bluuebunny/crossref_metadata_2025 huggingface dataset:
Diversity and Pattern in the Developing Spinal Cord
Authors: Tanabe Yasuto , Jessell Thomas M.
Published: July 2002

The generation of distinct neuronal cell types in appropriate numbers and at precise positions underlies the assembly of neural circuits that encode animal behavior. Despite the complexity of the vertebrate central nervous system, advances have been made in defining the principles that control the diversification and patterning of its component cells. A combination of molecular genetic, biochemical, and embryological assays has begun to reveal the identity and mechanism of action of molecules that induce and pattern neural tissue and the role of transcription factors in establishing generic and specific neuronal fates. Some of these advances are discussed here, focusing on the spinal cord as a model system for analyzing the molecular control of central nervous system development in vertebrates.
Learning Rediscovered
Authors: Bates Elizabeth , Elman Jeffrey
Published: July 2002

Infants can learn more and earlier than we thought. A new result in this week's issue [Saffran
et al
. (
p. 1926
)] reports that a surprisingly brief exposure to nonsense syllables can fuel the absorption of a sophisticated understanding of their use. Bates and Elman discuss these results in the context of the ongoing debate about whether and how language is a learned ability.
Ca
2+
-Dependent Protein Kinases and Stress Signal Transduction in Plants
Authors: Sheen Jen
Published: July 2002

Stress responses in plants involve changes in the transcription of specific genes. The constitutively active mutants of two related Ca
2+
-dependent protein kinases (CDPK1 and CDPK1a) activate a stress-inducible promoter, bypassing stress signals. Six other plant protein kinases, including two distinct CDPKs, fail to mimic this stress signaling. The activation is abolished by a CDPK1 mutation in the kinase domain and diminished by a constitutively active protein phosphatase 2C that is capable of blocking responses to the stress hormone abscisic acid. A variety of functions are mediated by different CDPKs. CDPK1 and CDPK1a may be positive regulators controlling stress signal transduction in plants.
Control of EGF Receptor Signaling by Clathrin-Mediated Endocytosis
Authors: Vieira Amandio V. , Lamaze Christophe , Schmid Sandra L.
Published: July 2002

Epidermal growth factor receptor (EGFR) signaling was analyzed in mammalian cells conditionally defective for receptor-mediated endocytosis. EGF-dependent cell proliferation was enhanced in endocytosis-defective cells. However, early EGF-dependent signaling events were not uniformly up-regulated. A subset of signal transducers required the normal endocytic trafficking of EGFR for full activation. Thus, endocytic trafficking of activated EGFR plays a critical role not only in attenuating EGFR signaling but also in establishing and controlling specific signaling pathways.
U.K. Universities—Jostling for Rank
Authors: Williams Nigel
Published: July 2002

London—The British government has just completed a massive peer review of the country's university departments and research institutes, grading them on the quality of their faculty members. Some universities tried to improve their ratings by withholding some faculty members from the review. At stake: $1.1 billion in infrastructure funding that will be distributed in part on the results of the reviews.
Asthma--An Epidemic in the Absence of Infection?
Authors: Cookson William O. C. M. , Moffatt Miriam F.
Published: July 2002

In a report in this issue of
Science
, Shirakawa
et al
. (
p. 77
) show an inverse relation between exposure to the bacterium that causes tuberculosis and the incidence of asthma, leading to the proposition that childhood infections can protect against later development of asthma and similar allergic reactions. In their Perspective, Cookson and Moffatt explain the immunological basis of this proposition and discuss its implications.
Influx of Industrial Funding Shifts Balance on Campus
Authors: Kim Chang-Yop , Normile Dennis
Published: July 2002

SEOUL
—:Increasing contributions from corporations eager to bolster their own technological capabilities have helped Korean universities erect new buildings, stock labs, and support first-class research. But they are driving a wedge between departments that cater to industry and those whose work has fewer commercial applications.
Too Radical for NIH? Try DARPA
Authors: Marshall Eliot
Published: July 2002

Alarmed by evidence that terrorists may exploit biological weapons, the Defense Advanced Research Projects Agency (DARPA)—best known as the originator of the Internet—is moving into biology with some serious money. It is looking for innovative proposals.
Tracing Molecules That Make the Brain-Body Connection
Authors: Pennisi Elizabeth
Published: July 2002

Researchers once considered the body's network of immune defenses a system unto itself, but they have learned over the past 15 years that it is intimately intertwined with the nervous and endocrine systems. Recently, researchers have begun unraveling the molecular links between these systems, which include the interleukins and hormones such as corticosteroids. And as these connections come to light, they are helping explain some previously mysterious correlations between mental and hormonal states and the immune system.
Nanofabrication of Small Copper Clusters on Gold(111) Electrodes by a Scanning Tunneling Microscope
Authors: Kolb D. M. , Ullmann R. , Will T.
Published: July 2002

The use of scanning tunneling microscopy in an electrochemical environment as a tool for the nanoscale modification of gold electrodes was demonstrated. Small copper clusters, typically two to four atomic layers in height, were precisely positioned on a gold(111) electrode by a process in which copper was first deposited onto the tip of the scanning tunneling microscope, which then acted as a reservoir from which copper could be transferred to the surface during an appropriate approach of the tip to the surface. Tip approach and position were controlled externally by a microprocessor unit, allowing the fabrication of various patterns, cluster arrays, and “conducting wires” in a very flexible and convenient manner.
Calmodulin Regulation of Calcium Stores in Phototransduction of
Drosophila
Authors: Arnon Assaf , Cook Boaz , Montell Craig , Selinger Zvi , Minke Baruch
Published: July 2002

