bluuebunny/crossref_metadata_2025 huggingface dataset:
Is Neural Noise Just a Nuisance?
Authors: Ferster David
Published: October 2006

The electrical activity of neurons triggered by a stimulus is characterized by a large component of noise. In his Perspective, Ferster discusses new results which reveal that, in the cortex of the brain, noise is not just noise at all, but contains information reflecting the activity in other parts of the brain. Optical imaging of cortical neurons by Arieli

et al

., reported in this week's issue (
p. 1868
), provides this new conclusion about neural noise.
Footprint Analysis of Replicating Murine Leukemia Virus Reverse Transcriptase
Authors: Wöhrl Birgitta M. , Georgiadis Millie M. , Telesnitsky Alice , Hendrickson Wayne A. , Le Grice Stuart F. J.
Published: October 2006

Replication complexes that contained either murine leukemia virus reverse transcriptase (MLV RT) or a variant reverse transcriptase without a ribonuclease (RNase) H domain (ΔRH MLV RT) were visualized by enzymatic footprinting. Wild-type MLV RT protected template nucleotides +6 to -27, and primer nucleotides -1 to -26 of primers that had first been extended by one or four nucleotides. Although it catalyzed DNA synthesis, ΔRH MLV RT stably bound template-primer only under conditions of reduced ionic strength and protected the duplex portion only as far as position -15. Despite altered hydrolysis profiles, both enzymes covered primarily the template-primer duplex, contradicting recent predictions based on the structure of rat DNA polymerase β.
Disruption of Retinal Axon Ingrowth by Ablation of Embryonic Mouse Optic Chiasm Neurons
Authors: Sretavan D. W. , Puré E. , Siegel M. W. , Reichardt L. F.
Published: October 2006

Mouse retinal ganglion cell axons growing from the eye encounter embryonic neurons at the future site of the optic chiasm. After in vivo ablation of these chiasm neurons with a monoclonal antibody and complement, retinal axons did not cross the midline and stalled at approximately the entry site into the chiasm region. Thus, in the mouse, the presence of early-generated neurons that reside at the site of the future chiasm is required for formation of the optic chiasm by retinal ganglion cell axons.
Conformation and Function of the N-Linked Glycan in the Adhesion Domain of Human CD2
Authors: Wyss Daniel F. , Choi Johnathan S. , Li Jing , Knoppers Maria H. , Willis Kevin J. , Arulanandam Antonio R. N. , Smolyar Alex , Reinherz Ellis L. , Wagner Gerhard
Published: October 2006

The adhesion domain of human CD2 bears a single N-linked carbohydrate. The solution structure of a fragment of CD2 containing the covalently bound high-mannose N-glycan [-(N-
N
-acetylglucosamine)
2
-(mannose)
5-8
] was solved by nuclear magnetic resonance. The stem and two of three branches of the carbohydrate structure are well defined and the mobility of proximal glycan residues is restricted. Mutagenesis of all residues in the vicinity of the glycan suggests that the glycan is not a component of the CD2-CD58 interface; rather, the carbohydrate stabilizes the protein fold by counterbalancing an unfavorable clustering of five positive charges centered about lysine-61 of CD2.
Inhibition of Cell Cycle Progression by the Alternatively Spliced Integrin β
1C
Authors: Meredith Jere , Takada Yoshikazu , Fornaro Mara , Languino Lucia R. , Schwartz Martin A.
Published: October 2006

Integrins regulate cell growth, differentiation, and behavior in many systems. Integrin β
1C
(β
1S
) is an alternatively spliced variant of integrin β
1
with a specific cytoplasmic domain and is expressed in several human tissues. Human β
1C
transiently expressed in mouse 10T1/2 fibroblasts showed a diffuse pattern of cell surface staining, whereas β
1
localized to focal adhesions. Moderate concentrations of β
1C
had no effect on actin stress fibers or focal adhesions, but markedly inhibited DNA synthesis. Inhibition by β
1C
mapped to the late G
1
phase of the cell cycle, near the G
1
-S boundary. Thus, alternative splicing of β
1
results in transmission of distinct signals that may regulate growth in vivo.
Induction of Metaphase Arrest in
Drosophila
Oocytes by Chiasma-Based Kinetochore Tension
Authors: Jang Janet Ko , Messina Lisa , Erdman Maria B. , Arbel Tamar , Hawley R. Scott
Published: October 2006

In normal
Drosophila melanogaster
oocytes, meiosis arrests at metaphase I and resumes after oocyte passage through the oviduct. Thus, metaphase arrest defines a control point in the meiotic cell cycle. Metaphase arrest only occurs in oocytes that have undergone at least one meiotic exchange. Here it is shown that crossovers between homologs attached to the same centromere do not induce metaphase arrest. Hence, exchanges induce metaphase arrest only when they physically conjoin two separate kinetochores. Thus, the signal that mediates metaphase arrest is not the exchange event per se but the resulting tension on homologous kinetochores.
Constitutively Activated Jak-STAT Pathway in T Cells Transformed with HTLV-I
Authors: Migone Thi-Sau , Lin Jian-Xin , Cereseto Anna , Mulloy James C. , O'Shea John J. , Franchini Genoveffa , Leonard Warren J.
Published: October 2006

