bluuebunny/crossref_metadata_2025 huggingface dataset:
Inescapable versus Escapable Shock Modulates Long-Term Potentiation in the Rat Hippocampus
Authors: Shors Tracey J. , Seib Thomas B. , Levine Seymour , Thompson Richard F.
Published: October 2006

A group of rats was trained to escape low-intensity shock in a shuttle-box test, while another group of yoked controls could not escape but was exposed to the same amount and regime of shock. After 1 week of training, long-term potentiation (LTP) was measured in vitro in hippocampal slices. Exposure to uncontrollable shock massively impaired LTP relative to exposure to the same amount and regime of controllable shock. These results provide evidence that controllability modulates plasticity at the cellular-neuronal level.
The Role of Cis-Acting Promoter Elements in Tissue-Specific Albumin Gene Expression
Authors: Maire Pascal , Wuarin Jérôme , Schibler Ueli
Published: October 2006

The mouse albumin gene promoter has six closely spaced binding sites for nuclear proteins that are located between the TATA motif and nucleotide position -170. In vitro transcription with liver or spleen nuclear extracts of templates containing either mutated or polymerized albumin promoter elements establishes a hierarchy of the different protein binding sites for tissue-specific albumin gene transcription. The HNF-1 and C/EBP binding sites strongly activate transcription in a tissue-specific manner. The NF-Y binding site has a lower activation potential and is less specific, being equally efficient in liver and spleen nuclear extracts. The remaining elements are relatively weak activator sites.
Neural Connections Between the Lateral Geniculate Nucleus and Visual Cortex in Vitro
Authors: Yamamoto Nobuhiko , Kurotani Tohru , Toyama Keisuke
Published: October 2006

Neural connections were established in cocultures of rat visual cortex (VC) and lateral geniculate nucleus (LGN), which were isolated in early infancy. Morphological and electrophysiological studies showed that the cortical laminar organization of afferent and efferent connections in the coculture preparations was similar to that in the adult VC. The results indicate the existence of intrinsic mechanisms in VC and LGN that guide the formation of synaptic connections with the appropriate targets.
Effects of Glucocorticoids and Norepinephrine on the Excitability in the Hippocampus
Authors: Joëls Marian , de Kloet E. Ronald
Published: October 2006

The CA1 pyramidal neurons in the hippocampus contain a high density of adrenal corticosteroid receptors. By intracellular recording, CA1 neurons in slices from adrenalectomized rats have been found to display a markedly reduced afterhyperpolarization (that is, the hyperpolarizing phase after a brief depolarizing current pulse) when compared with their sham controls. No differences were found for other tested membrane properties. Brief exposure of hippocampal slices from adrenalectomized rats to glucocorticoid agonists, 30 to 90 minutes before recording, greatly enhanced the afterhyperpolarization. In addition, glucocorticoids attenuated the norepinephrine-induced blockade of action potential accommodation in CA1 neurons. The findings indicate that glucocorticoids can reduce transmitter-evoked excitability in the hippocampus, presumably via a receptor-mediated genomic action.
Autoimmune Target in Heymann Nephritis Is a Glycoprotein with Homology to the LDL Receptor
Authors: Raychowdhury Raktima , Niles John L. , McCluskey Robert T. , Smith John A.
Published: October 2006

The pathogenesis of Heymann nephritis, a rat model of human membranous glomerulonephritis, depends on the interaction of autoantibodies with a renal glycoprotein (GP330) on glomerular podocytes. Partial complementary DNAs coding for GP330 were isolated and sequenced. The deduced amino acid sequence from 4.3 kilobases of complementary DNA contains the sequences identical to two peptides derived from the isolated glycoprotein. The deduced amino acid sequence of this protein contains regions with homology to the human low density lipoprotein (LDL) receptor, an indication that GP330 and the LDL receptor may be members of the same gene family. Autoantibodies from the kidneys of rats with Heymann nephritis reacted with a nonglycosylated segment of GP330 that contains cysteine-rich 40-amino acid repeats, which are also features of the LDL receptor. GP330 is also similar in some regions to the mouse epidermal growth factor precursor.
Interleukin-1 Costimulatory Activity on the Interleukin-2 Promoter Via AP-1
Authors: Muegge Kathrin , Williams Thomas M. , Kant Jeffrey , Karin Michael , Chiu Robert , Schmidt Albrecht , Siebenlist Ulrich , Young Howard A. , Durum Scott K.
Published: October 2006

Interleukin-1 (IL-1) is a major regulator of inflammation and immunity. IL-1 induces T lymphocyte growth by acting as a second signal (together with antigen) in enhancing the production of interleukin-2 (IL-2). An IL-1-responsive element in the promoter region of the human IL-2 gene was similar to the binding site for the transcription factor AP-1. IL-1 enhanced expression of c-
jun
messenger RNA, whereas the antigenic signal enhanced messenger RNA expression of c-
fos
. Thus, the two components of the AP-1 factor are independently regulated and the AP-1 factor may serve as a nuclear mediator for the many actions of IL-1 on cells.
Autocrine Stimulation of Intracellular PDGF Receptors in v-
sis
-Transformed Cells
Authors: Keating Mark T. , Williams Lewis T.
Published: October 2006

