bluuebunny/crossref_metadata_2025 huggingface dataset:
5‐Hydroxytryptamine3 Receptors Sited on Cholinergic Axon Terminals of Human Cerebral Cortex Mediate Inhibition of Acetylcholine Release
Authors: Maura Guido , Andrioli Gian Carlo , Cavazzani Paolo , Raiteri Maurizio
Published: October 2006

Abstract: Synaptosomes prepared from freshly obtained human cerebral cortex and labeled with [3H]choline have been used to investigate the modulation of [3H]acetylcholine ([3H]ACh) release by 5‐hydroxytryptamine (5‐HT). The Ca2+‐dependent release of [3H]‐ACh occurring when synaptosomes were exposed in supervision to 15 mM KCl was inhibited by 5‐HT (0.01‐1 μM) in a concentration‐dependent manner. The effect of 5‐HT was mimicked by 1‐phenylbiguanide, a 5‐HT3 receptor agonist, but not by 8‐hydroxy‐2‐(di‐n‐propylamino)tetralin, a 5‐HT1A receptor agonist. The 5‐HT3 receptor antagonists tropisetron and ondansetron blocked the effect of 5‐HT, whereas spiperone and ketanserin were ineffective. It is suggested that cholinergic axon terminals in the human cerebral cortex possess 5‐HT receptors that mediate inhibition of ACh release and appear to belong to the 5‐HT3 type.
Proline‐Directed Protein Kinase (p34cdc2/p58cyclin A) Phosphorylates Bovine Neurofilaments
Authors: Guan Rong Ji , Hall Frederick L. , Cohlberg Jeffrey A.
Published: October 2006

Abstract: Proline‐directed protein kinase (PDPK), a complex of p34cdc2 and p58cyclin A, phosphorylates bovine neurofilaments (NFs) in vitro. Incubation of intact filaments with PDPK led to strong labeling of the heavy (NF‐H) and middle (NF‐M) molecular weight NF proteins and weaker labeling of the low molecular weight protein (NF‐L). All three proteins were phosphorylated in solution, with the best substrate being NF‐H. Proteins that had been dephosphorylated by enzymatic treatment were better substrates than native proteins—as many as 6 mol of phosphate were incorporated per mole of NF‐H. Partial proteolytic cleavage experiments combined with two‐dimensional peptide mapping indicated that NF‐H and NF‐M were phosphorylated predominantly in the tail domains, with some phosphate also appearing in the heads. Soluble NF‐L is phosphorylated on the head domain peptide L‐3, whereas NF‐L within intact filaments is phosphorylated only on the tail domain peptide L‐1. Phosphorylation does not lead to filament disassembly. A possible role for PDPK in NF phosphorylation in vivo is discussed.
Effect of Brain Ischemia on Protein Kinase C
Authors: Domańska‐Janik Krystyna , Zalewska Teresa
Published: October 2006

Abstract: We examined the influence of brain ischemia on the activity and subcellular distribution of protein kinase C (PKC). Two different models of ischemic brain injury were used: postdecapitative ischemia in rat forebrain and transient (6‐min) cerebral ischemia in gerbil hippocampus. In the rat forebrain model, at 5 and 15 min postdecapitation there was a steady decrease of total PKC activity to 60% of control values. This decrease occurred without changes in the proportion of the particulate to the soluble enzyme pools. Isolated rat brain membranes also exhibited a concomitant decrease of [3H]phorbol 12,13‐dibutyrate ([3H]PDBu) binding with an apparent increase of the ligand affinity to the postischemic membranes. On the other hand, the ischemic gerbil hippocampus model displayed a 40% decrease of total PKC activity, which was accompanied by a relative increase of PKC activity in its membrane‐bound form. This resulted in an increase in the membrane/total activity ratio, indicating a possible enzyme translocation from cytosol to the membranes after ischemia. Moreover, after 1 day of recovery, a statistically significant enhancement of membrane‐bound PKC activity resulted in a further increase of its relative activity up to 162% of control values. In vitro experiments using a synaptoneurosomal particulate fraction were performed to clarify the mechanism of the rapid PKC inhibition observed in cerebral tissue after ischemia. These experiments showed a progressive, Ca2+‐dependent, antiprotease‐insensitive down‐regulation of PKC during incubation. This down‐regulation was significantly enhanced by prior phorbol (PDBu) treatment. It can be postulated that in the ischemic gerbil hippocampus model as well as during phorbol stimulation of the synaptoneurosomal fraction in vitro, the common phenomenon was an initial PKC activation (translocation) followed by a subsequent enhancement of Ca2+‐dependent enzyme inhibition. Experimental data suggest that the inhibition is localized in the membrane compartment.
τ Protein Kinase II Is Involved in the Regulation of the Normal Phosphorylation State of τ Protein
Authors: Arioka Manabu , Tsukamoto Masamitsu , Ishiguro Koichi , Kato Rika , Sato Kazuki , Imahori Kazutomo , Uchida Tsuneko
Published: October 2006

Abstract: To study the phosphorylation state of τ in vivo, we have prepared antisera by immunizing rabbits with synthetic phosphopeptides containing phosphoamino acids at specific sites that are potential targets for τ protein kinase II. Immunoblot experiments using these antisera demonstrated that τ in microtubule‐associated proteins is phosphorylated at Ser144 and at Ser315. Almost all τ variants separated on two‐dimensional gel electrophoresis were phosphorylated at Ser144 and nearly one‐half of them at Ser315. Phosphorylation at Ser144 and at Thr147 of τ isolated from heat‐stable brain extracts was shown to be developmentally regulated, with the highest level of phosphorylation found at postnatal week 1. In vitro phosphorylation of τ by τ protein kinase I, a kinase responsible for abnormal phosphorylation of τ found in paired helical filaments of patients with Alzheimer's disease, was enhanced by prior phosphorylation of τ by τ protein kinase II. Thus, we suggest that τ protein kinase II is indirectly involved, at least in part, in the regulation of the phosphorylation state of τ in neuronal cells.
Glucose Utilization Rates in Single Neurons and Neuropil Determined by Injecting Nontracer Amounts of 2‐Deoxyglucose
Authors: Akabayashi Akira , Kato Takahiko
Published: October 2006

