bluuebunny/crossref_metadata_2025 huggingface dataset:
Progestin Signaling through an Olfactory G Protein and Membrane Progestin Receptor-α in Atlantic Croaker Sperm: Potential Role in Induction of Sperm Hypermotility
Authors: Tubbs Christopher , Thomas Peter
Published: September 2008

Progestin stimulation of sperm hypermotility remains poorly understood despite having been described in numerous vertebrate species. We show here that progestin stimulation of sperm hypermotility in a teleost, the Atlantic croaker (Micropogonias undulatus) is associated with activation of an olfactory G protein (Golf). Furthermore, we provide evidence that this progestin action is mediated by membrane progestin receptor-α (mPRα). Golf was identified in croaker sperm membranes and was specifically activated after treatment with the progestin 17,20β,21-trihydroxy-4-pregnen-3-one (20β-S). Treatment of sperm membranes with 20β-S caused an increase in cAMP production, which was blocked by pretreatment with cholera toxin and two membrane adenylyl cyclase inhibitors: 2′,5′-dideoxyadenosine and SQ22536. Moreover, preincubation of croaker sperm with 2′,5′-dideoxyadenosine and SQ22536 resulted in a significant inhibition of 20β-S-stimulated hypermotility. Binding of [3H]20β-S to sperm membranes was decreased after pretreatment with GTPγS but not pertussis toxin, suggesting the receptor is coupled to a pertussis toxin-insensitive G protein. Golf and mPRα were coexpressed on the sperm midpiece and flagella and were coimmunoprecipitated from sperm membranes. Finally, expression of mPRα protein on sperm increased after in vivo treatment with LHRH and was associated with increased induction of sperm motility by 20β-S. These results suggest that 20β-S activates mPRα in croaker sperm, which in turn activates Golf and membrane adenylyl cyclase to stimulate sperm hypermotility. Taken together these findings provide a plausible mechanism by which progestins stimulate sperm hypermotility in croaker and provide the first evidence of hormonal activation of Golf in any species.

Progestin activation of an olfactory G protein pathway, likely through membrane progestin receptor alpha, is associated with induction of hypermotility in Atlantic croaker sperm.
Cortisol Reduces Gonadotropin-Releasing Hormone Pulse Frequency in Follicular Phase Ewes: Influence of Ovarian Steroids
Authors: Oakley Amy E. , Breen Kellie M. , Clarke Iain J. , Karsch Fred J. , Wagenmaker Elizabeth R. , Tilbrook Alan J.
Published: September 2008

Stress-like elevations in plasma glucocorticoids suppress gonadotropin secretion and can disrupt ovarian cyclicity. In sheep, cortisol acts at the pituitary to reduce responsiveness to GnRH but does not affect GnRH pulse frequency in the absence of ovarian hormones. However, in ewes during the follicular phase of the estrous cycle, cortisol reduces LH pulse frequency. To test the hypothesis that cortisol reduces GnRH pulse frequency in the presence of ovarian steroids, the effect of cortisol on GnRH secretion was monitored directly in pituitary portal blood of follicular phase sheep in the presence and absence of a cortisol treatment that elevated plasma cortisol to a level observed during stress. An acute (6 h) cortisol increase in the midfollicular phase did not lower GnRH pulse frequency. However, a more prolonged (27 h) increase in cortisol beginning just before the decrease in progesterone reduced GnRH pulse frequency by 45% and delayed the preovulatory LH surge by 10 h. To determine whether the gonadal steroid milieu of the follicular phase enables cortisol to reduce GnRH pulse frequency, GnRH was monitored in ovariectomized ewes treated with estradiol and progesterone to create an artificial follicular phase. A sustained increment in plasma cortisol reduced GnRH pulse frequency by 70% in this artificial follicular phase, in contrast to the lack of an effect in untreated ovariectomized ewes as seen previously. Thus, a sustained stress-like level of cortisol suppresses GnRH pulse frequency in follicular phase ewes, and this appears to be dependent upon the presence of ovarian steroids.

A sustained stress-like level of cortisol reduces GnRH pulse frequency in the follicular phase and appears to require the presence of ovarian steroids.
Regenerative Potentials of the Murine Thyroid in Experimental Autoimmune Thyroiditis: Role of CD24
Authors: Chen Cindy Y. , Kimura Hiroaki , Landek-Salgado Melissa A. , Hagedorn Judith , Kimura Miho , Suzuki Koichi , Westra William , Rose Noel R. , Caturegli Patrizio
Published: September 2008

Hashimoto thyroiditis can be partially reproduced in mice by immunization with thyroglobulin or, more recently, thyroperoxidase. This experimental autoimmune thyroiditis (EAT) model has been extensively characterized during early disease phases (up to d 35 after immunization). By extending the analysis of EAT to 100 d after immunization, we noted a remarkable regenerative capacity of the thyroid and the expression of Oct-4, suggesting in vivo the existence of adult thyroid stem cells. After an almost complete destruction of the follicular architecture, occurring between d 21 and 28, the thyroid was capable of restoring its follicles and reducing the mononuclear infiltration, so that by d 100 after immunization, it regained its normal morphology and function. During this regeneration process, thyrocytes expressed high levels of CD24. We therefore assessed the role of CD24 in thyroid regeneration by inducing EAT in mice lacking CD24. Regeneration was faster in the absence of CD24, likely a consequence of the effect of CD24 on the infiltrating lymphocytes. The study suggests that the EAT model can also be used as a tool to investigate adult thyroid stem cells.