Autocrine activation of platelet-derived growth factor (PDGF) receptors is the mechanism of transformation by the v-
sis
oncogene. Since the addition of PDGF does not transform normal cells, autocrine mechanisms may involve unique pathways of receptor activation. In this study autocrine stimulation of the PDGF receptor was observed in v-
sis
-transformed normal rat kidney (NRK) cells. In contrast to receptor activation in normal cells, autocrine activation of PDGF receptors in v-
sis
-transformed cells occurred in intracellular compartments, disrupting receptor processing and diverting receptors and their precursors to a chloroquine-sensitive degradation pathway. These findings show that intracellular activation of receptors by autocrine mechanisms may play a role in cell transformation.
The DNA-Binding Properties of the Major Regulatory Protein α4 of Herpes Simplex Viruses
Authors: Michael Nancy , Spector David , Mavromara-Nazos Penelope , Kristie Thomas M. , Roizman Bernard
Published: October 2006

The transition from the expression of α, the first set of five herpes simplex virus genes expressed after infection, to β and γ genes, expressed later in infection, requires the participation of infected cell protein 4 (α4), the major viral regulatory protein. The α4 protein is present in complexes formed by proteins extracted from infected cells and viral DNA fragments derived from promoter domains. This report shows that the α4 protein forms specific complexes with DNA fragments derived from 5′ transcribed noncoding domains of late (γ2) genes whose expression requires viral DNA synthesis as well as functional α4 protein. Some of the DNA fragments to which α4 binds do not contain homologs of the previously reported DNA binding site consensus sequence, suggesting that α4 may recognize and interact with more than one type of DNA binding site. The α4 proteins can bind to DNA directly. A posttranslationally modified form of the α4 protein designated α4c differs from the α4a and α4b forms with respect to its affinity for DNA fragments differing in the nucleotide sequences of the binding sites.
Aggregation of Lysine-Containing Zeins into Protein Bodies in
Xenopus
Oocytes
Authors: Wallace John C. , Galili Gad , Kawata Evelynn E. , Cuellar Richard E. , Shotwell Mark A. , Larkins Brian A.
Published: October 2006

Zeins, the storage proteins of maize, are totally lacking in the essential amino acids lysine and tryptophan. Lysine codons and lysine- and tryptophan-encoding oligonucleotides were introduced at several positions into a 19-kilodalton zein complementary DNA by oligonucleotide-mediated mutagenesis. A 450-base pair open reading frame from a simian virus 40 (SV40) coat protein was also engineered into the zein coding region. Messenger RNAs for the modified zeins were synthesized in vitro with an SP6 RNA polymerase system and injected into
Xenopus laevis
oocytes. The modifications did not affect the translation, signal peptide cleavage, or stability of the zeins. The ability of the modified zeins to assemble into structures similar to maize protein bodies was assayed by two criteria: assembly into membrane-bound vesicles resistant to exogenously added protease, and ability to self-aggregate into dense structures. All of the modified zeins were membrane-bound; only the one containing a 17-kilodalton SV40 protein fragment was unable to aggregate. These findings suggest that it may be possible to create high-lysine corn by genetic engineering.
A Sequence in M13 Phage Detects Hypervariable Minisatellites in Human and Animal DNA
Authors: Vassart Gilbert , Georges Michel , Monsieur Rita , Brocas Huguette , Lequarre Anne Sophie , Christophe Daniel
Published: October 2006

The term "DNA fingerprint" has been used to describe the extensive restriction fragment length polymorphism associated with hypervariable minisatellites present in the human genome. Until now, it was necessary to hybridize Southern blots to specific probes cloned from human genomic DNA in order to obtain individual-specific restriction patterns. The present study describes the surprising finding that the insert-free, wild-type M13 bacteriophage detects hypervariable minisatellites in human and in animal DNA, provided no competitor DNA is used during hybridization. The effective sequence in M13 was traced to two clusters of 15-base pair repeats within the protein III gene of the bacteriophage. This unexpected use of M13 renders the DNA fingerprinting technology more readily available to molecular biology laboratories.
erb
B-2 Is a Potent Oncogene When Overexpressed in NIH/3T3 Cells
Authors: Di Fiore Pier Paolo , Pierce Jacalyn H. , Kraus Matthias H. , Segatto Oreste , King C. Richter , Aaronson Stuart A.
Published: October 2006

A wide variety of human tumors contain an amplified or overexpressed
erb
B-2 gene, which encodes a growth factor receptor-like protein. When
erb
B-2 complementary DNA was expressed in NIH/3T3 cells under the control of the SV40 promoter, the gene lacked transforming activity despite expression of detectable levels of the
erb
B-2 protein. A further five- to tenfold increase in its expression under influence of the long terminal repeat of Moloney murine leukemia virus was associated with activation of
erb
B-2 as a potent oncogene. The high levels of the
erb
B-2 product associated with malignant transformation of NIH/3T3 cells were observed in human mammary tumor cells that overexpressed this gene. These findings demonstrate a new mechanism for acquisition of oncogenic properties by genes encoding growth factor receptor-like proteins and provide a functional basis for the role of their overexpression in the development of human malignancies.
A Newly Characterized HLA DQ
β
Allele Associated with Pemphigus Vulgaris
Authors: Sinha Animesh A. , Brautbar Chaim , Szafer Fanny , Friedmann Adam , Tzfoni Eli , Todd John A. , Steinman Lawrence , McDevitt Hugh O.
Published: October 2006

