bluuebunny/crossref_metadata_2025 huggingface dataset:
The Mitochondrial Genotype Can Influence Nuclear Gene Expression in Yeast
Authors: Parikh Vandana S. , Morgan Melissa M. , Scott Rose , Clements L. Scott , Butow Ronald A.
Published: October 2006

Isochromosomal, respiratory-deficient yeast strains, such as a mit
-
, a hypersuppressive petite, and a petite lacking mitochondrial DNA, are phenotypically identical in spite of differences in their mitochondrial genomes. Subtractive hybridizations of complementary DNA's to polyadenylated RNA isolated from derepressed cultures of these strains reveal the presence of nuclear-encoded transcripts whose abundance varies not only between them and their respiratory-competent parent, but among the respiratory-deficient strains themselves. Transcripts of some nuclear-encoded mitochondrial proteins, like cytochrome c and the α and β subunits of the mitochondrial adenosine triphosphatase, whose abundance is affected by glucose or heme, do not vary. In the absence of major metabolic variables, yeast cells seem to respond to the quality and quantity of mitochondrial DNA and modulate the levels of nuclear-encoded RNA's, perhaps as a means of intergenomic regulation.
Cloning of Large Segments of Exogenous DNA into Yeast by Means of Artificial Chromosome Vectors
Authors: Burke David T. , Carle Georges F. , Olson Maynard V.
Published: October 2006

Fragments of exogenous DNA that range in size up to several hundred kilobase pairs have been cloned into yeast by ligating them to vector sequences that allow their propagation as linear artificial chromosomes. Individual clones of yeast and human DNA that have been analyzed by pulsed-field gel electrophoresis appear to represent faithful replicas of the source DNA. The efficiency with which clones can be generated is high enough to allow the construction of comprehensive libraries from the genomes of higher organisms. By offering a tenfold increase in the size of the DNA molecules that can be cloned into a microbial host, this system addresses a major gap in existing experimental methods for analyzing complex DNA sources.
Derivation of Clones Close to
met
by Preparative Field Inversion Gel Electrophoresis
Authors: Michiels Frank , Burmeister Margit , Lehrach Hans
Published: October 2006

The molecular analysis of genes identified by mutations is a major problem in mammalian genetics. As a step toward this goal, preparative field inversion gel electrophoresis (FIGE) was used to selectively isolate clones from the environment of genetically linked markers, and to select a subset of these clones containing sequences next to specific restriction sites rare in mammalian DNA. This approach has been used to generate a library highly enriched in sequences closely linked to the cystic fibrosis marker
met
. One clone derived from the end of a Not I restriction fragment containing the
met
sequence was analyzed in detail and localized within a long range map to a position 300 kilobase pairs 5′ of the
met
D sequence.
Protein-DNA Interactions in Vivo Upstream of a Cell Cycle-Regulated Human H4 Histone Gene
Authors: Pauli U. , Chrysogelos S. , Stein G. , Stein J. , Nick H.
Published: October 2006

Cell cycle-dependent histone genes are transcribed at a basal level throughout the cell cycle, with a three- to fivefold increase during early S phase. Protein-DNA interactions in the 5′ promoter region of a cell cycle-regulated human H4 histone gene have been analyzed at single-nucleotide resolution in vivo. This region contains two sites, with four potential protein-binding domains, at which the DNA is protected from reaction with dimethyl sulfate in cells and from digestion with deoxyribonuclease I in nuclei. These protein-DNA interactions persist during all phases of the cell cycle and dissociate with 0.16 to 0.2
M
sodium chloride.
Cloning of Human Mineralocorticoid Receptor Complementary DNA: Structural and Functional Kinship with the Glucocorticoid Receptor
Authors: Arriza Jeffrey L. , Weinberger Cary , Cerelli Gail , Glaser Tom M. , Handelin Barbara L. , Housman David E. , Evans Ronald M.
Published: October 2006

Low-stringency hybridization with human glucocorticoid receptor (hGR) complementary DNA was used to isolate a new gene encoding a predicted 107-kilodalton polypeptide. Expression studies demonstrate its ability to bind aldosterone with high affinity and to activate gene transcription in response to aldosterone, thus establishing its identity as the human mineralocorticoid receptor (hMR). This molecule also shows high affinity for glucocorticoids and stimulates a glucocorticoid-responsive promoter. Together the hMR and hGR provide unexpected functional diversity in which hormone-binding properties, target gene interactions, and patterns of tissue-specific expression may be used in a combinatorial fashion to achieve complex physiologic control.
The Maize Transposable Element
Ds
Is Spliced from RNA
Authors: Wessler Susan R. , Baran George , Varagona Marguerite
Published: October 2006

In some instances, insertion of maize transposable elements into exons does not result in the total loss of enzymatic activity. In other instances, messenger RNAs of wild-type size are encoded by genes known to contain the maize transposable element
Dissociation
(
Ds
) in exons. To understand how
Ds
is processed from RNA, a study was made of transcripts encoded by two alleles of the maize
waxy
(
wx
) gene containing
Ds
insertions in exon sequences. The analysis was carried out in strains where the
Ds
element could not excise from the
wx
gene. Despite insertions of 4.3- and 1.5-
Ds
elements, the predominant transcripts encoded by these two genes were wild type in size. For both alleles, DNA sequencing of complementary DNAs revealed that the
Ds
elements had been spliced in a similar manner. Splicing was accomplished by the utilization of multiple 5′ donor splice sites in the
Ds
termini and a 3′ acceptor site within the
wx
gene adjacent to the
Ds
element. The net effect in both cases was the removal of most of the
Ds
element from the messenger RNA.
Hormonal Basis for Breeding Behavior in Female Frogs: Vasotocin Inhibits the Release Call of
Rana pipiens
Authors: Diakow Carol
Published: October 2006

