bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Postreplicative DNA Mismatch Repair in the Cytotoxic Action of Thioguanine
Authors: Swann Peter F. , Waters Timothy R. , Moulton David C. , Xu Yao-Zhong , Zheng Qinguo , Edwards Mina , Mace Raymond
Published: October 2006

It is proposed here that the delayed cytotoxicity of thioguanine involves the postreplicative DNA mismatch repair system. After incorporation into DNA, the thioguanine is chemically methylated by
S
-adenosylmethionine to form
S
6
-methylthioguanine. During DNA replication, the
S
6
-methylthioguanine directs incorporation of either thymine or cytosine into the growing DNA strand, and the resultant
S
6
-methylthioguanine-thymine pairs are recognized by the postreplicative mismatch repair system. Azathioprine, an immunosuppressant used in organ transplantation, is partly converted to thioguanine. Because the carcinogenicity of
N
-nitrosamines depends on formation of
O
6
-alkylguanine in DNA, the formation of the analog
S
6
-methylthioguanine during azathioprine treatment may partly explain the high incidence of cancer after transplantation.
Web Pits One Against the World
Authors: Seife Charles
Published: October 2006

On 26 August, chess champion Anatoli Karpov used the World Wide Web to take on everybody in the world—and drubbed all comers. Karpov's opponents on the Web played one game collectively, with a computer in Finland tallying their votes to choose each move. Karpov isn't the only champion playing techno-chess; Garry Kasparov, his longtime rival, is gearing up for a rematch with IBM's Deep Blue, the world's most capable chess computer, which he defeated early this year. Computers/Math
New Electron Emitters May Slim Down Computer Displays
Authors: Hellemans Alexander
Published: October 2006

Eindhoven, the Netherlands—Behind every desktop computer screen sits a chunky descendant of the first electronic devices ever made, the cathode ray tubes (CRTs). These tubes work well by firing a beam of electrons across a vacuum at the screen, but they're too big for many applications. So researchers are experimenting with small electron-emitting devices suited for flat-panel displays like those in laptop computers. The devices still have drawbacks, but new materials and fabrication methods are brightening the prospects for flat-panel CRTs.
Crystallographers Pinpoint What Goes Where
Authors: Service Robert F.
Published: October 2006

Seattle—In structural biology, as in real estate, location is key. And by tracking x-rays or other high-energy sources as they scatter off crystallized biomolecules, crystallographers can pinpoint locations of structures that perform crucial biological functions. At the International Union of Crystallography XVII Congress and General Assembly, held 8 to 17 August, researchers using the technique reported insights into how antibodies bind to cold viruses, why the AIDS drug AZT is not terribly effective, how a protein in the cellular “power plant” harnesses energy, and a frightening microbial weapon, among other topics.
Forskolin Stimulation of Water and Cation Permeability in Aquaporin1 Water Channels
Authors: Yool Andrea J. , Stamer W. Daniel , Regan John W.
Published: October 2006

Aquaporin1, a six-transmembrane domain protein, is a water channel present in many fluid-secreting and -absorbing cells. In
Xenopus
oocytes injected with aquaporin1 complementary RNA, the application of forskolin or cyclic 8-bromo- adenosine 3′,5′-monophosphate increased membrane permeability to water and triggered a cationic conductance. The cationic conductance was also induced by direct injection of protein kinase A (PKA) catalytic subunit, reduced by the kinase inhibitor H7, and blocked by HgCl
2
, an inhibitor of aquaporin1. The cationic permeability of the aquaporin1 channel is activated by a cyclic adenosine monophosphate-dependent mechanism that may involve direct or indirect phosphorylation by PKA.
New Source Proposed for Most Common Meteorites
Authors: Kerr Richard A.
Published: October 2006

Where do meteorites come from? For years, planetary scientists have puzzled over this problem, for almost no known asteroids matched the composition of the most common rocky meteorites, the ordinary chondrites. Now new analyses of the color (and therefore the composition) of the asteroid Hebe suggest that this single body may contribute up to half the known chondrites.
Probing Flowers' Genetic Past
Authors: Roush Wade
Published: October 2006

The discovery of a gene that controls both ovule development and the timing of flower formation in the plant
Arabidopsis thaliana
may provide a genetic clue to the origins and evolution of flowering plants.
Coherent Exciton Waves
Authors: Snoke D.
Published: October 2006

Excitons are electrically neutral energetic pairs of electrons and holes, created by the absorption of photons in a solid. These energy-carrying pairs can be used to produce light for microscopes and are used by plants to collect sunlight for photosynthesis. In his Perspective, Snoke describes work carried out at Ecolé Polytechnique in Palaiseau, France, and the University of Ottawa, Canada, in which excitons were produced by stimulated emission. Such processes may someday be used to create a laserlike source of excitons.
Airborne Particle Analysis for Climate Studies
Authors: Peter T.
Published: October 2006

Particles in the atmosphere greatly affect climate change and cause health problems and difficulties for high technology manufacturing. In his Perspective, Peter describes a new method for particulate measurements developed by Noble and Prather and reported in
Environmental Science and Technology
. The method allows in situ mass spectrometer studies of individual particles sampled from the atmosphere.
Senate Backs NASA Science Programs
Authors: Lawler Andrew
Published: October 2006

NASA scored three victories last week when the Senate preserved a controversial life sciences program involving orbiting monkeys, rejected a move to cancel the space station program, and protected a major earth sciences program from major cuts. But controversies over social programs, which are included in the appropriations bill that funds NASA, could make it hard for Congress and President Bill Clinton to reach agreement before the new fiscal year begins on 1 October.
New Mammals Discovered by Biology's New Explorers
Authors: Morell Virginia
Published: October 2006

