bluuebunny/crossref_metadata_2025 huggingface dataset:
Prophylactic treatment of bipolar disorder in pregnancy and breastfeeding: focus on emerging mood stabilizers
Authors: Gentile Salvatore
Published: May 2006

Objectives:  Bipolar disorders are reported to have a high incidence during childbearing years and the need may arise to start or continue a pharmacological treatment during pregnancy and the postpartum period. In the last few years several investigations have evaluated the efficacy of emerging mood‐stabilizing agents in the treatment of bipolar disorders, such as lamotrigine, olanzapine, risperidone, quetiapine, aripiprazole and ziprasidone. A number of studies, which examined the use of oxcarbazepine, point to its potential usefulness in prophylactic treatment. The aim of this review is to compare information from the literature on the safety of lamotrigine, oxcarbazepine, risperidone, olanzapine, and quetiapine to the safety data on classic mood stabilizers during pregnancy and the postpartum period.

Methods:  A computerized search carried out from 1980 to April 5, 2006 led to the summarization of the results. (References were updated after acceptance and prior to publication.)

Results:  Emerging mood stabilizers show uncertain safety parameters in pregnancy and lactation. Limited information on lamotrigine and oxcarbazepine does not suggest a clear increase in teratogenicity, while olanzapine appears to be associated with a higher risk of metabolic complications in pregnant women. Data about risperidone and quetiapine are still inconclusive. Finally, the literature on the safety of these compounds in breastfeeding is anecdotal.

Conclusions:  Untreated pregnant bipolar women are at an increased risk of poor obstetrical outcomes and relapse of affective symptoms. On the other hand, classic antiepileptic drugs are well‐known human teratogens, whereas data on lithium are partially ambiguous. The safety of emerging mood stabilizers in pregnancy and breastfeeding has not been examined extensively. Therefore, when approaching bipolar disorder, if possible, each episode must be considered separately.
Does inbreeding avoidance maintain gender dimorphism in Wurmbea dioica (Colchicaceae)?
Authors: Ramsey M. , Vaughton G. , Peakall R.
Published: May 2006

The maintenance of females in gender dimorphic populations requires that they have a fitness advantage to compensate for their loss of male reproductive function. We assess whether inbreeding avoidance provides this advantage in two subdioecious Wurmbea dioica populations by estimating seed production, outcrossing rates and inbreeding depression. Fruiting males produced less than half as many seeds as females, owing to low outcrossing rates and early acting inbreeding depression. Inbreeding coefficients of fruiting males demonstrated that progeny were more inbred than their parents, implying that few selfed progeny reach maturity, as confirmed by inbreeding depression estimates that exceeded 0.85. In a glasshouse experiment, open-pollinated females exhibited a fitness advantage of 3.7 relative to fruiting males, but when we increased fruiting male outcrossing rate, female advantage was only 1.4. This reduced advantage is insufficient to maintain females if nuclear genes control sex. Thus, inbreeding avoidance could maintain females at high frequencies, although this is contingent upon high frequencies of fruiting males, which can be altered by environmentally determined gender plasticity.
A change of expression in the conserved signaling gene MKK7 is associated with a selective sweep in the western house mouse Mus musculus domesticus
Authors: Harr B. , Voolstra C. , Heinen T. J. A. J. , Baines J. F. , Rottscheidt R. , Ihle S. , Müller W. , Bonhomme F. , Tautz D.
Published: May 2006

Changes in gene expression are known to occur between closely related species, but it is not yet clear how many of these are due to random fixation of allelic variants or due to adaptive events. In a microarray survey between subspecies of the Mus musculus complex, we identified the mitogen-activated protein-kinase-kinase MKK7 as a candidate for change in gene expression. Quantitative PCR experiments with multiple individuals from each subspecies confirmed a specific and significant up-regulation in the testis of M. m. domesticus. Northern blot analysis shows that this is due to a new transcript that is not found in other tissues, nor in M. m. musculus. A cis-trans test via allele specific expression analysis of the MKK7 gene in F1 hybrids between domesticus and musculus shows that the expression change is mainly caused by a mutation located in cis. Nucleotide diversity was found to be significantly reduced in a window of at least 20 kb around the MKK7 locus in domesticus, indicative of a selective sweep. Because the MKK7 gene is involved in modulating a kinase signalling cascade in a stress response pathway, it seems a plausible target for adaptive differences between subspecies, although the functional role of the new testis-specific transcripts will need to be further studied.
Mycelial growth and exclusion of Heterobasidion parviporum inoculated in branches of 15‐year‐old Picea abies clones
Authors: Swedjemark G. , Karlsson B.
Published: May 2006

Twigs of 22 clones of 15‐year‐old Picea abies grafts were inoculated with Heterobasidion parviporum in July and in September 2003. Fungal growth varied between clones and exclusion of the pathogen varied significantly among clones inoculated in July. The results indicate that twigs exhibit the same infection pattern as cuttings when inoculated with H. parviporum and that exclusion of the pathogen in twigs is a clone‐dependent character that occurs during the vegetation period.
The relationships between leptin concentrations and body fat reserves in lambs are reduced by short‐term fasting
Authors: Altmann M. , Sauerwein H. , Von Borell E.
Published: May 2006

