bluuebunny/crossref_metadata_2025 huggingface dataset:
Asparaginase Entrapped in Red Blood Cells: Action and Survival
Authors: Updike Stuart J. , Wakamiya Richard T. , Lightfoot Edwin N.
Published: October 2006

As a strategy to avoid serious allergic reactions to the antitumor agent asparaginase, this enzyme was entrapped in autologous red blood cells before intravenous injection into monkeys. Additional advantages of this approach are prolonged enzyme half-life and targeting of this agent into the reticuloendothelial system.
Isolation of the Cyclosporin-Sensitive T Cell Transcription Factor NFATp
Authors: McCaffrey Patricia G. , Luo Chun , Kerppola Tom K. , Jain Jugnu , Badalian Tina M. , Ho Andrew M. , Burgeon Emmanuel , Lane William S. , Lambert John N. , Curran Tom , Verdine Gregory L. , Rao Anjana , Hogan Patrick G.
Published: October 2006

Nuclear factor of activated T cells (NFAT) is a transcription factor that regulates expression of the cytokine interleukin-2 (IL-2) in activated T cells. The DNA-binding specificity of NFAT is conferred by NFATp, a phosphoprotein that is a target for the immunosuppressive compounds cyclosporin A and FK506. Here, the purification of NFATp from murine T cells and the isolation of a complementary DNA clone encoding NFATp are reported. A truncated form of NFATp, expressed as a recombinant protein in bacteria, binds specifically to the NFAT site of the murine IL-2 promoter and forms a transcriptionally active complex with recombinant c-Fos and c-Jun. Antisera to tryptic peptides of the purified protein or to the recombinant protein fragment react with T cell NFATp. The molecular cloning of NFATp should allow detailed analysis of a T cell transcription factor that is central to initiation of the immune response.
Determination of Type I Receptor Specificity by the Type II Receptors for TGF-β or Activin
Authors: Ebner Reinhard , Chen Ruey-Hwa , Lawler Sean , Zioncheck Thomas , Derynck Rik
Published: October 2006

Transforming growth factor-β (TGF-β) and activin signal primarily through interaction with type I and type II receptors, which are transmembrane serine-threonine kinases. Tsk 7L is a type I receptor for TGF-β and requires coexpression of the type II TGF-β receptor for ligand binding. Tsk 7L also specifically bound activin, when coexpressed with the type IIA activin receptor. Tsk 7L could associate with either type II receptor and the ligand binding specificity of Tsk 7L was conferred by the type II receptor. Tsk 7L can therefore act as type I receptor for both activin and TGF-β, and possibly other ligands.
An Archimedian Spiral: the Basal Disk of the
Wolinella
Flagellar Motor
Authors: Engelhardt Harald , Schuster Stephan C. , Baeuerlein Edmund
Published: October 2006

The motor that powers the rotation of the bacterial flagellum reaches through both membranes into the cytoplasm of Gram-negative bacteria. The flagellum is connected by a flexible link (hook) to the motor axis, which passes through the center of a structure called the basal disk. The basal disk functions with the L-P ring complex as a bushing, enabling the rotation of the motor in the cell wall. The protein subunits of the basal disk of
Wolinella succinogenes
form an Archimedian spiral. The polymerization of subunits from a nucleation point at the motor in the form of a spiral allows constant growth of the basal disk. The disk is thought to provide a reinforcement at the flagellar insertion at the cell pole and to disperse forces that are generated by the momentum of the flagellar rotation.
Replication-Specific Inactivation of the pT181 Plasmid Initiator Protein
Authors: Rasooly Avraham , Novick Richard P.
Published: October 2006

Replication of the
Staphylococcus aureus
plasmid pT181, which occurs by the rolling circle mechanism, is accompanied by the covalent attachment of a ≈ 12-residue oligodeoxy-nucleotide to one subunit of the dimeric plasmid-coded initiator protein, RepC. This oligonucleotide represents the plasmid sequence immediately 3′ to the initiating nick site. The resulting heterodimeric protein lacks the topoisomerase and replication activities of unmodified RepC, suggesting that the regulation of plasmid DNA replication requires post-replicational inactivation of the initiator protein as well as control of its synthesis.
A Ca-Dependent Early Step in the Release of Catecholamines from Adrenal Chromaffin Cells
Authors: von Rüden Ludolf , Neher Erwin
Published: October 2006

Intense stimuli, such as trains of depolarizing pulses or the caffeine-induced release of calcium from intracellular stores, readily depress the secretory response in neuroendocrine cells. Secretory responses are restored by rest periods of minutes in duration. This recovery was accelerated when the concentration of cytosolic calcium was moderately increased and probably resulted from calcium-dependent replenishment of a pool of release-ready granules. Continuously increased concentrations of calcium led to the overfilling of such a pool. Subsequently, secretory responses to stronger calcium stimuli were augmented. Hormone-induced calcium transients with a plateau phase of increased concentration of calcium may enhance the secretory response in this way.
Neuronal-Visceral GM
1
Gangliosidosis in a Dog with β-Galactosidase Deficiency
Authors: Read Deryck H. , Harrington Daniel D. , Keenan Thomas W. , Hinsman Edward J.
Published: October 2006

A 9-month-old dog with a history of progressive motor dysfunction was shown to have a deficiency in brain β-galactosidase activity. The canine disease, like that of children with GM
1
gangliosidosis, is characterized by accumulation of GM
1
ganglioside in the brain, liver, and spleen, and membranous cytoplasmic bodies in neurons. The dog's pedigree suggests an autosomal recessive pattern of inheritance.
Enzymatic Synthesis of a Bacterial Polyketide from Acetyl and Malonyl Coenzyme A
Authors: Shen Ben , Hutchinson C. Richard
Published: October 2006

