Showing papers in "Nature in 1981"
TL;DR: The establishment in tissue culture of pluripotent cell lines which have been isolated directly from in vitro cultures of mouse blastocysts are reported, able to differentiate either in vitro or after innoculation into a mouse as a tumour in vivo.
Abstract: Pluripotential cells are present in a mouse embryo until at least an early post-implantation stage, as shown by their ability to take part hi the formation of chimaeric animals1 and to form teratocarcinomas2. Until now it has not been possible to establish progressively growing cultures of these cells in vitro, and cell lines have only been obtained after teratocarcinoma formation in vivo. We report here the establishment in tissue culture of pluripotent cell lines which have been isolated directly from in vitro cultures of mouse blastocysts. These cells are able to differentiate either in vitro or after innoculation into a mouse as a tumour in vivo. They have a normal karyotype.
8,144 citations
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TL;DR: In the early 1990s, the NSF's Institute for Theoretical Physics in Santa Barbara devoted a 6-month program and an intensive 1-week workshop to the subject as discussed by the authors.
Abstract: In the past few years one of the most exciting areas of research in physics has been the interdisciplinary field of cosmology and particle physics. The NSF's Institute for Theoretical Physics in Santa Barbara devoted a 6-month program and an intensive 1-week workshop to the subject. A brief review is given of both the workshop and this field which is attracting attention, in part, because the early Universe seems to be the only laboratory in which to study grand unification.
3,436 citations
TL;DR: The haemagglutinin glycoprotein of influenza virus is a trimer comprising two structurally distinct regions: a triple-stranded coiled-coil of α-helices extends 76 Å from the membrane and a globular region of antiparallel β-sheet is positioned on top of this stem.
Abstract: The haemagglutinin glycoprotein of influenza virus is a trimer comprising two structurally distinct regions: a triple-stranded coiled-coil of alpha-helices extends 76 A from the membrane and a globular region of antiparallel beta-sheet, which contains the receptor binding site and the variable antigenic determinants, is positioned on top of this stem. Each subunit has an unusual loop-like topology, starting at the membrane, extending 135 A distally and folding back to enter the membrane.
2,444 citations
TL;DR: It is proposed that the H strand is transcribed into a single polycistronic RNA molecule, which is processed later into mature species by precise endonucleolytic cleavages which occur, in most cases, immediately before and after a tRNA sequence.
Abstract: A 3'-end proximal segment of most of the putative mRNAs encoded in the heavy strand of HeLa cell mtDNA has been partially sequences and aligned with the DNA sequence. In all cases, the 3'-end nucleotide of the individual mRNA coding sequences has been found to be immediately contiguous to a tRNA gene or another mRNA coding sequence. These and previous results indicate that the heavy (H) strand sequences coding for the rRNA, poly(A)-containing RNA and tRNA species form a continuum extending over almost the entire length of this strand. We propose that the H strand is transcribed into a single polycistronic RNA molecule, which is processed later into mature species by precise endonucleolytic cleavages which occur, in most cases, immediately before and after a tRNA sequence.
2,185 citations
TL;DR: The use of a tetracycline-resistance transposon, Tn10 (refs 5, 6), inserted in gene aroA to produce non-reverting, aromatic-requiring derivatives of virulent S. typhimurium strains were virtually non-virulent; their use as live vaccines conferred excellent protection against challenge with a virulent strain.
Abstract: An auxotrophic mutant which requires a metabolite not available in vertebrate tissues should be unable to grow in such tissue and thus be non-virulent. Most mutations to auxotrophy do not affect virulence1–3, presumably because the required metabolites are available at sufficient concentration. However, Bacon et al.1,2 noted that a Salmonella typhi mutant requiring p-amino-benzoic acid (p AB) was less virulent (for mice) than its parent. Salmonella, unlike vertebrates, cannot assimilate exogenous folate and must synthesize it from p AB; the virtual absence of p AB from vertebrate tissues is shown by the efficacy of sulphonamide chemotherapy. Yancey et al.4 reported reduced virulence for a S. typhimurium mutant with a requirement for 2,3-dihydroxybenzoate (DHB), the precursor of the bacterial iron-acquisition compound, enterochelin. As DHB is not a known vertebrate metabolite, it would be expected to be absent from mouse tissues. Salmonella synthesize p AB and DHB from chorismate, the final product of the aromatic biosynthetic (aro) pathway. A complete block at any step of this pathway should make S. typhimurium auxotrophic for two compounds not available in vertebrate tissues, and thus non-virulent. We describe here the use of a tetracycline-resistance transposon, Tn10 (refs 5, 6), inserted in gene aroA to produce non-reverting, aromatic-requiring derivatives of virulent S. typhimurium strains. These derivatives were virtually non-virulent; their use as live vaccines conferred excellent protection against challenge with a virulent strain.
