bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polar Localization of the Autotransporter Family of Large Bacterial Virulence Proteins
Authors: Jain Sumita , van Ulsen Peter , Benz Inga , Schmidt M. Alexander , Fernandez Rachel , Tommassen Jan , Goldberg Marcia B. 
Published: June 2006

ABSTRACTAutotransporters are an extensive family of large secreted virulence-associated proteins of gram-negative bacteria. Secretion of such large proteins poses unique challenges to bacteria. We demonstrate that autotransporters from a wide variety of rod-shaped pathogens, including IcsA and SepA ofShigella flexneri, AIDA-I of diffusely adherentEscherichia coli, and BrkA ofBordetella pertussis, are localized to the bacterial pole. The restriction of autotransporters to the pole is dependent on the presence of a complete lipopolysaccharide (LPS), consistent with known effects of LPS composition on membrane fluidity. Newly synthesized and secreted BrkA is polar even in the presence of truncated LPS, and all autotransporters examined are polar in the cytoplasm prior to secretion. Together, these findings are consistent with autotransporter secretion occurring at the poles of rod-shaped gram-negative organisms. Moreover, NalP, an autotransporter of spherically shapedNeisseria meningitidiscontains the molecular information to localize to the pole ofEscherichia coli. InN. meningitidis, NalP is secreted at distinct sites around the cell. These data are consistent with a model in which the secretion of large autotransporters occurs via specific conserved pathways located at the poles of rod-shaped bacteria, with profound implications for the underlying physiology of the bacterial cell and the nature of bacterial pathogen-host interactions.
Endothelial dysfunction and systemic inflammation in persons with echolucent carotid plaques
Authors: Mathiesen Ellisiv , Amiral Jean , Vissac Anne , Hansen John-Bjarne , Notø Ann-Trude 
Published: June 2006

SummaryEcholucent carotid plaques are associated with high risk for future ischemic cerebrovascular events independent of the degree of stenosis. Elevated levels of markers of systemic inflammation and endothelial dysfunction are predictors for future myocardial infarction and stroke.The present study was undertaken to investigate the relations between plaque morphology, endothelial dysfunction assessed by tissue-plasminogen activator antigen (t-PA ag) and von Willebrand factor (vWF), and systemic inflammation in persons with carotid stenosis.We conducteda crosssectional study including 133 persons with carotid stenosis and 138 controls without stenosis recruited from the populationbased Tromsø Study. High-resolution B-mode and colour Doppler/pulsed-wave Doppler ultrasonography of both carotid arteries was performed, and plaque morphology in terms of echogenicity was assessed. Persons with carotid stenosis had significantly higher plasma t-PA and vWF concentrations than controls. There was a significant inverse relationship between t-PA ag and plaque echogenicity (p=0.034).The increased plasma t-PA ag in persons with carotid stenosis was not associated with increased plasminogen activator inhibitor-I (PAI-1).Persons with echolucent carotid plaques had higher degree of systemic inflammation, and plasma t-PA and vWF concentration increased significantly across quartiles of WBC, fibrinogen, and hs-CRP. Our findings may suggest that plasma t-PA may be superior to vWF asa marker for endothelial dysfunction due to its ability to discriminate between various plaque echogenicity, and that the predictive role of t-PA ag in cardiovascular disease is independent of inhibited fibrinolysis.
Identification of factor inhibitors by diagnostic haemostasis laboratories
Authors: Bonar Roslyn , Duncan Elizabeth , Earl Gail , Low Joyce , Aboud Margaret , Just Sarah , Sioufi John , Street Alison , Marsden Katherine , Favaloro Emmanuel ,   on behalf of the RCPA QAP in Haematology Haemostasis Committe
Published: June 2006

