bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutations in the Rod Domains of Keratins 1 and 10 in Epidermolytic Hyperkeratosis
Authors: Rothnagel J. A. , Dominey A. M. , Dempsey L. D. , Longley M. A. , Greenhalgh D. A. , Gagne T. A. , Huber M. , Frenk E. , Hohl D. , Roop D. R.
Published: October 2006

Epidermolytic hyperkeratosis is a hereditary skin disorder characterized by blistering and a marked thickening of the stratum corneum. In one family, affected individuals exhibited a mutation in the highly conserved carboxyl terminal of the rod domain of keratin 1. In two other families, affected individuals had mutations in the highly conserved amino terminal of the rod domain of keratin 10. Structural analysis of these mutations predicts that heterodimer formation would be unaffected, although filament assembly and elongation would be severely compromised. These data imply that an intact keratin intermediate filament network is required for the maintenance of both cellular and tissue integrity.
An Overview of Energetic Particle Measurements in the Jovian Magnetosphere with the EPAC Sensor on Ulysses
Authors: Keppler E. , Blake J. B. , Fränz M. , Korth A. , Krupp N. , Quenby J. J. , Witte M. , Woch J.
Published: October 2006

Observations of ions and electrons of probable Jovian origin upstream of Jupiter were observed after a corotating interplanetary particle event. During the passage of Ulysses through the Jovian bow shock, magnetopause, and outer magnetosphere, the fluxes of energetic particles were surprisingly low. During the passage through the "middle magnetosphere," corotating fluxes were observed within the current sheet near the jovimagnetic equator. During the outbound pass, fluxes were variably directed; in the later part of the flyby, they were probably related to high-latitude phenomena.
Molecular Characterization of the Human β
3
-Adrenergic Receptor
Authors: Emorine Laurent J. , Marullo Stefano , Briend-Sutren Marie-M. , Patey Gilles , Tate Keri , Delavier-Klutchko Colette , Strosberg A. Donny
Published: October 2006

Since the classification of β-adrenergic receptors (β-ARs) into β
1
and β
2
subtypes, additional β-ARs have been implicated in the control of various metabolic processes by catecholamines. A human gene has been isolated that encodes a third β-AR, here referred to as the "β
3
-adrenergic receptor." Exposure of eukaryotic cells transfected with this gene to adrenaline or noradrenaline promotes the accumulation of adenosine 3′,5′-monophosphate; only 2 of 11 classical β-AR blockers efficiently inhibited this effect, whereas two others behaved as β
3
-AR agonists. The potency order of β-AR agonists for the β
3
-AR correlates with their rank order for stimulating various metabolic processes in tissues where atypical adrenergic sites are thought to exist. In particular, novel β-AR agonists having high thermogenic, antiobesity, and antidiabetic activities in animal models are among the most potent stimulators of the β
3
-AR.
Heterogeneity of 5
S
RNA in Fungal Ribosomes
Authors: Selker Eric U. , Stevens Judith N. , Metzenberg Robert L.
Published: October 2006

Neurospora crassa
has at least seven types of 5
S
RNA genes (α, β, γ, ε, δ, ζ, and η) with different coding regions. A high resolution gel electrophoresis system was developed to separate minor 5
S
RNA's from the major 5
S
RNA (α). A study of several
Neurospora crassa
strains, four other species in the genus
Neurospora
, members of two closely related genera, and three distantly related genera demonstrated that 5
S
RNA heterogeneity is common among fungi. In addition, different 5
S
RNA's are present in
Neurospora
ribosomes. The finding that fungal ribosomes are structurally heterogeneous suggests that ribosomes may be functionally heterogeneous as well.
An Experiment-Based Model for the Petrogenesis of High-Alumina Basalts
Authors: Beard J. S. , Lofgren G. E.
Published: October 2006

To understand magmatism at convergent margins, one must know the origin of their characteristic, plagioclase-rich, high-alumina basalts (HABs). Wet melting experiments on basalts at 3 kilobars yielded high-alumina liquids and a coexisting mineral assemblage with little or no plagioclase. An isothermal pressure drop to 1 kilobar caused 20 to 30 percent plagioclase crystallization in these melts, while mafic minerals underwent limited crystallization or even resorption. These results suggest that hydrous (≥4 percent H
2
O) HAB liquids, presumably formed by fractionation of a hydrous basalt at depth, will precipitate voluminous plagioclase as pressure drops during ascent and eruption. Plagioclase accumulation is not necessarily required to explain the petrogenesis of plagioclase-rich HAB.
Photoinduced Electron Transfer from a Conducting Polymer to Buckminsterfullerene
Authors: Sariciftci N. S. , Smilowitz L. , Heeger A. J. , Wudl F.
Published: October 2006

Evidence for photoinduced electron transfer from the excited state of a conducting polymer onto buckminsterfullerene, C
60
, is reported. After photo-excitation of the conjugated polymer with light of energy greater than the π- π* gap, an electron transfer to the C
60
molecule is initiated. Photoinduced optical absorption studies demonstrate a different excitation spectrum for the composite as compared to the separate components, consistent with photo-excited charge transfer. A photoinduced electron spin resonance signal exhibits signatures of both the conducting polymer cation and the C
60
anion. Because the photoluminescence in the conducting polymer is quenched by interaction with C
60
, the data imply that charge transfer from the excited state occurs on a picosecond time scale. The charge-separated state in composite films is metastable at low temperatures.
Synchronism of the Siberian Traps and the Permian-Triassic Boundary
Authors: Campbell I. H. , Czamanske G. K. , Fedorenko V. A. , Hill R. I. , Stepanov V.
Published: October 2006

