bluuebunny/crossref_metadata_2025 huggingface dataset:
Presynaptic Component of Long-Term Potentiation Visualized at Individual Hippocampal Synapses
Authors: Malgaroli Antonio , Ting Anthony E. , Wendland Beverly , Bergamaschi Andrea , Villa Antonello , Tsien Richard W. , Scheller Richard H.
Published: October 2006

Long-term potentiation has previously been studied with electrophysiological techniques that do not readily separate presynaptic and postsynaptic contributions. Changes in exocytotic-endocytotic cycling have now been monitored at synapses between cultured rat hippocampal neurons by measuring the differential uptake of antibodies that recognize the intraluminal domain of the synaptic vesicle protein synaptotagmin. Vesicular cycling increased markedly during glutamate-induced long-term potentiation. The degree of potentiation was heterogeneous, appearing greater at synapses at which the initial extent of vesicular turnover was low. Thus, changes in presynaptic activity were visualized directly and the spatial distribution of potentiation could be determined at the level of single synaptic boutons.
Integration of Visual and Linguistic Information in Spoken Language Comprehension
Authors: Tanenhaus Michael K. , Spivey-Knowlton Michael J. , Eberhard Kathleen M. , Sedivy Julie C.
Published: October 2006

Psycholinguists have commonly assumed that as a spoken linguistic message unfolds over time, it is initially structured by a syntactic processing module that is encapsulated from information provided by other perceptual and cognitive systems. To test the effects of relevant visual context on the rapid mental processes that accompany spoken language comprehension, eye movements were recorded with a head-mounted eye-tracking system while subjects followed instructions to manipulate real objects. Visual context influenced spoken word recognition and mediated syntactic processing, even during the earliest moments of language processing.
ILR1, an Amidohydrolase That Releases Active Indole-3-Acetic Acid from Conjugates
Authors: Bartel Bonnie , Fink Gerald R.
Published: October 2006

In plants, the growth regulator indole-3-acetic acid (IAA) is found both free and conjugated to a variety of amino acids, peptides, and carbohydrates. IAA conjugated to leucine has effects in
Arabidopsis thaliana
similar to those of free IAA. The
ilr1
mutant is insensitive to exogenous IAA-Leu and was used to positionally clone the
Arabidopsis
ILR1
gene.
ILR1
encodes a 48-kilodalton protein that cleaves IAA-amino acid conjugates in vitro and is homologous to bacterial amidohydrolase enzymes. DNA sequences similar to that of
ILR1
are found in other plant species.
p53 Transcriptional Activation Mediated by Coactivators TAF
II
40 and TAF
II
60
Authors: Thut Catherine J. , Chen Jin-Long , Klemm Richard , Tjian Robert
Published: October 2006

The tumor suppressor protein p53 is a transcriptional regulator that enhances the expression of proteins that control cellular proliferation. The multisubunit transcription factor IID (TFIID) is thought to be a primary target for site-specific activators of transcription. Here, a direct interaction between the activation domain of p53 and two subunits of the TFIID complex, TAF
II
40 and TAF
II
60, is reported. A double point mutation in the activation domain of p53 impaired the ability of this domain to activate transcription and, simultaneously, its ability to interact with both TAF
II
40 and TAF
II
60. Furthermore, a partial TFIID complex containing
Drosophila
TATA binding protein (dTBP), human TAF
II
250, dTAF
II
60, and dTAF
II
40 supported activation by a Gal4-p53 fusion protein in vitro, whereas TBP or a subcomplex lacking TAF
II
40 and TAF
II
60 did not. Together, these results suggest that TAF
II
40 and TAF
II
60 are important targets for transmitting activation signals between p53 and the initiation complex.
Single Cells as Biosensors for Chemical Separations
Authors: Shear Jason B. , Fishman Harvey A. , Allbritton Nancy L. , Garigan Delia , Zare Richard N. , Scheller Richard H.
Published: October 2006

A biosensor system based on the response of living cells was demonstrated that can detect specific components of a complex mixture fractionated by a microcolumn separation technique. This system uses ligand-receptor binding and signal-transduction pathways to biochemically amplify the presence of an analyte after electrophoretic separation. The transduced signal was measured by means of two approaches: (i) fluorescence determination of intracellular calcium concentrations in one or more rat PC-12 cells and (ii) measurement of transmembrane current in a
Xenopus laevis
oocyte microinjected with messenger RNA that encodes a specific receptor. This analysis system has the potential to identify biologically active ligands present in a complex mixture with exceptional sensitivity and selectivity.
A Proficient Enzyme
Authors: Radzicka Anna , Wolfenden Richard
Published: October 2006

Orotic acid is decarboxylated with a half-time (t
1/2
) of 78 million years in neutral aqueous solution at room temperature, as indicated by reactions in quartz tubes at elevated temperatures. Spontaneous hydrolysis of phosphodiester bonds, such as those present in the backbone of DNA, proceeds even more slowly at high temperatures, but the heat of activation is less positive, so that dimethyl phosphate is hydrolyzed with a t
1/2
of 130,000 years in neutral solution at room temperature. These values extend the known range of spontaneous rate constants for reactions that are also susceptible to catalysis by enzymes to more than 14 orders of magnitude. Values of the second-order rate constant
k
cat
/
K
m
for the corresponding enzyme reactions are confined to a range of only 600-fold, in contrast. Orotidine 5′-phosphate decarboxylase, an extremely proficient enzyme, enhances the rate of reaction by a factor of 10
17
and is estimated to bind the altered substrate in the transition state with a dissociation constant of less than 5 × 10
-24
M.
Big-Bang Nucleosynthesis and the Baryon Density of the Universe
Authors: Copi Craig J. , Schramm David N. , Turner Michael S.
Published: October 2006

