bluuebunny/crossref_metadata_2025 huggingface dataset:
Two new Cryptoxilos species (Hymenoptera:Braconidae:Euphorinae) from New Zealand and Fiji parasitising adult Scolytinae (Coleoptera)
Authors: Shaw Scott Richard , Berry Jocelyn A.
Published: December 2005

Two new species of Cryptoxilos are described from the South Pacific region. A new species from Auckland, New Zealand, Cryptoxilos thorpei Shaw & Berry, is described and illustrated. This is the first described species of the genus Cryptoxilos from New Zealand. The species is associated with a scolytine bark beetle, Chaetoptelius mundulus (Broun) (Coleoptera : Scolytinae), on a dead Pittosporum tree. A second new species, Cryptoxilos beaveri Shaw & Berry, is described from Fiji, also a new locality record for the genus. The species is associated with cryphaline ambrosia beetles, Hypothenemus curtipennis and Hypothenemus dorsosignatus, in the tree Commersonia bartramia. The existing subgenus classification system is discussed in relation to character states expressed in these two new species. Neither new species can be easily assigned to a subgenus based on the existing system. Given serious problems in the consistent application of the previous subgenus system, we recommend that subgenera be abandoned and we treat subgenus Cryptoxiloides simply as a junior synonym of Cryptoxilos.
Relationships among the three major lineages of the Acari (Arthropoda:Arachnida) inferred from small subunit rRNA: paraphyly of the Parasitiformes with respect to the Opilioacariformes and relative rates of nucleotide substitution
Authors: Murrell Anna , Dobson Susan J. , Walter David E. , Campbell Nick J. H. , Shao Renfu , Barker Stephen C.
Published: December 2005

We inferred phylogeny among the three major lineages of the Acari (mites) from the small subunit rRNA gene. Our phylogeny indicates that the Opilioacariformes is the sister-group to the Ixodida+Holothyrida, not the Ixodida+Mesostigmata+Holothyrida, as previously thought. Support for this relationship increased when sites with the highest rates of nucleotide substitution, and thus the greatest potential for saturation with nucleotide substitutions, were removed. Indeed, the increase in support (and resolution) was despite a 70% reduction in the number of parsimony-informative sites from 408 to 115. This shows that rather than ‘noisy’ sites having no impact on resolution of deep branches, ‘noisy’ sites have the potential to obscure phylogenetic relationships. The arrangement, Ixodida+Holothyrida+Opilioacariformes, however, may be an artefact of long-branch attraction since relative-rate tests showed that the Mesostigmata have significantly faster rates of nucleotide substitution than other parasitiform mites. Thus, the fast rates of nucleotide substitution of the Mesostigmata might have caused the Mesostigmata to be attracted to the outgroup in our trees. We tested the hypothesis that the high rate of nucleotide substitution in some mites was related to their short generation times. The Acari species that have high nucleotide substitution rates usually have short generation times; these mites also tend to be more active and thus have higher metabolic rates than other mites. Therefore, more than one factor may affect the rate of nucleotide substitution in these mites.
Effects of bovine oviduct epithelial cells, fetal calf serum and bovine serum albumin on gene expression in single bovine embryos produced in the synthetic oviduct fluid culture system
Authors: Pedersen Mona E. , Øzdas Øzen Banu , Farstad Wenche , Tverdal Aage , Olsaker Ingrid
Published: December 2005

In this study the synthetic oviduct fluid (SOF) system with bovine oviduct epithelial cell (BOEC) co-culture is compared with an SOF system with common protein supplements. One thousand six hundred bovine embryos were cultured in SOF media supplemented with BOEC, fetal calf serum (FCS) and bovine serum albumin (BSA). Eight different culture groups were assigned according to the different supplementation factors. Developmental competence and the expression levels of five genes, namely glucose transporter-1 (Glut-1), heat shock protein 70 (HSP), connexin43 (Cx43), β-actin (ACTB) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), analysed as mRNA by using reverse transcription–polymerase chain reaction, were measured on bovine embryos cultured for 9 days. Gene expression of these in vitro-produced embryos was compared with the gene expression of in vivo-produced embryos. There was no significant difference found in embryo developmental competence between the Day 9 embryos in BOEC co-culture, FCS and BSA supplements in SOF media. However, differences in gene expression were observed. With respect to gene expression in in vivo and in vitro embryos, BOEC co-culture affected the same genes as did supplementation with FCS and BSA. HSP was the only gene that differed significantly between in vitro and in vivo embryos. When the different in vitro groups were compared, a significant difference between the BOEC co-culture and the FCS supplementation groups due to Glut-1 expression was observed.
Early onset of embryonic mortality in sub-fertile families of rainbow trout (Oncorhynchus mykiss)
Authors: Stoddard J. W. , Parsons J. E. , Nagler J. J.
Published: December 2005

Survival during early embryonic development is highly variable in oviparous fishes and appears to be related to events associated with the female at the time of ovulation and spawning. The goal of this study was to identify critical periods of mortality associated with early embryonic development in egg batches from female rainbow trout (Oncorhynchus mykiss) that were checked for ovulation every 5–7 days. The experiment was designed to specifically remove post-ovulatory ageing and reduce paternal variability. Embryo viability in 269 single-pair-mated families was systematically tracked at the following five stages: second cleavage (0.5 days post fertilisation (dpf)), elevated blastula (2.5 dpf), embryonic shield (6 dpf), embryonic keel (9 dpf), and retinal pigmentation (19 dpf). At each of the five stages families with embryo viability assessments of <80% were classed as sub-fertile, whereas those with >80% embryo viability were classed as fertile. Embryo viability in sub-fertile families was distinctly reduced at 0.5 dpf, in contrast to fertile families, but remained constant from that point through to 19 dpf. These results suggest that the critical period of early embryonic mortality in sub-fertile families of rainbow trout parallels events that occur at or shortly after fertilisation and is independent of post-ovulatory aging.
Heterotrimeric G proteins precouple with G protein-coupled receptors in living cells
Authors: Nobles Muriel , Benians Amy , Tinker Andrew
Published: December 2005

Using fluorescence resonance energy transfer (FRET) microscopy, we investigate how heterotrimeric G proteins interact with G protein-coupled receptors (GPCRs). In the absence of receptor activation, the α2A adrenergic and muscarinic M4 receptors are present on the cell membrane as dimers. Furthermore, there is an interaction between the G protein subunits αo, β1, and γ2 and a number of GPCRs including M4, α2A, the adenosine A1 receptor, and the dopamine D2 receptor under resting conditions. The interaction between GPCRs and Gα proteins shows specificity: there is interaction between the α2A receptor and Go, but little interaction between the α2A receptor and Gs. In contrast, the predominantly Gs-coupled prostacyclin receptor interacted with Gs, but there was little interaction between the prostacyclin receptor and Go. Inverse agonists did not change the FRET ratio, whereas the addition of agonist resulted in a modest fall. Our work suggests that GPCR dimers and the G protein heterotrimer are present at the cell membrane in the resting state in a pentameric complex.
Controlling ligand substitution reactions of organometallic complexes: Tuning cancer cell cytotoxicity
Authors: Wang Fuyi , Habtemariam Abraha , van der Geer Erwin P. L. , Fernández Rafael , Melchart Michael , Deeth Robert J. , Aird Rhona , Guichard Sylvie , Fabbiani Francesca P. A. , Lozano-Casal Patricia , Oswald Iain D. H. , Jodrell Duncan I. , Parsons Simon , Sadler Peter J.
Published: December 2005

Organometallic compounds offer broad scope for the design of therapeutic agents, but this avenue has yet to be widely explored. A key concept in the design of anticancer complexes is optimization of chemical reactivity to allow facile attack on the target site (e.g., DNA) yet avoid attack on other sites associated with unwanted side effects. Here, we consider how this result can be achieved for monofunctional “piano-stool” ruthenium(II) arene complexes of the type [(η6-arene)Ru(ethylenediamine)(X)]n+. A potentially important activation mechanism for reactions with biomolecules is hydrolysis. Density functional calculations suggested that aquation (substitution of X by H2O) occurs by means of a concerted ligand interchange mechanism. We studied the kinetics and equilibria for hydrolysis of 21 complexes, containing, as X, halides and pseudohalides, pyridine (py) derivatives, and a thiolate, together with benzene (bz) or a substituted bz as arene, using UV-visible spectroscopy, HPLC, and electrospray MS. The x-ray structures of six complexes are reported. In general, complexes that hydrolyze either rapidly {e.g., X = halide [arene = hexamethylbenzene (hmb)]} or moderately slowly [e.g., X = azide, dichloropyridine (arene = hmb)] are active toward A2780 human ovarian cancer cells, whereas complexes that do not aquate (e.g., X = py) are inactive. An intriguing exception is the X = thiophenolate complex, which undergoes little hydrolysis and appears to be activated by a different mechanism. The ability to tune the chemical reactivity of this class of organometallic ruthenium arene compounds should be useful in optimizing their design as anticancer agents.
Information-based clustering
Authors: Slonim Noam , Atwal Gurinder Singh , Tkačik Gašper , Bialek William
Published: December 2005

In an age of increasingly large data sets, investigators in many different disciplines have turned to clustering as a tool for data analysis and exploration. Existing clustering methods, however, typically depend on several nontrivial assumptions about the structure of data. Here, we reformulate the clustering problem from an information theoretic perspective that avoids many of these assumptions. In particular, our formulation obviates the need for defining a cluster “prototype,” does not require an
a priori
similarity metric, is invariant to changes in the representation of the data, and naturally captures nonlinear relations. We apply this approach to different domains and find that it consistently produces clusters that are more coherent than those extracted by existing algorithms. Finally, our approach provides a way of clustering based on collective notions of similarity rather than the traditional pairwise measures.
A regulator of nutritional copper signaling in
Chlamydomonas
is an SBP domain protein that recognizes the GTAC core of copper response element
Authors: Kropat Janette , Tottey Stephen , Birkenbihl Rainer P. , Depège Nathalie , Huijser Peter , Merchant Sabeeha
Published: December 2005