Uranium-lead ages from an ion probe were taken for zircons from the ore-bearing Noril'sk I intrusion that is comagmatic with, and intrusive to, the Siberian Traps. These values match, within an experimental error of ±4 million years, the dates for zircons extracted from a tuff at the Permian-Triassic (P-Tr) boundary. The results are consistent with the hypothesis that the P-Tr extinction was caused by the Siberian basaltic flood volcanism. It is likely that the eruption of these magmas was accompanied by the injection of large amounts of sulfur dioxide into the upper atmosphere, which may have led to global cooling and to expansion of the polar ice cap. The P-Tr extinction event may have been caused by a combination of acid rain and global cooling as well as rapid and extreme changes in sea level resulting from expansion of the polar ice cap.
Monoclonal Antibody-Directed Radioimmunoassay Detects Cytochrome P-450 in Human Placenta and Lymphocytes
Authors: Song Byung-Joon , Gelboin Harry V. , Park Sang Shin , Tsokos George C. , Friedman Fred K.
Published: October 2006

A multiplicity of cytochromes P-450 is responsible for the detoxification and activation of xenobiotics such as drugs and carcinogens. Individual differences in sensitivity to these agents may reside in the cytochrome P-450 phenotype. A monoclonal antibody-directed radioimmunoassay was developed that detects epitope-specific cytochromes P-450 in human placentas and peripheral lymphocytes. Placentas from women who smoked cigarettes contained greater amounts of cytochrome P-450 with the monoclonal antibody-specific epitope than placentas from nonsmokers. The amount of this cytochrome P-450 in human peripheral lymphocytes increased after treatment of the mitogenized lymphocytes with the cytochrome P-450 inducer benz[
a
]anthracene.
1,25-Dihydroxyvitamin D-Responsive Element and Glucocorticoid Repression in the Osteocalcin Gene
Authors: Morrison Nigel A. , Shine John. , Fragonas Jean-Charles , Verkest Veronik , McMenemy M. Lynne , Eisman John A.
Published: October 2006

The active hormonal form of vitamin D
3
, 1,25-dihydroxyvitamin D
3
[1,25(OH), which regulates cellular replication and function in many tissues and has a role in bone and calcium homeostasis, acts through a hormone receptor homologous with other steroid and thyroid hormone receptors. A 1,25(OH)
2
D
3
-responsive element (VDRE), which is within the promoter for osteocalcin [a bone protein induced by 1,25(OH)
2
D
3
] is unresponsive to other steroid hormones, can function in a heterologous promoter, and contains a doubly palindromic DNA sequence (TT
GGTGA
C
TCACC
G
GGTGA
AC; -513 to -493 bp), with nucleotide sequence homology to other hormone responsive elements. The potent glucocorticoid repression of 1,25(OH)
2
D
3
induction and of basal activity of this promoter acts through a region between -196 and +34 bp, distinct from the VDRE.
Catastrophes of Every Ilk at The Geophysics Fest
Authors: Kerr Richard A.
Published: October 2006

At the annual meeting of the American Geophysics Union (AGU) in San Francisco on 7-11 December, catastrophes came in all sizes. On the molecular level, atmospheric chemists had news about the manmade compounds destroying the ozone shield—and for once the news was good. More earthshaking were signs of long-distance connections among earthquakes. And from farther afield came reports of odd-shaped debris from mini-planet collisions.
Population Structure and the Evolution of Virulence in Nematode Parasites of Fig Wasps
Authors: Herre Edward Allen
Published: October 2006

It is often assumed that parasitic and disease-producing organisms tend to evolve benign relationships with their hosts over time. In contrast, theoretical arguments suggest that increased opportunities for parasite transmission will promote the evolution of increased virulence. The natural history of species-specific nematodes that parasitize fig-pollinating wasps permits the testing of these predictions in natural populations. For 11 species of Panamanian fig wasps, those species characterized by population structures that result in increased opportunities for parasite transmission harbor more virulent species of nematodes. In addition, differences in population structure are also associated with differences in other intra- and interspecific phenomena, including sex ratios among the fig wasp species, the degree of tension in the wasp-fig mutualism, and lethal combat among the males of parasitic wasps.
Cyclosporin A Specifically Inhibits Function of Nuclear Proteins Involved in T Cell Activation
Authors: Emmel Elizabeth A. , Verweij Cornelis L. , Durand David B. , Higgins Kay M. , Lacy Elizabeth , Crabtree Gerald R.
Published: October 2006

One action of cyclosporin A thought to be central to many of its immunosuppressive effects is its ability to inhibit the early events of T lymphocyte activation such as lymphokine gene transcription in response to signals initiated at the antigen receptor. Cyclosporin A was found to specifically inhibit the appearance of DNA binding activity of NF-AT, AP-3, and to a lesser extent NF-κB, nuclear proteins that appear to be important in the transcriptional activation of the genes for interleukin-2 and its receptor, as well as several other lymphokines. In addition, cyclosporin A abolished the ability of the NF-AT binding site to activate a linked promoter in transfected mitogen-stimulated T lymphocytes and in lymphocytes from transgenic mice. These results indicate that cyclosporin A either directly inhibits the function of nuclear proteins critical to T lymphocyte activation or inhibits the action of a more proximal member of the signal transmission cascade leading from the antigen receptor to the nucleus.
Nile Delta: Recent Geological Evolution and Human Impact
Authors: Stanley Daniel Jean , Warne Andrew G.
Published: October 2006

