bluuebunny/crossref_metadata_2025 huggingface dataset:
5'-Deoxyribose Phosphate Lyase Activity of Human DNA Polymerase ɩ in Vitro
Authors: Bebenek Katarzyna , Tissier Agnès , Frank Ekaterina G. , McDonald John P. , Prasad Rajendra , Wilson Samuel H. , Woodgate Roger , Kunkel Thomas A.
Published: July 2002

DNA polymerase iota (pol ι) is one of several recently discovered DNA polymerases in mammalian cells whose function is unknown. We report here that human pol ι has an intrinsic 5′-deoxyribose phosphate (dRP) lyase activity. In reactions reconstituted with uracil-DNA glycosylase (UDG), apurinic/apyrimidinic (AP) endonuclease and DNA ligase I, pol ι can use its dRP lyase and polymerase activities to repair G•U and A•U pairs in DNA. These data and three distinct catalytic properties of pol ι implicate it in specialized forms of base excision repair (BER).
Requirement of ERK Activation for Visual Cortical Plasticity
Authors: Cristo Graziella Di , Berardi Nicoletta , Cancedda Laura , Pizzorusso Tommaso , Putignano Elena , Ratto Gian Michele , Maffei Lamberto
Published: July 2002

Experience-dependent plasticity in the developing visual cortex depends on electrical activity and molecular signals involved in stabilization or removal of inputs. Extracellular signal–regulated kinase 1,2 (also called p42/44 mitogen-activated protein kinase) activation in the cortex is regulated by both factors. We show that two different inhibitors of the ERK pathway suppress the induction of two forms of long-term potentiation (LTP) in rat cortical slices and that their intracortical administration to monocularly deprived rats prevents the shift in ocular dominance towards the nondeprived eye. These results demonstrate that the ERK pathway is necessary for experience-dependent plasticity and for LTP of synaptic transmission in the developing visual cortex.
Chemical Glycobiology
Authors: Bertozzi Carolyn R. , Kiessling and Laura L.
Published: July 2002

Chemical tools have proven indispensable for studies in glycobiology. Synthetic oligosaccharides and glycoconjugates provide materials for correlating structure with function. Synthetic mimics of the complex assemblies found on cell surfaces can modulate cellular interactions and are under development as therapeutic agents. Small molecule inhibitors of carbohydrate biosynthetic and processing enzymes can block the assembly of specific oligosaccharide structures. Inhibitors of carbohydrate recognition and biosynthesis can reveal the biological functions of the carbohydrate epitope and its cognate receptors. Carbohydrate biosynthetic pathways are often amenable to interception with synthetic unnatural substrates. Such metabolic interference can block the expression of oligosaccharides or alter the structures of the sugars presented on cells. Collectively, these chemical approaches are contributing great insight into the myriad biological functions of oligosaccharides.
Intracellular Iron Minerals in a Dissimilatory Iron-Reducing Bacterium
Authors: Glasauer Susan , Langley Sean , Beveridge Terry J.
Published: July 2002

Among prokaryotes, there are few examples of controlled mineral formation; the formation of crystalline iron oxides and sulfides [magnetite (Fe
3
O
4
) or greigite (Fe
3
S
4
)] by magnetotactic bacteria is an exception.
Shewanella putrefaciens
CN32, a Gram-negative, facultative anaerobic bacterium that is capable of dissimilatory iron reduction, produced microscopic intracellular grains of iron oxide minerals during growth on two-line ferrihydrite in a hydrogen-argon atmosphere. The minerals, formed at iron concentrations found in the soil and sedimentary environments where these bacteria are active, could represent an unexplored pathway for the cycling of iron by bacteria.
Adult-Onset Primary Open-Angle Glaucoma Caused by Mutations in Optineurin
Authors: Rezaie Tayebeh , Child Anne , Hitchings Roger , Brice Glen , Miller Lauri , Coca-Prados Miguel , Héon Elise , Krupin Theodore , Ritch Robert , Kreutzer Donald , Crick R. Pitts , Sarfarazi Mansoor
Published: July 2002

Primary open-angle glaucoma (POAG) affects 33 million individuals worldwide and is a leading cause of blindness. In a study of 54 families with autosomal dominantly inherited adult-onset POAG, we identified the causative gene on chromosome 10p14 and designated it
OPTN
(for “optineurin”). Sequence alterations in
OPTN
were found in 16.7% of families with hereditary POAG, including individuals with normal intraocular pressure. The
OPTN
gene codes for a conserved 66-kilodalton protein of unknown function that has been implicated in the tumor necrosis factor–α signaling pathway and that interacts with diverse proteins including Huntingtin, Ras-associated protein RAB8, and transcription factor IIIA. Optineurin is expressed in trabecular meshwork, nonpigmented ciliary epithelium, retina, and brain, and we speculate that it plays a neuroprotective role.
Transcriptional Regulation of Cortical Neuron Migration by POU Domain Factors
Authors: McEvilly Robert J. , de Diaz Marcela Ortiz , Schonemann Marcus D. , Hooshmand Farideh , Rosenfeld Michael G.
Published: July 2002

The identification of pathways mediated by the kinase Cdk5 and the ligand reelin has provided a conceptual framework for exploring the molecular mechanisms underlying proper lamination of the developing mammalian cerebral cortex. In this report, we identify a component of the regulation of Cdk5-mediated cortical lamination by genetic analysis of the roles of the class III POU domain transcription factors, Brn-1 and Brn-2, expressed during the development of the forebrain and coexpressed in most layer II-V cortical neurons. Brn-1 and Brn-2 appear to critically control the initiation of radial migration, redundantly regulating the cell-autonomous expression of the p35 and p39 regulatory subunits of Cdk5 in migrating cortical neurons, with
Brn-1
(
−
/−)/
Brn-2
(
−
/−) mice exhibiting cortical inversion.
Phototransduction by Retinal Ganglion Cells That Set the Circadian Clock
Authors: Berson David M. , Dunn Felice A. , Takao Motoharu
Published: July 2002