Inhibition of the release call in gravid female frogs facilitates maintenance of the male's clasp so that oviposition and spawning can occur. Arginine-8 vasotocin inhibits the release call by causing an accumulation of water and internal pressure.
Neuronal Cytomechanics: The Actin-Based Motility of Growth Cones
Authors: Smith Stephen J.
Published: October 2006

The patterns of synaptic connection that underlie brain function depend on the elaborate forms characteristic of neurons. It is therefore a central goal of neuroscience to understand the molecular basis for neuronal shape. Neuronal pathfinding during development is one major determinant of neuronal shape: growing nerve axons and dendrites must navigate, branch, and locate targets in response to extracellular cue molecules within the embryo. The leading tips of growing nerve processes, structures known as growth cones, contain especially high concentrations of the ubiquitous mechanochemical protein actin. Force generation involving this cytoskeletal molecule appears to be essential to the ability of growing nerve fibers to respond structurally to extracellular cues. New results from electronically enhanced light microscopy of living growth cones are helping to show how actin-based forces guide neurite growth and synapse formation.
Perspectives on Cognitive Neuroscience
Authors: Churchland Patricia S. , Sejnowski Terrence J.
Published: October 2006

How is it that we can perceive, learn and be aware of the world? The development of new techniques for studying large-scale brain activity, together with insights from computational modeling and a better understanding of cognitive processes, have opened the door for collaborative research that could lead to major advances in our understanding of ourselves.
Indirect Observation by
13
C NMR Spectroscopy of a Novel CO
2
Fixation Pathway in Methanogens
Authors: Evans Jeremy N. S. , Tolman Cynthia J. , Roberts Mary F.
Published: October 2006

High-field carbon-13 nuclear magnetic resonance (NMR) spectroscopy has been used to monitor the isotopic dilution of doubly carbon-13-labeled precursors for 2,3-cyclopyrophosphoglycerate, a novel primary metabolite that occurs in certain methanogens. A unique carbon dioxide fixation pathway that gives rise to asymmetric labeling of acetyl coenzyme A has been demonstrated in
Methanobacterium thermoautotrophicum
. The effect of selected metabolic inhibitors on the labeled species in the pathway has been examined by NMR. These techniques establish a general, sensitive method for the delineation of convergent biosynthetic pathways.
Trypanosoma cruzi
Infection Inhibited by Peptides Modeled from a Fibronectin Cell Attachment Domain
Authors: Ouaissi M. A. , Cornette J. , Afchain D. , Capron A. , Gras-Masse H. , Tartar A.
Published: October 2006

The mechanism by which
Trypanosoma cruzi
, the protozoan parasite that causes Chagas' disease, becomes attached to mammalian cells is not well understood. Fibronectin is thought to participate in the attachment, and in this study the region of fibronectin that interacts with the surface receptors of
T. cruzi
trypomastigotes was investigated by testing the binding of the amino acid sequence Arg-Gly-Asp-Ser, corresponding to the cell attachment site of fibronectin to
T. cruzi
trypomastigotes. Peptides with the sequence Arg-Gly-Asp-Ser, but not Arg-Phe-Asp-Ser, Arg-Phe-Asp-Ser-Ala-Ala-Arg-Phe-Asp, Ser-Lys-Pro, Glu-Ser-Gly, or Ala-Lys-Thr-Lys-Pro, bound to the parasite surface and inhibited cell invasion by the pathogen. Monoclonal antibodies to the cell attachment domain of fibronectin also inhibited cell infection by the parasite. The immunization of BALB/c mice with tetanus toxoid-conjugated peptide induced a significant protection against
T. cruzi
. The data support the notion that the sequence Arg-Gly-Asp-Ser of cell surface fibronectin acts as a recognition site for attachment of the parasites.
Isolation and Sequence of L3T4 Complementary DNA Clones: Expression in T Cells and Brain
Authors: Tourvieille Béatrice , Gorman Scott D. , Field Elizabeth H. , Hunkapiller Tim , Parnes Jane R.
Published: October 2006

T lymphocytes express on their surface not only a specific receptor for antigen and major histocompatibility complex proteins, but also a number of additional glycoproteins that are thought to play accessory roles in the processes of recognition and signal transduction. L3T4 is one such T-cell surface protein that is expressed on most mouse thymocytes and on mature mouse T cells that recognize class II (Ia) major histocompatibility complex proteins. Such cells are predominantly of the helper/inducer phenotype. In this study, complementary DNA clones encoding L3T4 were isolated and sequenced. The predicted protein sequence shows that L3T4 is a member of the immunoglobulin gene superfamily. It is encoded by a single gene that does not require rearrangement prior to expression. Although the protein has not previously been demonstrated on nonhematopoietic cells, two messenger RNA species specific for L3T4 are found in brain. The minor species comigrates with the L3T4 transcript in T cells, whereas the major species is 1 kilobase smaller.
The Cytoskeletal Protein Vinculin Contains Transformation-Sensitive, Covalently Bound Lipid
Authors: Burn Paul , Burger Max M.
Published: October 2006