Few countries in the world are as dependent on water from a single source as Egypt. The natural Nile cycle of flow and sediment discharge has been disrupted by human intervention, including closure of the High Aswan Dam; this intervention has resulted in a series of responses that now threaten the northern Nile delta. Erosion, salinization, and pollution are inducing a marked decline in agricultural productivity and loss of land and coastal lagoons at a time when the population is expanding exponentially. Geological analyses of radiocarbon-dated cores across the northern delta are used to interpret the interaction of sea-level changes, climatic oscillations, subsidence, and transport processes during the past 35,000 years. Recognition of long-term trends of these natural factors provides a basis to evaluate the profound impact of human activity and to assess future changes in the Nile delta ecosystem.
Interaction of the San Jacinto and San Andreas Fault Zones, Southern California: Triggered Earthquake Migration and Coupled Recurrence Intervals
Authors: Sanders Christopher O.
Published: October 2006

Two lines of evidence suggest that large earthquakes that occur on either the San Jacinto fault zone (SJFZ) or the San Andreas fault zone (SAFZ) may be triggered by large earthquakes that occur on the other. First, the great 1857 Fort Tejon earthquake in the SAFZ seems to have triggered a progressive sequence of earthquakes in the SJFZ. These earthquakes occurred at times and locations that are consistent with triggering by a strain pulse that propagated southeastward at a rate of 1.7 kilometers per year along the SJFZ after the 1857 earthquake. Second, the similarity in average recurrence intervals in the SJFZ (about 150 years) and in the Mojave segment of the SAFZ (132 years) suggests that large earthquakes in the northern SJFZ may stimulate the relatively frequent major earthquakes on the Mojave segment. Analysis of historic earthquake occurrence in the SJFZ suggests little likelihood of extended quiescence between earthquake sequences.
Unidirectional Spread of Secondary Sexual Plumage Traits Across an Avian Hybrid Zone
Authors: Parsons Thomas J. , Olson Storrs L. , Braun Michael J.
Published: October 2006

Theory predicts that traits under positive selection can rapidly cross a hybrid zone in spite of a substantial barrier to neutral gene flow between hybridizing taxa. An avian hybrid zone between
Manacus candei
(white-collared manakin) and
M. vitellinus
(golden-collared manakin) is reported here that displays an unusual pattern of noncoincident clines. Male secondary sexual traits of
M. vitellinus
have spread into populations that are genetically and morphometrically like
M. candei
. These birds have a lek breeding system in which male mating success is highly skewed, suggesting that sexual selection is driving male sexual traits across the zone.
Synthesis of Polycrystalline Chalcopyrite Semiconductors by Microwave Irradiation
Authors: Landry Christopher C. , Barron Andrew R.
Published: October 2006

Polycrystalline samples of the chalcopyrites CulnS
2
, CulnSe
2
, and CulnSSe were prepared from stoichiometric mixtures of the pure elements by microwave irradiation. The reactions were performed in sealed quartz tubes in as few as 3 minutes. The products were analyzed by x-ray diffraction, scanning electron microscopy, energy dispersive x-ray analysis, and x-ray photoelectron spectroscopy. The surface morphology and shape of the particles produced by this method suggest that the products are formed from liquid melts. This method could be applied to the production of bulk chalcopyrite as sources for thin film growth.
Observations of Time Variation in the Sun's Rotation
Authors: Woodard M. F. , Libbrecht K. G.
Published: October 2006

Observations of solar p-mode frequency splittings obtained at Big Bear Solar Observatory in 1986 and during 1988-90 reveal small (∼1 percent) changes in the sun's subsurface angular velocity with solar cycle. An asymptotic inversion of the splitting data yields the latitude dependence of the rotation rate and shows that the largest changes in the angular velocity, ≈4 nanohertz, occurred between 1986 and the later years, at high (≈60°) solar latitudes. Earlier helioseismic observations suggest that solar cycle changes in the ratio of magnetic to turbulent pressure in the solar convection zone are large enough to account for the magnitude of the observed angular velocity variations but a detailed model of the phenomenon does not exist.
Geophysical Investigations of the Tectonic Boundary Between East and West Antarctica
Authors: ten Brink U. S. , Bannister S. , Beaudoin B. C. , Stern T. A.
Published: October 2006

The Transantarctic Mountains (TAM), which separate the West Antarctic rift system from the stable shield of East Antarctica, are the largest mountains developed adjacent to a rift. The cause of uplift of mountains bordering rifts is poorly understood. One notion based on observations of troughs next to many uplifted blocks is that isostatic rebound produces a coeval uplift and subsidence. The results of an over-snow seismic experiment in Antarctica do not show evidence for a trough next to the TAM but indicate the extension of rifted mantle lithosphere under the TAM. Furthermore, stretching preceded the initiation of uplift, which suggests thermal buoyancy as the cause for uplift.
Electron Diffraction and Imaging of Uncompressed Monolayers of Amphiphilic Molecules on Vitreous and Hexagonal Ice
Authors: Majewski J. , Margulis L. , Jacquemain D. , Leveiller F. , Bohm C. , Arad T. , Talmon Y. , Lahav M. , Leiserowitz L.
Published: October 2006