Microorganisms and plants manufacture a large collection of medically and commercially useful natural products called polyketides by a process that resembles fatty acid biosynthesis. Genetically engineered microorganisms with modified polyketide synthase (PKS) genes can produce new metabolites that may have new or improved pharmacological activity. A potentially general method to prepare cell-free systems for studying bacterial type II PKS enzymes has been developed that facilitates the purification and reconstitution of their constituent proteins. Selective expression of different combinations of the
Streptomyces glaucescens
tetracenomycin (Tcm)
tcmJKLMN
genes in a
tcmGHIJKLMNO
null background has been used to show that the Tcm PKS consists of at least the TcmKLMN proteins. Addition of the TcmJ protein to the latter four enzymes resulted in a greater than fourfold increase of overall activity and thus represents the optimal Tcm PKS. Polyclonal antibodies raised against each of the TcmKLMN proteins strongly inhibit the Tcm PKS, as do known inhibitors targeted to the active site Cys and Ser residues of a fatty acid synthase. This system exhibits a strict starter unit specificity because neither propionyl, butyryl, or isobutyryl coenzyme A substitute for acetyl coenzyme A in assembly of the Tcm decaketide. Because the Tcm PKS activity is significantly diminished by removal of the TcmM acyl carrier protein and can be restored by addition of separately purified TcmM to two different types of TcmM-deficient PKS, it should be possible to use such preparations to assay for each of the constituents of the Tcm PKS.
Association of the
APC
Gene Product with β-Catenin
Authors: Rubinfeld Bonnee , Souza Brian , Albert Iris , Müller Oliver , Chamberlain Scott H. , Masiarz Frank R. , Munemitsu Susan , Polakis Paul
Published: October 2006

Mutations in the human
APC
gene are linked to familial adenomatous polyposis and to the progression of sporadic colorectal and gastric tumors. To gain insight into APC function, APC-associated proteins were identified by immunoprecipitation experiments. Antibodies to APC precipitated a 95-kilodalton protein that was purified and identified by sequencing as β-catenin, a protein that binds to the cell adhesion molecule E-cadherin. An antibody specific to β-catenin also recognized the 95-kilodalton protein in the immunoprecipitates. These results suggest that APC is involved in cell adhesion.
The Learning of Categories: Parallel Brain Systems for Item Memory and Category Knowledge
Authors: Knowlton Barbara J. , Squire Larry R.
Published: October 2006

A fundamental question about cognition concerns how knowledge about a category is acquired through encounters with examples of the category. Amnesic patients and control subjects performed similarly at classifying novel patterns according to whether they belonged to the same category as a set of training patterns. In contrast, the amnesic patients were impaired at recognizing which dot patterns had been presented for training. Category learning appears to be independent of declarative (explicit) memory for training instances and independent of the brain structures essential for declarative memory that are damaged in amnesia. Knowledge about categories can be acquired implicitly by cumulating information from multiple examples.
A Mitochondrial Protease with Two Catalytic Subunits of Nonoverlapping Specificities
Authors: Nunnari Jodi , Fox Thomas D. , Walter Peter
Published: October 2006

The mitochondrial inner membrane protease is required for the maturation of mitochondrial proteins that are delivered to the intermembrane space. In the yeast
Saccharomyces cerevisiae
, this protease is now shown to be a complex that contains two catalytic subunits, Imp2p and the previously identified Imp1p. Primary structure similarity indicates that Imp1p and Imp2p are related to each other and to the family of eubacterial and eukaryotic signal peptidases. Imp1p and Imp2p have separate, nonoverlapping substrate specificities. In addition to its catalyzing the cleavage of intermembrane space sorting signals, Imp2p is required for the stable and functional expression of Imp1p. Thus, inner membrane protease, and by analogy eukaryotic multisubunit signal peptidases, may have acquired multiple catalytic subunits by gene duplication to broaden their range of substrate specificity.
Perceptual Organization and the Judgment of Brightness
Authors: Adelson Edward H.
Published: October 2006

The perceived brightness of a gray patch depends on the surrounding context. For example, a medium-gray patch appears darker when placed on a bright background and brighter when placed on a dark background. Models to explain these effects are usually based on simple low-level mechanisms. A new set of brightness illusions cannot be explained by such models. In these illusions, the brightness percept is strongly influenced by the perceptual organization of the stimuli. Simple modifications of the stimuli that should have little effect on low-level mechanisms greatly alter the strength of the illusion. These effects may be ascribed to more complex mechanisms occurring later in the visual system.
N
-Acetyl Gramicidin: Single-Channel Properties and Implications for Channel Structure
Authors: Szabo Gabor , Urry Dan W.
Published: October 2006

Substitution of a methyl group for the
N
-terminal hydrogen of gramicidin greatly increased the rate of dissociation of conductive channels in lipid bilayer membranes. The finding of short lifetimes for conductive channels, comparable to those seen for the neuromuscular junction, lends support to the head-to-head dimer structure for the conductive channel.
Benzodiazepine Peptidomimetics: Potent Inhibitors of Ras Farnesylation In Animal Cells
Authors: James Guy L. , Goldstein Joseph L. , Brown Michael S. , Rawson Thomas E. , Somers Todd C. , McDowell Robert S. , Crowley Craig W. , Lucas Brian K. , Levinson Arthur D. , Marsters James C.
Published: October 2006