Phototransduction in
Drosophila
occurs through the ubiquitous phosphoinositide-mediated signal transduction system. Major unresolved questions in this pathway are the identity and role of the internal calcium stores in light excitation and the mechanism underlying regulation of Ca
2+
release from internal stores. Treatment of
Drosophila
photoreceptors with ryanodine and caffeine disrupted the current induced by light, whereas subsequent application of calcium-calmodulin (Ca-CaM) rescued the inactivated photoresponse. In calcium-deprived wild-type
Drosophila
and in calmodulin-deficient transgenic flies, the current induced by light was disrupted by a specific inhibitor of Ca-CaM. Furthermore, inhibition of Ca-CaM revealed light-induced release of calcium from intracellular stores. It appears that functional ryanodine-sensitive stores are essential for the photoresponse. Moreover, calcium release from these stores appears to be a component of
Drosophila
phototransduction, and Ca-CaM regulates this process.
Strontianite in Coral Skeletal Aragonite
Authors: Greegor Robert B. , Pingitore Nicholas E. , Lytle Farrel W.
Published: July 2002

An x-ray spectroscopic study of scleractinian coral skeletons indicated that, although some strontium substitutes for calcium in the aragonite structure, at concentrations of about 7500 parts per million, as much as 40 percent of the strontium resides in strontianite (SrCO
3
). A doublet peak in the Fourier transform of the extended x-ray absorption fine structure of the coral corresponded to six metal and 13 oxygen neighbors surrounding strontium at about 4.05 angstroms in strontium-substituted aragonite and at about 4.21 angstroms in strontianite. Thus, the mechanism of the temperature-sensitive partitioning of strontium between seawater and coral skeleton used for paleothermometry is unexpectedly complex.
Evaluation of the Rate of Evolution in Natural Populations of Guppies (
Poecilia reticulata
)
Authors: Reznick David N. , Shaw Frank H. , Rodd F. Helen , Shaw Ruth G.
Published: July 2002

Natural populations of guppies were subjected to an episode of directional selection that mimicked natural processes. The resulting rate of evolution of age and size at maturity was similar to rates typically obtained for traits subjected to artificial selection in laboratory settings and up to seven orders of magnitude greater than rates inferred from the paleontological record. Male traits evolved more rapidly than female traits largely because males had more genetic variation upon which natural selection could act. These results are considered in light of the ongoing debate about the importance of natural selection versus other processes in the paleontological record of evolution.
Integration of What and Where in the Primate Prefrontal Cortex
Authors: Rao S. Chenchal , Rainer Gregor , Miller Earl K.
Published: July 2002

The visual system separates processing of an object’s form and color (“what”) from its spatial location (“where”). In order to direct action to objects, the identity and location of those objects must somehow be integrated. To examine whether this process occurs within the prefrontal (PF) cortex, the activity of 195 PF neurons was recorded during a task that engaged both what and where working memory. Some neurons showed either object-tuned (what) or location-tuned (where) delay activity. However, over half (52 percent, or 64/123) of the PF neurons with delay activity showed both what and where tuning. These neurons may contribute to the linking of object information with the spatial information needed to guide behavior.
Orientation Selectivity in Pinwheel Centers in Cat Striate Cortex
Authors: Maldonado Pedro E. , Gödecke Imke , Gray Charles M. , Bonhoeffer Tobias
Published: July 2002

In primary visual cortex of higher mammals neurons are grouped according to their orientation preference, forming “pinwheels” around “orientation centers.” Although the general structure of orientation maps is largely resolved, the microscopic arrangement of neuronal response properties in the orientation centers has remained elusive. The tetrode technique, enabling multiple single-unit recordings, in combination with intrinsic signal imaging was used to reveal the fine-grain structure of orientation maps in these locations. The results show that orientation centers represent locations where orientation columns converge containing normal, sharply tuned neurons of different orientation preference lying in close proximity.
Peptide Agonist of the Thrombopoietin Receptor as Potent as the Natural Cytokine
Authors: Cwirla Steven E. , Balasubramanian Palaniappan , Duffin David J. , Wagstrom Christopher R. , Gates Christian M. , Singer Sara C. , Davis Ann M. , Tansik Robert L. , Mattheakis Larry C. , Boytos Chris M. , Schatz Peter J. , Baccanari David P. , Wrighton Nicholas C. , Barrett Ronald W. , Dower William J.
Published: July 2002

Two families of small peptides that bind to the human thrombopoietin receptor and compete with the binding of the natural ligand thrombopoietin (TPO) were identified from recombinant peptide libraries. The sequences of these peptides were not found in the primary sequence of TPO. Screening libraries of variants of one of these families under affinity-selective conditions yielded a 14–amino acid peptide (Ile-Glu-Gly-Pro-Thr-Leu-Arg-Gln-Trp-Leu-Ala-Ala-Arg-Ala) with high affinity (dissociation constant ≈ 2 nanomolar) that stimulates the proliferation of a TPO-responsive Ba/F3 cell line with a median effective concentration (EC
50
) of 400 nanomolar. Dimerization of this peptide by a carboxyl-terminal linkage to a lysine branch produced a compound with an EC
50
of 100 picomolar, which was equipotent to the 332–amino acid natural cytokine in cell-based assays. The peptide dimer also stimulated the in vitro proliferation and maturation of megakaryocytes from human bone marrow cells and promoted an increase in platelet count when administered to normal mice.
Transformation of Chicken Cells by the Gene Encoding the Catalytic Subunit of PI 3-Kinase
Authors: Chang Hwai Wen , Aoki Masahiro , Fruman David , Auger Kurt R. , Bellacosa Alfonso , Tsichlis Philip N. , Cantley Lewis C. , Roberts Thomas M. , Vogt Peter K.
Published: July 2002

