bluuebunny/crossref_metadata_2025 huggingface dataset:
Control of Viremia in Simian Immunodeficiency Virus Infection by CD8
+
Lymphocytes
Authors: Schmitz Jörn E. , Kuroda Marcelo J. , Santra Sampa , Sasseville Vito G. , Simon Meredith A. , Lifton Michelle A. , Racz Paul , Tenner-Racz Klara , Dalesandro Margaret , Scallon Bernhard J. , Ghrayeb John , Forman Meryl A. , Montefiori David C. , Rieber E. Peter , Letvin Norman L. , Reimann Keith A.
Published: July 2002

Clinical evidence suggests that cellular immunity is involved in controlling human immunodeficiency virus–1 (HIV-1) replication. An animal model of acquired immune deficiency syndrome (AIDS), the simian immunodeficiency virus (SIV)–infected rhesus monkey, was used to show that virus replication is not controlled in monkeys depleted of CD8
+
lymphocytes during primary SIV infection. Eliminating CD8
+
lymphocytes from monkeys during chronic SIV infection resulted in a rapid and marked increase in viremia that was again suppressed coincident with the reappearance of SIV-specific CD8
+
T cells. These results confirm the importance of cell-mediated immunity in controlling HIV-1 infection and support the exploration of vaccination approaches for preventing infection that will elicit these immune responses.
Mechanism of Zeolite A Nanocrystal Growth from Colloids at Room Temperature
Authors: Mintova Svetlana , Olson Norman H. , Valtchev Valentin , Bein Thomas
Published: July 2002

The formation and growth of crystal nuclei of zeolite A from clear solutions at room temperature were studied with low-dose, high-resolution transmission electron microscopy in field emission mode and with in situ dynamic light scattering. Single zeolite A crystals nucleated in amorphous gel particles of 40 to 80 nanometers within 3 days at room temperature. The resulting nanoscale single crystals (10 to 30 nanometers) were embedded in the amorphous gel particles. The gel particles were consumed during further crystal growth at room temperature, forming a colloidal suspension of zeolite A nanocrystals of 40 to 80 nanometers. On heating this suspension at 80°C, solution-mediated transport resulted in additional substantial crystal growth.
p53- and ATM-Dependent Apoptosis Induced by Telomeres Lacking TRF2
Authors: Karlseder Jan , Broccoli Dominique , Dai Yumin , Hardy Stephen , de Lange Titia
Published: July 2002

Although broken chromosomes can induce apoptosis, natural chromosome ends (telomeres) do not trigger this response. It is shown that this suppression of apoptosis involves the telomeric-repeat binding factor 2 (TRF2). Inhibition of TRF2 resulted in apoptosis in a subset of mammalian cell types. The response was mediated by p53 and the ATM (ataxia telangiectasia mutated) kinase, consistent with activation of a DNA damage checkpoint. Apoptosis was not due to rupture of dicentric chromosomes formed by end-to-end fusion, indicating that telomeres lacking TRF2 directly signal apoptosis, possibly because they resemble damaged DNA. Thus, in some cells, telomere shortening may signal cell death rather than senescence.
The Predictive Value of Changes in Effective Connectivity for Human Learning
Authors: Büchel C. , Coull J. T. , Friston K. J.
Published: July 2002

During learning, neural responses decrease over repeated exposure to identical stimuli. This repetition suppression is thought to reflect a progressive optimization of neuronal responses elicited by the task. Functional magnetic resonance imaging was used to study the neural basis of associative learning of visual objects and their locations. As expected, activation in specialized cortical areas decreased with time. However, with path analysis it was shown that, in parallel to this adaptation, increases in effective connectivity occurred between distinct cortical systems specialized for spatial and object processing. The time course of these plastic changes was highly correlated with individual learning performance, suggesting that interactions between brain areas underlie associative learning.
How Strong Is a Covalent Bond?
Authors: Grandbois Michel , Beyer Martin , Rief Matthias , Clausen-Schaumann Hauke , Gaub Hermann E.
Published: July 2002

The rupture force of single covalent bonds under an external load was measured with an atomic force microscope (AFM). Single polysaccharide molecules were covalently anchored between a surface and an AFM tip and then stretched until they became detached. By using different surface chemistries for the attachment, it was found that the silicon-carbon bond ruptured at 2.0 ± 0.3 nanonewtons, whereas the sulfur-gold anchor ruptured at 1.4 ± 0.3 nanonewtons at force-loading rates of 10 nanonewtons per second. Bond rupture probability calculations that were based on density functional theory corroborate the measured values.
Phase-Separated Composite Films for Liquid Crystal Displays
Authors: Vorflusev Valery , Kumar Satyendra
Published: July 2002

A method of preparing liquid crystal devices by phase separation of liquid crystal from its solution in a prepolymer, which results in adjacent layers of liquid crystal and polymer, is described. Liquid crystals in these phase-separated composite films exhibit electro-optical properties not observed in devices prepared by conventional methods, polymer dispersion, or polymer-stabilization methods. Devices incorporating ferroelectric liquid crystals have gray scale and switch 100 times faster at low fields than conventional surface-stabilized devices. This method makes it possible to prepare devices with liquid crystal film thickness comparable to optical wavelengths.
The Role of Local Actin Instability in Axon Formation
Authors: Bradke Frank , Dotti Carlos G.
Published: July 2002

