bluuebunny/crossref_metadata_2025 huggingface dataset:
The SCID-hu Mouse: Murine Model for the Analysis of Human Hematolymphoid Differentiation and Function
Authors: McCune J. M. , Namikawa R. , Kaneshima H. , Shultz L. D. , Lieberman M. , Weissman I. L.
Published: October 2006

The study of human hematopoietic cells and the human immune system is hampered by the lack of a suitable experimental model. Experimental data are presented showing that human fetal liver hematopoietic cells, human fetal thymus, and human fetal lymph node support the differentiation of mature human T cells and B cells after engraftment into mice with genetically determined severe combined immunodeficiency. The resultant SCID-hu mice are found to have a transient wave of human CD4
+
and CD8
+
T cells and human IgG (immunoglobulin G) in the peripheral circulation. The functional status of the human immune system within this mouse model is not yet known.
Detection of Two Viral Genomes in Single Cells by Double-Label Hybridization in Situ and Color Microradioautography
Authors: Haase A. T. , Walker D. , Stowring L. , Ventura P. , Geballe A. , Blum H. , Brahic M. , Goldberg R. , O'Brien K.
Published: October 2006

Double labeling and color microradioautography were used in a new method of hybridization in situ to identify different genes in individual cells. The method is based on the unequal penetration of
3
H and
3
H into two layers of nuclear track emulsion separated by a thin barrier film. Hybridization of a
3
H-labeled probe specific for one kind of gene results in silver grains over cells in both layers of emulsion; a
3
H-labeled probe for a second gene provides grains only in the first layer of emulsion. Silver grains are converted to magenta-colored grains in the first layer and to cyan-colored grains in the second to facilitate enumeration of grains in each layer. This technique should be widely applicable in analyses of differential gene expression in single cells or in discrete populations of cells.
Hypothalamic Reward Mechanism: Two First-Stage Fiber Populations with a Cholinergic Component
Authors: Gratton Alain , Wise Roy A.
Published: October 2006

Refractory periods were estimated for fibers of the hypothalamic substrate of brain stimulation reward. Two nonoverlapping populations were evident: a homogeneous fast population and a more heterogeneous slow population. Cholinergic blockade eliminated the contribution of the fast but not the slow fibers, while dopaminergic blockade reduced responding without significantly influencing either directly activated fiber population. These data indicate that the hypothalamic reward substrate is more complex than has been widely appreciated; it contains two or more parallel subsystems, and one of these subsystems has a cholinergic link.
A Region of the
Herpesvirus saimiri
Genome Required for Oncogenicity
Authors: Desrosiers Ronald C. , Bakker Anke , Kamine James , Falk Lawrence A. , Hunt Ronald D. , King Norval W.
Published: October 2006

Herpesvirus saimiri
naturally infects squirrel monkeys (
Saimiri sciureus
) without producing signs of disease; infection of other New World primates, however, results in a rapidly progressing, malignant, T-cell lymphoma. Results described in this report identify a region of the viral genome that is required for oncogenicity in owl monkeys (
Aotus trivirgatus
); this region is not required for replication of the virus. This is believed to be the first such genomic region identified in a herpesvirus system.
Vaccinia Virus Recombinant Expressing Herpes Simplex Virus Type 1 Glycoprotein D Prevents Latent Herpes in Mice
Authors: Cremer Kenneth J. , Mackett Michael , Wohlenberg Charles , Notkins Abner Louis , Moss Bernard
Published: October 2006

In humans, herpes simplex virus causes a primary infection and then often a latent ganglionic infection that persists for life. Because these latent infections can recur periodically, vaccines are needed that can protect against both primary and latent herpes simplex infections. Infectious vaccinia virus recombinants that contain the herpes simplex virus type 1 (HSV-1) glycoprotein D gene under control of defined early or late vaccinia virus promoters were constructed. Tissue culture cells infected with these recombinant viruses synthesized a glycosylated protein that had the same mass (60,000 daltons) as the glycoprotein D produced by HSV-1. Immunization of mice with one of these recombinant viruses by intradermal, subcutaneous, or intraperitoneal routes resulted in the production of antibodies that neutralized HSV-1 and protected the mice against subsequent lethal challenge with HSV-1 or HSV-2. Immunization with the recombinant virus also protected the majority of the mice against the development of a latent HSV-1 infection of the trigeminal ganglia. This is the first demonstration that a genetically engineered vaccine can prevent the development of latency.
Retinal S Antigen Identified as the 48K Protein Regulating Light-Dependent Phosphodiesterase in Rods
Authors: Pfister C. , Chabre M. , Plouet J. , Tuyen V. V. , De Kozak Y. , Faure J. P. , Kühn H.
Published: October 2006

Retinal S antigen chromatographically purified from whole retina, induces experimental autoimmune uveoretinitis in laboratory animals. The 48K protein, a soluble protein found in rod outer segments, is purified through its specific binding to photoexcited rhodopsin and is involved in the quenching of light-induced guanosine 3′,5′-monophosphate-phosphodiesterase activity. Biochemical, immunological, functional, and pathological tests showed that retinal S antigen and the 48K protein are identical.
Immunogenicity of Synthetic Peptides from Circumsporozoite Protein of
Plasmodium falciparum
Authors: Ballou W. Ripley , Rothbard Jonathan , Wirtz Robert A. , Gordon Daniel M. , Williams Joseph S. , Gore Rufus W. , Schneider Imogene , Hollingdale Michael R. , Beaudoin Richard L. , Maloy W. Lee , Miller Louis H. , Hockmeyer Wayne T.
Published: October 2006

