bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterogeneous Reaction Probabilities, Solubilities, and the Physical State of Cold Volcanic Aerosols
Authors: Toon O. , Browell E. , Gary B. , Lait L. , Livingston J. , Newman P. , Pueschel R. , Russell P. , Schoeberl M. , Toon G. , Traub W. , Valero F. P. J. , Selkirk H. , Jordan J.
Published: October 2006

On 19 January 1992, heterogeneous loss of HNO
3
, ClNO
3
, and HCl was observed in part of the Mount Pinatubo volcanic cloud that had cooled as a result of forced ascent. Portions of the volcanic cloud froze near 191 kelvin. The reaction probability of ClNO
3
and the solubility of HNO
3
were close to laboratory measurements on liquid sulfuric acid. The magnitude of the observed loss of HCl suggests that it underwent a heterogeneous reaction. Such reactions could lead to substantial loss of HCl on background sulfuric acid particles and so be important for polar ozone loss.
Evidence for a Low Surface Temperature on Pluto from Millimeter-Wave Thermal Emission Measurements
Authors: Stern S. Alan , Weintraub David A. , Festou Michel C.
Published: October 2006

Thermal continuum emission from the Pluto-Charon system has been detected at wavelengths of 800 and 1300 micrometers, and significant upper limits have been obtained at 450 and 1100 micrometers. After the subtraction of emission from Charon, the deduced surface temperature of much of Pluto is between 30 and 44 kelvin, probably near 35 to 37 kelvin. This range is significantly cooler than what radiative equilibrium models have suggested and cooler than the surface temperature derived by the Infrared Astronomy Satellite. The low temperature indicates that methane cannot be present at the microbar pressure levels indicated by the 1988 stellar occultation measurements and that the methane features in Pluto's spectrum are from solid, not gas-phase, absorptions. This result is evidence that Pluto's atmosphere is dominated by nitrogen or carbon monoxide rather than methane.
Nonlinear Optical Properties of Proteins Measured by Hyper-Rayleigh Scattering in Solution
Authors: Clays K. , Hendrickx E. , Triest M. , Verbiest T. , Persoons A. , Dehu C. , Brédas J.-L.
Published: October 2006

Hyper-Rayleigh scattering has been used to determine the nonlinear optical properties of a chromophore-containing protein in solution. Because the technique of hyper-Rayleigh scattering allows the measurement of hyperpolarizabilities in an isotropic solution without the application of an electric field, this method is ideally suited for the study of proteins that carry a net charge. The observed orientational correlation between the nonlinear optical chromophores in incompletely solubilized protein molecules suggests that guidelines from protein structures can be used for the engineering of supramolecular structures with high optical nonlinearity.
Fabrication of Conducting Polymer Interconnects
Authors: Curtis Corrine L. , Ritchie Jason E. , Sailor Michael J.
Published: October 2006

A nonmechanical approach to the construction of complex three-dimensional interconnect arrays has been developed with the use of conducting polymer dendrites. Electrically independent connections between pairs of wires in an array were successfully grown through alternating-current electrochemical polymerization of poly(3-methylthiophene), without mechanical or optical masking steps. The electrically active links were insulated by subsequent electropolymerization of 4-vinylpyridine or 2-methylthiophene or by the dip-coating of the connections in a polystyrene solution.
A General Method for Site-specific Incorporation of Unnatural Amino Acids into Proteins
Authors: Noren Christopher J. , Anthony-Cahill Spencer J. , Griffith Michael C. , Schultz Peter G.
Published: October 2006

A new method has been developed that makes it possible to site-specifically incorporate unnatural amino acids into proteins. Synthetic amino acids were incorporated into the enzyme β-lactamase by the use of a chemically acylated suppressor transfer RNA that inserted the amino acid in response to a stop codon substituted for the codon encoding residue of interest. Peptide mapping localized the inserted amino acid to a single peptide, and enough enzyme could be generated for purification to homogeneity. The catalytic properties of several mutants at the conserved Phe
66
were characterized. The ability to selectively replace amino acids in a protein with a wide variety of structural and electronic variants should provide a more detailed understanding of protein structure and function.
Enzymatic Catalysts in Organic Synthesis
Authors: Wong C.-H.
Published: October 2006

The synthetic value of enzymes is being increasingly recognized. With an understanding of enzyme-catalyzed reactions and the techniques now available for the low-cost production and rational alteration of enzymes and for the design of new enzymatic activities, biocatalytic synthesis should become one of the most valuable synthetic methods. The fundamental as well as the practical issues of this rapidly growing area are described and its impact on the technology pertaining to synthesis is considered.
The Molecular Basis of Muscular Dystrophy in the
mdx
Mouse: a Point Mutation
Authors: Sicinski Piotr , Geng Yan , Ryder-Cook Allan S. , Barnard Eric A. , Darlison Mark G. , Barnard Pene J.
Published: October 2006

The
mdx
mouse is an X-linked myopathic mutant, an animal model for human Duchenne muscular dystrophy. In both mouse and man the mutations lie within the dystrophin gene, but the phenotypic differences of the disease in the two species confer much interest on the molecular basis of the
mdx
mutation. The complementary DNA for mouse dystrophin has been cloned, and the sequence has been used in the polymerase chain reaction to amplify normal and
mdx
dystrophin transcripts in the area of the
mdx
mutation. Sequence analysis of the amplification products showed that the
mdx
mouse has a single base substitution within an exon, which causes premature termination of the polypeptide chain.
The Rat as an Experimental Animal
Authors: Gill Thomas J. , Smith Garry J. , Wissler Robert W. , Kunz Heinz W.
Published: October 2006