The role of localized instability of the actin network in specifying axonal fate was examined with the use of rat hippocampal neurons in culture. During normal neuronal development, actin dynamics and instability polarized to a single growth cone before axon formation. Consistently, global application of actin-depolymerizing drugs and of the Rho-signaling inactivator toxin B to nonpolarized cells produced neurons with multiple axons. Moreover, disruption of the actin network in one individual growth cone induced its neurite to become the axon. Thus, local instability of the actin network restricted to a single growth cone is a physiological signal specifying neuronal polarization.
The Maize
rough sheath2
Gene and Leaf Development Programs in Monocot and Dicot Plants
Authors: Tsiantis Miltos , Schneeberger Richard , Golz John F. , Freeling Michael , Langdale Jane A.
Published: July 2002

Leaves of higher plants develop in a sequential manner from the shoot apical meristem. Previously it was determined that perturbed leaf development in maize
rough sheath2
(
rs2
) mutant plants results from ectopic expression of
knotted1
-like (
knox
) homeobox genes. Here, the
rs2
gene sequence was found to be similar to the
Antirrhinum PHANTASTICA
(
PHAN
) gene sequence, which encodes a Myb-like transcription factor. RS2 and PHAN are both required to prevent the accumulation of
knox
gene products in maize and
Antirrhinum
leaves, respectively. However,
rs2
and
phan
mutant phenotypes differ, highlighting fundamental differences in monocot and dicot leaf development programs.
Propagation of a Magnetic Domain Wall in a Submicrometer Magnetic Wire
Authors: Ono T. , Miyajima H. , Shigeto K. , Mibu K. , Hosoito N. , Shinjo T.
Published: July 2002

The motion of a magnetic domain wall in a submicrometer magnetic wire was detected by use of the giant magnetoresistance effect. Magnetization reversal in a submicrometer magnetic wire takes place by the propagation of a magnetic domain wall, which can be treated as a “particle.” The propagation velocity of the magnetic domain wall was determined as a function of the applied magnetic field.
Synergistic Signaling in Fetal Brain by STAT3-Smad1 Complex Bridged by p300
Authors: Nakashima Kinichi , Yanagisawa Makoto , Arakawa Hirokazu , Kimura Naoki , Hisatsune Tatsuhiro , Kawabata Masahiro , Miyazono Kohei , Taga Tetsuya
Published: July 2002

The cytokines LIF (leukemia inhibitory factor) and BMP2 (bone morphogenetic protein–2) signal through different receptors and transcription factors, namely STATs (signal transducers and activators of transcription) and Smads. LIF and BMP2 were found to act in synergy on primary fetal neural progenitor cells to induce astrocytes. The transcriptional coactivator p300 interacts physically with STAT3 at its amino terminus in a cytokine stimulation–independent manner, and with Smad1 at its carboxyl terminus in a cytokine stimulation–dependent manner. The formation of a complex between STAT3 and Smad1, bridged by p300, is involved in the cooperative signaling of LIF and BMP2 and the subsequent induction of astrocytes from neural progenitors.
Visual Form Created Solely from Temporal Structure
Authors: Lee Sang-Hun , Blake Randolph
Published: July 2002

In several experiments, it was found that global perception of spatial form can arise exclusively from unpredictable but synchronized changes among local features. Within an array of nonoverlapping apertures, contours move in one of two directions, with direction reversing randomly over time. When contours within a region of the array reverse directions in synchrony, they stand out conspicuously from the rest of the array where direction reversals are unsynchronized. Clarity of spatial structure from synchronized change depends on the rate of motion reversal and on the proportion of elements reversing direction in synchrony. Evidently, human vision is sensitive to the rich temporal structure in these stochastic events.
Mammalian Transgenesis by Intracytoplasmic Sperm Injection
Authors: Perry Anthony C. F. , Wakayama Teruhiko , Kishikawa Hidefumi , Kasai Tsuyoshi , Okabe Masaru , Toyoda Yutaka , Yanagimachi Ryuzo
Published: July 2002

Coinjection of unfertilized mouse oocytes with sperm heads and exogenous DNA encoding either a green fluorescent protein (GFP) or β-galactosidase reporter produced 64 to 94 percent transgene-expressing embryos, reflecting DNA–sperm head association before coinjection. Nonselective transfer to surrogate mothers of embryos in the GFP series generated about 20 percent offspring expressing the integrated transgene. These data indicate that exogenous DNA can reproducibly be delivered into an oocyte by microinjected spermatozoa and suggest an adaptable method of transgenesis.
Rapid Spine Delivery and Redistribution of AMPA Receptors After Synaptic NMDA Receptor Activation
Authors: Shi Song-Hai , Hayashi Yasunori , Petralia Ronald S. , Zaman Shahid H. , Wenthold Robert J. , Svoboda Karel , Malinow Roberto
Published: July 2002

To monitor changes in α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor distribution in living neurons, the AMPA receptor subunit GluR1 was tagged with green fluorescent protein (GFP). This protein (GluR1-GFP) was functional and was transiently expressed in hippocampal CA1 neurons. In dendrites visualized with two-photon laser scanning microscopy or electron microscopy, most of the GluR1-GFP was intracellular, mimicking endogenous GluR1 distribution. Tetanic synaptic stimulation induced a rapid delivery of tagged receptors into dendritic spines as well as clusters in dendrites. These postsynaptic trafficking events required synaptic
N
-methyl-
d
-aspartate (NMDA) receptor activation and may contribute to the enhanced AMPA receptor–mediated transmission observed during long-term potentiation and activity-dependent synaptic maturation.
An Adhesin of the Yeast Pathogen
Candida glabrata
Mediating Adherence to Human Epithelial Cells
Authors: Cormack Brendan P. , Ghori Nafisa , Falkow Stanley
Published: July 2002

