bluuebunny/crossref_metadata_2025 huggingface dataset:
Axonal Self-Destruction and Neurodegeneration
Authors: Raff Martin C. , Whitmore Alan V. , Finn John T.
Published: July 2002

Neurons seem to have at least two self-destruct programs. Like other cell types, they have an intracellular death program for undergoing apoptosis when they are injured, infected, or not needed. In addition, they apparently have a second, molecularly distinct self-destruct program in their axon. This program is activated when the axon is severed and leads to the rapid degeneration of the isolated part of the cut axon. Do neurons also use this second program to prune their axonal tree during development and to conserve resources in response to chronic insults?
Time, Space, and Us
Authors: Unruh William G.
Published: July 2002

Our Cosmic Habitat
. Martin Rees. Princeton University Press, Princeton, NJ, 2001. 223 pp. $22.50. ISBN 0-691-08926-4. Weidenfeld and Nicolson, London, 2002. £14.99. ISBN 0-297-82901-7.

Rees offers general readers an overview of a cosmology focused on the possibility that "our entire universe is a fertile oasis within the multiverse."
Trans-Synaptic Eph Receptor-Ephrin Signaling in Hippocampal Mossy Fiber LTP
Authors: Contractor Anis , Rogers Cheryl , Maron Cornelia , Henkemeyer Mark , Swanson Geoffrey T. , Heinemann Stephen F.
Published: July 2002

The site of induction of long-term potentiation (LTP) at mossy fiber–CA3 synapses in the hippocampus is unresolved, with data supporting both pre- and postsynaptic mechanisms. Here we report that mossy fiber LTP was reduced by perfusion of postsynaptic neurons with peptides and antibodies that interfere with binding of EphB receptor tyrosine kinases (EphRs) to the PDZ protein GRIP. Mossy fiber LTP was also reduced by extracellular application of soluble forms of B-ephrins, which are normally membrane-anchored presynaptic ligands for the EphB receptors. The application of soluble ligands for presynaptic ephrins increased basal excitatory transmission and occluded both tetanus and forskolin-induced synaptic potentiation. These findings suggest that PDZ interactions in the postsynaptic neuron and trans-synaptic interactions between postsynaptic EphB receptors and presynaptic B-ephrins are necessary for the induction of mossy fiber LTP.
Resources Required for Global Tuberculosis Control
Authors: Floyd Katherine , Blanc Leopold , Raviglione Mario , Lee Jong-Wook
Published: July 2002

We estimate that to achieve the World Health Organization's tuberculosis control targets, the 22 high-burden countries (HBCs) that collectively account for approximately 80% of the world's tuberculosis cases require about $1 billion per year during the period 2001 to 2005. A further $0.2 billion per year is needed for low and lower-middle income countries outside the 22 HBCs. There is a resource gap of up to around $300 million per year. Substantial progress in tuberculosis control could be achieved with increased investment that is large in the context of existing spending, but small in the wider context of global health expenditure.
Premature Aging in Mice Deficient in DNA Repair and Transcription
Authors: de Boer Jan , Andressoo Jaan Olle , de Wit Jan , Huijmans Jan , Beems Rudolph B. , van Steeg Harry , Weeda Geert , van der Horst Gijsbertus T. J. , van Leeuwen Wibeke , Themmen Axel P. N. , Meradji Morteza , Hoeijmakers Jan H. J.
Published: July 2002

One of the factors postulated to drive the aging process is the accumulation of DNA damage. Here, we provide strong support for this hypothesis by describing studies of mice with a mutation in
XPD
, a gene encoding a DNA helicase that functions in both repair and transcription and that is mutated in the human disorder trichothiodystrophy (TTD). TTD mice were found to exhibit many symptoms of premature aging, including osteoporosis and kyphosis, osteosclerosis, early greying, cachexia, infertility, and reduced life-span. TTD mice carrying an additional mutation in
XPA
, which enhances the DNA repair defect, showed a greatly accelerated aging phenotype, which correlated with an increased cellular sensitivity to oxidative DNA damage. We hypothesize that aging in TTD mice is caused by unrepaired DNA damage that compromises transcription, leading to functional inactivation of critical genes and enhanced apoptosis.
TMV in the Lab and Life Sciences
Authors: de Chadarevian Soraya
Published: July 2002

The Life of a Virus
Tobacco Mosaic Virus as an Experimental Model, 1930-1965.
By Angela N. H. Creager
. University of Chicago Press, Chicago, 2002. 412 pp. $75, £47.50. ISBN 0-226-12025-2. Paper, $27.50, £16. ISBN 0-226-12026-0.

In this dual history of TMV research and Wendell Stanley's career, Creager discusses connections between biochemistry and molecular biology, the development of public funding of biomedical research, and a variety of institutional and political themes.
A Most Influential Problem Set
Authors: Gouvêa Fernando Q.
Published: July 2002

The Honors Class
Hilbert's Problems and Their Solvers. Benjamin H. Yandell. A. K. Peters, Natick, MA, 2002. 496 pp. $39. ISBN 1-56881-141-1.