Feed deprivation decreases plasma leptin concentrations depending on the amount of body fat reserves. While a greater response was observed in lean than in fat humans and rats, a few results for ruminants are inconsistent. The objective of this study was to determine the influence of feed deprivation on plasma leptin concentration in growing lambs with different body fat reserves and on the relationship between leptin and fatness. In addition, we included other hormones (growth hormone, GH; insulin‐like growth factor‐I, IGF‐I and insulin) involved in tissue development. Thirty male lambs of 40 kg live weight were used. Blood was sampled before and after a fasting period of 24 h. The lambs were slaughtered and dissected into several fat and lean tissues. Feed deprivation reduced plasma leptin by an average of 34.6% (p < 0.001). Obese lambs exhibited a greater decline of leptin than lean lambs (2.50 vs. 1.36 ng/ml, p < 0.05). The correlations between leptin and several fat tissues were lower in those lambs than that were fasted. This indicates that leptin concentrations after short‐term fasting scarcely reflect the extent of body fat reserves but reflect more the actual metabolic situation. Body fat did not significantly influence the response of GH, IGF‐I and insulin to fasting in most cases.
Short‐term effects of metformin in type 2 diabetes
Authors: Eriksson A. , Attvall S. , Bonnier M. , Eriksson J. W. , Rosander B. , Karlsson F. A.
Published: May 2006

Background:  Although metformin is widely used in the management of type 2 diabetes, its mechanism(s) of action is not fully known, and there have been remarkably few reports on short‐term effects of the drug. Here, we examined early effects on glucose and lipid metabolism, and on certain adipose tissue and inflammatory markers during treatment for 28 days.

Methods:  Twenty‐one patients were randomized to metformin (n = 16) or placebo (n = 5) and studied at baseline, 1, 2 and 4 weeks with blood sampling and oral glucose tolerance tests (OGTT). The active group received 500 mg metformin daily in week 1, 500 mg twice daily in week 2 and 1000 mg twice daily in week 3 and 4.

Results:  After 7 days of treatment, a reduced area under curve (AUC) for glucose at OGTT with no change in AUC for insulin levels was observed compared with baseline. Insulin sensitivity, as derived from the OGTT by Gutt’s index, was increased. Reductions in fasting plasma glucose, total and LDL‐cholesterol appeared after 14 days, and reductions in triglycerides, plasminogen activator inhibitor‐1 (PAI‐1) and leptin after 28 days of treatment. There were no changes in body weight, adiponectin or C‐reactive protein. Compared with placebo, the changes between day 0 and day 28 differed significantly with regard to AUC for glucose at OGTT and Gutt’s index, and showed strong trends for PAI‐1 and leptin.

Conclusions:  The data demonstrate that in type 2 diabetes metformin rapidly affects glucose handling without changing the concentrations of insulin. Reductions in PAI‐1 and leptin levels indicate that the early effects of metformin involve also the adipose tissue.
Social Policy & Administration: Journal and Discipline
Authors: Powell Martin
Published: May 2006

‘Social Policy & Administration’ is the oldest British social policy journal. This article charts its evolution over the last 40 years in the wider context of British social policy. It presents a timeline of the journal and discipline, an analysis of articles in the journal, and presents its most‐cited articles and most‐published authors. It uses this material to inform some impressions of the journal and discipline.
Access, Choice and Travel: Implications for Health Policy
Authors: Exworthy Mark , Peckham Stephen
Published: May 2006

The UK National Health Service is introducing policies offering patients a choice of the hospital where they would like to be treated. ‘Patient choice’ policies form part of a wider debate about the access to health care and the interaction between providers (including information, provision, performance and reputation) and patients (including knowledge, resources and willingness to travel). As the hospital of ‘choice’ might not necessarily be the ‘local’ provider, such policy developments are predicated on an assumption that some patients will be willing to travel further. This will, in turn, affect patients’ access to services. In general, use of services decreases with distance but this is dependent on accessibility to services, the organization of those services, the socio‐economic characteristics of the patient, perceptions of the provider and the condition for which they are to be treated. This article reviews the evidence on patients’ willingness to travel in terms of access to health care and assesses the emerging implications of and for current UK policy on patient choice.
Partisanship and Views about Immigration in Southern California: Just How Partisan is the Issue of Immigration?
Authors: Neiman Max , Johnson Martin , Bowler Shaun
Published: May 2006

Given the prevailing levels of elite partisan contentiousness over immigration issues, we expect to see mass attitudes towards immigration replicate this polarization. We explore the partisan implications of this issue by examining popular attitudes towards immigrants in California, where attitudes towards immigration and immigrants have formed central themes in a series of highly charged political campaigns and elite discourse on the issue is polarized. Yet even in California we find that many different kinds of voters share a surprisingly similar set of concerns about the flow of immigrants into the nation. We are particularly interested in whether Democrats and Republicans view the public policy consequences of immigration in similar or different ways. We find that Republicans more likely indicate they think immigration will have harmful effects on social and policy outcomes in the United States, but Democrats tend to share similar concerns. One consequence of this pattern is that the US Republican Party ‐ at least the party in California ‐ may be able to use the immigration issue as a wedge to attract support from people who tend to support Democratic candidates, often thought friendlier to immigrants.
Regulation of tyrosine hydroxylase gene expression by retinoic acid receptor
Authors: Jeong Hyerhan , Kim Mi‐Soo , Kim Sung‐Woo , Kim Kwang‐Soo , Seol Wongi
Published: May 2006

