bluuebunny/crossref_metadata_2025 huggingface dataset:
Synchrotron X-Ray Study of Iron at High Pressure and Temperature
Authors: Saxena S. K. , Dubrovinsky L. S. , Häggkvist P. , Cerenius Y. , Shen G. , Mao H. K.
Published: October 2006

X-ray synchrotron experiments with in situ laser heating of iron in a diamond-anvil cell show that the high-pressure ε phase, a hexagonal close-packed (hcp) structure, transforms to another phase (possibly a polytype double-layer hcp) at a pressure of about 38 gigapascals and at temperatures between 1200 and 1500 kelvin. This information has implications for the phase relations of iron in Earth's core.
Anisotropy and Spiral Organizing Centers in Patterned Excitable Media
Authors: Steinbock Oliver , Kettunen Petteri , Showalter Kenneth
Published: October 2006

Chemical wave behavior in a patterned Belousov-Zhabotinsky system prepared by printing the catalyst of the reaction on membranes with an ink jet printer is described. Cellular inhomogeneities give rise to global anisotropy in wave propagation, with specific local patterns resulting in hexagonal, diamond, and pentagonal geometries. Spiral wave sources appear spontaneously and serve as organizing centers of the surrounding wave activity. The experimental methodology offers flexibility for studies of excitable media with made-to-order spatial inhomogeneities.
Discrete Cortical Regions Associated with Knowledge of Color and Knowledge of Action
Authors: Martin Alex , Haxby James V. , Lalonde François M. , Wiggs Cheri L. , Ungerleider Leslie G.
Published: October 2006

The areas of the brain that mediate knowledge about objects were investigated by measuring changes in regional cerebral blood flow (rCBF) using positron emission tomography (PET). Subjects generated words denoting colors and actions associated with static, achromatic line drawings of objects in one experiment, and with the written names of objects in a second experiment. In both studies, generation of color words selectively activated a region in the ventral temporal lobe just anterior to the area involved in the perception of color, whereas generation of action words activated a region in the middle temporal gyrus just anterior to the area involved in the perception of motion. These data suggest that object knowledge is organized as a distributed system in which the attributes of an object are stored close to the regions of the cortex that mediate perception of those attributes.
Introduction
Authors: Holden Constance
Published: October 2006

The U.S. science Ph.D. seems to have hit a wall—hard. After decades of expansion, the number of scientists seeking research grants and research jobs appears, in the eyes of many, to have outstripped the money available to supply them. Cell biologist Richard McIntosh, former president of the American Society for Cell Biology, has described the situation as a “Malthusian crisis.” This special issue of Science examines the many effects of this crisis, from calls for Ph.D. “population control” to changes in graduate programs to make their graduates more marketable in an uncertain future.
Grad Schools Preview the Shape of Ph.D.s to Come
Authors: Moffat Anne Simon
Published: October 2006

While policy-makers and educators are thinking hard about making a more marketable Ph.D., a few universities have actually taken steps to equip their students with a broader doctorate. Some of those steps are examined here, and a sidebar takes a peek at a new science master's program, tailored for industry employment.
New Mission for the National Labs
Authors: Weisman Jonathan
Published: October 2006

What will the nuclear weapons labs do for a living now that the Cold War is over? The Clinton Administration has put together a $3 billion “stockpile stewardship” program of physics and computer research, designed to keep the arsenal reliable and weapons-designing skills sharp. Science provides an in-depth look at what the plan involves and its potential payoff for basic researchers.
Coherent Laser Control of the Product Distribution Obtained in the Photoexcitation of HI
Authors: Zhu Langchi , Kleiman Valeria , Li Xiaonong , Lu Shao Ping , Trentelman Karen , Gordon Robert J.
Published: October 2006

Active control of the distribution of products of a chemical reaction was demonstrated by using a method based on the principle of quantum mechanical interference. Hydrogen iodide (HI) molecules were simultaneously excited above their ionization threshold by two competing pathways. These paths were absorption of three ultraviolet photons of frequency ω
1
and one vacuum ultraviolet photon of frequency ω
3
= 3ω
1
. The HI
+
and I
+
signals were modulated as the phase between the lasers was varied, with the HI
+
signal lagging by 150° ± 15°. A mechanism consisting of autoionization and predissociation is proposed.
Dephosphorylation of Cdk2 Thr
160
by the Cyclin-Dependent Kinase-Interacting Phosphatase KAP in the Absence of Cyclin
Authors: Poon Randy Y. C. , Hunter Tony
Published: October 2006

The activation of cyclin-dependent kinases (CDKs) requires the phosphorylation of a conserved threonine (Thr
160
in Cdk2) by CDK-activating kinase (CAK). Human KAP (also called Cdi1), a CDK-associated phosphatase, was shown to dephosphorylate Thr
160
in human Cdk2. KAP was unable to dephosphorylate Tyr
15
and only dephosphorylated Thr
160
in native monomeric Cdk2. The binding of cyclin A to Cdk2 inhibited the dephosphorylation of Thr
160
by KAP but did not preclude the binding of KAP to the cyclin A-Cdk2 complex. Moreover, the dephosphorylation of Thr
160
by KAP prevented Cdk2 kinase activity upon subsequent association with cyclin A. These results suggest that KAP binds to Cdk2 and dephosphorylates Thr
160
when the associated cyclin subunit is degraded or dissociates.
NIH Gears Up to Test a Hotly Disputed Theory
Authors: Marshall Eliot
Published: October 2006