Because humans are mammals, this group is among the best known of all organisms. Yet in the last decade, partly because of a new round of exploratory field surveys, scientists have turned up a surprising variety of new mammals around the world, including primates, deer, ox, and many rodents. When all these new creatures are officially named, the number of known mammals may jump by up to 15%.
Glimpsing Myelin's Protein Glue
Authors: Barinaga Marcia
Published: October 2006

The rapid transmission of nerve signals in higher animals would not be possible if thenerves didn't have their insulating covering of myelin. Now determination of the structure of a key myelin protein, called P
0
, has helped explain how the tightly wrapped membranous layers that form the myelin are held together and also how some mutations weaken the glue, leading to neurological disease.
Budgets Stall But Forecasts Jump Forward
Authors: Kerr Richard A.
Published: October 2006

Anxious farmers and sodden picnickers may not believe it, but weather forecasts are actually getting better. Official U.S. daily forecasts reach only 5 days ahead, but meteorologists are now capable of making useful forecasts a week ahead of time. The National Weather Service plans to put the longer forecasts into practice in 1997, but its plans are being hampered by budget and personnel cuts.
A K
+
Channel Worthy of Attention
Authors: Hille Bertil
Published: October 2006

A new family of K
+
channels has been defined in a paper in this week's issue [see Köhler
et al
. (
p. 1709
)], reporting the cloning of three members. The Perspective by Hille explains why this class of channels may underlie the control of attention in the brain by the neurotransmitter norepinephrine.
Whose Genome Is It, Anyway?
Authors: Marshall Eliot
Published: October 2006

The Human Genome Project has issued guidelines to ensure that sequencing is done on DNA from diverse sources who have given informed consent and are anonymous. Most current sources don't meet those criteria, however. The DNA of major clone libraries now being fed into high-volume robotized labs appears to come primarily from four subjects, two of whommay not have been informed in advance that their genome would become part of a public database. Worse, not all the donors appear to be anonymous: Sequencers in U.S. labs say theyknow the names of two of them, because they are colleagues.
A Trinuclear Intermediate in the Copper-Mediated Reduction of O
2
: Four Electrons from Three Coppers
Authors: Cole Adam P. , Root David E. , Mukherjee Pulakesh , Solomon Edward I. , Stack T. D. P.
Published: October 2006

The reaction of metal complexes with dioxygen (O
2
) generally proceeds in 1:1, 2:1, or 4:1 (metal:O
2
) stoichiometry. A discrete, structurally characterized 3:1 product is presented. This mixed-valence trinuclear copper cluster, which contains copper in the highly oxidized trivalent oxidation state, exhibits O
2
bond scission and intriguing structural, spectroscopic, and redox properties. The relevance of this synthetic complex to the reduction of O
2
at the trinuclear active sites of multicopper oxidases is discussed.
Conformational States of the Nuclear Pore Complex Induced by Depletion of Nuclear Ca
2+
Stores
Authors: Perez-Terzic Carmen , Pyle Jason , Jaconi Marisa , Stehno-Bittel Lisa , Clapham David E.
Published: October 2006

The nuclear pore complex (NPC) is essential for the transit of molecules between the cytoplasm and nucleoplasm of a cell and until recently was thought to allow intermediate-sized molecules (relative molecular mass of ∼10,000) to diffuse freely across the nuclear envelope. However, the depletion of calcium from the nuclear envelope of
Xenopus laevis
oocytes was shown to regulate the passage of intermediate-sized molecules. Two distinct conformational states of the NPC were observed by field emission scanning electron microscopy and atomic force microscopy. A central plug occluded the NPC channel after nuclear calcium stores had been depleted and free diffusion of intermediate-sized molecules had been blocked. Thus, the NPC conformation appears to gate molecular movement across the nuclear envelope.
PTB Domain Binding to Signaling Proteins Through a Sequence Motif Containing Phosphotyrosine
Authors: Kavanaugh W. Michael , Turck Christoph W. , Williams Lewis T.
Published: October 2006

Src homology 2 (SH2) domains mediate assembly of signaling complexes by binding specifically to tyrosine-phosphorylated proteins. A phosphotyrosine binding (PTB) domain has been identified which also binds specifically to tyrosine-phosphorylated targets, but is structurally different from SH2 domains. Expression cloning was used to identify targets of PTB domains. PTB domains bound to phosphotyrosine within a sequence motif, asparagine- X
1
- X
2
-phosphotyrosine (where X represents any amino acid), that is found in many signaling proteins and is not recognized by SH2 domains. Mutational studies indicated that high affinity binding of PTB domains may require a specific conformation of the motif.
Vitamin K and Energy Transduction: A Base Strength Amplification Mechanism
Authors: Dowd Paul , Hershline Roger , Ham Seung Wook , Naganathan Sriram
Published: October 2006

Energy transfer provides an arrow in the metabolism of living systems. Direct energetic coupling of chemical transformations, such that the free energy generated in one reaction is channeled to another, is the essence of energy transfer, whereas the purpose is the production of high-energy chemical intermediates. Vitamin K provides a particularly instructive example of energy transfer. A key principle at work in the vitamin K system can be termed "base strength amplification." In the base strength amplification sequence, the free energy of oxygenation of vitamin K hydroquinone (vitamin KH2) is used to transform a weak base to a strong base in order to effect proton removal from selected glutamate (Glu) residues in the blood-clotting proteins.
Condensation of Methane, Ammonia, and Water and the Inhibition of Convection in Giant Planets
Authors: Guillot Tristan
Published: October 2006

