bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrapermeable, Reverse-Selective Nanocomposite Membranes
Authors: Merkel T. C. , Freeman B. D. , Spontak R. J. , He Z. , Pinnau I. , Meakin P. , Hill A. J.
Published: July 2002

Polymer nanocomposites continue to receive tremendous attention for application in areas such as microelectronics, organic batteries, optics, and catalysis. We have discovered that physical dispersion of nonporous, nanoscale, fumed silica particles in glassy amorphous poly(4-methyl-2-pentyne) simultaneously and surprisingly enhances both membrane permeability and selectivity for large organic molecules over small permanent gases. These highly unusual property enhancements, in contrast to results obtained in conventional filled polymer systems, reflect fumed silica–induced disruption of polymer chain packing and an accompanying subtle increase in the size of free volume elements through which molecular transport occurs, as discerned by positron annihilation lifetime spectroscopy. Such nanoscale hybridization represents an innovative means to tune the separation properties of glassy polymeric media through systematic manipulation of molecular packing.
Structure of a Cofactor-Deficient Nitrogenase MoFe Protein
Authors: Schmid Benedikt , Ribbe Markus W. , Einsle Oliver , Yoshida Mika , Thomas Leonard M. , Dean Dennis R. , Rees Douglas C. , Burgess Barbara K.
Published: July 2002

One of the most complex biosynthetic processes in metallobiochemistry is the assembly of nitrogenase, the key enzyme in biological nitrogen fixation. We describe here the crystal structure of an iron-molybdenum cofactor–deficient form of the nitrogenase MoFe protein, into which the cofactor is inserted in the final step of MoFe protein assembly. The MoFe protein folds as a heterotetramer containing two copies each of the homologous α and β subunits. In this structure, one of the three α subunit domains exhibits a substantially changed conformation, whereas the rest of the protein remains essentially unchanged. A predominantly positively charged funnel is revealed; this funnel is of sufficient size to accommodate insertion of the negatively charged cofactor.
Specialized DNA Polymerases, Cellular Survival, and the Genesis of Mutations
Authors: Friedberg Errol C. , Wagner Robert , Radman Miroslav
Published: July 2002

Cell death caused by arrested replication of damaged or structurally altered DNA can be avoided in prokaryotic and eukaryotic cells by multiple DNA polymerases that are specialized to bypass DNA damage. Some of these polymerases perform such translesion DNA synthesis of specific types of damage with high genetic fidelity. However, they exhibit greatly reduced fidelity when they operate on undamaged DNA or on DNA with lesions that are (apparently) not cognate substrates. The low fidelity of some of these specialized polymerases when copying undamaged DNA may be physiologically functional, including generating immunoglobulin diversity.
Alteration of Lymphocyte Trafficking by Sphingosine-1-Phosphate Receptor Agonists
Authors: Mandala Suzanne , Hajdu Richard , Bergstrom James , Quackenbush Elizabeth , Xie Jenny , Milligan James , Thornton Rosemary , Shei Gan-Ju , Card Deborah , Keohane CarolAnn , Rosenbach Mark , Hale Jeffrey , Lynch Christopher L. , Rupprecht Kathleen , Parsons William , Rosen Hugh
Published: July 2002

Blood lymphocyte numbers, essential for the development of efficient immune responses, are maintained by recirculation through secondary lymphoid organs. We show that lymphocyte trafficking is altered by the lysophospholipid sphingosine-1-phosphate (S1P) and by a phosphoryl metabolite of the immunosuppressive agent FTY720. Both species were high-affinity agonists of at least four of the five S1P receptors. These agonists produce lymphopenia in blood and thoracic duct lymph by sequestration of lymphocytes in lymph nodes, but not spleen. S1P receptor agonists induced emptying of lymphoid sinuses by retention of lymphocytes on the abluminal side of sinus-lining endothelium and inhibition of egress into lymph. Inhibition of lymphocyte recirculation by activation of S1P receptors may result in therapeutically useful immunosuppression.
Homologies in Leaf Form Inferred from
KNOXI
Gene Expression During Development
Authors: Bharathan Geeta , Goliber Thomas E. , Moore Christopher , Kessler Sharon , Pham Thinh , Sinha Neelima R.
Published: July 2002

KNOTTEDI-like homeobox (KNOXI) genes regulate development of the leaf from the shoot apical meristem (SAM) and may regulate leaf form. We examined KNOXI expression in SAMs of various vascular plants and found that KNOXI expression correlated with complex leaf primordia. However, complex primordia may mature into simple leaves. Therefore, not all simple leaves develop similarly, and final leaf morphology may not be an adequate predictor of homology.
Temporal Specificity in the Cortical Plasticity of Visual Space Representation
Authors: Fu Yu-Xi , Djupsund Kaj , Gao Hongfeng , Hayden Benjamin , Shen Kai , Dan Yang
Published: July 2002

The circuitry and function of mammalian visual cortex are shaped by patterns of visual stimuli, a plasticity likely mediated by synaptic modifications. In the adult cat, asynchronous visual stimuli in two adjacent retinal regions controlled the relative spike timing of two groups of cortical neurons with high precision. This asynchronous pairing induced rapid modifications of intracortical connections and shifts in receptive fields. These changes depended on the temporal order and interval between visual stimuli in a manner consistent with spike timing–dependent synaptic plasticity. Parallel to the cortical modifications found in the cat, such asynchronous visual stimuli also induced shifts in human spatial perception.
Evidence-Based Health Policy—Lessons from the Global Burden of Disease Study
Authors: Murray Christopher J. L. , Lopez Alan D.
Published: July 2002