The collection of problems David Hilbert presented at the dawn of the 20th century played a major role in shaping the subsequent course of mathematical research. Yandell's sketches of the lives of the people who tackled these problems place the research in its intellectual and philosophical context.
Equilibrium Information from Nonequilibrium Measurements in an Experimental Test of Jarzynski's Equality
Authors: Liphardt Jan , Dumont Sophie , Smith Steven B. , Tinoco Ignacio , Bustamante Carlos
Published: July 2002

Recent advances in statistical mechanical theory can be used to solve a fundamental problem in experimental thermodynamics. In 1997, Jarzynski proved an equality relating the irreversible work to the equilibrium free energy difference, Δ
G
. This remarkable theoretical result states that it is possible to obtain equilibrium thermodynamic parameters from processes carried out arbitrarily far from equilibrium. We test Jarzynski's equality by mechanically stretching a single molecule of RNA reversibly and irreversibly between two conformations. Application of this equality to the irreversible work trajectories recovers the Δ
G
profile of the stretching process to within
k
B
T
/2 (half the thermal energy) of its best independent estimate, the mean work of reversible stretching. The implementation and test of Jarzynski's equality provides the first example of its use as a bridge between the statistical mechanics of equilibrium and nonequilibrium systems. This work also extends the thermodynamic analysis of single molecule manipulation data beyond the context of equilibrium experiments.
AID Enzyme-Induced Hypermutation in an Actively Transcribed Gene in Fibroblasts
Authors: Yoshikawa Kiyotsugu , Okazaki Il-mi , Eto Tomonori , Kinoshita Kazuo , Muramatsu Masamichi , Nagaoka Hitoshi , Honjo Tasuku
Published: July 2002

Activation-induced cytidine deaminase (AID), a putative RNA-editing enzyme, is indispensable for somatic hypermutation (SHM), class switch recombination, and gene conversion of immunoglobulin genes, which indicates a common molecular mechanism for these phenomena. Here we show that ectopic expression of AID alone can induce hypermutation in an artificial
GFP
substrate in NIH 3T3 murine fibroblast cells. The frequency of mutations was closely correlated with the level of transcription of the target gene, and the distribution of mutations in NIH 3T3 cells was similar to those of SHM in B lymphocytes. These results indicate that AID is sufficient for the generation of SHM in an actively transcribed gene in fibroblasts, as well as B cells, and that any of the required cofactors must be present in these fibroblasts.
Protection from Natural Killer Cell-Mediated Lysis by HLA-G Expression on Target Cells
Authors: Pazmany Laszlo , Mandelboim Ofer , Valés-Gómez Mar , Davis Daniel M. , Reyburn Hugh T. , Strominger Jack L.
Published: July 2002

The outermost layer of the human placenta is devoid of classical class I human leukocyte antigens (HLA-A, HLA-B, and HLA-C) and class II proteins (HLA-DR, HLA-DQ, and HLA-DP). Although this prevents recognition by maternal T lymphocytes, the lack of class I molecules leaves these cells susceptible to attack by natural killer (NK) cells. However, trophoblast cells directly in contact with the maternal tissues express the class I molecule HLA-G, which may be involved in protecting the trophoblast from recognition by NK cells. Here evidence is provided that expression of HLA-G is sufficient to protect otherwise susceptible target cells from lysis by activated NK1 and NK2 cell lines and clones that are specific for distinct groups of HLA-C alleles. The receptors on NK cells that recognize HLA-G are also identified.
Three-Dimensional Imaging of Single Molecules Solvated in Pores of Poly(acrylamide) Gels
Authors: Dickson Robert M. , Norris D. J. , Tzeng Yih-Ling , Moerner W. E.
Published: July 2002

Individual fluorescent molecules and individual singly labeled proteins were observed in the water-filled pores of poly(acrylamide) gels by far-field microscopy. Brownian motion was markedly reduced by the gel framework, thus enabling extended study of single fluorophores in aqueous environments. A highly axially dependent laser field was used both to excite the fluorophores and to image the molecules in three dimensions. Single molecules were followed as they moved within and through the porous gel structure. In contrast to dry polymeric hosts, these water-based gels may form a useful medium for single-molecule studies of biological systems in vitro.
CKI1, a Histidine Kinase Homolog Implicated in Cytokinin Signal Transduction
Authors: Kakimoto Tatsuo
Published: July 2002

Although cytokinin plays a central role in plant development, little is known about cytokinin signal transduction. Five
Arabidopsis thaliana
mutants that exhibit typical cytokinin responses, including rapid cell division and shoot formation in tissue culture in the absence of exogenous cytokinin, were isolated by activation transferred DNA tagging. A gene,
CKI1
, which was tagged in four of the five mutants and induced typical cytokinin responses after introduction and overexpression in plants, was cloned.
CKI1
encodes a protein similar to the two-component regulators. These results suggest that CKI1 is involved in cytokinin signal transduction, possibly as a cytokinin receptor.
Uncoupling of Obesity from Insulin Resistance Through a Targeted Mutation in
aP2
, the Adipocyte Fatty Acid Binding Protein
Authors: Hotamisligil Gökhan S. , Johnson Randall S. , Distel Robert J. , Ellis Ramsey , Papaioannou Virginia E. , Spiegelman Bruce M.
Published: July 2002

Fatty acid binding proteins (FABPs) are small cytoplasmic proteins that are expressed in a highly tissue-specific manner and bind to fatty acids such as oleic and retinoic acid. Mice with a null mutation in
aP2
, the gene encoding the adipocyte FABP, were developmentally and metabolically normal. The
aP2
-deficient mice developed dietary obesity but, unlike control mice, they did not develop insulin resistance or diabetes. Also unlike their obese wild-type counterparts, obese

aP2
−/−

animals failed to express in adipose tissue tumor necrosis factor-α (TNF-α), a molecule implicated in obesity-related insulin resistance. These results indicate that
aP2
is central to the pathway that links obesity to insulin resistance, possibly by linking fatty acid metabolism to expression of TNF-α.
A Combined Experimental and Theoretical Study on the Formation of Interstellar C
3
H Isomers
Authors: Kaiser R. I. , Ochsenfeld C. , Head-Gordon M. , Lee Y. T. , Suits A. G.
Published: July 2002

