bluuebunny/crossref_metadata_2025 huggingface dataset:
Radiation drive in laser-heated hohlraums
Authors: Suter L. J. , Kauffman R. L. , Darrow C. B. , Hauer A. A. , Kornblum H. , Landen O. L. , Orzechowski T. J. , Phillion D. W. , Porter J. L. , Powers L. V. , Richard A. , Rosen M. D. , Thiessen A. R. , Wallace R.
Published: July 2002

Nearly 10 years of Nova [E. M. Campbell, Laser Part. Beams 9, 209 (1991)] experiments and analysis have lead to a relatively detailed quantitative and qualitative understanding of radiation drive in laser-heated hohlraums. Our most successful quantitative modeling tool is two-dimensional (2-D) LASNEX numerical simulations [G. B. Zimmerman and W. L. Kruer, Comments Plasma Phys. Controlled Fusion 2, 51 (1975)]. Analysis of the simulations provides us with insight into the physics of hohlraum drive. In particular we find hohlraum radiation conversion efficiency becomes quite high with longer pulses as the accumulated, high-Z blow-off plasma begins to radiate. Extensive Nova experiments corroborate our quantitative and qualitative understanding.
Study of radiative plasma structures in laser driven ablating plasmas
Authors: Hazak G. , Velikovich A. L. , Klapisch M. , Schmitt A. J. , Dahlburg J. P. , Colombant D. , Gardner J. H. , Phillips L.
Published: July 2002

The mechanism is analyzed that generates radiative plasma structures (RPS) [J. P. Dahlburg et al., J. Quant Spectros. Radiat. Transfer 54, 113 (1995)] in driven, ablating plasmas of subcritical density. A reduced set of radiation-hydrodynamics equations is derived which model the onset of RPS phenomenon.
Hohlraum energetics with smoothed laser beams
Authors: Glenzer S. H. , Suter L. J. , Berger R. L. , Estabrook K. G. , Hammel B. A. , Kauffman R. L. , Kirkwood R. K. , MacGowan B. J. , Moody J. D. , Rothenberg J. E. , Turner R. E.
Published: July 2002

Measurements of radiation temperatures from empty and gas-filled hohlraums heated at the Nova Laser Facility [E. M. Campbell et al., Laser Part. Beams 9, 209 (1991)] show efficient coupling of the laser power to the target when applying laser beam smoothing techniques. Scattering losses are reduced to the 3% level while the radiation temperatures increased by ∼15 eV for smoothed laser beams. The experimental findings and supporting calculations indicate that filamentation and gain for stimulated Raman and Brillouin scattering is suppressed in the hohlraum plasma for smoothed laser beams. The scaling of the radiation temperature is well described by integrated radiation hydrodynamic LASNEX modeling [G. B. Zimmerman and W. L. Kruer, Comments Plasma Phys. Controlled Fusion 2, 85 (1975)] following the Marshak scaling. Peak radiation temperatures are in excess of 230 eV in gas-filled hohlraums in agreement with the detailed LASNEX modeling.
Inductively generated, high voltage pulse using an electron beam controlled opening switch
Authors: Commisso R. J. , Fernsler R. F. , Scherrer V. E. , Vitkovitsky I. M.
Published: July 2002

An electron beam controlled opening switch with a conduction period of ∼1 μs has been used in an inductive store system to generate a 280-kV, 60-ns full width at half-maximum voltage pulse across an open circuit by interrupting a 10-kA discharge. The switch was pressurized to 5 atm with a 99:1 mixture of CH4:C2F6. Degraded voltage performance was obtained with pure CH4 or N2. These results support the conjecture that a judicious choice of gas mixture can lead to optimization of such an opening switch in a parameter regime of interest to pulsed power applications.
Long conduction time plasma erosion opening switch experiment
Authors: Hinshelwood D. D. , Boller J. R. , Commisso R. J. , Cooperstein G. , Meger R. A. , Neri J. M. , Ottinger P. F. , Weber B. V.
Published: July 2002

A plasma erosion opening switch, coupled to a small capacitor bank, conducts 120 kA for 400 ns before opening in 40 ns. Voltages above 170 kV are produced through the use of an electron beam diode. These voltages exceed the initial capacitor bank voltage by a factor of 4. Current and magnetic field measurements indicate that the same current conduction and opening processes observed in earlier erosion switch experiments are involved here at tenfold greater conduction times, verifying the current controlled nature of plasma erosion switch operation.
Annealing behavior of Si in ion-implanted α-Ti
Authors: Räisänen J. , Keinonen J.
Published: July 2002

The time evolution of the silicon concentration profiles in ion-implanted polycrystalline α-Ti has been studied in the temperature range 650–800 °C. Diffusion couples were created by ion implantation. The time-dependent concentration profiles were monitored by the use of the nuclear resonance broadening technique through the 30Si(p,γ)31P reaction. The values of 1.09±0.18 eV for the activation energy and (4.4±404.0)×10−7 cm2/s for the frequency factor were obtained. The solubilities of Si in Ti are reported. The present result is discussed in the framework of the Ti silicide formation.
Exciton effects in the index of refraction of multiple quantum wells and superlattices
Authors: Kahen K. B. , Leburton J. P.
Published: July 2002