The Global Burden of Disease Study, a comprehensive regional and global assessment of mortality and disability from 107 diseases and injuries and 10 risk factors, is an example of an evidence-based input to public health policy debate. The study, which includes projections of the burden through the year 2020, uses the disability-adjusted life year as a composite measure of years of life lost due to premature mortality and years lived with disability. Future patterns of death and disability are likely to change dramatically because of aging of the world's population, the epidemic of tobacco-related disease, the human immunodeficiency virus epidemic, and the likely reduction in death rates from communicable diseases in children.
Nested Retrotransposons in the Intergenic Regions of the Maize Genome
Authors: SanMiguel Phillip , Tikhonov Alexander , Jin Young-Kwan , Motchoulskaia Natasha , Zakharov Dmitrii , Melake-Berhan Admasu , Springer Patricia S. , Edwards Keith J. , Lee Michael , Avramova Zoya , Bennetzen Jeffrey L.
Published: July 2002

The relative organization of genes and repetitive DNAs in complex eukaryotic genomes is not well understood. Diagnostic sequencing indicated that a 280-kilobase region containing the maize
Adh1
-F and u22 genes is composed primarily of retrotransposons inserted within each other. Ten retroelement families were discovered, with reiteration frequencies ranging from 10 to 30,000 copies per haploid genome. These retrotransposons accounted for more than 60 percent of the
Adh1
-F region and at least 50 percent of the nuclear DNA of maize. These elements were largely intact and are dispersed throughout the gene-containing regions of the maize genome.
The Molecular Biology of Axon Guidance
Authors: Tessier-Lavigne Marc , Goodman Corey S.
Published: July 2002

Neuronal growth cones navigate over long distances along specific pathways to find their correct targets. The mechanisms and molecules that direct this pathfinding are the topics of this review. Growth cones appear to be guided by at least four different mechanisms: contact attraction, chemoattraction, contact repulsion, and chemorepulsion. Evidence is accumulating that these mechanisms act simultaneously and in a coordinated manner to direct pathfinding and that they are mediated by mechanistically and evolutionarily conserved ligand-receptor systems.
An Economics Approach to Hard Computational Problems
Authors: Huberman Bernardo A. , Lukose Rajan M. , Hogg Tad
Published: July 2002

A general method for combining existing algorithms into new programs that are unequivocally preferable to any of the component algorithms is presented. This method, based on notions of risk in economics, offers a computational portfolio design procedure that can be used for a wide range of problems. Tested by solving a canonical NP-complete problem, the method can be used for problems ranging from the combinatorics of DNA sequencing to the completion of tasks in environments with resource contention, such as the World Wide Web.
Visions of Black Holes
Authors: Glanz James
Published: July 2002

CHICAGO
—Black-hole theorists are leaving present observations far behind as they conceive and study strange variants of these superdense, light-swallowing objects, confident that observers will eventually catch up. They have conjured up donut-shaped black holes, discerned clues toa fundamental graininess of space-time in the properties of black holes, and—thanks to Hawking's latest brainstorm—contemplated the possibility that invisible black holes might be gobbling information right under our noses.
The Breakdown of Olivine to Perovskite and Magnesiowüstite
Authors: Wang Yanbin , Martinez Isabelle , Guyot François , Liebermann Robert C.
Published: July 2002

San Carlos olivine crystals under laboratory conditions of 26 gigapascals and 973 to 1473 kelvin (conditions typical of subducted slabs at a depth of 720 kilometers) for periods of a few minutes to 19 hours transformed to the phase assemblage of perovskite and magnesiowüstite in two stages: (i) the oxygen sublattice transformed into a cubic close-packed lattice, forming a metastable spinelloid, and (ii) at higher temperatures or longer run durations, this spinelloid broke down to perovskite and magnesiowüstite by redistributing silicon and magnesium while maintaining the general oxygen framework. The breakdown was characterized by a blocking temperature of 1000 kelvin, below which olivine remained metastable, and by rapid kinetics once the reaction was activated.
Alzheimer's Disease--Genotypes, Phenotype, and Treatments
Authors: Selkoe Dennis J.
Published: July 2002

What causes Alzheimer's disease? Selkoe's Perspective reviews recent research identifying four different genetic causes of Alzheimer's disease and suggests that all four point toward the deposition of amyloid beta in the brain as the initial trigger for the disease.
The Release of Cytochrome c from Mitochondria: A Primary Site for Bcl-2 Regulation of Apoptosis
Authors: Kluck Ruth M. , Bossy-Wetzel Ella , Green Douglas R. , Newmeyer Donald D.
Published: July 2002

In a cell-free apoptosis system, mitochondria spontaneously released cytochrome c, which activated DEVD-specific caspases, leading to fodrin cleavage and apoptotic nuclear morphology. Bcl-2 acted in situ on mitochondria to prevent the release of cytochrome c and thus caspase activation. During apoptosis in intact cells, cytochrome c translocation was similarly blocked by Bcl-2 but not by a caspase inhibitor, zVAD-fmk. In vitro, exogenous cytochrome c bypassed the inhibitory effect of Bcl-2. Cytochrome c release was unaccompanied by changes in mitochondrial membrane potential. Thus, Bcl-2 acts to inhibit cytochrome c translocation, thereby blocking caspase activation and the apoptotic process.
Marrow Stromal Cells as Stem Cells for Nonhematopoietic Tissues
Authors: Prockop Darwin J.
Published: July 2002

