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1121. Molecular and cellular mechanisms of general anaesthesia.
General anaesthetics are much more selective than is usually appreciated and may act by binding to only a small number of targets in the central nervous system. At surgical concentrations their principal effects are on ligand-gated (rather than voltage-gated) ion channels, with potentiation of postsynaptic inhibitory channel activity best fitting the pharmacological profile observed in general anaesthesia. Although the role of second messengers remains uncertain, it is now clear that anaesthetics act directly on proteins rather than on lipids.
1122. How B and T cells talk to each other.
The B cells of the immune system, which secrete antibodies against foreign antigens, are fully specific and effective only after maturation in lymph nodes and other lymphoid tissues. Immunocompetent T cells play a crucial part in this process, but the molecular details of the way in which the two cell types interact have only recently become apparent.
1123. Proteins regulating Ras and its relatives.
GTPases of the Ras superfamily regulate many aspects of cell growth, differentiation and action. Their functions depend on their ability to alternate between inactive and active forms, and on their cellular localization. Numerous proteins affecting the GTPase activity, nucleotide exchange rates and membrane localization of Ras superfamily members have now been identified. Many of these proteins are much larger and more complex than their targets, containing multiple domains capable of interacting with an intricate network of cellular enzymes and structures.
1124. The human IgE network.
IgE and its receptors are believed to have evolved as a mechanism to protect mammals against parasites. But other and intrinsically innocuous antigens can subvert this system to provoke an allergic response. For human populations in industrialized countries, allergy and asthma now represent a far greater threat than parasitic infection, and the main impetus for current studies of the IgE system is the hope of understanding and intervening in the aetiology of allergic diseases.
1125. Immunological modulation and evasion by helminth parasites in human populations.
作者: R M Maizels.;D A Bundy.;M E Selkirk.;D F Smith.;R M Anderson.
来源: Nature. 1993年365卷6449期797-805页
Helminth parasites are highly prevalent in human communities in developing countries. In an endemic area an infected individual may harbour parasitic worms for most of his or her life, and the ability of these infections to survive immunological attack has long been a puzzle. But new techniques are starting to expose the diverse mechanisms by which these agents modulate or evade their hosts' defences, creating a dynamic interaction between the human immune system and the parasite population.
1126. New roles for G-protein beta gamma-dimers in transmembrane signalling.
When a membrane-bound receptor acts on a G protein, the GTP-binding or G alpha subunit dissociates from the G beta gamma dimer. Until recently, the G alpha subunit alone was thought to act on the enzymes and ion channels controlled by these proteins. Newer evidence indicates that the G beta gamma dimer also plays a major part in signal transmission, enhancing the complexity of the possible interactions between the G proteins and their targets.
1127. Transcriptional antitermination.
Antiterminator proteins control gene expression by recognizing control signals near the promoter and preventing transcriptional termination which would otherwise occur at sites that may be a long way downstream. The N protein of bacteriophage lambda recognizes a sequence in the nascent RNA, and modifies RNA polymerase by catalysing the formation of a stable ribonucleoprotein complex on its surface, whereas the lambda Q protein recognizes a sequence in the DNA. These mechanisms of antitermination in lambda provide models for analysing antitermination in viruses such as HIV-1 and in eukaryotic genes.
1128. Primate origins: plugging the gaps.
Recent discoveries of fossil primate specimens have produced several surprises and challenged prevailing views of early primate evolution. Plesiadapiformes, long regarded as 'archaic primates', may perhaps be linked to the peculiar colugos instead. Inferred relationships of the earliest known undoubted primates (adapids and omomyids) are in turmoil. Both groups have been proposed as sources for the simian primates. Although the origin of the simian primates is obscure, new fossil evidence could push it further back by at least 10 million years. Such uncertainties reflect the low sampling level of the primate fossil record, which can potentially also lead to underestimation of times of origin within the primate tree.
1129. The pathogenesis of atherosclerosis: a perspective for the 1990s.
Atherosclerosis, the principal cause of heart attack, stroke and gangrene of the extremities, is responsible for 50% of all mortality in the USA, Europe and Japan. The lesions result from an excessive, inflammatory-fibroproliferative response to various forms of insult to the endothelium and smooth muscle of the artery wall. A large number of growth factors, cytokines and vasoregulatory molecules participate in this process. Our ability to control the expression of genes encoding these molecules and to target specific cell types provides opportunities to develop new diagnostic and therapeutic agents to induce the regression of the lesions and, possibly, to prevent their formation.