The murine thyroid is capable of restoring its architecture after an insult that almost completely destroys it.
Functional Characterization and Structural Modeling of Obesity Associated Mutations in the Melanocortin 4 Receptor
Authors: Tan Karen , Pogozheva Irina D. , Yeo Giles S. H. , Hadaschik Dirk , Keogh Julia M. , Haskell-Leuvano Carrie , O'Rahilly Stephen , Mosberg Henry I. , Farooqi I. Sadaf
Published: September 2008

Mutations in the melanocortin 4 receptor (MC4R) gene are the most common known cause of monogenic human obesity. The MC4R gene was sequenced in 2000 subjects with severe early-onset obesity. We detected seven different nonsense and 19 nonsynonymous mutations in a total of 94 probands, some of which have been reported previously by others. We functionally characterized the 11 novel obesity associated missense mutations. Seven of these mutants (L54P, E61K, I69T, S136P, M161T, T162I, and I269N) showed impaired cell surface trafficking, reduced level of maximal binding of the radioligand [125I]NDP-MSH, and reduced ability to generate cAMP in response to ligand. Four mutant MC4Rs (G55V, G55D, S136F, and A303T) displayed cell surface expression and agonist binding similar to the wild-type receptor but showed impaired cAMP production, suggesting that these residues are likely to be critical for conformational rearrangement essential for receptor activation. Homology modeling of these mutants using a model of MC4R based on the crystal structure of the β2-adrenoreceptor was used to provide insights into the possible structural basis for receptor dysfunction. Transmembrane (TM) domains 1, 3, 6, 7, and peripheral helix 8 appear to participate in the agonist-induced conformational rearrangement necessary for coupling of ligand binding to signaling. We conclude that G55V, G55D, S136F, and A303T mutations are likely to strengthen helix-helix interactions between TM1 and TM2, TM3 and TM6, and TM7 and helix 8, respectively, preventing relative movement of these helices during receptor activation. The combination of functional studies and structural modeling of naturally occurring pathogenic mutations in MC4R can provide valuable information regarding the molecular mechanism of MC4R activation and its dysfunction in human disease.

Among obesity-associated melanocortin-4 receptor mutations, four transmembrane domains and peripheral helix 8 are necessary for coupling of ligand binding to signaling.
Mice Lacking β-Adrenergic Receptors Have Increased Bone Mass but Are Not Protected from Deleterious Skeletal Effects of Ovariectomy
Authors: Bouxsein M. L. , Devlin M. J. , Glatt V. , Dhillon H. , Pierroz D. D. , Ferrari S. L.
Published: September 2008

Activation of β2-adrenergic receptors inhibits osteoblastic bone formation and enhances osteoclastic bone resorption. Whether β-blockers inhibit ovariectomy-induced bone loss and decrease fracture risk remains controversial. To further explore the role of β-adrenergic signaling in skeletal acquisition and response to estrogen deficiency, we evaluated mice lacking the three known β-adrenergic receptors (β-less). Body weight, percent fat, and bone mineral density were significantly higher in male β-less than wild-type (WT) mice, more so with increasing age. Consistent with their greater fat mass, serum leptin was significantly higher in β-less than WT mice. Mid-femoral cross-sectional area and cortical thickness were significantly higher in adult β-less than WT mice, as were femoral biomechanical properties (+28 to +49%, P < 0.01). Young male β-less had higher vertebral (1.3-fold) and distal femoral (3.5-fold) trabecular bone volume than WT (P < 0.001 for both) and lower osteoclast surface. With aging, these differences lessened, with histological evidence of increased osteoclast surface and decreased bone formation rate at the distal femur in β-less vs. WT mice. Serum tartrate-resistance alkaline phosphatase-5B was elevated in β-less compared with WT mice from 8–16 wk of age (P < 0.01). Ovariectomy inhibited bone mass gain and decreased trabecular bone volume/total volume similarly in β-less and WT mice. Altogether, these data indicate that absence of β-adrenergic signaling results in obesity and increased cortical bone mass in males but does not prevent deleterious effects of estrogen deficiency on trabecular bone microarchitecture. Our findings also suggest direct positive effects of weight and/or leptin on bone turnover and cortical bone structure, independent of adrenergic signaling.

Mice lacking ß-adrenergic receptors have increased body weight, bone mineral density, and bone turnover versus controls, but are not protected from bone loss due to deficiency of estrogens..
A Crucial Role for Gαq/11, But Not Gαi/o or Gαs, in Gonadotropin-Releasing Hormone Receptor-Mediated Cell Growth Inhibition
Authors: White Colin D. , Coetsee Marla , Morgan Kevin , Flanagan Colleen A. , Millar Robert P. , Lu Zhi-Liang
Published: September 2008

