Insertional mutagenesis in zebrafish rapidly identifies genes essential for early vertebrate development

To rapidly identify genes required for early vertebrate development, we are carrying out a large-scale, insertional mutagenesis screen in zebrafish, using mouse retroviral vectors as the mutagen. We will obtain mutations in 450 to 500 different genes--roughly 20% of the genes that can be mutated to produce a visible embryonic phenotype in this species--and will clone the majority of the mutated alleles. So far, we have isolated more than 500 insertional mutants. Here we describe the first 75 insertional mutants for which the disrupted genes have been identified. In agreement with chemical mutagenesis screens, approximately one-third of the mutants have developmental defects that affect primarily one or a small number of organs, body shape or swimming behavior; the rest of the mutants show more widespread or pleiotropic abnormalities. Many of the genes we identified have not been previously assigned a biological role in vivo. Roughly 20% of the mutants result from lesions in genes for which the biochemical and cellular function of the proteins they encode cannot be deduced with confidence, if at all, from their predicted amino-acid sequences. All of the genes have either orthologs or clearly related genes in human. These results provide an unbiased view of the genetic construction kit for a vertebrate embryo, reveal the diversity of genes required for vertebrate development and suggest that hundreds of genes of unknown biochemical function essential for vertebrate development have yet to be identified.     

The Viable System Model and Its Application to Complex Organizations

Stafford Beer’s Viable System Model is the best known of the many cybernetic models he constructed over a career spanning more than 50 years. He explored the necessary conditions for viability in any complex system whether an organism, an organization or a country. Although the model was first applied in his work in the steel industry, many further applications were made during his later work as a consultant. The best known of these was when he was invited by President Salvadore Allende of Chile in 1970 to model the social economy of that country. That experiment was brutally cut short in 1973 by the CIA assisted coup during which Allende was killed and Pinochet’s dictatorship installed. The model itself draws on mathematics, psychology, biology, neurophysiology, communication theory, anthropology and philosophy. It was first expressed in mathematical terms in ‘The Cybernetic Factory’; next it was described in neurophysiological terms in Brain of the firm; and finally according to logic and graphic presentation in Heart of Enterprise and Diagnosing the System for Organizations. This last version is the one that is most accessible. It enables people to address organizational issues in a way that skirts the usual categories and organization charts and gets down to the actual necessary functions, no matter who is performing them. With this model people can get a boost as they diagnose or design an organizations. One aspect is to discover what the organization’s critical variables are and to find or install the homeostats that will show that they are maintaining equilibrium. Within that context, the model will help you ascertain that the principle functions and communications channels are in place and can function effectively. A crucial aspect of the VSM is that it is recursive; that is that the same relationships can be traced from the shop floor to the corporation or from the village to the country. Two examples will be discussed: a small business and the Chilean work from the 1970s. It is hoped that this will encourage people to imagine a world that works much better than it does now and where management is not defeated by complexity. A version of this paper was delivered as the first Stafford Beer Memorial Lecture on July 8, 2007 at the World Multiconference on Systems, Cybernetics and Informatics in Orlando Florida.     

Increased membrane-bound polyribosome fraction in the brains of rats with hereditary diabetes insipidus

Summary Rats homozygous for hypothalamic diabetes insipidus were found to have a significantly higher concentration of membrane-bound polyribosomes thant their heterozygous littermates. There was no difference in the concentration of free polyribosomes.     

Alignment of the stellar spin with the orbits of a three-planet system

The Sun's equator and the planets' orbital planes are nearly aligned, which is presumably a consequence of their formation from a single spinning gaseous disk. For exoplanetary systems this well-aligned configuration is not guaranteed: dynamical interactions may tilt planetary orbits, or stars may be misaligned with the protoplanetary disk through chaotic accretion , magnetic interactions or torques from neighbouring stars. Indeed, isolated 'hot Jupiters' are often misaligned and even orbiting retrograde. Here we report an analysis of transits of planets over starspots on the Sun-like star Kepler-30 (ref. 8), and show that the orbits of its three planets are aligned with the stellar equator. Furthermore, the orbits are aligned with one another to within a few degrees. This configuration is similar to that of our Solar System, and contrasts with the isolated hot Jupiters. The orderly alignment seen in the Kepler-30 system suggests that high obliquities are confined to systems that experienced disruptive dynamical interactions. Should this be corroborated by observations of other coplanar multi-planet systems, then star-disk misalignments would be ruled out as the explanation for the high obliquities of hot Jupiters, and dynamical interactions would be implicated as the origin of hot Jupiters.