The reaction of ground-state carbon atoms with acetylene was studied under single-collision conditions in crossed beam experiments to investigate the chemical dynamics of forming cyclic and linear C
3
H isomers (
c
-C
3
H and
l
-C
3
H, respectively) in interstellar environments via an atom-neutral reaction. Combined state-of-the-art ab initio calculations and experimental identification of the carbon-hydrogen exchange channel to both isomers classify this reaction as an important alternative to ion-molecule encounters to synthesize C
3
H radicals in the interstellar medium. These findings strongly correlate with astronomical observations and explain a higher [
c
-C
3
H]/[
l
-C
3
H] ratio in the dark cloud TMC-1 than in the carbon star IRC+10216.
Molecular Mimicry of Human Cytokine and Cytokine Response Pathway Genes by KSHV
Authors: Moore Patrick S. , Boshoff Chris , Weiss Robin A. , Chang Yuan
Published: July 2002

Four virus proteins similar to two human macrophage inflammatory protein (MIP) chemokines, interleukin-6 (IL-6), and interferon regulatory factor (IRF) are encoded by the Kaposi's sarcoma-associated herpesvirus (KSHV) genome. vIL-6 was functional in B9 proliferation assays and primarily expressed in KSHV-infected hematopoietic cells rather than KS lesions. HIV-1 transmission studies showed that vMIP-I is similar to human MIP chemokines in its ability to inhibit replication of HIV-1 strains dependent on the CCR5 co-receptor. These viral genes may form part of the response to host defenses contributing to virus-induced neoplasia and may have relevance to KSHV and HIV-I interactions.
Hf-W Isotopic Evidence for Rapid Accretion and Differentiation in the Early Solar System
Authors: Lee Der-Chuen , Halliday Alex N.
Published: July 2002

The time scales over which inner solar system objects accreted and differentiated are unclear because the isotopic systems of many meteorites are disturbed.
182
Hf decays to
182
W with a half-life of 9 million years and is a particularly useful chronometer because both elements are highly refractory and immobile. Tungsten isotopic data for IIA, IIIA, IVA, and anomalous iron meteorites and H, L, and LL chondrites indicate that their parent bodies accreted rapidly and segregated metal within just a few million years.
Requirement for a Noncoding RNA in
Drosophila
Polar Granules for Germ Cell Establishment
Authors: Nakamura Akira , Amikura Reiko , Mukai Masanori , Kobayashi Satoru , Lasko Paul F.
Published: July 2002

In
Drosophila
embryos, germ cell formation is induced by specialized cytoplasm at the posterior of the egg, the pole plasm. Pole plasm contains polar granules, organelles in which maternally produced molecules required for germ cell formation are assembled. An untranslatable RNA, called
Polar granule component
(
Pgc
), was identified and found to be localized in polar granules. Most pole cells in embryos produced by transgenic females expressing antisense
Pgc
RNA failed to complete migration and to populate the embryonic gonads, and females that developed from these embryos often had agametic ovaries. These results support an essential role for
Pgc
RNA in germline development.
Early Onset of Reproductive Function in Normal Female Mice Treated with Leptin
Authors: Chehab Farid F. , Mounzih Khalid , Lu Ronghua , Lim Mary E.
Published: July 2002

Numerous studies have revealed an association between nutritional status, adiposity, and reproductive maturity. The role of leptin, a hormone secreted from adipose tissue, in the onset of reproductive function was investigated. Normal prepubertal female mice injected with leptin grew at a slower rate than controls as a result of the hormone's thinning effects, but they reproduced up to 9 days earlier than controls and showed earlier maturation of the reproductive tract. These results suggest that leptin acts as a signal triggering puberty, thus supporting the hypothesis that fat accumulation enhances maturation of the reproductive tract.
Observation of Interference Between Two Bose Condensates
Authors: Andrews M. R. , Townsend C. G. , Miesner H.-J. , Durfee D. S. , Kurn D. M. , Ketterle W.
Published: July 2002

Interference between two freely expanding Bose-Einstein condensates has been observed. Two condensates separated by ∼40 micrometers were created by evaporatively cooling sodium atoms in a double-well potential formed by magnetic and optical forces. High-contrast matter-wave interference fringes with a period of ∼15 micrometers were observed after switching off the potential and letting the condensates expand for 40 milliseconds and overlap. This demonstrates that Bose condensed atoms are “laser-like”; that is, they are coherent and show long-range correlations. These results have direct implications for the atom laser and the Josephson effect for atoms.
Micropatterning Fluid Lipid Bilayers on Solid Supports
Authors: Groves Jay T. , Ulman Nick , Boxer Steven G.
Published: July 2002

Lithographically patterned grids of photoresist, aluminum oxide, or gold on oxidized silicon substrates were used to partition supported lipid bilayers into micrometer-scale arrays of isolated fluid membrane corrals. Fluorescently labeled lipids were observed to diffuse freely within each membrane corral but were confined by the micropatterned barriers. The concentrations of fluorescent probe molecules in individual corrals were altered by selective photobleaching to create arrays of fluid membrane patches with differing compositions. Application of an electric field parallel to the surface induced steady-state concentration gradients of charged membrane components in the corrals. In addition to producing patches of membrane with continuously varying composition, these gradients provide an intrinsically parallel means of acquiring information about molecular properties such as the diffusion coefficient in individual corrals.
Direct Regulation of the
Akt
Proto-Oncogene Product by Phosphatidylinositol-3,4-bisphosphate
Authors: Franke Thomas F. , Kaplan David R. , Cantley Lewis C. , Toker Alex
Published: July 2002

The regulation of the serine-threonine kinase Akt by lipid products of phosphoinositide 3-kinase (PI 3-kinase) was investigated. Akt activity was found to correlate with the amount of phosphatidylinositol-3,4-bisphosphate (PtdIns-3,4-P
2
) in vivo, and synthetic PtdIns-3,4-P
2
activated Akt both in vitro and in vivo. Binding of PtdIns-3,4-P
2
occurred within the Akt pleckstrin homology (PH) domain and facilitated dimerization of Akt. Akt mutated in the PH domain was not activated by PI 3-kinase in vivo or by PtdIns-3,4-P
2
in vitro, and it was impaired in binding to PtdIns-3,4-P
2
. Examination of the binding to other phosphoinositides revealed that they bound to the Akt PH domain with much lower affinity than did PtdIns-3,4-P
2
and failed to increase Akt activity. Thus, Akt is apparently regulated by the direct interaction of PtdIns-3,4-P
2
with the Akt PH domain.
Interaction and Regulation of Subcellular Localization of CED-4 by CED-9
Authors: Wu Dayang , Wallen Herschel D. , Nuñez Gabriel
Published: July 2002

