bluuebunny/crossref_metadata_2025 huggingface dataset:
Polygynandry and sexual size dimorphism in the sea spiderAmmothea hilgendorfi(Pycnogonida: Ammotheidae), a marine arthropod with brood‐carrying males
Authors: BARRETO FELIPE S , AVISE JOHN C
Published: August 2008

Species that exhibit uniparental postzygotic investment by males are potentially good systems for investigating the interplay of sexual selection, parental care and mating systems. In all species of sea spiders (Class Pycnogonida), males exclusively provide postzygotic care by carrying fertilized eggs until they hatch. However, the mating systems of sea spiders are poorly known. Here we describe the genetic mating system of the sea spiderAmmothea hilgendorfiby assaying nearly 1400 embryos from a total of 13 egg‐carrying males across four microsatellite markers. We also determine the extent of sexual dimorphism in trunk and leg size, and assess how reproductive success in males varies with these morphological traits. We detected instances of multiple mating by both sexes, indicating that this species has a polygynandrous mating system. Genotypic assays also showed that: males do not mix eggs from different females in the same clusters; eggs from the same female are often partitioned into several clusters along a male's oviger; and clusters are laid chronologically from proximal to distal along ovigers. Females were on average larger than males with respect to leg length and width and trunk length, whereas males had wider trunks. Among the genotyped egg‐carrying males, neither the number of eggs carried nor the number of mates was correlated with body‐size traits. Nevertheless, the high variance in mating success, genetically documented, suggests that males differ in their ability to acquire mates, so future studies are needed to determine what traits are the targets of sexual selection in this species. In addition to providing the first description of the mating system in a sea spider, our study illustrates the potential uses of this group for testing hypotheses from parental investment and sexual selection theories.
Dissecting individual steps of nitrogen transcription factor cooperation in the Aspergillus nidulans nitrate cluster
Authors: Berger Harald , Basheer Asjad , Böck Sandra , Reyes‐Dominguez Yazmid , Dalik Thomas , Altmann Friedrich , Strauss Joseph
Published: July 2008

In the ascomycete fungus Aspergillus nidulans, the transcriptional activation of nitrate assimilating genes (niiA, niaD) depends on the cooperativity between a general nitrogen status‐sensing regulator (the GATA factor AreA) and a pathway‐specific activator (the Zn‐cluster regulator NirA). Because nitrate assimilation leads to intracellular ammonium formation, it is difficult to determine the individual contributions of NirA and AreA in this complex activation/inactivation process. In an attempt to find a suitable marker for the nitrogen status sensed by AreA, we determined the intracellular free amino acid levels on different nitrogen growth conditions. We show that the amount of glutamine (Gln) inversely correlates with all known AreA activities. We find that AreA mediates chromatin remodelling by increasing histone H3 acetylation, a process triggered by transcriptional activation and, independently of transcription, by nitrogen starvation. NirA also participates in the chromatin opening process during nitrate induction but its function is not related to histone acetylation. This chromatin remodelling function of NirA is dispensable only in nitrogen‐starved cells, conditions that lead to elevated AreA chromatin occupancy and histone H3 hyperacetylation. Continuous nitrate assimilation leads to self‐nitrogen metabolite repression but nitrate‐activated NirA is partially compensating for lowered AreA activities under these conditions.
Metabolic adaptation in Cryptococcus neoformans during early murine pulmonary infection
Authors: Hu Guanggan , Cheng Po‐Yan , Sham Anita , Perfect John R. , Kronstad James W.
Published: July 2008

The pathogenic fungus Cryptococcus neoformans generally initiates infection in mammalian lung tissue and subsequently disseminates to the brain. We performed serial analysis of gene expression (SAGE) on C. neoformans cells recovered from the lungs of mice and found elevated expression of genes for central carbon metabolism including functions for acetyl‐CoA production and utilization. Deletion of the highly expressed ACS1 gene encoding acetyl‐CoA synthetase revealed a requirement for growth on acetate and for full virulence. Transcripts for transporters (e.g. for monosaccharides, iron, copper and acetate) and for stress‐response proteins were also elevated thus indicating a nutrient‐limited and hostile host environment. The pattern of regulation was reminiscent of the control of alternative carbon source utilization and stress response by the Snf1 protein kinase in Saccharomyces cerevisiae. A snf1 mutant of C. neoformans showed defects in alternative carbon source utilization, the response to nitrosative stress, melanin production and virulence. However, loss of Snf1 did not influence the expression of a set of genes for carbon metabolism that were elevated upon lung infection. Taken together, the results reveal specific metabolic adaptations of C. neoformans during pulmonary infection and indicate a role for ACS1 and SNF1 in virulence.
Hierarchal type III secretion of translocators and effectors from Escherichia coli O157:H7 requires the carboxy terminus of SepL that binds to Tir
Authors: Wang Dai , Roe Andrew J. , McAteer Sean , Shipston Michael. J. , Gally David L.
Published: July 2008