2,090 citations
TL;DR: Research with texture pairs having identical second-order statistics has revealed that the pre-attentive texture discrimination system cannot globally process third- and higher- order statistics, and that discrimination is the result of a few local conspicuous features, called textons.
Abstract: Research with texture pairs having identical second-order statistics has revealed that the pre-attentive texture discrimination system cannot globally process third- and higher-order statistics, and that discrimination is the result of a few local conspicuous features, called textons. It seems that only the first-order statistics of these textons have perceptual significance, and the relative phase between textons cannot be perceived without detailed scrutiny by focal attention.
1,757 citations
TL;DR: In this article, an empirical model is constructed that may provide accurate crust-formation ages f or rocks of all ages, based on the isotopic data of major rock types of the basement underlying the Rocky Mountains in Colorado.
Abstract: Initial 143Nd/144Nd determined for major rock types of the basement underlying the Rocky Mountains in Colorado indicate that this segment of continental crust was formed from a homogeneous and previously depleted source material in the upper mantle 1,800 Myr ago and contains no identifiable component of older crust. Subsequent magmatic events at 1,670, 1,400 and 1,000 Myr represent mainly intracrustal differentiation with small or no further additions to the crust from the mantle. These results imply that a major increase in the mass of the North American continent occurred over a narrow time interval 1,800 Myr ago. From the isotopic data an empirical model is constructed that may provide accurate crust-formation ages f or rocks of all ages. Preliminary results suggest that existing estimates of crustal age distributions may require substantial revision.
1,716 citations
TL;DR: Four ‘antigenic sites’ on the three-dimensional structure of the influenza haemagglutinin are identified and at least one amino acid substitution in each site seems to be required for the production of new epidemic strains between 1968 and 1975.
Abstract: Four 'antigenic sites' on the three-dimensional structure of the influenza haemagglutinin are identified. At least one amino acid substitution in each site seems to be required for the production of new epidemic strains between 1968 and 1975.
1,530 citations
TL;DR: If dietary β-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.
Abstract: 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.
1,483 citations
TL;DR: The data indicate that, as a rare event, the ALV provirus integrates adjacent to the c-myc gene and that transcription, initiating from a viral promoter, causes enhanced expression of c- myc, leading to neoplastic transformation.
Abstract: Analyses of DNA and RNA from avian leukosis virus (ALV)-induced lymphomas have provided strong evidence that, in most tumours, ALV induces neoplastic disease by activating the c-myc gene, the cellular counterpart of the transforming gene of MC29 virus. The data indicate that, as a rare event, the ALV provirus integrates adjacent to the c-myc gene and that transcription, initiating from a viral promoter, causes enhanced expression of c-myc, leading to neoplastic transformation.
1,448 citations
TL;DR: A continuous culture line of leukaemic T cells from a patient with ATL was established and this cell line was found to carry type C virus particles and ATL-associated antigens (ATLA) which specifically reacted with sera from all ATL patients and about 25% of healthy adults in the endemic area.
Abstract: A recent nationwide survey of the lymphocyte subpopulations of leukaemia and lymphoma in Japan has disclosed a high incidence of adult T-cell leukaemia (ATL)1. One of the striking features of this disease is the clustering of patients in the southwestern part of Japan1,2. We have established a continuous culture line of leukaemic T cells from a patient with ATL3,4. This cell line, MT-1, was found to carry type C virus particles and ATL-associated antigens (ATLA) which specifically reacted with sera from all ATL patients and about 25% of healthy adults in the endemic area5. We report here that by co-culture of ATL cells from a female patient and normal human cord leukocytes from a male infant, a T-cell line of cord leukocyte origin was established. Numerous type C virus particles as well as ATLA were detected in this cell line.
