scispace - formally typeset
Search or ask a question

Showing papers in "Science in 1990"


Journal ArticleDOI
03 Aug 1990-Science
TL;DR: High-affinity nucleic acid ligands for a protein were isolated by a procedure that depends on alternate cycles of ligand selection from pools of variant sequences and amplification of the bound species.
Abstract: High-affinity nucleic acid ligands for a protein were isolated by a procedure that depends on alternate cycles of ligand selection from pools of variant sequences and amplification of the bound species. Multiple rounds exponentially enrich the population for the highest affinity species that can be clonally isolated and characterized. In particular one eight-base region of an RNA that interacts with the T4 DNA polymerase was chosen and randomized. Two different sequences were selected by this procedure from the calculated pool of 65,536 species. One is the wild-type sequence found in the bacteriophage mRNA; one is varied from wild type at four positions. The binding constants of these two RNA's to T4 DNA polymerase are equivalent. These protocols with minimal modification can yield high-affinity ligands for any protein that binds nucleic acids as part of its function; high-affinity ligands could conceivably be developed for any target molecule.

9,367 citations


Journal ArticleDOI
06 Apr 1990-Science
TL;DR: The fluorescence emission increased quadratically with the excitation intensity so that fluorescence and photo-bleaching were confined to the vicinity of the focal plane as expected for cooperative two-photon excitation.
Abstract: Molecular excitation by the simultaneous absorption of two photons provides intrinsic three-dimensional resolution in laser scanning fluorescence microscopy. The excitation of fluorophores having single-photon absorption in the ultraviolet with a stream of strongly focused subpicosecond pulses of red laser light has made possible fluorescence images of living cells and other microscopic objects. The fluorescence emission increased quadratically with the excitation intensity so that fluorescence and photo-bleaching were confined to the vicinity of the focal plane as expected for cooperative two-photon excitation. This technique also provides unprecedented capabilities for three-dimensional, spatially resolved photochemistry, particularly photolytic release of caged effector molecules.

8,905 citations


Journal ArticleDOI
21 Sep 1990-Science
TL;DR: CD14, a differentiation antigen of monocytes, was found to bind complexes of LPS and LBP, and blockade of CD14 with monoclonal antibodies prevented synthesis of TNF-alpha by whole blood incubated with LPS.
Abstract: Leukocytes respond to lipopolysaccharide (LPS) at nanogram per milliliter concentrations with secretion of cytokines such as tumor necrosis factor-alpha (TNF-alpha). Excess secretion of TNF-alpha causes endotoxic shock, an often fatal complication of infection. LPS in the bloodstream rapidly binds to the serum protein, lipopolysaccharide binding protein (LBP), and cellular responses to physiological levels of LPS are dependent on LBP. CD14, a differentiation antigen of monocytes, was found to bind complexes of LPS and LBP, and blockade of CD14 with monoclonal antibodies prevented synthesis of TNF-alpha by whole blood incubated with LPS. Thus, LPS may induce responses by interacting with a soluble binding protein in serum that then binds the cell surface protein CD14.

4,048 citations


Journal ArticleDOI
23 Mar 1990-Science
TL;DR: RNA and DNA expression vectors containing genes for chloramphenicol acetyltransferase, luciferase, and beta-galactosidase were separately injected into mouse skeletal muscle in vivo and expression was comparable to that obtained from fibroblasts transfected in vitro under optimal conditions.
Abstract: RNA and DNA expression vectors containing genes for chloramphenicol acetyltransferase, luciferase, and beta-galactosidase were separately injected into mouse skeletal muscle in vivo. Protein expression was readily detected in all cases, and no special delivery system was required for these effects. The extent of expression from both the RNA and DNA constructs was comparable to that obtained from fibroblasts transfected in vitro under optimal conditions. In situ cytochemical staining for beta-galactosidase activity was localized to muscle cells following injection of the beta-galactosidase DNA vector. After injection of the DNA luciferase expression vector, luciferase activity was present in the muscle for at least 2 months.