Light synchronizes mammalian circadian rhythms with environmental time by modulating retinal input to the circadian pacemaker—the suprachiasmatic nucleus (SCN) of the hypothalamus. Such photic entrainment requires neither rods nor cones, the only known retinal photoreceptors. Here, we show that retinal ganglion cells innervating the SCN are intrinsically photosensitive. Unlike other ganglion cells, they depolarized in response to light even when all synaptic input from rods and cones was blocked. The sensitivity, spectral tuning, and slow kinetics of this light response matched those of the photic entrainment mechanism, suggesting that these ganglion cells may be the primary photoreceptors for this system.
Protonic Diffusion in High-Pressure Ice VII
Authors: Katoh Eriko , Yamawaki H. , Fujihisa H. , Sakashita M. , Aoki K.
Published: July 2002

Near ambient pressures, molecular diffusion dominates protonic diffusion in ice. Theoretical studies have predicted that protonic diffusion will dominate at high pressures in ice. We measured the protonic diffusion coefficient for the highest temperature molecular phase of ice VII at 400 kelvin over its entire stable pressure region. The values ranged from 10
−17
to 10
−15
square meters per second at pressures of 10 to 63 gigapascals. The diffusion coefficients extrapolated to high temperatures close to the ice VII melting curve were less by a factor of 10
2
to 10
3
than a superionic criterion of ∼10
−8
square meters per second, at which protons would diffuse freely.
Chromium Isotopes and the Fate of Hexavalent Chromium in the Environment
Authors: Ellis Andre S. , Johnson Thomas M. , Bullen Thomas D.
Published: July 2002

Measurements of chromium (Cr) stable-isotope fractionation in laboratory experiments and natural waters show that lighter isotopes reacted preferentially during Cr(VI) reduction by magnetite and sediments. The
53
Cr/
52
Cr ratio of the product was 3.4 ± 0.1 per mil less than that of the reactant.
53
Cr/
52
Cr shifts in water samples indicate the extent of reduction, a critical process that renders toxic Cr(VI) in the environment immobile and less toxic.
Visualization of a Ran-GTP Gradient in Interphase and Mitotic
Xenopus
Egg Extracts
Authors: Kalab Petr , Weis Karsten , Heald Rebecca
Published: July 2002

The small guanosine triphosphatase Ran is loaded with guanosine triphosphate (GTP) by the chromatin-bound guanine nucleotide exchange factor RCC1 and releases import cargoes in the nucleus during interphase. In mitosis, Ran-GTP promotes spindle assembly around chromosomes by locally discharging cargoes that regulate microtubule dynamics and organization. We used fluorescence resonance energy transfer–based biosensors to visualize gradients of Ran-GTP and liberated cargoes around chromosomes in mitotic
Xenopus
egg extracts. Both gradients were required to assemble and maintain spindle structure. During interphase, Ran-GTP was highly enriched in the nucleoplasm, and a steep concentration difference between nuclear and cytoplasmic Ran-GTP was established, providing evidence for a Ran-GTP gradient surrounding chromosomes throughout the cell cycle.
Senescence Induced by Altered Telomere State, Not Telomere Loss
Authors: Karlseder Jan , Smogorzewska Agata , de Lange Titia
Published: July 2002

Primary human cells in culture invariably stop dividing and enter a state of growth arrest called replicative senescence. This transition is induced by programmed telomere shortening, but the underlying mechanisms are unclear. Here, we report that overexpression of TRF2, a telomeric DNA binding protein, increased the rate of telomere shortening in primary cells without accelerating senescence. TRF2 reduced the senescence setpoint, defined as telomere length at senescence, from 7 to 4 kilobases. TRF2 protected critically short telomeres from fusion and repressed chromosome-end fusions in presenescent cultures, which explains the ability of TRF2 to delay senescence. Thus, replicative senescence is induced by a change in the protected status of shortened telomeres rather than by a complete loss of telomeric DNA.
Role of a Ubiquitin-Like Modification in Polarized Morphogenesis
Authors: Dittmar Gunnar A. G. , Wilkinson Caroline R. M. , Jedrzejewski Paul T. , Finley Daniel
Published: July 2002

Type I ubiquitin-like proteins constitute a family of protein modifiers. Here we report the identification of a posttranslational protein modifier from
Saccharomyces cerevisiae
, Hub1. Overexpression of Hub1 resulted in enhanced conjugate formation when its carboxyl-terminal residue was deleted, suggesting that mature Hub1 may be produced by proteolytic processing. In vivo targets of Hub1 conjugation included cell polarity factors Sph1 and Hbt1. In the
hub1
Δ mutant, the subcellular localization of both Hbt1 and Sph1 was disrupted, and cell polarization during the formation of mating projections was defective. Consistent with these polarization defects, the
hub1
Δ mutant was deficient in mating.
Excavation of a Chimpanzee Stone Tool Site in the African Rainforest
Authors: Mercader Julio , Panger Melissa , Boesch Christophe
Published: July 2002

Chimpanzees from the Taı̈ forest of Côte d'Ivoire produce unintentional flaked stone assemblages at nut-cracking sites, leaving behind a record of tool use and plant consumption that is recoverable with archaeological methods. About 40 kilograms of nutshell and 4 kilograms of stone were excavated at the Panda 100 site. The data unearthed show that chimpanzees transported stones from outcrops and soils to focal points, where they used them as hammers to process foodstuff. The repeated use of activity areas led to refuse accumulation and site formation. The implications of these data for the interpretation of the earliest hominin archaeological record are explored.
Phenotypic Analysis of Antigen-Specific T Lymphocytes
Authors: Altman John D. , Moss Paul A. H. , Goulder Philip J. R. , Barouch Dan H. , McHeyzer-Williams Michael G. , Bell John I. , McMichael Andrew J. , Davis Mark M.
Published: July 2002