In a study of recombinant proteins that might be useful in developing a vaccine against malaria, synthetic peptides from the circumsporozoite (CS) protein of
Plasmodium falciparum
were found to be immunogenic for mice and rabbits. Antibody to peptides from the repeating region of the CS protein recognized native CS protein and blocked sporozoite invasion of human hepatoma cells in vitro. Antibodies to peptides from regions I and II had no biologic activity, although antibody to region I recognized processed CS protein by Western blot analysis. These data support the feasibility of developing a vaccine against the sporozoite stage of the malaria parasite by using synthetic peptides of the repeating region of the CS protein conjugated to a carrier protein.
Malignant Transformation of Erythroid Cells in Vivo by Introduction of a Nonreplicating Retrovirus Vector
Authors: Wolff Linda , Ruscetti Sandra
Published: October 2006

DNA from a replication-defective spleen focus-forming virus (SFFV) was reconstructed and transfected into ψ-2 cells containing a packaging-defective mutant of Moloney murine leukemia virus. Replication-incompetent retrovirus particles (helper virus-free containing genomes that express the transforming envelope gene of SFFV (gp52) transformed bone marrow cells in vitro and, after direct intravenous introduction of the vector, induced malignant erythroid disease in vivo. Disease induction was dependent on prior treatment of mice with phenylhydrazine, which probably increased the availability of erythroid target cells. Since there was no evidence of virus particle expression in mice with malignant disease, this study demonstrates the acute oncogenic potential of a limited number of erythroid cells expressing SFFV gp52. Direct inoculation of animals with nonreplicating retroviral vectors containing transforming genes may be useful in studying the oncogenic effects of such genes.
Constitutive and Conditional Suppression of Exogenous and Endogenous Genes by Anti-Sense RNA
Authors: Izant Jonathan G. , Weintraub Harold
Published: October 2006

Plasmid DNA directing transcription of the noncoding (anti-sense) DNA strand can specifically inhibit the expression of several test genes as well as normal, endogenous genes. The anti-sense plasmid constructions can be introduced into eukaryotic cells by transfection or microinjection and function in both transient and stable transformation assays. Anti-sense transcripts complementary to as little as 52 bases of 5′ untranslated target gene mRNA specifically suppress gene activity as well as, or more efficiently than, anti-sense transcripts directed against the protein coding domain alone. Conditional anti-sense inhibition is accomplished with the use of hormone-inducible promoter sequences. Suppression of endogenous actin gene activity by anti-sense RNA is detected as a decrease in growth rate and as a reduction in the number of actin microfilament cables. These observations suggest that anti-sense RNA may be generally useful for suppressing the expression of specific genes in vivo and may be a potential molecular alternative to classical genetic analysis.
Transposon Tagging to Detect a Latent Virus in
Myxococcus xanthus
Authors: Starich Todd , Cordes Paul , Zissler James
Published: October 2006

Transposon mutagenesis of the bacterium
Myxococcus xanthus
with the transposon Tn5 revealed a special class of bacterial mutants that transduced the transposon through culture supernatant fluids. Virus-like particles copurified with transducing activity. Transposon tagging for detecting these virus-like particles may be generally useful in isolating endogenous viral agents capable of transferring genetic information between cells.
Direct Evidence That Endogenous G
M1
Ganglioside Can Mediate Thymocyte Proliferation
Authors: Spiegel Sarah , Fishman Peter H. , Weber Richard J.
Published: October 2006

The B subunit of cholera toxin, which is multivalent and binds exclusively to a specific ganglioside, G
M1
, was mitogenic for rat thymocytes. When exposed to the B subunit, the cells proliferated, as measured by
3
H-labeled thymidine incorporation. Mitogenesis depended on the direct interaction of the B subunit with G
M1
on the surface of the cells. This demonstrates that endogenous plasma membrane gangliosides can mediate proliferation in lymphocytes.
Repression of the Immunoglobulin Heavy Chain Enhancer by the Adenovirus-2 E1A Products
Authors: Hen René , Borrelli Emiliana , Chambon P.
Published: October 2006

The products of the adenovirus-2 (Ad2) immortalizing oncogene E1A repress the activity of the SV40, polyoma virus and E1A enhancers. Evidence is presented that Ad2 infection of MPC11 plasmocytoma cells results in an inhibition of transcription of both the γ2b heavy chain (IgH) and the kappa light chain immunoglobulin genes. This inhibition is caused by the Ad2 E1A products. Furthermore, the Ad2 E1A products repress transcription activated by the immunoglobulin heavy chain enhancer in chimeric recombinants, which are either stably integrated in the genome of lymphoid cells or are present as episomes. The implications of negative regulation of cellular enhancers are discussed.
Gene Expression in Mice After High Efficiency Retroviral-Mediated Gene Transfer
Authors: Eglitis Martin A. , Kantoff Philip , Gilboa Eli , Anderson W. French
Published: October 2006

