bluuebunny/crossref_metadata_2025 huggingface dataset:
Low-Frequency Raman Scattering and the Fast Relaxation Process in Glycerol
Authors: Uchino Takashi , Yoko Toshinobu
Published: October 2006

Ab initio molecular orbital calculations were used to determine the structure and vibrational frequencies of the cyclic glycerol trimer, which represents the region of medium-range ordering in liquid and supercooled glycerol. The calculations reproduced the experimentally observed low-frequency Raman scattering peak (or the "boson peak") at ∼50 per centimeter, which suggests that the peak results from the localized collective motions of the cooperatively hydrogen-bonded hydroxyl groups. The calculations also suggest that the fast relaxation process may result from the translational motion of each glycerol molecule in the cyclic structure. On the basis of these results, a model of the glass transition was developed.
Four-Dimensional Imaging: Computer Visualization of 3D Movements in Living Specimens
Authors: Thomas C. , DeVries P. , Hardin J. , White J.
Published: October 2006

The study of many biological processes requires the analysis of three-dimensional (3D) structures that change over time. Optical sectioning techniques can provide 3D data from living specimens; however, when 3D data are collected over a period of time, the quantity of image information produced leads to difficulties in interpretation. A computer-based system is described that permits the analysis and archiving of 3D image data taken over time. The system allows a user to roam through the full range of time points and focal planes in the data set. The user can animate images as an aid to visualization and can append multicolored labels and text notes to identified structures during data analysis. The system provides a valuable tool for the study of embryogenesis and cytoplasmic movements within cells and has considerable potential as an educational tool.
Rural Research in Australia
Authors: Radcliffe John C. , Clarke Adrienne E.
Published: October 2006

Australia has a uniquely productive program of agricultural research that combines basic and applied approaches. Radcliffe and Clarke explain the historical origins of this system and outline some of its successes.
Regulation of Rate of Cartilage Differentiation by Indian Hedgehog and PTH-Related Protein
Authors: Vortkamp Andrea , Lee Kaechoong , Lanske Beate , Segre Gino V. , Kronenberg Henry M. , Tabin Clifford J.
Published: October 2006

Proper regulation of chondrocyte differentiation is necessary for the morphogenesis of skeletal elements, yet little is known about the molecular regulation of this process. A chicken homolog of Indian hedgehog (Ihh), a member of the conserved Hedgehog family of secreted proteins that is expressed during bone formation, has now been isolated. Ihh has biological properties similar to those of Sonic hedgehog (Shh), including the ability to regulate the conserved targets Patched (Ptc) and Gli. Ihh is expressed in the prehypertrophic chondrocytes of cartilage elements, where it regulates the rate of hypertrophic differentiation. Misexpression of Ihh prevents proliferating chondrocytes from initiating the hypertrophic differentiation process. The direct target of Ihh signaling is the perichondrium, where Gli and Ptc flank the expression domain of Ihh. Ihh induces the expression of a second signal, parathyroid hormone-related protein (PTHrP), in the periarticular perichondrium. Analysis of PTHrP (−/−) mutant mice indicated that the PTHrP protein signals to its receptor in the prehypertrophic chondrocytes, thereby blocking hypertrophic differentiation. In vitro application of Hedgehog or PTHrP protein to normal or PTHrP (−/−) limb explants demonstrated that PTHrP mediates the effects of Ihh through the formation of a negative feedback loop that modulates the rate of chondrocyte differentiation.
Gating as a Control Element in Constrictive Binding and Guest Release by Hemicarcerands
Authors: Houk K. N. , Nakamura Kensuke , Sheu Chimin , Keating Amy E.
Published: October 2006

Theoretical modeling of the dynamics of complexation and decomplexation of guest molecules by container molecules reveals that gating has a critical influence on the ease of formation and stability of host-guest complexes. Hosts equipped with gates can form very stable complexes with a variety of guests under readily achievable conditions. Gating involves conformational processes of the host molecule that alter the size of the portals through which guest molecules pass. “French door” and “sliding door” mechanisms of gate opening are identified.
Despite Anxiety, NIH Begins Merging Neuroscience Panels
Authors: Marshall Eliot
Published: October 2006

NIH staffers are discussing plans to merge the peer review systems of three formerly separate institutes—the National Institute of Mental Health, the National Institute of Alcohol Abuse and Alcoholism, and the National Institute on Drug Abuse—that were incorporated into the National Institutes of Health under a 1992 law. The prospect is causing anxiety among some scientists funded by the institutes who fear unsympathetic treatment of behavioral research proposals in a “hard science” environment. But NIH Director Harold Varmus and his extramural chief Wendy Baldwin have begun to nudge the reluctant partners together.
New Experiments Underscore Warnings on Maternal Drinking
Authors: Braun Stephen
Published: October 2006

Fetal alcohol syndrome, which is caused by heavy drinking during pregnancy is the leading preventable cause of mental retardation in the developed world. But exactly how much drinking is too much has been unclear. Now, recent findings suggest that even the kinds of alcohol concentrations produced in the blood by moderate drinking—defined as one to three drinks per day—can have deleterious effects on brain neurons. They may cause neurons to stick less well to one another, for example, and reduce long term potentiation, a strengthening of synaptic connections believed to play a role in learning.
The Public Health Risk of Animal Organ and Tissue Transplantation into Humans
Authors: Murphy Frederick A.
Published: October 2006

