bluuebunny/crossref_metadata_2025 huggingface dataset:
Lunar Phasing of the Thyroxine Surge Preparatory to Seaward Migration of Salmonid Fish
Authors: Grau E. Gordon , Dickhoff Walton W. , Nishioka Richard S. , Bern Howard A. , Folmar Leroy C.
Published: October 2006

Anadromous salmonid fish show a distinct surge in plasma thyroxine during the smoltification period prior to their migration to the sea. Analysis of 27 groups of hatchery-reared salmon and anadromous trout indicates that thyroxine levels peak coincident with the new moon. The ability to predict migratory readiness by lunar calendar would have substantial implications for the efficient culture of this economically important protein resource.
Neural Correlates of a Nonjammable Electrolocation System
Authors: Matsubara Joanne A.
Published: October 2006

The detection of objects by the electrosensory system of weakly electric fish is subject to electrical interference such as that produced by the electric organ discharges emitted by neighboring electric fish. Most electric fish species have a behavioral reflex, the jamming avoidance response, which protects their electrolocation system against jamming.
Sternopygus
is unique in that it has no jamming avoidance response, yet can electrolocate even in the presence of jamming. It appears that
Sternopygus
protects electrolocation not by a behavioral strategy but by first-order central processing mechanisms that can distinguish between localized changes in the amplitudes of electric organ discharges caused by objects and large-field amplitude modulations caused by jamming. This mechanism acts as a local contrast detector and is functionally similar to the one used by retinal cells to respond to local contrast in light but not to overall changes in illumination.
The Evolution of Cooperation
Authors: Axelrod Robert , Hamilton William D.
Published: October 2006

Cooperation in organisms, whether bacteria or primates, has been a difficulty for evolutionary theory since Darwin. On the assumption that interactions between pairs of individuals occur on a probabilistic basis, a model is developed based on the concept of an evolutionarily stable strategy in the context of the Prisoner's Dilemma game. Deductions from the model, and the results of a computer tournament show how cooperation based on reciprocity can get started in an asocial world, can thrive while interacting with a wide range of other strategies, and can resist invasion once fully established. Potential applications include specific aspects of territoriality, mating, and disease.
Non-Mendelian Inheritance of Mosquito Susceptibility to Infection with
Brugia malayi
and
Brugia pahangi
Authors: Trpis Milan , Duhrkopf Richard E. , Parker Karen L.
Published: October 2006

The mode of inheritance of susceptibility or refractoriness of insect vectors to medically important pathogens such as those causing malaria or filariasis is usually believed to follow normal Mendelian laws and to involve a single pair of alleles. In this report, experiments are described that demonstrate another mode of inheritance of mosquito susceptibility to filarial parasites. Crosses were made between susceptible and refractory species of the
Aedes scutellaris
complex, and the hybrid and backcross progeny were tested for susceptibility to infection by
Brugia malayi
and
Brugia pahangi
. The data indicate that inheritance follows a non-Mendelian pattern indicative of extrachromosomal factors inherited through the maternal parent.
Translocation of Repetitive RNA Sequences with the Germ Plasm in
Xenopus
Oocytes
Authors: Kloc Malgorzata , Spohr Georges , Etkin Laurence D.
Published: October 2006

Xlsirts are a family of interspersed repeat RNAs from
Xenopus laevis
that contain from 3 to 13 repeat units (each 79 to 81 nucleotides long) flanked by unique sequences. They are homologous to the mammalian
Xist
gene that is involved in X chromosome inactivation. Xlsirt RNA appears first in the mitochondrial cloud (Balbiani body) in stage 2 oocytes and is then translocated as island-like structures to the vegetal cortex at early stage 3 coincident with the localization of the germ plasm. Exogenous Xlsirt RNA injected into oocytes translocates to the location of the endogenous RNA at that particular stage. The Xlsirt RNA repeat sequences are required for translocation and can cause the translocation of heterologous unique RNAs to the vegetal cortex.
Endosteal Marrow: A Rich Source of Hematopoietic Stem Cells
Authors: Gong Joseph K.
Published: October 2006

Hematopoietic cells isolated from the endosteal bone surface, that is, the endosteal marrow cells, were found to consist mainly (60 to 80 percent) of lymphoid and late-stage normoblast-like cells. Unlike the cells they resemble, the endosteal marrow cells showed an affinity for Sudan black, demonstrable nucleoli (Feulgen reaction), and an absence of hemoglobin. Assays showed that over one-half of the endosteal marrow cell population may be the colony-forming units, the CFU-S of Till and McCulloch. Thus, high concentrations of stem cells could be obtained from the endosteal bone surface by means of the present isolation technique.
Adipose Expression of Tumor Necrosis Factor-α: Direct Role in Obesity-Linked Insulin Resistance
Authors: Hotamisligil Gökhan S. , Shargill Narinder S. , Spiegelman Bruce M.
Published: October 2006

Tumor necrosis factor-α (TNF-α) has been shown to have certain catabolic effects on fat cells and whole animals. An induction of TNF-α messenger RNA expression was observed in adipose tissue from four different rodent models of obesity and diabetes. TNF-α protein was also elevated locally and systemically. Neutralization of TNF-α in obese
fa
/
fa
rats caused a significant increase in the peripheral uptake of glucose in response to insulin. These results indicate a role for TNF-α in obesity and particularly in the insulin resistance and diabetes that often accompany obesity.
Double-Blind Pilot Trial of Oral Tolerization with Myelin Antigens in Multiple Sclerosis
Authors: Weiner Howard L. , Mackin Glenn A. , Matsui Makoto , Orav E. John , Khoury Samia J. , Dawson David M. , Hafler David A.
Published: October 2006

