bluuebunny/crossref_metadata_2025 huggingface dataset:
A Second Nuclear Protein Is Encoded by Epstein-Barr Virus in Latent Infection
Authors: Hennessy Kevin , Kieff Elliott
Published: October 2006

A region of the Epstein-Barr virus (EBV) genome that is important in inducing cell proliferation includes a single long open reading frame. Part of this open reading frame has been fused to the
lacZ
gene and expressed in
Escherichia coli
. Antisera to the fusion protein identify a protein in the nuclei of latently infected growth-transformed lymphocytes and in Burkitt tumor cells grown in vitro. This nuclear protein is encoded by a different virus gene than that which encodes the previously described EBV nuclear antigen, EBNA.
Protection from Genital Herpes Simplex Virus Type 2 Infection by Vaccination with Cloned Type 1 Glycoprotein D
Authors: Berman Phillip W. , Gregory Timothy , Crase Dietrich , Lasky Laurence A.
Published: October 2006

Guinea pigs were vaccinated with truncated herpes simplex virus type-1 (HSV-1) glycoprotein D produced in the genetically engineered mammalian cell line gD10.2. Vaccinated animals formed antibodies that neutralized both HSV-1 and herpes simplex virus type 2 (HSV-2) in an in vitro neutralization assay. Vaccinated animals were challenged with HSV-2 by intravaginal infection. Animals that received the immunogen in Freund's complete adjuvant were completely protected from the clinical manifestations of genital HSV-2 infection. Animals that received the immunogen incorporated in alum adjuvants were partly protected from clinical disease; the infections that did develop were significantly less severe than those that occurred in control animals injected with adjuvant alone. The results demonstrate that immunization with a purified viral protein can provide significant protection against primary genital infection by HSV-2 in guinea pigs.
Visual Pigment Homologies Revealed by DNA Hybridization
Authors: Martin R. L. , Wood C. , Baehr W. , Applebury M. L.
Published: October 2006

A bovine rhodopsin complementary DNA probe was used to detect homologous visual pigment genes in a variety of species. Under stringent DNA hybridization conditions, genomic DNA from most vertebrate species carried a single homologous fragment. Additional homologies were detected in some vertebrates by reducing the hybridization stringency. Homologous fragments were also detected in DNA isolated from invertebrate species, a unicellular alga, and an archaebacterium; many of these fragments were homologous to a
Drosophila
opsin probe. These results suggest that photosensory pigments in a wide variety of species arose from a common precursor.
The E5 Transforming Gene of Bovine Papillomavirus Encodes a Small, Hydrophobic Polypeptide
Authors: Schlegel Richard , Wade-Glass Marta , Rabson Michael S. , Yang Yu-Chung
Published: October 2006

Bovine papillomavirus (BPV-1) contains two independent transforming genes that have been mapped to the E5 and E6 open reading frames (ORF's). The E5 transforming protein was identified by means of an antiserum against a synthetic peptide corresponding to the 20 COOH-terminal amino acids of the E5 ORF. The E5 polypeptide is the smallest viral transforming protein yet characterized; it had an apparent size of 7 kilodaltons. The transforming polypeptide is encoded entirely within the second half of the E5 ORF and its predicted amino acid composition is very unusual; 68% of the amino acids are strongly hydrophobic and 34% are leucine. Cell fractionation studies localized this polypeptide predominantly to cellular membranes.
A Genetic Approach to Promoter Recognition During trans Induction of Viral Gene Expression
Authors: Coen Donald M. , Weinheimer Steven P. , McKnight Steven L.
Published: October 2006

Viral infection of mammalian cells entails the regulated induction of viral gene expression. The induction of many viral genes, including the herpes simplex virus gene encoding thymidine kinase (tk), depends on viral regulatory proteins that act in trans. Because recognition of the
tk
promoter by cellular transcription factors is well understood, its trans induction by viral regulatory proteins may serve as a useful model for the regulation of eukaryotic gene expression. A comprehensive set of mutations was therefore introduced into the chromosome of herpes simplex virus at the
tk
promoter to directly analyze the effects of promoter mutations on
tk
transcription. The promoter domains required for efficient
tk
expression under conditions of trans induction corresponded to those important for recognition by cellular transcription factors. Thus, trans induction of
tk
expression may be catalyzed initially by the interaction of viral regulatory proteins with cellular transcription factors.
Differentiating Limb Tissue Affects Neurite Growth in Spinal Cord Cultures
Authors: Pollack Emanuel D. , Leibig Veronica
Published: October 2006

Limb bud mesenchyme enhances and directs the growth of tadpole spinal cord nerve fibers in tissue culture. This effect on elongating neurites may involve alterations in nerve-substratum interactions by the presence of undifferentiated target tissues. The relationship between nerve fibers and their potential innervation sites can explain directed nerve growth to the developing limb.
Synthesis of a Site-Specific DNA-Binding Peptide
Authors: Bruist Michael F. , Horvath Suzanna J. , Hood Leroy E. , Steitz Thomas A. , Simon Melvin I.
Published: October 2006

The Hin recombinase binds to specific sites on DNA and mediates a recombination event that results in DNA inversion. In order to define the DNA-binding domain of the Hin protein two peptides 31 and 52 amino acids long were synthesized. Even though the 31mer encompassed the sequence encoding the putative helix-coil-helix-binding domain, it was not sufficient for binding to the 26-base pair DNA crossover site. However, the 52mer specifically interacted with the site and also effectively inhibited the Hin-mediated recombination reaction. The 52mer bound effectively to both the 26-base pair complete site and to a 14-base pair "half site." Nuclease and chemical protection studies with the 52mer helped to define the DNA base pairs that contributed to the specificity of binding. The synthetic peptide provides opportunities for new approaches to the study of the nature of protein-DNA interaction.
Stable Integration and Expression of a Bacterial Gene in the Mosquito
Anopheles gambiae
Authors: Miller Louis H. , Sakai Richard K. , Romans Patricia , Gwadz Robert W. , Kantoff Philip , Coon Hayden G.
Published: October 2006