The
CRR1
(Copper Response Regulator) locus, required for both activating and repressing target genes of a copper- and hypoxia-sensing pathway in
Chlamydomonas
, encodes a 1,232-residue candidate transcription factor with a plant-specific DNA-binding domain named SBP, ankyrin repeats, and a C-terminal Cys-rich region, with similarity to a
Drosophila
metallothionein. The recombinant SBP domain of Crr1 shows zinc-dependent binding to functionally defined copper-response elements associated with the
CYC6
and
CPX1
promoters that contain a critical GTAC core sequence. Competition experiments indicate equivalent selectivity for copper-response elements from either promoter and 10-fold greater selectivity for the wild-type sequence vs. a sequence carrying a single mutation in the GTAC core. The SBP domain of
Chlamydomonas
Crr1 binds also to a related GTAC-containing sequence in the
Arabidopsis AP1
promoter that is the binding site of a defining member of the SBP family of DNA-binding proteins.
Chlamydomonas
Crr1 is most similar to a subset of the
Arabidopsis
SBP domain proteins, which include SPL1, SPL7, and SPL12. The abundance of the
CRR1
mRNA is only marginally copper-responsive, and although two mRNAs that differ with respect to splicing of the first intron are detected, there is no indication that the splicing event is regulated by metal nutrition or hypoxia. It is likely that the dramatic copper-responsive action of Crr1 occurs at the level of the polypeptide.
Development of functional human embryonic stem cell-derived neurons in mouse brain
Authors: Muotri Alysson R. , Nakashima Kinichi , Toni Nicolas , Sandler Vladislav M. , Gage Fred H.
Published: December 2005

Human embryonic stem cells are pluripotent entities, theoretically capable of generating a whole-body spectrum of distinct cell types. However, differentiation of these cells has been observed only in culture or during teratoma formation. Our results show that human embryonic stem cells implanted in the brain ventricles of embryonic mice can differentiate into functional neural lineages and generate mature, active human neurons that successfully integrate into the adult mouse forebrain. Moreover, this study reveals the conservation and recognition of common signals for neural differentiation throughout mammalian evolution. The chimeric model will permit the study of human neural development in a live environment, paving the way for the generation of new models of human neurodegenerative and psychiatric diseases. The model also has the potential to speed up the screening process for therapeutic drugs.
Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis
Authors: Gobbi G. , Bambico F. R. , Mangieri R. , Bortolato M. , Campolongo P. , Solinas M. , Cassano T. , Morgese M. G. , Debonnel G. , Duranti A. , Tontini A. , Tarzia G. , Mor M. , Trezza V. , Goldberg S. R. , Cuomo V. , Piomelli D.
Published: December 2005

Although anecdotal reports suggest that cannabis may be used to alleviate symptoms of depression, the psychotropic effects and abuse liability of this drug prevent its therapeutic application. The active constituent of cannabis, Δ
9
-tetrahydrocannabinol, acts by binding to brain CB
1
cannabinoid receptors, but an alternative approach might be to develop agents that amplify the actions of endogenous cannabinoids by blocking their deactivation. Here, we show that URB597, a selective inhibitor of the enzyme fatty-acid amide hydrolase, which catalyzes the intracellular hydrolysis of the endocannabinoid anandamide, exerts potent antidepressant-like effects in the mouse tail-suspension test and the rat forced-swim test. Moreover, URB597 increases firing activity of serotonergic neurons in the dorsal raphe nucleus and noradrenergic neurons in the nucleus locus ceruleus. These actions are prevented by the CB
1
antagonist rimonabant, are accompanied by increased brain anandamide levels, and are maintained upon repeated URB597 administration. Unlike direct CB
1
agonists, URB597 does not exert rewarding effects in the conditioned place preference test or produce generalization to the discriminative effects of Δ
9
-tetrahydrocannabinol in rats. The findings support a role for anandamide in mood regulation and point to fatty-acid amide hydrolase as a previously uncharacterized target for antidepressant drugs.
A functional promoter polymorphism in monocyte chemoattractant protein–1 is associated with increased susceptibility to pulmonary tuberculosis
Authors: Flores-Villanueva Pedro O. , Ruiz-Morales Jorge A. , Song Chang-Hwa , Flores Ludmila M. , Jo Eun-Kyeong , Montaño Marta , Barnes Peter F. , Selman Moises , Granados Julio
Published: December 2005

We examined the distribution of single nucleotide polymorphisms (SNPs) in nitric oxide synthase 2A, monocyte chemoattractant protein–1 (MCP-1), regulated on activation, normal T cell expressed and secreted, and macrophage inflammatory protein–1α genes in tuberculosis patients and healthy controls from Mexico. The odds of developing tuberculosis were 2.3- and 5.4-fold higher in carriers of MCP-1 genotypes AG and GG than in homozygous AA. Cases of homozygous GG had the highest plasma levels of MCP-1 and the lowest plasma levels of IL-12p40, and these values were negatively correlated. Furthermore, stimulation of monocytes from healthy carriers of the genotype GG with Mycobacterium tuberculosis antigens yielded higher MCP-1 and lower IL-12p40 concentrations than parallel experiments with monocytes from homozygous AA. Addition of anti–MCP-1 increased IL-12p40 levels in cultures of M. tuberculosis–stimulated monocytes from homozygous GG, and addition of exogenous MCP-1 reduced IL-12p40 production by M. tuberculosis–stimulated monocytes from homozygous AA. Furthermore, we could replicate our results in Korean subjects, in whom the odds of developing tuberculosis were 2.8- and 6.9-fold higher in carriers of MCP-1 genotypes AG and GG than in homozygous AA. Our findings suggest that persons bearing the MCP-1 genotype GG produce high concentrations of MCP-1, which inhibits production of IL-12p40 in response to M. tuberculosis and increases the likelihood that M. tuberculosis infection will progress to active pulmonary tuberculosis.
Secretory leucoprotease inhibitor binds to NF-κB binding sites in monocytes and inhibits p65 binding
Authors: Taggart Clifford C. , Cryan Sally-Ann , Weldon Sinead , Gibbons Aileen , Greene Catherine M. , Kelly Emer , Low Teck Boon , O'Neill Shane J. , McElvaney Noel G.
Published: December 2005

