A pug-nosed crocodyliform from the Late Cretaceous of Madagascar

Although the image of crocodyliforms as 'unchanged living fossils' is naive, several morphological features of the group are thought to have varied only within narrow limits during the course of evolution. These include an elongate snout with an array of conical teeth, a dorsoventrally flattened skull and a posteriorly positioned jaw articulation, which provides a powerful bite force. Here we report an exquisitely preserved specimen of a new taxon from the Late Cretaceous of Madagascar that deviates profoundly from this Bauplan, possessing an extremely blunt snout, a tall, rounded skull, an anteriorly shifted jaw joint and clove-shaped, multicusped teeth reminiscent of those of some ornithischian dinosaurs. This last feature implies that the diet of the new taxon may have been predominantly if not exclusively herbivorous. A close relationship with notosuchid crocodyliforms, particularly Uruguaysuchus (Late Cretaceous, Uruguay) is suggested by several shared derived features; this supports a biogeographical hypothesis that Madagascar and South America were linked during the Late Cretaceous.     

Secretion and mechanism of action of the hole-forming toxin aerolysin

Aeromonas hydrophila exports aerolysin as a protoxin which is activated by proteolysis after release. Aerolysin binds to the eucaryotic cell receptor glycophorin and oligomerizes, forming holes in the membrane. Important regions of the molecule have been identified by site-directed mutagenesis, and channel formation has been studied in planar lipid bilayers.     

Mutations in ISPD cause Walker-Warburg syndrome and defective glycosylation of α-dystroglycan

Walker-Warburg syndrome (WWS) is an autosomal recessive multisystem disorder characterized by complex eye and brain abnormalities with congenital muscular dystrophy (CMD) and aberrant a-dystroglycan glycosylation. Here we report mutations in the ISPD gene (encoding isoprenoid synthase domain containing) as the second most common cause of WWS. Bacterial IspD is a nucleotidyl transferase belonging to a large glycosyltransferase family, but the role of the orthologous protein in chordates is obscure to date, as this phylum does not have the corresponding non-mevalonate isoprenoid biosynthesis pathway. Knockdown of ispd in zebrafish recapitulates the human WWS phenotype with hydrocephalus, reduced eye size, muscle degeneration and hypoglycosylated a-dystroglycan. These results implicate ISPD in a-dystroglycan glycosylation in maintaining sarcolemma integrity in vertebrates.     

Organic chemistry of embalming agents in Pharaonic and Graeco-Roman mummies.

Chemical treatments were an essential element of ancient Egyptian mummification. Although the inorganic salt natron is recognized as having a central role as a desiccant, without the application of organic preservatives the bodies would have decomposed in the humid environment of the tombs. The nature of the organic treatments remains obscure, because the ancient Egyptians left no written record of the process. Secondary textual evidence for mummification is provided by Herodotus, Diodorus Siculus, Strabo and Pliny. The most important account is that of Herodotus (about 450 yr bc), although archaeological evidence shows that by this time the process had declined significantly and the best results had been achieved centuries before. His account mentions myrrh, cassia, palm wine, 'cedar oil' (still widely disputed) and 'gum'; however, it is vague with respect to the specific natural products used. Here we report the results of chemical investigations of a substantial collection of samples of tissues, wrappings and 'resinous/bituminous' materials from provenanced and dated Egyptian mummies. We focused on examples of the 'classic' mummy-making culture of the Pharaonic or dynastic period, from which we can begin to track the development of mummification chronologically.     