Identification and characterization of antigen-specific T lymphocytes during the course of an immune response is tedious and indirect. To address this problem, the peptide-major histocompatability complex (MHC) ligand for a given population of T cells was multimerized to make soluble peptide-MHC tetramers. Tetramers of human lymphocyte antigen A2 that were complexed with two different human immunodeficiency virus (HIV)-derived peptides or with a peptide derived from influenza A matrix protein bound to peptide-specific cytotoxic T cells in vitro and to T cells from the blood of HIV-infected individuals. In general, tetramer binding correlated well with cytotoxicity assays. This approach should be useful in the analysis of T cells specific for infectious agents, tumors, and autoantigens.
India's Spreading Health Crisis Draws Global Arsenic Experts
Authors: Bagla Pallava , Kaiser Jocelyn
Published: July 2002

New Delhi--A potentially devastating health crisis is quietly unfolding in West Bengal, India, where high levels of arsenic have leached into well water and have put more than a million Indians at risk. The immense scale of the human tragedy has begun to attract the attention of scientists from around the world, who see in this grim event an unprecedented chance to learn more about the health effects of arsenic, a known carcinogen. “We're talking about numbers [of arsenic-poisoning victims] that have never been seen before in the world,” says University of California, Berkeley, epidemiologist Allan Smith.
Gastric Mucosa Abnormalities and Tumorigenesis in Mice Lacking the pS2 Trefoil Protein
Authors: Lefebvre Olivier , Chenard Marie-Pierre , Masson Régis , Linares José , Dierich Andrée , LeMeur Marianne , Wendling Corinne , Tomasetto Catherine , Chambon Pierre , Rio Marie-Christine
Published: July 2002

To determine the function of the pS2 trefoil protein, which is normally expressed in the gastric mucosa, the mouse
pS2
(
mpS2
) gene was inactivated. The antral and pyloric gastric mucosa of
mpS2
-null mice was dysfunctional and exhibited severe hyperplasia and dysplasia. All homozygous mutant mice developed antropyloric adenoma, and 30 percent developed multifocal intraepithelial or intramucosal carcinomas. The small intestine was characterized by enlarged villi and an abnormal infiltrate of lymphoid cells. These results indicate that
mpS2
is essential for normal differentiation of the antral and pyloric gastric mucosa and may function as a gastric-specific tumor suppressor gene.
Microtubule Architecture Specified by a β-Tubulin Isoform
Authors: Raff Elizabeth C. , Fackenthal James D. , Hutchens Jeffrey A. , Hoyle Henry D. , Turner F. Rudolf
Published: July 2002

In
Drosophila melanogaster
, a testis-specific β-tubulin (β2) is required for spermatogenesis. A sequence motif was identified in carboxyl termini of axonemal β-tubulins in diverse taxa. As a test of whether orthologous β-tubulins from different species are functionally equivalent, the moth
Heliothis virescens
β2 homolog was expressed in
Drosophila
testes. When coexpressed with β2, the moth isoform imposed the 16-protofilament structure characteristic of that found in the moth on the corresponding subset of
Drosophila
microtubules, which normally contain only 13-protofilament microtubules. Thus, the architecture of the microtubule cytoskeleton can be directed by a component β-tubulin.
An Icy World Looks Livelier
Authors: Kerr Richard A.
Published: July 2002

WASHINGTON, D.C.
—The latest images of Jupiter's moon Europa, released at aNASA press conference, reveal a landscape in turmoil. To team members poring over images returned bythe Galileo spacecraft, the wild jumble of ridges, grooves, pits, ice flows, and chaotic terrain showsever more signs that heat forged Europa's icy surface.

For images of Europa's surface, see the
Jet Propulsion Laboratory's Web page
.
Oxidative Thymine Dimer Repair in the DNA Helix
Authors: Dandliker Peter J. , Holmlin R. Erik , Barton Jacqueline K.
Published: July 2002

The metallointercalator Rh(phi)
2
DMB
3+
(phi, 9,10-phenanthrenequinone diimine; DMB, 4,4′-dimethyl-2,2′-bipyridine) catalyzed the repair of a thymine dimer incorporated site-specifically in a 16-base pair DNA duplex by means of visible light. This repair could be accomplished with rhodium noncovalently bound to the duplex and at long range (16 to 26 angstroms), with the rhodium intercalator tethered to either end of the duplex assembly. This long-range repair was mediated by the DNA helix. Repair efficiency did not decrease with increasing distance between intercalated rhodium and the thymine dimer, but it diminished with disruption of the intervening π-stack.
Neurogenesis in Postnatal Rat Spinal Cord: A Study in Primary Culture
Authors: Kehl Lois J. , Fairbanks Carolyn A. , Laughlin Tinna M. , Wilcox George L.
Published: July 2002

Spinal cord injuries result in paralysis, because when damaged neurons die they are not replaced. Neurogenesis of electrophysiologically functional neurons occurred in spinal cord cultured from postnatal rats. In these cultures, the numbers of immunocytochemically identified neurons increased over time. Additionally, neurons identified immunocytochemically or electrophysiologically incorporated bromodeoxyuridine, confirming they had differentiated from mitotic cells in vitro. These findings suggest that postnatal spinal cord retains the capacity to generate functional neurons. The presence of neuronal precursor cells in postnatal spinal cord may offer new therapeutic approaches for restoration of function to individuals with spinal cord injuries.
Control of Inflammation, Cytokine Expression, and Germinal Center Formation by BCL-6
Authors: Dent Alexander L. , Shaffer Arthur L. , Yu Xin , Allman David , Staudt Louis M.
Published: July 2002