Xenotransplantation—the use of animal organs or tissues for transplantation into humans—may overcome the severe problem posed by organ shortages. However, it also has the potential to compromise public health through the spread of novel viral diseases between species. Fundamental questions regarding the relative risks of viruses from potential donor species and different sources of donor material must be addressed. Policy developers must consider whether there are significant differences between xenografts and the unsterilized biological products derived from animals that are now commercially available. A national system for virus screening, discovery, detection, and diagnostics is necessary and will require infrastructural changes.
Oil-Water Interface Templating of Mesoporous Macroscale Structures
Authors: Schacht S. , Huo Q. , Voigt-Martin I. G. , Stucky G. D. , Schüth F.
Published: October 2006

Ordered mesostructured porous silicas that are also macroscopically structured were created by control of the interface on two different length scales simultaneously. Micellar arrays controlled the nanometer-scale assembly, and at the static boundary between an aqueous phase and an organic phase, control was achieved on the micrometer to centimeter scale. Acid-prepared mesostructures of silica were made with the
p
6,
Pm
3
n
, and the
P
6
3
/
mmc
structures in the form of porous fibers 50 to 1000 micrometers in length, hollow spheres with diameters of 1 to 100 micrometers, and thin sheets up to 10 centimeters in diameter and about 10 to 500 micrometers in thickness. These results might have implications for technical applications, such as slow drug-release systems or membranes, and in biomineralization, where many processes are also interface-controlled.
Activation of Pyk2 by Stress Signals and Coupling with JNK Signaling Pathway
Authors: Tokiwa G. , Dikic I. , Lev S. , Schlessinger J.
Published: October 2006

The c-Jun amino-terminal kinase (JNK) is activated by various heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors, inflammatory cytokines, and stress signals. Yet, upstream mediators that link extracellular signals with the JNK signaling pathway are currently unknown. The tyrosine kinase Pyk2 was activated by tumor necrosis factor α, by ultraviolet irradiation, and by changes in osmolarity. Overexpression of Pyk2 led to activation of JNK, and a dominant-negative mutant of Pyk2 interfered with ultraviolet light- or osmotic shock-induced activation of JNK. Pyk2 represents a cell type-specific, stress-sensitive mediator of the JNK signaling pathway.
Organic Light Emitters Gain Longevity
Authors: Service Robert F.
Published: October 2006

For much of the past decade, researchers have been promising to put thin films of light-emitting plastics and other organic materials on display: large, flexible, inexpensive, and efficient screens to be used for everything from lightweight backlights for computer displays to TVs that you can hang flat on the wall or roll up and put in your pocket. Yet, many of these promises have fallen flat as well. Organic lights have tended to burn out after just days or weeks of operation. Recently, however, researchers have been crafting films without as many burnout-causing defects and building devices with additional film layers to enhance light emission. As a result, the future prospects for their devices are beginning to shine.
Device Applications of Side-Chain Ferroelectric Liquid Crystalline Polymer Films
Authors: Blackwood K. M.
Published: October 2006

Side-chain ferroelectric liquid crystalline polymers are currently used in a number of applications, including displays and electrical sensors. Comparisons with existing technologies and materials indicate that relative to ceramics, such polymers have lower figures of merit but offer greater durability in sensor applications.
Short-Period Comets: Primordial Bodies or Collisional Fragments?
Authors: Farinella Paolo , Davis Donald R.
Published: October 2006

Modeling results show that collisions among Edgeworth-Kuiper Belt Objects (EKOs), a vast swarm of small bodies orbiting beyond Neptune, have been a major process affecting this population and its progeny, the short-period comets. Most EKOs larger than about 100 kilometers in diameter survive over the age of the solar system, but at smaller sizes collisional breakup is frequent, producing a cascade of fragments having a power law size-frequency distribution. Collisions are also a plausible mechanism for injecting EKOs 1 to 10 kilometers in diameter into dynamical resonances, where they can be transported into the inner solar system to become short-period comets. The fragmental nature of these comets may explain their physical properties, such as shape, color, and strength.
Coupling of the RAS-MAPK Pathway to Gene Activation by RSK2, a Growth Factor-Regulated CREB Kinase
Authors: Xing Jun , Ginty David D. , Greenberg Michael E.
Published: October 2006

A signaling pathway has been elucidated whereby growth factors activate the transcription factor cyclic adenosine monophosphate response element-binding protein (CREB), a critical regulator of immediate early gene transcription. Growth factor-stimulated CREB phosphorylation at serine-133 is mediated by the RAS-mitogen-activated protein kinase (MAPK) pathway. MAPK activates CREB kinase, which in turn phosphorylates and activates CREB. Purification, sequencing, and biochemical characterization of CREB kinase revealed that it is identical to a member of the pp90
RSK
family, RSK2. RSK2 was shown to mediate growth factor induction of CREB serine-133 phosphorylation both in vitro and in vivo. These findings identify a cellular function for RSK2 and define a mechanism whereby growth factor signals mediated by RAS and MAPK are transmitted to the nucleus to activate gene expression.
Scientists Plan Mercury Probe and Earth Satellite Campaign
Authors: Gavaghan Helen
Published: October 2006

Birmingham, U.K.—The European Space Agency 's (ESA's) science program is preparing to approve a billion-dollar mission to Mercury. Likely to fly late in the next decade, the mission would be humanity's first close-up look at Mercury since Mariner 10, some 20 years ago. One focus of the mission will be Mercury's unexpectedly strong and complex magnetic field. ESA scientists hope to explore the envelope of charged particles trapped by the field and learn what kind of metal core could be generating it.
Life's Last Domain
Authors: Morell Virginia
Published: October 2006

