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1101. Cytokine receptor signalling.
Many cell functions are regulated by members of the cytokine receptor superfamily. Signalling by these receptors depends upon their association with Janus kinases (JAKs), which couple ligand binding to tyrosine phosphorylation of signalling proteins recruited to the receptor complex. Among these are the signal transducers and activators of transcription (STATs), a family of transcription factors that contribute to the diversity of cytokine responses.
1102. Contrasting properties of two forms of long-term potentiation in the hippocampus.
Activity-dependent enhancement of synaptic transmission, referred to as long-term potentiation (LTP), is observed at many synapses in the central nervous system. In the hippocampus two distinct forms of LTP have been identified. One involves the activation of the NMDA (N-methyl-D-aspartate) subtype of glutamate receptor and a rise in postsynaptic Ca2+, whereas the other, which is found at mossy fibre synapses, is independent of NMDA receptors but does require a rise in presynaptic Ca2+. Although it is now generally accepted that mossy fibre LTP is expressed presynaptically, the locus of expression for NMDA-receptor-dependent LTP is controversial. Here the two forms of LTP are compared and it is argued that the balance of evidence favours a postsynaptic locus for NMDA-receptor-dependent LTP.
1103. Protein molecules as computational elements in living cells.
Many proteins in living cells appear to have as their primary function the transfer and processing of information, rather than the chemical transformation of metabolic intermediates or the building of cellular structures. Such proteins are functionally linked through allosteric or other mechanisms into biochemical 'circuits' that perform a variety of simple computational tasks including amplification, integration and information storage.
1104. Evolutionary theory of parent-offspring conflict.
Natural selection can act in different ways on genes expressed in parents and their young, giving rise to parent-offspring conflict. The way in which this genetic conflict manifests itself at the behavioural level is unclear, and there has been widespread dissatisfaction that the theory has provided few testable predictions. A recent shift in emphasis from models that define the possible extent of conflict to those that predict its resolution offers greater hope of a testable theory of parent-offspring conflict.
1105. The synaptic vesicle cycle: a cascade of protein-protein interactions.
The synaptic vesicle cycle at the nerve terminal consists of vesicle exocytosis with neurotransmitter release, endocytosis of empty vesicles, and regeneration of fresh vesicles. Of all cellular transport pathways, the synaptic vesicle cycle is the fastest and the most tightly regulated. A convergence of results now allows formulation of molecular models for key steps of the cycle. These developments may form the basis for a mechanistic understanding of higher neural function.
1106. Adenylyl cyclases and the interaction between calcium and cAMP signalling.
Adenylyl cyclase is the prototypical second messenger generator. Nearly all of the eight cloned adenylyl cyclases are regulated by one or other arm of the phospholipase C pathway. Functional and ultrastructural investigations have shown that adenylyl cyclases are intimately associated with sites of calcium ion entry into the cell. Oscillations in cellular cyclic AMP levels are predicted to arise because of feedback inhibition of adenylyl cyclase by Ca2+. Such findings inextricably intertwine cellular signalling by cAMP and internal Ca2+ and extend the known regulatory modes available to cAMP.
1107. The consequences of imperfect mixing in autocatalytic chemical and biological systems.
When chemical reactions whose rate increases with the concentration of a product species are carried out in imperfectly mixed systems, a variety of complex behaviours can occur. These phenomena, which have relevance for biological processes as well, include chaotic and stochastic behaviour and selection of one final state over an equally probable alternative.
1108. Principles of CDK regulation.
As key regulators of the cell cycle, the cyclin-dependent kinases must be tightly regulated by extra- and intracellular signals. The activity of cyclin-dependent kinases is controlled by four highly conserved biochemical mechanisms, forming a web of regulatory pathways unmatched in its elegance and intricacy.
1109. Protein modules and signalling networks.
Communication between cells assumes particular importance in multicellular organisms. The growth, migration and differentiation of cells in the embryo, and their organization into specific tissues, depend on signals transmitted from one cell to another. In the adult, cell signalling orchestrates normal cellular behaviour and responses to wounding and infection. The consequences of breakdowns in this signalling underlie cancer, diabetes and disorders of the immune and cardiovascular systems. Conserved protein domains that act as key regulatory participants in many of these different signalling pathways are highlighted.