Marrow stromal cells can be isolated from other cells in marrow by their tendency to adhere to tissue culture plastic. The cells have many of the characteristics of stem cells for tissues that can roughly be defined as mesenchymal, because they can be differentiated in culture into osteoblasts, chondrocytes, adipocytes, and even myoblasts. Therefore, marrow stromal cells present an intriguing model for examining the differentiation of stem cells. Also, they have several characteristics that make them potentially useful for cell and gene therapy.
A Newly Discovered Column in the Hieroglyphic Text on La Mojarra Stela 1: A Test of the Epi-Olmec Decipherment
Authors: Justeson John S. , Kaufman Terrence
Published: July 2002

A badly weathered column of hieroglyphs was discovered in November 1995 on the side of Stela 1 from La Mojarra in southern Veracruz, Mexico. Most of the signs in this column have now been identified by nighttime examination under artificial lighting, making possible a nearly complete transcription and translation of this column. This data expands the modest corpus of epi-Olmec hieroglyphic texts and confirms various aspects of the decipherment of the epi-Olmec script.
Murine Model of Niemann-Pick C Disease: Mutation in a Cholesterol Homeostasis Gene
Authors: Loftus Stacie K. , Morris Jill A. , Carstea Eugene D. , Gu Jessie Z. , Cummings Christiano , Brown Anthony , Ellison Jane , Ohno Kousaku , Rosenfeld Melissa A. , Tagle Danilo A. , Pentchev Peter G. , Pavan William J.
Published: July 2002

An integrated human-mouse positional candidate approach was used to identify the gene responsible for the phenotypes observed in a mouse model of Niemann-Pick type C (NP-C) disease. The predicted murine NPC1 protein has sequence homology to the putative transmembrane domains of the Hedgehog signaling molecule Patched, to the cholesterol-sensing regions of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and SREBP cleavage-activating protein (SCAP), and to the NPC1 orthologs identified in human, the nematode
Caenorhabditis elegans
, and the yeast
Saccharomyces cerevisiae
. The mouse model may provide an important resource for studying the role of NPC1 in cholesterol homeostasis and neurodegeneration and for assessing the efficacy of new drugs for NP-C disease.
A Cytoplasmic Inhibitor of the JNK Signal Transduction Pathway
Authors: Dickens Martin , Rogers Jeffrey S. , Cavanagh Julie , Raitano Art , Xia Zhengui , Halpern Jocelyn R. , Greenberg Michael E. , Sawyers Charles L. , Davis Roger J.
Published: July 2002

The c-Jun amino-terminal kinase (JNK) is a member of the stress-activated group of mitogen-activated protein (MAP) kinases that are implicated in the control of cell growth. A murine cytoplasmic protein that binds specifically to JNK [the JNK interacting protein-1 (JIP-1)] was characterized and cloned. JIP-1 caused cytoplasmic retention of JNK and inhibition of JNK-regulated gene expression. In addition, JIP-1 suppressed the effects of the JNK signaling pathway on cellular proliferation, including transformation by the
Bcr-Abl
oncogene. This analysis identifies JIP-1 as a specific inhibitor of the JNK signal transduction pathway and establishes protein targeting as a mechanism that regulates signaling by stress-activated MAP kinases.
Functional Role of High-Affinity Anandamide Transport, as Revealed by Selective Inhibition
Authors: Beltramo M. , Stella N. , Calignano A. , Lin S. Y. , Makriyannis A. , Piomelli D.
Published: July 2002

Anandamide, an endogenous ligand for central cannabinoid receptors, is released from neurons on depolarization and rapidly inactivated. Anandamide inactivation is not completely understood, but it may occur by transport into cells or by enzymatic hydrolysis. The compound
N
-(4-hydroxyphenyl)arachidonylamide (AM404) was shown to inhibit high-affinity anandamide accumulation in rat neurons and astrocytes in vitro, an indication that this accumulation resulted from carrier-mediated transport. Although AM404 did not activate cannabinoid receptors or inhibit anandamide hydrolysis, it enhanced receptor-mediated anandamide responses in vitro and in vivo. The data indicate that carrier-mediated transport may be essential for termination of the biological effects of anandamide, and may represent a potential drug target.
Conservation of the Chk1 Checkpoint Pathway in Mammals: Linkage of DNA Damage to Cdk Regulation Through Cdc25
Authors: Sanchez Yolanda , Wong Calvin , Thoma Richard S. , Richman Ron , Wu Zhiqi , Piwnica-Worms Helen , Elledge Stephen J.
Published: July 2002

In response to DNA damage, mammalian cells prevent cell cycle progression through the control of critical cell cycle regulators. A human gene was identified that encodes the protein Chk1, a homolog of the
Schizosaccharomyces pombe
Chk1 protein kinase, which is required for the DNA damage checkpoint. Human Chk1 protein was modified in response to DNA damage. In vitro Chk1 bound to and phosphorylated the dual-specificity protein phosphatases Cdc25A, Cdc25B, and Cdc25C, which control cell cycle transitions by dephosphorylating cyclin-dependent kinases. Chk1 phosphorylates Cdc25C on serine-216. As shown in an accompanying paper by Peng
et al
. in this issue, serine-216 phosphorylation creates a binding site for 14-3-3 protein and inhibits function of the phosphatase. These results suggest a model whereby in response to DNA damage, Chk1 phosphorylates and inhibits Cdc25C, thus preventing activation of the Cdc2–cyclin B complex and mitotic entry.
Regulation of Human Placental Development by Oxygen Tension
Authors: Genbacev Olga , Zhou Yan , Ludlow John W. , Fisher Susan J.
Published: July 2002