Vinculin, which is associated with the cytoskeleton of many cells, has been suggested as a possible linker between microfilament bundles and the plasma membrane. Here it will be shown that fatty acid is covalently attached to vinculin in vivo. Furthermore, in chicken embryo fibroblasts infected with a temperature-sensitive mutant of Rous sarcoma virus, tsNY68, the acylation of vinculin at the permissive temperature was less than one-third that at the nonpermissive temperature. Thus, the covalent binding of lipid to vinculin is a transformation-sensitive event. The covalent modification of vinculin by lipids could be directly or indirectly involved in its reversible association with membranes. This modification may also provide a mechanism to alter the organization of vinculin within cells and thereby play a regulatory role in anchoring or stabilizing microfilament bundles at plasma membranes.
Kainic Acid Injections Result in Degeneration of Cochlear Nucleus Cells Innervated by the Auditory Nerve
Authors: Bird Stephanie J. , Gulley Robert L. , Wenthold Robert J. , Fex Jorgen
Published: October 2006

When kainic acid, a putative neurotoxin for neurons with glutamatergic input, is injected into the brainstem, it produces a selective pattern of degeneration in the cochlear nucleus. The rate and extent of degeneration is correlated with the distribution of the primary auditory fibers. This evidence supports the hypothesis that glutamate is the neurotransmitter for primary auditory fibers.
Detection of Minimal Residual Cells Carrying the t(14;18) by DNA Sequence Amplification
Authors: Lee Ming-Sheng , Chang Kun-Sang , Cabanillas Fernando , Freireich Emil J. , Trujillo Jose M. , Stass Sanford A.
Published: October 2006

By means of the polymerase chain reaction (PCR) technique, DNA sequences were amplified that flank the crossover sites of a characteristic chromosomal translocation for follicular lymphomas, t(14;18)(q32;q21). This technique permitted the detection of cells carrying the t(14;18) hybrid DNA sequences at a dilution of 1:100,000. The remission marrow and blood samples of a patient with follicular lymphoma and the t(14;18) failed to show any abnormality by morphological examination and conventional Southern blot analysis. However, the t(14;18) hybrid DNA sequences were detected by the PCR technique. Thus, this technique is a highly sensitive tool to detect minimal residual cells carrying the t(14;18) and has the potential to identify a subpopulation of patients with subclinical disease.
Molecular Diversity of the Human T-Gamma Constant Region Genes
Authors: Pelicci Pier Giuseppe , Subar Milayna , Weiss Arthur , Dalla-Favera Riccardo , Littman Dan R.
Published: October 2006

The human T cell antigen-receptor γ chain, which is expressed on the surface of a subpopulation of CD3
+
T lymphocytes, exhibits size polymorphism and varies in its ability to form disulfide bonds with a second polypeptide. Analysis of both genomic and complementary DNA clones encoding the human γ polypeptide shows differences in lengths of the coding portions of the two constant region genes, Cγ1 and Cγ2. A single second-exon segment is always present in the Cγ1 gene. Cγ2 alleles containing either duplicated or triplicated second-exon segments are present in the normal human population and are expressed as messenger RNAs. Furthermore, a cysteine residue, encoded by the second exon of Cγ1 and probably involved in interchain disulfide bridging, is absent in all Cγ2 second-exon segments. These differences between Cγ1 and the two alleles of Cγ2 may explain the variability in molecular weight and disulfide bonding of γ molecules expressed in different cells.
Phylogenetic Relations of Humans and African Apes from DNA Sequences in the ψη-Globin Region
Authors: Miyamoto Michael M. , Slightom Jerry L. , Goodman Morris
Published: October 2006

Sequences from the upstream and downstream flanking DNA regions of the ψη-globin locus in
Pan troglodytes
(common chimpanzee),
Gorilla gorilla
(gorilla), and
Pongo pygmaeus
(orangutan, the closest living relative to
Homo
,
Pan
, and
Gorilla
) provided further data for evaluating the phylogenetic relations of humans and African apes. These newly sequenced orthologs [an additional 4.9 kilobase pairs (kbp) for each species] were combined with published ψη-gene sequences and then compared to the same orthologous stretch (a continuous 7.1-kbp region) available for humans. Phylogenetic analysis of these nucleotide sequences by the parsimony method indicated (i) that human and chimpanzee are more closely related to each other than either is to gorilla and (ii) that the slowdown in the rate of sequence evolution evident in higher primates is especially pronounced in humans. These results indicate that features (for example, knuckle-walking) unique to African apes (but not to humans) are primitive and that even local molecular clocks should be applied with caution.
Nuclear Factors in B Lymphoma Enhance Splicing of Mouse Membrane-Bound μ mRNA in
Xenopus
Oocytes
Authors: Tsurushita Naoya , Ho Lisa , Korn Laurence Jay
Published: October 2006

Regulation of the synthesis of membrane-bound and secreted immunoglobulin μ heavy chains at the level of RNA processing is an important element for B cell development. The precursor μ RNA is either polyadenylated at the upstream poly(A) site (for the secreted form) or spliced (for the membrane-bound form) in a mutually exclusive manner. When the mouse μ gene linked to the SV40/HSV-TK hybrid promoter was microinjected into
Xenopus
oocytes, the μ messenger RNA (mRNA) was processed primarily to the secreted form. The processing pattern of μ mRNA was altered by coinjection of nuclei of mouse surface IgM-bearing B-lymphoma cells to include the synthesis of the membrane-bound form. An increase in the membrane-bound form was not observed when nuclei of IgM-secreting hybridoma cells or fibroblast cells were coinjected. Deletion of the upstream poly(A) site did not eliminate the effect of B-lymphoma nuclei suggesting that membrane-specific splicing is stimulated. Further, splicing of other μ gene introns was not affected by coinjection of B-lymphoma nuclei. These results suggest that mature B cells contain one or more transacting nuclear factors that stimulate splicing specific for membrane-bound μ mRNA.
Fos-Associated Protein p39 Is the Product of the
jun
Proto-Oncogene
Authors: Rauscher Frank J. , Cohen Donna R. , Curran Tom , Bos Timothy J. , Vogt Peter K. , Bohmann Dirk , Tjian Robert , Franza B. Robert
Published: October 2006