The
Caenorhabditis elegans
survival gene
ced-9
regulates
ced-4
activity and inhibits cell death, but the mechanism by which this occurs is unknown. Through a genetic screen for CED-4-binding proteins, CED-9 was identified as an interacting partner of CED-4. CED-9, but not loss-of-function mutants, associated specifically with CED-4 in yeast or mammalian cells. The CED-9 protein localized primarily to intracellular membranes and the perinuclear region, whereas CED-4 was distributed in the cytosol. Expression of CED-9, but not a mutant lacking the carboxy-terminal hydrophobic domain, targeted CED-4 from the cytosol to intracellular membranes in mammalian cells. Thus, the actions of CED-4 and CED-9 are directly linked, which could provide the basis for the regulation of programmed cell death in
C. elegans.
Role for the Amino-Terminal Region of Human TBP in U6 snRNA Transcription
Authors: Mittal Vivek , Hernandez Nouria
Published: July 2002

Basal transcription from the human RNA polymerase III U6 promoter depends on a TATA box that recruits the TATA box-binding protein (TBP) and a proximal sequence element that recruits the small nuclear RNA (snRNA)-activating protein complex (SNAP
c
). TBP consists of a conserved carboxyl-terminal domain that performs all known functions of the protein and a nonconserved amino-terminal region of unknown function. Here, the amino-terminal region is shown to down-regulate binding of TBP to the U6 TATA box, mediate cooperative binding with SNAP
c
to the U6 promoter, and enhance U6 transcription.
Crystal Structure of Formate Dehydrogenase H: Catalysis Involving Mo, Molybdopterin, Selenocysteine, and an Fe
4
S
4
Cluster
Authors: Boyington Jeffrey C. , Gladyshev Vadim N. , Khangulov Sergei V. , Stadtman Thressa C. , Sun Peter D.
Published: July 2002

Formate dehydrogenase H from
Escherichia coli
contains selenocysteine (SeCys), molybdenum, two molybdopterin guanine dinucleotide (MGD) cofactors, and an Fe
4
S
4
cluster at the active site and catalyzes the two-electron oxidation of formate to carbon dioxide. The crystal structures of the oxidized [Mo(VI), Fe
4
S
4(ox)
] form of formate dehydrogenase H (with and without bound inhibitor) and the reduced [Mo(IV), Fe
4
S
4(red)
] form have been determined, revealing a four-domain αβ structure with the molybdenum directly coordinated to selenium and both MGD cofactors. These structures suggest a reaction mechanism that directly involves SeCys
140
and His
141
in proton abstraction and the molybdenum, molybdopterin, Lys
44
, and the Fe
4
S
4
cluster in electron transfer.
Will Dolly Send in the Clones?
Authors: Pennisi Elizabeth , Williams Nigel
Published: July 2002

Dolly, the lamb cloned from an udder cell of an adult ewe, has sparked an intense debate about the prospect of human cloning. But researchers say it's still unclear how practical cloning of animals, let alone humans, will be. The procedure so far is inefficient; the group that created Dolly made 277 previous attempts. And no one yet knows whether the cloning procedure, which involves transferring nuclei from adult cells into eggs whose own nuclei have been removed, will work with other species.
Thermal Structure of Jupiter's Upper Atmosphere Derived from the Galileo Probe
Authors: Seiff Alvin , Kirk Donn B. , Knight Tony C. D. , Young Leslie A. , Milos Frank S. , Venkatapathy Ethiraj , Mihalov John D. , Blanchard Robert C. , Young Richard E. , Schubert Gerald
Published: July 2002

Temperatures in Jupiter's atmosphere derived from Galileo Probe deceleration data increase from 109 kelvin at the 175-millibar level to 900 ± 40 kelvin at 1 nanobar, consistent with Voyager remote sensing data. Wavelike oscillations are present at all levels. Vertical wavelengths are 10 to 25 kilometers in the deep isothermal layer, which extends from 12 to 0.003 millibars. Above the 0.003-millibar level, only 90- to 270- kilometer vertical wavelengths survive, suggesting dissipation of wave energy as the probable source of upper atmosphere heating.
A Transmembrane Helix Dimer: Structure and Implications
Authors: MacKenzie Kevin R. , Prestegard James H. , Engelman Donald M.
Published: July 2002

The three-dimensional structure of the dimeric transmembrane domain of glycophorin A (GpA) was determined by solution nuclear magnetic resonance spectroscopy of a 40-residue peptide solubilized in aqueous detergent micelles. The GpA membrane-spanning helices cross at an angle of –40 degrees and form a small but well-packed interface that lacks intermonomer hydrogen bonds. The structure provides an explanation for the previously characterized sequence dependence of GpA dimerization and demonstrates that van der Waals interactions alone can mediate stable and specific associations between transmembrane helices.
Stem Cells in the Central Nervous System
Authors: McKay Ronald
Published: July 2002

In the vertebrate central nervous system, multipotential cells have been identified in vitro and in vivo. Defined mitogens cause the proliferation of multipotential cells in vitro, the magnitude of which is sufficient to account for the number of cells in the brain. Factors that control the differentiation of fetal stem cells to neurons and glia have been defined in vitro, and multipotential cells with similar signaling logic can be cultured from the adult central nervous system. Transplanting cells to new sites emphasizes that neuroepithelial cells have the potential to integrate into many brain regions. These results focus attention on how information in external stimuli is translated into the number and types of differentiated cells in the brain. The development of therapies for the reconstruction of the diseased or injured brain will be guided by our understanding of the origin and stability of cell type in the central nervous system.
Structural Basis for Ligand-Regulated Oligomerization of AraC
Authors: Soisson Stephen M. , MacDougall-Shackleton Beth , Schleif Robert , Wolberger Cynthia
Published: July 2002

