Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans

The efficacy and safety of biological molecules in cancer therapy, such as peptides and small interfering RNAs (siRNAs), could be markedly increased if high concentrations could be achieved and amplified selectively in tumour tissues versus normal tissues after intravenous administration. This has not been achievable so far in humans. We hypothesized that a poxvirus, which evolved for blood-borne systemic spread in mammals, could be engineered for cancer-selective replication and used as a vehicle for the intravenous delivery and expression of transgenes in tumours. JX-594 is an oncolytic poxvirus engineered for replication, transgene expression and amplification in cancer cells harbouring activation of the epidermal growth factor receptor (EGFR)/Ras pathway, followed by cell lysis and anticancer immunity. Here we show in a clinical trial that JX-594 selectively infects, replicates and expresses transgene products in cancer tissue after intravenous infusion, in a dose-related fashion. Normal tissues were not affected clinically. This platform technology opens up the possibility of multifunctional products that selectively express high concentrations of several complementary therapeutic and imaging molecules in metastatic solid tumours in humans.     

An Argentine ant aggregation factor

Summary (Z)-9-Hexadecenal, a general aggregation factor of the Argentine ant,Iridomyrmex humilis, has been isolated and chemically characterized. It is implicated as a component of the trail-pheromone complex on evidence that it is a constitutent of the ventral gland secretion, and that it both activates and attractsI. humilis workers.Acknowledgments. We thank the Australian Research Grants Committee, and the Reserve Bank of Australia, Rural Credits Development Fund for financial support.     

Fusion between a myogenic cell in the satellite cell position and undamaged adult myofibre segments.

In this report we demonstrate for the first time that differentiating myogenic cells, geographically located between the plasmalemma and external lamina of myofibres in the satellite cell position, can fuse directly with the plasmalemma of undamaged segments of mature myofibres.     

The structure of limonin

Zusammenfassung Die Struktur desepi-Limonol-jodoacetates (C₂₆H₃₁O₈) COCH₂I, wurde durch dreidimensionale Röntgenanalyse bestimmt. Es gelang, die Lage sämtlicher Atome in zwei kristallographisch unabhängigen, jedoch chemisch identischen Molekeln zu ermitteln. Dieses Resultat stellt eine vollständige Bestimmung der Konstitution und der Stereochemie des Limonins dar.     

Insect-mediated pollination in slickspot peppergrass, Lepidium papilliferum L. (Brassicaceae), and its implications for population viability

Field experiments on the pollination biology of slickspot peppergrass, Lepidium papilliferum L. (Brassicaceae), a rare species endemic to microsites in sagebrush-steppe habitat in southwestern Idaho, were conducted at 2 sites from May to July 2001. Site KB contained over 10,000 plants, whereas site WG contained less than 150 plants. Insect exclusion experiments revealed that seed production in L. papilliferum is dependent on insect-mediated pollination; median percent seed set dropped from 70% to 2% when insects were excluded from flowers. A total of 25 insect families from 5 orders visited L. papilliferum flowers: 24 families at KB and 11 families at WG. Only 9 families contained more than trace amounts of pollen on their bodies: Hymenoptera-Anthophoridae, Apidae, Colletidae, Halictidae, Sphecidae, Vespidae; Coleoptera-Cerambycidae, Dermestidae; Diptera-Syrphidae. Insects from these families are likely responsible for pollination of L. papilliferum , although some may be of only minor significance due to their infrequent visits to flowers. Two of the 4 most common and pollen-laden insects found at KB, honey bees ( Apis mellifera ) and colletid bees, were absent or rare at WG. Three other pollen-carrying families present at KB, Sphecidae, Vespidae, and Halictidae, were not found at WG. We raise several possible explanations for this disparity in pollinator communities between sites and discuss the importance of pollinator diversity to the long term viability of L. papilliferum .     

Consent and privacy in pharmacogenetic testing.

The clinical use of pharmacogenetic drugs will require that a sample of a patient's DNA be tested before a drug is prescribed. Although pharmacogenetic tests pose fewer risks than genetic tests for disease mutations, they might still reveal personal information that could be used adversely to a patient's interests. Informed consent and privacy of pharmacogenetic test results may be essential in most clinical uses of pharmacogenetic drugs.