Human T cell lymphotropic virus I (HTLV-I) is the etiological agent for adult T cell leukemia and tropical spastic paraparesis (also termed HTLV-I-associated myelopathy). HTLV-I-infected peripheral blood T cells exhibit an initial phase of interleukin-2 (IL-2)-dependent growth; over time, by an unknown mechanism, the cells become IL-2-independent. Whereas the Jak kinases Jak1 and Jak3 and the signal transducer and activator of transcription proteins Stat3 and Stat5 are activated in normal T cells in response to IL-2, this signaling pathway was constitutively activated in HTLV-I-transformed cells. In HTLV-I-infected cord blood lymphocytes, the transition from IL-2-dependent to IL-2-independent growth correlated with the acquisition of a constitutively activated Jak-STAT pathway, which suggests that this pathway participates in HTLV-I-mediated T cell transformation.
Binding of CO to Myoglobin from a Heme Pocket Docking Site to Form Nearly Linear Fe-C-O
Authors: Lim Manho , Jackson Timothy A. , Anfinrud Philip A.
Published: October 2006

The relative orientations of carbon monoxide (CO) bound to and photodissociated from myoglobin in solution have been determined with time-resolved infrared polarization spectroscopy. The bound CO is oriented ≤ = 7 degrees from the heme normal, corresponding to nearly linear Fe-C-O. Upon dissociation from the Fe, CO becomes trapped in a docking site that orientationally constrains it to lie approximately in the plane of the heme. Because the bound and "docked" CO are oriented in nearly orthogonal directions, CO binding from the docking site is suppressed. These solutions results help to establish how myoglobin discriminates against CO, a controversial issue dominated by the misconception that Fe-C-O is bent.
Candidate Gene for the Chromosome 1 Familial Alzheimer's Disease Locus
Authors: Levy-Lahad Ephrat , Wasco Wilma , Poorkaj Parvoneh , Romano Donna M. , Oshima Junko , Pettingell Warren H. , Yu Chang-en , Jondro Paul D. , Schmidt Stephen D. , Wang Kai , Crowley Annette C. , Fu Ying-Hui , Guenette Suzanne Y. , Galas David , Nemens Ellen , Wijsman Ellen M. , Bird Thomas D. , Schellenberg Gerard D. , Tanzi Rudolph E.
Published: October 2006

A candidate gene for the chromosome 1 Alzheimer's disease (AD) locus was identified (
STM2
). The predicted amino acid sequence for
STM2
is homologous to that of the recently cloned chromosome 14 AD gene (S182). A point mutation in
STM2
, resulting in the substitution of an isoleucine for an asparagine (N141I), was identified in affected people from Volga German AD kindreds. This N141I mutation occurs at an amino acid residue that is conserved in human S182 and in the mouse S182 homolog. The presence of missense mutations in AD subjects in two highly similar genes strongly supports the hypothesis that mutations in both are pathogenic.
The Chromodomain Protein Swi6: A Key Component at Fission Yeast Centromeres
Authors: Ekwall Karl , Javerzat Jean-Paul , Lorentz Axel , Schmidt Henning , Cranston Gwen , Allshire Robin
Published: October 2006

Centromeres attach chromosomes to the spindle during mitosis, thereby ensuring the equal distribution of chromosomes into daughter cells. Transcriptionally silent heterochromatin of unknown function is associated with centromeres in many organisms. In the fission yeast
Schizosaccharomyces pombe
, the silent mating-type loci, centromeres, and telomeres are assembled into silent heterochromatin-like domains. The Swi6 chromodomain protein affects this silencing, and now it is shown that Swi6p localizes with these three chromosomal regions. In cells lacking Swi6p, centromeres lag on the spindle during anaphase and chromosomes are lost at high rates. Thus, Swi6p is located at fission yeast centromeres and is required for their proper function.
Separation of Caveolae from Associated Microdomains of GPI-Anchored Proteins
Authors: Schnitzer Jan E. , McIntosh Deirdre P. , Dvorak Ann M. , Liu Jun , Oh Phil
Published: October 2006

In situ coating of the surface of endothelial cells in rat lung with cationic colloidal silica particles was used to separate caveolae from detergent-insoluble membranes rich in glycosyl phosphatidylinositol (GPI)-anchored proteins but devoid of caveolin. Immunogold electron microscopy showed that ganglioside G
M1
-enriched caveolae associated with an annular plasmalemmal domain enriched in GPI-anchored proteins. The purified caveolae contained molecular components required for regulated transport, including various lipid-anchored signaling molecules. Such specialized distinct microdomains may exist separately or together in the plasma membrane to organize signaling molecules and to process surface-bound ligands differentially.
Architectures of Class-Defining and Specific Domains of Glutamyl-tRNA Synthetase
Authors: Nureki Osamu , Vassylyev Dmitry G. , Katayanagi Katsuo , Shimizu Toshiyuki , Sekine Shun-ichi , Kigawa Takanori , Miyazawa Tatsuo , Yokoyama Shigeyuki , Morikawa Kosuke
Published: October 2006

The crystal structure of a class I aminoacyl-transfer RNA synthetase, glutamyl-tRNA synthetase (GluRS) from
Thermus thermophilus
, was solved and refined at 2.5 Å resolution. The amino-terminal half of GluRS shows a geometrical similarity with that of
Escherichia coli
glutaminyl-tRNA synthetase (GlnRS) of the same subclass in class I, comprising the class I-specific Rossmann fold domain and the intervening subclass-specific α/β domain. These domains were found to have two GluRS-specific, secondary-structure insertions, which then participated in the specific recognition of the D and acceptor stems of tRNA
Glu
as indicated by mutagenesis analyses based on the docking properties of GluRS and tRNA. In striking contrast to the β-barrel structure of the GlnRS carboxyl-terminal half, the GluRS carboxyl-terminal half displayed an all-α-helix architecture, an α-helix cage, and mutagenesis analyses indicated that it had a role in the anticodon recognition.
Synaptic Activation of Voltage-Gated Channels in the Dendrites of Hippocampal Pyramidal Neurons
Authors: Magee Jeffrey C. , Johnston Daniel
Published: October 2006