For almost 30 years, the predictions of big-bang nucleosynthesis have been used to test the big-bang model to within a fraction of a second of the bang. The agreement between the predicted and observed abundances of deuterium, helium-3, helium-4, and lithium-7 confirms the standard cosmology model and allows accurate determination of the baryon density, between 1.7 × 10
-31
and 4.1 × 10
-31
grams per cubic centimeter (corresponding to about 1 to 15 percent of the critical density). This measurement of the density of ordinary matter is pivotal to the establishment of two dark-matter problems: (i) most of the baryons are dark, and (ii) if the total mass density is greater than about 15 percent of the critical density, as many determinations indicate, the bulk of the dark matter must be "non-baryonic," composed of elementary particles left from the earliest moments.
Host Range of a Plant Pathogenic Fungus Determined by a Saponin Detoxifying Enzyme
Authors: Bowyer P. , Clarke B. R. , Lunness P. , Daniels M. J. , Osbourn A. E.
Published: October 2006

Antifungal saponins occur in many plant species and may provide a preformed chemical barrier to attack by phytopathogenic fungi. Some fungal pathogens can enzymatically detoxify host plant saponins, which suggests that saponin detoxification may determine the host range of these fungi. A gene encoding a saponin detoxifying enzyme was cloned from the cereal-infecting fungus
Gaeumannomyces graminis
. Fungal mutants generated by targeted gene disruption were no longer able to infect the saponin-containing host oats but retained full pathogenicity to wheat (which does not contain saponins). Thus, the ability of a phytopathogenic fungus to detoxify a plant saponin can determine its host range.
Solution Structure of the Epithelial Cadherin Domain Responsible for Selective Cell Adhesion
Authors: Overduin Michael , Harvey Timothy S. , Bagby Stefan , Tong Kit I. , Yau Patrick , Takeichi Masatoshi , Ikura Mitsuhiko
Published: October 2006

Cadherins are calcium-dependent cell adhesion molecules containing extracellular repeats of approximately 110 amino acids. The three-dimensional structure of the amino-terminal repeat of mouse epithelial cadherin was determined by multidimensional heteronuclear magnetic resonance spectroscopy. The calcium ion was bound by a short α helix and by loops at one end of the seven-stranded β-barrel structure. An exposed concave face is in a position to provide homophilic binding specificity and was also sensitive to calcium ligation. Unexpected structural similarities with the immunoglobulin fold suggest an evolutionary relation between calcium-dependent and calcium-independent cell adhesion molecules.
Transcription Factor ATF2 Regulation by the JNK Signal Transduction Pathway
Authors: Gupta Shashi , Campbell Debra , Dérijard Benoit , Davis Roger J.
Published: October 2006

Treatment of cells with pro-inflammatory cytokines or ultraviolet radiation causes activation of the c-Jun NH
2
-terminal protein kinase (JNK). Activating transcription factor-2 (ATF2) was found to be a target of the JNK signal transduction pathway. ATF2 was phosphorylated by JNK on two closely spaced threonine residues within the NH
2
-terminal activation domain. The replacement of these phosphorylation sites with alanine inhibited the transcriptional activity of ATF2. These mutations also inhibited ATF2-stimulated gene expression mediated by the retinoblastoma (Rb) tumor suppressor and the adenovirus early region 1A (E1A) oncoprotein. Furthermore, expression of dominant-negative JNK inhibited ATF2 transcriptional activity. Together, these data demonstrate a role for the JNK signal transduction pathway in transcriptional responses mediated by ATF2.
HIV Population Dynamics in Vivo: Implications for Genetic Variation, Pathogenesis, and Therapy
Authors: Coffin John M.
Published: October 2006

Several recent reports indicate that the long, clinically latent phase that characterizes human immunodeficiency virus (HIV) infection of humans is not a period of viral inactivity, but an active process in which cells are being infected and dying at a high rate and in large numbers. These results lead to a simple steady-state model in which infection, cell death, and cell replacement are in balance, and imply that the unique feature of HIV is the extraordinarily large number of replication cycles that occur during infection of a single individual. This turnover drives both the pathogenic process and (even more than mutation rate) the development of genetic variation. This variation includes the inevitable and, in principle, predictable accumulation of mutations such as those conferring resistance to antiviral drugs whose presence before therapy must be considered in the design of therapeutic strategies.
ζ Phosphorylation Without ZAP-70 Activation Induced by TCR Antagonists or Partial Agonists
Authors: Madrenas Joaquín , Wange Ronald L. , Wang Jennifer L. , Isakov Noah , Samelson Lawrence E. , Germain Ronald N.
Published: October 2006

Small changes in the peptide-major histocompatibility complex (MHC) molecule ligands recognized by antigen-specific T cell receptors (TCRs) can convert fully activating complexes into partially activating or even inhibitory ones. This study examined early TCR-dependent signals induced by such partial agonists or antagonists. In contrast to typical agonist ligands, both an antagonist and several partial agonists stimulated a distinct pattern of ζ chain phosphorylation and failed to activate associated ZAP-70 kinase. These results identify a specific step in the early tyrosine phosphorylation cascade that is altered after TCR engagement with modified peptide-MHC molecule complexes. This finding may explain the different biological responses to TCR occupancy by these variant ligands.
Cytostatic Gene Therapy for Vascular Proliferative Disorders with a Constitutively Active form of the Retinoblastoma Gene Product
Authors: Chang Mark W. , Barr Eliav , Seltzer Jonathan , Jiang Yue-Qin , Nabel Gary J. , Nabel Elizabeth G. , Parmacek Michael S. , Leiden Jeffrey M.
Published: October 2006