Cytotrophoblasts, specialized placental cells, proliferate early in pregnancy and then differentiate into tumor-like cells that establish blood flow to the placenta by invading the uterus and its vasculature. In this study, cytotrophoblasts cultured under hypoxic conditions (2 percent oxygen), mimicking the environment near the uterine surface before 10 weeks of gestation, continued proliferating and differentiated poorly. When cultured in 20 percent oxygen, mimicking the environment near uterine arterioles, the cells stopped proliferating and differentiated normally. Thus, oxygen tension determines whether cytotrophoblasts proliferate or invade, thereby regulating placental growth and cellular architecture.
Cichlid Fish Diversity Threatened by Eutrophication That Curbs Sexual Selection
Authors: Seehausen Ole , Alphen Jacques J. M. van , Witte Frans
Published: July 2002

Cichlid fish species of Lake Victoria can interbreed without loss of fertility but are sexually isolated by mate choice. Mate choice is determined on the basis of coloration, and strong assortative mating can quickly lead to sexual isolation of color morphs. Dull fish coloration, few color morphs, and low species diversity are found in areas that have become turbid as a result of recent eutrophication. By constraining color vision, turbidity interferes with mate choice, relaxes sexual selection, and blocks the mechanism of reproductive isolation. In this way, human activities that increase turbidity destroy both the mechanism of diversification and that which maintains diversity.
Total Solar Irradiance Trend During Solar Cycles 21 and 22
Authors: Willson Richard C.
Published: July 2002

Results from Active Cavity Radiometer Irradiance Monitor (ACRIM) experiments show an upward trend in total solar irradiance of 0.036 percent per decade between the minima of solar cycles 21 and 22. The trend follows the increasing solar activity of recent decades and, if sustained, could raise global temperatures. Trends of total solar irradiance near this rate have been implicated as causal factors in climate change on century to millennial time scales.
The Mechanism of a C-H Bond Activation Reaction in Room-Temperature Alkane Solution
Authors: Bromberg Steven E. , Yang Haw , Asplund Matthew C. , Lian T. , McNamara B. K. , Kotz K. T. , Yeston J. S. , Wilkens M. , Frei H. , Bergman Robert G. , Harris C. B.
Published: July 2002

Chemical reactions that break alkane carbon-hydrogen (C–H) bonds are normally carried out under conditions of high temperature and pressure because these bonds are extremely strong (∼100 kilocalories per mole), but certain metal complexes can activate C–H bonds in alkane solution under the mild conditions of room temperature and pressure. Time-resolved infrared experiments probing the initial femtosecond dynamics through the nano- and microsecond kinetics to the final stable products have been used to generate a detailed picture of the C–H activation reaction. Structures of all of the intermediates involved in the reaction of Tp*Rh(CO)
2
(Tp* = HB–Pz
3
*, Pz* = 3,5-dimethylpyrazolyl) in alkane solution have been identified and assigned, and energy barriers for each reaction step from solvation to formation of the final alkyl hydride product have been estimated from transient lifetimes.
Structure-Based Analysis of Catalysis and Substrate Definition in the HIT Protein Family
Authors: Lima Christopher D. , Klein Michael G. , Hendrickson Wayne A.
Published: July 2002

The histidine triad (HIT) protein family is among the most ubiquitous and highly conserved in nature, but a biological activity has not yet been identified for any member of the HIT family. Fragile histidine triad protein (FHIT) and protein kinase C interacting protein (PKCI) were used in a structure-based approach to elucidate characteristics of in vivo ligands and reactions. Crystallographic structures of apo, substrate analog, pentacovalent transition-state analog, and product states of both enzymes reveal a catalytic mechanism and define substrate characteristics required for catalysis, thus unifying the HIT family as nucleotidyl hydrolases, transferases, or both. The approach described here may be useful in identifying structure-function relations between protein families identified through genomics.
Gene Families: The Taxonomy of Protein Paralogs and Chimeras
Authors: Henikoff Steven , Greene Elizabeth A. , Pietrokovski Shmuel , Bork Peer , Attwood Teresa K. , Hood Leroy
Published: July 2002

Ancient duplications and rearrangements of protein-coding segments have resulted in complex gene family relationships. Duplications can be tandem or dispersed and can involve entire coding regions or modules that correspond to folded protein domains. As a result, gene products may acquire new specificities, altered recognition properties, or modified functions. Extreme proliferation of some families within an organism, perhaps at the expense of other families, may correspond to functional innovations during evolution. The underlying processes are still at work, and the large fraction of human and other genomes consisting of transposable elements may be a manifestation of the evolutionary benefits of genomic flexibility.
Sec-Independent Protein Translocation by the Maize Hcf106 Protein
Authors: Settles A. Mark , Yonetani Ann , Baron Aimee , Bush Daniel R. , Cline Kenneth , Martienssen Rob
Published: July 2002

The bacterial Sec and signal recognition particle (
ffh
-dependent) protein translocation mechanisms are conserved between prokaryotes and higher plant chloroplasts. A third translocation mechanism in chloroplasts [the proton concentration difference (ΔpH) pathway] was previously thought to be unique. The
hcf106
mutation of maize disrupts the localization of proteins transported through this ΔpH pathway in isolated chloroplasts. The
Hcf106
gene encodes a receptor-like thylakoid membrane protein, which shows homology to open reading frames from all completely sequenced bacterial genomes, which suggests that the ΔpH pathway has been conserved since the endosymbiotic origin of chloroplasts. Thus, the third protein translocation pathway, of which HCF106 is a component, is found in both bacteria and plants.
Independent Photoreceptive Circadian Clocks Throughout
Drosophila
Authors: Plautz Jeffrey D. , Kaneko Maki , Hall Jeffrey C. , Kay Steve A.
Published: July 2002

