bluuebunny/crossref_metadata_2025 huggingface dataset:
Regular mosaic pattern development: A study of the interplay between lateral inhibition, apoptosis and differential adhesion
Authors: Podgorski Gregory J , Bansal Mayank , Flann Nicholas S
Published: November 2007

Background

A significant body of literature is devoted to modeling developmental mechanisms that create patterns within groups of initially equivalent embryonic cells. Although it is clear that these mechanisms do not function in isolation, the timing of and interactions between these mechanisms during embryogenesis is not well known. In this work, a computational approach was taken to understand how lateral inhibition, differential adhesion and programmed cell death can interact to create a mosaic pattern of biologically realistic primary and secondary cells, such as that formed by sensory (primary) and supporting (secondary) cells of the developing chick inner ear epithelium.

Results

Four different models that interlaced cellular patterning mechanisms in a variety of ways were examined and their output compared to the mosaic of sensory and supporting cells that develops in the chick inner ear sensory epithelium. The results show that: 1) no single patterning mechanism can create a 2-dimensional mosaic pattern of the regularity seen in the chick inner ear; 2) cell death was essential to generate the most regular mosaics, even through extensive cell death has not been reported for the developing basilar papilla; 3) a model that includes an iterative loop of lateral inhibition, programmed cell death and cell rearrangements driven by differential adhesion created mosaics of primary and secondary cells that are more regular than the basilar papilla; 4) this same model was much more robust to changes in homo- and heterotypic cell-cell adhesive differences than models that considered either fewer patterning mechanisms or single rather than iterative use of each mechanism.

Conclusion

Patterning the embryo requires collaboration between multiple mechanisms that operate iteratively. Interlacing these mechanisms into feedback loops not only refines the output patterns, but also increases the robustness of patterning to varying initial cell states.
p38 MAPK, Microglial Signaling, and Neuropathic Pain
Authors: Ji Ru-Rong , Suter Marc R
Published: November 2007

Accumulating evidence over last several years indicates an important role of microglial cells in the pathogenesis of neuropathic pain. Signal transduction in microglia under chronic pain states has begun to be revealed. We will review the evidence that p38 MAPK is activated in spinal microglia after nerve injury and contributes importantly to neuropathic pain development and maintenance. We will discuss the upstream mechanisms causing p38 activation in spinal microglia after nerve injury. We will also discuss the downstream mechanisms by which p38 produces inflammatory mediators. Taken together, current data suggest that p38 plays a critical role in microglial signaling under neuropathic pain conditions and represents a valuable therapeutic target for neuropathic pain management.
Serum epidermal growth factor receptor and HER2 expression in primary and metastatic breast cancer patients
Authors: Asgeirsson Kristjan S , Agrawal Amit , Allen Claire , Hitch Anthony , Ellis Ian O , Chapman Caroline , Cheung Kwok L , Robertson John FR
Published: November 2007

Background

Breast tissue expression of the ERBB proto-oncogene family has been extensively studied. It was recently shown that expression of epidermal growth factor receptor (EGFR; c-erbB-1) and epidermal growth factor receptor (HER)2 (c-erbB-2) can be detected in the serum of breast cancer patients. The clinical relevance of this has not been fully established.

Methods

EGFR and HER2 immunoassays were conducted in blood from 57 patients in whom paired serum samples were available (from the times of primary and metastatic diagnoses), from 96 primary breast cancer patients and from 49 normal individuals. Of the 57 patients with paired serum samples, paired tissue samples for HER2 expression were available for eight.

Results

Serum levels of EGFR serum levels were significantly higher in normal individuals (median 75.3 ng/ml, range 43.2 to 114.2 ng/ml) than in patients with primary breast cancer (median 59.3 ng/ml, range 21.3 to 94.1 ng/ml; P < 0.001). In the paired serum samples, EGFR levels decreased significantly between the time of primary diagnosis (median 56.3 ng/ml, range 29.1 to 142.7 ng/ml) and metastatic diagnosis (median 30.9 ng/ml, range 10.9 to 106.4 ng/ml; P < 0.001). In six (11%) a change occurred from over-expression (>78 ng/ml) to normal expression. In contrast, no significant difference was seen in HER2 serum levels in normal individuals (median 12.2 ng/ml, range 7.8 to 20.9 ng/ml) and primary breast cancer patients (median 12.5 ng/ml, range 6.9 to 122.2 ng/ml; P = 0.511). However, in the paired serum samples, HER2 levels increased significantly between the time of primary (median 12.2 ng/ml, range 5.7 to 85.0 ng/ml) and metastasis (median 17.7 ng/ml, range 6.3 to 3,337.4 ng/ml; P < 0.001). HER2 over-expression (>15 ng/ml) was observed in 16 out of 57 patients (28%) at primary breast cancer diagnosis and in 31 out of 57 (54%) at metastasis. In 18 patients (32%) HER2 expression changed from normal to over-expression.

