- Email: [email protected]
Double dealing
C O M M E N T
R e s p o n s e from Lane and B u c h m e i e r e prefer the more appropriate and contemporary definition of W 'paradigm' of Webster's Collegiate Dictionary ( l Oth edn):
A philosophical and theoretical framework of a scientific school or discipline within which theories, laws, and generalizations and the experiments performed in support of them are formulated. As such an experimental model, the murine coronavirus system has much
to offer and we have attempted to highlight those features in our review. We did not maintain that the MHV infection should be considered an exclusive or literal model for multiple sclerosis (MS); to the contrary, we believe that data from all of the available sources and models should be integrated into any theory to account for the pathogenesis of MS. The real substance of Dr Christensen's objection to our model, and indeed to animal models in general, is revealed in her closing
statement 'and mice are not men', which reflects a bias that denies the landmark advances in biomedical science that have come from animal research. Indeed, while no animal model perfectly mimics the human, the parallels between the human and mouse immune systems and cytokine networks are outstanding examples of the value of such comparative studies. Thomas E. Lane and Michael J. Buchmeier Dept of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA
Horizons Deep life lthough suspected, there is now more evidence for the largescale existence of deep subsurface life growing on ancient sedimentary rocks rich in fossil nutrients. Krumholz and colleagues have taken cores from alternating New Mexican Cretaceous shale and sandstone deposits at 175-300 m depth. They found sulphate-reducing bacteria and acetogenic organisms concentrated at the sandstone-shale interfaces. The shale appears to be too dense to harbour proliferating life
and too impermeable to groundwater to sustain life by dissolved nutrient flow. Nevertheless, the shales contain higher concentrations of organic carbon than adjacent sandstones and probably contribute the nutrients to the interfacial microbial communities by diffusion into the upper layers of the moreaccommodating sandstone.
Lots in common oxsackie- and adenoviruses are common causes of human illness. Both viruses recognize a 46-kDa protein on human cells (that maps to human chromosome 21), which mediates virus attachment, as well as cell entry by coxsackievirus and gene transfer by adenovirus. This coxsackievirus and adenovirus receptor (CAR) is a 365-amino-acid transmembrane protein, with a large extracellular immunoglobulin-like segment, a membrane-spanning helix and a large conserved cytoplasmic domain. Monoclonal antibodies against CAR protect cells from infection by all six serotypes of coxsackievirus because they all compete for the same cell-surface
receptor. A depression on the coxsackievirus surface seems to be the site for receptor attachment, whereas adenovirus attachment is mediated by globular knobs at the tips of fibres attached to the virus capsule. Despite the structural differences, for a long time these viruses have been known to compete for a HeLa cell attachment site. One significant finding is that CAR expression enhances gene transfer by adenovirus, and manipulation of the tissue distribution of CAR could have important biotechnological potential.
Double dealing ecause of its importance in both the mosquito and mammalian host, a major surface protein of the sporozoite stage of the Plasmodium malaria parasite, the circumsporozoite protein (CS), has long been a target. The sporozoites are produced in oocysts in the mosquito midgut, migrate to the salivary glands and are injected with the insect's saliva into a mammal when the mosquito takes a blood meal. MSnard and colleagues discovered that their CS- P. berghei disruptants did not generate sporozoites in mosquitoes; moreover, it is known that in the vertebrate host, CS is required for attachment of sporozoites to hepatocytes. It turns out that both functions can be attributed to a domain of CS homologous to the type 1 repeats of thrombospondin (TSP). TSP repeats are known to play roles in cell attachment and locomotion and cell division. Similarly, in Plasm o d i u m , surface CS may, therefore, play a dual role in hepatocyte adhesion in the mammalian host and sporogony in the mosquito host.
Bergelson, J.M. et al. (1997) Isolation of a common receptor for coxsackie B viruses and adenoviruses 2 and 5, Science 275, 1320-1323
M~nard, R. et al. (1997) Circumsporozoite protein is required for development of malaria sporozoites in mosquitoes, Nature 385, 336-340
A
C
Krumholz, L.R. et al. (1997) Confined subsurface microbial communities in Cretaceous rock, Nature 386, 64-66
B
This selection from recent publications was compiled by Caroline Ash. If you would like to suggest papers for inclusion in Horizons, please e-mail: [email protected],uk Copyright © 1997 Elsevier Science Ltd. All rights reserved. 0966 842X/97/$17.00
TRENDS
IN MIC'R()BI()I.()(;Y
140
VOL.
5
N().