SummaryWe have assessed the proficiency of diagnostic haemostasis facilities to correctly identify coagulation factor abnormalities and inhibitors. Forty-two laboratories participating in the external Quality Assurance Program (QAP) conducted by the RCPA agreed to participate and were each sent a set of eight sample (each 3x1ml) for evaluation. They were asked to blind test these samples for the presence or absence of inhibitors, and wher identified, to perform further analysis (including specific inhibitor analysis). In order to make the exercise more challenging, in addition to true factor inhibitors, samples were provided that reflected potential pre-analytical variables that might arise and complicate inhibitor detection or lead to false inhibitor identification. In brief, the sample set comprised a true high level factor (F)V inhibitor, a true moderate level FVIII inhibitor (but sample was defibrinogenated),a true lupus anticoagulant (LA),a normal (but slightly aged) plasma sample, a normal serum sample, a normal EDTA sample, an oral anticoagulant/vitamin K deficiency sample, and a gross heparin (∼10U/ml) contaminated sample. Sixty-three percent of participants correctly identified the true FV inhibitor as such, although the reported range varied greatly [10 to >250 Bethesda units (BU/ml)] and 46% correctly identi fied the true FVIII inhibitor, despite the complication of the sample presentation, although the reported range also varied (7 to 64 BU/ml). Some laboratories either failed to identify the inhibitor present, or misidentified the inhibitor type. The LA, the oral anticoagulant/vitamin K deficiency, the normal serum sample, and the normal (aged) sample were also correctly identified by most laboratories, as was the absence of specific factor inhibitors in these samples. However, a small subset of laboratories incorrectly identified the presence of specific factor inhibitors in some of these samples. The heparin sample was also correctly identified by most (68%) laboratories. In contrast, the normal EDTA sample was misidentified as a FV and/or FVIII inhibitor by most (68%) laboratories, and only one laboratory correctly identified this as an EDTA sample. Thus, we conclude that although laboratories are able, in most cases, to identify the presence of true factor inhibitors, there is a large variation in identified inhibitor levels and there are also some significant errors in identification (i.e. false negatives and misidentifications). In addition, there is a significant false positive error rate where some laboratories will identify the presence of specific factor inhibitors where no such inhibitor exists (i.e. false positives).
Antithrombotic properties of Ixolaris, a potent inhibitor of the extrinsic pathway of the coagulation cascade
Authors: Nazareth Rômulo , Tomaz Luana , Ortiz-Costa Susana , Atella Geórgia , Ribeiro José , Francischetti Ivo , Monteiro Robson 
Published: June 2006

SummaryIxolaris is a two-Kunitz tick salivary gland protein identified in Ixodes scapularis that presents extensive sequence homology t TFPI.It binds to FXa or FX as scaffolds and inhibits tissue factor/ FVIIa complex (extrinsic Xnase). Differently from TFPI, ixolaris does not bind to the active site cleft of FXa. Instead, comple formation is mediated by the FXa heparin-binding exosite,which may also results in decreased FXa activity into the prothrombi nase complex.In this report,we show that recombinant 125I-ixo laris interacts with rat and human FX in plasma and prolongs the prothrombin time (PT) and activated partial thromboplastin time (aPTT) in vitro.We have also investigated the effects of ixo laris in vivo, using a venous thrombosis model. Subcutaneous (s.c.) or intravenous (i.v.) administration of ixolaris in rats caused a dose-dependent reduction in thrombus formation, with complete inhibition attained at 20 µg/kg and 10 µg/kg, re spectively. Antithrombotic effects were observed 3 h after s.c. administration of ixolaris and lasted for 24 h thereafter. Ex vivo experiments showed that ixolaris (up to 100 µg/kg) did not affect the aPTT,while the PT was increased by ∼0.4-fold at the hig hest ixolaris concentration. Remarkably, effective antithrom botic doses of ixolaris (20 µg/kg) was not associated with bleed ing which was significant only at higher doses of the anticoagulant (40 µg/kg).Our experiments demonstrate that ixolaris is an effective and possibly safe antithrombotic agen in viv .
The 5-HT2C receptor and antipsychoticinduced weight gain – mechanisms and genetics
Authors: Reynolds Gavin P. , Hill Matthew J. , Kirk Shona L. 
Published: June 2006

The mechanisms underlying weight gain resulting from antipsychotic drugs are not fully understood, although antagonism of the 5-HT2C receptor is likely to contribute. Animal studies indicate that the drugs most likely to cause weight gain, clozapine and olanzapine, have direct effects on the NPY-containing neurons of the hypothalamus; these neurons mediate the effects of the circulating anorexigenic hormone leptin on the control of food intake. The substantial differences between individuals in the extent of antipsychotic-induced weight gain suggest that genetic factors may be important. We have been studying pharmacogenetic correlates and find that a common 5-HT2C receptor promoter region polymorphisms demonstrates strong associations with weight gain in two first episode psychotic samples. In both series, we have found further association of antipsychotic drug-induced weight gain with a common and functional polymorphism of the gene for leptin. Along with initial BMI, these two pharmacogenetic factors account for almost 30% of the variance in drug-induced weight gain. Interestingly, the 5-HT2C polymorphism appears to determine levels of circulating leptin, providing a potential mechanism underlying the genetic association of the 5-HT2C receptor with weight gain. We have undertaken functional studies of haplotypes of the 5-HT2C promoter region and find the allele associated with protection from weight gain results in reduced promoter activity. These findings demonstrate the value of pharmacogenetics in determining liability to a major side effect of antipsychotic treatment, and indicate both the molecular and physiological mechanisms underlying this side effect.
Relevance of assessing drug concentration exposure in pharmacogenetic and imaging studies
Authors: Lotrich Francis E. , Bies Robert R. , Smith Gwenn S. , Pollock Bruce G. 
Published: June 2006

