bluuebunny/crossref_metadata_2025 huggingface dataset:
Insecticidal Toxins from the Bacterium
Photorhabdus luminescens
Authors: Bowen David , Rocheleau Thomas A. , Blackburn Michael , Andreev Olga , Golubeva Elena , Bhartia Rohit , ffrench-Constant Richard H.
Published: July 2002

Transgenic plants expressing
Bacillus thuringiensis
(Bt) toxins are currently being deployed for insect control. In response to concerns about Bt resistance, we investigated a toxin secreted by a different bacterium
Photorhabdus luminescens,
which lives in the gut of entomophagous nematodes. In insects infected by the nematode, the bacteria are released into the insect hemocoel; the insect dies and the nematodes and bacteria replicate in the cadaver. The toxin consists of a series of four native complexes encoded by toxin complex loci
tca, tcb, tcc,
and
tcd
. Both
tca
and
tcd
encode complexes with high oral toxicity to
Manduca sexta
and therefore they represent potential alternatives to Bt for transgenic deployment.
Design of a 20-Amino Acid, Three-Stranded β-Sheet Protein
Authors: Kortemme Tanja , Ramı́rez-Alvarado Marina , Serrano Luis
Published: July 2002

A 20-residue protein (named Betanova) forming a monomeric, three-stranded, antiparallel β sheet was designed using a structural backbone template and an iterative hierarchical approach. Structural and physicochemical characterization show that the β-sheet conformation is stabilized by specific tertiary interactions and that the protein exhibits a cooperative two-state folding-unfolding transition, which is a hallmark of natural proteins. The Betanova molecule constitutes a tractable model system to aid in the understanding of β-sheet formation, including β-sheet aggregation and amyloid fibril formation.
Diffusion Kinetics of Samarium and Neodymium in Garnet, and a Method for Determining Cooling Rates of Rocks
Authors: Ganguly J. , Tirone M. , Hervig R. L.
Published: July 2002

Experimental determinations of the diffusion coefficients of samarium and neodymium in almandine garnet and theoretical considerations show that one cannot assign a sufficiently restricted range of closure temperature,
T
C
, to the samarium-neodymium decay system in garnet for the purpose of constraining the cooling rate. However, it is shown that the samarium-neodymium cooling age of garnet can be used to calculate both cooling rate and
T
C
if the temperature and age at the peak metamorphic conditions are known.
Prevention of Allogeneic Fetal Rejection by Tryptophan Catabolism
Authors: Munn David H. , Zhou Min , Attwood John T. , Bondarev Igor , Conway Simon J. , Marshall Brendan , Brown Corrie , Mellor Andrew L.
Published: July 2002

In 1953 Medawar pointed out that survival of the genetically disparate (allogeneic) mammalian conceptus contradicts the laws of tissue transplantation. Rapid T cell–induced rejection of all allogeneic concepti occurred when pregnant mice were treated with a pharmacologic inhibitor of indoleamine 2,3-dioxygenase (IDO), a tryptophan-catabolizing enzyme expressed by trophoblasts and macrophages. Thus, by catabolizing tryptophan, the mammalian conceptus suppresses T cell activity and defends itself against rejection.
Onset of Catalytic Activity of Gold Clusters on Titania with the Appearance of Nonmetallic Properties
Authors: Valden M. , Lai X. , Goodman D. W.
Published: July 2002

Gold clusters ranging in diameter from 1 to 6 nanometers have been prepared on single crystalline surfaces of titania in ultrahigh vacuum to investigate the unusual size dependence of the low-temperature catalytic oxidation of carbon monoxide. Scanning tunneling microscopy/spectroscopy (STM/STS) and elevated pressure reaction kinetics measurements show that the structure sensitivity of this reaction on gold clusters supported on titania is related to a quantum size effect with respect to the thickness of the gold islands; islands with two layers of gold are most effective for catalyzing the oxidation of carbon monoxide. These results suggest that supported clusters, in general, may have unusual catalytic properties as one dimension of the cluster becomes smaller than three atomic spacings.
Europa's Differentiated Internal Structure: Inferences from Four Galileo Encounters
Authors: Anderson J. D. , Schubert G. , Jacobson R. A. , Lau E. L. , Moore W. B. , Sjogren W. L.
Published: July 2002

Radio Doppler data from four encounters of the Galileo spacecraft with the jovian moon Europa have been used to refine models of Europa's interior. Europa is most likely differentiated into a metallic core surrounded by a rock mantle and a water ice-liquid outer shell, but the data cannot eliminate the possibility of a uniform mixture of dense silicate and metal beneath the water ice-liquid shell. The size of a metallic core is uncertain because of its unknown composition, but it could be as large as about 50 percent of Europa's radius. The thickness of Europa's outer shell of water ice-liquid must lie in the range of about 80 to 170 kilometers.
Climate and Groundwater Recharge During the Last Glaciation in an Ice-Covered Region
Authors: Beyerle Urs , Purtschert Roland , Aeschbach-Hertig Werner , Imboden Dieter M. , Loosli Heinz H. , Wieler Rainer , Kipfer Rolf
Published: July 2002

A multitracer study of a small aquifer in northern Switzerland indicates that the atmosphere in central Europe cooled by at least 5°C during the last glacial period. The relation between oxygen isotope ratios (δ
18
O) and recharge temperatures reconstructed for this period is similar to the present-day one if a shift in the δ
18
O value of the oceans during the ice age is taken into account. This similarity suggests that the present-day δ
18
O-temperature relation can be used to reconstruct paleoclimate conditions in northern Switzerland. A gap in calculated groundwater age between about 17,000 and 25,000 years before the present indicates that during the last glacial maximum, local groundwater recharge was prevented by overlying glaciers.
Pathways to a Protein Folding Intermediate Observed in a 1-Microsecond Simulation in Aqueous Solution
Authors: Duan Yong , Kollman Peter A.
Published: July 2002