Retinoic acid (RA), a derivative of vitamin A, critically controls brain patterning and neurogenesis during embryogenesis, and is known to regulate morphological differentiation of catecholaminergic neuronal cells. In this study, we investigated whether the retinoic acid receptor (RAR), a transcription factor specifically activated by all‐trans‐RA, could directly regulate transcription of tyrosine hydroxylase (TH), the first and rate‐limiting step in the catecholamine biosynthesis pathway. First, treating TH‐expressing human neuroblastoma SK‐N‐BE(2)C cells with all‐trans RA resulted in an approximately 1.7‐fold increase in endogenous TH mRNA expression, as determined by real‐time PCR analysis. Second, when SK‐N‐BE(2)C cells were transiently co‐transfected with the TH promoter‐luciferase reporter construct, reporter gene expression was prominently activated by RAR in a ligand‐dependent manner. Third, we identified a putative RAR responsive cis‐regulatory element at − 1500 to − 1487 bp in the TH upstream promoter region by deletional and site‐directed mutational analysis. Finally, we demonstrated that this putative motif directly interacts with RAR protein in a sequence‐specific manner by means of an electrophoretic mobility shift assay. Taken together, our results indicate that the TH gene may be a direct downstream target of the RA signaling pathway and that RAR is able to activate TH transcription through interaction with an upstream sequence motif residing at − 1500 to − 1487 bp.
Molecular determinants of ginkgolide binding in the glycine receptor pore
Authors: Hawthorne Rebecca , Cromer Brett A. , Ng Hooi‐Ling , Parker Michael W. , Lynch Joseph W.
Published: May 2006

Ginkgolides are potent blockers of the glycine receptor Cl– channel (GlyR) pore. We sought to identify their binding sites by comparing the effects of ginkgolides A, B and C and bilobalide on α1, α2, α1β and α2β GlyRs. Bilobalide sensitivity was drastically reduced by incorporation of the β subunit. In contrast, the sensitivities to ginkgolides B and C were enhanced by β subunit expression. However, ginkgolide A sensitivity was increased in the α2β GlyR relative to the α2 GlyR but not in the α1β GlyR relative to the α1 GlyR. We hypothesised that the subunit‐specific differences were mediated by residue differences at the second transmembrane domain 2′ and 6′ pore‐lining positions. The increased ginkgolide A sensitivity of the α2β GlyR was transferred to the α1β GlyR by the G2′A (α1 to α2 subunit) substitution. In addition, the α1 subunit T6′F mutation abolished inhibition by all ginkgolides. As the ginkgolides share closely related structures, their molecular interactions with pore‐lining residues were amenable to mutant cycle analysis. This identified an interaction between the variable R2 position of the ginkgolides and the 2′ residues of both α1 and β subunits. These findings provide strong evidence for ginkgolides binding at the 2′ pore‐lining position.
Outcomes of involuntary hospital admission – a review
Authors: Katsakou C. , Priebe S.
Published: May 2006

Introduction:  This paper reviews studies on outcomes of involuntary hospital admissions in general adult psychiatry, and predictors of outcomes.

Method:  Studies assessing observer‐rated clinical change and self‐rated outcomes were identified. Relevant databases were searched and authors were contacted. Studies were classified according to quality criteria.

Results:  Eighteen studies fulfilled the inclusion criteria. Most involuntarily admitted patients show substantial clinical improvement over time. Retrospectively, between 33% and 81% of patients regard the admission as justified and/or the treatment as beneficial. Data on predictors of outcomes is limited and inconsistent. Patients with more marked clinical improvement tend to have more positive retrospective judgements.

Conclusion:  A substantial number of involuntary patients do retrospectively not feel that their admission was justified and beneficial. At least for this group, new approaches might have to be considered. Larger studies are required to identify predictors on which patients are likely to fall into this group.
Towards a Metaphorology of the Novel
Authors: Heyerick Koenraad
Published: May 2006

Most of the attempts to define the novel seem condemned in advance to an insignificant vagueness or a restricted view on the genre. Not surprisingly, writers have often resorted to analogy and metaphorical language to qualify the genre and talk about the essential aims of their work, thus overcoming the novel's resistance to definition. After briefly examining a number of theoretical implications that this question raises, I will investigate two metaphorical constellations with which the novelistic genre has been identified in early modern Europe (Mateo Alemán and the Marquis de Sade). I will tackle these metaphors not only as rhetorical devices, but also and foremost as authentic ways of grasping the connections between writer, novel form and reader on the one hand, and the novel and its larger cultural‐historical context on the other. As such, this essay wants to be a contribution to what one could call, in line with Hans Blumenberg, a metaphorology of the novel.
Structural basis for the recognition of complex‐type biantennary oligosaccharides by Pterocarpus angolensis lectin
Authors: Buts Lieven , Garcia‐Pino Abel , Imberty Anne , Amiot Nicolas , Boons Geert‐Jan , Beeckmans Sonia , Versées Wim , Wyns Lode , Loris Remy
Published: May 2006

The crystal structure of Pterocarpus angolensis lectin is determined in its ligand‐free state, in complex with the fucosylated biantennary complex type decasaccharide NA2F, and in complex with a series of smaller oligosaccharide constituents of NA2F. These results together with thermodynamic binding data indicate that the complete oligosaccharide binding site of the lectin consists of five subsites allowing the specific recognition of the pentasaccharide GlcNAcβ(1–2)Manα(1–3)[GlcNAcβ(1–2)Manα(1–6)]Man. The mannose on the 1–6 arm occupies the monosaccharide binding site while the GlcNAc residue on this arm occupies a subsite that is almost identical to that of concanavalin A (con A). The core mannose and the GlcNAcβ(1–2)Man moiety on the 1–3 arm on the other hand occupy a series of subsites distinct from those of con A.
Effects of repetitive TMS on visually evoked potentials and EEG in the anaesthetized cat: dependence on stimulus frequency and train duration
Authors: Aydin‐Abidin Selcen , Moliadze Vera , Eysel Ulf T. , Funke Klaus
Published: May 2006