The inheritance of particular alleles of major histocompatibility complex class II genes increases the risk for various human autoimmune diseases; however, only a small percentage of individuals having an allele associated with susceptibility develop disease. The identification of allelic variants more precisely correlated with disease susceptibility would greatly facilitate clinical screening and diagnosis. Oligonucleotide-primed gene amplification in vitro was used to determine the nucleotide sequence of a class II variant found almost exclusively in patients with the autoimmune skin disease pemphigus vulgaris. In addition to clinical implications, the disease-restricted distribution of this variant should provide insight into the molecular mechanisms underlying associations between diseases and HLA-class II genes.
Infection of HTLV-III/LAV in HTLV-I-Carrying Cells MT-2 and MT-4 and Application in a Plaque Assay
Authors: Harada Shinji , Koyanagi Yoshio , Yamamoto Naoki
Published: October 2006

The human T-cell lines MT-2 and MT-4 carry the human T-cell leukemia virus type I (HTLV-I). When MT-2 and MT-4 were infected with HTLV-III, the probable etiologic agent of the acquired immune deficiency syndrome (AIDS), rapid cytopathogenic effects and cytotoxicity were observed that made it possible to titrate the biologically active virus in a plaque-forming assay. The cytopathogenic effects were preceded by the rapid induction and increase of HTLV-III antigens as revealed by immunofluorescence and immunoprecipitation. Activities of HTLV-III were neutralized by the human antibodies against the virus when immunofluorescence and plaque assays were used. Essentially the same results were obtained with the lymphadenopathy-associated virus (LAV
1
).
Pathways of Protein Secretion in Eukaryotes
Authors: Kelly Regis B.
Published: October 2006

Protein secretion from cells can take several forms. Secretion is constitutive if proteins are secreted as fast as they are synthesized. In regulated secretion newly synthesized proteins destined for secretion are stored at high concentration in secretory vesicles until the cell receives an appropriate stimulus. When both constitutive and regulated protein secretion can take place in the same cell a mechanism must exist for sorting the correct secretory protein into the correct secretory vesicle. The secretory vesicle must then be delivered to the appropriate region of plasma membrane. Transfection of DNA encoding foreign secretory proteins into regulated secretory cells has provided insight into the specificity of sorting into secretory vesicles.
Functional Relation Between HTLV-II
x
and Adenovirus E1A Proteins in Transcriptional Activation
Authors: Chen Irvin S. Y. , Cann Alan J. , Shah Neil P. , Gaynor Richard B.
Published: October 2006

The mechanism of cellular transformation by the human T-cell leukemia viruses (HTLV) is thought to involve a novel gene known as the
x
gene. This gene is essential for HTLV replication and acts by enhancing transcription from the HTLV long terminal repeat. The HTLV
x
gene product may also cause aberrant transcription of normal cellular genes, resulting in transformation of the infected cells. Although there is no evidence as yet for such a mechanism, it was shown that the HTLV-II
x
gene product can activate transcription from adenovirus E1A-dependent early promoters and therefore has the potential to activate cellular genes. It was also shown that the adenovirus and herpes pseudorabies immediate early proteins activate expression from the HTLV-I and HTLV-II long terminal repeats, though at lower levels than with the
x
gene product. These findings indicate possible common mechanisms of action for transcription-regulatory genes of distinct viruses.
Genomic Heterogeneity of AIDS Retroviral Isolates from North America and Zaire
Authors: Benn Steven , Rutledge Rosamond , Folks Thomas , Gold Jonathan , Baker Louis , McCormick Joseph , Feorino Paul , Piot Peter , Quinn Thomas , Martin Malcolm
Published: October 2006

In an analysis of the genomic variation of AIDS retroviral isolates from patients living in New York, Alabama, and Zaire, restriction maps were constructed by using seven enzymes, each known to cleave the proviral DNA more than once, in conjunction with Southern blot analysis. The maps of LAV, HTLV-III, and ARV-2 as deduced from their published nucleotide sequences were included in this analysis. The results demonstrated that (i) several "signature" restriction sites were common to all isolates; (ii) with the exception of LAV and HTLV-III, the North American and European isolates were all different from one another and showed no geographical specificity; (iii) the African isolates as a group were more diverse than those from North America and Europe; and (iv) the genomic variability was concentrated within the
env
gene.
Corticotropin-Releasing Activity of Monokines
Authors: Woloski B. M. R. N. J. , Smith E. M. , Meyer W. J. , Fuller G. M. , Blalock J. E.
Published: October 2006

Hepatocyte-stimulating factor and interleukin-1 are proteins produced by monocytes in response to inflammatory challenge. Neither of these monokines had direct effects on steroid production by cultured adrenocortical cells. Both monokines stimulated pituitary cells (AtT-20) to release adrenocorticotropic hormone; interleukin-1 was equipotent with a combination of corticotropin-releasing factor and arginine vasopressin, and hepatocyte-stimulating factor was at least three times as effective. The synthetic glucocorticoid, dexamethasone, inhibited production of hepatocyte-stimulating factor by cultured monocytes. These results indicate an axis between monocytes and pituitary and adrenocortical cells which may play a role in regulating host defense.
Inhibition of Vasopressin Action by Atrial Natriuretic Factor
Authors: Dillingham Mark A. , Anderson Robert J.
Published: October 2006

Atrial natriuretic factor results in diuresis in animals and humans, perhaps because atrial natriuretic factor increases renal blood flow. The possibility that this diuresis is due to direct inhibition of renal tubular epithelial water transport was examined in rabbit collecting tubules perfused in vitro. Atriopeptin III inhibition of the hydraulic conductivity response to the hormone arginine vasopressin but not to either 3′5′-cyclic adenosine monophosphate or forskolin was found. These results suggest that atriopeptin III acts proximal to cyclic adenosine monophosphate formation to directly affect vasopressin-stimulated water transport in the mammalian nephron. They also suggest a potential role for inhibition by atrial natriuretic factor of the renal response to arginine vasopressin as a contributor to a diuretic state.
AIDS Retrovirus Induced Cytopathology: Giant Cell Formation and Involvement of CD4 antigen
Authors: Lifson Jeffrey D. , Reyes Gregory R. , McGrath Michael S. , Stein Barry S. , Engleman Edgar G.
Published: October 2006

