bluuebunny/crossref_metadata_2025 huggingface dataset:
Activated neutrophil-mediated sickle red blood cell adhesion to lung vascular endothelium: role of phosphatidylserine-exposed sickle red blood cells
Authors: Haynes Johnson , Obiako Boniface , King Judy A. , Hester Raymond B. , Ofori-Acquah Solomon
Published: May 2006

Activated neutrophils (ANs) increase sickle red blood cell (SRBC) retention/adhesion in the pulmonary circulation. This study investigates the role of neutrophil activation and SRBC retention/adhesion in the pulmonary circulation through a mechanism that involves increasing phosphatidylserine (PS) exposure on the external membrane surface of the SRBCs (PS-exposed). With the use of flow cytometry, double-labeling studies were performed with a calcium-dependent phospholipid-binding protein, annexin V-fluorescein isothiocyanate fluorescence, and the erythroid-specific marker glycophorin A to assess for the percentage of PS-exposed normal and SRBCs at baseline and after coincubation with ANs. Additional studies were performed that assessed retention/adhesion of SRBCs in the isolated rat lung using51Cr-labeled SRBC alone, SRBC + AN, SRBC + AN + zileuton, and SRBC + AN + annexin V. Specific activities of lung and perfusate were measured, and the number of retained SRBCs per gram lung was calculated. Flow cytometry demonstrated that ANs increased the percentage of PS-exposed normal and SRBCs. The 5-lipoxygenase inhibitor zileuton attenuated AN-mediated increases in PS-exposed SRBCs and decreased SRBC retention/adherence in the lung on histological sections. Similarly, in the isolated perfused lung and in histological lung sections, retention/adherence of SRBCs cloaked with annexin V was attenuated in the presence of ANs. We conclude that ANs enhance the adhesion of SRBCs to vascular endothelium by increasing red blood cell membrane externalization of PS. Zileuton attenuation of AN-mediated SRBC PS externalization suggests that a 5-lipoxygenase product(s), secreted by the AN, plays a vital role in altering the adhesive properties of PS-exposed SRBCs to vascular endothelium.
PAR2 activation interrupts E-cadherin adhesion and compromises the airway epithelial barrier: protective effect of β-agonists
Authors: Winter Michael C. , Shasby Sandra S. , Ries Dana R. , Shasby D. Michael
Published: May 2006

The airway epithelium is an important barrier between the environment and subepithelial tissues. The epithelium is also divided into functionally restricted apical and basolateral domains, and this restriction is dependent on the elements of the barrier. The protease-activated receptor-2 (PAR2) receptor is expressed in airway epithelium, and its activation initiates multiple effects including enhanced airway inflammation and reactivity. We hypothesized that activation of PAR2 would interrupt E-cadherin adhesion and compromise the airway epithelial barrier. The PAR2-activating peptide (PAR2-AP, SLIGRL) caused an immediate ∼50% decrease in the transepithelial resistance of primary human airway epithelium that persisted for 6–10 min. The decrease in resistance was accompanied by an increase in mannitol flux across the epithelium and occurred in cystic fibrosis transmembrane conductance receptor (CFTR) epithelium pretreated with amiloride to block Na and Cl conductances, confirming that the decrease in resistance represented an increase in paracellular conductance. In parallel experiments, activation of PAR2 interrupted the adhesion of E-cadherin-expressing L cells and of primary airway epithelial cells to an immobilized E-cadherin extracellular domain, confirming the hypothesis that activation of PAR2 interrupts E-cadherin adhesion. Selective interruption of E-cadherin adhesion with antibody to E-cadherin decreased the transepithelial resistance of primary airway epithelium by >80%. Pretreatment of airway epithelium or the E-cadherin-expressing L cells with the long-acting β-agonist salmeterol prevented PAR2 activation from interrupting E-cadherin adhesion and compromising the airway epithelial barrier. Activation of PAR2 interrupts E-cadherin adhesion and compromises the airway epithelial barrier.
Associative learning of visual and gustatory cues in the large cabbage white butterfly, Pieris brassicae
Authors: Smallegange Renate , Everaarts Tjarda , Van Loon Joop
Published: May 2006

The landing response of the large cabbage white butterfly Pieris brassicae was studied under controlled optical and gustatory stimulus conditions. Experience-based changes in landing behaviour were examined by offering cardboard circles of two different shades of green, treated with either an oviposition stimulant or a deterrent. We employed two training situations. In one situation the two shades of green, carrying either the stimulant or the deterrent, were offered simultaneously, in the other sequentially. During the 1 hour training periods, butterflies were either landing and drumming spontaneously or they were caught at the end of the period and placed on the artificial leaves until tarsal drumming ensued. Our experiments demonstrated that P. brassicae females can learn to associate visually detected substrate characteristics with contact-chemosensory information available only after landing. Furthermore, a learned preference for a substrate could be turned into a preference for the alternative substrate by exposing the insect to a deterrent on the previously preferred substrate. These results provide indications of aversion learning, thus far undocumented in oviposition behaviour of Lepidoptera. Bringing the butterflies into forced contact with the oviposition stimulant resulted in similar effects on landing preference compared to those of spontaneous landing, but spontaneous landing had a stronger effect on preference for associations involving the deterrent. The simultaneous training regime, which supposedly requires a less important role for short-term memory, was more effective in modifying landing preferences.
A comparison of naïve and conditioned responses of three generalist endoparasitoids of lepidopteran larvae to host-induced plant odours
Authors: Tamò Cristina , Ricard Ingrid , Held Matthias , Davison Anthony , Turlings Ted
Published: May 2006