Repetitive transcranial magnetic stimulation (rTMS) has been shown to alter cortical excitability that lasts beyond the duration of rTMS application itself. High‐frequency rTMS leads primarily to facilitation, whereas low‐frequency rTMS leads to inhibition of the treated cortex. However, the contribution of rTMS train duration is less clear. In this study, we investigated the effects of nine different rTMS protocols, including low and high frequencies, as well as short and long applications (1, 3 and 10 Hz applied for 1, 5 and 20 min), on visual cortex excitability in anaesthetized and paralysed cats by means of visual evoked potential (VEP) and electroencephalography (EEG) recordings. Our results show that 10 Hz rTMS applied for 1 and 5 min significantly enhanced early VEP amplitudes, while 1 and 3 Hz rTMS applied for 5 and 20 min significantly reduced them. No significant changes were found after 1 and 3 Hz rTMS applied for only 1 min, and 10 Hz rTMS applied for 20 min. EEG activity was only transiently (<20 s) affected, with increased delta activity after 1 and 3 Hz rTMS applied for 1 or 5 min. These findings indicate that the effects of rTMS on cortical excitability depend on the combination of stimulus frequency and duration (or total number of stimuli): short high‐frequency trains seem to be more effective than longer trains, and low‐frequency rTMS requires longer applications. Changes in the spectral composition of the EEG were not correlated to changes in VEP size.
Short‐term reorganization of input‐deprived motor vibrissae representation following motor disconnection in adult rats
Authors: Franchi Gianfranco , Veronesi Carlo
Published: May 2006

It has been proposed that abnormal vibrissae input to the motor cortex (M1) mediates short‐term cortical reorganization after facial nerve lesion. To test this hypothesis, we cut first the infraorbital nerve (ION cut) and then the facial nerve (VII cut) in order to evaluate M1 reorganization without any aberrant, facial‐nerve‐lesion‐induced sensory feedback. In each animal, M1 output was assessed in both hemispheres by mapping movements induced by intracortical microstimulation. M1 output was compared in different types of peripheral manipulations: (i) contralateral intact vibrissal pad (intact hemispheres), (ii) contralateral VII cut (VII hemispheres), (iii) contralateral ION cut (ION hemispheres), (iv) contralateral VII cut after contralateral ION cut (ION + VII hemispheres), (v) contralateral pad botulinum‐toxin‐injected after ION cut (ION + BTX hemispheres). Right and left hemispheres in untouched animals were the reference for normal M1 map (control hemispheres). Findings demonstrated that: (1) in ION hemispheres, the mean size of the vibrissae representation was not significantly different from those in intact and control hemispheres; (2) reorganization of the vibrissae movement representation clearly emerged only in hemispheres where the contralateral vibrissae pad had undergone motor output disconnection (VII cut hemispheres); (3) the persistent loss of vibrissae input did not change the M1 reorganization pattern during the first 48 h after motor paralysis (ION + VII cut and ION + BTX hemispheres). Thus, after motor paralysis, vibrissa input does not provide the gating signal necessary to trigger M1 reorganization.
Nerve growth factor affects Ca2+ currents via the p75 receptor to enhance prolactin mRNA levels in GH3 rat pituitary cells
Authors: López‐Domínguez Adriana M. , Espinosa Juan Luis , Navarrete Araceli , Avila Guillermo , Cota Gabriel
Published: May 2006

In clonal pituitary GH3 cells, spontaneous action potentials drive the opening of Cav1 (L‐type) channels, leading to Ca2+ transients that are coupled to prolactin gene transcription. Nerve growth factor (NGF) has been shown to stimulate prolactin synthesis by GH3 cells, but the underlying mechanisms are unknown. Here we studied whether NGF influences prolactin gene expression and Ca2+ currents. By using RT‐PCR, NGF (50 ng ml−1) was found to augment prolactin mRNA levels by ∼80% when applied to GH3 cells for 3 days. A parallel change in the prolactin content was detected by Western blotting. Both NGF‐induced responses were mimicked by an agonist (Bay K 8644) and prevented by a blocker (nimodipine) of L‐type channels. In whole‐cell patch‐clamp experiments, NGF enhanced the L‐type Ca2+ current by ∼2‐fold within 60 min. This effect reversed quickly upon growth factor withdrawal, but was maintained for days in the continued presence of NGF. In addition, chronic treatment (≥ 24 h) with NGF amplified the T‐type current, which flows through Cav3 channels and is thought to support pacemaking activity. Thus, NGF probably increases the amount of Ca2+ that enters per action potential and may also induce a late increase in spike frequency. MC192, a specific antibody for the p75 neurotrophin receptor, but not tyrosine kinase inhibitors (K252a and lavendustin A), blocked the effects of NGF on Ca2+ currents. Overall, the results indicate that NGF activates the p75 receptor to cause a prolonged increase in Ca2+ influx through L‐type channels, which in turn up‐regulates the prolactin mRNA.
Resource Letter TMGR-1: Teaching the mathematics of general relativity
Authors: Wald Robert M.
Published: May 2006

This Resource Letter provides some guidance on issues that arise in teaching general relativity at both the undergraduate and graduate levels. Particular emphasis is placed on strategies for presenting the mathematical material needed for the formulation of general relativity.
Random numbers and random matrices: Quantum chaos meets number theory
Authors: Timberlake Todd
Published: May 2006