The development and characterization of many inbred, congenic, and recombinant strains of rats in recent years has led to the detailed genetic description of this species, especially in regard to its major histocompatibility complex. This information has contributed substantially to the study of comparative genetics and has greatly enhanced the utility of the rat in a variety of areas of biomedical research. This article focuses on the use of the rat in immunogenetics, transplantation, cancer-risk assessment, cardiovascular diseases, and behavior.
Organization of the Human Brain
Authors: Gazzaniga Michael S.
Published: October 2006

Examination of structure-function correlates in the human brain reveals that there is a high degree of functional specificity in the information transmitted over neural systems. It also appears that the human brain has a modular organization consisting of identifiable component processes that participate in the generation of a cognitive state. The effects of isolating entire modular systems or of disconnecting the component parts can be observed. The features of a left hemisphere specialized capacity to interpret the actions of modules are discussed in terms of human consciousness.
Normal Expression of a Rearranged and Mutated c-
myc
Oncogene After Transfection into Fibroblasts
Authors: Richman Adam , Hayday Adrian
Published: October 2006

Expression of the c-
myc
oncogene is deregulated in a variety of malignancies. Rearrangement and mutation of the c-
myc
locus is a characteristic feature of human Burkitt's lymphoma. Whether deregulation is solely a result of mutation of c-
myc
or whether it is influenced by the transformed B cell context has not been determined. A translocated and mutated allele of c-
myc
was stably transfected into fibroblasts. The rearranged allele was expressed indistinguishably from a normal c-
myc
gene: it had serum-regulated expression, was transcribed with normal promoter preference, and was strongly attenuated. Thus mutations by themselves are insufficient to deregulate c-
myc
transcription.
Fetal Research
Authors: Hansen John T. , Sladek John R.
Published: October 2006

This article reviews some of the significant contributions of fetal research and fetal tissue research over the past 20 years. The benefits of fetal research include the development of vaccines, advances in prenatal diagnosis, detection of malformations, assessment of safe and effective medications, and the development of in utero surgical therapies. Fetal tissue research benefits vaccine development, assessment of risk factors and toxicity levels in drug production, development of cell lines, and provides a source of fetal cells for ongoing transplantation trials. Together, fetal research and fetal tissue research offer tremendous potential for the treatment of the fetus, neonate, and adult.
Modulation of Rod-Cone Coupling by Light
Authors: Yang Xiong-Li , Wu Samuel M.
Published: October 2006

Although electrical coupling between rods and cones in the retina has been assumed to be static, it has now been shown that rod-cone coupling can be strengthened by light. Increment threshold measurements reveal that cone input to rods increases progressively as background light becomes brighter. Current injection into cones produces larger responses in adjacent rods in the presence of background light than in darkness. Weak coupling under dark-adapted conditions facilitates synaptic transmission of small rod signals, and strong coupling under light-adapted conditions enhances transmission of large cone signals.
Membranes as the Energy Source in the Endergonic Transformation of Vitamin A to 11-
cis
-Retinol
Authors: Deigner Peter S. , Law Wing C. , Cañada Francisco J. , Rando Robert R.
Published: October 2006

The eye needs to biosynthesize 11-
cis
-retinoids because the chromophore of rhodopsin is 11-
cis
-retinal. The critical metabolic step is the endergonic isomerization of free all-
trans
-retinol (vitamin A) into 11-
cis
-retinol. This isomerization process can take place in isolated membranes from the retinal pigment epithelium in the absence of added energy sources. Specific binding proteins probably do not serve as an energy source, and since all of the reactions in the visual cycle are shown here to be reversible, trapping reactions also do not participate in the isomerization reaction. One previously unexplored possibility is that the chemical energy in the bonds of the membrane itself may drive the isomerization reaction. A group transfer reaction is proposed that forms a retinyl ester from a lipid acyl donor and vitamin A. This transfer can drive the isomerization reaction because the all-
trans
-retinyl ester is isomerized directly to 11-
cis
-retinol. Thus, the free energy of hydrolysis of the ester is coupled to the thermodynamically uphill
trans
to
cis
isomerization. The prediction of an obligate C-O bond cleavage in the vitamin A moiety during isomerization is borne out. Although the natural substrate for isomerization is not known, all-
trans
-retinyl palmitate is processed in vitro to 11-
cis
-retinol by pigment epithelial membranes.
Categorical Perception of a Natural Stimulus Continuum: Birdsong
Authors: Nelson Douglas A. , Marler Peter
Published: October 2006

A fundamental issue in perception and communication is how continuously varying stimuli are partitioned into discrete categories. In swamp sparrow songs, note duration is a critical feature distinguishing two note categories with different roles in song construction. Pairs of songs with initial notes from different categories contrast more in their effects on territorial males than song pairs with initial notes differing by the same amount but taken from within one note category. The results indicate categorical perception by wild swamp sparrows.
Pulmonary Blood Flow Regulation in an Aquatic Snake
Authors: Lillywhite Harvey B. , Donald John A.
Published: October 2006