The Fos protein complex and several Fos-related antigens (FRA) bind specifically to a sequence element referred to as the HeLa cell activator protein 1 (AP-1) binding site. A combination of structural and immunological comparisons has identified the Fos-associated protein (p39) as the protein product of the
jun
proto-oncogene (c-Jun). The p39/Jun protein is one of the major polypeptides identified in AP-1 oligonucleotide affinity chromatography extracts of cellular proteins. These preparations of AP-1 also contain Fos and several FRA's. Some of these proteins bind to the AP-1 site directly whereas others, like Fos, appear to bind indirectly via protein-protein interactions. Cell-surface stimulation results in an increase in c-
fos
and c-
jun
products. Thus, the products of two protooncogenes (and several related proteins), induced by extracellular stimuli, form a complex that associates with transcriptional control elements containing AP-1 sites, thereby potentially mediating the long-term responses to signals that regulate growth control and development.
Predator-Induced Trophic Shift of a Free-Living Ciliate: Parasitism of Mosquito Larvae by Their Prey
Authors: Washburn Jan O. , Gross Michael E. , Mercer David R. , Anderson John R.
Published: October 2006

Larvae of the treehole mosquito,
Aedes sierrensis
, release a waterborne factor that induces morphogenesis of one of their prey, the tetrahymenid ciliate
Lambornella clarki
. Induced free-living trophonts of
L. clarki
undergo a synchronous response in which cells divide and transform into parasitic cells (theronts) that encyst on larval predators. Parasitic ciliates penetrate the cuticle, enter the hemocoel, and ultimately kill their predator-host. In nature, this trophic shift can lead to predator extinction and dramatic changes in microbial populations. Facultative parasitism by this polymorphic ciliate may have evolved as an antipredator strategy. The experimentally inducible parasitic response of
L. clarki
provides a novel model for studying cellular morphogenesis of ciliated protozoa.
Expression of c-
fos
Protein in Brain: Metabolic Mapping at the Cellular Level
Authors: Sagar S. M. , Sharp F. R. , Curran T.
Published: October 2006

The proto-oncogene c-
fos
is expressed in neurons in response to direct stimulation by growth factors and neurotransmitters. In order to determine whether the c-
fos
protein (Fos) and Fos-related proteins can be induced in response to polysynaptic activation, rat hindlimb motor/sensory cortex was stimulated electrically and Fos expression examined immunohistochemically. Three hours after the onset of stimulation, focal nuclear Fos staining was seen in motor and sensory thalamus, pontine nuclei, globus pallidus, and cerebellum. Moreover, 24-hour water deprivation resulted in Fos expression in paraventricular and supraoptic nuclei. Fos immunohistochemistry therefore provides a cellular method to label polysynaptically activated neurons and thereby map functional pathways.
Congenital Poisoning by Polychlorinated Biphenyls and Their Contaminants in Taiwan
Authors: Rogan Walter J. , Gladen Beth C. , Hung Kun-Long , Koong Shin-Lan , Shih Ling-Yu , Taylor James S. , Wu Ying-Chin , Yang Dorothy , Ragan N. Beth , Hsu Chen-Chin
Published: October 2006

In 1979, a mass poisoning occurred in Taiwan from cooking oil contaminated by thermally degraded polychlorinated biphenyls. Because these chemicals persist in human tissue, children born to female patients after the outbreak were exposed in utero. In 1985, 117 children born to affected women and 108 unexposed controls were examined and evaluated. The exposed children were shorter and lighter than controls; they had abnormalities of gingiva, skin, nails, teeth, and lungs more frequently than did controls. The exposed children showed delay of developmental milestones, deficits on formal developmental testing, and abnormalities on behavioral assessment. These findings are most consistent with a generalized disorder of ectodermal tissue. This syndrome is one of very few documented to result from transplacental exposure to pollutant chemicals.
Cloning and Expression of the Human Interleukin-6 (BSF-2/IFNβ 2) Receptor
Authors: Yamasaki Katsuhiko , Taga Tetsuya , Hirata Yuuichi , Yawata Hideo , Kawanishi Yoshikazu , Seed Brian , Taniguchi Tadatsugu , Hirano Toshio , Kishimoto Tadamitsu
Published: October 2006

Interleukin-6 (IL-6/BSF-2/IFNβ 2) is a multifunctional cytokine that regulates the growth and differentiation of various tissues, and is known particularly for its role in the immune response and acute phase reactions. A complementary DNA encoding the human IL-6 receptor (IL-6-R) has now been isolated. The IL-6-R consists of 468 amino acids, including a signal peptide of ∼19 amino acids and a domain of ∼90 amino acids that is similar to a domain in the immunoglobulin (Ig) superfamily. The cytoplasmic domain of ∼82 amino acids lacks a tyrosine/kinase domain, unlike other growth factor receptors.
Tumor Formation Dependent on Proteoglycan Biosynthesis
Authors: Esko Jeffrey D. , Rostand Katherine S. , Weinke Julie L.
Published: October 2006