Type III secretion (T3S) from enteric bacteria is a co‐ordinated process with a hierarchy of secreted proteins. In enteropathogenic and enterohaemorrhagic Escherichia coli, SepL and SepD are essential for translocator but not effector protein export, but how they function to control this differential secretion is not known. This study has focused on the different activities of SepL including membrane localization, SepD binding, EspD export and Tir secretion regulation. Analyses of SepL truncates demonstrated that the different functions associated with SepL can be separated. In particular, SepL with a deletion of 11 amino acids from the C‐terminus was able to localize to the bacterial membrane, export translocon proteins but not regulate Tir or other effector protein secretion. From the repertoire of effector proteins only Tir was shown to bind directly to full‐length SepL and the C‐terminal 48 amino acids of SepL was sufficient to interact with Tir. By synchronizing induction of T3S, it was evident that the Tir‐binding capacity of SepL is important to delay the release of effector proteins while the EspADB translocon is secreted. The interaction between Tir and SepL is therefore a critical step that controls the timing of T3S in attaching and effacing pathogens.
tmRNA‐dependent trans‐translation is required for sporulation in Bacillus subtilis
Authors: Abe Teppei , Sakaki Kazutaka , Fujihara Ai , Ujiie Hiromi , Ushida Chisato , Himeno Hyouta , Sato Tsutomu , Muto Akira
Published: July 2008

Spore formation in Bacillus subtilis is significantly impaired by the deletion of the gene for tmRNA (ssrA), which facilitates the trans‐translation reaction that rescues stalled ribosomes and degrades incompletely synthesized peptides. Microscopic analysis revealed that the sporulation of most ΔssrA cells is blocked after forespore formation. Expression analysis of lacZ‐fused genes directed by several RNA polymerase σ factors showed that the synthesis of active σK, encoded by the sigK gene, is predominantly inhibited in ΔssrA cells. The defect in σK synthesis is attributable to a defect in the skin element excision, which generates the sigK gene, caused in turn by reduced expression of SpoIVCA (recombinase) in ΔssrA cells.
Depletion of thiol‐containing proteins in response to quinones in Bacillus subtilis
Authors: Liebeke Manuel , Pöther Dierk‐Christoph , Van Duy Nguyen , Albrecht Dirk , Becher Dörte , Hochgräfe Falko , Lalk Michael , Hecker Michael , Antelmann Haike
Published: July 2008

Quinones are highly toxic naturally occurring thiol‐reactive compounds. We have previously described novel pathways for quinone detoxification in the Gram‐positive bacterium Bacillus subtilis. In this study, we have investigated the extent of irreversible and reversible thiol modifications caused in vivo by electrophilic quinones. Exposure to toxic benzoquinone (BQ) concentrations leads to depletion of numerous Cys‐rich cytoplasmic proteins in the proteome of B. subtilis. Mass spectrometry and immunoblot analyses demonstrated that these BQ‐depleted proteins represent irreversibly damaged BQ aggregates that escape the two‐dimensional gel separation. This enabled us to quantify the depletion of thiol‐containing proteins which are the in vivo targets for thiol‐(S)‐alkylation by toxic quinone compounds. Metabolomic approaches confirmed that protein depletion is accompanied by depletion of the low‐molecular‐weight (LMW) thiol cysteine. Finally, no increased formation of disulphide bonds was detected in the thiol‐redox proteome in response to sublethal quinone concentrations. The glyceraldehyde‐3‐phosphate dehydrogenase (GapA) was identified as the only new target for reversible thiol modifications after exposure to toxic quinones. Together our data show that the thiol‐(S)‐alkylation reaction with protein and non‐protein thiols is the in vivo mechanism for thiol depletion and quinone toxicity in B. subtilis and most likely also in other bacteria.
Rapid autocatalytic activation of the M4 metalloprotease aureolysin is controlled by a conserved N‐terminal fungalysin‐thermolysin‐propeptide domain
Authors: Nickerson Nicholas N. , Joag Vineet , McGavin Martin J.
Published: July 2008

The Staphylococcus aureus proteolytic cascade consists of a metalloprotease aureolysin (Aur), which activates a serine protease zymogen proSspA, which in turn activates the SspB cysteine protease. As with other M4 metalloproteases, including elastase of Pseudomonas aeruginosa, the propeptide of proAur contains an N‐terminal fungalysin‐thermolysin‐propeptide (FTP) domain. Autocatalytic activation of proAur was initiated by processing at T85↓L86 in the FTP domain. This differed from the mechanism described for proElastase, where the FTP domain has an RY motif in place of TL86, and processing occurred at the junction of the propeptide and metalloprotease domains, which remained as an inactive complex during passage across the outer membrane. When TL86 in the FTP domain was replaced with RY, an intact N‐terminal propeptide was secreted, but the M4 metalloprotease domain was degraded. Consequently, this segment of the FTP domain promotes intramolecular processing of proAur while bestowing a chaperone function, but discourages processing within the FTP domain of proElastase, where activation must be co‐ordinated with passage across a second membrane. We conclude that the FTP domain of proAur is adapted to facilitate a rapid autocatalytic activation mechanism, consistent with the role or proAur as initiator of the staphylococcal proteolytic cascade.
Mutations in the signature motif in MutS affect ATP‐induced clamp formation and mismatch repair
Authors: Acharya Samir
Published: July 2008

MutS protein dimer recognizes and co‐ordinates repair of DNA mismatches. Mismatch recognition by the N‐terminal mismatch recognition domain and subsequent downstream signalling by MutS appear coupled to the C‐terminal ATP catalytic site, Walker box, through nucleotide‐mediated conformational transitions. Details of this co‐ordination are not understood. The focus of this study is a conserved loop in Escherichia coli MutS that is predicted to mediate cross‐talk between the two ATP catalytic sites in MutS homodimer. Mutagenesis was employed to assess the role of this loop in regulating MutS function. All mutants displayed mismatch repair defects in vivo. Biochemical characterization further revealed defects in ATP binding, ATP hydrolysis as well as effective mismatch recognition. The kinetics of initial burst of ATP hydrolysis was similar to wild type but the magnitude of the burst was reduced for the mutants. Given its proximity to the ATP bound in the opposing monomer in the crystal and its potential analogy with signature motif of ABC transporters, the results strongly suggest that the loop co‐ordinates ATP binding/hydrolysis in trans by the two catalytic sites. Importantly, our data reveal that the loop plays a direct role in co‐ordinating conformational changes involved in long‐range communication between Walker box and mismatch recognition domains.
Intestinal chronic obstruction affects motor responsiveness of rat hypertrophic longitudinal and circular muscles
Authors: Bertoni S. , Ballabeni V. , Flammini L. , Gobbetti T. , Impicciatore M. , Barocelli E.
Published: August 2008

