scispace - formally typeset
Search or ask a question

Showing papers in "Nature in 1989"


Journal ArticleDOI
20 Jul 1989-Nature
TL;DR: A novel genetic system to study protein-protein interactions between two proteins by taking advantage of the properties of the GAL4 protein of the yeast Saccharomyces cerevisiae, which may be applicable as a general method to identify proteins that interact with a known protein by the use of a simple galactose selection.
Abstract: Protein-protein interactions between two proteins have generally been studied using biochemical techniques such as crosslinking, co-immunoprecipitation and co-fractionation by chromatography. We have generated a novel genetic system to study these interactions by taking advantage of the properties of the GAL4 protein of the yeast Saccharomyces cerevisiae. This protein is a transcriptional activator required for the expression of genes encoding enzymes of galactose utilization. It consists of two separable and functionally essential domains: an N-terminal domain which binds to specific DNA sequences (UASG); and a C-terminal domain containing acidic regions, which is necessary to activate transcription. We have generated a system of two hybrid proteins containing parts of GAL4: the GAL4 DNA-binding domain fused to a protein 'X' and a GAL4 activating region fused to a protein 'Y'. If X and Y can form a protein-protein complex and reconstitute proximity of the GAL4 domains, transcription of a gene regulated by UASG occurs. We have tested this system using two yeast proteins that are known to interact--SNF1 and SNF4. High transcriptional activity is obtained only when both hybrids are present in a cell. This system may be applicable as a general method to identify proteins that interact with a known protein by the use of a simple galactose selection.

6,529 citations


Journal ArticleDOI
01 Dec 1989-Nature
TL;DR: In this paper, a global oxygen isotope record for ocean water has been calculated from the Barbados sea level curve, allowing separation of the ice volume component common to all isotope records measured in deep-sea cores.
Abstract: Coral reefs drilled offshore of Barbados provide the first continuous and detailed record of sea level change during the last deglaciation. The sea level was 121 ± 5 metres below present level during the last glacial maximum. The deglacial sea level rise was not monotonic; rather, it was marked by two intervals of rapid rise. Varying rates of melt-water discharge to the North Atlantic surface ocean dramatically affected North Atlantic deep-water production and oceanic oxygen isotope chemistry. A global oxygen isotope record for ocean water has been calculated from the Barbados sea level curve, allowing separation of the ice volume component common to all oxygen isotope records measured in deep-sea cores.

4,483 citations


Journal ArticleDOI
23 Mar 1989-Nature
TL;DR: It is demonstrated here that neurons in spatially separate columns can synchronize their oscillatory responses, which has, on average, no phase difference, depends on the spatial separation and the orientation preference of the cells and is influenced by global stimulus properties.
Abstract: A FUNDAMENTAL step in visual pattern recognition is the establishment of relations between spatially separate features. Recently, we have shown that neurons in the cat visual cortex have oscillatory responses in the range 40–60 Hz (refs 1,2) which occur in synchrony for cells in a functional column and are tightly correlated with a local oscillatory field potential. This led us to hypothesize that the synchronization of oscillatory responses of spatially distributed, feature selective cells might be a way to establish relations between features in different parts of the visual field2,3. In support of this hypothesis, we demonstrate here that neurons in spatially separate columns can synchronize their oscillatory responses. The synchronization has, on average, no phase difference, depends on the spatial separation and the orientation preference of the cells and is influenced by global stimulus properties.

4,028 citations


Journal ArticleDOI
21 Sep 1989-Nature
TL;DR: The subtlety of calcium regulation by inositol phosphates is emphasized by recent studies that have revealed oscillations in calcium concentration which are perhaps part of a frequency-encoded second-messenger system.
Abstract: Inositol 1,4,5-trisphosphate is a second messenger which regulates intracellular calcium both by mobilizing calcium from internal stores and, perhaps indirectly, by stimulating calcium entry. In these actions it may function with its phosphorylated metabolite, inositol 1,3,4,5-tetrakisphosphate. The subtlety of calcium regulation by inositol phosphates is emphasized by recent studies that have revealed oscillations in calcium concentration which are perhaps part of a frequency-encoded second-messenger system.

