摘要:

AbstractDependency relationships within the cell cycle allow cells to arrest the cycle reversibly in response to agents or conditions that interfere with specific aspects of its normal progression. In addition, overlapping pathways exist which also arrest the cell cycle in response to DNA damage. Collectively, these control mechanisms have become known as checkpoints. Analysis of checkpoints is facilitated by the fact that dependency relationships within the cell cycle, such as the dependency of mitosis on the completion of DNA synthesis, and the DNA damage checkpoint can be separated genetically. In fission yeast,Schizosaccharomyces pombe, the dependency of mitosis on prior completion of DNA synthesis is mediated through tyrosine‐15 phosphorylation of the ubiquitous mitotic regulator p34cdc2. In contrast, the arrest of mitosis caused by DNA damage acts through a separate mechanism that appears to be independent of tyrosine‐15 phosphorylation. Despite these distinct interactions with the mitotic machinery, the majority of fission yeast mutants that are deficient in mitotic arrest after DNA damage are also unable to respond to inhibition of DNA synthesis. In this essay we survey the current knowledge concerning feedback controls and checkpoints within fission yeast and relate this to information derived from other syst

ISSN:0265-9247    

DOI:10.1002/bies.950151202

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractThe cause of Paget's disease is still unknown, despite many years of intensive study. During this time, evidence has sporadically emerged to suggest that the disease may result from a slow viral infection by one or more of the Paramyxoviruses. More recently, epidemiologic and molecular studies have suggested that the canine paramyxovirus, canine distemper virus, is the virus responsible for the disease. If true, then along with rabies, this would be a further example of a canine virus causing human disease. Studies in the natural host have now supported these findings. Further investigations have proposed that the bony abnormalities seen in Paget's disease are due to the effects of the virus on osteoclastic interleukin‐6 and c‐FOS production, possibly via the transcription factor NF

ISSN:0265-9247    

DOI:10.1002/bies.950151203

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractThe dauer larva is a specialized third‐larval stage ofCaenorhabditis elegansthat is long‐lived and resistant to environmental insult. The dauer larva is formed in response to a high external concentration of a constitu‐tively secreted pheromone. Response to the dauer‐inducing pheromone ofC. elegansis a promising genetic model for metazoan chemosensory transduction. More than 20 genes have been identified that are required for normal pheromone response. The functions of these genes include production of the pheromone, exposure of sensory neuron endings to the environment, structural and functional integrity of those sensory endings, and the capacity of sensory neurons to make appropriate output. Genetic evidence suggests that two partially redundant sensory pathways act in concert to control dauer formation. At least two classes of chemosensory neurons, ADF and ASI, are implicated in the pheromone response. On the basis of on these findings, a speculative model for the pheromone response is proposed. In this model, the neurons ADF and ASI are pheromone sensors that repress dauer formation in the absence of pheromone and dere‐press dauer formation in response to pheromone. It is currently unclear whether or not the two genetically defined sensory pathways both act in AD

ISSN:0265-9247    

DOI:10.1002/bies.950151204

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractThe pathogenic, Gram‐negative bacteria,Neisseria gon‐orrhoeae, Neisseria meningitidis and Haemophilus influenzae, secrete immunoglobulin A1 proteases into their extracellular surroundings. An extraordinary feature in the secretory pathway of these putative virulence factors is a self‐directed outer membrane transport step allowing the proteins to be secreted autonomously, even from foreign Gram‐negative host cells likeEscherichia coli. Here we summarize recent achievements in the understanding of IgA protease outer membrane transl

ISSN:0265-9247    

DOI:10.1002/bies.950151205

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractAnamniote animals, such as fish and amphibians, are able to regenerate damaged CNS nerves following injury, but regeneration in the mammalian CNS tracts, such as the optic nerve, does not occur. However, severed adult mammalian retinal axons can regenerate into peripheral nerve segments grafted into the brain and this finding has emphasized the importance of the environment in explaining regenerative failure in the adult mammalian CNS. Following lesions, regenerating axons encounter the glial cells, oligodendrocytes and astro‐cytes, and their derivatives, respectively myelin and the astrocytic scar. Experiments to investigate the influence of these components on axon growth in culture have revealed cell‐surface and extracellular matrix molecules that inhibit axon extension and growth cone motility. Structural and functional characterization of these ligands and their receptors is underway, and may solve the interesting neurobiological conundrum posed by the failure of mammalian CNS regeneration. Simultaneously, this might allow new possibilities for treatment of the severe clinical disabilities resulting from injury to the brain and spinal c

ISSN:0265-9247    

DOI:10.1002/bies.950151206

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractTransmembrane receptor tyrosine kinases that bind to peptide factors transmit essential growth and differentiation signals. A growing list of orphan receptors, of which some are oncogenic, holds the promise that many unknown ligands may be discovered by tracking the corresponding surface molecules. Theneugene (also callederbB‐2 and HER‐2) encodes such a receptor tyrosine kinase whose oncogenic potential is released in the developing rodent nervous system through a point mutation. Amplification and overexpression ofneuare thought to contribute to malignancy of certain human adenocarcinomas. The search for soluble factors that interact with the Neu receptor led to the discovery of a 44 kDa glyco‐protein that induces phenotypic differentiation of cultured mammary tumor cells to growth‐arrested and milk‐producing cells. The Neu differentiation factor (NDF or heregulin), however, also acts as a mitogen for epithelial, Schwann and glial cells. Multiple forms of the factor are produced by alternative splicing and their expression is confined predominantly to the central and to the peripheral nervous systems. One identified neuronal function of this family of polypeptides is to control the formation of neuromuscular junctions, but their physiological role in secretory epithelia is still unknown. Other open questions relate to the transmembrane topology of various precursors, the identity of a putative co‐receptor, the possible existence of additional ligands of Neu and the functional significance of the interaction between Neu and at least three highly related receptor tyros

ISSN:0265-9247    

DOI:10.1002/bies.950151207

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

ISSN:0265-9247    

DOI:10.1002/bies.950151208

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

ISSN:0265-9247    

DOI:10.1002/bies.950151209

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractRecent mutagenesis studies have demonstrated that the chemotherapeutic agent, chlorambucll (CHL), is highly mutagenic in male germ cells of the mouse. Post‐melotic germ cells, and especially early spermatids, are the most sensitive to the cytotoxic and mutagenic effects of this agent. Genetic, cytogenetic and molecular analyses of many induced mutations have shown that, in these germ‐cell stages, CHL induces predominantly chromosomal rearrangements (deletions and translocations), and mutation‐rate studies show that, in terms of tolerated doses, CHL is perhaps five to ten times more efficient in inducing rearrangements than is radiation exposure. Appropriate breeding protocols, along with knowledge of the advantages and limitations associated with the use of CHL, can be used to expand the current resource of chromosomal rearrangements in the mouse and to provide new phenotype‐associated mutations amenable to positional‐cloning techniques. The analysis of CHL‐induced mutations has also contributed to understanding the factors that affect the yield and nature of chemically induced germline mutations

ISSN:0265-9247    

DOI:10.1002/bies.950151210

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

ISSN:0265-9247    

DOI:10.1002/bies.950151211

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY