bluuebunny/crossref_metadata_2025 huggingface dataset:
Glycoprotein Structure Determination by Mass Spectrometry
Authors: Dell Anne , Morris Howard R.
Published: July 2002

The human genome encodes 30,000 to 40,000 proteins, and a major challenge is to understand how posttranslational events, such as glycosylation, affect the activities and functions of these proteins in health and disease. Glycosylated proteins are ubiquitous components of extracellular matrices and cellular surfaces where their oligosaccharide moieties are implicated in a wide range of cell-cell and cell-matrix recognition events. The power of ultrahigh-sensitivity mass spectrometric strategies for defining the primary structures of highly complex mixtures of glycoprotein glycoforms is set to revolutionize structural glycobiology in the coming postgenomic era.
Vitamin C-Induced Decomposition of Lipid Hydroperoxides to Endogenous Genotoxins
Authors: Lee Seon Hwa , Oe Tomoyuki , Blair Ian A.
Published: July 2002

Epidemiological data suggest that dietary antioxidants play a protective role against cancer. This has led to the proposal that dietary supplementation with antioxidants such as vitamin C (vit C) may be useful in disease prevention. However, vit C has proved to be ineffective in cancer chemoprevention studies. In addition, concerns have been raised over potentially deleterious transition metal ion–mediated pro-oxidant effects. We have now determined that vit C induces lipid hydroperoxide decomposition to the DNA-reactive bifunctional electrophiles 4-oxo-2-nonenal, 4,5-epoxy-2(
E
)-decenal, and 4-hydroxy-2-nonenal. The compound 4,5-Epoxy-2(
E
)-decenal is a precursor of etheno-2′-deoxyadenosine, a highly mutagenic lesion found in human DNA. Vitamin C–mediated formation of genotoxins from lipid hydroperoxides in the absence of transition metal ions could help explain its lack of efficacy as a cancer chemoprevention agent.
Production of Polyunsaturated Fatty Acids by Polyketide Synthases in Both Prokaryotes and Eukaryotes
Authors: Metz James G. , Roessler Paul , Facciotti Daniel , Levering Charlene , Dittrich Franziska , Lassner Michael , Valentine Ray , Lardizabal Kathryn , Domergue Frederic , Yamada Akiko , Yazawa Kazunaga , Knauf Vic , Browse John
Published: July 2002

Polyunsaturated fatty acids (PUFAs) are essential membrane components in higher eukaryotes and are the precursors of many lipid-derived signaling molecules. Here, pathways for PUFA synthesis are described that do not require desaturation and elongation of saturated fatty acids. These pathways are catalyzed by polyketide synthases (PKSs) that are distinct from previously recognized PKSs in both structure and mechanism. Generation of cis double bonds probably involves position-specific isomerases; such enzymes might be useful in the production of new families of antibiotics. It is likely that PUFA synthesis in cold marine ecosystems is accomplished in part by these PKS enzymes.
Contribution of Aerobic Photoheterotrophic Bacteria to the Carbon Cycle in the Ocean
Authors: Kolber Zbigniew S. , Gerald F. , Plumley  , Lang Andrew S. , Beatty J. Thomas , Blankenship Robert E. , VanDover Cindy L. , Vetriani Costantino , Koblizek Michal , Rathgeber Christopher , Falkowski Paul G.
Published: July 2002

The vertical distribution of bacteriochlorophyll
a
, the numbers of infrared fluorescent cells, and the variable fluorescence signal at 880 nanometers wavelength, all indicate that photosynthetically competent anoxygenic phototrophic bacteria are abundant in the upper open ocean and comprise at least 11% of the total microbial community. These organisms are facultative photoheterotrophs, metabolizing organic carbon when available, but are capable of photosynthetic light utilization when organic carbon is scarce. They are globally distributed in the euphotic zone and represent a hitherto unrecognized component of the marine microbial community that appears to be critical to the cycling of both organic and inorganic carbon in the ocean.
Autosomal Recessive Hypercholesterolemia Caused by Mutations in a Putative LDL Receptor Adaptor Protein
Authors: Garcia Christine Kim , Wilund Kenneth , Arca Marcello , Zuliani Giovanni , Fellin Renato , Maioli Mario , Calandra Sebastiano , Bertolini Stefano , Cossu Fausto , Grishin Nick , Barnes Robert , Cohen Jonathan C. , Hobbs Helen H.
Published: July 2002

Atherogenic low density lipoproteins are cleared from the circulation by hepatic low density lipoprotein receptors (LDLR). Two inherited forms of hypercholesterolemia result from loss of LDLR activity: autosomal dominant familial hypercholesterolemia (FH), caused by mutations in the
LDLR
gene, and autosomal recessive hypercholesterolemia (ARH), of unknown etiology. Here we map the
ARH
locus to a ∼1-centimorgan interval on chromosome 1p35 and identify six mutations in a gene encoding a putative adaptor protein (ARH). ARH contains a phosphotyrosine binding (PTB) domain, which in other proteins binds NPXY motifs in the cytoplasmic tails of cell-surface receptors, including the LDLR. ARH appears to have a tissue-specific role in LDLR function, as it is required in liver but not in fibroblasts.
Regulation of Clock and NPAS2 DNA Binding by the Redox State of NAD Cofactors
Authors: Rutter Jared , Reick Martin , Wu Leeju C. , McKnight Steven L.
Published: July 2002

Clock:BMAL1 and NPAS2:BMAL1 are heterodimeric transcription factors that control gene expression as a function of the light-dark cycle. Although built to fluctuate at or near a 24-hour cycle, the clock can be entrained by light, activity, or food. Here we show that the DNA-binding activity of the Clock:BMAL1 and NPAS2:BMAL1 heterodimers is regulated by the redox state of nicotinamide adenine dinucleotide (NAD) cofactors in a purified system. The reduced forms of the redox cofactors, NAD(H) and NADP(H), strongly enhance DNA binding of the Clock:BMAL1 and NPAS2:BMAL1 heterodimers, whereas the oxidized forms inhibit. These observations raise the possibility that food, neuronal activity, or both may entrain the circadian clock by direct modulation of cellular redox state.
NPAS2: An Analog of Clock Operative in the Mammalian Forebrain
Authors: Reick Martin , Garcia Joseph A. , Dudley Carol , McKnight Steven L.
Published: July 2002

Neuronal PAS domain protein 2 (NPAS2) is a transcription factor expressed primarily in the mammalian forebrain. NPAS2 is highly related in primary amino acid sequence to Clock, a transcription factor expressed in the suprachiasmatic nucleus that heterodimerizes with BMAL1 and regulates circadian rhythm. To investigate the biological role of NPAS2, we prepared a neuroblastoma cell line capable of conditional induction of the NPAS2:BMAL1 heterodimer and identified putative target genes by representational difference analysis, DNA microarrays, and Northern blotting. Coinduction of NPAS2 and BMAL1 activated transcription of the endogenous
Per1
,
Per2
, and
Cry1
genes, which encode negatively activating components of the circadian regulatory apparatus, and repressed transcription of the endogenous
BMAL1
gene. Analysis of the frontal cortex of wild-type mice kept in a 24-hour light-dark cycle revealed that
Per1
,
Per2
, and
Cry1
mRNA levels were elevated during darkness and reduced during light, whereas
BMAL1
mRNA displayed the opposite pattern. In situ hybridization assays of mice kept in constant darkness revealed that
Per2
mRNA abundance did not oscillate as a function of the circadian cycle in NPAS2-deficient mice. Thus, NPAS2 likely functions as part of a molecular clock operative in the mammalian forebrain.
Evolutionary Dynamics of Plant
R
-Genes
Authors: Bergelson Joy , Kreitman Martin , Stahl Eli A. , Tian Dacheng
Published: July 2002

Plant
R
-genes involved in gene-for-gene interactions with pathogens are expected to undergo coevolutionary arms races in which plant specificity and pathogen virulence continually adapt in response to each other. Lending support to this idea, the solvent-exposed amino acid residues of leucine-rich repeats, a region of
R
-genes involved in recognizing pathogens, often evolve at unusually fast rates. But within-species polymorphism is also common in
R-
genes, implying that the adaptive substitution process is not simply one of successive selective sweeps. Here we document these features in available data and discuss them in light of the evolutionary dynamics they likely reflect.
Rapid Diversification of a Species-Rich Genus of Neotropical Rain Forest Trees
Authors: Richardson James E. , Pennington R. Toby , Pennington Terence D. , Hollingsworth Peter M.
Published: July 2002

Species richness in the tropics has been attributed to the gradual accumulation of species over a long geological period in stable equatorial climates or, conversely, to speciation in response to late Tertiary geological events and unstable Pleistocene climates. DNA sequence data are consistent with recent diversification in
Inga
, a species-rich neotropical tree genus. We estimate that speciation was concentrated in the past 10 million years, with many species arising as recently as 2 million years ago. This coincides with the more recent major uplifts of the Andes, the bridging of the Isthmus of Panama, and Quaternary glacial cycles.
Inga
may be representative of other species-rich neotropical genera with rapid growth and reproduction, which contribute substantially to species numbers in the world's most diverse flora.
A Small-Molecule Modulator of Poly-α2,8-Sialic Acid Expression on Cultured Neurons and Tumor Cells
Authors: Mahal Lara K. , Charter Neil W. , Angata Kiyohiko , Fukuda Minoru , Koshland Daniel E. , Bertozzi Carolyn R.
Published: July 2002

Poly-α2,8-sialic acid (PSA) has been implicated in numerous normal and pathological processes, including development, neuronal plasticity, and tumor metastasis. We report that cell surface PSA expression can be reversibly inhibited by a small molecule,
N
-butanoylmannosamine (ManBut). Inhibition occurs through a metabolic mechanism in which ManBut is converted to unnatural sialic acid derivatives that effectively act as chain terminators during cellular PSA biosynthesis.
N
-Propanoylmannosamine (ManProp), which differs from ManBut by a single methylene group, did not inhibit PSA biosynthesis. Modulation of PSA expression by chemical means has a role complementary to genetic and biochemical approaches in the study of complex PSA-mediated events.
Changes in Seismic Anisotropy After Volcanic Eruptions: Evidence from Mount Ruapehu
Authors: Miller Vicki , Savage Martha
Published: July 2002

The eruptions of andesite volcanoes are explosively catastrophic and notoriously difficult to predict. Yet changes in shear waveforms observed after an eruption of Mount Ruapehu, New Zealand, suggest that forces generated by such volcanoes are powerful and dynamic enough to locally overprint the regional stress regime, which suggests a new method of monitoring volcanoes for future eruptions. These results show a change in shear-wave polarization with time and are interpreted as being due to a localized stress regime caused by the volcano, with a release in pressure after the eruption.
A Trypanosome Structure Involved in Transmitting Cytoplasmic Information During Cell Division
Authors: Moreira-Leite Flávia F. , Sherwin Trevor , Kohl Linda , Gull Keith
Published: July 2002

African trypanosomes are protozoan parasites that cause sleeping sickness in humans through a tsetse fly vector. The procyclic form of
Trypanosoma brucei
has a single, attached flagellum that describes a helical path along the cell from posterior to anterior. During division, a specific flagellum-flagellum connection is elaborated between the new and old flagellum. This connector was present only during cell duplication and was found to be involved in the replication of the helical cell pattern and polarity. This finding implicates the concept of cytotaxis in cell morphogenesis in trypanosomes.
Biogeography and Ecological Setting of Indian Ocean Hydrothermal Vents
Authors: Van Dover C. L. , Humphris S. E. , Fornari D. , Cavanaugh C. M. , Collier R. , Goffredi S. K. , Hashimoto J. , Lilley M. D. , Reysenbach A. L. , Shank T. M. , Von Damm K. L. , Banta A. , Gallant R. M. , Götz D. , Green D. , Hall J. , Harmer T. L. , Hurtado L. A. , Johnson P. , McKiness Z. P. , Meredith C. , Olson E. , Pan I. L. , Turnipseed M. , Won Y. , Young C. R. , Vrijenhoek R. C.
Published: July 2002

Within the endemic invertebrate faunas of hydrothermal vents, five biogeographic provinces are recognized. Invertebrates at two Indian Ocean vent fields (Kairei and Edmond) belong to a sixth province, despite ecological settings and invertebrate-bacterial symbioses similar to those of both western Pacific and Atlantic vents. Most organisms found at these Indian Ocean vent fields have evolutionary affinities with western Pacific vent faunas, but a shrimp that ecologically dominates Indian Ocean vents closely resembles its Mid-Atlantic counterpart. These findings contribute to a global assessment of the biogeography of chemosynthetic faunas and indicate that the Indian Ocean vent community follows asymmetric assembly rules biased toward Pacific evolutionary alliances.
An Abundant Class of Tiny RNAs with Probable Regulatory Roles in
Caenorhabditis elegans
Authors: Lau Nelson C. , Lim Lee P. , Weinstein Earl G. , Bartel David P.
Published: July 2002

Two small temporal RNAs (stRNAs),
lin-4
and
let-7
, control developmental timing in
Caenorhabditis elegans
. We find that these two regulatory RNAs are members of a large class of 21- to 24-nucleotide noncoding RNAs, called microRNAs (miRNAs). We report on 55 previously unknown miRNAs in
C. elegans
. The miRNAs have diverse expression patterns during development: a
let-7
paralog is temporally coexpressed with
let-7
; miRNAs encoded in a single genomic cluster are coexpressed during embryogenesis; and still other miRNAs are expressed constitutively throughout development. Potential orthologs of several of these miRNA genes were identified in
Drosophila
and human genomes. The abundance of these tiny RNAs, their expression patterns, and their evolutionary conservation imply that, as a class, miRNAs have broad regulatory functions in animals.
High Geothermal Heat Flow, Basal Melt, and the Origin of Rapid Ice Flow in Central Greenland
Authors: Fahnestock Mark , Abdalati Waleed , Joughin Ian , Brozena John , Gogineni Prasad
Published: July 2002

Age-depth relations from internal layering reveal a large region of rapid basal melting in Greenland. Melt is localized at the onset of rapid ice flow in the large ice stream that drains north off the summit dome and other areas in the northeast quadrant of the ice sheet. Locally, high melt rates indicate geothermal fluxes 15 to 30 times continental background. The southern limit of melt coincides with magnetic anomalies and topography that suggest a volcanic origin.
Bayesian Inference of Phylogeny and Its Impact on Evolutionary Biology
Authors: Huelsenbeck John P. , Ronquist Fredrik , Nielsen Rasmus , Bollback Jonathan P.
Published: July 2002

As a discipline, phylogenetics is becoming transformed by a flood of molecular data. These data allow broad questions to be asked about the history of life, but also present difficult statistical and computational problems. Bayesian inference of phylogeny brings a new perspective to a number of outstanding issues in evolutionary biology, including the analysis of large phylogenetic trees and complex evolutionary models and the detection of the footprint of natural selection in DNA sequences.
Hydrophobicity at a Janus Interface
Authors: Zhang Xueyan , Zhu Yingxi , Granick Steve
Published: July 2002

Water confined between adjoining hydrophobic and hydrophilic surfaces (a Janus interface) is found to form stable films of nanometer thickness whose responses to shear deformations are extraordinarily noisy. The power spectrum of this noise is quantified. In addition, the frequency dependence of the complex shear modulus is a power law with slope one-half, indicating a distribution of relaxation processes rather than any dominant one. The physical picture emerges that whereas surface energetics encourage water to dewet the hydrophobic side of the interface, the hydrophilic side constrains water to be present, resulting in a flickering, fluctuating complex.
Toxic Proteins in Neurodegenerative Disease
Authors: Taylor J. Paul , Hardy John , Fischbeck Kenneth H.
Published: July 2002

A broad range of neurodegenerative disorders is characterized by neuronal damage that may be caused by toxic, aggregation-prone proteins. As genes are identified for these disorders and cell culture and animal models are developed, it has become clear that a major effect of mutations in these genes is the abnormal processing and accumulation of misfolded protein in neuronal inclusions and plaques. Increased understanding of the cellular mechanisms for disposal of abnormal proteins and of the effects of toxic protein accumulation on neuronal survival may allow the development of rational, effective treatment for these disorders.
Seismic Anisotropy: Tracing Plate Dynamics in the Mantle
Authors: Park Jeffrey , Levin Vadim
Published: July 2002

Elastic anisotropy is present where the speed of a seismic wave depends on its direction. In Earth's mantle, elastic anisotropy is induced by minerals that are preferentially oriented in a directional flow or deformation. Earthquakes generate two seismic wave types: compressional (
P
) and shear (
S
) waves, whose coupling in anisotropic rocks leads to scattering, birefringence, and waves with hybrid polarizations. This varied behavior is helping geophysicists explore rock textures within Earth's mantle and crust, map present-day upper-mantle convection, and study the formation of lithospheric plates and the accretion of continents in Earth history.
Single-Molecule Speckle Analysis of Actin Filament Turnover in Lamellipodia
Authors: Watanabe Naoki , Mitchison Timothy J.
Published: July 2002

