bluuebunny/crossref_metadata_2025 huggingface dataset:
Tempered endoscopy for real groups III: Inversion of transfer and 𝐿-packet structure
Authors: Shelstad D.
Published: October 2008

This paper examines adjoint relations for spectral analogues of the geometric transfer factors of Langlands and Shelstad in the case of the tempered spectrum of a real reductive algebraic group where the complex points are connected. Each tempered irreducible character is then expanded explicitly in terms of endoscopic characters. The analysis is also reinterpreted in terms of structure on

L
L

-packets in the form conjectured recently in much greater generality by Arthur. A triviality result is proved for the Whittaker normalization of spectral transfer factors which simplifies the results for certain inner forms of a quasi-split group.
Lipophilic and Stereospecific Interactions of Amino-amide Local Anesthetics with Human Kv1.1 Channels
Authors: Punke Mark A. , Friederich Patrick
Published: October 2008

Background

This study's aim was to investigate the interaction of amino-amide local anesthetics with human Kv1.1 potassium channels. These channels were chosen because of their proven physiologic role. By using a homolog series of local anesthetics with different lengths of the N-substituent, it was intended to elucidate the role of lipophilic interactions with Kv1.1. The use of stereoisomers allowed testing of the role of polar drug actions.

Methods

Human Kv1.1 channels were measured with the patch clamp technique. Concentration-response data were described by Hill functions. Gating changes were described by Boltzmann functions.

Results

Inhibition of Kv1.1 channels by dextrobupivacaine, bupivacaine, levobupivacaine, dextroropivacaine, levoropivacaine, and mepivacaine was concentration dependent, reversible, stereoselective, voltage dependent, and frequency independent. The IC(50) values were (mean +/- SEM) 41 +/- 3 microm (n = 20), 56 +/- 3 microm (n = 26), 76 +/- 8 microm (n = 24), 135 +/- 29 microm (n = 23), 313 +/- 32 microm (n = 25), and 1,451 +/- 351 microm (n = 23), respectively. The midpoint of current activation was shifted into the hyperpolarizing direction. The inhibitory potency as well as the potency to induce gating changes correlated with the number of CH(2) groups in the side chain of the drugs (r > 0.9, P < 0.05).

Conclusions

Kv1.1 channels constitute an important biophysical model for elucidating molecular mechanisms underlying local anesthetic drug effects. Inhibition likely results from an open state-dependent blocking mechanism. Interaction of local anesthetics with the ion channel protein is determined by lipophilic drug properties.
Helium-induced Preconditioning in Young and Old Rat Heart
Authors: Heinen Andre , Huhn Ragnar , Smeele Kirsten M. A. , Zuurbier Coert J. , Schlack Wolfgang , Preckel Benedikt , Weber Nina C. , Hollmann Markus W.
Published: October 2008

Background

The noble gas helium induces cardiac preconditioning. Whether activation of mitochondrial K(+) channels is involved in helium preconditioning (He-PC) is unknown. The authors investigated whether He-PC (1) is mediated by activation of Ca(2+) -sensitive potassium channels, (2) results in mitochondrial uncoupling, and (3) is age dependent.

Methods

Anesthetized Wistar rats were randomly assigned to six groups (n = 10 each). Young (2-3 months) control (Con) and aged (22-24 months) control animals (Age Con) were not treated further. Preconditioning groups (He-PC and Age He-PC) inhaled 70% helium for 3 x 5 min. The Ca(2+) -sensitive potassium channel blocker iberiotoxin was administered in young animals, with and without helium (He-PC+Ibtx and Ibtx). Animals underwent 25 min of regional myocardial ischemia and 120 min of reperfusion. In additional experiments, cardiac mitochondria were isolated, and the respiratory control index was calculated (state 3/state 4).

Results

Helium reduced infarct size in young rats from 61 +/- 7% to 36 +/- 14% (P < 0.05 vs. Con). Infarct size reduction was abolished by iberiotoxin (60 +/- 11%; P < 0.05 vs. He-PC), whereas iberiotoxin alone had no effect (59 +/- 8%; not significant vs. Con). In aged animals, helium had no effect on infarct size (Age Con: 59 +/- 7% vs. Age He-PC: 58 +/- 8%; not significant). Helium reduced respiratory control index in young animals (2.76 +/- 0.05 to 2.43 +/- 0.15; P < 0.05) but not in aged animals (Age Con: 2.87 +/- 0.17 vs. Age He-PC: 2.87 +/- 0.07; not significant). Iberiotoxin abrogated the helium effect on respiratory control index (2.73 +/- 0.15; P < 0.05 vs. He-PC) but had no effect itself on mitochondrial respiration (2.75 +/- 0.05; not significant vs. Con).

Conclusion

Helium causes mitochondrial uncoupling and induces preconditioning in young rats via Ca(2+) -sensitive potassium channel activation. However, these effects are lost in aged rats.
Reversal of Profound Rocuronium-induced Blockade with Sugammadex
Authors: Jones R Kevin , Caldwell James E. , Brull Sorin J. , Soto Roy G.
Published: October 2008

Background

Traditionally, reversal of nondepolarizing neuromuscular blocking agents was achieved using acetylcholinesterase inhibitors, but these are unable to adequately reverse profound blockade. Sugammadex is a novel reversal agent, reversing the effects of rocuronium by encapsulation. This study assessed the efficacy and safety of sugammadex versus neostigmine for reversal of profound rocuronium-induced neuromuscular blockade.