Multiple sclerosis (MS) is thought to be an autoimmune disease mediated by T lymphocytes that recognize myelin components of the central nervous system. In a 1-year double-blind study, 30 individuals with relapsing-remitting MS received daily capsules of bovine myelin or a control protein to determine the effect of oral tolerization to myelin antigens on the disease. Six of 15 individuals in the myelin-treated group had at least one major exacerbation; 12 of 15 had an attack in the control group. T cells reactive with myelin basic protein were reduced in the myelin-treated group. No toxicity or side effects were noted. Although conclusions about efficacy cannot be drawn from these data, they open an area of investigation for MS and other autoimmune diseases.
Released Form of CNTF Receptor α Component as a Soluble Mediator of CNTF Responses
Authors: Davis Samuel , Aldrich Thomas H. , Ip Nancy Y. , Stahl Neil , Scherer Steven , Farruggella Thomas , DiStefano Peter S. , Curtis Rory , Panayotatos Nikos , Gascan Hugues , Chevalier Sylvie , Yancopoulos George D.
Published: October 2006

The α component of the receptor for ciliary neurotrophic factor (CNTF) differs from other known growth factor receptors in that it is anchored to cell membranes by a glycosylphosphatidylinositol linkage. One possible function of this type of linkage is to allow for the regulated release of this receptor component. Cell lines not normally responsive to CNTF responded to treatment with a combination of CNTF and a soluble form of the CNTF α receptor component. These findings not only demonstrate that the CNTF receptor α chain is a required component of the functional CNTF receptor complex but also reveal that it can function in soluble form as part of a heterodimeric ligand. Potential physiological roles for the soluble CNTF receptor are suggested by its presence in cerebrospinal fluid and by its release from skeletal muscle in response to peripheral nerve injury.
Circularly Permuted tRNAs as Specific Photoaffinity Probes of Ribonuclease P RNA Structure
Authors: Nolan James M. , Burke Donald H. , Pace Norman R.
Published: October 2006

Regions of
Escherichia coli
ribonuclease P (RNase P) RNA in proximity to a bound transfer RNA (tRNA) substrate were mapped by photoaffinity. A photoaffinity cross-linking reagent was introduced at specific sites in the interior of the native tRNA structure by modification of the 5′ ends of circularly permuted tRNAs (cptRNAs). The polymerase chain reaction was used for the production of cptRNA templates. After the amplification of a segment of a tandemly duplicated tRNA gene, the cptRNA gene was transcribed in vitro to produce cptRNA. Modified cptRNAs were cross-linked to RNase P RNA, and the conjugation sites in RNase P RNA were determined by primer extension. These sites occur in phylogenetically conserved structures and sequences and identify regions of the ribozyme that form part of the tRNA binding site. The use of circularly permuted molecules to position specific modifications is applicable to the study of many inter- and intramolecular interactions.
Immunoglobulin V
H
3 Gene Products: Natural Ligands for HIV gp120
Authors: Berberian Linda , Goodglick Lee , Kipps Thomas J. , Braun Jonathan
Published: October 2006

Infection with human immunodeficiency virus-type 1 (HIV-1) depletes T cells expressing CD4 and B cells expressing immunoglobulin (Ig) V
H
3 gene products. A subpopulation of normal B cells from non-HIV-infected individuals was shown to bind to HIV gp120 by means of membrane Ig; most of these B cells expressed V
H
3 family Ig. Serum V
H
3 IgM from uninfected individuals also avidly bound gp120. Finally, gp120 selectively induced Ig secretion by V
H
3 B cells, indicating that the binding of gp120 functionally activated these cells. These results indicate that naturally occurring V
H
3 Ig is a second ligand for gp120 and a candidate superantigen for V
H
3 B cells.
Oxidative Stress, Glutamate, and Neurodegenerative Disorders
Authors: Coyle Joseph T. , Puttfarcken Pamela
Published: October 2006

There is an increasing amount of experimental evidence that oxidative stress is a causal, or at least an ancillary, factor in the neuropathology of several adult neurodegenerative disorders, as well as in stroke, trauma, and seizures. At the same time, excessive or persistent activation of glutamate-gated ion channels may cause neuronal degeneration in these same conditions. Glutamate and related acidic amino acids are thought to be the major excitatory neurotransmitters in brain and may be utilized by 40 percent of the synapses. Thus, two broad mechanisms—oxidative stress and excessive activation of glutamate receptors—are converging and represent sequential as well as interacting processes that provide a final common pathway for cell vulnerability in the brain. The broad distribution in brain of the processes regulating oxidative stress and mediating glutamatergic neurotransmission may explain the wide range of disorders in which both have been implicated. Yet differential expression of components of the processes in particular neuronal systems may account for selective neurodegeneration in certain disorders.
Representation of the Visual Field on the Medical Wall of Occipital-Parietal Cortex in the Owl Monkey
Authors: Allman John M. , Kaas Jon H.
Published: October 2006

The medial visual area is located on the medial wall of occipital-parietal cortex. A much larger proportion of this area is devoted to the representation of the more peripheral parts of the visual field than in any other cortical area or subcortical visual structure that has been mapped previously in any species of primate.
Mutation of Glycine Receptor Subunit Creates β-Alanine Receptor Responsive to GABA
Authors: Schmieden Volker , Kuhse Jochen , Betz Heinrich
Published: October 2006

The amino acid at position 160 of the ligand-binding subunit, α1, is an important determinant of agonist and antagonist binding to the glycine receptor. Exchange of the neighboring residues, phenylalanine at position 159 and tyrosine at position 161, increased the efficacy of amino acid agonists. Whereas wild-type α1 channels expressed in
Xenopus
oocytes required 0.7 millimolar β-alanine for a half-maximal response, the doubly mutated (F159Y,Y161F) α1 subunit had an affinity for β-alanine (which was more potent than glycine) that was 110-fold that of the wild type. Also, γ-aminobutyric acid and D-serine, amino acids that do not activate wild-type α1 receptors, efficiently gated the mutant channel. Thus, aromatic hydroxyl groups are crucial for ligand discrimination at inhibitory amino acid receptors.
Primate Flicker Sensitivity: Psychophysics and Electrophysiology
Authors: Kelly D. H. , Boynton R. M. , Baron W. S.
Published: October 2006

A quantitative comparison is made between the psychophysical flicker response of man and similar data obtained electrophysiologically from the cones of macaque monkeys. When the psychophysical data are obtained from an eye that is strongly light-adapted, there is excellent agreement between the two sets of data at high frequencies. Under this condition, both kinds of data fit a distributed-parameter model, whose time constant also agrees with that derived from studies of the phosphenes elicited by electrical stimulation of the human eye. On the other hand, psychophysical data obtained with fully modulated stimuli (which minimally adapt the eye) yield a longer time constant for the same model. These results imply that the psychophysical flicker thresholds are normally controlled by a distributed filtering process that is proximal to the receptor stage. This slower, psychophysical process is evidently desensitized by intense adapting lights, so that the faster one that governs the electrophysiological responses can be detected.
The Role of Backbone Flexibility in the Accommodation of Variants That Repack the Core of T4 Lysozyme
Authors: Baldwin E. P. , Hajiseyedjavadi O. , Baase W. A. , Matthews B. W.
Published: October 2006

To understand better how the packing of side chains within the core influences protein structure and stability, the crystal structures were determined for eight variants of T4 lysozyme, each of which contains three to five substitutions at adjacent interior sites. Concerted main-chain and side-chain displacements, with movements of helical segments as large as 0.8 angstrom, were observed. In contrast, the angular conformations of the mutated side chains tended to remain unchanged, with torsion angles within 20° of those in the wild-type structure. These observations suggest that not only the rotation of side chains but also movements of the main chain must be considered in the evaluation of which amino acid sequences are compatible with a given protein fold.
A Functional Recombinant Myosin II Lacking a Regulatory Light Chain-Binding Site
Authors: Uyeda Taro Q. P. , Spudich James A.
Published: October 2006

Myosin II, which converts the energy of adenosine triphosphate hydrolysis into the movement of actin filaments, is a hexamer of two heavy chains, two essential light chains, and two regulatory light chains (RLCs).
Dictyostelium
myosin II is known to be regulated in vitro by phosphorylation of the RLC. Cells in which the wild-type myosin II heavy chain was replaced with a recombinant form that lacks the binding site for RLC carried out cytokinesis and almost normal development, processes known to be dependent on functional myosin II. Characterization of the purified recombinant protein suggests that a complex of RLC and the RLC binding site of the heavy chain plays an inhibitory role for adenosine triphosphatase activity and a structural role for the movement of myosin along actin.
Generation of Impossible Cross-Peaks Between Bulk Water and Biomolecules in Solution NMR
Authors: Warren Warren S. , Richter Wolfgang , Andreotti Amy Hamilton , Farmer Bennett T.
Published: October 2006

Intermolecular multiple-quantum coherences between bulk water and a glycoprotein fragment at modest concentration (20 mM) have been experimentally produced and detected, although such coherences are inconceivable in the normal theoretical framework of nuclear magnetic resonance. A density matrix treatment explains these results by including the long-range dipolar interaction between spins and by discarding the high-temperature approximation. These results imply that peak intensities (critical for structural determinations) can be distorted in many gradient experiments, and show that magic-angle gradients provide substantial improvements with reduced gradient strengths. They also suggest methods for contrast enhancement in magnetic resonance imaging.
Activation of the Nigrostriatal Dopaminergic Pathway by Injection of Cholera Enterotoxin into the Substantia Nigra
Authors: Quenzer L. F. , Galli C. L. , Neff N. H.
Published: October 2006

Twenty-four hours after unilateral injection of cholera enterotoxin into the rat substantia nigra there is an increase, in the striatum on the injected side, of basal adenylate cyclase activity, 3,4-dihydroxyphenylacetic acid, and 3-methoxy-4-hydroxyphenylacetic acid. Moreover, there is an increase of motor activity, and rats tend to circle contralateral to the side of the injection. Injection of cholera enterotoxin into brain nuclei may be a useful procedure for pharmacologically activating selected neuronal systems of brain and for studying the pharmacology of drugs that are suspected of interacting with these systems.
Ixr1, a Yeast Protein That Binds to Platinated DNA and Confers Sensitivity to Cisplatin
Authors: Brown Steven J. , Kellett Patti J. , Lippard Stephen J.
Published: October 2006

Structure-specific recognition proteins (SSRPs) bind to DNA containing intrastrand cross-links formed by the anticancer drug cisplatin. A yeast gene encoding an SSRP, designated
IXR1
, was cloned and sequenced. The Ixr1 protein, a member of the high mobility group-box protein family, bound specifically to DNA modified with cisplatin but not inactive platinum compounds. A yeast strain with an inactivated
IXR1
gene was half as sensitive to cisplatin and accumulated one-third as many platinum-DNA lesions after treatment with cisplatin as the parental strain. These findings suggest that SSRPs play a role in mediating the cytotoxicity of cisplatin.
Metal Ion-Dependent Modulation of the Dynamics of a Designed Protein
Authors: Handel Tracy M. , Williams Scott A. , DeGrado William F.
Published: October 2006

The peptide α
4
is a designed four-helix bundle that contains a highly simplified hydrophobic core composed exclusively of leucine residues; its tertiary structure is therefore largely dictated by hydrophobic forces. This small protein adopts a structure with properties intermediate between those of the native and molten globule states of proteins: it is compact, globular, and has very stable helices, but its apolar side chains are mobile and not as well packed as in many natural proteins. To induce a more native-like state, two Zn
2+
-binding sites were introduced into the protein, thereby replacing some of the non-specific hydrophobic interactions with more geometrically restrictive metal-ligand interactions. In the metal-bound state, this protein has properties that approach those of native proteins. Thus, hydrophobic interactions alone are sufficient to drive polypeptide chain folding nearly to completion, but specific interactions are required for a unique structure.
Memory for Lists of Sounds by the Bottle-Nosed Dolphin: Convergence of Memory Processes with Humans?
Authors: Thompson Roger K. R. , Herman Louis M.
Published: October 2006

After listening to a list of as many as six discriminably different 2-second sounds, a bottle-nosed dolphin classified a subsequent probe sound as either "old" (from the list) or "new." The probability of recognizing an old probe was close to 1.0 if it matched the most recent sound in the list and decreased sigmoidally for successively earlier list sounds. Memory span was estimated to be at least four sounds. Overall probabilities of correctly classifying old and new probes corresponded closely, as if recognition decisions were made according to an optimum maximum likelihood criterion. The data bore many similarities to data obtained from humans tested on probe recognition tasks.
Circadian Organization in Lizards: The Role of the Pineal Organ
Authors: Underwood Herbert
Published: October 2006

After pinealectomy, the iguanid lizard
Sceloporus olivaceus
exhibits a "splitting" of the circadian activity rhythm into two components, marked changes in the period of the rhythm, or arrhythmicity. These effects are consistent with either of two hypotheses: (i) The pineal organ is a coupling device between circadian oscillators in a multioscillator system, or (ii) the pineal organ is itself a master oscillator, which entrains other circadian oscillators and imposes its frequency upon them.
Terrestrial Locomotion in Penguins: It Costs More to Waddle
Authors: Pinshow Berry , Fedak Michael A. , Schmidt-Nielsen Knut
Published: October 2006

The energetic cost for walking is relatively higher for penguins than for other birds or for quadrupeds of similar body mass. The morphology of penguins seems to represent a compromise between aquatic and terrestrial locomotion wherein both energy economy and speed suffer when the birds move on land.
Inhibition of an in Vivo Antigen-Specific IgE Response by Antibodies to CD23
Authors: Flores-Romo Leopoldo , Shields John , Humbert Yves , Graber Pierre , Aubry Jean-Pierre , Gauchat Jean-François , Ayala Guidon , Allet Bernard , Chavez Marcela , Bazin Hervé , Capron Monique , Bonnefoy Jean-Yves
Published: October 2006

Immunoglobulin E (IgE) mediates many allergic responses. CD23 is a 45-kilodalton type II transmembrane glycoprotein expressed in many cell types. It is a low-affinity IgE receptor and interacts specifically with CD21, thereby modulating IgE production by B lymphocytes in vitro. In an in vivo model of an allergen-specific IgE response, administration of a rabbit polyclonal antibody to recombinant human truncated CD23 resulted in up to 90 percent inhibition of ovalbumin-specific IgE synthesis. Both Fabs and intact IgG inhibited IgE production in vitro and in vivo. Thus, CD23 participates in the regulation of IgE synthesis in vivo and so could be important in allergic disease.
Fusion Between Transcription Factor CBFβ/PEBP2β and a Myosin Heavy Chain in Acute Myeloid Leukemia
Authors: Liu Pu , Tarlé Susan A. , Hajra Amitav , Claxton David F. , Marlton Paula , Freedman Matthew , Siciliano Michael J. , Collins Francis S.
Published: October 2006

The pericentric inversion of chromosome 16 [inv(16)(p13q22)] is a characteristic karyotypic abnormality associated with acute myeloid leukemia, most commonly of the M4Eo subtype. The 16p and 16q breakpoints were pinpointed by yeast artificial chromosome and cosmid cloning, and the two genes involved in this inversion were identified. On 16q the inversion occurred near the end of the coding region for CBFβ, also known as PEBP2β, a subunit of a heterodimeric transcription factor regulating genes expressed in T cells; on 16p a smooth muscle myosin heavy chain (SMMHC) gene (MYH11) was interrupted. In six of six inv(16) patient samples tested, an in-frame fusion messenger RNA was demonstrated that connected the first 165 amino acids of CBFβ with the tail region of SMMHC. The repeated coiled coil of SMMHC may result in dimerization of the CBFβ fusion protein, which in turn would lead to alterations in transcriptional regulation and contribute to leukemic transformation.
Life History Variables Preserved In Dental Cementum Microstructure
Authors: Lieberman Daniel E.
Published: October 2006

The age and season of death of mammals, as well as other aspects of their life history, can be estimated from seasonal bands in dental cementum that result from variations in microstructure. Scanning electron micrographs of goats fed controlled diets demonstrate that cementum bands preserve variations in the relative orientation of collagen fibers that reflect changes in the magnitude and frequency of occlusal forces from chewing different quality diets. Changes in the rate of tissue growth are also reflected in cementum bands as variations in the degree of mineralization.
Identification of a Structural Glycoprotein of an RNA Virus as a Ribonuclease
Authors: Schneider Rainer , Unger Gabriele , Stark Robert , Schneider-Scherzer Elisabeth , Thiel Heinz-Jürgen
Published: October 2006