Lamellipodia are thin, veil-like extensions at the edge of cells that contain a dynamic array of actin filaments. We describe an approach for analyzing spatial regulation of actin polymerization and depolymerization in vivo in which we tracked single molecules of actin fused to the green fluorescent protein. Polymerization and the lifetime of actin filaments in lamellipodia were measured with high spatial precision. Basal polymerization and depolymerization occurred throughout lamellipodia with largely constant kinetics, and polymerization was promoted within one micron of the lamellipodium tip. Most of the actin filaments in the lamellipodium were generated by polymerization away from the tip.
A Draft Sequence of the Rice Genome (
Oryza sativa
L. ssp.
indica
)
Authors: Yu Jun , Hu Songnian , Wang Jun , Wong Gane Ka-Shu , Li Songgang , Liu Bin , Deng Yajun , Dai Li , Zhou Yan , Zhang Xiuqing , Cao Mengliang , Liu Jing , Sun Jiandong , Tang Jiabin , Chen Yanjiong , Huang Xiaobing , Lin Wei , Ye Chen , Tong Wei , Cong Lijuan , Geng Jianing , Han Yujun , Li Lin , Li Wei , Hu Guangqiang , Huang Xiangang , Li Wenjie , Li Jian , Liu Zhanwei , Li Long , Liu Jianping , Qi Qiuhui , Liu Jinsong , Li Li , Li Tao , Wang Xuegang , Lu Hong , Wu Tingting , Zhu Miao , Ni Peixiang , Han Hua , Dong Wei , Ren Xiaoyu , Feng Xiaoli , Cui Peng , Li Xianran , Wang Hao , Xu Xin , Zhai Wenxue , Xu Zhao , Zhang Jinsong , He Sijie , Zhang Jianguo , Xu Jichen , Zhang Kunlin , Zheng Xianwu , Dong Jianhai , Zeng Wanyong , Tao Lin , Ye Jia , Tan Jun , Ren Xide , Chen Xuewei , He Jun , Liu Daofeng , Tian Wei , Tian Chaoguang , Xia Hongai , Bao Qiyu , Li Gang , Gao Hui , Cao Ting , Wang Juan , Zhao Wenming , Li Ping , Chen Wei , Wang Xudong , Zhang Yong , Hu Jianfei , Wang Jing , Liu Song , Yang Jian , Zhang Guangyu , Xiong Yuqing , Li Zhijie , Mao Long , Zhou Chengshu , Zhu Zhen , Chen Runsheng , Hao Bailin , Zheng Weimou , Chen Shouyi , Guo Wei , Li Guojie , Liu Siqi , Tao Ming , Wang Jian , Zhu Lihuang , Yuan Longping , Yang Huanming
Published: July 2002

We have produced a draft sequence of the rice genome for the most widely cultivated subspecies in China,
Oryza sativa
L. ssp.
indica
, by whole-genome shotgun sequencing. The genome was 466 megabases in size, with an estimated 46,022 to 55,615 genes. Functional coverage in the assembled sequences was 92.0%. About 42.2% of the genome was in exact 20-nucleotide oligomer repeats, and most of the transposons were in the intergenic regions between genes. Although 80.6% of predicted
Arabidopsis thaliana
genes had a homolog in rice, only 49.4% of predicted rice genes had a homolog in
A. thaliana
. The large proportion of rice genes with no recognizable homologs is due to a gradient in the GC content of rice coding sequences.
Singlet Diradicals: from Transition States to Crystalline Compounds
Authors: Scheschkewitz David , Amii Hideki , Gornitzka Heinz , Schoeller Wolfgang W. , Bourissou Didier , Bertrand Guy
Published: July 2002

Singlet diradicals are usually not energy minima. As observed by femtosecond spectroscopy, they readily couple to form σ bonds. Substituent effects allow lifetimes to increase into the microsecond range. Taking advantage of the properties of hetero-elements, a diradical has been prepared that is indefinitely stable at room temperature. The availability of diradicals that can be handled under standard laboratory conditions will lead to further insight into their chemical and physical properties, raising the likelihood of practical applications, especially in the field of molecular materials such as electrical conductors and ferromagnets.
Evidence for the Effect of Learning on Timing of Reproduction in Blue Tits
Authors: Grieco Fabrizio , van Noordwijk Arie J. , Visser Marcel E.
Published: July 2002

We experimentally show that in blue tits (
Parus caeruleus
) egg-laying date is causally linked to experience in the previous year. Females that received additional food in the nestling period in one year laid eggs later in the next year compared with the control birds, whatever the degree of synchronization with the natural food abundance in the previous year. As a result, they raised their brood much later than the peak period of nestling food availability in the next year. The response to experience is adaptive for blue tits, which live in heterogeneous habitats where the peak period of food varies, but once settled will breed at the same location for life.
Mammalian Dispersal at the Paleocene/Eocene Boundary
Authors: Bowen Gabriel J. , Clyde William C. , Koch Paul L. , Ting Suyin , Alroy John , Tsubamoto Takehisa , Wang Yuanqing , Wang Yuan
Published: July 2002

A profound faunal reorganization occurred near the Paleocene/Eocene boundary, when several groups of mammals abruptly appeared on the Holarctic continents. To test the hypothesis that this event featured the dispersal of groups from Asia to North America and Europe, we used isotope stratigraphy, magnetostratigraphy, and quantitative biochronology to constrain the relative age of important Asian faunas. The extinct family Hyaenodontidae appeared in Asia before it did so in North America, and the modern orders Primates, Artiodactyla, and Perissodactyla first appeared in Asia at or before the Paleocene/Eocene boundary. These results are consistent with Asia being a center for early mammalian origination.
Adaptive Immune Response of Vγ2Vδ2
+
T Cells During Mycobacterial Infections
Authors: Shen Yun , Zhou Dejiang , Qiu Liyou , Lai Xioamin , Simon Meredith , Shen Ling , Kou Zhongchen , Wang Qifan , Jiang Liming , Estep Jim , Hunt Robert , Clagett Michelle , Sehgal Prabhat K. , Li Yunyaun , Zeng Xuejun , Morita Craig T. , Brenner Michael B. , Letvin Norman L. , Chen Zheng W.
Published: July 2002