Many parasitic wasps that exploit herbivores as their hosts make use of herbivoreinduced plant odours to locate their victims and these wasps often exhibit an ability to learn to associate specific plant-produced odours with the presence of hosts. This associative learning is expected to allow generalist parasitoids to focus on cues that are most reliably associated with current host presence, but evidence supporting this hypothesis is ambiguous. Using a six-arm olfactometer we compared the responses of three generalist larval endoparasitoids, Cotesia marginiventris (Hymenoptera: Braconidae), Microplitis rufiventris (Hymenoptera: Braconidae) and Campoletis sonorensis (Hymenoptera: Ichneumonidae), to the induced odours of three plant species: maize (Zea mays), cowpea (Vigna unguiculata), and cotton (Gossypium hirsutum). We tested the responses of naïve females as well as of females that were first conditioned by parasitising host larvae feeding on one of the plant species. Despite similarities in biology and host range the three wasp species responded entirely differently. Naïve C. marginiventris and C. sonorensis chose equally among the induced odours of the three plants, whereas naïve M. rufiventris, which may have a somewhat more restricted host range, tended to prefer the odour of maize. After conditioning, most C. marginiventris females chose the odour of the plant species that they had experienced, but conditioned M. rufiventris showed an even stronger preference for maize odours, independently of the plant they had experienced. Cotesia sonorensis did not show any change in its preference after conditioning. We speculate that its extremely broad host range allows C. sonorensis females to use fixed responses to cues commonly associated with plants damaged by Lepidoptera. These results imply that different generalist parasitoids may employ different foraging strategies and that associative learning is not necessarily part of it.
Associative learning and memory duration in the parasitic wasp Lariophagus distinguendus
Authors: Müller  , Collatz  , Wieland  , Steidle
Published: May 2006

Lariophagus distinguendus (Pteromalidae, Hymenoptera) is an ectoparasitoid of larvae of the granary weevil Sitophilus granarius which develop inside grains. Female parasitoids were trained by keeping them for 1 h on grains infested with their hosts in the presence of the odorant furfurylheptanoate (FFH). In olfactometer experiments, these wasps afterwards preferred the odour field containing FFH as compared to control fields. Control experiments with; i) naïve wasps; ii) wasps exposed to infested grains only; iii) to FFH only; and iv) to infested grains first and FFH later, did not reveal any response to FFH. This indicates that the reaction to FFH is caused by associative learning due to host experience as unconditioned stimulus. Experiments on the durability of the learned response demonstrated that host experience in the presence of FFH induces a memory that can be observed for at least 144 h and most likely is equivalent to long-term memory in honey bee Apis mellifera and Drosophila melanogaster.
Learning signals within sensory environments: Does host cue learning in butterflies depend on background?
Authors: Snell-Rood Emilie , Papaj Daniel
Published: May 2006

Insects must detect and interpret stimuli embedded in a sensory environment of competing stimuli. While sensory environments vary in time and space, individuals may be able to learn local background characteristics, facilitating perceptual learning. This study on host search in butterflies examines the following questions in an ecologically relevant context: i) does cue learning depend on the sensory environment in which learning occurs; and ii) are background characteristics learned, such that performance on novel tasks in the same sensory environment is facilitated? Females of Battus philenor (Papilionidae: Lepidoptera) were trained to different coloured and shaped oviposition targets, against different background colours. Individuals trained to colours on a brown background but tested on a green background performed significantly worse than control individuals which were trained to the same colours but on a green background. Females pre-trained to discriminate green targets from red targets on a green background colour performed significantly better in a novel task (shape learning) involving green shapes on a green background than did individuals trained to discriminate the same colours on a brown background. These two results were unique to particular cue-background combinations, in particular cryptic conditions. Taken together, our results suggest that cue learning depends on an insect's sensory environment, and that learning characteristics of local backgrounds may confer benefits to habitat-faithful individuals.
Learning and memory formation in the honeybee (Apis mellifera) and its dependency on the cAMP-protein kinase A pathway
Authors: Eisenhardt Dorothea
Published: May 2006

The honeybee (Apis mellifera) is a model organism for the study of learning and memory formation and its underlying mechanisms. Honeybees have a rich behaviour that can be studied in the field as well as in the laboratory. In the latter case, olfactory conditioning of the proboscis extension response (PER) has been intensively studied with respect to the neuronal and molecular mechanisms underlying acquisition and memory formation. Quite a lot is known about the neuronal pathways of both the unconditioned and the conditioned stimulus, and molecular mechanisms that lead to memory formation have been identified. In particular, the role of the cAMP-protein kinase A pathway in memory formation has been analysed. Present knowledge about the molecular basis of memory formation is outlined here. The role of the cAMP-dependent signalling cascade in memory formation is summarised and the activation of this pathway by non-associative and associative learning is discussed.
The Impact Properties of High-temperature Fiber-Metal Laminates
Authors: Cortés P. , Cantwell W. J.
Published: May 2006