The crystal structure of the arabinose-binding and dimerization domain of the
Escherchia coli
gene regulatory protein AraC was determined in the presence and absence of
l
-arabinose. The 1.5 angstrom structure of the arabinose-bound molecule shows that the protein adopts an unusual fold, binding sugar within a β barrel and completely burying the arabinose with the amino-terminal arm of the protein. Dimer contacts in the presence of arabinose are mediated by an antiparallel coiled-coil. In the 2.8 angstrom structure of the uncomplexed protein, the amino-terminal arm is disordered, uncovering the sugar-binding pocket and allowing it to serve as an oligomerization interface. The ligand-gated oligomerization as seen in AraC provides the basis of a plausible mechanism for modulating the protein’s DNA-looping properties.
Spectroscopic Observation of the Formyl Cation in a Condensed Phase
Authors: de Rege Peter J. F. , Gladysz John A. , Horváth István T.
Published: July 2002

The formyl cation, HCO
+
, has long been believed to be an important intermediate in the chemistry of carbon monoxide (CO) in acidic environments, but its spectroscopic observation in solution has been elusive. This species was generated by the reaction of CO with the liquid superacid hydrofluoric acid–antimony pentafluoride (HF-SbF
5
) under pressure and was observed by nuclear magnetic resonance and infrared spectroscopy. Equilibria between CO in the gas phase, CO dissolved in HF-SbF
5
, the SbF
5
adduct of formyl fluoride, and HCO
+
associated with several equilibrating anions of the type [Sb

x

F

5
x
+1

]
−
are proposed to describe the system.
Light-Induced Structural Changes in Photosynthetic Reaction Center: Implications for Mechanism of Electron-Proton Transfer
Authors: Stowell M. H. B. , McPhillips T. M. , Rees D. C. , Soltis S. M. , Abresch E. , Feher G.
Published: July 2002

High resolution x-ray diffraction data from crystals of the
Rhodobacter sphaeroides
photosynthetic reaction center (RC) have been collected at cryogenic temperature in the dark and under illumination, and the structures were refined at 2.2 and 2.6 angstrom resolution, respectively. In the charge-separated D
+
Q
A
Q
B
−
state (where D is the primary electron donor (a bacteriochlorophyll dimer), and Q
A
and Q
B
are the primary and secondary quinone acceptors, respectively), Q
B
−
is located approximately 5 angstroms from the Q
B
position in the charge-neutral (DQ
A
Q
B
) state, and has undergone a 180° propeller twist around the isoprene chain. A model based on the difference between the two structures is proposed to explain the observed kinetics of electron transfer from Q
A
−
Q
B
to Q
A
Q
B
−
and the relative binding affinities of the different ubiquinone species in the Q
B
pocket. In addition, several water channels (putative proton pathways) leading from the Q
B
pocket to the surface of the RC were delineated, one of which leads directly to the membrane surface.
Aluminum Tolerance in Transgenic Plants by Alteration of Citrate Synthesis
Authors: de la Fuente Juan Manuel , Ramı́rez-Rodrı́guez Verenice , Cabrera-Ponce José Luis , Herrera-Estrella Luis
Published: July 2002

Aluminum when in soluble form, as found in acidic soils that comprise about 40 percent of the world’s arable land, is toxic to many crops. Organic acid excretion has been correlated with aluminum tolerance in higher plants. Overproduction of citrate was shown to result in aluminum tolerance in transgenic tobacco (
Nicotiana tabacum)
and papaya (
Carica papaya
) plants.
Isolation of a Bacterium That Reductively Dechlorinates Tetrachloroethene to Ethene
Authors: Maymó-Gatell Xavier , Chien Yueh-tyng , Gossett James M. , Zinder Stephen H.
Published: July 2002

Tetrachloroethene is a prominent groundwater pollutant that can be reductively dechlorinated by mixed anaerobic microbial populations to the nontoxic product ethene. Strain 195, a coccoid bacterium that dechlorinates tetrachloroethene to ethene, was isolated and characterized. Growth of strain 195 with H
2
and tetrachloroethene as the electron donor and acceptor pair required extracts from mixed microbial cultures. Growth of strain 195 was resistant to ampicillin and vancomycin; its cell wall did not react with a peptidoglycan-specific lectin and its ultrastructure resembled S-layers of Archaea. Analysis of the 16
S
ribosomal DNA sequence of strain 195 indicated that it is a eubacterium without close affiliation to any known groups.
Osmotic Activation of the HOG MAPK Pathway via Ste11p MAPKKK: Scaffold Role of Pbs2p MAPKK
Authors: Posas Francesc , Saito Haruo
Published: July 2002

Exposure of the yeast
Saccharomyces cerevisiae
to high extracellular osmolarity induces the Sln1p-Ypd1p-Ssk1p two-component osmosensor to activate a mitogen-activated protein (MAP) kinase cascade composed of the Ssk2p and Ssk22p MAP kinase kinase kinases (MAPKKKs), the Pbs2p MAPKK, and the Hog1p MAPK. A second osmosensor, Sho1p, also activated Pbs2p and Hog1p, but did so through the Ste11p MAPKKK. Although Ste11p also participates in the mating pheromone–responsive MAPK cascade, there was no detectable cross talk between these two pathways. The MAPKK Pbs2p bound to the Sho1p osmosensor, the MAPKKK Ste11p, and the MAPK Hog1p. Thus, Pbs2p may serve as a scaffold protein.
A Broad-Spectrum Chemokine Antagonist Encoded by Kaposi's Sarcoma-Associated Herpesvirus
Authors: Kledal Thomas N. , Rosenkilde Mette M. , Coulin Florence , Simmons Graham , Johnsen Anders H. , Alouani Sami , Power Christine A. , Lüttichau Hans R. , Gerstoft Jan , Clapham Paul R. , Clark-Lewis Ian , Wells Timothy N. C. , Schwartz Thue W.
Published: July 2002