A retroviral expression vector (N2) containing the selectable gene, neo
R
, has been used to determine the optimal conditions for infecting murine hematopoietic progenitor cells at high efficiency. After infected bone marrow cells were introduced into lethally irradiated mice, the presence, stability, and expression of the vector DNA sequences were analyzed either in individual spleen foci 10 days later or in the blood, bone marrow, and spleens of mice 4 months later. When bone marrow cells were cultured in medium containing virus with titers of more than 10
6
colony-forming units per milliliter in the presence of purified murine interleukin-3, more than 85 percent of the resulting foci contained vector DNA. This proviral vector DNA was intact. Efficient expression of the neo
R
gene was demonstrated in most of the DNA-positive foci examined. The spleens of reconstituted animals (over a long term) contained intact "vector DNA" and the blood and bone marrow expressed the neo
R
gene in some animals. Thus, a retroviral vector can be used to introduce intact exogenous DNA sequences into hematopoietic stem cells with high efficiency and with substantial expression.
Occurrence of Peptide and Clavine Ergot Alkaloids in Tall Fescue Grass
Authors: Lyons Philip C. , Plattner Ronald D. , Bacon Charles W.
Published: October 2006

Evidence is presented that ergot alkaloids are ubiquitous in tall fescue pastures infected with the clavicipitaceous fungal endophyte
Sphacelia typhina
(or
Acremonium coenophialum
). Ergopeptide alkaloids, predominantly ergovaline, constituted 10 to 50 percent of the total ergot alkaloid concentration, which was as high as 14 milligrams per kilogram in sheaths and 1.5 milligrams per kilogram in blades. Ergot alkaloid concentrations were substantially increased by application of large amounts (10 millimoles per liter) of potassium nitrate or ammonium chloride to infected plants in the greenhouse. The results indicate that ergot alkaloids are probably responsible for the toxicity to cattle of this common pasture and lawn grass and that ergotism-like toxicoses may be caused by clavicipitaceous fungi other than
Claviceps
.
Biochemical Topology: Applications to DNA Recombination and Replication
Authors: Wasserman Steven A. , Cozzarelli Nicholas R.
Published: October 2006

Processes of DNA rearrangement such as recombination or replication frequently have as products different subsets of the limitless number of distinguishable catenanes or knots. The use of gel electrophoresis and electron microscopy for analysis of these topological isomers has made it possible to deduce physical and geometric features of DNA structure and reaction mechanisms that are otherwise experimentally inaccessible. Quantitative as well as qualitative characterization is possible for any pathway in which the fate of a circular DNA can be followed. The history, theory, and techniques are reviewed and illustrative examples from recent studies are presented.
Insulin-Stimulated Hydrolysis of a Novel Glycolipid Generates Modulators of cAMP Phosphodiesterase
Authors: Saltiel Alan R. , Fox Judith A. , Sherline Peter , Cuatrecasas Pedro
Published: October 2006

Insulin action may involve the intracellular generation of low molecular weight substances that modulate certain key enzymes. The production of two substances that regulate the activity of adenosine 3′,5′-monophosphate phosphodiesterase was evaluated in cultured myocytes by incorporation of radiolabeled precursors. Insulin caused the rapid hydrolysis of a chemically undefined membrane glycolipid, resulting in the production of two related complex carbohydrates as well as diacylglycerol. Both the glycolipid precursor and the aqueous products were monitored by labeling with radioactive inositol and glucosamine. Depletion of the labeled precursor and the appearance of labeled water-soluble products and diacylglycerol occurred within 30 seconds after hormone treatment and was followed by rapid resynthesis of the precursor. The aqueous products that were radioactively labeled appeared chromatographically and electrophoretically identical to phosphodiesterase modulating activities produced by insulin from the same cells. The purified radiolabeled and bioactive substances had similar chemical properties. Hydrolysis of the glycolipid precursor and subsequent generation of products could be reproduced by incubation of extracted lipids with a phosphatidylinositol-specific phospholipase C. These studies suggest that insulin stimulates an endogenous, selective phospholipase C activity that hydrolyzes a novel glycolipid, resulting in the generation of a complex carbohydrate-phosphate substance containing inositol and glucosamine that may mediate some of the actions of the hormone.
Brominating Oxidants Generated by Human Eosinophils
Authors: Weiss Stephen J. , Test Samuel T. , Eckmann Carel M. , Roos Dirk , Regiani Sandra
Published: October 2006

Eosinophils are white blood cells that in humans are found in association with helminthic infections and various inflammatory disease processes. These cells contain a unique lysosomal peroxidase that oxidizes halides to generate highly reactive and toxic hypohalous acids. Although chloride is found in vivo at concentrations at least 1000-fold greater than those of other halides, human eosinophils did not preferentially oxidize chloride under physiologic conditions. Instead, eosinophils used bromide, a halide with a hitherto unknown function in humans, to generate a halogenating oxidant with characteristics similar, if not identical, to those of hypobromous acid. These results indicate that physiological concentrations of bromide arm human eosinophils with the ability to generate and release an unusual oxidant capable of destroying a wide range of prokaryotic and eukaryotic targets.
Synchronized Rearrangement of T-Cell γ and β Chain Genes in Fetal Thymocyte Development
Authors: Born Willi , Rathbun Gary , Tucker Philip , Marrack Philippa , Kappler John
Published: October 2006

