bluuebunny/crossref_metadata_2025 huggingface dataset:
Wolves, Moose, and Tree Rings on Isle Royale
Authors: McLaren B. E. , Peterson R. O.
Published: October 2006

Investigation of tree growth in Isle Royale National Park in Michigan revealed the influence of herbivores and carnivores on plants in an intimately linked food chain. Plant growth rates were regulated by cycles in animal density and responded to annual changes in primary productivity only when released from herbivory by wolf predation. Isle Royale's dendrochronology complements a rich literature on food chain control in aquatic systems, which often supports a trophic cascade model. This study provides evidence of top-down control in a forested ecosystem.
Symmetries of Hydrogen Bonds in Solution
Authors: Perrin Charles L.
Published: October 2006

The nuclear magnetic resonance method of isotopic perturbation can distinguish between single- and double-well potentials in intramolecularly hydrogen-bonded monoanions of dicarboxylic acids. These are classic cases of a "strong," symmetric hydrogen bond in the crystal. The observed carbon-13 isotope shifts induced by the substitution of oxygen-18 demonstrate that these monoanions exist as a single symmetric structure in a nonpolar solvent but as two equilibrating tautomers in aqueous solution. The change is attributed to the disorder of the aqueous environment. These are simple counterexamples to the hope that the crystal structure reveals the actual molecular structure in aqueous solution.
Doping Graphitic and Carbon Nanotube Structures with Boron and Nitrogen
Authors: Stephan O. , Ajayan P. M. , Colliex C. , Redlich Ph. , Lambert J. M. , Bernier P. , Lefin P.
Published: October 2006

Composite sheets and nanotubes of different morphologies containing carbon, boron, and nitrogen were grown in the electric arc discharge between graphite cathodes and amorphous boron-filled graphite anodes in a nitrogen atmosphere. Concentration profiles derived from electron energy-loss line spectra show that boron and nitrogen are correlated in a one-to-one ratio; core energy-loss fine structures reveal small differences compared to pure hexagonal boron nitride. Boron and carbon are anticorrelated, suggesting the substitution of boron and nitrogen into the carbon network. Results indicate that single-phase C

y

B

x

N

x

as well as separated domains (nanosize) of boron nitride in carbon networks may exist.
Evolutionary History of the Symbiosis Between Fungus-Growing Ants and Their Fungi
Authors: Chapela Ignacio H. , Rehner Stephen A. , Schultz Ted R. , Mueller Ulrich G.
Published: October 2006

The evolutionary history of the symbiosis between fungus-growing ants (Attini) and their fungi was elucidated by comparing phylogenies of both symbionts. The fungal phylogeny based on cladistic analyses of nuclear 28
S
ribosomal DNA indicates that, in contrast with the monophyly of the ants, the attine fungi are polyphyletic. Most cultivated fungi belong to the basidiomycete family Lepiotaceae; however, one ant genus,
Apterostigma
, has acquired a distantly related basidiomycete lineage. Phylogenetic patterns suggest that some primitive attines may have repeatedly acquired lepiotaceous symbionts. In contrast, the most derived attines have clonally propagated the same fungal lineage for at least 23 million years.
Sled-Type Motion on the Nanometer Scale: Determination of Dissipation and Cohesive Energies of C
60
Authors: Lüthi R. , Meyer E. , Haefke H. , Howald L. , Gutmannsbauer W. , Güntherodt H. -J.
Published: October 2006

The tribological properties of C
60
on the mesoscopic scale were investigated with a scanning force microscope, which allowed simultaneous measurements of normal and lateral forces under ultrahigh-vacuum conditions. Islands of C
60
, deposited on NaCl(001), could be moved by the action of the probing tip in a controlled way. Different modes of motion, such as translation and rotation, were observed. An extremely small dissipation energy of about 0.25 millielectron volt per molecule and a cohesive energy of 1.5 electron volts were determined in these nanometer-scale experiments. The corresponding shear strength of 0.05 to 0.1 megapascal was smaller by one order of magnitude than typical values of boundary lubricants. For C
60
on graphite, disruption of the islands was observed and collective motion of the islands could not be achieved. These results could find use in the field of nanotechnology; for example, C
60
islands could be developed into a sled-type transport system on the nanometer scale.
T Cell Deletion in High Antigen Dose Therapy of Autoimmune Encephalomyelitis
Authors: Critchfield Jeffrey M. , Racke Michael K. , Zúñiga-Pflücker Juan Carlos , Cannella Barbara , Raine Cedric S. , Goverman Joan , Lenardo Michael J.
Published: October 2006

Encounters with antigen can stimulate T cells to become activated and proliferate, become nonresponsive to antigen, or to die. T cell death was shown to be a physiological response to interleukin-2-stimulated cell cycling and T cell receptor reengagement at high antigen doses. This feedback regulatory mechanism attenuates the immune response by deleting a portion of newly dividing, antigen-reactive T cells. This mechanism deleted autoreactive T cells and abrogated the clinical and pathological signs of autoimmune encephalomyelitis in mice after repetitive administration of myelin basic protein.
Diversity of Endogenous Epitopes Bound to MHC Class II Molecules Limited by Invariant Chain
Authors: Bodmer Helen , Viville Stéphane , Benoist Christophe , Mathis Diane
Published: October 2006