Regulation of pulmonary blood flow was studied during voluntary diving in the aquatic file snake,
Acrochordus granulatus
. Measurements of pressure and blood flow in pulmonary and systemic vessels indicate that blood flow completely bypasses the lung for significant periods during prolonged and quiescent submergence (greater than 30 minutes). When the lung is ventilated, pulmonary blood flow increases to 36 milliliters per minute per kilogram of body mass (measured in the anterior pulmonary artery), and the cardiac output largely bypasses the systemic circulation. These reciprocating patterns of preferential blood flow reflect inverse relations between flow and vascular resistance, with the result that systemic and pulmonary arterial pressures remain virtually constant throughout repetitive dive cycles. Neuropharmacological studies of freely diving snakes and isolated, perfused lung preparations show that pulmonary blood flow is regulated by an interplay of adrenergic vasodilatation and cholinergic vasoconstriction within the densely innervated lung vasculature. The patterns of blood circulation shown by diving
Acrochordus
reflect an unusual lability of intracardiac shunts.
Buprenorphine Suppresses Cocaine Self-Administration by Rhesus Monkeys
Authors: Mello Nancy K. , Mendelson Jack H. , Bree Mark P. , Lukas Scott E.
Published: October 2006

Cocaine abuse has reached epidemic proportions in the United States, and the search for an effective pharmacotherapy continues. Because primates self-administer most of the drugs abused by humans, they can be used to predict the abuse liability of new drugs and for preclinical evaluation of new pharmacotherapies for drug abuse treatment. Daily administration of buprenorphine (an opioid mixed agonist-antagonist) significantly suppressed cocaine self-administration by rhesus monkeys for 30 consecutive days. The effects of buprenorphine were dose-dependent. The suppression of cocaine self-administration by buprenorphine did not reflect a generalized suppression of behavior. These data suggest that buprenorphine would be a useful pharmacotherapy for treatment of cocaine abuse. Because buprenorphine is a safe and effective pharmacotherapy for heroin dependence, buprenorphine treatment may also attenuate dual abuse of cocaine and heroin.
Postponement of Satiety by Blockade of Brain Cholecystokinin (CCK-B) Receptors
Authors: Dourish C. T. , Rycroft W. , Iversen S. D.
Published: October 2006

Exogenous cholecystokinin (CCK) decreases food intake and causes satiety in animals and man. However, it has not been established that endogenous CCK causes satiety or whether the response is mediated by peripheral-type (CCK-A) or brain-type (CCK-B) receptors. The development of potent and selective antagonists for CCK-A (MK-329) and CCK-B (L-365,260) receptors now allows these issues to be addressed. The CCK-A antagonist MK-329 and the CCK-B antagonist L-365,260 increased food intake in partially satiated rats and postponed the onset of satiety; however, L-365,260 was 100 times more potent than MK-329 in increasing feeding and preventing satiety. These results suggest that endogenous CCK causes satiety by an agonist action on CCK-B receptors in the brain.
A Novel Vasodilatory Peptide from the Salivary Glands of the Sand Fly
Lutzomyia longipalpis
Authors: Ribeiro José M. C. , Vachereau André , Modi Govind B. , Tesh Robert B.
Published: October 2006

Salivary gland lysates of the sand fly
Lutzomyia longipalpis
contain a potent vasodilator that aids the fly to feed on the blood of its vertebrate hosts. Chromatographic analysis, antibody reactivity, and data obtained from bioassays of the salivary erythema-inducing factor indicate striking similarity with human calcitonin gene-related peptide. The erythema-inducing factor is, however, at least one order of magnitude more potent than calcitonin gene-related peptide.
T Cells Against a Bacterial Heat Shock Protein Recognize Stressed Macrophages
Authors: Koga Tetsuya , Wand-Württenberger Angela , DeBruyn Jacqueline , Munk Martin E. , Schoel Bernd , Kaufmann Stefan H. E.
Published: October 2006

Heat shock proteins are evolutionarily highly conserved polypeptides that are produced under a variety of stress conditions to preserve cellular functions. A major antigen of tubercle bacilli of 65 kilodaltons is a heat shock protein that has significant sequence similarity and cross-reactivity with antigens of various other microbes. Monoclonal antibodies against this common bacterial heat shock protein were used to identify a molecule of similar size in murine macrophages. Macrophages subjected to various stress stimuli including interferon-γ activation and viral infection were recognized by class I-restricted CD8 T cells raised against the bacterial heat shock protein. These data suggest that heat shock proteins are processed in stressed host cells and that epitopes shared by heat shock proteins of bacterial and host origin are presented in the context of class I molecules.
Meiotic Recombination in Yeast: Alteration by Multiple Heterozygosities
Authors: Borts Rhona H. , Haber James E.
Published: October 2006

Although meiotic gene conversion has long been known to be accompanied by crossing-over, a direct test of the converse has not been possible. An experiment was designed to determine whether crossing-over is accompanied by gene conversion in
Saccharomyces cerevisiae
. Nine restriction site heterologies were introduced into a 9-kilobase chromosomal interval that exhibits 22 percent crossing-over. Of all the exchange events that occurred, at least 59 percent of meiotic crossovers are accompanied by gene conversion of one or more of the restriction site heterologies. The average gene conversion tract length was 1.5 kilobases. An unexpected result was that the introduction of as few as seven heterozygosities significantly altered the outcome of recombination events, reducing the frequency of crossovers by 50 percent and increasing the number of exceptional tetrads. This alteration results from a second recombination event induced by repair of heteroduplex DNA containing multiple mismatched base pairs.
HTLV-V: a New Human Retrovirus Isolated in a Tac-Negative T Cell Lymphoma/Leukemia
Authors: Manzari Vittorio , Gismondi Angela , Barillari Giovanni , Morrone Stefania , Modesti Andrea , Albonici Loredana , De Marchis Laura , Fazio Vito , Gradilone Angela , Zani Massimo , Frati Luigi , Santoni Angela
Published: October 2006