An implementation of classical molecular dynamics on parallel computers of increased efficiency has enabled a simulation of protein folding with explicit representation of water for 1 microsecond, about two orders of magnitude longer than the longest simulation of a protein in water reported to date. Starting with an unfolded state of villin headpiece subdomain, hydrophobic collapse and helix formation occur in an initial phase, followed by conformational readjustments. A marginally stable state, which has a lifetime of about 150 nanoseconds, a favorable solvation free energy, and shows significant resemblance to the native structure, is observed; two pathways to this state have been found.
Thalamic and Brainstem Contributions to Large-Scale Plasticity of Primate Somatosensory Cortex
Authors: Jones Edward G. , Pons Tim P.
Published: July 2002

After long-term denervation of an upper limb in macaque monkeys, the representation of the face in somatosensory cortex expands over many millimeters into the silenced representation of the hand. Various brainstem and cortical mechanisms have been proposed to explain this phenomenon. Reorganization in the thalamus has been largely ignored. In monkeys with deafferented upper limbs for 12 to 20 years, it was found that the brainstem cuneate and the thalamic ventral posterior nuclei had undergone severe transneuronal atrophy, and physiological mapping in the thalamus revealed that the face and trunk representations were adjoined while the normally small representation of the lower face had expanded comparable to the expansion in cortex. Reorganization of brainstem and thalamic nuclei associated with slow transneuronal atrophy is likely to be a progressive process. When coupled with divergence of ascending connections, it is likely to make a substantial contribution to representational changes in cortex.
Structure of Human Methionine Aminopeptidase-2 Complexed with Fumagillin
Authors: Liu Shenping , Widom Joanne , Kemp Christopher W. , Crews Craig M. , Clardy Jon
Published: July 2002

The fungal metabolite fumagillin suppresses the formation of new blood vessels, and a fumagillin analog is currently in clinical trials as an anticancer agent. The molecular target of fumagillin is methionine aminopeptidase-2 (MetAP-2). A 1.8 Å resolution crystal structure of free and inhibited human MetAP-2 shows a covalent bond formed between a reactive epoxide of fumagillin and histidine-231 in the active site of MetAP-2. Extensive hydrophobic and water-mediated polar interactions with other parts of fumagillin provide additional affinity. Fumagillin-based drugs inhibit MetAP-2 but not MetAP-1, and the three-dimensional structure also indicates the likely determinants of this specificity. The structural basis for fumagillin's potency and specificity forms the starting point for structure-based drug design.
Reovirus Therapy of Tumors with Activated Ras Pathway
Authors: Coffey Matthew C. , Strong James E. , Forsyth Peter A. , Lee Patrick W. K.
Published: July 2002

Human reovirus requires an activated Ras signaling pathway for infection of cultured cells. To investigate whether this property can be exploited for cancer therapy, severe combined immune deficient mice bearing tumors established from v-
erbB
–transformed murine NIH 3T3 cells or human U87 glioblastoma cells were treated with the virus. A single intratumoral injection of virus resulted in regression of tumors in 65 to 80 percent of the mice. Treatment of immune-competent C3H mice bearing tumors established from
ras
-transformed C3H-10T1/2 cells also resulted in tumor regression, although a series of injections were required. These results suggest that, with further work, reovirus may have applicability in the treatment of cancer.
Tankyrase, a Poly(ADP-Ribose) Polymerase at Human Telomeres
Authors: Smith Susan , Giriat Izabela , Schmitt Anja , de Lange Titia
Published: July 2002

Tankyrase, a protein with homology to ankyrins and to the catalytic domain of poly(adenosine diphosphate–ribose) polymerase (PARP), was identified and localized to human telomeres. Tankyrase binds to the telomeric protein TRF1 (telomeric repeat binding factor–1), a negative regulator of telomere length maintenance. Like ankyrins, tankyrase contains 24 ankyrin repeats in a domain responsible for its interaction with TRF1. Recombinant tankyrase was found to have PARP activity in vitro, with both TRF1 and tankyrase functioning as acceptors for adenosine diphosphate (ADP)–ribosylation. ADP-ribosylation of TRF1 diminished its ability to bind to telomeric DNA in vitro, suggesting that telomere function in human cells is regulated by poly(ADP-ribosyl)ation.
Role of Mouse Cryptochrome Blue-Light Photoreceptor in Circadian Photoresponses
Authors: Thresher Randy J. , Vitaterna Martha Hotz , Miyamoto Yasuhide , Kazantsev Aleksey , Hsu David S. , Petit Claude , Selby Christopher P. , Dawut Lale , Smithies Oliver , Takahashi Joseph S. , Sancar Aziz
Published: July 2002

Cryptochromes are photoactive pigments in the eye that have been proposed to function as circadian photopigments. Mice lacking the cryptochrome 2 blue-light photoreceptor gene (
mCry2
) were tested for circadian clock-related functions. The mutant mice had a lower sensitivity to acute light induction of
mPer1
in the suprachiasmatic nucleus (SCN) but exhibited normal circadian oscillations of
mPer1
and
mCry1
messenger RNA in the SCN. Behaviorally, the mutants had an intrinsic circadian period about 1 hour longer than normal and exhibited high-amplitude phase shifts in response to light pulses administered at circadian time 17. These data are consistent with the hypothesis that CRY2 protein modulates circadian responses in mice and suggest that cryptochromes have a role in circadian photoreception in mammals.
The Taxonomy of Developmental Control in
Caenorhabditis elegans
Authors: Ruvkun Gary , Hobert Oliver
Published: July 2002