One of the three structural glycoproteins of classical swine fever virus (CSFV) is E0, a disulfide-bonded homodimer that induces virus-neutralizing antibodies and occurs in a virion-bound as well as a secreted form. E0 was shown to be similar to a family of fungal and plant ribonucleases. Purified E0 from CSFV-infected cells was a potent ribonuclease specific for uridine and inhibitable by zinc ions.
Crystal Structure of a Five-Finger GLI-DNA Complex: New Perspectives on Zinc Fingers
Authors: Pavletich Nikola P. , Pabo Carl O.
Published: October 2006

Zinc finger proteins, of the type first discovered in transcription factor IIIA (TFIIIA), are one of the largest and most important families of DNA-binding proteins. The crystal structure of a complex containing the five Zn fingers from the human GLI oncogene and a high-affinity DNA binding site has been determined at 2.6 Å resolution. Finger one does not contact the DNA. Fingers two through five bind in the major groove and wrap around the DNA, but lack the simple, strictly periodic arrangement observed in the Zif268 complex. Fingers four and five of GLI make extensive base contacts in a conserved nine base-pair region, and this section of the DNA has a conformation intermediate between B-DNA and A-DNA. Analyzing the GLI complex and comparing it with Zif268 offers new perspectives on Zn finger-DNA recognition.
Effects of Oral Administration of Type II Collagen on Rheumatoid Arthritis
Authors: Trentham David E. , Dynesius-Trentham Roselynn A. , Orav E. John , Combitchi Daniel , Lorenzo Carlos , Sewell Kathryn Lea , Hafler David A. , Weiner Howard L.
Published: October 2006

Rheumatoid arthritis is an inflammatory synovial disease thought to involve T cells reacting to an antigen within the joint. Type II collagen is the major protein in articular cartilage and is a potential autoantigen in this disease. Oral tolerization to autoantigens suppresses animal models of T cell-mediated autoimmune disease, including two models of rheumatoid arthritis. In this randomized, double-blind trial involving 60 patients with severe, active rheumatoid arthritis, a decrease in the number of swollen joints and tender joints occurred in subjects fed chicken type II collagen for 3 months but not in those that received a placebo. Four patients in the collagen group had complete remission of the disease. No side effects were evident. These data demonstrate clinical efficacy of an oral tolerization approach for rheumatoid arthritis.
Mineralocorticoid and Glucocorticoid Receptor Activities Distinguished by Nonreceptor Factors at a Composite Response Element
Authors: Pearce David , Yamamoto Keith R.
Published: October 2006

Mineralocorticoid and glucocorticoid hormones elicit distinct physiologic responses, yet the mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) bind to and activate transcription similarly from a consensus simple hormone response element (HRE). The activities of GR and MR at plfG, a 25-base pair composite response element to which both the steroid receptors and transcription factor AP1 can bind, are analyzed here. Under conditions in which GR represses AP1-stimulated transcription from plfG, MR was inactive. With the use of MR-GR chimeras, a segment of the NH
2
-terminal region of GR (amino acids 105 to 440) was shown to be required for this repression. Thus, the distinct physiologic effects mediated by MR and GR may be determined by differential interactions of nonreceptor factors with specific receptor domains at composite response elements.
Rhythmic Exocytosis Stimulated by GnRH-Induced Calcium Oscillations in Rat Gonadotropes
Authors: Tse Amy , Tse Frederick W. , Almers Wolfhard , Hille Bertil
Published: October 2006

In pituitary gonadotropes, gonadotropin-releasing hormone (GnRH) induces the rhythmic release of Ca
2+
from an inositol 1,4,5-trisphosphate (IP
3
)-sensitive store. Simultaneous measurement of the concentration of cytosolic free Ca
2+
([Ca
2+
]
i
) and exocytosis in single identified gonadotropes showed that each elevation of [Ca
2+
]
i
induced a burst of exocytosis. These phenomena were largely suppressed by buffering of [Ca
2+
]
i
but persisted in the absence of extracellular Ca
2+
. Activation of voltage-gated Ca
2+
channels by brief depolarizations seldom supplied enough Ca
2+
for exocytosis, but [Ca
2+
]
i
elevations induced by photolysis of caged IP
3
did trigger exocytosis, confirming that GnRH-stimulated gonadotropic hormone secretion is closely coupled to intracellular Ca
2+
release. Agonist-induced oscillations of [Ca
2+
]
i
in secretory cells may be a mechanism to optimize the secretory output while avoiding the toxic effects of sustained elevation of [Ca
2+
]
i
.
A Divergence in the MAP Kinase Regulatory Network Defined by MEK Kinase and Raf
Authors: Lange-Carter Carol A. , Pleiman Chris M. , Gardner Anne M. , Blumer Kendall J. , Johnson Gary L.
Published: October 2006

Mitogen-activated protein kinases (MAPKs) are rapidly phosphorylated and activated in response to various extracellular stimuli in many different cell types. Such regulation of MAPK results from sequential activation of a series of protein kinases. The kinases that phosphorylate MAPKs, the MAP kinase kinases (MEKs) are also activated by phosphorylation. MEKs are related in sequence to the yeast protein kinases Byr1 (from
Schizosaccharomyces pombe
) and Ste7 (from
Saccharomyces cerevisiae
), which function in the pheromone-induced signaling pathway that results in mating. Byr1 and Ste7 are in turn regulated by the protein kinases Byr2 and Ste11. The amino acid sequence of the mouse homolog of Byr2 and Ste11, denoted MEKK (MEK kinase), was elucidated from a complementary DNA sequence encoding a protein of 672 amino acid residues (73 kilodaltons). MEKK was expressed in all mouse tissues tested, and it phosphorylated and activated MEK. Phosphorylation and activation of MEK by MEKK was independent of Raf, a growth factor-regulated protein kinase that also phosphorylates MEK. Thus, MEKK and Raf converge at MEK in the protein kinase network mediating the activation of MAPKs by hormones, growth factors, and neurotransmitters.
Identification of a Mobile Endogenous Transposon in
Arabidopsis thaliana
Authors: Tsay Yi-Fang , Frank Mary J. , Page Tania , Dean Caroline , Crawford Nigel M.
Published: October 2006