The condensation of chemical species of high molecular mass such as methane, ammonia, and water can inhibit convection in the hydrogen-helium atmospheres of the giant planets. Convection is inhibited in Uranus and Neptune when methane reaches an abundance of about 15 times the solar value and in Jupiter and Saturn if the abundance of water is more than about five times the solar value. The temperature gradient consequently becomes superadiabatic, which is observed in temperature profiles inferred from radio-occultation measurements. The planetary heat flux is then likely to be transported by another mechanism, possibly radiation in Uranus, or diffusive convection.
Modulation of Transcription Factor Ets-1 DNA Binding: DNA-Induced Unfolding of an α Helix
Authors: Petersen Jeannine M. , Skalicky Jack J. , Donaldson Logan W. , McIntosh Lawrence P. , Alber Tom , Graves Barbara J.
Published: October 2006

Conformational changes, including local protein folding, play important roles in protein-DNA interactions. Here, studies of the transcription factor Ets-1 provided evidence that local protein unfolding also can accompany DNA binding. Circular dichroism and partial proteolysis showed that the secondary structure of the Ets-1 DNA-binding domain is unchanged in the presence of DNA. In contrast, DNA allosterically induced the unfolding of an α helix that lies within a flanking region involved in the negative regulation of DNA binding. These findings suggest a structural basis for the intramolecular inhibition of DNA binding and a mechanism for the cooperative partnerships that are common features of many eukaryotic transcription factors.
FFA-1, a Protein That Promotes the Formation of Replication Centers Within Nuclei
Authors: Yan Hong , Newport John
Published: October 2006

In the nuclei of eukaryotic cells, initiation of DNA replication occurs at a discrete number of foci. One component of these foci is the DNA replication factor RP-A. Here, the process leading to the association of RP-A with foci was reconstituted with cytosolic fractions derived from
Xenopus
eggs. With the use of this fractionated system, a 170-kilodalton protein required for the assembly of RP-A into foci was identified and purified. The protein appears to be an integral component of the foci at which replication of DNA is initiated in eukaryotic nuclei.
Interaction of a Peptidomimetic Aminimide Inhibitor with Elastase
Authors: Peisach Ezra , Casebier David , Gallion Steven L. , Furth Paul , Petsko Gregory A. , Hogan Joseph C. , Ringe Dagmar
Published: October 2006

The crystal structure of an aminimide analog of a dipeptide inhibitor of porcine pancreatic elastase bound to its target serine protease has been solved. The peptidomimetic molecule binds in the same fashion as the class of dipeptides from which it was derived, making similar interactions with the subsites on the elastase surface. Because aminimides are readily synthesized from a wide variety of starting materials, they form the basis for a combinatorial chemistry approach to rational drug design.
Integration of MAP Kinase Signal Transduction Pathways at the Serum Response Element
Authors: Whitmarsh Alan J. , Shore Paul , Sharrocks Andrew D. , Davis Roger J.
Published: October 2006

The ternary complex factor (TCF) subfamily of ETS-domain transcription factors bind with serum response factor (SRF) to the serum response element (SRE) and mediate increased gene expression. The TCF protein Elk-1 is phosphorylated by the JNK and ERK groups of mitogen-activated protein (MAP) kinases causing increased DNA binding, ternary complex formation, and transcriptional activation. Activated SRE-dependent gene expression is induced by JNK in cells treated with interleukin-1 and by ERK after treatment with phorbol ester. The Elk-1 transcription factor therefore integrates MAP kinase signaling pathways in vivo to coordinate biological responses to different extracellular stimuli.
Weight-Reducing Effects of the Plasma Protein Encoded by the
obese
Gene
Authors: Halaas Jeffrey L. , Gajiwala Ketan S. , Maffei Margherita , Cohen Steven L. , Chait Brian T. , Rabinowitz Daniel , Lallone Roger L. , Burley Stephen K. , Friedman Jeffrey M.
Published: October 2006

The gene product of the
ob
locus is important in the regulation of body weight. The
ob
product was shown to be present as a 16-kilodalton protein in mouse and human plasma but was undetectable in plasma from C57BL/6J
ob
/
ob
mice. Plasma levels of this protein were increased in
diabetic
(
db
) mice, a mutant thought to be resistant to the effects of
ob
. Daily intraperitoneal injections of either mouse or human recombinant OB protein reduced the body weight of
ob
/
ob
mice by 30 percent after 2 weeks of treatment with no apparent toxicity but had no effect on
db
/
db
mice. The protein reduced food intake and increased energy expenditure in
ob
/
ob
mice. Injections of wild-type mice twice daily with the mouse protein resulted in a sustained 12 percent weight loss, decreased food intake, and a reduction of body fat from 12.2 to 0.7 percent. These data suggest that the OB protein serves an endocrine function to regulate body fat stores.
Paleomagnetic Age for Hominid Fossils at Atapuerca Archaeological Site, Spain
Authors: Parés Josep M. , Pérez-González Alfredo
Published: October 2006

A paleomagnetic investigation at the Gran Dolina site excavation (Atapuerca, Spain) shows that the sediments containing the recently discovered human occupation were deposited more than 780,000 years ago, near the time of the Matuyama-Brunhes boundary. Forty-one oriented samples were obtained from 22 sites along an 18-meter section of the Gran Dolina karst filling. The lower 16 sites displayed reversed-polarity magnetizations whereas the upper six sites were normal. The reversal spans the hominid finds at stratigraphic level TD6 (the Aurora stratum), and these hominid fossils are therefore the oldest in southern Europe.
Functional Significance of Symmetrical Versus Asymmetrical GroEL-GroES Chaperonin Complexes
Authors: Engel Andreas , Hayer-Hartl Manajit K. , Goldie Kenneth N. , Pfeifer Günter , Hegerl Reiner , Müller Shirley , da Silva Ana C. R. , Baumeister Wolfgang , Hartl F. Ulrich
Published: October 2006