In what many scientists are calling a tour de force, a team of researchers report in this issue of Science (page 1058) that they've sequenced the entire genome of the archaeon microbe Methanococcus jannaschii. With it researchers have their first chance to compare the complete genomes of organisms from what seem to be the three major branches of life: the archaea, bacteria, and eukarya (which includes multicellular organisms such as plants and animals). A startling 44% of the archaeon's 1700-odd genes are entirely new to science. Says one researcher: “That's about half of the organism! It shows just how little we know about life.”
Volcanic Dilemma--Flow or Blow?
Authors: Dingwell D. B.
Published: October 2006

Volcanic eruptions can be either slow outpourings of lava or explosive ejections of fragmented rock. In his Perspective, Dingwell discusses the physical and chemical properties of magma that lead to these two styles of eruption. New experiments and computer simulations are pointing to the involvement of solidlike behavior of liquid magma when it makes a transition to a glass.
An Excellent Lightness
Authors: Albright Thomas D.
Published: October 2006

In a report in this issue, Rossi
et al
. (
p. 1104
) describe neurons in the visual cortex that likely mediate part of the phenomenon of “brightness induction.” In his Perspective, Albright explains brightness induction, exploited by artists to increase the perceived range of light in a painting. The new work takes us closer toward understanding the basis of visual perception.
A Crosslinked Cofactor in Lysyl Oxidase: Redox Function for Amino Acid Side Chains
Authors: Wang Sophie Xuefei , Mure Minae , Medzihradszky Katalin F. , Burlingame Alma L. , Brown Doreen E. , Dooley David M. , Smith Alan J. , Kagan Herbert M. , Klinman Judith P.
Published: October 2006

A previously unknown redox cofactor has been identified in the active site of lysyl oxidase from the bovine aorta. Edman sequencing, mass spectrometry, ultraviolet-visible spectra, and resonance Raman studies showed that this cofactor is a quinone. Its structure is derived from the crosslinking of the ε-amino group of a peptidyl lysine with the modified side chain of a tyrosyl residue, and it has been designated lysine tyrosylquinone. This quinone appears to be the only example of a mammalian cofactor formed from the crosslinking of two amino acid side chains. This discovery expands the range of known quino-cofactor structures and has implications for the mechanism of their biogenesis.
Pilus Assembly by

Agrobacterium

T-DNA Transfer Genes
Authors: Fullner Karla Jean , Lara J. Cano , Nester Eugene W.
Published: October 2006

Agrobacterium tumefaciens
can genetically transform eukaryotic cells. In many bacteria, pili are required for interbacterial DNA transfer. The formation of pili by
Agrobacterium
required induction of tumor-inducing (Ti) plasmid-encoded virulence genes and growth at low temperature. A genetic analysis demonstrated that
virA
,
virG
,
virB1
through
virB11
, and
virD4
are the only Ti plasmid genes necessary for pilus assembly. The loss and gain of pili in various mutants correlated with the loss and gain of transferred DNA (T-DNA) transfer functions, which is consistent with the view that
Agrobacterium
pili are required for transfer of DNA to plant cells in a process similar to that of conjugation.
Trial Set to Focus on Peer Review
Authors: Marshall Eliot
Published: October 2006

More than a decade after it first began, a race to patent a biological molecule is about to be decided in a Seattle courtroom. But this will be no ordinary legal contest over patent law. After years of pretrial skirmishing, the contestants and their teams of experts have recently been homing in on an issue that's likely to resonate widely throughout the scientific community: Does the academic notion of confidential peer review—that reviewers are forbidden to disclose or use information they see in an unpublished manuscript—have any legal validity?
Debating the Big Questions
Authors: Glanz James
Published: October 2006

Princeton, New Jersey—In cosmology, the data have been so thin and theorists so resourceful that warring theories about the history and nature of the universe have seemed to coexist indefinitely. Earlier this summer, 200 of the world's most influential cosmologists met for a gloves-off debate in hopes that some of those disputes could actually be settled. The convergence in some areas was historic, but major sticking points remain, extending all the way back to the big bang.
The Klausner Revolution
Authors: Marshall Eliot
Published: October 2006

In his first year as head of the National Cancer Institute(NCI), cell biologist Richard Klausner has shaken up the cancer establishment and begun to change the culture of the place. He has given lab chiefs more direct control of their own budgets; shifted funds from NCI's own programs into the extramural, academic research community; and is moving to make cancer genetics a major focus of NCI's work.
Viewing Velvet Worms in Amber
Authors: Vogel Gretchen
Published: October 2006

The velvet worms, soft-bodied invertebrates that today roam the forest floors of the Southern Hemisphere, have been proposed to be an evolutionary link between the segmented worms, or annelids, and the wildly diverse arthropods. But the velvet worms' family relations have long been a source of debate, in part because their fossil record is so spotty. A Report on
page 1370
of this issue presents new specimens, 20 million to 40 million years old and preserved in amber, that may link even more ancient fossil forms and the living creatures.
Refining the Taxonomy of Memory
Authors: Robbins Trevor W.
Published: October 2006