This study investigates the low and high velocity impact properties of fiber–metal laminates (FMLs) based on carbon fiber-reinforced poly-ether-ether-ketone (CF/PEEK) and glass fiber-reinforced poly-ether-imide (GF/PEI) composites. The aim of this work is to develop a lightweight hybrid material for use in high temperature aerospace applications. Here, low velocity impact tests are undertaken using an instrumented impact tower and high velocity impact tests are conducted using a nitrogen gas gun. Low velocity impact testing has shown that the specific perforation energy of the CF/PEEK-based FMLs is similar to that offered by the CF/PEEK composite. In contrast, the specific perforation energy of the GF/PEI FML system is lower than that of the plain PEI composite. The experimental evidence suggests that the inclusion of strong titanium alloy plies does not improve the perforation resistance of these FMLs. High velocity impact tests resulted in failure processes similar to those observed under low velocity loading conditions, with the specific perforation energy of the GF/PEI-based FMLs being higher than those exhibited by the plain GF/PEI composite. An extensive and detailed optical microscope study has shown that interfacial and interlaminar delaminations are the principal energy-absorbing mechanisms during low and high velocity impacts.
Solid Particle Erosion Behavior of FRPs with Prior Impact Damage
Authors: Miyazaki N.
Published: May 2006

Experiments have been carried out to study the solid particle erosion of FRPs with prior impact damage. Two kinds of FRPs i.e., the epoxy resin reinforced by aramid fibers (AR/EP) and poly p-phenylene-benzobisoxazole fibers (PBO/EP) are used. The AR/EP and PBO/EP laminates with the same layout structure of 12-ply and [0°/90°]6s have the volume fractions of 55.8 and 53.8%, respectively. Prior to erosion tests, the test materials are impact damaged by the projectile shot from an air gun. The interlaminar shearing stress (ILSS) is obtained as a measure for impact damage of the FRPs. Solid particle erosion tests are then performed for the FRPs after they are damaged with a spherical projectile with the velocity of 130 m/s. The test results show that the erosion rates of the FRPs with prior impact damage are less than those of the virgin materials. Less erosion resistance of the FRPs with prior impact damage may be because the FRPs with prior impact damage have a lot of transverse cracks and delaminations, which absorb the kinetic energy of the solid particles used in the erosion tests.
Harmonic Shapes in Finite Elasticity
Authors: Wang G.F. , Schiavone P. , Ru C-Q.
Published: May 2006

We consider the design of harmonic shapes in a particular class of compressible hyperelastic materials of harmonic-type undergoing finite plane deformations. Harmonic shapes are characterized by a `harmonicity condition' imposed on the final stress field. The `harmonicity condition' used in this paper is a generalization of the original condition used in the corresponding problems of linear elasticity: specifically, that the first invariant of the stress tensor (i.e. the sum of the normal stresses) in the original stress field remains unchanged everywhere after the introduction of the harmonic hole or inclusion. Using complex variable techniques, we formulate the general equations for the identification of harmonic shapes in a material of harmonic-type subjected to plane deformations. Under the assumption of uniform biaxial loading, we identify shapes of harmonic rigid inclusions and harmonic free holes. Finally, comparisons are drawn to the analogous cases from linear elasticity.
Determination of Stresses from the Stress Trajectory Pattern in a Plane Elastic Domain
Authors: Mukhamediev Shamil A. , Galybin Alexander N.
Published: May 2006

Identification of stresses acting in a plane (homogeneous and isotropic) elastic domain is performed based on the analysis of principal stress trajectories. This problem, originated in photoelasticity, is now of great importance in geodynamics. Given stress trajectories, in photoelasticity stresses are found by solving a certain boundary value problem. We propose the solution of the problem without appealing to boundary conditions, which is advantageous to geodynamics where boundary stresses are poorly constrained. The analysis of the given stress trajectory pattern is equivalently reduced to the investigation of the argument, α, of the complex-valued bi-holomorphic function, D, which represents the stress deviator of the 2D stress tensor. Necessary and sufficient conditions for the stress trajectory pattern to be admissible in elasticity are established. A procedure to obtain a particular solution, D1, is presented. The general solution for D derived from D1 depends on four (if α is a harmonic function) or one (otherwise) arbitrary real constants. The procedure is illustrated by model examples for West European and Australian platforms.
Core set approach to reduce uncertainty of gene trees
Authors: Okabayashi Takahisa , Kitazoe Yasuhiro , Kishino Hirohisa , Watabe Teruaki , Nakajima Noriaki , Okuhara Yoshiyasu , O'Loughlin Samantha , Walton Catherine
Published: May 2006

Background

A genealogy based on gene sequences within a species plays an essential role in the estimation of the character, structure, and evolutionary history of that species. Because intraspecific sequences are more closely related than interspecific ones, detailed information on the evolutionary process may be available by determining all the node sequences of trees and provide insight into functional constraints and adaptations. However, strong evolutionary correlations on a few lineages make this determination difficult as a whole, and the maximum parsimony (MP) method frequently allows a number of topologies with a same total branching length.