Some physicians and patient advocates contend that many Lyme disease patients suffer a range of symptoms long after treatment. But most academic experts argue that there's little evidence for a chronic form of the disease. This debate, which has become rancorous at times, could be settled by a multimillion-dollar study about to be launched by the National Institutes of Health. But the study itself is also controversial.
Role of Transcriptional Activation of IκBα in Mediation of Immunosuppression by Glucocorticoids
Authors: Scheinman Robert I. , Cogswell Patricia C. , Lofquist Alan K. , Baldwin Albert S.
Published: October 2006

Glucocorticoids are potent immunosuppressive drugs, but their mechanism is poorly understood. Nuclear factor kappa B (NF-κB), a regulator of immune system and inflammation genes, may be a target for glucocorticoid-mediated immunosuppression. The activation of NF-κB involves the targeted degradation of its cytoplasmic inhibitor, IκBα, and the translocation of NF-κB to the nucleus. Here it is shown that the synthetic glucocorticoid dexamethasone induces the transcription of the IκBα gene, which results in an increased rate of IκBα protein synthesis. Stimulation by tumor necrosis factor causes the release of NF-κB from IκBα. However, in the presence of dexamethasone this newly released NF-κB quickly reassociates with newly synthesized IκBα, thus markedly reducing the amount of NF-κB that translocates to the nucleus. This decrease in nuclear NF-κB is predicted to markedly decrease cytokine secretion and thus effectively block the activation of the immune system.
Titins: Giant Proteins in Charge of Muscle Ultrastructure and Elasticity
Authors: Labeit Siegfried , Kolmerer Bernhard
Published: October 2006

In addition to thick and thin filaments, vertebrate striated muscle contains a third filament system formed by the giant protein titin. Single titin molecules extend from Z discs to M lines and are longer than 1 micrometer. The titin filament contributes to muscle assembly and resting tension, but more details are not known because of the large size of the protein. The complete complementary DNA sequence of human cardiac titin was determined. The 82-kilobase complementary DNA predicts a 3-megadalton protein composed of 244 copies of immunoglobulin and fibronectin type III (FN3) domains. The architecture of sequences in the A band region of titin suggests why thick filament structure is conserved among vertebrates. In the I band region, comparison of titin sequences from muscles of different passive tension identifies two elements that correlate with tissue stiffness. This suggests that titin may act as two springs in series. The differential expression of the springs provides a molecular explanation for the diversity of sarcomere length and resting tension in vertebrate striated muscles.
Attenuated
Shigella
as a DNA Delivery Vehicle for DNA-Mediated Immunization
Authors: Sizemore Donata R. , Branstrom Arthur A. , Sadoff Jerald C.
Published: October 2006

Direct inoculation of DNA, in the form of purified bacterial plasmids that are unable to replicate in mammalian cells but are able to direct cell synthesis of foreign proteins, is being explored as an approach to vaccine development. Here, a highly attenuated
Shigella
vector invaded mammalian cells and delivered such plasmids into the cytoplasm of cells, and subsequent production of functional foreign protein was measured. Because this
Shigella
vector was designed to deliver DNA to colonic mucosa, the method is a potential basis for oral and other mucosal DNA immunization and gene therapy strategies.
The Minimal Gene Complement of
Mycoplasma genitalium
Authors: Fraser Claire M. , Gocayne Jeannine D. , White Owen , Adams Mark D. , Clayton Rebecca A. , Fleischmann Robert D. , Bult Carol J. , Kerlavage Anthony R. , Sutton Granger , Kelley Jenny M. , Fritchman Janice L. , Weidman Janice F. , Small Keith V. , Sandusky Mina , Fuhrmann Joyce , Nguyen David , Utterback Teresa R. , Saudek Deborah M. , Phillips Cheryl A. , Merrick Joseph M. , Tomb Jean-Francois , Dougherty Brian A. , Bott Kenneth F. , Hu Ping-Chuan , Lucier Thomas S. , Peterson Scott N. , Smith Hamilton O. , Hutchison Clyde A. , Venter J. Craig
Published: October 2006

The complete nucleotide sequence (580,070 base pairs) of the
Mycoplasma genitalium
genome, the smallest known genome of any free-living organism, has been determined by whole-genome random sequencing and assembly. A total of only 470 predicted coding regions were identified that include genes required for DNA replication, transcription and translation, DNA repair, cellular transport, and energy metabolism. Comparison of this genome to that of
Haemophilus influenzae
suggests that differences in genome content are reflected as profound differences in physiology and metabolic capacity between these two organisms.
Life With 482 Genes
Authors: Goffeau André
Published: October 2006

A. Goffeau discusses the implications of the sequencing of the second complete genome—that of the small parasite
Mycoplasma genitalium
—by C. Fraser
et al.
, reported in this issue of
Science
. This technically impressive achievement now allows identification of minimal sets of genes necessary for various biological functions and comparisons to other complete genome sequences.
Cosmogenic Ages for Earthquake Recurrence Intervals and Debris Flow Fan Deposition, Owens Valley, California
Authors: Bierman Paul R. , Gillespie Alan R. , Caffee Marc W.
Published: October 2006

Model exposure ages (beryllium-10, aluminum-26) of boulders on an offset debris flow fan yield an earthquake recurrence interval between 5800 and 8000
10
Be:
26
Al years for a strand of the Owens Valley fault in California, which last ruptured in an earthquake of moment magnitude >7.5 in 1872. Cosmogenic age estimates for this and several nearby fan surfaces flanking the eastern Sierra Nevada are consistent with stratigraphic relations and suggest that these surfaces were abandoned after 1000, 8000, and 21,000
10
Be:
26
Al years ago. The wide scatter and nonconcordance of
10
Be:
26
Al ages on an older fan surface suggest that boulder erosion and lowering of the fan surface there have influenced apparent exposure ages.
Large Arctic Temperature Change at the Wisconsin-Holocene Glacial Transition
Authors: Cuffey Kurt M. , Clow Gary D. , Alley Richard B. , Stuiver Minze , Waddington Edwin D. , Saltus Richard W.
Published: October 2006