To examine the role of T cell receptor (TCR) in γδ T cells in adaptive immunity, a macaque model was used to follow Vγ2Vδ2
+
T cell responses to mycobacterial infections. These phosphoantigen-specific γδ T cells displayed major expansion during
Mycobacterium bovis
Bacille Calmette-Guérin (BCG) infection and a clear memory-type response after BCG reinfection. Primary and recall expansions of Vγ2Vδ2
+
T cells were also seen during
Mycobacterium tuberculosis
infection of naı̈ve and BCG-vaccinated macaques, respectively. This capacity to rapidly expand coincided with a clearance of BCG bacteremia and immunity to fatal tuberculosis in BCG-vaccinated macaques. Thus, Vγ2Vδ2
+
T cells may contribute to adaptive immunity to mycobacterial infections.
Crystal Structure of the Extracellular Segment of Integrin αVβ3 in Complex with an Arg-Gly-Asp Ligand
Authors: Xiong Jian-Ping , Stehle Thilo , Zhang Rongguang , Joachimiak Andrzej , Frech Matthias , Goodman Simon L. , Arnaout M. Amin
Published: July 2002

The structural basis for the divalent cation–dependent binding of heterodimeric αβ integrins to their ligands, which contain the prototypical Arg-Gly-Asp sequence, is unknown. Interaction with ligands triggers tertiary and quaternary structural rearrangements in integrins that are needed for cell signaling. Here we report the crystal structure of the extracellular segment of integrin αVβ3 in complex with a cyclic peptide presenting the Arg-Gly-Asp sequence. The ligand binds at the major interface between the αV and β3 subunits and makes extensive contacts with both. Both tertiary and quaternary changes are observed in the presence of ligand. The tertiary rearrangements take place in βA, the ligand-binding domain of β3; in the complex, βA acquires two cations, one of which contacts the ligand Asp directly and the other stabilizes the ligand-binding surface. Ligand binding induces small changes in the orientation of αV relative to β3.
Operant Reward Learning in
Aplysia
: Neuronal Correlates and Mechanisms
Authors: Brembs Björn , Lorenzetti Fred D. , Reyes Fredy D. , Baxter Douglas A. , Byrne John H.
Published: July 2002

Operant conditioning is a form of associative learning through which an animal learns about the consequences of its behavior. Here, we report an appetitive operant conditioning procedure in
Aplysia
that induces long-term memory. Biophysical changes that accompanied the memory were found in an identified neuron (cell B51) that is considered critical for the expression of behavior that was rewarded. Similar cellular changes in B51 were produced by contingent reinforcement of B51 with dopamine in a single-cell analog of the operant procedure. These findings allow for the detailed analysis of the cellular and molecular processes underlying operant conditioning.
Creation and Manipulation of Three-Dimensional Optically Trapped Structures
Authors: MacDonald M. P. , Paterson L. , Volke-Sepulveda K. , Arlt J. , Sibbett W. , Dholakia K.
Published: July 2002

An interferometric pattern between two annular laser beams is used to construct three-dimensional (3D) trapped structures within an optical tweezers setup. In addition to being fully translatable in three dimensions, the trapped structure can be rotated controllably and continuously by introducing a frequency difference between the two laser beams. These interference patterns could play an important role in the creation of extended 3D crystalline structures.
Volunteering as Red Queen Mechanism for Cooperation in Public Goods Games
Authors: Hauert Christoph , De Monte Silvia , Hofbauer Josef , Sigmund Karl
Published: July 2002

The evolution of cooperation among nonrelated individuals is one of the fundamental problems in biology and social sciences. Reciprocal altruism fails to provide a solution if interactions are not repeated often enough or groups are too large. Punishment and reward can be very effective but require that defectors can be traced and identified. Here we present a simple but effective mechanism operating under full anonymity. Optional participation can foil exploiters and overcome the social dilemma. In voluntary public goods interactions, cooperators and defectors will coexist. We show that this result holds under very diverse assumptions on population structure and adaptation mechanisms, leading usually not to an equilibrium but to an unending cycle of adjustments (a Red Queen type of evolution). Thus, voluntary participation offers an escape hatch out of some social traps. Cooperation can subsist in sizable groups even if interactions are not repeated, defectors remain anonymous, players have no memory, and assortment is purely random.
Isolating "Uncultivable" Microorganisms in Pure Culture in a Simulated Natural Environment
Authors: Kaeberlein T. , Lewis K. , Epstein S. S.
Published: July 2002

The majority (>99%) of microorganisms from the environment resist cultivation in the laboratory. Ribosomal RNA analysis suggests that uncultivated organisms are found in nearly every prokaryotic group, and several divisions have no known cultivable representatives. We designed a diffusion chamber that allowed the growth of previously uncultivated microorganisms in a simulated natural environment. Colonies of representative marine organisms were isolated in pure culture. These isolates did not grow on artificial media alone but formed colonies in the presence of other microorganisms. This observation may help explain the nature of microbial uncultivability.
Global Dispersal of Free-Living Microbial Eukaryote Species
Authors: Finlay Bland J.
Published: July 2002

The abundance of individuals in microbial species is so large that dispersal is rarely (if ever) restricted by geographical barriers. This “ubiquitous” dispersal requires an alternative view of the scale and dynamics of biodiversity at the microbial level, wherein global species number is relatively low and local species richness is always sufficient to drive ecosystem functions.
A Road Map for Those Who Don't Know JAK-STAT
Authors: Aaronson David S. , Horvath Curt M.
Published: July 2002