Results

Kitazoe et al. developed multidimensional vector-space representation of phylogeny. It converts additivity of evolutionary distances to orthogonality among the vectors expressing branches, and provides a unified index to measure deviations from the orthogoality. In this paper, this index is used to detect and exclude sequences with large deviations from orthogonality, and then selects a maximum subset ("core set") of sequences for which MP generates a single solution. Once the core set tree is formed whose all the node sequences are given, the excluded sequences are found to have basically two phylogenetic positions on this tree, respectively. Fortunately, since multiple substitutions are rare in intra-species sequences, the variance of nucleotide transitions is confined to a small range. By applying the core set approach to 38 partialenvsequences of HIV-1 in a single patient and also 198 mitochondrial COI and COII DNA sequences ofAnopheles dirus, we demonstrate how consistently this approach constructs the tree.

Conclusion

In the HIV dataset, we confirmed that the obtained core set tree is the unique maximum set for which MP proposes a single tree. In the mosquito data set, the fluctuation of nucleotide transitions caused by the sequences excluded from the core set was very small. We reproduced this core-set tree by simulation based on random process, and applied our approach to many sets of the obtained endpoint sequences. Consequently, the ninety percent of the endpoint sequences was identified as the core sets and the obtained node sequences were perfectly identical to the true ones.
Effect of 5'UTR introns on gene expression in Arabidopsis thaliana
Authors: Chung Betty YW , Simons Cas , Firth Andrew E , Brown Chris M , Hellens Roger P
Published: May 2006

Background

The majority of introns in gene transcripts are found within the coding sequences (CDSs). A small but significant fraction of introns are also found to reside within the untranslated regions (5'UTRs and 3'UTRs) of expressed sequences. Alignment of the whole genome and expressed sequence tags (ESTs) of the model plantArabidopsis thalianahas identified introns residing in both coding and non-coding regions of the genome.

Results

A bioinformatic analysis revealed some interesting observations: (1) the density of introns in 5'UTRs is similar to that in CDSs but much higher than that in 3'UTRs; (2) the 5'UTR introns are preferentially located close to the initiating ATG codon; (3) introns in the 5'UTRs are, on average, longer than introns in the CDSs and 3'UTRs; and (4) 5'UTR introns have a different nucleotide composition to that of CDS and 3'UTR introns. Furthermore, we show that the 5'UTR intron of theA. thalianaEF1α-A3 gene affects the gene expression and the size of the 5'UTR intron influences the level of gene expression.

Conclusion

Introns within the 5'UTR show specific features that distinguish them from introns that reside within the coding sequence and the 3'UTR. In the EF1α-A3 gene, the presence of a long intron in the 5'UTR is sufficient to enhance gene expression in plants in a size dependent manner.
Bilateral symmetrical lymphangiomas of the gingiva: case report
Authors: Motahhary Pouria , Sarrafpour Babak , Abdirad Afshin
Published: May 2006

Background

Lymphangioma is a benign lesion that is related to proliferation of lymphatic vessels. Lymphangioma of the gingiva is a rare lesion that manifest as a pebbly hyperplasia on gingiva. The purpose of this study is to report a case of bilateral symmetrical lymphangioma of the gingiva.

Case presentation

A 32-year-old man was presented with bilateral hyperplasia of gingiva in upper canine regions. The lesions were resected completely and evaluated histologically. The microscopic evaluation revealed lymphangioma.

Conclusion

Bilateral lymphangioma of the gingiva is a very rare lesion which its origin is controversial.
From dropping out to leading on? British counter-cultural back-to-the-land in a changing rurality
Authors: Halfacree Keith
Published: May 2006

Counter-cultural back-to-the-land experimentation is a very long-standing social phenomenon across the global North but has been little studied by geographers. This paper provides a critical overview of its manifestation in Britain over the last 40 years. It emphasizes the importance of placing it in its entangled context of the dominant form(s) that rural space takes. While 1960s/1970s back-to-the-land raised critical questions about the countryside, it mainly `diverted' marginal spaces to alternatives outside the mainstream. In contrast, it exists today at a time when rural spatiality's `productivist' alignment is being sorely challenged. This presents, in principle, greater scope both for its longer-term survival and for it to engage in a `productive' critique of the mainstream rurality that is emerging. The paper suggests that interrogating critically the extent of consubstantial relationships between land and everyday life is also essential for evaluating back-to-the-land experimentation.
Chlamydia pneumoniae infection and the risk of multiple sclerosis: a meta-analysis
Authors: Bagos P G , Nikolopoulos G , Ioannidis A
Published: May 2006

We conducted a meta-analysis of studies comparing the presence of Chlamydia pneumoniae (Cpn) between multiple sclerosis (MS) patients and other neurological diseases patients or healthy controls. We identified 26 studies with 1332 MS patients and 1464 controls. Using random-effects methods, MS patients were found more likely to have detectable levels of Cpn DNA (OR = 3.216; 95% CI: 1.204, 8.585) in their cerebrospinal fluid, and intrathecally synthesized immunoglobulins (OR = 3.842; 95% CI: 1.317, 11.212), compared to other patients with neurological diseases. There is no evidence for increased levels of serum immunoglobulins (OR = 1.068; 95% CI: 0.745, 1.530), even though this result is confounded by the presence of studies using normal subjects as controls. Similarly, there is no evidence for association of immunoglobulins against Cpn in the cerebrospinal fluid (OR = 3.815; 95% CI: 0.715, 20.369). Up to 59.7% of the between-studies variability could be explained by the inappropriate matching of cases and controls for gender. In random-effects meta-regressions, adjusting for the confounding effect of gender differences results in stronger and statistically significant associations of MS with detectable levels of Cpn DNA, intrathecally synthesized immunoglobulins and immunoglobulins in the cerebrospinal fluid. Even though the presence of Cpn is clearly more likely in MS patients, these findings are insufficient to establish an etiologic relation.
Mannosylated liposomes as antigen delivery vehicles for targeting to dendritic cells
Authors: White Karen L , Rades Thomas , Furneaux Richard H , Tyler Peter C , Hook Sarah
Published: May 2006

