Age-specific Effects of Novel Mutations in Drosophila Melanogaster I. Mortality

Theories for the evolution of aging rest on the assumption that at least some deleterious mutations have effects that are limited to certain ages. Many mutation accumulation studies have tried to measure the number and magnitude of deleterious mutations, but few studies have tried to determine the extent to which the effects of mutations are limited to particular ages. Here we estimate the age-specific effect of deleterious mutations on mortality rate in an outbred population of the fruit fly, Drosophila melanogaster. We used the ‘middle class neighborhood’ approach to accumulation mutations in populations of flies that had recently been obtained from the wild. There are mutations that increase mortality rates, but whose effects are limited to specific ages. The age-specificity of mutational effects differs between the sexes, between virgin and mated flies, and over time. After 10 and 20 generations of mutation accumulation, there were clear age-specific effects of mutations. After 30 generations, however, the degree of age-specificity decreased. In addition, mutation accumulation led to a steady increase in larval mortality and a small but significant increase in the sex ratio of eclosing flies. We discuss the implications of these results for models of aging, and suggest approaches that future studies should take to obtain accurate information on the age-specificity of novel mutations. This revised version was published online in July 2006 with corrections to the Cover Date.     

Leg length preservation with pedicled fillet of foot flaps after traumatic amputations

Six patients with insufficient soft-tissue coverage after lower limb trauma were treated with pedicled fillet of foot flaps to achieve primary stump closure and to preserve leg length. The flaps used were all based on either the posterior tibial neurovascular pedicle, the anterior tibial neurovascular pedicle, or both. Five flaps survived; one patient required conversion of a through-knee to an above-knee amputation and debridement of the flap because of venous thrombosis of the pedicle. In three of the cases, a functional knee joint was preserved. The patients ranged in age from 21 to 54 years, the mean hospital stay was 55.5 days (range, 28 to 76 days), and the mean follow-up time was 14.5 months. Despite an average of 4.3 procedures from initial admission to first discharge and an average of 2.0 postamputation procedures to achieve primary stump healing, all patients have achieved independent mobility with their prosthesis. The advantages of preserving leg length and, where possible, preserving a functional knee joint compensate for repeated procedures on these patients. When planned well, a pedicled fillet of foot flap therefore achieves the aims of amputation, namely, providing primary healing of a sensate, durable, cylindrical stump that is pain-free and preserves maximal leg length. This is achieved with no donor-site morbidity and with no need for microvascular reconstruction.     

cAMP and Schwann cells promote axonal growth and functional recovery after spinal cord injury

Central neurons regenerate axons if a permissive environment is provided; after spinal cord injury, however, inhibitory molecules are present that make the local environment nonpermissive. A promising new strategy for inducing neurons to overcome inhibitory signals is to activate cAMP signaling. Here we show that cAMP levels fall in the rostral spinal cord, sensorimotor cortex and brainstem after spinal cord contusion. Inhibition of cAMP hydrolysis by the phosphodiesterase IV inhibitor rolipram prevents this decrease and when combined with Schwann cell grafts promotes significant supraspinal and proprioceptive axon sparing and myelination. Furthermore, combining rolipram with an injection of db-cAMP near the graft not only prevents the drop in cAMP levels but increases them above those in uninjured controls. This further enhances axonal sparing and myelination, promotes growth of serotonergic fibers into and beyond grafts, and significantly improves locomotion. These findings show that cAMP levels are key for protection, growth and myelination of injured CNS axons in vivo and recovery of function.     

Mycosporine-like amino acid content in four species of sea anemones in the genus Anthopleura reflects phylogenetic but not environmental or symbiotic relationships

We examine the occurrence of UV-absorbing, mycosporine-like amino acids (MAAs) in four sympatric species of sea anemones in the genus Anthopleura, all collected from intertidal habitats on the Pacific Coast of temperate North America. We compare patterns of MAAs in A. elegantissima of several types: specimens having predominately zooxanthellae (dinoflagellates comprising at least two species) or zoochlorellae as symbionts; those containing algal endosymbionts of both kinds, and naturally occurring aposymbiotic specimens that lack the endosymbionts typically found in most specimens. We also compare MAAs in zooxanthellate specimens of A. sola and A. xanthogrammica, and specimens from the asymbiotic species A. artemisia. Our findings indicate that the complements of the four major MAAs in these species of Anthopleura (mycosporine-taurine, shinorine, porphyra-334, and mycosporine-2 glycine) broadly reflect phylogenetic differences among the anemones rather than the taxon of endosymbionts, presence or absence of symbionts, or environmental factors. An exception, however, occurs in A. elegantissima, where mycosporine-2 glycine increases in concentration with the density of zooxanthellae. Our evidence also shows that A. elegantissima can accumulate MAAs from its food, which may explain the occasional occurrence of minor MAAs in some individuals.     

Simultaneous Combined Pancreatic Test

A simultaneous combined pancreatic test can be performed in one morning with only one intubation of the duodenum. The test includes the measurement of exocrine pancreatic secretion of bicarbonate, enzymes, and radioactive selenium, pancreatic scanning, hypotonic duodenography, and cytology of the duodenal aspirate. In the first 70 patients it was found that a single secretion test was of only limited value in detecting pancreatic disease; cytology was the most reliable and scanning the least reliable single test; and that the combined test provided near-complete discrimination between patients with no pancreatic disease, with chronic pancreatitis, and with carcinoma of the pancreas.     

On the structure of coated vesicles

Electron micrographs of tilted specimens of coated vesicles show that their coats are based on polyhedral lattices constructed from 12 pentagons plus a variable number of hexagons. We have identified three such structures among the smaller particles, two containing 108 molecules of clathrin and a third containing 84. The coats of larger particles are believed to be constructed on similar principles. This polymorphism enables a variety of vesicles to be accommodated in an economical manner.