Foreign DNA was successfully introduced into the germline of the African mosquito vector of malaria
Anopheles gambiae
. Stable integration of genes into the germlines of insects had been achieved previously only in
Drosophila melanogaster
and related species and required the use of the P element transposon. In these experiments with
Anopheles gambiae
, the plasmid pUChsneo was used, which contains the selectable marker neo gene flanked by P element inverted repeats. Mosquitoes injected with this plasmid were screened for resistance to the neomycin analog G-418. A single event of plasmid insertion was recovered. Integration appears to be stable and, thus far, resistance to G-418 has been expressed for eight generations. The transformation event appears to be independent of P.
Intervacuole Exchange in the Yeast Zygote: A New Pathway in Organelle Communication
Authors: Weisman Lois S. , Wickner William
Published: October 2006

A new pathway of vesicle traffic between organelles has been identified. The vacuoles (lysosomes) of
Saccharomyces cerevisiae
zygotes rapidly exchange their contents at a specific point in the cell cycle. With the use of fluorescence microscopy, "tracks" were observed that connect the original parental vacuoles to the newly forming bud vacuoles. These observations suggest that vacuole-derived vesicles rapidly move along the tracks in both directions, equilibrating vacuole contents. This rapid vesicle movement may be responsible for vacuole formation in newly developing cells.
α
1
-Antitrypsin: The Presence of Excess Mannose in the Z Variant Isolated from Liver
Authors: Hercz Albert , Katona Emil , Cutz Ernest , Wilson James R. , Barton Marcela
Published: October 2006

The Z variant of α
1
-antitrypsin was isolated by a new technique from the liver of a patient homozygous for the Z allele of the protease inhibitor locus. The material was homogeneous and antigenically competent but had no protease inhibiting capacity. An interesting correlation was found between the subcellular localization and the carbohydrate composition of the Z variant from liver. Carbohydrate analysis of this glycoprotein showed an absence of galactose and sialic acid, an appreciable decrease in
N
-acetylglucosamine, and an almost twofold increase in mannose residues. These data indicate a considerable slowdown in the processing of the oligosaccharides of liver Z variant. In spite of the absence of sialyl residues, the liver Z variant was microheterogeneous by analytical isoelectric focusing. The isoproteins of liver Z variant coincided with those of asialo M variant in the focusing field.
Study of Aldose Reductase Inhibition in Intact Lenses by
13
C Nuclear Magnetic Resonance Spectroscopy
Authors: Williams W. F. , Odom J. D.
Published: October 2006

Carbon-13 nuclear magnetic resonance spectroscopy has been used in the study of glucose metabolism, specifically aldose reductase inhibition, in intact rabbit lenses maintained in organ culture. This technique provides an effective method of screening potential inhibitors of aldose reductase under conditions that more closely approximate in vivo conditions than do earlier methods. The aspirin substitutes acetaminophen and ibuprofen were studied as aldose reductase inhibitors and were found to be effective in reducing sorbitol accumulation in lenses exposed to high glucose stress. Results of this work with various inhibitors of aldose reductase are discussed in terms of lens metabolism and implications regarding diabetic complications such as cataract formation.
Induction of Altered c-
src
Product During Neural Differentiation of Embryonal Carcinoma Cells
Authors: Lynch Sally A. , Brugge Joan S. , Levine J. M.
Published: October 2006

The expression of the cellular
src
gene product pp60

c-
src

was examined in an embryonal carcinoma cell line that differentiates in vitro into neuronlike cells after being treated with retinoic acid. Quantitative and qualitative changes in c-
src
expression accompanied the events associated with neuronal differentiation. The levels of pp60

c-
src

increased 8- to 20-fold during the period when the cells elaborated neuritic processes and expressed neuron-specific proteins. The electrophoretic mobility of pp60

c-
src

induced in these cells was retarded in comparison with that in untreated cells or in treated cells before neurite elaboration. The shift in electrophoretic mobility was due to an alteration in the amino terminal 16,000 daltons of pp60

c-
src

and similar to an alteration of c-
src
protein found in neural tissues and in pure primary cultures of neuronal cells. These results indicate that expression of pp60

c-
src

induced by retinoic acid in these embryonal carcinoma cells mimics the expression of c-
src
in developing neurons. Therefore, this embryonal carcinoma cell line provides a model system to investigate the function of the
src
protein in neuronal differentiation.
Synthesis of a Sequence-Specific DNA-Cleaving Peptide
Authors: Sluka James P. , Horvath Suzanna J. , Bruist Michael F. , Simon Melvin I. , Dervan Peter B.
Published: October 2006

A synthetic 52-residue peptide based on the sequence-specific DNA-binding domain of Hin recombinase (139-190) has been equipped with ethylenediaminetetraacetic acid (EDTA) at the amino terminus. In the presence of Fe(II), this synthetic EDTA-peptide cleaves DNA at Hin recombination sites. The cleavage data reveal that the amino terminus of Hin(139-190) is bound in the minor groove of DNA near the symmetry axis of Hin recombination sites. This work demonstrates the construction of a hybrid peptide combining two functional domains: sequence-specific DNA binding and DNA cleavage.
Naturally Occurring Antihormones: Secretion of FSH Antagonists by Women Treated with a GnRH Analog
Authors: Dahl Kristine D. , Bicsak Thomas A. , Hsueh Aaron J. W.
Published: October 2006