A new human retrovirus was isolated from a continuous cell line derived from a patient with CD4
+
Tac
-
cutaneous T cell lymphoma/leukemia. This virus is related to but distinct from human T cell leukemia/lymphoma virus types I and II (HTLV-I and HTLV-II) and human immunodeficiency virus (HIV-1). With the use of a fragment of provirus cloned from one patient with T cell leukemia, closely related sequences were found in DNA of the cell line and of tumor cells from seven other patients with the same disease; these sequences were only distantly related to HTLV-I. The phenotype of the cells and the clinical course of the disease were clearly distinguishable from leukemia associated with HTLV-I. All patients and the wife of one patient showed a weak serological cross-reactivity with both HTLV-I and HIV-1 antigens. None of the patients proved to be at any apparent risk for HIV-1 infection. The name proposed for this virus is HTLV-V, and the date indicate that it may be a primary etiological factor in the major group of cutaneous T cell lymphomas/leukemias, including the sporadic lymphomas known as mycoses fungoides.
Isoform-Specific Modulation of Na
+
, K
+
-ATPase α-Subunit Gene Expression in Hypertension
Authors: Herrera Victoria L. M. , Chobanian Aram V. , Ruiz-Opazo Nelson
Published: October 2006

Sodium, potassium-adenosine triphosphatase (Na
+
,K
+
-ATPase) is hypothesized to be involved in systemic vascular hypertension through its effects on smooth muscle reactivity and myocardial contractility. By means of RNA blot analyses of cardiac, aortic, and skeletal muscle RNAs in two rat hypertensive models, Na
+
,K
+
-ATPase α-subunit messenger RNA isoforms (α2 and α3) were shown to be deinduced in response to increased intravascular pressure. The changes were observed after 48 hours or more of experimental hypertension. Under these conditions, there is coordinate induction of another α isoform (α1) and of β-subunit messenger RNAs, probably in response to alterations in sodium flux rather than to elevated blood pressure.
Putative Melatonin Receptors in a Human Biological Clock
Authors: Reppert Steven M. , Weaver David R. , Rivkees Scott A. , Stopa Edward G.
Published: October 2006

In vitro autoradiography with
125
I-labeled melatonin was used to examine melatonin binding sites in human hypothalamus. Specific
125
I-labeled melatonin binding was localized to the suprachiasmatic nuclei, the site of a putative biological clock, and was not apparent in other hypothalamic regions. Specific
125
I-labeled melatonin binding was consistently found in the suprachiasmatic nuclei of hypothalami from adults and fetuses. Densitometric analysis of competition experiments with varying concentrations of melatonin showed monophasic competition curves, with comparable half-maximal inhibition values for the suprachiasmatic nuclei of adults (150 picomolar) and fetuses (110 picomolar). Micromolar concentrations of the melatonin agonist 6-chloromelatonin completely inhibited specific
125
I-labeled melatonin binding, whereas the same concentrations of serotonin and norepinephrine caused only a partial reduction in specific binding. The results suggest that putative melatonin receptors are located in a human biological clock.
Sarafotoxin, a Novel Vasoconstrictor Peptide: Phosphoinositide Hydrolysis in Rat Heart and Brain
Authors: Kloog Y. , Ambar I. , Sokolovsky M. , Kochva E. , Wollberg Z. , Bdolah A.
Published: October 2006

Sarafotoxins, a group of 21-residue cardiotoxic peptides from snake venom that induce coronary vasoconstriction, show high-affinity binding to rat atrial and brain membranes and activate the hydrolysis of phosphoinositides. Neither their binding nor their activity is affected by blockers or activators of known receptors and ion channels, suggesting that sarafotoxins act either directly on the phosphoinositide phosphodiesterase system or on a novel receptor. Their amino acid sequence shows a high degree of homology with that of endothelin, a recently described 21-residue vasoconstrictor peptide found in porcine aortic endothelium. This is remarkable, since endothelin is a natural compound of the mammalian vascular system while sarafotoxins are highly toxic components of snake venom.
Early Biochemical Effects of an Organic Mercury Fungicide on Infants: "Dose Makes the Poison"
Authors: Gotelli Carlos A. , Astolfi Emilio , Cox Christopher , Cernichiari Elsa , Clarkson Thomas W
Published: October 2006

Phenylmercury absorbed through the skin from contaminated diapers affected urinary excretion in infants in Buenos Aires. The effects were reversible and quantitatively related to the concentration of urinary mercury. Excretion of γ-glutamyl transpeptidase, an enzyme in the brush borders of renal tubular cells, increased in a dose-dependent manner when mercury excretion exceeded a "threshold" value. Urine volume also increased but at a higher threshold with respect to mercury. The results support the threshold concept of the systemic toxicity of metals. γ-Glutamyl transpeptidase is a useful and sensitive marker for preclinical effects of toxic metals.
Assembly of Clathrin-Coated Pits Onto Purified Plasma Membranes
Authors: Moore Mary Shannon , Mahaffey David T. , Brodsky Frances M. , Anderson Richard G. W.
Published: October 2006