We present theoretical calculations of the index of refraction of multiple quantum wells and superlattices. The model incorporate both the bound and continuum exciton contributions for the Γ region transitions. In addition, the electronic band structure model has both superlattice and bulk alloy properties. Our results indicate that large light-hole masses, i.e., mlh∼0.23, produced by band mixing effects, are required to account for the experimental data. Furthermore, it is shown that superlattice effects rapidly decrease for energies greater than the confining potential barriers. Overall, the theoretical results are in very good agreement with the experimental data and show the importance of including exciton effects in the index of refraction.
GaAs traveling-wave polarization electro-optic waveguide modulator with bandwidth in excess of 20 GHz at 1.3 μm
Authors: Wang S. Y. , Lin S. H. , Houng Y. M.
Published: July 2002

We report a 1.3-μm GaAs traveling-wave electro-optic waveguide modulator with a 3-dB optical bandwidth in excess of 20 GHz. The bandwidth was determined by directly detecting the modulated optical signal with a high-speed InP/GaInAs photodiode. The modulator has a coplanar strip electrode configuration with a double heterojunction Al0.032Ga0.968As/GaAs/Al0.032Ga0.968As optical guide grown by low-pressure organometallic vapor phase epitaxy.
Interaction of a transcriptional repressor with the RNA polymerase II holoenzyme plays a crucial role in repression
Authors: Zaman Zafar , Ansari Aseem Z. , Koh Sang Seok , Young Richard , Ptashne Mark
Published: July 2002

The yeast transcriptional repressor Tup1, tethered to DNA,
represses to strikingly different degrees transcription elicited by
members of two classes of activators. Repression in both cases is
virtually eliminated by mutation of either member of the cyclin-kinase
pair Srb10/11. In contrast, telomeric chromatin affects both classes
of activators equally, and in neither case is that repression affected
by mutation of Srb10/11.
In vitro
, Tup1 interacts with
RNA polymerase II holoenzyme bearing Srb10 as well as with the
separated Srb10. These and other findings indicate that at least one
aspect of Tup1's action involves interaction with the RNA polymerase
II holoenzyme.
Isolation of a diterpenoid substance with potent neuroprotective activity from fetal calf serum
Authors: Kume Toshiaki , Asai Naoki , Nishikawa Hiroyuki , Mano Nariyasu , Terauchi Taro , Taguchi Ryota , Shirakawa Hisashi , Osakada Fumitaka , Mori Hiroki , Asakawa Naoki , Yonaga Masahiro , Nishizawa Yukio , Sugimoto Hachiro , Shimohama Shun , Katsuki Hiroshi , Kaneko Shuji , Akaike Akinori
Published: July 2002

Excess activation of glutamate receptors and production of free radicals including nitric oxide may result in severe and irreversible damage to the mammalian central nervous system (CNS), but endogenous defense systems that protect neurons from these insults are poorly understood. Here, we purified and isolated a neuroprotective substance, which has been named “serofendic acid,” from a lipophilic fraction of FCS based on the ability to protect rat primary cortical neurons against nitric oxide cytotoxicity. Mass spectrometry and NMR spectroscopy revealed the chemical structure of serofendic acid (15-hydroxy-17-methylsulfinylatisan-19-oic acid) as a sulfur-containing atisane-type diterpenoid, which is unique among known endogenous substances. Synthetic serofendic acid exhibited potent protective actions on cortical neurons against cytotoxicity of a nitric oxide donor as well as of glutamate, although it did not show appreciable influences on glutamate receptor-mediated responses in these neurons. Electron spin resonance analysis demonstrated that serofendic acid had no direct scavenging activity on nitric oxide radicals but was capable of inhibiting the generation of hydroxyl radical, a presumed “executor” radical in the nitric oxide-mediated neurotoxic cascade. These findings suggest that serofendic acid is a low-molecular-weight bioactive factor that promotes survival of CNS neurons, probably through the attenuation of free radical-mediated insults.
Protein folding from a highly disordered denatured state: The folding pathway of chymotrypsin inhibitor 2 at atomic resolution
Authors: Kazmirski Steven L. , Wong Kam-Bo , Freund Stefan M. V. , Tan Yee-Joo , Fersht Alan R. , Daggett Valerie
Published: July 2002

Previous experimental and theoretical studies have produced
high-resolution descriptions of the native and folding transition
states of chymotrypsin inhibitor 2 (CI2). In similar fashion,
here we use a combination of NMR experiments and molecular dynamics
simulations to examine the conformations populated by CI2 in the
denatured state. The denatured state is highly unfolded, but there is
some residual native helical structure along with hydrophobic
clustering in the center of the chain. The lack of persistent nonnative
structure in the denatured state reduces barriers that must be
overcome, leading to fast folding through a nucleation–condensation
mechanism. With the characterization of the denatured state, we have
now completed our description of the folding/unfolding pathway of CI2
at atomic resolution.
Inhibition of APC-mediated proteolysis by the meiosis-specific protein kinase Ime2
Authors: Bolte Melanie , Steigemann Patrick , Braus Gerhard H. , Irniger Stefan
Published: July 2002