Vascular smooth muscle cell (SMC) proliferation in response to injury is an important etiologic factor in vascular proliferative disorders such as atherosclerosis and restenosis after balloon angioplasty. The retinoblastoma gene product (Rb) is present in the unphosphorylated and active form in quiescent primary arterial SMCs, but is rapidly inactivated by phosphorylation in response to growth factor stimulation in vitro. A replication-defective adenovirus encoding a nonphosphorylatable, constitutively active form of Rb was constructed. Infection of cultured primary rat aortic SMCs with this virus inhibited growth factor-stimulated cell proliferation in vitro. Localized arterial infection with the virus at the time of balloon angioplasty significantly reduced SMC proliferation and neointima formation in both the rat carotid and porcine femoral artery models of restenosis. These results demonstrate the role of Rb in regulating vascular SMC proliferation and suggest a gene therapy approach for vascular proliferative disorders associated with arterial injury.
Sex Differences in Regional Cerebral Glucose Metabolism During a Resting State
Authors: Gur Ruben C. , Mozley Lyn Harper , Mozley P. David , Resnick Susan M. , Karp Joel S. , Alavi Abass , Arnold Steven E. , Gur Raquel E.
Published: October 2006

Positron emission tomography was used to evaluate the regional distribution of cerebral glucose metabolism in 61 healthy adults at rest. Although the profile of metabolic activity was similar for men and women, some sex differences and hemispheric asymmetries were detectable. Men had relatively higher metabolism than women in temporal-limbic regions and cerebellum and relatively lower metabolism in cingulate regions. In both sexes, metabolism was relatively higher in left association cortices and the cingulate region and in right ventro-temporal limbic regions and their projections. These results are consistent with the hypothesis that differences in cognitive and emotional processing have biological substrates.
Cloning of an Intrinsic Human TFIID Subunit That Interacts with Multiple Transcriptional Activators
Authors: Chiang Cheng-Ming , Roeder Robert G.
Published: October 2006

TFIID is a multisubunit protein complex comprised of the TATA-binding protein (TBP) and multiple TBP-associated factors (TAFs). The TAFs in TFIID are essential for activator-dependent transcription. The cloning of a complementary DNA encoding a human TFIID TAF, TAF
II
55, that has no known homolog in Drosophila TFIID is now described. TAF
II
55 is shown to interact with the largest subunit (TAF
II
230) of human TFIID through its central region and with multiple activators—including Sp1, YY1, USF, CTF, adenoviral E1A, and human immunodeficiency virus-type 1 Tat proteins—through a distinct amino-terminal domain. The TAF
II
55-interacting region of Sp1 was localized to its DNA-binding domain, which is distinct from the glutamine-rich activation domains previously shown to interact with
Drosophila
TAF
II
110. Thus, this human TFIID TAF may be a co-activator that mediates a response to multiple activators through a distinct mechanism.
Visual Appearance of Matte Surfaces
Authors: Nayar Shree K. , Oren Michael
Published: October 2006

All visual sensors, biological and artificial, are finite in resolution by necessity. As a result, the effective reflectance of surfaces in a scene varies with magnification. A reflectance model for matte surfaces is described that incorporates the effect of macroscopic surface undulations on image brightness. The model takes into account complex physical phenomena such as masking, shadowing, and interreflections between points on the surface, and it predicts the appearance of a wide range of natural surfaces. The implications of these results for human vision, machine vision, and computer graphics are demonstrated with both real and rendered images of three-dimensional objects. In particular, objects with extremely rough surfaces produce silhouette images devoid of shading, precluding visual perception of the object's shape.
Numbers and Ratios of Visual Pigment Genes for Normal Red-Green Color Vision
Authors: Neitz Maureen , Neitz Jay
Published: October 2006

Red-green color vision is based on middle-wavelength- and long-wavelength-sensitive visual pigments encoded by an array of genes on the X chromosome. The numbers and ratios of genes in this cluster were reexamined in men with normal color vision by means of newly refined methods. These methods revealed that many men had more pigment genes on the X chromosome than had previously been suggested and that many had more than one long-wave pigment gene. These discoveries challenge accepted ideas that are the foundation for theories of normal and anomalous color vision.
Correlation of Terminal Cell Cycle Arrest of Skeletal Muscle with Induction of p21 by MyoD
Authors: Halevy Orna , Novitch Bennett G. , Spicer Douglas B. , Skapek Stephen X. , Rhee James , Hannon Gregory J. , Beach David , Lassar Andrew B.
Published: October 2006

Skeletal muscle differentiation entails the coordination of muscle-specific gene expression and terminal withdrawal from the cell cycle. This cell cycle arrest in the G0 phase requires the retinoblastoma tumor suppressor protein (Rb). The function of Rb is negatively regulated by cyclin-dependent kinases (Cdks), which are controlled by Cdk inhibitors. Expression of MyoD, a skeletal muscle-specific transcriptional regulator, activated the expression of the Cdk inhibitor p21 during differentiation of murine myocytes and in nonmyogenic cells. MyoD-mediated induction of p21 did not require the tumor suppressor protein p53 and correlated with cell cycle withdrawal. Thus, MyoD may induce terminal cell cycle arrest during skeletal muscle differentiation by increasing the expression of p21.
Inhibition of Myogenic Differentiation in Proliferating Myoblasts by Cyclin D1-Dependent Kinase
Authors: Skapek Stephen X. , Rhee James , Spicer Douglas B. , Lassar Andrew B.
Published: October 2006