Conclusion

Decisions regarding the use of targeted therapies in the metastatic setting are often based on the oncogene expression of the primary tumour. Our results suggest that serum oncogene assessments may be complementary to this and could potentially widen the indications for these beneficial therapies.
Identification of the functional role of peroxiredoxin 6 in the progression of breast cancer
Authors: Chang Xin-Zhong , Li Da-Qiang , Hou Yi-Feng , Wu Jiong , Lu Jin-Song , Di Gen-Hong , Jin Wei , Ou Zhou-Luo , Shen Zhen-Zhou , Shao Zhi-Ming
Published: November 2007

Introduction

The molecular mechanisms involved in breast cancer metastasis still remain unclear to date. In our previous study, differential expression of peroxiredoxin 6 was found between the highly metastatic MDA-MB-435HM cells and their parental counterparts, MDA-MB-435 cells. In this study, we investigated the effects of peroxiredoxin 6 on the proliferation and metastatic potential of human breast cancer cells and their potential mechanism.

Methods

Expression of peroxiredoxin 6 in the highly metastatic MDA-MB-231HM cells was investigated by RT-PCR, real-time PCR and western blot. A recombinant expression plasmid of the human peroxiredoxin 6 gene was constructed and transfected into MDA-MB-231 and MDA-MB-435 cells. The effects of peroxiredoxin 6 on the proliferation and invasion of MDA-MB-231 and MDA-MB-435 cells were investigated by the Cell Counting Kit-8 method, colony-formation assay, adhesion assay, flow cytometry and invasion assay in vitro. miRNA was used to downregulate the expression of peroxiredoxin 6. Genes related to the invasion and metastasis of cancer were determined by RT-PCR, real-time PCR and western blot. The tumorigenicity and spontaneously metastatic capability regulated by peroxiredoxin 6 were determined using an orthotopic xenograft tumor model in athymic mice.

Results

Overexpression of peroxiredoxin 6 in MDA-MB-231HM cells compared with their parental counterparts was confirmed. Upregulation of peroxiredoxin 6 enhanced the in vitro proliferation and invasion of breast cancer cells. The enhancement was associated with decreasing levels of tissue inhibitor of matrix metalloproteinase (TIMP)-2 and increasing levels of the urokinase-type plasminogen activator receptor (uPAR), Ets-1 (E26 transformation-specific-1), matrix metalloproteinase (MMP)-9 and RhoC (ras homolog gene family, member C) expression. The results were further demonstrated by RNA interference experiments in vitro. In an in vivo study, we also demonstrated that peroxiredoxin 6-transfected breast cancer cells grew much faster and had more pulmonary metastases than control cells. By contrast, peroxiredoxin 6 knockdown breast cancer cells grew more slowly and had fewer pulmonary metastases. Effects similar to those of peroxiredoxin 6 on the uPAR, Ets-1, MMP-9, RhoC and TIMP-2 expression observed in in vitro studies were found in the in vivo study.

Conclusion

Overexpression of peroxiredoxin 6 leads to a more invasive phenotype and metastatic potential in human breast cancer, at least in part, through regulation of the levels of uPAR, Ets-1, MMP-9, RhoC and TIMP-2 expression.
Determinants of protein function revealed by combinatorial entropy optimization
Authors: Reva Boris , Antipin Yevgeniy , Sander Chris
Published: November 2007

We use a new algorithm (combinatorial entropy optimization [CEO]) to identify specificity residues and functional subfamilies in sets of proteins related by evolution. Specificity residues are conserved within a subfamily but differ between subfamilies, and they typically encode functional diversity. We obtain good agreement between predicted specificity residues and experimentally known functional residues in protein interfaces. Such predicted functional determinants are useful for interpreting the functional consequences of mutations in natural evolution and disease.
Vimentin autoantibodies induce platelet activation and formation of platelet-leukocyte conjugates via platelet-activating factor
Authors: Leong H S , Mahesh B M , Day J R , Smith J D , McCormack A D , Ghimire G , Podor T J , Rose M L
Published: November 2007