Kaposi's sarcoma–associated herpesvirus encodes a chemokine called vMIP-II. This protein displayed a broader spectrum of receptor activities than any mammalian chemokine as it bound with high affinity to a number of both CC and CXC chemokine receptors. Binding of vMIP-II, however, was not associated with the normal, rapid mobilization of calcium from intracellular stores; instead, it blocked calcium mobilization induced by endogenous chemokines. In freshly isolated human monocytes the virally encoded vMIP-II acted as a potent and efficient antagonist of chemotaxis induced by chemokines. Because vMIP-II could inhibit cell entry of human immunodeficiency virus (HIV) mediated through CCR3 and CCR5 as well as CXCR4, this protein may serve as a lead for development of broad-spectrum anti-HIV agents.
Maternal Care, Hippocampal Glucocorticoid Receptors, and Hypothalamic-Pituitary-Adrenal Responses to Stress
Authors: Liu Dong , Diorio Josie , Tannenbaum Beth , Caldji Christian , Francis Darlene , Freedman Alison , Sharma Shakti , Pearson Deborah , Plotsky Paul M. , Meaney Michael J.
Published: July 2002

Variations in maternal care affect the development of individual differences in neuroendocrine responses to stress in rats. As adults, the offspring of mothers that exhibited more licking and grooming of pups during the first 10 days of life showed reduced plasma adrenocorticotropic hormone and corticosterone responses to acute stress, increased hippocampal glucocorticoid receptor messenger RNA expression, enhanced glucocorticoid feedback sensitivity, and decreased levels of hypothalamic corticotropin-releasing hormone messenger RNA. Each measure was significantly correlated with the frequency of maternal licking and grooming (all
r
's > −0.6). These findings suggest that maternal behavior serves to “program” hypothalamic-pituitary-adrenal responses to stress in the offspring.
Fluorescence-Based Isolation of Bacterial Genes Expressed Within Host Cells
Authors: Valdivia Raphael H. , Falkow Stanley
Published: July 2002

A selection strategy was devised to identify bacterial genes preferentially expressed when a bacterium associates with its host cell. Fourteen
Salmonella typhimurium
genes, which were under the control of at least four independent regulatory circuits, were identified to be selectively induced in host macrophages. Four genes encode virulence factors, including a component of a type III secretory apparatus. This selection methodology should be generally applicable to the identification of genes from pathogenic organisms that are induced upon association with host cells or tissues.
Immunotherapy of Tumors with Autologous Tumor-Derived Heat Shock Protein Preparations
Authors: Tamura Yasuaki , Peng Ping , Liu Kang , Daou Maria , Srivastava Pramod K.
Published: July 2002

Immunotherapy of mice with preexisting cancers with heat shock protein preparations derived from autologous cancer resulted in retarded progression of the primary cancer, a reduced metastatic load, and prolongation of life-span. Treatment with heat shock protein preparations derived from cancers other than the autologous cancer did not provide significant protection. Spontaneous cancers (lung cancer and melanoma), chemically induced cancers (fibrosarcoma and colon carcinoma), and an ultraviolet radiation-induced spindle cell carcinoma were tested, and the results support the efficacy of autologous cancer–derived heat shock protein–peptide complexes in immunotherapy of cancers without the need to identify specific tumor antigenic epitopes.
The Holocene-Younger Dryas Transition Recorded at Summit, Greenland
Authors: Taylor K. C. , Mayewski P. A. , Alley R. B. , Brook E. J. , Gow A. J. , Grootes P. M. , Meese D. A. , Saltzman E. S. , Severinghaus J. P. , Twickler M. S. , White J. W. C. , Whitlow S. , Zielinski G. A.
Published: July 2002

Analysis of ice from Dye-3, Greenland, has demonstrated that the transition between the Younger Dryas and Holocene climate periods occurred over a 40-year period. A near annually resolved, multiparameter record of the transition recorded in the GISP2 core from Summit, Greenland, shows that most of the transition occurred in a series of steps with durations of about 5 years. Some climate proxies associated with mid-latitude sources appear to have changed about 15 years before climate proxies associated with more northern regions. Changes in atmospheric water vapor are likely to have played a large role in the climate transition.
Catalytic Galactose Oxidase Models: Biomimetic Cu(II)-Phenoxyl-Radical Reactivity
Authors: Wang Yadong , DuBois Jennifer L. , Hedman Britt , Hodgson Keith O. , Stack T. D. P.
Published: July 2002

Biomimetic functional models of the mononuclear copper enzyme galactose oxidase are presented that catalytically oxidize benzylic and allylic alcohols to aldehydes with O
2
under mild conditions. The mechanistic fidelity between the models and the natural system is pronounced. Modest structural mimicry proves sufficient to transfer an unusual ligand-based radical mechanism, previously unprecedented outside the protein matrix, to a simple chemical system.
Femtosecond Activation of Reactions and the Concept of Nonergodic Molecules
Authors: Diau Eric W.-G. , Herek Jennifer L. , Kim Zee Hwan , Zewail Ahmed H.
Published: July 2002