Follicle-stimulating hormone (FSH) is a glycoprotein essential for gonadal development and steroidogenesis. Recent studies suggest that deglycosylation of FSH results in the formation of antagonistic proteins that are capable of binding to gonadal receptors but that are devoid of bioactivity. Treatment of hypogonadal women with an antagonist of gonadotropin-releasing hormone substantially decreased serum FSH bioactivity with minimal changes in immunoreactivity. Chromatofocusing and size fractionation of the serum samples indicated the secretion of immunoreactive FSH isoforms that are devoid of bioactivity but that are capable of blocking FSH action in ovarian granulosa cells. These findings provide the first demonstration of naturally occurring circulating antihormones. These FSH antagonists may play an important role in the physiology and pathophysiology of the gonads.
H-Y Antigen: Behavior and Function
Authors: Silvers Willys K. , Wachtel Stephen S.
Published: October 2006

The factors are reviewed which affect the expression of H-Y antigen, a cell surface component that has been extensively analyzed in mice but which may be ubiquitous in all vertebrates. The phylogenetic stability of this antigen and its association with the Y chromosome indicate an important role in primary sex determination.
Neonatal Hepatitis Induced by α
1
-Antitrypsin: a Transgenic Mouse Model
Authors: Dycaico Mark J. , Grant Seth G. N. , Felts Katherine , Nichols W. Stephen , Geller Stephen A. , Hager Jeffrey H. , Pollard Amy J. , Kohler Steven W. , Short Heidi P. , Jirik Frank R. , Hanahan Douglas , Sorge Joseph A.
Published: October 2006

Transgenic mouse lineages were established that carry the normal (M) or mutant (Z) alleles of the human α
1
-antitrypsin (α
1
-Pi) gene. All of the α
1
-Pi transgenic mice expressed the human protein in the liver, cartilage, gut, kidneys, lymphoid macrophages, and thymus. The human M-allele protein was secreted normally into the serum. However, the human Z-allele protein accumulated in several cell types, but particularly in hepatocytes, and was found in serum in tenfold lower concentrations than the M-allele protein. Mice in one lineage carrying the mutant Z allele expressed high levels of human α
1
-Pi RNA and displayed significant runting (50% of normal weight) in the neonatal period. This lineage was found to have α
1
-Pi-induced liver pathology in the neonatal period, concomitant with the accumulation of human Z protein in diastase-resistant cytoplasmic globules that could be revealed in the Periodic acid-Schiff reaction (PAS). The phenotype of mice in the strain expressing high levels of the Z allele is remarkably similar to human neonatal hepatitis, and this strain may prove to be a useful animal model for studying this disease.
Aldolase Activity of a
Plasmodium falciparum
Protein with Protective Properties
Authors: Certa Ulrich , Ghersa Paola , Döbeli Heinz , Matile Hugues , Kocher Hans P. , Shrivastava Indresh K. , Shaw Alan R. , Perrin Luc H.
Published: October 2006

Immunization with a 41-kilodalton blood stage antigen (p41) of
Plasmodium falciparum
induces immunity to malaria in monkeys. However, antigenic polymorphism and repetitive amino acids commonly found in protective antigens complicate vaccine development. The gene encoding p41 has now been cloned and analyzed. Sequencing and hybridization studies revealed that the gene structure is highly conserved in 14 parasite isolates from three continents. This finding and the lack of repetitive amino acids in the translated DNA sequence may indicate that p41 has an essential function. In this study the protein was found to be 60 percent homologous to the key glycolytic enzyme aldolase from vertebrates, and the affinity-purified p41 protein from parasites showed aldolase activity.
Water-to-Air Transfer of Virus
Authors: Baylor Edward R. , Peters Virginia , Baylor Martha B.
Published: October 2006

Bubbles rising through suspensions of the bacteriophages T2 and T4 and ofEscherichia coliadsorb and eject these particles in droplets that are formed when the bubbles burst. The concentration of the viruses in ejected droplets, determined from electron microscopy, exceeded the suspension concentration by 50 times. Similar results were obtained forEscherichia coli. The viability of some of the adsorbed particles was established by biological counts.
Combinatorial Cassette Mutagenesis as a Probe of the Informational Content of Protein Sequences
Authors: Reidhaar-Olson John F. , Sauer Robert T.
Published: October 2006

A method of combinatorial cassette mutagenesis was designed to readily determine the informational content of individual residues in protein sequences. The technique consists of simultaneously randomizing two or three positions by oligonucleotide cassette mutagenesis, selecting for functional protein, and then sequencing to determine the spectrum of allowable substitutions at each position. Repeated application of this method to the dimer interface of the DNA-binding domain of λ repressor reveals that the number and type of substitutions allowed at each position are extremely variable. At some positions only one or two residues are functionally acceptable; at other positions a wide range of residues and residue types are tolerated. The number of substitutions allowed at each position roughly correlates with the solvent accessibility of the wild-type side chain.
Parallel Stranded DNA
Authors: van de Sande Johan H. , Ramsing Niels B. , Germann Markus W. , Elhorst Wim , Kalisch Bernd W. , v. Kitzing Eberhard , Pon Richard T. , Clegg Robert C. , Jovin Thomas M.
Published: October 2006