Humans can remember things by means of several types of memory. Two of the most important are declarative memory (conscious recollection of facts and events) and skill memory (gradual acquisition of motor abilities, but without conscious awareness). In a report in this issue, Knowlton
et al
. (
p. 1399
) show that patients with Parkinson's disease (and therefore with impaired dopamine input to the striatum) are impaired in skill memory, as measured by a newly designed discrimination learning task, but that their declarative memory is intact. Robbins, in his Perspective, explains what these results mean for the taxonomy of human memory.
Time-Sensitive Reversal of Hyperplasia in Transgenic Mice Expressing SV40 T Antigen
Authors: Ewald Dagmar , Li Minglin , Efrat Shimon , Auer Gert , Wall Robert J. , Furth Priscilla A. , Hennighausen Lothar
Published: October 2006

The role of viral oncoprotein expression in the maintenance of cellular transformation was examined as a function of time through controlled expression of simian virus 40 T antigen (TAg). Expression of TAg in the submandibular gland of transgenic mice from the time of birth induced cellular transformation and extensive ductal hyperplasia by 4 months of age. The hyperplasia was reversed when TAg expression was silenced for 3 weeks. When TAg expression was silenced after 7 months, however, the hyperplasia persisted even though TAg was absent. Although the polyploidy of ductal cells could be reversed at 4 months of age, cells at 7 months of age remained polyploid even in the absence of TAg. These results support a model of time-dependent multistep tumorigenesis, in which virally transformed cells eventually lose their dependence on the viral oncoprotein for maintenance of the transformed state.
Scientists Still Waiting for Promised Reforms
Authors: Williams Nigel
Published: October 2006

Dublin—Early last year, the Irish government promised to issue a white paper outlining its policies for the country's science and technology. The document was supposed to be the official response to a sheaf of recommendations—including proposals for a sharp increase in funds—that had been put forward by a high-level panel. But so far, the government has not fulfilled its promise. Patrick Rabbitte, the country's first Cabinet-level minister for science, says he still hopes that a policy statement will be forthcoming, but researchers are getting impatient.
Categorical Perception of Sound Frequency by Crickets
Authors: Wyttenbach Robert A. , May Michael L. , Hoy Ronald R.
Published: October 2006

Partitioning continuously varying stimuli into categories is a fundamental problem of perception. One solution to this problem, categorical perception, is known primarily from human speech, but also occurs in other modalities and in some mammals and birds. Categorical perception was tested in crickets by using two paradigms of human psychophysics, labeling and habituation-dishabituation. The results show that crickets divide sound frequency categorically between attractive (<16 kilohertz) and repulsive (>16 kilohertz) sounds. There is sharp discrimination between these categories but no discrimination between different frequencies of ultrasound. This demonstration of categorical perception in an invertebrate suggests that categorical perception may be a basic and widespread feature of sensory systems, from humans to invertebrates.
Redefining the Supercomputer
Authors: Taubes Gary
Published: October 2006

The government's high-performance computing program has an audacious new goal: building a computer more than 1000 times faster than today's fastest machine within 10 years. Ata thousand trillion computations per second—a measure of speed known as a petaflops—such a machine could squeeze a year's work for a powerful workstation into 30 seconds. As a first step, researchers are now studying designs for processors that could carry out operations in perhaps 10 trillionths of a second and architectures that could reduce latency—the “down time” when a processor waits for data.
Why the Glass Transition Is Still Interesting
Authors: Sokolov A. P.
Published: October 2006

Many liquids with vastly different properties can form glasses upon cooling. Although this phenomenon has been known since ancient times, no complete general understanding of the glass transition is available. In his Perspective, Sokolov reviews recent theoretical and experimental progress in unraveling the mysteries of glass formation.
Self-Assembly of a Two-Dimensional Superlattice of Molecularly Linked Metal Clusters
Authors: Andres Ronald P. , Bielefeld Jeffery D. , Henderson Jason I. , Janes David B. , Kolagunta Venkat R. , Kubiak Clifford P. , Mahoney William J. , Osifchin Richard G.
Published: October 2006

Close-packed planar arrays of nanometer-diameter metal clusters that are covalently linked to each other by rigid, double-ended organic molecules have been self-assembled. Gold nanocrystals, each encapsulated by a monolayer of alkyl thiol molecules, were cast from a colloidal solution onto a flat substrate to form a close-packed cluster monolayer. Organic interconnects (aryl dithiols or aryl di-isonitriles) displaced the alkyl thiol molecules and covalently linked adjacent clusters in the monolayer to form a two-dimensional superlattice of metal quantum dots coupled by uniform tunnel junctions. Electrical conductance through such a superlattice of 3.7-nanometer-diameter gold clusters, deposited on a SiO
2
substrate in the gap between two gold contacts and linked by an aryl di-isonitrile [1,4-di(4-isocyanophenylethynyl)-2-ethylbenzene], exhibited nonlinear Coulomb charging behavior.
Three Cognitive Markers of Unconscious Semantic Activation
Authors: Greenwald Anthony G. , Draine Sean C. , Abrams Richard L.
Published: October 2006

A "response window" technique is described and used to reliably demonstrate unconscious activation of meaning by subliminal (visually masked) words. Visually masked prime words were shown to influence judged meaning of following target words. This priming-effect marker was used to identify two additional markers of unconscious semantic activation: (i) the activation is very short-lived (the target word must occur within about 100 milliseconds of the subliminal prime); and (ii) unlike supraliminal prime-target pairs, a subliminal pair leaves no memory trace that can be observed in response to the next prime-target pair. Thus, unconscious semantic activation is shown to be a readily reproducible phenomenon but also very limited in the duration of its effect.
Congressional Scorecard Sparks Furor
Authors: Lawler Andrew
Published: October 2006