The formation of multinucleated giant cells with progression to cell death is a characteristic manifestation of the cytopathology induced by the AIDS retrovirus in infected T lymphoid cells. The mechanism of giant cell formation was studied in the CD4 (T4/Leu 3) positive T cell lines JM (Jurkat) and VB and in variants of these lines that are negative for cell surface CD4 antigen. By means of a two-color fluorescent labeling technique, multinucleated giant cells in infected cultures were shown to form through cell fusion. Antibody to CD4 specifically inhibited fusion, and uninfected CD4 negative cells, in contrast to uninfected CD4 positive cells, did not undergo fusion with infected cells, suggesting a direct role for the CD4 antigen in the process of syncytium formation. These results suggest that, in vivo, cell fusion involving the CD4 molecule may represent a mechanism whereby uninfected cells can be incorporated into AIDS virus infected syncytia. Because the giant cells die soon after they are formed, this process may contribute to the depletion of helper/inducer T cells characteristically observed in AIDS.
Early Signals in the Mitogenic Response
Authors: Rozengurt Enrique
Published: October 2006

Polypeptide growth factors, regulatory peptides, and a variety of pharmacological agents acting alone or synergistically induce mitogenesis in cultured fibroblasts. The early signals in the membrane, cytosol, and nucleus promoted by these extracellular factors, together with their mitogenic effectiveness, are integrated in a unified hypothesis for the regulation of fibroblast growth.
The Immunoglobulin Octanucleotide: Independent Activity and Selective Interaction with Enhancers
Authors: Parslow Tristram G. , Jones Susan Dana , Bond Barbara , Yamamoto Keith R.
Published: October 2006

The thymidine kinase (
tk
) promoter of herpes simplex virus includes an octanucleotide sequence motif (ATTTGCAT) that is also an essential component of immunoglobulin kappa gene promoters. In the absence of an enhancer,
tk
promoter derivatives that contain this element support a higher rate of transcription than those that lack it. The action of the kappa enhancer augments that of the octanucleotide in B lymphoid cells; when both elements are present,
tk
promoter activity is increased by more than an order of magnitude. In contrast, the presence of the octanucleotide in this promoter markedly reduces its response to a nonimmunoglobulin enhancer. These results suggest that the octanucleotide may mediate a selective interaction among promoters and enhancers.
Limitation of Excessive Myelopoiesis by the Intrinsic Modulation of Macrophage-Derived Prostaglandin E
Authors: Kurland Jeffrey I. , Bockman Richard S. , Broxmeyer Hal E. , Moore Malcolm A. S.
Published: October 2006

The clonal proliferation of the committed granulocyte-macrophage stem cell is controlled by a balance between mutually opposing factors, colony stimulating factor and prostaglandin E, both of monocyte-macrophage derivation. Increases beyond a critical concentration of colony stimulating factor within the local milieu of the mononuclear phagocyte induces the coincident elaboration of prostaglandin E, a self-regulated response which serves to limit the unopposed humoral stimulation of myelopoiesis.
On the Origin of Bacterial Resistance to Penicillin: Comparison of a β-Lactamase and a Penicillin Target
Authors: Kelly J. A. , Dideberg O. , Charlier P. , Wery J. P. , Libert M. , Moews P. C. , Knox J. R , Duez C. , Fraipont Cl. , Joris B. , Dusart J. , Frère J. M. , Ghuysen J. M.
Published: October 2006

Structural data are now available for comparing a penicillin target enzyme, the D-alanyl-D-alanine-peptidase from
Streptomyces
R61, with a penicillin-hydrolyzing enzyme, the β-lactamase from
Bacillus licheniformis
749/C. Although the two enzymes have distinct catalytic properties and lack relatedness in their overall amino acid sequences except near the active-site serine, the significant similarity found by x-ray crystallography in the spatial arrangement of the elements of secondary structure provides strong support for earlier hypotheses that β-lactamases arose from penicillin-sensitive D-alanyl-D-alanine-peptidases involved in bacterial wall peptidoglycan metabolism.
Induction of Macrophage Tumoricidal Activity by Granulocyte-Macrophage Colony-Stimulating Factor
Authors: Grabstein Kenneth H. , Urdal David L. , Tushinski Robert J. , Mochizuki Diane Y. , Price Virginia L. , Cantrell Michael A. , Gillis Steven , Conlon Paul J.
Published: October 2006

Monocytes are a subpopulation of peripheral blood leukocytes, which when appropriately activated by the regulatory hormones of the immune system, are capable of becoming macrophages—potent effector cells for immune response to tumors and parasites. A complementary DNA for the T lymphocyte-derived lymphokine, granulocyte-macrophage colony-stimulating factor (GM-CSF), has been cloned, and recombinant GM-CSF protein has been expressed in yeast and purified to homogeneity. This purified human recombinant GM-CSF stimulated peripheral blood monocytes in vitro to become cytotoxic for the malignant melanoma cell line A375. Another T cell-derived lymphokine, γ-interferon (IFN-γ), also stimulated peripheral blood monocytes to become tumoricidal against this malignant cell line. When IFN-γ activates monocytes to become tumoricidal, additional stimulation by exogenously added lipopolysaccharide is required. No such exogenous signals were required for the activation of monocytes by GM-CSF.
A Physiological Role of Epidermal Growth Factor in Male Reproductive Function
Authors: Tsutsumi Osamu , Kurachi Hirohisa , Oka Takami
Published: October 2006