Kinetics of mouse T-cell γ gene rearrangements in ontogeny were determined as an approach to understanding the possible role of these genes in the development of fetal thymocytes. Two of these genes (Cγ1 and Cγ2) rearranged rapidly during days 14 to 17 of the gestational period in BALB/c mice. Moreover, these rearrangements seemed to be tightly synchronized with rearrangements of T-cell receptor β chain genes in the same cells. It is suggested that the early transcriptional activity of γ genes, which precedes that of β chain genes, may not reflect the functional activation of these genes. Nevertheless, productive and therefore potentially functional γ gene rearrangements precede surface expression of T-cell receptors in the thymus by 2 to 3 days, which is compatible with a role for γ gene products in thymocyte development prior to antigen-specific stages.
Bilirubin Is an Antioxidant of Possible Physiological Importance
Authors: Stocker Roland , Yamamoto Yorihiro , McDonagh Antony F. , Glazer Alexander N. , Ames Bruce N.
Published: October 2006

Bilirubin, the end product of heme catabolism in mammals, is generally regarded as a potentially cytotoxic, lipid-soluble waste product that needs to be excreted. However, it is shown here that bilirubin, at micromolar concentrations in vitro, efficiently scavenges peroxyl radicals generated chemically in either homogeneous solution or multilamellar liposomes. The antioxidant activity of bilirubin increases as the experimental concentration of oxygen is decreased from 20% (that of normal air) to 2% (physiologically relevant concentration). Furthermore, under 2% oxygen, in liposomes, bilirubin suppresses the oxidation more than α-tocopherol, which is regarded as the best antioxidant of lipid peroxidation. The data support the idea of a "beneficial" role for bilirubin as a physiological, chain-breaking antioxidant.
A New Probe for the Diagnosis of Myotonic Muscular Dystrophy
Authors: Bartlett R. J. , Pericak-Vance M. A. , Yamaoka L. , Gilbert J. , Herbstreith M. , Hung W.-Y. , Lee J. E. , Mohandas T. , Bruns G. , Laberge C. , Thibault M.-C. , Ross D. , Roses A. D.
Published: October 2006

Myotonic muscular dystrophy (DM) is the most common muscular dystrophy, affecting adults as well as children. It is inherited as an autosomal dominant trait and is characterized by variable expressivity and late age-of-onset. Linkage studies have established the locus on chromosome 19. In order to identify tightly linked probes for diagnosis as well as to define in detail the DM gene region, chromosome 19 libraries were constructed and screened for restriction fragment length polymorphisms tightly linked to DM. A genomic clone, LDR152 (D19S19), was isolated that is tightly linked to DM; recombination fraction = 0.0 (95% confidence limits 0.0-0.03); lod score, 15.4.
Cellular Mechanisms of Epilepsy: A Status Report
Authors: Dichter Marc A. , Ayala G. F.
Published: October 2006

The cellular phenomena underlying focal epilepsy are currently understood in the context of contemporary concepts of cellular and synaptic function. Interictal discharges appear to be due to a combination of synaptic events and intrinsic currents, the exact proportion of which in any given neuron may vary according to the anatomic and functional substrate involved in the epileptic discharge and the epileptogenic agent used in a given model. The transition to seizure appears to be due to simultaneous increments in excitatory influences and decrements in inhibitory processes—both related to frequency-dependent neuronal events. A variety of specific hypotheses have been proposed to account for the increased excitability that occurs during epileptiform activity. Although each of the proposed mechanisms is likely to contribute significantly to the epileptic process, no single hypothesis provides an exclusive unifying framework within which all kinds of focal epilepsy can be understood. The spread of epileptic activity throughout the brain, the development of primary generalized epilepsy, the existence of "gating" mechanisms in specific anatomic locations, and the extrapolation of hypotheses derived from simple models of focal epilepsy to explain more complex forms of human epilepsy, all are not yet fully understood.
Functional Analysis of a Complementary DNA for the 50-Kilodalton Subunit of Calmodulin Kinase II
Authors: Hanley Rochelle M. , Means Anthony R. , Ono Tomio , Kemp Bruce E. , Burgin Karl E. , Waxham Neal , Kelly Paul T.
Published: October 2006

The calcium-calmodulin-dependent protein kinase II is a major component of brain synaptic junctions and has been proposed to play a variety of important roles in brain function. A complementary DNA representing a portion of the smaller 50-kilodalton subunit of the rat brain enzyme has been cloned and sequenced. The calmodulin-binding region has been identified and a synthetic analog prepared that binds calmodulin with high affinity in the presence of calcium. Like the 50-kilodalton kinase polypeptide, the concentration of the messenger RNA varies both neuroanatomically and during postnatal development of the brain. The broad tissue and species cross-reactivity of the complementary DNA suggests that the 50-kilodalton subunit found in rat brain is evolutionarily conserved and is the product of a single gene.
Reversal of Chloroquine Resistance in Malaria Parasite
Plasmodium falciparum
by Desipramine
Authors: Bitonti Alan J. , Sjoerdsma Albert , McCann Peter P , Kyle Dennis E. , Oduola A. M. J. , Rossan Richard N. , Milhous Wilbur K. , Davidson David E.
Published: October 2006

Desipramine and several other tricyclic antidepressant drugs reverse chloroquine resistance in
Plasmodium falciparum
in vitro at concentrations observed in the plasma of human patients treated for depression. Reversal of resistance is associated with increased chloroquine accumulation in the parasite, probably because of inhibition of a putative chloroquine efflux pump. When owl monkeys (
Aotus lemurinus lemurinus
) infected with chloroquine-resistant
Plasmodium falciparum
were treated with chloroquine plus desipramine, their parasitemias were rapidly suppressed. Desipramine was found to be one of the most effective compounds yet described for the reversal of chloroquine resistance both in vitro and in vivo.
The Intrinsic Electrophysiological Properties of Mammalian Neurons: Insights into Central Nervous System Function
Authors: Llinás Rodolfo R.
Published: October 2006

