Cytoplasmic Dynein, the Dynactin Complex, and Kinesin Are Interdependent and Essential for Fast Axonal Transport

In axons, organelles move away from (anterograde) and toward (retrograde) the cell body along microtubules. Previous studies have provided compelling evidence that conventional kinesin is a major motor for anterograde fast axonal transport. It is reasonable to expect that cytoplasmic dynein is a fast retrograde motor, but relatively few tests of dynein function have been reported with neurons of intact organisms. In extruded axoplasm, antibody disruption of kinesin or the dynactin complex (a dynein activator) inhibits both retrograde and anterograde transport. We have tested the functions of the cytoplasmic dynein heavy chain (cDhc64C) and the p150Glued (Glued) component of the dynactin complex with the use of genetic techniques in Drosophila. cDhc64C and Glued mutations disrupt fast organelle transport in both directions. The mutant phenotypes, larval posterior paralysis and axonal swellings filled with retrograde and anterograde cargoes, were similar to those caused by kinesin mutations. Why do specific disruptions of unidirectional motor systems cause bidirectional defects? Direct protein interactions of kinesin with dynein heavy chain and p150Glued were not detected. However, strong dominant genetic interactions between kinesin, dynein, and dynactin complex mutations in axonal transport were observed. The genetic interactions between kinesin and either Glued or cDhc64C mutations were stronger than those between Glued and cDhc64C mutations themselves. The shared bidirectional disruption phenotypes and the dominant genetic interactions demonstrate that cytoplasmic dynein, the dynactin complex, and conventional kinesin are interdependent in fast axonal transport.

A new Eocene archaeocete (Mammalia, Cetacea) from India and the time of origin of whales

Himalayacetus subathuensis is a new pakicetid archaeocete from the Subathu Formation of northern India. The type dentary has a small mandibular canal indicating a lack of auditory specializations seen in more advanced cetaceans, and it has Pakicetus-like molar teeth suggesting that it fed on fish. Himalayacetus is significant because it is the oldest archaeocete known and because it was found in marine strata associated with a marine fauna. Himalayacetus extends the fossil record of whales about 3.5 million years back in geological time, to the middle part of the early Eocene [≈53.5 million years ago (Ma)]. Oxygen in the tooth-enamel phosphate has an isotopic composition intermediate between values reported for freshwater and marine archaeocetes, indicating that Himalayacetus probably spent some time in both environments. When the temporal range of Archaeoceti is calibrated radiometrically, comparison of likelihoods constrains the time of origin of Archaeoceti and hence Cetacea to about 54–55 Ma (beginning of the Eocene), whereas their divergence from extant Artiodactyla may have been as early as 64–65 Ma (beginning of the Cenozoic).

Economic evaluation and randomised controlled trial of extracorporeal membrane oxygenation: UK collaborative trial

Objective: To compare the resource implications and short term outcomes of extracorporeal membrane oxygenation and conventional management for term babies with severe respiratory failure.