The
Caenorhabditis elegans
genome sequence was surveyed for transcription factor and signaling gene families that have been shown to regulate development in a variety of species. About 10 to 25 percent of the genes in most of the gene families already have been genetically analyzed in
C. elegans
, about half of the genes detect probable orthologs in other species, and about 10 to 25 percent of the genes are, at present, unique to
C. elegans
.
Caenorhabditis elegans
is also missing genes that are found in vertebrates and other invertebrates. Thus the genome sequence reveals universals in developmental control that are the legacy of metazoan complexity before the Cambrian explosion, as well as genes that have been more recently invented or lost in particular phylogenetic lineages.
Elevating the Vitamin E Content of Plants Through Metabolic Engineering
Authors: Shintani David , DellaPenna Dean
Published: July 2002

α-Tocopherol (vitamin E) is a lipid-soluble antioxidant synthesized only by photosynthetic organisms. α-Tocopherol is an essential component of mammalian diets, and intakes in excess of the U.S. recommended daily allowance are correlated with decreased incidence of a number of degenerative human diseases. Plant oils, the main dietary source of tocopherols, typically contain α-tocopherol as a minor component and high levels of its biosynthetic precursor, γ-tocopherol. A genomics-based approach was used to clone the final enzyme in α-tocopherol synthesis, γ-tocopherol methyltransferase. Overexpression of γ-tocopherol methyltransferase in
Arabidopsis
seeds shifted oil compositions in favor of α-tocopherol. Similar increases in agricultural oil crops would increase vitamin E levels in the average U.S. diet.
Superionic and Metallic States of Water and Ammonia at Giant Planet Conditions
Authors: Cavazzoni C. , Chiarotti G. L. , Scandolo S. , Tosatti E. , Bernasconi M. , Parrinello M.
Published: July 2002

The phase diagrams of water and ammonia were determined by constant pressure ab initio molecular dynamic simulations at pressures (30 to 300 gigapascal) and temperatures (300 to 7000 kelvin) of relevance for the middle ice layers of the giant planets Neptune and Uranus. Along the planetary isentrope water and ammonia behave as fully dissociated ionic, electronically insulating fluid phases, which turn metallic at temperatures exceeding 7000 kelvin for water and 5500 kelvin for ammonia. At lower temperatures, the phase diagrams of water and ammonia exhibit a superionic solid phase between the solid and the ionic liquid. These simulations improve our understanding of the properties of the middle ice layers of Neptune and Uranus.
Rapid Fluctuations in Sea Level Recorded at Huon Peninsula During the Penultimate Deglaciation
Authors: Esat Tezer M. , McCulloch Malcolm T. , Chappell John , Pillans Bradley , Omura Akio
Published: July 2002

About 140,000 years ago, the breakup of large continental ice sheets initiated the Last Interglacial period. Sea level rose and peaked around 135,000 years ago about 14 meters below present levels. A record of Last Interglacial sea levels between 116,000 years to 136,000 years ago is preserved at reef VII of the uplifted coral terraces of Huon Peninsula in Papua New Guinea. However, corals from a cave situated about 90 meters below the crest of reef VII are 130,000 ± 2000 years old and appear to have grown in conditions that were 6°C cooler than those at present. These observations imply a drop in sea level of 60 to 80 meters. After 130,000 years, sea level began rising again in response to the major insolation maximum at 126,000 to 128,000 years ago. The early (about 140,000 years ago) start of the penultimate deglaciation, well before the peak in insolation, is consistent with the Devils Hole chronology.
The Role of Locus Coeruleus in the Regulation of Cognitive Performance
Authors: Usher Marius , Cohen Jonathan D. , Servan-Schreiber David , Rajkowski Janusz , Aston-Jones Gary
Published: July 2002

Noradrenergic locus coeruleus (LC) neurons were recorded in monkeys performing a visual discrimination task, and a computational model was developed addressing the role of the LC brain system in cognitive performance. Changes in spontaneous and stimulus-induced patterns of LC activity correlated closely with fluctuations in behavioral performance. The model explains these fluctuations in terms of changes in electrotonic coupling among LC neurons and predicts improved performance during epochs of high coupling and synchronized LC firing. Cross correlations of simultaneously recorded LC neurons confirmed this prediction, indicating that electrotonic coupling in LC may play an important role in attentional modulation and the regulation of goal-directed versus exploratory behaviors.
A Chemically Functionalizable Nanoporous Material [Cu
3
(TMA)
2
(H
2
O)
3
]

n
Authors: Chui Stephen S.-Y. , Lo Samuel M.-F. , Charmant Jonathan P. H. , Orpen A. Guy , Williams Ian D.
Published: July 2002

Although zeolites and related materials combine nanoporosity with high thermal stability, they are difficult to modify or derivatize in a systematic way. A highly porous metal coordination polymer [Cu
3
(TMA)
2
(H
2
O)
3
]

n

(where TMA is benzene-1,3,5-tricarboxylate) was formed in 80 percent yield. It has interconnected [Cu
2
(O
2
CR)
4
] units (where R is an aromatic ring), which create a three-dimensional system of channels with a pore size of 1 nanometer and an accessible porosity of about 40 percent in the solid. Unlike zeolites, the channel linings can be chemically functionalized; for example, the aqua ligands can be replaced by pyridines. Thermal gravimetric analysis and high-temperature single-crystal diffractometry indicate that the framework is stable up to 240°C.
Increased Insulin Sensitivity and Obesity Resistance in Mice Lacking the Protein Tyrosine Phosphatase-1B Gene
Authors: Elchebly Mounib , Payette Paul , Michaliszyn Eva , Cromlish Wanda , Collins Susan , Loy Ailsa Lee , Normandin Denis , Cheng Alan , Himms-Hagen Jean , Chan Chi-Chung , Ramachandran Chidambaram , Gresser Michael J. , Tremblay Michel L. , Kennedy Brian P.
Published: July 2002