4,022 citations


Journal ArticleDOI
30 Nov 1990-Science
TL;DR: Germ line p53 mutations have been detected in all five LFS families analyzed and can now be examined in additional families with LFS, and in other cancer patients and families with clinical features that might be attributed to the mutation.
Abstract: Familial cancer syndromes have helped to define the role of tumor suppressor genes in the development of cancer. The dominantly inherited Li-Fraumeni syndrome (LFS) is of particular interest because of the diversity of childhood and adult tumors that occur in affected individuals. The rarity and high mortality of LFS precluded formal linkage analysis. The alternative approach was to select the most plausible candidate gene. The tumor suppressor gene, p53, was studied because of previous indications that this gene is inactivated in the sporadic (nonfamilial) forms of most cancers that are associated with LFS. Germ line p53 mutations have been detected in all five LFS families analyzed. These mutations do not produce amounts of mutant p53 protein expected to exert a trans-dominant loss of function effect on wild-type p53 protein. The frequency of germ line p53 mutations can now be examined in additional families with LFS, and in other cancer patients and families with clinical features that might be attributed to the mutation.

3,662 citations


Journal ArticleDOI
07 Dec 1990-Science
TL;DR: The differential effects of dopamine on striatonigral and striatopallidal neurons are mediated by their specific expression of D1 and D2 dopamine receptor subtypes, respectively.
Abstract: The striatum, which is the major component of the basal ganglia in the brain, is regulated in part by dopaminergic input from the substantia nigra. Severe movement disorders result from the loss of striatal dopamine in patients with Parkinson's disease. Rats with lesions of the nigrostriatal dopamine pathway caused by 6-hydroxydopamine (6-OHDA) serve as a model for Parkinson's disease and show alterations in gene expression in the two major output systems of the striatum to the globus pallidus and substantia nigra. Striatopallidal neurons show a 6-OHDA-induced elevation in their specific expression of messenger RNAs (mRNAs) encoding the D2 dopamine receptor and enkephalin, which is reversed by subsequent continuous treatment with the D2 agonist quinpirole. Conversely, striatonigral neurons show a 6-OHDA-induced reduction in their specific expression of mRNAs encoding the D1 dopamine receptor and substance P, which is reversed by subsequent daily injections of the D1 agonist SKF-38393. This treatment also increases dynorphin mRNA in striatonigral neurons. Thus, the differential effects of dopamine on striatonigral and striatopallidal neurons are mediated by their specific expression of D1 and D2 dopamine receptor subtypes, respectively.

2,946 citations


Journal ArticleDOI
06 Apr 1990-Science
TL;DR: This study shows that the E6 protein of HPV-16 is capable of binding to the cellular p53 protein, providing further evidence that the human papillomaviruses, the adenovirus type 5, and SV40 may effect similar cellular pathways in transformation.
Abstract: Human papillomavirus type 16 (HPV-16) is a DNA tumor virus that is associated with human anogenital cancers and encodes two transforming proteins, E6 and E7. The E7 protein has been shown to bind to the retinoblastoma tumor suppressor gene product, pRB. This study shows that the E6 protein of HPV-16 is capable of binding to the cellular p53 protein. The ability of the E6 proteins from different human papillomaviruses to form complexes with p53 was assayed and found to correlate with the in vivo clinical behavior and the in vitro transforming activity of these different papillomaviruses. The wild-type p53 protein has tumor suppressor properties and has also been found in association with large T antigen and the E1B 55-kilodalton protein in cells transformed by SV40 and by adenovirus type 5, respectively, providing further evidence that the human papillomaviruses, the adenoviruses, and SV40 may effect similar cellular pathways in transformation.

2,520 citations


Journal ArticleDOI
27 Jul 1990-Science
TL;DR: Tens of millions of short peptides can be easily surveyed for tight binding to an antibody, receptor or other binding protein using an "epitope library".
Abstract: Tens of millions of short peptides can be easily surveyed for tight binding to an antibody, receptor or other binding protein using an "epitope library." The library is a vast mixture of filamentous phage clones, each displaying one peptide sequence on the virion surface. The survey is accomplished by using the binding protein to affinity-purify phage that display tight-binding peptides and propagating the purified phage in Escherichia coli. The amino acid sequences of the peptides displayed on the phage are then determined by sequencing the corresponding coding region in the viral DNA's. Potential applications of the epitope library include investigation of the specificity of antibodies and discovery of mimetic drug candidates.