The gene encoding the BCL-6 transcriptional repressor is frequently translocated and mutated in diffuse large cell lymphoma. Mice with a disrupted BCL-6 gene developed myocarditis and pulmonary vasculitis, had no germinal centers, and had increased expression of T helper cell type 2 cytokines. The BCL-6 DNA recognition motif resembled sites bound by the STAT (signal transducers and activators of transcription) transcription factors, which mediate cytokine signaling. BCL-6 could repress interleukin-4 (IL-4)–induced transcription when bound to a site recognized by the IL-4–responsive transcription factor Stat6. Thus, dysregulation of STAT-responsive genes may underlie the inflammatory disease in BCL-6–deficient mice and participate in lymphoid malignancies.
Neurospora wc-1
and
wc-2
: Transcription, Photoresponses, and the Origins of Circadian Rhythmicity
Authors: Crosthwaite Susan K. , Dunlap Jay C. , Loros Jennifer J.
Published: July 2002

Circadian rhythmicity is universally associated with the ability to perceive light, and the oscillators (“clocks”) giving rise to these rhythms, which are feedback loops based on transcription and translation, are reset by light. Although such loops must contain elements of positive and negative regulation, the clock genes analyzed to date—
frq
in
Neurospora
and
per
and
tim
in
Drosophila
—are associated only with negative feedback and their biochemical functions are largely inferred. The
white collar–1
and
white collar–2
genes, both global regulators of photoresponses in
Neurospora
, encode DNA binding proteins that contain PAS domains and are believed to act as transcriptional activators. Data shown here suggest that
wc-1
is a clock-associated gene and
wc-2 is
a clock component; both play essential roles in the assembly or operation of the
Neurospora
circadian oscillator. Thus DNA binding and transcriptional activation can now be associated with a clock gene that may provide a positive element in the feedback loop. In addition, similarities between the PAS-domain regions of molecules involved in light perception and circadian rhythmicity in several organisms suggest an evolutionary link between ancient photoreceptor proteins and more modern proteins required for circadian oscillation.
Severe Fibronectin-Deposit Renal Glomerular Disease in Mice Lacking Uteroglobin
Authors: Zhang Zhongjian , Kundu Gopal C. , Yuan Chiun-Jye , Ward Jerrold M. , Lee Eric J. , DeMayo Francesco , Westphal Heiner , Mukherjee Anil B.
Published: July 2002

Despite myriads of biological activities ascribed to uteroglobin (UG), a steroid-inducible secreted protein, its physiological functions are unknown. Mice in which the uteroglobin gene was disrupted had severe renal disease that was associated with massive glomerular deposition of predominantly multimeric fibronectin (Fn). The molecular mechanism that normally prevents Fn deposition appears to involve high-affinity binding of UG with Fn to form Fn-UG heteromers that counteract Fn self-aggregation, which is required for abnormal tissue deposition. Thus, UG is essential for maintaining normal renal function in mice, which raises the possibility that an analogous pathogenic mechanism may underlie genetic Fn-deposit human glomerular disease.
Stochastic Dynamics and Deterministic Skeletons: Population Behavior of Dungeness Crab
Authors: Higgins Kevin , Hastings Alan , Sarvela Jacob N. , Botsford Louis W.
Published: July 2002

Ecologists have fiercely debated for many decades whether populations are self-regulated by density-dependent biological mechanisms or are controlled by exogenous environmental forces. Here, a stochastic mechanistic model is used to show that the interaction of these two forces can explain observed large fluctuations in Dungeness crab (
Cancer magister
) numbers. Relatively small environmental perturbations interact with realistic nonlinear (density dependent) biological mechanisms, to produce dynamics that are similar to observations. This finding has implications throughout population biology, suggesting both that the study of deterministic density-dependent models is highly problematic and that stochastic models must include biologically relevant nonlinear mechanisms.
Nondestructive Imaging of Dielectric-Constant Profiles and Ferroelectric Domains with a Scanning-Tip Microwave Near-Field Microscope
Authors: Lu Yalin , Wei Tao , Duewer Fred , Lu Yanqing , Ming Nai-Ben , Schultz P. G. , Xiang X.-D.
Published: July 2002

Variations in dielectric constant and patterns of microwave loss have been imaged in a yttrium-doped LiNbO
3
crystal with periodic ferroelectric domains with the use of a scanning-tip near-field microwave microscope. Periodic profiles of dielectric constant and images of ferroelectric domain boundaries were observed at submicrometer resolution. The combination of these images showed a growth-instability–induced defect of periodic domain structure. Evidence of a lattice-edge dislocation has also been observed through a stress-induced variation in dielectric constant.
Abnormal Lignin in a Loblolly Pine Mutant
Authors: Ralph John , MacKay John J. , Hatfield Ronald D. , O'Malley David M. , Whetten Ross W. , Sederoff Ronald R.
Published: July 2002

Novel lignin is formed in a mutant loblolly pine (
Pinus taeda
L.) severely depleted in cinnamyl alcohol dehydrogenase (E.C. 1.1.1.195), which converts coniferaldehyde to coniferyl alcohol, the primary lignin precursor in pines. Dihydroconiferyl alcohol, a monomer not normally associated with the lignin biosynthetic pathway, is the major component of the mutant's lignin, accounting for ∼30 percent (versus ∼3 percent in normal pine) of the units. The level of aldehydes, including new 2-methoxybenzaldehydes, is also increased. The mutant pines grew normally indicating that, even within a species, extensive variations in lignin composition need not disrupt the essential functions of lignin.
Depth Extent of the Lau Back-Arc Spreading Center and Its Relation to Subduction Processes
Authors: Zhao Dapeng , Xu Yingbiao , Wiens Douglas A. , Dorman LeRoy , Hildebrand John , Webb Spahr
Published: July 2002