Methods

This phase III, randomized study enrolled surgical patients, aged 18 yr or older with American Society of Anesthesiologists physical status I-IV. Patients were randomized to receive sugammadex (4.0 mg/kg) or neostigmine (70 microg/kg) plus glycopyrrolate (14 microg/kg). Anesthetized patients received an intubating dose of rocuronium (0.6 mg/kg), with maintenance doses (0.15 mg/kg) as required. Neuromuscular monitoring was performed by acceleromyography. Sugammadex or neostigmine was administered at reappearance of 1-2 posttetanic counts (profound neuromuscular blockade). The primary efficacy parameter was the time from sugammadex or neostigmine-glycopyrrolate administration to return of the train-of-four ratio to 0.9.

Results

In the intent-to-treat population (n = 37 in each group), geometric mean time to recovery to a train-of-four ratio of 0.9 with sugammadex was 2.9 min versus 50.4 min with neostigmine-glycopyrrolate (P < 0.0001) (median, 2.7 min vs. 49.0 min). Most sugammadex patients (97%) recovered to a train-of-four ratio of 0.9 within 5 min after administration. In contrast, most neostigmine patients (73%) recovered between 30 and 60 min after administration, with 23% requiring more than 60 min to recover to a train-of-four ratio of 0.9.

Conclusions

Recovery from profound rocuronium-induced neuromuscular blockade was significantly faster with sugammadex versus with neostigmine, suggesting that sugammadex has a unique ability to rapidly reverse profound rocuronium neuromuscular blockade.
Long-term Outcome in Chest Trauma
Authors: Leone Marc , Brégeon Fabienne , Antonini François , Chaumoître Kathia , Charvet Aude , Ban Leang H. , Jammes Yves , Albanèse Jacques , Martin Claude
Published: October 2008

Background

Currently, there are limited data available describing the long-term outcomes of chest trauma survivors. Here, the authors sought to describe chest trauma survivor outcomes 6 months and 1 yr after discharge from the intensive care unit, paying special attention to pulmonary outcomes.

Methods

A cohort of 105 multiple trauma patients with blunt chest trauma admitted to the intensive care unit was longitudinally evaluated. After 6 months, a chest computed tomography scan, pulmonary function testing (PFT), and quality of life were collected in 55 of these patients. A subgroup of 38 patients was followed up for 1 yr.

Results

At least one abnormal PFT result was found in 39 patients (71%). Compared with normalized data of the age- and sex-matched population, physical function was decreased in 38 patients (70%). The 6-min walk distance was reduced for 29 patients (72%). Although pathologic images were observed on the chest computed tomography scan from 33 patients (60%), no relation was found between PFT and computed tomography. A ratio of arterial oxygen pressure to inspired oxygen fraction less than 200 at admission to the intensive care unit predicted an abnormal PFT result at 6 months. One year after discharge from the intensive care unit, paired comparisons showed a significant increase in forced vital capacity (P = 0.02) and Karnofsky Performance Status (P < 0.001).

Conclusions

Survivors of multiple traumas including chest trauma demonstrate a persistent decrease in the 6-min walk distance, impairment on PFT, and reduced pulmonary-specific quality of life.
On sexual dimorphism in immune function
Authors: Nunn Charles L , Lindenfors Patrik , Pursall E. Rhiannon , Rolff Jens
Published: October 2008

Sexual dimorphism in immune function is a common pattern in vertebrates and also in a number of invertebrates. Most often, females are more ‘immunocompetent’ than males. The underlying causes are explained by either the role of immunosuppressive substances, such as testosterone, or by fundamental differences in male and female life histories. Here, we investigate some of the main predictions of the immunocompetence handicap hypothesis (ICHH) in a comparative framework using mammals. We focus specifically on the prediction that measures of sexual competition across species explain the observed patterns of variation in sex-specific immunocompetence within species. Our results are not consistent with the ICHH, but we do find that female mammals tend to have higher white blood cell counts (WBC), with some further associations between cell counts and longevity in females. We also document positive covariance between sexual dimorphism in immunity, as measured by a subset of WBC, and dimorphism in the duration of effective breeding. This is consistent with the application of ‘Bateman's principle’ to immunity, with females maximizing fitness by lengthening lifespan through greater investment in immune defences. Moreover, we present a meta-analysis of insect immunity, as the lack of testosterone in insects provides a means to investigate Bateman's principle for immunity independently of the ICHH. Here, we also find a systematic female bias in the expression of one of the two components of insect immune function that we investigated (phenoloxidase). From these analyses, we conclude that the mechanistic explanations of the ICHH lack empirical support. Instead, fitness-related differences between the sexes are potentially sufficient to explain many natural patterns in immunocompetence.
Surface-expressed viral proteins in feline infectious peritonitis virus-infected monocytes are internalized through a clathrin- and caveolae-independent pathway
Authors: Dewerchin Hannah L. , Cornelissen Els , Van Hamme Evelien , Smits Kaatje , Verhasselt Bruno , Nauwynck Hans J.
Published: October 2008

Infection with feline infectious peritonitis virus (FIPV), a feline coronavirus, frequently leads to death in spite of a strong humoral immune response. In previous work, we reported that infected monocytes, thein vivotarget cells of FIPV, express viral proteins in their plasma membranes. These proteins are quickly internalized upon binding of antibodies. As the cell surface is cleared from viral proteins, internalization might offer protection against antibody-dependent cell lysis. Here, the internalization and subsequent trafficking of the antigen–antibody complexes were characterized using biochemical, cell biological and genetic approaches. Internalization occurred through a clathrin- and caveolae-independent pathway that did not require dynamin, rafts, actin or rho-GTPases. These findings indicate that the viral antigen–antibody complexes were not internalized through any of the previously described pathways. Further characterization showed that this internalization process was independent from phosphatases and tyrosine kinases but did depend on serine/threonine kinases. After internalization, the viral antigen–antibody complexes passed through the early endosomes, where they resided only briefly, and accumulated in the late endosomes. Between 30 and 60 min after antibody addition, the complexes left the late endosomes but were not degraded in the lysosomes. This study reveals what is probably a new internalization pathway into primary monocytes, confirming once more the complexity of endocytic processes.
Lipid of white-spot syndrome virus originating from host-cell nuclei
Authors: Zhou Qing , Li Hui , Qi Yi-Peng , Yang Feng
Published: October 2008