Candida glabrata
is an important fungal pathogen of humans that is responsible for about 15 percent of mucosal and systemic candidiasis.
Candida glabrata
adhered avidly to human epithelial cells in culture. By means of a genetic approach and a strategy allowing parallel screening of mutants, it was possible to clone a lectin from a
Candida
species. Deletion of this adhesin reduced adherence of
C. glabrata
to human epithelial cells by 95 percent. The adhesin, encoded by the
EPA1
gene, is likely a glucan–cross-linked cell-wall protein and binds to host-cell carbohydrate, specifically recognizing asialo-lactosyl–containing carbohydrates.
Single-Mode Photonic Band Gap Guidance of Light in Air
Authors: Cregan R. F. , Mangan B. J. , Knight J. C. , Birks T. A. , Russell P. St. J. , Roberts P. J. , Allan D. C.
Published: July 2002

The confinement of light within a hollow core (a large air hole) in a silica-air photonic crystal fiber is demonstrated. Only certain wavelength bands are confined and guided down the fiber, each band corresponding to the presence of a full two-dimensional band gap in the photonic crystal cladding. Single-mode vacuum waveguides have a multitude of potential applications from ultrahigh-power transmission to the guiding of cold atoms.
Yeast Gene for a Tyr-DNA Phosphodiesterase that Repairs Topoisomerase I Complexes
Authors: Pouliot Jeffrey J. , Yao Kevin C. , Robertson Carol A. , Nash Howard A.
Published: July 2002

Covalent intermediates between topoisomerase I and DNA can become dead-end complexes that lead to cell death. Here, the isolation of the gene for an enzyme that can hydrolyze the bond between this protein and DNA is described. Enzyme-defective mutants of yeast are hypersensitive to treatments that increase the amount of covalent complexes, indicative of enzyme involvement in repair. The gene is conserved in eukaryotes and identifies a family of enzymes that has not been previously recognized. The presence of this gene in humans may have implications for the effectiveness of topoisomerase I poisons, such as the camptothecins, in chemotherapy.
The Olfactory Bulb: Coding and Processing of Odor Molecule Information
Authors: Mori Kensaku , Nagao Hiroshi , Yoshihara Yoshihiro
Published: July 2002

Olfactory sensory neurons detect a large variety of odor molecules and send information through their axons to the olfactory bulb, the first site for the processing of olfactory information in the brain. The axonal connection is precisely organized so that signals from 1000 different types of odorant receptors are sorted out in 1800 glomeruli in the mouse olfactory bulb. Individual glomerular modules presumably represent a single type of receptor and are thus tuned to specific molecular features of odorants. Local neuronal circuits in the bulb mediate lateral inhibition among glomerular modules to sharpen the tuning specificity of output neurons. They also mediate synchronized oscillatory discharges among specific combinations of output neurons and may contribute to the integration of signals from distinct odorant receptors in the olfactory cortex.
Nongenomic Transmission Across Generations of Maternal Behavior and Stress Responses in the Rat
Authors: Francis Darlene , Diorio Josie , Liu Dong , Meaney Michael J.
Published: July 2002

In the rat, variations in maternal care appear to influence the development of behavioral and endocrine responses to stress in the offspring. The results of cross-fostering studies reported here provide evidence for (i) a causal relationship between maternal behavior and stress reactivity in the offspring and (ii) the transmission of such individual differences in maternal behavior from one generation of females to the next. Moreover, an environmental manipulation imposed during early development that alters maternal behavior can then affect the pattern of transmission in subsequent generations. Taken together, these findings indicate that variations in maternal care can serve as the basis for a nongenomic behavioral transmission of individual differences in stress reactivity across generations.
The Male Determinant of Self-Incompatibility in
Brassica
Authors: Schopfer Christel R. , Nasrallah Mikhail E. , Nasrallah June B.
Published: July 2002

In the
S
locus–controlled self-incompatibility system of
Brassica
, recognition of self-related pollen at the surface of stigma epidermal cells leads to inhibition of pollen tube development. The female (stigmatic) determinant of this recognition reaction is a polymorphic transmembrane receptor protein kinase encoded at the
S
locus. Another highly polymorphic, anther-expressed gene,
SCR
, also encoded at the
S
locus, fulfills the requirements for the hypothesized pollen determinant. Loss-of-function and gain-of-function studies prove that the SCR gene product is necessary and sufficient for determining pollen self-incompatibility specificity, possibly by acting as a ligand for the stigmatic receptor.
Predicting the Evolution of Human Influenza A
Authors: Bush Robin M. , Bender Catherine A. , Subbarao Kanta , Cox Nancy J. , Fitch Walter M.
Published: July 2002

Eighteen codons in the HA1 domain of the hemagglutinin genes of human influenza A subtype H3 appear to be under positive selection to change the amino acid they encode. Retrospective tests show that viral lineages undergoing the greatest number of mutations in the positively selected codons were the progenitors of future H3 lineages in 9 of 11 recent influenza seasons. Codons under positive selection were associated with antibody combining site A or B or the sialic acid receptor binding site. However, not all codons in these sites had predictive value. Monitoring new H3 isolates for additional changes in positively selected codons might help identify the most fit extant viral strains that arise during antigenic drift.
Bacteriophytochromes: Phytochrome-Like Photoreceptors from Nonphotosynthetic Eubacteria
Authors: Davis Seth J. , Vener Alexander V. , Vierstra Richard D.
Published: July 2002