TL;DR: It is believed that P9A and P9B play an important part in the humoral immune responses described previously and that the P9 proteins represent a new class of antibacterial agents for which the name cecropins is proposed.
Abstract: Immune responses have been described for many different insect species. However, it is generally acknowledged that immune systems must therefore differ from those of vertebrates. An effective humoral immune response has been found in pupae of the cecropia moth, Hyalophora cecropia. The expression of this multicomponent system requires de novo synthesis of RNA and proteins and its broad antibacterial activity is due to at least three independent mechanisms, the most well known of which is the insect lysozyme. However, this enzyme is bactericidal for only a limited number of Gram-positive bacteria. WE recently purified and characterized P9A and P9B, which are two small, basic proteins with potent antibacterial activity against Escherichia coli and several other Gram-negative bacteria. We believe that P9A and P9B plays an important part in the humoral immune responses described previously and that the P9 proteins represent a new class of antibacterial agents for which we propose the name cecropins. We describe here the primary structures of cecropins A and B. We also show that cecropin A is specific for bacteria in contrast to melittin, the main lytic component in bee venom which lyses both bacteria and eukaryotic cells.
TL;DR: The main properties of a representative of this novel class of specific benzodiazepine antagonists are described, whose unique pharmacological activity is to prevent or abolish in a highly selective manner at the receptor level all the characteristic centrally mediated effects of active Benzodiazepines.
Abstract: Benzodiazepines produce most, if not all, of their numerous effects on the central nervous system (CNS) primarily by increasing the function of those chemical synapses that use gamma-amino butyric acid (GABA) as transmitter. This specific enhancing effect on GABAergic synaptic inhibition is initiated by the interaction of benzodiazepines with membrane proteins of certain central neurones, to which drugs of this chemical class bind with high affinity and specificity. The molecular processes triggered by the interaction of these drugs with central benzodiazepine receptors, and which result in facilitation of GABAergic transmission, are still incompletely understood. Theoretically, benzodiazepines could mimic the effect of hypothetical endogenous ligands for the benzodiazepine receptors, although there is no convincing evidence for their existence; in vitro studies indicate that benzodiazepines might compete with a modulatory peptide which is present in the supramolecular assembly formed by GABA receptor, chloride ionophore and benzodiazepine receptor and which reduces the affinity of the GABA receptor for its physiological ligand. The mechanisms of action of benzodiazepines at the molecular level are likely to be better understood following our recent discovery of benzodiazepine derivatives, whose unique pharmacological activity is to prevent or abolish in a highly selective manner at the receptor level all the characteristic centrally mediated effects of active benzodiazepines. Here, we describe the main properties of a representative of this novel class of specific benzodiazepine antagonists.
TL;DR: Clones of homozygous fish have been produced from individual homozygotes and associated genetic methods facilitate genetic analyses of this vertebrate.
Abstract: Homozygous diploid zebra fish have been produced on a large scale by the application of simple physical treatments. Clones of homozygous fish have been produced from individual homozygotes. These clones and associated genetic methods will facilitate genetic analyses of this vertebrate.
TL;DR: To investigate the sequences necessary for proper initiation of transcription of SV40 early genes, several deletion mutants are constructed in the promoter region of the TATA box region.
Abstract: To investigate the sequences necessary for proper initiation of transcription of SV40 early genes, we have constructed several deletion mutants in the promoter region. The TATA box region is apparently involved in fixing initiation precisely within a narrow area, but is dispensable for gene expression, while the sequences located more than 150 base pairs upstream are indispensable.
TL;DR: The authors suggest that these areas may be an extensional analogue to thin-skinned compressional orogens, a process which may even dominate active Basin and Range Province (BRP) tectonics.
Abstract: Cenozoic normal fault mosaics bounded beneath by a basal fault in the Basin and Range Province (BRP) have traditionally been described either in terms of large-scale surficial gravity sliding or by some form of in situ lower plate accommodation. I suggest here that these areas may be an extensional analogue to thin-skinned compressional orogens, a process which may even dominate active BRP tectonics.