The hypothesis that white-spot syndrome virus (WSSV) generates its envelope in the nucleoplasm is based on electron microscopy observations; however, as yet there is no direct evidence for this. In the present study, the lipids of WSSV and the nuclei of its host, the crayfishProcambarus clarkii, were extracted and the neutral lipid and phospholipid contents were analysed by high-performance liquid chromatography, thin-layer chromatography and gas chromatography/mass spectrometry. Phosphatidylcholine (PC) and phosphatidylethanolamine comprised 62.9 and 25.8 %, respectively, of WSSV phospholipids, whereas they comprised 58.5 and 30 %, respectively, of crayfish nuclei phospholipids. These two phospholipids were the dominant phospholipids, and amounts of other phospholipids were very low in the total WSSV and crayfish nuclei phospholipids. The data indicate that the phospholipid profile of WSSV and crayfish nuclei are similar, which is in agreement with the model that the lipids of WSSV are from the host-cell nuclei. However, the fatty acid chains of PC were different between the WSSV virions and crayfish nuclei, and the viral neutral lipid component was also found to be somewhat more complicated than that of the host nuclei. The number of species of cholesterol and hydrocarbon in virus neutral lipid was increased compared with that in host-cell nuclei neutral lipid. It is suggested that the differences between WSSV and its host are either due to selective sequestration of lipids or reflect the fact that the lipid metabolism of the host is changed by WSSV infection.
Interaction of severe acute respiratory syndrome-coronavirus and NL63 coronavirus spike proteins with angiotensin converting enzyme-2
Authors: Mathewson Alison C. , Bishop Alexandra , Yao Yongxiu , Kemp Fred , Ren Junyuan , Chen Hongying , Xu Xiaodong , Berkhout Ben , van der Hoek Lia , Jones Ian M.
Published: October 2008

Although in different groups, the coronaviruses severe acute respiratory syndrome-coronavirus (SARS-CoV) and NL63 use the same receptor, angiotensin converting enzyme (ACE)-2, for entry into the host cell. Despite this common receptor, the consequence of entry is very different; severe respiratory distress in the case of SARS-CoV but frequently only a mild respiratory infection for NL63. Using a wholly recombinant system, we have investigated the ability of each virus receptor-binding protein, spike or S protein, to bind to ACE-2 in solution and on the cell surface. In both assays, we find that the NL63 S protein has a weaker interaction with ACE-2 than the SARS-CoV S protein, particularly in solution binding, but the residues required for contact are similar. We also confirm that the ACE-2-binding site of NL63 S lies between residues 190 and 739. A lower-affinity interaction with ACE-2 might partly explain the different pathological consequences of infection by SARS-CoV and NL63.
Post-translational modification of α-dystroglycan is not critical for lymphocytic choriomeningitis virus receptor function in vivo
Authors: Imperiali Mauro , Spörri Roman , Hewitt Jane , Oxenius Annette
Published: October 2008

α-Dystroglycan (α-DG) is a ubiquitously expressed molecule that has been identified as a cellular receptor for lymphocytic choriomeningitis virus (LCMV) and other arenaviruses. Recently, it was demonstrated that LCMV receptor function is critically dependent on post-translational modifications, namely glycosylation. In particular, it was shown that O-mannosylation, a rare type of mammalian O-linked glycosylation, is important in determining the binding of LCMV to its cellular receptor. All studies carried out so far showed a dependence on glycosylation in LCMV receptor function in vitro. This work extended these studies to two in vivo models of α-DG hypoglycosylation. The results confirm earlier findings on the in vitro dependence of carbohydrate modifications in LCMV receptor function. However, experiments in animal models showed that this dependence was only very weak in vivo. It is likely that alternative receptors or alternative entry pathways may account for this attenuated in vivo phenotype.
Epstein–Barr virus nuclear antigen-1 renders lymphocytes responsive to IL-2 but not IL-15 for survival
Authors: Tsimbouri Penelope , Al-Sheikh Yazeed , Drotar Mark E. , Cushley William , Wilson Joanna B.
Published: October 2008

Epstein–Barr virus nuclear antigen-1 (EBNA-1) is the only latent protein expressed in all virus-associated tumours. It plays a critical role in viral propagation and in the replication, episomal maintenance and partitioning of the viral genome. However, its tumorigenic potential is debated. We have previously shown that lymphocytes from a tumour-prone, EBNA-1-expressing, transgenic mouse line show increased responsiveness to interleukin-2 (IL-2). It was important to determine whether this property was unique to the transgenic line or whether it is a general consequence of EBNA-1 expression in B cells. In order to distinguish between these possibilities, explanted lymphocytes from two independent transgenic mouse lines were examined. The lymphocytes from both lines showed enhanced proliferation rates compared with controls. The transgenic lymphocytes survived for extended periods in culture, dependent on the dose of IL-2, while IL-15 (the receptor of which shares theβandγchain components of the IL-2 receptor) induced little effect. In accordance with this, transgenic B cells showed enhanced induction of expression of the IL-2 receptorαchain (CD25), which modulates affinity for the ligand. As this phenotype is evident in lymphocytes from mice of both lines, it is necessarily independent of any transgene insertion site effects and may be attributed to EBNA-1 expression. Furthermore, 10/12 tumour-bearing transgenic mice had elevated IL-2 levels in serum and 4/6 tumours were CD25 positive. IL-2 is normally produced by activated T cellsin vivo; thus, chronic immune activation or modulation could elicit this unique mode of virus-infected cell survival.
Antitumor activity of cetuximab against malignant glioma cells overexpressing EGFR deletion mutant variant III
Authors: Fukai Junya , Nishio Kazuto , Itakura Toru , Koizumi Fumiaki
Published: October 2008