Protein tyrosine phosphatase–1B (PTP-1B) has been implicated in the negative regulation of insulin signaling. Disruption of the mouse homolog of the gene encoding PTP-1B yielded healthy mice that, in the fed state, had blood glucose concentrations that were slightly lower and concentrations of circulating insulin that were one-half those of their PTP-1B
+/+
littermates. The enhanced insulin sensitivity of the PTP-1B
−/−
mice was also evident in glucose and insulin tolerance tests. The PTP-1B
−/−
mice showed increased phosphorylation of the insulin receptor in liver and muscle tissue after insulin injection in comparison to PTP-1B
+/+
mice. On a high-fat diet, the PTP-1B
−/−
and PTP-1B
+/−
mice were resistant to weight gain and remained insulin sensitive, whereas the PTP-1B
+/+
mice rapidly gained weight and became insulin resistant. These results demonstrate that PTP-1B has a major role in modulating both insulin sensitivity and fuel metabolism, thereby establishing it as a potential therapeutic target in the treatment of type 2 diabetes and obesity.
Protein Sorting by Directed Maturation of Golgi Compartments
Authors: Allan Bernard B. , Balch William E.
Published: July 2002

How does the Golgi stack mediate transport of cargo from the endoplasmic reticulum (ER) to the cell surface? A possibility is that cargo-containing vesicles derived from the ER form early Golgi compartments that then mature by retrieval of processing enzymes from later Golgi compartments. Maturation continues at terminal Golgi compartments by retrieval of transport components from the endocytic pathway to promote sorting of cargo to multiple cellular destinations. Hence, retrograde movement may integrate exocytic and endocytic pathways in eukaryotic cells and coordinate membrane flow and cargo transport through the Golgi stack.
Experimental Detection of Hydrogen Trioxide
Authors: Cacace F. , de Petris G. , Pepi F. , Troiani A.
Published: July 2002

Hydrogen trioxide (HO
3
) has long been postulated as a key intermediate in important atmospheric processes but has proved difficult to detect. The molecule was unequivocally detected in experiments based on neutralization-reionization and neutralization-reionization/collisionally activated dissociation mass spectrometry, using protonated ozone (HO
3
+
) as the charged precursor. Hydrogen trioxide is a relatively stable species and has a H-O-O-O connectivity and a lifetime exceeding 10
–6
seconds at ambient temperature.
Minimum Field Strength in Precessional Magnetization Reversal
Authors: Back C. H. , Allenspach R. , Weber W. , Parkin S. S. P. , Weller D. , Garwin E. L. , Siegmann H. C.
Published: July 2002

Ultrafast magnetic field pulses as short as 2 picoseconds are able to reverse the magnetization in thin, in-plane, magnetized cobalt films. The field pulses are applied in the plane of the film, and their direction encompasses all angles with the magnetization. At a right angle to the magnetization, maximum torque is exerted on the spins. In this geometry, a precessional magnetization reversal can be triggered by fields as small as 184 kiloamperes per meter. Applications in future ultrafast magnetic recording schemes can be foreseen.
Hf Isotope Evidence for Pelagic Sediments in the Source of Hawaiian Basalts
Authors: Blichert-Toft J. , Frey F. A. , Albarède F.
Published: July 2002

Lead, oxygen, and osmium isotopic ratios measured on Hawaiian basalts can be matched with the isotopic ratios inferred for recycled ancient oceanic crust. High-precision hafnium isotopic data for lavas from several Hawaiian volcanoes identify old pelagic sediments in their source. These observations support the recycling hypothesis, whereby the mantle source of ocean island basalts includes ancient subducted oceanic crust. Hyperbolic lead-hafnium isotopic relations among Hawaiian basalts further indicate that upper mantle material is not involved in the production of hot spot basalts.
Anti-inflammatory Properties of Cytochrome P450 Epoxygenase-Derived Eicosanoids
Authors: Node Koichi , Huo Yuqing , Ruan Xiulu , Yang Baichun , Spiecker Martin , Ley Klaus , Zeldin Darryl C. , Liao James K.
Published: July 2002

The epoxyeicosatrienoic acids (EETs) are products of cytochrome P450 epoxygenases that have vasodilatory properties similar to that of endothelium-derived hyperpolarizing factor. The cytochrome P450 isoform CYP2J2 was cloned and identified as a potential source of EETs in human endothelial cells. Physiological concentrations of EETs or overexpression of CYP2J2 decreased cytokine-induced endothelial cell adhesion molecule expression, and EETs prevented leukocyte adhesion to the vascular wall by a mechanism involving inhibition of transcription factor NF-κB and IκB kinase. The inhibitory effects of EETs were independent of their membrane-hyperpolarizing effects, suggesting that these molecules play an important nonvasodilatory role in vascular inflammation.
Spatially Inhomogeneous Metal-Insulator Transition in Doped Manganites
Authors: Fäth M. , Freisem S. , Menovsky A. A. , Tomioka Y. , Aarts J. , Mydosh J. A.
Published: July 2002

Scanning tunneling spectroscopy was used to investigate single crystals and thin films of La
1–

x

Ca

x

MnO
3
(with
x
of about 0.3), which exhibit colossal magnetoresistance. The different spectroscopic signatures of the insulating (paramagnetic) and metallic (ferromagnetic) phases enable their spatial extent to be imaged down to a lateral scale of the order of 10 nanometers. Above the bulk transition temperature
T
c
, the images show mostly insulating behavior. Below
T
c
, a phase separation is observed where inhomogeneous structures of metallic and more insulating areas coexist and are strongly field dependent in their size and structure. Insulating areas are found to persist far below
T
c
. These results suggest that the transition and the associated magnetoresistance behavior should be viewed as a percolation of metallic ferromagnetic domains.
Seismic Velocity and Density Jumps Across the 410- and 660-Kilometer Discontinuities
Authors: Shearer Peter M. , Flanagan Megan P.
Published: July 2002