2,494 citations


Journal ArticleDOI
21 Dec 1990-Science
TL;DR: Ch Chromosome 17q21 appears to be the locale of a gene for inherited susceptibility to breast cancer in families with early-onset disease, and genetic analysis yields a lod score of 5.98 for linkage of breast cancer susceptibility to D17S74 in early-ONSet families and negative lod scores in familiesWith late-onsets disease.
Abstract: Human breast cancer is usually caused by genetic alterations of somatic cells of the breast, but occasionally, susceptibility to the disease is inherited. Mapping the genes responsible for inherited breast cancer may also allow the identification of early lesions that are critical for the development of breast cancer in the general population. Chromosome 17q21 appears to be the locale of a gene for inherited susceptibility to breast cancer in families with early-onset disease. Genetic analysis yields a lod score (logarithm of the likelihood ratio for linkage) of 5.98 for linkage of breast cancer susceptibility to D17S74 in early-onset families and negative lod scores in families with late-onset disease. Likelihood ratios in favor of linkage heterogeneity among families ranged between 2000:1 and greater than 10(6):1 on the basis of multipoint analysis of four loci in the region.

2,448 citations


Journal ArticleDOI
21 Dec 1990-Science
TL;DR: Widespread burning of biomass serves to clear land for shifting cultivation, to convert forests to agricultural and pastoral lands, and to remove dry vegetation in order to promote agricultural productivity and the growth of higher yield grasses, but it may also disturb biogeochemical cycles, especially that of nitrogen.
Abstract: The use of fire as a tool to manipulate the environment has been instrumental in the human conquest of Earth, the first evidence of the use of fires by early hominids dating back to 1–1.5 million years ago [1]. Even today, most human-ignited vegetation fires take place on the African continent, and its widespread, frequently burned savannas bear ample witness to this. Although natural fires can occur even in tropical forest regions [2, 3], the extent of fires has greatly expanded on all continents with the arrival of Homo sapiens. Measurements of charcoal in dated sediment cores have shown clear correlations between the rate of burning and human settlement [4]. Pollen records show a shift with human settlement from pyrophobic vegetation to pyrotolerant and pyrophilic species, testimony to the large ecological impact of human-induced fires.

2,424 citations


Journal ArticleDOI
02 Mar 1990-Science
TL;DR: Studies of ecosystem processes on the Jornada Experimental Range in southern New Mexico suggest that longterm grazing of semiarid grasslands leads to an increase in the spatial and temporal heterogeneity of water, nitrogen, and other soil resources, which leads to the desertification of formerly productive land.
Abstract: Studies of ecosystem processes on the Jornada Experimental Range in southern New Mexico suggest that longterm grazing of semiarid grasslands leads to an increase in the spatial and temporal heterogeneity of water, nitrogen, and other soil resources. Heterogeneity of soil resources promotes invasion by desert shrubs, which leads to a further localization of soil resources under shrub canopies. In the barren area between shrubs, soil fertility is lost by erosion and gaseous emissions. This positive feedback leads to the desertification of formerly productive land in southern New Mexico and in other regions, such as the Sahel. Future desertification is likely to be exacerbated by global climate warming and to cause significant changes in global biogeochemical cycles.

Journal ArticleDOI
28 Sep 1990-Science
TL;DR: Conventional forms of drug administration generally rely on pills, eye drops, ointments, and intravenous solutions, but a number of novel drug delivery approaches have been developed, which may revolutionize the way many drugs are delivered.
Abstract: Conventional forms of drug administration generally rely on pills, eye drops, ointments, and intravenous solutions. Recently, a number of novel drug delivery approaches have been developed. These approaches include drug modification by chemical means, drug entrapment in small vesicles that are injected into the bloodstream, and drug entrapment within pumps or polymeric materials that are placed in desired bodily compartments (for example, the eye or beneath the skin). These techniques have already led to delivery systems that improve human health, and continued research may revolutionize the way many drugs are delivered.

Journal ArticleDOI
16 Mar 1990-Science
TL;DR: Comparison of different sequences with similar messages can reveal key features of the code and improve understanding of how a protein folds and how it performs its function.
Abstract: An amino acid sequence encodes a message that determines the shape and function of a protein. This message is highly degenerate in that many different sequences can code for proteins with essentially the same structure and activity. Comparison of different sequences with similar messages can reveal key features of the code and improve understanding of how a protein folds and how it performs its function.