Anti-vimentin antibodies (AVA) are associated with autoimmunity and solid organ transplantation, conditions associated with vascular disease, but their contribution to disease pathogenesis is unknown. Here, we have examined interactions between AVA (mAb and serum from patients) and various leukocyte populations using whole blood and flow cytometry. Normal blood treated with patient sera containing high AVA-IgM titers or with a vimentin-specific monoclonal IgM led to activation of platelets and other leukocytes, as demonstrated by induced expression of P-selectin, fibrinogen, tissue factor, and formation of platelet:leukocyte (P:L) conjugates and a reduction in platelet counts. This activity was antigen (vimentin)-specific and was not mediated by irrelevant IgM antibodies. Flow cytometry demonstrated that AVA do not bind directly to resting platelets in whole blood, but they bind to ∼10% of leukocytes. Supernatant, derived from AVA-treated leukocytes, induced platelet activation, as measured by the generation of platelet microparticles, when added to platelet-rich plasma. When AVA were added to whole blood in the presence of CV-6209, a platelet-activating factor (PAF) receptor inhibitor, platelet depletion was inhibited. This suggests that PAF is one of the mediators released from AVA-activated leukocytes that leads to P:L conjugation formation and platelet activation. In summary, AVA bind to leukocytes, resulting in release of a PAF and prothrombotic factor that exert a paracrine-activating effect on platelets. Overall, this proposed mechanism may explain the pathogenesis of thrombotic events in autoimmune diseases associated with AVA.
Estrogen-Enhanced Gene Expression of Lipoprotein Lipase in Heart Is Antagonized by Progesterone
Authors: Liu Dianxin , Deschamps Anne , Korach Kenneth S. , Murphy Elizabeth
Published: November 2007

Although estrogen has effects on the heart, little is known regarding which genes in the heart are directly responsive to estrogen. We have shown previously that lipoprotein lipase (LPL) expression was increased in female hearts compared with male hearts. To test whether LPL gene expression in heart is regulated by estrogen, we perfused mouse hearts from ovariectomized females with 100 nM 17β-estradiol or vehicle for 2 h, after which hearts were frozen, and RNA was isolated. The SYBR green real-time PCR method was used to detect LPL gene expression. We found that addition of 17β-estradiol to hearts from ovariectomized females resulted in a significant increase in LPL mRNA. This estrogen effect on LPL gene expression in mouse heart can be blocked by the estrogen receptor (ER) antagonist ICI 182,780 or by progesterone. We also identified a potential estrogen receptor element (ERE) enhancer sequence located in the first intron of the mouse LPL gene. The potential ERE sequence was linked to a TATA-luciferase (LUC) reporter plasmid in HeLa cells. Both ERα and ERβ stimulated strong activity on the heterologous promoter reporter in Hela cells upon estrogen addition. Both ERα and ERβ activities on the LPL ERE reporter were abrogated by the ER antagonist ICI 182,780. Progesterone also dose dependently inhibited the estrogen-mediated increase in LPL ERE reporter activity. These results show that heart LPL is an estrogen-responsive gene exhibiting an intronic regulatory sequence.
Inhibition of Agouti-Related Peptide Expression by Glucose in a Clonal Hypothalamic Neuronal Cell Line Is Mediated by Glycolysis, Not Oxidative Phosphorylation
Authors: Cheng Hui , Isoda Fumiko , Belsham Denise D. , Mobbs Charles V.
Published: November 2007

