bluuebunny/crossref_metadata_2025 huggingface dataset:
Association Between Dopamine Receptor D1 Gene Dde I polymorphism and Sensation Seeking in Alcohol‐Dependent Men
Authors: Limosin Frédéric , Loze Jean‐Yves , Rouillon Frédéric , Adès Jean , Gorwood Philip
Published: November 2003

Background: Among genetic and biopsychological factors involved in alcohol‐dependence vulnerability, dopamine receptor subtypes genes and temperament's dimensions, such as sensation seeking, have been particularly incriminated. Moreover, it is suggested that higher levels of sensation seeking could be associated with a modification of sensitivity to dopamine in postsynaptic receptors.

Methods: We investigated whether the DRD1 Dde I polymorphism could be associated with the sensation‐seeking level among a sample of 72 alcohol‐dependent male and female patients. Analyses of variance were performed to test for an effect between the DRD1 Dde I genotypes and sensation‐seeking scores according to the 40‐item Zuckerman scale.

Results: When comparing the DRD1 Dde I genotypes and the Zuckerman scores, we found a significant association only in men (p= 0.01).

Conclusions: That is the first report of a male limited association between the DRD1 gene polymorphism and sensation‐seeking score in alcohol‐dependent subjects.
Alleles of a Functional Serotonin Transporter Promoter Polymorphism Are Associated With Major Depression in Alcoholics
Authors: Nellissery Maggie , Feinn Richard S. , Covault Jonathan , Gelernter Joel , Anton Raymond F. , Pettinati Helen , Moak Darlene , Mueller Timothy , Kranzler Henry R.
Published: November 2003

Background: Serotonergic neurotransmission has been implicated in the pathogenesis of both alcohol dependence and mood disorders and may therefore be important in understanding the pathophysiology of comorbid alcohol dependence and major depression. Studies of the association of these disorders with a functional polymorphism in the promoter region of the gene encoding the serotonin transporter protein (locus SLC6A4) have yielded inconsistent results. Because the convergence of these disorders may provide a refined phenotype, we examined the association of serotonin (5‐HT) transporter linked polymorphic region (5‐HTTLPR) alleles to comorbid alcohol dependence and major depression.

Methods: A sample of 296 European American and 16 African American patients with comorbid alcohol dependence and major depression was recruited from treatment studies. The control group included 260 European Americans and 43 African Americans; all were screened to exclude the presence of a mood or substance use disorder. DNA isolated from whole blood was polymerase chain reaction–amplified, and genotypes were assigned on the basis of agarose gel size fractionation.

Results: The frequency of the short allele in the patient group was in the range of those previously reported for samples with unipolar depression but was significantly more common than among controls (short allele frequency of cases, 45.8%; controls, 39.8%; χ21= 4.02; p= 0.045).

Conclusions: With respect to the frequency of the short allele at the SLC6A4 locus (5‐HTTLPR), major depression in alcoholics is similar to major depression in nonalcoholics. Further efforts to characterize depressed alcoholics and to examine genetic predictors of response to antidepressant treatment seem warranted.
Test‐Retest Reliability of the Alcohol Use Disorder Identification Test in a General Population Sample
Authors: Selin Klara Hradilova
Published: November 2003

Background: A number of different screening tests are frequently used in alcohol research, but our knowledge about the reliability of many of them is quite limited. Recently, this problem has received more attention. This article examines the test‐retest reliability of one of these instruments—the Alcohol Use Disorder Identification Test (AUDIT)—in a general population sample.

Methods: A general population sample (n= 457) was tested and, after approximately 1 month, was retested by using the AUDIT. Correlation between the two tests has been examined with the intraclass correlation coefficient and the κ coefficient in analysis of dichotomous variables. Specificity and sensitivity at a number of different cutoff scores have also been analyzed by using the first test as a criterion.

Results: On the item level, the correlations ranged between 0.6 and 0.8. The overall reliability of total AUDIT scores was 0.84. When stratified by gender, age, and consumer status, the total score reliability approximated 0.80 for all the categories except low alcohol consumers (0.51). Agreement using the recommended cutoff score of 8+ was also examined. The reliability (κ) observed in the whole sample was 0.691, which was interpreted as a substantial agreement. By this cutoff, 91% were correctly classified at retest compared with the first test. AUDIT 8+ showed higher reliability for males, young people, and moderate consumers and low reliability among low consumers. In terms of reliability, the most optimal cutoff for women turned out to be 6 or more.

Conclusions: According to these results, the test‐retest reliability of AUDIT is high. The next step might be to examine to what extent the findings apply within health‐care settings, which is what the test originally was designed for.
Effect of Ethanol on Reductions in Norepinephrine Electrochemical Signal in the Rostral Ventrolateral Medulla and Hypotension Elicited by I1‐Receptor Activation in Spontaneously Hypertensive Rats
Authors: Mao Limin , Li Guichu , Abdel‐Rahman Abdel A.
Published: November 2003

Background: The mechanism of the antagonistic hemodynamic interaction between ethanol and centrally acting sympatholytics is not known. In this study, we tested the hypothesis that the imidazoline (I1)‐receptor modulation of norepinephrine (NE) release within the rostral ventrolateral medulla (RVLM) plays a pivotal role in this clinically relevant hemodynamic interaction.

Method: In anesthetized spontaneously hypertensive rats, the effects of centrally acting sympatholytics on RVLM NE electrochemical signal were investigated by in vivo electrochemistry along with cardiovascular responses in the absence and presence of ethanol. In vivo microdialysis in conscious spontaneously hypertensive rats was used to confirm the electrochemical findings.