A mobile endogenous transposable element,
Tag1
, has been identified in the plant
Arabidopsis thaliana
.
Tag1
was found in the nitrate transporter gene,
CHL1
, of a chlorate-resistant mutant present in a population of plants containing an active maize Ac transposon.
Tag1
excises from the
chl1
gene producing chlorate-sensitive revertants with
Tag1
or
Tag1
-related elements at different loci.
Tag1
and related elements are present in the Landsberg but not Columbia or Wassilewskija ecotypes of
Arabidopsis
. Thus,
Tag1
provides a tool for the insertional mutagenesis of plant genes essential for biological processes of agronomic importance.
Ryanodine Receptor Adaptation: Control Mechanism of Ca
2+
-Induced Ca
2+
Release in Heart
Authors: Györke Sandor , Fill Michael
Published: October 2006

Adaptation of single cardiac ryanodine receptor (RyR) channels was demonstrated by application of the caged calcium ion (Ca
2+
) methodology. In contrast to conventional desensitization found in surface membrane ligand-gated channels, single cardiac RyR channels adapted to maintained Ca
2+
stimuli, preserving their ability to respond to a second (larger) Ca
2+
stimulus. RyR adaptation may represent a molecular control mechanism for smoothly graded Ca
2+
-induced Ca
2+
release in heart and may be a fundamental feature of channels, including the inositol trisphosphate receptor, that are involved in intracellular Ca
2+
signaling in many cell types.
Strained-Layer van der Waals Epitaxy in a Langmuir-Blodgett Film
Authors: Viswanathan R. , Zasadzinski J. A. , Schwartz D. K.
Published: October 2006

Atomic force microscope images of Langmuir-Blodgett films of lead and manganese fatty acid salts show that these monolayers have long-range order and are oriented with respect to the mica substrate, although the lattice symmetries of the monolayers and substrate are dramatically different. The surface lattice of sequentially thicker films evolves toward the bulk structure while retaining the substrate alignment. This behavior is in distinct contrast to films of cadmium fatty acid salts on mica, or all films on amorphous silicon oxide, in which the monolayer structure is disordered and a three-layer-thick film displays the bulk structure.
Reconstitution of Chromatin Subunits
Authors: Woodcock C. L. F.
Published: October 2006

The recovery of the subunit structure of chromatin after dissociation and reconstitution is markedly affected by the procedure used. Some procedures give complete regeneration of subunits, but the procedure most commonly used for reconstitution gives poor yields of subunit-containing chromatin.
An Inhibitor of p34

CDC28

Protein Kinase Activity from
Saccharomyces cerevisiae
Authors: Mendenhall Michael D.
Published: October 2006

The p34

CDC28

protein from
Saccharomyces cerevisiae
is a homolog of the p34

cdc2

protein kinase, a fundamental regulator of cell division in all eukaryotic cells. Once activated it initiates the visible events of mitosis (chromosome condensation, nuclear envelope breakdown, and spindle formation). The p34

CDC28

protein also has a critical role in the initiation of DNA synthesis. The protein kinase activity is regulated by cycles of phosphorylation and dephosphorylation and by periodic association with cyclins. An endogenous 40-kilodalton protein (p40) originally identified as a substrate of the p34

CDC28

protein kinase was purified. The p40 protein bound tightly to p34

CDC28

and inhibited the activity of the kinase. The p40 protein may provide another mechanism to regulate p34

CDC28

protein kinase activity.
Antibody Catalysis of a Disfavored Chemical Transformation
Authors: Janda Kim D. , Shevlin Charles G. , Lerner Richard A.
Published: October 2006

Organic reactions are often limited by stereoelectronic constrains that appear along the reaction coordinate. An antibody has been generated that overcomes these constraints and catalyzes a highly disfavored chemical transformation. The antibody facilitates the difficult 6-endo-tet ring closure of an epoxy-alcohol to form a tetrahydropyran. The catalyzed process is in formal violation of what has become known as Baldwin's rules for ring-closure reactions. In addition to controlling the regiochemistry of the disfavored cyclization reaction, these catalytic antibodies resolve enantiomeric substrates to afford a stereochemically pure product. The principles demonstrated in this study may be applicable to other disfavored chemical processes.
Activation of the Sphingomyelin Signaling Pathway in Intact EL4 Cells and in a Cell-Free System By IL-1β
Authors: Mathias Shalini , Younes Anas , Kan Chu-Cheng , Orlow Irene , Joseph Cecil , Kolesnick Richard N.
Published: October 2006

The mechanism of interleukin-1 (IL-1) signaling is unknown. Tumor necrosis factor-α uses a signal transduction pathway that involves sphingomyelin hydrolysis to ceramide and stimulation of a ceramide-activated protein kinase. In intact EL4 thymoma cells, IL-1β similarly stimulated a rapid decrease of sphingomyelin and an elevation of ceramide, and enhanced ceramide-activated protein kinase activity. This cascade was also activated by IL-1β in a cell-free system, demonstrating tight coupling to the receptor. Exogenous sphingomyelinase, but not phospholipases A
2
, C, or D, in combination with phorbol ester replaced IL-1β to stimulate IL-2 secretion. Thus, IL-1β signals through the sphingomyelin pathway.
Editing of Transfer RNAs in
Acanthamoeba castellanii
Mitochondria
Authors: Lonergan Kim M. , Gray Michael W.
Published: October 2006

