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Showing papers by "Rockefeller University published in 1983"


Journal ArticleDOI
TL;DR: This article centers on the properties and dynamics of the endocytic vacuole membrane and stresses observations on cultured mouse macrophages with which the authors are most familier.
Abstract: The study of endocytosis has traditionally focused on the contents of endocytic vacuoles, i.e., extracellular fluid, dissolved solutes, and macromolecules or particles which specifically or nonspecifically bind to the plasma membrane (PM). Substances that are endocytosed include important nutrients, toxins, effector molecules (growth factors, hormones, antibodies), enzymes, and pathogens. This article centers on the properties and dynamics of the endocytic vacuole membrane. In many instances we will stress observations on cultured mouse macrophages with which we are most familier. We will emphasize four points: (a) Movement of vesicles is rapid such that endocytosed membrane and contents move from one cellular compartment to another in seconds to minutes. (b) Vesicular movement requires the interiorization and flow of large amounts of PM) (c) In many instances, internalized PM must recycle or return intact to the cell surface. (d) During recycling, contents and membrane components can be sorted from one another; e.g., endocytosed contents can accumulate within the cell while the container (membrane) can move into and out of the cell after one or more fusion events with other endocytic vacuoles, lysosomes (Ly), or Golgi apparatus. While it has been difficult to obtain direct evidence, the literature is replete with examples in which rapid membrane flow and recycling readily explains the data. Two of the more striking examples derive from studies of pinocytosis in cultured ceils. Fibroblasts, for instance, interiorize the equivalent of 50% of their surface area and 5-10% of their cell volume during each hour of pinocytic activity. Yet, the overall dimensions of the cells and the vacuolar system remain constant throughout hours, even days, of endocytic activity. Since it is unlikely that internalized PM is rapidly degraded, it was proposed that

1,413 citations


Journal ArticleDOI
04 Feb 1983-Science
TL;DR: The neuron-specific molecule is involved in early embryonic events but also mediates neurite fasciculation, neuromuscular interaction, and orderly layering of neural tissue and a failure of this process is closely correlated with connectional disorders in the staggerer mutant of the mouse.
Abstract: It has been proposed that cell-cell recognition occurs by means of local cell surface modulation of a small number of proteins rather than by expression of large numbers of different cell surface markers. Several different cell adhesion molecules (CAM's) have now been found in a number of vertebrate species in different tissues such as liver and striated muscle and even in a single complex structure such as the brain, where different molecules specific for neurons and glia have been identified. The neuron-specific molecule is involved in early embryonic events but also mediates neurite fasciculation, neuromuscular interaction, and orderly layering of neural tissue. It undergoes local surface modulation with loss of sialic acid during development. A failure of this process is closely correlated with connectional disorders in the staggerer mutant of the mouse. The accumulated data on this and other CAM's favor modulation theories rather than strict chemoaffinity theories of cell-cell recognition.

973 citations


Journal ArticleDOI
01 Dec 1983-Cell
TL;DR: Antibody treatment delayed the onset of pulmonary metastasis, indicating that plasminogen activator is required during early stages of the process.

660 citations


Journal ArticleDOI
01 Jan 1983-Nature
TL;DR: During extensive studies in which the immunocytochemical method for localizing LHRH neurones was optimized and made compatible with the autoradiographic method for detecting oestrogen-concentrating neurones, doubly-labelled cells were very rarely seen, suggesting that genomic regulatory effects of oestrogens which depend on nuclear retention are not exerted directly on most L HRH neurone, but rather must be mediated by another class of neurones.
Abstract: Oestrogen, acting in both the brain and pituitary, has a critical role in regulating the reproductive cycle in most mammals1,2. In the brain, oestrogen regulates the release of luteinizing hormone-releasing hormone (LHRH) partly through a mechanism that is blocked by inhibitors of DNA-dependent RNA synthesis3,4 or protein synthesis4. The distributions of oestrogen-concentrating neurones5 and of LHRH neurones6,7 overlap. The present study was undertaken to determine whether genomic effects of oestrogen mediated by nuclear oestradiol concentration include a direct effect on LHRH-containing neurones. During extensive studies in which the immunocytochemical method for localizing LHRH neurones was optimized and made compatible with the autoradiographic method for detecting oestrogen-concentrating neurones, doubly-labelled cells were very rarely seen. This suggests that genomic regulatory effects of oestrogen which depend on nuclear retention are not exerted directly on most LHRH neurones, but rather must be mediated by another class of neurones.