Activation of dendritic voltage-gated ion channels by local synaptic input was tested by simultaneous dendrite-attached patch-clamp recordings and whole-cell somatic voltage recordings made from CA1 pyramidal neurons in hippocampal slices. Schaffer collateral stimulation elicited subthreshold excitatory postsynaptic potentials (EPSPs) that opened voltage-gated sodium and calcium channels in the apical dendrites. The EPSP-activated sodium channels opened near the peak of the EPSP, whereas low voltage-activated calcium channels opened near the EPSP peak and during the decay phase. Dendritic high voltage-activated channels required somatic action potential generation or suprathreshold synaptic trains for activation. Dendritic voltage-gated channels are, therefore, likely to participate in dendritic integration of synaptic events.
Mercury-199 NMR of the Metal Receptor Site in MerR and Its Protein-DNA Complex
Authors: Utschig Lisa M. , Bryson James W. , O'Halloran Thomas V.
Published: October 2006

Structural insights have been provided by mercury-199 nuclear magnetic resonance (NMR) into the metal receptor site of the MerR metalloregulatory protein alone and in a complex with the regulatory target, DNA. The one- and two-dimensional NMR data are consistent with a trigonal planar Hg-thiolate coordination environment consisting only of Cys side chains and resolve structural aspects of both metal ion recognition and the allosteric mechanism. These studies establish
199
Hg NMR techniques as useful probes of the metal coordination environment of regulatory proteins, copper enzymes, and zinc transcription factor complexes as large as 50 kilodaltons.
Generation and Assembly of Secretory Antibodies in Plants
Authors: Ma Julian K.-C. , Hiatt Andrew , Hein Mich , Vine Nicholas D. , Wang Fei , Stabila Paul , van Dolleweerd Craig , Mostov Keith , Lehner Thomas
Published: October 2006

Four transgenic
Nicotiana tabacum
plants were generated that expressed a murine monoclonal antibody kappa chain, a hybrid immunoglobulin A-G heavy chain, a murine joining chain, and a rabbit secretory component, respectively. Successive sexual crosses between these plants and filial recombinants resulted in plants that expressed all four protein chains simultaneously. These chains were assembled into a functional, high molecular weight secretory immunoglobulin that recognized the native streptococcal antigen I/II cell surface adhesion molecule. In plants, single cells are able to assemble secretory antibodies, whereas two different cell types are required in mammals. Transgenic plants may be suitable for large-scale production of recombinant secretory immunoglobulin A for passive mucosal immunotherapy. Plant cells also possess the requisite mechanisms for assembly and expression of other complex recombinant protein molecules.
Classical Electrostatics in Biology and Chemistry
Authors: Honig Barry , Nicholls Anthony
Published: October 2006

A major revival in the use of classical electrostatics as an approach to the study of charged and polar molecules in aqueous solution has been made possible through the development of fast numerical and computational methods to solve the Poisson-Boltzmann equation for solute molecules that have complex shapes and charge distributions. Graphical visualization of the calculated electrostatic potentials generated by proteins and nucleic acids has revealed insights into the role of electrostatic interactions in a wide range of biological phenomena. Classical electrostatics has also proved to be a successful quantitative tool yielding accurate descriptions of electrical potentials, diffusion limited processes, pH-dependent properties of proteins, ionic strength-dependent phenomena, and the solvation free energies of organic molecules.
Water on the Sun
Authors: Wallace Lloyd , Bernath Peter , Livingston William , Hinkle Kenneth , Busler Jennifer , Guo Bujin , Zhang Keqing
Published: October 2006

High-resolution infrared spectra of sunspot umbrae have been recorded with the 1-meter Fourier transform spectrometer on Kitt Peak. The spectra contain a very large number of water absorption features originating on the sun. These lines have been assigned to the pure rotation and the vibration-rotation transitions of hot water by comparison with high-temperature laboratory emission spectra.
Requirement for Phosphatidylinositol Transfer Protein in Epidermal Growth Factor Signaling
Authors: Kauffmann-Zeh Andrea , Thomas Geraint M. H. , Ball Andrew , Prosser Simon , Cunningham Emer , Cockcroft Shamshad , Hsuan J. Justin
Published: October 2006

Stimulation of phosphatidylinositol-4,5-bisphosphate (PIP
2
) hydrolysis is a widespread mechanism for receptor-mediated signaling in eukaryotes. Cytosolic phosphatidylinositol transfer protein (PITP) is necessary for guanosine triphosphate (GTP)-dependent hydrolysis of PIP
2
by phospholipase C-β (PLC-β), but the role of PITP is unclear. Stimulation of phospholipase C-γ (PLC-γ) in A431 human epidermoid carcinoma cells treated with epidermal growth factor (EGF) required PITP. Stimulation of PI-4 kinase in cells treated with EGF also required PITP. Coprecipitation studies revealed an EGF-dependent association of PITP with the EGF receptor, with PI-4 kinase, and with PLC-γ.
Crystal Structure of
lac
Repressor Core Tetramer and Its Implications for DNA Looping
Authors: Friedman Alan M. , Fischmann Thierry O. , Steitz Thomas A.
Published: October 2006