Epidermal growth factor (EGF) stimulates the proliferation of various mammalian cells in culture, but its physiological role is not well defined. In mature male mice, large amounts of EGF are produced in the submandibular gland; it is present in the circulation at approximately 5 nanograms of EGF per milliliter of plasma. Sialoadenectomy (removal of the submandibular glands) decreased the amount of circulating EGF to an undetectable level but did not affect the circulating levels of testosterone or follicle-stimulating hormone. The number of mature sperm in the epididymis decreased by as much as 55 percent; the number of spermatids in the testis decreased by 40 to 50 percent; and the number of spermatocytes increased by about 20 percent. Administration of EGF to sialoadenectomized mice restored both the sperm content of the epididymis and the number of spermatids in the testis to normal. Thus, EGF may play a role in male reproductive function by stimulating the meiotic phase of spermatogenesis.
Prenatal Tetrodotoxin Infusion Blocks Segregation of Retinogeniculate Afferents
Authors: Shatz Carla J. , Stryker Michael P.
Published: October 2006

In the adult mammalian visual system, ganglion cell axons from the two eyes are segregated from each other into separate layers within their principal target, the lateral geniculate nucleus. The involvement of spontaneously generated action potential activity in the process of segregation was investigated during the fetal period in which segregation normally occurs in the cat, between embryonic day 45 (E45) and birth (E65). Tetrodotoxin, which blocks the voltage-sensitive sodium channel, was used to prevent action potentials. Fetuses received continuous intracranial infusions of tetrodotoxin from osmotic minipumps implanted in utero on E42. After a 2-week infusion, intraocular injections of anterograde tracers revealed that tetrodotoxin prevented segregation. The contralateral projection filled the lateral geniculate nucleus uniformly, and the ipsilateral projection expanded to occupy most of what would normally be contralaterally innervated layer A. Thus, in the fetus, long before the onset of vision, spontaneous action potential activity is likely to be present in the visual system and to contribute to the segregation of the retinogeniculate pathway.
Screening λgt Recombinant Clones by Hybridization to Single Plaques in Situ
Authors: Benton W. David , Davis Ronald W.
Published: October 2006

A rapid, direct method for screening single plaques of λgt recombinant phage is described. The method allows at least 10
6
clones to be screened per day and simplifies physical containment of recombinants.
Prolactin-Like Immunoreactivity: Localization in Nerve Terminals of Rat Hypothalamus
Authors: Fuxe Kjell , Hökfelt Tomas , Eneroth Peter , Gustafsson Jan-Åke , Skett Paul
Published: October 2006

Antibodies to rat prolactin were used in immunohistochemical studies of the hypothalamus and preoptic area of the rat. Evidence was obtained that a protein immunochemically related to prolactin was stored in networks of nerve terminals of many hypothalamic areas such as the arcuate nucleus, the dorsomedial hypothalamic nucleus, and periventricular regions of the hypothalamus and preoptic area. The neuronal storage of a prolactin-like protein in the hypothalamus was unaffected by hypophysectomy.
Macrophage Tumor Killing: Influence of the Local Environment
Authors: Hibbs John B. , Taintor Read R. , Chapman Harold A. , Weinberg J. Brice
Published: October 2006

Tumor killing by activated macrophages is not a highly determined biologic event, but a relative capability influenced by the local environment. An intrinsic macrophage cytotoxic effector system is modulated by serum and other environmental factors that can either enhance or suppress tumor killing. Activated macrophages kill tumor cells only when a regulating threshold drops to a critically low level.
Local Embryonic Matrices Determine Region-Specific Phenotypes in Neural Crest Cells
Authors: Perris Roberto , von Boxberg Ysander , Löfberg Jan
Published: October 2006

Membrane microcarriers were used to determine the ability of regional extracellular matrices to direct neural crest cell differentiation in culture. Neural crest cells from the axolotl embryo responded to extracellular matrix material explanted from the subepidermal migratory pathway by dispersing and by differentiating into pigment cells. In contrast, matrix material from the presumptive site of dorsal root ganglia stimulated pronounced cell-cell association and neurotypic expression. Cell line segregation during ontogeny of the neural crest that leads to diversification into pigment cells of the skin or into elements of the peripheral nervous system appears to be controlled in part by local cell-matrix interactions.
Human Endothelial Cell Growth Factor: Cloning, Nucleotide Sequence, and Chromosome Localization
Authors: Jaye Michael , Howk Richard , Burgess Wilson , Ricca George A. , Chiu Ing-Ming , Ravera Mark W. , O'Brien Stephen J. , Modi William S. , Maciag Thomas , Drohan William N.
Published: October 2006

Several of the endothelial cell polypeptide mitogens that have been described probably play a role in blood vessel homeostasis. Two overlapping complementary DNA clones encoding human endothelial cell growth factor (ECGF) were isolated from a human brain stem complementary DNA library. Southern blot analysis suggested that there is a single copy of the ECGF gene and that it maps to human chromosome 5 at bands 5q31.3 to 33.2. A 4.8-kilobase messenger RNA was present in human brain stem messenger RNA. The complete amino acid sequence of human ECGF was deduced from the nucleic acid sequence of these clones; it encompasses all the well-characterized acidic endothelial cell polypeptide mitogens described by several laboratories. The ECGF-encoding open reading frame is flanked by translation stop codons and provides no signal peptide or internal hydrophobic domain for the secretion of ECGF. This property is shared by human interleukin-1, which is approximately 30 percent homologous to ECGF.
Participation of c-
myc
Protein in DNA Synthesis of Human Cells
Authors: Studzinski George P. , Brelvi Zamir S. , Feldman Susan C. , Watt Rosemary A.
Published: October 2006