A scorecard of lawmakers' votes on science-related issues, released last week by a group of distinguished scientists, has provoked a storm of criticism on Capitol Hill and among some science lobbyists. At issue is whether its conclusion—that Democrats are far more pro-science than are Republicans—might do more harm than good in building political support for the cause. Lobbyists are particularly upset that some legislators considered tobe staunch friends of science, including Representative John Porter (R-IL), chair of the spending panel that oversees NIH's budget, were given very low scores.
CD40 Ligand-Dependent T Cell Activation: Requirement of B7-CD28 Signaling Through CD40
Authors: Yang Yiping , Wilson James M.
Published: October 2006

The role of CD40 ligand (CD40L) in the primary activation of T cells is not clear. The cellular and humoral immune responses to adenoviral vectors in a murine model of liver-directed gene transfer were studied to define the mechanisms responsible for CD40L-dependent T cell priming. CD40L-deficient mice did not develop effective cytotoxic T cells to transduced hepatocytes, and T cell-dependent B cell responses were absent. Full reconstitution of cellular and humoral immunity was achieved in CD40L-deficient mice by administration of an activating antibody to CD40 that increased expression of B7.2 on spleen cells. Wild-type mice could be made nonresponsive to vector by administration of antibodies to B7. Thus, CD40L-dependent activation of T cells occurs through signaling of CD40 in the antigen-presenting cell to enhance requisite costimulatory pathways that include B7.
Suppression of ICE and Apoptosis in Mammary Epithelial Cells by Extracellular Matrix
Authors: Boudreau Nancy , Sympson Carolyn J. , Werb Zena , Bissell Mina J.
Published: October 2006

Apoptosis (programmed cell death) plays a major role in development and tissue regeneration. Basement membrane extracellular matrix (ECM), but not fibronectin or collagen, was shown to suppress apoptosis of mammary epithelial cells in tissue culture and in vivo. Apoptosis was induced by antibodies to β
1
integrins or by overexpression of stromelysin-1, which degrades ECM. Expression of interleukin-1β converting enzyme (ICE) correlated with the loss of ECM, and inhibitors of ICE activity prevented apoptosis. These results suggest that ECM regulates apoptosis in mammary epithelial cells through an integrin-dependent negative regulation of ICE expression.
Modulation of Chemotropism in the Developing Spinal Cord by Substance P
Authors: De Felipe Carmen , Pinnock Robert D. , Hunt Stephen P.
Published: October 2006

Developing axons find their targets through direct contact with cues in the extracellular environment and in response to gradients of diffusible factors. The floor plate, a neuroepithelial structure, guides developing commissural axons in the spinal cord by release of chemoattractants. Floor plate cells express neurokinin-1 receptors, and a transiently appearing subpopulation of commissural axons contains substance P, the neuropeptide ligand for this receptor. Substance P increases the amount of axon outgrowth from dorsal horn explants cocultured with floor plate explants. Results of experiments with embryonic rats suggest that substance P released from pioneering neuronal pathways may regulate the release of chemoattractants from floor plate cells.
Bent Helix Formation Between RNA Hairpins with Complementary Loops
Authors: Marino John P. , Gregorian Razmic S. , Csankovszki Györgyi , Crothers Donald M.
Published: October 2006

The initial interaction between the ColE1 plasmid specific transcripts RNA I and RNA II, which function as antisense regulators of plasmid replication, comprises a transient complex between complementary loops found within the RNA secondary structures. Multidimensional heteronuclear magnetic resonance spectroscopy was used to characterize complexes formed between model RNA hairpins having seven nucleotide complementary loops. Seven base pairs are formed in the loop-loop helix, with continuous helical stacking of the loop residues on the 3′ side of their helical stems. A sharp bend in the loop-loop helix, documented by gel electrophoresis, narrows the major groove and allows bridging of the phosphodiester backbones across the major groove in order to close the hairpin loops at their 5′-ends. The bend is further enhanced by the binding of Rom, a ColE1 encoded protein that regulates replication.
Interaction of a Tyrosine Kinase from Human Sperm with the Zona Pellucida at Fertilization
Authors: Burks D. J. , Carballada R. , Moore H. D. , Saling P. M.
Published: October 2006

A 95-kilodalton mouse sperm protein with characteristics of a protein tyrosine kinase has been identified as a receptor for ZP3, a glycoprotein in the egg's extracellular matrix. The structure of the human homolog was determined by screening an expression library from human testis; a testis-specific complementary DNA was isolated that encodes a protein similar to receptor tyrosine kinases and appears to be expressed only in testicular germ cells. Antibodies against a synthetic peptide from the intracellular domain recognized a 95-kilodalton human sperm protein that contains phosphotyrosine; human ZP3 stimulates the kinase activity of this sperm protein. Synthetic peptides corresponding to regions of the predicted extracellular domain inhibited sperm binding to human zona pellucida. Availability of the primary sequence of a receptor for ZP3 provides a rational starting point for sperm-targeted contraceptive development.
CD1-Restricted T Cell Recognition of Microbial Lipoglycan Antigens
Authors: Sieling P. A. , Chatterjee D. , Porcelli S. A. , Prigozy T. I. , Mazzaccaro R. J. , Soriano T. , Bloom B. R. , Brenner M. B. , Kronenberg M. , Brennan P. J. , Modlin R. L.
Published: October 2006