RGD peptides induce apoptosis by direct caspase-3 activation

Synthetic peptides containing the arginine-glycine-aspartate (RGD) motif have been used extensively as inhibitors of integrin-ligand interactions in studies of cell adhesion, migration, growth and differentiation, because the RGD motif is an integrin-recognition motif found in many ligands. Here we report that RGD-containing peptides are able to directly induce apoptosis without any requirement for integrin-mediated cell clustering or signals. We show that RGD-containing peptides enter cells and directly induce autoprocessing and enzymatic activity of procaspase-3, a pro-apoptotic protein. Using the breast carcinoma cell line MCF-7, which has a functional deletion of the caspase-3 gene, we confirm that caspase-3 is required for RGD-mediated cell death. In addition to an RGD motif, pro-caspase-3 also contains a potential RGD-binding motif, aspartate-aspartate-methionine (DDM), near the site of processing to produce the p12 and p17 subunits. On the basis of the ability of RGD-DDX interactions to trigger integrin activation, we suggest that RGD peptides induce apoptosis by triggering conformational changes that promote pro-caspase-3 autoprocessing and activation. These findings provide an alternative molecular explanation for the potent proapoptotic properties of RGD peptides in models of angiogenesis, inflammation and cancer metastasis.     

Disappearance of radioactivity from plasma following intravenous administration of tritiated thyrotrophin-releasing hormone (Ro 8-6270) to man

Zusammenfassung Nach i. v. Verabreichung von Thyrotrophin-releasing Hormonen an Versuchspersonen ergibt sich eine biphasische Kurve für den Abfall der Tritiumaktivität im Plasma mit einer Exkretions-Halbwertszeit von 3 h.

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Acknowledgements. The authors wish to express their gratitude to Hoffmann-La Roche and Co. AG, Basel for the research funds which supported this work. We are indebted to Dr.C. Metzler, Upjohn Co., Kalamazoo for a gift of the NON-LIN computer programme.     

Apoptosis disables CD31-mediated cell detachment from phagocytes promoting binding and engulfment

Macrophage recognition and ingestion of 'self' cells undergoing apoptosis in vivo protects tissues from the toxic contents of dying cells and modulates macrophage regulation of inflammatory and immune responses. However, the complex molecular mechanisms mediating macrophage discrimination between viable and apoptotic cells are poorly understood. In particular, little is known of why viable nucleated cells are not engulfed by macrophages. To reveal active repulsion of viable cells and to seek specific capture or 'tethering' of apoptotic cells, we studied macrophage binding of viable and apoptotic leukocytes under conditions of flow. We found that homophilic ligation of CD31 (ref. 4) on viable leukocytes promoted their active, temperature-dependent detachment under low shear, whereas such CD31-mediated detachment was disabled in apoptotic leukocytes, promoting tight binding and macrophage ingestion of dying cells. Here we propose that CD31 (also known as platelet-endothelial cell adhesion molecule-1, PECAM-1) is an example of a cell-surface molecule that prevents phagocyte ingestion of closely apposed viable cells by transmitting 'detachment' signals, and which changes function on apoptosis, promoting tethering of dying cells to phagocytes.     

Reversal of the net dinitrogen gas flux in coastal marine sediments

The flux of nitrogen from land and atmosphere to estuaries and the coastal ocean has increased substantially in recent decades. The observed increase in nitrogen loading is caused by population growth, urbanization, expanding water and sewer infrastructure, fossil fuel combustion and synthetic fertilizer consumption. Most of the nitrogen is removed by denitrification in the sediments of estuaries and the continental shelf, leading to a reduction in both cultural eutrophication and nitrogen pollution of the open ocean. Nitrogen fixation, however, is thought to be a negligible process in sub-tidal heterotrophic marine systems. Here we report sediment core data from Narragansett Bay, USA, which demonstrate that heterotrophic marine sediments can switch from being a net sink to being a net source of nitrogen. Mesocosm and core incubation experiments, together with a historic data set of mean annual chlorophyll production, support the idea that a climate-induced decrease in primary production has led to a decrease in organic matter deposition to the benthos and the observed reversal of the net sediment nitrogen flux. Our results suggest that some estuaries may no longer remove nitrogen from the water column. Instead, nitrogen could be exported to the continental shelf and the open ocean and could shift the effect of anthropogenic nitrogen loading beyond the immediate coastal zone.