Abstract: A nontracer amount of 2‐deoxyglucose (DG) was intravenously injected into rats, which were frozen 2 and 4 min later in liquid nitrogen. The freeze‐dried samples of cell bodies of anterior horn cells, dorsal root ganglion cells, and cerebellar Purkinje cells, as well as the neuropil adjacent to anterior horn cell bodies, were prepared. Their contents of glucose, glucose 6‐phosphate, DG, and 2‐deoxyglucose 6‐phosphate were microassayed using an enzymatic amplification reaction, NADP cycling. Based on the resulting data and theoretical equations previously described, glucose utilization rate (GUR) and apparent distribution volumes (DVs) of glucose and DG were determined. Anterior horn cell bodies had the highest GUR and their neuropil the lowest, although apparent DVs of glucose and DG were similar in both. This indicates that the glucose supply was equally balanced in all, but that the cell bodies had higher functional activity supported by hexokinase (and other enzymes) related to their energy demands. Dorsal root ganglion cells showed the lowest 2‐deoxyglucose 6‐phosphate formation rate, but their GUR was slightly higher than that of neuropil because of their markedly large DV of glucose, thus demonstrating that the abundant glucose supply supports the neuronal function. Purkinje cells indicated GUR and apparent DVs similar to molecular and granular layers.
Inhibition by 2‐Deoxyglucose and 1,5‐Gluconolactone of Glycogen Mobilization in Astroglia‐Rich Primary Cultures
Authors: Dringen Ralf , Hamprecht Bernd
Published: October 2006

Abstract: The presence of glycogen in astroglia‐rich primary cultures derived from the brains of newborn rats depends on the availability of glucose in the culture medium. On glucose deprivation, glycogen vanishes from the astroglial cultures. This decrease of glycogen content is completely prevented if 2‐deoxyglucose in a concentration of > 1 mM or 1,5‐gluconolactone (20 mM) is present in the culture medium. 2‐Deoxyglucose itself or 3‐O‐methylglucose, a glucose derivative that is not phosphorylated by hexokinase, does not reduce the activity of glycogen phosphorylase purified from bovine brain or in the homogenate of astroglia‐rich rat primary cultures. In contrast, deoxyglucose‐6‐phosphate strongly inhibits the glycogen phosphorylase activities of the preparations. Half‐maximal effects were obtained at deoxyglucose‐6‐phosphate concentrations of 0.75 (phosphorylase a, astroglial culture), 5 (phosphorylase b, astroglial culture), 2 (phosphorylase a, bovine brain), or 9 mM (phosphorylase b, bovine brain). Thus, the block of glycogen degradation in these cells appears to be due to inhibition of glycogen phosphorylase by deoxyglucose‐6‐phosphate rather than deoxyglucose itself. These results suggest that glucose‐6‐phosphate, rather than glucose, acts as a physiological negative feedback regulator of the brain isoenzyme of phosphorylase and thus of glycogen degradation in astrocytes.
Extracellular Glutamate Is Increased in Thalamus During Thiamine Deficiency‐Induced Lesions and Is Blocked by MK‐801
Authors: Langlais Philip J. , Zhang Shu Xing
Published: October 2006

The current study measured extracellular fluid (ECF) levels of excitatory amino acids before and during the onset of thiamine deficiency‐induced pathologic lesions. Male Sprague‐Dawley rats were treated with daily pyrithiamine (0.25 mg/kg i.p.) and a thiamine‐deficient diet (PTD). Microdialysates were simultaneously collected from probes inserted acutely via guide cannulae into right paracentral and ventrolateral nuclei of thalamus and left hippocampus of PTD and pair‐fed controls. Hourly samples were collected from unanesthetized and freely moving animals. Basal levels obtained at a prelesion stage (day 12 of PTD treatment) were unchanged from levels in pairfed controls. In samples collected 4–5 h after onset of seizures (day 14 of PTD), the levels of glutamate were elevated an average 640% of basal levels in medial thalamus and 200% in hippocampus. Glutamine levels declined, taurine and glycine were elevated, and aspartate, GABA, and alanine were unchanged during this period. Within 7 h after seizure onset glutamine was undetectable in both areas, whereas glutamate had declined to ∼200% in thalamus and 70% in hippocampus. No significant change in glutamate, aspartate, or other amino acids was observed in dialysates collected from probes located in undamaged dorsal‐lateral regions of thalamus. Number of neurons within ventrolateral nucleus of thalamus was significantly greater in PTD animals in which the probe was dialyzed compared with nondialyzed, suggesting that removal of excitatory amino acids was protective. No significant pathologic damage was evident in hippocampus. Pretreatment with MK‐801 completely blocked the rise of ECF glutamate and significantly reduced the pathologic damage within thalamus of PTD rats and produced a significant decrease in ECF glutamate in control rats.
Depression of Neuronal Protein Synthesis Initiation by Protein Tyrosine Kinase Inhibitors
Authors: Hu Bing Ren , Ou Yang Yi Bing , Wieloch Tadeusz
Published: October 2006