The regulation of neuroendocrine electrical activity and gene expression by glucose is mediated through several distinct metabolic pathways. Many studies have implicated AMP and ATP as key metabolites mediating neuroendocrine responses to glucose, especially through their effects on AMP-activated protein kinase (AMPK), but other studies have suggested that glycolysis, and in particular the cytoplasmic conversion of nicotinamide adenine dinucleotide (NAD+) to reduced NAD (NADH), may play a more important role than oxidative phosphorylation for some effects of glucose. To address these molecular mechanisms further, we have examined the regulation of agouti-related peptide (AgRP) in a clonal hypothalamic cell line, N-38. AgRP expression was induced monotonically as glucose concentrations decreased from 10 to 0.5 mm glucose and with increasing concentrations of glycolytic inhibitors. However, neither pyruvate nor 3-β-hydroxybutyrate mimicked the effect of glucose to reduce AgRP mRNA, but on the contrary, produced the opposite effect of glucose and actually increased AgRP mRNA. Nevertheless, 3β-hydroxybutyrate mimicked the effect of glucose to increase ATP and to decrease AMPK phosphorylation. Similarly, inhibition of AMPK by RNA interference increased, and activation of AMPK decreased, AgRP mRNA. Additional studies demonstrated that neither the hexosamine nor the pentose/carbohydrate response element-binding protein pathways mediate the effects of glucose on AgRP expression. These studies do not support that either ATP or AMPK mediate effects of glucose on AgRP in this hypothalamic cell line but support a role for glycolysis and, in particular, NADH. These studies support that cytoplasmic or nuclear NADH, uniquely produced by glucose metabolism, mediates effects of glucose on AgRP expression.
Functional Vitamin D Receptor (VDR) in the T-Tubules of Cardiac Myocytes: VDR Knockout Cardiomyocyte Contractility
Authors: Tishkoff Daniel X. , Nibbelink Karl A. , Holmberg Kristina H. , Dandu Loredana , Simpson Robert U.
Published: November 2007

We have previously shown that the active form of vitamin D, 1,25 dihydroxyvitamin D3 [1,25(OH)2D3], has both genomic and rapid nongenomic effects in heart cells; however, the subcellular localization of the vitamin D receptor (VDR) in heart has not been studied. Here we show that in adult rat cardiac myocytes the VDR is primarily localized to the t-tubule. Using immunofluorescence and Western blot analysis, we show that the VDR is closely associated with known t-tubule proteins. Radioligand binding assays using 3H-labeled 1,25(OH)2D3 demonstrate that a t-tubule membrane fraction isolated from homogenized rat ventricles contains a 1,25(OH)2D3-binding activity similar to the classic VDR. For the first time, we show that cardiac myocytes isolated from VDR knockout mice show accelerated rates of contraction and relaxation as compared with wild type and that 1,25(OH)2D3 directly affects contractility in the wild-type but not the knockout cardiac myocyte. Moreover, we observed that acute (5 min) exposure to 1,25(OH)2D3 altered the rate of relaxation. A receptor localized to t-tubules in the heart is ideally positioned to exert an immediate effect on signal transduction mediators and ion channels. This novel discovery is fundamentally important in understanding 1,25(OH)2D3 signal transduction in heart cells and provides further evidence that the VDR plays a role in heart structure and function.
Role of Agouti-Related Protein-Expressing Neurons in Lactation
Authors: Phillips Colin T. , Palmiter Richard D.
Published: November 2007

Hypothalamic neurons that express agouti-related protein (AgRP) and neuropeptide Y (NPY) are thought to be important for regulation of feeding, especially under conditions of negative energy balance. The expression of NPY and AgRP increases during lactation and may promote the hyperphagia that ensues. We explored the role of AgRP neurons in reproduction and lactation, using a mouse model in which AgRP-expressing neurons were selectively ablated by the action of diphtheria toxin. We show that ablation of AgRP neurons in neonatal mice does not interfere with pregnancy, parturition, or lactation, suggesting that early ablation allows compensatory mechanisms to become established. However, ablation of AgRP neurons after lactation commences results in rapid starvation, indicating that both basal feeding and lactation-induced hyperphagia become dependent on AgRP neurons in adulthood. We also show that constitutive inactivation of Npy and Agrp genes does not prevent pregnancy or lactation, nor does it protect lactating dams from diphtheria toxin-induced starvation.
Effect of Dexamethasone on Glucose Tolerance and Fat Metabolism in a Diet-Induced Obesity Mouse Model
Authors: Gounarides John S. , Korach-André Marion , Killary Karen , Argentieri Gregory , Turner Oliver , Laurent Didier
Published: November 2007