Proteolysis triggered by the anaphase-promoting complex (APC) is needed for sister chromatid separation and the exit from mitosis. APC is a ubiquitin ligase whose activity is tightly controlled during the cell cycle. To identify factors involved in the regulation of APC-mediated proteolysis, a
Saccharomyces cerevisiae GAL-cDNA
library was screened for genes whose overexpression prevented degradation of an APC target protein, the mitotic cyclin Clb2. Genes encoding G
1
, S, and mitotic cyclins were identified, consistent with previous data showing that the cyclin-dependent kinase Cdk1 associated with different cyclins is a key factor for inhibiting APC
Cdh1
activity from late-G
1
phase until mitosis. In addition, the meiosis-specific protein kinase Ime2 was identified as a negative regulator of APC-mediated proteolysis. Ectopic expression of
IME2
in G
1
arrested cells inhibited the degradation of mitotic cyclins and of other APC substrates.
IME2
expression resulted in the phosphorylation of Cdh1 in G
1
cells, indicating that Ime2 and Cdk1 regulate APC
Cdh1
in a similar manner. The expression of
IME2
in cycling cells inhibited bud formation and caused cells to arrest in mitosis. We show further that Ime2 itself is an unstable protein whose proteolysis occurs independently of the APC and SCF (Skp1/Cdc53/F-box) ubiquitin ligases. Our findings suggest that Ime2 represents an unstable, meiosis-specific regulator of APC
Cdh1
.
Design and self-assembly of wide and robust coordination cages
Authors: Pirondini Laura , Bertolini Francesca , Cantadori Barbara , Ugozzoli Franco , Massera Chiara , Dalcanale Enrico
Published: July 2002

The self-assembly of a new class of coordination cages formed from two tetrapyridyl-substituted cavitands connected through four square-planar palladium or platinum complexes is reported. The shape of the internal cavity resembles an ellipsoid with a calculated volume of 840 Å
3
. The four lateral portals have a diameter of about 6 Å, large enough to allow the fast entrance/egress of counterions in solution. The platinum cages 3a,e cannot be disassembled using triethylamine as competitive ligand and they are kinetically stable at room temperature, whereas the palladium cages 3b-d, 3f-h are disassembled and kinetically labile under the same conditions. The different solubility properties of the cage components have allowed the extension of this self-assembly protocol to the liquid–liquid interface.
Generation of functional antigen-specific T cells in defined genetic backgrounds by retrovirus-mediated expression of TCR cDNAs in hematopoietic precursor cells
Authors: Yang Lili , Qin Xiao-Feng , Baltimore David , Van Parijs Luk
Published: July 2002

We have developed an alternative to transgenesis for producing antigen-specific T cellsin vivo. In this system, clonal naive T cells with defined antigen specificity are generated by retrovirus-mediated expression of T cell antigen receptor cDNAs in RAG1-deficient murine hematopoietic precursor cells. These T cells can be stimulated to proliferate and produce cytokines by exposure to antigenin vitro, and they become activated and expandin vivoafter immunization. IL-2-deficient T cells generated by this technique show decreased proliferation and cytokine production, both of which can be rescued by exogenous addition of this growth factor. Thus, retrovirus-mediated expression of T cell antigen receptor cDNAs in hematopoietic precursor cells permits the rapid and efficient analysis of the life history of antigen-specific T cells in different genetic backgrounds and may allow for the long-term production of antigen-specific T cells with different functional properties for prophylactic and therapeutic purposes.
Restructuring of an RNA polymerase holoenzyme elongation complex by lambdoid phage Q proteins
Authors: Marr Michael T. , Datwyler Saul A. , Meares Claude F. , Roberts Jeffrey W.
Published: July 2002

The structure of an intermediate in the initiation to elongation transition of
Escherichia coli
RNA polymerase has been visualized through region-specific DNA cleavage by the hydroxyl radical reagent FeBABE. FeBABE was tethered to specific sites of the σ
70
subunit and incorporated into two specialized paused elongation complexes that obligatorily retain the σ
70
initiation subunit and are targets for modification by lambdoid phage late gene antiterminators. The FeBABE cleavage pattern reveals structures similar to open complex, except for notable changes to region 3 of σ
70
that might reflect the presence of stably bound transcript. Binding of the antiterminator protein Q displaces the reactivity of FeBABE conjugated to region 4 of σ
70
, suggesting that σ
70
subunit rearrangement is a step in conversion of RNAP to the antiterminating form.
RaSH, a rapid subtraction hybridization approach for identifying and cloning differentially expressed genes
Authors: Jiang Hongping , Kang Dong-chul , Alexandre Deborah , Fisher Paul B.
Published: July 2002

Human melanoma cells growth-arrest irreversibly and terminally
differentiate on treatment with a combination of fibroblast interferon
and the protein kinase C activator mezerein. This experimental protocol
also results in a loss of tumorigenic potential and profound changes in
gene expression. Various cloning and cDNA microarray strategies are
being used to determine the complete spectrum of gene expression
changes underlying these alterations in human melanoma cells. An
efficient approach, Rapid Subtraction Hybridization (RaSH), has been
developed that is permitting the identification of genes of potential
relevance to cancer growth control and terminal cell differentiation.
RaSH cDNA libraries are prepared from double-stranded cDNAs that are
enzymatically digested into small fragments, ligated to adapters, and
PCR amplified followed by incubation of tester and driver PCR
fragments. This subtraction hybridization scheme is technically simple
and results in the identification of a high proportion of
differentially expressed sequences, including known genes and those not
described in current DNA databases. The RaSH approach represents an
efficient methodology for identifying and cloning genes displaying
differential expression that associate with and potentially regulate
complex biological processes.
Genetic mosaic analysis based on Cre recombinase and navigated laser capture microdissection
Authors: Wong Melissa H. , Saam Jennifer R. , Stappenbeck Thaddeus S. , Rexer Charles H. , Gordon Jeffrey I.
Published: July 2002