Pharmacodynamic differences are difficult to interpret without drug concentration data. In particular, variability in drug exposure may confound the interpretation of pharmacogenetic, therapeutic outcome, and neuroimaging studies. Inter-individual variability in concentrations can be quite high due to variable adherence and pharmacokinetics. For example, clearance may be influenced by genetics, drug interactions, age and illness. We review findings that acute responses to selective serotonin reuptake inhibitors can have a concentration–response relationship using positron emission tomography and neuroendocrine measures. We also present preliminary evidence that the concentration–response relationship for paroxetine is influenced by genotypic differences at the serotonin transporter promoter.In large clinical studies, the accurate assessment of drug exposure can be challenging, with several techniques used to assess exposure. Population pharmacokinetics (Pop PK) is a method that is ideally suited for analysing concentration data from large trials because both patient-specific and population parameters can be determined with only a small number of plasma samples per patient. As opposed to relying on prescribed doses or a single trough level, the ability to determine more accurately exposure with Pop PK reduces the heterogeneity introduced by exposure variability. Pop PK hierarchic Bayesian approaches have been effective for characterizing anticonvulsants, antibiotics, antineoplastics and antiarrhythmics. We have recently successfully incorporated these pop PK analyses into routine assessments of elderly patients in clinical trials of selective serotonin reuptake inhibitors (SSRIs) and second generation antipsychotics. For the design and interpretation of neuroimaging, pharmacogenetic, and behavioural studies, the assessment of drug concentration exposure is therefore feasible and has potentially important ramifications.
The contractile vacuole in Ca2+-regulation in Dictyostelium: its essential function for cAMP-induced Ca2+-influx
Authors: Malchow Dieter , Lusche Daniel F , Schlatterer Christina , De Lozanne Arturo , Müller-Taubenberger Annette 
Published: June 2006

Abstract
Background
cAMP-induced Ca2+-influx in Dictyostelium is controlled by at least two non-mitochondrial Ca2+-stores: acidic stores and the endoplasmic reticulum (ER). The acidic stores may comprise the contractile vacuole network (CV), the endosomal compartment and acidocalcisomes. Here the role of CV in respect to function as a potential Ca2+-store was investigated.

Results
Dajumin-GFP labeled contractile vacuoles were purified 7-fold by anti-GFP-antibodies in a magnetic field. The purified CV were shown for the first time to accumulate and release Ca2+. Release of Ca2+ was elicited by arachidonic acid or the calmodulin antagonist W7, the latter due to inhibition of the pump. The characteristics of Ca2+-transport and Ca2+-release of CV were compared to similarly purified vesicles of the ER labeled by calnexin-GFP. Since the CV proved to be a highly efficient Ca2+-compartment we wanted to know whether or not it takes part in cAMP-induced Ca2+-influx. We made use of the LvsA--mutant expected to display reduced Ca2+-transport due to loss of calmodulin. We found a severe reduction of cAMP-induced Ca2+-influx into whole cells.

Conclusion
The contractile vacuoles in Dictyostelium represent a highly efficient acidic Ca2+-store that is required for cAMP-induced Ca2+-influx.
In vitro antimicrobial activity of natural toxins and animal venoms tested against Burkholderia pseudomallei
Authors: Perumal Samy R , Pachiappan A , Gopalakrishnakone P , Thwin Maung M , Hian Yap E , Chow Vincent TK , Bow Ho , Weng Joseph T 
Published: June 2006

Abstract

Background

Burkholderia pseudomallei are the causative agent of melioidosis. Increasing resistance of the disease to antibiotics is a severe problem in treatment regime and has led to intensification of the search for new drugs. Antimicrobial peptides are the most ubiquitous in nature as part of the innate immune system and host defense mechanism.