Prolonged exposure to elevated glucocorticoid levels is known to produce insulin resistance (IR), a hallmark of diabetes mellitus. Although not fully elucidated, the underlying molecular mechanisms by which glucocorticoids induce IR may provide potential targets for pharmacological interventions. Here we characterized muscle lipid metabolism in a dexamethasone-aggravated diet-induced obesity murine model of IR. Male C57BL/6 mice on a high-fat diet for 2 months when challenged with dexamethasone showed elevated food consumption and weight gain relative to age and diet-matched animals dosed with saline only. Dexamethasone treatment impaired glucose tolerance and significantly increased the intramyocellular lipid content in the tibialis anterior muscle (TA). A good correlation (r = 0.76, P < 0.01) was found between accumulation in intramyocellular lipid content in the TA and visceral adiposity. The linoleic acid (18:2) to polyunsaturated acid ratio was increased in the dexamethasone-treated animals (+29%; P < 0.01), suggesting a possible increase in stearoyl-CoA desaturase 2 activity, as reported in Sertoli cells. The treatment was also accompanied by a reduction in the percent fraction of ω-3 and long-chain polyunsaturated fatty acids in the TA. Analysis of the low-molecular-weight metabolites from muscle extracts showed that there was no dysregulation of muscle amino acids, as has been associated with dexamethasone-induced muscle proteolysis. In conclusion, dexamethasone-induced insulin resistance in diet-induced obese mice is associated with a profound perturbation of lipid metabolism. This is particularly true in the muscle, in which an increased uptake of circulating lipids along with a conversion into diabetogenic lipids can be observed.
Granulosa cells regulate oocyte intracellular pH against acidosis in preantral follicles by multiple mechanisms
Authors: FitzHarris Greg , Siyanov Violetta , Baltz Jay M.
Published: November 2007

Mammalian oocytes grow within ovarian follicles in which the oocyte is coupled to surrounding granulosa cells by gap junctions. We report here that growing oocytes isolated from mouse preantral follicles are incapable of recovering from an experimentally induced acidosis, and that oocytes acquire the ability to manage acid loads by activating Na+/H+exchange during growth. By contrast, granulosa cells from similar preantral follicles possess substantial Na+/H+ exchange capacity,which is attributable to the simultaneous action of two Na+/H+ exchanger isoforms: NHE1 and NHE3. Granulosa cells were also found to possess a V-type H+-ATPase that drives partial acidosis recovery when Na+/H+ exchange is inactivated. By monitoring intracellular pH (pHi) in small follicle-enclosed oocytes, we found that the oocyte has access to each of these acidosis-correcting activities, such that small follicle-enclosed oocytes readily recover from acidosis in a manner resembling granulosa cells. However, follicle-enclosed oocytes are unable to access these activities if gap-junction communication within the follicle is inhibited. Together, these experiments identify the NHE isoforms involved in regulating oocyte pHi, indicate that gap junctions allow granulosa cells to exogenously regulate oocyte pHi against acidosis until the oocyte has acquired endogenous pHi regulation, and reveal that granulosa cells possess multiple mechanisms for carrying out this function.
A wave of EGFR signaling determines cell alignment and intercalation in theDrosophilatracheal placode
Authors: Nishimura Mayuko , Inoue Yoshiko , Hayashi Shigeo
Published: November 2007

Invagination of organ placodes converts flat epithelia into three-dimensional organs. Cell tracing in the Drosophila tracheal placode revealed that, in the 30-minute period before invagination, cells enter mitotic quiescence and form short rows that encircle the future invagination site. The cells in the rows align to form a smooth boundary(`boundary smoothing'), accompanied by a transient increase in myosin at the boundary and cell intercalation oriented in parallel with the cellular rows. Cells then undergo apical constriction and invaginate, followed by radially oriented mitosis in the placode. Prior to invagination, ERK MAP kinase is activated in an outward circular wave, with the wave front often correlating with the smoothing cell boundaries. EGFR signaling is required for myosin accumulation and cell boundary smoothing, suggesting its propagation polarizes the planar cell rearrangement in the tracheal placode, and coordinates the timing and position of intrinsic cell internalization activities.
Nucleocytoplasmic shuttling mediates the dynamic maintenance of nuclear Dorsal levels duringDrosophilaembryogenesis
Authors: DeLotto Robert , DeLotto Yvonne , Steward Ruth , Lippincott-Schwartz Jennifer
Published: November 2007