Defining molecular interactions that occur at the interface
between “normal” and “abnormal” cell populations represents
an important but often underexplored aspect of the pathogenesis of
diseases with focal origins. Here, we illustrate an approach for
conducting such analyses based on mosaic patterns of Cre recombinase
expression in the adult mouse intestinal epithelium. Transgenic mice
were generated that express Cre in the stem cell niche of crypts
located in specified regions of their intestine. Some of these mice
were engineered to allow for doxycycline-inducible Cre expression.
Recombination in all pedigrees was mosaic: Cre-expressing crypts that
supported recombination in all of their active multipotent stem cells
were located adjacent to “control” crypts that did not express
Cre at detectable levels. Cre-mediated recombination of a floxed LacZ
reporter provided direct evidence that adult small-intestinal crypts
contain more than one active multipotent stem cell, and that these
cells can be retained in both small-intestinal and colonic crypts for
at least 80 d. A method was developed to recover epithelial cells
from crypts with or without recombination for subsequent gene
expression profiling. Stained sections of intestine were used to create
electronic image templates to guide laser capture microdissection (LCM)
of adjacent frozen sections. This navigated form of LCM overcomes
problems with mRNA degradation encountered when cells are marked
directly by immunohistochemical methods. Combining Cre-engineered
genetic mosaic mice with navigated-LCM will allow biology and
pathobiology to be explored at the junction between normal and
perturbed cellular cohorts.
Dexamethasone responsiveness of a major glucocorticoid-inducible CYP3A gene is mediated by elements unrelated to a glucocorticoid receptor binding motif.
Authors: Huss J M , Wang S I , Astrom A , McQuiddy P , Kasper C B
Published: July 2002

Elements responsible for dexamethasone responsiveness of CYP3A23, a major glucocorticoid-inducible member of the CYP3A gene family, have been identified. DNase I footprint analysis of the proximal promoter region revealed three protected sites (sites A, B, and C) within the sequence defined by -167 to -60. Mutational analysis demonstrated that both sites B and C were necessary for maximum glucocorticoid responsiveness and functioned in a cooperative manner. Interestingly, neither site contained a glucocorticoid responsive element. Embedded in site C was an imperfect direct repeat (5'-AACTCAAAGGAGGTCA-3'), showing homology to an AGGTCA steroid receptor motif, typically recognized by the estrogen receptor family, while site B contained an ATGAACT direct repeat; these core sequences were designated dexamethasone response elements 1 and 2 (DexRE-1 and -2), respectively. Neither element has previously been associated with a glucocorticoid-activated transcriptional response. Conversion of the DexRE-1 to either a perfect thyroid hormone or vitamin D3 responsive element further enhanced induction by dexamethasone. Gel-shift analysis demonstrated that glucocorticoid receptor did not associate with either DexRE-1 or -2; hence, glucocorticoid receptor does not directly mediate glucocorticoid induction of CYP3A23. These unusual features suggest an alternate pathway through which glucocorticoids exert their effects.
A rigid trans-spanning dinitrile ligand.
Authors: Shimizu K D , Rebek J
Published: July 2002

A rigid dinitrile ligand was synthesized from two xanthene units condensed to a naphthalene-1,4,5,8-diimide spacer. The rigidity and C shape of the ligand gave exclusively trans complexes with Pd(II), Ag(I), and Au(I). Evidence for complexation, coordination geometry, and stoichiometry was provided by a combination of 1H NMR, 19F NMR, and IR spectroscopy. The AuBF4 and PdCl2 complexes were shown to have a 1:1 (metal-to-ligand) stoichiometry and the AgBF4 complex was shown to have a 1:2 stoichiometry in solution. The preorganization of the dinitrile ligand resulted in complexes much more stable than their monodentate counterparts.
Reduced fertility in mice deficient for the POU protein sperm-1
Authors: Pearse Richard V. , Drolet Daniel W. , Kalla Kristin A. , Hooshmand Farideh , Bermingham John R. , Rosenfeld Michael G.
Published: July 2002

Members of the POU-homeodomain gene family encode transcriptional regulatory molecules that play important roles in terminal differentiation of many organ systems. Sperm-1 (Sprm-1) is a POU domain factor that is exclusively expressed in the differentiating male germ cell. We show here that the Sprm-1 protein is expressed in the haploid spermatid and that 129/Sv
Sprm-1
(
−/−
) mice are subfertile when compared with wild-type or heterozygous littermates yet exhibit normal testicular morphology and produce normal numbers of mobile spermatozoa. Our data suggest that the Sprm-1 protein plays a discrete regulatory function in the haploid spermatid, which is required for the optimal function, but not the terminal differentiation, of the male germ cell.
A mutation of the atrial natriuretic peptide (guanylyl cyclase-A) receptor results in a constitutively hyperactive enzyme
Authors: Wedel Barbara J. , Foster David C. , Miller Deborah E. , Garbers David L.
Published: July 2002

Mutation of an invariant glutamate residue found within the catalytic domain of guanylyl cyclases resulted in a dramatic 14-fold increase in the activity of the guanylyl cyclase-A receptor. Even in the presence of Mn
2+
/Triton X-100, a treatment previously thought to yield hormone-independent and maximum cyclase activity, the mutant enzyme remained 7-fold more active; to our knowledge, this is the first example of a protein modification or of an added agent that significantly increases cyclase activity in the presence of Mn
2+
/Triton X-100. Intracellular concentrations of cGMP in cells expressing the mutant (E974A) cyclase were only marginally elevated by the addition of atrial natriuretic peptide, and in broken-cell preparations, the mutant enzyme also was relatively insensitive to ligand/regulatory nucleotide. The marked increase in cyclase activity was not due to a relief of protein kinase domain inhibition, since the point mutation caused 7- to 13-fold elevations in guanylyl cyclase-A activity when the protein kinase homology domain was deleted. The E974A mutation also altered the kinetics from positive cooperative to linear with respect to MnGTP, suggesting disruption of subunit–subunit interactions. Thus, a single point mutation within the catalytic domain of a guanylyl cyclase results in a constitutively hyperactive enzyme that is independent of protein kinase domain regulation.
Development and function of T cells in T cell antigen receptor/CD3 ζ knockout mice reconstituted with FcɛRI γ
Authors: Liu Chih-Pin , Lin Wei-Jen , Huang Manley , Kappler John W. , Marrack Philippa
Published: July 2002

