Malignant activation of a K-ras oncogene in lung carcinoma but not in normal tissue of the same patient

A single genetic alteration, a guanine-to-cytosine transversion, is responsible for the acquisition of malignant properties by K-ras genes of two human tumor cell lines established from carcinomas of the bladder (A1698) and lung (A2182). As a consequence, arginine instead of the normal glycine is incorporated into the K-ras-coded p21 proteins at amino acid position 12. This mutation creates a restriction enzyme polymorphism that can be used to screen human cells for transforming K-ras genes. This approach was used to identify the mutational event responsible for the malignant activation of a K-ras oncogene in a squamous cell lung carcinoma of a 66-year-old man; this point mutation was not present in either the normal bronchial or parenchymal tissue or in the blood lymphocytes. Hence, malignant activation of a ras oncogene appears to be specifically associated with the development of a human neoplasm.     

Identification of a DNA nonhomologous end-joining complex in bacteria

In eukaryotic cells, double-strand breaks (DSBs) in DNA are generally repaired by the pathway of homologous recombination or by DNA nonhomologous end joining (NHEJ). Both pathways have been highly conserved throughout eukaryotic evolution, but no equivalent NHEJ system has been identified in prokaryotes. The NHEJ pathway requires a DNA end-binding component called Ku. We have identified bacterial Ku homologs and show that these proteins retain the biochemical characteristics of the eukaryotic Ku heterodimer. Furthermore, we show that bacterial Ku specifically recruits DNA ligase to DNA ends and stimulates DNA ligation. Loss of these proteins leads to hypersensitivity to ionizing radiation in Bacillus subtilis. These data provide evidence that many bacteria possess a DNA DSB repair apparatus that shares many features with the NHEJ system of eukarya and suggest that this DNA repair pathway arose before the prokaryotic and eukaryotic lineages diverged.     

Intensive beach management as an improved sea turtle conservation strategy in Mexico

We evaluate the role of intensive beach management, meaning intense patrolling and nest reburial to a central hatchery, as a strategy for improving the success of sea turtle conservation at nesting sites in Mexico. We report the results of an experimental program at Playa Cuixmala, Jalisco, western Mexico. Sea turtle conservation efforts in Mexico have, in general, poor results because of lack of funds, which leads to insufficient beach protection and severe negative effects of nest removal on hatching success and sex ratios. Alternative strategies are needed to optimize limited resources. We predicted that intensive beach management, which included intense patrolling and careful nest reburial, could be an effective way to maximize nest survival and hatchling release under limited financial and human resources. The results of our 9-year study were very positive. Survival rate increased several fold during the study period. Hatching success and sex ratios were not significantly different between in-situ and removed nests. Survival in removed nests was, however, much higher that in-situ nests, because of predation and beach erosion. In total, the small (3 km length) Playa Cuixmala became the second most productive sea turtle nesting beach in the region because of these concentrated efforts. Intense beach management can be an important technique for sea turtle conservation, and can be properly applied to small beaches or the most productive sections of large beaches.     

Evaluation of oral and subcutaneous delivery of an experimental canarypox recombinant canine distemper vaccine in the Siberian polecat (Mustela eversmanni).