Anti‐epidermal growth factor receptor (EGFR) monoclonal antibody, cetuximab, is a promising targeted drug for EGFR‐expressing tumors. Glioblastomas frequently overexpress EGFR including not only the wild type but also a deletion mutant form called ‘variant III (vIII)’, which lacks exon 2–7, does not bind to ligands, and is constitutively activated. In this study, we investigated the antitumor activity of cetuximab against malignant glioma cells overexpressing EGFRvIII. For this purpose, we transfected human malignant glioma cell lines with the retroviral vector containing cDNA for EGFRvIII, and analyzed the mode of cetuximab‐induced action on the EGFRvIII in the cells. Immunoprecipitation and immunofluorescence revealed binding of cetuximab to EGFRvIII. Notably, immunoblotting analyses showed that cetuximab treatment resulted in reduced expression levels of the EGFRvIII. However, cetuximab alone did not exhibit a growth‐inhibitory effect against the EGFRvIII‐expressing cells. On the other hand, an assay for antibody‐dependent cell‐mediated cytotoxicity (ADCC) demonstrated cetuximab‐induced cytolysis in the presence of human peripheral blood mononuclear cells in a dose‐dependent manner. These results suggest that deletion mutant EGFRvIII can be a target of cetuximab and that ADCC activity substantially contributes to the antitumor efficacy of cetuximab against the EGFRvIII‐expressing glioma cells. Thus, cetuximab could be a promising therapy in malignant gliomas that express EGFRvIII. (Cancer Sci 2008; 99: 2062–2069)
Antitumor activities of synthetic and natural stilbenes through antiangiogenic action
Authors: Kimura Yoshiyuki , Sumiyoshi Maho , Baba Kimiye
Published: October 2008

We reported that the antitumor and antimetastatic actions of resveratrol might be due to the inhibition of tumor‐induced angiogenesis. To search for anticancer agents with stronger activity than resveratrol, we examined the antiangiogenic effects of 21 synthetic and/or natural stilbenes. Among these 21 stilbenes, 2,3‐, 3,4‐, and 4,4′‐dihydroxystilbene inhibited the pro‐matrix metalloproteinase (pro‐MMP)–9 production in colon 26 cells at 5–25 µM, vascular endothelial growth factor (VEGF)–induced human umbilical vein endothelial cell (HUVEC) migration at 10 and 25 µM, and VEGF‐induced angiogenesis at 5–50 µM. Resvertarol inhibited the pro‐MMP‐9 production and VEGF‐induced angiogenesis at 25 or 50 µM. Thus, the inhibition of pro‐MMP‐9 production in colon 26 cells and VEGF‐induced angiogenesis by three dihydroxystilbenes were greater than those of resveratrol. The three dihydroxystilbenes (8 mg/kg, intraperitoneal injection) inhibited the tumor‐induced neovascularization in colon 26–packed chamber‐bearing mice and the tumor growth in colon 26–bearing mice. Furthermore, the three dihydroxystilbenes inhibited VEGF‐induced VEGFR‐2 phosphorylation. On the other hand, the three dihydroxystilbenes had no effect on VEGFR‐1 and‐2 expression, and VEGF‐induced VEGFR‐1 phosphorylation in HUVECs. These findings suggest that the inhibition of tumor‐induced neovascularization by these three dihydroxystilbenes may be due to the inhibition of VEGF‐induced endothelial cell migration and VEGF‐induced angiogenesis through the inhibition of VEGF‐induced VEGFR‐2 phosphorylation in endothelial cells and pro‐MMP‐9 expression in colon 26 cells. (Cancer Sci 2008; 99: 2083–2096)
Structural and functional diversity in the PAR1b/MARK2‐binding region of Helicobacter pylori CagA
Authors: Lu Huai‐Sheng , Saito Yasuhiro , Umeda Mayumi , Murata‐Kamiya Naoko , Zhang Hong‐Mei , Higashi Hideaki , Hatakeyama Masanori
Published: October 2008