This article reviews the electroresponsive properties of single neurons in the mammalian central nervous system (CNS). In some of these cells the ionic conductances responsible for their excitability also endow them with autorhythmic electrical oscillatory properties. Chemical or electrical synaptic contacts between these neurons often result in network oscillations. In such networks, autorhythmic neurons may act as true oscillators (as pacemakers) or as resonators (responding preferentially to certain firing frequencies). Oscillations and resonance in the CNS are proposed to have diverse functional roles, such as (i) determining global functional states (for example, sleep-wakefulness or attention), (ii) timing in motor coordination, and (iii) specifying connectivity during development. Also, oscillation, especially in the thalamo-cortical circuits, may be related to certain neurological and psychiatric disorders. This review proposes that the autorhythmic electrical properties of central neurons and their connectivity form the basis for an intrinsic functional coordinate system that provides internal context to sensory input.
Thyrotropin-Releasing Hormone Precursor: Characterization in Rat Brain
Authors: Lechan Ronald M. , Wu Ping , Jackson Ivor M. D. , Wolf Hugh , Cooperman Sharon , Mandel Gail , Goodman Richard H.
Published: October 2006

To characterize the precursor of mammalian thyrotropin-releasing hormone (TRH), a rat hypothalamic λgt11 library was screened with an antiserum directed against a synthetic peptide representing a portion of the rat TRH prohormone. The nucleotide sequence of the immunopositive complementary DNA encoded a protein with a molecular weight of 29,247. This protein contained five copies of the sequence Gln-His-Pro-Gly flanked by paired basic amino acids and could therefore generate five TRH molecules. In addition, potential cleavage sites in the TRH precursor could produce other non-TRH peptides, which may be secreted. In situ hybridization to rat brain sections demonstrated that the pre-proTRH complementary DNA detected neurons concentrated in the parvocellular division of the paraventricular nucleus, the same location as cells detected by immunohistochemistry. These findings indicate that mammalian TRH arises by posttranslational processing of a larger precursor protein. The ability of the TRH prohormone to generate multiple copies of the bioactive peptide may be an important mechanism in the amplification of hormone production.
Separation of DNA Binding from the Transcription-Activating Function of a Eukaryotic Regulatory Protein
Authors: Keegan Liam , Gill Grace , Ptashne Mark
Published: October 2006

The yeast GAL4 protein (881 amino acids) binds to specific DNA sites upstream of target genes and activates transcription. Derivatives of this protein bearing as few as 74 amino terminal residues bind to these sites but fail to activate transcription. When appropriately positioned in front of a gene these derivatives act as repressors. These and related findings support the idea that GAL4 activates transcription by touching other DNA-bound proteins.
Interspecific Genetic Control of Courtship Song Production and Reception in
Drosophila
Authors: Kyriacou C. P. , Hall Jeffrey C.
Published: October 2006

The genetic control of courtship song differences between
Drosophila melanogaster
and
Drosophila simulans
males was investigated by producing hybrids from reciprocal crosses. The song rhythm difference between the parental species appears to be due to sex-linked genes, whereas the basic interpulse-interval difference is autosomally inherited. Hybrid females show selective preferences for artificially generated songs carrying intermediate "hybrid" characteristics.
Abnormal Proteins Serve as Eukaryotic Stress Signals and Trigger the Activation of Heat Shock Genes
Authors: Ananthan Jayakumar , Goldberg Alfred L. , Voellmy Richard
Published: October 2006

Heat shock protein (hsp) genes, a group of ubiquitous genes, are activated by various metabolic stresses. The suggestion that denaturation of intracellular proteins may be produced by the metabolic stresses and then signal the activation of the hsp genes was examined by co-injection of purified proteins and hsp genes into frog oocytes. Activation of hsp genes was observed if the proteins were denatured prior to injection but not if they were introduced in their native form. Furthermore, the activation of hsp genes by abnormal proteins and by heat shock appears to occur by a common mechanism. A model for the transcriptional regulation of the genes is based on competition for degradation between abnormal intracellular proteins and a labile regulatory factor.
Mechanisms of Memory
Authors: Squire Larry R.
Published: October 2006

Recent studies of animals with complex nervous systems, including humans and other primates, have improved our understanding of how the brain accomplishes learning and memory. Major themes of recent work include the locus of memory storage, the taxonomy of memory, the distinction between declarative and procedural knowledge, and the question of how memory changes with time, that is, the concepts of forgetting and consolidation. An important recent advance is the development of an animal model of human amnesia in the monkey. The animal model, together with newly available neuropathological information from a well-studied human patient, has permitted the identification of brain structures and connections involved in memory functions.
Upstream Operators Enhance Repression of the
lac
Promoter
Authors: Mossing Michael C. , Record M. Thomas
Published: October 2006

To study regulation of transcription by distant elements, a wild-type
lac
operator was inserted upstream of a promoter-constitutive operator control region. The upstream operator is shown to aid in repression of transcription from the mutant control region. The effectiveness of the upstream operator as a function of its distance from the mutant control region parallels the length dependence observed for DNA cyclization. A quantitative model is proposed for action-at-a-distance of DNA control sites in which protein-protein and protein-DNA interactions are mediated by DNA looping. In this model, the effective concentrations of interacting proteins that are tethered by DNA are determined by the length of the intervening DNA and by its inherent bending and torsional stiffness. This model makes a number of predictions for both eukaryotic and prokaryotic control sequences located far from their sites of action.
Eye-Specific Termination Bands in Tecta of Three-Eyed Frogs
Authors: Constantine-Paton Martha , Law Margaret I.
Published: October 2006