Results: Clonidine (30 μg/kg, intravenously) or rilmenidine (400, 600, or 800 μg/kg) significantly reduced RVLM NE electrochemical signal (index of neuronal activity) and mean arterial pressure; rilmenidine effects were dose‐related, and ethanol (1 g/kg) counteracted these responses. Ethanol (1 g/kg) pretreatment increased both RVLM NE electrochemical signal and blood pressure but did not influence the reductions in both variables elicited by subsequently administered clonidine. The α2‐adrenergic antagonist 2‐methoxyidazoxan (30 μg/kg) counteracted rilmenidine (800 μg/kg)‐evoked responses. In vivo microdialysis in conscious spontaneously hypertensive rats confirmed the electrochemical findings since clonidine‐ (30 μg/kg, intravenously) evoked reductions in RVLM NE and the associated hypotension were counteracted by ethanol (1 g/kg).

Conclusions: (1) Ethanol counteracts centrally mediated hypotension, at least in part, by increasing RVLM NE; (2) the interaction involves the I1 receptor modulation of RVLM neuronal activity; (3) the α2‐adrenergic receptor contributes to the electrochemical and cardiovascular effects of high doses of rilmenidine, and (4) the RVLM is a neuroanatomical target for systemically administered ethanol.
Psychometric Properties of the Short Index of Problems as a Measure of Recent Alcohol‐Related Problems
Authors: Feinn Richard , Tennen Howard , Kranzler Henry R.
Published: November 2003

Background: The Drinker Inventory of Consequences (DrInC) measures overall consequences of drinking and yields five subscale scores. A short form of the DrInC, the Short Index of Problems (SIP), was developed for use when time does not permit completion of the DrInC. This study investigates the psychometric properties of the SIP.

Methods: The study sample consisted of 153 problem drinkers who were participants in a placebo‐controlled trial of naltrexone and brief counseling.

Results: The SIP showed good internal consistency, good concurrent validity, and adequate stability. Four of the five SIP subscales contributed unique variance beyond general drinking consequences.

Conclusions: The SIP is useful for measuring drinking consequences in a sample of problem drinkers, and the subscale scores can be interpreted clinically. Further research on the SIP in other populations is warranted.
Ethanol Modulation of Excitatory and Inhibitory Synaptic Transmission in Rat and Monkey Dentate Granule Neurons
Authors: Ariwodola O. J. , Crowder T. L. , Grant K. A. , Daunais J. B. , Friedman D. P. , Weiner J. L.
Published: November 2003

Background: The physiological mechanisms underlying the behavioral and cognitive effects of ethanol are not fully understood. However, there is now compelling evidence that ethanol acts, at least in part, by modulating the function of a small group of proteins that mediate excitatory and inhibitory synaptic transmission. For example, intoxicating concentrations of ethanol have been shown to enhance GABAergic synaptic inhibition and depress glutamatergic excitatory neurotransmission in a number of brain regions. Because all of these electrophysiological studies have been performed in rodent brain slice or neuronal culture preparations, direct evidence that ethanol exerts similar effects on synaptic transmission in the primate central nervous system is lacking.

Methods: We have therefore developed methods to perform patch‐clamp electrophysiological recordings from neurons in acutely prepared monkey (Macaca fascicularis) hippocampal slices. We have used these methods to compare the acute effects of ethanol on excitatory and inhibitory synaptic transmission in rat and monkey dentate granule neurons.

Results: Under our recording conditions, ethanol significantly potentiated γ‐aminobutyric acid type A inhibitory postsynaptic currents in both rat and monkey neurons. In addition, ethanol significantly inhibited NMDA, but not AMPA, excitatory postsynaptic currents in dentate granule neurons from both species. Notably, no significant differences were observed in any of the pharmacological properties of inhibitory or excitatory synaptic responses recorded from rat and monkey neurons.

Conclusions: These data suggest that the differences in the behavioral effects of ethanol that have been observed between rats and higher‐order mammals, such as monkeys and humans, may not reflect differences in the sensitivity of some of the major synaptic sites of ethanol action. Moreover, our results provide empirical evidence for the use of rodent brain slice preparations in elucidating synaptic mechanisms of ethanol action in the primate central nervous system.
Recommendations on Use of Biomarkers in Alcoholism Treatment Trials
Authors: Allen John P. , Litten Raye Z.
Published: November 2003

Background: Biochemical markers of heavy drinking are playing increasingly prominent roles in alcohol treatment efficacy studies, especially in those designed to evaluate medications. Among these roles are serving as inclusion or exclusion criteria for research participants, corroboration of self‐report of drinking status, assessment of the safety of the agent being evaluated, and determination of treatment outcome.

Methods: Recent alcohol medication development trials that included biomarker information were reviewed and critiqued from the perspectives of how biomarker measures were used and how findings on them were reported.

Results: Although generally the application of biomarkers as inclusion criteria is not recommended, they may aid in exclusion of potential subjects (e.g., elevated liver function measures in trials of agents that could result in liver damage). Biomarkers are most commonly used as indicators of outcome, usually serving as secondary outcome variables. The relationship of outcome findings on biomarker and self‐report measures is positive, but only moderate. As used to date, biomarkers of drinking tend to be less sensitive than well‐standardized and properly administered self‐report measures. Nevertheless, they do provide a useful, unique source of information on drinking status.