The invariant chain (Ii) binds nascent major histocompatibility complex (MHC) class II molecules, blocking peptide binding until the complex dissociates in the endosomes. This may serve to differentiate the MHC class I and II antigen presentation pathways and enable class II molecules to efficiently bind peptides in the endosomes. This hypothesis was addressed by probing spleen cells from a combination of knock-out and transgenic mice with a large panel of T cell hybridomas. The Ii molecule blocked the presentation of a range of endogenously synthesized epitopes, but some epitopes actually required Ii. Thus, the influence of Ii on presentation does not follow simple rules. In addition, mice expressing Ii were not tolerant to epitopes unmasked in its absence, a finding with possible implications for autoimmunity.
High-Resolution Molecular Discrimination by RNA
Authors: Jenison Robert D. , Gill Stanley C. , Pardi Arthur , Polisky Barry
Published: October 2006

Species of RNA that bind with high affinity and specificity to the bronchodilator theophylline were identified by selection from an oligonucleotide library. One RNA molecule binds to theophylline with a dissociation constant
K
d
of 0.1 μM. This binding affinity is 10,000-fold greater than the RNA molecule's affinity for caffeine, which differs from theophylline only by a methyl group at nitrogen atom N-7. Analysis by nuclear magnetic resonance indicates that this RNA molecule undergoes a significant change in its conformation or dynamics upon theophylline binding. Binding studies of compounds chemically related to theophylline have revealed structural features required for the observed binding specificity. These results demonstrate the ability of RNA molecules to exhibit an extremely high degree of ligand recognition and discrimination.
Role of Bone Marrow-Derived Cells in Presenting MHC Class I-Restricted Tumor Antigens
Authors: Huang Alex Y. C. , Golumbek Paul , Ahmadzadeh Mojgan , Jaffee Elizabeth , Pardoll Drew , Levitsky Hyam
Published: October 2006

Many tumors express tumor-specific antigens capable of being presented to CD8
+
T cells by major histocompatibility complex (MHC) class I molecules. Antigen presentation models predict that the tumor cell itself should present these antigens to T cells. However, when conditions for the priming of tumor-specific responses were examined in mice, no detectable presentation of MHC class I-restricted tumor antigens by the tumor itself was found. Rather, tumor antigens were exclusively presented by host bone marrow-derived cells. Thus, MHC class I-restricted antigens are efficiently transferred in vivo to bone marrow-derived antigen-presenting cells, which suggests that human leukocyte antigen matching may be less critical in the application of tumor vaccines than previously thought.
Inhibition of Hepatic Chylomicron Remnant Uptake by Gene Transfer of a Receptor Antagonist
Authors: Willnow Thomas E. , Sheng Zeqi , Ishibashi Shun , Herz Joachim
Published: October 2006

The low density lipoprotein receptor-related protein (LRP) has been proposed to mediate in concert with the LDL receptor (LDLR) the uptake of dietary lipoproteins into the hepatocytes. This hypothesis was tested by transient inactivation of LRP in vivo. Receptor-associated protein (RAP), a dominant negative regulator of LRP function, was transferred by an adenoviral vector to the livers of mice lacking LDLR (LDLR
-/-
). The inactivation of LRP by RAP was associated with a marked accumulation of chylomicron remnants in LDLR
-/-
mice and to a lesser degree in normal mice, suggesting that both LDLR and LRP are involved in remnant clearance.
Structures of Ternary Complexes of Rat DNA Polymerase β, a DNA Template-Primer, and ddCTP
Authors: Pelletier Huguette , Sawaya Michael R. , Kumar Amalendra , Wilson Samuel H. , Kraut Joseph
Published: October 2006

Two ternary complexes of rat DNA polymerase β (pol β), a DNA template-primer, and dideoxycytidine triphosphate (ddCTP) have been determined at 2.9 Å and 3.6 Å resolution, respectively. ddCTP is the triphosphate of dideoxycytidine (ddC), a nucleoside analog that targets the reverse transcriptase of human immunodeficiency virus (HIV) and is at present used to treat AIDS. Although crystals of the two complexes belong to different space groups, the structures are similar, suggesting that the polymerase-DNA-ddCTP interactions are not affected by crystal packing forces. In the pol β active site, the attacking 3′-OH of the elongating primer, the ddCTP phosphates, and two Mg
2+
ions are all clustered around Asp
190
, Asp
192
, and Asp
256
. Two of these residues, Asp
190
and Asp
256
, are present in the amino acid sequences of all polymerases so far studied and are also spatially similar in the four polymerases—the Klenow fragment of
Escherichia coli
DNA polymerase I, HIV-1 reverse transcriptase, T7 RNA polymerase, and rat DNA pol β—whose crystal structures are now known. A two-metal ion mechanism is described for the nucleotidyl transfer reaction and may apply to all polymerases. In the ternary complex structures analyzed, pol β binds to the DNA template-primer in a different manner from that recently proposed for other polymerase-DNA models.
Fas and Perforin Pathways as Major Mechanisms of T Cell-Mediated Cytotoxicity
Authors: Kägi David , Vignaux Françoise , Ledermann Birgit , Bürki Kurt , Depraetere Valérie , Nagata Shigekazu , Hengartner Hans , Golstein Pierre
Published: October 2006

Two molecular mechanisms of T cell-mediated cytotoxicity, one perforin-based, the other Fas-based, have been demonstrated. To determine the extent of their contribution to T cell-mediated cytotoxicity, a range of effector cells from normal control or perforin-deficient mice were tested against a panel of target cells with various levels of Fas expression. All cytotoxicity observed was due to either of these mechanisms, and no third mechanism was detected. Thus, the perforin- and Fas-based mechanisms may account for all T cell-mediated cytotoxicity in short-term in vitro assays.
Treatment of Murine Lupus with CTLA4Ig
Authors: Finck Barbara K. , Linsley Peter S. , Wofsy David
Published: October 2006