TL;DR: Density is related approximately reciprocally to individual metabolic requirements, indicating that the energy used by the local population of a species in the community is independent of its body size.
Abstract: There seems to be an inverse relationship between the size of an animal species and its local abundance. Here I describe the interspecific seating of population density and body mass among mammalian primary consumers (herbivores, broadly defined). Density is related approximately reciprocally to individual metabolic requirements, indicating that the energy used by the local population of a species in the community is independent of its body size. I suggest that this is a more general rule of community structure.
TL;DR: A simple technique which loads Ca2+-selective chelators into the cytoplasm of intact cells in suspension and avoids the disadvantages of previous methods is described.
Abstract: Present methods for measuring or buffering intracellular free calcium concentrations are almost entirely limited to robust and well anchored cells which can tolerate insertion of ion-selective microelectrodes or microinjection of calcium indicators or buffers into one cell at a time. A very few types of small cells can be loaded with buffers or indicators during controlled lysis, but such procedures grossly perturb membrane integrity and soluble cytoplasmic constituents. Liposome fusion releases only trace quantities of the trapped solute into the cytoplasm and incorporates foreign lipid into the target cell membranes. I now describe a simple technique which loads Ca2+-selective chelators into the cytoplasm of intact cells in suspension and avoids the disadvantages of previous methods. The chelators are made temporarily membrane permeable by masking their four carboxylates with special esterifying groups which then hydrolyse inside the cells, regenerating and trapping the original chelators. The method is demonstrated on red cells, mast cells and lymphocytes.
TL;DR: The identification of three proteins which interact with the pheromone of the wild silk moth Antheraea polyphemus are reported: a phersomone-binding protein and a pherOMone-degrading esterase, both uniquely located in the pothole-sensitive sensilla; and a second ester enzyme common to all cuticular tissues except the sensilla.
Abstract: The antennae of male silk moths are extremely sensitive to the female sex pheromone such that a male moth can find a female up to 4.5 km away1. This remarkable sensitivity is due to both the morphological and biochemical design of these antennae. Along the branches of the plumose antennae are the sensilla trichodea, each consisting of a hollow cuticular hair containing two unbranched dendrites bathed in a fluid, the receptor lymph2,3. The dendrites and receptor lymph are isolated from the haemolymph by a barrier of epidermal cells which secreted the cuticular hair4–6. Pheromone molecules are thought to diffuse down 100 A-wide pore tubules through the cuticular wall and across the receptor lymph space to receptors located in the dendritic membrane6,7. To prevent the accumulation of residual stimulant and hence sensory adaptation, the pheromone molecules are subsequently inactivated in an apparent two-step process of rapid ‘early inactivation’ followed by much slower enzymatic degradation8,9. The biochemistry involved in this sequence of events is largely unknown. We report here the identification of three proteins which interact with the pheromone of the wild silk moth Antheraea polyphemus: a pheromone-binding protein and a pheromone-degrading esterase, both uniquely located in the pheromone-sensitive sensilla; and a second esterase common to all cuticular tissues except the sensilla.
TL;DR: The 8,332-nucleotide structure of the genome of Moloney murine leukaemia virus is determined and the coding frame for the gag gene is the same as that for pol, separated only by a single amber triplet.
Abstract: We have determined the 8,332-nucleotide structure of the genome of Moloney murine leukaemia virus. The coding frame for the gag gene is the same as that for pol, separated only by a single amber triplet. The pol gene encodes 132,000 daltons of protein, larger than the 70,000 daltons required for the reverse transcriptase. The env gene overlaps the pol gene.
TL;DR: It is reported that high-affinity saturable binding of 3H-baclof en and3H-G AB A to the GABAB site can be detected in fragments of crude synaptic membranes prepared from rat brain and that GABA and baclofen can compete for the same recognition site.