Although the myogenic regulator MyoD is expressed in proliferating myoblasts, differentiation of these cells is limited to the G
0
phase of the cell cycle. Forced expression of cyclin D1, but not cyclins A, B, or E, inhibited the ability of MyoD to transactivate muscle-specific genes and correlated with phosphorylation of MyoD. Transfection of myoblasts with cyclin-dependent kinase (Cdk) inhibitors p21 and p16 augmented muscle-specific gene expression in cells maintained in high concentrations of serum, suggesting that an active cyclin-Cdk complex suppresses MyoD function in proliferating cells.
Temporal Information Transformed into a Spatial Code by a Neural Network with Realistic Properties
Authors: Buonomano Dean V. , Merzenich Michael M.
Published: October 2006

Neurons exhibit a wide range of properties in addition to postsynaptic potential (PSP) summation and spike generation. Although other neuronal properties such as paired-pulse facilitation (PPF) and slow PSPs are well characterized, their role in information processing remains unclear. It is possible that these properties contribute to temporal processing in the range of hundreds of milliseconds, a range relevant to most complex sensory processing. A continuous-time neural network model based on integrate-and-fire elements that incorporate PPF and slow inhibitory postsynaptic potentials (IPSPs) was developed here. The time constants of the PPF and IPSPs were estimated from empirical data and were identical and constant for all elements in the circuit. When these elements were incorporated into a circuit inspired by neocortical connectivity, the network was able to discriminate different temporal patterns. Generalization emerged spontaneously. These results demonstrate that known time-dependent neuronal properties enable a network to transform temporal information into a spatial code in a self-organizing manner—that is, with no need to assume a spectrum of time delays or to custom-design the circuit.
Molecular Cloning and Characterization of an Inner Ear-Specific Structural Protein
Authors: Davis James G. , Oberholtzer J. Carl , Burns Frank R. , Greene Mark I.
Published: October 2006

Molecular biological studies of the mammalian inner ear have been limited by the relatively small size of the sensory endorgans contained within. The saccular otolithic organ in teleostian fish is structurally similar to its mammalian counterpart but can contain an order of magnitude more sensory cells. The prospect of the evolutionary conservation of proteins utilized in the vertebrate inner ear and the relative abundance of teleostian saccular sensory tissue made this an attractive system for molecular biological studies. A complementary DNA obtained by differential screening of a saccular complementary DNA library was identified that encodes an inner ear-specific collagen molecule.
Prevention of Atherosclerosis in Apolipoprotein E-Deficient Mice by Bone Marrow Transplantation
Authors: Linton MacRae F. , Atkinson James B. , Fazio Sergio
Published: October 2006

Apolipoprotein E (apoE) deficiency causes severe hyperlipidemia and atherosclerosis in humans and in gene-targeted mice. Although the majority of apoE in plasma is of hepatic origin, apoE is synthesized by a variety of cell types, including macrophages. Because macrophages derive from hematopoietic cells, bone marrow transplantation was used to examine the potential of apoE synthesized by bone marrow-derived cells to correct the hyperlipidemia and atherosclerosis caused by apoE deficiency. After transplantation of bone marrow from mice with the normal apoE gene into apoE-deficient mice, apoE was detected in serum and promoted clearance of lipoproteins and normalization of serum cholesterol levels. ApoE-deficient mice given transplants of normal bone marrow showed virtually complete protection from diet-induced atherosclerosis.
The Chemistry of John Dalton's Color Blindness
Authors: Hunt David M. , Dulai Kanwaijit S. , Bowmaker James K. , Mollon John D.
Published: October 2006

John Dalton described his own color blindness in 1794. In common with his brother, he confused scarlet with green and pink with blue. Dalton supposed that his vitreous humor was tinted blue, selectively absorbing longer wavelengths. He instructed that his eyes should be examined after his death, but the examination revealed that the humors were perfectly clear. In experiments presented here, DNA extracted from his preserved eye tissue showed that Dalton was a deuteranope, lacking the middlewave photopigment of the retina. This diagnosis is shown to be compatible with the historical record of his phenotype, although it contradicts Thomas Young's belief that Dalton was a protanope.
The Hubble Space Telescope (HST) Observing Campaign on Comet Shoemaker-Levy 9
Authors: Weaver H. A. , A'Hearn M. F. , Arpigny C. , Boice D. C. , Feldman P. D. , Larson S. M. , Lamy P. , Levy D. H. , Marsden B. G. , Meech K. J. , Noll K. S. , Scotti J. V. , Sekanina Z. , Shoemaker, C. S. , Shoemaker, E. M. , Smith T. E. , Stern S. A. , Storrs A. D. , Trauger J. T. , Yeomans D. K. , Zellner B.
Published: October 2006