Journal ArticleDOI
19 Jan 1990-Science
TL;DR: Evidence is converging for the proposition that priming is an expression of a perceptual representation system that operates at a pre-semantic level; it emerges early in development, and access to it lacks the kind of flexibility characteristic of other cognitive memory systems.
Abstract: Priming is a nonconscious form of human memory, which is concerned with perceptual identification of words and objects and which has only recently been recognized as separate from other forms of memory or memory systems. It is currently under intense experimental scrutiny. Evidence is converging for the proposition that priming is an expression of a perceptual representation system that operates at a pre-semantic level; it emerges early in development, and access to it lacks the kind of flexibility characteristic of other cognitive memory systems. Conceptual priming, however, seems to be based on the operations of semantic memory.

Journal ArticleDOI
16 Feb 1990-Science
TL;DR: It is demonstrated that P210bcr/abl expression can induce chronic myelogenous leukemia and retrovirus-mediated expression of the protein provides a murine model system for further analysis of the disease.
Abstract: In tumor cells from virtually all patients with chronic myelogenous leukemia, the Philadelphia chromosome, a fusion of chromosomes 9 and 22, directs the synthesis of the P210bcr/abl protein. The protein-tyrosine kinase activity and hybrid structure of P210bcr/abl are similar to the oncogene product of the Abelson murine leukemia virus, P160gag/v-abl, which induces acute lymphomas. To determine whether P210bcr/abl can induce chronic myelogenous leukemia, murine bone marrow was infected with a retrovirus encoding P210bcr/abl and transplanted into irradiated syngeneic recipients. Transplant recipients developed several hematologic malignancies; prominent among them was a myeloproliferative syndrome closely resembling the chronic phase of human chronic myelogenous leukemia. Tumor tissue from diseased mice harbored the provirus encoding P210bcr/abl. These results demonstrate that P210bcr/abl expression can induce chronic myelogenous leukemia. Retrovirus-mediated expression of the protein provides a murine model system for further analysis of the disease.

Journal ArticleDOI
12 Oct 1990-Science
TL;DR: The amyloid beta protein could function as a neurotrophic factor for differentiating neurons, but at high concentrations in mature neurons, as in Alzheimer's disease, could cause neuronal degeneration.
Abstract: The amyloid beta protein is deposited in the brains of patients with Alzheimer's disease but its pathogenic role is unknown. In culture, the amyloid beta protein was neurotrophic to undifferentiated hippocampal neurons at low concentrations and neurotoxic to mature neurons at higher concentrations. In differentiated neurons, amyloid beta protein caused dendritic and axonal retraction followed by neuronal death. A portion of the amyloid beta protein (amino acids 25 to 35) mediated both the trophic and toxic effects and was homologous to the tachykinin neuropeptide family. The effects of the amyloid beta protein were mimicked by tachykinin antagonists and completely reversed by specific tachykinin agonists. Thus, the amyloid beta protein could function as a neurotrophic factor for differentiating neurons, but at high concentrations in mature neurons, as in Alzheimer's disease, could cause neuronal degeneration.

Journal ArticleDOI
23 Mar 1990-Science
TL;DR: The observed differences between the partial pressure of CO2 in the surface waters of the Northern Hemisphere and the atmosphere are too small for the oceans to be the major sink of fossil fuel CO2, and a large amount of the CO2 is apparently absorbed on the continents by terrestrial ecosystems.
Abstract: Observed atmospheric concentrations of CO2 and data on the partial pressures of CO2 in surface ocean waters are combined to identify globally significant sources and sinks of CO2. The atmospheric data are compared with boundary layer concentrations calculated with the transport fields generated by a general circulation model (GCM) for specified source-sink distributions. In the model the observed north-south atmospheric concentration gradient can be maintained only if sinks for CO2 are greater in the Northern than in the Southern Hemisphere. The observed differences between the partial pressure of CO2 in the surface waters of the Northern Hemisphere and the atmosphere are too small for the oceans to be the major sink of fossil fuel CO2. Therefore, a large amount of the CO2 is apparently absorbed on the continents by terrestrial ecosystems.