The avian sarcoma virus 16 (ASV 16) is a retrovirus that induces hemangiosarcomas in chickens. Analysis of the ASV 16 genome revealed that it encodes an oncogene that is derived from the cellular gene for the catalytic subunit of phosphoinositide 3-kinase (PI 3-kinase). The gene is referred to as v-
p3k
, and like its cellular counterpart c-
p3k
, it is a potent transforming gene in cultured chicken embryo fibroblasts (CEFs). The products of the viral and cellular
p3k
genes have PI 3-kinase activity. CEFs transformed with either gene showed elevated levels of phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate and activation of Akt kinase.
Positive Effects of Combined Antiretroviral Therapy on CD4
+
T Cell Homeostasis and Function in Advanced HIV Disease
Authors: Autran B. , Carcelain G. , Li T. S. , Blanc C. , Mathez D. , Tubiana R. , Katlama C. , Debré P. , Leibowitch J.
Published: July 2002

Highly active antiretroviral therapy (HAART) increases CD4
+
cell numbers, but its ability to correct the human immunodeficiency virus (HIV)–induced immune deficiency remains unknown. A three-phase T cell reconstitution was demonstrated after HAART, with: (i) an early rise of memory CD4
+
cells, (ii) a reduction in T cell activation correlated to the decreasing retroviral activity together with an improved CD4
+
T cell reactivity to recall antigens, and (iii) a late rise of “naı̈ve” CD4
+
lymphocytes while CD8
+
T cells declined, however, without complete normalization of these parameters. Thus, decreasing the HIV load can reverse HIV-driven activation and CD4
+
T cell defects in advanced HIV-infected patients.
Bypass of Senescence After Disruption of p21

CIP1/WAF1

Gene in Normal Diploid Human Fibroblasts
Authors: Brown Jeremy P. , Wei Wenyi , Sedivy John M.
Published: July 2002

Most somatic cells die after a finite number of cell divisions, a phenomenon described as senescence. The p21

CIP1/WAF1

gene encodes an inhibitor of cyclin-dependent kinases. Inactivation of p21 by two sequential rounds of targeted homologous recombination was sufficient to bypass senescence in normal diploid human fibroblasts. At the checkpoint between the prereplicative phase of growth and the phase of chromosome replication, cells lacking p21 failed to arrest the cell cycle in response to DNA damage, but their apoptotic response and genomic stability were unaltered. These results establish the feasibility of using gene targeting for genetic studies of normal human cells.
Sulfur and Hydrogen Isotope Anomalies in Meteorite Sulfonic Acids
Authors: Cooper George W. , Thiemens Mark H. , Jackson Teresa L. , Chang Sherwood
Published: July 2002

Intramolecular carbon, hydrogen, and sulfur isotope ratios were measured on a homologous series of organic sulfonic acids discovered in the Murchison meteorite. Mass-independent sulfur isotope fractionations were observed along with high deuterium/hydrogen ratios. The deuterium enrichments indicate formation of the hydrocarbon portion of these compounds in a low-temperature environment that is consistent with that of interstellar clouds. Sulfur-33 enrichments observed in methanesulfonic acid could have resulted from gas-phase ultraviolet irradiation of a precursor, carbon disulfide. The source of the sulfonic acid precursors may have been the reactive interstellar molecule carbon monosulfide.
Dynamic Molecular Combing: Stretching the Whole Human Genome for High-Resolution Studies
Authors: Michalet Xavier , Ekong Rosemary , Fougerousse Françoise , Rousseaux Sophie , Schurra Catherine , Hornigold Nick , Slegtenhorst Marjon van , Wolfe Jonathan , Povey Sue , Beckmann Jacques S. , Bensimon Aaron
Published: July 2002

DNA in amounts representative of hundreds of eukaryotic genomes was extended on silanized surfaces by dynamic molecular combing. The precise measurement of hybridized DNA probes was achieved directly without requiring normalization. This approach was validated with the high-resolution mapping of cosmid contigs on a yeast artificial chromosome (YAC) within yeast genomic DNA. It was extended to human genomic DNA for precise measurements ranging from 7 to 150 kilobases, of gaps within a contig, and of microdeletions in the tuberous sclerosis 2 gene on patients' DNA. The simplicity, reproducibility, and precision of this approach makes it a powerful tool for a variety of genomic studies.
Mutation of the Stargardt Disease Gene (
ABCR
) in Age-Related Macular Degeneration
Authors: Allikmets Rando , Shroyer Noah F. , Singh Nanda , Seddon Johanna M. , Lewis Richard Alan , Bernstein Paul S. , Peiffer Andy , Zabriskie Norman A. , Li Yixin , Hutchinson Amy , Dean Michael , Lupski James R. , Leppert Mark
Published: July 2002

Age-related macular degeneration (AMD) is the leading cause of severe central visual impairment among the elderly and is associated both with environmental factors such as smoking and with genetic factors. Here, 167 unrelated AMD patients were screened for alterations in
ABCR
, a gene that encodes a retinal rod photoreceptor protein and is defective in Stargardt disease, a common hereditary form of macular dystrophy. Thirteen different AMD-associated alterations, both deletions and amino acid substitutions, were found in one allele of
ABCR
in 26 patients (16%). Identification of
ABCR
alterations will permit presymptomatic testing of high-risk individuals and may lead to earlier diagnosis of AMD and to new strategies for prevention and therapy.
Mediation of Neuronal Apoptosis by Enhancement of Outward Potassium Current
Authors: Yu Shan Ping , Yeh Chen-Hsiung , Sensi Stefano L. , Gwag Byoung J. , Canzoniero Lorella M. T. , Farhangrazi Z. Shadi , Ying Howard S. , Tian Min , Dugan Laura L. , Choi Dennis W.
Published: July 2002