Secretory leucoprotease inhibitor (SLPI) is a nonglycosylated protein produced by epithelial cells. In addition to its antiprotease activity, SLPI has been shown to exhibit antiinflammatory properties, including down-regulation of tumor necrosis factor α expression by lipopolysaccharide (LPS) in macrophages and inhibition of nuclear factor (NF)-κB activation in a rat model of acute lung injury. We have previously shown that SLPI can inhibit LPS-induced NF-κB activation in monocytic cells by inhibiting degradation of IκBα without affecting the LPS-induced phosphorylation and ubiquitination of IκBα. Here, we present evidence to show that upon incubation with peripheral blood monocytes (PBMs) and the U937 monocytic cell line, SLPI enters the cells, becoming rapidly localized to the cytoplasm and nucleus, and affects NF-κB activation by binding directly to NF-κB binding sites in a site-specific manner. SLPI can also prevent p65 interaction with the NF-κB consensus region at concentrations commensurate with the physiological nuclear levels of SLPI and p65. We also demonstrate the presence of SLPI in nuclear fractions of PBMs and alveolar macrophages from individuals with cystic fibrosis and community-acquired pneumonia. Therefore, SLPI inhibition of NF-κB activation is mediated, in part, by competitive binding to the NF-κB consensus-binding site.
Hydronephrosis associated with antiurothelial and antinuclear autoantibodies in BALB/c-Fcgr2b
−/−
Pdcd1
−/− mice
Authors: Okazaki Taku , Otaka Yumi , Wang Jian , Hiai Hiroshi , Takai Toshiyuki , Ravetch Jeffrey V. , Honjo Tasuku
Published: December 2005

Because most autoimmune diseases are polygenic, analysis of the synergistic involvement of various immune regulators is essential for a complete understanding of the molecular pathology of these diseases. We report the regulation of autoimmune diseases by epistatic effects of two immunoinhibitory receptors, low affinity type IIb Fc receptor for IgG (FcγRIIB) and programmed cell death 1 (PD-1). Approximately one third of the BALB/c-Fcgr2b−/−Pdcd1−/− mice developed autoimmune hydronephrosis, which is not observed in either BALB/c-Fcgr2b−/− or BALB/c-Pdcd1−/− mice. Hydronephrotic mice produced autoantibodies (autoAbs) against urothelial antigens, including uroplakin IIIa, and these antibodies were deposited on the urothelial cells of the urinary bladder. In addition, ∼15% of the BALB/c-Fcgr2b−/−Pdcd1−/− mice produced antinuclear autoAbs. In contrast, the frequency of the autoimmune cardiomyopathy and the production of anti–parietal cell autoAb, which were observed in BALB/c-Pdcd1−/− mice, were not affected by the additional FcγRIIB deficiency. These observations suggest cross talk between two immunoinhibitory receptors, FcγRIIB and PD-1, on the regulation of autoimmune diseases.
English‐language academic journals from China: a great opportunity
Authors: Xian Jia
Published: December 2005

The conditions for developing English‐language academic journals in China are now favourable. Government investment in scientific research is increasing annually, there are many researchers at a high academic level with good English, and many key scientific research laboratories and engineering research centres have been established. There is also a big increase in the number of editors qualified in English. At present both the number and quality of English‐language journals are low, so the Chinese government is acting to support such journals and remedy their defects. There is thus a great opportunity for the development of such journals.
Documentation for institutional repositories
Authors: Probets Steve , Jenkins Celia
Published: December 2005

The documentation of seven academic institutional repositories (IRs) was compared and contrasted. This was followed by semi‐structured interviews with six practitioners experienced in the set‐up, management and maintenance of IRs, including representatives of three JISC FAIR projects. The aim was to identify the requirements of policy documentation provided by IRs. Although many issues were found to be handled differently, several common factors emerged. These included the importance of developing documentation in collaboration with academics, departments and senior management. Policies should be formulated only when the aims of the IR have been clearly defined and the documentation itself should be concise and understandable, with the rights and responsibilities of stakeholders clearly presented.
Iron Accumulation in Alcoholic Liver Diseases
Authors: Kohgo Yutaka , Ohtake Takaaki , Ikuta Katsuya , Suzuki Yasuaki , Hosoki Yayoi , Saito Hiroyuki , Kato Junji
Published: December 2005

Abstract: Increased hepatic iron is one of the important key factors which contribute alcohol toxicity of liver due to the production of reactive oxygen species. In patients with alcoholic liver diseases (ALD), liver iron is increased and the resulted lipid metabolite 4‐hydroxynonenal‐protein adduct was also increased. In general, iron is deposited in both parenchymal cells and and Kupffer cells in ALD. However, in patients with mild ALD, the parenchymal iron deposition is dominant rather than reticuloendothelial iron deposition, while the latter iron deposition is domimant in severe ALD, possibly due to endotoxemia and overproduction of inflammatory cytokines. We speculated that a parenchymal iron deposition in mild ALD is an important factor to trigger hepatocytes injury by ethanol, and the possible cause of parencynal iron deposition may be an increase of cellular iron uptake via serum transferrin in hepatocytes after ethanol exposure. By immuno‐histochemical study of biopsied liver samples, the expression of transferrin receptor 1 (TfR1), which mediates cellular iron uptake by serum transferrin was increased. This increase of TfR1 by ethanol is confirmed by in vitro experiment using HepG2 cells and primary rat hepatocytes culture. 59Fe‐labeled transferrin incorporation (but not transferrin nonbound iron (NTBI)) into the cells is also increased, suggesting that the increased TfR1 is functional. The increase of TfR1 expression is partially due to the increased activity of iron regulatory protein (IRP) by oxidative stress of ethanol metabolism. Thus, the post‐transcriptional regulation of iron uptake by ethanol is involved in the hepatocyte iron accumulation. Another possibility is an increase of intestinal iron absorption. Our recent finding regarding the increase of pro‐hepcidin serum in alcoholic patients with high serum ferritin support this assumption.
Molecular Pathogenesis of Alcohol‐Induced Hepatic Fibrosis
Authors: Siegmund Sören V. , Brenner David A.
Published: December 2005