The interaction of B7-related molecules on antigen-presenting cells with CD28 or CTLA-4 antigens on T cells provides a second signal for T cell activation. Selective inhibition of the B7-CD28 or B7-CTLA-4 interactions produces antigen-specific T cell unresponsiveness in vitro and suppresses immune function in vivo. To determine whether selective inhibition of the B7-CD28 or B7-CTLA-4 interactions could suppress spontaneous autoimmune disease, a B7-binding protein was generated by genetic fusion of the extracellular domain of murine CTLA-4 to the Fc portion of a mouse immunoglobulin G2a monoclonal antibody (muCTLA4Ig). In lupus-prone NZB/NZW filial generation (F
1
) mice, treatment with muCTLA4Ig blocked autoantibody production and prolonged life, even when treatment was delayed until the most advanced stage of clinical illness. These findings suggest a possible role for human CTLA4Ig in the treatment of autoimmune diseases in humans.
Involvement of Nitric Oxide in the Elimination of a Transient Retinotectal Projection in Development
Authors: Wu Hope H. , Williams Cheri V. , McLoon Steven C.
Published: October 2006

The adult pattern of axonal connections from the eye to the brain arises during development through the refinement of a roughly ordered set of connections. In the chick visual system, refinement normally results in the loss of the ipsilateral retinotectal connections. Inhibition of nitric oxide synthesis reduced the loss of these transient connections. Because nitric oxide is expressed by tectal cells with which retinal axons connect and because reduction of nitric oxide synthesis by tectal cells resulted in a change in the connections of retinal axons, nitric oxide probably serves as a messenger from tectal cells back to retinal axons during development.
Cystic Fibrosis Heterozygote Resistance to Cholera Toxin in the Cystic Fibrosis Mouse Model
Authors: Gabriel Sherif E. , Brigman Kristen N. , Koller Beverly H. , Boucher Richard C. , Stutts M. Jackson
Published: October 2006

The effect of the number of cystic fibrosis (CF) alleles on cholera toxin (CT)-induced intestinal secretion was examined in the CF mouse model. CF mice that expressed no CF transmembrane conductance regulator (CFTR) protein did not secrete fluid in response to CT. Heterozygotes expressed 50 percent of the normal amount of CFTR protein in the intestinal epithelium and secreted 50 percent of the normal fluid and chloride ion in response to CT. This correlation between CFTR protein and CT-induced chloride ion and fluid secretion suggests that CF heterozygotes might possess a selective advantage of resistance to cholera.
The Stereochemical Course of Group II Intron Self-Splicing
Authors: Padgett Richard A. , Podar Mircea , Boulanger Scott C. , Perlman Philip S.
Published: October 2006

The stereochemical specificities and reaction courses for both self-splicing steps of a group II intron have been determined by phosphorothioate substitution at the 5′ and 3′ splice site phosphodiester bonds. Both steps of the splicing reaction proceeded with a phosphorothioate in the
S
p configuration but were blocked by the
R
p diastereomer. Both steps also proceeded with inversion of stereochemical configuration around phosphorus, consistent with a concerted transesterification reaction. These results are identical to those found for nuclear precursor mRNA (pre-mRNA) splicing and provide support for the hypothesis that group II introns and nuclear pre-mRNA introns share a common evolutionary history.
Splicing of the
rolA
Transcript of
Agrobacterium rhizogenes
in
Arabidopsis
Authors: Magrelli Armando , Langenkemper Kerstin , Dehio Christoph , Schell Jeff , Spena Angelo
Published: October 2006

The
rolA
gene encoded on the Ri plasmid A4 of
Agrobacterium rhizogenes
is one of the transferred (T
L
-DNA) genes involved in the pathogenesis of hairy-root disease in plants. The function of the 100-amino acid protein product of
rolA
is unknown, although its expression causes physiological and developmental alterations in transgenic plants. The
rolA
gene of
A. rhizogenes
contains an intron in its untranslated leader region that has features typical of plant pre-messenger RNA introns. Transcription and splicing of the
rolA
pre-messenger RNA occur in the plant cell.
Crystal Structure of the Catalytic Domain of HIV-1 Integrase: Similarity to Other Polynucleotidyl Transferases
Authors: Dyda Fred , Hickman Alison B. , Jenkins Timothy M. , Engelman Alan , Craigie Robert , Davies David R.
Published: October 2006

HIV integrase is the enzyme responsible for inserting the viral DNA into the host chromosome; it is essential for HIV replication. The crystal structure of the catalytically active core domain (residues 50 to 212) of HIV-1 integrase was determined at 2.5 Å resolution. The central feature of the structure is a five-stranded β sheet flanked by helical regions. The overall topology reveals that this domain of integrase belongs to a superfamily of polynucleotidyl transferases that includes ribonuclease H and the Holliday junction resolvase RuvC. The active site region is identified by the position of two of the conserved carboxylate residues essential for catalysis, which are located at similar positions in ribonuclease H. In the crystal, two molecules form a dimer with an extensive solvent-inaccessible interface of 1300 Å
2
per monomer.
A Receptor Component of the Chloroplast Protein Translocation Machinery
Authors: Hirsch Stephan , Muckel Eva , Heemeyer Frank , von Heijne Gunnar , Soll Jürgen
Published: October 2006

The chloroplast outer envelope protein OEP86 functions as a receptor in precursor protein translocation into chloroplasts. Sequence analysis suggests that the precursor of OEP86 is directed to the chloroplast outer envelope by a cleavable, negatively charged, and unusually long amino-terminal peptide. This presequence is unlike other potential targeting signals and suggests the existence of another membrane insertion pathway. Insertion of precursor OEP86 required the hydrolysis of adenosine triphosphate and the existence of surface exposed chloroplast membrane components, and it was not competed by another precursor protein destined for the internal plastid compartments.
Coordinate Initiation of
Drosophila
Development by Regulated Polyadenylation of Maternal Messenger RNAs
Authors: Sallés Fernando J. , Lieberfarb Marshal E. , Wreden Christopher , Gergen J. Peter , Strickland Sidney
Published: October 2006