The statistical analysis of the eigenvalues of quantum systems has become an important tool in understanding the connections between classical and quantum physics. The statistical properties of the eigenvalues of a quantum system whose classical counterpart is integrable match those of random numbers. The eigenvalues of a chaotic classical system have statistical properties like those of the eigenvalues of random Hermitian matrices. The statistical properties of random numbers and eigenvalues of random Hermitian matrices are examined and the connection between these properties and the statistics of eigenvalues of quantum systems is illustrated, using the quantum standard map as an example. The relevance of these ideas to some problems in the theory of prime numbers is explored.
Sequential Immunization with V3 Peptides from Primary Human Immunodeficiency Virus Type 1 Produces Cross-Neutralizing Antibodies against Primary Isolates with a Matching Narrow-Neutralization Sequence Motif
Authors: Eda Yasuyuki , Takizawa Mari , Murakami Toshio , Maeda Hiroaki , Kimachi Kazuhiko , Yonemura Hiroshi , Koyanagi Satoshi , Shiosaki Kouichi , Higuchi Hirofumi , Makizumi Keiichi , Nakashima Toshihiro , Osatomi Kiyoshi , Tokiyoshi Sachio , Matsushita Shuzo , Yamamoto Naoki , Honda Mitsuo
Published: May 2006

An antibody response capable of neutralizing not only homologous but also heterologous forms of the CXCR4-tropic human immunodeficiency virus type 1 (HIV-1) MNp and CCR5-tropic primary isolate HIV-1 JR-CSF was achieved through sequential immunization with a combination of synthetic peptides representing HIV-1 Env V3 sequences from field and laboratory HIV-1 clade B isolates. In contrast, repeated immunization with a single V3 peptide generated antibodies that neutralized only type-specific laboratory-adapted homologous viruses. To determine whether the cross-neutralization response could be attributed to a cross-reactive antibody in the immunized animals, we isolated a monoclonal antibody, C25, which neutralized the heterologous primary viruses of HIV-1 clade B. Furthermore, we generated a humanized monoclonal antibody, KD-247, by transferring the genes of the complementary determining region of C25 into genes of the human V region of the antibody. KD-247 bound with high affinity to the “PGR” motif within the HIV-1 Env V3 tip region, and, among the established reference antibodies, it most effectively neutralized primary HIV-1 field isolates possessing the matching neutralization sequence motif, suggesting its promise for clinical applications involving passive immunizations. These results demonstrate that sequential immunization with B-cell epitope peptides may contribute to a humoral immune-based HIV vaccine strategy. Indeed, they help lay the groundwork for the development of HIV-1 vaccine strategies that use sequential immunization with biologically relevant peptides to overcome difficulties associated with otherwise poorly immunogenic epitopes.
Gangliosides Are Essential for Bovine Adeno-Associated Virus Entry
Authors: Schmidt Michael , Chiorini John A.
Published: May 2006

Recombinant adeno-associated viruses (AAV) are promising gene therapy vectors. We have recently identified a bovine adeno-associated virus (BAAV) that demonstrates unique tropism and transduction activity compared to primate AAVs. To better understand the entry pathway and cell tropism of BAAV, we have characterized the initial cell surface interactions required for transduction with BAAV vectors. Like a number of AAVs, BAAV requires cell surface sialic acid groups for transduction and virus attachment. However, glycosphingolipids (GSLs), not cell surface proteins, were required for vector entry and transduction. Incorporation of gangliosides, ceramide-based glycolipids containing one or more sialic acid groups, into the cytoplasmic cell membranes of GSL-depleted COS cells partially reconstituted BAAV transduction. The dependency of BAAV on gangliosides for transduction was further confirmed by studies with C6 cells, a rat glioma cell line that is deficient in the synthesis of complex gangliosides. C6 cells were resistant to transduction by BAAV. Addition of gangliosides to C6 cells prior to transduction rendered the cells susceptible to transduction by BAAV. Therefore, gangliosides are a likely receptor for BAAV.
Deletion of Open Reading Frame UL26 from the Human Cytomegalovirus Genome Results in Reduced Viral Growth, Which Involves Impaired Stability of Viral Particles
Authors: Lorz Kerstin , Hofmann Heike , Berndt Anja , Tavalai Nina , Mueller Regina , Schlötzer-Schrehardt Ursula , Stamminger Thomas
Published: May 2006

We previously showed that open reading frame (ORF) UL26 of human cytomegalovirus, a member of the US22 multigene family of betaherpesviruses, encodes a novel tegument protein, which is imported into cells in the course of viral infection. Moreover, we demonstrated that pUL26 contains a strong transcriptional activation domain and is capable of stimulating the major immediate-early (IE) enhancer-promoter. Since this suggested an important function of pUL26 during the initiation of the viral replicative cycle, we sought to ascertain the relevance of pUL26 by construction of a viral deletion mutant lacking the UL26 ORF using the bacterial artificial chromosome mutagenesis procedure. The resulting deletion virus was verified by PCR, enzyme restriction, and Southern blot analyses. After infection of human foreskin fibroblasts, the UL26 deletion mutant showed a small-plaque phenotype and replicated to significantly lower titers than wild-type or revertant virus. In particular, we noticed a striking decrease of infectious titers 7 days postinfection in a multistep growth experiment, whereas the release of viral DNA from infected cells was not impaired. A further investigation of this aspect revealed a significantly diminished stability of viral particles derived from the UL26 deletion mutant. Consistent with this, we observed that the tegument composition of the deletion mutant deviates from that of the wild-type virus. We therefore hypothesize that pUL26 plays a role not only in the onset of IE gene transcription but also in the assembly of the viral tegument layer in a stable and correct manner.
Quantification of genetic relationships among A genomes of wheats
Authors: Brandolini A , Vaccino P , Boggini G , Özkan H , Kilian B , Salamini F
Published: May 2006