Abstract  Extensive morphological and neurochemical changes have been experimentally and clinically documented in the hypertrophied intestine located orally to a chronic partial stenosis of the lumen. Functional studies revealed not only disruption of the interdigestive motor complex in vivo and decreased efficiency of contraction but also preservation of the peristaltic reflex in vitro. Given the critical role played in intestinal peristalsis by the coordinated activity of the longitudinal (LM) and circular muscle (CM), this work focuses on the motor responses of LM and CM isolated from rat hypertrophied ileum following mechanical obstruction. Maximal contractions to both receptor (acetylcholine and substance P) and non‐receptor (K+) mediated stimuli were up to 10‐fold increased in hypertrophic CM rings compared with control tissues, while a higher potency of substance P was revealed in both hypertrophied muscle layers. Relaxations to vasoactive intestinal polypeptide and 8‐Br‐cGMP were more intense on prostaglandin F2α‐contracted hypertrophic LM strips compared with control tissues and a general tendency towards increased relaxation was shared also by hypertrophic CM basal tone. The present results collectively suggest that hypertrophic growth leads to hyperresponsiveness to contractile agents, particularly evident in the CM, and to increased sensitivity to relaxing mediators, especially exhibited by the LM. In this regard, the complementary role exerted by each muscle layer and the plasticity of the intestinal tissue could both come into play to preserve the intestinal functions in a changing environment.
Sedimentology, petrography and geochemistry of a limestone breccia (Pietra di Billiemi) from north‐west Sicily, Italy: implications for evolution of the Tethyan basins around the Triassic/Jurassic boundary
Authors: SCOPELLITI GIOVANNA , NERI RODOLFO , BELLANCA ADRIANA , DI STEFANO PIETRO , BARBIERI MARIO
Published: July 2008

In this study, the Pietra di Billiemi, a famous dimension stone, is investigated because it records the tectonic evolution of the south Tethys continental margin and preserves a record of major environmental changes occurring near the Triassic/Jurassic boundary. The Pietra di Billiemi is a grey, coarse‐grained and clast‐supported limestone breccia cropping out in an area of the Palermo Mountains representing a segment of the Apennine–Maghrebian chain in western Sicily. The rock consists of metre‐sized to centimetre‐sized angular clasts, derived from Upper Triassic sponge boundstones and rudstones, with a differently coloured, silt‐grained matrix. Fitted fragments are observed commonly which suggest an in situ origin for the bulk of the breccia. The matrix is characterized by the absence of biogenic components and by variable mineralogy and geochemistry. Petrographic features and Sr‐isotope values indicate that the most important and earliest fillings of the breccia consist of black matrix and white matrix temporally referable to Hettangian–Sinemurian times. Clotted micrite, carbonate fluorapatite and abundant pyrite, in addition to relatively high contents of redox‐sensitive elements (V, Ni, Zn and S), are consistent with deposition in anoxic conditions that favoured microbial mediation for authigenic carbonate (calcite and dolomite) precipitation in the matrix. As a whole, the Billiemi breccia can be considered a product of tectonic fragmentation of a Tethyan carbonate platform edge around the Triassic/Jurassic boundary, formed when the drowned platform edge was covered by hemipelagic mudstones recording the anoxic conditions existing during Early Jurassic times.
Native kidney post‐transplant lymphoproliferative disorder in a non‐renal transplant patient
Authors: Araya Carlos E. , Mehta Mansi B. , González‐Peralta Regino P. , Hunger Stephen P. , Dharnidharka Vikas R.
Published: July 2008

Abstract:  PTLD is an important post‐transplant complication. Although PTLD affects kidney allografts after renal transplantation, it has not been reported in native kidneys of other solid organ recipients. Herein, we report a child who underwent an orthotropic liver transplant for cryptogenic cholestatic hepatitis and developed fever, generalized lymphadenopathy, chronic EBV viremia, and lymphatic PTLD. Subsequently, she also developed gross hematuria and nephrotic range proteinuria. Kidney histology revealed EBV‐positive mononuclear infiltrates within the renal parenchyma consistent with PTLD. Electron microscopy examination demonstrated subepithelial electron‐dense deposits consistent with a membranous glomerulopathy pattern. The PTLD was successfully treated with reduced immunosuppression and cyclic cyclophosphamide, rituximab, and prednisone, but the renal disease progressed to end‐stage renal failure within two yr. Repeat kidney histology showed chronic nephropathy and membranous glomerulopathy without PTLD infiltrates or detectable EBV staining, although chronic viremia persisted. To our knowledge, this is the first such child to be reported and highlights the importance of remaining vigilant for renal PTLD even in non‐kidney organ recipients.
Comparative Bone Histology of Adult Horses (Equus caballus) and Cows (Bos taurus)
Authors: Zedda M. , Lepore G. , Manca P. , Chisu V. , Farina V.
Published: July 2008