The description of chemical reaction dynamics often assumes that vibrational modes are well coupled (ergodic) and redistribute energy rapidly with respect to the course of the reaction. To experimentally probe nonergodic, nonstatistical behavior, studies of a series of reactions induced by femtosecond activation for molecules of varying size but having the same reaction coordinates [CH
2
− (CH
2
)

n

−
2
− C = O
†
→ products, with
n
= 4, 5, 6, and 10] were performed. Comparison of the experimental results with theoretical electronic structure and rate calculations showed a two to four orders of magnitude difference, indicating that the basic assumption of statistical energy redistribution is invalid. These results suggest that chemical selectivity can be achieved with femtosecond activation even at very high energies.
Impaired Locomotion and Dopamine Signaling in Retinoid Receptor Mutant Mice
Authors: Krȩz˙el Wojciech , Ghyselinck Norbert , Samad Tarek A. , Dupé Valérie , Kastner Philippe , Borrelli Emiliana , Chambon Pierre
Published: July 2002

In the adult mouse, single and compound null mutations in the genes for retinoic acid receptor β and retinoid X receptors β and γ resulted in locomotor defects related to dysfunction of the mesolimbic dopamine signaling pathway. Expression of the D1 and D2 receptors for dopamine was reduced in the ventral striatum of mutant mice, and the response of double null mutant mice to cocaine, which affects dopamine signaling in the mesolimbic system, was blunted. Thus, retinoid receptors are involved in the regulation of brain functions, and retinoic acid signaling defects may contribute to pathologies such as Parkinson's disease and schizophrenia.
Mismatch Repair Co-opted by Hypermutation
Authors: Cascalho Marilia , Wong Jamie , Steinberg Charles , Wabl Matthias
Published: July 2002

Mice homozygous for a disrupted allele of the mismatch repair gene
Pms2
have a mutator phenotype. When this allele is crossed into quasi-monoclonal (QM) mice, which have a very limited B cell repertoire, homozygotes have fewer somatic mutations at the immunoglobulin heavy chain and λ chain loci than do heterozygotes or wild-type QM mice. That is, mismatch repair seems to contribute to somatic hypermutation rather than stifling it. It is suggested that at immunoglobulin loci in hypermutable B cells, mismatched base pairs are “corrected” according to the newly synthesized DNA strand, thereby fixing incipient mutations instead of eliminating them.
Distribution of
Thiobacillus ferrooxidans
and
Leptospirillum ferrooxidans
: Implications for Generation of Acid Mine Drainage
Authors: Schrenk Matthew O. , Edwards Katrina J. , Goodman Robert M. , Hamers Robert J. , Banfield Jillian F.
Published: July 2002

Although
Thiobacillus ferrooxidans
and
Leptospirillum ferrooxidans
are widely considered to be the microorganisms that control the rate of generation of acid mine drainage, little is known about their natural distribution and abundance. Fluorescence in situ hybridization studies showed that at Iron Mountain, California,
T. ferrooxidans
occurs in peripheral slime-based communities (at pH over 1.3 and temperature under 30°C) but not in important subsurface acid-forming environments (pH 0.3 to 0.7, temperature 30° to 50°C).
Leptospirillum ferrooxidans
is abundant in slimes and as a planktonic organism in environments with lower pH.
Thiobacillus ferrooxidans
affects the precipitation of ferric iron solids but plays a limited role in acid generation, and neither species controls direct catalysis at low pH at this site.
Structure of Nitric Oxide Synthase Oxygenase Dimer with Pterin and Substrate
Authors: Crane Brian R. , Arvai Andrew S. , Ghosh Dipak K. , Wu Chaoqun , Getzoff Elizabeth D. , Stuehr Dennis J. , Tainer John A.
Published: July 2002

Crystal structures of the murine cytokine-inducible nitric oxide synthase oxygenase dimer with active-center water molecules, the substrate
l
-arginine (
l
-Arg), or product analog thiocitrulline reveal how dimerization, cofactor tetrahydrobiopterin, and
l
-Arg binding complete the catalytic center for synthesis of the essential biological signal and cytotoxin nitric oxide. Pterin binding refolds the central interface region, recruits new structural elements, creates a 30 angstrom deep active-center channel, and causes a 35° helical tilt to expose a heme edge and the adjacent residue tryptophan-366 for likely reductase domain interactions and caveolin inhibition. Heme propionate interactions with pterin and
l
-Arg suggest that pterin has electronic influences on heme-bound oxygen.
l
-Arginine binds to glutamic acid–371 and stacks with heme in an otherwise hydrophobic pocket to aid activation of heme-bound oxygen by direct proton donation and thereby differentiate the two chemical steps of nitric oxide synthesis.
Targeting the Receptor-G
q
Interface to Inhibit in Vivo Pressure Overload Myocardial Hypertrophy
Authors: Akhter Shahab A. , Luttrell Louis M. , Rockman Howard A. , Iaccarino Guido , Lefkowitz Robert J. , Koch Walter J.
Published: July 2002

Hormones and neurotransmitters may mediate common responses through receptors that couple to the same class of heterotrimeric guanine nucleotide–binding (G) protein. For example, several receptors that couple to G
q
class proteins can induce cardiomyocyte hypertrophy. Class-specific inhibition of G
q
-mediated signaling was produced in the hearts of transgenic mice by targeted expression of a carboxyl-terminal peptide of the α subunit Gα
q
. When pressure overload was surgically induced, the transgenic mice developed significantly less ventricular hypertrophy than control animals. The data demonstrate the role of myocardial G
q
in the initiation of myocardial hypertrophy and indicate a possible strategy for preventing pathophysiological signaling by simultaneously blocking multiple receptors coupled to G
q
.
Deep-Sea Coral Evidence for Rapid Change in Ventilation of the Deep North Atlantic 15,400 Years Ago
Authors: Adkins Jess F. , Cheng Hai , Boyle Edward A. , Druffel Ellen R. M. , Edwards R. Lawrence
Published: July 2002