The role proteoglycans play in tumor formation was examined by measuring the tumorigenicity of proteoglycan-deficient Chinese hamster ovary cell mutants in nude mice. When 10
7
cells were injected subcutaneously, mutants with less than about 15% of the wild-type level of proteoglycan synthesis did not produce tumors. Mutants defective in the synthesis of heparan sulfate proteoglycans also did not form tumors, whereas mutants with altered chondroitin sulfate proteoglycans were tumorigenic. Tumors arose from mixtures of wild-type and nontumorigenic mutant cells and contained both cell types, suggesting that wild-type cell proteoglycans enabled mutant cells to survive. The failure of heparan sulfate-deficient mutants to form tumors depended on the ability of the host to mount a B cell-mediated immune reaction.
Mammalian
ZFY
Sequences Exist in Reptiles Regardless of Sex-Determining Mechanism
Authors: Bull J. J. , Hillis David M. , O'Steen Shyril
Published: October 2006

In some reptiles, egg incubation temperature determines whether the embryo hatches as male or female; in others, sex chromosomes determine sex. A cloned gene (
ZFY
) representing the putative testis-determining factor in mammals was hybridized to genomic DNA of reptiles with sex chromosomes and to DNA of reptiles with temperature-dependent sex determination. No sex differences in hybridization patterns were observed. Hybridization of
ZFY
to polyadenylated RNA indicates that reptilian versions of this gene are expressed in embryos of both sexes during the temperature-sensitive period. If these highly conserved sequences are important in reptilian sex determination, then temperature-dependent and genotypic sex determination may have a similar molecular basis. For reptiles with XX/XY or ZZ/ZW systems, the absence of sex differences in hybridization patterns raises the question of whether the
ZFY
sequences reside on their sex chromosomes.
Induction of κ Transcription by Interferon-γ Without Activation of NF-κB
Authors: Briskin Michael , Kuwabara Michio D. , Sigman David S. , Wall Randolph
Published: October 2006

The induction of immunoglobulin κ light chain expression in 70Z/3 pre-B cells treated with bacterial lipopolysaccharide (LPS) requires the activation of the B cell-specific factor NF-κB, which binds to the κ enhancer motif, GGGACTTTCC. This sequence alone can function as a tissue-specific enhancer for LPS-induced gene expression. A potent inhibitor of B lymphopoiesis [transforming growth factor-β (TGF-β)] was used to explore the mechanisms in the activation of κ transcription by LPS and by interferon-γ (IFN-γ). TGF-β inhibited LPS-induced κ transcription but not the activation and in vitro binding of NF-κB. This indicates that NF-κB activation, while necessary, is not sufficient for LPS-induced κ transcription. TGF-β had no effect on IFN-γ-induced κ transcription, and NF-κB was not activated by IFN-γ. These results reveal that LPS and IFN-γ activate transcription through different mechanisms.
Muscle Contraction and Free Energy Transduction in Biological Systems
Authors: Eisenberg Evan , Hill Terrell L.
Published: October 2006

Muscle contraction occurs when the actin and myosin filaments in muscle are driven past each other by a cyclic interaction of adenosine triphosphate (ATP) and actin with cross-bridges that extend from myosin. Current biochemical studies suggest that, during each adenosine triphosphatase cycle, the myosin cross-bridge alternates between two main conformations, which differ markedly in their strength of binding to actin and in their overall structure. Binding of ATP to the cross-bridge induces the weak-binding conformation, whereas inorganic phosphate release returns the cross-bridge to the strong-binding conformation. This cross-bridge cycle is similar to the kinetic cycle that drives active transport and illustrates the general principles of free energy transduction by adenosine triphosphatase systems.
Protein-Specific Helper T-Lymphocyte Formation Initiated by Dendritic Cells
Authors: Inaba Kayo , Steinman Ralph M.
Published: October 2006

Antibody responses to hapten-polypeptide conjugates require peptide-specific helper T cells. The latter can be primed in tissue culture by providing small numbers of dendritic cells. Primed, irradiated helper T cells then induce B-cell growth and differentiation in the apparent absence of dendritic cells. Both stages of the antibody response—the induction of helper T lymphoblasts by dendritic cells and the delivery of help from T to B cell—occur in discrete cell aggregates that can be isolated by velocity sedimentation. If helper T blasts revert to smaller "memory" lymphocytes, dendritic cells again are needed to initiate the antibody response.
Cigarette Smoking Induces Functional Antiprotease Deficiency in the Lower Respiratory Tract of Humans
Authors: Gadek James E. , Fells Gerald A. , Crystal Ronald G.
Published: October 2006

Current concepts of the pathogenesis of emphysema suggest that it results from an imbalance of elastase and antielastase activity within the alveolar structures. Although emphysema that is associated with hereditary deficiency of serum α
1
-antitrypsin conforms to this scheme, the major risk factor in the more common form of emphysema is cigarette smoking. A study was designed to evaluate the premise that cigarette smoking may be associated with an acquired, functional defect in lung α
1
-antitrypsin. Determination of the antielastase activity of α
1
-antitrypsin obtained from the lungs of smoking and nonsmoking individuals revealed a nearly twofold reduction in the functional activity of this elastase inhibitor in the lungs of cigarette smokers. These data suggest that cigarette smokers may lose some of the normal antielastase protective screen of the lower respiratory tract, making them more vulnerable to destructive lung disease.
Parallel Integration of Vision Modules
Authors: Poggio T. , Gamble E. B. , Little J. J.
Published: October 2006