Bone microstructure of domestic herbivores is still not completely understood. Indeed, works focused on the bone histology of numerous Mammalian species frequently led to misunderstandings because of the high number of variations such as the kind of bone, section orientation, species, breed and age. Moreover, attempts to identify the species in archaeozoological studies by a mere qualitative approach have not been encouraging and in recent years quantitative methods, based on image processing and statistical analysis, have appeared. The present study was undertaken to determine whether morphometrical and morphological differences exist in the compact bone structure of the femur and humerus between horses and cows. Measurements such as area, perimeter, minimum and maximum diameter of osteons and Haversian canals as well as the osteonal density were carried out on cross sections of eight humeri and eight femurs of the two herbivores investigated. In agreement with other authors, the qualitative investigation confirmed that the compact bone of horses and cows can be classified as dense Haversian tissue. Osteons of the horse were more numerous and composed of a higher number of well‐defined lamellae when compared with the cow. Diameter, perimeter and area of osteons and Haversian canals were always higher in horses than in cows and this pattern could be related to the different locomotor behaviour of these animals.
Textilien mit antimykotischen und antibakteriellen Eigenschaften
Authors: Hipler U. C.
Published: July 2008

Auf der Basis des ZIMMER Lyocell Verfahrens erfolgt die Herstellung von SeaCell® und SeaCell® Active Fasern. Eine besondere Fähigkeit der SeaCell® Faser ist, Stoffe zu binden und zu absorbieren. Die spezielle Fähigkeit der Metallsorption wird bei der Aktivierung von SeaCell® Fasern ausgenutzt. Dabei kann das bakterizid wirkende Metall Silber vom bereits fertig ausgeformten cellulosischen Faserkörper absorbiert werden. Die vorliegende Studie zeigt die antimykotische Wirkung von SeaCell®Active in einem In‐vitro‐Testsystem gegenüber Candida albicans (DSM 11225), Candida tropicalis (ATCC 1169) und Candida krusei (ATCC 6258). Darüber hinaus wurde die antibakterielle Aktivität der Fasern mit unterschiedlichen Mengen an SeaCell® Active dosisabhängig gegenüber Staphylococcus aureus (ATCC 22923) und Escherichia coli (ATCC 35218) nachgewiesen. Ob diese Faser in bioaktiven Textilien Verwendung finden kann, die für spezifische anatomische Regionen und Hautbedingungen mit einer Suszeptibilität für Pilz‐und Bakterieninfektionen, speziell Candida‐Spezies, Staphylococcus aureus und Escherichia coli geeignet ist, muss durch weitere Untersuchungen, insbesondere in‐vivo‐Tests am Menschen, unter Berücksichtigung möglicher allergischer und toxischer Effekte der Fasern, sichergestellt werden.
Lungenembolie durch Aspergillose (sog. Pilzembolie) Pulmonary embolism by aspergillosis (so called fungal embolism)
Authors: Schwesinger G. , Eckel L. , Wollert H.‐G.
Published: July 2008

Ein 71jähriger Mann entwickelte bei einem Zustand nach Schrittmacherimplantation bei Arrhythmie und Mehrfachrevisionen wegen Schrittmachertascheninfektionen einen Tumor im rechten Ventrikel. Notfallmäßiger Trikuspidalklappenersatz durch ein Carpentier Edwards Xenograft. Die Schrittmachersonden und das Endokard waren durch Aspergillus in Gestalt eines Aspergilloms infiziert. Durch dieses Material kam es zu einer Lungenembolie, was relativ selten ist.
Fall‐Bericht: Analyse der kritischen Zeitverzögerungen vom Fieberanstieg bis zur ersten Antimykotika‐Gabe bei der Diagnostik einer Candidämie
Authors: Kappe Reinhard , Fuchs Erika , Gorges Alexander , Rimek Dagmar
Published: July 2008

In einem Schwerpunkt‐Klinikum mit eigenem mikrobiologischen Labor wurde bei einer 84‐jährigen Patientin mit Candidämie die Zeitdauer der einzelnen diagnostischen Schritte vom Fieberbeginn bis zur Verabreichung der ersten Antimykotika‐Dosis bestimmt. Die Gesamtdauer betrug 25 Stunden und zehn Minuten. Die größte Verzögerung von acht Stunden lag zwischen dem positiven Signal der Blutkultur in der Nacht und dem Beginn der Verarbeitung der Blutkultur frühmorgens. Beschleunigungen erscheinen sowohl im klinischen als auch im labormedizinischen Bereich erreichbar durch Optimierung von Präanalytik, Analytik und Postanalytik.
Mapping of rhizoctonia root rot resistance genes in sugar beet using pathogen response‐related sequences as molecular markers
Authors: Lein J. C. , Sagstetter C. M. , Schulte D. , Thurau T. , Varrelmann M. , Saal B. , Koch G. , Borchardt D. C. , Jung C.
Published: July 2008

Rhizoctonia root and crown rot caused by the fungus Rhizoctonia solani is a serious disease of sugar beet. An F2:3 population from a cross between a resistant and a susceptible parent has been tested for R. solani resistance and a genetic map has been constructed from the corresponding F2 parents. The map encompasses 38 expressed sequence tags (ESTs) with high similarity to genes which are involved in resistance reactions of plants (R‐ESTs) and 25 bacterial artificial chromosomes (BACs) containing nucleotide binding site (NBS)‐motifs typical for disease resistance genes. Three quantitative trait loci (QTL) for R. solani resistance were found on chromosomes 4, 5 and 7 collectively explaining 71% of the total phenotypic variation. A number of R‐ESTs were mapped in close distance to the R. solani resistance QTL. In contrast, the NBS‐BACs mapped to chromosomes 1, 3, 7 and 9 with two major clusters of NBS‐BACs on chromosome 3. No linkage between NBS‐BACs and R. solani resistance QTL was found. The data are discussed with regard to using R‐ESTs and NBS markers for mapping quantitative disease resistances.
Cryo‐scanning Electron Microscopy Discloses Differences in Dehydration of Frozen Boar Semen Stored in Large Containers
Authors: Ekwall H
Published: July 2008