Journal ArticleDOI
15 Jun 1990-Science
TL;DR: The T cell enters an unresponsive state known as clonal anergy in which the T cell is incapable of producing its own growth hormone, interleukin-2, on restimulation.
Abstract: T lymphocytes respond to foreign antigens both by producing protein effector molecules known as lymphokines and by multiplying. Complete activation requires two signaling events, one through the antigen-specific receptor and one through the receptor for a costimulatory molecule. In the absence of the latter signal, the T cell makes only a partial response and, more importantly, enters an unresponsive state known as clonal anergy in which the T cell is incapable of producing its own growth hormone, interleukin-2, on restimulation. Our current understanding at the molecular level of this modulatory process and its relevance to T cell tolerance are reviewed.

Journal ArticleDOI
11 May 1990-Science
TL;DR: Staphylococcal enterotoxins and a group of related proteins made by Streptococci cause food poisoning and shock in man and animals and it is likely that some or all of the pathological effects of these toxins are caused by their ability to activate quickly so many T cells.
Abstract: Staphylococcal enterotoxins and a group of related proteins made by Streptococci cause food poisoning and shock in man and animals. These proteins share an ability to bind to human and mouse major histocompatibility complex proteins. The complex ligand so formed has specificity for a particular part of T cell receptors, V beta, and by engaging V beta can stimulate many T cells. It is likely that some or all of the pathological effects of these toxins are caused by their ability to activate quickly so many T cells. It is also possible that encounters with such toxins have caused mice, at least, to evolve mechanisms for varying their T cell V beta repertoires, such that they are less susceptible to attack by the toxins.

Journal ArticleDOI
21 Sep 1990-Science
TL;DR: The postulated role of excessive activity in the subthalamic nucleus in Parkinson's disease is supported by the effects of lesions evaluated in monkeys rendered parkinsonian by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
Abstract: Although it is known that Parkinson's disease results from a loss of dopaminergic neurons in the substantia nigra, the resulting alterations in activity in the basal ganglia responsible for parkinsonian motor deficits are still poorly characterized. Recently, increased activity in the subthalamic nucleus has been implicated in the motor abnormalities. To test this hypothesis, the effects of lesions of the subthalamic nucleus were evaluated in monkeys rendered parkinsonian by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The lesions reduced all of the major motor disturbances in the contralateral limbs, including akinesia, rigidity, and tremor. This result supports the postulated role of excessive activity in the subthalamic nucleus in Parkinson's disease.

Journal ArticleDOI
21 Dec 1990-Science
TL;DR: Results provide direct evidence for the in vivo role of apoptosis in the development of antigen-induced tolerance in mice transgenic for a T cell receptor that reacts to this peptide.
Abstract: In order to examine the mechanisms by which clonal deletion of autoreactive T cells occurs, a peptide antigen was used to induce deletion of antigen-reactive thymocytes in vivo. Mice transgenic for a T cell receptor (TCR) that reacts to this peptide contain thymocytes that progress from the immature to the mature phenotype. Intraperitoneal administration of the peptide antigen to transgenic mice results in a rapid deletion of the immature CD4+ CD8+ TCRlo thymocytes. Apoptosis of cortical thymocytes can be seen within 20 hours of treatment. These results provide direct evidence for the in vivo role of apoptosis in the development of antigen-induced tolerance.

Journal ArticleDOI
26 Jan 1990-Science
TL;DR: It is reported that cultured hippocampal astrocytes can respond to glutamate with a prompt and oscillatory elevation of cytoplasmic free calcium, visible through use of the fluorescent calcium indicator fluo-3.
Abstract: The finding that astrocytes possess glutamate-sensitive ion channels hinted at a previously unrecognized signaling role for these cells. Now it is reported that cultured hippocampal astrocytes can respond to glutamate with a prompt and oscillatory elevation of cytoplasmic free calcium, visible through use of the fluorescent calcium indicator fluo-3. Two types of glutamate receptor--one preferring quisqualate and releasing calcium from intracellular stores and the other preferring kainate and promoting surface-membrane calcium influx--appear to be involved. Moreover, glutamate-induced increases in cytoplasmic free calcium frequently propagate as waves within the cytoplasm of individual astrocytes and between adjacent astrocytes in confluent cultures. These propagating waves of calcium suggest that networks of astrocytes may constitute a long-range signaling system within the brain.