Conclusions: The contribution of biomarkers to alcoholism clinical research would be enhanced if certain design strategies were incorporated into their application and if critical information were included in the research publication. This article offers a series of recommendations to improve on their use in a research context.
Hypericum perforatum CO2 Extract and Opioid Receptor Antagonists Act Synergistically to Reduce Ethanol Intake in Alcohol‐Preferring Rats
Authors: Perfumi Marina , Santoni Manuela , Cippitelli Andrea , Ciccocioppo Roberto , Froldi Rino , Massi Maurizio
Published: November 2003

Background: Hypericum perforatum extracts attenuate ethanol intake in alcohol‐preferring rats. The opioid receptor antagonists, naloxone and naltrexone, reduce ethanol intake in rats and humans. The combination of different agents that reduce ethanol intake has been proposed as an approach to the pharmacotherapy of alcoholism. This study evaluated the effect on ethanol intake of the combined administration of a CO2H. perforatum extract and naloxone or naltrexone in genetically selected Marchigian Sardinian alcohol‐preferring rats.

Methods: Ten percent (v/v) ethanol intake was offered 2 hr per day at the beginning of the dark phase of the reverse light‐dark cycle. H. perforatum CO2 extract was given intragastrically, 1 hr before access to ethanol. Naloxone or naltrexone was given by intraperitoneal injection 10 min before the extract.

Results: H. perforatum CO2 extract reduced ethanol intake at 31 or 125 mg/kg, but not 7 mg/kg. These doses neither modified food or water intake during access to ethanol, nor reduce 0.2% saccharin intake. Naloxone reduced ethanol and food intake at 3 or 5 mg/kg, but not 1 mg/kg. When naloxone 1 mg/kg was combined with the three doses of H. perforatum CO2 extract, the attenuation of ethanol intake was more pronounced than that observed after the administration of the extract alone. Alcohol intake was also significantly reduced by 7 mg/kg of H. perforatum CO2 extract combined with naloxone 1 mg/kg. The combined treatments never modified the rat's locomotor activity nor the simultaneous intake of food, water or 0.2% saccharin. Naltrexone reduced ethanol intake at 1 and 3 mg/kg, but not at 0.5 mg/kg. When naltrexone 0.5 mg/kg was combined with H. perforatum CO2 extract 7 mg/kg, ethanol intake was markedly reduced.

Conclusions: These findings provide evidence that H. perforatum CO2 extract and opiate receptor antagonists act synergistically to induce a pronounced and selective reduction of voluntary ethanol consumption in alcohol‐preferring rats.
Conserved Nucleotides within the J Domain of the Encephalomyocarditis Virus Internal Ribosome Entry Site Are Required for Activity and for Interaction with eIF4G
Authors: Clark Angela T. , Robertson Morwenna E. M. , Conn Graeme L. , Belsham Graham J.
Published: November 2003

The internal ribosome entry site (IRES) elements of cardioviruses (e.g., encephalomyocarditis virus [EMCV] and foot-and-mouth disease virus) are predicted to have very similar secondary structures. Among these complex RNA structures there is only rather limited complete sequence conservation. Within the J domain of the EMCV IRES there are four highly conserved nucleotides (A704, C705, G723, and A724)., which are predicted to be unpaired and have been targeted for mutagenesis. Using an IRES-dependent cell selection system, we have isolated functional IRES elements from a pool of up to 256 mutants. All changes to these conserved nucleotides resulted in IRES elements that were less efficient at directing internal initiation of translation than the wild-type element, and even some of the single point mutants were highly defective. Each of the mutations adversely affected the ability of the RNAs to interact with the translation initiation factor eIF4G.
Rise and Survival of Bovine Herpesvirus 1 Recombinants after Primary Infection and Reactivation from Latency
Authors: Schynts Frédéric , Meurens François , Detry Bruno , Vanderplasschen Alain , Thiry Etienne
Published: November 2003

Recombination is thought to be an important source of genetic variation in herpesviruses. Several studies, performed in vitro or in vivo, detected recombinant viruses after the coinoculation of two distinguishable strains of the same herpesvirus species. However, none of these studies investigated the evolution of the relative proportions of parental versus recombinant progeny populations after coinoculation of the natural host, both during the excretion and the reexcretion period. In the present study, we address this by studying the infection of cattle with bovine herpesvirus 1 (BoHV-1). The recombination of two BoHV-1 mutants lacking either glycoprotein C (gC−/gE+) or E (gC+/gE−) was investigated after inoculation of cattle by the natural route of infection. The results demonstrated that (i) recombination is a frequent event in vivo since recombinants (gC+/gE+and gC−/gE−) were detected in all coinoculated calves, (ii) relative proportions of progeny populations evolved during the excretion period toward a situation where two populations (gC+/gE+and gC−/gE+) predominated without fully outcompeting the presence of the two other detected populations (gC+/gE−and gC−/gE−), and (iii) after reactivation from latency, no gC+/gE−and gC−/gE−progeny viruses were detected, although gC+/gE−mutants, when inoculated alone, were detected after reactivation treatment. In view of these data, the importance of gE in the biology of BoHV-1 infection and the role of recombination in herpesvirus evolution are discussed.
The Differential Requirement for Cyclin-Dependent Kinase Activities Distinguishes Two Functions of Herpes Simplex Virus Type 1 ICP0
Authors: Davido David J. , von Zagorski William F. , Maul Gerd G. , Schaffer Priscilla A.
Published: November 2003