Abstract— Growth factors stimulate cellular protein synthesis, but the intracellular signaling mechanisms that regulate initiation of mRNA translation in neurons have not been clarified. A rate‐limiting step in the initiation of protein synthesis is the formation of the ternary complex among GTP, eukaryotic initiation factor 2 (elF‐2), and the initiator tRNA. Here we report that genistein, a specific tyrosine kinase inhibitor, decreases tyrosine kinase activity and the content of phosphotyrosine proteins in cultured primary cortical neurons. Genistein inhibits protein synthesis by >80% in a dose‐dependent manner (10–80 μg/ml) and concurrently decreases ternary complex formation by 60%. At the doses investigated, genistein depresses tyrosine kinase activity and concomitantly stimulates PKC activity. We propose that a protein tyrosine kinase participates in the initiation of protein synthesis in neurons, by affecting the activity of elF‐2 directly or through a protein kinase cascade.
The Dark Side of Information and Market Efficiency in E‐Markets*
Authors: Grover Varun , Lim Jaejoo , Ayyagari Ramakrishna
Published: October 2006

Price dispersion reflects the differences in prices for identical products. While in physical markets such dispersion is prevalent due to high search costs, many researchers argue that search costs and price dispersion will be much lower in electronic markets (e‐markets). Empirical evidence does not support this contention, and researchers have studied search costs, market factors, and service‐quality factors to explain this dispersion. Previous research has largely assumed that more information is better. By ignoring the dark side of information, we argue that only a partial understanding of price dispersion is possible. In this article, information overload and equivocality are studied as two dark attributes of information that lead sellers to different pricing decisions in e‐markets. Hypotheses relating these attributes to price dispersion are supported through analysis of 161 product markets. This work opens up new avenues in the study of e‐markets and discusses the implications of these findings for research and practice on consumer and seller decisions.
Incidental Langerhans cell histiocytosis of the parotid gland resembling marginal zone B‐cell lymphoma: a case report
Authors: Kojima Masaru , Itoh Hideaki , Shimizu Kazuhiko , Matsuda Hazuki , Sakata Noriyuki , Masawa Nobuhide
Published: October 2006

Langerhans cell histiocytosis (LCH) manifesting as a parotid gland mass is an extremely rare clinical presentation. We report a case of LCH involving the bilateral parotid glands in an 81‐year‐old Japanese female. Pathologically, the lesion was characterized by numerous lymphoid follicles, dense lymphoplasmacytoid infiltrate and cystic dilatation of the parotid gland duct in addition to nodular and diffuse proliferation of LCs. Moreover, both LCs and small T‐lymphocytes invaded the ductal epithelium forming a lymphoepithelial lesion‐like morphology. The present case indicates that LCHs should be added to the different diagnosis for marginal zone B‐cell lymphoma of mucosa‐associated lymphoid tissue type involving the salivary glands.
Exciton determination of strain parameters in InSb∕AlxIn1−xSb quantum wells
Authors: Kasturiarachchi T. , Brown F. , Dai N. , Khodaparast G. A. , Doezema R. E. , Goel N. , Chung S. J. , Santos M. B.
Published: October 2006

Excitons in semiconductors can be used as a tool to probe various material and structural properties. The authors studied strain-related materials parameters in InSb∕AlxIn1−xSb quantum well structures. By changing the Al concentration in the barrier layers (0.03<x<0.23), the strain in the quantum wells can be tuned continuously. Using infrared transmission measurements, the authors traced strain-induced shifts in the energies of the confined states. The different strain dependences of the light- and heavy-hole band edges allow us to determine deformation potentials α and β simultaneously.
Thermal stability study on nanoscale polysilicide resistors
Authors: Chen Yen-Ming , Wang Ying-Lang , Hwang Gwo-Jen , Juang Yungder , Lee Wen-His
Published: October 2006

In this study, the thermal stability behavior of nanoscale polysilicide resistors with different dopant types was investigated in 90nm complementary metal oxide semiconductor process. It was found that thermal stability performance of polysilicide resistors was impacted not only by the silicide thickness but also by the relation between silicide grain size distribution and the actual poly linewidth. A quantitative equation for thermal stability was derived by the combination of thickness and linewidth. This equation showed good correlation with the activation energy of the degradation for the narrow poly width resistors.
Substrate temperature effects on 193nm photoresist deformation and self-aligned contact hole etching performances
Authors: Kim Myeong-Cheol , Bai Keun-Hee , Kang Chang-Jin , Cho Han-Ku
Published: October 2006

The authors managed to accomplish an etching condition for a self-aligned contact (SAC) structure patterned with the 193nm lithography. With lowering the substrate temperature from the previous SAC etching condition optimized for the 248nm lithography, they could minimize the 193nm photoresist deformation. The low-temperature setting is found to form relatively thicker, more uniform, and more carbon-rich fluorocarbon polymer film on the photoresist top and sidewall, which effectively prevents the ion-enhanced selective volatilization of carbonyl groups of the 193nm photoresist [Ling et al. J. Vac. Sci. Technol. B 22, 2594 (2004)]. Along the contact hole, the transmission electron microscope-energy dispersive x-ray spectrometry and field emission-Auger analyses were performed for the two temperature settings. At the low-temperature setting, relatively thinner fluorocarbon film with high fluorine content is observed within the contact hole, which is consistent with the observed etching phenomena of both the decrease in the etching selectivity of SiO2 to Si3N4 and the increase in the etching open strength within the SAC narrow slit. They could maintain the proper Si3N4 etching selectivity even at the low temperature with utilizing a part of the increased etching open strength endowed by decreasing the substrate temperature. They propose a model consistently describing most of all the SAC etching phenomena and surface analysis results observed in this work. The model separates the fluorocarbon radicals into the two groups, the carbon- and fluorine-abundant ones and considers the carbon-abundant radicals much stickier.
Children hear the forest
Authors: Nittrouer Susan
Published: October 2006