Engagement of α–β T cell receptors (TCRs) induces many events in the T cells bearing them. The proteins that transduce these signals to the inside of cells are the TCR-associated CD3 polypeptides and ζ–ζ or ζ–η dimers. Previous experiments using knockout (KO) mice that lacked ζ (ζKO) showed that ζ is required for good surface expression of TCRs on almost all T cells and for normal T cell development. Surprisingly, however, in ζKO mice, a subset of T cells in the gut of both ζKO and normal mice bore nearly normal levels of TCR on its surface. This was because ζ was replaced by the FcɛRI γ (FcRγ). These cells were relatively nonreactive to stimuli via their TCRs. In addition, a previous report showed that ζ replacement by the FcRγ chain also might occur on T cells in mice bearing tumors long term. Again, these T cells were nonreactive. To understand the consequences of ζ substitution by FcRγ for T cell development and functionin vivo, we produced ζKO mice expressing FcRγ in all of their T cells (FcRγTG ζKO mice). In these mice, TCR expression on immature thymocytes was only slightly reduced compared with controls, and thymocyte selection occurred normally and gave rise to functional, mature T cells. Therefore, the nonreactivity of the FcRγ+lymphocytes in the gut or in tumor-bearing mice must be caused by some other phenomenon. Unexpectedly, the TCR levels of mature T cells in FcRγTG ζKO mice were lower than those of controls. This was particularly true for the CD4+T cells. We conclude that FcRγ can replace the functions of ζ in T cell developmentin vivobut that TCR/CD3 complexes associated with FcRγ rather than ζ are less well expressed on cells. Also, these results revealed a difference in the regulation of expression of the TCR/CD3 complex on CD4+and CD8+T cells.
The replication initiation protein of the broad-host-range plasmid RK2 is activated by the ClpX chaperone
Authors: Konieczny Igor , Helinski Donald R.
Published: July 2002

Initiation and control of replication of the broad-host-range plasmid RK2 requires two plasmid-encoded elements, the replication origin (
oriV
) and the initiation protein TrfA. Purified TrfA is largely in the form of a dimer; however, only the monomeric form of the protein can bind specifically to the direct repeats (iterons) at the RK2 origin. The largely dimeric form of wild-type TrfA is inactive in the initiation of replication of RK2 in an
in vitro
replication system reconstituted from purified components. However, preincubation of the TrfA protein with the ClpX molecular chaperone isolated from
Escherichia coli
activates the initiator protein for replication in the purified system. We further observed that ClpX, in an ATP-dependent reaction, greatly increases the proportion of TrfA monomers and, therefore, the ability of this protein to bind to iterons localized within RK2 origin. Finally, a copy-up mutant of the TrfA protein which is largely in the monomer form is active in the reconstituted
in vitro
replication system, and its activity is not affected by ClpX.
Alzheimer’s-specific effects of soluble β-amyloid on protein kinase C-α and -γ degradation in human fibroblasts
Authors: Favit Antonella , Grimaldi Maurizio , Nelson Thomas J. , Alkon Daniel L.
Published: July 2002

Alzheimer’s disease (AD) is a multifactorial disease in which β-amyloid peptide (βAP) plays a critical role. We report here that the soluble fraction 1–40 of βAP differentially degrades protein kinase C-α and -γ (PKCα and PKCγ) isoenzymes in normal (age-matched controls, AC) and AD fibroblasts most likely through proteolytic cascades. Treatment with nanomolar concentrations of βAP(1–40) induced a 75% decrease in PKCα, but not PKCγ, immunoreactivity in AC fibroblasts. In the AD fibroblasts, a 70% reduction of the PKCγ, but not PKCα, immunoreactivity was observed after βAP treatment. Preincubation of AC or AD fibroblasts with 50 μM lactacystine, a selective proteasome inhibitor, prevented β-AP(1–40)-mediated degradation of PKCα in the AC cells, and PKCγ in the AD fibroblasts. The effects of βAP(1–40) on PKCα in AC fibroblasts were prevented by inhibition of protein synthesis and reversed by PKC activation. A 3-hr treatment with 100 nM phorbol 12-myristate 13-acetate restored the PKCα signal in treated AC cells but it did not reverse the effects of βAP(1–40) on PKCγ in the AD fibroblasts. Pretreatment with the protein synthesis inhibitor, cycloheximide (CHX, 100 μM), inhibited the effects of βAP(1–40) on PKCα and blocked the rescue effect of phorbol 12-myristate 13-acetate in AC fibroblasts but did not modify PKCγ immunoreactivity in AD cells. These results suggest that βAP(1–40) differentially affects PKC regulation in AC and AD cells via proteolytic degradation and that PKC activation exerts a protective role viade novoprotein synthesis in normal but not AD cells.
Unexpected homology between inducible cell wall protein QID74 of filamentous fungi and BR3 salivary protein of the insect
Chironomus
Authors: Rey Manuel , Ohno Susumu , Pintor-Toro Jose A. , Llobell Antonio , Benitez Tahia
Published: July 2002