The average seismic velocity and density jumps across the 410- and 660-kilometer discontinuities in the upper mantle were determined by modeling the observed range dependence in long-period seismic wave arrivals that reflect off of these interfaces. The preliminary reference Earth model (PREM) is within the computed 95 percent confidence ellipse for the 410-km discontinuity but outside the allowed jumps across the 660-kilometer discontinuity. Current pyrolite mantle models appear consistent with the constraints for the 410-kilometer discontinuity but overpredict amplitudes for the 660-kilometer reflections. The density jump across the 660-kilometer discontinuity is between 4 and 6 percent, below the PREM value of 9.3 percent commonly used in mantle convection calculations.
Sulfuric Acid on Europa and the Radiolytic Sulfur Cycle
Authors: Carlson R. W. , Johnson R. E. , Anderson M. S.
Published: July 2002

A comparison of laboratory spectra with Galileo data indicates that hydrated sulfuric acid is present and is a major component of Europa's surface. In addition, this moon's visually dark surface material, which spatially correlates with the sulfuric acid concentration, is identified as radiolytically altered sulfur polymers. Radiolysis of the surface by magnetospheric plasma bombardment continuously cycles sulfur between three forms: sulfuric acid, sulfur dioxide, and sulfur polymers, with sulfuric acid being about 50 times as abundant as the other forms. Enhanced sulfuric acid concentrations are found in Europa's geologically young terrains, suggesting that low-temperature, liquid sulfuric acid may influence geological processes.
Crystal Structure of the Ectodomain of Human Transferrin Receptor
Authors: Lawrence C. Martin , Ray Sanjoy , Babyonyshev Marina , Galluser Renate , Borhani David W. , Harrison Stephen C.
Published: July 2002

The transferrin receptor (TfR) undergoes multiple rounds of clathrin-mediated endocytosis and reemergence at the cell surface, importing iron-loaded transferrin (Tf) and recycling apotransferrin after discharge of iron in the endosome. The crystal structure of the dimeric ectodomain of the human TfR, determined here to 3.2 angstroms resolution, reveals a three-domain subunit. One domain closely resembles carboxy- and aminopeptidases, and features of membrane glutamate carboxypeptidase can be deduced from the TfR structure. A model is proposed for Tf binding to the receptor.
Origin of Magnetization Decay in Spin-Dependent Tunnel Junctions
Authors: McCartney Martha R. , Dunin-Borkowski Rafal E. , Scheinfein Michael R. , Smith David J. , Gider Savas , Parkin Stuart S. P.
Published: July 2002

Spin-dependent tunnel junctions based on magnetically hard and soft ferromagnetic layers separated by a thin insulating barrier have emerged as prime candidates for information storage. However, the observed instability of the magnetically hard reference layer, leading to magnetization decay during field cycling of the adjacent soft layer, is a serious concern for future device applications. Using Lorentz electron microscopy and micromagnetic simulations, the hard-layer decay was found to result from large fringing fields surrounding magnetic domain walls in the magnetically soft layer. The formation and motion of these walls causes statistical flipping of magnetic moments in randomly oriented grains of the hard layer, with a progressive trend toward disorder and eventual demagnetization.
Global Transposon Mutagenesis and a Minimal Mycoplasma Genome
Authors: Hutchison Clyde A. , Peterson Scott N. , Gill Steven R. , Cline Robin T. , White Owen , Fraser Claire M. , Smith Hamilton O. , Craig Venter J.
Published: July 2002

Mycoplasma genitalium
with 517 genes has the smallest gene complement of any independently replicating cell so far identified. Global transposon mutagenesis was used to identify nonessential genes in an effort to learn whether the naturally occurring gene complement is a true minimal genome under laboratory growth conditions. The positions of 2209 transposon insertions in the completely sequenced genomes of
M. genitalium
and its close relative
M. pneumoniae
were determined by sequencing across the junction of the transposon and the genomic DNA. These junctions defined 1354 distinct sites of insertion that were not lethal. The analysis suggests that 265 to 350 of the 480 protein-coding genes of
M. genitalium
are essential under laboratory growth conditions, including about 100 genes of unknown function.
Severely Reduced Female Fertility in CD9-Deficient Mice
Authors: Le Naour François , Rubinstein Eric , Jasmin Claude , Prenant Michel , Boucheix Claude
Published: July 2002

CD9 is a widely expressed cell surface molecule that belongs to the tetraspanin superfamily of proteins. The tetraspanins CD9, KAI-1/CD82, and CD63 are involved in metastasis suppression, an effect that may be related to their association with β1 integrins. Knockout mice lacking CD9 were created to evaluate the physiological importance of CD9. CD9
−/−
females displayed a severe reduction of fertility. Oocytes were ovulated but were not successfully fertilized because sperm did not fuse with the oocytes from CD9
−/−
females. Thus, CD9 appears to be essential for sperm-egg fusion, a process involving the CD9-associated integrin α6β1.
Cloning and Heterologous Expression of the Epothilone Gene Cluster
Authors: Tang Li , Shah Sanjay , Chung Loleta , Carney John , Katz Leonard , Khosla Chaitan , Julien Bryan
Published: July 2002