Seismic tomography and wave form inversion revealed that very slow velocity anomalies (5 to 7 percent) beneath the active Lau spreading center extend to 100-kilometer depth and are connected to moderately slow anomalies (2 to 4 percent) in the mantle wedge to 400-kilometer depth. These results indicate that geodynamic systems associated with back-arc spreading are related to deep processes, such as the convective circulation in the mantle wedge and deep dehydration reactions in the subducting slab. The slow regions associated with the Tonga arc and the Lau back arc are separated at shallow levels but merge at depths greater than 100 kilometers, suggesting that slab components of back-arc magmas occur through mixing at these depths.
Structure of the Carboxyl-Terminal Dimerization Domain of the HIV-1 Capsid Protein
Authors: Gamble Theresa R. , Yoo Sanghee , Vajdos Felix F. , von Schwedler Uta K. , Worthylake David K. , Wang Hui , McCutcheon John P. , Sundquist Wesley I. , Hill Christopher P.
Published: July 2002

The carboxyl-terminal domain, residues 146 to 231, of the human immunodeficiency virus–1 (HIV-1) capsid protein [CA(146–231)] is required for capsid dimerization and viral assembly. This domain contains a stretch of 20 residues, called the major homology region (MHR), which is conserved across retroviruses and is essential for viral assembly, maturation, and infectivity. The crystal structures of CA(146–231) and CA(151–231) reveal that the globular domain is composed of four helices and an extended amino-terminal strand. CA(146–231) dimerizes through parallel packing of helix 2 across a dyad. The MHR is distinct from the dimer interface and instead forms an intricate hydrogen-bonding network that interconnects strand 1 and helices 1 and 2. Alignment of the CA(146–231) dimer with the crystal structure of the capsid amino-terminal domain provides a model for the intact protein and extends models for assembly of the central conical core of HIV-1.
Evidence of Shallow Fault Zone Strengthening After the 1992
M
7.5 Landers, California, Earthquake
Authors: Li Yong-Gang , Vidale John E. , Aki Keiiti , Xu Fei , Burdette Thomas
Published: July 2002

Repeated seismic surveys of the Landers, California, fault zone that ruptured in the magnitude (
M
) 7.5 earthquake of 1992 reveal an increase in seismic velocity with time.
P
,
S
, and fault zone trapped waves were excited by near-surface explosions in two locations in 1994 and 1996, and were recorded on two linear, three-component seismic arrays deployed across the Johnson Valley fault trace. The travel times of
P
and
S
waves for identical shot-receiver pairs decreased by 0.5 to 1.5 percent from 1994 to 1996, with the larger changes at stations located within the fault zone. These observations indicate that the shallow Johnson Valley fault is strengthening after the main shock, most likely because of closure of cracks that were opened by the 1992 earthquake. The increase in velocity is consistent with the prevalence of dry over wet cracks and with a reduction in the apparent crack density near the fault zone by approximately 1.0 percent from 1994 to 1996.
Identification of a Cullin Homology Region in a Subunit of the Anaphase-Promoting Complex
Authors: Yu Hongtao , Peters Jan-Michael , King Randall W. , Page Andrew M. , Hieter Philip , Kirschner Marc W.
Published: July 2002

The anaphase-promoting complex is composed of eight protein subunits, including BimE (APC1), CDC27 (APC3), CDC16 (APC6), and CDC23 (APC8). The remaining four human APC subunits, APC2, APC4, APC5, and APC7, as well as human CDC23, were cloned. APC7 contains multiple copies of the tetratrico peptide repeat, similar to CDC16, CDC23, and CDC27. Whereas APC4 and APC5 share no similarity to proteins of known function, APC2 contains a region that is similar to a sequence in cullins, a family of proteins implicated in the ubiquitination of G
1
phase cyclins and cyclin-dependent kinase inhibitors. The
APC2
gene is essential in
Saccharomyces cerevisiae
, and
apc2
mutants arrest at metaphase and are defective in the degradation of Pds1p. APC2 and cullins may be distantly related members of a ubiquitin ligase family that targets cell cycle regulators for degradation.
Rapid Turnover of T Lymphocytes in SIV-Infected Rhesus Macaques
Authors: Mohri Hiroshi , Bonhoeffer Sebastian , Monard Simon , Perelson Alan S. , Ho David D.
Published: July 2002

Studies of lymphocyte turnover in animal models have implications for understanding the mechanism of cell killing and the extent of lymphocyte regeneration in human immunodeficiency virus infection. Quantitative analyses of the sequential changes in bromodeoxyuridine labeling of CD4 and CD8 T lymphocytes not only revealed the normal proliferation and death rates of these cell populations in uninfected macaques, but also showed a substantial increase in these rates associated with simian immunodeficiency virus (SIV) infection. Faster labeling and delabeling in memory and naı̈ve T lymphocyte subpopulations as well as in NK (natural killer) and B cells were also observed in infected macaques, suggesting a state of generalized activation induced by SIV.
Rock and the Role of Microbiology
Authors: Lovley Derek R.
Published: July 2002

Geomicrobiology: Interactions Between Microbes and Minerals.
JILLIAN F. BANFIELD and KENNETH H. NEALSON, Eds. Mineralogical Society of America, Washington, DC, 1997. xvi, 448 pp., illus. Paper, $32. ISBN 0-939950-45-6. Reviews in Mineralogy, vol. 35.
Abrupt Shift in Subsurface Temperatures in the Tropical Pacific Associated with Changes in El Niño
Authors: Guilderson Thomas P. , Schrag Daniel P.
Published: July 2002