Contents

In general, freezing in flat plastic polyethylene terephthalate (PET) bags (FlatPacks) at 50°C/min gives better post‐thaw viability, in terms of sperm motility and membrane integrity, than does freezing in plastic maxi‐straws, probably owing to differences in cryobiology. To test the hypothesis that this better survival post‐thaw relates to the degree of sperm dehydration during freezing, the present study investigated the structure of boar semen in a frozen state using cryo‐scanning electron microscopy (cryo‐SEM) to compare two different packages (FlatPacks and maxi‐straws) for single artificial insemination (AI) doses, and three different freezing rates. The semen was split‐sample frozen in maxi‐straws or FlatPacks (both holding 5 ml) using 3% glycerol as cryoprotectant. Three freezing rates were applied from −5°C to −100°C, namely 2°C/min, 50°C/min and 1200°C/min, the lattermost by plunging the samples into liquid nitrogen (LN2). The samples were thereafter fractured into LN2 and larger areas of extra‐cellular, unbound frozen water (‘ice lakes’) were measured to determine the degree of dehydration of the spermatozoa. These areas decreased in size with an increase in cooling rate, the differences in size being more dramatic for maxi‐straws than for FlatPacks. Size of ice lakes was also influenced by location within package in relation to cooling rate, the central values being always smaller in maxi‐straws than in Flatpacks (p < 0.05 at 2°C/min and 50°C/min) but not at 1200°C/min, which suggested the FlatPack allows for more homogenous freezing of boar semen.
ELECTROPHYSIOLOGICAL EFFECTS OF KETAMINE ON HUMAN ATRIAL MYOCYTES AT THERAPEUTICALLY RELEVANT CONCENTRATIONS
Authors: Deng Chun‐Yu , Yu Xi‐Yong , Kuang Su‐Juan , Rao Fang , Yang Min , Shan Zhi‐Xin , Qian Wei‐Min , Zhou Zhi‐Ling , Lin Qiu‐Xiong , Wu Shu‐Lin , Zhang You‐Yi , Lin Shu‐Guang
Published: July 2008

Ketamine is widely used for the induction of anaesthesia in high‐risk patients with cardiovascular instability or severe hypovolaemia. However, the ionic mechanisms involved in the effects of ketamine at therapeutically relevant concentrations in human cardiac myocytes are unclear. The present study was designed to investigate the effects of ketamine on L‐type Ca2+ (ICa), transient outward K+ (Ito), ultra‐rapid delayed rectifier K+ (IKur) and inward rectifier potassium (IK1) currents, as well as on action potentials, in human isolated atrial myocytes.

Atrial myocytes were isolated enzymatically from specimens of human atrial appendage obtained from patients undergoing coronary artery bypass grafting. The action potential and membrane currents were recorded in both current‐ and voltage‐clamp modes using the patch‐clamp technique.

Ketamine inhibited ICa with an IC50 of 1.8 µmol/L. In addition, 10 µmol/L ketamine decreased the ICa peak current at +10 mV from 5.1 ± 0.3 to 2.1 ± 0.4 pA/pF (P < 0.01), but did not change the threshold potential, peak current potential and reverse potential.

Ketamine had no effect on Ito, IKur or IK1, but it reversibly shortened the duration of the action potential in human atrial myocytes.

In conclusion, ketamine, at a clinically relevant concentration, shortens the action potential duration of the human atrial myocytes, probably by inhibiting ICa.
DOES MODERATE PRETERM BIRTH LEAD TO ALTERED ARTERIAL PRESSURE? STUDIES IN SHEEP
Authors: De Matteo Robert , Stacy Victoria , Probyn Megan E , Brew Nadine , Blasch Natasha , Harding Richard
Published: July 2008

Low birth weight (LBW) is associated with an increased risk of cardiovascular disease. Preterm birth is a major determinant of LBW and has been shown to result in elevated arterial pressure (AP) in humans, but few studies have investigated the effects of preterm birth in the absence of potentially confounding factors. Our aim was to determine whether moderately preterm birth per se alters the postnatal development of AP in lambs.

Preterm lambs were delivered approximately 14 days before term (i.e. ~133 days of gestation); controls were born at term (~147 days). Mean arterial pressure (MAP), heart rate (HR), blood composition and indices of growth were measured at 4 and 8 weeks post term‐equivalent age (PTEA). We also studied a separate cohort of preterm and term sheep as young adults (~1.1 years).

Preterm lambs had significantly lower birth weights than term lambs, but bodyweights were not significantly different by Day 12 PTEA. In addition, MAP, HR and most blood variables did not differ between term and preterm lambs at 4 or 8 weeks PTEA. Preterm birth per se did not alter MAP or HR in young adult sheep.