The polyketide epothilone is a potential anticancer agent that stabilizes microtubules in a similar manner to Taxol. The gene cluster responsible for epothilone biosynthesis in the myxobacterium
Sorangium cellulosum
was cloned and completely sequenced. It encodes six multifunctional proteins composed of a loading module, one nonribosomal peptide synthetase module, eight polyketide synthase modules, and a P450 epoxidase that converts desoxyepothilone into epothilone. Concomitant expression of these genes in the actinomycete
Streptomyces coelicolor
produced epothilones A and B.
Streptomyces coelicolor
is more amenable to strain improvement and grows about 10-fold as rapidly as the natural producer, so this heterologous expression system portends a plentiful supply of this important agent.
Temporal Trends in Deep Ocean Redfield Ratios
Authors: Pahlow Markus , Riebesell Ulf
Published: July 2002

The Redfield ratio [carbon:nitrogen:phosphorus (C:N:P)] of particle flux to the deep ocean is a key factor in marine biogeochemical cycling. Changes in oceanic carbon sequestration have been linked to variations in the Redfield ratio on geological time scales, but this ratio generally is assumed to be constant with time in the modern ocean. However, deep-water Redfield ratios in the northern hemisphere show evidence for temporal trends over the past five decades. The North Atlantic Ocean exhibits a rising N:P ratio, which may be related to increased deposition of atmospheric nitrous oxides from anthropogenic N emissions. In the North Pacific Ocean, increasing C:N and C:P ratios are accompanied by rising remineralization rates, which suggests intensified export production. Stronger export of carbon in this region may be due to enhanced bioavailability of aeolian iron. These findings imply that the biological part of the marine carbon cycle currently is not in steady state.
Mammalian Neural Stem Cells
Authors: Gage Fred H.
Published: July 2002

Neural stem cells exist not only in the developing mammalian nervous system but also in the adult nervous system of all mammalian organisms, including humans. Neural stem cells can also be derived from more primitive embryonic stem cells. The location of the adult stem cells and the brain regions to which their progeny migrate in order to differentiate remain unresolved, although the number of viable locations is limited in the adult. The mechanisms that regulate endogenous stem cells are poorly understood. Potential uses of stem cells in repair include transplantation to repair missing cells and the activation of endogenous cells to provide “self-repair.” Before the full potential of neural stem cells can be realized, we need to learn what controls their proliferation, as well as the various pathways of differentiation available to their daughter cells.
Extreme Oxygen Sensitivity of Electronic Properties of Carbon Nanotubes
Authors: Collins Philip G. , Bradley Keith , Ishigami Masa , Zettl A.
Published: July 2002

The electronic properties of single-walled carbon nanotubes are shown here to be extremely sensitive to the chemical environment. Exposure to air or oxygen dramatically influences the nanotubes' electrical resistance, thermoelectric power, and local density of states, as determined by transport measurements and scanning tunneling spectroscopy. These electronic parameters can be reversibly “tuned” by surprisingly small concentrations of adsorbed gases, and an apparently semiconducting nanotube can be converted into an apparent metal through such exposure. These results, although demonstrating that nanotubes could find use as sensitive chemical gas sensors, likewise indicate that many supposedly intrinsic properties measured on as-prepared nanotubes may be severely compromised by extrinsic air exposure effects.
DNA Damage-Induced Activation of p53 by the Checkpoint Kinase Chk2
Authors: Hirao Atsushi , Kong Young-Yun , Matsuoka Shuhei , Wakeham Andrew , Ruland Jürgen , Yoshida Hiroki , Liu Dou , Elledge Stephen J. , Mak Tak W.
Published: July 2002

Chk2 is a protein kinase that is activated in response to DNA damage and may regulate cell cycle arrest. We generated Chk2-deficient mouse cells by gene targeting. Chk2
−/−
embryonic stem cells failed to maintain γ-irradiation–induced arrest in the G
2
phase of the cell cycle. Chk2
−/−
thymocytes were resistant to DNA damage–induced apoptosis. Chk2
−/−
cells were defective for p53 stabilization and for induction of p53-dependent transcripts such as p21 in response to γ irradiation. Reintroduction of the Chk2 gene restored p53-dependent transcription in response to γ irradiation. Chk2 directly phosphorylated p53 on serine 20, which is known to interfere with Mdm2 binding. This provides a mechanism for increased stability of p53 by prevention of ubiquitination in response to DNA damage.
Warming of the World Ocean
Authors: Levitus Sydney , Antonov John I. , Boyer Timothy P. , Stephens Cathy
Published: July 2002

We quantify the interannual-to-decadal variability of the heat content (mean temperature) of the world ocean from the surface through 3000-meter depth for the period 1948 to 1998. The heat content of the world ocean increased by ∼2 × 10
23
joules between the mid-1950s and mid-1990s, representing a volume mean warming of 0.06°C. This corresponds to a warming rate of 0.3 watt per meter squared (per unit area of Earth's surface). Substantial changes in heat content occurred in the 300- to 1000-meter layers of each ocean and in depths greater than 1000 meters of the North Atlantic. The global volume mean temperature increase for the 0- to 300-meter layer was 0.31°C, corresponding to an increase in heat content for this layer of ∼10
23
joules between the mid-1950s and mid-1990s. The Atlantic and Pacific Oceans have undergone a net warming since the 1950s and the Indian Ocean has warmed since the mid-1960s, although the warming is not monotonic.
Advances in the Physics of High-Temperature Superconductivity
Authors: Orenstein J. , Millis A. J.
Published: July 2002

The high-temperature copper oxide superconductors are of fundamental and enduring interest. They not only manifest superconducting transition temperatures inconceivable 15 years ago, but also exhibit many other properties apparently incompatible with conventional metal physics. The materials expand our notions of what is possible, and compel us to develop new experimental techniques and theoretical concepts. This article provides a perspective on recent developments and their implications for our understanding of interacting electrons in metals.
Localization of a Short-Term Memory in
Drosophila
Authors: Zars T. , Fischer † M. , Schulz R. , Heisenberg M.
Published: July 2002