A new approach is described for probing domains of ordered self-assemblies of amphiphilic monolayers at the aqueous solution interface. The method has potential importance for the study of membrane structure, Langmuir-Blodgett films, and nucleation processes of two-and three-dimensional crystals. Electron diffraction (ED) patterns indicative of two-dimensional crystalline self-assembly were obtained from samples, which were examined by cryo-electron microscopy, of monolayers of water-insoluble amphiphiles on vitrified aqueous substrates. The apparent hexagonal symmetry of an ED pattern from a C
16
H
33
OH monolayer was interpreted in terms of multiple twinning. Monolayers of the CL
31
H
63
OH and cadmium salt of C
19
H
39
CO
2
H that were studied by dark-field techniques displayed faceted two-dimensional crystallites with a maximal size of 1 to 2 micrometers. Epitaxial nucleation of hexagonal ice by the C
31
H
63
OH monolayer has also been demonstrated by ED.
Teosinte glume architecture 1
: A Genetic Locus Controlling a Key Step in Maize Evolution
Authors: Dorweiler Jane , Stec Adrian , Kermicle Jerry , Doebley John
Published: October 2006

Teosinte, the probable progenitor of maize, has kernels that are encased in hardened fruitcases, which interfere with the use of the kernels as food. Although the components of the fruitcase are present in maize, their development is disrupted so that the kernels are not encased as in teosinte but exposed on the ear. The change from encased to exposed kernels represents a key step in maize evolution. The locus that largely controls this morphological difference between maize and teosinte,
teosinte glume architecture 1
, is described and genetically mapped.
Evidence for Large Upward Trends of Ultraviolet-B Radiation Linked to Ozone Depletion
Authors: Kerr J. B. , McElroy C. T.
Published: October 2006

Spectral measurements of ultraviolet-B radiation made at Toronto since 1989 indicate that the intensity of light at wavelengths near 300 nanometers has increased by 35 percent per year in winter and 7 percent per year in summer. The wavelength dependence of these trends indicates that the increase is caused by the downward trend in total ozone that was measured at Toronto during the same period. The trend at wavelengths between 320 and 325 nanometers is essentially zero.
Geologists Get Together to Dissect Earth's Thin Skin
Authors: Kerr Richard A.
Published: October 2006

At the annual meeting of the Geological Society of America in Boston during late October, Earth's crust came in for close scrutiny. One surprise was its age: Chemical and isotopic evidence suggested the crust formed soon after the planet did. Participants also discussed features of today's crust, including a horizontal slice beneath San Francisco and the possibility that a particular kind of crustal stretching, long envisioned, may not actually take place.
Discovery of a Main-Belt Asteroid Resembling Ordinary Chondrite Meteorites
Authors: Binzel Richard P. , Xu Shui , Bus Schelte J. , Skrutskie M. F. , Meyer Michael R. , Knezek Patricia , Barker Edwin S.
Published: October 2006

Although ordinary chondrite material dominates meteorite falls, the identification of a main-belt asteroid source has remained elusive. From a new survey of more than 80 small main-belt asteroids comes the discovery of one having a visible and near-infrared reflectance spectrum similar to L6 and LL6 ordinary chondrite meteorites. Asteroid 3628 Božněmcová has an estimated diameter of 7 kilometers and is located in the vicinity of the 3:1 Jovian resonance, a predicted meteorite source region. Although the discovery of a spectral match may indicate the existence of ordinary chondrite material within the main asteroid belt, the paucity of such detections remains an unresolved problem.
Unity in Function in the Absence of Consensus in Sequence: Role of Leader Peptides in Export
Authors: Randall L. L. , Hardy S. J. S.
Published: October 2006

Passage of proteins across membranes during export from their site of synthesis to their final destination is mediated by leader peptides that paradoxically exhibit a unity of function in spite of a diversity of sequence. These leader peptides act in at least two stages of the export process: at entry into the pathway and subsequently during translocation across the membrane. How selectivity is imposed on the system in the absence of a consensus among the sequences of leader peptides is the main issue discussed here.
Clinical Versus Actuarial Judgment
Authors: Dawes Robyn M. , Faust David , Meehl Paul E.
Published: October 2006

Professionals are frequently consulted to diagnose and predict human behavior; optimal treatment and planning often hinge on the consultant's judgmental accuracy. The consultant may rely on one of two contrasting approaches to decision-making—the clinical and actuarial methods. Research comparing these two approaches shows the actuarial method to be superior. Factors underlying the greater accuracy of actuarial methods, sources of resistance to the scientific findings, and the benefits of increased reliance on actuarial approaches are discussed.
The Purine Path to Chemotherapy
Authors: Elion Gertrude B.
Published: October 2006

Research on antimetabolites of nucleic acid purines led to drugs for the treatment of acute leukemia (6-mercaptopurine and thioguanine), gout and hyperuricemia (allopurinol), and herpesvirus infections (acyclovir), and for the prevention of organ transplant rejection (azathioprine).
Cetaceans
Authors: Würsig Bernd
Published: October 2006

Cetaceans display numerous anatomic and physiologic adaptations to life in a dense, three-dimensional medium. Their bodies have changed radically from those of their terrestrial ancestors, yet their behaviors and types of social organization are broadly similar to those of animals on land. An exploration of cetacean ways helps in understanding how habitat influences habits. For example, it is now recognized that in some important ways, cetacean residents of the open ocean resemble some of their mammalian relatives on the savanna. As air breathers that are inseparably tied to the surface, cetaceans are highly trackable; they may thus help in the monitoring of habitat degradation and other long-term ecologic change.
DNA Mismatch Correction in a Defined System
Authors: Lahue R. S. , Au K. G. , Modrich P.
Published: October 2006