Low birth weight due to preterm birth does not result in an altered AP during early postnatal life or at maturity. Moderate intrauterine growth restriction (IUGR) due to twinning, which further reduces birth weight, does not affect MAP in preterm lambs. Other factors, such as the degree of prematurity or IUGR, exposure to corticosteroids or postnatal nutrition, may be important in the later development of elevated AP.
COMPARATIVE PROTEIN BINDING, STABILITY AND DEGRADATION OF SATRAPLATIN, JM118 AND CISPLATIN IN HUMAN PLASMA IN VITRO
Authors: Bell Deanna N , Liu Johnson J , Tingle Malcolm D , Rattel Benno , Meyer Thorsten Ulf , McKeage Mark J
Published: July 2008

Satraplatin is an investigational orally administered platinum‐based antitumour drug. The present study compared the plasma protein binding, stability and degradation of satraplatin with that of its active metabolite JM118 and cisplatin.

The platinum complexes were incubated in human plasma for up to 2 h at 37°C and quantified in plasma fractions by inductively coupled plasma–mass spectrometry on‐ or off‐line to high‐performance liquid chromatography.

All three platinum drugs became irreversibly bound to plasma proteins and showed negligible reversible protein binding. They were also unstable in plasma and generated one or more platinum‐containing degradation products during their incubation. However, the three platinum complexes differed in the kinetics of their instability and protein binding, as well as in the number of degradation products formed during their incubation.

In conclusion, the plasma protein binding, instability and degradation of satraplatin and its active metabolite JM118 are qualitatively similar to that of cisplatin and other clinically approved platinum‐based drugs. Quantitative differences in their irreversible protein binding and degradation were related to their respective physiochemical properties and bioactivation mechanisms.
SPATIAL AND TEMPORAL ASPECTS OF cAMP SIGNALLING IN CARDIAC MYOCYTES
Authors: Iancu Radu V , Ramamurthy Gopalakrishnan , Harvey Robert D
Published: July 2008

β1‐Adrenoceptor and M2 muscarinic receptor regulation of cAMP production plays a pivotal role in autonomic regulation of cardiac myocyte function. However, not all responses are easily explained by a uniform increase or decrease in cAMP activity throughout the entire cell.

Adenovirus expression of fluorescence resonance energy transfer (FRET)‐based biosensors can be used to monitor cAMP activity in protein kinase A (PKA) signalling domains, as well as the bulk cytoplasmic domain of intact adult cardiac myocytes.

Data obtained using FRET‐based biosensors expressed in different cellular microdomains have been used to develop a computational model of compartmentalized cAMP signalling.

A systems biology approach that uses quantitative computational modelling together with experimental data obtained using FRET‐based biosensors has been used to provide evidence for the idea that compartmentation of cAMP signalling is necessary to explain the stimulatory responses to β1‐adrenoceptor activation as well as the complex temporal responses to M2 muscarinic receptor activation.
Serotoninergic modulation of sensory transmission to brainstem reticulospinal cells
Authors: Antri Myriam , Auclair François , Albrecht Jonathan , Djeudjang Nsima , Dubuc Réjean
Published: August 2008

Sensory inputs are subjected to modulation by central neural networks involved in controlling movements. It has been shown that serotonin (5‐HT) modulates sensory transmission. This study examines in lampreys the effects of 5‐HT on sensory transmission to brainstem reticulospinal (RS) neurons and the distribution of 5‐HT cells that innervate RS cells. Cells were recorded intracellularly in the in vitro isolated brainstem of larval lampreys. Trigeminal nerve stimulation elicited disynaptic excitatory responses in RS neurons, and bath application of 5‐HT reduced the response amplitude with maximum effect at 10 μm. Local ejection of 5‐HT either onto the RS cells or onto the relay cells decreased sensory‐evoked excitatory postsynaptic potentials (EPSPs) in RS cells. The monosynaptic EPSPs elicited from stimulation of the relay cells were also reduced by 5‐HT. The reduction was maintained after blocking either N‐methyl‐d‐aspartate (NMDA) or α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA) receptors. The local ejection of glutamate over RS cells elicited excitatory responses that were only slightly depressed by 5‐HT. In addition, 5‐HT increased the threshold for eliciting sustained depolarizations in response to trigeminal nerve stimulation but did not prevent them. Combined 5‐HT immunofluorescence with axonal tracing revealed that the 5‐HT innervation of RS neurons of the middle rhombencephalic reticular nucleus comes mainly from neurons in the isthmic region, but also from neurons located in the pretectum and caudal rhombencephalon. Our results indicate that 5‐HT modulates sensory transmission to lamprey brainstem RS cells.
Decrease of D2 receptor binding but increase in D2‐stimulated G‐protein activation, dopamine transporter binding and behavioural sensitization in brains of mice treated with a chronic escalating dose ‘binge’ cocaine administration paradigm
Authors: Bailey A. , Metaxas A. , Yoo J. H. , McGee T. , Kitchen I.
Published: July 2008

Understanding the neurobiology of the transition from initial drug use to excessive drug use has been a challenge in drug addiction. We examined the effect of chronic ‘binge’ escalating dose cocaine administration, which mimics human compulsive drug use, on behavioural responses and the dopaminergic system of mice and compared it with a chronic steady dose (3 × 15 mg/kg/day) ‘binge’ cocaine administration paradigm. Male C57BL/6J mice were injected with saline or cocaine in an escalating dose paradigm for 14 days. Locomotor and stereotypy activity were measured and quantitative autoradiographic mapping of D1 and D2 receptors, dopamine transporters and D2‐stimulated [35S]GTPγS binding was performed in the brains of mice treated with this escalating and steady dose paradigm. An initial sensitization to the locomotor effects of cocaine followed by a dose‐dependent increase in the duration of the locomotor effect of cocaine was observed in the escalating but not the steady dose paradigm. Sensitization to the stereotypy effect of cocaine and an increase in cocaine‐induced stereotypy score was observed from 3 × 20 to 3 × 25 mg/kg/day cocaine. There was a significant decrease in D2 receptor density, but an increase in D2‐stimulated G‐protein activity and dopamine transporter density in the striatum of cocaine‐treated mice, which was not observed in our steady dose paradigm. Our results document that chronic ‘binge’ escalating dose cocaine treatment triggers profound behavioural and neurochemical changes in the dopaminergic system, which might underlie the transition from drug use to compulsive drug use associated with addiction, which is a process of escalation.
Short‐acting insulin analogues vs. regular human insulin in type 2 diabetes: a meta‐analysis
Authors: Mannucci E. , Monami M. , Marchionni N.
Published: July 2008