The immune stimulating ability of mannosylated liposomes containing FITC-ovalbumin as a model antigen and displaying either a branched tri-mannose or a mono-mannose ligand on the liposome surface was investigated in human monocyte-derived dendritic cells (MoDCs) and murine bone-marrow-derived dendritic cells (BMDCs). Uptake of liposomes, dendritic cell activation and proliferation of CD8+ T cells from OT-I transgenic mice were determined by flow cytometry. Uptake of liposomes displaying the tri-mannose ligand was enhanced in human MoDCs compared with both non-mannosylated liposomes and liposomes displaying mono-mannose ligands. However, this increased uptake did not result in an increase in expression of CD80 or CD86 on the surface of the MoDCs. In contrast, neither tri-mannose- nor mono-mannose-containing liposomes were taken up by murine BMDCs to a greater extent than non-mannose-containing liposomes. The expression of CD86 and CD40 on the surface of BMDCs was not increased after exposure to mannosylated lipo-somes and BMDCs incubated with mannosylated liposomes were not able to stimulate proliferation of CD8+ T cells to any greater extent than BMDCs incubated with non-mannosylated liposomes. These findings suggest that while mannose-containing ligands can enhance the uptake of antigen-containing liposomes by some dendritic cells, important differences in the affinity of carbohydrate-binding receptors for mannose-containing ligands do exist between species. In addition, the increase in uptake of antigen by dendritic cells using mannosylated liposomes does not necessarily result in enhanced dendritic cell activation.
Biodegradable nanoparticle delivery of a Th2-biased peptide for induction of Th1 immune responses
Authors: Lutsiak M E Christine , Kwon Glen S , Samuel John
Published: May 2006

The type of immune response developed against the hepatitis B virus (HBV) is crucial in determining the outcome of the disease. The protective effects of vaccine-induced antibody responses against subsequent exposure to HBV are well-established. After the establishment of chronic HBV infection, cell-mediated immune response is curative while humoral response is detrimental. A therapeutic vaccine that could switch the type of response could lead to disease resolution. Hepatitis B core antigen (HBcAg)129–140 has been identified as a Th2-biased peptide in H-2b mice when it is administered along with complete Freund's adjuvant (CFA). We formulated HBcAg129–140 along with monophosphoryl lipid A in poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles. Naïve mice immunized with the nanoparticle formulation developed a strong Th1-type response while mice immunized with the control formulation of CFA and peptide did not. We then primed mice with CFA and peptide to establish a Th2-type immune response before administering the nanoparticle formulation. Mice receiving the nanoparticle formulation being primed with CFA still developed a strong Th1-type response, while mice that received incomplete Freund's adjuvant and peptide instead of nanoparticles did not. The ability of PLGA nanoparticles to alter the type of immune response elicited by a peptide, even in the context of an ongoing immune response, makes PLGA nanoparticles a strong candidate for the formulation of therapeutic vaccines.
Development of vaccines against bovine tuberculosis
Authors: Hogarth P J , Hewinson R G , Vordermeier H M
Published: May 2006

Bovine tuberculosis caused by Mycobacterium bovis remains an economically important problem in Great Britain with potential zoonotic consequences, and the incidence is rising exponentially. In 1997 an independent scientific review recommended that the best option for disease control in Great Britain was the development of a cattle vaccine. Bovine tuberculosis remains a significant problem in countries of the developing world. Indeed, more than 94% of the world's population live in countries in which the control of bovine tuberculosis in buffalos or cattle is limited or absent. Effective vaccination strategies would have a major impact in countries that cannot afford expensive test and slaughter-based control strategies. Here, we present a review of progress toward that goal, and discuss how this progress has shaped our research strategy for the development of a vaccine.
HIV-1 neutralizing antibodies elicited by the candidate CBD1 epitope vaccine react with the conserved caveolin-1 binding motif of viral glycoprotein gp41
Authors: Rey-Cuillé Marie-Anne , Svab Josette , Benferhat Rima , Krust Bernard , Briand Jean-Paul , Muller Sylviane , Hovanessian Ara G
Published: May 2006