4
APRIl.
1 997
R e s p o n s e from Lane and B u c h m e i e r e prefer the more appropriate and contemporary definition of W 'paradigm' of Webster's Collegiate Dictionary ( l Oth edn):
A philosophical and theoretical framework of a scientific school or discipline within which theories, laws, and generalizations and the experiments performed in support of them are formulated. As such an experimental model, the murine coronavirus system has much
to offer and we have attempted to highlight those features in our review. We did not maintain that the MHV infection should be considered an exclusive or literal model for multiple sclerosis (MS); to the contrary, we believe that data from all of the available sources and models should be integrated into any theory to account for the pathogenesis of MS. The real substance of Dr Christensen's objection to our model, and indeed to animal models in general, is revealed in her closing
statement 'and mice are not men', which reflects a bias that denies the landmark advances in biomedical science that have come from animal research. Indeed, while no animal model perfectly mimics the human, the parallels between the human and mouse immune systems and cytokine networks are outstanding examples of the value of such comparative studies. Thomas E. Lane and Michael J. Buchmeier Dept of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA
Horizons Deep life lthough suspected, there is now more evidence for the largescale existence of deep subsurface life growing on ancient sedimentary rocks rich in fossil nutrients. Krumholz and colleagues have taken cores from alternating New Mexican Cretaceous shale and sandstone deposits at 175-300 m depth. They found sulphate-reducing bacteria and acetogenic organisms concentrated at the sandstone-shale interfaces. The shale appears to be too dense to harbour proliferating life
and too impermeable to groundwater to sustain life by dissolved nutrient flow. Nevertheless, the shales contain higher concentrations of organic carbon than adjacent sandstones and probably contribute the nutrients to the interfacial microbial communities by diffusion into the upper layers of the moreaccommodating sandstone.
Lots in common oxsackie- and adenoviruses are common causes of human illness. Both viruses recognize a 46-kDa protein on human cells (that maps to human chromosome 21), which mediates virus attachment, as well as cell entry by coxsackievirus and gene transfer by adenovirus. This coxsackievirus and adenovirus receptor (CAR) is a 365-amino-acid transmembrane protein, with a large extracellular immunoglobulin-like segment, a membrane-spanning helix and a large conserved cytoplasmic domain. Monoclonal antibodies against CAR protect cells from infection by all six serotypes of coxsackievirus because they all compete for the same cell-surface
receptor. A depression on the coxsackievirus surface seems to be the site for receptor attachment, whereas adenovirus attachment is mediated by globular knobs at the tips of fibres attached to the virus capsule. Despite the structural differences, for a long time these viruses have been known to compete for a HeLa cell attachment site. One significant finding is that CAR expression enhances gene transfer by adenovirus, and manipulation of the tissue distribution of CAR could have important biotechnological potential.
Double dealing ecause of its importance in both the mosquito and mammalian host, a major surface protein of the sporozoite stage of the Plasmodium malaria parasite, the circumsporozoite protein (CS), has long been a target. The sporozoites are produced in oocysts in the mosquito midgut, migrate to the salivary glands and are injected with the insect's saliva into a mammal when the mosquito takes a blood meal. MSnard and colleagues discovered that their CS- P. berghei disruptants did not generate sporozoites in mosquitoes; moreover, it is known that in the vertebrate host, CS is required for attachment of sporozoites to hepatocytes. It turns out that both functions can be attributed to a domain of CS homologous to the type 1 repeats of thrombospondin (TSP). TSP repeats are known to play roles in cell attachment and locomotion and cell division. Similarly, in Plasm o d i u m , surface CS may, therefore, play a dual role in hepatocyte adhesion in the mammalian host and sporogony in the mosquito host.
Bergelson, J.M. et al. (1997) Isolation of a common receptor for coxsackie B viruses and adenoviruses 2 and 5, Science 275, 1320-1323
M~nard, R. et al. (1997) Circumsporozoite protein is required for development of malaria sporozoites in mosquitoes, Nature 385, 336-340
A
C
Krumholz, L.R. et al. (1997) Confined subsurface microbial communities in Cretaceous rock, Nature 386, 64-66
B
This selection from recent publications was compiled by Caroline Ash. If you would like to suggest papers for inclusion in Horizons, please e-mail: [email protected],uk Copyright © 1997 Elsevier Science Ltd. All rights reserved. 0966 842X/97/$17.00
TRENDS
IN MIC'R()BI()I.()(;Y
140
VOL.
5
N().
4
APRIl.
1 997