A gene,
qid74
, of mycoparasitic filamentous fungus
Trichoderma harzianum
and its allies encodes a cell wall protein that is induced by replacing glucose in the culture medium with chitin (simulated mycoparasitism conditions). Because no trace of this gene can be detected in related species such as
Gibberella fujikuroi
and
Saccharomyces cerevisiae
, the
qid74
gene appears to have arisen
de novo
within the genus
Trichoderma
. Qid74 protein, 687 residues long, is now seen as highly conserved tandem repeats of the 59-residue-long unit. This unit itself, however, may have arisen as tandem repeats of the shorter 13-residue-long basic unit. Within the genus
Trichoderma
, the amino acid sequence of Qid74 proteins has been conserved
in toto
. The most striking is the fact that Qid74 shares 25.3% sequence identity with the carboxyl-terminal half of the 1,572-residue-long BR3 protein of the dipteran insect
Chironomus tentans
. BR3 protein is secreted by the salivary gland of each aquatic larva of
Chironomus
to form a tube to house itself. Furthermore, the consensus sequence derived from these 59-residue-long repeating units resembles those of epidermal growth factor-like domains found in divergent invertebrate and vertebrate proteins as to the positions of critical cysteine residues and homology of residues surrounding these cysteines.
Fibrinogen deficiency reduces vascular accumulation of apolipoprotein(a) and development of atherosclerosis in apolipoprotein(a) transgenic mice
Authors: Lou Xing Jian , Boonmark Nataya W. , Horrigan Frank T. , Degen Jay L. , Lawn Richard M.
Published: July 2002

To test directly whether fibrin(ogen) is a key binding site for apolipoprotein(a) [apo(a)] in vessel walls, apo(a) transgenic mice and fibrinogen knockout mice were crossed to generate fibrin(ogen)-deficient apo(a) transgenic mice and control mice. In the vessel wall of apo(a) transgenic mice, fibrin(ogen) deposition was found to be essentially colocalized with focal apo(a) deposition and fatty-streak type atherosclerotic lesions. Fibrinogen deficiency in apo(a) transgenic mice decreased the average accumulation of apo(a) in vessel walls by 78% and the average lesion (fatty streak type) development by 81%. Fibrinogen deficiency in wild-type mice did not significantly reduce lesion development. Our results suggest that fibrin(ogen) provides one of the major sites to which apo(a) binds to the vessel wall and participates in the generation of atherosclerosis.
Reciprocal subtraction differential RNA display: An efficient and rapid procedure for isolating differentially expressed gene sequences
Authors: Kang Dong-chul , LaFrance Raphael , Su Zao-zhong , Fisher Paul B.
Published: July 2002

A reciprocal subtraction differential RNA display (RSDD) approach has been developed that permits the rapid and efficient identification and cloning of both abundant and rare differentially expressed genes. RSDD comprises reciprocal subtraction of cDNA libraries followed by differential RNA display. The RSDD strategy was applied to analyze the gene expression alterations resulting during cancer progression as adenovirus-transformed rodent cells developed an aggressive transformed state, as documented by elevated anchorage-independence and enhanced
in vivo
oncogenesis in nude mice. This approach resulted in the identification and cloning of both known and a high proportion (>65%) of unknown sequences, including cDNAs displaying elevated expression as a function of progression (progression-elevated gene) and cDNAs displaying suppressed expression as a function of progression (progression-suppressed gene). Sixteen differentially expressed genes, including five unknown progression-elevated genes and six unknown progression-suppressed genes, have been characterized. The RSDD scheme should find wide application for the effective detection and isolation of differentially expressed genes.
Matchings and phylogenetic trees
Authors: Diaconis Persi W. , Holmes Susan P.
Published: July 2002

This paper presents a natural coordinate system for phylogenetic trees using a correspondence with the set of perfect matchings in the complete graph. This correspondence produces a distance between phylogenetic trees, and a way of enumerating all trees in a minimal step order. It is useful in randomized algorithms because it enables moves on the space of trees that make random optimization strategies “mix” quickly. It also promises a generalization to intermediary trees when data are not decisive as to their choice of tree, and a new way of constructing Bayesian priors on tree space.
Interactions of
Escherichia coli
σ
70
within the transcription elongation complex
Authors: Daube Shirley S. , von Hippel Peter H.
Published: July 2002

A functional transcription elongation complex can be formed without passing through a promoter by adding a complementary RNA primer and core
Escherichia coli
RNA polymerase in trans to an RNA-primed synthetic bubble-duplex DNA framework. This framework consists of a double-stranded DNA sequence with an internal noncomplementary DNA “bubble” containing a hybridized RNA primer. On addition of core polymerase and the requisite NTPs, the RNA primer is extended in a process that manifests most of the properties of
in vitro
transcription elongation. This synthetic elongation complex can also be assembled by using holo rather than core RNA polymerase, and in this study we examine the interactions and fate of the σ
70
specificity subunit of the holopolymerase in the assembly process. We show that the addition of holopolymerase to the bubble-duplex construct triggers the dissociation of the sigma factor from some complexes, whereas in others the RNA oligomer is released into solution instead. These results are consistent with an allosteric competition between σ
70
and the nascent RNA strand within the elongation complex and suggest that both cannot be bound to the core polymerase simultaneously. However, the dissociation of σ
70
from the complex can also be stimulated by binding of the holopolymerase to the DNA bubble duplex in the absence of a hybridized RNA primer, suggesting that the binding of the core polymerase to the bubble-duplex construct also triggers a conformational change that additionally weakens the sigma–core interaction.
A complex signaling module governs the activity of MalT, the prototype of an emerging transactivator family
Authors: Danot Olivier
Published: July 2002