To date, candidate HIV-1 vaccines that have been tested in clinical trials have failed to induce broadly neutralizing activities and/or antibodies that inhibit infection by primary isolates of HIV-1. We recently identified a conserved caveolin-1 binding motif, WNNMTWMQW, in the ectodomain of HIV-1 transmembrane envelope glycoprotein gp41. We designed the synthetic CBD1 peptide SLEQIWNNMTWMQWDK, corresponding to the consensus caveolin-1 binding domain (CBD) in gp41, and showed that it elicits in rabbits the production of antibodies that inhibit infection of primary CD4+ T lymphocytes by various primary HIV-1 isolates. Although a conserved and highly homologous caveolin-1 binding motif is present in the transmembrane envelope glycoprotein of different HIV-2 isolates, anti-CBD1 immune sera do not inhibit HIV-2 infection. Here we show that anti-CBD1 antibodies are directed against the conserved caveolin-1 binding motif WNNMTWMQW in the CBD1 epitope. In spite of this, anti-CBD1 antibodies do not react with the CBD2 peptide SLTPDWNNMTWQEWER, corresponding to the potential consensus caveolin-1 binding domain in HIV-2. The presence of a conserved proline residue upstream of the caveolin-1 binding motif in CBD2 might affect the presentation of this motif, and thus account for the lack of reactivity of the immune sera. Anti-CBD1 antibodies therefore appear to be directed against a conformational epitope mimicked by the synthetic CBD1 peptide. In accordance with this, anti-CBD1 immune sera react with the native but not denatured gp41. The reactivity of anti-CBD1 immune sera with a highly conserved conformational epitope could explain the broad inhibitory activity of such antipeptide antibodies against HIV-1 isolates of various clades.
Impact of formulation excipients on human intestinal transit
Authors: Schulze Julia D R , Ashiru Diane A I , Khela Mandeep K , Evans David F , Patel Rajesh , Parsons Gary E , Coffin Mark D , Basit Abdul W
Published: May 2006

The accelerating effect of polyethylene glycol 400 on small intestinal transit has been previously reported. The aim of this study was to investigate the influence of other solubility-enhancing excipient, propylene glycol, D-α-tocopheryl-polyethylene glycol-1000 succinate (VitE-TPGS) and Capmul MCM, on human intestinal transit. A 5-g dose of each excipient was administered to seven healthy male subjects. Propylene glycol and VitE-TPGS were administered dissolved in 150 mL water. Capmul MCM was administered in the form of four 000 hard gelatin capsules to mask its taste and then given with 150 mL water. On a separate occasion, 150 mL water was administered as the control. Each formulation was radiolabelled with technetium-99 m to follow its transit using a gamma camera. The mean small intestinal transit times were 234, 207, 241 and 209 min for the control, propylene glycol, VitE-TPGS and Capmul MCM treatments, respectively. Although there were differences in the small intestinal transit times for the excipients investigated compared with the control, none of the results were statistically significant. Unlike polyethylene glycol 400 at the same dose of 5g, the excipients tested (propylene glycol, VitE-TPGS and Capmul MCM) had little or no impact on small intestinal transit.
Application of a sample pooling method for the accelerated assessment of the rate of uptake of drugs by the brain in rats
Authors: Kim Kang-Pil , Ahn Sung-Hoon , Sung Jong-Hyuk , Koo Tae-Sung , Byun Myong-Joo , Kim Dae-Duk , Shim Chang-Koo , Chung Suk-Jae
Published: May 2006

The purpose of this study was to examine the feasibility of applying a sample pooling method to the accelerated estimation of the uptake clearance of drugs to the brain in rats. Brain uptake clearances (CLuptake) were estimated for five model compounds using the sample pooling method and an integration plot analysis. CLuptake was also evaluated for caffeine and theophylline by brain micro-dialysis. The parameters and throughput of the pooling method were compared with those of typically used standard methods. The correlation for CLuptake was statistically significant (P < 0.005) between the integration plot and the current method; the throughput of evaluation was 15-fold higher for the sample pooling method. A comparison of CLuptake values indicated that the three methods showed comparable results for caffeine while the CLuptake of theophylline using the proposed method was significantly different from those of the other methods. A kinetic analysis indicated that a compound with a slower CLuptake and longer half-life (e.g., theophylline) is more prone to error and that the lower limit of the CLuptakeof 0.17 mL min−1 (g brain)−1 may beset so as to have an error less than 20% of the estimation. These results suggest that the sample pooling method is applicable for use in the accelerated estimation of the uptake clearance of compounds in the brain for which the value is greater than 0.17 mL min−1 (g brain)−1.
Vobasinyl-iboga bisindole alkaloids, potent acetylcholinesterase inhibitors from Tabernaemontana divaricata root
Authors: Ingkaninan Kornkanok , Changwijit Kanokwan , Suwanborirux Khanit
Published: May 2006

The roots of the Thai medicinal plant, Tabernaemontana divaricata (L.) R. Br. ex Roem. & Schult., were investigated for their content of acetylcholinesterase inhibitors. Bioassay-guided fractionation using the Ellman colorimetric method led to the isolation of two bisindole alkaloids, 19,20-dihydrotabernamine and 19,20-dihydroervahanine A. The compounds showed higher inhibitory activity on acetylcholinesterase in comparison with galanthamine, a well-known acetylcholinesterase inhibitor. The inhibitory activity of 19,20-dihydroervahanine A was proved to be specific, reversible and competitive. During the separation process, two inactive bisindole alkaloids, conodurine and tabernaelegantine A, were also isolated. The data suggest that the substitutions at the carbons 11′, 12′ and 16′ might affect the acetylcholinesterase inhibitory activity.
Endovenous laser obliteration for the treatment of primary varicose veins
Authors: Vuylsteke M , Van den Bussche D , Audenaert E A , Lissens P
Published: May 2006

Objective: The aim of this study was to compare the minimally invasive endovenous laser technique for treatment of primary varicose veins with the conventional stripping operation in terms of short-term recovery and cost for economically active patients.