Herpes simplex virus type 1 (HSV-1) ICP0 directs the degradation of cellular proteins associated with nuclear structures called ND10, a function thought to be closely associated with its broad transactivating activity. Roscovitine (Rosco), an inhibitor of cyclin-dependent kinases (cdks), inhibits the replication of HSV-1, HSV-2, human cytomegalovirus, varicella-zoster virus, and human immunodeficiency virus type 1 by inhibiting specific steps or activities of viral regulatory proteins, indicating the broad and pleiotropic effects that cdks have on the replication of these viruses. We previously demonstrated that Rosco inhibits the transactivating activity of ICP0. In the present study, we asked whether Rosco also affects the ability of ICP0 to direct the degradation of ND10-associated proteins. For this purpose, WI-38 cells treated with cycloheximide (CHX) were mock infected or infected with wild-type HSV-1 or an ICP0−mutant (7134). After release from the CHX block, the infections were allowed to proceed for 2 h in the presence or absence of Rosco at a concentration known to inhibit ICP0's transactivating activity. The cells were then examined for the presence of ICP0 and selected ND10-associated antigens (promyelocytic leukemia antigen [PML], sp100, hDaxx, and NDP55) by immunofluorescence. Staining for the ND10-associated antigens was detected in ≤20% of KOS-infected cells in the presence or absence of Rosco, demonstrating that Rosco-sensitive kinases are not required for ICP0's ability to direct the dispersal or degradation of these antigens. In contrast, >90% of 7134- and mock-infected cells stained positive for all ND10-associated antigens in the presence or absence of Rosco. Similar results were obtained with a non-ND10-associated antigen, DNA-PKcs, a known target of ICP0-directed degradation. The results of the PML and DNA-PKcsimmunofluorescence studies correlated with a decrease in the levels of these proteins as determined by Western blotting. Thus, the differential requirement for Rosco-sensitive cdk activities distinguishes ICP0's ability to direct the dispersal or degradation of cellular proteins from its transactivating activity.
Endoplasmic Reticulum Stress Is a Determinant of Retrovirus-Induced Spongiform Neurodegeneration
Authors: Dimcheff Derek E. , Askovic Srdjan , Baker Audrey H. , Johnson-Fowler Cedar , Portis John L.
Published: November 2003

FrCasEis a mouse retrovirus that causes a fatal noninflammatory spongiform neurodegenerative disease with pathological features strikingly similar to those induced by transmissible spongiform encephalopathy (TSE) agents. Neurovirulence is determined by the sequence of the viral envelope protein, though the specific role of this protein in disease pathogenesis is not known. In the present study, we compared host gene expression in the brain stems of mice infected with either FrCasEor the avirulent virus F43, differing from FrCasEin the sequence of the envelope gene. Four of the 12 disease-specific transcripts up-regulated during the preclinical period represent responses linked to the accumulation of unfolded proteins in the endoplasmic reticulum (ER). Among these genes was CHOP/GADD153, which is induced in response to conditions that perturb endoplasmic reticulum function. In vitro studies with NIH 3T3 cells revealed up-regulation of CHOP as well as BiP, calreticulin, and Grp58/ERp57 in cells infected with FrCasEbut not with F43. Immunoblot analysis of infected NIH 3T3 cells demonstrated the accumulation of uncleaved envelope precursor protein in FrCasE- but not F43-infected cells, consistent with ER retention. These results suggest that retrovirus-induced spongiform neurodegeneration represents a protein-folding disease and thus may provide a useful tool for exploring the causal link between protein misfolding and the cytopathology that it causes.
Blocking Immune Evasion as a Novel Approach for Prevention and Treatment of Herpes Simplex Virus Infection
Authors: Judson Kara A. , Lubinski John M. , Jiang Ming , Chang Yueh , Eisenberg Roselyn J. , Cohen Gary H. , Friedman Harvey M.
Published: November 2003

Many microorganisms encode immune evasion molecules to escape host defenses. Herpes simplex virus type 1 glycoprotein gC is an immunoevasin that inhibits complement activation by binding complement C3b. gC is expressed on the virus envelope and infected cell surface, which makes gC potentially accessible to blocking antibodies. Mice passively immunized with gC monoclonal antibodies prior to infection were protected against herpes simplex virus challenge only if the gC antibodies blocked C3b binding. Mice treated 1 or 2 days postinfection with gC monoclonal antibodies that block C3b binding had less severe disease than control mice treated with nonimmune immunoglobulin G (IgG). Mice immunized with gC protein produced antibodies that blocked C3b binding to gC. Immunized mice were significantly protected against challenge by wild-type virus, but not against a gC mutant virus lacking the C3b binding domain, suggesting that protection was mediated by antibodies that target the gC immune evasion domain. IgG and complement from subjects immunized with an experimental herpes simplex virus glycoprotein gD vaccine neutralized far more mutant virus defective in immune evasion than wild-type virus, supporting the importance of immune evasion molecules in reducing vaccine potency. These results suggest that it is possible to block immune evasion domains on herpes simplex virus and that this approach has therapeutic potential and may enhance vaccine efficacy.
Interactions between Human Cytomegalovirus IE1-72 and Cellular p107: Functional Domains and Mechanisms of Up-Regulation of Cyclin E/cdk2 Kinase Activity
Authors: Zhang Zhigang , Huong Shu-Mei , Wang Xin , Huang David Y. , Huang Eng-Shang
Published: November 2003