Abstract: The presence of a novel receptor for the neurotransmitter gamma-aminobutyric acid (GABA) on peripheral autonomic nerve terminals and in mammalian brain slices has been described recently. This receptor differs from the classical GABA site as it is unaffected by recognized GABA antagonists such as bicuculline and is not sensitive to the majority of accepted GABA-mimetics such as 3-aminopropanesulphonic acid (3-APS) or isoguvacine. We propose to designate the classical site as the GABA A and the novel site as the GABA B receptor. The beta-p-chlorophenyl derivative of GABA, baclofen, is stereospecifically active at the GABA B site whereas it is devoid of activity at the classical GABA A3 site. We now report that high-affinity saturable binding of 3H-baclofen and 3H-GABA to the GABA B site can be detected in fragments of crude synaptic membranes prepared from rat brain. The results support the concept of a novel GABA receptor within the mammalian brain and show that GABA and baclofen can compete for the same recognition site.
TL;DR: This book is very referred for you because it gives not only the experience but also lesson, that's not about who are reading this sexual differentiation of the brain book but about this book that will give wellness for all people from many societies.
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TL;DR: It is confirmed that the natural gait at any speed indeed entails the smallest possible energy expenditure, and rates of oxygen consumption as an indicator of rates of energy consumption are used.
Abstract: It seems reasonable that quadrupeds should change gait from a walk to a trot to a gallop in such a way as to minimize their energy consumption, as human beings are known1 to change from a walk to a run at a particular speed (2.4 m s−1) below which walking requires less energy than running and above which the opposite is true. Thus by changing gait, human beings keep the energy cost of locomotion to a minimum as their speed increases. One reason this relation holds is that in humans, metabolic rate increases curvilinearly with walking speed1. If metabolism were a curvilinear function of speed within each of the gaits used by quadrupeds, it would support the hypothesis that they also change gait to minimize energetic cost. There is an old controversy about whether metabolic rate increases linearly or curvilinearly in running humans1,2 but all previous reports have suggested that metabolic rate increases linearly with speed in quadrupeds. Extended gaits were an important experimental tool in the study of human gait changes; thus we have trained three small horses (110–170 kg) to walk, trot and gallop on a motorized treadmill, and to extend their gaits on command. We report here that, using measurements of rates of oxygen consumption as an indicator of rates of energy consumption, we have confirmed that the natural gait at any speed indeed entails the smallest possible energy expenditure.
TL;DR: The hypothesis that selection will favour the male that can deposit the largest number of sperm means that the volume of spermatogenic tissue and hence testis size is far greater in the chimpanzee than in the gorilla or orangutan, and the results support the hypothesis.
Abstract: It has long been known that primate species differ greatly in the weight of their testes relative to body weight1. Recently it has been suggested that among the three species of Pongidae (the great apes), the disparity in testes weights is associated with their different breeding systems2–4. Male gorillas and orangutans copulate infrequently, and when a female comes into oestrus she normally mates with only one male. However, in the chimpanzee, several males mate frequently with the oestrous females, so that each male has to deposit enough sperm to compete with the presence of sperm from other males. For the chimpanzee, therefore, we hypothesize that selection will favour the male that can deposit the largest number of sperm; thus the volume of spermatogenic tissue and hence testis size is far greater in the chimpanzee than in the gorilla or orangutan. If this is correct, it implies that primates in which more than one male mates with each oestrous female should have larger testes relative to their body weight than those with single-male breeding systems. We have tested this prediction across a wide range of primates, and the results support the hypothesis. The relative size of testes may, therefore, provide a valuable clue to the breeding system of a primate species.
TL;DR: It is shown here that stimulation of the D-2 receptor is followed by a reduction in cyclic AMP formation induced by V stimulation with D-1 agonists.
Abstract: Two types of dopamine receptor whose stimulation affects cellular cyclic AMP have now been identified. In tissues as different as insect ganglia and mammalian neostriatum, stimulation of the dopamine receptor called D-1 increases formation of cyclic AMP1–6, whereas stimulation of the second type of dopamine receptor (D-2)7–11, first identified in the rat pituitary gland, reduces cyclic AMP formation. Recently, a receptor with the pharmacological properties of the D-2 receptor has also been found12–14 in the rat neostriatum; we show here that stimulation of this receptor is followed by a reduction in cyclic AMP formation induced by V stimulation with D-1 agonists.
TL;DR: It is proposed that this morphogenetic rearrangement of extracellular matrices is the primary function of fibroblast traction and explains its excessive strength.