GnRH acts on its cognate receptor in pituitary gonadotropes to regulate the biosynthesis and secretion of gonadotropins. It may also have direct extrapituitary actions, including inhibition of cell growth in reproductive malignancies, in which GnRH activation of the MAPK cascades is thought to play a pivotal role. In extrapituitary tissues, GnRH receptor signaling has been postulated to involve coupling of the receptor to different G proteins. We examined the ability of the GnRH receptor to couple directly to Gαq/11, Gαi/o, and Gαs, their roles in the activation of the MAPK cascades, and the subsequent cellular effects. We show that in Gαq/11-negative cells stably expressing the GnRH receptor, GnRH did not induce activation of ERK, jun-N-terminal kinase, or P38 MAPK. In contrast to Gαi or chimeric Gαqi5, transfection of Gαq cDNA enabled GnRH to induce phosphorylation of ERK, jun-N-terminal kinase, and P38. Furthermore, no GnRH-mediated cAMP response or inhibition of isoproterenol-induced cAMP accumulation was observed. In another cellular background, [35S]GTPγS binding assays confirmed that the GnRH receptor was unable to directly couple to Gαi but could directly interact with Gαq/11. Interestingly, GnRH stimulated a marked reduction in cell growth only in cells expressing Gαq, and this inhibition could be significantly rescued by blocking ERK activation. We therefore provide direct evidence, in multiple cellular backgrounds, that coupling of the GnRH receptor to Gαq/11, but not to Gαi/o or Gαs, and consequent activation of ERK plays a crucial role in GnRH-mediated cell death.
Steroidal Androgens and Nonsteroidal, Tissue-Selective Androgen Receptor Modulator, S-22, Regulate Androgen Receptor Function through Distinct Genomic and Nongenomic Signaling Pathways
Authors: Narayanan Ramesh , Coss Christopher C. , Yepuru Muralimohan , Kearbey Jeffrey D. , Miller Duane D. , Dalton James T.
Published: September 2008

Androgen receptor (AR) ligands are important for the development and function of several tissues and organs. However, the poor oral bioavailability, pharmacokinetic properties, and receptor cross-reactivity of testosterone, coupled with side effects, place limits on its clinical use. Selective AR modulators (SARMs) elicit anabolic effects in muscle and bone, sparing reproductive organs like the prostate. However, molecular mechanisms underlying the tissue selectivity remain ambiguous. We performed a variety of in vitro studies to compare and define the molecular mechanisms of an aryl propionamide SARM, S-22, as compared with dihydrotestosterone (DHT). Studies indicated that S-22 increased levator ani muscle weight but decreased the size of prostate in rats. Analysis of the upstream intracellular signaling events indicated that S-22 and DHT mediated their actions through distinct pathways. Modulation of these pathways altered the recruitment of AR and its cofactors to the PSA enhancer in a ligand-dependent fashion. In addition, S-22 induced Xenopus laevis oocyte maturation and rapid phosphorylation of several kinases, through pathways distinct from steroids. These studies reveal novel differences in the molecular mechanisms by which S-22, a nonsteroidal SARM, and DHT mediate their pharmacological effects.
PECAM-1 is a critical mediator of atherosclerosis
Authors: Stevens Hazel Y. , Melchior Benoît , Bell Kelly S. , Yun Sujin , Yeh Jiunn-Chern , Frangos John A.
Published: September 2008

Atherosclerosis is a chronic inflammatory disease of large arteries in which lesion development preferentially occurs at vessel sites exposed to rapid changes in flow. We have previously shown that platelet endothelial cell adhesion molecule (PECAM-1), a surface receptor of the immunoglobulin superfamily, is involved in mechanosensing of rapid changes in flow. We wondered whether apolipoprotein E deficient (ApoE−/−) mice, predisposed to development of atheromas, would be protected from atherosclerosis by deficiency in PECAM-1. Using double knockout (DKO) mice for both PECAM-1 and ApoE (ApoE−/−/PECAM-1−/−) we found a significant reduction of sudanophilic lesions in their aortae compared to single knockout (SKO) (ApoE−/−/PECAM-1+/+) mice maintained on a high-fat Western diet. Immunostaining of aortic sinus cross sections demonstrated significantly lower ICAM-1 expression in DKO lesions compared with SKO lesions, and en face preparations of vessel regions subjected to disturbed and laminar flow showed less disruption of junctional connexin 43 in DKO than in SKO mice. Thus, PECAM-1 deficiency reduced the extent of lesions at the aortic arch and the aortic sinus, and lowered atherogenic indices. These results suggest that PECAM-1 is an important factor in the atherogenic changes seen in the ApoE-deficient mouse model and thus should be considered as a potential target for protection against atherosclerosis.
An innate immune response of blood cells to tumors and tissue damage in Drosophila
Authors: Pastor-Pareja José Carlos , Wu Ming , Xu Tian
Published: September 2008

Studies in mice and humans have demonstrated a role for the immune system in preventing the growth of tumors. Deciphering the mechanisms involved in the immune response to tumors is essential to our understanding of immune recognition and cancer progression. Here we report an innate immune response to tumors in Drosophila melanogaster. We found that circulating blood cells, termed hemocytes, adhere to tumors upon detection of basement membrane disruption, and subsequently counter their growth. Basement membrane components are remarkably conserved throughout the animal kingdom, providing a unique structure for the immune system to sense tissue integrity. Further, we show that tissue damage activates JNK signaling in both tumors and aseptic wounds, causing expression of JAK/STAT-activating cytokines. Cytokine secretion from the injured tissue is amplified into a systemic response through the induction of additional cytokine expression in the hemocytes and the fat body, resulting in hemocyte proliferation. Our findings reveal common mechanisms in the response to tumors and wounds in flies. A similar innate reaction may underlie the response to tumors and tissue damage in vertebrates and humans.
Natural variation in plasticity of glucose homeostasis and food intake
Authors: Kaun Karla R. , Chakaborty-Chatterjee Munmun , Sokolowski Marla B.
Published: September 2008