548 citations


Journal ArticleDOI
01 Mar 1983-Cell
TL;DR: The nucleotide sequences of all coding regions and a significant part of the flanking regions of the chicken c- src gene, which is a cellular homolog of the v-src gene of Rous sarcoma virus, are determined and it is suggested that the c-src sequence was captured by a virus through recombination at both sides of the c -src gene, and that the recombinations occurred at the level of proviral DNA.

481 citations


Journal ArticleDOI
TL;DR: The interneuron pools that project to the orofacial motoneurons provide one further link in understanding the brain‐stem substrates for integrating oral and ingestive behaviors.
Abstract: Projections to the trigeminal, facial, ambiguus, and hypoglossal motor nuclei were determined by using horseradish peroxidase histochemistry. Most of the afferent projections to these motor nuclei were from the brainstem reticular formation, frequently in areas adjacent to other synergetic motor nuclei. The reticular formation lateral to the hypoglossal nucleus and reticular structures surrounding the trigeminal motor nucleus projected to each of these other brainstem motor nuclei involved in oral-facial function. Afferent projections to these motor nuclei also were organized along the rostrocaudal axis. Within the reticular formation most of the afferent projections to the trigeminal motor nucleus originated rostral to the majority of neurons projecting to the hypoglossal and ambiguus nuclei, which in turn were rostral to the primary source of reticular afferents to the facial nucleus. In comparison, projections from the sensory trigeminal nuclei and nucleus of the solitary tract were sparse. The interneuron pools that project to the orofacial motoneurons provide one further link in understanding the brainstem substrates for integrating oral and ingestive behaviors.

466 citations


Journal ArticleDOI
13 Oct 1983-Nature
TL;DR: Protein phosphorylation represents an approach, sometimes the only approach available, to study the molecular basis for a wide variety of neurophysiological phenomena.
Abstract: Protein phosphorylation represents an approach, sometimes the only approach available, to study the molecular basis for a wide variety of neurophysiological phenomena. The injection of protein kinases or protein kinase inhibitors into neurones has provided direct evidence that activation of protein kinases has an obligatory role in the mechanisms by which numerous extracellular signals produce specific physiological responses in neurones. A diversity of substrate proteins for the kinases have already been found. In several instances, the identity and functional role of these substrate proteins have been established.

412 citations


Journal ArticleDOI
23 Sep 1983-Science
TL;DR: The results demonstrate that corticosteroid independent mechanisms participate in the suppression of lymphocyte function by stressors, indicating that the modulation of immunity by stress is complex and multidetermined.
Abstract: Stress-induced suppression of lymphocyte stimulation by phytohemagglutinin was demonstrated in Isolated lymphocytes and in cultures of whole blood from adrenalectomized rats. The results demonstrate that corticosteroid independent mechanisms participate in the suppression of lymphocyte function by stressors. Stress-induced lymphopenia, however, was found to be adrenal dependent, indicating that the modulation of immunity by stress is complex and multidetermined.

386 citations


Journal ArticleDOI
TL;DR: The observed preference for sweetened high-fat foods may have implications for the development of dietary-induced obesity in man and changes in hedonic responsiveness were monitored using a mathematical modelling technique known as the Response Surface Method.

380 citations


Journal ArticleDOI
18 Nov 1983-Science
TL;DR: The mechanism of stable complex formation and its relevance to transcriptional regulation were examined in light of the various factors and the promoter sequences recognized by these factors.
Abstract: Class III genes require multiple cellular factors for transcription by RNA polymerase III; these genes form stable transcription complexes, which in the case of Xenopus 5S genes are correlated with differential expression in vivo. The minimal number and identity of the factors required to form both stable and metastable complexes on three class III genes (encoding, respectively, 5S RNA, transfer RNA, and adenovirus VA RNA species) were determined. Stable complex formation requires one common factor, whose recognition site was analyzed, and either no additional factors (the VA gene), a second common factor (the transfer RNA gene), or a third gene-specific factor (the 5S gene). The mechanism of stable complex formation and its relevance to transcriptional regulation were examined in light of the various factors and the promoter sequences recognized by these factors.