Radiocarbon (
14
C) content of surface waters inferred from a coral record from the Galápagos Islands increased abruptly during the upwelling season (July through September) after the El Niño event of 1976. Sea-surface temperatures (SSTs) associated with the upwelling season also shifted after 1976. The synchroneity of the shift in both
14
C and SST implies that the vertical thermal structure of the eastern tropical Pacific changed in 1976. This change may be responsible for the increase in frequency and intensity of El Niño events since 1976.
Infrared MALDI Mass Spectrometry of Large Nucleic Acids
Authors: Berkenkamp Stefan , Kirpekar Finn , Hillenkamp Franz
Published: July 2002

Mass spectrometry has become an increasingly important tool of high accuracy, efficiency, and speed for the routine analysis of nucleic acids. To make it useful for large-scale sequencing of genomic material as required for example in genotyping and clinical diagnosis, it is necessary to find approaches that allow the analysis of sequences much larger than the 100 nucleotides currently possible. Matrix-assisted laser desorption/ionization (MALDI) mass spectra of synthetic DNA, restriction enzyme fragments of plasmid DNA, and RNA transcripts up to a size of 2180 nucleotides are reported. The demonstrated mass accuracy of 1 percent or better and the sample requirement of a few femtomoles or less surpass all currently available techniques for the analysis of large nucleic acids. DNA and RNA can be analyzed with only a limited investment in sample purification.
Room Temperature-Operating Spin-Valve Transistors Formed by Vacuum Bonding
Authors: Monsma D. J. , Vlutters R. , Lodder J. C.
Published: July 2002

Functional integration between semiconductors and ferromagnets was demonstrated with the spin-valve transistor. A ferromagnetic multilayer was sandwiched between two device-quality silicon substrates by means of vacuum bonding. The emitter Schottky barrier injected hot electrons into the spin-valve base. The collector Schottky barrier accepts only ballistic electrons, which makes the collector current very sensitive to magnetic fields. Room temperature operation was accomplished by preparing Si-Pt-Co-Cu-Co-Si devices. The vacuum bonding technique allows the realization of many ideas for vertical transport devices and forms a permanent link that is useful in demanding adhesion applications.
Boundary Formation in
Drosophila
Wing: Notch Activity Attenuated by the POU Protein Nubbin
Authors: Neumann Carl J. , Cohen Stephen M.
Published: July 2002

Cell interactions mediated by Notch-family receptors have been implicated in the specification of tissue boundaries in vertebrate and insect development. Although Notch ligands are often widely expressed, tightly localized activation of Notch is critical for the formation of sharp boundaries. Evidence is presented here that the POU domain protein Nubbin contributes to the formation of a sharp dorsoventral boundary in the
Drosophila
wing. Nubbin represses Notch-dependent target genes and sets a threshold for Notch activity that defines the spatial domain of boundary-specific gene expression.
Variation of Interplate Fault Zone Properties with Depth in the Japan Subduction Zone
Authors: Bilek Susan L. , Lay Thorne
Published: July 2002

The depth dependence of physical properties along the Japan subduction zone interface was explored using teleseismic recordings of earthquake signals. Broadband body waves were inverted to determine the duration of rupture and source depth for 40 interplate thrust earthquakes located offshore of Honshu between 1989 and 1995. After scaling for differences in seismic moment, there is a systematic decrease in rupture duration with increasing depth along the subducting plate interface. This indicates increases in rupture velocity or stress drop with depth, likely related to variation in rigidity of sediments on the megathrust.
The Role of Far1p in Linking the Heterotrimeric G Protein to Polarity Establishment Proteins During Yeast Mating
Authors: Butty Anne-Christine , Pryciak Peter M. , Huang Linda S. , Herskowitz Ira , Peter Matthias
Published: July 2002

Heterotrimeric guanosine triphosphate (GTP)–binding proteins (G proteins) determine tissue and cell polarity in a variety of organisms. In yeast, cells orient polarized growth toward the mating partner along a pheromone gradient by a mechanism that requires Far1p and Cdc24p. Far1p bound Gβγ and interacted with polarity establishment proteins, which organize the actin cytoskeleton. Cells containing mutated Far1p unable to bind Gβγ or polarity establishment proteins were defective for orienting growth toward their mating partner. In response to pheromones, Far1p moves from the nucleus to the cytoplasm. Thus, Far1p functions as an adaptor that recruits polarity establishment proteins to the site of extracellular signaling marked by Gβγ to polarize assembly of the cytoskeleton in a morphogenetic gradient.
Proofreading and Aminoacylation of tRNAs Before Export from the Nucleus
Authors: Lund Elsebet , Dahlberg James E.
Published: July 2002

After synthesis and processing in the nucleus, mature transfer RNAs (tRNAs) are exported to the cytoplasm in a Ran·guanosine triphosphate–dependent manner. Export of defective or immature tRNAs is avoided by monitoring both structure and function of tRNAs in the nucleus, and only tRNAs with mature 5′ and 3′ ends are exported. All tRNAs examined can be aminoacylated in nuclei of
Xenopus
oocytes, thereby providing a possible mechanism for functional proofreading of newly made tRNAs. Inhibition of aminoacylation of a specific tRNA retards its appearance in the cytoplasm, indicating that nuclear aminoacylation promotes efficient export.
Controlling the Morphology of Amorphous Solid Water
Authors: Stevenson K. P. , Kimmel Greg A. , Dohnálek Z. , Smith R. Scott , Kay Bruce D.
Published: July 2002

The morphology of amorphous solid water grown by vapor deposition was found to depend strongly on the angular distribution of the water molecules incident from the gas phase. Systematic variation of the incident angle during deposition using a collimated beam of water led to the growth of nonporous to highly porous amorphous solid water. The physical and chemical properties of amorphous solid water are of interest because of its presence in astrophysical environments. The ability to control its properties in the laboratory may shed light on some of the outstanding conflicts related to this important material.
NMDA Receptor-Mediated K
+
Efflux and Neuronal Apoptosis
Authors: Yu S. P. , Yeh C.-H. , Strasser U. , Tian M. , Choi D. W.
Published: July 2002