3,834 citations


Journal ArticleDOI
18 May 1989-Nature
TL;DR: The exquisite sensitivity of the polymerase chain reaction means DNA contamination can ruin an entire experiment and adherence to a strict set of protocols can avoid disaster.
Abstract: The exquisite sensitivity of the polymerase chain reaction means DNA contamination can ruin an entire experiment. Tidiness and adherence to a strict set of protocols can avoid disaster.

3,543 citations


Journal ArticleDOI
07 Dec 1989-Nature
TL;DR: It is suggested that most tumours with allelic deletions of chromosome 17p contain p53 point mutations resulting in amino-acid substitutions, and p53 gene mutations are clustered in four 'hot-spots' which exactly coincide with the four most highly conserved regions of the gene.
Abstract: The p53 gene has been a constant source of fascination since its discovery nearly a decade ago. Originally considered to be an oncogene, several convergent lines of research have indicated that the wild-type gene product actually functions as a tumour suppressor gene. For example, expression of the neoplastic phenotype is inhibited, rather than promoted, when rat cells are transfected with the murine wild-type p53 gene together with mutant p53 genes and/or other oncogenes. Moreover, in human tumours, the short arm of chromosome 17 is often deleted. In colorectal cancers, the smallest common region of deletion is centred at 17p13.1; this region harbours the p53 gene, and in two tumours examined in detail, the remaining (non-deleted) p53 alleles were found to contain mutations. This result was provocative because allelic deletion coupled with mutation of the remaining allele is a theoretical hallmark of tumour-suppressor genes. In the present report, we have attempted to determine the generality of this observation; that is, whether tumours with allelic deletions of chromosome 17p contain mutant p53 genes in the allele that is retained. Our results suggest that (1) most tumours with such allelic deletions contain p53 point mutations resulting in amino-acid substitutions, (2) such mutations are not confined to tumours with allelic deletion, but also occur in at least some tumours that have retained both parental 17p alleles, and (3) p53 gene mutations are clustered in four 'hot-spots' which exactly coincide with the four most highly conserved regions of the gene. These results suggest that p53 mutations play a role in the development of many common human malignancies.

2,708 citations


Journal ArticleDOI
23 Nov 1989-Nature
TL;DR: The nucleotide sequence of the human HGF cDNA reveals that both α- andβ-chains are contained in a single open reading frame coding for a pre-pro precursor protein of 728 amino acids, which indicates that the activity of HGF is not species-specific.
Abstract: Hepatocyte growth factor (HGF) is the most potent mitogen for mature parenchymal hepatocytes in primary culture, and seems to be a hepatotrophic factor that acts as a trigger for liver regeneration after partial hepatectomy and liver injury. The partial purification and characterization of HGF have been reported. We have demonstrated that pure HGF from rat platelets is a new growth factor effective at concentrations as low as 1 ng ml-1. The effects of HGF and epidermal growth factor (EGF) are additive. The activity of HGF is not species-specific, although it does not stimulate growth in Swiss 3T3 fibroblasts. HGF has a relative molecular mass (Mr) of 82,000 and is a heterodimer composed of a large alpha-subunit of Mr 69,000 and a small beta-subunit of Mr 34,000. Here we report the amino-acid sequence of human HGF determined by complementary DNA cloning and the expression of biologically active human HGF from COS-1 cells transfected with cloned cDNA. The nucleotide sequence of the human HGF cDNA reveals that both alpha- and beta-chains are contained in a single open reading frame coding for a pre-pro precursor protein of 728 amino acids.

2,190 citations


Journal ArticleDOI
09 Feb 1989-Nature
TL;DR: In this article, the authors used second-harmonic generation and the related technique of infrared-visible light sum-frequency generation to monitor surface dynamics and reactions with sub-picosecond time resolution.
Abstract: Optical second-harmonic generation and the related technique of infrared – visible light sum-frequency generation are extremely versatile tools for studies of many kinds of surfaces and interfaces. With the help of ultra-short laser pulses, they can be used to monitor surface dynamics and reactions with sub-picosecond time resolution.