It has long been the paradigm that T cells recognize peptide antigens presented by major histocompatibility complex (MHC) molecules. However, nonpeptide antigens can be presented to T cells by human CD1b molecules, which are not encoded by the MHC. A major class of microbial antigens associated with pathogenicity are lipoglycans. It is shown here that human CD1b presents the defined mycobacterial lipoglycan lipoarabinomannan (LAM) to αβ T cell receptor-bearing lymphocytes. Presentation of these lipoglycan antigens required internalization and endosomal acidification. The T cell recognition required mannosides with α(1→2) linkages and a phosphatidylinositol unit. T cells activated by LAM produced interferon γ and were cytolytic. Thus, an important class of microbial molecules, the lipoglycans, is a part of the universe of foreign antigens recognized by human T cells.
Molecular Identification of an IgE-Dependent Histamine-Releasing Factor
Authors: MacDonald Susan M. , Rafnar Thorunn , Langdon Jacqueline , Lichtenstein Lawrence M.
Published: October 2006

An immunoglobulin E (IgE)-dependent histamine-releasing factor (HRF) produced by lymphocytes of atopic children and present in biological fluids of allergic patients has been identified and purified. Amino-terminal sequencing revealed extensive homology to a mouse protein, p21, and its human homolog, p23. Both recombinant proteins caused histamine release from the human basophils of a subpopulation of donors, and this release was dependent on IgE. Polyclonal antibodies recognized and removed the biological activity of recombinant and native HRF. HRF identifies a heterogeneity of IgE and is believed to play a prominent role in chronic allergic disease processes.
Global Distribution of Persistent Organochlorine Compounds
Authors: Simonich Staci L. , Hites Ronald A.
Published: October 2006

The global distribution of 22 potentially harmful organochlorine compounds was investigated in more than 200 tree bark samples from 90 sites worldwide. High concentrations of organochlorines were found not only in some developing countries but also in industrialized countries, which continue to be highly contaminated even though the use of many of these compounds is restricted. The distribution of relatively volatile organochlorine compounds (such as hexachlorobenzene) is dependent on latitude and demonstrates the global distillation effect, whereas less volatile organochlorine compounds (such as endosulfan) are not as effectively distilled and tend to remain in the region of use.
An Internal Model for Sensorimotor Integration
Authors: Wolpert Daniel M. , Ghahramani Zoubin , Jordan Michael I.
Published: October 2006

On the basis of computational studies it has been proposed that the central nervous system internally simulates the dynamic behavior of the motor system in planning, control, and learning; the existence and use of such an internal model is still under debate. A sensorimotor integration task was investigated in which participants estimated the location of one of their hands at the end of movements made in the dark and under externally imposed forces. The temporal propagation of errors in this task was analyzed within the theoretical framework of optimal state estimation. These results provide direct support for the existence of an internal model.
Mutations of
GTBP
in Genetically Unstable Cells
Authors: Papadopoulos Nickolas , Nicolaides Nicholas C. , Liu Bo , Parsons Ramon , Lengauer Christoph , Palombo Fabio , D'Arrigo Antonello , Markowitz Sanford , Willson James K. V. , Kinzler Kenneth W. , Jiricny Josef , Vogelstein Bert
Published: October 2006

The molecular defects responsible for tumor cell hypermutability in humans have not yet been fully identified. Here the gene encoding a G/T mismatch-binding protein (GTBP) was localized to within 1 megabase of the related
hMSH2
gene on chromosome 2 and was found to be inactivated in three hypermutable cell lines. Unlike cells defective in other mismatch repair genes, which display widespread alterations in mononucleotide, dinucleotide, and other simple repeated sequences, the GTBP-deficient cells showed alterations primarily in mononucleotide tracts. These results suggest
GTBP
is important for maintaining the integrity of the human genome and document molecular defects accounting for variation in mutator phenotype.
Inactivation of the Mouse Huntington's Disease Gene Homolog
Hdh
Authors: Duyao Mabel P. , Auerbach Anna B. , Ryan Angela , Persichetti Francesca , Barnes Glenn T. , McNeil Sandra M. , Ge Pei , Vonsattel Jean-Paul , Gusella James F. , Joyner Alexandra L. , MacDonald Marcy E.
Published: October 2006

Huntington's disease (HD) is a dominant neurodegenerative disorder caused by expansion of a CAG repeat in the gene encoding huntingtin, a protein of unknown function. To distinguish between "loss of function" and "gain of function" models of HD, the murine
HD
homolog
Hdh
was inactivated by gene targeting. Mice heterozygous for
Hdh
inactivation were phenotypically normal, whereas homozygosity resulted in embryonic death. Homozygotes displayed abnormal gastrulation at embryonic day 7.5 and were resorbing by day 8.5. Thus, huntingtin is critical early in embryonic development, before the emergence of the nervous system. That
Hdh
inactivation does not mimic adult HD neuropathology suggests that the human disease involves a gain of function.
Monitoring Release of Neurotrophic Activity in the Brains of Awake Rats
Authors: Humpel Christian , Lindqvist Eva , Söderström Stine , Kylberg Annika , Ebendal Ted , Olson Lars
Published: October 2006

Intracerebral microdialysis of awake rats was used to monitor the possible release of neurotrophic factors from brain cells in response to injury and excitation. Perfusates were tested with ganglia bioassays and enzyme immunoassay. Trophic activity was released after implantation of the microdialysis probe into the hippocampus but not into the striatum, as assessed by increased nerve fiber outgrowth from Remak's ganglion. Kainic acid treatment significantly increased the release of trophic activity from hippocampal sites. These findings suggest that the brain responds to mechanical injury as well as to certain excitatory stimuli by regional extracellular release of neurotrophic activity that is not identical to the actions of known neurotrophic factors.
Depression in Women: Implications for Health Care Research
Authors: Weissman Myrna M. , Olfson Mark
Published: October 2006