A series of four hairpin deoxyoligonucleotides was synthesized with a four-nucleotide central loop (either C or G) flanked by the complementary sequences d(T)
10
and d(A)
10
. Two of the molecules contain either a 3′-p-3′ or 5′-p-5′ linkage in the loop, so that the strands in the stem have the same, that is, parallel (ps) polarity. The pair of reference oligonucleotides have normal phosphodiester linkages throughout and antiparallel (aps) stem regions. All the molecules adopt a duplex helical structure in that (i) the electrophoretic mobilities in polyacrylamide gels of the ps and aps oligomers are similar. (ii) The ps hairpins are substrates for T4 polynucleotide kinase, T4 DNA ligase, and
Escherichia coli
exonuclease III. (iii) Salt-dependent thermal transitions are observed for all hairpins, but the ps molecules denature 10°C lower than the corresponding aps oligomers. (iv) The ultraviolet absorption and circular dichroism spectra are indicative of a base-paired duplex in the stems of the ps hairpins but differ systematically from those of the aps counterparts. (v) The bis-benzimidazole drug Hoechst-33258, which binds in the minor groove of B-DNA, exhibits very little fluorescence in the presence of the ps hairpins but a normal, enhanced emission with the aps oligonucleotides. In contrast, the intercalator ethidium bromide forms a strongly fluorescent complex with all hairpins, the intensity of which is even higher for the ps species. (vi) The pattern of chemical methylation is the same for both the ps and aps hairpins. The combined results are consistent with the prediction from force field analysis of a parallel stranded right-handed helical form of d(A)

n

⋅d(T)

n

with a secondary structure involving reverse Watson-Crick base pairs and a stability not significantly different from that of the B-DNA double helix. Models of the various hairpins optimized with force field calculations are described.
Correction of Murine β-Thalassemia by Gene Transfer into the Germ Line
Authors: Costantini Frank , Chada Kiran , Magram Jeanne
Published: October 2006

A murine β-thalassemia was corrected by the transfer of cloned β-globin genes into the mouse germ line. The cloned mouse β
maj
-globin gene or the cloned human β-globin gene was introduced into mice deficient in β-globin synthesis because of a deletion of the β
maj
-globin gene. Both introduced genes produced functional β-globin chains, leading to a reduction in one case, and elimination in another case, of the anemia and associated abnormalities of the red blood cells.
Synaptic Potentials Effect the Release of Transmitter from Locust Nonspiking Interneurons
Authors: Burrows M.
Published: October 2006

An excitatory synaptic potential in a local nonspiking interneuron of a locust is able to effect the release of chemical transmitter. The consequence is that a discrete inhibitory synaptic potential is evoked in an identified postsynaptic motoneuron. These local interactions between interneurons and motoneurons are of behavioral significance in that they ensure the correct operation of a resistance reflex.
A Fertility Reaction to a Historical Event: Southern White Birthrates and the 1954 Desegregation Ruling
Authors: Rindfuss Ronald R. , Reed John Shelton , St. John Craig
Published: October 2006

On 17 May 1954 the Supreme Court, in its decision in
Brown v. Board of Education
, declared de jure segregation of the public schools to be unconstitutional. It is argued here that a consequence of that decision was a decline in childbearing among white Southerners. In the nation as a whole, period fertility rates increased between 1954 and 1955, but in 9 of the 11 former Confederate states they decreased. Further analysis shows that these Southern fertility decreases began about 12 months after the Supreme Court decision. This variation in behavior in reaction to a historical event has important implications for the explanation and prediction of fertility.
Leader Peptidase of
Escherichia coli
: Critical Role of a Small Domain in Membrane Assembly
Authors: Dalbey Ross E. , Wickner William
Published: October 2006

Leader peptidase spans the
Escherichia coli
plasma membrane with its amino-terminal domain facing the cytoplasm and its carboxyl terminus facing the periplasm. It is made without a cleavable leader sequence. The three apolar domains near the amino terminus of the peptidase are candidates for internal "signal sequences" and they anchor the protein to the lipid bilayer. Oligonucleotide-directed deletion was used to show that only the second domain has an essential function in membrane assembly. While this second apolar domain is crucial for membrane assembly, its continued function when disrupted by arginine suggests that its apolar character per se is not its only important feature.
Localization of Inorganic Phosphate in the Pancreatic B Cell and Its Loss on Glucose Stimulation
Authors: Freinkel N. , Pedley K. C. , Wooding P. , Dawson R. M. C.
Published: October 2006

Perifusion experiments have shown that there is a discharge of inorganic phosphate into the medium when insulin secretion from isolated islets is stimulated by glucose. Histochemical and microprobe examination of resting pancreatic islets in the electron microscope shows a specific accumulation of inorganic phosphate adjacent to the plasmalemma and nucleolus of the B (beta) cells. This phosphate is lost from the cells during secretory stimulation of islets with high concentrations of glucose.
Changes in the Distribution of American Family Incomes, 1947 to 1984
Authors: Levy Frank
Published: October 2006

The American family income distribution now lies at the center of several controversies. Some observers argue that the American middle class is vanishing, but U.S. census income statistics show income inequality has not changed appreciably since 1947. A second controversy involves whether average living standards have risen or fallen since the major oil price increase of 1973-74. These controversies can be partially resolved by understanding the sharp slowdown in the growth of workers' wages which occurred after 1973 and the demographic trends which kept per capita living standards rising despite stagnant wages, including more working women and low birthrates.
Chemistry of Pheromone and Hormone Metabolism in Insects
Authors: Prestwich Glenn D.
Published: October 2006