An extra eye primordium was implanted into the forebrain region of embryonic
Rana pipiens
. During development both normal and supernumerary optic tracts terminated within a single, previously uninnervated tectal lobe. Autoradiographic tracing of either the normal or supernumerary eye's projection revealed distinct, eye-specific bands of radioactivity running rostrocaudally through the dually innervated tectum. Interactions among axons of retinal ganglion cells, possibly mediated through tectal neurons, must be invoked to explain this stereotyped disruption of the normally continuous retinal termination pattern.
Common Mechanism of Chromosome Inversion in B- and T-Cell Tumors: Relevance to Lymphoid Development
Authors: Denny Christopher T. , Hollis Gregory F. , Hecht Frederick , Morgan Rodman , Link Michael P. , Smith Stephen D. , Kirsch Ilan R.
Published: October 2006

An inversion of chromosome 14 present in the tumor cells of a patient with childhood acute lymphoblastic leukemia of B-cell lineage was shown to be the result of a site-specific recombination event between an immunoglobulin heavy-chain variable gene and the joining segment of a T-cell receptor α chain. This rearrangement resulted in the formation of a hybrid gene, part immunoglobulin and part T-cell receptor. Furthermore, this hybrid gene was transcribed into messenger RNA with a completely open reading frame. Thus, two loci felt to be normally activated at distinct and disparate points in lymphocyte development were unified and expressed in this tumor.
Serotonin Shifts the Phase of the Circadian Rhythm from the
Aplysia
Eye
Authors: Corrent G. , McAdoo D. J. , Eskin A.
Published: October 2006

A putative neurotransmitter, serotonin, may be used to transmit temporal information in the eye of
Aplysia
, because it can shift the phase of the circadian rhythm of spontaneous optic nerve impulses from the eye and the eye contains a significant quantity of serotonin. Serotonin acts either directly on the cell, or cells, containing the circadian pacemaker or on cells electronically coupled to the pacemaker cells.
Dorsal
, an Embryonic Polarity Gene in
Drosophila
, Is Homologous to the Vertebrate Proto-Oncogene, c-
rel
Authors: Steward Ruth
Published: October 2006

The
Drosophila
gene,
dorsal
, is a maternal effect locus that is essential for the establishment of dorsal-ventral polarity in the developing embryo. The
dorsal
protein was predicted from the complementary DNA sequence; it is almost 50 percent identical, over an extensive region, to the protein encoded by the avian oncogene v-
rel
, its cellular homolog, c-
rel
, and a human c-
rel
fragment. The oncogene v-
rel
is highly oncogenic in avian lymphoid, spleen, and bone marrow cells.
Early Restriction of the Human Antibody Repertoire
Authors: Schroeder Harry W. , Hillson Jan L. , Perlmutter Roger M.
Published: October 2006

Diversification of the antibody repertoire in mammals results from a series of apparently random somatically propagated gene rearrangement and mutational events. Nevertheless, it is well known that the adult repertoire of antibody specificities is acquired in a developmentally programmed fashion. As previously shown, rearrangement of the gene segments encoding the heavy-chain variable regions (V
H
) of mouse antibodies is also developmentally ordered: the number of V
H
gene segments rearranged in B lymphocytes of fetal mice is small but increases progressively after birth. In this report, human fetal B-lineage cells were also shown to rearrange a highly restricted set of V
H
gene segments. In a sample of heavy-chain transcripts from a 130-day human fetus the most frequently expressed human V
H
element proved to be closely related to the V
H
element most frequently expressed in murine fetal B-lineage cells. These observations are important in understanding the development of immunocompetence.
Distinct Cloned Class II MHC DNA Binding Proteins Recognize the X Box Transcription Element
Authors: Liou Hsiou-Chi , Boothby Mark R. , Glimcher Laurie H.
Published: October 2006

The class II (Ia) major histocompatibility complex (MHC) antigens are a family of integral membrane proteins whose expression is limited to certain cell types. A pair of consensus sequences, X and Y, is found upstream of all class II genes, and deletion of each of these sequences eliminates expression of transfected genes. Furthermore, the absence of a specific X box binding protein in patients with severe combined immunodeficiency disease whose cells lack class II suggests an important role for these proteins in class II regulation. Here, the cloning of two λgt11 complementary DNAs encoding DNA binding proteins (murine X box binding proteins λmXBP and λmXBP-2) is reported. Both phage-encoded fusion proteins bind specifically to the X box of the Aα, but not to Eα or Eβ class II genes. These two independent isolates do not cross-hybridize. The λmXBP complementary DNA hybridizes to two RNA species, 6.2 and 3.0 kilobases in mouse, that are expressed in both Ia positive and Ia negative cells. By means of DNA blot analysis with the λmXBP complementary DNA insert and probes generated from each end of this complementary DNA insert, λmXBP was found to arise from a multigene family. These data illustrate the high degree of complexity in the transcriptional control of this coordinately regulated gene family.
Evidence for Degenerative and Regenerative Changes in Neostriatal Spiny Neurons in Huntington's Disease
Authors: Graveland G. A. , Williams R. S. , DiFiglia M.
Published: October 2006