The
Escherichia coli
chaperonin GroEL and its regulator GroES are thought to mediate adenosine triphosphate-dependent protein folding as an asymmetrical complex, with substrate protein bound within the GroEL cylinder. In contrast, a symmetrical complex formed between one GroEL and two GroES oligomers, with substrate protein binding to the outer surface of GroEL, was recently proposed to be the functional chaperonin unit. Electron microscopic and biochemical analyses have now shown that unphysiologically high magnesium concentrations and increased pH are required to assemble symmetrical complexes, the formation of which precludes the association of unfolded polypeptide. Thus, the functional significance of GroEL:(GroES)
2
particles remains to be demonstrated.
Ab Initio Calculation of the Sound Velocity of Dense Hydrogen: Implications for Models of Jupiter
Authors: Alavi Ali , Parrinello Michele , Frenkel Daan
Published: October 2006

First-principles molecular dynamics simulations were used to calculate the sound velocity of dense hydrogen, and the results were compared with extrapolations of experimental data that currently conflict with either astrophysical models or data obtained from recent global oscillation measurements of Jupiter. Excellent agreement with the extrapolated experimental data was obtained. These results strongly support the notion that the existing models for the jovian interior need to be revised.
Direct Evaluation of Electronic Coupling Mediated by Hydrogen Bonds: Implications for Biological Electron Transfer
Authors: de Rege Peter J. F. , Williams Scott A. , Therien Michael J.
Published: October 2006

Three supramolecular bischromophoric systems featuring zinc(II) and iron(III) porphyrins have been synthesized to evaluate the relative magnitudes of electronic coupling provided by hydrogen, σ, and π bonds. Laser flash excitation generates the highly reducing singlet excited state of the (porphinato)zinc chromophore that can subsequently be electron transfer quenched by the (porphinato)iron(III) chloride moiety. Measurement of the photoinduced electron transfer rate constants enables a direct comparison of how well these three types of chemical interactions facilitate electron tunneling. In contrast to generally accepted theory, electronic coupling modulated by a hydrogen-bond interface is greater than that provided by an analogous interface composed entirely of carbon-carbon σ bonds. These results bear considerably on the analysis of through-protein electron transfer rate data as well as on the power of theory to predict the path traversed by the tunneling electron in a biological matrix; moreover, they underscore the cardinal role played by hydrogen bonds in biological electron transfer processes.
Native
Escherichia coli
OmpF Porin Surfaces Probed by Atomic Force Microscopy
Authors: Schabert Frank A. , Henn Christian , Engel Andreas
Published: October 2006

Topographs of two-dimensional porin OmpF crystals reconstituted in the presence of lipids were recorded in solution by atomic force microscopy (AFM) to a lateral resolution of 10 angstroms and a vertical resolution of 1 angstrom. Protein-protein interactions were demonstrated on the basis of the AFM results and earlier crystallographic findings. To assess protein-lipid interactions, the bilayer was modeled with kinked lipids by fitting the head groups to contours determined with AFM. Finally, two conformations of the extracellular porin surface were detected at forces of 0.1 nanonewton, demonstrating the potential of AFM to monitor conformational changes with high resolution.
Cloning of the β Cell High-Affinity Sulfonylurea Receptor: a Regulator of Insulin Secretion
Authors: Aguilar-Bryan Lydia , Nichols Colin G. , Wechsler Sérgio W. , Clement John P. , Boyd A. E. , González Gabriela , Herrera-Sosa Haydée , Nguy Kimberly , Bryan Joseph , Nelson Daniel A.
Published: October 2006

Sulfonylureas are a class of drugs widely used to promote insulin secretion in the treatment of non-insulin-dependent diabetes mellitus. These drugs interact with the sulfonylurea receptor of pancreatic β cells and inhibit the conductance of adenosine triphosphate (ATP)-dependent potassium (K
ATP
) channels. Cloning of complementary DNAs for the high-affinity sulfonylurea receptor indicates that it is a member of the ATP-binding cassette or traffic ATPase superfamily with multiple membrane-spanning domains and two nucleotide binding folds. The results suggest that the sulfonylurea receptor may sense changes in ATP and ADP concentration, affect K
ATP
channel activity, and thereby modulate insulin release.
Crystal Structure of DCoH, a Bifunctional, Protein-Binding Transcriptional Coactivator
Authors: Endrizzi James A. , Cronk Jeff D. , Wang Weidong , Crabtree Gerald R. , Alber Tom
Published: October 2006

DCoH, the dimerization cofactor of hepatocyte nuclear factor-1, stimulates gene expression by associating with specific DNA binding proteins and also catalyzes the dehydration of the biopterin cofactor of phenylalanine hydroxylase. The x-ray crystal structure determined at 3 angstrom resolution reveals that DCoH forms a tetramer containing two saddle-shaped grooves that comprise likely macromolecule binding sites. Two equivalent enzyme active sites flank each saddle, suggesting that there is a spatial connection between the catalytic and binding activities. Structural similarities between the DCoH fold and nucleic acid-binding proteins argue that the saddle motif has evolved to bind diverse ligands or that DCoH unexpectedly may bind nucleic acids.
Role of the Chaperone Protein Hsp104 in Propagation of the Yeast Prion-Like Factor [
psi
+
]
Authors: Chernoff Yury O. , Lindquist Susan L. , Ono Bun-ichiro , Inge-Vechtomov Sergei G. , Liebman Susan W.
Published: October 2006