Helicobacter pylori (H. pylori) cagA‐positive strains are associated with gastritis, peptic ulcerations, and gastric adenocarcinoma. Upon delivery into gastric epithelial cells, the cagA‐encoded CagA protein specifically binds and aberrantly activates SHP‐2 oncoprotein in a manner that is dependent on CagA tyrosine phosphorylation. CagA‐deregulated SHP‐2 then elicits aberrant Erk activation while causing an elongated cell shape known as the hummingbird phenotype. In polarized epithelial cells, CagA also binds to PAR1b/MARK2 and inhibits the PAR1b kinase activity, thereby disrupting tight junctions and epithelial cell polarity independent of CagA tyrosine phosphorylation. We show here that the CagA‐multimerization (CM) sequence that mediates interaction of CagA with PAR1b is not only essential for the CagA‐triggered junctional defects but also plays an important role in induction of the hummingbird phenotype by potentiating CagA‐SHP‐2 complex formation. We also show that the CM sequence of CagA isolated from East Asian H. pylori (referred to as the E‐CM sequence) binds PAR1b more strongly than that of CagA isolated from Western H. pylori (referred to as the W‐CM sequence). Within Western CagA species, the ability to bind PAR1b is proportional to the number of W‐CM sequences. Furthermore, the level of PAR1b‐binding activity of CagA correlates with the magnitude of junctional defects and the degree of hummingbird phenotype induction. Our findings reveal that structural diversity in the CM sequence is an important determinant for the degree of virulence of CagA, a bacterial oncoprotein that is associated with gastric carcinogenesis. (Cancer Sci 2008; 99: 2004–2011)
Role of the RUNX1‐EVI1 fusion gene in leukemogenesis
Authors: Maki Kazuhiro , Yamagata Tetsuya , Mitani Kinuko
Published: October 2008

RUNX1‐EVI1 is a chimeric gene generated by t(3;21)(q26;q22) observed in patients with aggressive transformation of myelodysplastic syndrome or chronic myelogenous leukemia. RUNX1‐EVI1 has oncogenic potentials through dominant‐negative effect over wild‐type RUNX1, inhibition of Jun kinase (JNK) pathway, stimulation of cell growth via AP‐1, suppression of TGF‐β‐mediated growth inhibition and repression of C/EBPα. Runx1‐EVI1 heterozygous knock‐in mice die in uteri due to central nervous system (CNS) hemorrhage and severe defects in definitive hematopoiesis as Runx1–/– mice do, indicating that RUNX1‐EVI1 dominantly suppresses functions of wild‐type RUNX1 in vivo. Acute myelogenous leukemia is induced in mice transplanted with bone marrow cells expressing RUNX1‐EVI1, and a Runx1‐EVI1 knock‐in chimera mouse developed acute megakaryoblastic leukemia. These results suggest that RUNX1‐EVI1 plays indispensable roles in leukemogenesis of t(3;21)‐positive leukemia. Major leukemogenic effect of RUNX1‐EVI1 is mainly through histone deacetyltransferase recruitment via C‐terminal binding protein. Histone deacetyltransferase could be a target in molecular therapy of RUNX1‐EVI1‐expressing leukemia. (Cancer Sci 2008; 99: 1878–1883)
Oviposition preferences of Maculinea alcon as influenced by aphid (Aphis gentianae) and fungal (Puccinia gentianae) infestation of larval host plants
Authors: ÁRNYAS ERVIN , BERECZKI JUDIT , TÓTH ANDREA , VARGA KATALIN , PECSENYE KATALIN , TARTALLY ANDRÁS , KÖVICS GYÖRGY , KARSA DÓRA , VARGA ZOLTÁN
Published: October 2008

Abstract 1. The influence of infestation of the larval host plant Gentiana cruciata on the egg‐laying preferences of the xerophilous ecotype of Alcon Blue butterfly (Maculinea alcon) was studied in a semi‐dry grassland area (Aggtelek Karst Region, Northern Hungary).

2. We examined whether oviposition patterns of females differed when G. cruciata stems were uninfested compared with when they were infested by an aphid (Aphis gentianae) or a rust (Puccinia gentianae) species.

3. Females laid more than 90% of their eggs on fertile, uninfested G. cruciata stems, although these stems comprised only ∼ 50% of the total stems available. Stems infested by aphids were similar to uninfested ones in properties that had a strong correlation with egg numbers, and yet there were significantly fewer eggs on infested stems than on intact ones.

4. Females never laid eggs on parts of Gentiana stems infested by aphids, and the presence of Lasius paralienus ants, which have a mutualistic interaction with Aphis gentianae, did not increase the repulsive effect of aphids. Infection of Gentiana by Puccinia did not influence the egg‐laying behaviour of females, even though the flowers and buds of infested stems exhibited a delayed development.

5. Aphid infestation can influence butterfly oviposition patterns through both direct and indirect effects. The presence of aphids directly excluded oviposition, but our data also indicated the possibility of an indirect effect of aphid infestation. Stems that had no aphids at the last egg counting, but were infested prior to it, had significantly fewer eggs than those that were never infested.
Deriving effects of pressure depletion on elastic framework moduli from sonic logs
Authors: Furre Anne‐Kari , Andersen Mona , Moen Anita Smalø , Tønnessen Randi Kristin
Published: October 2008

We have developed a method to determine the effect of pore pressure depletion on elastic framework moduli, by utilizing sonic logs from wells drilled at different locations through a reservoir at varying depletion stages. This is done by first inverting the sonic logs for elastic framework bulk and shear moduli, thus carefully removing pressure dependent fluid effects. By crossplotting these elastic framework moduli against an increase in net stress (which is directly related to depletion), we derive the stress sensitivity of the elastic framework moduli. We found that the observed stress sensitivity was consistent with time‐lapse seismic results and that the sensitivity derived from the sonic logs was much smaller than predicted by hydrostatic measurements on core samples. This method is applicable to depletion scenarios in mature fields and can be used both for modelling and inverting time‐lapse seismic data for effects of pore pressure depletion on seismic data.
NUCLEAR FACTOR‐κB MEDIATES CYTOPROTECTION OF HYDROGEN PEROXIDE PRECONDITIONING AGAINST APOPTOSIS INDUCED BY OXIDATIVE STRESS IN PC12 CELLS
Authors: Zhang Mei , Guo Rui‐Xian , Mo Li‐Qiu , Liao Xin‐Xue , Li Wei , Zhi Jun‐Li , Sun Sheng‐Nan , Wang Yan‐Li , Cui Yu , Liu Wei , Feng Jian‐Qiang , Chen Pei‐Xi
Published: October 2008

Cytoprotection by H2O2 preconditioning against oxidative stress‐induced apoptosis of PC12 cells has been demonstrated previously. In the present study, we investigated the effects of H2O2 preconditioning on nuclear factor (NF)‐κB activation and the role of NF‐κB in the adaptive cytoprotection of H2O2 preconditioning in PC12 cells.