Pattern formation in
Drosophila
depends initially on the translational activation of maternal messenger RNAs (mRNAs) whose protein products determine cell fate. Three mRNAs that dictate anterior, dorsoventral, and terminal specification—bicoid, Toll, and torso, respectively—showed increases in polyadenylate [poly(A)] tail length concomitant with translation. In contrast, posteriorly localized nanos mRNA, although also translationally activated, was not regulated by poly(A) status. These results implicate at least two mechanisms of mRNA activation in flies. Studies with bicoid mRNA showed that cytoplasmic polyadenylation is necessary for translation, establishing this pathway as essential for embryogenesis. Combined, these experiments identify a regulatory pathway that can coordinate initiation of maternal pattern formation systems in
Drosophila
.
Enhancer Point Mutation Results in a Homeotic Transformation in
Drosophila
Authors: Shimell Mary Jane , Simon Jeffrey , Bender Welcome , O'Connor Michael B.
Published: October 2006

In
Drosophila
, the misexpression or altered activity of genes from the bithorax complex results in homeotic transformations. One of these genes,
abd-A
, normally specifies the identity of the second through fourth abdominal segments (A2 to A4). In the dominant
Hyperabdominal
mutations (
Hab
), portions of the third thoracic segment (T3) are transformed toward A2 as the result of ectopic
abd-A
expression. Sequence analysis and deoxyribonuclease I footprinting demonstrate that the misexpression of
abd-A
in two independent
Hab
mutations results from the same single base change in a binding site for the gap gene
Krüppel
protein. These results establish that the spatial limits of the homeotic genes are directly regulated by gap gene products.
Postsynaptic Induction and Presynaptic Expression of Hippocampal Long-Term Depression
Authors: Bolshakov Vadim Y. , Siegelbaum Steven A.
Published: October 2006

Long-term depression (LTD) is an activity-dependent decrease in synaptic efficacy that together with its counterpart, long-term potentiation, is thought to be an important cellular mechanism for learning and memory in the mammalian brain. The induction of LTD in hippocampal CA1 pyramidal neurons in neonatal rats is shown to depend on postsynaptic calcium ion entry through L-type voltage-gated calcium channels paired with the activation of metabotropic glutamate receptors. Although induced postsynaptically, LTD is due to a long-term decrease in transmitter release from presynaptic terminals. This suggests that LTD is likely to require the production of a retrograde messenger.
G
h
: a GTP-Binding Protein with Transglutaminase Activity and Receptor Signaling Function
Authors: Nakaoka Hideaki , Perez Dianne M. , Baek Kwang Jin , Das Tanya , Husain Ahsan , Misono Kunio , Im Mie-Jae , Graham Robert M.
Published: October 2006

The α
1
-adrenergic receptors activate a phospholipase C enzyme by coupling to members of the large molecular size (approximately 74 to 80 kilodaltons) Gα
h
family of guanosine triphosphate (GTP)-binding proteins. Rat liver Gα
h
is now shown to be a tissue transglutaminase type II (TGase II). The transglutaminase activity of rat liver TGase II expressed in COS-1 cells was inhibited by the nonhydrolyzable GTP analog guanosine 5′-
O
-(3-thiotriphosphate) or by α
1
-adrenergic receptor activation. Rat liver TGase II also mediated α
1
-adrenergic receptor stimulation of phospholipase C activity. Thus, Gα
h
represents a new class of GTP-binding proteins that participate in receptor signaling and may be a component of a complex regulatory network in which receptor-stimulated GTP binding switches the function of Gα
h
from transglutamination to receptor signaling.
Gem: an Induced, Immediate Early Protein Belonging to the Ras Family
Authors: Maguire Jean , Santoro Thomas , Jensen Peter , Siebenlist Ulrich , Yewdell John , Kelly Kathleen
Published: October 2006

A gene encoding a 35-kilodalton guanosine triphosphate (GTP)-binding protein, Gem, was cloned from mitogen-induced human peripheral blood T cells. Gem and Rad, the product of a gene overexpressed in skeletal muscle in individuals with Type II diabetes, constitute a new family of Ras-related GTP-binding proteins. The distinct structural features of this family include the G3 GTP-binding motif, extensive amino- and carboxyl-terminal extensions beyond the Ras-related domain, and a motif that determines membrane association. Gem was transiently expressed in human peripheral blood T cells in response to mitogenic stimulation; the protein was phosphorylated on tyrosine residues and localized to the cytosolic face of the plasma membrane. Deregulated Gem expression prevented proliferation of normal and transformed 3T3 cells. These results suggest that Gem is a regulatory protein, possibly participating in receptor-mediated signal transduction at the plasma membrane.
Dynamics of the Chaperonin ATPase Cycle: Implications for Facilitated Protein Folding
Authors: Todd Matthew J. , Viitanen Paul V. , Lorimer George H.
Published: October 2006

The
Escherichia coli
chaperonins GroEL and GroES facilitate protein folding in an adenosine triphosphate (ATP)-dependent manner. After a single cycle of ATP hydrolysis by the adenosine triphosphatase (ATPase) activity of GroEL, the bi-toroidal GroEL formed a stable asymmetric ternary complex with GroES and nucleotide (bulletlike structures). With each subsequent turnover, ATP was hydrolyzed by one ring of GroEL in a quantized manner, completely releasing the adenosine diphosphate and GroES that were tightly bound to the other ring as a result of the previous turnover. The catalytic cycle involved formation of a symmetric complex (football-like structures) as an intermediate that accumulated before the rate-determining hydrolytic step. After one to two cycles, most of the substrate protein dissociated still in a nonnative state, which is consistent with intermolecular transfer of the substrate protein between toroids of high and low affinity. A unifying model for chaperonin-facilitated protein folding based on successive rounds of binding and release, and partitioning between committed and kinetically trapped intermediates, is proposed.
Role of a Conserved Retinoic Acid Response Element in Rhombomere Restriction of
Hoxb-1
Authors: Studer Michèle , Pöpperl Heike , Marshall Heather , Kuroiwa Atsushi , Krumlauf Robb
Published: October 2006