The crystal structure of the tryptic core fragment of the lac repressor of
Escherichia coli
(LacR) complexed with the inducer isopropyl-β-D-thiogalactoside was determined at 2.6 Å resolution. The quaternary structure consists of two dyad-symmetric dimers that are nearly parallel to each other. This structure places all four DNA binding domains of intact LacR on the same side of the tetramer, and results in a deep, V-shaped cleft between the two dimers. Each monomer contributes a carboxyl-terminal helix to an antiparallel four-helix bundle that functions as a tetramerization domain. Some of the side chains whose mutation reduce DNA binding form clusters on a surface near the amino terminus. Placing the structure of the DNA binding domain complexed with operator previously determined by nuclear magnetic resonance onto this surface results in two operators being adjacent and nearly parallel to each other. Structural considerations suggest that the two dimers of LacR may flexibly alter their relative orientation in order to bind to the known varied spacings between two operators.
Requirement of Carbon Dioxide for in Vitro Assembly of the Urease Nickel Metallocenter
Authors: Park Il-Seon , Hausinger Robert P.
Published: October 2006

Assembly of protein metallocenters is not well understood. Urease offers a tractable system for examination of this process. Formation of the urease metallocenter in vivo is known to require four accessory proteins: UreD, postulated to be a urease-specific molecular chaperone; UreE, a nickel(II)-binding protein; and UreF and UreG, of unknown function. Activation of purified
Klebsiella aerogenes
urease apoprotein was accomplished in vitro by providing carbon dioxide (half-maximal activation at ∼0.2 percent carbon dioxide) in addition to nickel ion. Activation coincided with carbon dioxide incorporation into urease in a pH-dependent reaction (p
K
a
≥ 9, where
K
a
is the acid constant). The concentration of carbon dioxide also affected the amount of activation of UreD-urease apoprotein complexes. These results suggest that carbon dioxide binding to urease apoprotein generates a ligand that facilitates productive nickel binding.
Circadian Clock Mutants in
Arabidopsis
Identified by Luciferase Imaging
Authors: Millar Andrew J. , Carré Isabelle A. , Strayer Carl A. , Chua Nam-Hai , Kay Steve A.
Published: October 2006

The cycling bioluminescence of
Arabidopsis
plants carrying a firefly luciferase fusion construct was used to identify mutant individuals with aberrant cycling patterns. Both long- and short-period mutants were recovered. A semidominant short-period mutation, timing of
CAB
expression (
toc1
), was mapped to chromosome 5. The
toc1
mutation shortens the period of two distinct circadian rhythms, the expression of chlorophyll
a/b
-binding protein (
CAB
) genes and the movements of primary leaves, although
toc1
mutants do not show extensive pleiotropy for other phenotypes.
The Regulation of Circadian Period by Phototransduction Pathways in
Arabidopsis
Authors: Millar Andrew J. , Straume Martin , Chory Joanne , Chua Nam-Hai , Kay Steve A.
Published: October 2006

Transgenic
Arabidopsis
plants expressing a luciferase gene fused to a circadian-regulated promoter exhibited robust rhythms in bioluminescence. The cyclic luminescence has a 24.7-hour period in white light but 30- to 36-hour periods under constant darkness. Either red or blue light shortened the period of the wild type to 25 hours. A phytochrome-deficient mutation lengthened the period in continuous red light but had little effect in continuous blue light, whereas seedlings carrying mutations that activate light-dependent pathways in darkness maintained shorter periods in constant darkness. These results suggest that both phytochrome- and blue light-responsive photoreceptor pathways control the period of the circadian clock.
Participation of the Protein G
o
in Multiple Aspects of Behavior in
C. elegans
Authors: Mendel Jane E. , Korswagen Hendrik C. , Liu Katharine S. , Hajdu-Cronin Yvonne M. , Simon Melvin I. , Plasterk Ronald H. A. , Sternberg Paul W.
Published: October 2006

The
goa-1
gene encoding the alpha subunit of the heterotrimeric guanosine triphosphate-binding protein (G protein) G
o
from
Caenorhabditis elegans
is expressed in most neurons, and in the muscles involved in egg laying and male mating. Reduction-of-function mutations in
goa-1
caused a variety of behavioral defects including hyperactive movement, premature egg laying, and male impotence. Expression of the activated G
o
alpha subunit (Gα
o
) in transgenic nematodes resulted in lethargic movement, delayed egg laying, and reduced mating efficiency. Induced expression of activated Gα
o
in adults was sufficient to cause these phenotypes, indicating that Gα
o
mediates behavior through its role in neuronal function and the functioning of specialized muscles.
Skeletal Repair by in Situ Formation of the Mineral Phase of Bone
Authors: Constantz Brent R. , Ison Ira C. , Fulmer Mark T. , Poser Robert D. , Smith Susanne T. , VanWagoner Michelle , Ross John , Goldstein Steven A. , Jupiter Jesse B. , Rosenthal Daniel I.
Published: October 2006

A process has been developed for the in situ formation of the mineral phase of bone. Inorganic calcium and phosphate sources are combined to form a paste that is surgically implanted by injection. Under physiological conditions, the material hardens in minutes concurrent with the formation of dahllite. After 12 hours, dahllite formation was nearly complete, and an ultimate compressive strength of 55 megapascals was achieved. The composition and crystal morphology of the dahllite formed are similar to those of bone. Animal studies provide evidence that the material is remodeled in vivo. A novel approach to skeletal repair is being tested in human trials for various applications; in one of the trials the new biomaterial is being percutaneously placed into acute fractures. After hardening, it serves as internal fixation to maintain proper alignment while healing occurs.
Kinectin, an Essential Anchor for Kinesin-Driven Vesicle Motility
Authors: Kumar Janardan , Yu Hanry , Sheetz Michael P.
Published: October 2006

The membrane anchor for the molecular motor kinesin is a critical site involved in intracellular membrane trafficking. Monoclonal antibodies specific for the cytoplasmic surface of chick brain microsomes were used to define proteins involved in microtubule-dependent transport. One of four antibodies tested inhibited plus-end-directed vesicle motility by approximately 90 percent even as a monovalent Fab fragment and reduced kinesin binding to vesicles. This antibody bound to the cytoplasmic domain of kinectin, an integral membrane protein of the endoplasmic reticulum that binds to kinesin. Thus, kinectin acted as a membrane anchor protein for kinesin-driven vesicle motility.
Epithelial cyst of the cardiac papillary muscle: case report and review of the literature: Figure 1
Authors: Soilleux E J , Davies D R
Published: October 2006

Background:Reports of endodermal heterotopia (previously known as inclusion cysts) in cardiac atria are rare and there is only a single previous case report of endodermal heterotopia in a cardiac papillary muscle.