Apoptosis of mouse neocortical neurons induced by serum deprivation or by staurosporine was associated with an early enhancement of delayed rectifier (
I
K
) current and loss of total intracellular K
+
. This
I
K
augmentation was not seen in neurons undergoing excitotoxic necrosis or in older neurons resistant to staurosporine-induced apoptosis. Attenuating outward K
+
current with tetraethylammonium or elevated extracellular K
+
, but not blockers of Ca
2+
, Cl
−
, or other K
+
channels, reduced apoptosis, even if associated increases in intracellular Ca
2+
concentration were prevented. Furthermore, exposure to the K
+
ionophore valinomycin or the K
+
-channel opener cromakalim induced apoptosis. Enhanced K
+
efflux may mediate certain forms of neuronal apoptosis.
Accretion Rates of Meteorites and Cosmic Dust in the Early Ordovician
Authors: Schmitz Birger , Peucker-Ehrenbrink Bernhard , Lindström Maurits , Tassinari Mario
Published: July 2002

Abundant fossil meteorites in marine, condensed Lower Ordovician limestones from Kinnekulle, Sweden, indicate that accretion rates of meteorites were one to two orders of magnitude higher during an interval of the Early Ordovician than at present. Osmium isotope and iridium analyses of whole-rock limestone indicate a coeval enhancement of one order of magnitude in the influx rate of cosmic dust. Enhanced accretion of cosmic matter may be related to the disruption of the L chondrite parent body around 500 million years ago.
The Structure of Nitric Oxide Synthase Oxygenase Domain and Inhibitor Complexes
Authors: Crane Brian R. , Arvai Andrew S. , Gachhui Ratan , Wu Chaoqun , Ghosh Dipak K. , Getzoff Elizabeth D. , Stuehr Dennis J. , Tainer John A.
Published: July 2002

The nitric oxide synthase oxygenase domain (NOS
ox
) oxidizes arginine to synthesize the cellular signal and defensive cytotoxin nitric oxide (NO). Crystal structures determined for cytokine-inducible NOS
ox
reveal an unusual fold and heme environment for stabilization of activated oxygen intermediates key for catalysis. A winged β sheet engenders a curved α-β domain resembling a baseball catcher's mitt with heme clasped in the palm. The location of exposed hydrophobic residues and the results of mutational analysis place the dimer interface adjacent to the heme-binding pocket. Juxtaposed hydrophobic O
2
- and polar
l
-arginine–binding sites occupied by imidazole and aminoguanidine, respectively, provide a template for designing dual-function inhibitors and imply substrate-assisted catalysis.
Forward and Backward Propagation of Dendritic Impulses and Their Synaptic Control in Mitral Cells
Authors: Chen Wei R. , Midtgaard Jens , Shepherd Gordon M.
Published: July 2002

The site of impulse initiation is crucial for the integrative actions of mammalian central neurons, but this question is currently controversial. Some recent studies support classical evidence that the impulse always arises in the soma-axon hillock region, with back-propagation through excitable dendrites, whereas others indicate that the dendrites are sufficiently excitable to initiate impulses that propagate forward along the dendrite to the soma-axon hillock. This issue has been addressed in the olfactory mitral cell, in which excitatory synaptic input is restricted to the distal tuft of a single primary dendrite. In rat olfactory bulb slices, dual whole cell recordings were made at or near the soma and from distal sites on the primary dendrite. The results show that the impulse can be initiated in either the soma-axon hillock or in the distal primary dendrite, and that the initiation site is controlled physiologically by the excitatory synaptic inputs to the distal tuft and inhibitory synaptic inputs near the soma.
Functional Coherence of the Human Y Chromosome
Authors: Lahn Bruce T. , Page David C.
Published: July 2002

A systematic search of the nonrecombining region of the human Y chromosome (NRY) identified 12 novel genes or families, 10 with full-length complementary DNA sequences. All 12 genes, and six of eight NRY genes or families previously isolated by less systematic means, fell into two classes. Genes in the first group were expressed in many organs; these housekeeping genes have X homologs that escape X inactivation. The second group, consisting of Y-chromosomal gene families expressed specifically in testes, may account for infertility among men with Y deletions. The coherence of the NRY's gene content contrasts with the apparently haphazard content of most eukaryotic chromosomes.
Human Cancer Syndromes: Clues to the Origin and Nature of Cancer
Authors: Fearon Eric R.
Published: July 2002

More than 20 different hereditary cancer syndromes have now been defined and attributed to specific germline mutations in various inherited cancer genes. Collectively, the syndromes affect about 1 percent of cancer patients. An individual who carries a mutant allele of an inherited cancer gene has a variable risk of cancer that is influenced by the particular mutation, other cellular genes, and dietary, lifestyle, and environmental factors. Though hereditary cancer syndromes are rare, their study has provided powerful insights into more common forms of cancer. Somatic mutations in sporadic cancers frequently alter the inherited cancer genes, and the functions of cell signaling pathways have been illuminated by study of the affected genes. Further investigation of inherited mutations that affect susceptibility to cancer will aid efforts to effectively prevent, detect, and treat the disease.
A mRNA Signal for the Type III Secretion of Yop Proteins by
Yersinia enterocolitica
Authors: Anderson Deborah M. , Schneewind Olaf
Published: July 2002