Transgenic
Drosophila
that expressed either luciferase or green fluorescent protein driven from the promoter of the clock gene
period
were used to monitor the circadian clock in explanted head, thorax, and abdominal tissues. The tissues (including sensory bristles in the leg and wing) showed rhythmic bioluminescence, and the rhythms could be reset by light. The photoreceptive properties of the explanted tissues indicate that unidentified photoreceptors are likely to contribute to photic signal transduction to the clock. These results show that autonomous circadian oscillators are present throughout the body, and they suggest that individual cells in
Drosophila
are capable of supporting their own independent clocks.
Specific Inhibition of Stat3 Signal Transduction by PIAS3
Authors: Chung Chan D. , Liao Jiayu , Liu Bin , Rao Xiaoping , Jay Philippe , Berta Philippe , Shuai Ke
Published: July 2002

The signal transducer and activator of transcription–3 (Stat3) protein is activated by the interleukin 6 (IL-6) family of cytokines, epidermal growth factor, and leptin. A protein named PIAS3 (protein inhibitor of activated STAT) that binds to Stat3 was isolated and characterized. The association of PIAS3 with Stat3 in vivo was only observed in cells stimulated with ligands that cause the activation of Stat3. PIAS3 blocked the DNA-binding activity of Stat3 and inhibited Stat3-mediated gene activation. Although Stat1 is also phosphorylated in response to IL-6, PIAS3 did not interact with Stat1 or affect its DNA-binding or transcriptional activity. The results indicate that PIAS3 is a specific inhibitor of Stat3.
Human Factor IX Transgenic Sheep Produced by Transfer of Nuclei from Transfected Fetal Fibroblasts
Authors: Schnieke Angelika E. , Kind Alexander J. , Ritchie William A. , Mycock Karen , Scott Angela R. , Ritchie Marjorie , Wilmut Ian , Colman Alan , Campbell Keith H. S.
Published: July 2002

Ovine primary fetal fibroblasts were cotransfected with a neomycin resistance marker gene (
neo
) and a human coagulation factor IX genomic construct designed for expression of the encoded protein in sheep milk. Two cloned transfectants and a population of neomycin (G418)–resistant cells were used as donors for nuclear transfer to enucleated oocytes. Six transgenic lambs were liveborn: Three produced from cloned cells contained factor IX and
neo
transgenes, whereas three produced from the uncloned population contained the marker gene only. Somatic cells can therefore be subjected to genetic manipulation in vitro and produce viable animals by nuclear transfer. Production of transgenic sheep by nuclear transfer requires fewer than half the animals needed for pronuclear microinjection.
Spin-Transition Polymers: From Molecular Materials Toward Memory Devices
Authors: Kahn O. , Martinez C. Jay
Published: July 2002

Some 3d
n
(4 ≤ n ≤ 7) transition metal compounds exhibit a cooperative transition between a low-spin (LS) and a high-spin (HS) state. This transition is abrupt and occurs with a thermal hysteresis, which confers a memory effect on the system. The intersite interactions and thus the cooperativity are magnified in polymeric compounds such as [Fe(Rtrz)
3
]A
2
·nH
2
O in which the Fe
2+
ions are triply bridged by 4-R-substituted-1,2,4-triazole molecules. Moreover, in these compounds, the spin transition is accompanied by a well-pronounced change of color between violet in the LS state and white in the HS state. The transition temperatures of these materials can be fine tuned, using an approach based on the concept of a molecular alloy. In particular, it is possible to design a compound for which room temperature falls in the middle of the thermal hysteresis loop. These materials have many potential applications, for example, as temperature sensors, as active elements of various types of displays, and in information storage and retrieval.
Sensitivity of Boreal Forest Carbon Balance to Soil Thaw
Authors: Goulden M. L. , Wofsy S. C. , Harden J. W. , Trumbore S. E. , Crill P. M. , Gower S. T. , Fries T. , Daube B. C. , Fan S.-M. , Sutton D. J. , Bazzaz A. , Munger J. W.
Published: July 2002

We used eddy covariance; gas-exchange chambers; radiocarbon analysis; wood, moss, and soil inventories; and laboratory incubations to measure the carbon balance of a 120-year-old black spruce forest in Manitoba, Canada. The site lost 0.3 ± 0.5 metric ton of carbon per hectare per year (ton C ha
−1
year
−1
) from 1994 to 1997, with a gain of 0.6 ± 0.2 ton C ha
−1
year
−1
in moss and wood offset by a loss of 0.8 ± 0.5 ton C ha
−1
year
−1
from the soil. The soil remained frozen most of the year, and the decomposition of organic matter in the soil increased 10-fold upon thawing. The stability of the soil carbon pool (∼150 tons C ha
−1
) appears sensitive to the depth and duration of thaw, and climatic changes that promote thaw are likely to cause a net efflux of carbon dioxide from the site.
Import of Mitochondrial Carriers Mediated by Essential Proteins of the Intermembrane Space
Authors: Koehler Carla M. , Jarosch Ernst , Tokatlidis Kostas , Schmid Karl , Schweyen Rudolf J. , Schatz Gottfried
Published: July 2002

In order to reach the inner membrane of the mitochondrion, multispanning carrier proteins must cross the aqueous intermembrane space. Two essential proteins of that space, Tim10p and Tim12p, were shown to mediate import of multispanning carriers into the inner membrane. Both proteins formed a complex with the inner membrane protein Tim22p. Tim10p readily dissociated from the complex and was required to transport carrier precursors across the outer membrane; Tim12p was firmly bound to Tim22p and mediated the insertion of carriers into the inner membrane. Neither protein was required for protein import into the other mitochondrial compartments. Both proteins may function as intermembrane space chaperones for the highly insoluble carrier proteins.
Cancer Treatment by Targeted Drug Delivery to Tumor Vasculature in a Mouse Model
Authors: Arap Wadih , Pasqualini Renata , Ruoslahti Erkki
Published: July 2002