The Hubble Space Telescope made systematic observations of the split comet P/Shoemaker-Levy 9 (SL9) (P designates a periodic comet) starting in July 1993 and continuing through mid-July 1994 when the fragments plunged into Jupiter's atmosphere. Deconvolutions of Wide Field Planetary Camera images indicate that the diameters of some fragments may have been as large as ∼2 to 4 kilometers, assuming a geometric albedo of 4 percent, but significantly smaller values (that is, < 1 kilometer) cannot be ruled out. Most of the fragments (or nuclei) were embedded in circularly symmetric inner comae from July 1993 until late June 1994, implying that there was continuous, but weak, cometary activity. At least a few nuclei fragmented into separate, condensed objects well after the breakup of the SL9 parent body, which argues against the hypothesis that the SL9 fragments were swarms of debris with no dominant, central bodies. Spectroscopic observations taken on 14 July 1994 showed an outburst in magnesium ion emission that was followed closely by a threefold increase in continuum emission, which may have been caused by the electrostatic charging and subsequent explosion of dust as the comet passed from interplanetary space into the jovian magnetosphere. No OH emission was detected, but the derived upper limit on the H
2
O production rate of ∼10
27
molecules per second does not necessarily imply that the object was water-poor.
Impact Debris Particles in Jupiter's Stratosphere
Authors: West Robert A. , Karkoschka Erich , Friedson A. James , Seymour Mark , Baines Kevin H. , Hammel Heidi B.
Published: October 2006

The aftermath of the impacts of periodic comet Shoemaker-Levy 9 on Jupiter was studied with the Wide Field Planetary Camera 2 on the Hubble Space Telescope. The impact debris particles may owe their dark brown color to organic material rich in sulfur and nitrogen. The total volume of aerosol 1 day after the last impact is equal to the volume of a sphere of radius 0.5 kilometer. In the optically thick core regions, the particle mean radius is between 0.15 and 0.3 micrometer, and the aerosol is spread over many scale heights, from approximately 1 millibar to 200 millibars of pressure or more. Particle coagulation can account for the evolution of particle radius and total optical depth during the month following the impacts.
HST Spectroscopic Observations of Jupiter After the Collision of Comet Shoemaker-Levy 9
Authors: Noll K. S. , McGrath M. A. , Trafton L. M. , Atreya S. K. , Caldwell J. J. , Weaver H. A. , Yelle R. V. , Barnet C. , Edgington S.
Published: October 2006

Ultraviolet spectra obtained with the Hubble Space Telescope identified at least 10 molecules and atoms in the perturbed stratosphere near the G impact site, most never before observed in Jupiter. The large mass of sulfur-containing material, more than 10
14
grams in S
2
alone, indicates that many of the sulfur-containing molecules S
2
, CS
2
, CS, H
2
S, and S
+
may be derived from a sulfur-bearing parent molecule native to Jupiter. If so, the fragment must have penetrated at least as deep as the predicted NH
4
SH cloud at a pressure of approximately 1 to 2 bars. Stratospheric NH
3
was also observed, which is consistent with fragment penetration below the cloud tops. Approximately 10
7
grams of neutral and ionized metals were observed in emission, including Mg II, Mg I, Si I, Fe I, and Fe II. Oxygen-containing molecules were conspicuous by their absence; upper limits for SO
2
, SO, CO, SiO, and H
2
O are derived.
Contribution of STAT SH2 Groups to Specific Interferon Signaling by the Jak-STAT pathway
Authors: Heim Markus H. , Kerr lan M. , Stark George R. , Darnell James E.
Published: October 2006

In response to specific ligands, various STAT proteins (signal transducers and activators of transcription) are phosphorylated on tyrosine by Jak protein kinases and translocated to the nucleus to direct gene transcription. Selection of a STAT at the interferon γ receptor as well as specific STAT dimer formation depended on the presence of particular SH2 groups (phosphotyrosine-binding domains), whereas the amino acid sequence surrounding the phosphorylated tyrosine on the STAT could vary. Thus, SH2 groups in STAT proteins may play crucial roles in specificity at the receptor kinase complex and in subsequent dimerization, whereas the kinases are relatively nonspecific.
Choice of STATs and Other Substrates Specified by Modular Tyrosine-Based Motifs in Cytokine Receptors
Authors: Stahl Neil , Farruggella Thomas J. , Boulton Teri G. , Zhong Zhong , Darnell James E. , Yancopoulos George D.
Published: October 2006

Many members of the cytokine receptor superfamily initiate intracellular signaling by activating members of the Jak family of tyrosine kinases. Activation of the same Jaks by multiple cytokines raises the question of how these cytokines activate distinct intracellular signaling pathways. Selection of particular substrates—the transcriptional activator Stat3 and protein tyrosine phosphatase PTP1D—that characterize responses to the ciliary neurotrophic factor-interleukin-6 cytokine family depended not on which Jak was activated, but was instead determined by specific tyrosine-based motifs in the receptor components—gp130 and LIFR—shared by these cytokines. Further, these tyrosine-based motifs were modular, because addition of a Stat3-specifying motif to another cytokine receptor, that for erythropoietin, caused it to activate Stat3 in a ligand-dependent fashion.
A p53-Dependent Mouse Spindle Checkpoint
Authors: Cross Shawn M. , Sanchez Carissa A. , Morgan Catherine A. , Schimke Melana K. , Ramel Stig , Idzerda Rejean L. , Raskind Wendy H. , Reid Brian J.
Published: October 2006

Cell cycle checkpoints enhance genetic fidelity by causing arrest at specific stages of the cell cycle when previous events have not been completed. The tumor suppressor p53 has been implicated in a G1 checkpoint. To investigate whether p53 also participates in a mitotic checkpoint, cultured fibroblasts from p53-deficient mouse embryos were exposed to spindle inhibitors. The fibroblasts underwent multiple rounds of DNA synthesis without completing chromosome segregation, thus forming tetraploid and octaploid cells. Deficiency of p53 was also associated with the development of tetraploidy in vivo. These results suggest that murine p53 is a component of a spindle checkpoint that ensures the maintenance of diploidy.
Apoptosis in the Pathogenesis and Treatment of Disease
Authors: Thompson Craig B.
Published: October 2006