The yeast non-Mendelian factor [
psi
+
] has been suggested to be a self-modified protein analogous to mammalian prions. Here it is reported that an intermediate amount of the chaperone protein Hsp104 was required for the propagation of the [
psi
+
] factor. Overproduction or inactivation of Hsp104 caused the loss of [
psi
+
]. These results suggest that chaperone proteins play a role in prion-like phenomena, and that a certain level of chaperone expression can cure cells of prions without affecting viability. This may lead to antiprion treatments that involve the alteration of chaperone amounts or activity.
Evidence for a Basalt-Free Surface on Mercury and Implications for Internal Heat
Authors: Jeanloz Raymond , Mitchell David L. , Sprague Ann L. , de Pater Imke
Published: October 2006

Microwave and mid-infrared observations reveal that Mercury's surface contains less FeO + TiO
2
and at least as much feldspar as the lunar highlands. The results are compatible with the high albedo (brightness) of Mercury's surface at visible wavelengths in suggesting a rock and soil composition that is devoid of basalt, the primary differentiate of terrestrial mantles. The occurrence of a basalt-free, highly differentiated crust is in accord with recent models of the planet's thermal evolution and suggests that Mercury has retained a hot interior as a result of a combination of inefficient mantle convection and minimal volcanic heat loss.
Crystal Structure of a Purple Acid Phosphatase Containing a Dinuclear Fe(III)-Zn(II) Active Site
Authors: Sträter Norbert , Klabunde Thomas , Tucker Paul , Witzel Herbert , Krebs Bernt
Published: October 2006

Kidney bean purple acid phosphatase (KBPAP) is an Fe(III)-Zn(II) metalloenzyme resembling the mammalian Fe(III)-Fe(II) purple acid phosphatases. The structure of the homodimeric 111-kilodalton KBPAP was determined at a resolution of 2.9 angstroms. The enzyme contains two domains in each subunit. The active site is located in the carboxyl-terminal domain at the carboxy end of two sandwiched βαβαβ motifs. The two metal ions are 3.1 angstroms apart and bridged monodentately by Asp
164
. The iron is further coordinated by Tyr
167
, His
325
, and Asp
135
, and the zinc by His
286
, His
323
, and Asn
201
. The active-site structure is consistent with previous proposals regarding the mechanism of phosphate ester hydrolysis involving nucleophilic attack on the phosphate group by an Fe(III)-coordinated hydroxide ion.
Electron Tunneling in Proteins: Coupling Through a β Strand
Authors: Langen Ralf , Chang I-Jy , Germanas Juris P. , Richards John H. , Winkler Jay R. , Gray Harry B.
Published: October 2006

Electron coupling through a β strand has been investigated by measurement of the intramolecular electron-transfer (ET) rates in ruthenium-modified derivatives of the β barrel blue copper protein
Pseudomonas aeruginosa
azurin. Surface histidines, introduced on the methionine-121 β strand by mutagenesis, were modified with a Ru(2,2′-bipyridine)
2
(imidazole)
2+
complex. The Cu
+
to Ru
3+
rate constants yielded a distance-decay constant of 1.1 per angstrom, a value close to the distance-decay constant of 1.0 per angstrom predicted for electron tunneling through an idealized β strand. Activationless ET rate constants in combination with a tunneling-pathway analysis of the structures of azurin and cytochrome c confirm that there is a generally efficient network for coupling the internal (native) redox center to the surface of both proteins.
Common Mechanisms of Visual Imagery and Perception
Authors: Ishai Alumit , Sagi Dov
Published: October 2006

Detection of a visual target can be facilitated by flanking visual masks. A similar enhancement in detection thresholds was obtained when observers imagined the previously perceived masks. Imagery-induced facilitation was detected for as long as 5 minutes after observation of the masks by the targeted eye. These results indicated the existence of a low-level (monocular) memory that stores the sensory trace for several minutes and enables reactivation of early representations by higher processes. This memory, with its iconic nature, may subserve the interface between mental images and percepts.
Shared Neural Substrates Controlling Hand Movements in Human Motor Cortex
Authors: Sanes Jerome N. , Donoghue John P. , Thangaraj Venkatesan , Edelman Robert R. , Warach Steven
Published: October 2006

Voluntary hand movements in humans involve the primary motor cortex (M1). A functional magnetic resonance imaging method that measures relative cerebral blood flow was used to identify a distributed, overlapping pattern of hand movement representation within the posterior precentral gyrus, which contains M1. The observed pattern resembles those reported in nonhuman primates and differs from a somatotopically organized plan typically used to portray human motor cortex organization. Finger and wrist movements activated a wide expanse of the posterior precentral gyrus, and representations for different finger movements overlapped each other and the wrist representation. Multiple sites of activation occurred in the precentral gyrus for all movements. The overlapping representations may mediate motor and cognitive functions requiring coordinated neural processing for finger and wrist actions rather than discrete control implied by somatotopic maps.
Activation of
RET
as a Dominant Transforming Gene by Germline Mutations of MEN2A and MEN2B
Authors: Santoro Massimo , Carlomagno Francesca , Romano Alfredo , Bottaro Donald P. , Dathan Nina A. , Grieco Michele , Fusco Alfredo , Vecchio Giancarlo , Matoskova Brona , Kraus Matthias H. , Di Fiore Pier Paolo
Published: October 2006

Multiple endocrine neoplasia types 2A and 2B (MEN2A and MEN2B) and familial medullary thyroid carcinoma are dominantly inherited cancer syndromes. All three syndromes are associated with mutations in
RET
, which encodes a receptor-like tyrosine kinase. The altered
RET
alleles were shown to be transforming genes in NIH 3T3 cells as a consequence of constitutive activation of the RET kinase. The MEN2A mutation resulted in RET dimerization at steady state, whereas the MEN2B mutation altered RET catalytic properties both quantitatively and qualitatively. Oncogenic conversion of
RET
in these neoplastic syndromes establishes germline transmission of dominant transforming genes in human cancer.
Metal Ions in the Atmosphere of Neptune
Authors: Lyons James R.
Published: October 2006