The protein product of oncogene c-
myc
is believed to be important in regulation of the cell cycle. However, its direct role in DNA synthesis has not been explored. Experiments presented here show that the addition of affinity-purified antibodies against the human c-
myc
protein to nuclei isolated from several types of human cells reversibly inhibited DNA synthesis and DNA polymerase activity of these nuclei. This suggests that c-
myc
encodes a protein that is functionally involved in DNA synthesis.
Fertility in the United States
Authors: Westoff Charles F.
Published: October 2006

From the postwar high of 3.8 births per woman at the peak of the baby boom, the total fertility rate in the United States has fallen to 1.8, where it has remained unchanged for nearly a decade. This below-replacement level of fertility has, in recent decades, characterized most Western countries, some of which have shown declines to well below 1.5 births per woman. Were it not for the continued infusion of immigrants, the U.S. population, which already shows the aging characteristic of low fertility, would stop growing and begin to decline before the middle of the next century. The low fertility in the United States has been accomplished by a postponement of marriage and by the widespread use of contraception, with heavy reliance on surgical sterilization as a contraceptive method. Judging from the experience of other Western countries and from our own historical experience of two centuries of fertility decline interrupted only by the baby boom, as well as from the absence of social trends that would counteract those contributing to that decline, the prognosis is for a continued low level of fertility in the United States.
Japanese Quail Can Learn Phonetic Categories
Authors: Kluender Keith R. , Diehl Randy L. , Killeen Peter R.
Published: October 2006

Japanese quail (
Coturnix coturnix
) learned a category for syllable-initial [d] followed by a dozen different vowels. After learning to categorize syllables consisting of [d], [b], or [g] followed by four different vowels, quail correctly categorized syllables in which the same consonants preceded eight novel vowels. Acoustic analysis of the categorized syllables revealed no single feature or pattern of features that could support generalization, suggesting that the quail adopted a more complex mapping of stimuli into categories. These results challenge theories of speech sound classification that posit uniquely human capacities.
Protein, DNA, and Virus Crystallography with a Focused Imaging Proportional Counter
Authors: Durbin R. M. , Burns R. , Moulai J. , Metcalf P. , Freymann D. , Blum M. , Anderson J. E. , Harrison S. C. , Wiley D. C.
Published: October 2006

A set of programs has been developed for rapid collection of x-ray intensity data from protein and virus crystals with a commercially available two-dimensional focused geometry electronic detector. The detector is compact and portable, with unusually high spatial resolution comparable to that used in oscillation photography. It has allowed x-ray data collection on weakly diffracting crystals with large unit cells, as well as more conventional "diffractometer-quality" crystals. The quality of the data is compared with that from oscillation photography and automated diffractometry in the range of unit cells from 96.3 to 383.2 angstroms. Isomorphous and anomalous difference Pattersons, based on detector data, are shown for a variable surface glycoprotein mercury derivative and for a repressor-DNA bromine derivative, which has been solved at 7 angstroms with detector data only.
A Macrophage-Derived Factor Required by Plasmacytomas for Survival and Proliferation in Vitro
Authors: Nordan Richard P. , Potter Michael
Published: October 2006

Plasmacytoma (PCT) cell lines dependent for proliferation and survival on a factor elaborated by the murine macrophage cell line, P388D1, were established in vitro. Adherent peritoneal cells induced by pristane produced 50-fold greater amounts of this activity in vitro than did resident cells. The molecules responsible for plasmacytoma growth were distinct from a number of characterized factors including interleukin-1, -2, and -3, macrophage colony-stimulating factor, B-cell stimulatory factor-1, B-cell growth factor II, epidermal growth factor, transforming growth factor-β, and γ- and β-interferon, none of which were able to support the growth of the factor-dependent PCT cell lines. These results suggest that PCT growth factor may be a novel factor that has not been previously characterized and, further, that its production is associated with the pristane-induced, chronic peritoneal inflammatory response that precedes plasmacytoma formation.
Two Magnetoreception Pathways in a Migratory Salamander
Authors: Phillips John B.
Published: October 2006

Male eastern red-spotted newts (
Notophthalmus viridescens
) under controlled laboratory conditions exhibit unimodal magnetic compass orientation either in a trained compass direction or in the direction of their home pond. If the vertical component of the magnetic field is inverted, newts exhibiting the simple-compass response undergo a 180° reversal in orientation, whereas newts orienting in the home direction are unaffected by this treatment. These results indicate that newts use an axial compass mechanism for simple-compass orientation similar to that found in migrating birds. However, a distinct magnetoreception pathway with polar response properties is involved in homing and is possibly linked in some way to the navigational map.
Toxaphene, a Complex Mixture of Polychloroterpenes and a Major Insecticide, Is Mutagenic
Authors: Hooper N. Kim , Ames Bruce N. , Saleh Mahmoud Abbas , Casida John E.
Published: October 2006