With the discovery of RNA editing, a process whereby the primary sequence of RNA is altered after transcription, traditional concepts of genetic information transfer had to be revised. The known RNA editing systems act mainly on messenger RNAs, introducing sequence changes that alter their coding properties. An editing system that acts on transfer RNAs is described here. In the mitochondria of
Acanthamoeba castellanii
, an amoeboid protozoan, certain transfer RNAs differ in sequence from the genes that encode them. The changes consist of single-nucleotide conversions (U to A, U to G, and A to G) that appear to arise posttranscriptionally, are localized in the acceptor stem, and have the effect of correcting mismatched base pairs. Editing thus restores the base pairing expected of a normal transfer RNA in this region.
Identification of a Ten-Amino Acid Proline-Rich SH3 Binding Site
Authors: Ren Ruibao , Mayer Bruce J. , Cicchetti Piera , Baltimore David
Published: October 2006

The Src homology 3 (SH3) region is a small protein domain present in a very large group of proteins, including cytoskeletal elements and signaling proteins. It is believed that SH3 domains serve as modules that mediate protein-protein associations and, along with Src homology 2 (SH2) domains, regulate cytoplasmic signaling. The SH3 binding sites of two SH3 binding proteins were localized to a nine- or ten-amino acid stretch very rich in proline residues. Similar SH3 binding motifs exist in the formins, proteins that function in pattern formation in embryonic limbs of the mouse, and one subtype of the muscarinic acetylcholine receptor. Identification of the SH3 binding site provides a basis for understanding the interaction between the SH3 domains and their targets.
Crystal Structure of a Synthetic Triple-Stranded α-Helical Bundle
Authors: Lovejoy Brett , Choe Seunghyon , Cascio Duilio , McRorie Donald K. , DeGrado William F. , Eisenberg David
Published: October 2006

The x-ray crystal structure of a peptide designed to form a double-stranded parallel coiled coil shows that it is actually a triple-stranded coiled coil formed by three α-helices. Unlike the designed parallel coiled coil, the helices run up-up-down. The structure is stabilized by a distinctive hydrophobic interface consisting of eight layers. As in the design, each α-helix in the coiled coil contributes one leucine side chain to each layer. The structure suggests that hydrophobic interactions are a dominant factor in the stabilization of coiled coils. The stoichiometry and geometry of coiled coils are primarily determined by side chain packing in the solvent-inaccessible interior, but electrostatic interactions also contribute.
A Mixed-Valent Polyiron Oxo Complex that Models the Biomineralization of the Ferritin Core
Authors: Taft Kingsley L. , Papaefthymiou Georgia C. , Lippard Stephen J.
Published: October 2006

A novel polyiron oxo complex, [Fe
III
4
Fe
II
8
(O)
2
(OCH
3
)
18
(O
2
CCH
3
)
6
(CH
3
OH)
4.67
] (1), has been prepared from ferrous acetate and lithium methoxide in methanol by slow addition of dioxygen. The three-dimensional close-packed layered structure found in 1 closely mimics that proposed for the inorganic core in the iron storage protein ferritin. The Mössbauer spectra of 1 reveal superparamagnetic relaxation at temperatures below 15 K, a property characteristic of the ferritin core. The small size and mixed-valent nature of 1 suggest that it is a reasonable model for intermediates formed in the biomineralization of iron during ferritin core formation. A related compound, with the same iron-oxygen framework found in 1 but containing only two ferric ions, has also been structurally characterized. Because the clusters exhibit properties of both discrete molecules and extended solids, they are representative of a new class of nanometer-sized compounds that bridge the molecular solid-state boundary.
Evolution of Endothermy in Fish: Mapping Physiological Traits on a Molecular Phylogeny
Authors: Block Barbara A. , Finnerty John R. , Stewart Alexandre F. R. , Kidd Jessica
Published: October 2006

Mackerels, tunas, and billfishes (suborder Scombroidei and Teleostei) provide an ideal taxonomic context in which to examine the evolution of endothermy. Multiple origins and diverse strategies for endothermy exist among these fish. Here a molecular phylogeny of the Scombroidei has been determined by direct sequencing of a portion of the mitochondrial
cytochrome b
gene. The distribution of endothermic species within this proposed genealogy indicates that the ability to warm the brain and retina arose independently in three lineages, each time in association with a movement into colder water. This suggests that the evolution of cranial endothermy in fish was selected in order to permit thermal niche expansion and not selected for increased aerobic capacity.
Monophyletic Origins of the Metazoa: an Evolutionary Link with Fungi
Authors: Wainright Patricia O. , Hinkle Gregory , Sogin Mitchell L. , Stickel Shawn K.
Published: October 2006

A phylogenetic framework inferred from comparisons of small subunit ribosomal RNA sequences describes the evolutionary origin and early branching patterns of the kingdom Animalia. Maximum likelihood analyses show the animal lineage is monophyletic and includes choanoflagellates. Within the metazoan assemblage, the divergence of sponges is followed by the Ctenophora, the Cnidaria plus the placozoan
Trichoplax adhaerens
, and finally by an unresolved polychotomy of bilateral animal phyla. From these data, it was inferred that animals and fungi share a unique evolutionary history and that their last common ancestor was a flagellated protist similar to extant choanoflagellates.
Social Structure of Pilot Whales Revealed by Analytical DNA Profiling
Authors: Amos Bill , Schlötterer Christian , Tautz Diethard
Published: October 2006

Long-finned pilot whales swim in large, extremely cohesive social groups known as pods. Molecular typing revealed that pod members form a single extended family. Mature males neither disperse from nor mate within their natal pods, a situation unusual for mammals. Such behavior could be explained in terms of inclusive fitness benefits gained by adult males helping the large number of female relatives with which they swim.
Regulation of V(D)J Recombination Activator Protein RAG-2 by Phosphorylation
Authors: Lin Weei-Chin , Desiderio Stephen
Published: October 2006