After activation in mesoderm and neuroectoderm, expression of the
Hoxb-1
gene is progressively restricted to rhombomere (r) 4 in the hindbrain. Analysis of the chick and mouse
Hoxb-1
genes identified positive and negative regulatory regions that cooperate to mediate segment-restricted expression during rhombomere formation. An enhancer generates expression extending into r3 and r5, and a repressor limits this domain to r4. The repressor contains a conserved retinoic acid response element, point mutations in which allow expression to spread into adjacent rhombomeres. Retinoids and their nuclear receptors may therefore participate in sharpening segment-restricted expression of
Hoxb-1
during rhombomere boundary formation.
Release of Adenosine by Activation of NMDA Receptors in the Hippocampus
Authors: Manzoni Olivier J. , Manabe Toshiya , Nicoll Roger A.
Published: October 2006

Adenosine is present in the mammalian brain in large amounts and has potent effects on neuronal activity, but its role in neural signaling is poorly understood. The glutamate receptor agonist
N
-methyl-D-aspartate (NMDA) caused a presynaptic depression of excitatory synaptic transmission in the CA1 region of guinea pig hippocampal slices. This depression was blocked by an adenosine A1 receptor antagonist, which suggests that activation of the NMDA subtype of glutamate receptor raises the concentration of extracellular adenosine, which acts on presynaptic inhibitory A1 receptors. Strong tetanic stimulation caused a heterosynaptic inhibition that was blocked by both NMDA and A1 receptor antagonists. Enkephalin, which selectively inhibits interneurons, antagonized the heterosynaptic inhibition. These findings suggest that synaptically released glutamate activates NMDA receptors, which in turn releases adenosine, at least in part from interneurons, that acts at a distance to inhibit presynaptically the release of glutamate from excitatory synapses. Thus, interneurons may mediate a widespread purinergic presynaptic inhibition.
Quantitative Trait Locus for Reading Disability on Chromosome 6
Authors: Cardon Lon R. , Smith Shelley D. , Fulker David W. , Kimberling William J. , Pennington Bruce F. , DeFries John C.
Published: October 2006

Interval mapping of data from two independent samples of sib pairs, at least one member of whom was reading disabled, revealed evidence for a quantitative trait locus (QTL) on chromosome 6. Results obtained from analyses of reading performance from 114 sib pairs genotyped for DNA markers localized the QTL to 6p21.3. Analyses of corresponding data from an independent sample of 50 dizygotic twin pairs provided evidence for linkage to the same region. In combination, the replicate samples yielded a χ
2
value of 16.73 (P =0.0002). Examination of twin and kindred siblings with more extreme deficits in reading performance yielded even stronger evidence for a QTL (χ
2
= 27.35, P < 0.00001). The position of the QTL was narrowly defined with a 100:1 confidence interval to a 2-centimorgan region within the human leukocyte antigen complex.
Increased Recruitment of TATA-Binding Protein to the Promoter by Transcriptional Activation Domains in Vivo
Authors: Klein Charles , Struhl Kevin
Published: October 2006

The rate at which the TATA-binding protein (TBP) interacts with the TATA element and promotes transcription by RNA polymerase II was determined in yeast cells. A TBP derivative with altered TATA-element specificity was rapidly induced, and transcription from promoters with appropriately mutated TATA elements was measured. Without a functional activator protein, basal transcription was observed only after a lag of several hours. In contrast, GCN4-activated transcription occurred rapidly upon induction of the TBP derivative. These results suggest that accessibility of TBP to the chromatin template in vivo is rate limiting and that activation domains increase recruitment of TBP to the promoter.
Restoration of X-ray Resistance and V(D)J Recombination in Mutant Cells by Ku cDNA
Authors: Smider Vaughn , Rathmell W. Kimryn , Lieber Michael R. , Chu Gilbert
Published: October 2006

Three genetic complementation groups of rodent cells are defective for both repair of x-ray-induced double-strand breaks and V(D)J recombination. Cells from one group lack a DNA end-binding activity that is biochemically and antigenically similar to the Ku autoantigen. Transfection of complementary DNA (cDNA) that encoded the 86-kilodalton subunit of Ku rescued these mutant cells for DNA end-binding activity, x-ray resistance, and V(D)J recombination activity. These results establish a role for Ku in DNA repair and recombination. Furthermore, as a component of a DNA-dependent protein kinase, Ku may initiate a signaling pathway induced by DNA damage.
Thalamic Abnormalities in Schizophrenia Visualized Through Magnetic Resonance Image Averaging
Authors: Andreasen Nancy C. , Arndt Stephan , Swayze Victor , Cizadlo Ted , Flaum Michael , O'Leary Daniel , Ehrhardt James C. , Yuh William T. C.
Published: October 2006