Aim and methods:A cyst in a cardiac papillary muscle was identified during the autopsy of an 87-year-old man who had died from an unrelated myocardial infarction. The cyst was examined histologically and mucin staining and immunostaining were carried out.

Results:We report a unilocular cyst in a cardiac papillary muscle, which is lined by low cuboidal, pseudostratified and occasionally ciliated respiratory-type epithelium, surrounded by a layer of smooth muscle. The immunohistochemical features (MNF116+, cytokeratin (CK)7+, CK8+, CK18+, CK19+, epithelial membrane antigen positive, scattered cells positive for neuroendocrine markers) suggest that this is an endodermal heterotopia. Immunostaining of positive thyroid transcription factor-1 provides evidence for bronchogenic differentiation.

Discussion:The differential diagnoses of cystic structures in cardiac papillary muscle and the origin and importance of endodermal heterotopias are discussed.
Chronic allopurinol administration ameliorates maladaptive alterations in Ca2+ cycling proteins and β-adrenergic hyporesponsiveness in heart failure
Authors: Saliaris Anastasios P. , Amado Luciano C. , Minhas Khalid M. , Schuleri Karl H. , Lehrke Stephanie , St. John Marcus , Fitton Torin , Barreiro Chris , Berry Cristine , Zheng Meizi , Kozielski Kristen , Eneboe Virginia , Brawn Jeff , Hare Joshua M.
Published: October 2006

Xanthine oxidase (XO) activity contributes to both abnormal excitation-contraction (EC) coupling and cardiac remodeling in heart failure (HF). β-Adrenergic hyporesponsiveness and abnormalities in Ca2+ cycling proteins are mechanistically linked features of the HF phenotype. Accordingly, we hypothesized that XO influences β-adrenergic responsiveness and expression of genes whose products participate in deranged EC coupling. We measured inotropic (dP/d tmax), lusitropic (τ), and vascular (elastance; Ea) responses to β-adrenergic (β-AR) stimulation with dobutamine in conscious dogs administered allopurinol (100 mg po daily) or placebo during a 4-wk induction of pacing HF. With HF induction, the decreases in both baseline and dobutamine-stimulated inotropic responses were offset by allopurinol. Additionally, allopurinol converted a vasoconstrictor effect to dobutamine to a vasodilator response and enhanced both lusitropic and preload reducing effects. To assess molecular correlates for this phenotype, we measured myocardial sarcoplasmic reticulum Ca2+-ATPase 2a (SERCA), phospholamban (PLB), phosphorylated PLB (P-PLB), and Na+/Ca2+ transporter (NCX) gene expression and protein. Although SERCA mRNA and protein concentrations did not change with HF, both PLB and NCX were upregulated ( P < 0.05). Additionally, P-PLB and protein kinase A activity were greatly reduced. Allopurinol ameliorated all of these molecular alterations and preserved the PLB-to-SERCA ratio. Preventing maladaptive alterations of Ca2+ cycling proteins represents a novel mechanism for XO inhibition-mediated preservation of cardiac function in HF, raising the possibility that anti-oxidant therapies for HF may ameliorate transcriptional changes associated with adverse cardiac remodeling and β-adrenergic hyporesponsiveness.
Noninvasive assessment of left ventricular and myocardial contractility in middle-aged men and women: disparate evolution above the age of 50?
Authors: Claessens T. E. , Rietzschel E. R. , De Buyzere M. L. , De Bacquer D. , De Backer G. , Gillebert T. C. , Verdonck P. R. , Segers P.
Published: October 2006

End-systolic elastance ( Ees) is a frequently used index of left ventricular (LV) contractility. However, because of its inherent dependence on LV geometry, Ees cannot be used to compare myocardial contractile state between ventricles with different geometries, which is the case in any cross-sectional study. Various normalization methods for Ees have been proposed in the literature, but a standardized method is still lacking. In this study, we introduced a novel alternative normalization technique and compared it with three previously suggested methods. We tested all normalization methods to assess the age- and sex-related differences in myocardial contractility in a large population sample of 2,184 middle-aged (ages, 35–55 yr) untreated subjects free from overt cardiovascular disease. Ventricular contractility Ees was determined using a previously validated noninvasive single-beat method, based on two-dimensional echocardiographic and brachial blood pressure measurements. Myocardial contractility was estimated as 1) Ees·end-diastolic volume (EDV); 2) Ees·LV mass (LVM); 3) 0.433· Ees·LVM/relative wall thickness (RWT), based on a theoretical LV model; and 4) 0.0941· Ees·LVM0.455·RWT−0.159, a novel semiempirical expression derived in this study. Because of the difference in their underlying assumptions, the various myocardial contractility indexes do not provide consistent information with respect to sex differences. Despite these discrepancies, it was found that myocardial contractility in women appears to be better preserved after the age of 50 yr compared with that in men. The physiological mechanisms behind this potentially clinically important phenomenon at population level require further investigation.
Longer muscle lengths recapitulate force suppression in swine carotid artery
Authors: Rembold Christopher M. , Meeks Melissa K. , Ripley Marcia L. , Han Shaojie
Published: October 2006