In Drosophila, the NF-κB/REL family transcription factor,Dorsal, redistributes from the cytoplasm to nuclei, forming a concentration gradient across the dorsoventral axis of the embryo. Using live imaging techniques in conjunction with embryos expressing a chimeric Dorsal-GFP, we demonstrate that the redistribution of Dorsal from cytoplasm to nucleus is an extremely dynamic process. Nuclear Dorsal concentration changes continuously over time in all nuclei during interphase. While Dorsal appears to be nuclearly localized primarily in ventral nuclei, it is actively shuttling into and out of all nuclei, including nuclei on the dorsal side. Nuclear export is blocked by leptomycin B, a potent inhibitor of Exportin 1 (CRM1)-mediated nuclear export. We have developed a novel in vivo assay revealing the presence of a functional leucine-rich nuclear export signal within the carboxyterminal 44 amino acids of Dorsal. We also find that diffusion of Dorsal is partially constrained to cytoplasmic islands surrounding individual syncitial nuclei. A model is proposed in which the generation and maintenance of the Dorsal gradient is a consequence of an active process involving both restricted long-range diffusion and the balancing of nuclear import with nuclear export.
Sound production and spectral hearing sensitivity in the Hawaiian sergeant damselfish, Abudefduf abdominalis
Authors: Maruska Karen P. , Boyle Kelly S. , Dewan Laura R. , Tricas Timothy C.
Published: November 2007

Sounds provide important signals for inter- and intraspecific communication in fishes, but few studies examine fish acoustic behavior in the context of coevolution of sound production and hearing ability within a species. This study characterizes the acoustic behavior in a reproductive population of the Hawaiian sergeant fish, Abudefduf abdominalis, and compares acoustic features to hearing ability, measured by the auditory evoked potential (AEP)technique. Sergeant fish produce sounds at close distances to the intended receiver (⩽1–2 body lengths), with different pulse characteristics that are associated primarily with aggression, nest preparation and courtship–female-visit behaviors. Energy peaks of all sounds were between 90 and 380 Hz, whereas courtship–visit sounds had a pulse repetition rate of 125 Hz with harmonic intervals up to 1 kHz. AEP threshold,which is probably higher than the behavioral threshold, indicates best sensitivity at low frequencies (95–240 Hz), with the lowest threshold at 125 Hz (123–127 dBrms re: 1 μPa). Thus, sound production and hearing in A. abdominalis are closely matched in the frequency domain and are useful for courtship and mating at close distances. Measured hearing thresholds did not differ among males and females during spawning or non-spawning periods, which indicates a lack of sex differences and seasonal variation in hearing capabilities. These data provide the first evidence that Abudefduf uses true acoustic communication on a level similar to that of both more derived (e.g. Dascyllus, Chromis) and more basal (e.g. Stegastes) soniferous pomacentrids. This correlation between sound production and hearing ability is consistent with the sensory drive model of signal evolution in which the sender and receiver systems coevolve within the constraints of the environment to maximize information transfer of acoustic signals.
Histamine operates Cl–-gated channels in crayfish neurosecretory cells
Authors: Cebada Jorge , García Ubaldo
Published: November 2007

We describe a histamine-activated Cl– conductance in the X-organ neurons from crayfish Cherax quadricarinatus, which has comparable properties to the homomultimeric histamine-gated ion channels described in Drosophila. Topical application of histamine inhibited spontaneous neuronal firing in the X-organ sinus gland tract, concomitant with an increase in the membrane conductance. In X-organ neurons in culture and under voltage-clamp conditions, histamine evoked outward currents at –40 mV that reversed at the Cl– equilibrium potential. Histamine sensitivity in these neurons had a half-maximal response(EC50)=3.3±1 μmol l–1, with a Hill number of 2.6±0.4. The histamine-evoked current was blocked by tiotidine, cimetidine, ranitidine and 256±11 and 483±11 μmol l–1, respectively) and d-tubocurarine(IC50=21±2 μmol l–1), but was insensitive to picrotoxin, bicuculline and strychnine. Neither GABA nor glutamate was capable of desensitizing the histamine response, indicating that histamine activates a particular Cl– conductance. The presence of immunoreactive neurons to histamine in the medulla terminalis with axonal projections to the neuropile suggests a possible histaminergic modulation of the X-organ sinus gland system.
Olfactory memory formation and the influence of reward pathway during appetitive learning by honey bees
Authors: Wright Geraldine A. , Mustard Julie A. , Kottcamp Sonya M. , Smith Brian H.
Published: November 2007