Analysis of borehole temperature and Greenland Ice Sheet Project II ice-core isotopic composition reveals that the warming from average glacial conditions to the Holocene in central Greenland was large, approximately 15°C. This is at least three times the coincident temperature change in the tropics and mid-latitudes. The coldest periods of the last glacial were probably 21°C colder than at present over the Greenland ice sheet.
T Lymphocyte-Directed Gene Therapy for ADA
−
SCID: Initial Trial Results After 4 Years
Authors: Blaese R. Michael , Culver Kenneth W. , Miller A. Dusty , Carter Charles S. , Fleisher Thomas , Clerici Mario , Shearer Gene , Chang Lauren , Chiang Yawen , Tolstoshev Paul , Greenblatt Jay J. , Rosenberg Steven A. , Klein Harvey , Berger Melvin , Mullen Craig A. , Ramsey W. Jay , Muul Linda , Morgan Richard A. , Anderson W. French
Published: October 2006

In 1990, a clinical trial was started using retroviral-mediated transfer of the adenosine deaminase (ADA) gene into the T cells of two children with severe combined immunodeficiency (ADA
−
SCID). The number of blood T cells normalized as did many cellular and humoral immune responses. Gene treatment ended after 2 years, but integrated vector and ADA gene expression in T cells persisted. Although many components remain to be perfected, it is concluded here that gene therapy can be a safe and effective addition to treatment for some patients with this severe immunodeficiency disease.
Physical Map and Organization of
Arabidopsis thaliana
Chromosome 4
Authors: Schmidt Renate , West Joanne , Love Karina , Lenehan Zoë , Lister Clare , Thompson Helen , Bouchez David , Dean Caroline
Published: October 2006

A physical map of
Arabidopsis thaliana
chromosome 4 was constructed in yeast artificial chromosome clones and used to analyze the organization of the chromosome. Mapping of the nucleolar organizing region and the centromere integrated the physical and cytogenetic maps. Detailed comparison of physical with genetic distances showed that the frequency of recombination varied substantially, with relative hot and cold spots occurring along the whole chromosome. Eight repeated DNA sequence families were found in a complex arrangement across the centromeric region and nowhere else on the chromosome.
Mechanisms for Lithium Insertion in Carbonaceous Materials
Authors: Dahn J. R. , Zheng Tao , Liu Yinghu , Xue J. S.
Published: October 2006

Lithium can be inserted reversibly within most carbonaceous materials. The physical mechanism for this insertion depends on the carbon type. Lithium intercalates in layered carbons such as graphite, and it adsorbs on the surfaces of single carbon layers in nongraphitizable hard carbons. Lithium also appears to reversibly bind near hydrogen atoms in carbonaceous materials containing substantial hydrogen, which are made by heating organic precursors to temperatures near 700°C. Each of these three classes of materials appears suitable for use in advanced lithium batteries.
Biostratigraphic and Geochronologic Constraints on Early Animal Evolution
Authors: Grotzinger John P. , Bowring Samuel A. , Saylor Beverly Z. , Kaufman Alan J.
Published: October 2006

Two distinct evolutionary pulses, represented by the Vendian Ediacaran fauna and Cambrian small shelly faunas, are generally thought to characterize the emergence of macroscopic animals at the end of Precambrian time. Biostratigraphic and uranium-lead zircon age data from Namibia indicate that most globally distributed Ediacaran fossils are no older than 549 million years old and some are as young as 543 million years old, essentially coincident with the Precambrian-Cambrian boundary. These data suggest that the most diverse assemblages of Ediacaran animals existed within 6 million years of the Precambrian-Cambrian boundary and that simple discoid animals may have appeared at least 50 million years earlier.
Nano-Elastohydrodynamics: Structure, Dynamics, and Flow in Nonuniform Lubricated Junctions
Authors: Gao Jianping , Luedtke W. D. , Lman Uzi
Published: October 2006

Structure, flow, and response characteristics of molecularly thin films of hexadecane, sheared by topographically nonuniform solid gold surfaces sliding at a relative velocity of 10 meters per second, were investigated with molecular dynamics simulations. The simulations reveal three characteristics: spatial and temporal variations in the density and pressure of the lubricant in the region confined by the approaching asperities, accompanied by asperity-induced molecular layering transitions that are reflected in oscillatory patterns in the friction force; asperity deformations and microstructural transformations mediated by the lubricant; and an onset of cavitated zones in the lubricant after the asperity-asperity collision process. The simulations extend micrometer-scale elastohydrodynamic investigations into the nanometer-scale regime and provide molecular-scale insights into the fundamental mechanisms of ultrathin film lubrication phenomena under extreme conditions.
Rapid Clay Mineral Formation in Amazon Delta Sediments: Reverse Weathering and Oceanic Elemental Cycles
Authors: Michalopoulos Panagiotis , Aller Robert C.
Published: October 2006

Formation of aluminosilicate minerals in marine sediments was proposed over 30 years ago as a potentially important control on the chemistry of the oceans. Until now, this reverse weathering process has been largely discounted because of insufficient direct evidence for its existence. Experiments with unaltered, anoxic, Amazon delta sediments showed that substantial quantities of K-Fe-Mg clay minerals precipitated on naturally occurring solid substrates over times of ∼12 to 36 months at ∼28°C. A range of pore-water, solute-flux, and solid-phase criteria indicates that comparable clay mineral precipitation processes occur throughout Amazon shelf sediments, contributing ≳3 percent of the weight of the deposits and consuming ∼10 percent of the global riverine K
+
flux.
Megascopic Multicellular Organisms from the 1700-Million-Year-Old Tuanshanzi Formation in the Jixian Area, North China
Authors: Shixing Zhu , Huineng Chen
Published: October 2006