DNA mismatch correction is a strand-specific process involving recognition of noncomplementary Watson-Crick nucleotide pairs and participation of widely separated DNA sites. The
Escherichia coli
methyl-directed reaction has been reconstituted in a purified system consisting of MutH, MutL, and MutS proteins, DNA helicase II, single-strand DNA binding protein, DNA polymerase III holoenzyme, exonuclease I, DNA ligase, along with ATP (adenosine triphosphate), and the four deoxynucleoside triphosphates. This set of proteins can process seven of the eight base-base mismatches in a strand-specific reaction that is directed by the state of methylation of a single d(GATC) sequence located 1 kilobase from the mispair.
Oscillation and Chaos in Physiological Control Systems
Authors: Mackey Michael C. , Glass Leon
Published: October 2006

First-order nonlinear differential-delay equations describing physiological control systems are studied. The equations display a broad diversity of dynamical behavior including limit cycle oscillations, with a variety of wave forms, and apparently aperiodic or "chaotic" solutions. These results are discussed in relation to dynamical respiratory and hematopoietic diseases.
Host Control of Tumor Growth
Authors: Ting C. C. , Tsai S. C. , Rogers M. J.
Published: October 2006

A humoral factor (molecular weight less than 60,000) that was present in the ascitic fluid of mice bearing intraperitoneal tumors and in pleural effusions from human cancer patients was found to promote the growth of a murine tumor and to suppress cell-mediated tumor immunity. However, the hosts that had recovered from the immunosuppressive state produced a serum factor that could neutralize the immunosuppressive effect.
Phi Bodies: Peroxidatic Particles that Produce Crystalloidal Cellular Inclusions
Authors: Hanker Jacob S. , Romanovicz Dwight K.
Published: October 2006

Unique, spindle-shaped particles (φ bodies) and rods with peroxidatic activity are found in certain epithelial cells of normal mice, clofibrate-fed rats, and in leukemic leukocytes. The ellipsoidal shape of φ bodies apparently results from the deformation of spherical granules by extrusion of axial crystalloid that subsequently fragments into rods.
Dominoes and Clocks: the Union of Two Views of the Cell Cycle
Authors: Murray Andrew W. , Kirschner Marc W.
Published: October 2006

We review the recent advances in understanding transitions within the cell cycle. These have come from both genetic and biochemical approaches. We discuss the phylogenetic conservation of the mechanisms that induce mitosis and their implications for other transitions in the cell cycle.
Central Synaptic Inputs to Identified Leech Neurons Determined by Peripheral Targets
Authors: Loer Curtis M. , Kristan William B.
Published: October 2006

Developing Retzius (Rz) neurons in different segments of the central nervous system of the medicinal leech have different peripheral targets: Rz cells in standard segments innervate the body wall, whereas Rz cells in the reproductive segments innervate reproductive tissue. Early removal of reproductive tissue primordia causes reproductive Rz cells to develop morphologically like their standard segmental homologs, suggesting that Rz cells depend on peripheral targets for signals that determine their central and peripheral morphology. Furthermore, after removal of reproductive tissue, reproductive Rz cells also receive synaptic inputs normally appropriate for standard Rz cells. These results suggest that the functional identity of these neurons is specified by the target they contact during embryogenesis.
Enhanced Activity and Altered Specificity of Phospholipase A
2
by Deletion of a Surface Loop
Authors: Kuipers Oscar P. , Thunnissen Marjolein M. G. M. , de Geus Pieter , Dijkstra Bauke W. , Drenth Jan , Verheij Hubertus M. , de Haas Gerard H.
Published: October 2006

Protein engineering and x-ray crystallography have been used to study the role of a surface loop that is present in pancreatic phospholipases but is absent in snake venom phospholipases. Removal of residues 62 to 66 from porcine pancreatic phospholipase A
2
does not change the binding constant for micelles significantly, but it improves catalytic activity up to 16 times on micellar (zwitterionic) lecithin substrates. In contrast, the decrease in activity on negatively charged substrates is greater than fourfold. A crystallographic study of the mutant enzyme shows that the region of the deletion has a well-defined structure that differs from the structure of the wild-type enzyme. No structural changes in the active site of the enzyme were detected.
Images of the DNA Double Helix in Water
Authors: Lindsay S. M. , Thundat T. , Nagahara L. , Knipping U. , Rill R. L.
Published: October 2006

The scanning tunneling microscope can image uncoated DNA submerged in water. The grooves of the double helix were clearly resolved in images of the 146-base pair fragment extracted from calf thymus nucleosome. In contrast to images obtained with dry DNA, the helix pitch varied only a small amount (36 ± 5 angstroms). The path of the helix shows considerable variation. It is quite straight when the molecules are densely packed, but it curves and bends in isolated molecules.
Contragestion and Other Clinical Applications of RU 486, an Antiprogesterone at the Receptor
Authors: Baulieu Etienne-Emile
Published: October 2006

RU 486, a steroid with high affinity for the progesterone receptor, is the first available active antiprogesterone. It has been used successfully as a medical alternative for early pregnancy interruption, and it also has other potential applications in medicine and for biochemical and pathophysiological endocrine research.
Recombinant Fragment of Protein Kinase Inhibitor Blocks Cyclic AMP-Dependent Gene Transcription
Authors: Grove J. Russell , Price Daniel J. , Goodman Howard M. , Avruch Joseph
Published: October 2006

Transcriptional regulation by cyclic adenosine monophosphate (cAMP) in mammalian cells could be mediated by a phosphoprotein substrate of the cAMP-dependent protein kinase or, as in prokaryotes, by a cAMP-binding protein. Two synthetic genes that code for an active fragment of the protein inhibitor of this kinase and a mutant inactive fragment were constructed and used to distinguish these alternatives. Transient expression of the active peptide product specifically inhibited the cAMP-stimulated expression of a cotransfected reporter gene by more than 90 percent, whereas the expression of the inactive peptide did not alter cAMP-stimulated gene expression. The results indicate that an active kinase catalytic subunit is a necessary intermediate in the cAMP stimulation of gene transcription.
Helix Signals in Proteins
Authors: Presta Leonard G. , Rose George D.
Published: October 2006