Epidemiologic data from around the world demonstrate that major depression is approximately twice as common in women than men and that its first onset peaks during the childbearing years. Progress has been made in understanding the epidemiology of depression and in developing effective treatments. Much remains to be learned about the basic pathogenesis of depression and the specific treatment needs of depressed women and their offspring, especially during the reproductive years.
Regulatory Subunit Of Protein Kinase A: Structure of Deletion Mutant with cAMP Binding Domains
Authors: Su Y. , Dostmann W. R. G. , Herberg F. W. , Durick K. , Xuong N-h. , Ten Eyck L. , Taylor S. S. , Varughese K. I.
Published: October 2006

In the molecular scheme of living organisms, adenosine 3′,5′-monophosphate (cyclic AMP or cAMP) has been a universal second messenger. In eukaryotic cells, the primary receptors for cAMP are the regulatory subunits of cAMP-dependent protein kinase. The crystal structure of a 1-91 deletion mutant of the type Iα regulatory subunit was refined to 2.8 Å resolution. Each of the two tandem cAMP binding domains provides an extensive network of hydrogen bonds that buries the cyclic phosphate and the ribose between two β strands that are linked by a short α helix. Each adenine base stacks against an aromatic ring that lies outside the β barrel. This structure provides a molecular basis for understanding how cAMP binds cooperatively to its receptor protein, thus mediating activation of the kinase.
Parietal Contributions to Visual Feature Binding: Evidence from a Patient with Bilateral Lesions
Authors: Friedman-Hill Stacia R. , Robertson Lynn C. , Treisman Anne
Published: October 2006

Neurophysiologists have documented the existence of multiple cortical areas responsive to different visual features. This modular organization has sparked theoretical interest in how the "binding problem" is solved. Recent data from a neurological patient (R.M.) with bilateral parietal-occipital lesions demonstrates that the binding problem is not just a hypothetical construct; it can be a practical problem, as rare as the selective inability to perceive motion or color. R.M. miscombines colors and shapes even under free viewing conditions and is unable to judge either relative or absolute visual locations. The evidence suggests that a single explanation—an inadequate spatial representation—can account for R.M.'s spatial judgment and feature-binding deficits.
Similarity of
sli-1
, a Regulator of Vulval Development in
C. elegans
, to the Mammalian Proto-Oncogene c-
cbl
Authors: Yoon Charles H. , Lee Junho , Jongeward Gregg D. , Sternberg Paul W.
Published: October 2006

Vulval induction during
Caenorhabditis elegans
development is mediated by LET-23, a homolog of the mammalian epidermal growth factor receptor tyrosine kinase. The sli-1 gene is a negative regulator of LET-23 and is shown here to encode a protein similar to c-Cbl, a mammalian proto-oncoprotein. SLI-1 and c-Cbl share approximately 55 percent amino acid identity over a stretch of 390 residues, which includes a C
3
HC
4
zinc-binding motif known as the RING finger, and multiple consensus binding sites for Src homology 3 (SH3) domains. SLI-1 and c-Cbl may define a new class of proteins that modify receptor tyrosine kinase-mediated signal transduction.
Temperature Measurements of Shock-Compressed Liquid Hydrogen: Implications for the Interior of Jupiter
Authors: Nellis W. J. , Ross M. , Holmes N. C.
Published: October 2006

Shock temperatures of hydrogen up to 5200 kelvin were measured optically at pressures up to 83 gigapascals (830 kilobars). At highest pressures, the measured temperatures are substantially lower than predicted. These lower temperatures are caused by a continuous dissociative phase transition above 20 gigapascals. Because hydrogen is in thermal equilibrium in shock-compression experiments, the theory derived from the shock data can be applied to Jupiter. The planet's molecular envelope is cooler and has much less temperature variation than previously believed. The continuous dissociative phase transition suggests that there is no sharp boundary between Jupiter's molecular mantle and its metallic core. A possible convectively quiescent boundary layer might induce an additional layer in the molecular region, as has been predicted.
Microlithography by Using Neutral Metastable Atoms and Self-Assembled Monolayers
Authors: Berggren Karl K. , Bard Andreas , Wilbur James L. , Gillaspy John D. , Helg Andreas G. , McClelland Jabez J. , Rolston Steven L. , Phillips William D. , Prentiss Mara , Whitesides George M.
Published: October 2006

Lithography can be performed with beams of neutral atoms in metastable excited states to pattern self-assembled monolayers (SAMs) of alkanethiolates on gold. An estimated exposure of a SAM of dodecanethiolate (DDT) to 15 to 20 metastable argon atoms per DDT molecule damaged the SAM sufficiently to allow penetration of an aqueous solution of ferricyanide to the surface of the gold. This solution etched the gold and transformed the patterns in the SAMs into structures of gold; these structures had edge resolution of less than 100 nanometers. Regions of SAMs as large as 2 square centimeters were patterned by exposure to a beam of metastable argon atoms. These observations suggest that this system may be useful in new forms of micro- and nanolithography.
Adaptive Mutation in
Escherichia coli
: a Role for Conjugation
Authors: Radicella J. Pablo , Park Peter U. , Fox Maurice S.
Published: October 2006