Oncogenic Ras proteins transform animal cells to a malignant phenotype only when modified by farnesyl residues attached to cysteines near their carboxyl termini. The farnesyltransferase that catalyzes this reaction recognizes tetrapeptides of the sequence
CAAX
, where C is cysteine,
A
is an aliphatic amino acid, and
X
is a carboxyl-terminal methionine or serine. Replacement of the two aliphatic residues with a benzodiazepine-based mimic of a peptide turn generated potent inhibitors of farnesyltransferase [50 percent inhibitory concentration (IC
50
) < 1 nM]. Unlike tetrapeptides, the benzodiazepine peptidomimetics enter cells and block attachment of farnesyl to Ras, nuclear lamins, and several other proteins. At micromolar concentrations, these inhibitors restored a normal growth pattern to Ras-transformed cells. The benzodiazepine peptidomimetics may be useful in the design of treatments for tumors in which oncogenic Ras proteins contribute to abnormal growth, such as that of the colon, lung, and pancreas.
A Linkage Between DNA Markers on the X Chromosome and Male Sexual Orientation
Authors: Hamer Dean H. , Hu Stella , Magnuson Victoria L. , Hu Nan , Pattatucci Angela M. L.
Published: October 2006

The role of genetics in male sexual orientation was investigated by pedigree and linkage analyses on 114 families of homosexual men. Increased rates of same-sex orientation were found in the maternal uncles and male cousins of these subjects, but not in their fathers or paternal relatives, suggesting the possibility of sex-linked transmission in a portion of the population. DNA linkage analysis of a selected group of 40 families in which there were two gay brothers and no indication of nonmaternal transmission revealed a correlation between homosexual orientation and the inheritance of polymorphic markers on the X chromosome in approximately 64 percent of the sib-pairs tested. The linkage to markers on Xq28, the subtelomeric region of the long arm of the sex chromosome, had a multipoint lod score of 4.0 (
P
= 10
-5
), indicating a statistical confidence level of more than 99 percent that at least one subtype of male sexual orientation is genetically influenced.
Assessing the Quality of Solution Nuclear Magnetic Resonance Structures by Complete Cross-Validation
Authors: Brünger Axel T. , Clore G. Marius , Gronenborn Angela M. , Saffrich Rainer , Nilges Michael
Published: October 2006

Structure determination of macromolecules in solution by nuclear magnetic resonance (NMR) spectroscopy involves the fitting of atomic models to the observed nuclear Overhauser effect (NOE) data. Complete cross-validation has been used to define reliable and unbiased criteria for the quality of solution NMR structures. The method is based on the partitioning of NOE data into test sets and the cross-validation of statistical quantities for each of the test sets. A high correlation between cross-validated measures of fit, such as distance bound violations and NMR R values, and the quality of solution NMR structures was observed. Less complete data resulted in poorer satisfaction of the cross-validated measures of fit. Optimization of cross-validated measures of fit will likely produce solution NMR structures with maximal information content.
How Somatotopic Is the Motor Cortex Hand Area?
Authors: Schieber Marc H. , Hibbard Lyndon S.
Published: October 2006

The primary motor cortex (M1) is thought to control movements of different body parts from somatotopically organized cortical territories. Electrical stimulation suggests, however, that territories controlling different fingers overlap. Such overlap might be artifactual or else might indicate that activation of M1 to produce a finger movement occurs over a more widespread cortical area than usually assumed. These possibilities were distinguished in monkeys moving different fingers. Recordings showed that single M1 neurons were active with movements of different fingers. Neuronal populations active with movements of different fingers overlapped extensively. Control of any finger movement thus appears to utilize a population of neurons distributed throughout the M1 hand area rather than a somatotopically segregated population.
Signal Sequence Trap: a Cloning Strategy for Secreted Proteins and Type I Membrane Proteins
Authors: Tashiro Kei , Tada Hideaki , Heilker Ralf , Shirozu Michio , Nakano Toru , Honjo Tasuku
Published: October 2006

A method was developed to clone, without the use of specific functional assays, complementary DNAs (cDNAs) that carry specific amino-terminal signal sequences, such as those encoding intercellular signal-transducing molecules and receptors. The vector used in this system directed the cell surface expression of interleukin-2 receptor fusion proteins when inserts with signal sequences were cloned in-frame with the correct orientation. An expression cDNA library was constructed from a bone marrow stromal cell line, which contained 5′ portion-enriched cDNAs (the average size was 400 base pairs). Two cDNAs that encoded putative cytokine molecules, stromal cell-derived factor-1α (SDF-1α) and SDF-1β, which belong to the intercrine-macrophage inflammatory protein superfamily, were cloned.
Transition Metals in Control of Gene Expression
Authors: O'Halloran Thomas V.
Published: October 2006

Metalloproteins play structural and catalytic roles in gene expression. The metalloregulatory proteins are a subclass that exerts metal-responsive control of genes involved in respiration, metabolism, and metal-specific homeostasis or stress-response systems, such as iron uptake and storage, copper efflux, and mercury detoxification. Two allosteric mechanisms for control of gene expression were first discovered in metalloregulatory systems: an iron-responsive translational control mechanism for ferritin production and a mercury-responsive DNA-distortion mechanism for transcriptional control of detoxification genes. These otherwise unrelated mechanisms give rise to a rapid physiological response when metal ion concentrations exceed a dangerous threshold. Molecular recognition in these allosteric metal ion receptors is achieved through atypical coordination geometries, cluster formation, or complexes with prosthetic groups, such as sulfide and heme. Thus, many of the inorganic assemblies that otherwise buttress the structure of biopolymers or catalyze substrate transformation in active sites of enzymes have also been adapted to serve sensor functions in the metalloregulatory proteins. Mechanistic studies of these metal-sensor protein interactions are providing new insights into fundamental aspects of inorganic chemistry, molecular biology, and cellular physiology.
Sexual Calling Behavior in Primitive Ants
Authors: Hölldobler Bert , Haskins Caryl P.
Published: October 2006