In multicellular organisms, homeostasis is maintained through a balance between cell proliferation and cell death. Although much is known about the control of cell proliferation, less is known about the control of cell death. Physiologic cell death occurs primarily through an evolutionarily conserved form of cell suicide termed apoptosis. The decision of a cell to undergo apoptosis can be influenced by a wide variety of regulatory stimuli. Recent evidence suggests that alterations in cell survival contribute to the pathogenesis of a number of human diseases, including cancer, viral infections, autoimmune diseases, neurodegenerative disorders, and AIDS (acquired immunodeficiency syndrome). Treatments designed to specifically alter the apoptotic threshold may have the potential to change the natural progression of some of these diseases.
Structure of a Hyperthermophilic Tungstopterin Enzyme, Aldehyde Ferredoxin Oxidoreductase
Authors: Chan Michael K. , Mukund Swarnalatha , Kletzin Arnulf , Adams Michael W. W. , Rees Douglas C.
Published: October 2006

The crystal structure of the tungsten-containing aldehyde ferredoxin oxidoreductase (AOR) from
Pyrococcus furiosus
, a hyperthermophilic archaeon (formerly archaebacterium) that grows optimally at 100°C, has been determined at 2.3 angstrom resolution by means of multiple isomorphous replacement and multiple crystal form averaging. AOR consists of two identical subunits, each containing an Fe
4
S
4
cluster and a molybdopterin-based tungsten cofactor that is analogous to the molybdenum cofactor found in a large class of oxotransferases. Whereas the general features of the tungsten coordination in this cofactor were consistent with a previously proposed structure, each AOR subunit unexpectedly contained two molybdopterin molecules that coordinate a tungsten by a total of four sulfur ligands, and the pterin system was modified by an intramolecular cyclization that generated a three-ringed structure. In comparison to other proteins, the hyperthermophilic enzyme AOR has a relatively small solvent-exposed surface area, and a relatively large number of both ion pairs and buried atoms. These properties may contribute to the extreme thermostability of this enzyme.
Crystal Structure of the Tetramerization Domain of the p53 Tumor Suppressor at 1.7 Angstroms
Authors: Jeffrey Philip D. , Gorina Svetlana , Pavletich Nikola P.
Published: October 2006

The p53 protein is a tetrameric transcription factor that plays a central role in the prevention of neoplastic transformation. Oligomerization appears to be essential for the tumor suppressing activity of p53 because oligomerization-deficient p53 mutants cannot suppress the growth of carcinoma cell lines. The crystal structure of the tetramerization domain of p53 (residues 325 to 356) was determined at 1.7 angstrom resolution and refined to a crystallographic
R
factor of 19.2 percent. The monomer, which consists of a β strand and an α helix, associates with a second monomer across an antiparallel β sheet and an antiparallel helix-helix interface to form a dimer. Two of these dimers associate across a second and distinct parallel helix-helix interface to form the tetramer.
Massive Cell Death of Immature Hematopoietic Cells and Neurons in Bcl-x-Deficient Mice
Authors: Motoyama Noboru , Wang Fanping , Roth Kevin A. , Sawa Hirofumi , Nakayama Kei-ichi , Nakayama Keiko , Negishi Izumi , Senju Satoru , Zhang Qing , Fujii Satoshi , Loh Dennis Y.
Published: October 2006

bcl-x
is a member of the
bcl-2
gene family, which may regulate programmed cell death. Mice were generated that lacked Bcl-x. The Bcl-x-deficient mice died around embryonic day 13. Extensive apoptotic cell death was evident in postmitotic immature neurons of the developing brain, spinal cord, and dorsal root ganglia. Hematopoietic cells in the liver were also apoptotic. Analyses of
bcl-x
double-knockout chimeric mice showed that the maturation of Bcl-x-deficient lymphocytes was diminished. The life-span of immature lymphocytes, but not mature lymphocytes, was shortened. Thus, Bcl-x functions to support the viability of immature cells during the development of the nervous and hematopoietic systems.
Storage of 7 ± 2 Short-Term Memories in Oscillatory Subcycles
Authors: Lisman John E. , Idiart Marco A. P.
Published: October 2006

Psychophysical measurements indicate that human subjects can store approximately seven short-term memories. Physiological studies suggest that short-term memories are stored by patterns of neuronal activity. Here it is shown that activity patterns associated with multiple memories can be stored in a single neural network that exhibits nested oscillations similar to those recorded from the brain. Each memory is stored in a different high-frequency ("40 hertz") subcycle of a low-frequency oscillation. Memory patterns repeat on each low-frequency (5 to 12 hertz) oscillation, a repetition that relies on activity-dependent changes in membrane excitability rather than reverberatory circuits. This work suggests that brain oscillations are a timing mechanism for controlling the serial processing of short-term memories.
Seeing Through the Dust: Martian Crustal Heterogeneity and Links to the SNC Meteorites
Authors: Mustard John F. , Sunshine Jessica M.
Published: October 2006

Through the application of new analytical techniques to high spatial resolution imaging spectrometer data, the ferrous mineralogy of major volcanic terrains on Mars is shown to consist of significant fractions of both low- and high-calcium pyroxene. Changes in the relative abundances of these pyroxenes are observed for units of different age and morphology, even in regions with higher degrees of alteration and contamination from dust. Volcanic rocks with these characteristics are uncommon on Earth but are typical of the basaltic SNC meteorites (shergottites, nakhlites, and chassignites) thought to be from Mars. Thus, it is possible to infer, even through the veil of dust, that the SNC meteorites have mineralogic affinities to major volcanic provinces on Mars and are therefore truly representative of the heterogeneity observed on the surface of the "red planet".
Modulation of Serotonin-Controlled Behaviors by G
o
in
Caenorhabditis elegans
Authors: Ségalat Laurent , Elkes Daniel A. , Kaplan Joshua M.
Published: October 2006