1110. Punishment in animal societies.
Although positive reciprocity (reciprocal altruism) has been a focus of interest in evolutionary biology, negative reciprocity (retaliatory infliction of fitness reduction) has been largely ignored. In social animals, retaliatory aggression is common, individuals often punish other group members that infringe their interests, and punishment can cause subordinates to desist from behaviour likely to reduce the fitness of dominant animals. Punishing strategies are used to establish and maintain dominance relationships, to discourage parasites and cheats, to discipline offspring or prospective sexual partners and to maintain cooperative behaviour.
1111. How molecular motors work.
What is the molecular basis of cell movement and changes in cell shape? The integration of three approaches is revealing how the molecular motors that drive these processes move and produce force.
1112. Gene inhibition using antisense oligodeoxynucleotides.
Antisense oligodeoxynucleotides (ODNs) have great promise as agents for the specific manipulation of gene expression. Until recently, nonspecific effects of ODNs often confounded the interpretation of antisense studies. Improvements in ODN chemistry and cellular delivery techniques now allow for more potent and specific gene inhibition. This review critically evaluates recent progress in the development of antisense ODNs.
1113. Signal transduction and regulation in smooth muscle.
Smooth muscle cells in the walls of many organs are vital for most bodily functions, and their abnormalities contribute to a range of diseases. Although based on a sliding-filament mechanism similar to that of striated muscles, contraction of smooth muscle is regulated by pharmacomechanical as well as by electromechanical coupling mechanisms. Recent studies have revealed previously unrecognized contractile regulatory processes, such as G-protein-coupled inhibition of myosin light-chain phosphatase, regulation of myosin light-chain kinase by other kinases, and the functional effects of smooth muscle myosin isoforms. Abnormalities of these regulatory mechanisms and isoform variations may contribute to diseases of smooth muscle, and the G-protein-coupled inhibition of protein phosphatase is also likely to be important in regulating non-muscle cell functions mediated by cytoplasmic myosin II.
1114. Chromosomal translocations in human cancer.
Chromosomal abnormalities in tumours were recognized at the end of the last century but their significance has only recently become clear. Distinct translocations in leukaemias and in solid tumours lead to the activation of proto-oncogene products or, more commonly, creation of tumour-specific fusion proteins. The proteins in both categories are often transcription factors and thus disruption of transcriptional control plays a major role in the aetiology of cancer. Fusion proteins formed after chromosomal translocations are common in a range of tumour types; these are unique tumour antigens and are therefore potential targets for therapy design.
1115. Mechanisms of intracellular protein transport.
Recent advances have uncovered the general protein apparatus used by all eukaryotes for intracellular transport, including secretion and endocytosis, and for triggered exocytosis of hormones and neurotransmitters. Membranes are shaped into vesicles by cytoplasmic coats which then dissociate upon GTP hydrolysis. Both vesicles and their acceptor membranes carry targeting proteins which interact specifically to initiate docking. A general apparatus then assembles at the docking site and fuses the vesicle with its target.
1116. The ancient regulatory-protein family of WD-repeat proteins.
WD proteins are made up of highly conserved repeating units usually ending with Trp-Asp (WD). They are found in all eukaryotes but not in prokaryotes. They regulate cellular functions, such as cell division, cell-fate determination, gene transcription, transmembrane signalling, mRNA modification and vesicle fusion. Here we define the common features of the repeating units, and criteria for grouping such proteins into functional subfamilies.
1117. Dynamics of chemical processes in polar solvents.
Understanding solution-phase chemistry requires a microscopic description of the electronic structure of the reacting molecules, and of the complex influence of the solvent medium on the reaction energetics and dynamics. Processes involving reactant charge-transfer are of particular importance in chemistry and biochemistry, and are strongly influenced by polar media. Recent advances in experimental ultrafast laser spectroscopy and in computer simulation are working together to provide insight into the underlying molecular principles governing this class of processes in solution.
1118. Vesicle fusion from yeast to man.
Membrane budding and fusion occur in all eukaryotic cells. Their underlying mechanisms have been studied in mammalian neurons and in yeast, a simple eukaryote. The differences between these two systems would suggest that fusion events in yeast and the neuron would operate by different mechanisms, but recent advances indicate that this is not true.
1119. Catch and move--cut or fuse.
Still almost unbelievable, but true: light exerts force. With these forces it is indeed possible to catch and move cells or small particles and microsurgically to process them without any mechanical contact. As if by magic, objects are moved via focused laser light.
1120. Paternal exposure not to blame.
The "Gardner hypothesis" suggests that an excess of childhood leukaemia near a nuclear reprocessing plant is caused by paternal exposure to ionizing radiation. But the evidence shows that this explanation is wrong.
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