The Janus kinase–signal transducer and activator of transcription (JAK-STAT) pathway transmits information received from extracellular polypeptide signals, through transmembrane receptors, directly to target gene promoters in the nucleus, providing a mechanism for transcriptional regulation without second messengers. Evolutionarily conserved in eukaryotic organisms from slime molds to humans, JAK-STAT signaling appears to be an early adaptation to facilitate intercellular communication that has co-evolved with myriad cellular signaling events. This co-evolution has given rise to highly adapted, ligand-specific signaling pathways that control gene expression. In addition, the JAK-STAT signaling pathways are regulated by a vast array of intrinsic and environmental stimuli, which can add plasticity to the response of a cell or tissue.
Connections and Regulation of the Human Estrogen Receptor
Authors: McDonnell Donald P. , Norris John D.
Published: July 2002

Estrogen regulates a plethora of functionally dissimilar processes in a broad range of tissues. Recent progress in the study of the molecular mechanism of action of estrogen(s) has revealed why different cells can respond to the same hormone in a different manner. Three of these findings are of particular importance: (i) There are two genetically and functionally distinct estrogen receptors that have distinct expression patterns in vivo; (ii) the positive and negative transcriptional activities of these receptors require them to engage transcription cofactors (coactivators or corepressors) in target cells; and (iii) not all cofactors are functionally equivalent, nor are they expressed in the same manner in all cells. Thus, although the estrogen receptor is required for a cell to respond to an estrogenic stimulus, the nature and extent of that response are determined by the proteins, pathways, and processes with which the receptor interacts.
Chattering Cells: Superficial Pyramidal Neurons Contributing to the Generation of Synchronous Oscillations in the Visual Cortex
Authors: Gray Charles M. , McCormick David A.
Published: July 2002

In response to visual stimulation, a subset of neurons in the striate and prestriate cortex displays synchronous rhythmic firing in the gamma frequency band (20 to 70 hertz). This finding has raised two fundamental questions: What is the functional significance of synchronous gamma-band activity and how is it generated? This report addresses the second of these two questions. By means of intracellular recording and staining of single cells in the cat striate cortex in vivo, a biophysically distinct class of pyramidal neuron termed “chattering cells” is described. These neurons are located in the superficial layers of the cortex, intrinsically generate 20- to 70-hertz repetitive burst firing in response to suprathreshold depolarizing current injection, and exhibit pronounced oscillations in membrane potential during visual stimulation that are largely absent during periods of spontaneous activity. These properties suggest that chattering cells may make a substantial intracortical contribution to the generation of synchronous cortical oscillations and thus participate in the recruitment of large populations of cells into synchronously firing assemblies.
Brain Activation Modulated by Sentence Comprehension
Authors: Just Marcel Adam , Carpenter Patricia A. , Keller Timothy A. , Eddy William F. , Thulborn Keith R.
Published: July 2002

The comprehension of visually presented sentences produces brain activation that increases with the linguistic complexity of the sentence. The volume of neural tissue activated (number of voxels) during sentence comprehension was measured with echo-planar functional magnetic resonance imaging. The modulation of the volume of activation by sentence complexity was observed in a network of four areas: the classical left-hemisphere language areas (the left laterosuperior temporal cortex, or Wernicke's area, and the left inferior frontal gyrus, or Broca's area) and their homologous right-hemisphere areas, although the right areas had much smaller volumes of activation than did the left areas. These findings generally indicate that the amount of neural activity that a given cognitive process engenders is dependent on the computational demand that the task imposes.
Electrically Conductive Crust in Southern Tibet from INDEPTH Magnetotelluric Surveying
Authors: Chen Leshou , Booker John R. , Jones Alan G. , Wu Nong , Unsworth Martyn J. , Wei Wenbo , Tan Handong
Published: July 2002

The crust north of the Himalaya is generally electrically conductive below depths of 10 to 20 km. This conductive zone approaches the surface beneath the Kangmar dome (dipping north) and extends beneath the Zangbo suture. A profile crossing the northern Yadong-Gulu rift shows that the high conductivity region extends outside the rift, and its top within the rift coincides with a bright spot horizon imaged on the INDEPTH CMP (common midpoint) profiles. The high conductivity of the middle crust is atypical of stable continental regions and suggests that there is a regionally interconnected fluid phase in the crust of the region.
Fly Sex Drive Traced to
fru
Gene
Authors: Roush Wade
Published: July 2002

The fruit fly
Drosophila melanogaster
, whose males stalk the females and woo them with song before mating, can have sex lives as complicated as those of humans. Now researchers have identified a single gene, called
fruitless (fru)
, as responsible for the development of male sexual behavior in the fly.
Statistical Learning by 8-Month-Old Infants
Authors: Saffran Jenny R. , Aslin Richard N. , Newport Elissa L.
Published: July 2002

Learners rely on a combination of experience-independent and experience-dependent mechanisms to extract information from the environment. Language acquisition involves both types of mechanisms, but most theorists emphasize the relative importance of experience-independent mechanisms. The present study shows that a fundamental task of language acquisition, segmentation of words from fluent speech, can be accomplished by 8-month-old infants based solely on the statistical relationships between neighboring speech sounds. Moreover, this word segmentation was based on statistical learning from only 2 minutes of exposure, suggesting that infants have access to a powerful mechanism for the computation of statistical properties of the language input.
Regulation of Synaptic Efficacy by Coincidence of Postsynaptic APs and EPSPs
Authors: Markram Henry , Lübke Joachim , Frotscher Michael , Sakmann Bert
Published: July 2002

