Evolution of the cytoskeleton

The eukaryotic cytoskeleton appears to have evolved from ancestral precursors related to prokaryotic FtsZ and MreB. FtsZ and MreB show 40-50% sequence identity across different bacterial and archaeal species. Here I suggest that this represents the limit of divergence that is consistent with maintaining their functions for cytokinesis and cell shape. Previous analyses have noted that tubulin and actin are highly conserved across eukaryotic species, but so divergent from their prokaryotic relatives as to be hardly recognizable from sequence comparisons. One suggestion for this extreme divergence of tubulin and actin is that it occurred as they evolved very different functions from FtsZ and MreB. I will present new arguments favoring this suggestion, and speculate on pathways. Moreover, the extreme conservation of tubulin and actin across eukaryotic species is not due to an intrinsic lack of variability, but is attributed to their acquisition of elaborate mechanisms for assembly dynamics and their interactions with multiple motor and binding proteins. A new structure-based sequence alignment identifies amino acids that are conserved from FtsZ to tubulins. The highly conserved amino acids are not those forming the subunit core or protofilament interface, but those involved in binding and hydrolysis of GTP.     

Survey of the year 2006 commercial optical biosensor literature

We identified 1219 articles published in 2006 that described work performed using commercial optical biosensor platforms. It is interesting to witness how the biosensor market is maturing with an increased number of instrument manufacturers offering a wider variety of platforms. However, it is clear from a review of the results presented that the advances in technology are outpacing the skill level of the average biosensor user. While we can track a gradual improvement in the quality of the published work, we clearly have a long way to go before we capitalize on the full potential of biosensor technology. To illustrate what is right with the biosensor literature, we highlight the work of 10 groups who have their eye on the ball. To help out the rest of us who have the lights on but nobody home, we use the literature to address common myths about biosensor technology.     

The discovery of 6-[2-(5-chloro-2-{[(2,4-difluorophenyl)methyl]oxy}phenyl)-1-cyclopenten-1-yl]-2-pyridinecarboxylic acid, GW848687X, a potent and selective prostaglandin EP1 receptor antagonist for the treatment of inflammatory pain

The discovery of a series of selective EP1 receptor antagonists based on a 1,2-diarylcyclopentene template is described. After defining the structural requirements for EP1 potency and selectivity, heterocyclic rings were incorporated to reduce logD and improve in vitro pharmacokinetic properties. The 2,6-substituted pyridines and pyridazines gave an appropriate balance of potency, in vivo pharmacokinetic properties and a low potential for inhibiting a range of CYP450 enzymes. From this series, GW848687X was shown to have an excellent profile in models of inflammatory pain and was selected as a development candidate.     

Foetal age determination and development in elephants

Elephants have the longest pregnancy of all mammals, with an average gestation of around 660 days, so their embryonic and foetal development have always been of special interest. Hitherto, it has only been possible to estimate foetal ages from theoretical calculations based on foetal mass. The recent development of sophisticated ultrasound procedures for elephants has now made it possible to monitor the growth and development of foetuses of known gestational age conceived in captivity from natural matings or artificial insemination. We have studied the early stages of pregnancy in 10 captive Asian and 9 African elephants by transrectal ultrasound. Measurements of foetal crown-rump lengths have provided the first accurate growth curves, which differ significantly from the previous theoretical estimates based on the cube root of foetal mass. We have used these to age 22 African elephant foetuses collected during culling operations. Pregnancy can be first recognized ultrasonographically by day 50, the presumptive yolk sac by about day 75 and the zonary placenta by about day 85. The trunk is first recognizable by days 85-90 and is distinct by day 104, while the first heartbeats are evident from around day 80. By combining ultrasonography and morphology, we have been able to produce the first reliable criteria for estimating gestational age and ontological development of Asian and African elephant foetuses during the first third of gestation.     

Forest giants on different evolutionary branches: Ecomorphological convergence in helicopter damselflies*

The convergent evolution of analogous features is an evolutionary process occurring independently across the tree of life. From the evolution of echolocation, prehensile tail, viviparity, or winged flight, environmental factors often drive this astonishing phenomenon. However, convergent evolution is not always conspicuous or easily identified. Giant damselflies count among the largest flying insects on Earth, and have astonishing ecologies including orb‐web spider plucking and oviposition in phytotelmata. One species occurs in the Afrotropics and 18 species are found in the Neotropics. Convergent evolution was historically hypothesized based on the ecological and morphological affinities of these two geographically distant lineages but was not supported by earlier phylogenetic inferences supporting their monophyly. Using a molecular supermatrix approach and a large selection of outgroups, we revisit and reject the monophyly of Afrotropical and Neotropical giant damselflies that is otherwise supported by a morphological phylogeny. Molecular divergence time estimation suggests an origin of Afrotropical giant damselflies in the late Paleogene, and of Neotropical ones at the Cretaceous/Paleogene boundary, thereby rejecting a long‐standing West Gondwana vicariance hypothesis. The strong ecological and morphological resemblances between these two independent lineages represents an astonishing case of Amphi‐Atlantic tropical convergent evolution.