Chemical evidence is needed in both insect endocrinology and sensory physiology to understand hormone and pheromone action at the molecular level. Radiolabeled pheromones and hormones have been synthesized and used to identify binding and catabolic proteins from insect tissues. Chemically modified analogs, including photoaffinity labels and enzyme inhibitors, are among the tools used to covalently modify the specific acceptor or catalytic sites. Such targeted agents can also provide leads for the design of growth and mating disruptants by allowing manipulation of the physiologically important interactions of the chemical signals with macromolecules.
Estrogen-Induced Factors of Breast Cancer Cells Partially Replace Estrogen to Promote Tumor Growth
Authors: Dickson Robert B. , McManaway Mary E. , Lippman Marc E.
Published: October 2006

The hormone 17β-estradiol acts through its receptor system to induce MCF-7 human breast cancer cells to form tumors in athymic mice. In vitro studies have identified the production of estrogen-induced growth factors from MCF-7 cells that may have a role in growth control. These induced growth factors were sufficient to stimulate MCF-7 tumor growth in ovariectomized athymic mice, thus partially replacing estradiol. Growth factors may act as estrogen-induced "second messengers" in estrogen-responsive growth of human breast cancer.
Interferon Inhibits the Establishment of Competence in G
0
/S-phase Transition
Authors: Lin Stanley L. , Kikuchi T. , Pledger W. J. , Tamm Igor
Published: October 2006

Addition of mouse interferon-α/β (IFN) to confluent, quiescent BALB/c 3T3 (clone A31) mouse fibroblasts resulted in a block or delay in serum-induced activation of the cell cycle. It was necessary to add IFN within 6 hours after serum stimulation to inhibit nuclear labeling with [
3
H]thymidine. This is consistent with the time required for platelet-derived growth factor (PDGF) to induce cells to become competent to respond to additional growth factors present in platelet-poor plasma. Simultaneous addition of IFN with PDGF inhibited the PDGF-induced synthesis of a 29-kilodalton and a 35-kilodalton protein that normally occurs within 1 hour after PDGF addition. IFN also suppressed the general increase in protein synthesis that occurs by the fifth hour after PDGF addition. These results show that IFN antagonizes the action of PDGF, thereby interfering with the activation of G
0
cells for G
1
traverse and S-phase entry.
A Novel Human Gene Closely Related to the
abl
Proto-Oncogene
Authors: Kruh Gary D. , King C. Richter , Kraus Matthias H. , Popescu Nicolae C. , Amsbaugh Suzanne C. , McBride Wesley O. , Aaronson Stuart A.
Published: October 2006

A DNA sequence related to the
abl
proto-oncogene was identified in human placenta. Molecular cloning and nucleotide sequence analysis revealed two putative exons whose predicted amino acid sequence was most homologous to the corresponding sequences of c-
abl
and v-
abl
but was related to other tyrosine kinase genes as well. The new sequence was localized by in situ hybridization and somatic cell genetic analysis to human chromosome 1q24-25, which differs from the location of any previously identified tyrosine kinase gene. The detection of a novel 12-kb transcript by this gene in human normal and tumor cells establishes it as a new member of the tyrosine kinase family that is closely related to but distinct from c-
abl
.
Lipid Domains in Fluid Membranes: A Quick-Freeze Differential Scanning Calorimetry Study
Authors: Melchior Donald L.
Published: October 2006

The application of rapid-freezing techniques to differential scanning calorimetry (DSC) provides a new approach for understanding the organization of lipids in biomembranes. Use of quick-freeze DSC on membranes of mixed lipid composition supports the existence of nonrandom distributions of lipids (domains) in fluid bilayers. In addition to allowing investigations on the organization of lipids in fluid bilayers, the quick-freeze technique now allows calorimetric studies to be carried out on mammalian membranes which, because of their high cholesterol content, have not been previously amenable to study by DSC.
Restoration of LDL Receptor Activity in Mutant Cells by Intercellular Junctional Communication
Authors: Hobbie Lawrence , Kingsley David M. , Kozarsky Karen F. , Jackman Robert W. , Krieger Monty
Published: October 2006

Exchange of small molecules between cells through intercellular junctions is a widespread phenomenon implicated in many physiological and developmental processes. This type of intercellular communication can restore the activity of low-density lipoprotein (LDL) receptors in mammalian cells that are deficient in the enzyme UDP-Gal/UDP-GalNAc 4-epimerase. Pure cultures of the 4-epimerase mutant are unable to synthesize normal carbohydrate chains on LDL receptors and many other glycoproteins and therefore do not express LDL receptor activity. When these cells are cocultivated with cells expressing normal 4-epimerase activity, the structure and function of LDL receptors are restored to normal by the transfer of this enzyme's products through intercellular junctions. The formation of functional junctions does not require normal glycosylation of membrane proteins. Because many convenient assays and selections for LDL receptor activity are available, this mutant can provide a powerful new tool for biochemical and genetic studies of intercellular junctional communication.
Transition from B to Z DNA: Contribution of Internal Fluctuations to the Configurational Entropy Difference
Authors: Irikura K. K. , Tidor B. , Brooks B. R. , Karplus M.
Published: October 2006