The wingless virgin females of the ponerine ant
Rhytidoponera metallica
attract males by the release of a pheromone from the tergal gland, a hitherto unrecognized exocrine gland located between the last two abdominal segments. This is the first evidence for sexual chemical communication in the large and primitive subfamily Ponerinae.
Hormonal Chemoprevention of Cancer in Women
Authors: Henderson Brian E. , Ross Ronald K. , Pike Malcolm C.
Published: October 2006

The use of oral contraceptives in the United States during the past three decades has led to a dramatic decline in the incidence of cancers of the ovary and endometrium. The magnitude of these declines was predictable both from epidemiologic data and from the biologic effects of oral contraceptives on these tissues. Although the incidence of breast cancer has not been substantially affected by current oral contraceptives, it may be possible to develop alternative forms of contraception that provide protection against all three cancers. The major goal of hormonal chemoprevention of cancer is to reduce cell proliferation in the relevant epithelial tissue. New chemopreventive agents such as tamoxifen exemplify the application of this principle.
Cyclin-Dependent Regulation of G
1
in Mammalian Fibroblasts
Authors: Ohtsubo Motoaki , Roberts James M.
Published: October 2006

Eukaryotic cells become committed to proliferate during the G
1
phase of the cell cycle. In budding yeast, commitment occurs when the catalytic subunit of a protein kinase, encoded by the
CDC28
gene (the homolog of the fission yeast
cdc
2
+
gene), binds to a positively acting regulatory subunit, a cyclin. Related kinases are also required for progression through the G
1
phase in higher eukaryotes. The role of cyclins in controlling G
1
progression in mammalian cells was tested by construction of fibroblasts that constitutively overexpress human cyclin E. This was found to shorten the duration of G
1
, decrease cell size, and diminish the serum requirement for the transition from G
1
to S phase. These observations show that cyclin levels can be rate-limiting for G
1
progression in mammalian cells and suggest that cyclin synthesis may be the target of physiological signals that control cell proliferation.
Structure of the Retinoid X Receptor α DNA Binding Domain: a Helix Required for Homodimeric DNA Binding
Authors: Lee Min S. , Kliewer Steven A. , Provencal Joan , Wright Peter E. , Evans Ronald M.
Published: October 2006

The three-dimensional solution structure of the DNA binding domain (DBD) of the retinoid X receptor α (RXRα) was determined by nuclear magnetic resonance spectroscopy. The two zinc fingers of the RXR DBD fold to form a single structural domain that consists of two perpendicularly oriented helices and that resembles the corresponding regions of the glucocorticoid and estrogen receptors (GR and ER, respectively). However, in contrast to the DBDs of the GR and ER, the RXR DBD contains an additional helix immediately after the second zinc finger. This third helix mediates both protein-protein and protein-DNA interactions required for cooperative, dimeric binding of the RXR DBD to DNA. Identification of the third helix in the RXR DBD thus defines a structural feature required for selective dimerization of the RXR on hormone response elements composed of half-sites (5′-AGGTCA-3′) arranged as tandem repeats.
Effects of cAMP Simulate a Late Stage of LTP in Hippocampal CA1 Neurons
Authors: Frey U. , Huang Y.-Y. , Kandel E. R.
Published: October 2006

Hippocampal long-term potentiation (LTP) is thought to serve as an elementary mechanism for the establishment of certain forms of explicit memory in the mammalian brain. As is the case with behavioral memory, LTP in the CA1 region has stages: a short-term early potentiation lasting 1 to 3 hours, which is independent of protein synthesis, precedes a later, longer lasting stage (L-LTP), which requires protein synthesis. Inhibitors of cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) blocked L-LTP, and analogs of cAMP induced a potentiation that blocked naturally induced L-LTP. The action of the cAMP analog was blocked by inhibitors of protein synthesis. Thus, activation of PKA may be a component of the mechanism that generates L-LTP.
An Essential Role for Protein Phosphatases in Hippocampal Long-Term Depression
Authors: Mulkey Rosel M. , Herron Caroline E. , Malenka Robert C.
Published: October 2006

The effectiveness of long-term potentiation (LTP) as a mechanism for information storage would be severely limited if processes that decrease synaptic strength did not also exist. In area CA1 of the rat hippocampus, prolonged periods of low-frequency afferent stimulation elicit a long-term depression (LTD) that is specific to the stimulated input. The induction of LTD was blocked by the extracellular application of okadaic acid or calyculin A, two inhibitors of protein phosphatases 1 and 2A. The loading of CA1 cells with microcystin LR, a membrane-impermeable protein phosphatase inhibitor, or calmodulin antagonists also blocked or attenuated LTD. The application of calyculin A after the induction of LTD reversed the synaptic depression, suggesting that phosphatase activity is required for the maintenance of LTD. These findings indicate that the synaptic activation of protein phosphatases plays an important role in the regulation of synaptic transmission.
Regulation of Heat Shock Factor Trimer Formation: Role of a Conserved Leucine Zipper
Authors: Rabindran Sridhar K. , Haroun Raymond I. , Clos Joachim , Wisniewski Jan , Wu Carl
Published: October 2006