Balancing the acquisition, allocation and storage of energy during periods of food deprivation is critical for survival. We show that natural variation in the foraging (for) gene, which encodes a cGMP-dependent protein kinase (PKG) in the fruit fly Drosophila melanogaster,affects behavioral and physiological responses to short-term food deprivation. Rover and sitter, natural allelic variants of for, differ in their stored carbohydrate reserves as well as their response to short-term deprivation. Fewer carbohydrates are stored in the fat body of rovers compared with sitters, and more labeled glucose is allocated to lipid stores compared with carbohydrate stores during a short feeding bout. Short-term food deprivation decreases hemolymph glucose levels in rovers but not in sitters. After food deprivation, rovers increase their food intake more slowly than sitters, and rover hemolymph levels take longer to respond to re-feeding. Finally, rovers have lower adipokinetic hormone (akh) mRNA levels than sitters. Our data suggest that for mediates larval responses to short-term food deprivation by altering food intake and blood glucose levels.
African penguins (Spheniscus demersus) can detect dimethyl sulphide, a prey-related odour
Authors: Cunningham Gregory B. , Strauss Venessa , Ryan Peter G.
Published: September 2008

Although it is well established that certain procellariiform seabirds use odour cues to find prey, it is not clear whether penguins use olfactory cues to forage. It is commonly assumed that penguins lack a sense of smell, yet they are closely related to procellariiforms and forage on similar types of prey in similar areas to many procellariiforms. Such regions are characterized by having high levels of dimethyl sulphide (DMS) a scented compound that many marine animals use to locate foraging grounds. If penguins can smell, DMS may be a biologically relevant scented compound that they may be sensitive to in nature. To test this hypothesis, we investigated whether adult African penguins (Spheniscus demersus) could detect DMS using two separate experiments. We tested wild penguins on Robben Island, South Africa, by deploying μmolar DMS solutions in the colonies, and found that birds slowed down their walking speeds. We also tested captive penguins in a Y-maze. In both cases, our data convincingly demonstrate that African penguins have a functioning sense of smell and are attracted to DMS. The implication of this work is that the detection of changes in the odour landscape (DMS) may assist penguins in identifying productive areas of the ocean for foraging. At-sea studies are needed to investigate this issue further.
Fluid dynamics of feeding behaviour in white-spotted bamboo sharks
Authors: Nauwelaerts Sandra , Wilga Cheryl D. , Lauder George V. , Sanford Christopher P.
Published: September 2008

Although the motor control of feeding is presumed to be generally conserved, some fishes are capable of modulating the feeding behaviour in response to prey type and or prey size. This led to the `feeding modulation hypothesis', which states that rapid suction strikes are pre-programmed stereotyped events that proceed to completion once initiated regardless of sensory input. If this hypothesis holds true, successful strikes should be indistinguishable from unsuccessful strikes owing to a lack of feedback control in specialized suction feeding fishes. The hydrodynamics of suction feeding in white-spotted bamboo sharks (Chiloscyllium plagiosum) was studied in three behaviours: successful strikes, intraoral transports of prey and unsuccessful strikes. The area of the fluid velocity region around the head of feeding sharks was quantified using time-resolved digital particle image velocimetry (DPIV). The maximal size of the fluid velocity region is 56%larger in successful strikes than unsuccessful strikes (10.79 cm2vs 6.90 cm2), but they do not differ in duration,indicating that strikes are modulated based on some aspect of the prey or simply as a result of decreased effort on the part of the predator. The hydrodynamic profiles of successful and unsuccessful strikes differ after 21 ms, a period probably too short to provide time to react through feedback control. The predator-to-prey distance is larger in missed strikes compared with successful strikes, indicating that insufficient suction is generated to compensate for the increased distance. An accuracy index distinguishes unsuccessful strikes (–0.26) from successful strikes (0.45 to 0.61). Successful strikes occur primarily between the horizontal axis of the mouth and the dorsal boundary of the ingested parcel of water, and missed prey are closer to the boundary or beyond. Suction transports are shorter in duration than suction strikes but have similar maximal fluid velocity areas to move the prey through the oropharyngeal cavity into the oesophagus (54 ms vs 67 ms).
The kinematic determinants of anuran swimming performance: an inverse and forward dynamics approach
Authors: Richards Christopher T.
Published: September 2008