Phytochromes are a family of photoreceptors used by green plants to entrain their development to the light environment. The distribution of these chromoproteins has been expanded beyond photoautotrophs with the discovery of phytochrome-like proteins in the nonphotosynthetic eubacteria
Deinococcus radiodurans
and
Pseudomonas aeruginosa
. Like plant phytochromes, the
D. radiodurans
receptor covalently binds linear tetrapyrroles autocatalytically to generate a photochromic holoprotein. However, the attachment site is distinct, using a histidine to potentially form a Schiff base linkage. Sequence homology and mutational analysis suggest that
D. radiodurans
bacteriophytochrome functions as a light-regulated histidine kinase, which helps protect the bacterium from visible light.
Protein Interaction Mapping in
C. elegans
Using Proteins Involved in Vulval Development
Authors: Walhout Albertha J. M. , Sordella Raffaella , Lu Xiaowei , Hartley James L. , Temple Gary F. , Brasch Michael A. , Thierry-Mieg Nicolas , Vidal Marc
Published: July 2002

Protein interaction mapping using large-scale two-hybrid analysis has been proposed as a way to functionally annotate large numbers of uncharacterized proteins predicted by complete genome sequences. This approach was examined in
Caenorhabditis elegans
, starting with 27 proteins involved in vulval development. The resulting map reveals both known and new potential interactions and provides a functional annotation for approximately 100 uncharacterized gene products. A protein interaction mapping project is now feasible for
C. elegans
on a genome-wide scale and should contribute to the understanding of molecular mechanisms in this organism and in human diseases.
Tbx5 and the Retinotectum Projection
Authors: Koshiba-Takeuchi Kazuko , Takeuchi Jun K. , Matsumoto Ken , Momose Tsuyoshi , Uno Kenichiro , Hoepker Veit , Ogura Keiko , Takahashi Naoki , Nakamura Harukazu , Yasuda Kunio , Ogura Toshihiko
Published: July 2002

Dorsal and ventral aspects of the eye are distinct from the early stages of development. The developing eye cup grows dorsally, and the choroidal fissure is formed on its ventral side. Retinal axons from the dorsal and ventral retina project to the ventral and dorsal tectum, respectively. Misexpression of the
Tbx5
gene induced dorsalization of the ventral side of the eye and altered projections of retinal ganglion cell axons. Thus, Tbx5 is involved in eye morphogenesis and is a topographic determinant of the visual projections between retina and tectum.
Communication Through a Diffusive Medium: Coherence and Capacity
Authors: Moustakas Aris L. , Baranger Harold U. , Balents Leon , Sengupta Anirvan M. , Simon Steven H.
Published: July 2002

Coherent wave propagation in disordered media gives rise to many fascinating phenomena as diverse as universal conductance fluctuations in mesoscopic metals and speckle patterns in light scattering. Here, the theory of electromagnetic wave propagation in diffusive media is combined with information theory to show how interference affects the information transmission rate between antenna arrays. Nontrivial dependencies of the information capacity on the nature of the antenna arrays are found, such as the dimensionality of the arrays and their direction with respect to the local scattering medium. This approach provides a physical picture for understanding the importance of scattering in the transfer of information through wireless communications.
Redox Signaling in Chloroplasts: Cleavage of Disulfides by an Iron-Sulfur Cluster
Authors: Dai Shaodong , Schwendtmayer Cristina , Schürmann Peter , Ramaswamy S. , Eklund Hans
Published: July 2002

Light generates reducing equivalents in chloroplasts that are used not only for carbon reduction, but also for the regulation of the activity of chloroplast enzymes by reduction of regulatory disulfides via the ferredoxin:thioredoxin reductase (FTR) system. FTR, the key electron/thiol transducer enzyme in this pathway, is unique in that it can reduce disulfides by an iron-sulfur cluster, a property that is explained by the tight contact of its active-site disulfide and the iron-sulfur center. The thin, flat FTR molecule makes the two-electron reduction possible by forming on one side a mixed disulfide with thioredoxin and by providing on the opposite side access to ferredoxin for delivering electrons.
Signaling and Circuitry of Multiple MAPK Pathways Revealed by a Matrix of Global Gene Expression Profiles
Authors: Roberts Christopher J. , Nelson Bryce , Marton Matthew J. , Stoughton Roland , Meyer Michael R. , Bennett Holly A. , He Yudong D. , Dai Hongyue , Walker Wynn L. , Hughes Timothy R. , Tyers Mike , Boone Charles , Friend † Stephen H.
Published: July 2002

Genome-wide transcript profiling was used to monitor signal transduction during yeast pheromone response. Genetic manipulations allowed analysis of changes in gene expression underlying pheromone signaling, cell cycle control, and polarized morphogenesis. A two-dimensional hierarchical clustered matrix, covering 383 of the most highly regulated genes, was constructed from 46 diverse experimental conditions. Diagnostic subsets of coexpressed genes reflected signaling activity, cross talk, and overlap of multiple mitogen-activated protein kinase (MAPK) pathways. Analysis of the profiles specified by two different MAPKs—Fus3p and Kss1p—revealed functional overlap of the filamentous growth and mating responses. Global transcript analysis reflects biological responses associated with the activation and perturbation of signal transduction pathways.
Regulation of Cell Fate Decision of Undifferentiated Spermatogonia by GDNF
Authors: Meng Xiaojuan , Lindahl Maria , Hyvönen Mervi E. , Parvinen Martti , de Rooij Dirk G. , Hess Michael W. , Raatikainen-Ahokas Anne , Sainio Kirsi , Rauvala Heikki , Lakso Merja , Pichel José G. , Westphal Heiner , Saarma Mart , Sariola Hannu
Published: July 2002