The genetic relationships of A genomes of Triticum urartu (Au) and Triticum monococcum (Am) in polyploid wheats are explored and quantified by AFLP fingerprinting. Forty-one accessions of A-genome diploid wheats, 3 of AG-genome wheats, 19 of AB-genome wheats, 15 of ABD-genome wheats, and 1 of the D-genome donor Ae. tauschii have been analysed. Based on 7 AFLP primer combinations, 423 bands were identified as potentially A genome specific. The bands were reduced to 239 by eliminating those present in autoradiograms of Ae. tauschii, bands interpreted as common to all wheat genomes. Neighbour-joining analysis separates T. urartu from T. monococcum. Triticum urartu has the closest relationship to polyploid wheats. Triticum turgidum subsp. dicoccum and T. turgidum subsp. durum lines are included in tightly linked clusters. The hexaploid spelts occupy positions in the phylogenetic tree intermediate between bread wheats and T. turgidum. The AG-genome accessions cluster in a position quite distant from both diploid and other polyploid wheats. The estimates of similarity between A genomes of diploid and polyploid wheats indicate that, compared with Am, Auhas around 20% higher similarity to the genomes of polyploid wheats. Triticum timo pheevii AG genome is molecularly equidistant from those of Auand Amwheats.Key words: A genome, Triticum, genetic relationships, AFLP.
A genetic linkage map ofSilene vulgarisbased on AFLP markers
Authors: Bratteler Martin , Lexer Christian , Widmer Alex
Published: May 2006

A genetic linkage map of an intraspecific cross between 2 Silene vulgaris s.l. ecotypes is presented. Three-hundred AFLP markers from 2 different restriction enzyme combinations were used to genotype an F2mapping population. Maternal and paternal pure-coupling phase maps with 114 and 186 markers on 12 and 13 linkage groups, respectively, were constructed. Total map length of the paternal and maternal maps are 547 and 446 Kosambi cM, respectively. Nearly half of the markers (49%) exhibited significant transmission ratio distortion. Genome coverage and potential causes of the observed segregation ratio distortions are discussed. The maps represent a first step towards the identification of quantitative trait loci associated with habitat adaptation in the non-model species Silene vulgaris.Key words: AFLP, genome mapping, segregation distortion, Silene vulgaris.
Linkage and mapping analyses of the densonucleosis non-susceptible gene nsd-Z in the silkworm Bombyx mori using SSR markers
Authors: Li Muwang , Guo Qiuhong , Hou Chengxiang , Miao Xuexia , Xu Anying , Guo Xijie , Huang Yongping
Published: May 2006

In the silkworm Bombyx mori, non-susceptibility to the Zhenjiang (China) strain of the densonucleosis virus (DNV-Z) is controlled by the recessive gene nsd-Z (non-susceptible to DNV-Z), which is located on chromosome 15. Owing to a lack of crossing over in females, reciprocal backcrossed F1 (BC1) progeny were used for linkage analysis and mapping of the nsd-Z gene using silkworm strains Js and L10, which are classified as being highly susceptible and non-susceptible to DNV-Z, respectively. BC1 larvae were inoculated with the DNV-Z virus at the first instar, and DNA was extracted from the individual surviving pupae and analyzed for simple sequence repeat (SSR) markers. The nsd-Z gene was found to be linked to 7 SSR markers, as all the surviving larvae in the BC1♀ (F1♀ × L10♂) showed the homozygous profile of strain L10, and the sick larvae in the BC1♀ (F1♀ × L10♂) showed the heterozygous profile of Js × L10 F1 hybrids. Using a reciprocal BC1♂ (L101♀ × F1♂) cross, we constructed a linkage map of 80.6 cM, with nsd-Z mapped at 30 cM and the closest SSR marker at a distance of 4.4 cM.Key words: SSR markers, densonucleosis virus, non-susceptible gene, silkworm, Bombyx mori.
Prediction and functional analysis of the replication origin of the linear plasmid pSCL2 inStreptomyces clavuligerus
Authors: Wu Wei , Leblanc Shannon K. D , Piktel James , Jensen Susan E , Roy Kenneth L
Published: May 2006

pSCL2 (120 kb), one of the linear plasmids found in Streptomyces clavuligerus NRRL3585, was isolated and partially sequenced. Computational analysis of the central region of pSCL2 revealed the presence of two open reading frames that appear to encode proteins highly homologous to RepL1 and RepL2, replication proteins from pSLA2-L, the large linear plasmid in Streptomyces rochei. The S. clavuligerus open reading frames were designated repC1 and repC2, encoding the proteins RepC1 (150 amino acids) and RepC2 (102 amino acids), respectively. The RepC and RepL proteins have identical translation features and very similar predicted secondary and tertiary structures. Functional analysis confirmed that RepC1 is essential for replication initiation of pSCL2, whereas RepC2 is dispensable but may play a role in copy number control. The RepC and RepL proteins do not show similarity to any other bacterial plasmid replication proteins. Three regions of DNA sequence, Box 1 (1050–850 bp), Box 2 (723–606 bp), and Box 3 (224–168 bp), located upstream of repC1, were also shown to be essential or very important for replication of pSCL2.Key words: pSCL2, Streptomyces clavuligerus, replication origin.
Transcriptional analysis of thePseudomonas aeruginosa toxAregulatory geneptxR
Authors: Colmer-Hamood Jane A , Aramaki Hironori , Gaines Jennifer M , Hamood Abdul N
Published: May 2006