The aims of this study were to explore the hydrodynamic mechanism of Xenopus laevis swimming and to describe how hind limb kinematics shift to control swimming performance. Kinematics of the joints, feet and body were obtained from high speed video of X. laevis frogs (N=4)during swimming over a range of speeds. A blade element approach was used to estimate thrust produced by both translational and rotational components of foot velocity. Peak thrust from the feet ranged from 0.09 to 0.69 N across speeds ranging from 0.28 to 1.2 m s–1. Among 23 swimming strokes, net thrust impulse from rotational foot motion was significantly higher than net translational thrust impulse, ranging from 6.1 to 29.3 N ms,compared with a range of –7.0 to 4.1 N ms from foot translation. Additionally, X. laevis kinematics were used as a basis for a forward dynamic anuran swimming model. Input joint kinematics were modulated to independently vary the magnitudes of foot translational and rotational velocity. Simulations predicted that maximum swimming velocity (among all of the kinematics patterns tested) requires that maximal translational and maximal rotational foot velocity act in phase. However, consistent with experimental kinematics, translational and rotational motion contributed unequally to total thrust. The simulation powered purely by foot translation reached a lower peak stroke velocity than the pure rotational case (0.38 vs 0.54 m s–1). In all simulations, thrust from the foot was positive for the first half of the power stroke, but negative for the second half. Pure translational foot motion caused greater negative thrust(70% of peak positive thrust) compared with pure rotational simulation (35%peak positive thrust) suggesting that translational motion is propulsive only in the early stages of joint extension. Later in the power stroke, thrust produced by foot rotation overcomes negative thrust (due to translation). Hydrodynamic analysis from X. laevis as well as forward dynamics give insight into the differential roles of translational and rotational foot motion in the aquatic propulsion of anurans, providing a mechanistic link between joint kinematics and swimming performance.
Pitching stabilizationviacaudal fin-wave propagation in a forward-sinking parrot cichlid (Cichlasoma citrinellum×Cichlasoma synspilum)
Authors: Ting S. C. , Yang J. T.
Published: September 2008

Caudal fin-wave propagation (CFP) is a commonly observed behavior in a fish but has been little investigated. Our objective is to understand the function of a CFP for a forward-sinking parrot cichlid that adopts a tilted-down swimming posture. We utilized stereoscopic digital particle-image velocimetry to measure the velocity fields in the wake of both the caudal fin and the pectoral fins and to evaluate the corresponding hydrodynamic forces. The tilted-down posture of this fish is inherently unstable because of the presence of the head-down pitching moment induced from the buoyant force of the body. The down-stroke of the pectoral fins results also in a head-down pitching moment that destabilizes the fish. Our results indicate that a CFP facilitates the pitching stabilization of a fish. In a forward-sinking parrot cichlid, a CFP produces periodic jets (CFP jets) that are oriented laterally and posterodorsally, which result in both thrust and negative lift that induce a head-up pitching moment. The CFP jets are initially trapped by the ventral part of the caudal fin, strengthened and reoriented by the dorsally propagating fin wave, and expelled near the dorsal part of the caudal fin.
Foraging bats avoid noise
Authors: Schaub Andrea , Ostwald Joachim , Siemers Björn M.
Published: September 2008

Ambient noise influences the availability and use of acoustic information in animals in many ways. While much research has focused on the effects of noise on acoustic communication, here, we present the first study concerned with anthropogenic noise and foraging behaviour. We chose the greater mouse-eared bat (Myotis myotis) as a model species because it represents the especially vulnerable group of gleaning bats that rely on listening for prey rustling sounds to find food (i.e. `passive listening'). In a choice experiment with two foraging compartments, we investigated the influence of background noise on foraging effort and foraging success. We tested the hypotheses that: (1) bats will avoid foraging areas with particularly loud background noise; and (2) the frequency–time structure of the noise will determine, in part, the degree to which it deters bats. We found a clear effect of the type of noise on the allocation of foraging effort to the compartments and on the distribution of prey capture events. When playing back silence, the bats made equal use of and were equally successful in both compartments. In the other three treatments (where a non-silent sound was played back), the bats avoided the playback compartment. The degree to which the background noise deterred bats from the compartment increased from traffic noise to vegetation movement noise to broadband computer-generated noise. Vegetation noise, set 12 dB below the traffic noise amplitude, had a larger repellent effect; presumably because of its acoustic similarity with prey sounds. Our experimental data suggest that foraging areas very close to highways and presumably also to other sources of intense, broadband noise are degraded in their suitability as foraging areas for such `passive listening'bats.
The effect of nitroglycerin ointment on great saphenous vein targeted venous access site diameter with endovenous laser treatment
Authors: Hogue R S , Schul M W , Dando C F , Erdman B E
Published: September 2008

Objectives

To assess the effect of topically applied nitroglycerin (NTG) ointment (2%) on preoperative targeted venous access site great saphenous vein (GSV) diameter in patients undergoing endovenous laser treatment (ELT).

Methods

In this double-blinded randomized study design, 75 patients received either (A) treadmill ambulation only, (B) topically applied NTG ointment only, or (C) topically applied NTG ointment + treadmill ambulation. Targeted venous access vein diameters were measured before therapeutic intervention and then repeated after approximately 30 min following pretreatment intervention. Presence of venospasm and the number of ultrasound-guided venous access attempts during each ELT procedure were assessed during the study.

Results

The mean pretreatment vein diameter was 2.6 mm (range 0.9–4.9 mm). The post-treatment percentage change in vein diameter for group A (treadmill ambulation only) was +2.7% ( P = 0.403), whereas group B (NTG only) and group C (NTG + treadmill ambulation) demonstrated significant venodilatation of +69.0% ( P < 0.0001) and +51.7% ( P < 0.0001), respectively. Statistical analysis of variances and multivariate linear regression model revealed topically applied NTG ointment and ‘C’ classification of clinical, aetiological, anatomical and pathological elements (CEAP) were each significant predictors for venodilatation percentage change ( P < 0.001 and = 0.028, respectively).