Computer algorithms have been developed for several early vision processes, such as edge detection, stereopsis, motion, texture, and color, that give separate cues to the distance from the viewer of three-dimensional surfaces, their shape, and their material properties. Not surprisingly, biological vision systems still greatly outperform computer vision programs. One of the keys to the reliability, flexibility, and robustness of biological vision systems is their ability to integrate several visual cues. A computational technique for integrating different visual cues has now been developed and implemented with encouraging results on a parallel supercomputer.
Growth and Transparency in the Lens, an Epithelial Tissue, Stimulated by Pulses of PDGF
Authors: Brewitt Barbara , Clark John I.
Published: October 2006

The rat lens undergoes dramatic growth during early postnatal development. Lens weight increased by a factor of 23 in 26 days. Growth rate per day oscillated between 0 and 87 percent. A new culture system was designed to study the oscillations in growth during development. Lens growth and transparency in vitro required pulsatile delivery of platelet-derived growth factor (PDGF) in HL-1 serum-free medium. Continuous delivery of HL-1 medium with PDGF or pulsatile delivery of HL-1 medium without PDGF resulted in lens opacity and no growth. These results provide direct evidence that PDGF stimulates an epithelial tissue and that oscillations in growth occur during normal development of the rat lens.
Protection of Cattle Against Rinderpest with Vaccinia Virus Recombinants Expressing the HA or F Gene
Authors: Yilma Tilahun , Hsu David , Jones Leslie , Owens Sally , Grubman Marvin , Mebus Charles , Yamanaka Miles , Dale Beverly
Published: October 2006

Rinderpest is a highly contagious ruminant viral disease manifested by a rapid course and greater than 90% mortality. Infectious vaccinia virus recombinants were constructed that express either the hemagglutinin or the fusion gene of rinderpest virus. All cattle vaccinated with either recombinant or with the combined recombinants produced neutralizing antibodies against rinderpest virus and were protected against the disease when challenged with more than 1000 times the lethal dose of the virus.
Lithium: Effects on Subjective Functioning and Morphine-Induced Euphoria
Authors: Jasinski Donald R. , Nutt John G. , Haertzen Charles A. , Griffith John D. , Bunney William E.
Published: October 2006

The therapeutic usefulness of lithium in decreasing the euphoria and other symptoms associated with manic behavior and the hypothesis of a common final mechanism for elevations in mood have led to speculation that lithium may block the euphoria induced by drugs of abuse. In this study, lithium alone was antieuphoric in drug-free opiate addicts and, further, did not block morphine-induced euphoria.
Human T Cell Leukemia Viruses Use a Receptor Determined by Human Chromosome 17
Authors: Sommerfelt Maja A. , Williams Brenda P. , Clapham Paul R. , Solomon Ellen , Goodfellow Peter N. , Weiss Robin A.
Published: October 2006

Human T cell leukemia viruses (HTLV-I and HTLV-II) can infect many cell types in vitro. HTLV-I and HTLV-II use the same cell surface receptor, as shown by interference with syncytium formation and with infection by vesicular stomatitis virus (VSV) pseudotypes bearing the HTLV envelope glycoproteins. Human-mouse somatic cell hybrids were used to determine which human chromosome was required to confer susceptibility to VSV(HTLV) infection. The only human chromosome common to all susceptible cell hybrids was chromosome 17, and the receptor gene was localized to 17cen-qter. Antibodies to surface antigens known to be determined by genes on 17q did not block the HTLV receptor.
Functional Specificity of Thymus-Dependent Lymphocytes
Authors: Paul William E. , Benacerraf Baruj
Published: October 2006

Thymus-dependent lymphocytes display a restricted range of specificity when compared to thymus-independent (B) lymphocytes. They react particularly to thymus-dependent protein and cell surface antigens and to products of genes encoded in the MHC. In addition, T lymphocytes have important functions in regulating the immune response and in discriminating of self from nonself. Recent work indicates that individual T lymphocytes possess receptors that interact with both thymus-dependent antigens and MHC gene products, either independently or as associated structures. We attempt to relate this complex specificity pattern to the regulatory and surveillance functions of T lymphocytes.
EK2 Derivatives of Bacteriophage Lambda Useful in the Cloning of DNA from Higher Organisms: The λgt
WES
System
Authors: Leder P. , Tiemeier D. , Enquist L.
Published: October 2006

A derivative of bacteriophage λ has been modified and tested together with an appropriate host system to meet the criteria of EK2 biologic containment for cloning DNA from higher organisms. In this report certain of the safety features are summarized and some of the tests carried out to confirm the containment properties of the vector are described. The cloning efficiency of this system, together with available gene purification and hybrid screening technology, indicate that it can be used to clone DNA fragments carrying specific, unique mammalian genes.
Five Hundredfold Overproduction of DNA Ligase After Induction of a Hybrid Lambda Lysogen Constructed in Vitro
Authors: Panasenko Sharon M. , Cameron John R. , Davis Ronald W. , Lehman I. R.
Published: October 2006

A lambda vector that contains the gene for
Escherichia coli
DNA ligase (λgt4-
lop
-11
lig
+
) has been modified to achieve overproduction of this enzyme. The third Eco RI site in the lambda chromosome has been altered by mutation, and the left-hand Eco RI fragment has been shortened. The new vector, λgt4-
lop
-11
lig
+
, forms a stable lysogen which, upon induction, produces a 100-fold increase in DNA ligase activity. Introduction of a phage mutation (S7) that prevents cell lysis results in an even greater increase (500-fold).
Chromosomal Gene Transfer in
Spiroplasma citri
Authors: Barroso Gerard , Labarère Jacques
Published: October 2006

