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1281. The role of protein phosphorylation in neural and hormonal control of cellular activity.
Protein phosphorylation is now recognized to be the major general mechanism by which intracellular events in mammalian tissues are controlled by external physiological stimuli. However, only recently has the idea that different cellular functions are controlled by common protein kinases and protein phosphatases started to gain widespread acceptance. Thus there is an integrated network of regulatory pathways, mediated by phosphorylation-dephosphorylation, that allows diverse cellular events to be coordinated by neural and hormonal stimuli. The evidence that supports this concept is reviewed, with emphasis on the role of protein phosphorylation in enzyme regulation.
1283. lambda Repressor and cro--components of an efficient molecular switch.
作者: A D Johnson.;A R Poteete.;G Lauer.;R T Sauer.;G K Ackers.;M Ptashne.
来源: Nature. 1981年294卷5838期217-23页
In a lysogen, most genes of phage lambda are repressed; in response to a transient induction signal, they are efficiently switched on. The switch, which consists in part of a tripartite operator to which two regulatory proteins bind, depends not only on DNA--protein interactions, but also on effects transmitted from one DNA-bound protein to another. lambda Exemplifies a strategy that facilitates efficient switching between two physiological states in response to a transient signal.
1284. A new era in mammalian gene mapping: somatic cell genetics and recombinant DNA methodologies.
Mammalian gene mapping techniques are now sufficiently advanced to contribute significantly to prenatal diagnosis and to human molecular genetics. Restriction fragment mapping can be used to place polymorphic genetic markers at random sites within the genome, and these sites used to assign genes responsible for disease conditions to a chromosomal region. Somatic cell genetic techniques can then be applied to saturate that region with additional restriction fragment markers, some of which will be closely linked to the disease gene. Closely linked restriction fragment markers, especially flanking pairs of markers, can act as predictors for the transmission of defective genes to offspring. A series of tightly linked flanking restriction markers might in addition contribute to the eventual isolation and cloning of the disease gene itself.
1285. Microtubule treadmills--possible molecular machinery.
Microtubule polymerization in vitro is the summation of different reactions occurring at each end of the polymer. In steady-state conditions in vitro, net tubulin addition on the microtubule occurs at one end of the polymer, and net tubulin loss occurs at the opposite end. Thus, a unidirectional flux of tubulin from one end of the microtubule to the other, or "treadmilling', can occur. The opposite end assembly--disassembly behaviour of microtubules, if it occurs within cells, could be fundamentally linked to the functions of microtubules, as, for example, in the translocation of chromosomes during mitosis.
1287. Actions of cholera toxin and the prevention and treatment of cholera.
The drastic intestinal secretion of fluid and electrolytes that is characteristic of cholera is the result of reasonably well understood cellular and biochemical actions of the toxin secreted by Vibrio cholerae. Based on this understanding it is possible to devise new techniques for the treatment and prophylaxis of cholera to complement those based on fluid replacement therapy and sanitation.
1288. Tempo and mode in hominid evolution.
The nature of human evolution has been viewed recently as a specific example of a more general model of evolution termed "punctuated equilibrium". The characteristics of this model are long periods of little or not evolutionary change (stasis) interspersed with periods of rapid (punctuated) morphological change. Careful analysis of the hominid fossil record over the past 4.0 million years, however, suggests no well documented examples of either stasis or punctuation. The evidence for the evolution of the hominid lineage is most reasonably interpreted by a model of more gradual change with periods of varying rates of evolution.
1289. Mechanisms of slow postsynaptic potentials.
Classical views of synaptic transmission have to be modified to take account of slow postsynaptic potentials (p.s.ps), which are often mediated by novel ionic and molecular mechanisms and which are sometimes evoked by neuropeptides. Understanding slow p.s.ps will provide insights into the mechanisms of biological signal transduction and long-term signalling in the nervous system.