Conclusion

Pretreatment with topically applied NTG ointment (2%) produced a statistically significant, as well as subjective clinically significant venodilatation change in the targeted venous access site diameter of patients undergoing ELT of the GSV in this study.
Endovenous laser ablation: mechanism of action
Authors: Fan C-M , Rox-Anderson R
Published: September 2008

Objectives

The objective of this study is to review the basics of laser and established tissue response patterns to thermal injury, with specific reference to endovenous laser ablation (EVLA). This study also reviews the current theories and supporting aspects for the mechanism of action of EVLA in the treatment of superficial venous reflux.

Methods

The method involves the review of published literature and original investigation of histological effects of 810 nm and 980 nm wavelength EVLA on explanted blood-filled bovine saphenous vein in an in vitro system.

Results

The existing histological reports confirm that EVLA produces a transmural vein wall injury, typically associated with perforations and carbonization. The pattern of injury is eccentrically distributed, with maximum injury occurring along the path of laser contact. Intravenous temperature monitoring studies during EVLA have confirmed that the peak temperatures at the fibre tip exceed 1000°C, and continuous temperatures of at least 300°C are maintained in the firing zone for the majority of the procedure. Steam production during EVLA, which occurs early in the photothermolytic process when temperatures reach 100°C, accounts for only 2% of applied energy dose, and is therefore unlikely to be the primary mechanism of action of thermal injury during the procedure.

Conclusion

EVLA causes permanent vein closure through a high-temperature photothermolytic process at the point of contact between the vein and the laser.
Concrete Shrinkage and Creep in Recycled Aggregate Concrete-Filled Steel Tubes
Authors: Yang You Fu , Han Lin Hai , Wu Xin
Published: September 2008

Concrete shrinkage and creep in recycled aggregate concrete-filled steel tubes (RACFST) were experimentally studied and the results were presented in this paper. The measurements on the shrinkage and creep lasted for about eighteen months. The main parameters varied in the tests are: (1) sectional types, circular and square; (2) in-fill concrete types, recycled aggregate concrete (RAC) and normal concrete; and (3) long-term sustained load levels, 0.3 and 0.6. The test results showed that the time-history of the concrete shrinkage and creep in RACFST was similar to that of the corresponding normal CFST. However, the shrinkage and creep strains of RACFST specimens were larger than those of the normal CFST specimens. Finally, the predictive models based on previously issued provision for time-dependent behaviour of the composite member were calibrated with the tests, and recommendations for the calculations on the shrinkage and creep of the concrete core in RACFST were also suggested.
Experimental and Analytical Studies on Static and Dynamic Characteristics of Steel Box Girder for Runyang Cable-Stayed Bridge
Authors: Ding Youliang , Li Aiqun , Sun Jun , Deng Yang
Published: September 2008

In this study, a multi-scale computational model and methodology is presented for a comprehensive simulation of the static and dynamic characteristics of the steel box girder of Runyang Cable-stayed Bridge. The global-scale finite element model uses the shell elements with the equivalent orthotropic materials to simulate the top/bottom plate and its U-shape rib, which leads to accurate modeling of structural properties of the steel box girder in terms of vertical, lateral, torsional and warping stiffness. The local-scale finite element modeling of the girder is essentially a combination of fine finite element sub-models of selected details and the global-scale shell element model of the steel box girder by using the submodeling method. The developed three-dimensional global-scale and local-scale FE models have achieved a good correlation with the field load tests and ambient vibration tests. The static and dynamic characteristics of steel box girder of Runyang Cable-stayed Bridge under vehicle load tests and ambient vibration tests are further discussed.
Numerical Prediction of Reinforced Concrete Exterior Wall Response to Blast Loading
Authors: Zhou X. Q. , Hao H.
Published: September 2008

It is of interest to know the response of the unretrofitted reinforced concrete exterior walls under blast loading because some infrastructures might be targets of terrorist attack. Detailed numerical simulation and analysis of a typical concrete wall under different blast loads is presented in this study. The concrete material model used in the study includes a dynamic plastic damage model, a modified damage dependent piece-wise Drucker-Prager strength envelope, and a nonlinear equation of state considering the heterogeneity and porosity of concrete materials. The strain rate effect on tensile and compressive strength is considered separately. The concrete damage is based on Mazars' damage model, which combines tensile and compressive damage. The present numerical model was calibrated first by comparing the numerical results with laboratory blast test results of reinforced concrete slabs. The calibrated model is then employed to simulate the response of a typical reinforced concrete exterior wall under blast loads. TNT charge weights corresponding to some typical terrorist bombs, that is, from 10kg to 5000kg, are considered. In terms of different TNT charge weights, the responses of the reinforced concrete wall at different stand-off distances are simulated. Based on the numerical results, critical curves that relate damage levels with the explosion conditions are derived. The safe stand-off distances to resist different terrorist bombing scenarios are suggested.
Free Vibration of Structures with Trignometric SIN(R) Function in the Dual Reciprocity Boundary Element Analysis
Authors: Rashed Youssef F.
Published: September 2008