Animals possess the ability to assess food quality via taste and via changes in state that occur after ingestion. Here, we investigate the extent to which a honey bee's ability to assess food quality affected the formation of association with an odor stimulus and the retention of olfactory memories associated with reward. We used three different conditioning protocols in which the unconditioned stimulus (food) was delivered as sucrose stimulation to the proboscis (mouthparts), the antennae or to both proboscis and antennae. All means of delivery of the unconditioned stimulus produced robust associative conditioning with an odor. However, the memory of a conditioned odor decayed at a significantly greater rate for subjects experiencing antennal-only stimulation after either multiple- or single-trial conditioning. Finally, to test whether the act of feeding on a reward containing sucrose during conditioning affected olfactory memory formation, we conditioned honey bees to associate an odor with antennal stimulation with sucrose followed by feeding on a water droplet. We observed that a honey bee's ability to recall the conditioned odor was not significantly different from that of subjects conditioned with an antennal-only sucrose stimulus. Our results show that stimulation of the sensory receptors on the proboscis and/or ingestion of the sucrose reward during appetitive olfactory conditioning are necessary for long-term memory formation.
Endurance swimming activates trout lipoprotein lipase: plasma lipids as a fuel for muscle
Authors: Magnoni Leonardo , Weber Jean-Michel
Published: November 2007

Fish endurance swimming is primarily powered by lipids supplied to red muscle by the circulation, but the mechanism of delivery remains unknown. By analogy to mammals, previous studies have focused on non-esterified fatty acids (NEFA bound to albumin), but lipoproteins have not been considered as an energy shuttle to working muscles. The effects of exercise on fish lipoprotein lipase (LPL) have never been investigated. We hypothesized that LPL and circulating lipoproteins would be modified by prolonged swimming. Because LPL is naturally bound to the endothelium, we have used heparin to release the enzyme in the circulation and to characterize reserve capacity for lipoprotein catabolism. The effects of exercise (4 days at 1.5 body lengths s–1 in a swim tunnel) were measured for red muscle LPL,post-heparin plasma LPL, and lipoprotein concentration/composition. Red muscle LPL activity increased from 18±5 (rest) to 49± 9 nmol fatty acids min–1 g–1 (swimming). In resting fish,heparin administration caused a 27-fold increase in plasma LPL activity that reached a maximum of 1.32± 0.67 μmol fatty acids min–1 ml–1 plasma. This heparin-induced response of plasma LPL was not different between resting controls and exercised fish. Heparin or prolonged swimming had no effect on the concentration/composition of lipoproteins that contain 92% of the energy in total plasma lipids. We conclude that (1) red muscle LPL is strongly activated by endurance swimming, (2) rainbow trout have a high reserve capacity for hydrolyzing lipoproteins, and (3) future studies should aim to measure lipoprotein flux because their concentration does not reflect changes in flux. These novel characteristics of fish LPL imply that lipoproteins are used as a metabolic shuttle between fat reserves and working muscles, a strategy exploiting an abundant source of energy in rainbow trout.
Oligopeptide transporter PepT1 in Atlantic cod (Gadus morhuaL.): cloning, tissue expression and comparative aspects
Authors: Rønnestad Ivar , Gavaia Paulo J. , Viegas Carla S. B. , Verri Tiziano , Romano Alessandro , Nilsen Tom Ole , Jordal Ann-Elise O. , Kamisaka Yuko , Cancela M. Leonor
Published: November 2007