Abstract: Alcohol abuse is a main cause of liver fibrosis and cirrhosis in the western world. Although the major mechanisms of fibrogenesis are independent of the origin of liver injury, alcoholic liver fibrosis features distinctive characteristics, including the pronounced inflammatory response of immune cells due to elevated gut‐derived endotoxin plasma levels, increased formation of reactive oxygen species (ROS), ethanol‐induced pericentral hepatic hypoxia or formation of cell‐toxic and pro‐fibrogenic ethanol metabolites (e.g., acetaldehyde or lipid oxidation products). These factors are together responsible for increased hepatocellular cell death and activation of hepatic stellate cells (HSCs), the key cell type of liver fibrogenesis. To date, removing the causative agent is the most effective intervention to prevent the manifestation of liver cirrhosis. A novel experimental approach in fibrosis therapy is the selective induction of cell death in HSCs. Substances such as gliotoxin, anandamide or antibody against tissue inhibitor of metalloproteinase (TIMP)‐1 can selectively induce cell death in activated HSCs. These new results in basic science are encouraging for the search of new antifibrotic treatment.
Glycine as a Therapeutic Immuno‐Nutrient for Alcoholic Liver Disease
Authors: Yamashina Shunhei , Ikejima Kenichi , Enomoto Nobuyuki , Takei Yoshiyuki , Sato Nobuhiro
Published: December 2005

Abstract: Activation of Kupffer cells by gut‐derived endotoxin is an important factor in ethanol hepatotoxicity. Further, it was shown that ethanol modulates both the expression and activity of several intracellular signaling molecules and transcription factors in Kupffer cells and chronic ethanol treatment enhances Kupffer cell sensitivity to endotoxin. These findings suggest that inhibition of Kupffer cell activation is effective for clinical application in alcoholic hepatitis. Recently, accumulating lines of evidence suggest a possibility that glycine is useful as an immuno‐modulating amino acid. It has been shown that a diet containing glycine improved survival in endotoxin shock by preventing Kupffer cell activation. Glycine most likely prevents the LPS‐induced elevation of intracellular Ca2+ concentration in Kupffer cells, thereby minimizing LPS receptor signaling and cytokine production. Indeed, glycine prevents alcohol‐induced liver injury in a long‐term enteral ethanol feeding rats (Tsukamoto‐French) by decreasing production of TNF‐α in the liver. Moreover, glycine is protective against apoptosis of sinusoidal endothelial cells (SECs) that is one of the initial events in the development of liver injury. On the other hand, epidemiologic data have identified chronic alcohol consumption as a significant risk factor for carcinogenesis. Interestingly, glycine inhibits growth of tumor in vivo most likely because of the inhibition of angiogenesis. It was shown that the inhibitory effect of glycine on growth and migration of endothelial cells is due to activation of a glycine‐gated Cl− channel. It is hypothesized that the opening of this anion channel hyperpolarizes the cell membrane, blocks influx of Ca2+ through voltage‐dependent Ca2+ channel, thereby blunting growth factor‐mediated signaling. Therefore, glycine can be used not only for treatment of alcoholic hepatitis, but also for chemoprevention and treatment of hepatocellular carcinoma in alcoholic cirrhosis. Taken together, it is concluded that glycine is a potent therapeutic immuno‐nutrient for various kinds of chronic liver diseases including alcoholic liver disease (ALD).
Anti‐TGF‐β Strategies for the Treatment of Chronic Liver Disease
Authors: Breitkopf Katja , Haas Stephan , Wiercinska Eliza , Singer Manfred V , Dooley Steven
Published: December 2005