How do children develop the ability to recognize phonetic structure in their native language with the accuracy and efficiency of adults? In particular, how do children learn what information in speech signals is relevant to linguistic structure in their native language, and what information is not? These questions are the focus of considerable investigation, including several studies by Catherine Mayo and Alice Turk. In a proposed Letter by Mayo and Turk, the comparative role of the isolated consonant-vowel formant transition in children’s and adults’ speech perception was questioned. Although Mayo and Turk ultimately decided to withdraw their letter, this note, originally written as a reply to their letter, was retained. It highlights the fact that the isolated formant transition must be viewed as part of a more global aspect of structure in the acoustic speech stream, one that arises from the rather slowly changing adjustments made in vocal-tract geometry. Only by maintaining this perspective of acoustic speech structure can we ensure that we design stimuli that provide valid tests of our hypotheses and interpret results in a meaningful way.
Comment on "Pairing and Phase Separation in a Polarized Fermi Gas"
Authors: Zwierlein Martin W. , Ketterle Wolfgang
Published: October 2006

Partridge
et al
. (Reports, 27 January 2006, p. 503) reported pairing and phase separation in a polarized Fermi gas. We argue that it is not possible to distinguish the superfluid from the normal regimes in the presented data, or to discern which clouds were phase-separated. Some of the reported conclusions are inconsistent with recent experiments.
Wind Streaks on Venus: Clues to Atmospheric Circulation
Authors: Greeley Ronald , Schubert Gerald , Limonadi Daniel , Bender Kelly C. , Newman William I. , Thomas Peggy E. , Weitz Catherine M. , Wall Stephen D.
Published: October 2006

Magellan images reveal surface features on Venus attributed to wind processes. Sand dunes, wind-sculpted hills, and more than 5830 wind streaks have been identified. The streaks serve as local "wind vanes," representing wind direction at the time of streak formation and allowing the first global mapping of near-surface wind patterns on Venus. Wind streaks are oriented both toward the equator and toward the west. When streaks associated with local transient events, such as impact cratering, are deleted, the westward component is mostly lost but the equatorward component remains. This pattern is consistent with a Hadley circulation of the lower atmosphere.
Emission of Methyl Bromide from Biomass Burning
Authors: Manö Stein , Andreae Meinrat O.
Published: October 2006

Bromine is, per atom, far more efficient than chlorine in destroying stratospheric ozone, and methyl bromide is the single largest source of stratospheric bromine. The two main previously known sources of this compound are emissions from the ocean and from the compound's use as an agricultural pesticide. Laboratory biomass combustion experiments showed that methyl bromide was emitted in the smoke from various fuels tested. Methyl bromide was also found in smoke plumes from wildfires in savannas, chaparral, and boreal forest. Global emissions of methyl bromide from biomass burning are estimated to be in the range of 10 to 50 gigagrams per year, which is comparable to the amount produced by ocean emission and pesticide use and represents a major contribution (≈30 percent) to the stratospheric bromine budget.
On the Frequency-Locked Orbits of Two Particles in a Paul Trap
Authors: Hoffnagle J. , Brewer R. G.
Published: October 2006

Calculations are presented that show frequency-locking to be a prominent phenomenon in the dynamics of two ions in a Paul trap, provided that damping is linear and small. The frequency-locked attractors that exist when dissipation is present correspond to stable, periodic orbits of the underlying Hamiltonian system, which appear to be infinite in number. The accuracy of the calculations is illustrated by comparing an orbit observed in a Paul trap for microspheres with the solution of the equations of motion.
Mobile Point Defects and Atomic Basis for Structural Transformations of a Crystal Surface
Authors: Hwang Ing-Shouh , Theiss Silva K. , Golovchenko J. A.
Published: October 2006

Structural transformations on elemental semiconductor surfaces typically occur above several hundred degrees Celsius, and the atomic motions involved are extremely rapid and difficult to observe. However, on the (111) surface of germanium, a few lead atoms catalyze atomic motions so that they can be observed with a tunneling microscope at temperatures below 80°C. Mass transport and structural changes are caused by the creation and propagation of both vacancy-like and interstitial-like point defects within the crystal surface. The availability of dangling bonds on the surface is critical. A detailed atomic model for the observed motions has been developed and is used to explain the structural phase transition Ge(111)-c(2×8) ↔ 1×1, which occurs near 300°C.
Reduction of Permeability in Granite at Elevated Temperatures
Authors: Moore Diane E. , Lockner David A. , Byerlee James D.
Published: October 2006

The addition of hydrothermal fluids to heated, intact granite leads to permeability reductions in the temperature range of 300° to 500°C, with the rate of change generally increasing with increasing temperature. The addition of gouge enhances the rate of permeability reduction because of the greater reactivity of the fine material. Flow rate is initially high in a throughgoing fracture but eventually drops to the level of intact granite. These results support the fault-valve model for the development of mesothermal ore deposits, in which seals are formed at the base of the seismogenic zone of high-angle thrust faults. The lower temperature results yield varying estimates of mineral-sealing rates at shallower depths in fault zones, although they generally support the hypothesis that such seals develop in less time than the recurrence interval for moderate to large earthquakes on the San Andreas fault.
Effect of Noble Gas Doping in Single-Bubble Sonoluminescence
Authors: Hiller Robert , Weninger Keith , Putterman Seth J. , Barber Bradley P.
Published: October 2006