In vivo selection of phage display libraries was used to isolate peptides that home specifically to tumor blood vessels. When coupled to the anticancer drug doxorubicin, two of these peptides—one containing an α
v
integrin–binding Arg-Gly-Asp motif and the other an Asn-Gly-Arg motif—enhanced the efficacy of the drug against human breast cancer xenografts in nude mice and also reduced its toxicity. These results indicate that it may be possible to develop targeted chemotherapy strategies that are based on selective expression of receptors in tumor vasculature.
Protein Kinase B Kinases That Mediate Phosphatidylinositol 3,4,5-Trisphosphate-Dependent Activation of Protein Kinase B
Authors: Stephens Len , Anderson Karen , Stokoe David , Erdjument-Bromage Hediye , Painter Gavin F. , Holmes Andrew B. , Gaffney Piers R. J. , Reese Colin B. , McCormick Frank , Tempst Paul , Coadwell J. , Hawkins Phillip T.
Published: July 2002

Protein kinase B (PKB) is activated in response to phosphoinositide 3-kinases and their lipid products phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P
3
] and PtdIns(3,4)P
2
in the signaling pathways used by a wide variety of growth factors, antigens, and inflammatory stimuli. PKB is a direct target of these lipids, but this regulation is complex. The lipids can bind to the pleckstrin homologous domain of PKB, causing its translocation to the membrane, and also enable upstream, Thr
308
-directed kinases to phosphorylate and activate PKB. Four isoforms of these PKB kinases were purified from sheep brain. They bound PtdIns(3,4,5)P
3
and associated with lipid vesicles containing it. These kinases contain an NH
2
-terminal catalytic domain and a COOH-terminal pleckstrin homologous domain, and their heterologous expression augments receptor activation of PKB, which suggests they are the primary signal transducers that enable PtdIns(3,4,5)P
3
or PtdIns- (3,4)P
2
to activate PKB and hence to control signaling pathways regulating cell survival, glucose uptake, and glycogen metabolism.
Meiotic Synapsis in the Absence of Recombination
Authors: McKim Kim S. , Green-Marroquin Becky L. , Sekelsky Jeff J. , Chin Gregory , Steinberg Carrie , Khodosh Rita , Hawley R. Scott
Published: July 2002

Although in
Saccharomyces cerevisiae
the initiation of meiotic recombination, as indicated by double-strand break formation, appears to be functionally linked to the initiation of synapsis, meiotic chromosome synapsis in
Drosophila
females occurs in the absence of meiotic exchange. Electron microscopy of oocytes from females homozygous for either of two meiotic mutants (
mei-W68
and
mei-P22
), which eliminate both meiotic crossing over and gene conversion, revealed normal synaptonemal complex formation. Thus, synapsis in
Drosophila
is independent of meiotic recombination, consistent with a model in which synapsis is required for the initiation of meiotic recombination. Furthermore, the basic processes of early meiosis may have different functional or temporal relations, or both, in yeast and
Drosophila
.
The Postspinel Phase Boundary in Mg
2
SiO
4
Determined by in Situ X-ray Diffraction
Authors: Irifune Tetsuo , Nishiyama Norimasa , Kuroda Koji , Inoue Toru , Isshiki Maiko , Utsumi Wataru , Funakoshi Ken-ichi , Urakawa Satoru , Uchida Takeyuki , Katsura Tomoo , Ohtaka Osamu
Published: July 2002

The phase boundary between spinel (γ phase) and MgSiO
3
perovskite + MgO periclase in Mg
2
SiO
4
was determined by in situ x-ray measurements by a combination of the synchrotron radiation source (SPring-8) and a large multianvil high-pressure apparatus. The boundary was determined at temperatures between 1400° to 1800°C, demonstrating that the postspinel phase boundary has a negative Clapeyron slope as estimated by quench experiments and thermodynamic analyses. The boundary was located at 21.1 (±0.2) gigapascals, at 1600°C, which is ∼2 gigapascals lower than earlier estimates based on other high-pressure studies.
Classical Conditioning and Brain Systems: The Role of Awareness
Authors: Clark Robert E. , Squire Larry R.
Published: July 2002

Classical conditioning of the eye-blink response, perhaps the best studied example of associative learning in vertebrates, is relatively automatic and reflexive, and with the standard procedure (simple delay conditioning), it is intact in animals with hippocampal lesions. In delay conditioning, a tone [the conditioned stimulus (CS)] is presented just before an air puff to the eye [the unconditioned stimulus (US)]. The US is then presented, and the two stimuli coterminate. In trace conditioning, a variant of the standard paradigm, a short interval (500 to 1000 ms) is interposed between the offset of the CS and the onset of the US. Animals with hippocampal lesions fail to acquire trace conditioning. Amnesic patients with damage to the hippocampal formation and normal volunteers were tested on two versions of delay conditioning and two versions of trace conditioning and then assessed for the extent to which they became aware of the temporal relationship between the CS and the US. Amnesic patients acquired delay conditioning at a normal rate but failed to acquire trace conditioning. For normal volunteers, awareness was unrelated to successful delay conditioning but was a prerequisite for successful trace conditioning. Trace conditioning is hippocampus dependent because, as in other tasks of declarative memory, conscious knowledge must be acquired across the training session. Trace conditioning may provide a means for studying awareness in nonhuman animals, in the context of current ideas about multiple memory systems and the function of the hippocampus.
Role of Rac1 and Oxygen Radicals in Collagenase-1 Expression Induced by Cell Shape Change
Authors: Kheradmand Farrah , Werner Erica , Tremble Patrice , Symons Marc , Werb Zena
Published: July 2002