369 citations


Journal ArticleDOI
TL;DR: Observations support the concept that there is an age-related loss of sensitivity of the brain and pituitary to the inhibitory effects of high circulating levels of corticosterone on ACTH release.

Journal ArticleDOI
TL;DR: Fast moving groups containing three or more adult humpback whales are found in the winter on Silver Bank in the West Indies, and off Hawaii, and the pattern of interactions strongly suggests that the escorts are males competing for access to a central female.
Abstract: Fast moving groups containing three or more adult humpback whales are found in the winter on Silver Bank in the West Indies, and off Hawaii. Many of these groups have a definite structure: a central Nuclear Animal, with or without a calf, is surrounded by escorts who compete, sometimes violently, for proximity to the Nuclear Animal. This competition involves fluke thrashes, the blowing of bubblestreams, and physical contact, some of which appears designed to hurt an opponent: bleeding wounds are seen on the competing escorts. Escorts sometimes leave these groups and start singing, and singers sometimes stop to join large groups. The pattern of interactions strongly suggests that the escorts are males competing for access to a central female. Off Hawaii singers respond to such groups at ranges of up to approximately 7.5 km. On Silver Bank, Principal Escorts maintained a position of closest proximity to the Nuclear Animal for an average of 7.5 hours before replacement.

Journal ArticleDOI
TL;DR: Hadronic elastic scattering, inclusive diffraction dissociation and total cross sections are reviewed in this article, with emphasis on phenomenological descriptions of experimental results, and a review of the results is given.

Journal ArticleDOI
18 Feb 1983-Science
TL;DR: The variety of morphological, chemical, and electrical effects of estrogens and progestins allow for a multiplicity in the cellular functions controlled by these hormones.
Abstract: Estrogens and progestins alter electrical and chemical features of nerve cells, particularly in hypothalamus. Temporally, these events follow nuclear receptor occupation by these steroids, although not all effects have been proved to depend on translocation of receptors to the nucleus. Narrowing studies to focus on particular medial hypothalamic cells has been useful for understanding some of the actions of these steroids in brain. The variety of morphological, chemical, and electrical effects allow for a multiplicity in the cellular functions controlled by these hormones.

Journal ArticleDOI
TL;DR: Elevated testosterone and high levels of aggression were unrelated to social status during the period of social stability, but were traits associated with dominant individuals during the unstable period.
Abstract: The relationships among social status and the cortisol and testosterone stress-response were studied in the non-natal male members of a troop of olive baboons (Papio anubis) before and during a period of social instability. The unstable period was characterized by dominance interactions that were more frequent, more inconsistent, and produced less linear hierarchies than during the stable period. These changes occurred predominantly among the high-ranking males. Such males engaged in coalitions and consortship harassments at a higher rate during the unstable period than during the stable period. Finally, high-ranking males had the highest rates of involvement in and initiation of escalated fighting during the unstable period, in contrast with the stable period. A number of endocrine correlates of instability emerged. During the stable period, high-ranking males (by reproductive criteria) showed an endocrine profile different from that of subordinates. They had the lowest basal cortisol titers, the largest and fastest increases in cortisol titer during stress, and had elevated testosterone titers during stress. None of these attributes was found in high-ranking males during the unstable period. Males during the unstable period had elevated basal cortisol titers, suppressed cortisol responsiveness to stress, and no longer showed elevated testosterone titers during stress. When psychological advantages associated with social status in a stable social environment were lost, endocrine efficiency previously associated with social status was apparently also lost. Further, high-ranking males, who were most aggressive exclusively during the unstable period, had the highest absolute titers of testosterone exclusively during the unstable period. Thus, elevated testosterone and high levels of aggression were unrelated to social status during the period of social stability, but were traits associated with dominant individuals during the unstable period.