Abstract: To make visible the traction forces exerted by individual cells, we have previously developed a method of culturing them on thin distortable sheets of silicone rubber1. We have now used this method to compare the forces exerted by various differentiated cell types and have examined the effects of cellular traction on re-precipitated collagen matrices. We find that the strength of cellular traction differs greatly between cell types and this traction is paradoxically weakest in the most mobile and invasive cells (leukocytes and nerve growth cones). Untransformed fibroblasts exert forces very much larger than those actually needed for locomotion. This strong traction distorts collagen gels dramatically, creating patterns similar to tendons and organ capsules. We propose that this morphogenetic rearrangement of extracellular matrices is the primary function of fibroblast traction and explains its excessive strength.
TL;DR: The primary structure of the poliovirus genome has been determined and Twelve viral polypeptides have been mapped by amino acid sequence analysis and were found to be proteolytic cleavage products of the polyprotein, cleavages occurring predominantly at Gln-Gly pairs.
Abstract: The primary structure of the poliovirus genome has been determined. The RNA molecule is 7,433 nucleotides long, polyadenylated at the 3' terminus, and covalently linked to a small protein (VPg) at the 5' terminus. An open reading frame of 2,207 consecutive triplets spans over 89% of the nucleotide sequence and codes for the viral polyprotein NCVPOO. Twelve viral polypeptides have been mapped by amino acid sequence analysis and were found to be proteolytic cleavage products of the polyprotein, cleavages occurring predominantly at Gln-Gly pairs.
TL;DR: A further activity of IL-2 is reported, one previously attributed solely to interferon—the ability to augment the cytotoxic activity of natural killer cells.
Abstract: The lymphokine interleukin-2 (IL-2; also termed T-cell growth factor) causes the proliferation of activated T-cell clones1,2. Effector T-cell lines exhibiting suppressor, helper and cytotoxic activities have been established by growth of appropriately stimulated cells in IL-2-containing medium3,4. In addition, IL-2 has been shown to provide requisite T-cell ‘help’ in a number of in vitro immune response assays, including the generation of cytotoxic T cells from thymocyte (and nude spleen cell) cultures5 and the induction of erythrocyte-specific antibody in T cell-deficient populations6. We report here a further activity of IL-2, one previously attributed solely to interferon—the ability to augment the cytotoxic activity of natural killer (NK) cells. This conclusion was reached from the observation that preparations of IL-2, which lacked interferon, caused a rapid increase in NK cell activity. This ability to augment cytotoxity was removed from IL-2 preparations, not only by absorption with IL-2 receptor bearing cells, but also by precipitation with a monoclonal antibody directed against IL-2.
TL;DR: Evidence is presented that polymorphonuclear leukocytes infiltrate tissues in response to an inflammatory stimulus to remove invading microorganisms and cell debris and have another, more sophisticated role in that they are involved in the control of fluid efflux through the blood vessel wall which leads to tissue oedema.
Abstract: Polymorphonuclear leukocytes infiltrate tissues in response to an inflammatory stimulus to remove invading microorganisms and cell debris. We present evidence that these scavenging cells have another, more sophisticated role in that they are involved in the control of fluid efflux through the blood vessel wall which leads to tissue oedema.
TL;DR: DNAs obtained from human, rabbit and mouse bladder carcinomas lines, a lung carcinoma line and rat neuroblastoma and mouse glioma lines, are able to induce transformation of NIH3T3 cells on transfection.
Abstract: We have previously demonstrated that DNA of mouse fibroblasts transformed by 3-methylcholanthrene (3-MC) induced foci of transformed cells when applied to monolayer cultures of NIH3T3 cells, which indicates that at least a part of this phenotype is encoded in DNA sequences. However, our conclusions were confined to the effects of DNAs of 3-MC-transformed mouse fibroblasts on recipient NIH3T3 cells, also of mouse fibroblast origin. To elucidate this phenomenon further, we have prepared DNAs from a series of mouse and non-mouse tumour lines of non-fibroblastic origin and investigated whether tumour transforming genes can act across tissue and species barriers to transform NIH3T3 cells. We find that DNAs obtained from human, rabbit and mouse bladder carcinoma lines, a lung carcinoma line and rat neuroblastoma and mouse glioma lines, are able to induce transformation of NIH3T3 cells on transfection.