The human and
Drosophila
heat shock transcription factors (HSFs) are multi-zipper proteins with high-affinity binding to DNA that is regulated by heat shock-induced trimerization. Formation of HSF trimers is dependent on hydrophobic heptad repeats located in the amino-terminal region of the protein. Two subregions at the carboxyl-terminal end of human HSF1 were identified that maintain the monomeric form of the protein under normal conditions. One of these contains a leucine zipper motif that is conserved between vertebrate and insect HSFs. These results suggest that the carboxyl-terminal zipper may suppress formation of trimers by the amino-terminal HSF zipper elements by means of intramolecular coiled-coil interactions that are sensitive to heat shock.
A
wingless
-Dependent Polar Coordinate System in
Drosophila
Imaginal Discs
Authors: Couso Juan Pablo , Bate Michael , Martínez-Arias Alfonso
Published: October 2006

The patterning of the imaginal discs in
Drosophila melanogaster
is a progressive process that, like the patterning of the larval epidermis during embryogenesis, requires the activity of segment polarity genes. One segment polarity gene,
wingless
, encodes a homolog of the mouse proto-oncogene
Wnt-1
and plays a prominent role in the patterning of the larval epidermis and the imaginal discs. However, whereas the function of
wingless
in the embryo is initially associated with a pattern of stripes along the anteroposterior axis that are part of a Cartesian coordinate system, it is shown here that during imaginal development
wingless
is associated with a pattern of sectors that provide references for a polar coordinate system homologous to that postulated in a well-known model for the regeneration of insect and vertebrate limbs.
CNTF Protection of Oligodendrocytes Against Natural and Tumor Necrosis Factor-Induced Death
Authors: Louis Jean-Claude , Magal Ella , Takayama Seiji , Varon Silvio
Published: October 2006

A proportion of developing oligodendrocytes undergo natural cell death by apoptosis, and mature oligodendrocytes die, either by apoptosis or necrosis, in response to injurious signals such as cytotoxic cytokines and complement. Ciliary neurotrophic factor (CNTF), a trophic factor found in astrocytes in the central nervous system (CNS), promoted the survival and maturation of cultured oligodendrocytes. This trophic factor also protected oligodendrocytes from death induced by tumor necrosis factors (apoptosis) but not against complement (necrosis). These results suggest that CNTF functions in the survival of oligodendrocytes during development and may lead to therapeutic approaches for degenerative diseases of the CNS that involve oligodendrocyte destruction.
Restoration of T Cell Development in RAG-2-Deficient Mice by Functional TCR Transgenes
Authors: Shinkai Yoichi , Koyasu Shigeo , Nakayama Kei-ichi , Murphy Kenneth M. , Loh Dennis Y. , Reinherz Ellis L. , Alt Frederick W.
Published: October 2006

Introduction of TCRα transgene, TCRβ transgene, or both into RAG-2
-/-
mice differentially rescues T cell development. RAG-2
-/-
mice have small numbers of TCR
-
CD4
-
CD8
-
(double negative, DN) thymocytes that express CD3γδε and ζ proteins intracellularly. Introduction of a TCRβ transgene, but not a TCRα transgene, into the RAG-2
-/-
background restored normal numbers of thymocytes. These cells were CD4
+
CD8
+
(double positive, DP) and expressed small amounts of surface TCRβ chain dimers in association with CD3γδε but not ζ. RAG-2
-/-
mice that expressed α and β TCR transgenes developed both DP and single positive thymocytes. Thus, the TCRβ subunit, possibly in association with a novel CD3 complex, participates in the DN to the DP transition.
Anti-Oncogenic and Oncogenic Potentials of Interferon Regulatory Factors-1 and -2
Authors: Harada Hisashi , Kitagawa Motoo , Tanaka Nobuyuki , Yamamoto Hitomi , Harada Kenji , Ishihara Masahiko , Taniguchi Tadatsugu
Published: October 2006

Interferon regulatory factor-1 (IRF-1), a transcriptional activator, and IRF-2, its antagonistic repressor, have been identified as regulators of type I interferon and interferon-inducible genes. The
IRF-1
gene is itself interferon-inducible and hence may be one of the target genes critical for interferon action. When the
IRF-2
gene was overexpressed in NIH 3T3 cells, the cells became transformed and displayed enhanced tumorigenicity in nude mice. This transformed phenotype was reversed by concomitant overexpression of the
IRF-1
gene. Thus, restrained cell growth depends on a balance between these two mutually antagonistic transcription factors.
A Complete Second Gut Induced by Transplanted Micromeres in the Sea Urchin Embryo
Authors: Ransick Andrew , Davidson Eric H.
Published: October 2006

Founder cells for most early lineages of the sea urchin embryo are probably specified through inductive intercellular interactions. It is shown here that a complete respecification of cell fate occurs when 16-cell stage micromeres from the vegetal pole of a donor embryo are implanted into the animal pole of an intact recipient embryo. Animal pole cells adjacent to the transplanted micromeres are respecified from presumptive ectoderm into vegetal plate founder cells. These induced vegetal plate cells express the entire battery of genes characteristic of the endogenous vegetal plate cells. The ectopic vegetal plate invaginates during gastrulation to form a second archenteron which differentiates properly into a tripartite gut, as shown by the spatial pattern of expression of an endoderm-specific marker gene. Thus, transplanted micromeres can signal neighboring cells to induce them to change their fate.
A Functional Role for GTP-Binding Proteins in Synaptic Vesicle Cycling
Authors: Hess S. D. , Doroshenko P. A. , Augustine G. J.
Published: October 2006