Previous work has demonstrated that the human cytomegalovirus IE1-72 protein is able to bind to the N terminus of p107, and IE1-72 alone is sufficient for alleviation of p107-mediated cell growth suppression. However, the mechanism of this alleviation is unclear. Here, we show that IE1-72 can alleviate p107 inhibition of cyclin E/cdk2 kinase activity. We cotransfected various IE1-72 and p107 constructs into C33A cells and demonstrated that IE1-72 could activate the kinase activity of cyclin E/cdk2. Conversely, IE2-86 did not activate this activity, suggesting that the interaction between p107 and IE1-72 and the subsequent kinase activation are specific. By the use of a series of deletion and point mutants of IE1-72 and p107, we observed that a mutation of the loop region of helix-loop-helix-turn-helix in exon 3 of IE1-72 as well as a mutation of the leucine zipper-2 region in exon 4 of IE1-72 abolished binding to p107. In addition, these two IE1-72 mutants did not alleviate p107 inhibition of cyclin E/cdk2 kinase activity and also failed to alleviate p107 inhibition of the E2F-responsive promoter. Meanwhile, deletion of the N-terminal aa 1 to 175 of p107 abolished both p107 binding with IE1-72 and p107 inhibition of cyclin E/cdk2 kinase activity. This result confirms that the N-terminus aa 1 to 175 region of p107 is a common region where both IE1-72 protein and cyclin E/cdk2 bind. We propose a mechanism in which binding of IE1-72 to p107 displaces cyclin E/cdk2 from p107. Once released from p107, cyclin E/cdk2 is able to function as an active kinase.
Neutralization of Infectivity of Diverse R5 Clinical Isolates of Human Immunodeficiency Virus Type 1 by gp120-Binding 2′F-RNA Aptamers
Authors: Khati Makobetsa , Schüman Michael , Ibrahim Jamal , Sattentau Quentin , Gordon Siamon , James William
Published: November 2003

Human immunodeficiency virus type 1 (HIV-1) has evolved a number of strategies to resist current antiretroviral drugs and the selection pressures of humoral and cellular adaptive immunity. For example, R5 strains, which use the CCR5 coreceptor for entry and are the dominant viral phenotype for HIV-1 transmission and AIDS pathogenesis, are relatively resistant to neutralization by antibodies, as are other clinical isolates. In order to overcome these adaptations, we raised nucleic acid aptamers to the SU glycoprotein (gp120) of the R5 strain, HIV-1Ba-L. These not only bound gp120 with high affinity but also neutralized HIV-1 infectivity in human peripheral blood mononuclear cells (PBMCs) by more than 1,000-fold. Furthermore, these aptamers were able to neutralize the infectivity of R5 clinical isolates of HIV-1 derived from group M (subtypes A, C, D, E, and F) and group O. One aptamer defined a site on gp120 that overlaps partially with the conserved, chemokine receptor-binding, CD4-induced epitope recognized by monoclonal antibody 17b. In contrast to the antibody, the site is accessible to aptamer in the absence of CD4 binding. Neutralizing aptamers such as this could be exploited to provide leads in developing alternative, efficacious anti-HIV-1 drugs and lead to a deeper understanding of the molecular interactions between the virus and its host cell.
Characterization of the Chromosomal Binding Sites andDimerization Partners of the Viral Oncoprotein Meq in Marek'sDisease Virus-Transformed TCells
Authors: Levy Alon M. , Izumiya Yoshihiro , Brunovskis Peter , Xia Liang , Parcells Mark S. , Reddy Sanjay M. , Lee Lucy , Chen Hong-Wu , Kung Hsing-Jien
Published: November 2003

Marek's disease virus (MDV) is an acute transforming alphaherpesvirus that causes T-cell lymphomas in chickens. We previously reported the identification of a putative oncogene,meq, that is encoded only by the oncogenic serotype of MDV. The gene product, Meq, is a latent protein that is consistently expressed in MDV-transformed lymphoblastoid cells and tumor cells. Meq has a bZIP (basic leucine zipper) structure resembling the family of Jun/Fos. The mechanism whereby Meq transforms T cells remains poorly understood. In this study, we explored the properties of Meq as a transcriptional factor. We analyzed Meq's dimerization partners and its target genes in MSB-1, an MDV-transformed T-cell line. By using in vitro assays, we first demonstrated Meq's potential to dimerize with a variety of bZIP proteins. We then identified c-Jun as the primary dimerization partner of Meq. Both are found to be colocalized in the nucleus and corecruited to promoters with AP-1 sequences. By using chromatin immunoprecipitation (ChIP), we scanned the entire MDV genome for Meq binding sites and found three regions that were enriched with Meq binding: the MDV lytic replication origin, the promoter for Meq, and the promoter for ICP4. Transactivation assays using the above promoters showed that Meq/Meq homodimers exhibited repression activity, whereas Meq/Jun heterodimers showed activation. Finally, we were able to show by ChIP that Meq is recruited to the interleukin-2 promoter in a region encompassing an AP-1 site. Thus, in addition to providing general knowledge about the transcriptional properties of Meq, our studies revealed for the first time the ability of Meq to interact with the latent MDV and host genomes. Our data suggest, therefore, a role for Meq in viral genome regulation during latency, in addition to its putative causal role in T-cell transformation.
Varicella-Zoster Virus-Infected Human Sensory Neurons Are Resistant to Apoptosis, yet Human Foreskin Fibroblasts Are Susceptible: Evidence for a Cell-Type-Specific Apoptotic Response
Authors: Hood C. , Cunningham A. L. , Slobedman B. , Boadle R. A. , Abendroth A.
Published: November 2003