The α helix, first proposed by Pauling and co-workers, is a hallmark of protein structure, and much effort has been directed toward understanding which sequences can form helices. The helix hypothesis, introduced here, provides a tentative answer to this question. The hypothesis states that a necessary condition for helix formation is the presence of residues flanking the helix termini whose side chains can form hydrogen bonds with the initial four-helix > N-H groups and final four-helix > C-O groups; these eight groups would otherwise lack intrahelical partners. This simple hypothesis implies the existence of a stereochemical code in which certain sequences have the hydrogen-bonding capacity to function as helix boundaries and thereby enable the helix to form autonomously. The three-dimensional structure of a protein is a consequence of the genetic code, but the rules relating sequence to structure are still unknown. The ensuing analysis supports the idea that a stereochemical code for the α helix resides in its boundary residues.
The Yeast Cell Cycle Gene
CDC34
Encodes a Ubiquitin-Conjugating Enzyme
Authors: Goebl Mark G. , Yochem John , Jentsch Stefan , McGrath John P. , Varshavsky Alexander , Byers Breck
Published: October 2006

Mutants in the gene
CDC34
of the yeast
Saccharomyces cerevisiae
are defective in the transition from G
1
to the S phase of the cell cycle. This gene was cloned and shown to encode a 295-residue protein that has substantial sequence similarity to the product of the yeast
RAD6
gene. The
RAD6
gene is required for a variety of cellular functions including DNA repair and was recently shown to encode a ubiquitin-conjugating enzyme. When produced in
Escherichia coli
, the
CDC34
gene product catalyzed the covalent attachment of ubiquitin to histones H2A and H2B in vitro, demonstrating that the CDC34 protein is another distinct member of the family of ubiquitin-conjugating enzymes. The cell cycle function of
CDC34
is thus likely to be mediated by the ubiquitin-conjugating activity of its product.
β1-6 Branching of Asn-Linked Oligosaccharides Is Directly Associated with Metastasis
Authors: Dennis James W. , Laferté Suzanne , Waghorne Carol , Breitman Martin L. , Kerbel Robert S.
Published: October 2006

Neoplastic transformation has been associated with a variety of structural changes in cell surface carbohydrates, most notably increased sialylation and β1-6-linked branching of complex-type asparagine (Asn)-linked oligosaccharides (that is, -GlcNAcβ1-6Manα1-6Manβ1-). However, little is known about the relevant glycoproteins or how these transformation-related changes in oligosaccharide biosynthesis may affect the malignant phenotype. Here it is reported that a cell surface glycoprotein, gp130, is a major target of increased β1-6-linked branching and that the expression of these oligosaccharide structures is directly related to the metastatic potential of the cells. Glycosylation mutants of a metastatic tumor cell line were selected that are deficient in both β1-6 GlcNAc transferase V activity and metastatic potential in situ. Moreover, induction of increased β1-6 branching in clones of a nonmetastatic murine mammary carcinoma correlated strongly with acquisition of metastatic potential. The results indicate that increased β1-6-linked branching of complex-type oligosaccharides on gp130 may be an important feature of tumor progression related to increased metastatic potential.
Deletion in Chromosome 11p Associated with a Hepatitis B Integration Site in Hepatocellular Carcinoma
Authors: Rogler C. E. , Sherman M. , Su C. Y. , Shafritz D. A. , Summers J. , Shows T. B. , Henderson A. , Kew M.
Published: October 2006

Hepatitis B virus (HBV), a virus with known carcinogenic potential, integrates into cellular DNA during long-term persistent infection in man. Hepatocellular carcinomas isolated from viral carriers often contain clonally propagated viral DNA integrations. As small chromosomal deletions are associated with several types of carcinomas, the occurrence of chromosomal deletions in association with HBV integration in hepatocellular carcinoma was studied. HBV integration was accompanied by a deletion of at least 13.5 kilobases of cellular sequences in a human hepatocellular carcinoma. The viral DNA integration and deletion of cellular sequences occurred on the short arm of chromosome 11 at location 11p13-11p14. The cellular sequences that were deleted at the site of HBV integration were lost from the tumor cells, leaving only a single copy of the remaining cellular allele.
Inhibition of Lymphocyte Proliferation by a Synthetic Peptide Homologous to Retroviral Envelope Proteins
Authors: Cianciolo George J. , Copeland Terry D. , Oroszlan Stephen , Snyderman Ralph
Published: October 2006

The retroviral transmembrane envelope protein p15E is immunosuppressive in that it inhibits immune responses of lymphocytes, monocytes, and macrophages. A region of p15E has been conserved among murine and feline retroviruses; a homologous region is also found in the transmembrane envelope proteins of the human retroviruses HTLV-I and HTLV-II and in a putative envelope protein encoded by an endogenous C-type human retroviral DNA. A peptide (CKS-17) was synthesized to correspond to this region of homology and was examined for its effects on lymphocyte proliferation. CKS-17 inhibited the proliferation of an interleukin-2-dependent murine cytotoxic T-cell line as well as alloantigen-stimulated proliferation of murine and human lymphocytes. Four other peptides, representing different regions of virus proteins, were inactive. These results suggest that the immunosuppressive portion of retroviral transmembrane envelope proteins may reside, at least in part, in a conserved sequence represented by the CKS-17 peptide.
Vestibular Stimulation Influence on Motor Development in Infants
Authors: Clark David L. , Kreutzberg  , Chee Francis K. W.
Published: October 2006