Abstract: Permanent alcohol abuse may lead to chronic liver injury with deleterious sequelae such as liver cirrhosis and hepatocellular carcinoma. Mechanisms of fibrogenesis encompass recruitment of inflammatory cells at the site of injury and cytokine mediated activation of hepatic stellate cells (HSC) with accumulation of interstitial collagens. HSC transdifferentiation and accompanying apoptosis result in destruction of liver architecture and are therefore key steps of disease progression. TGF‐β represents the main profibrogenic cytokine in liver fibrosis and other fibroproliferative disorders by inducing extracellular matrix deposition as part of the wound healing response. In parallel, TGF‐β triggers hepatocytes that are strongly responsive for this cytokine, to undergo apoptosis, thereby providing space for HSC proliferation and generation of a collagenous matrix. Anti TGF‐β approaches were established and successfully utilized for the treatment of experimental fibrogenesis. Dominant negative TGF‐β receptors (TβR), generated by fusing the Fc domain of human IgG and the N‐terminal (extracellular) fragment of TβRII (Fc:TβRII) were applied to suppress fibrosis. Similarly TGF‐β binding proteins like decorin, antagonistic cytokines such as bone morphogenetic protein‐7, hepatocyte growth factor, IL‐10, or IFN‐γ were as efficient as camostat mesilate, a protease inhibitor that possibly abrogated proteolytic activation of TGF‐β. Further, our group recently overexpressed Smad7 in bile duct ligation induced liver fibrosis and achieved efficient inhibition of intracellular TGF‐β signaling, thereby counteracting profibrogenic effects in cultured HSC and in vivo. A direct link between the effect of alcohol and TGF‐β exists through reactive oxygen species that are generated in liver cells by alcohol metabolism and represent activators of TGF‐β signaling. Thus, soluble TβRII expression reduced experimental fibrogenesis in vitro and in vivo partially by decreasing intracellular ROS and inhibiting NADH oxidase. Approaches that specifically target profibrogenic TGF‐β signaling are promising to treat alcoholic liver disease in the future. However, to ensure safety for the patients to be treated, approaches with strong specificity need to be established. Therefore, it is essential to delineate the profibrogenic actions of TGF‐β and the influence of alcohol abuse in molecular detail.
Autologous Transplantation of Fascia into the Vocal Fold: Long‐Term Result of Type‐1 Transplantation and the Future
Authors: Tsunoda Koichi , Kondou Kenji , Kaga Kimitaka , Niimi Seiji , Baer Thomas , Nishiyama Koichiro , Hirose Hajime
Published: December 2005

Objectives: Since 1997, we have performed the autologous transplantation of fascia into the vocal fold (ATFV) procedure on cases of sulcus vocalis. In what follows, we report the long‐term results of our new surgical approach and discuss the role of these transplantations. We also review and report some complications that can be caused by ATFV. Finally, we discuss the ATFV technique as a contribution to the phonosurgery of the future.

Study Design: Prospective study.

Methods: We were able to obtain long‐term results from 10 volunteer cases (2 female and 8 male, age: 15–71, mean 46.5 years old) who could be followed up for at least 3 years after transplantation. All were cases of pathologic sulcus vocalis.

We measured maximum phonation time (MPT) and carried out pre‐ and postsurgical clinical observation and laryngeal stroboscopy in all cases. These measurements and observations were made before the ATFV and at 6 months, 1 year, 2 years, and 3 years after surgery.

Results: In stroboscopic observation 1 year after the ATFV, satisfactory glottal closure and excellent mucosal wave were observed for all cases, and there was no case with hyperadduction of the false vocal folds. MPT measures remained at an improved level 2 years and 3 years after the transplantations. Paired‐sample t tests showed that the improvement relative to preATFV levels was significant for all postsurgical measurements up to 3 years.

Conclusions: We conclude that ATFV is a successful surgical procedure for sulcus vocalis and scarred vocal folds. Other phonosurgical clinical applications may also be envisioned.
Histopathologic spectrum of erythema nodosum
Authors: Thurber Stacy , Kohler Sabine
Published: December 2005

Abstract:  Erythema nodosum (EN) is the most common panniculitis and histologically represents the prototype of a septal panniculitis. However, the histologic findings can be quite variable. We describe four patients with EN who each underwent two consecutive biopsies. In each case, the first biopsy showed histopathologic features that fall outside the usual spectrum of disease. Two cases showed predominantly neutrophilic infiltrates with focal suppuration as well as vasculitis of medium‐sized arteries. The areas of suppuration were more extensive in the first case prompting special stains for microorganisms that were all negative. The third case demonstrated a lobular panniculitis with a predominantly lymphohistiocytic infiltrate. Special stains were negative in this case as well. The fourth case revealed vasculitis of a medium sized artery, small vessel vasculitis, and a mixed septal and lobular panniculitis with a polyclonal population of atypical lymphocytes. In all patients, the clinical course and the subsequent biopsy were classic for EN. We conclude that lobular neutrophilic panniculitis with suppuration, small vessel vasculitis, and even medium vessel arteritis may rarely occur in EN. There are few clues in these unusual cases that allow for a specific diagnosis from the start, and often, a second biopsy is required.
A New Paradigm for the Teaching of Business Law and Legal Environment Classes
Authors: Lampe Marc
Published: December 2005

There is a need to develop curriculum and materials on law‐related topics better designed for business students planning a career in business. Except incidentally, business school legal faculty are not teaching future lawyers or paralegals. The world of the business practitioner is very different from that of the lawyer. For most business people the law and lawyers are a necessary nuisance. Furthermore, the legal world is changing. For example, methods of alternative dispute resolution (ADR) have become mainstream. Opportunities for “self‐help law” have proliferated. These trends, and other opportunities considered in this article, offer substantial benefits to the business community. To meet the needs of today's business person, college business law and legal environment courses must stress economical, intelligent prevention of legal problems and resolution of conflict. This article is about empowering future business managers by utilizing their class time to educate them to more directly meet these goals. Topical coverage and pedagogical approaches for implementing a new paradigm in a business school introductory law course are detailed. Faculty members should not allow fear of change to deter a needed overhauling of the curriculum, as such procrastination could harm the profession's future standing.
The application of response surface methodology to the production of phenolic extracts of lemon grass, galangal, holy basil and rosemary
Authors: Juntachote T. , Berghofer Emmerich , Bauer F. , Siebenhandl S.
Published: December 2005