Hundreds of specimens of megascopic carbonaceous fossils shaped like leaves have been found at the ∼1700-million-year-old Tuanshanzi Formation of the uppermost Paleoproterozoic Changcheng Group (1600 to 1850 million years old) in the Jixian area, north China. These leaflike fossils mostly resemble the
Longfengshania
; each consists of a blade (with spoonlike, lanceolate, or ribbonlike shapes) with a single stipe, a holdfast, or both. On the basis of their megascopic dimensions, preliminary differentiation of organs or tissues, and possible remains of multicellular structures, they are benthic, multicellular algal fossils similar to the longfengshanids. These fossils indicate that multicellular organisms originated at least 1700 million years ago.
A Methylnickel Intermediate in a Bimetallic Mechanism of Acetyl-Coenzyme A Synthesis by Anaerobic Bacteria
Authors: Kumar Manoj , Qiu Di , Spiro Thomas G. , Ragsdale Stephen W.
Published: October 2006

Resonance Raman (RR) spectroscopy was used to identify a methylnickel adduct (ν
Ni-C
= 422 wave numbers) of carbon monoxide dehydrogenase (CODH) from
Clostridium thermoaceticum
. Formed at a nickel/iron-sulfur cluster on CODH called center A, the methylnickel species is the precursor of the methyl group of acetyl-coenzyme A in an anaerobic pathway of carbon monoxide or carbon dioxide fixation. Rapid kinetic and RR studies demonstrated that methylation of nickel occurs by heterolysis of the methyl-cobalt bond (ν
Co-C
= 429 wave numbers) of a methylated corrinoid/iron-sulfur protein. In combination with the earlier finding of an iron-carbonyl adduct at center A, detection of the methylnickel intermediate establishes a bimetallic mechanism for acetyl-coenzyme A synthesis.
Muscular Dystrophies—Diseases of the Dystrophin-Glycoprotein Complex
Authors: Worton Ronald
Published: October 2006

Defects in the gene for the muscle protein dystrophin cause many cases of muscular dystrophy. Worton discusses three new papers, one in this issue of
Science
(Noguchi
et al
.,
p. 819
) and two in the November issue of
Nature Genetics
, which report that defects in the sarcoglycans, transmembrane glycoproteins that associate with dystrophin, underlie certain other types of muscular dystrophy.
Mutations in the Dystrophin-Associated Protein γ-Sarcoglycan in Chromosome 13 Muscular Dystrophy
Authors: Noguchi Satoru , McNally Elizabeth M. , Othmane Kamel Ben , Hagiwara Yasuko , Mizuno Yuji , Yoshida Mikiharu , Yamamoto Hideko , Bönnemann Carsten G. , Gussoni Emanuela , Denton Peter H. , Kyriakides Theodoros , Middleton Lefkos , Hentati Faycal , Hamida Mongi Ben , Nonaka Ikuya , Vance Jeffery M. , Kunkel Louis M. , Ozawa Eijiro
Published: October 2006

Severe childhood autosomal recessive muscular dystrophy (SCARMD) is a progressive muscle-wasting disorder common in North Africa that segregates with microsatellite markers at chromosome 13q12. Here, it is shown that a mutation in the gene encoding the 35-kilodalton dystrophin-associated glycoprotein, γ-sarcoglycan, is likely to be the primary genetic defect in this disorder. The human γ-sarcoglycan gene was mapped to chromosome 13q12, and deletions that alter its reading frame were identified in three families and one of four sporadic cases of SCARMD. These mutations not only affect γ-sarcoglycan but also disrupt the integrity of the entire sarcoglycan complex.
Elementary Computation of Object Approach by a Wide-Field Visual Neuron
Authors: Hatsopoulos Nicholas , Gabbiani Fabrizio , Laurent Gilles
Published: October 2006

An essential function of the brain is to detect threats, such as those posed by objects or predators on a collision course. A wide-field, movement-sensitive visual neuron in the brain of the locust was studied by presenting simulated approaching, receding, and translating objects. The neuron's responses could be described simply by multiplying the velocity of the image edge (
d
θ/
dt
) with an exponential function of the size of the object's image on the retina (
e
−αθ
). Because this product peaks before the image reaches its maximum size during approach, this neuron can anticipate collision. The neuron's activity peaks approximately when the approaching object reaches a certain angular size. Because this neuron receives distinct inputs about image size and velocity, the dendritic tree of a single neuron may function as a biophysical device that can carry out a multiplication of two independent input signals.
Urgently Needed: Policies on Access to Data by Erstwhile Collaborators
Authors: Mishkin Barbara
Published: October 2006

What happens when a research team splits up? A consideration of recent court cases and university policies suggests the need for federal regulatory standards that might help scientists avoid some conflicts relating to authorship or access to data.
A First-Order Phase Transition Induced by a Magnetic Field
Authors: Kuwahara H. , Tomioka Y. , Asamitsu A. , Moritomo Y. , Tokura Y.
Published: October 2006

An electronic (metal-to-insulator) phase transition of the first order, which can be caused by an external magnetic field, was discovered in Nd
1/2
Sr
1/2
MnO
3
. A clear hysteresis was observed during the increase and decrease of an external magnetic field at a fixed temperature. The hysteretic field region was observed to depend critically on temperature and to drastically expand with a decrease of temperature, perhaps as a result of suppression of the effect of thermal fluctuations on the first-order phase transition. Although it has seldom been observed, this is thought to be a generic feature of the first-order phase transition at low temperatures near 0 kelvin.
Supramolecular Second-Order Nonlinearity of Polymers with Orientationally Correlated Chromophores
Authors: Kauranen Martti , Verbiest Thierry , Boutton Carlo , Teerenstra M. N. , Clays Koen , Schouten A. J. , Nolte R. J. M. , Persoons André
Published: October 2006