Coupled radiocarbon and thorium-230 dates from benthic coral species reveal that the ventilation rate of the North Atlantic upper deep water varied greatly during the last deglaciation. Radiocarbon ages in several corals of the same age, 15.41 ± 0.17 thousand years, and nearly the same depth, 1800 meters, in the western North Atlantic Ocean increased by as much as 670 years during the 30- to 160-year life spans of the samples. Cadmium/calcium ratios in one coral imply that the nutrient content of these deep waters also increased. Our data show that the deep ocean changed on decadal-centennial time scales during rapid changes in the surface ocean and the atmosphere.
Adolescent Sexual Behavior, Drug Use, and Violence: Increased Reporting with Computer Survey Technology
Authors: Turner C. F. , Ku L. , Rogers S. M. , Lindberg L. D. , Pleck J. H. , Sonenstein F. L.
Published: July 2002

Surveys of risk behaviors have been hobbled by their reliance on respondents to report accurately about engaging in behaviors that are highly sensitive and may be illegal. An audio computer-assisted self-interviewing (audio-CASI) technology for measuring those behaviors was tested with 1690 respondents in the 1995 National Survey of Adolescent Males. The respondents were randomly assigned to answer questions using either audio-CASI or a more traditional self-administered questionnaire. Estimates of the prevalence of male-male sex, injection drug use, and sexual contact with intravenous drug users were higher by factors of 3 or more when audio-CASI was used. Increased reporting was also found for several other risk behaviors.
Tracking the Evolution of a Hydrothermal Event Plume with a RAFOS Neutrally Buoyant Drifter
Authors: Lupton John E. , Baker Edward T. , Garfield Newell , Massoth Gary J. , Feely Richard A. , Cowen James P. , Greene Ronald R. , Rago Thomas A.
Published: July 2002

The migration and evolution of a deep ocean hydrothermal event plume were tracked with a neutrally buoyant RAFOS float. The float remained entrained in the plume for 60 days, and the plume vorticity was calculated directly from the anticyclonic motion of the float. Concentrations of suspended particles, particulate iron, and dissolved manganese in the plume did not decay significantly during the 60 days, which indicates that event plumes would be easily detectable a year after formation.
Requirement for γδ T Cells in Allergic Airway Inflammation
Authors: Zuany-Amorim Claudia , Ruffié Claude , Hailé Solomon , Vargaftig B. Boris , Pereira Pablo , Pretolani Marina
Published: July 2002

The factors that contribute to allergic asthma are unclear but the resulting condition is considered a consequence of a type-2 T helper (T
H
2) cell response. In a model of pulmonary allergic inflammation, mice that lacked γδ T cells had decreases in specific immunoglobulin E (IgE) and IgG1 and pulmonary interleukin-5 (IL-5) release as well as in eosinophil and T cell infiltration compared with wild-type mice. These responses were restored by administration of IL-4 to γδ T cell-deficient mice during the primary immunization. Thus, γδ T cells are essential for inducing IL-4-dependent IgE and IgG1 responses and for T
H
2-mediated airway inflammation to peptidic antigens.
Impairment of Mycobacterial Immunity in Human Interleukin-12 Receptor Deficiency
Authors: Altare Frédéric , Durandy Anne , Lammas David , Emile Jean-François , Lamhamedi Salma , Le Deist Françoise , Drysdale Pam , Jouanguy Emmanuelle , Döffinger Rainer , Bernaudin Françoise , Jeppsson Olle , Gollob Jared A. , Meinl Edgar , Segal Antony W. , Fischer Alain , Kumararatne Dinakantha , Casanova Jean-Laurent
Published: July 2002

In humans, interferon γ (IFN-γ) receptor deficiency leads to a predisposition to mycobacterial infections and impairs the formation of mature granulomas. Interleukin-12 (IL-12) receptor deficiency was found in otherwise healthy individuals with mycobacterial infections. Mature granulomas were seen, surrounded by T cells and centered with epithelioid and multinucleated giant cells, yet reduced IFN-γ concentrations were found to be secreted by activated natural killer and T cells. Thus, IL-12–dependent IFN-γ secretion in humans seems essential in the control of mycobacterial infections, despite the formation of mature granulomas due to IL-12–independent IFN-γ secretion.
Atmosphere-Surface Interactions on Mars: Δ
17
O Measurements of Carbonate from ALH 84001
Authors: Farquhar James , Thiemens Mark H. , Jackson Teresa
Published: July 2002

Oxygen isotope measurements of carbonate from martian meteorite ALH 84001 (δ
18
O = 18.3 ± 0.4 per mil, δ
17
O = 10.3 ± 0.2 per mil, and Δ
17
O = 0.8 ± 0.05 per mil) are fractionated with respect to those of silicate minerals. These measurements support the existence of two oxygen isotope reservoirs (the atmosphere and the silicate planet) on Mars at the time of carbonate growth. The cause of the atmospheric oxygen isotope anomaly may be exchange between CO
2
and O(
1
D) produced by the photodecomposition of ozone. Atmospheric oxygen isotope compositions may be transferred to carbonate minerals by CO
2
-H
2
O exchange and mineral growth. A sink of
17
O-depleted oxygen, as required by mass balance, may exist in the planetary regolith.
Axonal Swellings and Degeneration in Mice Lacking the Major Proteolipid of Myelin
Authors: Griffiths Ian , Klugmann Matthias , Anderson Thomas , Yool Donald , Thomson Christine , Schwab Markus H. , Schneider Armin , Zimmermann Frank , McCulloch Mailise , Nadon Nancy , Nave Klaus-Armin
Published: July 2002

Glial cells produce myelin and contribute to axonal morphology in the nervous system. Two myelin membrane proteolipids, PLP and DM20, were shown to be essential for the integrity of myelinated axons. In the absence of PLP-DM20, mice assembled compact myelin sheaths but subsequently developed widespread axonal swellings and degeneration, associated predominantly with small-caliber nerve fibers. Similar swellings were absent in dysmyelinated
shiverer
mice, which lack myelin basic protein (MBP), but recurred in MBP*PLP double mutants. Thus, fiber degeneration, which was probably secondary to impaired axonal transport, could indicate that myelinated axons require local oligodendroglial support.