Predicting evolutionary patterns of mammalian teeth from development

One motivation in the study of development is the discovery of mechanisms that may guide evolutionary change. Here we report how development governs relative size and number of cheek teeth, or molars, in the mouse. We constructed an inhibitory cascade model by experimentally uncovering the activator-inhibitor logic of sequential tooth development. The inhibitory cascade acts as a ratchet that determines molar size differences along the jaw, one effect being that the second molar always makes up one-third of total molar area. By using a macroevolutionary test, we demonstrate the success of the model in predicting dentition patterns found among murine rodent species with various diets, thereby providing an example of ecologically driven evolution along a developmentally favoured trajectory. In general, our work demonstrates how to construct and test developmental rules with evolutionary predictability in natural systems.     

Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines

The nervous system senses peripheral damage through nociceptive neurons that transmit a pain signal. TRPA1 is a member of the Transient Receptor Potential (TRP) family of ion channels and is expressed in nociceptive neurons. TRPA1 is activated by a variety of noxious stimuli, including cold temperatures, pungent natural compounds, and environmental irritants. How such diverse stimuli activate TRPA1 is not known. We observed that most compounds known to activate TRPA1 are able to covalently bind cysteine residues. Here we use click chemistry to show that derivatives of two such compounds, mustard oil and cinnamaldehyde, covalently bind mouse TRPA1. Structurally unrelated cysteine-modifying agents such as iodoacetamide (IA) and (2-aminoethyl)methanethiosulphonate (MTSEA) also bind and activate TRPA1. We identified by mass spectrometry fourteen cytosolic TRPA1 cysteines labelled by IA, three of which are required for normal channel function. In excised patches, reactive compounds activated TRPA1 currents that were maintained at least 10 min after washout of the compound in calcium-free solutions. Finally, activation of TRPA1 by disulphide-bond-forming MTSEA is blocked by the reducing agent dithiothreitol (DTT). Collectively, our data indicate that covalent modification of reactive cysteines within TRPA1 can cause channel activation, rapidly signalling potential tissue damage through the pain pathway.     

Supercontinent cycles and the calculation of absolute palaeolongitude in deep time

Traditional models of the supercontinent cycle predict that the next supercontinent--'Amasia'--will form either where Pangaea rifted (the 'introversion' model) or on the opposite side of the world (the 'extroversion' models). Here, by contrast, we develop an 'orthoversion' model whereby a succeeding supercontinent forms 90° away, within the great circle of subduction encircling its relict predecessor. A supercontinent aggregates over a mantle downwelling but then influences global-scale mantle convection to create an upwelling under the landmass. We calculate the minimum moment of inertia about which oscillatory true polar wander occurs owing to the prolate shape of the non-hydrostatic Earth. By fitting great circles to each supercontinent's true polar wander legacy, we determine that the arc distances between successive supercontinent centres (the axes of the respective minimum moments of inertia) are 88° for Nuna to Rodinia and 87° for Rodinia to Pangaea--as predicted by the orthoversion model. Supercontinent centres can be located back into Precambrian time, providing fixed points for the calculation of absolute palaeolongitude over billion-year timescales. Palaeogeographic reconstructions additionally constrained in palaeolongitude will provide increasingly accurate estimates of ancient plate motions and palaeobiogeographic affinities.     

Expertise revisited,Part I—Interactional expertise

In Part I of this two part paper we try to set out the ‘essence’ of the notion of interactional expertise by starting with its origins. In Part II we will look at the notion of contributory expertise. The exercise has been triggered by recent discussion of these concepts in this journal by Plaisance and Kennedy and by Goddiksen.     

Growth inhibition and occurrence of cleft palates due to hypervitaminosis A

Summary DNA synthesis in palatal processes obtained from fetal rats was 36% lower in the presence of excess vitamin A, but vitamin A-exposed maxillary explants showed only a modest decrease. Scanning electron micrographs of fetuses exposed to hypervitaminosis A in utero demonstrated both decreased head size and stunted palatal processes. The results suggest that cleft palates occur in this model system because the palatal processes are more sensitive to the actions of vitamin A than are the surrounding maxillary tissues.Acknowledgments. We thank Dr Samuel M. Meller, Assistant Professor of Anatomy, Harvard Medical School, for his assistance in obtaining the scanning electron micrographs. This project was supported in part by grant DE-04684 from the National Institute of Dental Research.     

Constituents of Egyptian Euphorbiaceae. IX. Irritant and cytotoxic ingenane esters fromEuphorbia paralias L.

Summary The irritant and cytotoxic constituents of the latex ofEuphorbia paralias L. were separated from the hydrocarbon fraction by means of solvent partition. 3 new ingenane esters were identified from the toxic ether fraction. The major compound was 3-angelyl-20-deoxyingenol and the 2 minor compounds were 3-hexanoyl-20-deoxyingenol and 3-angelylingenol. These compounds were of a similar potency to podophyllin in the inhibition of³H-thymidine uptake by TLX/5 mouse lymphoma cells. In addition the compounds produced a persistent erythema of the mouse ear in sub-microgram doses.Acknowledgments. F.J. Evans is grateful to the Royal Society for a travel grant.     

Insect anti-juvenile hormone and juvenile hormone activity from plants in the genusNama

Summary The insect anti-juvenile hormones precocene I and II (7-methoxy-2,2-dimethyl-2H-1-benzopyran and 6,7-dimethoxy-2,2-dimethyl-2H-1-benzopyran) were identified in three of nineNama (Hydrophyllaceae) species. Precocene I occurred inN. lobbii while precocene II occurred inN. hispidum, N. lobbii andN. sandwicense. N. hispidum contained the highest concentration (ca 0.5% dry weight) of precocene II, which was found in the leaves, stems, seed capsules, corolla, glandular trichomes, and seeds. In addition to the anti-juvenile hormone, insect juvenile hormone activity was detected in the organosoluble extracts ofN. rothrockii andN. sandwicense. N. sandwicense is the first plant discovered to contain compounds with both anti- and juvenile hormone activity.