Methods: One hundred and sixty four patients with varicose veins caused by great saphenous vein insufficiency were assigned to the endovenous laser obliteration procedure ( n = 80, 118 legs) or stripping operation ( n = 84, 124 legs). Postoperative morbidity, the need for analgesics and the duration of sick leave were recorded. The comparison of costs included both direct medical costs and costs resulting from lost productivity of the patients.

Results: Overall there were less postoperative complications in the laser group. Sick leave was significantly shorter in the endovenous obliteration group ( P<0.001). Although the variable costs of the conventional stripping operation were lower than those of the endovenous laser procedure, the total costs at public expense were higher because of the difference in lost productivity of the patients.

Conclusions: Endovenous laser obliteration may offer advantages over the stripping operation in terms of reduced postoperative pain, shorter sick leave and faster return to usual occupational activities, and it appears to be cost-saving for society.
Concomitance of varicoceles and chronic venous insufficiency in young males
Authors: Bolcal C , Sargin M , Mataraci I , Iyem H , Doganci S , Kilic S , Temizkan V , Demirkilic U , Tatar H
Published: May 2006

Introduction: The aim of this article was to evaluate the concomitance of symptomatic varicose veins and varicoceles in a young male patient group.

Method: The study was conducted as a prospective, multicentre study in the cardiovascular outpatient clinics of two major military hospitals. The data of 1500 young male patients with symptomatic venous insufficiency were recorded regarding symptomatic varicoceles.

Results: The median age of the patients was 21.2 ± 1.3 years. Symptomatic varicocele was a concomitant finding in 46.0% of the patients. In patients with chronic venous insufficiency, higher body mass index, high levels of smoking, standing occupation, positive family history, longer duration of symptoms and constipation were found as potential factors for concomitant varicocele in both univariate and multivariate analysis. A statistically significant, moderately positive correlation was found between grades of venous reflux in saphenofemoral junction and varicocele (Spearman's rho correlation r = 0.637, P <0.001).

Conclusion: With the observation that varicoceles may be concomitant in nearly half of patients with venous insufficiency, it is thought that just a simple question in history taking may help these patients to be diagnosed and get treated for this potential cause of infertility.
Cost consequences of preoperative duplex examination before varicose vein surgery: a randomized clinical trial
Authors: Blomgren L , Zethraeus N , Johansson G , Jönsson B , Bergqvist D
Published: May 2006

Objectives: To investigate the cost consequences of the addition of a duplex scan to the routine clinical examination prior to surgery for varicose veins (VV).

Methods: Cost data are based on a prospective study, which randomized 293 VV patients for surgery either with or without a preoperative duplex scan. Costs are collected during a two-year follow-up time and include direct costs for primary surgery and reoperation.

Results: The mean cost for the primary operation was SEK 12,827 (€1410) in the duplex group and SEK 9856 (€1083) in the control group ( P<0.001). A significant part of this increase was due to more extensive primary surgery. Costs for redo surgery decreased by SEK 1131 (€124) ( P = 0.011). The mean net cost increase because of duplex is estimated to be SEK 1840 (€202) ( P<0.003).

Conclusion: The savings in costs for redo surgery did not offset the costs for preoperative duplex examination before VV surgery during a two-year follow-up period.
Seroprevalence of HSV-1 and 2 among sex workers attending a sexually transmitted infection clinic in Singapore
Authors: Theng T S C , Sen P R , Tan H H , Wong M L , Chan K W R
Published: May 2006

We studied the seroprevalence of herpes simplex virus (HSV)-1 and 2 in sex workers attending a sexually transmitted infection clinic in Singapore and examined their knowledge and attitudes towards HSV infection. A total of 300 participants were recruited. Questionnaires were administered and blood was taken and analysed, using the HerpeSelect 1 and 2 Elisa IgG assays (type-specific serological test). HSV-1 serology was positive in 230 (76.7%), negative in 67 (22.3%) sex workers and indeterminate in three (1.0%) sex workers. HSV-2 serology was positive in 237 (79.0%) and negative in 63 (21.0%) sex workers. On univariate analysis, there was significant association between HSV-2 seropositivity and increasing age, nationality (locals) ( P <0.001) and marital status ( P <0.01). Adjusting for age, marital status and condom use, HSV-2 prevalence increased significantly with duration of years of practice of sex work. Most of the respondents (86.0%) were aware that HSV could be spread through sex without a condom and about two-thirds of them were aware that HSV could be spread in the absence of symptoms. In conclusion, HSV-2 is a common infection among sex workers in Singapore with the risk increasing with years of practice.
Pediculosis pubis: presentation to ophthalmologist as pthriasis palpebrarum associated with corneal epithelial keratitis
Authors: Manjunatha N P , Jayamanne G R , Desai S P , Moss T R , Lalik J , Woodland Alison
Published: May 2006

Pthiriasis palpebrarum caused by infestation with Pthirus pubis (crab louse) draws attention to pediculosis in the pubic and inguinal region. As pthiriasis is usually transmitted by sexual contact, many cases are likely to have other sexually transmitted diseases. A multidisciplinary approach is essential in the management of these cases. In this case report, we highlight the above and report for the first time associated keratitis.
Sexual health services – a patient preference survey
Authors: Hambly Sally , Luzzi Graz
Published: May 2006