The trillionfold concentration of sound energy by a trapped gas bubble, so as to emit picosecond flashes of ultraviolet light, is found to be extremely sensitive to doping with a noble gas. Increasing the noble gas content of a nitrogen bubble to about 1% dramatically stabilizes the bubble motion and increases the light emission by over an order of magnitude to a value that exceeds the sonoluminescence of either gas alone. The spectrum also strongly depends on the nature of the gas inside the bubble: Xenon yields a spectral peak at about 300 nanometers, whereas the helium spectrum is so strongly ultraviolet that its peak is obscured by the cutoff of water.
Composite Fermions in the Quantum Hall Regime
Authors: Jain J. K.
Published: October 2006

Recent progress in the understanding of the two-dimensional electron system under the influence of a strong magnetic field is reviewed. This system is characterized by the existence of a particle called the composite fermion, which manifests itself in several dramatic experimental observations.
Origin of Storm Footprints on the Sea Seen by Synthetic Aperture Radar
Authors: Atlas David
Published: October 2006

Spaceborne synthetic aperture radar can detect storm footprints on the sea. Coastal weather radar from Cape Hatteras provides evidence that the echo-free hole at the footprint core is the result of wave damping by rain. The increased radar cross section of the sea surrounding the echo-free hole results from the divergence of the precipitation-forced downdraft impacting the sea. The footprint boundary is the gust front; its orientation is aligned with the direction of the winds aloft, which are transported down with the downdraft, and its length implies downdraft impact 1 hour earlier at a quasi-stationary impact spot. The steady, localized nature of the storm remains a mystery.
Capturing Sound, Light, and Strength With New Materials
Authors: Service Robert F.
Published: October 2006

Physicists, chemists, and other scientists gathered in Boston from 28 November to 2 December for the fall meeting of the Materials Research Society (MRS) to explore everything from the behavior of single atoms to bulk structures. Among the more than 4000 papers and posters presented, attendees learned about novel devices that convert light directly to sound, new techniques for studying minuscule structures called quantum dots, and organic-inorganic hybrid materials.
An Alternative to SH2 Domains for Binding Tyrosine-Phosphorylated Proteins
Authors: Kavanaugh W. Michael , Williams Lewis T.
Published: October 2006

Src homology 2 (SH2) domains bind specifically to tyrosine-phosphorylated proteins that participate in signaling by growth factors and oncogenes. A protein domain was identified that bound specifically to the tyrosine-phosphorylated form of its target protein but differs from known SH2 sequences. Phosphotyrosine-binding (PTB) domains were found in two proteins: SHC, a protein implicated in signaling through Ras; and SCK, encoded by a previously uncharacterized gene. The PTB domain of SHC specifically bound to a tyrosine-phosphorylated 145-kilodalton protein. PTB domains are an alternative to SH2 domains for specifically recruiting tyrosine-phosphorylated proteins into signaling complexes and are likely to take part in signaling by many growth factors.
Differential Regulation of RNA Polymerases I, II, and III by the TBP-Binding Repressor Dr1
Authors: White Robert J. , Khoo Bernard C.-E. , Inostroza Juan A. , Reinberg Danny , Jackson Stephen P.
Published: October 2006

RNA polymerases I, II, and III each use the TATA-binding protein (TBP). Regulators that target this shared factor may therefore provide a means to coordinate the activities of the three nuclear RNA polymerases. The repressor Dr1 binds to TBP and blocks the interaction of TBP with polymerase II- and polymerase III-specific factors. This enables Dr1 to coordinately regulate transcription by RNA polymerases II and III. Under the same conditions, Dr1 does not inhibit polymerase I transcription. By selectively repressing polymerases II and III, Dr1 may shift the physiological balance of transcriptional output in favor of polymerase I.
Functional Consequences of Posttranslational Isomerization of Ser
46
in a Calcium Channel Toxin
Authors: Heck Steven D. , Siok Chester J. , Krapcho Karen J. , Kelbaugh Paul R. , Thadeio Peter F. , Welch Melissa J. , Williams Robert D. , Ganong Alan H. , Kelly Mary E. , Lanzetti Anthony J. , Gray William R. , Phillips Douglas , Parks Thomas N. , Jackson Hunter , Ahlijanian Michael K. , Saccomano Nicholas A. , Volkmann Robert A.
Published: October 2006

The venom of the funnel-web spider
Agelenopsis aperta
contains several peptides that paralyze prey by blocking voltage-sensitive calcium channels. Two peptides, ω-Aga-IVB (IVB) and ω-Aga-IVC (IVC), have identical amino acid sequences, yet have opposite absolute configurations at serine 46. These toxins had similar selectivities for blocking voltage-sensitive calcium channel subtypes but different potencies for blocking P-type voltage-sensitive calcium channels in rat cerebellar Purkinje cells as well as calcium-45 influx into rat brain synaptosomes. An enzyme purified from venom converts IVC to IVB by isomerizing serine 46, which is present in the carboxyl-terminal tail, from the L to the D configuration. Unlike the carboxyl terminus of IVC, that of IVB was resistant to the major venom protease. These results show enzymatic activities in
A. aperta
venom being used in an unprecedented strategy for coproduction of necessary neurotoxins that possess enhanced stability and potency.
A Neurochemically Distinct Third Channel in the Macaque Dorsal Lateral Geniculate Nucleus
Authors: Hendry Stewart H. C. , Yoshioka Takashi
Published: October 2006

The primate visual system is often divided into two channels, designated M and P, whose signals are relayed to the cerebral cortex by neurons in the magnocellular and parvicellular layers of the dorsal lateral geniculate nucleus. We have identified a third population of geniculocortical neurons in the dorsal lateral geniculate nucleus of macaques, which is immunoreactive for the α subunit of type II calmodulin-dependent protein kinase. This large third population occupies interlaminar regions (intercalated layers) ventral to each principal layer. Retrograde labeling of kinase-immunoreactive cells from the primary visual cortex shows that they provide the geniculocortical input to cytochrome oxidase-rich puffs in layers II and III.
Sex Determination and Dosage Compensation: Lessons from Flies and Worms
Authors: Parkhurst Susan M. , Meneely Philip M.
Published: October 2006