Pathogenic
Yersinia
species have a specialized secretion system (type III) to target cytotoxic Yop proteins during infection. The signals of YopE and YopN sufficient for the secretion of translational reporter fusions were mapped to the first 15 codons. No common amino acid or peptide sequence could be identified among the secretion signals. Systematic mutagenesis of the secretion signal yielded mutants defective in Yop translation; however, no point mutants could be identified that specifically abolished secretion. Frameshift mutations that completely altered the peptide sequences of these signals also failed to prevent secretion. Thus, the signal that leads to the type III secretion of Yop proteins appears to be encoded in their messenger RNA rather than the peptide sequence.
Vigorous HIV-1-Specific CD4
+
T Cell Responses Associated with Control of Viremia
Authors: Rosenberg Eric S. , Billingsley James M. , Caliendo Angela M. , Boswell Steven L. , Sax Paul E. , Kalams Spyros A. , Walker Bruce D.
Published: July 2002

Virus-specific CD4
+
T helper lymphocytes are critical to the maintenance of effective immunity in a number of chronic viral infections, but are characteristically undetectable in chronic human immunodeficiency virus–type 1 (HIV-1) infection. In individuals who control viremia in the absence of antiviral therapy, polyclonal, persistent, and vigorous HIV-1–specific CD4
+
T cell proliferative responses were present, resulting in the elaboration of interferon-γ and antiviral β chemokines. In persons with chronic infection, HIV-1–specific proliferative responses to p24 were inversely related to viral load. Strong HIV-1–specific proliferative responses were also detected following treatment of acutely infected persons with potent antiviral therapy. The HIV-1–specific helper cells are likely to be important in immunotherapeutic interventions and vaccine development.
Crystal Structure of the Adenylyl Cyclase Activator G
s
α
Authors: Sunahara Roger K. , Tesmer John J. G. , Gilman Alfred G. , Sprang Stephen R.
Published: July 2002

The crystal structure of G
s
α
, the heterotrimeric G protein α subunit that stimulates adenylyl cyclase, was determined at 2.5 Å in a complex with guanosine 5′-
O
-(3-thiotriphosphate) (GTPγS). G
s
α
is the prototypic member of a family of GTP-binding proteins that regulate the activities of effectors in a hormone-dependent manner. Comparison of the structure of G
s
α
·GTPγS with that of G
i
α
·GTPγS suggests that their effector specificity is primarily dictated by the shape of the binding surface formed by the switch II helix and the α3-β5 loop, despite the high sequence homology of these elements. In contrast, sequence divergence explains the inability of regulators of G protein signaling to stimulate the GTPase activity of G
s
α
. The βγ binding surface of G
s
α
is largely conserved in sequence and structure to that of G
i
α
, whereas differences in the surface formed by the carboxyl-terminal helix and the α4-β6 loop may mediate receptor specificity.
Asymmetry of Chimpanzee Planum Temporale: Humanlike Pattern of Wernicke's Brain Language Area Homolog
Authors: Gannon Patrick J. , Holloway Ralph L. , Broadfield Douglas C. , Braun Allen R.
Published: July 2002

The anatomic pattern and left hemisphere size predominance of the planum temporale, a language area of the human brain, are also present in chimpanzees (
Pan troglodytes
). The left planum temporale was significantly larger in 94 percent (17 of 18) of chimpanzee brains examined. It is widely accepted that the planum temporale is a key component of Wernicke's receptive language area, which is also implicated in human communication-related disorders such as schizophrenia and in normal variations such as musical talent. However, anatomic hemispheric asymmetry of this cerebrocortical site is clearly not unique to humans, as is currently thought. The evolutionary origin of human language may have been founded on this basal anatomic substrate, which was already lateralized to the left hemisphere in the common ancestor of chimpanzees and humans 8 million years ago.
Stabilization of Dendritic Arbor Structure in Vivo by CaMKII
Authors: Wu Gang-Yi , Cline Hollis T.
Published: July 2002

Calcium-calmodulin–dependent protein kinase II (CaMKII) promotes the maturation of retinotectal glutamatergic synapses in
Xenopus
. Whether CaMKII activity also controls morphological maturation of optic tectal neurons was tested using in vivo time-lapse imaging of single neurons over periods of up to 5 days. Dendritic arbor elaboration slows with maturation, in correlation with the onset of CaMKII expression. Elevating CaMKII activity in young neurons by viral expression of constitutively active CaMKII slowed dendritic growth to a rate comparable to that of mature neurons. CaMKII overexpression stabilized dendritic structure in more mature neurons, whereas CaMKII inhibition increased their dendritic growth. Thus, endogenous CaMKII activity limits dendritic growth and stabilizes dendrites, and it may act as an activity-dependent mediator of neuronal maturation.
Frameshift Mutants of β Amyloid Precursor Protein and Ubiquitin-B in Alzheimer's and Down Patients
Authors: van Leeuwen Fred W. , de Kleijn Dominique P. V. , van den Hurk Helma H. , Neubauer Andrea , Sonnemans Marc A. F. , Sluijs Jacqueline A. , Köycü Soner , Ramdjielal Ravindra D. J. , Salehi Ahmad , Martens Gerard J. M. , Grosveld Frank G. , Burbach J. Peter H. , Hol Elly M.
Published: July 2002

The cerebral cortex of Alzheimer's and Down syndrome patients is characterized by the presence of protein deposits in neurofibrillary tangles, neuritic plaques, and neuropil threads. These structures were shown to contain forms of β amyloid precursor protein and ubiquitin-B that are aberrant (+1 proteins) in the carboxyl terminus. The +1 proteins were not found in young control patients, whereas the presence of ubiquitin-B
+1
in elderly control patients may indicate early stages of neurodegeneration. The two species of +1 proteins displayed cellular colocalization, suggesting a common origin, operating at the transcriptional level or by posttranscriptional editing of RNA. This type of transcript mutation is likely an important factor in the widely occurring nonfamilial early- and late-onset forms of Alzheimer's disease.
Postsynaptic Membrane Fusion and Long-Term Potentiation
Authors: Lledo Pierre-Marie , Zhang Xiangyang , Südhof Thomas C. , Malenka Robert C. , Nicoll Roger A.
Published: July 2002