Aim:  Short‐acting insulin analogues, in comparison with regular human insulin (HRI), provide a greater control of postprandial glucose, while their superiority on haemoglobin A1c (HbA1c) is controversial.

Method:  All randomized controlled trials (RCTs) with a duration >4 weeks comparing short‐acting insulin analogues (lispro, aspart or glulisine) with HRI in type 2 diabetic patients were retrieved; data on HbA1c and postprandial glucose et end‐point and incidence of severe hypoglycaemia were extracted and meta‐analysed.

Results:  A total of 13 RCTs (7, 4 and 2 with lispro, aspart and glulisine, respectively) were retrieved and included in the analysis. Short‐acting analogues reduced HbA1c by 0.4% (0.1–0.6%) (p = 0.027) in comparison with HRI. A significant improvement was observed also in self‐monitored 2 h postbreakfast and dinner blood glucose. The overall rate of severe hypoglycaemia was not significantly different with short‐acting analogues and HRI [Mantel–Haenszel odds ratio for 95% confidence interval 0.61 (0.25–1.45)].

Conclusion:  In type 2 diabetic patients, short‐acting insulin analogues provide a better control of HbA1c and postprandial glucose than regular human insulin, without any significant reduction of the risk of severe hypoglycaemia.
Subclinical haemostatic activation and current surgeon volume predict bleeding with open radical retropubic prostatectomy
Authors: Tagawa Scott T. , Dorff Tanya B. , Rochanda Leanne , Ye Wei , Boyle Soames , Raghavan Derek , Lieskovsky Gary , Skinner Donald G. , Quinn David I. , Liebman Howard A.
Published: July 2008

OBJECTIVE

To assess subclinical haemostatic activation and clinical variables to predict bleeding during radical retropubic prostatectomy (RP), as haemostatic activation is common in cancer and might be useful for predicting outcomes, but routine coagulation screening does not correlate with bleeding.

PATIENTS AND METHODS

Clinical data and blood samples were collected from 153 patients (median age 63 years; prostate‐specific antigen, PSA, level 5.92 ng/mL) before RP and lymph node dissection. Plasma was assayed for d‐dimer and thrombin‐antithrombin complex (TAT). Univariable then multivariable analyses were used to identify associations between plasma markers and clinical variables for bleeding and thrombosis.

RESULTS

Most patients (77%) were stage T1c and most (76.5%) had organ‐confined cancer (≤pT2). Pathological Gleason scores were ≤6 in 68 (44.4%) and ≥8 in 14 (9%) of the patients. The median (range) estimated blood loss (EBL) was 400 (50–3000) mL, the median decrease in haemoglobin level 3.5 (−0.1, 6.6) g/dL, and eight men (5.2%) required a transfusion. In the univariable analysis, a lower TAT before RP (P < 0.001) and d‐dimer level (P = 0.023) correlated with a greater decline in haemoglobin level. The platelet count, international normalised ratio, and activated partial thromboplastin time (aPTT) did not predict the EBL nor change in haemoglobin level; the eight transfused patients had lower platelet counts before RP (P = 0.004). Higher surgical volume predicted a lower EBL (P < 0.001) and lower decrease in haemoglobin (P < 0.05). Multivariable linear regression showed that TAT remained significant for the decrease in haemoglobin, and surgical volume for EBL and decrease in haemoglobin.

CONCLUSIONS

Haemostatic activation before RP was associated with significantly less bleeding when assessed by objective measures, predicting the decrease in haemoglobin level better than prothrombin time, aPTT or platelet counts. Current surgeon volume might also predict both subjective and objective bleeding variables.
Laparoscopic adrenalectomy for pheochromocytoma: evaluation of experience and strategy at a single institute
Authors: Kasahara Takashi , Nishiyama Tsutomu , Takahashi Kota
Published: July 2008

OBJECTIVE

To assess the utility, safety and feasibility of laparoscopic adrenalectomy (LA) for pheochromocytoma. We reviewed our experience, focusing on surgical outcomes compared with our historical open adrenalectomy (OA) and modifications in surgical procedures.

PATIENTS AND METHODS

Between 1997 and 2007, 23 patients with pheochromocytoma underwent LA at our institution. As controls, 18 patients undergoing OA were examined retrospectively. In the first cases of LA, we used an abdominal wall‐lifting device with low pneumoperitoneal pressure and initial ligation of the adrenal vein. In subsequent cases, we adopted similar methods to those we perform for other benign adrenal tumours, including a ‘regular’ pneumoperitoneal pressure, and disconnection of the adrenal vein as the last step of tumour dissection.