In both
Drosophila melanogaster
and
Caenorhabditis elegans
somatic sex determination, germline sex determination, and dosage compensation are controlled by means of a chromosomal signal known as the X:A ratio. A variety of mechanisms are used for establishing and implementing the chromosomal signal, and these do not appear to be similar in the two species. Instead, the study of sex determination and dosage compensation is providing more general lessons about different types of signaling pathways used to control alternative developmental states of cells and organisms.
Mitotic Repression of RNA Polymerase III Transcription in Vitro Mediated by Phosphorylation of a TFIIIB Component
Authors: Gottesfeld Joel M. , Wolf Veronica J. , Dang Tam , Forbes Douglass J. , Hartl Philippe
Published: October 2006

Interphase cytosol extracts prepared from
Xenopus laevis
eggs are active in RNA polymerase III (Pol III) transcription. Addition of recombinant B1 cyclin to these extracts activates mitotic protein kinases that repress transcription. Affinity-purified p34

cdc2

-cyclin B kinase (mitosis-promoting factor) is sufficient to effect this repression in a simplified Pol III transcription system. This mitotic repression involves the direct phosphorylation of a component of the Pol III transcription initiation factor TFIIIB, which consists of the TATA box-binding protein (TBP) and associated Pol III-specific factors. The transcriptional activity of the TFIIIB-TBP fraction can be modulated in vitro by phosphorylation with mitotic kinases and by dephosphorylation with immobilized alkaline phosphatase.
inhA
, a Gene Encoding a Target for Isoniazid and Ethionamide in
Mycobacterium tuberculosis
Authors: Banerjee Asesh , Dubnau Eugenie , Quemard Annaik , Balasubramanian V. , Um Kyung Sun , Wilson Theresa , Collins Des , de Lisle Geoffrey , Jacobs William R.
Published: October 2006

Isoniazid (isonicotinic acid hydrazide, INH) is one of the most widely used antituberculosis drugs, yet its precise target of action on
Mycobacterium tuberculosis
is unknown. A missense mutation within the mycobacterial
inhA
gene was shown to confer resistance to both INH and ethionamide (ETH) in
M. smegmatis
and in
M. bovis
. The wild-type
inhA
gene also conferred INH and ETH resistance when transferred on a multicopy plasmid vector to
M. smegmatis
and
M. bovis
BCG. The InhA protein shows significant sequence conservation with the
Escherichia coli
enzyme EnvM, and cell-free assays indicate that it may be involved in mycolic acid biosynthesis. These results suggest that InhA is likely a primary target of action for INH and ETH.
Adenosine Inhibition of Mesopontine Cholinergic Neurons: Implications for EEG Arousal
Authors: Rainnie Donald G. , Grunze Heinz C. R. , McCarley Robert W. , Greene Robert W.
Published: October 2006

Increased discharge activity of mesopontine cholinergic neurons participates in the production of electroencephalographic (EEG) arousal; such arousal diminishes as a function of the duration of prior wakefulness or of brain hyperthermia. Whole-cell and extracellular recordings in a brainstem slice show that mesopontine cholinergic neurons are under the tonic inhibitory control of endogenous adenosine, a neuromodulator released during brain metabolism. This inhibitory tone is mediated postsynaptically by an inwardly rectifying potassium conductance and by an inhibition of the hyperpolarization-activated current. These data provide a coupling mechanism linking neuronal control of EEG arousal with the effects of prior wakefulness, brain hyperthermia, and the use of the adenosine receptor blockers caffeine and theophylline.
Comparison of Human Immunodeficiency Virus Type 1-Specific Inhibitory Activities in Saliva and Other Human Mucosal Fluids
Authors: Kazmi Shamim H. , Naglik Julian R. , Sweet Simon P. , Evans Robert W. , O'Shea Siobhan , Banatvala Jangu E. , Challacombe Stephen J.
Published: October 2006

Several human mucosal fluids are known to possess an innate ability to inhibit human immunodeficiency virus type 1 (HIV-1) infection and replication in vitro. This study compared the HIV-1 inhibitory activities of several mucosal fluids, whole, submandibular/sublingual (sm/sl), and parotid saliva, breast milk, colostrum, seminal plasma, and cervicovaginal secretions, from HIV-1-seronegative donors by using a 3-day microtiter infection assay. A wide range of HIV-1 inhibitory activity was exhibited in all mucosal fluids tested, with some donors exhibiting high levels of activity while others showed significantly lower levels. Colostrum, whole milk, and whole saliva possessed the highest levels of anti-HIV-1 activity, seminal fluid, cervicovaginal secretions, and sm/sl exhibited moderate levels, and parotid saliva consistently demonstrated the lowest levels of HIV-1 inhibition. Fast protein liquid chromatography gel filtration studies revealed the presence of at least three distinct peaks of inhibitory activity against HIV-1 in saliva and breast milk. Incubation of unfractionated and fractionated whole saliva with antibodies raised against human lactoferrin (hLf), secretory leukocyte protease inhibitor (SLPI), and, to a lesser extent, MG2 (high-molecular-weight mucinous glycoprotein) reduced the HIV-1 inhibitory activity significantly. The results suggest that hLf and SLPI are two key components responsible for HIV-1 inhibitory activity in different mucosal secretions. The variation in HIV inhibitory activity between the fluids and between individuals suggests that there may be major differences in susceptibility to HIV infection depending both on the individual and on the mucosal fluid involved.
High Levels of Serum Thromboxane B2 Are Generated during Human Pulmonary Dirofilariosis
Authors: Morchón R. , López-Belmonte J. , Rodríguez-Barbero A. , Simón F.
Published: October 2006