1290. The traditional and a new version of the mouse H-2 complex.
The H-2 complex has traditionally been interpreted as a maze of regions, subregions and loci coding for different traits. The two main theses presented here are, first, that a single H-2 locus is pleiomorphic in that it controls several functions such as allograft rejection, cell-mediated lymphocytotoxicity, mixed lymphocyte reaction, immune response, immune suppression and restriction of T-cell specificity; and second, that the physiological function of the H-2 complex is to guide T lymphocytes in their function of distinguishing self from non-self, and that all other H-2-controlled traits are artificial derivatives of this basic function. These two theses lead to a new, simplified interpretation of the H-2 complex.
1291. Can dietary beta-carotene materially reduce human cancer rates?
Human cancer risks are inversely correlated with (a) blood retinol and (b) dietary beta-carotene. Although retinol in the blood might well be truly protective, this would be of little immediate value without discovery of the important external determinants of blood retinol which (in developed countries) do not include dietary retinol or beta-carotene. If dietary beta-carotene is truly protective--which could be tested by controlled trials--there are a number of theoretical mechanisms whereby it might act, some of which do not directly involve its 'provitamin A' activity.
1292. Attenuation in the control of expression of bacterial operons.
Bacterial operons concerned with the biosynthesis of amino acids are often controlled by a process of attenuation. The translation product of the initial segment of the transcript of each operon is a peptide rich in the amino acid that the particular operon controls. If the amino acid is in short supply translation is stalled at the relevant codons of the transcript long enough for the succeeding segment of the transcript to form secondary structures that allow the transcribing RNA polymerase molecule to proceed through a site that otherwise dictates termination of transcription. This site is the attenuator; the process is attenuation.
1293. Dendritic release of dopamine in the substantia nigra.
Dopamine can be released in the substantia nigra for the dendrites of nigrostriatal dopaminergic neurones, to be involved there in the self-regulation of the dopaminergic cells, to control the release of neurotransmitters from nigral afferent fibres and to influence the activity of nigral non-dopaminergic cells.
1294. The origin of human cancers.
The limited evidence available suggests that most human cancers are not caused by conventional mutagens but are more likely to be the result of genetic transpositions. Although the molecular biology of transposition is starting to be understood, the external factors that influence its frequency have not yet been studied in any detail.
1295. Hormone families: pancreatic hormones and homologous growth factors.
The growing realization that biologically active polypeptides can be grouped in families, the members of which show structural and functional relatedness, is illustrated by the four families which are represented in the pancreas by the hormones insulin, glucagon, somatostatin and pancreatic polypeptide.
1296. Compound eyes: old and new optical mechanisms.
Over the last twenty years classical views of how compound eyes work optically have undergone a series of overhauls. Exner's central concept of an optically inhomogeneous lens cylinder has survived, and such devices are now made commercially. He was wrong, however, about some crustacean eyes. They produce images by a mirror mechanism that was not discovered until 1975, and which now shows promise as an optical system capable of development.
1297. Transcription and RNA processing by the DNA tumour viruses.
Messenger RNA synthesis by the DNA tumour viruses proceeds by a complex but versatile series of transcription and RNA processing steps. The major mechanistic features of this pathway are probably very similar to those used by the animal cell host itself. The viruses have, however, evolved intricate arrangements of protein coding sequences and sites for RNA initiation, polyadenylation and splicing which allow them to use their genetic information to maximum advantage.
1298. Calmodulin--an intracellular calcium receptor.
Calmodulin, a protein that binds calcium with high affinity and specificity, is structurally conserved and functionally preserved throughout the animal and plant kingdoms. It serves as an intracellular Ca2+-receptor and mediates the Ca2+ regulation of cyclic nucleotide and glycogen metabolism, secretion, motility and Ca2+ transport. Calmodulin is also a dynamic component of the mitotic apparatus.
1299. Peptidergic neurones.
作者: T Hökfelt.;O Johansson.;A Ljungdahl.;J M Lundberg.;M Schultzberg.
来源: Nature. 1980年284卷5756期515-21页
More than 20 peptides have been identified in neurones of the brain, spinal cord and periphery. In several cases a peptide occurs together with a 'classical' transmitter in the same neurone. This raises new questions about the process of neurotransmission and may have important implications for our understanding and treatment of mental disorders.
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