RESULTS

Rates of hypertension crisis (systolic blood pressure (sBP) of >200 mmHg) and sudden hypotension subsequent to ligation of the adrenal vein (sBP of <80 mmHg) were 17% and 48% in the LA group, and 44% and 72% in the OA group, respectively. Instability of blood pressure was not amplified by the modifications in surgical procedures of laparoscopy. The groups were comparable for operative duration. The intraoperative blood loss among LA patients in whom adrenalectomy was completed laparoscopically was significantly less than that among OA patients, at a median (range) of 70 (10–530) mL vs 400 (10–990) mL (P < 0.001). However, four LA patients with conversion to open surgery had severe blood loss. Regarding postoperative complications and convalescence, the LA group had more favourable outcomes.

CONCLUSION

Laparoscopic removal of pheochromocytoma can be safely and feasibly accomplished by surgical approaches similar to those used for other pathological conditions of the adrenal gland. However, conversion to open surgery should be considered in cases with unexpected difficulty in dissection, invasion or adhesion.
MORAL KNOWLEDGE, EPISTEMIC EXTERNALISM, AND INTUITIONISM
Authors: Star Daniel
Published: August 2008

This paper explores the generally overlooked relevance of an important contemporary debate in mainstream epistemology to philosophers working within ethics on questions concerning moral knowledge. It is argued that this debate, between internalists and externalists about the accessibility of epistemic justification, has the potential to be both significantly influenced by, and have a significant impact upon, the study of moral knowledge. The moral sphere provides a particular type of strong evidence in favour of externalism, and mainstream epistemologists might benefit from paying attention to this fact. At the same time, the terrain of moral epistemology (approached as a sub‐field of metaethics) needs to be reshaped by the realisation that externalists can steal the thunder of intuitionists when it comes to knowledge constituted by seemingly self‐evident beliefs.1
Sticking it all together: A critical assessment of the group cohesion–performance literature
Authors: Casey‐Campbell Milly , Martens Martin L.
Published: July 2008

Although group cohesion is a widely studied construct in the group dynamics literature, there is a considerable lack of consistency and agreement regarding the construct. This paper reviews the current state of the cohesiveness literature. Cohesion is now generally defined as the group members’ inclinations to forge social bonds, resulting in the group sticking together and remaining united. Unfortunately, the large number of definitions and measures used by researchers has created a literature that is inconsistent and confusing. This review focuses on the considerable research on the cohesion–performance relationship. The general consensus of this research is that there is a generally positive association between cohesion and performance, but the theoretical and operational mechanisms creating this association are unclear. This lack of clarity may be due to the wide range of measures and assessments of cohesion and the cohesion–performance association. Two underlying contentious issues within this aspect of the literature are whether cohesion is unidimensional or multidimensional and the appropriate level of analysis required for measuring the construct. The resolution of these inconsistencies requires researchers to take a step back toward grounding the research in broader theoretical frameworks, to determine whether the cohesion–performance association has an underlying common cause, and to use longitudinal studies that use more sophisticated analytical models.
Motion picture performance: A review and research agenda
Authors: Hadida Allègre L.
Published: July 2008

This paper provides a comprehensive literature review of empirical studies of motion picture performance published from 1977 to 2006 inclusive in the following five disciplines of the social sciences: strategy, organization theory, marketing, cultural economics and sociology. It introduces a novel framework which organizes the various dimensions and explanatory factors of movie performance into five distinct categories and underscores their relationships. The paper, which uses this model as a roadmap for discussions of film success, serves two complementary purposes. First, it clarifies the current state of the literature, stresses core contributions and exposes limitations in existing research by emphasizing hitherto neglected independent explanatory factors, dependent dimensions and correlations between them. Second, it introduces five conceptual, methodological and empirical suggestions for further cinema performance research aimed at addressing these limitations and, accordingly, at providing better accounts of motion picture performance in view of the fast‐changing conditions of cinema production, marketing and consumption.
Modulation of basal and stress‐induced amygdaloid substance P release by the potent and selective NK1 receptor antagonist L‐822429
Authors: Singewald Nicolas , Chicchi Gary G. , Thurner Clemens C. , Tsao Kwei‐Lan , Spetea Mariana , Schmidhammer Helmut , Sreepathi Hari Kishore , Ferraguti Francesco , Singewald Georg M. , Ebner Karl
Published: July 2008

It has been shown that anxiety and stress responses are modulated by substance P (SP) released within the amygdala. However, there is an important gap in our knowledge concerning the mechanisms regulating extracellular SP in this brain region. To study a possible self‐regulating role of SP, we used a selective neurokinin‐1 (NK1) receptor antagonist to investigate whether blockade of NK1 receptors results in altered basal and/or stress‐evoked SP release in the medial amygdala (MeA), a critical brain area for a functional involvement of SP transmission in enhanced anxiety responses induced by stressor exposure.In vitrobinding and functional receptor assays revealed that L‐822429 represents a potent and selective rat NK1 receptor antagonist. Intra‐amygdaloid administration of L‐822429 via inverse microdialysis enhanced basal, but attenuated swim stress‐induced SP release, while the low‐affinity enantiomer of L‐822429 had no effect. Using light and electron microscopy, synaptic contacts between SP‐containing fibres and dendrites expressing NK1 receptors was demonstrated in the medial amygdala. Our findings suggest self‐regulatory capacity of SP‐mediated neurotransmission that differs in the effect on basal and stress‐induced release of SP. Under basal conditions endogenous SP can serve as a signal that tonically inhibits its own release via a NK1 receptor‐mediated negative feedback action, while under stress conditions SP release is further facilitated by activation of NK1 receptors, likely leading to high local levels of SP and activation of receptors to which SP binds with lower affinity.