The canine parasite
Dirofilaria immitis
can infect humans. Patients with pulmonary dirofilariosis develop significantly higher thromboxane B2 levels than healthy individuals living in areas where dirofilariosis is endemic and in areas where dirofilariosis is not endemic. The possible role of
Wolbachia
bacteria in the appearance of this eicosanoid is discussed.
The Intracellular Siderophore Ferricrocin Is Involved in Iron Storage, Oxidative-Stress Resistance, Germination, and Sexual Development in
Aspergillus nidulans
Authors: Eisendle Martin , Schrettl Markus , Kragl Claudia , Müller Daniela , Illmer Paul , Haas Hubertus
Published: October 2006

Iron is required by most organisms, but an excess of this metal is potentially toxic. Consequently, uptake and intracellular storage of iron are tightly controlled. The filamentous fungus
A. nidulans
lacks the iron storage compound ferritin but possesses an intracellular siderophore, which is accumulated in a highly regulated manner as iron-free desferri-ferricrocin or iron-containing ferricrocin via transcriptional regulation of the nonribosomal peptide synthetase SidC. Biosynthesis of desferri-ferricrocin was low during iron-replete conditions but up-regulated by both iron starvation and intracellular iron excess, the latter caused by either a shift from iron-depleted to high-iron conditions or deregulation of iron uptake. Consequently, ferricrocin constituted only about 5% of the total iron content under iron-replete conditions but up to 64% during conditions of intracellular excess. In contrast, during iron starvation, desferri-ferricrocin was accumulated, which appears to represent a proactive strategy to prevent iron toxicity. Accumulation of the intracellular siderophore was also up-regulated by oxidative stress, which underscores the intertwining of iron metabolism and oxidative stress. Lack of the intracellular siderophore causes pleiotropic effects, as SidC deficiency results in (i) less-efficient utilization of iron, indicated by reduced growth under iron-depleted conditions and a higher iron demand under iron-replete conditions, (ii) delayed germination under iron-depleted conditions, (iii) increased sensitivity of conidia to oxidative stress, and (iv) elimination of cleistothecia formation in homothallic conditions.
Gis4, a New Component of the Ion Homeostasis System in the Yeast
Saccharomyces cerevisiae
Authors: Ye Tian , García-Salcedo Raúl , Ramos José , Hohmann Stefan
Published: October 2006

Gis4 is a new component of the system required for acquisition of salt tolerance in
Saccharomyces cerevisiae
. The
gis4
Δ mutant is sensitive to Na
+
and Li
+
ions but not to osmotic stress. Genetic evidence suggests that Gis4 mediates its function in salt tolerance, at least partly, together with the Snf1 protein kinase and in parallel with the calcineurin protein phosphatase. When exposed to salt stress, mutants lacking
gis4
Δ display a defect in maintaining low intracellular levels of Na
+
and Li
+
ions and exporting those ions from the cell. This defect is due to diminished expression of the
ENA1
gene, which encodes the Na
+
and Li
+
export pump. The protein sequence of Gis4 is poorly conserved and does not reveal any hints to its molecular function. Gis4 is enriched at the cell surface, probably due to C-terminal farnesylation. The CAAX box at the C terminus is required for cell surface localization but does not seem to be strictly essential for the function of Gis4 in salt tolerance. Gis4 and Snf1 seem to share functions in the control of ion homeostasis and
ENA1
expression but not in glucose derepression, the best known role of Snf1. Together with additional evidence that links Gis4 genetically and physically to Snf1, it appears that Gis4 may function in a pathway in which Snf1 plays a specific role in controlling ion homeostasis. Hence, it appears that the conserved Snf1 kinase plays roles in different pathways controlling nutrient as well as stress response.
CFD SIMULATION AND CHARACTERIZATION OF A DEVICE FOR POWDERED PHARMACEUTICALS AND BIOLOGICALS DELIVERY
Authors: LIU FANG , HE WEI , CAO CHUNLI , LIU YI
Published: October 2006

Advances in molecular biology have produced a wide range of protein and peptide-based drugs. Equally, it is required to explore various technologies and capabilities to deliver those drugs. A unique medical device, the hand-held biolistics, is developed for powdered pharmaceuticals/biologicals transdermal delivery. The underlying principle is to accelerate micro-particles by means of a high-speed helium gas to an appropriate momentum to penetrate the outer layer of the skin to elicit desirable pharmaceutical/biological effects. The novelty of this hand-held biolistics is using the venturi effect to entrain micron-sized protein and peptide drugs into an established quasi-steady transonic jet flow and accelerate them toward the target. In this paper, computational fluid dynamics is utilized to characterize prototype biolistic system. The key features of gas dynamics and gas–particle interaction are presented. The overall capability of the biolistic delivery system is discussed and demonstrated. The statistical analyses show that the particles have achieved a mean velocity of 628 m/s as representatives of extracellular vaccine delivery applications.
NUMERICAL STUDY ON UNIDIRECTIONAL FLOW GENERATION AND GAS TRANSPORT ENHANCEMENT IN AVIAN LUNG SYSTEM
Authors: SAKAI EIJI , WATANABE TOSHINORI , HIMENO TAKEHIRO
Published: October 2006