The possibility that membrane fusion events in the postsynaptic cell may be required for the change in synaptic strength resulting from long-term potentiation (LTP) was examined. Introducing substances into the postsynaptic cell that block membrane fusion at a number of different steps reduced LTP. Introducing SNAP, a protein that promotes membrane fusion, into cells enhanced synaptic transmission, and this enhancement was significantly less when generated in synapses that expressed LTP. Thus, postsynaptic fusion events, which could be involved either in retrograde signaling or in regulating postsynaptic receptor function or both, contribute to LTP.
The Role of Visual Experience in the Development of Columns in Cat Visual Cortex
Authors: Crair Michael C. , Gillespie Deda C. , Stryker Michael P.
Published: July 2002

The role of experience in the development of the cerebral cortex has long been controversial. Patterned visual experience in the cat begins when the eyes open about a week after birth. Cortical maps for orientation and ocular dominance in the primary visual cortex of cats were found to be present by 2 weeks. Early pattern vision appeared unimportant because these cortical maps developed identically until nearly 3 weeks of age, whether or not the eyes were open. The naı̈ve maps were powerfully dominated by the contralateral eye, and experience was needed for responses to the other eye to become strong, a process unlikely to be strictly Hebbian. With continued visual deprivation, responses to both eyes deteriorated, with a time course parallel to the well-known critical period of cortical plasticity. The basic structure of cortical maps is therefore innate, but experience is essential for specific features of these maps, as well as for maintaining the responsiveness and selectivity of cortical neurons.
Structure of the Amino-Terminal Protein Interaction Domain of STAT-4
Authors: Vinkemeier Uwe , Moarefi Ismail , Darnell James E. , Kuriyan John
Published: July 2002

STATs (signal transducers and activators of transcription) are a family of transcription factors that are specifically activated to regulate gene transcription when cells encounter cytokines and growth factors. The crystal structure of an NH
2
-terminal conserved domain (N-domain) comprising the first 123 residues of STAT-4 was determined at 1.45 angstroms. The domain consists of eight helices that are assembled into a hook-like structure. The N-domain has been implicated in several protein-protein interactions affecting transcription, and it enables dimerized STAT molecules to polymerize and to bind DNA cooperatively. The structure shows that N-domains can interact through an extensive interface formed by polar interactions across one face of the hook. Mutagenesis of an invariant tryptophan residue at the heart of this interface abolished cooperative DNA binding by the full-length protein in vitro and reduced the transcriptional response after cytokine stimulation in vivo.
Changes in Auxin Response from Mutations in an
AUX/IAA
Gene
Authors: Rouse Dean , Mackay Pamela , Stirnberg Petra , Estelle Mark , Leyser Ottoline
Published: July 2002

Transcription of the
AUX/IAA
family of genes is rapidly induced by the plant hormone auxin, but evidence that
AUX/IAA
genes mediate further responses to auxin has been elusive. Changes in diverse auxin responses result from mutations in the
Arabidopsis AXR3
gene.
AXR3
was shown to be a member of the
AUX/IAA
family, providing direct evidence that
AUX/IAA
genes are central in auxin signaling. Molecular characterization of
axr3
gain-of-function and loss-of-function mutations established the functional importance of domains conserved among AUX/IAA proteins.
Muscle Regeneration by Bone Marrow-Derived Myogenic Progenitors
Authors: Ferrari Giuliana , Cusella– Gabriella , Angelis De , Coletta Marcello , Paolucci Egle , Stornaiuolo Anna , Cossu Giulio , Mavilio Fulvio
Published: July 2002

Growth and repair of skeletal muscle are normally mediated by the satellite cells that surround muscle fibers. In regenerating muscle, however, the number of myogenic precursors exceeds that of resident satellite cells, implying migration or recruitment of undifferentiated progenitors from other sources. Transplantation of genetically marked bone marrow into immunodeficient mice revealed that marrow-derived cells migrate into areas of induced muscle degeneration, undergo myogenic differentiation, and participate in the regeneration of the damaged fibers. Genetically modified, marrow-derived myogenic progenitors could potentially be used to target therapeutic genes to muscle tissue, providing an alternative strategy for treatment of muscular dystrophies.
Conservation of T Cell Receptor Conformation in Epidermal γδ Cells with Disrupted Primary V
γ
Gene Usage
Authors: Mallick-Wood Caroline A. , Lewis Julia M. , Richie Lauren I. , Owen Michael J. , Tigelaar Robert E. , Hayday Adrian C.
Published: July 2002

A feature that distinguishes γδ T cell subsets from most αβ T cells and B cells is the association of expression of single T cell receptor (TCR) γ and δ variable (V) region gene segments with specific anatomic sites. Mice lacking the TCR V
γ
5 chain normally expressed by most dendritic epidermal T cells were shown to retain a conformational determinant (idiotype) ordinarily expressed exclusively by such V
γ
5
+
cells. Conservation by shuffled γδ TCR chains of an idiotype associated with a specific anatomic site indicates that for TCRγδ, as for immunoglobulin, conformation is associated to a greater extent with the function or development of lymphocyte repertoires than is the use of particular gene segments.
Crystal Structure and Evolution of a Transfer RNA Splicing Enzyme
Authors: Li Hong , Trotta Christopher R. , Abelson John
Published: July 2002