Golgi impregnations of neostriatum from deceased Huntington's disease patients and controls were examined. In all cases of Huntington's disease the morphology of dendrites of medium-sized spiny neurons was markedly altered by the appearance of recurved endings and appendages, a decrease or increase in the density of spines, and abnormalities in the size and shape of spines. Pathological changes were rarely observed in medium-sized and large aspiny neostriatal neurons. The findings provide evidence for simultaneous degeneration and growth of spiny neurons in Huntington's disease and support the view that a specific population of neostriatal neurons is selectively involved in its pathogenesis.
Ser-Leu-Arg-Arg-Atriopeptin III: The Major Circulating Form of Atrial Peptide
Authors: Schwartz David , Geller David M. , Manning Pamela T. , Siegel Ned R. , Fok Kam F. , Smith Christine E. , Needleman Philip
Published: October 2006

Vasopressin induces a concentration-dependent increase in atriopeptin immunoreactivity in plasma. Rat plasma, rat atrial extract, and synthetic atriopeptin III (APIII) produced parallel displacement curves of iodine-125-labeled APIII binding to specific antiserum. Fractionation of plasma atriopeptin immunoreactivity by reverse-phase high-performance liquid chromatography showed that the major portion consists of two species of low molecular weight peptides in a ratio of 10 to 1. Both peaks exhibited potent vasorelaxant activity, suggesting the presence of the carboxyl terminal Phe-Arg sequence of atriopeptin in each species. Sequence determination of the purified peptides indicated that the major peptide is Ser-Leu-Arg-Arg-APIII and the minor peptide APIII. It appears that the former is the major species of atrial peptide in the rat circulation and that it is the product of selective cleavage of the high molecular weight precursor.
Estrogen Binding, Receptor mRNA, and Biologic Response in Osteoblast-Like Osteosarcoma Cells
Authors: Komm Barry S. , Terpening Christopher M. , Benz David J. , Graeme Kimberlie A. , Gallegos Alfred , Korc Murray , Greene Geoffrey L. , O'Malley Bert W. , Haussler Mark R.
Published: October 2006

High specific activity estradiol labeled with iodine-125 was used to detect approximately 200 saturable, high-affinity (dissociation constant ≅ 1.0 n
M
) nuclear binding sites in rat (ROS 17/2.8) and human (HOS TE85) clonal osteoblast-like osteosarcoma cells. Of the steroids tested, only testosterone exhibited significant cross-reactivity with estrogen binding. RNA blot analysis with a complementary DNA probe to the human estrogen receptor revealed putative receptor transcripts of 6 to 6.2 kilobases in both rat and human osteosarcoma cells. Type I procollagen and transforming growth factor-β messenger RNA levels were enhanced in cultured human osteoblast-like cells treated with 1 n
M
estradiol. Thus, estrogen can act directly on osteoblasts by a receptor-mediated mechanism and thereby modulate the extracellular matrix and other proteins involved in the maintenance of skeletal mineralization and remodeling.
Heat Shock Is Lethal to Fibroblasts Microinjected with Antibodies Against hsp70
Authors: Riabowol Karl T. , Mizzen Lee A. , Welch William J.
Published: October 2006

Synthesis of a small group of highly conserved proteins in response to elevated temperature and other agents that induce stress is a universal feature of prokaryotic and eukaryotic cells. Although correlative evidence suggests that these proteins play a role in enhancing survival during and after stress, there is no direct evidence to support this in mammalian cells. To assess the role of the most highly conserved heat shock protein (hsp) family during heat shock, affinity-purified monoclonal antibodies to hsp70 were introduced into fibroblasts by needle microinjection. In addition to impairing the heat-induced translocation of hsp70 proteins into the nucleus after mild heat shock treatment, injected cells were unable to survive a brief incubation at 45°C. Cells injected with control antibodies survived a similar heat shock. These results indicate that functional hsp70 is required for survival of these cells during and after thermal stress.
Phenolic Plant Compounds Functioning as Reproductive Inhibitors in
Microtus montanus
Authors: Berger Patricia J. , Sanders Edward H. , Gardner Pete D. , Negus Norman C.
Published: October 2006

Naturally occurring cinnamic acids and their related vinylphenols were found to inhibit reproductive function in
Microtus montanus
. When fed on these compounds, the rodents exhibited decreased uterine weight, inhibition of follicular development, and a cessation of breeding activity. It is suggested that these animals utilize plant compounds as a cue to terminate their reproductive effort in natural populations.
Experimental Triggering of Reproduction in a Natural Population of
Microtus montanus
Authors: Negus Norman C. , Berger Patricia J.
Published: October 2006

A nonbreeding winter population of
Microtus montanus
was given limited supplements of fresh green wheatgrass over a 2-week period. The population was sampled at the end of the feeding period and compared to an adjacent population receiving no grass supplements. All of the experimental females were pregnant, while animals from the control area remained in nonbreeding condition. Replication of the experiment during the next winter produced similar results. The data suggest that
Microtus montanus
cues reproductive effort from chemical signals in the plant food resources.
Recognition and Transport of Adenine Derivatives with Synthetic Receptors
Authors: Benzing Tom , Tjivikua Tjama , Wolfe Judith , Rebek Julius
Published: October 2006