1130. Instability and decay of the primary structure of DNA.
Although DNA is the carrier of genetic information, it has limited chemical stability. Hydrolysis, oxidation and nonenzymatic methylation of DNA occur at significant rates in vivo, and are counteracted by specific DNA repair processes. The spontaneous decay of DNA is likely to be a major factor in mutagenesis, carcinogenesis and ageing, and also sets limits for the recovery of DNA fragments from fossils.
1131. Optimality, mutation and the evolution of ageing.
Evolutionary explanations of ageing fall into two classes. Organisms might have evolved the optimal life history, in which survival and fertility late in life are sacrificed for the sake of early reproduction and survival. Alternatively, the life history might be depressed below this optimal compromise by deleterious mutations: because selection against late-acting mutations is weaker, these will impose a greater load on late life. Evidence for the importance of both is emerging, and unravelling their relative importance presents experimentalists with a major challenge.
1132. The powers and pitfalls of parsimony.
Parsimony analysis is a powerful tool for the study of biological evolution. It is used to construct phylogenetic trees, to evaluate alternative hypotheses objectively, and to study evolutionary pattern and process. Yet, as comparative data sets expand, the pitfalls of parsimony analysis are catching experts and novices alike.
1133. Inositol trisphosphate and calcium signalling.
Inositol trisphosphate is a second messenger that controls many cellular processes by generating internal calcium signals. It operates through receptors whose molecular and physiological properties closely resemble the calcium-mobilizing ryanodine receptors of muscle. This family of intracellular calcium channels displays the regenerative process of calcium-induced calcium release responsible for the complex spatiotemporal patterns of calcium waves and oscillations. Such a dynamic signalling pathway controls many cellular processes, including fertilization, cell growth, transformation, secretion, smooth muscle contraction, sensory perception and neuronal signalling.
1134. Biospecific interaction analysis using biosensor technology.
Fundamental information that enhances our understanding of biospecific interactions can be obtained using a new analytical system based on biosensor technology. The functional characteristics of biospecific interaction, such as kinetics, affinity and binding position, are examined by label-free analysis of proteins in free solution binding to an immobilized ligand at a hydrophilic sensor surface.
1135. A synaptic model of memory: long-term potentiation in the hippocampus.
Long-term potentiation of synaptic transmission in the hippocampus is the primary experimental model for investigating the synaptic basis of learning and memory in vertebrates. The best understood form of long-term potentiation is induced by the activation of the N-methyl-D-aspartate receptor complex. This subtype of glutamate receptor endows long-term potentiation with Hebbian characteristics, and allows electrical events at the postsynaptic membrane to be transduced into chemical signals which, in turn, are thought to activate both pre- and postsynaptic mechanisms to generate a persistent increase in synaptic strength.
1136. Evolution and environment in the Hominoidea.
Between 10 and 20 million years ago, a variety of hominoid primates lived in Africa, Europe and Asia. The question of which of these, if any, lie closest to the ancestries of humans and modern apes remains a lively source of debate. Recent fossil discoveries, though, shed light on the environments in which the various groups of hominoid emerged and, it is hoped, on their evolution. But the lack of a hominid fossil record before about 5 million years ago--and any fossil record for the African apes--is still a frustrating barrier.
1137. Stable dye-DNA intercalation complexes as reagents for high-sensitivity fluorescence detection.
Fluorescent intercalation complexes of certain polycationic ligands with double-stranded DNA provide a new class of multichromophore labels for fluorescence assays.
1138. Creative blocks: cell-cycle checkpoints and feedback controls.
Before division, cells must ensure that they finish DNA replication, DNA repair and chromosome segregation. They do so by using feedback controls which can detect the failure to complete replication, repair or spindle assembly to arrest the progress of the cell cycle at one of three checkpoints. Failures in feedback controls can contribute to the generation of cancer.
1139. Automated real-time immunoassay of biomolecules.
ImmunoDetection is a novel technique combining perfusion chromatography technology with antibodies to perform the steps of an immunoassay in a flow-through column format. Sensitive and precise measurements are performed in seconds to minutes using automated liquid chromatography instrumentation.
1140. Molecular replication.
Simple replicating molecules are likely to have played a critical role in the origin of life. Recent experiments show that non-enzymatic replication is conceivable in a wide range of synthetic chemical systems. The challenge now facing these studies is how to develop information-coding systems from simple prebiotic precursors.
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