Nonlinear optical chromophores can be organized as orientationally correlated side groups of polymers with a rigid backbone. In such an organization, each chromophore contributes coherently to the second-order nonlinear response of the polymer structure. A first hyperpolarizability exceeding 5000 × 10
−30
electrostatic units was measured for a poly(isocyanide) structure containing ∼100 chromophores by means of hyper-Rayleigh scattering. Electric field-induced second-harmonic generation measurements confirmed that the product of the permanent dipole moment and the first hyperpolarizability was enhanced for the polymer structure. These results provide guidelines for future efforts to optimize supramolecular structures for applications in second-order nonlinear optics.
Crystal Structure of the Biphenyl-Cleaving Extradiol Dioxygenase from a PCB-Degrading Pseudomonad
Authors: Han Seungil , Eltis Lindsay D. , Timmis Kenneth N. , Muchmore Steven W. , Bolin Jeffrey T.
Published: October 2006

Polychlorinated biphenyls (PCBs) typify a class of stable aromatic pollutants that are targeted by bioremediation strategies. In the aerobic degradation of biphenyl by bacteria, the key step of ring cleavage is catalyzed by an Fe(II)-dependent extradiol dioxygenase. The crystal structure of 2,3-dihydroxybiphenyl 1,2-dioxygenase from a PCB-degrading strain of
Pseudomonas cepacia
has been determined at 1.9 angstrom resolution. The monomer comprises amino- and carboxyl-terminal domains. Structural homology between and within the domains reveals evolutionary relationships within the extradiol dioxygenase family. The iron atom has five ligands in square pyramidal geometry: one glutamate and two histidine side chains, and two water molecules.
Asian Hominids Grow Older
Authors: Culotta Elizabeth
Published: October 2006

In the conventional view, the first hominid to leave Africa was
Homo erectus
who departed about 1 million years ago. But new evidence suggests that early
Homo reached
central China between 1.7 million and 1.9 million years ago—800,000 years earlier than previously thought—and that this ancient wayfarer was not
Homo erectus
itself but an even earlier hominid. If this controversial scenario is correct, it could mean that
Homo erectus
is an Asian side branch of the hominid evolutionary tree, rather than part of the African lineage that led to humans.
China's Unique Environment Favors Large Intervention Trials
Authors: Mervis Jeffrey
Published: October 2006

Beijing—With some of the highest rates of certain cancers and other diseases, and a compliant population with limited geographical mobility, China offers unparalleled opportunities for large-scale intervention trials. Several studies, some with international collaborators, are under way to try to reduce the incidence of diseases ranging from stomach cancer to neural tube defects.
Concerted Signaling by Retinal Ganglion Cells
Authors: Meister Markus , Lagnado Leon , Baylor Denis A.
Published: October 2006

To analyze the rules that govern communication between eye and brain, visual responses were recorded from an intact salamander retina. Parallel observation of many retinal ganglion cells with a microelectrode array showed that nearby neurons often fired synchronously, with spike delays of less than 10 milliseconds. The frequency of such synchronous spikes exceeded the correlation expected from a shared visual stimulus up to 20-fold. Synchronous firing persisted under a variety of visual stimuli and accounted for the majority of action potentials recorded. Analysis of receptive fields showed that concerted spikes encoded information not carried by individual cells; they may represent symbols in a multineuronal code for vision.
Requirement of
Saccharomyces cerevisiae
Ras for Completion of Mitosis
Authors: Morishita Takashi , Mitsuzawa Hiroshi , Nakafuku Masato , Nakamura Shun , Hattori Seisuke , Anraku Yasuhiro
Published: October 2006

In the yeast
Saccharomyces cerevisiae
, Ras regulates adenylate cyclase, which is essential for progression through the G
1
phase of the cell cycle. However, even when the adenosine 3′,5′-monophosphate (cAMP) pathway was bypassed, the double disruption of
RAS1
and
RAS2
resulted in defects in growth at both low and high temperatures. Furthermore, the simultaneous disruption of
RAS1
,
RAS2
, and the
RAS
-related gene
RSR1
was lethal at any temperature. The triple-disrupted cells were arrested late in the mitotic (M) phase, which was accompanied by an accumulation of cells with divided chromosomes and sustained histone H1 kinase activity. The lethality of the triple disruption was suppressed by the multicopies of
CDC5
,
CDC15
,
DBF2
,
SPO12
, and
TEM1
, all of which function in the completion of the M phase. Mammalian
ras
also suppressed the lethality, which suggests that a similar signaling pathway exists in higher eukaryotes. These results demonstrate that
S. cerevisiae
Ras functions in the completion of the M phase in a manner independent of the Ras-cAMP pathway.
Resistance to Radiation
Authors: Daly Michael J. , Minton Kenneth W.
Published: October 2006

The bacterium
Deinococcus radiodurans
can survive extremely large doses of radiation without mutagenesis. Daly and Minton suggest how this organism repairs its radiation-damaged DNA so efficiently and why such a system may have evolved.
Opposing Effects of ERK and JNK-p38 MAP Kinases on Apoptosis
Authors: Xia Zhengui , Dickens Martin , Raingeaud Joël , Davis Roger J. , Greenberg Michael E.
Published: October 2006