2,013 citations


Journal ArticleDOI
04 May 1989-Nature
TL;DR: It is reported here that angiogenic activity first appears in a subset of hyperplastic islets before the onset of tumour formation, suggesting that induction of angiogenesis is an important step in carcinogenesis.
Abstract: It is now well established that unrestricted growth of tumours is dependent upon angiogenesis. Previous studies on tumour growth, however, have not revealed when or how the transition to an angiogenic state occurs during early tumour development. The advent of transgenic mice carrying oncogenes that reproducibly elicit tumours of specific cell types is providing a new format for studying multi-step tumorigenesis. In one of these models, transgenic mice expressing an oncogene in the beta-cells of the pancreatic islets heritably recapitulate a progression from normality to hyperplasia to neoplasia. We report here that angiogenic activity first appears in a subset of hyperplastic islets before the onset of tumour formation. A novel in vitro assay confirms that hyperplasia per se does not obligate angiogenesis. Rather, a few hyperplastic islets become angiogenic in vitro at a time when such islets are neovascularized in vivo and at a frequency that correlates closely with subsequent tumour incidence. These findings suggest that induction of angiogenesis is an important step in carcinogenesis.

1,995 citations


Journal ArticleDOI
13 Jul 1989-Nature
TL;DR: In this paper, it was pointed out that neutron-star collisions should synthesize neutron-rich heavy elements, thought to be formed by rapid neutron capture (the r-process), and these collisions should produce neutrino bursts and resultant bursts of gamma rays; the latter should comprise a subclass of observable gamma-ray bursts.
Abstract: It is pointed out here that neutron-star collisions should synthesize neutron-rich heavy elements, thought to be formed by rapid neutron capture (the r-process). Furthermore, these collisions should produce neutrino bursts and resultant bursts of gamma rays; the latter should comprise a subclass of observable gamma-ray bursts. It is argued that observed r-process abundances and gamma-ray burst rates predict rates for these collisions that are both significant and consistent with other estimates.

1,986 citations


Journal ArticleDOI
12 Oct 1989-Nature
TL;DR: Isolated variable domains may offer an alternative to monoclonal antibodies and serve as the key to building high-affinity human antibodies and the name 'single domain antibodies (dAbs)' is suggested for these antigen binding demands.
Abstract: IN antibodies, a heavy and a light chain variable domain, VH and VL, respectively, pack together and the hypervariable loops on each domain contribute to binding antigen1–4. We find, however, that isolated VH domains with good antigen-binding affinities can also be prepared. Using the polymerase chain reaction5, diverse libraries of VH genes were cloned from the spleen genomic DNA of mice immunized with either lysozyme or keyhole-limpet haemocyanin. From these libraries, VH domains were expressed and secreted from Escherichia coli. Binding activities were detected against both antigens, and two VH domains were characterized with affinities for lysozyme in the 20 nM range. Isolated variable domains may offer an alternative to monoclonal antibodies and serve as the key to building high-affinity human antibodies. We suggest the name 'single domain antibodies (dAbs)' for these antigen binding demands.

Journal ArticleDOI
26 Jan 1989-Nature
TL;DR: The essential RNA component of this ribonucleoprotein enzyme has now been cloned and found to contain the sequence CAACCCCAA, which seems to be the template for the synthesis of TTGGGG repeats.
Abstract: The telomerase enzyme of Tetrahymena synthesizes repeats of the telomeric DNA sequence TTGGGG de novo in the absence of added template. The essential RNA component of this ribonucleoprotein enzyme has now been cloned and found to contain the sequence CAACCCCAA, which seems to be the template for the synthesis of TTGGGG repeats.

Journal ArticleDOI
01 Dec 1989-Nature
TL;DR: There is a small repertoire of main-chain conformations for at least five of the six hypervariable regions of antibodies, and that the particular conformation adopted is determined by a few key conserved residues.
Abstract: On the basis of comparative studies of known antibody structures and sequences it has been argued that there is a small repertoire of main-chain conformations for at least five of the six hypervariable regions of antibodies, and that the particular conformation adopted is determined by a few key conserved residues. These hypotheses are now supported by reasonably successful predictions of the structures of most hypervariable regions of various antibodies, as revealed by comparison with their subsequently determined structures.