The expression of the exotoxin A gene (toxA) in Pseudomonas aeruginosa is a complicated process that involves several regulators, including ptxR, which enhances toxA expression by 4- to 5-fold. Available evidence suggests that ptxR is expressed from two separate promoters, P1 and P2. Previous evidence indicated the presence, within the ptxR upstream region, of binding sites for several regulatory proteins, including PtxS, which negatively regulates ptxR expression. We utilized nested deletion and in vitro transcription analyses to examine the regulation of ptxR expression. The results from nested deletion analysis suggest that under aerobic conditions in iron-deficient medium, ptxR expression follows a biphasic curve that involves the P1 promoter only. Iron eliminated the second peak of ptxR expression but did not affect expression from the P2 promoter. Under microaerobic conditions, iron represses ptxR expression from subclones that carry P1 alone or P2 alone at both early and late stages of growth. Under anaerobic conditions, ptxR expression increases considerably. In addition, our results suggest that different segments of the ptxR upstream region play specific roles in ptxR expression; their deletion caused variations in the level as well as the pattern of ptxR expression. Our results also indicate that negative regulation of ptxR expression by PtxS does not occur through the PtxS binding site within the ptxR–ptxS intergenic region. In vitro transcription analysis using σ70-reconstituted P. aeruginosa RNA polymerase produced one transcript that closely resembles T1, indicating that P1 is recognized by σ70. RNA polymerase reconstituted with either RpoS or AlgU produced no transcripts. However, a transcript was produced by RpoH-reconstituted RNA polymerase.Key words: ptxR, regulation, Pseudomonas aeruginosa, PAO1.
Predisposing conditions forCandidaspp. carriage in the oral cavity of denture wearers and individuals with natural teeth
Authors: Lyon Juliana Pereira , da Costa Sérgio Carvalho , Totti Valéria Maria Gomes , Munhoz Maira Forestti Vieira , de Resende Maria Aparecida
Published: May 2006

Candida species are a normal commensal present in a large percentage of healthy individuals. Denture wearers are predisposed to the development of candidosis and to the presence of Candida spp. The presence of the yeast, even in healthy subjects, should be considered more carefully. We investigated the prevalence of Candida spp. in 112 denture wearers and 103 individuals with natural teeth, patients from the clinic of total prosthesis of the Dental School of the Federal University of Minas Gerais, Brazil, and from the School of Pharmacy and Dentistry of Alfenas, Brazil. Factors like gender, age over 60 years, low education, and xerostomia were directly associated with the presence of Candida yeasts at a significance level of 5% (p > 0.05). However, the major predisposing factor for the carrier state was wearing dentures (p = 0.001). Candida isolates were identified using morphological and biochemical profiles. Seventy-one isolates were identified as C. albicans (65.1%), 15 as C. glabrata (13.7%), 8 as C. parapsilosis (7.3%), 3 as C. krusei (2.7%), and 12 as C. tropicalis (11.0%). Susceptibility testing to fluconazole and itraconazole was also performed with the strains obtained. Both drugs showed a strong inhibition against most oral isolates.Key words: yeast infection, prosthetic devices, oral cavity.
Cerebellar fastigial nuclei activity during blood pressure challenges
Authors: Rector D. M. , Richard C. A. , Harper R. M.
Published: May 2006

The cerebellar fastigial nuclei (FN) assist in regulating compensatory responses to large blood pressure changes and show structural injury and functional impairment to cardiovascular challenges in syndromes with sleep-disordered breathing. The patterned time course of FN responses to elevation or lowering of blood pressure and location of responsive regions within the nuclei are unclear. We evaluated FN neural activity in six anesthetized rats using optical imaging procedures during elevation and lowering of arterial pressure by phenylephrine and nitroprusside, respectively. Hypertension diminished optical correlates of FN neural activity, while measures of activity increased to hypotension, with peak neural responses occurring 5–10 s later than peak blood pressure changes. Blood pressure responses were followed by heart rate changes, and peak respiratory rates developed even later, in close temporal proximity to FN activity patterns. Although overall topographical response trends were similar, regional patterns of altered neural activity appeared to both hypertension and hypotension. The extent of neural change was greater during recovery from hypertension than for hypotension at high-dose levels. Blood pressure levels saturated with increasing phenylephrine doses, while FN activity continued to decline. No saturation appeared in heart or respiratory rate trends. The findings suggest that the FN compensate for large blood pressure changes by sympathoexcitatory and inhibitory processes, which accompany late-developing somatic or respiratory adjustments.
Matrix Metalloproteinase 2 Activation of Transforming Growth Factor-β1 (TGF-β1) and TGF-β1–Type II Receptor Signaling Within the Aged Arterial Wall
Authors: Wang Mingyi , Zhao Di , Spinetti Gaia , Zhang Jing , Jiang Li-Qun , Pintus Gianfranco , Monticone Robert , Lakatta Edward G.
Published: May 2006

Objective—

To study matrix metalloproteinase 2 (MMP-2) effects on transforming growth factor-β1 (TGF-β1) activation status and downstream signaling during arterial aging.