Integrin-mediated reorganization of cell shape leads to an altered cellular phenotype. Disruption of the actin cytoskeleton, initiated by binding of soluble antibody to α5β1 integrin, led to increased expression of the collagenase-1 gene in rabbit synovial fibroblasts. Activation of the guanosine triphosphate–binding protein Rac1, which was downstream of the integrin, was necessary for this process, and expression of activated Rac1 was sufficient to increase expression of collagenase-1. Rac1 activation generated reactive oxygen species that were essential for nuclear factor kappa B–dependent transcriptional regulation of interleukin-1α, which, in an autocrine manner, induced collagenase-1 gene expression. Remodeling of the extracellular matrix and consequent alterations of integrin-mediated adhesion and cytoarchitecture are central to development, wound healing, inflammation, and malignant disease. The resulting activation of Rac1 may lead to altered gene regulation and alterations in cellular morphogenesis, migration, and invasion.
Identification of Water Ice on the Centaur 1997 CU26
Authors: Brown Robert H. , Cruikshank Dale P. , Pendleton Yvonne , Veeder Glenn J.
Published: July 2002

Spectra of the Centaur 1997 CU26 were obtained at the Keck Observatory on 27 October 1997 (universal time). The data show strong absorptions at 1.52 and 2.03 micrometers attributable to water ice on the surface of 1997 CU26. The reflectance spectrum of 1997 CU26 is matched by the spectrum of a mixture of low-temperature, particulate water ice and spectrally featureless but otherwise red-colored material. Water ice dominates the spectrum of 1997 CU26, whereas methane or methane-like hydrocarbons apparently dominate the spectrum of the Kuiper belt object 1993 SC, perhaps indicating different origins, thermal histories, or both for these two objects.
Continuity in Evolution: On the Nature of Transitions
Authors: Fontana Walter , Schuster Peter
Published: July 2002

To distinguish continuous from discontinuous evolutionary change, a relation of nearness between phenotypes is needed. Such a relation is based on the probability of one phenotype being accessible from another through changes in the genotype. This nearness relation is exemplified by calculating the shape neighborhood of a transfer RNA secondary structure and provides a characterization of discontinuous shape transformations in RNA. The simulation of replicating and mutating RNA populations under selection shows that sudden adaptive progress coincides mostly, but not always, with discontinuous shape transformations. The nature of these transformations illuminates the key role of neutral genetic drift in their realization.
Teratogen-Mediated Inhibition of Target Tissue Response to
Shh
Signaling
Authors: Cooper Michael K. , Porter Jeffery A. , Young Keith E. , Beachy Philip A.
Published: July 2002

Veratrum alkaloids and distal inhibitors of cholesterol biosynthesis have been studied for more than 30 years as potent teratogens capable of inducing cyclopia and other birth defects. Here, it is shown that these compounds specifically block the Sonic hedgehog (Shh) signaling pathway. These teratogens did not prevent the sterol modification of Shh during autoprocessing but rather inhibited the response of target tissues to Shh, possibly acting through the sterol sensing domain within the Patched protein regulator of Shh response.
Caspases: Enemies Within
Authors: Thornberry Nancy A. , Lazebnik Yuri
Published: July 2002

REVIEW

Apoptosis, an evolutionarily conserved form of cell suicide, requires specialized machinery. The central component of this machinery is a proteolytic system involving a family of proteases called caspases. These enzymes participate in a cascade that is triggered in response to proapoptotic signals and culminates in cleavage of a set of proteins, resulting in disassembly of the cell. Understanding caspase regulation is intimately linked to the ability to rationally manipulate apoptosis for therapeutic gain.
Biological Action of Leptin as an Angiogenic Factor
Authors: Sierra-Honigmann M. Rocı́o , Nath Anjali K. , Murakami Chiaki , Garcı́a-Cardeña Guillermo , Papapetropoulos Andreas , Sessa William C. , Madge Lisa A. , Schechner Jeffrey S. , Schwabb Michael B. , Polverini Peter J. , Flores-Riveros Jaime R.
Published: July 2002

Leptin is a hormone that regulates food intake, and its receptor (OB-Rb) is expressed primarily in the hypothalamus. Here, it is shown that OB-Rb is also expressed in human vasculature and in primary cultures of human endothelial cells. In vitro and in vivo assays revealed that leptin has angiogenic activity. In vivo, leptin induced neovascularization in corneas from normal rats but not in corneas from
fa/fa
Zucker rats, which lack functional leptin receptors. These observations indicate that the vascular endothelium is a target for leptin and suggest a physiological mechanism whereby leptin-induced angiogenesis may facilitate increased energy expenditure.
A Carrot Leucine-Rich-Repeat Protein That Inhibits Ice Recrystallization
Authors: Worrall Dawn , Elias Luisa , Ashford David , Smallwood Maggie , Sidebottom Chris , Lillford Peter , Telford Julia , Holt Chris , Bowles Dianna
Published: July 2002

Many organisms adapted to live at subzero temperatures express antifreeze proteins that improve their tolerance to freezing. Although structurally diverse, all antifreeze proteins interact with ice surfaces, depress the freezing temperature of aqueous solutions, and inhibit ice crystal growth. A protein purified from carrot shares these functional features with antifreeze proteins of fish. Expression of the carrot complementary DNA in tobacco resulted in the accumulation of antifreeze activity in the apoplast of plants grown at greenhouse temperatures. The sequence of carrot antifreeze protein is similar to that of polygalacturonase inhibitor proteins and contains leucine-rich repeats.
Ordering of the Numerosities 1 to 9 by Monkeys
Authors: Brannon Elizabeth M. , Terrace Herbert S.
Published: July 2002

