fleisch pneumotachometer: a comparative study for exercise testing

The purpose of this study was to investigate the characteristics of a newly developed turbine flowmeter (Alpha Technologies, model VMM-2) for use in an exercise testing system by comparing its measurement of expiratory flow (VE), O2 uptake (VO2), and CO2 output (VCO2) with the Fleisch pneumotachometer. An IBM PC/AT-based breath-by-breath system was developed, with turbine flowmeter and dual-Fleisch pneumotachometers connected in series. A normal subject was tested twice at rest, 100-W, and 175-W of exercise. Expired gas of 24-32 breaths was collected in a Douglas bag. VE was within 4% accuracy for both flowmeter systems. The Fleisch pneumotachometer system had 5% accuracy for VO2 and VCO2 at rest and exercise. The turbine flowmeter system had up to 20% error for VO2 and VCO2 at rest. Errors decreased as work load increased. Visual observations of the flow curves revealed the turbine signal always lagged the Fleisch signal at the beginning of inspiration or expiration. At the end of inspiration or expiration, the turbine signal continued after the Fleisch signal had returned to zero. The "lag-before-start" and "spin-after-stop" effects of the turbine flowmeter resulted in larger than acceptable error for the VO2 and VCO2 measurements at low flow rates.     

Biomolecular structure prediction at a low resolution using a neural network and the double-iterated kalman filter technique

We report the application of an integrated computational approach for biomolecular structure determination at a low resolution. In particular, a neural network is trained to predict the spatial proximity of C-alpha atoms that are less than a given threshold apart, whereas a Kalman filter algorithm is employed to outline the biomolecular fold, with a constraints set that includes these pairwise atomic distances, and the distances and angles that define the structure as it is known from the protein's sequence. The results for Crambin demonstrate that this integrated approach is useful for molecular structure prediction at a low resolution and may also complement existing experimental distance data for a protein structure determination. © 1996 John Wiley & Sons, Inc.