Seven transmembrane receptors and their associated heterotrimeric guanine nucleotide-binding proteins (G proteins) have been proposed to play a key role in modulating the activities of neurons and muscles. The physiological function of the
Caenorhabditis elegans
G protein G
o
has been genetically characterized. Mutations in the goa-1 gene, which encodes an α subunit of G
o
(Gα
o
), cause behavioral defects similar to those observed in mutants that lack the neurotransmitter serotonin (5-HT), and
goa-1
mutants are partially resistant to exogenous 5-HT. Mutant animals that lack Gα
o
and transgenic animals that overexpress Gα
o
[
goa-1
(
xs
) animals] have reciprocal defects in locomotion, feeding, and egg laying behaviors. In normal animals, all of these behaviors are regulated by 5-HT. These results demonstrate that the level of G
o
activity is a critical determinant of several
C. elegans
behaviors and suggest that G
o
mediates many of the behavioral effects of 5-HT.
Development of a Mouse Model of
Helicobacter pylori
Infection that Mimics Human Disease
Authors: Marchetti Marta , Aricò Beatrice , Burroni Daniela , Figura Natale , Rappuoli Rino , Ghiara Paolo
Published: October 2006

The human pathogen
Helicobacter pylori
is associated with gastritis, peptic ulcer disease, and gastric cancer. The pathogenesis of
H. pylori
infection in vivo was studied by adapting fresh clinical isolates of bacteria to colonize the stomachs of mice. A gastric pathology resembling human disease was observed in infections with cytotoxin-producing strains but not with noncytotoxic strains. Oral immunization with purified
H. pylori
antigens protected mice from bacterial infection. This mouse model will allow the development of therapeutic agents and vaccines against
H. pylori
infection in humans.
Induction of Ectopic Eyes by Targeted Expression of the
eyeless
Gene in
Drosophila
Authors: Halder Georg , Callaerts Patrick , Gehring Walter J.
Published: October 2006

The
Drosophila
gene
eyeless
(
ey
) encodes a transcription factor with both a paired domain and a homeodomain. It is homologous to the mouse
Small eye
(
Pax-6
) gene and to the Aniridia gene in humans. These genes share extensive sequence identity, the position of three intron splice sites is conserved, and these genes are expressed similarly in the developing nervous system and in the eye during morphogenesis. Loss-of-function mutations in both the insect and in the mammalian genes have been shown to lead to a reduction or absence of eye structures, which suggests that
ey
functions in eye morphogenesis. By targeted expression of the
ey
complementary DNA in various imaginal disc primordia of
Drosophila
, ectopic eye structures were induced on the wings, the legs, and on the antennae. The ectopic eyes appeared morphologically normal and consisted of groups of fully differentiated ommatidia with a complete set of photoreceptor cells. These results support the proposition that
ey
is the master control gene for eye morphogenesis. Because homologous genes are present in vertebrates, ascidians, insects, cephalopods, and nemerteans,
ey
may function as a master control gene throughout the metazoa.
Switch Transcripts in Immunoglobulin Class Switching
Authors: Lorenz Matthias , Jung Steffen , Radbruch Andreas
Published: October 2006

B cells can exchange gene segments for the constant region of the immunoglobulin heavy chain, altering the class and effector function of the antibodies that they produce. Class switching is directed to distinct classes by cytokines, which induce transcription of the targeted DNA sequences. These transcripts are processed, resulting in spliced "switch" transcripts. Switch recombination can be directed to immunoglobulin G1 (IgG1) by the heterologous human metallothionein IIA promoter in mutant mice. Induction of the structurally conserved, spliced switch transcripts is sufficient to target switch recombination to IgG1, whereas transcription alone is not.
Role of Steroidogenic Acute Regulatory Protein in Adrenal and Gonadal Steroidogenesis
Authors: Lin Dong , Sugawara Teruo , Strauss Jerome F. , Clark Barbara J. , Stocco Douglas M. , Saenger Paul , Rogol Alan , Miller Walter L.
Published: October 2006

Congenital lipoid adrenal hyperplasia is an autosomal recessive disorder that is characterized by impaired synthesis of all adrenal and gonadal steroid hormones. In three unrelated individuals with this disorder, steroidogenic acute regulatory protein, which enhances the mitochondrial conversion of cholesterol into pregnenolone, was mutated and nonfunctional, providing genetic evidence that this protein is indispensable for normal adrenal and gonadal steroidogenesis.
1/
f
Noise in Human Cognition
Authors: Gilden D. L. , Thornton T. , Mallon M. W.
Published: October 2006

When a person attempts to produce from memory a given spatial or temporal interval, there is inevitably some error associated with the estimate. The time course of this error was measured in a series of experiments where subjects repeatedly attempted to replicate given target intervals. Sequences of the errors in both spatial and temporal replications were found to fluctuate as 1/
f
noises. 1/
f
noise is encountered in a wide variety of physical systems and is theorized to be a characteristic signature of complexity.
Bilateral chronic fungal dacryocystitis caused byCandida dubliniensisin a neutropenic patient: Figure 1
Authors: Obi E , Roy A , Bates V , Sandy C
Published: October 2006