Mechanisms of unidirectional flow generation and gas transport enhancement in oscillatory flow of avian lungs were numerically studied with bifurcation models of avian trachea. Model systems of right-angled branched tubes with single and multi-bifurcating tubes were adopted for the numerical simulation. The effect of constriction near the bifurcation was also investigated. Main concern was placed on the effects of bifurcation structure on unidirectional flow generation and axial gas transport enhancement. Oscillatory flow fields as well as concentration fields were numerically analyzed with a developed code based on SIMPLE and CIP methods. Similar to the previous experiment by the authors, unidirectional net flow was observed from side-daughter tube to daughter tube. Strongly affecting on the oscillatory flow fields and flow distribution, the constriction and the multi-bifurcation structure were found to improve unidirectional net flow generation. In particular, multi-bifurcation structure was found not only to improve the unidirectional flow generation and gas transport but also to reduce the total pressure drop of the system.
In vitro antagonism of endophytic Fusarium oxysporum isolates against the burrowing nematode Radopholus similis
Authors: Niere Bjoern , Athman Shahasi , Viljoen Altus , Gold Clifford , Dubois Thomas , Ragama Philip , Coyne Daniel , Labuschagne Nico
Published: October 2006

Radopholus similis is one of the key pests of banana worldwide. In this study, nine endophytic Fusarium oxysporum isolates were screened for the production of secondary metabolites antagonistic to R. similis in culture. Undiluted and diluted culture filtrates were tested against motile stages and eggs of R. similis. All isolates tested demonstrated in vitro antagonistic activity, causing paralysis of R. similis motile stages. The percentage of paralysed nematodes increased with increase in the length of exposure time to culture filtrates. After 24 h exposure in culture filtrates up to 100% of the treated nematodes were paralysed compared to 26.5% in the control treatments. Nematode mortality rates after 24 h exposure in culture filtrates ranged from 76.4% to 100%. Paralysis was reversible at lower filtrate concentrations. Radopholus similis males were more sensitive to culture filtrates than females. Culture filtrates of all isolates demonstrated inhibitory effects on hatching of R. similis eggs. The results demonstrate the potential for using endophytic F. oxysporum as biological control agents against R. similis and for toxic derivatives from their secondary metabolism to be used as potential nematicides.
Symptoms, findings, and methods of diagnosis in patients with acoustic neuroma
Authors: Mathew Gregory D. , Facer George W. , Suh Ku W. , Houser O. Wayne , O'Brien Peter C.
Published: October 2006

The records of 225 patients with surgically documented acoustic neuromas seen at the Mayo Clinic between 1966 and 1976 were studied. Included in this group were 4 patients who had von Recklinghausen's disease with bilateral ear involvement, 7 patients with recurrence of acoustic neuroma, and 8 patients who were referred because of recurrent acoustic neuroma. Symptoms, clinical findings, and results of audiologic, vestibular, and roentgenographic studies were analyzed. Nine patients had a history of sudden onset of hearing loss, and 11 had a history of vertigo. A correlation between the size of the lesion and the symptoms, physical findings, and roentgenographic accuracy was made in an attempt to gain further knowledge of the natural course of the pathologic processes involved.
Fibrous histiocytoma of the head and neck: A case report
Authors: Hutchinson James C. , Friedberg Stanton A.
Published: October 2006

Fibrous histiocytomas are soft tissue tumors of histiocytic origin. One percent prove to be malignant. Reliable histologic criteria of malignancy are few, if any, and the diagnosis of malignancy often must be made on clinical (metastases) rather than histologic grounds. Thirty‐five cases originating in various deep structures of the head and neck, excluding the orbit, have been reported in the literature since 1972. One additional case, a malignant tumor of the submandibular gland, is added herewith. Recurrence following initial surgery has been common and stems from inadequate excision of the primary lesion. Microscopic spread of this tumor from its primary site calls for radical rather than conservative surgical excision. At present, radiotherapy and chemotherapy appear to be of little value in the treatment of these tumors.
Hypermobility of the incudostapedial joint: A clinical entity?
Authors: Miller Gale W. , Keith Robert W.
Published: October 2006

During exploratory tympanotomy for conductive deafness, the surgeon is occasionally perplexed to find no apparent cause for the air‐bone gap. This unexplained deafness has been called “inner ear conductive hearing loss” because of the apparent absence of pathology in the middle ear.

The incudostapedial joint was studied in 68 vertically sectioned temporal bones and the anatomy is presented. Varying amounts of laxity is observed in the normal joint capsule at the time of surgery. A theory is suggested in which an elongated capsule allows incus motion without energy transmission to the stapes. It is proposed that hypermobility of the incudostapedial joint may exist and explain conductive hearing loss of undetermined etiology.
Carcinoid apudoma arising in a glomus jugulare tumor: Review of endocrine activity in glomus jugulare tumors
Authors: Farrior Jay B. , Hyams Vincent J. , Benke Roy H. , Farrior J. Brown
Published: October 2006

Previous reports of endocrine activity of glomus jugulare tumors have been of pheochromocytomas but not carcinoid apudomas. This paper is to alert the otolaryngologist to the presence of carcinoid apudomas in glomus jugulare tumors. A patient with a long history of explosive diarrhea, facial flushing, and violent headaches, the symptom of carcinoid syndrome, was cured after removal of his large glomus jugulare tumor. The diagnosis of carcinoid syndrome is made with a good history and confirmed with a 24 hour urine collection for 5 Hydroxy indole acetic acid (5 HIAA). A series of patients treated at the Johns Hopkins Hospital for glomus jugulare tumors is reviewed for the presence of endocrine activity and the literature on endocrine active glomus jugulare tumors is presented. Preoperative evaluation for the presence of both pheochromocytoma and carcinoid apudoma is recommended for all patients with glomus jugulare tumors.