This paper presents a new boundary element formulation for two-dimensional free vibration problems. Both plane strain and stress conditions are considered. The main idea of the present formulation is to approximate the inertia terms using the trigonometric radial basis function sin ( R). The dual reciprocity method (DRM) with the static-type fundamental solution is used to obtain the eigen-value problem. The fictitious displacement and traction trigonometric particular solution kernels are derived and given in explicit forms. Several examples are presented to demonstrate the validity and the accuracy of the present formulation.
Experimental Study of Modular Falsework System with Wooden Shores under Various Path Loads
Authors: Kuo Ching Chi , Peng Jui Lin , Yen Tsong , Chan Siu Lai
Published: September 2008

The study involves full-scale loading tests to evaluate the performance of an assembly of modular falsework system with wooden shores under different path loadings. Sandbag loads with different load paths were adopted to simulate the weight of fresh concrete during construction. The topics investigated in this study include the relationship between actual path loads and the designed uniform loads, the influence line effect, the areas of larger axial tube reaction forces, lateral displacements versus early-warning planning and reinforcement of lateral bracing. The test results reveal that the largest axial tube reaction forces occur during the load placing rather than after the load placing, but discrepancies in the largest values during and after loadings are not large under different load paths. According to the distributions of the axial tube reaction forces under different load paths, the influence line effect is not evident in the modular falsework system with wooden shores. The areas enclosed by the larger tube reaction forces in the modular falsework system can be used as references in early-warning planning. During loading processes, the measured forces of reinforced lateral bracing and lateral displacements are small.
Structural Analyses of the Submerged Floating Tunnel Prototype in Qiandao Lake (PR of China)
Authors: Mazzolani F. M. , Landolfo R. , Faggiano B. , Esposto M. , Perotti F. , Barbella G.
Published: September 2008

In this paper, after a general presentation of the Submerged Floating Tunnel (SFT) as an attractive technical solution for waterway crossings, the SFT prototype to be built in Qiandao Lake (People's Republic of China) is introduced. The main peculiarities of such an innovative system are briefly summarized and the importance of realizing a SFT prototype is underlined. The types of action that the SFTs can be generally subjected to are illustrated and the specific load conditions for the SFT prototype in Qiandao Lake are presented. The numerical analyses carried out for investigating the system behaviour in presence of the environmental loads, such as waves, currents and earthquakes, are focused. Three cables configurations are considered for the hydrodynamic analyses, in order to select the most performing one, which is subsequently analyzed also under seismic loads. The model assumptions and the results of the performed analyses are shown and critically discussed. Finally, the displacement and strength safety checks are shown, which allow to state that the designed SFT prototype is able to withstand the environmental design actions in Qiandao Lake.
“I Like Others to Not Try to Fix Me”: Agency, Independence, and Autism
Authors: Rossetti Zachary , Ashby Christine , Arndt Katrina , Chadwick Marilyn , Kasahara Maho
Published: September 2008

This article is based on an interpretevist, qualitative research project conducted with individuals labeled with autism who type to communicate. Researchers engaged in participant observation and conducted open-ended interviews with 9 participants who were working to develop independent typing skills. Three findings emerged from this research. First, participants shaped a notion of independence that included dependence on various supports. Second, researchers recognized the concept of agency in the interactions between participants and their communication facilitators. Third, participants exercised control of their lives through these expressions of agency.
Quantitation of Serum Free Light Chains in Combination with Protein Electrophoresis and Clinical Information for Diagnosing Multiple Myeloma in a General Hospital Population
Authors: Piehler Armin P , Gulbrandsen Nina , Kierulf Peter , Urdal Petter
Published: September 2008

Background: Serum free light chain (SFLC) measurements have recently come into use as an aid for diagnosing monoclonal gammopathy. We evaluated SFLC measurements in combination with serum protein electrophoresis (SPE) and clinical information for diagnosing multiple myeloma (MM) in a hospital population.

Methods: We measured SFLCs in 3818 sera received for SPE over a 1-year period when patient symptoms or biochemical findings suggested myeloma-related tissue damage (n = 1067). We reviewed SPE and SFLC results from 489 patients together with their final diagnoses obtained from the hospital information technology department.

Results: SFLC measurement, combined with SPE and clinical information, allowed identification of 95% of patients (38 of 40) with previously undiagnosed MM, macroglobulinemia, or primary amyloidosis. Additionally, we identified 45 patients with monoclonal gammopathy of undetermined significance (MGUS) and 4 with plasmacytoma. Of patients followed at our hospital in whom SFLCs were not measured, only 1 patient was diagnosed with MM. This patient had anemia and was mistakenly not tested for SFLCs. An abnormal κ/λ ratio was found in 26 of 29 patients with MM but also in 36 of 203 patients with renal impairment, polyclonal immunoresponse, or other nonhematological diagnoses. None of the 203 patients with nonhematological disease had a κ/λ ratio <0.05 or >10.

Conclusions: The combined use of SPE, SFLC measurements, and clinical criteria allows MM to be efficiently diagnosed or excluded based on serum measurements only.
Quantification of Thyroglobulin, a Low-Abundance Serum Protein, by Immunoaffinity Peptide Enrichment and Tandem Mass Spectrometry
Authors: Hoofnagle Andrew N , Becker Jessica O , Wener Mark H , Heinecke Jay W
Published: September 2008

Background: Quantification of serum tumor markers plays an important role in determining whether patients treated for cancer require further therapy. Whereas large-scale proteomic efforts aim to identify novel tumor markers to facilitate early detection, optimization of methods for quantifying known tumor markers offers another approach to improving management of malignancies. For example, immunoassays used in clinical practice to measure established tumor markers suffer from potential interference from endogenous immunoglobulins and imperfect concordance across platforms—problems that also plague many other immunoassays. To address these important limitations, this study used peptide immunoaffinity enrichment in concert with liquid chromatography–tandem mass spectrometry (LC-MS/MS) to quantify thyroglobulin, a well-characterized tumor marker.