Preambulatory, normal human infants were exposed to sessions of mild semicircular canal stimulation on 2 days per week for 4 weeks. The gross motor ability of each child was assessed before and after the 4-week period. The vestibular stimulation effected a significant improvement in gross motor skills.
A Deletion Truncating the Gonadotropin-Releasing Hormone Gene Is Responsible for Hypogonadism in the
hpg
Mouse
Authors: Mason Anthony J. , Hayflick Joel S. , Zoeller R. Thomas , Young W. Scott , Phillips Heidi S. , Nikolics Karoly , Seeburg Peter H.
Published: October 2006

Hereditary hypogonadism in the hypogonadal (
hpg
) mouse is caused by a deletional mutation of at least 33.5 kilobases encompassing the distal half of the gene for the common biosynthetic precursor of gonadotropin-releasing hormone (GnRH) and GnRH-associated peptide (GAP). The partially deleted gene is transcriptionally active as revealed by in situ hybridization histochemistry of
hpg
hypothalamic tissue sections, but immunocytochemical analysis failed to show the presence of antigen corresponding to any part of the precursor protein.
Heritable Somatic Excision of a
Drosophila
Transposon
Authors: Bryan Glenn J. , Jacobson James W. , Hartl Daniel L.
Published: October 2006

A mutation in the
white
gene of
Drosophila mauritiana
that results from insertion of the transposable element
mariner
is genetically unstable in both germ cells and somatic cells. Somatic instability is indicated by the occurrence of animals having mosaic eyes with patches of pigmented cells on a peach-colored background. Normally uncommon, the frequency of mosaicism is so greatly enhanced in a particular mutant strain that virtually every animal in the strain is an eye-color mosaic. The molecular basis of the mosaicism is the excision of the
mariner
element from its location in the DNA of the
white
gene in somatic cells. The phenomenon results from a single dominant genetic factor located in chromosome 3. Genetic control over the excision of transposable elements may play a role in determining the persistence of transposable elements in the genome.
Sugar and Signal-Transducer Binding Sites of the
Escherichia coli
Galactose Chemoreceptor Protein
Authors: Vyas Nand K. , Vyas Meenakshi N. , Quiocho Florante A.
Published: October 2006

D-Galactose-binding (or chemoreceptor) protein of
Escherichia coli
serves as an initial component for both chemotaxis towards galactose and glucose and high-affinity active transport of the two sugars. Well-refined x-ray structures of the liganded forms of the wild-type and a mutant protein isolated from a strain defective in chemotaxis but fully competent in transport have provided a molecular view of the sugar-binding site and of a site for interacting with the Trg transmembrane signal transducer. The geometry of the sugar-binding site, located in the cleft between the two lobes of the bilobate protein, is novel in that it is designed for tight binding and sequestering of either the α or β anomer of the D-stereoisomer of the 4-epimers galactose and glucose. Binding specificity and affinity are conferred primarily by polar planar side-chain residues that form intricate networks of cooperative and bidentate hydrogen bonds with the sugar substrates, and secondarily by aromatic residues that sandwich the pyranose ring. Each of the pairs of anomeric hydroxyls and epimeric hydroxyls is recognized by a distinct Asp residue. The site for interaction with the transducer is about 18 Å from the sugar-binding site. Mutation of Gly
74
to Asp at this site, concomitant with considerable changes in the local ordered water structures, contributes to the lack of productive interaction with the transmembrane signal transducer.
The Hypogonadal Mouse: Reproductive Functions Restored by Gene Therapy
Authors: Mason Anthony J. , Pitts Sharon L. , Nikolics Karoly , Szonyi Eva , Wilcox Josiah N. , Seeburg Peter H. , Stewart Timothy A.
Published: October 2006

The hypogonadal (
hpg
) mouse lacks a complete gonadotropin-releasing hormone (GnRH) gene and consequently cannot reproduce. Introduction of an intact GnRH gene into the genome of these mutant mice resulted in complete reversal of the hypogonadal phenotype. Transgenic
hpg
/
hpg
homozygotes of both sexes were capable of mating and producing offspring. Pituitary and serum concentrations of luteinizing hormone, follicle-stimulating hormone, and prolactin were restored to those of normal animals. Immunocytochemistry and in situ hybridization showed that GnRH expression was restored in the appropriate hypothalamic neurons of the transgenic
hpg
animals, an indication of neural-specific expression of the introduced gene.
Interferon-γ and B Cell Stimulatory Factor-1 Reciprocally Regulate Ig Isotype Production
Authors: Snapper Clifford M. , Paul William E.
Published: October 2006

Gamma interferon (IFN-γ) and B cell stimulatory factor-1 (BSF-1), also known as interleukin-4, are T cell-derived lymphokines that have potent effects on B cell proliferation and differentiation. They are often secreted by distinct T cell clones. It is now shown that IFN-γ stimulates the expression of immunoglobulin (Ig) of the IgG2a isotype and inhibits the production of IgG3, IgG1, IgG2b, and IgE. By contrast, BSF-1 has powerful effects in promoting switching to the expression of IgG1 and IgE but markedly inhibits IgM, IgG3, IgG2a, and IgG2b. These results indicate that BSF-1 and IFN-γ as well as the T cells that produce them may act as reciprocal regulatory agents in the determination of Ig isotype responses. The effects of IFN-γ and BSF-1 on isotype expression are independent.
Single-Chain Antigen-Binding Proteins
Authors: Bird Robert E. , Hardman Karl D. , Jacobson James W. , Johnson Syd , Kaufman Bennett M. , Lee Shwu-Maan , Lee Timothy , Pope Sharon H. , Riordan Gary S. , Whitlow Marc
Published: October 2006