Microwave propagation experiments performed with Voyager 2 at Neptune revealed sharp layers of electrons in Neptune's lower ionosphere with densities of ∼10
4
per cubic centimeter. These layers are reminiscent of the sporadic-E layers in the Earth's ionosphere, and when taken together with data from the other giant planets, these data confirm the importance of the magnetic field in layer formation. A photochemical model that incorporates species produced by meteoroid ablation predicts that singly ionized magnesium is the most likely metal to be found in the layers, although laboratory data on the kinetics of metallic atoms and ions in a reducing environment are lacking. The metal chemistry discussed here is directly relevant to the abundant metals observed at the impact site of the G fragment of comet Shoemaker Levy 9 on Jupiter.
Independent Human MAP-Kinase Signal Transduction Pathways Defined by MEK and MKK Isoforms
Authors: Dérijard Benoit , Raingeaud Joël , Barrett Tamera , Wu I-Huan , Han Jiahuai , Ulevitch Richard J. , Davis Roger J.
Published: October 2006

Mammalian mitogen-activated protein (MAP) kinases include extracellular signal-regulated protein kinase (ERK), c-Jun amino-terminal kinase (JNK), and p38 subgroups. These MAP kinase isoforms are activated by dual phosphorylation on threonine and tyrosine. Two human MAP kinase kinases (MKK3 and MKK4) were cloned that phosphorylate and activate p38 MAP kinase. These MKK isoforms did not activate the ERK subgroup of MAP kinases, but MKK4 did activate JNK. These data demonstrate that the activators of p38 (MKK3 and MKK4), JNK (MKK4), and ERK (MEK1 and MEK2) define independent MAP kinase signal transduction pathways.
Synergistic Roles for Receptor Occupancy and Aggregation in Integrin Transmembrane Function
Authors: Miyamoto Shingo , Akiyama Steven K. , Yamada Kenneth M.
Published: October 2006

Integrin receptors mediate cell adhesion, signal transduction, and cytoskeletal organization. How a single transmembrane receptor can fulfill multiple functions was clarified by comparing roles of receptor occupancy and aggregation. Integrin occupancy by monovalent ligand induced receptor redistribution, but minimal tyrosine phosphorylation signaling or cytoskeletal protein redistribution. Aggregation of integrins by noninhibitory monoclonal antibodies on beads induced intracellular accumulations of pp125
FAK
and tensin, as well as phosphorylation, but no accumulation of other cytoskeletal proteins such as talin. Combining antibody-mediated clustering with monovalent ligand occupancy induced accumulation of seven cytoskeletal proteins, including α-actinin, talin, and F-actin, thereby mimicking multivalent interactions with fibronectin or polyvalent peptides. Integrins therefore mediate a complex repertoire of functions through the distinct effects of receptor aggregation, receptor occupancy, or both together.
DNA-Dependent Kinase (p350) as a Candidate Gene for the Murine SCID Defect
Authors: Kirchgessner Cordula U. , Patil Christopher K. , Evans James W. , Cuomo Christina A. , Fried Laura M. , Carter Timothy , Oettinger Marjorie A. , Brown J. Martin
Published: October 2006

Severe combined immunodeficient (SCID) mice are deficient in a recombination process utilized in both DNA double-strand break repair and in V(D)J recombination. The phenotype of these mice involves both cellular hypersensitivity to ionizing radiation and a lack of B and T cell immunity. The catalytic subunit of DNA-dependent protein kinase, p350, was identified as a strong candidate for the murine gene
SCID
. Both p350 and a gene complementing the SCID defect colocalize to human chromosome 8q11. Chromosomal fragments expressing p350 complement the SCID phenotype, and p350 protein levels are greatly reduced in cells derived from SCID mice compared to cells from wild-type mice.
HST Far-Ultraviolet Imaging of Jupiter During the Impacts of Comet Shoemaker-Levy 9
Authors: Clarke John T. , Prangé Renée , Ballester Gilda E. , Trauger John , Evans Robin , Rego Daniel , Stapelfeldt Karl , Ip Wing , Gérard Jean-Claude , Hammel Heidi , Ballav Manish , Jaffel Lotfi Ben , Bertaux Jean-Loup , Crisp David , Emerich Claude , Harris Walter , Horanyi Mihaly , Miller Steven , Storrs Alex , Weaver Harold
Published: October 2006

Hubble Space Telescope far-ultraviolet images of Jupiter during the Shoemaker-Levy 9 impacts show the impact regions darkening over the 2 to 3 hours after the impact, becoming darker and more extended than at longer wavelengths, which indicates that ultraviolet-absorbing gases or aerosols are more extended, more absorbing, and at higher altitudes than the absorbers of visible light. Transient auroral emissions were observed near the magnetic conjugate point of the K impact site just after that impact. The global auroral activity was fainter than average during the impacts, and a variable auroral emission feature was observed inside the southern auroral oval preceding the impacts of fragments Q1 and Q2.
Requirement of RNA Polymerase III Transcription Factors for in Vitro Position-Specific Integration of a Retroviruslike Element
Authors: Kirchner Jacqueline , Connolly Charles M. , Sandmeyer Suzanne B.
Published: October 2006