During receptor-mediated endocytosis, coated pits invaginate to form coated vesicles, clathrin and associated proteins dissociate from the vesicle membrane, and these proteins form new coated pits at the cell surface. As a means of elucidating molecular mechanisms that govern the function of coated pits, the assembly phase of this cycle was reconstituted by incubating purified membranes that were treated to remove endogenous coated pits with cytoplasm extracted from cultured cells. The in vitro assembly of coated pits on these membranes satisfactorily mimics many features of coated pit formation in the intact cell. These studies indicate that: (i) the membranes contain a limited number of coated pit assembly sites that bind clathrin with high affinity; (ii) the half-time for assembly is 5 minutes both at 4°C and 37°C; (iii) during assembly, proteins with molecular sizes of 180, 110, and 36 kilodaltons are recruited to the plasma membrane; and (iv) assembly is not dependent on adenosine triphosphate, but this nucleotide triggers a temperature-dependent loss of coated pits that are assembled in the absence of adenosine triphosphate.
A DNA Segment Encoding Two Genes Very Tightly Linked to Huntington's Disease
Authors: Gilliam T. Conrad , Bucan Maja , MacDonald Marcy E. , Zimmer Michael , Haines Jonathan L. , Cheng Shirley V. , Pohl Thomas M. , Meyers Richard H. , Whaley William L. , Allitto Bernice A. , Faryniarz Anne , Wasmuth John J. , Frischauf Anna-Maria , Conneally P. Michael , Lehrach Hans , Gusella James F.
Published: October 2006

The discovery of D4S10, an anonymous DNA marker genetically linked to Huntington's disease (HD), introduced the capacity for limited presymptomatic diagnosis in this late-onset neurodegenerative disorder and raised the hope of cloning and characterizing the defect based on its chromosomal location. Progress on both fronts has been limited by the absence of additional DNA markers closer to the HD gene. An anonymous DNA locus, D4S43, has now been found that shows extremely tight linkage to
HD
. Like the disease gene, D4S43 is located in the most distal region of the chromosome 4 short arm, flanked by D4S10 and the telomere. In three extended HD kindreds, D4S43 displays no recombination with HD, placing it within 0 to 1.5 centimorgans of the genetic defect. Expansion of the D4S43 region to include 108 kilobases of cloned DNA has allowed identification of eight restriction fragment length polymorphisms and at least two independent coding segments. In the absence of crossovers, these genes must be considered candidates for the site of the HD defect, although the D4S43 restriction fragment length polymorphisms do not display linkage disequilibrium with the disease gene.
The Perception of Intention
Authors: Dasser Verena , Ulbaek Ib , Premack David
Published: October 2006

Classical work on the perception of causality in humans is extended to the perception of intention. Two experiments explored the sensitivity of preschool children to intentional events that can be stated in terms of time and distance only. In habituation-dishabituation of attention tests, preschool children differentiated between intentional movement patterns of two balls and the nonintentional control events where the movements were desynchronized. Also, reversal of the roles of the balls produced more recovery of attention in the intentional case than it did in the nonintentional case.
Identification of a T Helper Cell-Derived Lymphokine That Activates Resting T Lymphocytes
Authors: Milanese Claudio , Richardson Neil E. , Reinherz Ellis L.
Published: October 2006

A novel lymphokine with apparent molecular size of 10 to 12 kilodaltons is secreted from helper T cell clones within hours after cross-linking their T cell antigen-MHC (major histocompatibility complex) receptors (T3-Ti). This lymphokine, termed interleukin-4A (IL-4A), stimulates resting lymphocytes by binding to a surface component (or components) of the alternative T11 pathway and subsequently by inducing interleukin-2 (IL-2) receptors. The activation process is neither dependent on antigen specificities of the recruited population or the presence of macrophages. It appears, therefore, that IL-4A is a mediator involved in amplifying the T cell immune response.
Amyloid β Protein Gene: cDNA, mRNA Distribution, and Genetic Linkage Near the Alzheimer Locus
Authors: Tanzi Rudolph E. , Gusella James F. , Watkins Paul C. , Bruns Gail A. P. , St George-Hyslop Peter , Van Keuren Margaret L. , Patterson David , Pagan Susan , Kurnit David M. , Neve Rachael L.
Published: October 2006

The amyloid β protein has been identified as an important component of both cerebrovascular amyloid and amyloid plaques of Alzheimer's disease and Down syndrome. A complementary DNA for the β protein suggests that it derives from a larger protein expressed in a variety of tissues. Overexpression of the gene in brain tissue from fetuses with Down syndrome (trisomy 21) can be explained by dosage since the locus encoding the β protein maps to chromosome 21. Regional localization of this gene by both physical and genetic mapping places it in the vicinity of the genetic defect causing the inherited form of Alzheimer's disease.
Use of Restriction Fragment Length Polymorphisms to Determine the Clonal Origin of Human Tumors
Authors: Vogelstein Bert , Fearon Eric R. , Hamilton Stanley R. , Feinberg Andrew P.
Published: October 2006

A novel strategy to determine the clonal origin of human tumors has been devised. The strategy involves the use of a cloned polymorphic X-chromosomal gene and two restriction endonucleases. The first endonuclease distinguishes the paternal and maternal copies of the gene through a DNA polymorphism of restriction fragment length. The second endonuclease distinguishes active from inactive copies of this gene through changes in DNA methylation. As illustrations of this strategy, three human cancers were each shown to be monoclonal. The analysis described should have a wide variety of clinical and experimental applications.
Interaction of Calcitonin and Calcitonin Gene-Related Peptide at Receptor Sites in Target Tissues
Authors: Goltzman David , Mitchell Jane
Published: October 2006