Memories are thought to be due to lasting synaptic modifications in the brain. The search for memory traces has relied predominantly on determining regions that are necessary for the process. However, a more informative approach is to define the smallest sufficient set of brain structures. The
rutabaga
adenylyl cyclase, an enzyme that is ubiquitously expressed in the
Drosophila
brain and that mediates synaptic plasticity, is needed exclusively in the Kenyon cells of the mushroom bodies for a component of olfactory short-term memory. This demonstrates that synaptic plasticity in a small brain region can be sufficient for memory formation.
Large-Scale Thermal Events in the Solar Nebula: Evidence from Fe,Ni Metal Grains in Primitive Meteorites
Authors: Meibom Anders , Desch Steven J. , Krot Alexander N. , Cuzzi Jeffrey N. , Petaev Michael I. , Wilson Lionel , Keil Klaus
Published: July 2002

Chemical zoning patterns in some iron, nickel metal grains from CH carbonaceous chondrites imply formation at temperatures from 1370 to 1270 kelvin by condensation from a solar nebular gas cooling at a rate of ∼0.2 kelvin per hour. This cooling rate requires a large-scale thermal event in the nebula, in contrast to the localized, transient heating events inferred for chondrule formation. In our model, mass accretion through the protoplanetary disk caused large-scale evaporation of precursor dust near its midplane inside of a few astronomical units. Gas convectively moved from the midplane to cooler regions above it, and the metal grains condensed in these parcels of rising gas.
Coalescence of Single-Walled Carbon Nanotubes
Authors: Terrones M. , Terrones H. , Banhart F. , Charlier J.-C. , Ajayan P. M.
Published: July 2002

The coalescence of single-walled nanotubes is studied in situ under electron irradiation at high temperature in a transmission electron microscope. The merging process is investigated at the atomic level, using tight-binding molecular dynamics and Monte Carlo simulations. Vacancies induce coalescence via a zipper-like mechanism, imposing a continuous reorganization of atoms on individual tube lattices along adjacent tubes. Other topological defects induce the polymerization of tubes. Coalescence seems to be restricted to tubes with the same chirality, explaining the low frequency of occurrence of this event.
High Frequency of Hypermutable
Pseudomonas aeruginosa
in Cystic Fibrosis Lung Infection
Authors: Oliver Antonio , Cantón Rafael , Campo Pilar , Baquero Fernando , Blázquez Jesús
Published: July 2002

The lungs of cystic fibrosis (CF) patients are chronically infected for years by one or a few lineages of
Pseudomonas aeruginosa.
These bacterial populations adapt to the highly compartmentalized and anatomically deteriorating lung environment of CF patients, as well as to the challenges of the immune defenses and antibiotic therapy. These selective conditions are precisely those that recent theoretical studies predict for the evolution of mechanisms that augment the rate of variation. Determination of spontaneous mutation rates in 128
P. aeruginosa
isolates from 30 CF patients revealed that 36% of the patients were colonized by a hypermutable (mutator) strain that persisted for years in most patients. Mutator strains were not found in 75 non-CF patients acutely infected with
P. aeruginosa
. This investigation also reveals a link between high mutation rates in vivo and the evolution of antibiotic resistance.
Role for Rapid Dendritic Protein Synthesis in Hippocampal mGluR-Dependent Long-Term Depression
Authors: Huber Kimberly M. , Kayser Matthew S. , Bear Mark F.
Published: July 2002

A hippocampal pyramidal neuron receives more than 10
4
excitatory glutamatergic synapses. Many of these synapses contain the molecular machinery for messenger RNA translation, suggesting that the protein complement (and thus function) of each synapse can be regulated on the basis of activity. Here, local postsynaptic protein synthesis, triggered by synaptic activation of metabotropic glutamate receptors, was found to modify synaptic transmission within minutes.
Electron-Induced Inversion of Helical Chirality in Copper Complexes of
N
,
N
-Dialkylmethionines
Authors: Zahn Steffen , Canary James W.
Published: July 2002

Stereodynamic complexes of copper were found to undergo inversion of a helical chiral element upon oxidation or reduction. The amino acid methionine was derivatized by the attachment of two chromophores to the nitrogen atom. The resultant ligands formed stable complexes with Cu
I
and Cu
II
salts. For a derivative of a given absolute chirality, the complexes afford nearly mirror image circular dichroism spectra. The spectral changes originate from reorientation of the nitrogen-attached chromophores due to a conformation interconversion driven by the exchange of a carboxylate for a sulfide ligand. The electrically induced chirality inversion coupled with strong interactions with polarized light is unique and may lead to novel chiral molecular devices.
A Ferroelectric Liquid Crystal Conglomerate Composed of Racemic Molecules
Authors: Walba David M. , Körblova Eva , Shao Renfan , Maclennan Joseph E. , Link Darren R. , Glaser Matthew A. , Clark Noel A.
Published: July 2002

We describe the design and synthesis of a ferroelectric liquid crystal composed of racemic molecules. The ferroelectric polarization results from spontaneous polar symmetry breaking in a fluid smectic. The ferroelectric phase is also chiral, resulting in the formation of a mixture of macroscopic domains of either handedness at the isotropic-to-liquid crystal phase transition. This smectic liquid crystal is thus a fluid conglomerate. Detailed investigation of the electrooptic and polarization current behavior within individual domains in liquid crystal cells shows the thermodynamically stable structure to be a uniformly tilted smectic bow-phase (banana phase), with all layer pairs homochiral and ferroelectric (SmC
S
P
F
).
Isotopic Dating of Strain Fringe Increments: Duration and Rates of Deformation in Shear Zones
Authors: Müller Wolfgang , Aerden Domingo , Halliday Alex N.
Published: July 2002