Toxaphene, the most widely used chlorinated insecticide, is mutagenic in the
Salmonella
test without requiring liver homogenate for activity. This insecticide is a complex mixture (more than 177 polychloroterpenes) with carcinogenic activity in rodents. Some but not all of the mutagenic components are easily separated from the insecticidal ingredients.
Uroporphyrinogen Decarboxylase Structural Mutant (Gly281→Glu) in a Case of Porphyria
Authors: de Verneuil Hubert , Grandchamp Bernard , Beaumont Carole , Picat Christiane , Nordmann Yves
Published: October 2006

Uroporphyrinogen decarboxylase deficiency in man is responsible for familial porphyria cutanea tarda and hepatoerythropoietic porphyria. A recent study of a family with hepatoerythropoietic porphyria showed that the enzyme defect resulted from rapid degradation of the protein in vivo. Cloning and sequencing of a complementary DNA for the mutated gene revealed that the mutation was due to the replacement of a glycine residue by a glutamic acid residue at position 281. This base change leads to a protein that is very rapidly degraded in the presence of cell lysate. Characterization of the mutation will allow comparison of this defect in a homozygous patient with defects in other patients with familial porphyria cutanea tarda.
Regulation of Pro-Opiomelanocortin Gene Transcription in Individual Cell Nuclei
Authors: Fremeau Robert T. , Lundblad James R. , Pritchett Dolan B. , Wilcox Josiah N. , Roberts James L.
Published: October 2006

A nonrepetitive complementary RNA probe specific for an intervening sequence of the rat pro-opiomelanocortin (POMC) gene primary transcript was used to analyze the hormonal regulation of POMC gene transcription in individual cell nuclei in the rat pituitary by in situ hybridization. This probe recognized only full-length POMC heterogeneous nuclear RNA, as verified by Northern blots of pituitary RNA. When pituitary sections were hybridized with this
3
H-labeled POMC intron A probe, silver grains were predominantly localized over the nuclei of cells that expressed POMC in the anterior and intermediate lobes. Adrenalectomy increased both the average grain density over corticotroph nuclei and the number of cells in the anterior pituitary with significant numbers of silver grains over their nucleus. Dexamethasone administration to intact or adrenalectomized rats results in the rapid (within 30 minutes) disappearance of silver grains over the nuclei of corticotrophs in the anterior lobe, suggesting that POMC gene transcription had been inhibited. However, adrenalectomy or dexamethasone administration did not alter the silver grain density over nuclei of intermediate lobe melanotrophs. Thus, this in situ hybridization assay utilizing an intervening sequence-specific POMC probe can measure rapid physiological changes in POMC heterogeneous nuclear RNA in individual cell nuclei.
A Macrophage Factor Inhibits Adipocyte Gene Expression: An in Vitro Model of Cachexia
Authors: Torti Frank M. , Dieckmann Barbara , Beutler Bruce , Cerami Anthony , Ringold Gordon M.
Published: October 2006

Certain infections and malignancies in mammals cause the development of a condition known as cachexia in which the animal continues to lose weight, often while consuming an adequate diet. When macrophages are stimulated with an endotoxin, they produce a factor or factors, termed cachectin, that inhibits the activity of fat-producing (lipogenic) enzymes in cultured adipocytes. This effect may reflect one of the physiological bases for cachexia. In the present study, clones of complementary DNA from genes whose expression is increased during the differentiation of adipocytes were used to study the molecular basis of cachectin's actions. In the presence of cachectin, the expression of the corresponding genes was reversibly and specifically inhibited. Furthermore, when mature adipocytes were exposed to cachectin, the messenger RNA's of those genes diminished and rapidly approached the levels present before differentiation.
Acid Precipitation and Embryonic Mortality of Spotted Salamanders,
Ambystoma maculatum
Authors: Pough F. Harvey
Published: October 2006

Spotted salamanders breed in temporary pools formed in early spring by melted snow and rain. Many of these pools reflect the low pH of precipitation in the northeastern United States. Egg mortality is low (< 1 percent) in pools near neutrality, but high (> 60 percent) in pools more acid than pH 6. Developmental anomalies and the embryonic stage at which death occurs are the same in field situations as at corresponding pH's in laboratory experiments.
Sequence of the Alpha Subunit of Photoreceptor G Protein: Homologies Between Transducin,
ras
, and Elongation Factors
Authors: Lochrie Michael A. , Hurley James B. , Simon Melvin I.
Published: October 2006

A bovine retinal complementary DNA clone encoding the α subunit of transducin (T
α
) was isolated with the use of synthetic oligodeoxynucleotides as probes, and the complete nucleotide sequence of the insert was determined. The predicted protein sequence of 354 amino acids includes the known sequences of four tryptic peptides and sequences adjacent to the residues that undergo adenosine diphosphate ribosylation by cholera toxin and pertussis toxin. On the basis of homologies to other proteins, such as the elongation factors of protein synthesis and the
ras
oncogene proteins, regions are identified that are predicted to be acylated and involved in guanine nucleotide binding and hydrolysis. Amino acid sequence similarity between T
α
and
ras
is confined to these regions of the molecules.
Single-Carbon Chemistry of Acetogenic and Methanogenic Bacteria
Authors: Zeikus J. G. , Kerby R. , Krzycki J. A.
Published: October 2006