The yeast retroviruslike element Ty3 inserts at the transcription initiation sites of genes transcribed by RNA polymerase III (Pol III). An in vitro integration assay was developed with the use of Ty3 viruslike particles and a modified
SUP2
tyrosine transfer RNA (tRNA
Tyr
) gene target. Integration was position-specific and required Ty3 integrase, Pol III transcription extract, and a transcriptionally competent tRNA gene. Use of individual transcription factor (TF) IIIB-, TFIIIC-, and Pol III-containing fractions showed that TFIIIB and TFIIIC, together, were sufficient for position-specific Ty3 integration, but not for transcription. This report demonstrates that in vitro integration of a retroelement can be targeted by cellular proteins.
Hepatic angiomyolipoma with trace amounts of fat: a case report and literature review
Authors: Wang S-N , Tsai K-B , Lee K-T
Published: October 2006

Hepatic angiomyolipoma (AML), a rare benign mesenchymal tumour, is characterised by the presence of mature adipose tissue, smooth-muscle cells and thick-walled blood vessels. Increasing attention to hepatic AMLs has led to the discovery that sufficient proportions of fat often allow for definite diagnoses preoperatively. However, the proportion of fatty tissue in these tumours is highly variable. One case of hepatic AML is reported, where the amount of fat was <1%. In this case, the viral hepatitis markers, including hepatitis B antigen and anti-hepatitis C virus antibody, were negative. The serum α-fetoprotein level was 3.4 ng/ml and in the normal range. Abdominal ultrasonography showed a hypoechoic mass measuring 5 cm in diameter and without an obvious capsule in the left lobe of the liver. A dynamic computed tomography scan showed a well-defined and slightly enhanced mass in the medial segment of the left lobe of the liver. Angiography showed that the mass was hypervascular in character. As hepatocellular carcinoma was highly suspected from these preoperative image studies, a left lobectomy was carried out. Microscopically, the amount of fat was too low to establish a diagnosis of hepatic AML. However, positive homatropine methylbromide 45 immunoreactivity of the smooth-muscle cells seemed to assist in arriving at the diagnosis.
B-type natriuretic peptide in reversible myocardial ischaemia: Table 1
Authors: Chatha K , Alsoud M , Griffiths M J , Elfatih A , Abozguia K , Horton R C , Dunmore S J , Gama R
Published: October 2006

Background:Coronary heart disease is associated with increased B-type natriuretic peptides (BNPs), and, although controversial, may cause exaggerated exercise-induced BNP secretion. We investigated BNP in relation to reversible myocardial ischaemia.

Materials and methods:Serum N-terminal proBNP (NT-proBNP) was measured before and after an exercise electrocardiogram test (ETT) in 14 patients with and 45 patients without exercise-induced myocardial ischaemia. Statistical analysis was carried out on logarithmically transformed data. Results, however, are pre-transformed data.

Results:NT-proBNP increased with exercise both in ETT-positive patients (mean (SD) 71.4 (41.2)v76.8 (44.0) ng/l; p<0.001) and ETT-negative patients (54.0 (61.2)v60.1 (69.0) ng/l; p<0.001). Pre-exercise and post-exercise NT-proBNP were higher (p<0.05) in ETT-positive than in ETT-negative patients. Incremental NT-proBNP was similar in ETT-positive (4.7 (4.2) ng/l) and ETT-negative (6.2 (8.6) ng/l) patients.

Conclusion:Serum NT-proBNP concentrations are higher in patients with exercise-induced myocardial ischaemia than in those without. Exercise-induced electrocardiographic myocardial ischaemia, however, is not associated with exaggerated BNP secretion.
Giant Sertoli cell nodule of the testis: distinction from other Sertoli cell lesions: Figure 1
Authors: Barghorn A , Alioth H-R , Hailemariam S , Bannwart F , Ulbright T M
Published: October 2006

The case of a 33-year-old man with a clinically suspected testicular neoplasm is reported here. The radical orchidectomy specimen showed a sharply demarcated, firm, yellow–white 1-cm nodule beneath the tunica albuginea at the upper pole. Microscopical examination showed the encapsulated nodule to be composed of tubules lined by immature Sertoli cells with interspersed spermatogonia and an interwoven network of hyalinised basement membrane having foci of calcification. Immunohistochemical studies verified the fetal phenotype of the Sertoli cells and the non-neoplastic nature of the germ cell component. Except for the large size, the findings were identical to those of a Sertoli cell nodule—a typically microscopic, unencapsulated lesion commonly detected in cryptorchid testes. The term “giant Sertoli cell nodule” is used for this unique, hitherto undescribed lesion and its distinction from other Sertoli cell lesions of the testis is considered here.
INTRINSIC PERIODICITY OF TIME AND NONMAXIMAL ENTROPY OF UNIVERSE
Authors: NIELSEN HOLGER B. , NINOMIYA MASAO
Published: October 2006

The universe is certainly not yet in a total thermodynamical equilibrium. Thus some law of special initial conditions is needed. A universe or a system imposed to behave periodically will then require "initial conditions." Those initial conditions will not look like the type we already have, which have been suffered the heat death. In other words, the required initial conditions should not have been obtained the maximal entropy — like a random state. The intrinsic periodicity successfully explains why entropy is not maximal but it fails, phenomenologically, in leading to a constant entropy.
BOUNDARY TERMS IN SUPERGRAVITY AND SUPERSYMMETRY
Authors: VAN NIEUWENHUIZEN PETER , REBHAN ANTON , VASSILEVICH DMITRI V. , WIMMER ROBERT
Published: October 2006

We begin with the simplest possible introduction to supergravity, and then discuss its spin-3/2 stress tensor. Next, we discuss boundary conditions on fields and boundary actions for N = 1 supergravity. Finally, we discuss new boundary contributions to the mass and central charge of monopoles in N = 4 super Yang–Mills theory. All models are in (3+1) dimensions.
GRAND UNIFICATION AS A BRIDGE BETWEEN STRING THEORY AND PHENOMENOLOGY
Authors: PATI JOGESH C.
Published: October 2006

