Inactivation of the apoptosis effector Apaf-1 in malignant melanoma

Metastatic melanoma is a deadly cancer that fails to respond to conventional chemotherapy and is poorly understood at the molecular level. p53 mutations often occur in aggressive and chemoresistant cancers but are rarely observed in melanoma. Here we show that metastatic melanomas often lose Apaf-1, a cell-death effector that acts with cytochrome c and caspase-9 to mediate p53-dependent apoptosis. Loss of Apaf-1 expression is accompanied by allelic loss in metastatic melanomas, but can be recovered in melanoma cell lines by treatment with the methylation inhibitor 5-aza-2'-deoxycytidine (5aza2dC). Apaf-1-negative melanomas are invariably chemoresistant and are unable to execute a typical apoptotic programme in response to p53 activation. Restoring physiological levels of Apaf-1 through gene transfer or 5aza2dC treatment markedly enhances chemosensitivity and rescues the apoptotic defects associated with Apaf-1 loss. We conclude that Apaf-1 is inactivated in metastatic melanomas, which leads to defects in the execution of apoptotic cell death. Apaf-1 loss may contribute to the low frequency of p53 mutations observed in this highly chemoresistant tumour type.     

Genome sequencing in microfabricated high-density picolitre reactors

The proliferation of large-scale DNA-sequencing projects in recent years has driven a search for alternative methods to reduce time and cost. Here we describe a scalable, highly parallel sequencing system with raw throughput significantly greater than that of state-of-the-art capillary electrophoresis instruments. The apparatus uses a novel fibre-optic slide of individual wells and is able to sequence 25 million bases, at 99% or better accuracy, in one four-hour run. To achieve an approximately 100-fold increase in throughput over current Sanger sequencing technology, we have developed an emulsion method for DNA amplification and an instrument for sequencing by synthesis using a pyrosequencing protocol optimized for solid support and picolitre-scale volumes. Here we show the utility, throughput, accuracy and robustness of this system by shotgun sequencing and de novo assembly of the Mycoplasma genitalium genome with 96% coverage at 99.96% accuracy in one run of the machine.     

Computer analysis of cross sections of leaves of Chrysothamnus taxa and their relation to environmental conditions

Thirty-eight accessions of 20 taxa (species and subspecies) of Chrysothamnus from a range of environments were grown in a uniform garden. During mid-June, terminal and lateral leaves were removed, fixed, and processed for light-microscopy studies. Area and perimeter measurements of ink tracings of midleaf vein cross sections were measured using computer-scan techniques. Leaf area and perimeter were compared with vein perimeter and area measurements. Area and perimeter of these Chrysothamnus leaves varied in response to the environment at the collection location. Plants native to hot, dry conditions had small, thick leaves, whereas plants native to cooler, more mesic conditions had relatively large, thin leaves. Similarly, leaves with round veins were adapted to hot, dry environments and leaves with elliptical veins were adapted to cooler, more mesic environments. Both terminal (young) and lateral (older) leaves were sampled. Terminal leaves showed significant (p < .05) correlational responses to environmental parameters, whereas the lateral leaves, while fronding in the predicted morphological directions, did not generally show significant responses. The different responses of terminal and lateral leaves may have been due to canopy position and uniform environmental conditions of the garden. Leaves with large cross sections characteristically had large veins, and leaves with small cross sections characteristically had small veins. Large leaf cross sections were normally flat. Small leaf cross sections were normally round. Decreasing leaf size and increasing leaf thickness were correlated with aridity.     

A new Hypsiglena from Tiburon island, Sonora, Mexico

This third report on the herpetofauna of Chihuahua deals exclusively with amphibians. The first plethodonid salamander is reported, species Ambystoma rosaceum is discussed in greater detail than before, and two subspecies are recognized. Spea is elevated from subgeneric to generic rank, and S. stagnalis Cope is removed from synonymy and is recognized as a subspecies of hammondii . The species listed include the following: 2 salamanders and 19 anurans (1 Scaphiopus , 2 Spea , 9 Bufo , 1 Eleutherodactylus , 2 Hyla , 3 Rana , and 1 Microhyla ). Reference is made to vaious habitats that are associated with elevations arising form lower deserts and extending into the western mountains. The role played by the dry and wet annual cycles is also noted.     

Growth of juvenile American lobsters in semiopen and closed culture systems using formulated diets

Growth of juvenile American lobsters, Homarus americanus , raised in four semiopen culture systems, with daily water exchange rates ranging from 29 percent to 3.3 percent, was compared with growth in a completely closed system. Animals were fed a formulated pelleted ration, water quality factors were measured daily, and changes in concentration of nitrate, orthophosphate, and total organic carbon were monitored. Results of two 90-day trials indicate that growth increased in the system with the lower water exchange rates. Maximum growth occurred in the closed system.     

Buccal floor of reptiles, a summary

A general survey of the information presently available on the osteology and myology of the hyobranchial apparatus. Included in the survey are examples of the hyobranchial skeleton of the major groups of reptiles, including the Chelonia, Crocodilia, Rhynchocephalia, and Squamata. The myology treats the muscles directly associated with the hyoid as well as those associated with the functioning of the apparatus, but not arising or inserted directly on or from the hyoid. The innervation of the hyobranchial apparatus is reviewed and briefly discussed based on the information available in a few major studies. An attempt is made to cite all pertinent literature references, and in Tables 1 and 2 the references to basic areas are indicated. Twenty - nine plates and figures are included, some of which represent original research.     

Terrestrial vertebrate fauna of the Kaiparowits Basin

This report includes data collected during an investigation by Brigham Young University personnel from 1971 to 1976, as well as a literature review. The fauna of the Kaiparowits Basin is represented by 7 species of amphibians (1 salamander, 5 toads, and 1 tree frog), 29 species of reptiles (1 turtle, 16 lizards, and 12 snakes), 183 species of birds (plus 2 hypothetical), and 74 species of mammals. Geographic distribution of the various species within the basin are discussed. Birds are categorized according to their population and seasonal status. Avian habitat relationships are discussed, and extensions of range are reported for 5 species of birds. Three threatened or endangered avian species occur in the basin. Four avian species seem to have declined significantly in numbers in recent years.