The study of resistance marker rearrangement in
Spiroplasma citri
mutants provides evidence of transfer of chromosomal information followed by recombination. This is the first report of such a transfer in vivo in the mollicutes—that is, in the smallest self-replicating organisms. The double-resistant phenotypes obtained are stable even without selection pressure. The mechanism of gene transfer is insensitive to deoxyribonuclease, requires contact, and possibly, areas of fusion of the cell membranes; it shares properties with the transfer by protoplast fusion in Gram-positive bacteria. The extensive degenerative evolution of mollicutes has retained, in
S. citri
, bacterial functions of chromosomal transfer and recombination.
A Novel Gene of HIV-1,
vpu
, and Its 16-Kilodalton Product
Authors: Strebel Klaus , Klimkait Thomas , Martin Malcolm A.
Published: October 2006

A 16-kilodalton protein expressed in cells producing the human immunodeficiency virus (HIV-1) was identified as the gene product of the
vpu
open reading frame. When expressed in vitro, the 81-amino acid
vpu
protein reacted with about one-third of the serum samples from AIDS patients that were tested, indicating that the
vpu
open reading frame is expressed in vivo as well. Introduction of a frame-shift mutation into the
vpu
open reading frame did not significantly interfere with expression of the major viral proteins in a transient expression system. However, a five- to tenfold reduction in progeny virions was observed after the infection of T lymphocytes with the mutant virus. These data suggest that the
vpu
gene product is required for efficient virus replication and may have a role in assembly or maturation of progeny virions.
Antiserums to Neurons and to Oligodendroglia from Mammalian Brain
Authors: Poduslo S. E. , McFarland H. F. , McKhann G. M.
Published: October 2006

Two specific antiserums were produced, one to rat neurons and one to lamb oligodendroglia isolated in bulk from brain. On the basis of immunofluorescence and absorption studies with bulk isolated cells, the antiserums were produced to specific surface components. The antiserums are useful as markers for cell identification and for studying proteins in plasma membranes.
One Strand Equivalent of the
Escherichia coli
Genome Is Transcribed: Complexity and Abundance Classes of mRNA
Authors: Hahn William E. , Pettijohn David E. , Van Ness Jeffrey
Published: October 2006

DNA-RNA hybridization experiments show that essentially all of the genomic information is transcribed. High, intermediate, and rare abundance classes of messenger RNA (mRNA) are present, and their estimated complexities are equal to about 240, 1300, and 700 average-sized mRNA species, respectively. The high abundance mRNA species are present, on average, two to three copies per cell and constitute about 95 percent of the mRNA mass. Intermediate abundance mRNA species are present, on average, about once per 35 cells. The relative abundance and complexity of these mRNA classes correspond well with previous respective measurements on protein. Rare RNA species are thought to represent maximally repressed genes. Analysis of RNA synthesized in vitro by isolated nucleoids (chromosomes) suggests that sense and nonsense sequences are extensively interspersed on a given strand of the DNA.
Structural and Functional Roles of Glycosyl-Phosphatidylinositol in Membranes
Authors: Low Martin G. , Saltiel Alan R.
Published: October 2006

Glycosylated forms of phosphatidylinositol, which have only recently been described in eukaryotic organisms, are now known to play important roles in biological membrane function. These molecules can serve as the sole means by which particular cell-surface proteins are anchored to the membrane. Lipids with similar structures may also be involved in signal transduction mechanisms for the hormone insulin. The utilization of this novel class of lipid molecules for these two distinct functions suggests new mechanisms for the regulation of proteins in biological membranes.
AIDS: an International Perspective
Authors: Piot Peter , Plummer Francis A. , Mhalu Fred S. , Lamboray Jean-Louis , Chin James , Mann Jonathan M.
Published: October 2006

The acquired immunodeficiency syndrome (AIDS) and infection with the human immunodeficiency virus type 1 (HIV-1) constitute a worldwide public health problem. Whereas in Europe and in most of the Americas transmission of HIV-1 has occurred predominantly among homosexual men and intravenous drug abusers, in Africa a distinct epidemiologic pattern has emerged that indicates that HIV-1 infection is mainly heterosexually acquired. Heterosexual transmission appears to be increasing in some parts of Latin America and the Caribbean, and possibly in the United States. In addition to HIV-1, at least one other human retrovirus, namely HIV-2, has been implicated as a cause of AIDS in Africa and Europe. Factors that influence heterosexual transmission of HIV-1 include genital ulcerations, early or late stages of HIV-1 infection in the index case, and possibly oral contraception and immune activation. The rate of perinatal transmission is enhanced when the mother's illness is more advanced. AIDS and HIV-1 infection may have a significant impact not only on public health, but also on the demography and socioeconomic conditions of some developing countries. Programs for the prevention and control of AIDS should be an immediate priority in all countries.
Donor-Derived Cells in the Central Nervous System of Twitcher Mice After Bone Marrow Transplantation
Authors: Hoogerbrugge Peter M. , Suzuki Kinuko , Suzuki Kunihiko , Poorthuis Ben J. H. M. , Kobayashi Takuro , Wagemaker Gerard , van Bekkum Dirk W.
Published: October 2006