Single-chain antigen-binding proteins are novel recombinant polypeptides, composed of an antibody variable light-chain amino acid sequence (V
L
) tethered to a variable heavy-chain sequence (V
H
) by a designed peptide that links the carboxyl terminus of the V
L
sequence to the amino terminus of the V
H
sequence. These proteins have the same specificities and affinities for their antigens as the monoclonal antibodies whose V
L
and V
H
sequences were used to construct the recombinant genes that were expressed in
Escherichia coli
. Three of these proteins, one derived from the sequence for a monoclonal antibody to growth hormone and two derived from the sequences of two different monoclonal antibodies to fluorescein, were designed, constructed, synthesized, purified, and assayed. These proteins are expected to have significant advantages over monoclonal antibodies in a number of applications.
Cigarette Smoke Inhalation Decreases α
1
-Antitrypsin Activity in Rat Lung
Authors: Janoff A. , Carp H. , Lee D. K. , Drew R. T.
Published: October 2006

Brief inhalation exposure of rats to three or six puffs of cigarette smoke significantly decreases elastase inhibitory capacity per milligram of α
1
-antitrypsin in lung lavage fluid. This effect is not observed in ozone-tolerant rats and can be reversed by treating the lung lavage fluid from smoke-exposed rats with reducing agents. Samples of human serum obtained immediately after smoking also show decreased elastase inhibitory capacity per milligram of α
1
-antitrypsin. Again, elastase inhibitory capacity can be restored by treatment with a reducing agent. Cigarette smoking may cause emphysema by inactivating α
1
-antitrypsin through oxidation.
Single Strands, Triple Strands, and Kinks in H-DNA
Authors: Htun Han , Dahlberg James E.
Published: October 2006

A naturally occurring (dT-dC)
18
:(dA-dG)
18
repeat in the H conformation of DNA was shown to contain single-stranded nucleotides in the center of the TC
18
repeat and on one half of the AG
18
repeat. These results support the model that H-DNA is a structure containing both triple-stranded and single-stranded regions. The stability of this structure was affected by both
p
H and the degree of negative supercoiling: at
p
H 7.6 to 7.7, a high level of supercoiling was needed to keep about half of the molecules in the H conformation; at
p
H 6 and
p
H 5, normal levels of supercoiling supported H-DNA; and at
p
H 4, no supercoiling was required. At mildly alkaline
p
H, the TC/AG18 repeat assumed a novel conformation called J-DNA that differed from both the B and H forms. A three-dimensional model for the structure of H-DNA is proposed that accounts both for the single-strandedness of the nucleotides and for the influence of supercoiling on H-DNA formation. This model predicts and evidence is presented that H-DNA introduces a sharp kink in the DNA. Moreover, the angle of this kink appears not to be fixed, so that H-DNA is also a hinged-DNA.
Identification of a Putative Regulator of Early T Cell Activation Genes
Authors: Shaw Jeng-Pyng , Utz Paul J. , Durand David B. , Toole J. Jay , Emmel Elizabeth Ann , Crabtree Gerald R.
Published: October 2006

Molecules involved in the antigen receptor-dependent regulation of early T cell activation genes were investigated with the use of functional sequences of the T cell activation-specific enhancer of interleukin-2 (IL-2). One of these sequences forms a protein complex, NFAT-1, specifically with nuclear extracts of activated T cells. This complex appeared 10 to 25 minutes before the activation of the IL-2 gene. Studies with inhibitors of protein synthesis indicated that the time of synthesis of the activator of the IL-2 gene in Jurkat T cells corresponds to the time of appearance of NFAT-1. NFAT-1, or a very similar protein, bound functional sequences of the long terminal repeat (LTR) of the human immunodeficiency virus type 1; the LTR of this virus is known to be stimulated during early T cell activation. The binding site for this complex activated a linked promoter after transfection into antigen receptor-activated T cells but not other cell types. These characteristics suggest that NFAT-1 transmits signals initiated at the T cell antigen receptor.
Molecular Phylogeny of the Animal Kingdom
Authors: Field Katharine G. , Olsen Gary J. , Lane David J. , Giovannoni Stephen J. , Ghiselin Michael T. , Raff Elizabeth C. , Pace Norman R. , Raff Rudolf A.
Published: October 2006

A rapid sequencing method for ribosomal RNA was applied to the resolution of evolutionary relationships among Metazoa. Representatives of 22 classes in 10 animal phyla were used to infer phylogenetic relationships, based on evolutionary distances determined from pairwise comparisons of the 18
S
ribosomal RNA sequences. The classical Eumetazoa are divided into two groups. Cnidarians arose from a protist ancestry different from the second group, the Bilateria. Within the Bilateria, an early split gave rise to Platyhelminthes (flatworms) and the coelomate lineage. Coelomates are thus monophyletic, and they radiated rapidly into four groups: chordates, echinoderms, arthropods, and eucoelomate protostomes.
The Nematode
Caenorhabditis elegans
Authors: Kenyon Cynthia
Published: October 2006

In
Caenorhabditis elegans
patterns of cell division, differentiation, and morphogenesis can be observed with single-cell resolution in intact, living animals. Mechanisms that determine behaviors of individual cells during development are being dissected by means of genetic, cell biological, and molecular approaches.