Journal ArticleDOI
19 Oct 1989-Nature
TL;DR: It is shown that antigen-receptor cross-linking increases the strength of the adhesion mechan-ism between lymphocyte function-associated molecule-1 (LFA-1) and intercellular adhesion molecules (ICAMs), with intracellular signals trans-mitted from the T-cell antigen receptor to the LFA- 1 adhesion molecule.
Abstract: Effective interaction between T cells and their targets requires that recognition of specific antigen be coordinated with increased cell-cell adhesion. We show that antigen-receptor cross-linking increases the strength of the adhesion mechanism between lymphocyte function-associated molecule-1 (LFA-1) and intercellular adhesion molecules (ICAMs), with intracellular signals transmitted from the T-cell antigen receptor to the LFA-1 adhesion molecule. The increase in avidity is rapid and transient, providing a dynamic mechanism for antigen-specific regulation of lymphocyte adhesion and de-adhesion.

Journal ArticleDOI
10 Aug 1989-Nature
TL;DR: Using a new method for quantitative enumeration, up to 2.5 x IO8 virus particles per millilitre in natural waters indicate that virus infection may be an important factor in the ecological control of planktonic micro-organisms.
Abstract: The concentration of bacteriophages in natural unpolluted waters is in general believed to be low, and they have therefore been considered ecologically unimportant. Using a new method for quantitative enumeration, we have found up to 2.5 x 10(8) virus particles per millilitre in natural waters. These concentrations indicate that virus infection may be an important factor in the ecological control of planktonic micro-organisms, and that viruses might mediate genetic exchange among bacteria in natural aquatic environments.

Journal ArticleDOI
01 Mar 1989-Nature
TL;DR: For most of the toxic metals, the natural fluxes are small compared with emissions from industrial activities, implying that mankind has become the key agent in the global atmospheric cycle of trace metals and metalloids as mentioned in this paper.
Abstract: A PROPER inventory of atmospheric emissions from natural sources is basic to our understanding of the atmospheric cycle of the trace metals (and metalloids), and is also needed for assessing the extent of regional and global pollution by toxic metals1. It is generally presumed that the principal natural sources of trace metals in the atmosphere are wind-borne soil particles, volcanoes, seasalt spray and wild forest fires2–6. Recent studies have shown, however, that particulate organic matter is the dominant component of atmospheric aerosols in non-urban areas7–10 and that over 60% of the airborne trace metals in forested regions can be attributed to aerosols of biogenic origin11,12. Here I estimate that biogenic sources can account for 30–50% of the global baseline emissions of trace metals. For most of the toxic metals, the natural fluxes are small compared with emissions from industrial activities, implying that mankind has become the key agent in the global atmospheric cycle of trace metals and metalloids.

Journal ArticleDOI
01 Sep 1989-Nature
TL;DR: The full primary structure of brain-derived neurotrophic factor is reported and it is established that these two neurotrophic factors are related both functionally and structurally.
Abstract: During the development of the vertebrate nervous system, many neurons depend for survival on interactions with their target cells. Specific proteins are thought to be released by the target cells and to play an essential role in these interactions. So far, only one such protein, nerve growth factor, has been fully characterized. This has been possible because of the extraordinarily (and unexplained) large quantities of this protein in some adult tissues that are of no relevance to the developing nervous system. Whereas the dependency of many neurons on their target cells for normal development, and the restricted neuronal specificity of nerve growth factor have long suggested the existence of other such proteins, their low abundance has rendered their characterization difficult. Here we report the full primary structure of brain-derived neurotrophic factor. This very rare protein is known to promote the survival of neuronal populations that are all located either in the central nervous system or directly connected with it. The messenger RNA for brain-derived neurotrophic factor was found predominantly in the central nervous system, and the sequence of the protein indicates that it is structurally related to nerve growth factor. These results establish that these two neurotrophic factors are related both functionally and structurally.

Journal ArticleDOI
30 Mar 1989-Nature

Journal ArticleDOI
01 Jan 1989-Nature
TL;DR: In this paper, a family of superconducting copper oxides in which the carriers are electrons was discovered, with the formula Ln2−xCexCuO4−y, where Ln stands for lanthanides Pr, Nd or Sm.
Abstract: Since the discovery of high-temperature superconductivity in cop-per oxide compounds1, there has been much effort to understand what is required for a compound to have a high transition tem-perature (Tc). Up to now, all of the families of high-Tc copper oxide superconductors have contained two-dimensional sheets of Cu–O pyramids or octahedra, and the carriers of the superconduct-ing current have been electron vacancies, or 'holes'. By contrast, we report here the discovery of a family of superconducting copper oxides in which the carriers are electrons. The new superconductors are Ce4+-doped compounds, with the formula Ln2–xCexCuO4–y, where Ln stands for the lanthanides Pr, Nd or Sm. The compounds have the Nd2CuO4 (T′-phase) structure2, which is composed of sheets of Cu–O squares (see Fig. la). This structure has no apical oxygen atoms, in contrast to the T-phase structure with Cu–O octahedra (Fig. 1b), as observed in La2–xSrxCuO4 (refs 1, 2), and the T*-phase structure with Cu–O pyramids (Fig. 1c), as in Nd2–x–z Cex Srz CuO4 (ref. 3 and Y. T. et al., manuscript in preparation).