The induction of apoptosis or programmed cell death in virus-infected cells is an important antiviral defense mechanism of the host, and some herpesviruses have evolved strategies to modulate apoptosis in order to enhance their survival and spread. In this study, we examined the ability of varicella-zoster virus (VZV) to induce apoptosis in primary human dorsal root ganglion neurons and primary human foreskin fibroblasts (HFFs). Three independent methods (annexin V, TUNEL [terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling] staining, and electron microscopy) were used to assess apoptosis in these cells on days 1, 2, and 4 postinoculation. By all three methods, apoptosis was readily detected in VZV-infected HFFs. In stark contrast, apoptosis was not detected during productive VZV infection of neurons. The low-passage clinical isolate Schenke and the tissue culture-adapted ROka strain both induced apoptosis in HFFs but not in neurons, suggesting that this cell-type-specific apoptotic phenotype was not VZV strain specific. These data show that the regulation of apoptosis differs markedly between HFFs and neurons during productive VZV infection. Inhibition of apoptosis during infection of neurons may play a significant role in the establishment, maintenance, and reactivation of latent infection by promoting survival of these postmitotic cells.
Development and Characterization of Novel Empty Adenovirus Capsids and Their Impact on Cellular Gene Expression
Authors: Stilwell Jackie L. , McCarty Douglas M. , Negishi Atsuko , Superfine Richard , Samulski R. Jude
Published: November 2003

Adenovirus (Ad) has been extensively studied as a eukaryotic viral vector. As these vectors have evolved from first-generation vectors to vectors that contain either very few or no viral genes (“gutless” Ad), significant reductions in the host innate immune response upon infection have been observed. Regardless of these vector improvements an unknown amount of toxicity has been associated with the virion structural proteins. Here we demonstrate the ability to generate high particle numbers (10
11
to 10
12
) of Ad empty virions based on a modification of Cre/lox gutless Ad vectors. Using a battery of analyses (electron microscopy, atomic force microscopy, confocal images, and competition assays) we characterized this reagent and determined that it (i) makes intact virion particles, (ii) competes for receptor binding with wild-type Ad, and (iii) enters the cell proficiently, demonstrating an ability to carry out essential steps of viral entry. To further study the biological impact of these Ad empty virions on infected cells, we carried out DNA microarray analysis. Compared to that for recombinant Ad, the number of mRNAs modulated upon infection was significantly reduced but the expression signatures were similar. This reagent provides a valuable tool for studies of Ad in that researchers can examine the effect of infection in the presence of the virion capsid alone.
Rat Model of Borna Disease Virus Transmission: Epidemiological Implications
Authors: Sauder Christian , Staeheli Peter
Published: November 2003

Rapid transmission of Borna disease virus occurred upon cohabitation of persistently infected and naive rats. Infectious virus, which was abundantly present in fresh urine samples of carrier rats, entered the brains of recipient rats via the olfactory route. Thus, susceptible farm animals possibly acquire the virus from persistently infected rats.
PARTICLE MODELS FOR DEVICE SIMULATION
Authors: KOSINA HANS , NEDJALKOV MIHAIL
Published: November 2003

A theoretical analysis of the Monte Carlo (MC) method for both semiclassical and quantum device simulation is presented. A link between physically-based MC methods for semiclassical transport calculations and the numerical MC method for solving integrals and integral equations is established. The integral representations of the transient and the stationary Boltzmann equations are presented as well as the respective conjugate equations. The structure of the terms of the Neumann series and their evaluation by MC integration is discussed. Using this formal approach the standard MC algorithms and a variety of new algorithms is derived, such as the backward and the weighted algorithms, and algorithms for linear small-signal analysis. Applying this theoretical framework to the Wigner-Boltzmann equation enables the development of particle models for quantum transport problems.
SELF-CONSISTENT MODELING OF MOSFET QUANTUM EFFECTS BY SOLVING THE SCHRÖDINGER AND BOLTZMANN SYSTEM OF EQUATIONS
Authors: GOLDSMAN NEIL , HUANG CHUNG-KUANG
Published: November 2003

A new method for investigating quantum confinement effects in MOSFETs is presented. The method is based on the numerical solution of the Schrödinger and Boltzmann system of equations. A quantum Boltzmann equation is developed by replacing the classical potential with a quantum potential. The technique naturally accounts for highly nonequilibrium effects including velocity overshoot. The subbands are calculated and then populated using nonequilibrium statistics. Modeling results show the electron concentration and electron current density peaks shifted away from the interface. Calculations show reduced channel concentration which leads to lower drain current for the quantum case. A quantum distribution function is obtained.
SUPPORT VECTOR MACHINE CLASSIFICATION OF PHYSICAL AND BIOLOGICAL DATASETS
Authors: CAI CONG-ZHONG , WANG WAN-LU , CHEN YU-ZONG
Published: November 2003

The support vector machine (SVM) is used in the classification of sonar signals and DNA-binding proteins. Our study on the classification of sonar signals shows that SVM produces a result better than that obtained from other classification methods, which is consistent from the findings of other studies. The testing accuracy of classification is 95.19% as compared with that of 90.4% from multilayered neural network and that of 82.7% from nearest neighbor classifier. From our results on the classification of DNA-binding proteins, one finds that SVM gives a testing accuracy of 82.32%, which is slightly better than that obtained from an earlier study of SVM classification of protein–protein interactions. Hence, our study indicates the usefulness of SVM in the identification of DNA-binding proteins. Further improvements in SVM algorithm and parameters are suggested.
ENERGY, OSCILLATOR STRENGTH AND HYPERFINE STRUCTURE OF THE LOW-LYING EXCITED STATES FOR Be-LIKE SYSTEM
Authors: WANG FEI , GOU BINGCONG , WU XIAOLI , HAN LIHONG
Published: November 2003