The molecular control of self-renewal and differentiation of stem cells has remained enigmatic. Transgenic loss-of-function and overexpression models now show that the dosage of glial cell line–derived neurotrophic factor (GDNF), produced by Sertoli cells, regulates cell fate decisions of undifferentiated spermatogonial cells that include the stem cells for spermatogenesis. Gene-targeted mice with one
GDNF
-null allele show depletion of stem cell reserves, whereas mice overexpressing GDNF show accumulation of undifferentiated spermatogonia. They are unable to respond properly to differentiation signals and undergo apoptosis upon retinoic acid treatment. Nonmetastatic testicular tumors are regularly formed in older GDNF-overexpressing mice. Thus, GDNF contributes to paracrine regulation of spermatogonial self-renewal and differentiation.
The Catalytic Pathway of Cytochrome P450cam at Atomic Resolution
Authors: Schlichting Ilme , Berendzen Joel , Chu Kelvin , Stock Ann M. , Maves Shelley A. , Benson David E. , Sweet Robert M. , Ringe Dagmar , Petsko Gregory A. , Sligar Stephen G.
Published: July 2002

Members of the cytochrome P450 superfamily catalyze the addition of molecular oxygen to nonactivated hydrocarbons at physiological temperature—a reaction that requires high temperature to proceed in the absence of a catalyst. Structures were obtained for three intermediates in the hydroxylation reaction of camphor by P450cam with trapping techniques and cryocrystallography. The structure of the ferrous dioxygen adduct of P450cam was determined with 0.91 angstrom wavelength x-rays; irradiation with 1.5 angstrom x-rays results in breakdown of the dioxygen molecule to an intermediate that would be consistent with an oxyferryl species. The structures show conformational changes in several important residues and reveal a network of bound water molecules that may provide the protons needed for the reaction.
Epitopes Involved in Antibody-Mediated Protection from Ebola Virus
Authors: Wilson Julie A. , Hevey Michael , Bakken Russell , Guest Shawn , Bray Mike , Schmaljohn Alan L. , Hart Mary Kate
Published: July 2002

To determine the ability of antibodies to provide protection from Ebola viruses, monoclonal antibodies (mAbs) to the Ebola glycoprotein were generated and evaluated for efficacy. We identified several protective mAbs directed toward five unique epitopes on Ebola glycoprotein. One of the epitopes is conserved among all Ebola viruses that are known to be pathogenic for humans. Some protective mAbs were also effective therapeutically when administered to mice 2 days after exposure to lethal Ebola virus. The identification of protective mAbs has important implications for developing vaccines and therapies for Ebola virus.
A
Drosophila
Complementary DNA Resource
Authors: Rubin Gerald M. , Hong Ling , Brokstein Peter , Evans-Holm Martha , Frise Erwin , Stapleton Mark , Harvey Damon A.
Published: July 2002

Collections of nonredundant, full-length complementary DNA (cDNA) clones for each of the model organisms and humans will be important resources for studies of gene structure and function. We describe a general strategy for producing such collections and its implementation, which so far has generated a set of cDNAs corresponding to over 40% of the genes in the fruit fly
Drosophila melanogaster
.
Positioning of Longitudinal Nerves in
C. elegans
by Nidogen
Authors: Kim Seonhee , Wadsworth William G.
Published: July 2002

Basement membranes can help determine pathways of migrating axons. Although members of the nidogen (entactin) protein family are structural components of basement membranes, we find that nidogen is not required for basement membrane assembly in the nematode
Caenorhabditis elegans
. Nidogen is localized to body wall basement membranes and is required to direct longitudinal nerves dorsoventrally and to direct axons at the midlines. By examining migration of a single axon in vivo, we show that nidogen is required for the axon to switch from circumferential to longitudinal migration. Specialized basement membranes may thus regulate nerve position.
Resetting Central and Peripheral Circadian Oscillators in Transgenic Rats
Authors: Yamazaki Shin , Numano Rika , Abe Michikazu , Hida Akiko , Takahashi Ri-ichi , Ueda Masatsugu , Block Gene D. , Sakaki Yoshiyuki , Menaker Michael , Tei Hajime
Published: July 2002

In multicellular organisms, circadian oscillators are organized into multitissue systems which function as biological clocks that regulate the activities of the organism in relation to environmental cycles and provide an internal temporal framework. To investigate the organization of a mammalian circadian system, we constructed a transgenic rat line in which luciferase is rhythmically expressed under the control of the mouse
Per1
promoter. Light emission from cultured suprachiasmatic nuclei (SCN) of these rats was invariably and robustly rhythmic and persisted for up to 32 days in vitro. Liver, lung, and skeletal muscle also expressed circadian rhythms, which damped after two to seven cycles in vitro. In response to advances and delays of the environmental light cycle, the circadian rhythm of light emission from the SCN shifted more rapidly than did the rhythm of locomotor behavior or the rhythms in peripheral tissues. We hypothesize that a self-sustained circadian pacemaker in the SCN entrains circadian oscillators in the periphery to maintain adaptive phase control, which is temporarily lost following large, abrupt shifts in the environmental light cycle.
Interacting Molecular Loops in the Mammalian Circadian Clock
Authors: Shearman Lauren P. , Sriram Sathyanarayanan , Weaver David R. , Maywood Elizabeth S. , Chaves Inẽs , Zheng Binhai , Kume Kazuhiko , Lee Cheng Chi , van der Gijsbertus T. J. , Horst  , Hastings Michael H. , Reppert Steven M.
Published: July 2002

We show that, in the mouse, the core mechanism for the master circadian clock consists of interacting positive and negative transcription and translation feedback loops. Analysis of
Clock/Clock
mutant mice, homozygous