The effects of independent variables (ethanol:water ratio, temperature and time) on the extraction yield and antioxidant properties of phenolic extracts from lemon grass, galangal, holy basil and rosemary were studied. The extraction solvent ratio of ethanol to water was found to have a significant (P < 0.05) influence on extraction yield, reducing power and total phenolic content, but not on the antioxidant activity of all herb and spice samples, while extraction temperature had only minor effects. Extraction time had a significant (P < 0.05) effect only on the reducing power of holy basil extracts. The optimum extraction conditions, i.e. extraction solvent ratio of ethanol to water, extraction temperature and extraction time for maximum total phenolic content, were 3:1 at 25 °C for 30 min for lemon grass, 3:1 at 75 °C for 90 min for galangal and holy basil and 3:1 at 75 °C for 30 min for rosemary.
A combined phage display ScFv library againstMyxobolus rotundusinfecting crucian carp,Carassius auratus auratus(L.), in China
Authors: Zhang J Y , Wang J G , Wu Y S , Li M , Li A H , Gong X L
Published: December 2005

Immunological methods have been developed for the diagnosis ofMyxobolus rotundusbut their use has been limited for the prevention and therapy of this serious parasitic pathogen. Phage display antibody libraries are a powerful technique for the development of antibodies to molecules of interest and have advantages over traditional hybridroma approaches. In the present study, four antigen fractions related toM. rotunduswere prepared and a combined phage display single‐chain antibody fragments (ScFv) library was constructed against this parasite. Preliminary analysis indicated that a combined antibody library of about 2.08 × 105individual clones and high diversity was generated. After four rounds of screening (bio‐panning) against soluble spore protein prepared from lysed, intact, matureM. rotundusspores, a strain monoclonal phage display ScFv, termed pCAN‐6H9, with better affinity, was isolated. The pCAN‐6H9 gene fragment was sequenced and analysed. The specificity of pCAN‐6H9 was further demonstrated by dot‐blot. In competition enzyme‐linked immunosorbent assay, both the original and enriched phage‐displayed ScFv repertoire showed significant inhibition of mouse anti‐M. rotundusserum binding to coated antigen, while the inhibition rate of monoclonal pCAN‐6H9 phage particles was only 11.83%.
Efficacy of injection vaccines against Flavobacterium psychrophilum in rainbow trout, Oncorhynchus mykiss (Walbaum)
Authors: Madetoja J , Lönnström L‐G , Björkblom C , Uluköy G , Bylund G , Syvertsen C , Gravningen K , Norderhus E‐A , Wiklund T
Published: December 2005

Efficacy of mineral oil‐based experimental injection vaccines against Flavobacterium psychrophilum were tested in rainbow trout, Oncorhynchus mykiss (Walbaum), under laboratory and field conditions. The vaccines consisted of formalin‐ or heat‐inactivated whole bacterium cell preparations of two different serotypes (Fd and Th) or a combination of serologically different F. psychrophilum (Fd and/or Th and/or FpT;Th). Specific antibody responses against the bacterium in plasma and skin mucus were evaluated post‐vaccination with enzyme‐linked immunosorbent assay. Efficacy of the vaccinations was determined by challenge trials to F. psychrophilum with the vaccinated rainbow trout. Significantly higher antibody levels in plasma were detected in vaccinated fish compared with mock‐vaccinated fish. Injection vaccination did not trigger specific antibody production in the skin mucus. Significantly higher survival of i.p. vaccinated fish compared with non‐vaccinated fish was observed during the challenge. The results suggest that mineral oil‐based injectable vaccines containing formalin‐ or heat‐inactivated virulent cells of F. psychrophilum effectively triggered specific antibody production and protected the fish against bacterial cold water disease.
Oxylipins act as determinants of natural product biosynthesis and seed colonization in Aspergillus nidulans
Authors: Tsitsigiannis Dimitrios I. , Keller Nancy P.
Published: December 2005

Secreted, hormone‐like lipogenic molecules, called oxylipins, mediate the balance of asexual to sexual spore ratio in Aspergillus nidulans. Oxylipin production in this fungus is dependent on developmental regulation of three conserved fatty acid oxygenases, PpoA, PpoB and PpoC. Here, we show that in addition to altering spore ratios, loss of ppo genes affect natural product biosynthesis and seed colonization. ΔppoA;ΔppoC and ΔppoA;ΔppoB;ΔppoC mutants were unable to produce the mycotoxin sterigmatocystin (ST) in vitro or in planta but in contrast overproduced the antibiotic penicillin (PN). These findings were correlated with decreased expression of genes involved in ST biosynthesis and increased expression of a PN biosynthetic gene, thus suggesting that oxylipin species regulate secondary metabolites at the transcriptional level. Additionally, the ΔppoA;ΔppoC and the ΔppoA;ΔppoB;ΔppoC mutants were defective in colonization of peanut seeds as reflected by a decrease in conidiation and production of the seed degradative enzyme lipase. These results indicate that oxylipin production is important for host colonization and mycotoxin production and may provide a promising target for future control strategies.
Memory B cell responses and malaria
Authors: WYKES M. , GOOD M. F.
Published: December 2005

Malaria is a serious cause of morbidity and mortality in millions of individuals each year. People living in endemic areas build up partial immunity only after repeated attacks of malaria over several years. At this meeting we discussed current knowledge about long‐term protection and the challenges we face in the development of an effective malaria vaccine.
Protective and pathogenic roles of CD8+ T cells during malaria infection
Authors: HAFALLA J. C. R. , COCKBURN I. A. , ZAVALA F.
Published: December 2005