In the first part of this paper, we explain what empirical evidence points to the need for having an effective grand unification-like symmetry possessing the symmetry SU(4)-color in 4D. If one assumes the premises of a future predictive theory including gravity — be it string/M-theory or a reincarnation — this evidence then suggests that such a theory should lead to an effective grand unification-like symmetry as above in 4D, near the string-GUT-scale, rather than the standard model symmetry. Advantages of an effective supersymmetric G (224) = SU (2) L × SU (2) R × SU (4)c or SO(10) symmetry in 4D in explaining (i) observed neutrino oscillations, (ii) baryogenesis via leptogenesis, and (iii) certain fermion mass-relations are noted. And certain distinguishing tests of a SUSY G(224) or SO(10)-framework involving CP and flavor violations (as in μ → eγ, τ → μγ, edm's of the neutron and the electron) as well as proton decay are briefly mentioned.

Recalling some of the successes we have had in our understanding of nature so far, and the current difficulties of string/M-theory as regards the large multiplicity of string vacua, some comments are made on the traditional goal of understanding vis a vis the recently evolved view of landscape and anthropism.
QUANTUM CYLINDRICAL WAVES AND PARAMETRIZED FIELD THEORY
Authors: VARADARAJAN MADHAVAN
Published: October 2006

In this article, we review some illustrative results in the study of two related toy models for quantum gravity, namely cylindrical waves (which are cylindrically symmetric gravitational fields)and parametrized field theory (which is just free scalar field theory on a flat space–time in generally covariant disguise). In the former, we focus on the phenomenon of unexpected large quantum gravity effects in regions of weak classical gravitational fields and on an analysis of causality in a quantum geometry. In the latter, we focus on Dirac quantization, argue that this is related to the unitary implementability of free scalar field evolution along curved foliations of the flat space–time and review the relevant results for unitary implementability.
Maternal renal insufficiency alters plasma composition and renal function in the fetal sheep
Authors: Gibson Karen J. , Boyce Amanda C. , Karime Bilal M. , Lumbers Eugenie R.
Published: October 2006

To determine the effects of chronic maternal renal insufficiency on fetal renal function, we studied nine fetuses whose mothers underwent subtotal nephrectomy at least 2 mo before mating (STNxF) and seven fetuses from intact ewes (IntF) (126–128 days of gestation, term 150 days). STNxF had lower hematocrit ( P < 0.05), plasma chloride ( P < 0.01), and creatinine levels ( P < 0.01), and the length-to-width ratio of their kidneys was reduced ( P < 0.05). They excreted twice as much urine ( P < 0.05) and sodium ( P < 0.01). Total ( P = 0.01) and proximal fractional sodium reabsorptions ( P < 0.05) were lower in STNxF; distal delivery of sodium ( P < 0.05) and distal fractional sodium reabsorption ( P < 0.05) were higher. They tended to have suppressed renin levels ( P = 0.06). Infusions of amino acids (alanine, glycine, proline, and serine at 0.32 mmol/min for 1 h and 0.64 mmol/min for 2 h intravenously), known to stimulate renal blood flow and glomerular filtration rate in fetal sheep, did so in IntF ( P < 0.01). Arterial pressure also increased ( P < 0.01). These effects were not observed in STNxF. In summary, chronic maternal renal insufficiency was associated with profound alterations in fetal renal excretion of fluid and electrolytes and impaired renal hemodynamic and glomerular responses to amino acid infusion. Whether these marked changes in the renal function of fetuses carried by STNx ewes are associated with alterations in renal function in postnatal or adult life remains to be determined.
Increased fatigue resistance of respiratory muscles during exercise after respiratory muscle endurance training
Authors: Verges Samuel , Lenherr Oliver , Haner Andrea C. , Schulz Christian , Spengler Christina M.
Published: October 2006

Respiratory muscle fatigue develops during exhaustive exercise and can limit exercise performance. Respiratory muscle training, in turn, can increase exercise performance. We investigated whether respiratory muscle endurance training (RMT) reduces exercise-induced inspiratory and expiratory muscle fatigue. Twenty-one healthy, male volunteers performed twenty 30-min sessions of either normocapnic hyperpnoea ( n = 13) or sham training (CON, n = 8) over 4–5 wk. Before and after training, subjects performed a constant-load cycling test at 85% maximal power output to exhaustion (PREEXH, POSTEXH). A further posttraining test was stopped at the pretraining duration (POSTISO) i.e., isotime. Before and after cycling, transdiaphragmatic pressure was measured during cervical magnetic stimulation to assess diaphragm contractility, and gastric pressure was measured during thoracic magnetic stimulation to assess abdominal muscle contractility. Overall, RMT did not reduce respiratory muscle fatigue. However, in subjects who developed >10% of diaphragm or abdominal muscle fatigue in PREEXH, fatigue was significantly reduced after RMT in POSTISO(inspiratory: −17 ± 6% vs. −9 ± 10%, P = 0.038, n = 9; abdominal: −19 ± 10% vs. −11 ± 11%, P = 0.038, n = 9), while sham training had no significant effect. Similarly, cycling endurance in POSTEXHdid not improve after RMT ( P = 0.071), while a significant improvement was seen in the subgroup with >10% of diaphragm fatigue after PREEXH( P = 0.017), but not in the sham training group ( P = 0.674). However, changes in cycling endurance did not correlate with changes in respiratory muscle fatigue. In conclusion, RMT decreased the development of respiratory muscle fatigue during intensive exercise, but this change did not seem to improve cycling endurance.