Activity-driven modifications in synaptic connections between neurons in the neocortex may occur during development and learning. In dual whole-cell voltage recordings from pyramidal neurons, the coincidence of postsynaptic action potentials (APs) and unitary excitatory postsynaptic potentials (EPSPs) was found to induce changes in EPSPs. Their average amplitudes were differentially up- or down-regulated, depending on the precise timing of postsynaptic APs relative to EPSPs. These observations suggest that APs propagating back into dendrites serve to modify single active synaptic connections, depending on the pattern of electrical activity in the pre- and postsynaptic neurons.
Cancer Chemopreventive Activity of Resveratrol, a Natural Product Derived from Grapes
Authors: Jang Meishiang , Cai Lining , Udeani George O. , Slowing Karla V. , Thomas Cathy F. , Beecher Christopher W. W. , Fong Harry H. S. , Farnsworth Norman R. , Kinghorn A. Douglas , Mehta Rajendra G. , Moon Richard C. , Pezzuto John M.
Published: July 2002

Resveratrol, a phytoalexin found in grapes and other food products, was purified and shown to have cancer chemopreventive activity in assays representing three major stages of carcinogenesis. Resveratrol was found to act as an antioxidant and antimutagen and to induce phase II drug-metabolizing enzymes (anti-initiation activity); it mediated anti-inflammatory effects and inhibited cyclooxygenase and hydroperoxidase functions (antipromotion activity); and it induced human promyelocytic leukemia cell differentiation (antiprogression activity). In addition, it inhibited the development of preneoplastic lesions in carcinogen-treated mouse mammary glands in culture and inhibited tumorigenesis in a mouse skin cancer model. These data suggest that resveratrol, a common constituent of the human diet, merits investigation as a potential cancer chemopreventive agent in humans.
Reconstruction of Current Flow and Imaging of Current-Limiting Defects in Polycrystalline Superconducting Films
Authors: Pashitski A. E. , Gurevich A. , Polyanskii A. A. , Larbalestier D. C. , Goyal A. , Specht E. D. , Kroeger D. M. , DeLuca J. A. , Tkaczyk J. E.
Published: July 2002

Magneto-optical imaging was used to visualize the inhomogeneous penetration of magnetic flux into polycrystalline TlBa
2
Ca
2
Cu
3
O

x

films with high critical current densities, to reconstruct the local two-dimensional supercurrent flow patterns and to correlate inhomogeneities in this flow with the local crystallographic misorientation. The films have almost perfect
c
-axis alignment and considerable local
a
- and
b
-axis texture because the grains tend to form colonies with only slightly misaligned
a
and
b
axes. Current flows freely over these low-angle grain boundaries but is strongly reduced at intermittent colony boundaries of high misorientation. The local (<10-micrometer scale) critical current density
J
c
varies widely, being up to 10 times as great as the transport
J
c
(scale of ∼1 millimeter), which itself varies by a factor of about 5 in different sections of the film. The combined experiments show that the magnitude of the transport
J
c
is largely determined by a few high-angle boundaries.
DCP-1, a
Drosophila
Cell Death Protease Essential for Development
Authors: Song Zhiwei , McCall Kimberly , Steller Hermann
Published: July 2002

Apoptosis, a form of cellular suicide, involves the activation of CED-3-related cysteine proteases (caspases). The regulation of caspases by apoptotic signals and the precise mechanism by which they kill the cell remain unknown. In
Drosophila
, different death-inducing stimuli induce the expression of the apoptotic activator
reaper
. Cell killing by
reaper
and two genetically linked apoptotic activators,
hid
and
grim
, requires caspase activity. A
Drosophila
caspase, named
Drosophila
caspase-1 (DCP-1), was identified and found to be structurally and biochemically similar to
Caenorhabditis elegans
CED-3. Loss of zygotic DCP-1 function in
Drosophila
caused larval lethality and melanotic tumors, showing that this gene is essential for normal development.
Origin of the High-Frequency Doublet in the Vibrational Spectrum of Vitreous SiO
2
Authors: Sarnthein Johannes , Pasquarello Alfredo , Car Roberto
Published: July 2002

The vibrational properties of amorphous SiO
2
were studied within first-principles density functional theory. The calculated spectrum is in good agreement with neutron data, showing, in particular, a double peak in the high-frequency region. This doublet results from different local modes of the tetrahedral subunits and cannot be ascribed to a longitudinal-optic-transverse-optic (LO-TO) effect. This solves a long-standing controversy about the origin of the doublet in neutron spectra. A LO-TO splitting is recovered only when the long-wavelength limit is probed, as in optical experiments. These findings should be a general feature of tetrahedral AX
2
amorphous networks.
Permo-Triassic Boundary Superanoxia and Stratified Superocean: Records from Lost Deep Sea
Authors: Isozaki Yukio
Published: July 2002

Pelagic cherts of Japan and British Columbia, Canada, recorded a long-term and worldwide deep-sea anoxic (oxygen-depleted) event across the Permo-Triassic (or Paleozoic and Mesozoic) boundary (251 ± 2 million years ago). The symmetry in lithostratigraphy and redox condition of the boundary sections suggest that the superocean Panthalassa became totally stratified for nearly 20 million years across the boundary. The timing of onset, climax, and termination of the oceanic stratification correspond to global biotic events including the end-Guadalupian decline, the end-Permian extinction, and mid-Triassic recovery.
Activated Acetic Acid by Carbon Fixation on (Fe,Ni)S Under Primordial Conditions
Authors: Huber Claudia , Wächtershäuser Günter
Published: July 2002