The internal motions of the double-stranded DNA oligomer (dCdG)
3
(dC, deoxycytidylate; dG, deoxyguanylate) in the B and Z forms have been calculated in the harmonic approximation. A complete vibrational analysis has been made, and the resulting normal mode frequencies have been used to evaluate the vibrational entropy of B and Z DNA. The greater flexibility of the B DNA hexamer leads to an entropic stabilization relative to the stiffer Z DNA hexamer of 22 calories per mole per kelvin at 300 K. The calculated value is of the same order as that (21 to 27 calories per mole per kelvin) obtained from nuclear magnetic resonance measurements on the methylated duplexes (m
5
dCdG)
3
and (dCdGm
5
dCdGdCdG). This result demonstrates the importance of internal motions, which have been neglected in earlier studies of the transition from B to Z DNA, in the stability of different nucleic acid conformers.
Systematic Variation in DNA Length Yields Highly Ordered Repressor-Operator Cocrystals
Authors: Jordan Steven R. , Whitcombe Timothy V. , Berg Jeremy M. , Pabo Carl O.
Published: October 2006

Crystals have been grown that contain the operator-binding domain of the λ repressor and the λ operator site O
L
1. Crystallization conditions were tested with a set of DNA fragments, ranging in length from 17 to 23 base pairs. The best crystals were grown with a 20-base pair DNA fragment. These crystals have space-group symmetry P2
1
, with unit cell dimensions a = 37.1 Å, b = 68.8 Å, c = 56.8 Å, and a β angle of 91.5°. They diffracted to at least 2.5 Å resolution. High resolution data from these crystals should allow the direct determination of how a repressor recognizes its operator site.
Active T-Cell Receptor Genes Have Intron Deoxyribonuclease Hypersensitive Sites
Authors: Bier Ethan , Hashimoto Yasuhiro , Greene Mark I. , Maxam Allan M.
Published: October 2006

The T-cell receptor β-chain gene has a nuclease hypersensitive site in several kinds of T cells, which does not appear in B cells expressing immunoglobulins. Conversely, the κ immunoglobulin gene shows a known hypersensitive site at its enhancer element in B cells, as expected, but this site is absent in T cells. As is the case with immunoglobulin genes, the T-cell receptor site lies within the gene, in the intron separating joining and constant region segments. These nuclease hypersensitive DNA configurations in the introns of active T-cell receptor and immunoglobulin genes may arise from control elements that share ancestry but have diverged to the extent that each normally acts only in lymphoid cells which use the proximal gene product.
Karyotype Analysis of
Leishmania
Species and Its Use in Classification and Clinical Diagnosis
Authors: Giannini Suzanne Holmes , Schittini Mario , Keithly Jan S. , Warburton Peter W. , Cantor Charles R. , Van der Ploeg Lex H. T.
Published: October 2006

Chromosomes of four species of
Leishmania
represented by ten different geographic isolates were analyzed by pulsed field gradient gel electrophoresis (PFG) to assess chromosome stability in these parasitic protozoans. Among different geographic isolates of the same subspecies, more than two-thirds of chromosomes had similar sizes, ethidium bromide staining intensities, and locations of α,β-tubulin genes. However, among New World
Leishmania
, members of different species or subspecies have fewer than one-third of their chromosomes in common. Therefore, PFG karyotypes of
Leishmania
exhibit intraspecific variability similar to that reported for other parasitic protozoans. The greater similarities of the karyotypes of members of the same
Leishmania
subspecies may indicate that they represent valid taxa. These similarities also allowed the use of PFG in clinical diagnosis for rapid and accurate typing of patient isolates.
Multiple Organ Carcinogenicity of 1,3-Butadiene in B6C3F1Mice After 60 Weeks of Inhalation Exposure
Authors: Huff J. E. , Melnick R. L. , Solleveld H. A. , Haseman J. K. , Powers M. , Miller R. A.
Published: October 2006

Groups of 50 male and 50 female B6C3F1mice were exposed 6 hours per day, 5 days per week, for 60 to 61 weeks to air containing 0, 625, or 1250 parts per million 1,3-butadiene. These concentrations are somewhat below and slightly above the Occupational Safety and Health Administration standard of 1000 parts per million for butadiene. The study was designed for 104-week exposures but had to be ended early due to cancer-related mortality in both sexes at both exposure concentrations. There were early induction and significantly increased incidences of hemangiosarcomas of the heart, malignant lymphomas, alveolar-bronchiolar neoplasms, squamous cell neoplasms of the forestomach in males and females and acinar cell carcinomas of the mammary gland, granulosa cell neoplasms of the ovary, and hepatocellular neoplasms in females. Current workplace standards for exposure to butadiene should be reexamined in view of these findings.
Heat Generated by the Dark-Adapted Squid Retina in Response to Light Pulses
Authors: Tasaki Ichiji , Nakaye Toshio
Published: October 2006

A rapid increase in the temperature of the dark-adapted squid retina evoked by a brief light pulse was detected with a pyroelectric detector. The amount of heat generated by the retina in response to a pulse of blue light of moderate intensity was far greater than that produced by direct conversion of the stimulating light by the retinal pigments into thermal energy. D-Glucose in the medium was required to maintain the ability of the retina to produce light-evoked thermal responses.
Isolation of Eukaryotic DNA Fragments Containing Structural Genes and the Adjacent Sequences
Authors: Georgiev G. P. , Ilyin Yu. V. , Ryskov A. P. , Tchurikov N. A. , Yenikolopov G. N. , Gvozdev V. A. , Ananiev E. V.
Published: October 2006

In
Drosophila melanogaster
structural genes are located close to moderately reiterated sequences. One of the clones obtained contains the DNA related to intercalary heterochromatin of
D. melanogaster
. These are individual differences in the distribution of genetic material in polytenic chromosomes of different stocks of
D. melanogaster
. The techniques that allow isolation of DNA fragments containing structural genes at the beginning, in the middle, or the end of the coding strand have been elaborated.
Diversity of Circumsporozoite Antigen Genes from Two Strains of the Malarial Parasite
Plasmodium knowlesi
Authors: Sharma Shobhona , Svec Pamela , Mitchell G. H. , Godson G. Nigel
Published: October 2006