Journal ArticleDOI
TL;DR: Modulation of beta adrenergic and 5HT2 receptors by ovarian hormones might be relevant to hormone-linked affective changes such as premenstrual tension and post-partum depression.

Journal ArticleDOI
01 Sep 1983-Cell
TL;DR: A rapid procedure was developed to disassemble SRP into native protein and RNA components and the proteins are shown to reassociate stoichiometrically with 7SL-RNA to form fully active 11S SRP.

Journal ArticleDOI
01 Oct 1983-Cell
TL;DR: The sulfhydryl reagent iodoacetamidofluorescein (IAF) was used to probe the structure of chromatin subunits in transcribed and nontranscribed regions of Physarum rDNA, finding that most of the extended rDNA chromatin contains all four core histones and other prominent proteins.

Journal ArticleDOI
01 Nov 1983-Cell
TL;DR: A plasmid containing the adenovirus E2 gene, a gene normally requiring E1A-mediated induction during viral infection, is expressed very poorly upon transfection into mouse L cells, but if the samePlasmid is transfected into 293 cells, or into L cells together with a plasmids containing the E 1A gene, the E 2 gene is expressed at higher levels.

Journal ArticleDOI
TL;DR: A full–length cDNA clone encoding the precursor to the small subunit of wheat ribulose–1,5–bisphosphate carboxylase is isolated and characterized and it is deduced that the precursor contains the mature small sub unit and an amino–terminal transit sequence.
Abstract: We have isolated and characterized a full–length cDNA clone encoding the precursor to the small subunit of wheat ribulose–1,5–bisphosphate carboxylase. From the nucleotide sequence, we deduce that the precursor contains the mature small subunit of 128 amino acid residues and an amino–terminal transit sequence of 47 amino acid residues. Southern blot analysis reveals that the small subunit precursor is encoded by a multigene family. One member of the family has been isolated. Nucleotide sequence and R–loop analyses show that it contains only one intron which separates the coding sequence of the transit peptide from that of the mature protein. This gene is expressed in vivo, as shown by mRNA hybridization to a specific probe from its 3′ non–coding region.

Journal ArticleDOI
01 Sep 1983-Cell
TL;DR: Most of the 17 mutations that were not associated with DNA insertions can be placed within coding sequences of the 37 kb transcription unit and are estimated to correspond to approximately 275 kb.

Journal ArticleDOI
TL;DR: It is suggested that binding involving N-CAM may be an important early step in synaptogenesis, and that rapid adhesion mediated by this molecule occurs between spinal cord membranes and muscle cells.
Abstract: Previous studies in this laboratory have described a cell surface glycoprotein, called neural cell adhesion molecule or N-CAM, that appears to be a ligand in the adhesion between neural membranes. N-CAM antigenic determinants were also shown to be present on embryonic muscle and an N-CAM-dependent adhesion was demonstrated between retinal cell membranes and muscle cells in short-term assays. The present studies indicate that these antigenic determinants are associated with the N-CAM polypeptide, and that rapid adhesion mediated by this molecule occurs between spinal cord membranes and muscle cells. Detailed examination of the effects of anti-(N-CAM) Fab' fragments in cultures of spinal cord with skeletal muscle showed that the Fab' fragments specifically block adhesion of spinal cord neurites and cells to myotubes. The Fab' did not affect binding of neurites to fibroblasts and collagen substrate, and did not alter myotube morphology. These results indicate that N-CAM adhesion is essential for the in vitro establishment of physical associations between nerve and muscle, and suggest that binding involving N-CAM may be an important early step in synaptogenesis.

Journal ArticleDOI
TL;DR: A simple method was devised for counting small numbers (10(4)-10(6) of adherent mononuclear phagocytes, including populations containing multinucleated giant cells, which often arise during cultivation of human blood monocytes.