Schizophrenia is a complex illness characterized by multiple types of symptoms involving many aspects of cognition and emotion. Most efforts to identify its underlying neural substrates have focused on a strategy that relates a single symptom to a single brain region. An alternative hypothesis, that the variety of symptoms could be explained by a lesion in midline neural circuits mediating attention and information processing, is explored. Magnetic resonance images from patients and controls were transformed with a "bounding box" to produce an "average schizophrenic brain" and an "average normal brain." After image subtraction of the two averages, the areas of difference were displayed as an effect size map. Specific regional abnormalities were observed in the thalamus and adjacent white matter. An abnormality in the thalamus and related circuitry explains the diverse symptoms of schizophrenia parsimoniously because they could all result from a defect in filtering or gating sensory input, which is one of the primary functions of the thalamus in the human brain.
Folding of VSV G Protein: Sequential Interaction with BiP and Calnexin
Authors: Hammond Craig , Helenius Ari
Published: October 2006

The endoplasmic reticulum (ER) contains molecular chaperones that facilitate the folding of proteins in mammalian cells. Biosynthetic labeling was used to study the interactions of two chaperones, BiP and calnexin, with vesicular stomatitis virus (VSV) glycoprotein (G protein). Coimmunoprecipitation of G protein with the chaperones showed that BiP bound maximally to early folding intermediates of G protein, whereas calnexin bound after a short lag to more folded molecules. Castanospermine, an inhibitor of ER glucosidases, blocked the binding of proteins to calnexin and inhibited G protein folding. Interaction with calnexin was necessary for efficient folding of G protein and for retention of partially folded forms.
Anatomical Evidence for Cerebellar and Basal Ganglia Involvement in Higher Cognitive Function
Authors: Middleton Frank A. , Strick Peter L.
Published: October 2006

The possibility that neurons in the basal ganglia and cerebellum innervate areas of the cerebral cortex that are involved in cognitive function has been a controversial subject. Here, retrograde transneuronal transport of herpes simplex virus type 1 (HSV1) was used to identify subcortical neurons that project via the thalamus to area 46 of the primate prefrontal cortex. This cortical area is known to be involved in spatial working memory. Many neurons in restricted regions of the dentate nucleus of the cerebellum and in the internal segment of the globus pallidus were labeled by transneuronal transport of virus from area 46. The location of these neurons was different from those labeled after HSV1 transport from motor areas of the cerebral cortex. These observations define an anatomical substrate for the involvement of basal ganglia and cerebellar output in higher cognitive function.
Formation of a Monomeric DNA Binding Domain by Skn-1 bZIP and Homeodomain Elements
Authors: Blackwell T. Keith , Bowerman Bruce , Priess James R. , Weintraub Harold
Published: October 2006

Maternally expressed Skn-1 protein is required for the correct specification of certain blastomere fates in early
Caenorhabditis elegans
embryos. Skn-1 contains a basic region similar to those of basic leucine zipper (bZIP) proteins but, paradoxically, it lacks a leucine zipper dimerization segment. Random sequence selection methods were used to show that Skn-1 binds to specific DNA sequences as a monomer. The Skn-1 basic region lies at the carboxyl terminus of an 85-amino acid domain that binds preferentially to a bZIP half-site and also recognizes adjacent 5′ AT-rich sequences in the minor groove, apparently with an amino (NH
2
)-terminal "arm" related to those of homeodomain proteins. The intervening residues appear to stabilize interactions of these two subdomains with DNA. The Skn-1 DNA binding domain thus represents an alternative strategy for promoting binding of a basic region segment recognition helix to its cognate half-site. The results point to an underlying modularity in subdomains within established DNA binding domains.
Role of Oocyte Position in Establishment of Anterior-Posterior Polarity in
Drosophila
Authors: González-Reyes Acaimo , St Johnston Daniel
Published: October 2006

The polarized microtubule cytoskeleton of the
Drosophila
oocyte directs the localization of the maternal determinants which establish the anterior-posterior (AP) axis of the embryo. Because the formation of this microtubule array is dependent on signals from the follicle cells that surround the oocyte, it has been proposed that AP polarity originates in the follicle cells. Here it is shown that the movement of the oocyte to the posterior of the egg chamber early in oogenesis determines AP polarity in the follicle cell layer, and also in the oocyte. Moreover, the generation of AP asymmetry requires signaling from the germ line to the soma and back again.
PHAS-I as a Link Between Mitogen-Activated Protein Kinase and Translation Initiation
Authors: Lin Tai-An , Kong Xianming , Haystead Timothy A. J. , Pause Arnim , Belsham Graham , Sonenberg Nahum , Lawrence John C.
Published: October 2006

PHAS-I is a heat-stable protein (relative molecular mass ≈ 12,400) found in many tissues. It is rapidly phosphorylated in rat adipocytes incubated with insulin or growth factors. Nonphosphorylated PHAS-I bound to initiation factor 4E (eIF-4E) and inhibited protein synthesis. Serine-64 in PHAS-I was rapidly phosphorylated by mitogen-activated (MAP) kinase, the major insulin-stimulated PHAS-I kinase in adipocyte extracts. Results obtained with antibodies, immobilized PHAS-I, and a messenger RNA cap affinity resin indicated that PHAS-I did not bind eIF-4E when serine-64 was phosphorylated. Thus, PHAS-I may be a key mediator of the stimulation of protein synthesis by the diverse group of agents and stimuli that activate MAP kinase.
Direct Measurement of the Forces Between Complementary Strands of DNA
Authors: Lee Gil U , Chrisey Linda A. , Colton Richard J.
Published: October 2006

Interaction forces between single strands of DNA were measured with the atomic force microscope by a procedure in which DNA oligonucleotides were covalently attached to a spherical probe and surface. Adhesive forces measured between complementary 20-base strands fell into three distinct distributions centered at 1.52, 1.11, and 0.83 nano-newtons, which are associated with the rupture of the interchain interaction between a single pair of molecules involving 20, 16, and 12 base pairs, respectively. When a third long DNA molecule was coupled between complementary surfaces, both intra- and interchain forces were observed. The intrachain interaction resulting from the molecule's elasticity manifested itself as a long-range cohesive force.
SecA Homolog in Protein Transport Within Chloroplasts: Evidence for Endosymbiont-Derived Sorting
Authors: Yuan Jianguo , Henry Ralph , McCaffery Michael , Cline Kenneth
Published: October 2006