The squid giant synapse was used to test the hypothesis that guanosine-5′-triphosphate (GTP)-binding proteins regulate the local distribution of synaptic vesicles within nerve terminals. Presynaptic injection of the nonhydrolyzable GTP analog GTPγS irreversibly inhibited neurotransmitter release without changing either the size of the calcium signals produced by presynaptic action potentials or the number of synaptic vesicles docked at presynaptic active zones. Neurotransmitter release was also inhibited by injection of the nonhydrolyzable guanosine diphosphate (GDP) analog GDPβS but not by injection of AIF
4
-
. These results suggest that a small molecular weight GTP-binding protein directs the docking of synaptic vesicles that occurs before calcium-dependent neurotransmitter release. Depletion of undocked synaptic vesicles by GTPγS indicates that additional GTP-binding proteins function in the terminal at other steps responsible for synaptic vesicle replenishment.
Heterologous Protection Against Influenza by Injection of DNA Encoding a Viral Protein
Authors: Ulmer Jeffrey B. , Donnelly John J. , Parker Suezanne E. , Rhodes Gary H. , Felgner Philip L. , Dwarki V. J. , Gromkowski Stanislaw H. , Deck R. Randall , DeWitt Corrille M. , Friedman Arthur , Hawe Linda A. , Leander Karen R. , Martinez Douglas , Perry Helen C. , Shiver John W. , Montgomery Donna L. , Liu Margaret A.
Published: October 2006

Cytotoxic T lymphocytes (CTLs) specific for conserved viral antigens can respond to different strains of virus, in contrast to antibodies, which are generally strain-specific. The generation of such CTLs in vivo usually requires endogenous expression of the antigen, as occurs in the case of virus infection. To generate a viral antigen for presentation to the immune system without the limitations of direct peptide delivery or viral vectors, plasmid DNA encoding influenza A nucleoprotein was injected into the quadriceps of BALB/c mice. This resulted in the generation of nucleoprotein-specific CTLs and protection from a subsequent challenge with a heterologous strain of influenza A virus, as measured by decreased viral lung titers, inhibition of mass loss, and increased survival.
Structural Relationship of Bacterial RecA Proteins to Recombination Proteins from Bacteriophage T4 and Yeast
Authors: Story Randall M. , Bishop Douglas K. , Kleckner Nancy , Steitz Thomas A.
Published: October 2006

RecA protein is essential in eubacteria for homologous recombination and promotes the homologous pairing and strand exchange of DNA molecules in vitro. Recombination proteins with weak sequence similarity to bacterial RecA proteins have been identified in bacteriophage T4, yeast, and other higher organisms. Analysis of the primary sequence relationships of DMC1 from
Saccharomyces cerevisiae
and UvsX of T4 relative to the three-dimensional structure of RecA from
Escherichia coli
suggests that both proteins are structural homologs of bacterial RecA proteins. This analysis argues that proteins in this group are members of a single family that diverged from a common ancestor that existed prior to the divergence of prokaryotes and eukaryotes.
Charon Phages: Safer Derivatives of Bacteriophage Lambda for DNA Cloning
Authors: Blattner Frederick R. , Williams Bill G. , Blechl Ann E. , Denniston-Thompson Katherine , Faber Harvey E. , Furlong Lesley-Anne , Grunwald David J. , Kiefer Delight O. , Moore David D. , Schumm James W. , Sheldon Edward L. , Smithies Oliver
Published: October 2006

The Charon λ bacteriophages have been developed as vectors for cloning. Their construction incorporates mutations that make them simple to use and also greatly increases their safety for the biological containment of cloned recombinant DNA. Three of the Charon vector phages, 3A, 4A, and 16A, have been certified for use as EK2 vector-host systems, when propagated in bulk in a special bacterial host, DP50SupF. We present here some of the data on which the safety of these systems was evaluated. DNA fragments ranging in size from 0 to 2.2 × 10
4
base pairs can be cloned in these EK2 Charon phages.
Where Plants Make Oxygen: a Structural Model for the Photosynthetic Oxygen-Evolving Manganese Cluster
Authors: Yachandra Vittal K. , DeRose Victoria J. , Latimer Matthew J. , Mukerji Ishita , Sauer Kenneth , Klein Melvin P.
Published: October 2006

In the photosynthetic evolution of oxygen, water oxidation occurs at a catalytic site that includes four manganese atoms together with the essential cofactors, the calcium and chlorine ions. A structural model and a determination of the manganese oxidation states based on x-ray absorption spectroscopy are presented. The salient features, in both higher plants and cyanobacteria, are a pair of di-μ-oxo bridged manganese binuclear clusters linked by a mono-μ-oxo bridge, one proximal calcium atom, and one halide. In dark-adapted samples, manganese occurs in oxidation states (III) and (IV). Data from oriented membranes display distinct dichroism, precluding highly symmetrical structures for the manganese complex.
The Basic Science of Gene Therapy
Authors: Mulligan Richard C.
Published: October 2006

The development over the past decade of methods for delivering genes to mammalian cells has stimulated great interest in the possibility of treating human disease by gene-based therapies. However, despite substantial progress, a number of key technical issues need to be resolved before gene therapy can be safely and effectively applied in the clinic. Future technological developments, particularly in the areas of gene delivery and cell transplantation, will be critical for the successful practice of gene therapy.
Kinetics of Folding of the All-β Sheet Protein Interleukin-1β
Authors: Varley Paul , Gronenborn Angela M. , Christensen Henriette , Wingfield Paul T. , Pain Roger H. , Clore G. Marius
Published: October 2006