Period2
Brdm1

mutants, and
Cryptochrome
-deficient mice reveals substantially altered
Bmal1
rhythms, consistent with a dominant role of PERIOD2 in the positive regulation of the
Bmal1
loop. In vitro analysis of CRYPTOCHROME inhibition of CLOCK: BMAL1-mediated transcription shows that the inhibition is through direct protein:protein interactions, independent of the PERIOD and TIMELESS proteins. PERIOD2 is a positive regulator of the
Bmal1
loop, and CRYPTOCHROMES are the negative regulators of the
Period
and
Cryptochrome
cycles.
Scaling Up HIV/AIDS Programs to National Coverage
Authors: Binswanger Hans P.
Published: July 2002

The most important issue in the fight against HIV/AIDS is how to scale up existing programs that are only reaching small numbers of people to the national level. Here, I present suggestions on how to tackle the daunting challenge of building truly national HIV/AIDS programs, based on insights gained from participatory, decentralized rural development experiences and from HIV/AIDS programs.
High-Strength Welds in Metallocene Polypropylene/Polyethylene Laminates
Authors: Chaffin Kimberly A. , Knutsen Jeffrey S. , Brant Patrick , Bates Frank S.
Published: July 2002

Spectacular advances in organometallic chemistry over the past two decades have resulted in single-site catalysts that are revolutionizing production of polyethylene (PE) and isotactic polypropylene (
i
PP). This report describes an unanticipated benefit of metallocene-catalyzed semicrystalline polyolefins, namely welded joint strengths in PE/
i
PP laminates that can exceed the cohesive strength of the constituents. We propose that interfacial polymer entanglements, established in the molten state and subsequently anchored in chain-folded lamellae upon crystallization, are responsible for this intrinsic property. The poor adhesion exhibited by traditional Ziegler-Natta–catalyzed polyolefins is shown to derive from the accumulation of amorphous polymer, a by-product of the polymerization reactions, at the interface. These results should facilitate fabrication and improve the properties of composites based on materials that dominate the plastics industry.
Activating Mineralocorticoid Receptor Mutation in Hypertension Exacerbated by Pregnancy
Authors: Geller David S. , Farhi Anita , Pinkerton Nikki , Fradley Michael , Moritz Michael , Spitzer Adrian , Meinke Gretchen , Tsai Francis T. F. , Sigler Paul B. , Lifton Richard P.
Published: July 2002

Hypertension and pregnancy-related hypertension are major public health problems of largely unknown causes. We describe a mutation in the mineralocorticoid receptor (MR), S810L, that causes early-onset hypertension that is markedly exacerbated in pregnancy. This mutation results in constitutive MR activity and alters receptor specificity, with progesterone and other steroids lacking 21-hydroxyl groups, normally MR antagonists, becoming potent agonists. Structural and biochemical studies indicate that the mutation results in the gain of a van der Waals interaction between helix 5 and helix 3 that substitutes for interaction of the steroid 21-hydroxyl group with helix 3 in the wild-type receptor. This helix 5–helix 3 interaction is highly conserved among diverse nuclear hormone receptors, suggesting its general role in receptor activation.
O
2
Activation by Nonheme Iron Complexes: A Monomeric Fe(III)-Oxo Complex Derived From O
2
Authors: MacBeth Cora E. , Golombek Adina P. , Young Victor G. , Yang Cheng , Kuczera Krzysztof , Hendrich Michael P. , Borovik A. S.
Published: July 2002

Iron species with terminal oxo ligands are implicated as key intermediates in several synthetic and biochemical catalytic cycles. However, there is a dearth of structural information regarding these types of complexes because their instability has precluded isolation under ambient conditions. The isolation and structural characterization of an iron(III) complex with a terminal oxo ligand, derived directly from dioxygen (O
2
), is reported. A stable structure resulted from placing the oxoiron unit within a synthetic cavity lined with hydrogen-bonding groups. The cavity creates a microenvironment around the iron center that aids in regulating O
2
activation and stabilizing the oxoiron unit. These cavities share properties with the active sites of metalloproteins, where function is correlated strongly with site structure.
Primordial Carbonylated Iron-Sulfur Compounds and the Synthesis of Pyruvate
Authors: Cody George D. , Boctor Nabil Z. , Filley Timothy R. , Hazen Robert M. , Scott James H. , Sharma Anurag , Yoder Hatten S.
Published: July 2002

Experiments exploring the potential catalytic role of iron sulfide at 250°C and elevated pressures (50, 100, and 200 megapascals) revealed a facile, pressure-enhanced synthesis of organometallic phases formed through the reaction of alkyl thiols and carbon monoxide with iron sulfide. A suite of organometallic compounds were characterized with ultraviolet-visible and Raman spectroscopy. The natural synthesis of such compounds is anticipated in present-day and ancient environments wherever reduced hydrothermal fluids pass through iron sulfide–containing crust. Here, pyruvic acid was synthesized in the presence of such organometallic phases. These compounds could have provided the prebiotic Earth with critical biochemical functionality.
Structural Evidence for Evolution of the β/α Barrel Scaffold by Gene Duplication and Fusion
Authors: Lang Dietmar , Thoma Ralf , Henn-Sax Martina , Sterner Reinhard , Wilmanns Matthias
Published: July 2002

The atomic structures of two proteins in the histidine biosynthesis pathway consist of β/α barrels with a twofold repeat pattern. It is likely that these proteins evolved by twofold gene duplication and gene fusion from a common half-barrel ancestor. These ancestral domains are not visible as independent domains in the extant proteins but can be inferred from a combination of sequence and structural analysis. The detection of subdomain structures may be useful in efforts to search genome sequences for functionally and structurally related proteins.
Molecular Evidence for the Early Evolution of Photosynthesis
Authors: Xiong Jin , Fischer William M. , Inoue Kazuhito , Nakahara Masaaki , Bauer Carl E.
Published: July 2002