Antigen receptor genes are assembled by site-specific DNA rearrangement. The recombination activator genes
RAG-1
and
RAG-2
are essential for this process, termed V(D)J rearrangement. The activity and stability of the RAG-2 protein have now been shown to be regulated by phosphorylation. In fibroblasts RAG-2 was phosphorylated predominantly at two serine residues, one of which affected RAG-2 activity in vivo. The threonine at residue 490 was phosphorylated by p34

cdc2

kinase in vitro; phosphorylation at this site in vivo was associated with rapid degradation of RAG-2. Instability was transferred to chimeric proteins by a 90-residue portion of RAG-2. Mutation of the p34

cdc2

phosphorylation site of the tumor suppressor protein p53 conferred a similar phenotype, suggesting that this association between phosphorylation and degradation is a general mechanism.
Induction of Gα
iI2
-Specific Antisense RNA in Vivo Inhibits Neonatal Growth
Authors: Moxham Christopher M. , Hod Yaacov , Malbon Craig C.
Published: October 2006

Guanosine triphosphate-binding regulatory proteins (G proteins) are key elements in transmembrane signaling and have been implicated as regulators of more complex biological processes such as differentiation and development. The G protein Gα
i2
is capable of mediating the inhibitory control of adenylylcyclase and regulates stem cell differentiation to primitive endoderm. Here an antisense RNA to Gα
i2
was expressed in a hybrid RNA construct whose expression was both tissue-specific and induced at birth. Transgenic mice in which the antisense construct was expressed displayed a lack of normal development in targeted organs that correlated with the absence of Gα
i2
. The loss of Gα
i2
expression in adipose tissue of the transgenic mice was correlated with a rise in basal levels of adenosine 3′,5′-monophosphate (cAMP) and the loss of receptor-mediated inhibition of adenylylcyclase. These data expand our understanding of G protein function in vivo and demonstrate the necessity for Gα
i2
in the development of liver and fat.
A Nonpeptidyl Growth Hormone Secretagogue
Authors: Smith Roy G. , Cheng Kang , Schoen William R. , Pong Sheng-Shung , Hickey Gerard , Jacks Tom , Butler Bridget , Chan Wanda W.-S. , Chaung Lee-Yuh P. , Judith Fred , Taylor Joyce , Wyvratt Matthew J. , Fisher Michael H.
Published: October 2006

A nonpeptidyl secretagogue for growth hormone of the structure 3-amino-3-methyl-N-(2,3,4,5-tetrahydro-2-oxo-1-{[2′-(1H-tetrazol-5-yl) (1,1′-biphenyl)-4-yl]methyl}-1H-1-benzazepin-3(R)-yl)-butanamide (L-692,429) has been identified. L-692,429 synergizes with the natural growth hormone secretagogue growth hormone-releasing hormone and acts through an alternative signal transduction pathway. The mechanism of action of L-692,429 and studies with peptidyl and nonpeptidyl antagonists suggest that this molecule is a mimic of the growth hormone-releasing hexapeptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH2(GHRP-6). L-692,429 is an example of a nonpeptidyl specific secretagogue for growth hormone.
Evidence of DNA Bending in Transcription Complexes Imaged by Scanning Force Microscopy
Authors: Rees William A. , Keller Rebecca W. , Vesenka James P. , Yang Guoliang , Bustamante Carlos
Published: October 2006

Complexes of
Escherichia coli
RNA polymerase with DNA containing the λ

P
L

promoter have been deposited on mica and imaged in air with a scanning force microscope. The topographic images reveal the gross spatial relations of the polymerase relative to the DNA template. The DNA appears bent in open promoter complexes containing RNA polymerase bound to the promoter and appears more severely bent in elongation complexes in which RNA polymerase has synthesized a 15-nucleotide transcript. This difference could be related to the conformational changes that accompany the maturation of open promoter complexes into elongation complexes and suggests that formation of the elongation complex involves a considerable modification of the spatial relations between the polymerase and the DNA template.
DNA Sequence Determination by Hybridization: a Strategy for Efficient Large-Scale Sequencing
Authors: Drmanac R. , Drmanac S. , Strezoska Z. , Paunesku T. , Labat I. , Zeremski M. , Snoddy J. , Funkhouser W. K. , Koop B. , Hood L. , Crkvenjakov R.
Published: October 2006

The concept of sequencing by hybridization (SBH) makes use of an array of all possible
n
-nucleotide oligomers (
n
-mers) to identify
n
-mers present in an unknown DNA sequence. Computational approaches can then be used to assemble the complete sequence. As a validation of this concept, the sequences of three DNA fragments, 343 base pairs in length, were determined with octamer oligonucleotides. Possible applications of SBH include physical mapping (ordering) of overlapping DNA clones, sequence checking, DNA fingerprinting comparisons of normal and disease-causing genes, and the identification of DNA fragments with particular sequence motifs in complementary DNA and genomic libraries. The SBH techniques may accelerate the mapping and sequencing phases of the human genome project.
Assortative Mating by Unwed Biological Parents of Adopted Children
Authors: Plomin Robert , DeFries J. C. , Roberts M. K.
Published: October 2006

Analyses of data obtained from 662 unwed couples whose children were relinquished for adoption reveal that biological parents of adopted children mate assortatively. For physical characters, assortative mating of unwed parents was similar to that of wed parents; for behavioral characters, however, there was less assortative mating by the unwed parents. Because assortative mating inflates estimates of genetic parameters in adoption studies, future studies should collect information on both biological parents.