The SecA protein is an essential, azide-sensitive component of the bacterial protein translocation machinery. A SecA protein homolog (CPSecA) now identified in pea chloroplasts was purified to homogeneity. CPSecA supported protein transport into thylakoids, the chloroplast internal membrane network, in an azide-sensitive fashion. Only one of three pathways for protein transport into thylakoids uses the CPSecA mechanism. The use of a bacteria-homologous mechanism in intrachloroplast protein transport provides evidence for conservative sorting of proteins within chloroplasts.
Transformation of Lupus-Inducing Drugs to Cytotoxic Products by Activated Neutrophils
Authors: Jiang Xiaoxia , Khursigara Gus , Rubin Robert L.
Published: October 2006

Drug-induced lupus is a serious side effect of certain medications, but the chemical features that confer this property and the underlying pathogenesis are puzzling. Prototypes of all six therapeutic classes of lupus-inducing drugs were highly cytotoxic only in the presence of activated neutrophils. Removal of extracellular hydrogen peroxide before, but not after, exposure of the drug to activated neutrophils prevented cytotoxicity. Neutrophil-dependent cytotoxicity required the enzymatic action of myeloperoxidase, resulting in the chemical transformation of the drug to a reactive product. The capacity of drugs to serve as myeloperoxidase substrates in vitro was associated with the ability to induce lupus in vivo.
Electrical Turbulence in Three-Dimensional Heart Muscle
Authors: Winfree A. T.
Published: October 2006

Rotors or vortex action potentials with a diameter of about 1 centimeter and a rotation period of about 0.1 second occur in normal myocardium just before transition to fibrillation, a disorderly pattern of action potential propagation. Numerical models and corresponding mathematical analysis have recently suggested candidate mechanisms, all two-dimensional, for this transition from periodic electrical activity to something resembling turbulence. However, comparably recent experiments unanimously show that rotors, and the spiral waves they radiate, remain stably periodic in two-dimensional myocardium. This seeming paradox suggests a transition mediated through disorderly dynamics of the electrical vortex in three dimensions, as a "vortex filament."
Probing Individual Molecules with Confocal Fluorescence Microscopy
Authors: Nie Shuming , Chiu Daniel T. , Zare Richard N.
Published: October 2006

Confocal fluorescence microscopy coupled with a diffraction-limited laser beam and a high-efficiency detection system has been used to study the diffusive movement and emission process of individual fluorescent molecules in the liquid phase at room temperature. The high detection sensitivity achieved at fast data acquisition speeds (greater than 1 kilohertz) allows real-time observation of single-molecule fluorescence without statistical analysis. The results show fluorescence-cycle saturation at the single-molecule level and multiple recrossings of a single molecule into and out of the probe volume as well as the triplet state.
Crystal Structure of β-D-Cellotetraose Hemihydrate with Implications for the Structure of Cellulose II
Authors: Geßler Katrin , Krauß Norbert , Steiner Thomas , Betzel Christian , Sandmann Claus , Saenger Wolfram
Published: October 2006

The crystal structure of β-D-cellotetraose shows the same molecular packing as cellulose II, with two antiparallel molecules in the unit cell. For cellulose II, the orientation of the C6-O6 bonds has been described as gauche-trans and trans-gauche, respectively, for the two antiparallel molecules, which otherwise have identical conformations. In contrast, in β-D-cellotetraose all C6-O6 bonds are gauche-trans, but the conformations of the two antiparallel molecules are different. Energy minimization and molecular dynamics studies suggest that the structure of cellulose II should be reinvestigated in light of these findings.
Identification of Two GTP-Binding Proteins in the Chloroplast Protein Import Machinery
Authors: Kessler Felix , Blobel Günter , Patel Hitesh A. , Schnell Danny J.
Published: October 2006

Two of four proteins that associated with translocation intermediates during protein import across the outer chloroplast envelope membrane were identified as guanosine triphosphate (GTP)-binding proteins. Both proteins are integral membrane proteins of the outer chloroplast membrane, and both are partially exposed on the chloroplast surface where they were accessible to thermolysin digestion. Engagement of the outer membrane's import machinery by an import substrate was inhibited by slowly hydrolyzable or non-hydrolyzable GTP analogs. Thus, these GTP-binding proteins may function in protein import into chloroplasts.
Coding of Visual Space by Premotor Neurons
Authors: Graziano Michael S. A. , Yap Gregory S. , Gross Charles G.
Published: October 2006

In primates, the premotor cortex is involved in the sensory guidance of movement. Many neurons in ventral premotor cortex respond to visual stimuli in the space adjacent to the hand or arm. These visual receptive fields were found to move when the arm moved but not when the eye moved; that is, they are in arm-centered, not retinocentric, coordinates. Thus, they provide a representation of space near the body that may be useful for the visual control of reaching.
Horizontal Propagation of Excitation in Rat Visual Cortical Slices Revealed by Optical Imaging
Authors: Tanifuji Manabu , Sugiyama Takeshi , Murase Kazuyuki
Published: October 2006

Optical imaging with high spatial and temporal resolution of neural activity in rat cortical slices was used to investigate the dynamics of signal transmission through neural connections in the visual cortex. When inhibition due to γ-aminobutyric acid was slightly suppressed, horizontal propagation of excitation in both the supra- and infragranular layers became prominent. This propagation was not affected by vertical cuts in either the supra- or infragranular layer, which suggests that excitation is at least partially conveyed horizontally by reciprocal vertical connections between neurons in these layers.
A Molecular Determinant for Submillisecond Desensitization in Glutamate Receptors
Authors: Mosbacher J. , Schoepfer R. , Monyer H. , Burnashev N. , Seeburg P. H. , Ruppersberg J. P.
Published: October 2006