In experiments modeling the reactions of the reductive acetyl–coenzyme A pathway at hydrothermal temperatures, it was found that an aqueous slurry of coprecipitated NiS and FeS converted CO and CH
3
SH into the activated thioester CH
3
-CO-SCH
3
, which hydrolyzed to acetic acid. In the presence of aniline, acetanilide was formed. When NiS-FeS was modified with catalytic amounts of selenium, acetic acid and CH
3
SH were formed from CO and H
2
S alone. The reaction can be considered as the primordial initiation reaction for a chemoautotrophic origin of life.
Solution Structure of 3-Oxo-Δ
5
-Steroid Isomerase
Authors: Wu Zheng Rong , Ebrahimian Soheila , Zawrotny Michael E. , Thornburg Lora D. , Perez-Alvarado Gabriela C. , Brothers Paul , Pollack Ralph M. , Summers Michael F.
Published: July 2002

The three-dimensional structure of the enzyme 3-oxo-Δ
5
-steroid isomerase (E.C. 5.3.3.1), a 28-kilodalton symmetrical dimer, was solved by multidimensional heteronuclear magnetic resonance spectroscopy. The two independently folded monomers pack together by means of extensive hydrophobic and electrostatic interactions. Each monomer comprises three α helices and a six-strand mixed β-pleated sheet arranged to form a deep hydrophobic cavity. Catalytically important residues Tyr
14
(general acid) and Asp
38
(general base) are located near the bottom of the cavity and positioned as expected from mechanistic hypotheses. An unexpected acid group (Asp
99
) is also located in the active site adjacent to Tyr
14
, and kinetic and binding studies of the Asp
99
to Ala mutant demonstrate that Asp
99
contributes to catalysis by stabilizing the intermediate.
Partitioning of Large and Minichromosomes in
Trypanosoma brucei
Authors: Ersfeld Klaus , Gull Keith
Published: July 2002

The
Trypanosoma brucei
nuclear genome contains about 100 minichromosomes of between 50 to 150 kilobases and about 20 chromosomes of 0.2 to 6 megabase pairs. Minichromosomes contain nontranscribed copies of variant surface glycoprotein (VSG) genes and are thought to expand the VSG gene pool. Varying VSG expression allows the parasite to avoid elimination by the host immune system. The mechanism of inheritance of
T. brucei
chromosomes was investigated by in situ hybridization in combination with immunofluorescence. The minichromosome population segregated with precision, by association with the central intranuclear mitotic spindle. However, their positional dynamics differed from that of the large chromosomes, which were partitioned by kinetochore microtubules.
Ligand-Specific Opening of a Gated-Porin Channel in the Outer Membrane of Living Bacteria
Authors: Jiang Xunqing , Payne Marvin A. , Cao Zhenghua , Foster Samuel B. , Feix Jimmy B. , Newton Salete M. C. , Klebba Phillip E.
Published: July 2002

Ligand-gated membrane channels selectively facilitate the entry of iron into prokaryotic cells. The essential role of iron in metabolism makes its acquisition a determinant of bacterial pathogenesis and a target for therapeutic strategies. In Gram-negative bacteria, TonB-dependent outer membrane proteins form energized, gated pores that bind iron chelates (siderophores) and internalize them. The time-resolved operation of the
Escherichia coli
ferric enterobactin receptor FepA was observed in vivo with electron spin resonance spectroscopy by monitoring the mobility of covalently bound nitroxide spin labels. A ligand-binding surface loop of FepA, which normally closes its transmembrane channel, exhibited energy-dependent structural changes during iron and toxin (colicin) transport. These changes were not merely associated with ligand binding, but occurred during ligand uptake through the outer membrane bilayer. The results demonstrate by a physical method that gated-porin channels open and close during membrane transport in vivo.
Angiopoietin-2, a Natural Antagonist for Tie2 That Disrupts in vivo Angiogenesis
Authors: Maisonpierre Peter C. , Suri Chitra , Jones Pamela F. , Bartunkova Sona , Wiegand Stanley J. , Radziejewski Czeslaw , Compton Debra , McClain Joyce , Aldrich Thomas H. , Papadopoulos Nick , Daly Thomas J. , Davis Samuel , Sato Thomas N. , Yancopoulos George D.
Published: July 2002

Angiogenesis is thought to depend on a precise balance of positive and negative regulation. Angiopoietin-1 (Ang1) is an angiogenic factor that signals through the endothelial cell–specific Tie2 receptor tyrosine kinase. Like vascular endothelial growth factor, Ang1 is essential for normal vascular development in the mouse. An Ang1 relative, termed angiopoietin-2 (Ang2), was identified by homology screening and shown to be a naturally occurring antagonist for Ang1 and Tie2. Transgenic overexpression of Ang2 disrupts blood vessel formation in the mouse embryo. In adult mice and humans, Ang2 is expressed only at sites of vascular remodeling. Natural antagonists for vertebrate receptor tyrosine kinases are atypical; thus, the discovery of a negative regulator acting on Tie2 emphasizes the need for exquisite regulation of this angiogenic receptor system.
Mating Type Switching in Yeast Controlled by Asymmetric Localization of
ASH1
mRNA
Authors: Long Roy M. , Singer Robert H. , Meng Xiuhua , Gonzalez Isabel , Nasmyth Kim , Jansen Ralf-Peter
Published: July 2002

Cell divisions that produce progeny differing in their patterns of gene expression are key to the development of multicellular organisms. In the budding yeast
Saccharomyces cerevisiae
, mother cells but not daughter cells can switch mating type because they selectively express the
HO
endonuclease gene. This asymmetry is due to the preferential accumulation of an unstable transcriptional repressor protein, Ash1p, in daughter cell nuclei. Here it is shown that
ASH1
messenger RNA (mRNA) preferentially accumulates in daughter cells by a process that is dependent on actin and myosin. A cis-acting element in the 3′-untranslated region of
ASH1
mRNA is sufficient to localize a chimeric RNA to daughter cells. These results suggest that localization of mRNA may have been an early property of the eukaryotic lineage.