In recent years, candida species other thanCandida albicanshave emerged as causes of human candidiasis, particularly in HIV-infected and other immunocompromised people.C dubliniensis, a recently described species closely related toC albicans, first isolated from patients with AIDS in Dublin, has been implicated as an agent of oral candidiasis in HIV-positive people. However, it has also been recovered from HIV-negative people, with clinical signs of oral candidiasis and from the genital tract of some women with vaginitis. The first case of bilateral chronic fungal dacryocystitis caused byC dubliniensisis described in an HIV-negative woman.
Meningococcal meningitis in two patients with primary antibody deficiency treated with replacement intravenous immunoglobulin
Authors: Lear S , Eren E , Findlow J , Borrow R , Webster D , Jolles S
Published: October 2006

The current treatment of primary antibody deficiency (PAD) is the early recognition of the condition and replacement immunoglobulin combined with prompt treatment of infections and complications. The route of administration (intravenous or subcutaneous), dose and frequency of administration of immunoglobulin still vary between centres and countries. Most infections in patients with PAD are reduced but not entirely prevented by replacement immunoglobulin, with sinopulmonary infections accounting for the bulk of the remainder. Although there have been reports of meningitis in patients with PAD before replacement treatment, we describe the first two cases of bacterial meningitis (group BNeisseria meningitidis) on adequate immunoglobulin replacement and discuss the involvement of potential cofactors.
Primary effusion lymphoma with skin involvement
Authors: Inoue S , Miyamoto T , Yoshino T , Yamadori I , Hagari Y , Yamamoto O
Published: October 2006

Primary effusion lymphoma (PEL) was once defined as a body cavity-based lymphoma without identifiable contiguous tumour mass, but is now recognised as an independent clinicopathological entity. The case of a 67-year-old Japanese woman with PEL is reported, in which the clinical findings showed a pericardial effusion and multiple erythema on the hypogastrium and inguinal region. The histopathological findings showed a diffuse infiltration of large neoplastic B cells from the dermis to the subcutis. After the disappearance of pericardial effusion without any treatment, she received several rounds of chemotherapy to resolve the skin eruption, but she finally died from multiple organ failure. No tumour mass was observed during the course of her disease.
MEASUREMENT OF THE EXCLUSIVE LIGHT HADRON DECAYS OF THE ψ″ IN e+e- EXPERIMENTS
Authors: WANG P. , MO X. H. , YUAN C. Z.
Published: October 2006

The measurement of the exclusive light hadron decays of the ψ″ in e+e- experiments with significant interference between the ψ″ and continuum amplitudes is discussed. The radiative correction and the Monte Carlo simulation are studied. It is possible to verify the destructive interference for the detectors with energy–momentum resolution of (1~2)%.
BABY UNIVERSES AND STRING THEORY
Authors: DIJKGRAAF ROBBERT , GOPAKUMAR RAJESH , OOGURI HIROSI , VAFA CUMRUN
Published: October 2006

The description of 4D BPS black holes in terms of branes wrapped on various cycles in a Calabi–Yau space gives us the opportunity to study various issues in quantum gravity in a definite way by means of the worldvolume theory of the branes. In the particular example discussed here, there is a simple worldvolume description in terms of 2D Yang–Mills theory. The latter is an exactly solvable system of free fermions in one dimension. The exact answer for the free energy of this system can be written in a way that suggests an interpretation in terms of contributions from multiple (baby) universes.
CONSISTENT DISCRETIZATION AND CANONICAL, CLASSICAL AND QUANTUM REGGE CALCULUS
Authors: GAMBINI RODOLFO , PULLIN JORGE
Published: October 2006

We apply the "consistent discretization" technique to the Regge action for (Euclidean and Lorentzian) general relativity in arbitrary number of dimensions. The result is a well-defined canonical theory that is free of constraints and where the dynamics is implemented as a canonical transformation. In the Lorentzian case, the framework appears to be naturally free of the "spikes" that plague traditional formulations. It also provides a well-defined recipe for determining the integration measure for quantum Regge calculus.
Effect of SCP-x gene ablation on branched-chain fatty acid metabolism
Authors: Atshaves Barbara P. , McIntosh Avery L. , Landrock Danilo , Payne H. Ross , Mackie John T. , Maeda Nobuyo , Ball Judith , Schroeder Friedhelm , Kier Ann B.
Published: October 2006

Despite the importance of peroxisomal oxidation in branched-chain lipid (phytol, cholesterol) detoxification, little is known regarding the factors regulating the peroxisomal uptake, targeting, and metabolism of these lipids. Although in vitro data suggest that sterol carrier protein (SCP)-x plays an important role in branched-chain lipid oxidation, the full physiological significance of this peroxisomal enzyme is not completely clear. To begin to resolve this issue, SCP-x-null mice were generated by gene ablation of SCP-x from the SCP-x/SCP-2 gene and fed a phytol-enriched diet to characterize the effects of lipid overload in a system with minimal 2/3-oxoacyl-CoA thiolytic activity. It was shown that SCP-x gene ablation 1) did not result in reduced expression of SCP-2 (previously thought to be derived in considerable part by posttranslational cleavage of SCP-x); 2) increased expression levels of key enzymes involved in α- and β-oxidation; and 3) altered lipid distributions, leading to decreased hepatic fatty acid and triglyceride levels. In response to dietary phytol, lack of SCP-x resulted in 1) accumulation of phytol metabolites despite substantial upregulation of hepatic peroxisomal and mitochondrial enzymes; 2) reduced body weight gain and fat tissue mass; and 3) hepatic enlargement, increased mottling, and necrosis. In summary, the present work with SCP-x gene-ablated mice demonstrates, for the first time, a direct physiological relationship between lack of SCP-x and decreased ability to metabolize branched-chain lipids.