The complexities of skeletal biology

For a long time, the skeleton was seen as an amorphous tissue of little biological interest. But such a view ignored the large number of genetic and degenerative diseases affecting this organ. Over the past 15 years, molecular and genetic studies have modified our understanding of skeletal biology. By so doing this progress has affected our understanding of diseases and suggested in many instances new therapeutic opportunities.     

p53 mutant mice that display early ageing-associated phenotypes.

The p53 tumour suppressor is activated by numerous stressors to induce apoptosis, cell cycle arrest, or senescence. To study the biological effects of altered p53 function, we generated mice with a deletion mutation in the first six exons of the p53 gene that express a truncated RNA capable of encoding a carboxy-terminal p53 fragment. This mutation confers phenotypes consistent with activated p53 rather than inactivated p53. Mutant (p53+/m) mice exhibit enhanced resistance to spontaneous tumours compared with wild-type (p53+/+) littermates. As p53+/m mice age, they display an early onset of phenotypes associated with ageing. These include reduced longevity, osteoporosis, generalized organ atrophy and a diminished stress tolerance. A second line of transgenic mice containing a temperature-sensitive mutant allele of p53 also exhibits early ageing phenotypes. These data suggest that p53 has a role in regulating organismal ageing.     

Marine aerosol formation from biogenic iodine emissions

The formation of marine aerosols and cloud condensation nuclei--from which marine clouds originate--depends ultimately on the availability of new, nanometre-scale particles in the marine boundary layer. Because marine aerosols and clouds scatter incoming radiation and contribute a cooling effect to the Earth's radiation budget, new particle production is important in climate regulation. It has been suggested that sulphuric acid derived from the oxidation of dimethyl sulphide is responsible for the production of marine aerosols and cloud condensation nuclei. It was accordingly proposed that algae producing dimethyl sulphide play a role in climate regulation, but this has been difficult to prove and, consequently, the processes controlling marine particle formation remains largely undetermined. Here, using smog chamber experiments under coastal atmospheric conditions, we demonstrate that new particles can form from condensable iodine-containing vapours, which are the photolysis products of biogenic iodocarbons emitted from marine algae. Moreover, we illustrate, using aerosol formation models, that concentrations of condensable iodine-containing vapours over the open ocean are sufficient to influence marine particle formation. We suggest therefore that marine iodocarbon emissions have a potentially significant effect on global radiative forcing.     

The chemotactic receptor for human C5a anaphylatoxin.

Host defence and inflammatory responses are controlled and amplified by receptor-mediated events often initiated by a chemotactic factor that directs the approach of phagocytic cells. Complement receptors CR1 and CR3 are responsible for the phagocytic and adhesive properties of neutrophils, whereas the C5a receptor mediates the pro-inflammatory and chemotactic actions of the complement anaphylatoxin C5a. In addition to stimulating chemotaxis, granule enzyme release and superoxide anion production, this receptor stimulates upregulation of expression and activity of the adhesion molecule MAC-1, and of CR1, and a decrease in cell-surface glycoprotein 100MEL-14 on neutrophils. In vivo, the C5a receptor may participate in anaphylactoid and septic shock. The human C5a receptor was cloned from U937 and HL-60 cells and identified by high affinity binding when expressed in COS-7 cells. The deduced amino-acid sequence of the receptor reveals the expected motifs befitting its interaction with cellular GTP-binding proteins.     

Soft knowledge accumulation,or the rise of competence

Of late, many new methodologies have appeared which purport to help improve organizations and the activities of their clients. The language of observation—instrumental in producing high-quality observations on results and methods—provides the main tool for evaluating these methodologies. Having been designed for different purposes it may, however, curtail the power of such methodologies. The language of access provides a better tool. It requires coordination of actorsin situ and emphasizes the coordinating role of artificial languages such as the problem-solving language or the language of decision.     

The genome of the choanoflagellate Monosiga brevicollis and the origin of metazoans

Choanoflagellates are the closest known relatives of metazoans. To discover potential molecular mechanisms underlying the evolution of metazoan multicellularity, we sequenced and analysed the genome of the unicellular choanoflagellate Monosiga brevicollis. The genome contains approximately 9,200 intron-rich genes, including a number that encode cell adhesion and signalling protein domains that are otherwise restricted to metazoans. Here we show that the physical linkages among protein domains often differ between M. brevicollis and metazoans, suggesting that abundant domain shuffling followed the separation of the choanoflagellate and metazoan lineages. The completion of the M. brevicollis genome allows us to reconstruct with increasing resolution the genomic changes that accompanied the origin of metazoans.     

Towards a Hierarchical Definition of Life,the Organism,and Death

Despite hundreds of definitions, no consensus exists on a definition of life or on the closely related and problematic definitions of the organism and death. These problems retard practical and theoretical development in, for example, exobiology, artificial life, biology and evolution. This paper suggests improving this situation by basing definitions on a theory of a generalized particle hierarchy. This theory uses the common denominator of the “operator” for a unified ranking of both particles and organisms, from elementary particles to animals with brains. Accordingly, this ranking is called “the operator hierarchy”. This hierarchy allows life to be defined as: matter with the configuration of an operator, and that possesses a complexity equal to, or even higher than the cellular operator. Living is then synonymous with the dynamics of such operators and the word organism refers to a select group of operators that fit the definition of life. The minimum condition defining an organism is its existence as an operator, construction thus being more essential than metabolism, growth or reproduction. In the operator hierarchy, every organism is associated with a specific closure, for example, the nucleus in eukaryotes. This allows death to be defined as: the state in which an organism has lost its closure following irreversible deterioration of its organization. The generality of the operator hierarchy also offers a context to discuss “life as we do not know it”. The paper ends with testing the definition’s practical value with a range of examples.     

Reactive Extraction of Alcohols from Apolar Hydrocarbons with Aqueous Solutions

Introduction Oxygenates like carboxylic acids, aldehydes/ketones, and alcohols are often present in less than 10 wt.% concentrations in apolar organic solvents from which they are industrially recovered by a highly energy-consuming distillation in which t…