The origin and evolution of photosynthesis have long remained enigmatic due to a lack of sequence information of photosynthesis genes across the entire photosynthetic domain. To probe early evolutionary history of photosynthesis, we obtained new sequence information of a number of photosynthesis genes from the green sulfur bacterium
Chlorobium tepidum
and the green nonsulfur bacterium
Chloroflexus aurantiacus
. A total of 31 open reading frames that encode enzymes involved in bacteriochlorophyll/porphyrin biosynthesis, carotenoid biosynthesis, and photosynthetic electron transfer were identified in about 100 kilobase pairs of genomic sequence. Phylogenetic analyses of multiple magnesium-tetrapyrrole biosynthesis genes using a combination of distance, maximum parsimony, and maximum likelihood methods indicate that heliobacteria are closest to the last common ancestor of all oxygenic photosynthetic lineages and that green sulfur bacteria and green nonsulfur bacteria are each other's closest relatives. Parsimony and distance analyses further identify purple bacteria as the earliest emerging photosynthetic lineage. These results challenge previous conclusions based on 16
S
ribosomal RNA and Hsp60/Hsp70 analyses that green nonsulfur bacteria or heliobacteria are the earliest phototrophs. The overall consensus of our phylogenetic analysis, that bacteriochlorophyll biosynthesis evolved before chlorophyll biosynthesis, also argues against the long-held Granick hypothesis.
Historical Trends in Lake and River Ice Cover in the Northern Hemisphere
Authors: Magnuson John J. , Robertson Dale M. , Benson Barbara J. , Wynne Randolph H. , Livingstone David M. , Arai Tadashi , Assel Raymond A. , Barry Roger G. , Card Virginia , Kuusisto Esko , Granin Nick G. , Prowse Terry D. , Stewart Kenton M. , Vuglinski Valery S.
Published: July 2002

Freeze and breakup dates of ice on lakes and rivers provide consistent evidence of later freezing and earlier breakup around the Northern Hemisphere from 1846 to 1995. Over these 150 years, changes in freeze dates averaged 5.8 days per 100 years later, and changes in breakup dates averaged 6.5 days per 100 years earlier; these translate to increasing air temperatures of about 1.2°C per 100 years. Interannual variability in both freeze and breakup dates has increased since 1950. A few longer time series reveal reduced ice cover (a warming trend) beginning as early as the 16th century, with increasing rates of change after about 1850.
Interhemispheric Asymmetries of the Modular Structure in Human Temporal Cortex
Authors: Galuske Ralf A. W. , Schlote Wolfgang , Bratzke Hansjürgen , Singer Wolf
Published: July 2002

Language-relevant processing of auditory signals is lateralized and involves the posterior part of Brodmann area 22. We found that the functional lateralization in this area was accompanied by interhemispheric differences in the organization of the intrinsic microcircuitry. Neuronal tract tracing revealed a modular network of long-range intrinsic connections linking regularly spaced clusters of neurons. Although the cluster diameter was similar in both hemispheres, their spacing was about 20 percent larger in the left hemisphere. Assuming similar relations between functional and anatomical architecture as in visual cortex, the present data suggest that more functionally distinct columnar systems are included per surface unit in the left than in the right area 22.
A Function for Kinesin I in the Posterior Transport of
oskar
mRNA and Staufen Protein
Authors: Brendza Robert P. , Serbus Laura R. , Duffy Joseph B. , Saxton William M.
Published: July 2002

The asymmetric localization of messenger RNA (mRNA) and protein determinants plays an important role in the establishment of complex body plans. In
Drosophila
oocytes, the anterior localization of
bicoid
mRNA and the posterior localization of
oskar
mRNA are key events in establishing the anterior-posterior axis. Although the mechanisms that drive
bicoid
and
oskar
localization have been elusive, oocyte microtubules are known to be essential. Here we report that the plus end–directed microtubule motor kinesin I is required for the posterior localization of
oskar
mRNA and an associated protein, Staufen, but not for the anterior-posterior localization of other asymmetric factors. Thus, a complex containing
oskar
mRNA and Staufen may be transported along microtubules to the posterior pole by kinesin I.
Spin-Dependent Tunneling in Self-Assembled Cobalt-Nanocrystal Superlattices
Authors: Black C. T. , Murray C. B. , Sandstrom R. L. , Sun Shouheng
Published: July 2002

Self-assembled devices composed of periodic arrays of 10-nanometer-diameter cobalt nanocrystals display spin-dependent electron transport. Current-voltage characteristics are well described by single-electron tunneling in a uniform array. At temperatures below 20 kelvin, device magnetoresistance ratios are on the order of 10%, approaching the maximum predicted for ensembles of cobalt islands with randomly oriented preferred magnetic axes. Low-energy spin-flip scattering suppresses magnetoresistance with increasing temperature and bias-voltage.
Rapid Changes in the Hydrologic Cycle of the Tropical Atlantic During the Last Glacial
Authors: Peterson Larry C. , Haug Gerald H. , Hughen Konrad A. , Röhl Ursula
Published: July 2002

Sedimentary time series of color reflectance and major element chemistry from the anoxic Cariaco Basin off the coast of northern Venezuela record large and abrupt shifts in the hydrologic cycle of the tropical Atlantic during the past 90,000 years. Marine productivity maxima and increased precipitation and riverine discharge from northern South America are closely linked to interstadial (warm) climate events of marine isotope stage 3, as recorded in Greenland ice cores. Increased precipitation at this latitude during interstadials suggests the potential for greater moisture export from the Atlantic to Pacific, which could have affected the salinity balance of the Atlantic and increased thermohaline heat transport to high northern latitudes. This supports the notion that tropical feedbacks played an important role in modulating global climate during the last glacial period.
Extended Life-Span Conferred by Cotransporter Gene Mutations in
Drosophila
Authors: Rogina Blanka , Reenan Robert A. , Nilsen Steven P. , Helfand Stephen L.
Published: July 2002