The PC12 cells were preconditioned with 100 µmol/L H2O2 for 90 min, followed by 24 h recovery and subsequent exposure to 300 µmol/L H2O2 for a further 12 h.

The results showed that preconditioning with 100 µmol/L H2O2 upregulated NF‐κB expression and enhanced its nuclear translocation and DNA binding activity. In addition to its own effects on NF‐κB expression, H2O2 preconditioning also promoted the overexpression of NF‐κB induced by a lethal concentration of H2O2 (300 µmol/L).

N‐Tosyl‐l‐phenylalanine chloromethyl ketone (TPCK; 20 µmol/L), an inhibitor of NF‐κB, was administered 20 min before preconditioning with 100 µmol/L H2O2. At this concenteration, TPCK blocked the overexpression of NF‐κB induced by H2O2 preconditioning, accompanied by attenuation of H2O2 preconditioning‐induced cytoprotection. The inhibition of NF‐κB by TPCK enhanced caspase 3 activity induced by 300 µmol/L H2O2.

5. The findings of the present study provide novel evidence for the effects of preconditioning with H2O2 on constitutive activation of NF‐κB, which contributes to the adaptive cytoprotection of H2O2 preconditioning against PC12 cells apoptosis.
Loss of functional diversity under land use intensification across multiple taxa
Authors: Flynn Dan F. B. , Gogol‐Prokurat Melanie , Nogeire Theresa , Molinari Nicole , Richers Bárbara Trautman , Lin Brenda B. , Simpson Nicholas , Mayfield Margaret M. , DeClerck Fabrice
Published: October 2008

Land use intensification can greatly reduce species richness and ecosystem functioning. However, species richness determines ecosystem functioning through the diversity and values of traits of species present. Here, we analyze changes in species richness and functional diversity (FD) at varying agricultural land use intensity levels. We test hypotheses of FD responses to land use intensification in plant, bird, and mammal communities using trait data compiled for 1600+ species. To isolate changes in FD from changes in species richness we compare the FD of communities to the null expectations of FD values. In over one‐quarter of the bird and mammal communities impacted by agriculture, declines in FD were steeper than predicted by species number. In plant communities, changes in FD were indistinguishable from changes in species richness. Land use intensification can reduce the functional diversity of animal communities beyond changes in species richness alone, potentially imperiling provisioning of ecosystem services.
THE GOVERNANCE OF CEO INCENTIVES IN ENGLISH NHS HOSPITAL TRUSTS
Authors: Ballantine Joan , Forker John , Greenwood Margaret
Published: October 2008

Institutional arrangements for the governance of CEO pay and turnover in English NHS Hospital Trusts replicate best practice for listed companies but with the additional feature of centrally imposed performance measurement. In this paper we investigate the impact of this unique combination of incentives on the relationship between CEO pay/turnover and Trust financial and operating performance in the period 1998–2005. We identify a strong association between poor Trust performance and CEO turnover but find little evidence that remuneration committees relate pay to performance in the best performing Trusts. Our findings raise questions about the economic rationale for remuneration committees in the governance of NHS Hospital Trusts.
AN EXAMINATION OF THE CONTENT OF COMMUNITY FINANCIAL REPORTS IN QUEENSLAND LOCAL GOVERNMENT AUTHORITIES
Authors: Stanley Trevor , Jennings Natalee , Mack Janet
Published: October 2008

Annual reports, including general purpose financial statements, have been adopted as a key mechanism by which public sector entities discharge their accountability. However, there is concern about the complexity of public sector general purpose financial statements and consequently their effectiveness as an accountability mechanism. In Australia, the Queensland government has moved to address this issue in local government authorities by introducing a Community Financial Report as a means of simplifying the financial statements. A feature of this initiative was the lack of prescription given to local government authorities in the preparation of this report. This paper examines the form and content included in Community Financial Reports and also uses a disclosure index to determine the level of disclosure in the reports. The results of this research show that the form and content of the Community Financial Reports varied considerably. There was no definitive style, with each report being unique. The disclosure index revealed low levels of disclosure by local government authorities in the first year of the report as well as a lack of analysis of the Statements of Financial Performance, Position and Cash Flows. As well, there was a significant difference in the disclosures made by rural local government authorities compared with urban local government authorities. The results of this research will be of interest to local government authorities and local government regulators as they aim to provide useful, understandable information for stakeholders.
PERFORMANCE MANAGEMENT AND BEST VALUE AUDIT IN SCOTLAND: A RESEARCH NOTE ON THEORY AND PRACTICE
Authors: Midwinter Arthur
Published: October 2008

This paper appraises the theory and practice of Best Value Audit in Scotland, and in particular the central assumption that a robust performance management system is essential for continuous improvement in service delivery, within a rational planning model of governance. The reviews of Best Value Audit in practice reveal important gaps between theory and practice, with an overemphasis on monitoring process rather than performance. There is, therefore, considerable scope to reduce the demands of the audit process on local government, and Best Value Audit, needs to move from a theoretical model to an evidence‐based model of good practice if real progress is to be made.
Do Women Need the Renaissance?
Authors: Wiesner‐Hanks Merry E.
Published: October 2008