Apoptosis plays an important role during neuronal development, and defects in apoptosis may underlie various neurodegenerative disorders. To characterize molecular mechanisms that regulate neuronal apoptosis, the contributions to cell death of mitogen-activated protein (MAP) kinase family members, including ERK (extracellular signal-regulated kinase), JNK (c-JUN NH
2
-terminal protein kinase), and p38, were examined after withdrawal of nerve growth factor (NGF) from rat PC-12 pheochromocytoma cells. NGF withdrawal led to sustained activation of the JNK and p38 enzymes and inhibition of ERKs. The effects of dominant-interfering or constitutively activated forms of various components of the JNK-p38 and ERK signaling pathways demonstrated that activation of JNK and p38 and concurrent inhibition of ERK are critical for induction of apoptosis in these cells. Therefore, the dynamic balance between growth factor-activated ERK and stress-activated JNK-p38 pathways may be important in determining whether a cell survives or undergoes apoptosis.
Fission Track Evidence on the Initial Rifting of the Red Sea: Two Pulses, No Propagation
Authors: Omar Gomaa I. , Steckler Michael S.
Published: October 2006

Fission track analyses indicate that the Red Sea initially opened simultaneously along its entire length. Two distinct pulses of uplift and erosion characterized the early stages of rifting in the Red Sea throughout Egypt and in southwestern Saudi Arabia. The first pulse began at ∼34 million years ago (Ma). The second pulse began in the early Miocene (21 to 25 Ma) and marked the start of the main phase of extension. These data support a rigid plate model for continental extension. These results also indicate that the initiation of rift flank uplift, and therefore rifting, and volcanism occurred nearly simultaneously. This conflicts with classical models of active and passive extension that predict sequential development of these features.
Selective Opioid Inhibition of Small Nociceptive Neurons
Authors: Taddese Abraha , Nah Seung-Yeol , McCleskey Edwin W.
Published: October 2006

Opioid analgesia, the selective suppression of pain without effects on other sensations, also distinguishes between different types of pain: severe, persistent pain is potently inhibited by opioids, but they fail to conceal the sensation of a pinprick. The cellular basis for this specificity was analyzed by means of patch-clamp experiments performed on fluorescently labeled nociceptive neurons (nociceptors) that innervate rat tooth pulp. Activation of the μ opioid receptor inhibited calcium channels on almost all small nociceptors but had minimal effect on large nociceptors. Somatostatin had the opposite specificity, preferentially inhibiting calcium channels on the large cells. Because persistent pain is mediated by slow-conducting, small nociceptors, opioids are thus likely to inhibit neurotransmitter release only at those primary synapses specialized for persistent pain.
Regulated Expression of the Neural Cell Adhesion Molecule L1 by Specific Patterns of Neural Impulses
Authors: Itoh Kouichi , Stevens Beth , Schachner Melitta , Fields R. Douglas
Published: October 2006

Development of the mammalian nervous system is regulated by neural impulse activity, but the molecular mechanisms are not well understood. If cell recognition molecules [for example, L1 and the neural cell adhesion molecule (NCAM)] were influenced by specific patterns of impulse activity, cell-cell interactions controlling nervous system structure could be regulated by nervous system function at critical stages of development. Low-frequency electrical pulses delivered to mouse sensory neurons in culture (0.1 hertz for 5 days) down-regulated expression of L1 messenger RNA and protein (but not NCAM). Fasciculation of neurites, adhesion of neuroblastoma cells, and the number of Schwann cells on neurites was reduced after 0.1-hertz stimulation, but higher frequencies or stimulation after synaptogenesis were without effect.
Myths About Test Score Comparisons
Authors: Rotberg Iris C.
Published: October 2006

In recent years, expectations about what can be learned from testing students have become increasingly unrealistic. This paper discusses a set of myths that surround standardized testing. It concludes that test score comparisons are highly misleading indicators of the quality of education and are irrelevant to decisions about the wisdom of any particular school reform.
Crystal Structure of the Ternary Complex of Phe-tRNA
Phe
, EF-Tu, and a GTP Analog
Authors: Nissen Poul , Kjeldgaard Morten , Thirup Søren , Polekhina Galina , Reshetnikova Ludmila , Clark Brian F. C. , Nyborg Jens
Published: October 2006

The structure of the ternary complex consisting of yeast phenylalanyl-transfer RNA (Phe-tRNA
Phe
),
Thermus aquaticus
elongation factor Tu (EF-Tu), and the guanosine triphosphate (GTP) analog GDPNP was determined by x-ray crystallography at 2.7 angstrom resolution. The ternary complex participates in placing the amino acids in their correct order when messenger RNA is translated into a protein sequence on the ribosome. The EF-Tu-GDPNP component binds to one side of the acceptor helix of Phe-tRNA
Phe
involving all three domains of EF-Tu. Binding sites for the phenylalanylated CCA end and the phosphorylated 5′ end are located at domain interfaces, whereas the T stem interacts with the surface of the β-barrel domain 3. The binding involves many conserved residues in EF-Tu. The overall shape of the ternary complex is similar to that of the translocation factor, EF-G-GDP, and this suggests a novel mechanism involving "molecular mimicry" in the translational apparatus.
Solution Structure of the Activator Contact Domain of the RNA Polymerase α Subunit
Authors: Jeon Young Ho , Negishi Tomofumi , Shirakawa Masahiro , Yamazaki Toshio , Fujita Nobuyuki , Ishihama Akira , Kyogoku Yoshimasa
Published: October 2006