Journal ArticleDOI
31 Aug 1989-Nature
TL;DR: A subset of growth hormone-secreting human pituitary tumours carries somatic mutations that inhibit GTPase activity of a G protein α chain, αs, which results in the activation of adenylyl cyclase, which bypasses the cells' normal requirement for trophic hormone.
Abstract: A subset of growth hormone-secreting human pituitary tumours carries somatic mutations that inhibit GTPase activity of a G protein alpha chain, alpha(s) The resulting activation of adenylyl cyclase bypasses the cells' normal requirement for trophic hormone Amino acids substituted in the putative gsp oncogene identify a domain of G protein alpha-chains required for intrinsic ability to hydrolyse GTP This domain may serve as a built-in counter-part of the separate GTPase-activating proteins required for GTP hydrolysis by small GTP-binding proteins such as p21ras

Journal ArticleDOI
13 Apr 1989-Nature
TL;DR: The isolation of a cloned cDNA encoding a new GABAA receptor subunit, termed γ2, which shares approximately 40% sequence identity with α-and β-subunits and whose messenger RNA is prominently localized in neuronal subpopulations throughout the CNS.
Abstract: NEUROTRANSMISSION effected by GABA (γ-aminobutyric acid) is predominantly mediated by a gated chloride channel intrinsic to the GABAA receptor. This heterooligomeric receptor1 exists in most inhibitory synapses in the vertebrate central nervous system (CNS) and can be regulated by clinically important compounds such as benzodiazepines and barbiturates2. The primary structures of GABAA receptor α- and β-subunits have been deduced from cloned complementary DNAs3,4. Co-expression of these subunits in heterologous systems generates receptors which display much of the pharmacology of their neural counterparts, including potentiation by barbiturates3–5. Conspicuously, however, they lack binding sites for, and consistent electrophysiological responses to, benzodiazepines4,5. We now report the isolation of a cloned cDNA encoding a new GABAA receptor subunit, termed γ2, which shares approximately 40% sequence identity with α-and β-subunits and whose messenger RNA is prominently localized in neuronal subpopulations throughout the CNS. Importantly, coexpression of the γ2 subunit with α1 and β1 subunits produces GABAA receptors displaying high-affinity binding for central benzodiazepine receptor ligands.

Journal ArticleDOI
16 Mar 1989-Nature
TL;DR: These results indicate that the HIV-1 rev gene product induces HIV- 1 structural gene expression by activating the sequence-specific nuclear export of incompletely spliced HIV-2 RNA species.
Abstract: HUMAN immunodeficiency virus type 1 (HIV-1) replication requires the expression of two classes of viral mRNA. The early class of HIV-1 transcripts is fully spliced and encodes viral regulatory gene products. The functional expression of one of these nuclear regulatory proteins, termed Rev (formerly Art or Trs), induces the cytoplasmic expression of the incompletely spliced, late class of HIV-1 mRNAs that encode the viral structural proteins, including Gag and Env1–6. Here, we provide evidence that this induction reflects the export from the cell nucleus to the cytoplasm of a pool of unspliced viral RNA constitutively expressed in the nucleus. The hypothesis that Rev acts on RNA transport, rather than splicing, is further supported by the observation that the cytoplasmic expression of a non-spliceable HIV-1 env gene sequence is also subject to Rev regulation. Here we show that this Rev response requires a specific target sequence which coincides with a complex RNA secondary structure present in the env gene. The response to Rev is fully maintained when this sequence is relocated to other exonic or intronic locations within env but is ablated by inversion. These results indicate that the HIV-1 rev gene product induces HIV-1 structural gene expression by activating the sequence-specific nuclear export of incompletely spliced HIV-1 RNA species.