The decay of excitatory postsynaptic currents in central neurons mediated by α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptors is likely to be shaped either by receptor desensitization or by offset after removal of glutamate from the synaptic cleft. Native AMPA receptors show desensitization time constants of 1 to about 10 milliseconds, but the underlying molecular determinants of these large differences are unknown. Cloned AMPA receptors carrying the "flop" splice variants of glutamate receptor subtype C (GluR-C) and GluR-D are shown to have desensitization time constants of around 1 millisecond, whereas those with the "flip" variants are about four times slower. Cerebellar granule cells switch their expression of GluR-D splice variants from mostly flip forms in early stages to predominantly flop forms in the adult rat brain. These findings suggest that rapid desensitization of AMPA receptors can be regulated by the expression and alternative splicing of GluR-D gene transcripts.
Activation of the Myogenic Lineage by MEF2A, a Factor that Induces and Cooperates with MyoD
Authors: Kaushal Sunjay , Schneider Jay W. , Nadal-Ginard Bernardo , Mahdavi Vijak
Published: October 2006

Muscle enhancer factor-2A (MEF2A), a member of the MADS family, induced myogenic development when ectopically expressed in clones of nonmuscle cells of human clones, a function previously limited to the muscle basic helix-loop-helix (bHLH) proteins. During myogenesis, MEF2A and bHLH proteins cooperatively activate skeletal muscle genes and physically interact through the MADS domain of MEF2A and the three myogenic amino acids of the muscle bHLH proteins. Thus, skeletal myogenesis is mediated by two distinct families of mutually inducible and interactive muscle transcription factors, either of which can initiate the developmental cascade.
Tissue-Specific Targeting of Retroviral Vectors Through Ligand-Receptor Interactions
Authors: Kasahara Noriyuki , Dozy Andrée M. , Kan Yuet Wai
Published: October 2006

The development of retroviral vectors that target specific cell types could have important implications for the design of gene therapy strategies. A chimeric protein containing the polypeptide hormone erythropoietin and part of the
env
protein of ecotropic Moloney murine leukemia virus was engineered into the virus. This murine virus became several times more infectious for murine cells bearing the erythropoietin receptor, and it also became infectious for human cells bearing the erythropoietin receptor. This type of tissue-specific targeting by means of ligand-receptor interactions may have broad applications to a variety of gene delivery systems.
The PCL2 (ORFD)-PHO85 Cyclin-Dependent Kinase Complex: a Cell Cycle Regulator in Yeast
Authors: Measday Vivien , Moore Lynda , Ogas Joseph , Tyers Mike , Andrews Brenda
Published: October 2006

Cyclin-dependent kinase (cdk) complexes are essential activators of cell cycle progression in all eukaryotes. In contrast to mammalian cells, in which multiple cdk's contribute to cell cycle regulation, the yeast cell cycle is largely controlled by the activity of a single cdk, CDC28. Analysis of the putative G
1
cyclin PCL2 (ORFD) identified a second cyclin-cdk complex that contributes to cell cycle progression in yeast. PCL2 interacted with the cdk PHO85 in vivo and in vitro and formed a kinase complex that had G
1
-periodic activity. Under genetic conditions in which the Start transition was compromised, PHO85 and its associated cyclin subunits were essential for cell cycle commitment. Because PHO85 and another cyclin-like molecule, PHO80, also take part in inorganic phosphate metabolism, this cdk enzyme may integrate responses to nutritional conditions with the cell cycle.
Lymphotactin: a Cytokine that Represents a New Class of Chemokine
Authors: Kelner Gregory S. , Kennedy Jacqueline , Bacon Kevin B. , Kleyensteuber Sarah , Largaespada David A. , Jenkins Nancy A. , Copeland Neal G. , Bazan J. Fernando , Moore Kevin W. , Schall Thomas J. , Zlotnik Albert
Published: October 2006

In this study, the cytokine-producing profile of progenitor T cells (pro-T cells) was determined. During screening of a complementary DNA library generated from activated mouse pro-T cells, a cytokine designated lymphotactin was discovered. Lymphotactin is similar to members of both the Cys-Cys and Cys-X-Cys chemokine families but lacks two of the four cysteine residues that are characteristic of the chemokines. Lymphotactin is also expressed in activated CD8
+
T cells and CD4
-
CD8
-
T cell receptor αβ
+
thymocytes. It has chemotactic activity for lymphocytes but not for monocytes or neutrophils. The gene encoding lymphotactin maps to chromosome one. Taken together, these observations suggest that lymphotactin represents a novel addition to the chemokine superfamily.
Polyglycylation of Tubulin: a Posttranslational Modification in Axonemal Microtubules
Authors: Redeker Virginie , Levilliers Nicolette , Schmitter Jean-Marie , Le Caer Jean-Pierre , Rossier Jean , Adoutte André , Bré Marie-Hélène
Published: October 2006

A posttranslational modification was detected in the carboxyl-terminal region of axonemal tubulin from
Paramecium
. Tubulin carboxyl-terminal peptides were isolated and analyzed by Edman degradation sequencing, mass spectrometry, and amino acid analysis. All of the peptides, derived from both α and β tubulin subunits, were modified by polyglycylation, containing up to 34 glycyl units covalently bound to the γ carboxyl group of glutamyl residues. This modification, present in one of the most stable microtubular systems, may influence microtubule stability or axoneme function, or both.