Discrete receptor sites for calcitonin (CT) and calcitonin gene-related peptide (CGRP) were found in the nervous system and in peripheral tissues. Each peptide was capable of cross-reacting with the specific receptor of the other. In contrast to CT receptors, CGRP receptors were not linked to adenylate cyclase. However, CGRP could stimulate adenylate cyclase in CT target tissues apparently by interacting with CT receptors. The relative abilities of CGRP and mammalian CT to inhibit CT binding suggest that CGRP could serve as an endogenous ligand for CT receptors in the central nervous system.
Endogenous Anticonvulsant Substance in Rat Cerebrospinal Fluid After a Generalized Seizure
Authors: Tortella Frank C. , Long Joseph B.
Published: October 2006

Cerebrospinal fluid taken from rats subjected to electroshock-induced seizures and injected into the cerebral ventricles of rats that had not been shocked increased the seizure threshold of the recipients. The anticonvulsant activity of the donor cerebrospinal fluid was antagonized by opioid antagonists and enhanced by peptidase inhibitors. These results suggest the existence of an endogenous anticonvulsant substance in rat cerebrospinal fluid, possibly opioid in nature, which is activated as a consequence of a seizure and which may play a critical role in postseizure inhibition.
A Transcriptional Activator Protein Encoded by the x-
lor
Region of the Human T-Cell Leukemia Virus
Authors: Sodroski Joseph , Rosen Craig , Goh Wei Chun , Haseltine William
Published: October 2006

Human T-cell leukemia viruses type I and II (HTLV-I and -II) exhibit several features characteristic of this retroviral family: the presence of an x-
lor
gene encoding a nuclear protein, transformation properties suggesting the involvement of a virus-associated
trans
-acting factor, and transcriptional
trans
-activation of the long terminal repeat (LTR) in infected cells. In the study described here the HTLV x-
lor
products, in the absence of other viral proteins, were able to activate gene expression in
trans
directed by the HTLV LTR. The regulation of the expression of particular genes in
trans
by HTLV x-
lor
products suggests that they play a role in viral replication and possibly in transformation of T lymphocytes.
Recombinant Vaccinia Virus: Immunization Against Multiple Pathogens
Authors: Perkus Marion E. , Piccini Antonia , Lipinskas Bernard R. , Paoletti Enzo
Published: October 2006

The coding sequences for the hepatitis B virus surface antigen, the herpes simplex virus glycoprotein D, and the influenza virus hemagglutinin were inserted into a single vaccinia virus genome. Rabbits inoculated intravenously or intradermally with this polyvalent vaccinia virus recombinant produced antibodies reactive to all three authentic foreign antigens. In addition, the feasibility of multiple rounds of vaccination with recombinant vaccinia virus was demonstrated.
Transcription of Class III Genes Activated by Viral Immediate Early Proteins
Authors: Gaynor Richard B. , Feldman Larry T. , Berk Arnold J.
Published: October 2006

The adenovirus EIA and pseudorabies virus immediate early (IE) proteins induce transcription from transfected viral and nonviral genes transcribed by RNA polymerase II (class II genes). These proteins have now been shown also to activate transcription of transfected genes transcribed by RNA polymerase III (class III genes). As previously observed for class II genes, this stimulation of class III gene transcription was much greater for transfected genes than for the major endogenous cellular class III genes. Extracts made from cell lines stably expressing a transfected pseudorabies virus IE gene were 10 to 20 times more active in the in vitro transcription of exogenously added class III genes than extracts of the parental cell line. These results indicate that the E1A and IE proteins stimulate the expression of class III genes by a mechanism similar to the mechanism for stimulation of class II gene transcription by these proteins.
Detection of Human Cytomegalovirus in Peripheral Blood Lymphocytes in a Natural Infection
Authors: Schrier Rachel D. , Nelson Jay A. , Oldstone Michael B. A.
Published: October 2006

In situ hybridization was used to detect human cytomegalovirus (HCMV) in the peripheral blood mononuclear cells of some naturally infected (seropositive) individuals. A subpopulation of cells hybridized specifically to a portion of the HCMV genome that is heavily transcribed during the immediate-early period of infection. The hybridization signal was markedly reduced by base hydrolysis and ribonuclease, and therefore the probe appears to be detecting viral RNA. A fluorescence-activated cell sorter was used to select lymphocytes bearing the OKT4 and OKT8 markers. Hybridization with the HCMV probe revealed a higher proportion of positive cells in the OKT4 than in the OKT8 subset. This observation specifically identifies lymphocytes as a cell population involved in natural HCMV infection and suggests that lymphocytes may be a reservoir for maintaining infection and may also serve as a vehicle for its spread by blood transfusion.
Prevention of Autoimmunity in Experimental Lupus Erythematosus by Soluble Immune Response Suppressor
Authors: Krakauer R. S. , Strober W. , Rippeon D. L. , Waldmann T. A.
Published: October 2006

Young NZB/W mice, treated with injections of soluble immune response suppressor (SIRS) (supernatant from mouse spleen cells exposed to concanavalin A), showed decreased immunoglobulin levels, less antibody to cell nuclei, less proteinuria, and less renal pathology as compared with NZB/W mice receiving a control preparation. Thus, SIRS administration beginning at an early age appears to be an effective therapy of the autoimmune disease in NZB/W mice.
Human β-Adrenoceptors: Relation of Myocardial and Lymphocyte β-Adrenoceptor Density
Authors: Brodde Otto-Erich , Kretsch Roland , Ikezono Katsumi , Zerkowski Hans-Reinhard , Reidemeister Jürgen Christoph
Published: October 2006