CD8+ T cells play a key role in protection against pre‐erythrocytic stages of malaria infection. Many vaccine strategies are based on the idea of inducing a strong infection‐blocking CD8+ T cell response. Here, we summarize what is known about the development, specificity and protective effect of malaria‐specific CD8+ T cells and report on recent developments in the field. Although work in mouse models continues to make progress in our understanding of the basic biology of these cells, many questions remain to be answered – particularly on the roles of these cells in human infections. Increasing evidence is also emerging of a harmful role for CD8+ T cells in the pathology of cerebral malaria in rodent systems. Once again, the relevance of these results to human disease is one of the primary questions facing workers in this field.
Trichosporon asahii fatal infection in a non‐neutropenic patient after orthotopic liver transplantation
Authors: Abdala E. , Lopes R.I. , Chaves C.N. , Heins‐Vaccari E.M. , Shikanai‐Yasuda M.A.
Published: December 2005

Abstract: Trichosporon asahii is a yeast that may cause systemic infection, especially in neutropenic patients. To our knowledge, only two cases of invasive infection with Trichosporon were previously described in liver transplant recipients. We describe an additional case of T. asahii infection after orthotopic liver transplantation in a non‐neutropenic patient who had no known risk factor for invasive fungal infection, and died in spite of amphotericin B therapy.
Low‐dose amphotericin for prevention of serious fungal infection following liver transplantation
Authors: Shah T. , Lai W.K. , Gow P. , Leeming J. , Mutimer D.
Published: December 2005

Abstract: Aims. This study advances previously performed clinical studies of antifungal prophylaxis and prospectively evaluates the efficacy of low‐dose amphotericin B preparations for the prevention of invasive fungal infection (IFI) in high‐risk liver transplant (LT) recipients.

Methods. High‐risk LT patients were recruited and randomised to openly receive intravenously either conventional amphotericin B (amB) at a dose of 15 mg daily, or liposomal amphotericin B (amBisome) 50 mg daily. Prophylaxis was continued until discharge from the intensive care unit (ICU), until patient death, or until time of conversion to high‐dose amBisome for treatment of suspected or confirmed IFI.

Results. During the study period, 360 adult LTs were performed; 132 patients were eligible for 149 recruitment episodes into the trial, and 83 patients were recruited for 92 episodes. Of the 92, 48 patient episodes were randomised to receive amBisome prophylaxis, and 44 to receive amB. IFI was uncommon, diagnosed for 3 patients in the amBisome group, and for 2 in the amB group. Furthermore, Aspergillus was isolated on a single occasion during 92 episodes of prophylaxis. Fungal colonisation scores did not differ significantly between the 2 groups. There was a significant difference in the rates of survival to ICU discharge between the 2 groups (79.6% amBisome vs. 59.5% amB, P=0.038). Renal function measures including creatinine clearance at commencement and conclusion of prophylaxis, and at 12 months post transplant were not statistically different between the 2 groups.

Conclusion. The use of amphotericin B, liposomal or non‐liposomal preparations at low doses, for prophylaxis of IFI in high‐risk LT patients, is associated with a low incidence of serious fungal infection. In this randomised study, low‐dose amBisome prophylaxis was associated with an increased likelihood of successful discharge from the ICU.
A qualitative systematic review of peri‐operative dextromethorphan in post‐operative pain
Authors: Duedahl T. H. , Rømsing J. , Møiniche S. , Dahl J. B.
Published: December 2005

Background:  The N‐methyl‐d‐aspartate (NMDA) receptor antagonist, dextromethorphan (DM), has received interest as an adjunctive agent in post‐operative pain management. Clinical trials have been contradictory. This systematic review aims to evaluate the available literature examining the analgesic efficacy of DM in post‐operative patients.

Methods:  Twenty‐eight randomized, double‐blind, clinical studies, with 40 comparisons, including a variety of dosing regimens comparing DM treatment with placebo, were included. Meta‐analysis was intended but deemed to be inappropriate because of the substantial difference in methodology and reporting between trials. The outcome measures (pain scores at rest, time to first analgesic request and supplemental analgesic consumption) were evaluated qualitatively by significant difference (P < 0.05) as reported in the original investigations.

Results:  DM did not reduce the post‐operative pain score with a clinically significant magnitude. The time to first analgesic request was significantly prolonged in most comparisons with DM. Significant decreases in supplemental opioid consumption were observed in the majority of parenteral DM studies and in about one‐half of the oral studies. The decreases were of questionable clinical importance in most comparisons, although a relationship between a decrease in opioid consumption and opioid‐related side‐effects was established in some studies.

Conclusion:  Based on the studies available, DM has the potential to be a safe adjunctive agent to opioid analgesia in post‐operative pain management, but the consistency of the potential opioid‐sparing and pain‐reducing effect must be questioned. Consequently, it is not possible to recommend dose regimens or routine clinical use of DM in post‐operative pain. The route of administration may be important for the beneficial effect.
A case of suspected non‐neurosurgical adult fatal propofol infusion syndrome
Authors: Eriksen J. , Povey H. M. R.
Published: December 2005

A previously healthy woman (20 years old) was admitted to our hospital with several fractures after a car accident. She was sedated with propofol, etc. in doses ranging from 1.4 to 5.1 mg/kg/h for 88 h. She developed multiple organ failure with rhabdomyolysis and died. This case fulfils (except acidosis) the criteria of propofol–infusion syndrome (PRIS) in a young adult.