MalT, the specific activator of the maltose regulon, is the
prototype of a family of high-molecular-mass ATP-binding bacterial
transcription activators. On binding of its two positive effectors, the
inducer maltotriose and ATP, MalT oligomerizes to an active state
competent for promoter binding and transcription activation. In
addition to its previously known DNA-binding domain, limited
proteolysis showed that MalT contains three other domains, the
boundaries of which were accurately delimited by N-terminal
microsequencing. The N-terminal domain alone binds ATP. Maltotriose
binding involves an extended region corresponding to domains 2 and 3,
although weak binding to domain 3 alone was also observed. Moreover,
maltotriose binding induces a conformational shift involving a movement
of both domains 1 and 3 with respect to domain 2, leading to the active
form of the protein. Sequence examination of the MalT homologues
suggests that these three domains might constitute a signaling module.
Psychological Science in Australia
Authors: Cumming Geoff , Siddle David , Hyslop Wendy
Published: July 2002

This paper is a brief account of the Australian Strategic Review of the Psychology Discipline and its Research. Issues discussed include Australia's contribution to world research in psychological science, research funding, the age and qualifications of researchers, the social and economic benefits arising from the applications of research outcomes, multidisciplinary issues, the role of psychology in industry, links between the discipline and the profession of psychology, professional training, cross‐cultural issues, and educational issues. Priorities for development of research and postgraduate training are identified, and include human factors and other areas related to technological change, clinical psychology with particular attention to health psychology, industrial and organizational psychology, and neuroscience and physiological psychology.
Social Cognition and Evolutionary Psychology: Physical Attractiveness and Contrast Effects on Women's Self‐perceived Body Image
Authors: Wade T. Joel , Abetz Heather
Published: July 2002

Self‐evaluations of body image were examined in a 2 (attractiveness of stimulus person) × 2 (sex of stimulus person) design to determine if contrast effects consistent with evolutionary psychology occur for women's self‐perceptions of their body image. Main effects for attractiveness were hypothesized. Higher self‐ratings for figure‐related aspects of body image were predicted for women exposed to an unattractive male or female. These effects were significant. Women exposed to an unnattractive male or female had more positive feelings about figure‐related aspects of their body image than women exposed to an attractive male or female. Contrast effects in accordance with evolutionary theory occur for aspects of body image that play a role in inferences regarding reproductive fitness.
Stress and Social Support in Parents whose Children are Hepatitis B Virus (HBV) Carriers: A Comparison of Three Groups in Guangzhou
Authors: Lai Alice Cheng , Salili Farideh
Published: July 2002

The present study compared the moderating effect of social support on parental stress variables and mental health among three groups of parents: parents of HBV (Hepatitis B Virus) children who attended the special health kindergarten, parents of HBV children who stayed at home, and parents of healthy children who attended the ordinary kindergarten. These families resided in the city of Guangzhou.

A set of questionnaires measuring parental stress and social support were given to the mothers after a one‐hour interview. Results showed that parents of HBV children were significantly more stressed and psychologically at risk than parents of healthy children. They also sought help from social resources more often than the parents of healthy children. Parents of healthy children who attended the ordinary kindergarten reported the highest levels of overall social support, i.e. the number of very close friends and relatives with whom they could form close emotional attachments. Although they reported a lower number of acquaintances available, they also reported the most satisfactory relationships with the support provided by their acquaintances, lower levels of stress, fewer somatic problems, more adequate general health, and more perceived meaning in life than did parents of HBV children, and social support is one of the main influences on stress or parental health. The findings call for further research to focus on parents' well‐being and social support that is helpful in addressing the needs of the family.
A study of event‐related potential—P3 characteristics in children of alcoholics
Authors: SHARMA AVNEET , MALHOTRA SAVITA , RAGHUNATHAN MURUGESCHACHETTY , MALHOTRA ANIL
Published: July 2002

Abstract Auditory P3 characteristics were studied in children (aged 8‐14 years) of male alcoholics without psychiatric problems and children of normal parents employing an oddball auditory paradigm. All the children of alcoholics were from families with multiple cases of alcoholism (each child had an average of 4.3 first‐ and second‐degree relatives including the father, meeting criteria for alcoholism). Subjects were presented with high and low pitched tones with global probabilities of 25% and 75% of total trials, respectively. The amplitude of P3 component was significantly reduced in high‐risk children (p < 0.001). Implications of the findings, including the role of P3 as biologi cal marker of risk for alcoholism, are discussed.
Alcoholic beverages and lipid peroxidation: relevance to cardiovascular disease
Authors: PUDDEY IAN B. , CROFT KEVIN
Published: July 2002