In human right atria obtained from 21 patients during open-heart surgery, β-adrenoceptor density [assessed by iodine-125-labeled (-)-cyanopindolol binding] and responsiveness (positive inotropic responses to isoprenaline) were linearly related to the β-adrenoceptor density in the corresponding circulating lymphocytes. This direct relation of human myocardial and lymphocyte β-adrenoceptor alterations, therefore, makes it possible to monitor drug- or disease-induced β-adrenoceptor changes in tissues not easily accessible in humans.
Calcium Antagonist Receptors in Cardiomyopathic Hamster: Selective Increases in Heart, Muscle, Brain
Authors: Wagner John A. , Reynolds Ian J. , Weisman Harlan F. , Dudeck Pamela , Weisfeldt Myron L. , Snyder Solomon H.
Published: October 2006

The Syrian cardiomyopathic hamster has a hereditary disease in which a progressive myocardial necrosis mimics human forms of cardiac hypertrophy. Lesions are associated with calcium overload and can be prevented with the calcium antagonist verapamil. Numbers of receptor binding sites for calcium antagonists in heart, brain, skeletal muscle, and smooth muscle were markedly increased in cardiomyopathic hamsters. The uptake of calcium-45 into brain synaptosomes was also increased in cardiomyopathic hamsters. The increase in calcium antagonist receptors and related voltage-sensitive calcium channels may be involved in the pathogenesis of this cardiomyopathy.
Detection of AIDS Virus in Macrophages in Brain Tissue from AIDS Patients with Encephalopathy
Authors: Koenig Scott , Gendelman Howard E. , Orenstein Jan M. , Dal Canto Mauro C. , Pezeshkpour Gholam H. , Yungbluth Margaret , Janotta Frank , Aksamit Allen , Martin Malcolm A. , Fauci Anthony S.
Published: October 2006

One of the common neurological complications in patients with the acquired immune deficiency syndrome (AIDS) is a subacute encephalopathy with progressive dementia. By using the techniques of cocultivation for virus isolation, in situ hybridization, immunocytochemistry, and transmission electron microscopy, the identity of an important cell type that supports replication of the AIDS retrovirus in brain tissue was determined in two affected individuals. These cells were mononucleated and multinucleated macrophages that actively synthesized viral RNA and produced progeny virions in the brains of the patients. Infected brain macrophages may serve as a reservoir for virus and as a vehicle for viral dissemination in the infected host.
Introduction of a Normal Human Chromosome 11 into a Wilms' Tumor Cell Line Controls Its Tumorigenic Expression
Authors: Weissman Bernard E. , Saxon Paul J. , Pasquale Steve R. , Jones Gary R. , Geiser Andrew G. , Stanbridge Eric J.
Published: October 2006

The development of Wilms' tumor, a pediatric nephroblastoma, has been associated with a deletion in the p13 region of chromosome 11. The structure and function or functions of this deleted genetic material are unknown. The role of this deletion in the process of malignant transformation was investigated by introducing a normal human chromosome 11 into a Wilms' tumor cell line by means of the microcell transfer technique. These variant cells, derived by microcell hybridization, expressed similar transformed traits in culture as the parental cell line. Furthermore, expression of several proto-oncogenes by the parental cells was unaffected by the introduction of this chromosome. However, the ability of these cells to form tumors in nude mice was completely suppressed. Transfer of other chromosomes, namely X and 13, had no effect on the tumorigenicity of the Wilms' tumor cells. These studies provide support for the existence of genetic information on chromosome 11 which can control the malignant expression of Wilms' tumor cells.
Expression of Functional Cell-Cell Channels from Cloned Rat Liver Gap Junction Complementary DNA
Authors: Dahl G. , Miller T. , Paul D. , Voellmy R. , Werner R.
Published: October 2006

An oocyte expression system was used to test the relation between a complementary DNA (cDNA) clone encoding the liver gap junction protein and cell-cell channels. Total liver polyadenylated messenger RNA injected into oocytes induced cell-cell channels between paired oocytes. This induction was blocked by simultaneous injection of antisense RNA transcribed from the gap junction cDNA. Messenger RNA selected by hybridization to the cDNA clone and translated in oocyte pairs yielded a higher junctional conductance than unselected liver messenger RNA. Cell-cell channels between oocytes were also formed when the cloned cDNA was expressed under the control of a heat-shock promoter. A concentration-dependent induction of channels was observed in response to injection with in vitro transcribed gap junction messenger RNA. Thus, the liver gap junction cDNA encodes a protein that is essential for the formation of functional cell-cell channels.
Rearrangement of the Bacterial Chromosome: Forbidden Inversions
Authors: Segall Anca , Mahan Michael J. , Roth John R.
Published: October 2006

The order of genes in the chromosome of enteric bacteria has been evolutionarily conserved despite the existence of mechanisms for rearrangement. Homologous chromosomal sequences in the same orientation recombine to form deletions or duplications. When homologous sequences in inverse orientation recombine, one expects to form an inversion of the intervening chromosomal segment. This expectation was tested by placing pairs of homologous sequences in inverse order at various points in the chromosome. Sequences at many pairs of sites (permissive) do recombine to generate the expected inversion, while the same sequences placed at other pairs of sites (nonpermissive) do not form an inversion. For the one nonpermissive interval tested, the missing inversion type can be constructed by an alternative transductional method; strains with this inversion are viable. Thus mechanistic limitations must prevent sequences at particular sites from undergoing the recombination event required to form an inversion.
Symmetrical Erosive Peripheral Polyarthritis in the Late Archaic Period of Alabama
Authors: Rothschild Bruce M. , Turner Kenneth R. , DeLuca Michael A.
Published: October 2006