A fundamental question in cognitive science is whether animals can represent numerosity (a property of a stimulus that is defined by the number of discriminable elements it contains) and use numerical representations computationally. Here, it was shown that rhesus monkeys represent the numerosity of visual stimuli and detect their ordinal disparity. Two monkeys were first trained to respond to exemplars of the numerosities 1 to 4 in an ascending numerical order (1 → 2 → 3 → 4). As a control for non-numerical cues, exemplars were varied with respect to size, shape, and color. The monkeys were later tested, without reward, on their ability to order stimulus pairs composed of the novel numerosities 5 to 9. Both monkeys responded in an ascending order to the novel numerosities. These results show that rhesus monkeys represent the numerosities 1 to 9 on an ordinal scale.
Extended Life-Span and Stress Resistance in the
Drosophila
Mutant
methuselah
Authors: Lin Yi-Jyun , Seroude Laurent , Benzer Seymour
Published: July 2002

Toward a genetic dissection of the processes involved in aging, a screen for gene mutations that extend life-span in
Drosophila melanogaster
was performed. The mutant line
methuselah
(
mth
) displayed approximately 35 percent increase in average life-span and enhanced resistance to various forms of stress, including starvation, high temperature, and dietary paraquat, a free-radical generator. The
mth
gene predicted a protein with homology to several guanosine triphosphate–binding protein–coupled seven–transmembrane domain receptors. Thus, the organism may use signal transduction pathways to modulate stress response and life-span.
Membrane Phospholipid Control of Nucleotide Sensitivity of K
ATP
Channels
Authors: Shyng S.-L. , Nichols C. G.
Published: July 2002

Adenosine triphosphate (ATP)–sensitive potassium (K
ATP
) channels couple cell metabolism to electrical activity. Phosphatidylinositol phosphates (PIPs) profoundly antagonized ATP inhibition of K
ATP
channels when applied to inside-out membrane patches. It is proposed that membrane-incorporated PIPs can bind to positive charges in the cytoplasmic region of the channel's K
ir
6.2 subunit, stabilizing the open state of the channel and antagonizing the inhibitory effect of ATP. The tremendous effect of PIPs on ATP sensitivity suggests that in vivo alterations of membrane PIP levels will have substantial effects on K
ATP
channel activity and hence on the gain of metabolism-excitation coupling.
PIP
2
and PIP as Determinants for ATP Inhibition of K
ATP
Channels
Authors: Baukrowitz Thomas , Schulte Uwe , Oliver Dominik , Herlitze Stefan , Krauter Tobias , Tucker Stephen J. , Ruppersberg J. Peter , Fakler Bernd
Published: July 2002

Adenosine triphosphate (ATP)–sensitive potassium (K
ATP
) channels couple electrical activity to cellular metabolism through their inhibition by intracellular ATP. ATP inhibition of K
ATP
channels varies among tissues and is affected by the metabolic and regulatory state of individual cells, suggesting involvement of endogenous factors. It is reported here that phosphatidylinositol-4,5-bisphosphate (PIP
2
) and phosphatidylinositol-4-phosphate (PIP) controlled ATP inhibition of cloned K
ATP
channels (K
ir
6.2 and SUR1). These phospholipids acted on the K
ir
6.2 subunit and shifted ATP sensitivity by several orders of magnitude. Receptor-mediated activation of phospholipase C resulted in inhibition of K
ATP
-mediated currents. These results represent a mechanism for control of excitability through phospholipids.
Liquid Morphologies on Structured Surfaces: From Microchannels to Microchips
Authors: Gau Hartmut , Herminghaus Stephan , Lenz Peter , Lipowsky Reinhard
Published: July 2002

Liquid microchannels on structured surfaces are built up using a wettability pattern consisting of hydrophilic stripes on a hydrophobic substrate. These channels undergo a shape instability at a certain amount of adsorbed volume, from a homogeneous state with a spatially constant cross section to a state with a single bulge. This instability is quite different from the classical Rayleigh Plateau instability and represents a bifurcation between two different morphologies of constant mean curvature. The bulge state can be used to construct channel networks that could be used as fluid microchips or microreactors.
The Transcriptional Program in the Response of Human Fibroblasts to Serum
Authors: Iyer Vishwanath R. , Eisen Michael B. , Ross Douglas T. , Schuler Greg , Moore Troy , Lee Jeffrey C. F. , Trent Jeffrey M. , Staudt Louis M. , Hudson James , Boguski Mark S. , Lashkari Deval , Shalon Dari , Botstein David , Brown Patrick O.
Published: July 2002

The temporal program of gene expression during a model physiological response of human cells, the response of fibroblasts to serum, was explored with a complementary DNA microarray representing about 8600 different human genes. Genes could be clustered into groups on the basis of their temporal patterns of expression in this program. Many features of the transcriptional program appeared to be related to the physiology of wound repair, suggesting that fibroblasts play a larger and richer role in this complex multicellular response than had previously been appreciated.
A Tenuous Carbon Dioxide Atmosphere on Jupiter's Moon Callisto
Authors: Carlson Robert W.
Published: July 2002

An off-limb scan of Callisto was conducted by the Galileo near-infrared mapping spectrometer to search for a carbon dioxide atmosphere. Airglow in the carbon dioxide ν
3
band was observed up to 100 kilometers above the surface and indicates the presence of a tenuous carbon dioxide atmosphere with surface pressure of 7.5 × 10
−12
bar and a temperature of about 150 kelvin, close to the surface temperature. A lifetime on the order of 4 years is suggested, based on photoionization and magnetospheric sweeping. Either the atmosphere is transient and was formed recently or some process is currently supplying carbon dioxide to the atmosphere.