The folding of the all-β sheet protein, interleukin-1β, was studied with nuclear magnetic resonance (NMR) spectroscopy, circular dichroism, and fluorescence. Ninety percent of the β structure present in the native protein, as monitored by far-ultraviolet circular dichroism, was attained within 25 milliseconds, correlating with the first kinetic phase determined by tryptophan and 1-anilinonaphthalene-8-sulfonate fluorescence. In contrast, formation of stable native secondary structure, as measured by quenched-flow deuterium-hydrogen exchange experiments, began after only 1 second. Results from the NMR experiments indicated the formation of at least two intermediates with half-lives of 0.7 to 1.5 and 15 to 25 seconds. The final stabilization of the secondary structure, however, occurs on a time scale much greater than 25 seconds. These results differ from previous results on mixed α helix-β sheet proteins in which both the α helices and β sheets were stabilized very rapidly (less than 10 to 20 milliseconds).
Feedback Regulation Mechanisms for the Control of GTP Cyclohydrolase I Activity
Authors: Harada Toshie , Kagamiyama Hiroyuki , Hatakeyama Kazuyuki
Published: October 2006

Guanosine triphosphate (GTP) cyclohydrolase I, the rate-limiting enzyme in the biosynthesis of tetrahydrobiopterin (BH
4
), is subject to feedback inhibition by BH
4
, a cofactor for phenylalanine hydroxylase. Inhibition was found to depend specifically on BH
4
and the presence of another protein (p35). The inhibition occurred through BH
4
-dependent complex formation between p35 protein and GTP cyclohydrolase I. Furthermore, the inhibition was specifically reversed by phenylalanine, and, in conjunction with p35, phenylalanine reduced the cooperativity of GTP cyclohydrolase I. These findings also provide a molecular basis for high plasma BH
4
concentrations observed in patients with hyperphenylalaninemia caused by phenylalanine hydroxylase deficiency.
Myasthenic Immunoglobulin Accelerates Acetylcholine Receptor Degradation
Authors: Kao Ing , Drachman Daniel B.
Published: October 2006

Degradation of acetylcholine receptors by cultured rat skeletal muscle cells was determined from the release of
125
I from bound
125
I-labeled α-bungarotoxin. Addition of immunoglobulin from patients with myasthenia gravis to the culture medium accelerated the degradation rate to a mean of 8.51 ± 0.44 percent per hour, compared with the mean control rate of 3.97 ± 0.14 percent per hour (
P
< <.001). A similar mechanism may possibly be involved in the autoimmune pathogenesis of myasthenia gravis in man.
From RNA to DNA, Why So Many Ribonucleotide Reductases?
Authors: Reichard Peter
Published: October 2006

It is generally accepted that DNA appeared after RNA during the chemical evolution of life. To synthesize DNA, deoxyribonucleotides are required as building blocks. At present, these are formed from the corresponding ribonucleotides through the enzymatic action of ribonucleotide reductases. Three classes of enzymes are present in various organisms. There is little sequence similarity among the three classes of reductases. However, enzymic mechanisms and the allosteric behavior of the enzymes from various organisms are strongly conserved, suggesting that the enzymes might have evolved from a common ancestor, with the class III anaerobic
Escherichia coli
reductase as its closest relative.
Rapid Remodeling of Axonal Arbors in the Visual Cortex
Authors: Antonini Antonella , Stryker Michael P.
Published: October 2006

If vision in one eye is blurred or occluded during a critical period in postnatal development, neurons in the visual cortex lose their responses to stimulation through that eye within a few days. Anatomical changes in the nerve terminals that provide input to the visual cortex have previously been observed only after weeks of deprivation, suggesting that synapses become physiologically ineffective before the branches on which they sit are withdrawn. Reconstruction of single geniculocortical axonal arbors in the cat after either brief or prolonged monocular occlusion revealed striking axonal rearrangements in both instances. Rapid withdrawal of the branches of deprived-eye arbors suggests that axonal branches bearing synapses respond quickly to changing patterns of neuronal activity.
Motor Vehicle Fatalities Increase Just After Publicized Suicide Stories
Authors: Phillips David P.
Published: October 2006

The average increase in motor vehicle fatalities is 9.12 percent in the week after a suicide story. The more publicity given to the story, the greater the rise in motor vehicle deaths thereafter. This rise apparently occurs because suicide stories stimulate a wave of imitative suicides, some of which are disguised as motor vehicle accidents.
Cardiac Glycosides in the Defensive Secretion of Chrysomelid Beetles: Evidence for Their Production by the Insects
Authors: Pasteels Jacques M. , Daloze Désiré
Published: October 2006

The defensive secretions of some chrysomelid beetles belonging to the genera
Chrysolina
,
Chrysochloa
, and
Dlochrysa
contain complex mixtures of cardenolides. The spectral data for some of these compounds suggest that they are monohydroxylated digitoxigenin derivatives linked to a pentose (such as xylose or arabinose). Evidence indicates that the beetles do not sequester these steroid glycosides from their host plants.
Efferent Optic Nerve Fibers Mediate Circadian Rhythms in the
Limulus
Eye
Authors: Barlow Robert B. , Bolanowski Stanley J. , Brachman Michael L.
Published: October 2006

When the horseshoe crab is kept in constant darkness, the lateral eye produces larger electroretinographic and optic nerve responses at night than during the day. These circadian rhythms are mediated by synchronous bursts of efferent impulses in the optic nerve trunk. The endogenous efferent activity appears to increase both the gain and the quantum catch of the photoreceptors.
Catechol Estrogens: Presence in Brain and Endocrine Tissues
Authors: Paul Steven M. , Axelrod Julius
Published: October 2006