Journal ArticleDOI
02 Feb 1989-Nature
TL;DR: The results indicate that this enzyme is probably identical to cyclophilin, a recently discovered mammalian protein which binds tightly to cyclosporin A (CsA), which is thought to be linked to the immunosuppressive action of CsA.
Abstract: The enzyme peptidyl-prolyl cis-trans isomerase (PPIase) was recently discovered in mammalian tissues and purified from porcine kidney. It catalyses the slow cis-trans isomerization of proline peptide (Xaa-Pro) bonds in oligopeptides and accelerates slow, rate-limiting steps in the folding of several proteins. Here, we report the N-terminal sequence of PPIase together with further chemical and enzymatic properties. The results indicate that this enzyme is probably identical to cyclophilin, a recently discovered mammalian protein which binds tightly to cyclosporin A (CsA). Cyclophilin is thought to be linked to the immunosuppressive action of CsA. The first 38 amino-acid residues of porcine PPIase and of bovine cyclophilin are identical and the two proteins both have a relative molecular mass of about 17,000 (ref. 7). The catalysis of prolyl isomerization in oligopeptides and of protein folding by PPIase are strongly inhibited in the presence of low levels of CsA. The activities of both PPIase and cyclophilin depend on a single sulphydryl group. At present it is unknown whether the inhibition of prolyl isomerase activity is related with the immunosuppressive action of CsA.

Journal ArticleDOI
26 Oct 1989-Nature
TL;DR: The FKBP and cyclophilin appear to be members of an emerging class of novel proteins that regulate T cell activation and other metabolic processes, perhaps by the recognition (and possibly the isomerization) of proline-containing epitopes in target proteins.
Abstract: THE structurally novel macrolide FK506 (refs 1,2) has recently been demonstrated to have potent immunosuppressive activity3–7 at concentrations several hundredfold lower than cyclosporin A (CsA). Cyclosporin A, a cyclic peptide, has found widespread clinical use in the prevention of graft rejection following bone marrow and organ transplantation8. The mechanisms of immunosuppression mediated by FK506 and CsA appear to be remarkably similar, suggesting that these unrelated structures act on a common receptor or on similar molecular targets, perhaps the CsA receptor, cyclophilin9–11, which has recently been shown by Fischer etal.12 and Takahashi etal.13 to have cis–trans peptidyl-prolyl isomerase activity. We have prepared an FK506 affinity matrix and purified a binding protein for FK506 from bovine thymus and from human spleen. This FK506-binding protein (FKBP) has a relative molecular mass (Mr) of ∼14,000(14K), a pi of 8.8–8.9, and does not cross-react with antisera against cyclophilin. The first 40 N-terminal residues of the bovine and 16 residues of the human FKBP were determined; the 16-residue fragments are identical to each other and unrelated to any known sequences. This protein catalyses the cis–trans isomerization of the proline amide in a tetrapeptide substrate and FK506 inhibits the action of this new isomerase. The FKBP and cyclophilin appear to be members of an emerging class of novel proteins that regulate T cell activation and other metabolic processes, perhaps by the recognition (and possibly the isomerization) of proline-containing epitopes in target proteins.

Journal ArticleDOI
25 May 1989-Nature
TL;DR: In this paper, the addition of exogenous cyclin mRNA is sufficient to produce multiple cell cycles and the newly synthesized cyclin protein accumulates during each interphase and is degraded at the end of each mitosis.
Abstract: We have produced extracts of frog eggs that can perform multiple cell cycles in vitro. Destruction of the endogenous messenger RNA arrests the extracts in interphase. The addition of exogenous cyclin mRNA is sufficient to produce multiple cell cycles. The newly synthesized cyclin protein accumulates during each interphase and is degraded at the end of each mitosis.

Journal ArticleDOI
22 Jun 1989-Nature
TL;DR: Evidence is provided that the positive charges in segment S4 are involved in the voltage–sensing mechanism for activation of the channel and that the region between repeats III and IV is important for its inactivation.
Abstract: Structure-function relationships of the sodium channel expressed in Xenopus oocytes have been investigated by the combined use of site-directed mutagenesis and patch-clamp recording. This study provides evidence that the positive charges in segment S4 are involved in the voltage-sensing mechanism for activation of the channel and that the region between repeats III and IV is important for its inactivation.