Methanogenic and acetogenic bacteria metabolize carbon monoxide, methanol, formate, hydrogen and carbon dioxide gases and, in the case of certain methanogens, acetate, by single-carbon (C
1
) biochemical mechanisms. Many of these reactions occur while the C
1
compounds are linked to pteridine derivatives and tetrapyrrole coenzymes, including corrinoids, which are used to generate, reduce, or carbonylate methyl groups. Several metalloenzymes, including a nickel-containing carbon monoxide dehydrogenase, are used in both catabolic and anabolic oxidoreductase reactions. We propose biochemical models for coupling carbon and electron flow to energy conservation during growth on C
1
compounds based on the carbon flow pathways inherent to acetogenic and methanogenic metabolism. Biological catalysts are therefore available which are comparable to those currently in use in the Monsanto process. The potentials and limitations of developing biotechnology based on these organisms or their enzymes and coenzymes are discussed.
Regulation of Extravascular Coagulation by Microvascular Permeability
Authors: Dvorak H. F. , Senger D. R. , Dvorak A. M. , Harvey V. S. , McDonagh J.
Published: October 2006

Extravascular coagulation is a prominent feature of such important pathological processes as cellular immunity and neoplasia and has been thought to result from procoagulants associated with the inflammatory or tumor cells peculiar to these entities. It was found that increased microvascular permeability alone is sufficient to induce equivalent extravascular coagulation in several normal tissues. The results indicate that saturating levels of procoagulant are present even in normal tissues and that microvascular permeability is a rate-limiting step in extravascular coagulation.
On the Nature of a Defect in Cells from Individuals with Ataxia-Telangiectasia
Authors: Cornforth Michael N. , Bedford Joel S.
Published: October 2006

The cells and tissues of patients with ataxia-telangiectasia (A-T), an inherited disease characterized by a high degree of proneness to cancer, are abnormally sensitive to ionizing radiation. Noncycling cultures of normal human and A-T fibroblasts were exposed to x-rays so that the breakage and rejoining of prematurely condensed chromosomes in the G
1
phase could be compared. After a dose of 6.0 grays, both cell types had the same initial frequency of breaks and the same rate for rejoining of the breaks, but the fraction of breaks that did not rejoin was five to six times greater for the A-T cells. The results also show that progression of cells into the S phase is not a prerequisite for the increased frequency of chromosome fragments that appear in mitosis after A-T cells are irradiated in the G
1
or G
0
phase.
Activated Proto-onc Genes: Sufficient or Necessary for Cancer?
Authors: Duesberg Peter H.
Published: October 2006

Proto-onc genes are normal cellular genes that are related to the transforming (onc) genes of retroviruses. Because of this relationship these genes are now widely believed to be potential cancer genes. In some tumors, proto-onc genes are mutated or expressed more than in normal cells. Under these conditions, proto-onc genes are hypothesized to be active cancer genes in one of two possible ways: The one gene-one cancer hypothesis suggests that one activated proto-onc gene is sufficient to cause cancer. The multigene-one cancer hypothesis suggests that an activated proto-onc gene is a necessary but not a sufficient cause of cancer. However, mutated or transcriptionally activated proto-onc genes are not consistently associated with the tumors in which they are occasionally found and do not transform primary cells. Further, no set of an activated proto-onc gene and a complementary cancer gene with transforming function has yet been isolated from a tumor. Thus, there is still no proof that activated proto-onc genes are sufficient or even necessary to cause cancer.
Adherent Bacterial Colonization in the Pathogenesis of Osteomyelitis
Authors: Gristina Anthony G. , Oga Masayoshi , Webb Lawrence X. , Hobgood Cherri D.
Published: October 2006

Direct scanning electron microscopy of material obtained during surgical debridement of osteomyelitic bone showed that the infecting bacteria grew in coherent microcolonies in an adherent biofilm so extensive it often obscured the infected bone surfaces. Transmission electron microscopy showed this biofilm to have a fibrous matrix, to contain some host cells, and to contain many bacteria around which matrix fibers were often concentrated. Many bacterial morphotypes were present in these biofilms, and each bacterium was surrounded by exopolysaccharide polymers, which are known to mediate formation of microcolonies and adhesion of bacteria to surfaces in natural ecosystems and in infections related to biomaterials. The adherent mode of growth may reduce the susceptibility of these organisms to host clearance mechanisms and antibiotic therapy and thus may be a fundamental factor in acute and chronic osteomyelitis.
Predisposition to Hookworm Infection in Humans
Authors: Schad G. A. , Anderson R. M.
Published: October 2006

Frequency distributions of parasitic helminths within human communities are invariably highly aggregated, the majority of worms occurring in relatively small fractions of the host populations. It has been suggested that the heavily infected individuals are predisposed to this state, not by chance, but by as yet undefined genetic, ecological, behavioral, or social factors. Analyses of individual post-treatment patterns of hookworm reinfection among 112 villagers in an endemic area of West Bengal provide quantitative evidence of predisposition to heavy infection. This observation has implications for the design of control programs based on chemotherapy because of the potential economic advantage of selective or targeted treatment as opposed to mass or blanket treatment.
Mechanism of Suppression in
Drosophila
: Control of Sepiapterin Synthase at the Purple Locus
Authors: Yim John J. , Grell E. H. , Jacobson K. Bruce
Published: October 2006

The amounts of sepiapterin and red pteridine eye pigments (drosopterins) in
Drosophila melanogaster
are known to be reduced in the purple mutant and restored to normal by a suppressor mutation. We show here that sepiapterin synthase activity is 30 percent of normal in
pr
and
pr
bw
, two naturally occurring alleles of purple, and is restored to nearly normal levels by the suppressor
su
(
s
)
2
. A heterozygote of two newly induced alleles of
pr
has even lower enzyme activity (< 10 percent). The sepiapterin synthase activity is proportional to the number of wild-type
pr
alleles in flies when one and two copies of the allele are present and is higher in three- than in two-dose flies. We hypothesize that the purple locus may be a structural gene for sepiapterin synthase in
Drosophila
.