Cyclic nucleotide can relax arterial smooth muscle without reductions in myosin regulatory light chain (MRLC) phosphorylation, a process termed force suppression. Smooth muscle contractile force also depends on tissue length. It is not known how tissue length affects force suppression. Swine carotid artery rings were equilibrated at various lengths (as a fraction of Lo, the optimal length for force development). They were then frozen during contractile activation with or without forskolin-induced relaxation. Frozen tissue homogenates were then analyzed for Ser19-MRLC phosphorylation and Ser16-heat shock protein 20 (HSP20) phosphorylation (HSP20 is the proposed mediator of force suppression). Higher values of MRLC phosphorylation were required to induce a histamine contraction at longer tissue lengths. At 1.4 Lo, the dependence of force on MRLC phosphorylation observed with histamine stimulation alone was shifted to the right, a response similar to that observed during force suppression at 1.0 Lo. The rightward shift in the dependence of force on MRLC phosphorylation seen with histamine stimulation alone at 1.4 Lowas not associated with increased HSP20 phosphorylation. Addition of forskolin to histamine-stimulated tissues at 1.4 Loinduced a relaxation associated with increased HSP20 phosphorylation and reduced MRLC phosphorylation, i.e., there was no additional force suppression. At shorter tissue lengths (0.6 Lo), the dependence of force on MRLC phosphorylation with histamine stimulation alone was steep, a response similar to that observed during normal contractile activation at 1.0 Lo. Addition of forskolin induced force suppression at 0.6 Lo. The sensitivity of swine carotid to the concentration of histamine was greater at longer tissue lengths compared with shorter tissue lengths, suggesting a physiological mechanism to restore optimal tissue length. These data suggest that longer tissue lengths induced a force suppression-like state that was 1) not additive with forskolin and 2) not associated with HSP20 phosphorylation. Further research is required to determine this length-dependent mechanism.
The nonpeptide angiotensin-(1–7) receptor Mas agonist AVE-0991 attenuates heart failure induced by myocardial infarction
Authors: Ferreira Anderson J. , Jacoby Bruno A. , Araújo Cícero A. A. , Macedo Filipe A. F. F. , Silva Gerluza A. B. , Almeida Alvair P. , Caliari Marcelo V. , Santos Robson A. S.
Published: October 2006

The nonpeptide AVE-0991, which has been reported as a selective ligand for the angiotensin-(1–7) [ANG-(1–7)] receptor Mas, has actions similar to those attributed to the cardioprotective product of the renin-angiotensin system, ANG-(1–7). In this study, we evaluated the cardiac effects of AVE-0991 in normal and infarcted male Wistar rats. Myocardial infarction was induced by left coronary artery ligation. At the end of the treatment, the Langendorff technique was used to analyze cardiac function. Left ventricle serial sections were dyed with Gomori trichrome stain to quantify the infarcted area. In normal hearts, AVE-0991 produced a significant decrease in perfusion pressure and an increase in systolic tension, rate of tension rise and fall (±dT/d t), and heart rate. These effects were completely blocked by the perfusion of the hearts with a solution containing the selective ANG-(1–7) antagonist A-779. NG-nitro-l-arginine methyl ester treatment abolished the AVE-0991-induced vasodilation in isolated hearts. AVE-0991 significantly attenuated the decrease in systolic tension (sham operated, 13.00 ± 1.02 g; infarction, 7.18 ± 0.66 g; AVE treated, 9.23 ± 1.05 g, n = 5), +dT/d t, −dT/d t, and heart rate induced by myocardial infarction. Infarction-induced vasoconstriction was completely prevented by AVE-0991 treatment. Furthermore, AVE-0991 significantly decreased the infarcted area (6.98 ± 1.01 vs. 3.94 ± 1.04 mm2in AVE-treated rats). These data indicate that the compound AVE-0991 produces beneficial effects in isolated perfused rat hearts involving the ANG-(1–7) receptor Mas and the release of nitric oxide. In addition, our results indicate that AVE-0991 attenuates postischemic heart failure.
Endoreduplication of human smooth muscle cells induced by 2-methoxyestradiol: a role for cyclin-dependent kinase 2
Authors: Gui Yu , Yin Hao , He Jia-Yin , Yang Song-Hua , Walsh Michael P. , Zheng Xi-Long
Published: October 2006

Endoreduplication has been suggested to contribute to the development of hypertrophy of smooth muscle cells (SMCs) in hypertension. However, endoreduplication in vascular SMCs and the underlying molecular mechanisms are not clear. Treatment of human SMCs with 10 μM 2-methoxyestradiol (2-ME) for 24 h induces accumulation of cells with ≥4N DNA content, and some polyploid/aneuploid cells actively synthesize their DNA, suggesting the occurrence of endoreduplication. In addition, 2-ME treatment upregulates the expression of cyclin-dependent kinase 2 (Cdk2). The present study was designed to characterize endoreduplication of human SMCs and explore the potential roles of Cdk2 in endoreduplication induced by 2-ME. Treatment with 2-ME (10 μM) for 2–4 days not only caused increases in >4N cells and their reentry into S phase but also induced overduplication of chromosomes. Furthermore, 2-ME increased the kinase activity of Cdk2 and its interaction with cyclin E. Inducible overexpression of dominant-negative Cdk2 in human SMCs inhibited both DNA synthesis of >4N cells and the accumulation of >4N cells induced by 2-ME. We conclude that 2-ME induces endoreduplication of human SMCs and Cdk2 plays an important role in endoreduplication in response to 2-ME.
C-Peptide Induces Vascular Smooth Muscle Cell Proliferation
Authors: Walcher Daniel , Babiak Christina , Poletek Paulina , Rosenkranz Stephan , Bach Helga , Betz Susanne , Durst Renate , Grüb Miriam , Hombach Vinzenz , Strong Jack , Marx Nikolaus
Published: October 2006