The splicing of transfer RNA precursors is similar in Eucarya and Archaea. In both kingdoms an endonuclease recognizes the splice sites and releases the intron, but the mechanism of splice site recognition is different in each kingdom. The crystal structure of the endonuclease from the archaeon
Methanococcus jannaschii
was determined to a resolution of 2.3 angstroms. The structure indicates that the cleavage reaction is similar to that of ribonuclease A and the arrangement of the active sites is conserved between the archaeal and eucaryal enzymes. These results suggest an evolutionary pathway for splice site recognition.
Modular Organization of Cognitive Systems Masked by Interhemispheric Integration
Authors: Baynes Kathleen , Eliassen James C. , Lutsep Helmi L. , Gazzaniga Michael S.
Published: July 2002

After resection of the corpus callosum, V.J., a left-handed woman with left-hemisphere dominance for spoken language, demonstrated a dissociation between spoken and written language. In the key experiment, words flashed to V.J.'s dominant left hemisphere were easily spoken out loud, but could not be written. However, when the words were flashed to her right hemisphere, she could not speak them out loud, but could write them with her left hand. This marked dissociation supports the view that spoken and written language output can be controlled by independent hemispheres, even though before her hemispheric disconnection, they appeared as inseparable cognitive entities.
Distinct WNT Pathways Regulating AER Formation and Dorsoventral Polarity in the Chick Limb Bud
Authors: Kengaku Mineko , Capdevila Javier , Rodriguez-Esteban Concepción , De La Peña Jennifer , Johnson Randy L. , Belmonte Juan Carlos Izpisúa , Tabin Clifford J.
Published: July 2002

The apical ectodermal ridge (AER) is an essential structure for vertebrate limb development.
Wnt3a
is expressed during the induction of the chick AER, and misexpression of
Wnt3a
induces ectopic expression of AER-specific genes in the limb ectoderm. The genes β
-catenin
and
Lef1
can mimic the effect of
Wnt3a
, and blocking the intrinsic
Lef1
activity disrupts AER formation. Hence,
Wnt3a
functions in AER formation through the β-catenin/LEF1 pathway. In contrast, neither β
-catenin
nor
Lef1
affects the
Wnt7a
-regulated dorsoventral polarity of the limb. Thus, two related
Wnt
genes elicit distinct responses in the same tissues by using different intracellular pathways.
The Tetrameric Structure of a Glutamate Receptor Channel
Authors: Rosenmund Christian , Stern-Bach Yael , Stevens Charles F.
Published: July 2002

The subunit stoichiometry of several ligand-gated ion channel receptors is still unknown. A counting method was developed to determine the number of subunits in one family of brain glutamate receptors. Successful application of this method in an HEK cell line provides evidence that ionotropic glutamate receptors share a tetrameric structure with the voltage-gated potassium channels. The average conductance of these channels depends on how many subunits are occupied by an agonist.
Closing the Circadian Loop: CLOCK-Induced Transcription of Its Own Inhibitors
per
and
tim
Authors: Darlington Thomas K. , Wager-Smith Karen , Ceriani M. Fernanda , Staknis David , Gekakis Nicholas , Steeves Thomas D. L. , Weitz Charles J. , Takahashi Joseph S. , Kay Steve A.
Published: July 2002

The circadian oscillator generates a rhythmic output with a period of about 24 hours. Despite extensive studies in several model systems, the biochemical mode of action has not yet been demonstrated for any of its components. Here, the
Drosophila
CLOCK protein was shown to induce transcription of the circadian rhythm genes
period
and
timeless
. dCLOCK functioned as a heterodimer with a
Drosophila
homolog of BMAL1. These proteins acted through an E-box sequence in the
period
promoter. The
timeless
promoter contains an 18–base pair element encompassing an E-box, which was sufficient to confer dCLOCK responsiveness to a reporter gene. PERIOD and TIMELESS proteins blocked dCLOCK's ability to transactivate their promoters via the E-box. Thus, dCLOCK drives expression of
period
and
timeless,
which in turn inhibit dCLOCK's activity and close the circadian loop.
Inhibition of Cell Migration, Spreading, and Focal Adhesions by Tumor Suppressor PTEN
Authors: Tamura Masahito , Gu Jianguo , Matsumoto Kazue , Aota Shin-ichi , Parsons Ramon , Yamada Kenneth M.
Published: July 2002

The tumor suppressor PTEN is a phosphatase with sequence similarity to the cytoskeletal protein tensin. Here the cellular roles of PTEN were investigated. Overexpression of PTEN inhibited cell migration, whereas antisense PTEN enhanced migration. Integrin-mediated cell spreading and the formation of focal adhesions were down-regulated by wild-type PTEN but not by PTEN with an inactive phosphatase domain. PTEN interacted with the focal adhesion kinase FAK and reduced its tyrosine phosphorylation. Overexpression of FAK partially antagonized the effects of PTEN. Thus, PTEN phosphatase may function as a tumor suppressor by negatively regulating cell interactions with the extracellular matrix.
The NIMH Multisite HIV Prevention Trial: Reducing HIV Sexual Risk Behavior
Authors:   The National Institute of Mental Health (NIMH) Multisite HIV Prevention Trial Group*
Published: July 2002