Rheumatoid arthritis was first described unambiguously in 1800, but its etiology and historical origins are still obscure. Definite rheumatoid arthritis has not been demonstrated in pre-19th century Old World skeletal remains. Six individuals who lived 3000 to 5000 years ago in northwestern Alabama and present erosive polyarthritis characteristic of rheumatoid arthritis are described. The diagnosis raises the possibility that rheumatoid arthritis can be associated with a New World pathogen or allergen.
tRNA
i
met
Functions in Directing the Scanning Ribosome to the Start Site of Translation
Authors: Cigan A. Mark , Feng Lan , Donahue Thomas F.
Published: October 2006

The mechanism by which the scanning ribosome recognizes the first AUG codon nearest the 5′ end of eukaryotic messenger RNA has not been established. To investigate this an anticodon change (3′-UCC-5′) was introduced into one of the four methionine initiator (tRNA
i
met
) genes of
Saccharomyces cerevisiae
. The ability of the mutant transfer RNA to restore growth properties to
his4
initiator codon mutant yeast strains in the absence of histidine was then assayed. Only the complementary codon, AGG, at the
his4
initiator region supported His
+
growth. The mutant transfer RNA also directed the ribosome to initiate at an AGG placed in the upstream region of the
his4
message. Initiation at this upstream AGG precluded initiation at a downstream AGG in accordance with the "scanning" model. Therefore, an anticodon: codon interaction between tRNA
i
met
as part of the scanning ribosome and the first AUG must function in directing the ribosome to the eukaryotic initiator region.
Alterations in T4 (CD4) Protein and mRNA Synthesis in Cells Infected with HIV
Authors: Hoxie James A. , Alpers James D. , Rackowski Jerome L. , Huebner Kay , Haggarty Beth S. , Cedarbaum Andrew J. , Reed John C.
Published: October 2006

Cells infected with the human immunodeficiency virus (HIV) show decreased expression of the 58-kilodalton T4 (CD4) antigen on their surface. In this study, the effect of HIV infection on the synthesis of T4 messenger RNA (mRNA) and protein products was evaluated in T-cell lines. Metabolically labeled lysates from the T4
+
cell line Sup-T1 were immunoprecipitated with monoclonal antibodies to T4. Compared with uninfected cells, HIV-infected Sup-T1 cells showed decreased amounts of T4 that coprecipitated with both the 120-kilodalton viral envelope and the 150-kilodalton envelope precursor molecules. In four of five HIV-producing T-cell lines studied, the steady-state levels of T4 mRNA were also reduced. Thus, the decreased T4 antigen on HIV-infected cells is due to at least three factors: reduced steady-state levels of T4-specific mRNA, reduced amounts of immunoprecipitable T4 antigen, and the complexing of available T4 antigen with viral envelope gene products. The data suggested that the T4 protein produced after infection may be complexed with viral envelope gene products within infected cells. Retroviral envelope-receptor complexes may thus participate in a general mechanism by which receptors for retroviruses are down-modulated and alterations in cellular function develop after infection.
Regional Changes in Calcium Underlying Contraction of Single Smooth Muscle Cells
Authors: Williams David A. , Becker Peter L. , Fay Frederic S.
Published: October 2006

The role of calcium in regulating the contractile state of smooth muscle has been investigated by measuring calcium and contraction in single smooth muscle cells with the calcium-sensitive dye fura-2 and the digital imaging microscope. The concentration of free calcium in the cytoplasm increased after stimulation of the cells by depolarization with high potassium or by application of carbachol. Changes in calcium always preceded contraction. The increase in calcium induced by these stimuli was limited to less than 1 μ
M
. Calcium within the nucleus was also subject to a limitation of its rise during contraction. Intranuclear calcium rose from 200 n
M
at rest to no more than 300 n
M
while cytoplasmic calcium rose to over 700 n
M
. These apparent ceilings for both cytoplasmic and intranuclear calcium may result either from negative feedback of calcium on cytoplasmic and nuclear calcium channel gating mechanisms, respectively, or from the presence of calcium pumps that are strongly activated at the calcium ceilings.
Genome Rearrangement and Nitrogen Fixation in
Anabaena
Blocked by Inactivation of
xisA
Gene
Authors: Golden James W. , Wiest Deborah R.
Published: October 2006

Two genome rearrangements involving 11- and 55-kilobase DNA elements occur during the terminal differentiation of an
Anabaena
photosynthetic vegetative cell into a nitrogen-fixing heterocyst. The
xisA
gene, located on the
nifD
11-kilobase DNA element, was inactivated by recombination between the chromosome and a copy of the
xisA
gene that was mutated by inserting an antibiotic gene cassette. Site-directed inactivation of the
Anabaena
xisA
gene blocked rearrangement of the 11-kilobase element and nitrogen fixation, but did not affect rearrangement of the 55-kilobase element, heterocyst differentiation, or heterocyst pattern formation.
The
elav
Gene Product of
Drosophila
, Required in Neurons, Has Three RNP Consensus Motifs
Authors: Robinow Steven , Campos Ana Regina , Yao Kwok-Ming , White Kalpana
Published: October 2006

A sequence of developmental events transforms neurons from their immature state to their mature, terminally differentiated state. The
elav
locus is one of the first examples of a gene that is expressed in neurons early during this developmental sequence. This gene has been shown to be required for the proper development of young neurons and for the maintenance of mature neurons. DNA sequence data presented in this report suggest that the
elav
gene product is an RNA binding protein, based on the presence of RNP (ribonucleoprotein) consensus sequences. This leads to the proposal that this protein is involved in the RNA metabolism of neurons.