Several new synthetic agents show high affinity for binding adenine derivatives. The structures feature complementary hydrogen bonds that cause the molecular chelation of the purine nucleus. The high lipophilicity of the new agents permits the transport of adenosine and deoxyadenosine across organic liquid membranes. The use of synthetic receptors for small biological targets may have application in drug delivery.
Mechanism of Carbon Isotope Fractionation Associated with Lipid Synthesis
Authors: DeNiro Michael J. , Epstein Samuel
Published: October 2006

The low carbon-13/carbon-12 ratio of lipids is shown to result from isotopic fractionation during the oxidation of pyruvate to acetyl coenzyme A. In vitro analysis of the kinetic isotope effects of this reaction indicates that there will be a large, temperature-dependent difference in the carbon-13/carbon-12 ratio between the methyl and carbonyl carbon atoms of acetyl coenzyme A and between those carbon atoms of lipid components which derive from them.
In Vitro Growth of
Mycobacterium lepraemurium
, an Obligate Intracellular Microbe
Authors: Dhople A. M. , Hanks J. H.
Published: October 2006

By using an ultrasensitive technique to measure adenosine triphosphate in terms of functional biomass, we have confirmed that
Mycobacterium lepraemurium
(the agent of rat leprosy and a classical obligate intracellular microbe) grows in vitro in the Nakamura system. By using a sulfhydryl-containing medium that occupies 65 to 75 percent of the culture tube volume, together with the five supplements recommended by Nakamura, we have obtained growth rates some eight times above the original. The new physicochemical environment and the use of adenosine triphosphate as an index of energy status in the presence and absence of growth provide a basis for investigating the physiology and growth of other noncultivated microbes.
Molecular Cloning of the Zeta Chain of the T Cell Antigen Receptor
Authors: Weissman Allan M. , Baniyash Michal , Hou Damon , Samelson Lawrence E. , Burgess Wilson H. , Klausner Richard D.
Published: October 2006

The T cell antigen receptor is a multi-subunit receptor complex present on the surface of all mature and many developing T cells. It consists of clonotypic heterodimers noncovalently linked to five invariant chains that are encoded by four genes and referred to as the CD3 complex. The CD3 gamma, delta, and epsilon chains have been molecularly characterized. In this report the molecular cloning of a complementary DNA encoding the zeta chain of the murine T cell antigen receptor is described. The predicted protein sequence of the zeta chain suggests a structure distinct from those of any of the previously described receptor subunits.
Retroviruses
Authors: Varmus Harold
Published: October 2006

First brought to scientific attention as infectious cancer-causing agents nearly 80 years ago, retroviruses are popular in contemporary biology for many reasons. (i) The virus life cycle includes several events—in particular, reverse transcription of the viral RNA genome into DNA, orderly integration of viral DNA into host chromosomes, and utilization of host mechanisms for gene expression in response to viral signals—which are broadly informative about eukaryotic cells and viruses. (ii) Retroviral oncogenesis usually depends on transduction or insertional activation of cellular genes, and isolation of those genes has provided the scientific community with many of the molecular components now implicated in the control of normal growth and in human cancer. (iii) Retroviruses include many important veterinary pathogens and two recently discovered human pathogens, the causative agents of the acquired immunodeficiency syndrome (AIDS) and adult T cell leukemia/lymphoma. (iv) Retroviruses are genetic vectors in nature and can be modified to serve as genetic vectors for both experimental and therapeutic purposes. (v) Insertion of retroviral DNA into host chromosomes can be used to mark cell lineages and to make developmental mutants. Progress in these and other areas of retrovirus-related biology has been enormous during the past two decades, but many practical and theoretical problems remain to be solved.
Astrocyte Mitogen Inhibitor Related to Epidermal Growth Factor Receptor
Authors: Nieto-Sampedro Manuel
Published: October 2006

Epidermal growth factor (EGF) is a well-characterized polypeptide hormone with diverse biological activities, including stimulation of astrocyte division. A soluble astrocyte mitogen inhibitor, immunologically related to the EGF receptor, is present in rat brain. Injury to the brain causes a time-dependent reduction in the levels of this inhibitor and the concomitant appearance of EGF receptor on the astrocyte surface. Intracerebral injection of antibody capable of binding the inhibitor caused the appearance of numerous reactive astrocytes. EGF receptor-related inhibitors may play a key role in the control of glial cell division in both normal and injured brain.
Redesigning Nature's Poisons to Create Anti-Tumor Reagents
Authors: Vitetta Ellen S. , Fulton R. Jerrold , May Richard D. , Till Mark , Uhr Jonathan W.
Published: October 2006

Immunotoxins are conjugates of cell-reactive antibodies and toxins or their subunits. In this report, the chemistry, biology, pharmacokinetics, and anti-tumor effects of first generation immunotoxins; the preparation of improved second generation immunotoxins that display greater anti-tumor efficacy; and the role of genetic engineering in creating third-generation immunotoxins are discussed.
Regeneration of Sensory Hair Cells After Acoustic Trauma
Authors: Corwin Jeffrey T. , Cotanche Douglas A.
Published: October 2006

Any loss of cochlear hair cells has been presumed to result in a permanent hearing deficit because the production of these cells normally ceases before birth. However, after acoustic trauma, injured sensory cells in the mature cochlea of the chicken are replaced. New cells appear to be produced by mitosis of supporting cells that survive at the lesion site and do not divide in the absence of trauma. This trauma-induced division of normally postmitotic cells may lead to recovery from profound hearing loss.