The Rayleigh–Ritz variational method is carried out with a multiconfiguration-interaction wave function and restricted variational method to obtain the relativistic energies of the 1s22s2p 1Po , 1s22s2p 3Po , and 1s22p23P states for the beryllium-like isoelectronic sequence (Z=4–10), including the mass polarization and relativistic corrections. The oscillator strengths and transition rates are also calculated. The results are compared with other theoretical and experimental data in the literature. The hyperfine structure of the low-lying excited states for this system is also explored.
ON PATTERNS IN AFFECTIVE MEDIA
Authors: ADAMATZKY ANDREW
Published: November 2003

In computational experiments with cellular automaton models of affective solutions, where chemical species represent happiness, anger, fear, confusion and sadness, we study phenomena of space–time dynamic of emotions. We demonstrate feasibility of the affective solution paradigm in example of emotional abuse therapy. Results outlined in the present paper offer unconventional but promising technique to design, analyze and interpret spatio-temporal dynamic of mass moods in crowds.
CELLULAR AUTOMATA WITH ACCUMULATIVE MEMORY: LEGAL RULES STARTING FROM A SINGLE SITE SEED
Authors: ALONSO-SANZ RAMÓN , MARTÍN MARGARITA
Published: November 2003

Standard Cellular Automata (CA) are ahistoric (memoryless), i.e., the new state of a cell depends only on the neighborhood configuration at the preceding time step. This article introduces an extension of the standard framework of CA by considering automata implementing memory capabilities. While the update rules of the CA remains the same, each site remembers a weighted mean of all its past states, with a decreasing weight of states farther back in the past. The historic weighting is defined by a potential series of coefficients, tk, k acting as a forgetting factor. This paper considers the time evolution of one-dimensional, legal CA rules with accumulative memory.
MMPI Manifestations of Chinese Migraine Syndromes: A Control Study
Authors: Fan Arthur Yin , Zhou An-Nan
Published: November 2003

The investigation of personality traits of patients suffering from migraine headache with the Minnesota Multiphasic Personality Inventory (MMPI) is an important line of research, and differentiating syndromes in treating this disease is one of the characteristics of Chinese Medicine (CM). This study presents the MMPI-(Chinese edition) responses of 80 Chinese subjects with migraine and 40 non-headache healthy control subjects. Among them, migraine fire syndrome (MF) group consisted of 45 subjects (10 men, 35 women); migraine Qi stasis syndrome (MQ) group, 35 subjects (8 men, 27 women). The healthy control group was divided into healthy Qi stasis syndrome (HQ) group, 9 subjects (2 men, 7 women); and healthy normal (HN) group, 31 subjects (7 men, 24 women) according to CM diagnostic criteria. Statistical analysis was performed by pairs among four groups. The results revealed that both MF and MQ groups' MMPI profiles were significantly higher than that of the Normal (HN) group, and formed a 1.2.3.7 type slope. Profile deviation in the MQ group was slight, but in the MF group was serious and accompanied by a significant rising scores in F, paranoia (6), schizophrenia (8) and social introversion (0) subtests; HQ group's MMPI profile had a similar deviation as in the MQ group. The results suggest that CM migraine syndromes have an exact expression on MMPI profile, and that MMPI as an effective diagnostic method could be applied for CM syndrome discrimination. The "deviation of migraineurs' personality" may not be a special characteristic held only by migraineurs. The existence of different syndromes in migraine is one of the reasons that different scholars have reported different results on migraine by means of MMPI.
Evaluation of the Antioxidant Activities ofErycibe Osbtusifolia
Authors: Hsu Hsue-Yin , Chen Jen-Yin , Yang Jenq-Jer , Lin Chun-Ching
Published: November 2003

Free radicals may be involved in various pathogenesis processes. Tissue damage and cellular toxicity of some chemicals mediated by oxygen free radicals can be monitored by studying the levels of lipid peroxidation in the tissues. The study reported here is to investigate the MDA concentrations in different tissues after various doses of Erycibe obtusifolia (EO) treatments. EO given at doses of 10, 20 and 30 mg/kg body weight is experimentally tested through oral administration. The antioxidant effect of EO extract is assessed by the measurements of hepatic, renal and splenic lipid peroxides (measured as malondialdehyde; MDA) after treatments. The results show no significant time-related and dose-dependent increase or decrease of MDA concentrations in the liver, kidney and spleen after EO administrations, respectively. The peak of antioxidant activities is found on the first day and the 6 hrs after treatments for liver and kidney, respectively. In contrast, the MDA concentrations in spleen after EO administrations remained above the normal values. This result suggests that a high dose of EO administration may contribute a little antioxidant activity in both liver and kidney.
Applied Studies of the Plant Meridian System II.
Authors: Hou T.Z. , Mooneyham R.E.
Published: November 2003