Increased levels of C-peptide, a cleavage product of proinsulin, circulate in patients with insulin resistance and early type 2 diabetes mellitus. Recent data suggest a potential causal role of C-peptide in atherogenesis by promoting monocyte and T-lymphocyte recruitment into the vessel wall. The present study examined the effect of C-peptide on vascular smooth muscle cells (VSMCs) proliferation and evaluated intracellular signaling pathways involved. In early arteriosclerotic lesions of diabetic subjects, C-peptide colocalized with VSMCs in the media. In vitro, stimulation of human or rat VSMCs with C-peptide induced cell proliferation in a concentration-dependent manner with a maximal 2.6±0.8-fold induction at 10 nmol/L human C-peptide (
P
<0.05 compared with unstimulated cells; n=9) and a 1.8±0.2-fold induction at 0.5 nmol/L rat C-peptide (
P
<0.05 compared with unstimulated cells; n=7), respectively, as shown by [H3]-thymidin incorporation. The proliferative effect of C-peptide on VSMCs was inhibited by Src short interference RNA transfection, PP2, an inhibitor of Src-kinase, LY294002, an inhibitor of PI-3 kinase, and the ERK1/2 inhibitor PD98059. Moreover, C-peptide induced phosphorylation of Src, as well as activation of PI-3 kinase and ERK1/2, suggesting that these signaling molecules are involved in C-peptide–induced VSMC proliferation. Finally, C-peptide induced cyclin D1 expression as well as phosphorylation of Rb in VSMCs. Our results demonstrate that C-peptide induces VSMC proliferation through activation of Src- and PI-3 kinase as well as ERK1/2. These data suggest a novel mechanism how C-peptide may contribute to plaque development and restenosis formation in patients with insulin resistance and early type 2 diabetes mellitus.
Impact of Carotid Endarterectomy on Medical Secondary Prevention After a Stroke or a Transient Ischemic Attack
Authors: Touzé Emmanuel , Mas Jean-Louis , Röther Joachim , Goto Shinya , Hirsch Alan T. , Ikeda Yasuo , Liau Chiau-Suong , Ohman E. Magnus , Richard Alain J. , Wilson Peter W. F. , Steg P. Gabriel , Bhatt Deepak L.
Published: October 2006

Background and Purpose—

Whether a history of carotid endarterectomy influences patient compliance with medical treatments and physician attitude toward treatments after ischemic stroke or transient ischemic attack (TIA) is not well known.

Methods—

We studied the baseline data of 18 467 ischemic stroke and TIA patients from the international REduction of Atherothrombosis for Continued Health (REACH) Registry and investigated the impact of a history of endarterectomy on the secondary medical prevention measured by the use of antiplatelet agents and statins, and by the control of cholesterol level, glucose level, and blood pressure.

Results—

Among the patients with a history of ischemic stroke or TIA, those with a history of endarterectomy (n=1474) were more likely to receive antiplatelet agents and statins, to have a blood pressure <140/90 mm Hg, and a fasting total cholesterol <200 mg/dL. In diabetic patients, endarterectomy was associated with lower fasting blood glucose levels. In multivariate logistic regression analyses, endarterectomy was significantly associated with the use of antiplatelet agents (odds ratio [OR], 1.6; 95% CI, 1.3 to 1.9;
P
<0.0001) and statins (OR, 1.8; 1.6 to 2.0;
P
<0.0001), and with a cholesterol level <200 mg/dL (OR, 1.3; 1.2 to 1.5;
P
<0.0001). By contrast, the associations with blood pressure and blood glucose levels were no longer significant. There was no heterogeneity across the world regions or among the specialists who enrolled the patients.

Conclusions—

Carotid endarterectomy is associated with a higher use of antiplatelet agents and statins in stroke/TIA patients. The absence of such an association with blood pressure and blood glucose control suggests that the individual determinants of the quality of the secondary medical prevention vary from one risk factor to another and from one class of drugs to another.
Hierarchical and Linear Sequence Processing: An Electrophysiological Exploration of Two Different Grammar Types
Authors: Bahlmann Jörg , Gunter Thomas C. , Friederici Angela D.
Published: October 2006

The present study investigated the processing of two types of artificial grammars by means of event-related brain potentials. Two categories of meaningless CV syllables were applied in each grammar type. The two grammars differed with regard to the type of the underlying rule. The finite-state grammar (FSG) followed the rule (AB) n , thereby generating local transitions between As and Bs (e.g., n = 2, ABAB). The phrase structure grammar (PSG) followed the rule A n B n , thereby generating center-embedded structures in which the first A and the last B embed the middle elements (e.g., n = 2, [A[AB]B]). Two sequence lengths (n = 2, n = 4) were used. Violations of the structures were introduced at different positions of the syllable sequences. Early violations were situated at the beginning of a sequence, and late violations were placed at the end of a sequence. A posteriorly distributed early negativity elicited by violations was present only in FSG. This effect was interpreted as the possible reflection of a violated local expectancy. Moreover, both grammar-type violations elicited a late positivity. This positivity varied as a function of the violation position in PSG, but not in FSG. These findings suggest that the late positivity could reflect difficulty of integration in PSG sequences.
Neural Bases of Motivated Reasoning: An fMRI Study of Emotional Constraints on Partisan Political Judgment in the 2004 U.S. Presidential Election
Authors: Westen Drew , Blagov Pavel S. , Harenski Keith , Kilts Clint , Hamann Stephan
Published: October 2006