Neuronal death induced by activating
N
-methyl-
d
-aspartate (NMDA) receptors has been linked to Ca
2+
and Na
+
influx through associated channels. Whole-cell recording from cultured mouse cortical neurons revealed a NMDA-evoked outward current,
I
NMDA-K
, carried by K
+
efflux at membrane potentials positive to –86 millivolts. Cortical neurons exposed to NMDA in medium containing reduced Na
+
and Ca
2+
(as found in ischemic brain tissue) lost substantial intracellular K
+
and underwent apoptosis. Both K
+
loss and apoptosis were attenuated by increasing extracellular K
+
, even when voltage-gated Ca
2+
channels were blocked. Thus NMDA receptor–mediated K
+
efflux may contribute to neuronal apoptosis after brain ischemia.
Neck Posture and Feeding Habits of Two Jurassic Sauropod Dinosaurs
Authors: Stevens Kent A. , Parrish J. Michael
Published: July 2002

Articulated digital reconstructions of two diplodocid sauropods revealed cervical poses and feeding envelopes. The necks of
Diplodocus
and
Apatosaurus
were nearly straight but gently declined such that the heads, which were themselves angled downward relative to the neck, were close to ground level in their neutral, undeflected posture. Both necks were less flexible than conventionally depicted, and
Diplodocus
was less capable of lateral and dorsal curvature than
Apatosaurus
. The results suggest that these sauropods were adapted to ground feeding or low browsing, contrary to the view that diplodocid sauropods were high browsers.
Purification and Cloning of Aggrecanase-1: A Member of the ADAMTS Family of Proteins
Authors: Tortorella M. D. , Burn T. C. , Pratta M. A. , Abbaszade I. , Hollis J. M. , Liu R. , Rosenfeld S. A. , Copeland R. A. , Decicco C. P. , Wynn R. , Rockwell A. , Yang F. , Duke J. L. , Solomon K. , George H. , Bruckner R. , Nagase H. , Itoh Y. , Ellis D. M. , Ross H. , Wiswall B. H. , Murphy K. , Hillman M. C. , Hollis G. F. , Newton R. C. , Magolda R. L. , Trzaskos J. M. , Arner E. C.
Published: July 2002

We purified, cloned, and expressed aggrecanase, a protease that is thought to be responsible for the degradation of cartilage aggrecan in arthritic diseases. Aggrecanase-1 [a disintegrin and metalloproteinase with thrombospondin motifs–4 (ADAMTS-4)] is a member of the ADAMTS protein family that cleaves aggrecan at the glutamic acid-373–alanine-374 bond. The identification of this protease provides a specific target for the development of therapeutics to prevent cartilage degradation in arthritis.
Positive Feedbacks in the Fire Dynamic of Closed Canopy Tropical Forests
Authors: Cochrane Mark A. , Alencar Ane , Schulze Mark D. , Souza Carlos M. , Nepstad Daniel C. , Lefebvre Paul , Davidson Eric A.
Published: July 2002

The incidence and importance of fire in the Amazon have increased substantially during the past decade, but the effects of this disturbance force are still poorly understood. The forest fire dynamics in two regions of the eastern Amazon were studied. Accidental fires have affected nearly 50 percent of the remaining forests and have caused more deforestation than has intentional clearing in recent years. Forest fires create positive feedbacks in future fire susceptibility, fuel loading, and fire intensity. Unless current land use and fire use practices are changed, fire has the potential to transform large areas of tropical forest into scrub or savanna.
Chemical Etiology of Nucleic Acid Structure
Authors: Eschenmoser Albert
Published: July 2002

Systematic chemical studies indicate that the capability of Watson-Crick base-pairing is widespread among potentially natural nucleic acid alternatives taken from RNA's close structural neighborhood. A comparison of RNA and such alternatives with regard to chemical properties that are fundamental to the biological function of RNA provides chemical facts that may contain clues to RNA's origin.
HMG-1 as a Late Mediator of Endotoxin Lethality in Mice
Authors: Wang Haichao , Bloom Ona , Zhang Minghuang , Vishnubhakat Jaideep M. , Ombrellino Michael , Che Jiantu , Frazier Asia , Yang Huan , Ivanova Svetlana , Borovikova Lyudmila , Manogue Kirk R. , Faist Eugen , Abraham Edward , Andersson Jan , Andersson Ulf , Molina Patricia E. , Abumrad Naji N. , Sama Andrew , Tracey Kevin J.
Published: July 2002

Endotoxin, a constituent of Gram-negative bacteria, stimulates macrophages to release large quantities of tumor necrosis factor (TNF) and interleukin-1 (IL-1), which can precipitate tissue injury and lethal shock (endotoxemia). Antagonists of TNF and IL-1 have shown limited efficacy in clinical trials, possibly because these cytokines are early mediators in pathogenesis. Here a potential late mediator of lethality is identified and characterized in a mouse model. High mobility group–1 (HMG-1) protein was found to be released by cultured macrophages more than 8 hours after stimulation with endotoxin, TNF, or IL-1. Mice showed increased serum levels of HMG-1 from 8 to 32 hours after endotoxin exposure. Delayed administration of antibodies to HMG-1 attenuated endotoxin lethality in mice, and administration of HMG-1 itself was lethal. Septic patients who succumbed to infection had increased serum HMG-1 levels, suggesting that this protein warrants investigation as a therapeutic target.
Extensive Nuclear DNA Sequence Diversity Among Chimpanzees
Authors: Kaessmann Henrik , Wiebe Victor , Pääbo Svante
Published: July 2002