Journal ArticleDOI
12 Jan 1989-Nature
TL;DR: It is shown that engaging the CD3/TCR complex of immature mouse thymocytes with anti-CD3 antibodies produces DNA degradation and cell death through the endogenous pathway of apoptosis.
Abstract: The receptors found on most T lymphocytes bind to antigen presented on major histocompatibility complex proteins and consist of dimers of alpha- and beta-polypeptides associated with the invariant CD3 complex. A fully competent immune system requires a diverse array of T-cell antigen receptors (TCRs) with different specificities. This diversity is generated by rearrangement of TCR alpha- and beta-chain gene segments within the thymus where the receptors are first expressed. Any cells carrying self-reactive receptors must be eliminated, suppressed or inactivated so that destructive autoimmunity is avoided. Recently, compelling evidence has shown that one process involved in producing such self-tolerance is clonal deletion of autoreactive cells within the thymus by an as-yet-undefined mechanism. Here we show that engaging the CD3/TCR complex of immature mouse thymocytes with anti-CD3 antibodies produces DNA degradation and cell death through the endogenous pathway of apoptosis. Activation of this process in immature T cells by the binding of the TCR to self-antigens may therefore be the mechanism which produces clonal deletion and consequently self-tolerance.

Journal ArticleDOI
02 Nov 1989-Nature
TL;DR: The cdc2+ protein kinase (pp34) is found to be phosphorylated on tyrosine as well as serine and threonine residues in exponentially growing Schizosaccharomyces pombe, establishing that tyrosines phosphorylation/dephosphorylation directly regulates pp34 function.
Abstract: The cdc2+ protein kinase (pp34) is found to be phosphorylated on tyrosine as well as serine and threonine residues in exponentially growing Schizosaccharomyces pombe. At mitosis, the level of pp34 phosphorylation on both threonine and tyrosine residues decreases. The single detectable site of tyrosine phosphorylation in pp34 has been mapped to Tyr 15, a residue within the presumptive ATP-binding domain. Substitution of this tyrosine by phenylalanine advances cells prematurely into mitosis, establishing that tyrosine phosphorylation/dephosphorylation directly regulates pp34 function.

Journal ArticleDOI
04 May 1989-Nature
TL;DR: It is shown that cross-linkage of FcεRI on a series of non-transformed murine mast cell lines, or treatment of these cells with calcium ionophores, stimulates increased messenger RNA levels and secretion of a group of lymphokines classically produced by a subset of murine T cell lines (TH2cells).
Abstract: The cross-linkage of high affinity Fc epsilon receptors (Fc epsilon RI) on mast cells and basophils is central to the induction of allergic inflammatory responses. As a result of such cross-linkage, mast cells secrete a variety of preformed biologically active substances, such as histamine, and newly synthesized arachidonic acid metabolites. Here we show that cross-linkage of Fc epsilon RI on a series of nontransformed murine mast cell lines, or treatment of these cells with calcium ionophores, stimulates increased messenger RNA levels and secretion of a group of lymphokines classically produced by a subset of murine T cell lines (TH2 cells). These factors include interleukin-3 (a mast cell growth factor)s interleukin-4 (an IgE 'switch factor'), interleukin-5 (an eosinophil differentiation factor) and interleukin-6 (a factor controlling immunoglobulin secretion). The production of these polypeptide factors by mast cells may have great importance in the induction of allergic and anti-parasite inflammatory responses.

Journal ArticleDOI
07 Sep 1989-Nature
TL;DR: It is suggested that under the authors' conditions, psychophysical judgements could be based on the activity of a relatively small number of neurons.
Abstract: THE relationship between neuronal activity and psychophysical judgement has long been of interest to students of sensory processing. Previous analyses of this problem have compared the performance of human or animal observers in detection or discrimination tasks with the signals carried by individual neurons, but have been hampered because neuronal and perceptual data were not obtained at the same time and under the same conditions1–4. We have now measured the performance of monkeys and of visual cortical neurons while the animals performed a psychophysical task well matched to the properties of the neurons under study. Here we report that the reliability and sensitivity of most neurons on this task equalled or exceeded that of the monkeys. We therefore suggest that under our conditions, psychophysical judgements could be based on the activity of a relatively small number of neurons.