The complete nucleotide sequence of the coding region of the circumsporozoite antigen gene (CS gene) of the Nuri strain of the malarial parasite
Plasmodium knowlesi
is presented. The gene from the Nuri strain exhibits a novel form of sequence diversity when compared to the CS gene from the H strain. Instead of the 12 tandem repeating 36-base pair units of the H strain, the Nuri strain contains 16 tandem repeating 27-base pair units of a different nucleotide sequence that encodes a different repeating peptide. In contrast, the 5′ and 3′ coding and noncoding sequences flanking the repeats are 98 percent conserved in both strains.
Relation of Spectral Types to Oil Droplets in Cones of Turtle Retina
Authors: Ohtsuka Teruya
Published: October 2006

The spectral sensitivities and color of oil droplets of cone photoreceptors in the retina of the red-eared turtle (
Pseudemys scripta elegans
) were investigated by intracellular recording and injections of Lucifer yellow dye. Six morphological types of cones could be distinguished by the color of the oil droplets located in the outermost inner segments. Single cones containing either red or pale green oil droplets were sensitive to red light, cones with yellow oil droplets to green, and cones with clear oil droplets to blue. Contrary to previous reports, both principal and accessory members of double cones were sensitive to red, and no diffusion of dye was detected between the two apposed members. Thus, the oil droplets provide a reliable morphological basis for further investigation of the neuroanatomical networks underlying the processing of color information in the vertebrate retina.
Ascorbic Acid and the Behavioral Response to Haloperidol: Implications for the Action of Antipsychotic Drugs
Authors: Rebec George V. , Centore Josephine M. , White Laura K. , Alloway Kevin D.
Published: October 2006

Haloperidol, a widely used antipsychotic drug, was tested for its ability to block the behavioral response to amphetamine and to elicit catalepsy in rats treated with saline or ascorbic acid (1000 milligrams per kilogram of body weight). By itself, ascorbic acid failed to exert significant behavioral effects, but it enhanced the antiamphetamine and cataleptogenic effects of haloperidol (0.1 or 0.5 milligrams per kilogram). These results, combined with a growing body of biochemical evidence, suggest that ascorbic acid plays an important role in modulating the behavioral effects of haloperidol and related antipsychotic drugs.
Covalent Labeling of the Tetrodotoxin Receptor in Excitable Membranes
Authors: Guillory Richard J. , Rayner Martin D. , D'Arrigo Joseph S.
Published: October 2006

A photoaffinity labeling technique is described by which a tetrodotoxin analog is covalently bound to receptor sites associated with the sodium pores of excitable membranes. The biological activity of the toxin analog is retained after the covalent binding reaction.
Erythrocyte Carbonic Anhydrase I: Inherited Deficiency in Humans
Authors: Kendall Alan G. , Tashian Richard E.
Published: October 2006

The virtually complete absence of erythrocyte carbonic anhydrase I is reported in three members of a family from the Greek island of Icaria. Two members with moderately reduced levels are believed to be heterozygous for the deficiency. There are no obvious hematological or renal consequences of the severe deficiency state.
Thyrotropin-Releasing Hormone: Abundance in the Skin of the Frog,
Rana pipiens
Authors: Jackson Ivor M. D. , Reichlin Seymour
Published: October 2006

Thyrotropin-releasing hormone, a hypothalamic tripeptide that stimulates the secretion of pituitary thyroid-stimulating hormone in mammalian species and is widely distributed throughout the brain of vertebrates, is present in the skin of the frog (
Rana pipiens
) in concentrations twice that found in the hypothalamus of this amphibian. A skin extract shows biologic activity appropriate to its immunoreactive content. Apart from the brain and spinal cord, immunoreactive thyrotropin-releasing hormone is found only in the blood and retina in significant concentrations. The results imply that frog skin is a huge endocrine organ that synthesizes and secretes this hormone.
Flatworm Control of Mosquito Larvae in Rice Fields
Authors: Case Ted J. , Washino Robert K.
Published: October 2006

We describe some flatworms (some in the genus
Mesostoma
) that kill mosquito larvae and may account for the variability in the population densities of
Culex tarsalis
and
Anopheles freeborni
in rice fields. When mosquito larvae brush against these worms, the larvae immediately become paralyzed and die. When
C. tarsalis
larvae are placed inside floating cages that exclude flatworms (50-micromter mesh), there is a fourfold increase in their survival. Rice fields that have abundant mosquito populations lack flatworms. Most such fields have only recently been turned over to rice production, suggesting that the flatworms have difficulty dispersing to new fields but, once established, are able to overwinter and control mosquitoes for the subsequent years of rice production.
Nanosecond X-Ray Diffraction from Biological Samples with a Laser-Produced Plasma Source
Authors: Frankel Robert D. , Forsyth James M.
Published: October 2006

By using 4.45-angstrom radiation generated by Cl
+15
ions in a laser plasma and nanosecond exposures, low-angle x-ray diffraction patterns were obtained from dried rat spinal nerves and a powder of cholesterol. Three to four 400-picosecond, 45-joule pulses were required for the exposure. This new technique should have wide application in structural kinetic studies.
Normal Anterior Endoderm Corrects the Heart Defect in Cardiac Mutant Salamanders (
Ambystoma mexicanum
)
Authors: Lemanski Larry F. , Paulson Daniel J. , Hill Craig S.
Published: October 2006