Methods
Here, we investigated a group of venoms (snakes, scorpions and honey bee venoms) for antimicrobial properties against two strains of Gram-negative bacteria Burkholderia pseudomallei by using disc-diffusion assay for in vitro susceptibility testing. The antibacterial activities of the venoms were compared with that of the isolated L-amino acid oxidase (LAAO) and phospholipase A2 (PLA2s) enzymes. MICs were determined using broth dilution method. Bacterial growth was assessed by measurement of optical density at the lowest dilutions (MIC 0.25 mg/ml). The cell viability was measured using tetrazolium salts (XTT) based cytotoxic assay.

Results
The studied venoms showed high antimicrobial activity. The venoms of C. adamanteus, Daboia russelli russelli, A. halys, P. australis, B. candidus and P. guttata were equally as effective as Chloramphenicol and Ceftazidime (30 μg/disc). Among those tested, phospholipase A2 enzymes (crotoxin B and daboiatoxin) showed the most potent antibacterial activity against Gram-negative (TES) bacteria. Naturally occurring venom peptides and phospholipase A2 proved to possess highly potent antimicrobial activity against Burkholderia pseudomallei. The XTT-assay results showed that the cell survival decreased with increasing concentrations (0.05–10 mg/mL) of Crotalus adamanteus venom, with no effect on the cell viability evident at 0.5 mg/mL.

Conclusion
This antibacterial profile of snake venoms reported herein will be useful in the search for potential antibacterial agents against drug resistant microorganisms like B. pseudomallei.
High incidence of metastatic disease in primary high grade and large extremity soft tissue sarcomas treated without chemotherapy
Authors: Leidinger Benedikt , Heyse Thomas , Schuck Andreas , Buerger Horst , Mommsen Philipp , Bruening Thomas , Fuchs Susanne , Gosheger Georg 
Published: June 2006

Abstract

Background
The risk of metastasis and the survival in patients with primary extremity soft tissue sarcomas is worse when tumour size is large and the grade of malignancy is high. Such tumours may receive chemotherapy and/or radiation therapy (RTX) for optimising local control. Irradiation can either be applied preoperatively or after tumour resection. The question arises if the kind of RTX in the absence of chemotherapy influences the outcome concerning local control, metastatic disease, survival and complications.

Methods
We retrospectively reviewed the clinical outcome of 233 patients with a primary extremity soft tissue sarcoma treated between 1990 – 2000 with a mean follow-up of 35.8 (4–120) months in our institute. 41 patients had high grade, deep and large tumours (>8 cm), an AJCC stage III (no evidence of metastasis prior to treatment) and were treated with limb salvage surgery and irradiation but stayed without additional chemotherapy. Two groups of patients were compared: the first group received postoperative RTX after tumour resection (n = 33); the second group was treated with preoperative RTX (n = 8). Both groups did not differ concerning clinical parameters. We analysed primary and secondary outcomes.

Results
56% (23/41) of the population developed metastatic disease, 24% (10/41) local recurrence. The risk of metastasis was higher in the group with preoperative irradiation (p = 0.046). The overall (p = 0.0248) and relapse free survival (p = 0.104) were worse in this group. The delay to tumour resection amounted 8 weeks on average in the preoperative group. Local control was not different (p = 0.38) in both study groups. Wound infections and other combined therapy related complications were equally distributed (p = 0.22).

Conclusion
Without chemotherapy there remains a high risk of metastasis in AJCC grade 3 patients. In high risk patients treated without chemotherapy the elapsed time to tumour resection after preoperative radiation might contribute to the development of metastasis. This outcome may support the thesis that a combination of RTX and offensive multimodal treatment protocols is advantageous in such a subset of patients
Effect of pH on trout blood vessels and gill vascular resistance
Authors: Smith Michael P. , Dombkowski Ryan A. , Wincko Jeffrey T. , Olson Kenneth R. 
Published: June 2006