We assessed the safety and efficacy of an experimental canarypox-vectored recombinant canine distemper virus (CDV) subunit vaccine in the Siberian polecat (Mustela eversmanni), a close relative of the black-footed ferret, (M. nigripes), an endangered species that is highly susceptible to the virus. Siberian polecats were randomized into six treatment groups. Recombinant canine distemper vaccine was administered s.c. at three dose levels (10(4.5), 10(5.0), and 10(5.5) plaque-forming units [PFU] per dose) and was administered orally by spraying the vaccine into the oropharnyx at two dose levels (10(5.5), 10(8.0) PFU per dose). The sixth group of control animals was not vaccinated. For both routes of administration, two 1-ml doses of reconstituted vaccine were delivered 4 wk apart, followed by live virus challenge 3 wk after the second vaccination. During the challenge, Synder Hill test strain CDV obtained from the National Veterinary Services Laboratory in Ames, Iowa, was administered i.p. Serial blood samples for CDV serology were collected immediately before vaccination and challenge, and 10, 15, and 20 days after challenge. Clinical signs and body weights were recorded up to 32 days after challenge. The survival rate in animals receiving vaccine at the highest oral dose (10(8.0) PFU per dose) was 83.3%. Survival rate was 50.0% in the high s.c. and 60.0% in the medium s.c. groups. All animals in the low-s.c. dose, low-oral dose, and control groups died after exposure. Vaccine dose overall (oral and s.c.) and dose in response to s.c. administration when considered alone were significant predictors of survival (P = 0.006 and P = 0.04, respectively). Among the polecats challenged with virulent virus, those that died became sick sooner than those that survived. Animals that died lost significantly more weight during the 10 days after challenge than did animals that survived (P = 0.02). Survival rates did not differ by sex, founder female status, or breeding pedigree in any of the treatment groups. Survival rates were higher in animals with increasing serum neutralization titers (P = 0.027). This study demonstrates the efficacy of oral delivery of a recombinant CDV vaccine in the Siberian polecat. Further studies are needed to evaluate the safety and efficacy of vectored recombinant vaccines in highly susceptible species and especially in those species in which vaccination with modified live CDV has led to disease.     

Concurrent Fusarium chlamydosporum and Microsphaeropsis arundinis infections in a cat

A 7-year-old cat was presented initially with multiple draining sinuses on the metatarsal region of its right hindlimb. Another lesion had appeared at the same time on the fifth proximal interphalangeal joint of the left forelimb. Histopathological examination of a biopsy from the right hindlimb lesion revealed chronic pyogranulomatous inflammation associated with yeast-like bodies and septate mycelia; a fungus was cultured on conventional media but not identified further. Culture of a swab collected from the left forelimb lesion demonstrated a pigmented fungus, also not characterised further. Although there was initially a favourable response to ketoconazole (Nizoral, Janssen-Cilag Pty. Ltd) and beta-lactam therapy, the infection in the hind limb relapsed subsequently, and Fusarium chlamydosporum was cultured from deep biopsy specimens. Clinical improvement followed debridement and itraconazole (Sporanox, Janssen-Cilag Pty. Ltd; 100 mg orally once daily), however amputation of the limb represented the best chance for a cure. The cat made an uncomplicated recovery following surgery and remained well for five months until the lesion on the left forelimb recurred. Amputation of the distal fourth digit was then performed, and the resected tissue submitted for culture. The dematiaceous fungus Microsphaeropsis arundinis was subsequently cultured. The cat remained well for several months, until a further F. chlamydosporum infection developed on the body wall. This was excised 7 months ago, and no lesions have recurred in this area. Importantly, this is the first reported case of M. arundinis infection in a mammalian host.     

Impact features on Stardust: implications for comet 81P/Wild 2 dust

Particles emanating from comet 81P/Wild 2 collided with the Stardust spacecraft at 6.1 kilometers per second, producing hypervelocity impact features on the collector surfaces that were returned to Earth. The morphologies of these surprisingly diverse features were created by particles varying from dense mineral grains to loosely bound, polymineralic aggregates ranging from tens of nanometers to hundreds of micrometers in size. The cumulative size distribution of Wild 2 dust is shallower than that of comet Halley, yet steeper than that of comet Grigg-Skjellerup.     

Impacts of biodiversity loss on ocean ecosystem services

Human-dominated marine ecosystems are experiencing accelerating loss of populations and species, with largely unknown consequences. We analyzed local experiments, long-term regional time series, and global fisheries data to test how biodiversity loss affects marine ecosystem services across temporal and spatial scales. Overall, rates of resource collapse increased and recovery potential, stability, and water quality decreased exponentially with declining diversity. Restoration of biodiversity, in contrast, increased productivity fourfold and decreased variability by 21%, on average. We conclude that marine biodiversity loss is increasingly impairing the ocean's capacity to provide food, maintain water quality, and recover from perturbations. Yet available data suggest that at this point, these trends are still reversible.