Methods: We identified 3 peptides in tryptic digests of thyroglobulin that were detected at low concentrations by tandem mass spectrometry, raised polyclonal antibodies to those peptides, and used the antibodies to extract the 3 corresponding peptides from tryptic digests of human serum. We quantified each endogenous peptide using LC-MS/MS and multiple reaction monitoring with external calibrators.

Results: The detection limit for endogenous thyroglobulin in serum was 2.6 μg/L (4 pmol/L). Direct comparison with immunoassay revealed good correlation (r2 = 0.81).

Conclusions: Immunoaffinity peptide enrichment–tandem mass spectrometry can detect tryptic peptides of thyroglobulin at picomolar concentrations while also digesting the endogenous immunoglobulins that can potentially interfere with traditional immunoassays. Our observations suggest a general analytical strategy for using immunoaffinity isolation together with tandem mass spectrometry to quantify tumor antigens and other low-abundance proteins in human serum.
Prospective Isolation of Skeletal Muscle Stem Cells with a Pax7 Reporter
Authors: Bosnakovski Darko , Xu Zhaohui , Li Wei , Thet Suwannee , Cleaver Ondine , Perlingeiro Rita C.R. , Kyba Michael
Published: September 2008

Muscle regeneration occurs through activation of quiescent satellite cells whose progeny proliferate, differentiate, and fuse to make new myofibers. We used a transgenic Pax7-ZsGreen reporter mouse to prospectively isolate stem cells of skeletal muscle by flow cytometry. We show that Pax7-expressing cells (satellite cells) in the limb, head, and diaphragm muscles are homogeneous in size and granularity and uniformly labeled by certain cell surface markers, including CD34 and CD29. The frequency of the satellite cells varies between muscle types and with age. Clonal analysis demonstrated that all colonies arising from single cells within the Pax7-sorted fraction have myogenic potential. In response to injury, Pax7+ cells reduce CD34, CD29, and CXCR4 expression, increase in size, and acquire Sca-1. When directly isolated and cultured in vitro, Pax7+ cells display the hallmarks of activation and proliferate, initially as suspension aggregates and later distributed between suspension and adherence. During in vitro expansion, Pax7 (ZsGreen) and CD34 expression decline, whereas expression of PSA-NCAM is acquired. The nonmyogenic, Pax7neg cells expand as Sca1+ PDGRα+ PSA-NCAMneg cells. Satellite cells expanded exclusively in suspension can engraft and produce dystrophin+ fibers in mdx−/− mice. These results establish a novel animal model for the study of muscle stem cell physiology and a culture system for expansion of engraftable muscle progenitors.

Disclosure of potential conflicts of interest is found at the end of this article.
Secreted Proteoglycans Directly Mediate Human Embryonic Stem Cell-Basic Fibroblast Growth Factor 2 Interactions Critical for Proliferation
Authors: Levenstein Mark E. , Berggren W. Travis , Lee Ji Eun , Conard Kevin R. , Llanas Rachel A. , Wagner Ryan J. , Smith Lloyd M. , Thomson James A.
Published: September 2008

Human embryonic stem (ES) cells can be maintained in an undifferentiated state if the culture medium is first conditioned on a layer of mouse embryonic fibroblast (MEF) feeder cells. Here we show that human ES cell proliferation is coordinated by MEF-secreted heparan sulfate proteoglycans (HSPG) in conditioned medium (CM). These HSPG and other heparinoids can stabilize basic fibroblast growth factor (FGF2) in unconditioned medium at levels comparable to those observed in CM. They also directly mediate binding of FGF2 to the human ES cell surface, and their removal from CM impairs proliferation. Finally, we have developed a purification scheme for MEF-secreted HSPG in CM. Using column chromatography, immunoblotting, and mass spectrometry-based proteomic analysis, we have identified multiple HSPG species in CM. The results demonstrate that HSPG are key signaling cofactors in CM-based human ES cell culture.

Disclosure of potential conflicts of interest is found at the end of this article.
The adaptation of an experimental protocol to the durability of cement engineered barriers for nuclear waste storage
Authors: Perlot C. , Bourbon X. , Carcasses M. , Ballivy G.
Published: September 2008

Within the French context of nuclear waste disposal in deep geological formation, concrete will be used as the building material for structures as well as for engineered barrier systems (EBSs). With regard to the durability that is necessary to keep the disposal facilities safe and secure, the long-term behaviour of cement-based materials has to be modelled. To assess the long-term evolution of physical and chemical properties of concrete, it is necessary to perform short-term experiments in conditions allowing extrapolations. The aim of this project was to determine the variation of transfer properties (diffusivity, permeation) with hydrolysis/decalcification. To simulate the two time phases of the structure life according to the external conditions, transfer properties were examined through two decalcification tests: a dynamic (temperature between 20 and 80°C, under a hydraulic pressure drop from 2 to 10 MPa) and a static test (NH4NO3 attack). The results could be used as input data in the long-term modelling of the disposal confinement capacity.