Journal ArticleDOI
24 Aug 1990-Science
TL;DR: It is shown that the wild-type gene can specifically suppress the growth of human colorectal carcinoma cells in vitro and that an in vivo-derived mutation resulting in a single conservative amino acid substitution in the p53 gene product abrogates this suppressive ability.
Abstract: Mutations of the p53 gene occur commonly in colorectal carcinomas and the wild-type p53 allele is often concomitantly deleted. These findings suggest that the wild-type gene may act as a suppressor of colorectal carcinoma cell growth. To test this hypothesis, wild-type or mutant human p53 genes were transfected into human colorectal carcinoma cell lines. Cells transfected with the wild-type gene formed colonies five- to tenfold less efficiently than those transfected with a mutant p53 gene. In those colonies that did form after wild-type gene transfection, the p53 sequences were found to be deleted or rearranged, or both, and no exogenous p53 messenger RNA expression was observed. In contrast, transfection with the wild-type gene had no apparent effect on the growth of epithelial cells derived from a benign colorectal tumor that had only wild-type p53 alleles. Immunocytochemical techniques demonstrated that carcinoma cells expressing the wild-type gene did not progress through the cell cycle, as evidenced by their failure to incorporate thymidine into DNA. These studies show that the wild-type gene can specifically suppress the growth of human colorectal carcinoma cells in vitro and that an in vivo-derived mutation resulting in a single conservative amino acid substitution in the p53 gene product abrogates this suppressive ability.

Journal ArticleDOI
23 Feb 1990-Science
TL;DR: The pacemaker role of the suprachiasmatic nucleus in a mammalian circadian system was tested by neural transplantation by using a mutant strain of hamster that shows a short circadian period to restore circadian rhythms to arrhythmic animals whose own nucleus had been ablated.
Abstract: The pacemaker role of the suprachiasmatic nucleus in a mammalian circadian system was tested by neural transplantation by using a mutant strain of hamster that shows a short circadian period. Small neural grafts from the suprachiasmatic region restored circadian rhythms to arrhythmic animals whose own nucleus had been ablated. The restored rhythms always exhibited the period of the donor genotype regardless of the direction of the transplant or genotype of the host. The basic period of the overt circadian rhythm therefore is determined by cells of the suprachiasmatic region.

Journal ArticleDOI
21 Dec 1990-Science
TL;DR: Results from a prospective study of a representative sample of 309 children indicated that physical abuse is indeed a risk factor for later aggressive behavior even when the other ecological and biological factors are known.
Abstract: Two questions concerning the effect of physical abuse in early childhood on the child's development of aggressive behavior are the focus of this article. The first is whether abuse per se has deleterious effects. In earlier studies, in which samples were nonrepresentative and family ecological factors (such as poverty, marital violence, and family instability) and child biological variables (such as early health problems and temperament) were ignored, findings have been ambiguous. Results from a prospective study of a representative sample of 309 children indicated that physical abuse is indeed a risk factor for later aggressive behavior even when the other ecological and biological factors are known. The second question concerns the processes by which antisocial development occurs in abused children. Abused children tended to acquire deviant patterns of processing social information, and these may mediate the development of aggressive behavior.

Journal ArticleDOI
05 Jan 1990-Science
TL;DR: A contiguous stretch of DNA comprising 370 kilobase pairs has now been cloned from a region of chromosome 18q suspected to reside near the DCC gene, which may play a role in the pathogenesis of human colorectal neoplasia, perhaps through alteration of the normal cell-cell interactions controlling growth.
Abstract: Allelic deletions involving chromosome 18q occur in more than 70 percent of colorectal cancers. Such deletions are thought to signal the existence of a tumor suppressor gene in the affected region, but until now a candidate suppressor gene on this chromosomal arm had not been identified. A contiguous stretch of DNA comprising 370 kilobase pairs (kb) has now been cloned from a region of chromosome 18q suspected to reside near this gene. Potential exons in the 370-kb region were defined by human-rodent sequence identities, and the expression of potential exons was assessed by an "exon-connection" strategy based on the polymerase chain reaction. Expressed exons were used as probes for cDNA screening to obtain clones that encoded a portion of a gene termed DCC; this cDNA was encoded by at least eight exons within the 370-kb genomic region. The predicted amino acid sequence of the cDNA specified a protein with sequence similarity to neural cell adhesion molecules and other related cell surface glycoproteins. While the DCC gene was expressed in most normal tissues, including colonic mucosa, its expression was greatly reduced or absent in most colorectal carcinomas tested. Somatic mutations within the DCC gene observed in colorectal cancers included a homozygous deletion of the 5' end of the gene, a point mutation within one of the introns, and ten examples of DNA insertions within a 0.17-kb fragment immediately downstream of one of the exons. The DCC gene may play a role in the pathogenesis of human colorectal neoplasia, perhaps through alteration of the normal cell-cell interactions controlling growth.