Overall there is good evidence that alcohol consumption induces oxidative stress, and leads to lipid peroxidation, effects which have been linked to alcohol‐related toxicity and disease and may be relevant to alcoholatherosclerosis interrelationships. On the other hand, a protective effect of light to moderate alcohol consumption against cardiovascular disease is well recognized, with the further hypothesis that red wine offers extra cardiovascular protection due to its rich content of antioxidant phenolic compounds. Although this hypothesis is given some credence from in vitro data, controlled studies in humans have produced conflicting results. Clearly, the equally well described pro‐oxidant effects of alcohol and its metabolism have been insufficiently considered in the pursuit of what to many is an intuitively attractive hypothesis. Further studies are required to determine if red wine phenolics are actually absorbed from the gut and whether they offer any overall antioxidant protection in vivo. The hypothesis that red wine offers extra cardiovascular protection compared to other alcoholic beverages is not proven and must await the outcome of studies in which the full spectrum of the pro‐oxidant and antioxidant effects of alcoholic beverages are duly considered. In the absence of such studies, there are no grounds at present for the promotion of the consumption of alcoholic beverages on the basis of their putative “antioxidant” properties.
No allelic association of an exon 13 polymorphism of the Gsα gene to alcohol and/or drug dependence
Authors: KRANZLER HENRY R. , McCAUL MARY E. , GELERNTER JOEL , WAND GARY S.
Published: July 2002

The adenylyl cyclase signal transduction system, a ubiquitous second messenger system, has been identified as a potential marker for genetic risk of alcohol and drug dependence. Using the polymerase chain reaction (PCR) to amplify exon 13 of the Gsα gene, two alleles were distinguished by denaturing gradient gel electrophoresis. One allele, designed A, contained the previously published C in the codon for asparagine 371, while the second allele, designated A, contains a C‐T transition that conserves the asparagine residue at codon 371. The neutral polymorphism eliminates a Fok I restriction enzyme cleavage site, allowing use of restriction fragment length polymorphisms of PCR products to determine allelic frequency in 235 subjects with alcohol and/or drug dependence and in 85 control subjects. Since allele frequencies differ significantly by race, comparisons between affected individuals and controls were conducted separately for white and black groups. Within race, there were no significant differences in the frequency of the A allele among alcoholics, subjects dependent on cocaine or opioids, subjects dependent on these drugs and alcohol, and controls. We conclude that there is no association between alcohol and/or drug dependence and alleles of an exon 13 polymorphism of the Gsα gene in either black or white individuals.
The effect of acetaldehyde on human brain transketolase activity
Authors: ROOPRAI H. K. , PRATT O. E.
Published: July 2002

Chronic alcoholism and thiamine deficiency are well documented factors in the aetiology of Wernicke‐Korsakoff Syndrome. More recently, acetaldehyde (ACH) has been implicated as a possible aetiological factor. In the present investigation the direct effect of ACH was studied on the activity of transketolase, a thiaminedependent enzyme, as well as two non‐thiamine‐dependent enzymes (aspartate aminotransferase and lactate dehydrogenase), isolated from five control human brains. The concentration of ACH required to inhibit 50% activity of holo‐ and apo‐transketolase was 80 mM and 60 mM, respectively, whereas that for aspartate aminotransferase and lactate dehydrogenase was 14 mM and 10 mM, respectively. None of the enzymes were completely inhibited by the range of ACH concentrations used in the study. It was concluded that the thiamineindependent enzymes were markedly affected by the concentrations of ACH which did not affect the thiaminedependent enzyme, transketolase. In vitro studies with homogenates pre‐treated with ACH in the presence of various concentrations of glutathione showed that the latter had a protective effect against loss of transketolase activity.
How useful is aminolevulinic acid dehydratase as a marker of recent alcohol intake?
Authors: AUBIN HENRI‐JEAN , LAUREAUX CHANTAL , TILIKETE SAMIR , GILLET CLAUDINE , LEPETITCORPS ANNICK , NGUYEN THU , TROUPEL SOLANGE , PAILLE FRANCOIS , BARRUCAND DOMINIQUE
Published: July 2002

Abstract Erythroycte delta aminolevulinic acid dehydratase (ALAD) has been suggested as a marker for detecting recent alcohol intake. Unlike other markers, ALAD activity decreases after alcohol intake. Review of the literature suggests that the main interest in this marker is because it increases rapidly after withdrawal. The present study investigated the changes in erythrocyte ALAD and serum gamma‐glutamyltransferase activities after alcohol withdrawal in 120 alcoholics. Our data showed that ALAD is less sensitive than GGT as an indicator of recent alcohol intake (56% and 84% abnormal, respectively). The increase in ALAD activity was greater between day 12 and 18 after withdrawal (11%) than between day 1 and 12 after withdrawal (5%). There were as many patients returning to normal values 12 and 18 days after withdrawal, for GGT as for ALAD. Thus, our results contradict the claim that ALAD rises rapidly after withdrawal. ALAD shows no advantage over GGT as a marker of recent alcohol intake.
Brain GABA metabolism after chronic ethanol consumption and withdrawal in rats
Authors: KANUNNIKOVA NINA P. , VINITSKAYA ANNA G. , DOROSHENKO YEVGENI M. , ZIMATKIN SERGEI M.
Published: July 2002

Abstract We have studied the activities of the GABA metabolizing enzymes‐GABA aminotransferase (GABA‐AT), succinic semialdehyde dehydrogenase (SSA‐DH) and SSA reductase (SSA‐R) and the levels of GABA, glutamine and glutamate in rats preferring water (WP) or ethanol (EP) after 6 months of ethanol consumption and 12 hours to 7 days after withdrawal. We showed decreased GABA levels in the brain stem, decreased GABA‐AT activity in the hemispheres and brain stem, and enhanced GABA‐AT activity in the striatum of EP rats compared with the control or WP animals following chronic consumption of ethanol. We found decreased activity of SSA‐R and SSA‐DH in the hemispheres and brain stems of alcohol‐treated rats compared to the control rats. Withdrawal (0.5‐7 days) induced numerous profound changes in GABA metabolism.