The structure of the carboxyl-terminal domain of the
Escherichia coli
RNA polymerase α subunit (αCTD), which is regarded as the contact site for transcription activator proteins and for the promoter UP element, was determined by nuclear magnetic resonance spectroscopy. Its compact structure of four helices and two long arms enclosing its hydrophobic core shows a folding topology distinct from those of other DNA-binding proteins. The UP element binding site was found on the surface comprising helix 1, the amino-terminal end of helix 4, and the preceding loop. Mutation experiments indicated that the contact sites for transcription activator proteins are also on the same surface.
Definition of Two Angiogenic Pathways by Distinct α
v
Integrins
Authors: Friedlander Martin , Brooks Peter C. , Shaffer Robert W. , Kincaid Christine M. , Varner Judith A. , Cheresh David A.
Published: October 2006

Angiogenesis depends on cytokines and vascular cell adhesion events. Two cytokine-dependent pathways of angiogenesis were shown to exist and were defined by their dependency on distinct vascular cell integrins. In vivo angiogenesis in corneal or chorioallantoic membrane models induced by basic fibroblast growth factor or by tumor necrosis factor-α depended on α
v
β
3
, whereas angiogenesis initiated by vascular endothelial growth factor, transforming growth factor-α, or phorbol ester depended on α
v
β
5
. Antibody to each integrin selectively blocked one of these pathways, and a cyclic peptide antagonist of both integrins blocked angiogenesis stimulated by each cytokine tested. These pathways are further distinguished by their sensitivity to calphostin C, an inhibitor of protein kinase C that blocked angiogenesis potentiated by α
v
β
5
but not by α
v
β
3
.
Gametic Imprinting in Mammals
Authors: Barlow Denise P.
Published: October 2006

Embryonic development in mammals is distinct from that in other vertebrates because it depends on a small number of imprinted genes that are specifically expressed from either the maternal or paternal genome. Why mammals are uniquely dependent on sexual reproduction and how this dependency is dictated at a molecular level are questions that have been intensively investigated during the past 2 years. Gene inactivation experiments have confirmed predictions that imprinted genes regulate embryonic and placental growth and that DNA methylation is part of the imprinting mechanism. Despite these considerable achievements, the reason why imprinted hemizygosity is used as a mechanism to regulate the intrauterine growth of mammalian embryos remains elusive.
Device Fabrication by Scanned Probe Oxidation
Authors: Dagata John A.
Published: October 2006

Precision Engineering Division, National Institute of Standards and Technology, Gaithersburg, MD 20899, USA. E-mail:
john.dagata@nist.gov
Imaging by scanning a tiny probe across a surface is a well-established technique for nanometer microscopy; now researchers are using these probes to manipulate matter and create small structures. In his Perspective, Dagata describes “an important milestone” reported in the same issue by Snow and Campbell (
p. 1639
), in which small oxidized structures were created with a scanning probe microscope.
Minimization of a Polypeptide Hormone
Authors: Li Bing , Tom Jeff Y. K. , Oare David , Yen Randy , Fairbrother Wayne J. , Wells James A. , Cunningham Brian C.
Published: October 2006

A stepwise approach for reducing the size of a polypeptide hormone, atrial natriuretic peptide (ANP), from 28 residues to 15 while retaining high biopotency is described. Systematic structural and functional analysis identified a discontinuous functional epitope for receptor binding and activation, most of which was placed onto a smaller ring (Cys
6
to Cys
17
) that was created by repositioning the ANP native disulfide bond (Cys
7
to Cys
23
). High affinity was subsequently restored by optimizing the remaining noncritical residues by means of phage display. Residues that flanked the mini-ring structure were then deleted in stages, and affinity losses were rectified by additional phage-sorting experiments. Thus, structural and functional data on hormones, coupled with phage display methods, can be used to shrink the hormones to moieties more amenable to small-molecule design.
Sodium-Driven Potassium Uptake by the Plant Potassium Transporter HKT1 and Mutations Conferring Salt Tolerance
Authors: Rubio Francisco , Gassmann Walter , Schroeder Julian I.
Published: October 2006

Sodium (Na
+
) at high millimolar concentrations in soils is toxic to most higher plants and severely reduces agricultural production worldwide. However, the molecular mechanisms for plant Na
+
uptake remain unknown. Here, the wheat root high-affinity potassium (K
+
) uptake transporter HKT1 was shown to function as a high-affinity K
+
-Na
+
cotransporter. High-affinity K
+
uptake was activated by micromolar Na
+
concentrations; moreover, high-affinity Na
+
uptake was activated by K
+
(half-activation constant, 2.8 μM K
+
). However, at physiologically detrimental concentrations of Na
+
, K
+
accumulation mediated by HKT1 was blocked and low-affinity Na
+
uptake occurred (Michaelis constant, ∼16 mM Na
+
), which correlated to Na
+
toxicity in plants. Point mutations in the sixth putative transmembrane domain of HKT1 that increase Na
+
tolerance were isolated with the use of yeast as a screening system. Na
+
uptake and Na
+
inhibition of K
+
accumulation indicate a possible role for HKT1 in physiological Na
+
toxicity in plants.
A Human Telomeric Protein
Authors: Chong Laura , van Steensel Bas , Broccoli Dominique , Erdjument-Bromage Hediye , Hanish John , Tempst Paul , de Lange Titia
Published: October 2006

Telomeres are multifunctional elements that shield chromosome ends from degradation and end-to-end fusions, prevent activation of DNA damage checkpoints, and modulate the maintenance of telomeric DNA by telomerase. A major protein component of human telomeres has been identified and cloned. This factor, TRF, contains one Myb-type DNA-binding repeat and an amino-terminal acidic domain. Immunofluorescent labeling shows that TRF specifically colocalizes with telomeric DNA in human interphase cells and is located at chromosome ends during metaphase. The presence of TRF along the telomeric TTAGGG repeat array demonstrates that human telomeres form a specialized nucleoprotein complex.
Early-Onset Epilepsy and Postnatal Lethality Associated with an Editing-Deficient
GluR-B
Allele in Mice
Authors: Brusa Rossella , Zimmermann Frank , Koh Duk-Su , Feldmeyer Dirk , Gass Peter , Seeburg Peter H. , Sprengel Rolf
Published: October 2006