Agri-wave technology is composed of both a special frequency sound wave and a microelement fertilizer. In both components, the effect of sound waves on plants is more than that of fertilizers, but the best function is a combination of the two. Treatment by Agri-wave technology stimulated the growth rate and increased the yield of spinach. In small plot tests, the length and width of the treated spinach leaf was 50.8 cm and 20.3 cm, respectively, whereas the untreated leaves were 29.20 cm and 8.9 cm. The fresh weight of treated spinach was 0.42 kg. This was 5.5 times higher than that of the untreated spinach. In large area testing (17 hectares), the results of two tests show that the yields of the treated spinach were increased 22.7% and 22.2% over those of the control group. Sugar content of the treated spinach was increased by 37.5%, vitamin A, C, and B were increased 35.63%, 41.67% and 40.00%, respectively, above the levels of the control group. Niacin content was decreased by 7.69%. Of 33 elements analyzed in the spinach, 29 elements were increased by Agri-wave technology. The spinach was infected with "rot disease" in the control group while there was no disease present in the treated group. In greenhouse testing, the average weight of 3 species of lettuce treated by Agri-wave technology was increased 44.10% over that of the control group (P < 0.000 1). The average weight of 3 species of lettuce by only sound and only fertilizer treated separately increased 29.92% and 16.19% above that of the control group (p < 0.0001). Sampling survey results in the field test were comparable to the above mentioned greenhouse test. The fresh weight of treated lettuce by Agri-wave technology was increased 41.67% over that of the control group (p < 0.0001). The fresh weight of treated lettuce by only sound and only fertilizer was increased 30.88% and 19.61%, respectively, over the control group (both P < 0.0001).
Effects of ChunDoSunBup Qi-training on Growth Hormone, Insulin-Like Growth Factor-I, and Testosterone in Young and Elderly Subjects
Authors: Lee Myeong Soo , Kang Chang Won , Ryu Hoon , Kim Jong-Duak , Chung Hun-Taeg
Published: November 2003

We observed the response of plasma growth hormone(GH), insulin-like growth factor-I(IGF-I) and testosterone(T) to an acute period of ChunDoSunBup(CDSB) Qi-training. Although the basal level of GH was not different between the two groups, after the portion of the training in which the subjects were physically active (the mid-training point), plasma GH levels increased by 7.26 fold (p < 0.05) in the elderly trainees and by 1.66 fold (p < 0.05) in the young. In response to CDSB Qi-training, IGF-I levels in the young increased significantly at mid-training point, but there were no increase in the elderly. Significant correlations existed between GH and IGF-I levels in the young subjects, but not in the elderly. The T level at the mid-training point increased significantly in elderly subjects but not in the young. These results suggest that CDSB Qi-training is a potential method for modulating of the secretion of growth factor in the young and the elderly, but that the elderly IGF-I response does not equal that of the young. In addition, our study suggests CDSB Qi-training may be one mode of therapy applicable to growth factor related disorders such as GH deficiency in children and osteoporosis in the elderly, especially women.
Induction of T Lymphocyte Apoptosis by Treatment with Glycyrrhizin
Authors: Oh Chanho , Kim Youngahn , Eun Jaesoon , Yokoyama Toshihiro , Kato Masashi , Nakashima Izumi
Published: November 2003

The effect of glycyrrhizin (GL), a Chinese herbal drug extracted from licolice roots, on murine lymphocytes for inducing apoptotic cell death was studied. Addition of GL (25-400 μg/ml) to cultured splenocytes and thymocytes from BALB/c mice definitely promoted DNA fragmentation. A single injection of GL (100 μg/mouse) into BALB/c mice did not cause any detectable DNA fragmentation or cell death of splenocytes and thymocytes. Cytofluorometric analysis of these cells, however, demonstrated a reduction in mitochondrial transmembrane potentials (ΔΨm). Repeated injections of GL (100 μg/mouse/day) into mice for 7 days actually resulted in induction of low grade DNA fragmentation selectively in splenocytes. Cell population analysis of viable lymphocytes suggested that both CD4+Th lymphocytes and CD8+Tc lymphocytes may have been relatively more sensitive than B220+B lymphocytes for the apoptotic cell death. We concluded from these results that GL acts as a rather selective inducer of mature T lymphocyte apoptosis with a reduction in ΔΨm potentially preceding lymphocyte death.
A Minnesota Multiphasic Personality Inventory Profile of ChunDoSunBup Qi-Trainees: A Preliminary Study
Authors: Lee Myeong Soo , Jeong Seong Min , Kim Byung Gi , Ryu Hoon , Oh Sang Woo , Chung Bun-Taeg
Published: November 2003

The aim of this study is to explore the effects of ChunDoSunBup Qi-training on personality traits. Twenty-six normal healthy subjects (mean age = 26.58 ± 6.56) and 26 CDSB Qi-trainees (mean age = 27.74 ± 5.21) participated in this study. Analysis of MMPI profiles showed that CDSB Qi-trainees scored significantly lower on Depression (D), Hysteria (Hy), Paranoia (Pa), Schizophrenia (Sc) and Frequency (F) and significantly higher on the Correction (K) Scales. In addition, CDSB Qi-trainees reported a significantly lower Cook-Medley Hostility (Ho) scale than that of controls. This preliminary study suggests that CDSB Qi-training may be effective in protection as well as restoration of emotional, psychological symptomatology and personality trait disorder.
DE RHAM WAVE EQUATION FOR TENSOR VALUED p-FORMS
Authors: BINI DONATO , CHERUBINI CHRISTIAN , JANTZEN ROBERT T. , RUFFINI REMO
Published: November 2003

The de Rham Laplacian Δ (dR) for differential forms is a geometric generalization of the usual covariant Laplacian Δ, and it may be extended naturally to tensor-valued p-forms using the exterior covariant derivative associated with a metric connection. Using it the wave equation satisfied by the curvature tensors in general relativity takes its most compact form. This wave equation leads to the Teukolsky equations describing integral spin perturbations of black hole spacetimes.