Although data on nucleotide sequence variation in the human nuclear genome have begun to accumulate, little is known about genomic diversity in chimpanzees (
Pan troglodytes
) and bonobos (
Pan paniscus
). A 10,154–base pair sequence on the chimpanzee X chromosome is reported, representing all major subspecies and bonobos. Comparison to humans shows the diversity of the chimpanzee sequences to be almost four times as high and the age of the most recent common ancestor three times as great as the corresponding values of humans. Phylogenetic analyses show the sequences from the different chimpanzee subspecies to be intermixed and the distance between some chimpanzee sequences to be greater than the distance between them and the bonobo sequences.
Class II-Independent Generation of CD4 Memory T Cells from Effectors
Authors: Swain Susan L. , Hu Hui , Huston Gail
Published: July 2002

The factors required for the generation of memory CD4 T cells remain unclear, and whether there is a continuing requirement for antigen stimulation is critical to design of vaccine strategies. CD4 effectors generated in vitro from naı̈ve CD4 T cells of mice efficiently gave rise to small resting memory cells after transfer to class II–deficient hosts, indicating no requirement for further antigen or class II recognition.
Transmission of Chronic Nociception by Spinal Neurons Expressing the Substance P Receptor
Authors: Nichols Michael L. , Allen Brian J. , Rogers Scott D. , Ghilardi Joseph R. , Honore Prisca , Luger Nancy M. , Finke Matthew P. , Li Jun , Lappi Douglas A. , Simone Donald A. , Mantyh Patrick W.
Published: July 2002

Substance P receptor (SPR)–expressing spinal neurons were ablated with the selective cytotoxin substance P–saporin. Loss of these neurons resulted in a reduction of thermal hyperalgesia and mechanical allodynia associated with persistent neuropathic and inflammatory pain states. This loss appeared to be permanent. Responses to mildly painful stimuli and morphine analgesia were unaffected by this treatment. These results identify a target for treating persistent pain and suggest that the small population of SPR-expressing neurons in the dorsal horn of the spinal cord plays a pivotal role in the generation and maintenance of chronic neuropathic and inflammatory pain.
Exciton Storage in Semiconductor Self-Assembled Quantum Dots
Authors: Lundstrom T. , Schoenfeld W. , Lee H. , Petroff P. M.
Published: July 2002

Storage and retrieval of excitons were demonstrated with semiconductor self-assembled quantum dots (QDs). The optically generated excitons were dissociated and stored as separated electron-hole pairs in coupled QD pairs. A bias voltage restored the excitons, which recombined radiatively to provide a readout optical signal. The localization of the spatially separated electron-hole pair in QDs was responsible for the ultralong storage times, which were on the order of several seconds. The present limits of this optical storage medium are discussed.
Linkage Disequilibrium and Recombination in Hominid Mitochondrial DNA
Authors: Awadalla Philip , Eyre-Walker Adam , Smith John Maynard
Published: July 2002

The assumption that human mitochondrial DNA is inherited from one parent only and therefore does not recombine is questionable. Linkage disequilibrium in human and chimpanzee mitochondrial DNA declines as a function of the distance between sites. This pattern can be attributed to one mechanism only: recombination.
Population Dynamical Consequences of Climate Change for a Small Temperate Songbird
Authors: Sæther B.-E. , Tufto J. , Engen S. , Jerstad K. , Røstad O. W. , Skåtan J. E.
Published: July 2002

Predicting the effects of an expected climatic change requires estimates and modeling of stochastic factors as well as density-dependent effects in the population dynamics. In a population of a small songbird, the dipper (
Cinclus cinclus
), environmental stochasticity and density dependence both influenced the population growth rate. About half of the environmental variance was explained by variation in mean winter temperature. Including these results in a stochastic model shows that an expected change in climate will strongly affect the dynamics of the population, leading to a nonlinear increase in the carrying capacity and in the expected mean population size.
Identification of a Cellular Cofactor Required for Infection by Feline Leukemia Virus
Authors: Anderson Maria M. , Lauring Adam S. , Burns Cara C. , Overbaugh Julie
Published: July 2002

Retroviral infection involves continued genetic variation, leading to phenotypic and immunological selection for more fit virus variants in the host. For retroviruses that cause immunodeficiency, pathogenesis is linked to the emergence of T cell–tropic, cytopathic viruses. Here we show that an immunodeficiency-inducing, T cell–tropic feline leukemia virus (FeLV) has evolved such that it cannot infect cells unless both a classic multiple membrane-spanning receptor molecule (Pit1) and a second coreceptor or entry factor are present. This second receptor component, which we call FeLIX, was identified as an endogenously expressed protein that is similar to a portion of the FeLV envelope protein. This cellular protein can function either as a transmembrane protein or as a soluble component to facilitate infection.
Genomic Medicine and the Future of Health Care
Authors: Sander Chris
Published: July 2002

Genomic technologies and computational advances are leading to an information revolution in biology and medicine. Simulations of molecular processes in cells and predictions of drug effects in humans will advance pharmaceutical research and speed up clinical trials. Computational prognostics and diagnostics that combine clinical data with genotyping and molecular profiling may soon cause fundamental changes in the practice of health care.
Thermal, Catalytic, Regiospecific Functionalization of Alkanes
Authors: Chen Huiyuan , Schlecht Sabine , Semple Thomas C. , Hartwig John F.
Published: July 2002

The formation of a single product from terminal functionalization of linear alkanes from a transition metal–catalyzed reaction is reported. The rhodium complex Cp*Rh(η
4
-C
6
Me
6
) (Cp*, C
5
Me
5
; Me, methyl) catalyzes the high-yield formation of linear alkylboranes from commercially available borane reagents under thermal conditions. These reactions now allow catalytic, regiospecific functionalization of alkanes under thermal conditions. The organoborane products are among the most versatile synthetic intermediates in chemistry and serve as convenient precursors to alcohols, amines, and other common classes of functionalized molecules.