Catechol estrogens have been identified and measured in rat brain and various endocrine tissues with the use of a sensitive radioenzymatic assay. The specificity of this assay was confirmed by thin-layer chromatography and mass spectral analysis of the reaction products. The concentration of catechol estrogens in the hypothalamus and pituitary are at least ten times higher than reported previously for the parent estrogens. Catechol estrogens have potent endocrine effects and, because of their normal occurrence in the hypothalamic-pituitary axis, they may have an important role in neuroendocrine regulation.
Molecular Graphics: Application to the Structure Determination of a Snake Venom Neurotoxin
Authors: Tsernoglou Demetrius , Petsko Gregory A. , McQueen John E. , Hermans Jan
Published: October 2006

Atomic coordinates have been determined for a snake venom α-neurotoxic protein by fitting a molecular model to a crystallographically derived 2.2-angstrom electron density map. The fitting was carried out entirely on a computer-operated molecular graphics system without going through any mechanical model stage.
Clockwise Growth of Neurites from Retinal Explants
Authors: Heacock Anne M. , Agranoff Bernard W.
Published: October 2006

When retinal explants from goldfish are grown on a polycation substratum, a marked tendency for directionality of neurite outgrowth is observed. While the direct relevance to nerve growth in vivo is not known, the phenomenon is interpreted as reflecting an inherent helicity of the neurites.
Spatial Frequency and the Mediation of Short-Term Visual Storage
Authors: Meyer Glenn E. , Maguire William M.
Published: October 2006

The perceived duration of a photopically illuminated, fixated grating presented for 50 milliseconds increased (from 300 to 500 milliseconds) with spatial frequency (0.9 to 15 cycles per degree). This suggests a sustained neural channel contribution to short-term visual storage, and argues against a pure photoreceptor, especially a rod, locus for such storage.
The Code of the Scientist and Its Relationship to Ethics
Authors: Cournand André
Published: October 2006

Scientist's norms (principally honesty, objectivity, tolerance, doubt of certitude, and unselfish engagement) are in danger of serious distortion unless broadened to apply to the relations between scientists and nonscientists. Also needing supplementation is an ethic of development appropriate to a fast-changing society and advanced as an approach to the more effective and humane regulation of cultural and technological development. Because of their genetic relationships the code of the scientist and the ethic of development are probably complementary and together may overcome the shortcomings of each taken separately. Taken together, furthermore, they indicate the possibility of a humane world order based on the cooperation of a community of scientists and its public.
Liposome Accumulation in Regions of Experimental Myocardial Infarction
Authors: Caride Vicente J. , Zaret Barry L.
Published: October 2006

The uptake of liposomes bearing positive, negative, or no net charge on their membrane and containing a radioactive tracer, [
99m
Tc]diethylenetriamine pentaacetic acid, was studied in 12 intact dogs 24 hours after the induction of myocardial infarction, and compared to the relative regional myocardial blood flow determined from radioactive microspheres. Positively charged and neutral liposomes concentrate in infarcted regions against a flow gradient, while negative liposomes are passively distributed according to regional blood flow. Because positively charged and neutral liposomes concentrate in infarct areas and have the ability to incorporate pharmacologic agents in their aqueous or lipid phase, they may serve as vehicles for drug delivery to infarct zones of low flow.
Postnatal Development of the Human Lateral Geniculate Nucleus: Relationship to a Critical Period for the Visual System
Authors: Hickey T. L.
Published: October 2006

The cross-sectional areas of 31,800 dorsal lateral geniculate nucleus cells were measured in 53 human brains ranging in age from newborn to 40 years. Geniculate cells increase in size rapidly during the first 6 to 12 months of postnatal life, with cells in the parvocellular layers developing faster than cells in the magnocellular layers. At least 2 years are required before all cells have reached their adult size.
Morphine Analgesic Tolerance: Its Situation Specificity Supports a Pavlovian Conditioning Model
Authors: Siegel Shepard
Published: October 2006

Rats were made tolerant to morphine in either of two environments and then assessed for morphine-induced alteration of pain sensitivity in both environments. Analgesic tolerance was displayed when rats were tested in that environment in which they previously received morphine, but not in the alternative environment. The results indicate than an association between environmental cues and the systemic effects of morphine is crucial to tolerance development.
Functional Development of Prefrontal Cortex in Rats Continues into Adolescence
Authors: Kolb Bryan , Nonneman Arthur J.
Published: October 2006

Bilateral removal of the sulcal prefrontal cortex in rats at 60 days of age and older results in aphagia and adipsia, but removal of this area before 60 days of age does not affect food or water regulation. Apparently the development of the role of this neocortical region in feeding and drinking continues well beyond the time of weaning in the rat.
Two Functional Effects of Decreased Conductance EPSP's: Synaptic Augmentation and Increased Electrotonic Coupling
Authors: Carew Thomas J. , Kandel Eric R.
Published: October 2006

Three electronically coupled motor neurons, which mediate inking behavior in
Aplysia californica
, receive both increased and decreased conductance excitatory postsynaptic potentials (EPSP's). The increased conductance EPSP's reduce electrical coupling among the cells, whereas the decreased conductance EPSP's increase electrical coupling. The decreased conductance EPSP's also augment the action of a previously ineffective sensory input and this augmentation is enhanced by the increase in electrical coupling. Both effects combine to trigger a stereotypic behavioral response.