Journal ArticleDOI
01 Jul 1983-Diabetes
TL;DR: Excessive nonenzymatic glycosylation of the main peripheral and central nervous system myelin components may contribute to the functional abnormalities of myelinated neurons associated with diabetes.
Abstract: The amount of nonenzymatic glycosylation present in normal and diabetic rat peripheral nerve myelin, whole brain, brain myelin, and individual myelin protein components was determined using NaB 3 H 4 reduction followed by either boronic acid affinity chromatography or SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Diabetic peripheral nerve myelin (PNS-M) showed a 5.2-fold increase over normal, indicating that myelin is the major peripheral nerve component undergoing excessive glycosylation in diabetes. SDS-PAGE of diabetic and normal PNS-M showed no differences in the pattern of protein bands or in the distribution of glycosylated adducts. However, in the diabetic, the amount of incorporated radioactivity was 3.74 times greater in the P0 protein and 2.8 times greater in the high-molecular-weight material that did not enter the gel. In whole brain, a 2.4-fold increase in the amount of nonenzymatic glycosylation was observed when diabetic was compared with normal, while diabetic brain myelin (CNS-M) was 3.8 times more glycosylated than normal brain myelin. SDS-PAGE of diabetic and normal CNS-M, like that of PNS-M, showed no differences in the pattern of protein bands or in the distribution of glycosylated adducts. The amount of incorporated radioactivity, however, was 3.18 times greater in the proteolipid region, 2.37 times greater for basic myelin protein, and 2.9 times greater for the high-molecular-weight proteins that did not enter the gel. This excessive nonenzymatic glycosylation of the main peripheral and central nervous system myelin components may contribute to the functional abnormalities of myelinated neurons associated with diabetes.

Journal ArticleDOI
TL;DR: Significant declines were seen in hippocampus and amygdala quantitatively comparable to the decline observed in nuclear binding in these loci, which suggests that the primary deficit leading to nuclear depletion may be the reduction of cytosolic receptor number, rather than other possible factors such as the reduction in receptor affinity or translocation of steroid-receptor complex.

Journal ArticleDOI
01 Dec 1983-Virology
TL;DR: The results suggest that the oligopeptides react with receptor sites on the cell membrane and inhibit membrane-fusing activity by competing with the F1 polypeptide for such sites.

Journal ArticleDOI
01 Sep 1983-Cell
TL;DR: In this paper, the authors constructed mutants of Rous sarcoma virus expressing p60 src that are underphosphorylated on serine or tyrosine, by linker insertion or insertion/deletion into cloned Rous sarsa virus DNA, and recovery of mutant virus by transfection of chicken embryo fibroblasts.

Journal ArticleDOI
TL;DR: Both albumin and IgG (anti-BSA) bound to nonenzymatically glycosylated collagen retained their ability to form immune complexes in situ with free antibody and antigen.
Abstract: The chronic tissue damage associated with long-term diabetes mellitus may arise in part from in situ immune complex formation by accumulated immunoglobulins and/or antigens bound to long-lived structural proteins that have undergone excessive nonenzymatic glycosylation. In this report, we have tested this hypothesis using nonenzymatically glycosylated collagen. Binding of both albumin and IgG averaged four times the amount bound to unmodified collagen. Both albumin and IgG (anti-BSA) bound to nonenzymatically glycosylated collagen retained their ability to form immune complexes in situ with free antibody and antigen.

Journal ArticleDOI
01 Dec 1983-Cell
TL;DR: It is found that both SRP displacement and binding of the elongation-arrested ribosome to the membrane can occur at 0 degrees C, by a mechanism that is independent of chain elongation.

Journal ArticleDOI
21 Oct 1983-Science
TL;DR: It is concluded that peripheral hormones modulate binding by serotonin 1 receptors, and the status of the serotonin receptor system may affect the reproductive capacity of an organism and may be related to sex-linked emotional disturbances in humans.
Abstract: Male and female rats exhibit sex differences in binding by serotonin 1 receptors in discrete areas of the brain, some of which have been implicated in the control of ovulation and of gonadotropin release. The sex-specific changes in binding, which occur in response to the same hormonal (estrogenic) stimulus, are due to changes in the number of binding sites. Castration alone also affects the number of binding sites in certain areas. The results lead to the conclusion that peripheral hormones modulate binding by serotonin 1 receptors. The status of the serotonin receptor system may affect the reproductive capacity of an organism and may be related to sex-linked emotional disturbances in humans.