The arginine residue at position 586 of the GluR-B subunit renders heteromeric α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-sensitive glutamate receptor channels impermeable to calcium. The codon for this arginine is introduced at the precursor messenger RNA (pre-mRNA) stage by site-selective adenosine editing of a glutamine codon. Heterozygous mice engineered by gene targeting to harbor an editing-incompetent
GluR-B
allele synthesized unedited GluR-B subunits and, in principal neurons and interneurons, expressed AMPA receptors with increased calcium permeability. These mice developed seizures and died by 3 weeks of age, showing that GluR-B pre-mRNA editing is essential for brain function.
Pineal Serotonin
N
-Acetyltransferase: Expression Cloning and Molecular Analysis
Authors: Coon Steven L. , Roseboom Patrick H. , Baler Ruben , Weller Joan L. , Namboodiri M. A. A. , Koonin Eugene V. , Klein David C.
Published: October 2006

Pineal serotonin
N
-acetyltransferase (arylalkylamine
N
-acetyltransferase, or AA-NAT) generates the large circadian rhythm in melatonin, the hormone that coordinates daily and seasonal physiology in some mammals. Complementary DNA encoding ovine AA-NAT was cloned. The abundance of AA-NAT messenger RNA (mRNA) during the day was high in the ovine pineal gland and somewhat lower in retina. AA-NAT mRNA was found unexpectedly in the pituitary gland and in some brain regions. The night-to-day ratio of ovine pineal AA-NAT mRNA is less than 2. In contrast, the ratio exceeds 150 in rats. AA-NAT represents a family within a large superfamily of acetyltransferases.
Solution-Liquid-Solid Growth of Crystalline III-V Semiconductors: An Analogy to Vapor-Liquid-Solid Growth
Authors: Trentler Timothy J. , Hickman Kathleen M. , Goel Subhash C. , Viano Ann M. , Gibbons Patrick C. , Buhro William E.
Published: October 2006

Until now, micrometer-scale or larger crystals of the III-V semiconductors have not been grown at low temperatures for lack of suitable crystallization mechanisms for highly covalent nonmolecular solids. A solution-liquid-solid mechanism for the growth of InP, InAs, and GaAs is described that uses simple, low-temperature (≤203°C), solution-phase reactions. The materials are produced as polycrystalline fibers or near-single-crystal whiskers having widths of 10 to 150 nanometers and lengths of up to several micrometers. This mechanism shows that processes analogous to vapor-liquid-solid growth can operate at low temperatures; similar synthesis routes for other covalent solids may be possible.
Ethylene-Binding Sites Generated in Yeast Expressing the
Arabidopsis ETR1
Gene
Authors: Schaller G. Eric , Bleecker Anthony B.
Published: October 2006

Mutations in the
ETR1
gene of
Arabidopsis thaliana
confer insensitivity to ethylene, which indicates a role for the gene product in ethylene signal transduction. Saturable binding sites for [
14
C]ethylene were detected in transgenic yeast expressing the ETR1 protein, whereas control yeast lacking ETR1 showed no detectable ethylene binding. Yeast expressing a mutant form of ETR1 (
etr1-1
) also showed no detectable ethylene binding, which provides an explanation for the ethylene-insensitive phenotype observed in plants carrying this mutation. Expression of truncated forms of ETR1 in yeast provided evidence that the amino-terminal hydrophobic domain of the protein is the site of ethylene binding. It was concluded from these results that ETR1 acts as an ethylene receptor in
Arabidopsis
.
Identification of RANTES, MIP-1α, and MIP-1β as the Major HIV-Suppressive Factors Produced by CD8
+
T Cells
Authors: Cocchi Fiorenza , DeVico Anthony L. , Garzino-Demo Alfredo , Arya Suresh K. , Gallo Robert C. , Lusso Paolo
Published: October 2006

Evidence suggests that CD8
+
T lymphocytes are involved in the control of human immunodeficiency virus (HIV) infection in vivo, either by cytolytic mechanisms or by the release of HIV-suppressive factors (HIV-SF). The chemokines RANTES, MIP-1α, and MIP-1β were identified as the major HIV-SF produced by CD8
+
T cells. Two active proteins purified from the culture supernatant of an immortalized CD8
+
T cell clone revealed sequence identity with human RANTES and MIP-1α. RANTES, MIP-1α, and MIP-1β were released by both immortalized and primary CD8
+
T cells. HIV-SF activity produced by these cells was completely blocked by a combination of neutralizing antibodies against RANTES, MIP-1α, and MIP-1β. Recombinant human RANTES, MIP-1α, and MIP-1β induced a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). These data may have relevance for the prevention and therapy of AIDS.
DNA Template and Activator-Coactivator Requirements for Transcriptional Synergism by
Drosophila
Bicoid
Authors: Sauer Frank , Hansen Stig K. , Tjian Robert
Published: October 2006

The template and coactivator requirements for synergistic transcription directed by a single activator, Bicoid (BCD), bound to multiple sites have been determined. Mutagenesis studies in combination with protein binding experiments and reconstituted transcription reactions identified two independent activation domains of BCD that target different coactivator subunits (TAF
II
110 and TAF
II
60) of the basal transcription factor IID (TFIID). The presence of both coactivators is required for BCD to recruit the TATA binding protein (TBP)-TAF complex to the promoter and direct synergistic activation of transcription. Thus, contact between multiple activation domains of BCD and different targets within the TFIID complex can mediate transcriptional synergism.