Joan Kelly's path‐breaking article, ‘Did Women have a Renaissance?’, first published in 1977, led historians of women in many fields to question the applicability of chronological categories derived from male experience. Thirty years later, the questioning continues, augmented by doubts about whether all systems of periodisation over‐simplify the diversity of gender. This paper examines what might be lost if feminist historians, in their sensitivity to difference, refuse to apply structures of periodisation. It looks at challenges to both ‘Renaissance’ and ‘early modern’ as conceptual categories and suggests ways in which gender is and must remain central to understandings of these eras.
Gender as a Question of Historical Analysis
Authors: Boydston Jeanne
Published: October 2008

This article examines the historically and culturally specific valence of ‘gender’ as currently deployed in the field of gender and women's history. It draws broadly on the scholarship on gender since the 1980s, while focusing particularly on the case of the British North American colonies and the early United States republic. The essay argues against the common practice of assuming that gender, understood as an oppositional binary, functions virtually universally as a primary process for representing differential power. It concludes by calling for a way of thinking about gender that can recognise important historical and cultural alternatives.
Prospective combined brain and spinal cord MRI in clinically isolated syndromes and possible early multiple sclerosis: impact on dissemination in space and time
Authors: Jacobi C. , Hähnel S. , Martinez‐Torres F. , Rieger S. , Jüttler E. , Heiland S. , Jarius S. , Meyding‐Lamadè U. , Storch‐Hagenlocher B. , Wildemann B.
Published: October 2008

Background:  The diagnosis of multiple sclerosis (MS) is based on dissemination in space (DIS) and time (DIT). The aim of the study was to assess the impact of spinal cord (SC) imaging on the evidence of DIS and DIT.

Methods:  Thirty‐five treatment‐naive patients with a first clinical symptom suggestive of MS were examined in a 2‐year prospective longitudinal follow‐up assessment. Brain and SC magnetic resonance imaging (MRI), Expanded Disability Status Scale and multiple sclerosis functional composite were analysed at baseline and after 1 and 2 years.

Results:  At study entry, 21 patients were classified as clinically isolated syndrome suggestive of MS (CIS) and 14 patients as possible early MS. SC lesions were detected at baseline in 14 CIS patients (67%, median: 1.0, enhancing 29%) and in 11 patients with possible early MS (79%, median: 2.0, enhancing 29%). DIS as depicted by additive SC imaging was detected in two additional individuals according to the revised versus the 2001 McDonald criteria. All patients with emerging cord lesions showed new brain lesions. Five individuals developed clinically asymptomatic cord lesions.

Conclusions:  Spinal cord abnormalities are frequent in CIS patients and in patients with possible early MS. SC imaging slightly improved the establishment of DIS, but had no impact on the evidence of DIT.
Equating Innocent Threats and Bystanders
Authors: FROWE HELEN
Published: October 2008

abstract  Michael Otsuka claims that it is impermissible to kill innocent threats because doing so is morally equivalent to killing bystanders. I show that Otsuka's argument conflates killing as a means with treating a person herself as a means. The killing of a person can be a means only if that person is instrumental in the threat to Victim's life. A permission to kill a person as a means will not permit killing bystanders. I also defend a permission to kill innocent threats against Otsuka's Trolley Cases. Otsuka depicts a person tied to an oncoming trolley as a bystander. I argue that such characters are threats whom Victim can permissibly kill.
Comparison of symptomatic versus functional changes in children and adolescents with ADHD during randomized, double‐blind treatment with psychostimulants, atomoxetine, or placebo
Authors: Buitelaar Jan K. , Wilens Timothy E. , Zhang Shuyu , Ning Yu , Feldman Peter D.
Published: October 2008

Background:  This meta‐analysis was designed to determine the relationship between reduction of attention‐deficit/hyperactivity disorder (ADHD) symptoms and improvement in functioning by examining short‐term changes in functional and symptomatic scores in children and adolescents with ADHD.

Methods:  Search of atomoxetine’s clinical trial database identified four studies involving a symptomatic measure, the ADHD Rating Scale‐IV‐Parent Version:Investigator‐administered and ‐scored (ADHDRS‐IV‐Parent:Inv), and a functional measure, the Life Participation Scale for ADHD (LPS).

Results:  Correlation analysis revealed a moderate‐to‐strong association between changes in the LPS total versus ADHDRS‐IV‐Parent:Inv total (r: −.68). The LPS Self‐control subscale showed higher correlations than the Happy/Social subscale with the symptomatic measures. Regression analysis also showed high sensitivity for functional measures to changes in symptom severity. Stratified analysis of mean changes in ADHDRS‐IV‐Parent:Inv scores corresponding to standardized changes in LPS functional scores indicated that a threshold reduction of 16–18 points on the ADHDRS‐IV‐Parent:Inv total score was needed for functional improvements to become evident.

Conclusions:  Subjects’ symptomatic improvements appear to be reflected in improvements in their social and behavioral function as measured by the LPS. These initial findings warrant verification by replication with other outcome measures.
Inoculum potential ofRhizopogonspores increases with time over the first 4 yr of a 99‐yr spore burial experiment
Authors: Bruns Thomas D. , Peay Kabir G. , Boynton Primrose J. , Grubisha Lisa C. , Hynson Nicole A. , Nguyen Nhu H. , Rosenstock Nicholas P.
Published: October 2008

DOI:10.1111/j.1469-8137.2008.02691.xCommentary p 245
Alterations in VO2max and the VO2 plateau with manipulation of sampling interval
Authors: Astorino Todd A.
Published: October 2008

Background:  The most accepted criterion for confirming attainment of VO2max is a plateau in oxygen consumption (VO2) at VO2max, but its incidence varies.