We sought to determine the extent to which attenders at a genitourinary (GU) medicine clinic would be willing to see their general practitioner (GP) for sexual health services, and the factors that were important to them in making this decision. Fifty-nine percent of 209 patients expressed a preference for the GU clinic, and 30% for seeing a GP. Sixty-two percent of patients would accept an appointment with a GP if this meant being seen more quickly. The two most important factors reported by patients in deciding where to be seen were confidentiality (81% rated this 'very important') and attitudes of staff (75%). Range of tests available and specialist knowledge were also highly valued (65%). The findings support the development of sexual health services in primary care settings.
An atypical herpetic vulval ulcer in an African woman: an important lesson
Authors: Palamaras Ioulios , Richardson Daniel , Healy Vourneen , Lyons Deirdre , Byrne Micheline , Lamba Harpal
Published: May 2006

A 43-year-old woman from Southern Africa presented with an eight-month history of a painless vulval ulcer. She did not have any relevant past medical or drug history. She had never had, or ever been offered an HIV antibody test despite being from an endemic region. On examination, there was an ulcer on her right labia and a painless right inguinal lymph node. Herpes simplex virus (HSV) type 2 culture was positive. The HIV antibody test was also positive. Other cultures and serology including syphilis were negative. A biopsy was suggestive of herpes simplex. The vulval ulcer resolved on oral aciclovir only.

Atypical genital herpes has been described in HIV disease, although it is often painful. This case emphasises the importance of offering an HIV antibody test to patients presenting with atypical genital ulcers. Moreover, it reinforces the paradigm that 'any anogenital ulcer (painful or not) can be herpetic in origin'.
Conserved zinc fingers mediate multiple functions of ZFP100, a U7snRNP associated protein
Authors: Wagner Eric J. , Ospina Jason K. , Hu Yue , Dundr Miroslav , Matera A. Gregory , Marzluff William F.
Published: May 2006

Formation of the 3′ end of replication-dependent histone mRNAs is most robust during S phase and is mediated by both the stem–loop binding protein (SLBP) and the U7 snRNP. We previously identified a 100-kDa zinc finger protein (ZFP100) as a component of U7 snRNP that interacts with the SLBP/pre-mRNA complex. Here, we show that myc- or GFP-tagged ZFP100 overexpressed after transfection is concentrated in Cajal bodies (CBs), and unlike components of the spliceosomal snRNPs, photobleaching experiments demonstrate that ZFP100 is stably associated with CBs. Of the 18 zinc fingers contained within ZFP100, the region encompassing fingers 2–6 is sufficient to maintain CB localization. Zn fingers 5–10 are required for maximal binding of ZFP100 to a 20-amino-acid region of Lsm11, a U7 snRNP core protein. Expression of ZFP100 stimulates histone mRNA processing in vivo, assayed by activation of a reporter gene that encodes a GFP mRNA ending in a histone 3′ end. Importantly, the domain that is required for CB localization and Lsm11 binding is also sufficient to stimulate histone pre-mRNA processing in vivo. Comparisons with other mammalian ZFP100 orthologs show that the central Zn fingers sufficient for in vivo activity are most highly conserved, whereas the number and sequence of the Zn fingers in the N- and C-terminal domains vary.
Yeast transcripts cleaved by an internal ribozyme provide new insight into the role of the cap and poly(A) tail in translation and mRNA decay
Authors: Meaux Stacie , Van Hoof Ambro
Published: May 2006

It has been proposed that the 7-methylguanosine cap and poly(A) tail of mRNAs have important functions in translation and transcript stability. To directly test these roles of the cap and poly(A) tail, we have constructed plasmids with a ribozyme within the coding region or 3′ UTR of reporter genes. We show that the unadenylated 5′ cleavage product is translated and is rapidly degraded by the cytoplasmic exosome. This exosome-mediated decay is independent of the nonstop mRNA decay pathway, and, thus, reveals an additional substrate for exosome-mediated decay that may have physiological equivalents. The rapid decay of this transcript in the cytoplasm indicates that this unadenylated cleavage product is rapidly exported from the nucleus. We also show that this cleavage product is not subject to rapid decapping; thus, the lack of a poly(A) tail does not always trigger rapid decapping of the transcript. We show that the 3′ cleavage product is rapidly degraded by Xrn1p in the cytoplasm. We cannot detect any protein from this 3′ cleavage product, which supports previous data concluding that the 5′ cap is required for translation. The reporter genes we have utilized in these studies should be generally useful tools in studying the importance of the poly(A) tail and 5′ cap of a transcript for export, translation, mRNA decay, and other aspects of mRNA metabolism in vivo
The potential role of ribosomal frameshifting in generating aberrant proteins implicated in neurodegenerative diseases
Authors: Wills Norma M. , Atkins John F.
Published: May 2006

Aberrant forms of proteins ubiquitin B and β-amyloid precusor protein, UBB+1 and APP+1, are implicated in human neurodegenerative diseases. They have their carboxyl-terminal regions derived from an alternative reading frame. Transcription slippage has been invoked to explain the production of these proteins from abnormal mRNA. However, ribosomal frameshifting on wild-type mRNA may account for the great majority of the aberrant protein. Ribosomal frameshifting may also be involved in the progression of triplet expansion diseases such as Huntington's and spinocerebellar ataxias. In a particular spinocerebellar ataxia, SCA3, Toulouse and colleagues recently discovered −1 frameshifting in a transcript containing an expanded CAG-repeat. Antibiotics that affect mammalian ribosomes may have complex effects on frameshifting and disease progression.