Journal ArticleDOI
21 Sep 1990-Science
TL;DR: The identification of this pathway for LPS-induced monocyte stimulation may aid in the development of treatments for diseases in which Gram-negative sepsis or endotoxemia are involved.
Abstract: The primary structure of lipopolysaccharide binding protein (LBP), a trace plasma protein that binds to the lipid A moiety of bacterial lipopolysaccharides (LPSs), was deduced by sequencing cloned complementary DNA. LBP shares sequence identity with another LPS binding protein found in granulocytes, bactericidal/permeability-increasing protein, and with cholesterol ester transport protein of the plasma. LBP may control the response to LPS under physiologic conditions by forming high-affinity complexes with LPS that bind to monocytes and macrophages, which then secrete tumor necrosis factor. The identification of this pathway for LPS-induced monocyte stimulation may aid in the development of treatments for diseases in which Gram-negative sepsis or endotoxemia are involved.

Journal ArticleDOI
30 Nov 1990-Science
TL;DR: Corn seedlings release large amounts of terpenoid volatiles after they have been fed upon by caterpillars, and females of the parasitic wasp Cotesia marginiventris (Cresson) learn to take advantage of those plant-producedvolatiles to locate hosts when exposed to these volatile in association with hosts or host by-products.
Abstract: Corn seedlings release large amounts of terpenoid volatiles after they have been fed upon by caterpillars. Artificially damaged seedlings do not release these volatiles in significant amounts unless oral secretions from the caterpillars are applied to the damaged sites. Undamaged leaves, whether or not they are treated with oral secretions, do not release detectable amounts of the terpenoids. Females of the parasitic wasp Cotesia marginiventris (Cresson) learn to take advantage of those plant-produced volatiles to locate hosts when exposed to these volatiles in association with hosts or host by-products. The terpenoids may be produced in defense against herbivores but may also serve a secondary function in attracting the natural enemies of these herbivores.

Journal ArticleDOI
07 Sep 1990-Science
TL;DR: DNA binding of the Fos-Jun heterodimer was modulated by reduction-oxidation of a single conserved cysteine residue in the DNA-binding domains of the two proteins, suggesting that transcriptional activity mediated by AP-1 binding factors may be regulated by a redox mechanism.
Abstract: The proto-oncogenes c-fos and c-jun function cooperatively as inducible transcription factors in signal transduction processes. Their protein products, Fos and Jun, form a heterodimeric complex that interacts with the DNA regulatory element known as the activator protein-1 (AP-1) binding site. Dimerization occurs via interaction between leucine zipper domains and serves to bring into proper juxtaposition a region in each protein that is rich in basic amino acids and that forms a DNA-binding domain. DNA binding of the Fos-Jun heterodimer was modulated by reduction-oxidation (redox) of a single conserved cysteine residue in the DNA-binding domains of the two proteins. Furthermore, a nuclear protein was identified that reduced Fos and Jun and stimulated DNA-binding activity in vitro. These results suggest that transcriptional activity mediated by AP-1 binding factors may be regulated by a redox mechanism.

Journal ArticleDOI
19 Jan 1990-Science
TL;DR: In a pedigree derived from a mouse treated with the mutagen ethylnitrosourea, a mutation has been identified that predisposes to spontaneous intestinal cancer.
Abstract: In a pedigree derived from a mouse treated with the mutagen ethylnitrosourea, a mutation has been identified that predisposes to spontaneous intestinal cancer. The mutant gene was found to be dominantly expressed and fully penetrant. Affected mice developed multiple adenomas throughout the entire intestinal tract at an early age.