Research on political judgment and decision-making has converged with decades of research in clinical and social psychology suggesting the ubiquity of emotion-biased motivated reasoning. Motivated reasoning is a form of implicit emotion regulation in which the brain converges on judgments that minimize negative and maximize positive affect states associated with threat to or attainment of motives. To what extent motivated reasoning engages neural circuits involved in “cold” reasoning and conscious emotion regulation (e.g., suppression) is, however, unknown. We used functional neuroimaging to study the neural responses of 30 committed partisans during the U.S. Presidential election of 2004. We presented subjects with reasoning tasks involving judgments about information threatening to their own candidate, the opposing candidate, or neutral control targets. Motivated reasoning was associated with activations of the ventromedial prefrontal cortex, anterior cingulate cortex, posterior cingulate cortex, insular cortex, and lateral orbital cortex. As predicted, motivated reasoning was not associated with neural activity in regions previously linked to cold reasoning tasks and conscious (explicit) emotion regulation. The findings provide the first neuroimaging evidence for phenomena variously described as motivated reasoning, implicit emotion regulation, and psychological defense. They suggest that motivated reasoning is qualitatively distinct from reasoning when people do not have a strong emotional stake in the conclusions reached.
Roars of black howler monkeys (Alouatta caraya): evidence for a function in inter-group spacing
Authors: Byrne Richard W. , da Cunha Rogério Grassetto Teixeira
Published: October 2006

Loud calls can be expected to play an important role in the lives of howler monkeys, given the specialised anatomy of howler vocal apparatus and the time and energy invested in calling. Here we present observational and experimental data aimed at understanding the function(s) of the roars of black howler monkeys (Alouatta caraya). Most roars were given spontaneously, especially around dawn, although inter-group encounters and extreme weather events triggered calling. Roars were given throughout the home range, but not uniformly; variations in calling frequency with location were not well predicted by frequency of use, and calling was not more frequent at borders. Predator presence was neither necessary nor sufficient to stimulate calling. We experimentally played back loud calls from stranger groups, either inside the home range of the study group, simulating invasions, or in border areas. In response to simulated invasions, the alpha male roared more frequently than expected, usually in the vicinity of the playback site, moved off sooner and travelled to or near to the playback site. When playback was in border areas, the alpha male roared infrequently and significantly later, and did not travel towards the playback site. These results are not consistent with the hypotheses that roaring functions in predation deterrence and/or mate defence. Instead, they suggest that roaring allows regulation of the space use, by means of regular advertisement of occupancy but not by mutual avoidance or boundary defence. We believe that roars also provide a mechanism for reinforcing occupancy during encounters, and may sometimes serve to settle disputes without chases and fights.
Migratory behaviour of captive white-crowned sparrows, Zonotrichia leucophrys gambelii, differs during autumn and spring migration
Authors: Ramenofsky Marilyn , Agatsuma Renée
Published: October 2006

Gambel's white-crown sparrow (Zonotorichia leucophrys gambelii) is a long-distance, over-land migrant. In captivity birds display many characteristics of the autumn and spring migratory life history stages that include hyperphagia, fattening and high intensity nocturnal activity termed migratory restlessness or Zugunruhe. We recorded the behaviour of captive birds while simultaneously collecting 24 h locomotor activity. These data were used to define the behaviour displayed by captive birds during autumn and spring in order to compare the two migratory stages and to draw inferences for free-living birds. The predominant behaviour during day and nighttime was rest. Feeding occurred only during daylight hours but at a greater frequency in autumn than spring. Birds generally used their feet as the primary source of locomotion during the day termed 'jump'. During the night, two distinct behaviours, 'beak-up flight' and 'beak-up' involving high intensity wing motions were observed and considered components of migratory restlessness. The frequency of the 'beak-up flight' was greatest during spring and associated with the enhanced tempo of vernal migration. In both stages, migratory restlessness was preceded by a quiescent phase, the occurrence of which differed and related to time available for foraging and length of the night. Given these findings, we hypothesize that diel behaviours displayed by autumn and spring migrants in captivity highlight distinctions between the two life history stages.
Individual leadership and boldness in shoals of golden shiners (Notemigonus crysoleucas)
Authors: Reebs Stéphan G. , Leblond Caroline
Published: October 2006

Shoals of golden shiners (Notemigonus crysoleucas) often swim along the perimeter of their large indoor tank at dawn and dusk, and can also be trained to anticipate food arrival by swimming directly towards the food source at midday. In this study all golden shiners in six shoals of 8-12 fish were individually marked with a visible implant elastomer, and shoal movement was video taped in order to determine whether some individuals consistently occupied front positions even when all shoal members were of similar size and experience. There were significant correlations between all three times of day (dawn, midday, dusk) in the mean position (from 1 = first at the front of the shoal to 12 = last at the back) occupied by each fish. In each shoal, 1-3 fish were leaders: all three daily times combined, they had more than twice the occupancy rate of the front two or three positions as expected from chance. In subsequent boldness tests there was a tendency (p = 0.096) for these leaders to pass through dark U-shaped tubes more readily than non-leaders. However, after being dipnetted and transferred to a refuge, leaders did not emerge earlier than non-leaders. Individual tendencies to lead may have been underlain by a motivation to feed (which may differ even in fish of similar size and experience) or by intrinsic mobility. On the other hand, a link between leadership and risk-taking remains to be established for captive golden shiners.