Recessive mutant gene
c
in axolotl embryos results in an absence of heart function. Normal (+/+) anterior endoderm cultured with mutant (
c
/
c
) hearts totally corrects the defect.
Laterality for Stereognostic Accuracy of Children for Words, Shapes, and Bigrams: A Sex Difference for Bigrams
Authors: Cioffi Joseph , Kandel Gillray L.
Published: October 2006

Children identified nonsense shapes by touch better with their left hand and words better with their right hand. Bigrams were processed by boys as shapes and by girls as words, which suggests a sexual dimorphism of brain functioning for bigrams. A relative specialization of the hemisphere for stereognostic processing is also suggested, since the accuracy of identification by both hands was greater than chance for all three types of stimuli.
Dissociations Between the Effects of LSD on Behavior and Raphe Unit Activity in Freely Moving Cats
Authors: Trulson Michael E. , Jacobs Barry L.
Published: October 2006

The hypothesis that the action of hallucinogenic drugs is mediated by a depression of the activity of brain serotonergic (raphe) neurons was tested by examining the behavioral effects of
d
-lysergic acid diethylamide (LSD) while studying the activity of raphe neurons in freely moving cats. Although the results provide general support for the hypothesis, there were several important dissociations. (i) Low doses of LSD produced only small decreases in raphe unit activity but significant behavioral changes; (ii) LSD-induced behavioral changes outlasted the depression of raphe unit activity; and (iii) raphe neurons were at least as responsive to LSD during tolerance as they were in the nontolerant condition.
Insulin Receptor Binding in Obesity: A Reassessment
Authors: Misbin Robert I. , O'Leary J. Patrick , Pulkkinen Andrea
Published: October 2006

A defect in the binding of insulin to circulating monocytes occurs when obese patients are hospitalized and fed a liberal carbohydrate diet. Under ordinary circumstances, most obese patients have normal insulin binding despite very high concentrations of serum insulin. These results show that insulin does not necessarily regulate its own receptor in vivo—as it does in vitro.
Saccharin Metabolism and Tumorigenicity
Authors: Sweatman T. W. , Renwick A. G.
Published: October 2006

Exposure of male Charles River CD1 rats to a 5 percent saccharin diet in utero and throughout weaning, conditions associated with tumor induction, did not induce detectable metabolism (< 0.4 percent of the oral dose) of tritiated saccharin in vivo. No metabolites (< 0.06 microgram per kilogram per 24 hours) were detected in the urine of normal rats given a tracer dose. Pretreatment with 3-methylcholanthrene did not induce saccharin metabolism.
Cerebral Specialization, Writing Posture, and Motor Control of Writing in Left-Handers
Authors: Herron Jeannine , Galin David , Johnstone Jack , Ornstein Robert E.
Published: October 2006

It has been suggested that the inverted hand position of left-handers during writing indicates the left hemisphere of their brain is linguistically specialized and that the writing of these left-handers may be controlled via ipsilateral pathways. Electroencephalograph alpha asymmetry measures at central and parietal leads, as well as dichotic tests, differentiated right-handers from left-handers, but not inverters from noninverters. Electroencephalograph differences between hand posture groups did appear, but only at occipital leads during reading and writing tasks. Regardless of hand posture or speech lateralization, the right central region of the brain is significantly involved in the control of left-handed writing.
Metabolism of Americium-241 in Man: An Unusual Case of Internal Contamination of a Child and His Father
Authors: Cohen Norman , Sasso Thomas Lo , Wrenn McDonald E.
Published: October 2006

The metabolism of americium-241 has been studied during an 8-year period in an adult male and his son who, at the ages of 50 and 4 years, respectively, were accidentally and unknowingly contaminated within their home by means of inhalation. Chelation therapy with calcium trisodium pentetate was more effective in enhancing the removal of americium-241 from the child than from the father.
Dopamine Auto- and Postsynaptic Receptors: Electrophysiological Evidence for Differential Sensitivity to Dopamine Agonists
Authors: Skirboll L. R. , Grace A. A. , Bunney B. S.
Published: October 2006

The responses of dopamine cells in the substantia nigra to iontophoretically administered dopamine and intravenous apomorphine were compared to the responses of spontaneously active neurons in the caudate nucleus. Dopaminergic cells were six to ten times more sensitive to dopamine and intravenous apomorphine than 86 percent of the caudate cells tested. This differential sensitivity of dopamine auto- and postsynaptic receptors may explain the apparently paradoxical behavioral effects induced by small compared to large doses of some dopamine agonists and may provide a means of developing new types of drugs to antagonize dopaminergic influence in the central nervous system.
Differential Competition with Cytotoxic Agents: An Approach to Selectivity in Cancer Chemotherapy
Authors: Rabinowitz Marco , Uehara Yoshimasa , Vistica David T.
Published: October 2006

An approach to increasing the selectivity of cancer chemotherapeutic agents is presented in which noncytotoxic competitive substrates are used to discern the differences in structural requirements for transport of cytotoxic agents between tumor cells and a sensitive host tissue, the hematopoietic precursor cells of the bone marrow. Examples are given for two such systems, one responsible for the transport of nucleosides and another for the transport of amino acids. Cytidine is twice as effective in reducing the toxicity of showdomycin for murine bone marrow cells in culture as it is for murine L1210 leukemia cells. Conversely, homoleucine is twice as effective in reducing the toxicity of melphalan for L1210 cells as it is for bone marrow cells. These observations can serve as a basis for the development of bone marrow protective agents and for the design of cytotoxic agents that may be preferentially transported into tumor cells.