Aging is genetically determined and environmentally modulated. In a study of longevity in the adult fruit fly,
Drosophila melanogaster
, we found that five independent P-element insertional mutations in a single gene resulted in a near doubling of the average adult life-span without a decline in fertility or physical activity. Sequence analysis revealed that the product of this gene, named
Indy
(for
I'm not dead yet
), is most closely related to a mammalian sodium dicarboxylate cotransporter—a membrane protein that transports Krebs cycle intermediates.
Indy
was most abundantly expressed in the fat body, midgut, and oenocytes: the principal sites of intermediary metabolism in the fly. Excision of the P element resulted in a reversion to normal life-span. These mutations may create a metabolic state that mimics caloric restriction, which has been shown to extend life-span.
A Lost-Wax Approach to Monodisperse Colloids and Their Crystals
Authors: Jiang Peng , Bertone Jane F. , Colvin Vicki L.
Published: July 2002

We report a nanoscale “lost-wax” method for forming colloids with size distributions around 5% and their corresponding colloidal crystals. Macroporous polymer templates are first prepared from a silica colloidal crystal. We then use the uniform and interconnected voids of the porous polymer to generate a wide variety of highly monodisperse inorganic, polymeric, and metallic solid and core-shell colloids, as well as hollow colloids with controllable shell thickness, as colloidal crystals. We can also uniformly deform the polymer template to alter colloidal shape and demonstrate the formation of elliptical particles with precisely controlled aspect ratios.
Capture of a Single Molecule in a Nanocavity
Authors: Gu Li-Qun , Cheley Stephen , Bayley Hagan
Published: July 2002

We describe a heptameric protein pore that has been engineered to accommodate two different cyclodextrin adapters simultaneously within the lumen of a transmembrane β barrel. The volume between the adapters is a cavity of ∼4400 cubic angstroms. Analysis of single-channel recordings reveals that individual charged organic molecules can be pulled into the cavity by an electrical potential. Once trapped, an organic molecule shuttles back and forth between the adapters for hundreds of milliseconds. Such self-assembling nanostructures are of interest for the fabrication of multianalyte sensors and could provide a means to control chemical reactions.
The
d
-Alanine Residues of
Staphylococcus aureus
Teichoic Acids Alter the Susceptibility to Vancomycin and the Activity of Autolytic Enzymes
Authors: Peschel Andreas , Vuong Cuong , Otto Michael , Götz Friedrich
Published: July 2002

Recently,
Staphylococcus aureus
strains with intermediate resistance to vancomycin, the antibiotic of last resort, have been described. Multiple changes in peptidoglycan turnover and structure contribute to the resistance phenotype. Here, we describe that structural changes of teichoic acids in the cell envelope have a considerable influence on the susceptibility to vancomycin and other glycopeptides.
S. aureus
cells lacking
d
-alanine esters in teichoic acids exhibited an at least threefold-increased sensitivity to glycopeptide antibiotics. Furthermore, the autolytic activity of the
d
-alanine mutant was reduced compared to the wild-type, and the mutant was more susceptible to the staphylolytic enzyme lysostaphin. Vancomycin inhibited autolysis at very high concentrations but neither in the wild-type nor in the mutant was the autolytic activity influenced in the range of the MIC. Mutant cells had a considerably higher capacity to bind vancomycin.
Characterization of the Metallo-β-Lactamase Determinant of
Acinetobacter baumannii
AC-54/97 Reveals the Existence of
bla
IMP
Allelic Variants Carried by Gene Cassettes of Different Phylogeny
Authors: Riccio Maria Letizia , Franceschini Nicola , Boschi Letizia , Caravelli Berardo , Cornaglia Giuseppe , Fontana Roberta , Amicosante Gianfranco , Rossolini Gian Maria
Published: July 2002

The metallo-β-lactamase determinant of
Acinetobacter baumannii
AC-54/97, a clinical isolate from Italy that was previously shown to produce an enzyme related to IMP-1, was isolated by means of a PCR methodology which targets amplification of gene cassette arrays inserted into class 1 integrons. Sequencing revealed that this determinant was an allelic variant (named
bla
IMP-2
) of
bla
IMP
found in Japanese isolates and that it was divergent from the latter by 12% of its nucleotide sequence, which evidently had been acquired independently. Similar to
bla
IMP
,
bla
IMP-2
was also carried by an integron-borne gene cassette. However, the 59-base element of the
bla
IMP-2
cassette was unrelated to those of the
bla
IMP
cassettes found in Japanese isolates, indicating a different phylogeny for the gene cassettes carrying the two allelic variants. Expression of the integron-borne
bla
IMP-2
gene in
Escherichia coli
resulted in a significant decrease in susceptibility to a broad array of β-lactams (ampicillin, carbenicillin, cephalothin, cefoxitin, ceftazidime, cefepime, and carbapenems). The IMP-2 enzyme was purified from an
Escherichia coli
strain carrying the cloned determinant, and kinetic parameters were determined with several β-lactam substrates. Compared to IMP-1, the kinetic parameters of IMP-2 were similar overall with some β-lactam substrates (cefoxitin, ceftazidime, cefepime, and imipenem) but remarkably different with others (ampicillin, carbenicillin, cephaloridine, and meropenem), revealing a functional significance of at least some of the mutations that differentiate the two IMP variants. Present findings suggest that the environmental reservoir of
bla
IMP
alleles could be widespread and raise a question about the global risk of their transfer to clinically relevant species.