Aims:  To compare VO2max and VO2 plateau incidence across various sampling intervals, and to examine predictors of the change in VO2 (ΔVO2) at VO2max.

Methods:  Sedentary, recreationally‐active, and endurance‐trained subjects (n = 108, age = 24·2 ± 6·2 year) completed incremental exercise on the treadmill or cycle ergometer. Gas exchange data were obtained breath‐by‐breath and time‐averaged every 15, 30, and 60 s. VO2max attainment was verified with the Taylor et al. (1955) criterion (ΔVO2 at VO2max ≤2·1 ml kg−1 min−1). Multiple regression was used to examine predictors of ΔVO2 at VO2max.

Results:  VO2 plateau incidence was higher using breath‐by‐breath (81%) and 15 (91%) and 30 s time averaging (89%) versus 60 s averaging (59%). Compared to 60 s averaging, VO2max was significantly higher (P<0·05) when data were obtained breath‐by‐breath and with 15 and 30 s time‐averaging compared to 60 s sampling. VO2max was not related to VO2 plateau incidence. Respiratory rate was a significant predictor of ΔVO2 at VO2max in endurance‐trained subjects.

Conclusion:  More frequent data acquisition revealed higher VO2max and incidence of the VO2 plateau compared to 60 s time averaging. Secondary criteria to verify VO2max attainment should not be used, as they do not discern between subjects who do and do not reveal a plateau in VO2 at VO2max.
Alpha7 cholinergic‐agonist prevents systemic inflammation and improves survival during resuscitation
Authors: Cai Bolin , Chen Fei , Ji Yan , Kiss Levente , de Jonge Wouter J. , Conejero‐Goldberg Concepcion , Szabo Csaba , Deitch Edwin A. , Ulloa Luis
Published: October 2008

Severe haemorrhage is a common cause of death despite the recent advances in critical care. Conventional resuscitation fluids are designed to re‐establish tissue perfusion, but they fail to prevent inflammatory responses during resuscitation. Our previous studies indicated that the vagus nerve can modulate systemic inflammationviathe alpha7 nicotinic acetylcholine receptor (α7nAchR). Here, we report that the alpha7nAChR‐agonist, GTS, restrains systemic inflammation and improves survival during resuscitation. Resuscitation with GTS rescued all the animals from lethal haemorrhage in a concentration‐dependent manner. Unlike conventional resuscitation fluids, GTS inhibited the production of characteristic inflammatory and cardiodepressant factors including tumour necrosis factor (TNF) and high mobility group B protein‐1 (HMGB1). Resuscitation with GTS was particularly effective in restraining systemic TNF responses and inhibiting its production in the spleen. At the molecular level, GTS inhibited p65RelA but not RelB NF‐κB during resuscitation. Unlike non‐specific nicotinic agonists, GTS inhibited serum protein TNF levels in both normal and splenectomized, haemorrhagic animals. Resuscitation with GTS inhibited poly(ADP‐ribose) polymerase and systemic HMGB1 levels. Our studies suggest that GTS provides significant advantages as compared with non‐specific nicotinic agonists, and it could be a promising anti‐inflammatory supplement to improve survival during resuscitation.
Evaluation of Patient Expectations and Treatment Satisfaction After 1-Year Tadalafil Therapy for Erectile Dysfunction: The DETECT Study
Authors: Perimenis Petros , Roumeguere Thierry , Heidler Helmut , Roos Erik , Belger Mark , Schmitt Henry
Published: October 2008

Introduction

Erectile dysfunction (ED) is a self-reported condition and satisfaction with sexual performance is individual, subjective, and multi-factorial. Treatment success depends on several outcomes. Tadalafil is a long-acting, selective inhibitor of phosphodiesterase 5 that has been shown to be effective at treating men with ED.

Aim

To investigate patient’s ED treatment expectations at baseline; patient satisfaction with tadalafil treatment after 12 months; factors associated with satisfaction; and effect of early tadalafil treatment satisfaction on tadalafil continuation at 12 months.

Methods

The Determinants of Continued Use of Tadalafil study is a 12-month, prospective, pan-European, noninterventional, observational study, which enrolled 1,900 patients with ED wishing to initiate or change their treatment to tadalafil. Assessments were made on predefined treatment outcomes in a routine clinical setting.

Main Outcome Measures

International Index of Erectile Function-erectile function domain scores (at baseline, 1, 6, and 12 month visit), ED Inventory of Treatment Satisfaction (EDITS) scores (after 1, 6, and 12 months), and patient expectation questionnaire (at baseline visit) were analyzed for these patients.

Results

Data were available from 1,567 patients (82%) after 12 months, with similar baseline characteristics as the initial cohort. Treatment expectations identified as important included: erection hardness and ability to maintain erection through intercourse completion (>92% of patients); confidence, partner satisfaction, and naturalness (>84% of patients); rapid effect and long duration of treatment (>75% of patients). Continued tadalafil use from 1,319 (84%) patients at 12 months were reported. Total EDITS scores for those continuing treatment was 85.9 (95% CI: 85.1–86.7). Increased satisfaction was associated with higher effectiveness, number of sexual attempts, partner support, good relationships, and good drug tolerance. Treatment satisfaction at 1 month was best predictive of treatment continuation at 12 months.

Conclusions

Eighty-four percent of patients reported continued use of tadalafil after 12 months. High satisfaction after first month of treatment was the best predictor of treatment continuation.