The efficacy of a behavioral intervention to reduce human immunodeficiency virus (HIV) risk behaviors was tested in a randomized, controlled trial with three high-risk populations at 37 clinics from seven sites across the United States. Compared with the 1855 individuals in the control condition, the 1851 participants assigned to a small-group, seven-session HIV risk reduction program reported fewer unprotected sexual acts, had higher levels of condom use, and were more likely to use condoms consistently over a 12-month follow-up period. On the basis of clinical record review, no difference in overall sexually transmitted disease (STD) reinfection rate was found between intervention and control condition participants. However, among men recruited from STD clinics, those assigned to the intervention condition had a gonorrhea incidence rate one-half that of those in the control condition. Intervention condition participants also reported fewer STD symptoms over the 12-month follow-up period. Study outcomes suggest that behavioral interventions can reduce HIV-related sexual risk behavior among low-income women and men served in public health settings. Studies that test strategies for reducing sexual risk behavior over longer periods of time are needed, especially with populations that remain most vulnerable to HIV infection.
Corelease of Two Fast Neurotransmitters at a Central Synapse
Authors: Jonas Peter , Bischofberger Josef , Sandkühler Jürgen
Published: July 2002

It is widely accepted that individual neurons in the central nervous system release only a single fast transmitter. The possibility of corelease of fast neurotransmitters was examined by making paired recordings from synaptically connected neurons in spinal cord slices. Unitary inhibitory postsynaptic currents generated at interneuron-motoneuron synapses consisted of a strychnine-sensitive, glycine receptor–mediated component and a bicuculline-sensitive, γ-aminobutyric acid (GABA)
A
receptor–mediated component. These results indicate that spinal interneurons release both glycine and GABA to activate functionally distinct receptors in their postsynaptic target cells. A subset of miniature synaptic currents also showed both components, consistent with corelease from individual synaptic vesicles.
Distance Modulation of Neural Activity in the Visual Cortex
Authors: Dobbins Allan C. , Jeo Richard M. , Fiser József , Allman John M.
Published: July 2002

Humans use distance information to scale the size of objects. Earlier studies demonstrated changes in neural response as a function of gaze direction and gaze distance in the dorsal visual cortical pathway to parietal cortex. These findings have been interpreted as evidence of the parietal pathway's role in spatial representation. Here, distance-dependent changes in neural response were also found to be common in neurons in the ventral pathway leading to inferotemporal cortex of monkeys. This result implies that the information necessary for object and spatial scaling is common to all visual cortical areas.
Coupled Gating Between Individual Skeletal Muscle Ca
2+
Release Channels (Ryanodine Receptors)
Authors: Marx Steven O. , Ondrias Karol , Marks Andrew R.
Published: July 2002

Excitation-contraction coupling in skeletal muscle requires the release of intracellular calcium ions (Ca
2+
) through ryanodine receptor (RyR1) channels in the sarcoplasmic reticulum. Half of the RyR1 channels are activated by voltage-dependent Ca
2+
channels in the plasma membrane. In planar lipid bilayers, RyR1 channels exhibited simultaneous openings and closings, termed “coupled gating.” Addition of the channel accessory protein FKBP12 induced coupled gating, and removal of FKBP12 uncoupled channels. Coupled gating provides a mechanism by which RyR1 channels that are not associated with voltage-dependent Ca
2+
channels can be regulated.
Structure and Asn-Pro-Phe Binding Pocket of the Eps15 Homology Domain
Authors: de Beer Tonny , Carter Royston E. , Lobel-Rice Katherine E. , Sorkin Alexander , Overduin Michael
Published: July 2002

Eps15 homology (EH) domains are eukaryotic signaling modules that recognize proteins containing Asn-Pro-Phe (NPF) sequences. The structure of the central EH domain of Eps15 has been solved by heteronuclear magnetic resonance spectroscopy. The fold consists of a pair of EF hand motifs, the second of which binds tightly to calcium. The NPF peptide is bound in a hydrophobic pocket between two α helices, and binding is mediated by a critical aromatic interaction as revealed by structure-based mutagenesis. The fold is predicted to be highly conserved among 30 identified EH domains and provides a structural basis for defining EH-mediated events in protein trafficking and growth factor signaling.
Major Compositional Units of the Moon: Lunar Prospector Thermal and Fast Neutrons
Authors: Feldman W. C. , Barraclough B. L. , Maurice S. , Elphic R. C. , Lawrence D. J. , Thomsen D. R. , Binder A. B.
Published: July 2002

Global maps of thermal and fast neutron fluxes from the moon suggest three end-member compositional units. A high thermal and low fast neutron flux unit correlates with the lunar highlands and is consistent with feldspathic rocks. The South Pole–Aitken basin and a strip that surrounds the nearside maria have intermediate thermal and fast neutron flux levels, consistent with more mafic rocks. There appears to be a smooth transition between the most mafic and feldspathic compositions, which correspond to low and high surface altitudes, respectively. The maria show low thermal and high fast neutron fluxes, consistent with basaltic rocks.
CBP: A Signal-Regulated Transcriptional Coactivator Controlled by Nuclear Calcium and CaM Kinase IV
Authors: Chawla Sangeeta , Hardingham Giles E. , Quinn David R. , Bading Hilmar
Published: July 2002

Recruitment of the coactivator, CREB binding protein (CBP), by signal-regulated transcription factors, such as CREB [adenosine 3′,5′-monophosphate (cAMP) response element binding protein], is critical for stimulation of gene expression. The mouse pituitary cell line AtT20 was used to show that the CBP recruitment step (CREB phosphorylation on serine-133) can be uncoupled from CREB/CBP–activated transcription. CBP was found to contain a signal-regulated transcriptional activation domain that is controlled by nuclear calcium and calcium/calmodulin–dependent (CaM) protein kinase IV and by cAMP. Cytoplasmic calcium signals that stimulate the Ras mitogen–activated protein kinase signaling cascade or expression of the activated form of Ras provided the CBP recruitment signal but did not increase CBP activity and failed to activate CREB- and CBP-mediated transcription. These results identify CBP as a signal-regulated transcriptional coactivator and define a regulatory role for nuclear calcium and cAMP in CBP-dependent gene expression.