Methods and Results—

Western blotting and immunostaining showed that latent and activated TGF-β1 are markedly increased within the aorta of aged Fisher 344 cross-bred Brown Norway (30 months of age) rats compared with adult (8 months of age) rats. Aortic TGF-β1–type II receptor (TβRII), its downstream molecules p-similar to mad-mother against decapentaplegic (SMAD)2/3 and SMAD4, fibronectin, and collagen also increased with age. Moreover, TGF-β1 staining is colocalized with that of activated MMP-2 within the aged arterial wall and vascular smooth muscle cell (VSMC) in vitro, and this physical association was confirmed by coimmunoprecipitation. Incubation of young aortic rings ex vivo or VSMCs in vitro with activated MMP-2 enhanced active TGF-β1, collagen, and fibronectin expression to the level of untreated old counterparts, and this effect was abolished via inhibitors of MMP-2. Interestingly, in old untreated rings or VSMCs, the increased TGF-β1, fibronectin, and collagen were also substantially reduced by inhibition of MMP-2.

Conclusions—

Active TGF-β1, its receptor, and receptor-mediated signaling increase within the aortic wall with aging. TGF-β1 activation is dependent, in part at least, by a concomitant age-associated increase in MMP-2 activity. Thus, MMP-2–activated TGF-β1, and subsequently TβRII signaling, is a novel molecular mechanism for arterial aging.
Early apoptosis of blood monocytes in the septic host: is it a mechanism of protection in the event of septic shock?
Authors: Giamarellos-Bourboulis Evangelos J , Routsi Christina , Plachouras Diamantis , Markaki Vassiliki , Raftogiannis Maria , Zervakis Dimitrios , Koussoulas Vassilios , Orfanos Stylianos , Kotanidou Anastasia , Armaganidis Apostolos , Roussos Charis , Giamarellou Helen
Published: May 2006

Introduction

Based on the central role of the triggering of monocytes for the initiation of the septic cascade, it was investigated whether apoptosis of blood monocytes in septic patients is connected to their final outcome.

Methods

Blood monocytes were isolated from 90 patients with septic syndrome due to ventilator-associated pneumonia on days 1, 3, 5 and 7 from the initiation of symptoms. Apoptosis was defined after incubation with annexin-V-fluorescein isothiocyanate and propidium iodine and reading by a flow cytometer. The function of first-day monocytes was evaluated from the concentrations of tumour necrosis factor alpha (TNFα) and IL-6 in supernatants of cell cultures after triggering with endotoxins. TNFα, IL-6 and IL-8 were estimated in serum by an enzyme immunoassay.

Results

Mortality rates of patients with apoptosis ≤50% compared with patients with apoptosis >50% were 49.12% and 15.15%, respectively (P < 0.0001). Kaplan-Meier analysis showed a 28-day survival benefit in patients with septic shock and monocyte apoptosis >50% compared with those patients with apoptosis ≤50% (P = 0.0032). Production of IL-6 by monocytes on the first day by patients with apoptosis ≤50% was similar compared with monocytes isolated from healthy controls. Serum concentrations of TNFα were higher in patients with monocyte apoptosis ≤50% and septic shock compared with patients with apoptosis >50% on day 7; similar findings occurred for serum IL-6 on days 1 and 7 and for serum IL-8 on days 1 and 5.

Conclusion

Early apoptosis of monocytes upon presentation of clinical signs of sepsis is connected to a favourable outcome. These findings are of particular importance for the patient with septic shock, where they might constitute a mechanism of pathogenesis.
Point‐of‐care Test Identifies Diabetic Ketoacidosis at Triage
Authors: Naunheim Rosanne , Jang Timothy J. , Banet Gerald , Richmond Alec , McGill Janet
Published: May 2006

Background:
Diabetic ketoacidosis (DKA) is a common, life‐threatening complication of diabetes. The diagnosis of DKA relies on signs and symptoms, plus laboratory findings of blood glucose (BG) of >250 mg/dL, an anion gap (AG) of ≥15 mmol/L, and carbon dioxide (CO2) of ≤18 mmol/L when other causes of acidosis are excluded.

Objectives:
To compare the results of a point‐of‐care test for the ketone beta‐hydroxybutyrate (β‐OHB) with standard measures for accuracy in predicting DKA.

Methods:
After providing informed consent, 160 patients who presented with BG of >250 mg/dL underwent testing for β‐OHB with the Precision Xtra meter (Abbott Laboratories, North Chicago, IL) at triage in a large urban hospital emergency department. The diagnosis of DKA was made by clinicians by using standard clinical criteria without knowledge of the β‐OHB test.

Results:
A diagnosis of DKA was made in 57 of 160 subjects. The β‐OHB values correlated strongly with AG (r= 0.66, p < 0.001) and with CO2 (r=−0.69, p < 0.001), as well as with glucose (r= 0.31, p < 0.001). Cross‐classification of DKA vs. β‐OHB yielded sensitivity of 98% (95% CI = 91% to 100%), specificity of 85% (95% CI = 78% to 91%), with a positive likelihood ratio of 6.7 (95% CI = 4.22 to 10.78), and negative likelihood ratio of 0.021 (95% CI = 0.003 to 0.144) at the manufacturer‐suggested β‐OHB level of 1.5.

Conclusions: The point‐of‐care test for β‐OHB was as sensitive as more established indicators of DKA. It is more useful than glucose alone for the diagnosis of DKA and offers immediate diagnosis of patients at triage.