When subjected to selective conditions that impose starvation, a bacterial population can accumulate mutations, called adaptive, that allow colony formation. Here, the reversion of a
lac
allele under selective conditions, in a model system using
Escherichia coli
with the
lac
mutation on an F' plasmid, was shown to require the conjugational capacity of the plasmid. Reversion associated with transfer was shown, and when the same
lac
allele was chromosomal, reversion to Lac
+
was 25 to 50 times less frequent. Postplating reversion was 25 times less when mating was inhibited by the presence of detergent. Mutability associated with conjugation provides new ways of thinking about the origin of adaptive mutations.
Measurement of Interhelical Electrostatic Interactions in the GCN4 Leucine Zipper
Authors: Lumb Kevin J. , Kim Peter S.
Published: October 2006

The dimerization specificity of the bZIP transcription factors resides in the leucine zipper region. It is commonly assumed that electrostatic interactions between oppositely charged amino acid residues on different helices of the leucine zipper contribute favorably to dimerization specificity. Crystal structures of the GCN4 leucine zipper contain interhelical salt bridges between Glu
20
and Lys
15′
and between Glu
22
and Lys
27′
.
13
C-nuclear magnetic resonance measurements of the glutamic acid p
K
a
values at physiological ionic strength indicate that the salt bridge involving Glu
22
does not contribute to stability and that the salt bridge involving Glu
20
is unfavorable, relative to the corresponding situation with a neutral (protonated) Glu residue. Moreover, the substitution of Glu
20
by glutamine is stabilizing. Thus, salt bridges will not necessarily contribute favorably to bZIP dimerization specificity and may indeed be unfavorable, relative to alternative neutral-charge interactions.
Loss of Atmosphere from Mars Due to Solar Wind-Induced Sputtering
Authors: Kass D. M. , Yung Y. L.
Published: October 2006

Because Mars does not have a strong intrinsic magnetic field, the atmosphere is eroded by interactions with the solar wind. Early solar-system conditions enhanced the sputtering loss. It is calculated that ∼3 bars of carbon dioxide (CO
2
) have been sputtered over the last 3.5 billion years. This significant increase over the previous estimate by Luhmann
et al.
of ∼0.14 bar of CO
2
is the result of the development of a more complete model. The model also predicts slightly greater loss of water—∼80 meters instead of the ∼50 meters predicted by Luhmann et al. Because estimates of CO
2
on early Mars range from 0.5 to 5 bars, the 0.14-bar estimate is insignificant but the ∼3-bar estimate will have a large effect on our understanding of the planet's evolution.
A Neuropeptide Gene Defined by the
Drosophila
Memory Mutant
amnesiac
Authors: Feany Mel B. , Quinn William G.
Published: October 2006

Mutations in genes required for associative learning and memory in
Drosophila
exist, but isolation of the genes has been difficult because most are defined by a single, chemically induced allele. Here, a simplified genetic screen was used to identify candidate genes involved in learning and memory. Second site suppressors of the
dunce
(
dnc
) female sterility phenotype were isolated with the use of transposon mutagenesis. One suppressor mutation that was recovered mapped in the
amnesiac
(
amn
) gene. Cloning of the locus revealed that
amn
encodes a previously uncharacterized neuropeptide gene. Thus, with the cloning of
amn
, specific neuropeptides are implicated in the memory process.
Mutagenesis and Laue Structures of Enzyme Intermediates: Isocitrate Dehydrogenase
Authors: Bolduc Jill M. , Dyer David H. , Scott William G. , Singer Paul , Sweet Robert M. , Koshland Daniel E. , Stoddard Barry L.
Published: October 2006

Site-directed mutagenesis and Laue diffraction data to 2.5 Å resolution were used to solve the structures of two sequential intermediates formed during the catalytic actions of isocitrate dehydrogenase. Both intermediates are distinct from the enzyme-substrate and enzyme-product complexes. Mutation of key catalytic residues changed the rate determining steps so that protein and substrate intermediates within the overall reaction pathway could be visualized.
Fibroblasts as Efficient Antigen-Presenting Cells in Lymphoid Organs
Authors: Kündig Thomas M. , Bachmann Martin F. , DiPaolo Claudio , Simard John J. L. , Battegay Manuel , Lother Heinz , Gessner André , Kühlcke Klaus , Ohashi Pamela S. , Hengartner Hans , Zinkernagel Rolf M.
Published: October 2006

Only so-called "professional" antigen-presenting cells (APCs) of hematopoietic origin are believed capable of inducing T lymphocyte responses. However, fibroblasts transfected with viral proteins directly induced antiviral cytotoxic T lymphocyte responses in vivo, without involvement of host APCs. Fibroblasts induced T cells only in the milieu of lymphoid organs. Thus, antigen localization affects self-nonself discrimination and cell-based vaccine strategies.
Superresolution Three-Dimensional Images of Fluorescence in Cells with Minimal Light Exposure
Authors: Carrington Walter A. , Lynch Ronald M. , Moore Edwin D. W. , Isenberg Gerrit , Fogarty Kevin E. , Fay Fredric S.
Published: October 2006

Fluorescent probes offer insight into the highly localized and rapid molecular events that underlie cell function. However, methods are required that can efficiently transform the limited signals from such probes into high-resolution images. An algorithm has now been developed that produces highly accurate images of fluorescent probe distribution inside cells with minimal light exposure and a conventional light microscope. This method provides resolution nearly four times greater than that currently available from any fluorescence microscope and was used to study several biological problems.