The twitcher mouse is an animal model of galactosylceramidase deficiency, comparable to Krabbe's disease, a lysosomal storage disease in humans. As in most lysosomal storage diseases, neurological deterioration is a prominent feature of the disease in these mice. Transplantation of enzymatically normal congenic bone marrow was earlier found to result in prolonged survival and increased levels of galactosylceramidase in the visceral organs of twitcher mice. It is now reported that bone marrow transplantation results in increased galactosylceramidase levels in the central nervous system (CNS). Concomitantly, the levels of psychosine, a highly toxic lipid that progressively accumulates in the CNS of untreated twitcher mice, stabilized at much lower levels in the CNS of treated twitcher mice. Histologically, a gradual disappearance of globoid cells, the histological hallmark of Krabbe's disease, and the appearance of foamy macrophages capable of metabolizing the storage product were seen in the CNS. By immunohistochemical labeling it was demonstrated that these foamy macrophages were of donor origin. The infiltration of enzymatically competent, donor-derived macrophages was accompanied by extensive remyelination in the CNS. It is concluded that after bone marrow transplantation, donor-derived macrophages infiltrate the affected brain tissue and are capable of inducing a partial reversal of the enzyme deficiency.
Evolving Legal Standards for the Admissibility of Scientific Evidence
Authors: Black Bert
Published: October 2006

Ensuring the scientific validity of scientific evidence has always posed problems for judges and lawyers largely untrained in science. As recent cases involving the health effects of chemicals and drugs make clear, however, irrational and inconsistent decisions result when courts do not hold expert witnesses to the standards and criteria of their own disciplines. A trend toward more thorough judicial review of scientific claims has developed, and it should be encouraged.
The Neural Cell Adhesion Molecule (NCAM) as a Regulator of Cell-Cell Interactions
Authors: Rutishauser Urs , Acheson Ann , Hall Alison K. , Mann Dennis M. , Sunshine Jeffrey
Published: October 2006

The neural cell adhesion molecule (NCAM) can influence a number of diverse intercellular events, including junctional communication, the association of axons with pathways and targets, and signals that alter levels of neurotransmitter enzymes. These pleiotropic effects appear to reflect the ability of NCAM to regulate membrane-membrane contact required to initiate specific interactions between other molecules. Such regulation can occur through changes in either NCAM expression or the molecule's content of polysialic acid (PSA). When NCAM with a low PSA content is expressed, adhesion is increased and contact-dependent events are triggered. In contrast, the large excluded volume of NCAM PSA can inhibit cell-cell interactions through hindrance of overall membrane apposition.
Oral
Salmonella typhimurium
Vaccine Expressing Circumsporozoite Protein Protects Against Malaria
Authors: Sadoff Jerald C. , Ballou W. Ripley , Baron Louis S. , Majarian William R. , Brey Robert N. , Hockmeyer Wayne T. , Young James F , Cryz Stanley J. , Ou Jonathan , Lowell George H. , Chulay Jeffrey D.
Published: October 2006

Immunization with radiation-attenuated malaria sporozoites induces potent cellular immune responses, but the target antigens are unknown and have not previously been elicited by subunit vaccines prepared from the circumsporozoite (CS) protein. A method is described here for inducing protective cell-mediated immunity to sporozoites by immunization with attenuated
Salmonella typhimurium
transformed with the
Plasmodium berghei
CS gene. These transformants constitutively express CS antigens and, when used to immunize mice orally, colonize the liver, induce antigen-specific cell-mediated immunity, and protect mice against sporozoite challenge in the absence of antisporozoite antibodies. These data indicate that the CS protein contains T cell epitopes capable of inducing protective cell-mediated immunity, and emphasize the importance of proper antigen presentation in generating this response. Analogous, orally administered vaccines against human malaria might be feasible.
Apolipoprotein E: Cholesterol Transport Protein with Expanding Role in Cell Biology
Authors: Mahley Robert W.
Published: October 2006

Apolipoprotein E is a plasma protein that serves as a ligand for low density lipoprotein receptors and, through its interaction with these receptors, participates in the transport of cholesterol and other lipids among various cells of the body. A mutant form of apolipoprotein E that is defective in binding to low density lipoprotein receptors is associated with familial type III hyperlipoproteinemia, a genetic disorder characterized by elevated plasma cholesterol levels and accelerated coronary artery disease. Apolipoprotein E is synthesized in various organs, including liver, brain, spleen, and kidney, and is present in high concentrations in interstitial fluid, where it appears to participate in cholesterol redistribution from cells with excess cholesterol to those requiring cholesterol. Apolipoprotein E also appears to be involved in the repair response to tissue injury; for example, markedly increased amounts of apolipoprotein E are found at sites of peripheral nerve injury and regeneration. Other functions of apolipoprotein E, unrelated to lipid transport, are becoming known, including immunoregulation and modulation of cell growth and differentiation.
Insulin-Resistant Diabetes Due to a Point Mutation That Prevents Insulin Proreceptor Processing
Authors: Yoshimasa Yasunao , Seino Susumu , Whittaker Jonathan , Kakehi Takako , Kosaki Atsushi , Kuzuya Hideshi , Imura Hiroo , Bell Graeme I. , Steiner Donald F.
Published: October 2006

A point mutation in the human insulin receptor gene in a patient with type A insulin resistance alters the amino acid sequence within the tetrabasic processing site of the proreceptor molecule from Arg-Lys-Arg-Arg to Arg-Lys-Arg-Ser. Epstein-Barr virus-transformed lymphocytes from this patient synthesize an insulin receptor precursor that is normally glycosylated and inserted into the plasma membrane but is not cleaved to mature α and β subunits. Insulin binding to these cells is severely reduced but can be increased about fivefold by gentle treatment with trypsin, accompanied by the appearance of normal α subunits. These results indicate that proteolysis of the proreceptor is necessary for its normal full insulin-binding sensitivity and signal-transducing activity and that a cellular protease that is more stringent in its specificity than trypsin is required to process the receptor precursor.