SUMMARY
pH is recognized as a modulator of vascular smooth muscle (VSM) tone in mammalian vessels, but little is known about its effects on fish VSM. We investigated the effects of extracellular and intracellular pH (pHoand pHi, respectively) on isolated vessels from steelhead and rainbow trout (Oncorhynchus mykiss, Skamania and Kamloops strains,respectively) and of pHo on perfused gills from rainbow trout. In otherwise unstimulated (resting) efferent branchial (EBA) and coeliaco-mesenteric arteries (CMA), anterior cardinal veins (ACV) and perfused gills, increasing pHo from 6.8 to 8.8–9.0 produced a dose-dependent contraction or increase in gill resistance(RGILL) with an estimated half-maximal response of 8.0–8.2. pHo interactions with other contractile stimuli were agonist specific; more force was developed at low pHo in ligand-mediated (arginine vasotocin) contractions, whereas depolarization-mediated (40–80 mmol l–1 KCl)contractions were greatest at high pHo. Increasing pHiby application of 40 mmol l–1 NH4Cl produced sustained contraction in afferent branchial arteries (ABA) suggesting that these vessels could not readily restore pHi. NH4Cl application only transiently contracted EBA and CMA in Hepes buffer, whereas it produced a slight, but prolonged, relaxation of EBA and CMA in Cortland buffer. The buffer effect was due to the presence of Hepes and in this environment EBA and CMA appeared to readily restore pHi. Increasing pHi in KCl-contracted EBA in Hepes produced an additional contraction, whereas ligand-contracted (thromboxane A2 analog,U-46619) EBA relaxed. Reducing pHi (NH4Cl washout)transiently contracted resting EBA and CMA in both Hepes and Cortland buffer. NH4Cl washout produced an additional, transient contraction of both KCl- and U-46619-contracted EBA in Hepes. EBA contractions produced by increased pHi depend primarily on intracellular Ca2+,whereas both intracellular and extracellular Ca2+ contributed to the response to decreased pHi. Three cycles of perfusate acidification (pHo 7.8 to 6.2 and back to 7.8) reproducibly halved,then restored RGILL with no adverse effects, indicating that this was not a pathophysiological response. These studies show that the general effects of pH on VSM are phylogenetically conserved from fish to mammals but even within a species there are vessel-specific differences. Furthermore, as fish are exposed to substantial fluctuations in environmental(and therefore plasma) pH, the obligatory response of fish VSM to these changes may have substantial impact on cardiovascular homeostasis.
Synthesis of and Ferromagnetic Coupling in Poly(phenylenevinylene)s Bearing Built-in t-Butyl Nitroxides
Authors: Nishide Hiroyuki , Kaneko Takashi , Toriu Shuichi , Kuzumaki Yoshihiro , Tsuchida Eishun 
Published: June 2006

Abstract
Poly[[2- or 4-[N-t-butyl-N-(triethylsiloxy- or t-butyldimethylsiloxy)amino]-1,4- or 1,2-phenylene]vinylene] was synthesized by polymerizing 4- or 2-bromo-2- or 4-[N-t-butyl-N-(triethylsiloxy- or t-butyldimethylsiloxy)amino]styrene with a palladium catalyst, respectively. They were deprotected and chemically oxidized to yield poly(1,4- or 1,2-phenylenevinylene)s bearing a 2- or 4-substituted built-in nitroxide radical. The polyradicals were chemically stable, and their spin concentration was increased to 0.8 spin/unit. A SQUID measurement which included the corresponding diradicals and triradicals indicated that a partial, but strong, intramolecular ferromagnetic coupling was established through the conjugated backbone, despite a spin defect in the side radical moiety, for the poly(1,2- phenylenevinylene) bearing 4-substituted built-in nitroxide radical.
Photooxygenation of 1,1-Diarylethylenes via Addition of Oxygen to the 1,4-Dimer Radical Cations, Catalyzed by 10-Methylacridinium Ion
Authors: Fujita Morifumi , Shindo Akira , Ishida Akito , Majima Tetsuro , Takamuku Setsuo , Fukuzumi Shunichi 
Published: June 2006

Abstract
Photooxygenation of 1,1-diarylethylene occurs efficiently using 10-methylacridinium ion as a photocatalyst to yield the 1,2-dioxane and/or the diaryl ketone depending on the substituents on the aryl groups. The reaction mechanism is revealed based on the dependence of the quantum yields on the concentrations of the alkene and oxygen, the fluorescence quenching of 10-methylacridinium ion by the alkene, and the direct detection of reactive intermediates by applying laser flash spectroscopy as well as pulse radiolysis. The photooxygenation proceeds via photoinduced electron transfer from the alkene to the singlet excited state of 10-methylacridinium ion. The alkene radical cation formed by the photoinduced electron transfer reacts with alkene to give the 1,4-dimer radical cation, which then reacts with oxygen to produce the oxygenated 1,6-radical cation. The subsequent one-electron reduction of the 1,6-radical cation results in formation of the 1,6-biradical which cyclizes to yield 1,2-dioxane derivative or fragmentates to yield diaryl ketone. When the 1,6-biradical is reduced by the alkene itself, the alkene radical cation is regenerated to repeat the radical chain process.