The time scales over which deformation in the Earth's crust remains localized in shear zones are poorly known, as are the associated strain rates. We have determined the longevity and rates of deformation using rubidium-strontium (Rb-Sr) microsampling dating of increments of fibrous strain fringes from a Pyrenean shear zone. The fibers grew quasi-continuously through a protracted deformation history between 87 and 50 million years ago, over a period comparable to that of an orogeny. During a short interval between 66 and 62 million years, a rise in strain rate from 1.1 × 10
−15
to 7.7 × 10
−15
seconds
−1
occurred. This acceleration correlates with an abrupt change in fiber-growth direction and a stress-field inversion from gravitational collapse to renewed horizontal crustal shortening.
Cooperative Regulation of Cell Polarity and Growth by
Drosophila
Tumor Suppressors
Authors: Bilder David , Li Min , Perrimon Norbert
Published: July 2002

Loss of cell polarity and tissue architecture are characteristics of malignant cancers derived from epithelial tissues. We provide evidence from
Drosophila
that a group of membrane-associated proteins act in concert to regulate both epithelial structure and cell proliferation. Scribble (Scrib) is a cell junction–localized protein required for polarization of embryonic and, as demonstrated here, imaginal disc and follicular epithelia. We show that the tumor suppressors
lethal giant larvae
(
lgl
) and
discs-large
(
dlg
) have identical effects on all three epithelia, and that
scrib
also acts as a tumor suppressor. Scrib and Dlg colocalize and overlap with Lgl in epithelia; activity of all three genes is required for cortical localization of Lgl and junctional localization of Scrib and Dlg.
scrib
,
dlg
, and
lgl
show strong genetic interactions. Our data indicate that the three tumor suppressors act together in a common pathway to regulate cell polarity and growth control.
Structure of the Cytoplasmic β Subunit--T1 Assembly of Voltage-Dependent K
+
Channels
Authors: Gulbis Jacqueline M. , Zhou Ming , Mann Sabine , MacKinnon Roderick
Published: July 2002

The structure of the cytoplasmic assembly of voltage-dependent K
+
channels was solved by x-ray crystallography at 2.1 angstrom resolution. The assembly includes the cytoplasmic (T1) domain of the integral membrane α subunit together with the oxidoreductase β subunit in a fourfold symmetric T1
4
β
4
complex. An electrophysiological assay showed that this complex is oriented with four T1 domains facing the transmembrane pore and four β subunits facing the cytoplasm. The transmembrane pore communicates with the cytoplasm through lateral, negatively charged openings above the T1
4
β
4
complex. The inactivation peptides of voltage-dependent K
+
channels reach their site of action by entering these openings.
fw2.2
: A Quantitative Trait Locus Key to the Evolution of Tomato Fruit Size
Authors: Frary Anne , Nesbitt T. Clint , Frary Amy , Grandillo Silvana , Knaap Esther van der , Cong Bin , Liu Jiping , Meller Jaroslaw , Elber Ron , Alpert Kevin B. , Tanksley Steven D.
Published: July 2002

Domestication of many plants has correlated with dramatic increases in fruit size. In tomato, one quantitative trait locus (QTL),
fw2.2
, was responsible for a large step in this process. When transformed into large-fruited cultivars, a cosmid derived from the
fw2.2
region of a small-fruited wild species reduced fruit size by the predicted amount and had the gene action expected for
fw2.2
. The cause of the QTL effect is a single gene,
ORFX
, that is expressed early in floral development, controls carpel cell number, and has a sequence suggesting structural similarity to the human oncogene c-H-
ras
p21. Alterations in fruit size, imparted by
fw2.2
alleles, are most likely due to changes in regulation rather than in the sequence and structure of the encoded protein.
ORCA3, a Jasmonate-Responsive Transcriptional Regulator of Plant Primary and Secondary Metabolism
Authors: van der Fits Leslie , Memelink Johan
Published: July 2002

Biosynthesis of many classes of secondary metabolites in plants is induced by the stress hormone jasmonate. The gene for ORCA3, a jasmonate-responsive APETALA2 (AP2)-domain transcription factor from
Catharanthus roseus
, was isolated by transferred DNA activation tagging.
Orca3
overexpression resulted in enhanced expression of several metabolite biosynthetic genes and, consequently, in increased accumulation of terpenoid indole alkaloids. Regulation of metabolite biosynthetic genes by jasmonate-responsive AP2-domain transcription factors may link plant stress responses to changes in metabolism.
Crystal Structure of Rhodopsin: A G Protein-Coupled Receptor
Authors: Palczewski Krzysztof , Kumasaka Takashi , Hori Tetsuya , Behnke Craig A. , Motoshima Hiroyuki , Fox Brian A. , Trong Isolde Le , Teller David C. , Okada Tetsuji , Stenkamp Ronald E. , Yamamoto Masaki , Miyano Masashi
Published: July 2002

Heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptors (GPCRs) respond to a variety of different external stimuli and activate G proteins. GPCRs share many structural features, including a bundle of seven transmembrane α helices connected by six loops of varying lengths. We determined the structure of rhodopsin from diffraction data extending to 2.8 angstroms resolution. The highly organized structure in the extracellular region, including a conserved disulfide bridge, forms a basis for the arrangement of the seven-helix transmembrane motif. The ground-state chromophore, 11-
cis
-retinal, holds the transmembrane region of the protein in the inactive conformation. Interactions of the chromophore with a cluster of key residues determine the wavelength of the maximum absorption. Changes in these interactions among rhodopsins facilitate color discrimination. Identification of a set of residues that mediate interactions between the transmembrane helices and the cytoplasmic surface, where G-protein activation occurs, also suggests a possible structural change upon photoactivation.