A novel full-length cDNA that encodes for the Atlantic cod (Gadus morhua L.) PepT1-type oligopeptide transporter has been cloned. This cDNA(named codPepT1) was 2838 bp long, with an open reading frame of 2190 bp encoding a putative protein of 729 amino acids. Comparison of the predicted Atlantic cod PepT1 protein with zebrafish, bird and mammalian orthologs allowed detection of many structural features that are highly conserved among all the vertebrate proteins analysed, including (1) a larger than expected area of hydrophobic amino acids in close proximity to the N terminus; (2) a single highly conserved cAMP/cGMP-dependent protein kinase phosphorylation motif; (3) a large N-glycosylation-rich region within the large extracellular loop; and (4) a conserved and previously undescribed stretch of 8–12 amino acid residues within the large extracellular loop. Expression analysis at the mRNA level indicated that Atlantic cod PepT1 is mainly expressed at intestinal level, but that it is also present in kidney and spleen. Analysis of its regional distribution along the intestinal tract of the fish revealed that PepT1 is ubiquitously expressed in all segments beyond the stomach,including the pyloric caeca, and through the whole midgut. Only in the last segment, which included the hindgut, was there a lower expression. Atlantic cod PepT1, the second teleost fish PepT1-type transporter documented to date,will contribute to the elucidation of the evolutionary and functional relationships among vertebrate peptide transporters. Moreover, it can represent a useful tool for the study of gut functional regionalization, as well as a marker for the analysis of temporal and spatial expression during ontogeny.
Cloning and characterization of AgCA9, a novel α-carbonic anhydrase from Anopheles gambiae Giles sensu stricto (Diptera:Culicidae) larvae
Authors: Smith Kristin E. , VanEkeris Leslie A. , Linser Paul J.
Published: November 2007

Mosquito larvae generate a luminal pH as high as 10.5 in the anterior region of their midgut. The mechanisms responsible for the generation and maintenance of this alkaline pH are largely unknown, but there is evidence suggesting a role for the enzyme carbonic anhydrase (CA). CA has been cloned from the alimentary canal epithelium of Anopheles gambiae larvae and can generate bicarbonate, which is implicated as a buffer for the larval lumen. The question remains as to how the bicarbonate is transported from the cells into the lumen. We hypothesize the presence of a CA within the lumen itself to generate bicarbonate from CO2 produced by the metabolically active alimentary canal cells. Here, we report the cloning and characterization of a novel cytoplasmic-type α-CA from the larval An. gambiae alimentary canal. Antibody immunolocalization reveals a unique protein distribution pattern that includes the ectoperitrophic fluid,`transitional region' of the alimentary canal, Malpighian tubules and a subset of cells in the dorsal anterior region of the rectum. Localization of this CA within the lumen of the alimentary canal may be a key to larval pH regulation,while detection within the rectum reveals a novel subset of cells in An. gambiae not described to date. Phylogenetic analysis of members of theα-CA family from the Homo sapiens, Drosophila melanogaster, Aedes aegypti and An. gambiae genomes shows a clustering of the novel CA with Homo sapiens CAs but not with other insect CAs. Finally, a universal system for naming newly cloned An. gambiae CAs is suggested.
Functional significance of the uncinate processes in birds
Authors: Tickle Peter G. , Ennos A. Roland , Lennox Laura E. , Perry Steven F. , Codd Jonathan R.
Published: November 2007

The functional significance of the uncinate processes to the ventilatory mechanics of birds was examined by combining analytical modeling with morphological techniques. A geometric model was derived to determine the function of the uncinate processes and relate their action to morphological differences associated with locomotor specializations. The model demonstrates that uncinates act as levers, which improve the mechanical advantage for the forward rotation of the dorsal ribs and therefore lowering of the sternum during respiration. The length of these processes is functionally important;longer uncinate processes increasing the mechanical advantage of the Mm. appendicocostales muscle during inspiration. Morphological studies of four bird species showed that the uncinate process increased the mechanical advantage by factors of 2–4. Using canonical variate analysis and analysis of variance we then examined the variation in skeletal parameters in birds with different primary modes of locomotion (non-specialists, walking and diving). Birds clustered together in distinct groups, indicating that uncinate length is more similar in birds that have the same functional constraint, i.e. specialization to a locomotor mode. Uncinate processes are short in walking birds, long in diving species and of intermediate length in non-specialist birds. These results demonstrate that differences in the breathing mechanics of birds may be linked to the morphological adaptations of the ribs and rib cage associated with different modes of locomotion.
Unique role of skeletal muscle contraction in vertical lymph movement in anurans
Authors: Drewes Robert C. , Hedrick Michael S. , Hillman Stanley S. , Withers Philip C.
Published: November 2007

Electromyographic (EMG) activity of skeletal muscles that either insert on the skin or are associated with the margins of subcutaneous lymph sacs was monitored for two species of anurans, Chaunus marinus and Lithobates catesbeiana (formerly Bufo marinus and Rana catesbeiana). Our hypothesis was that contraction of these muscles varies the volume, and hence pressure, within these lymph sacs, and that this pressure is responsible for moving lymph from ventral, gravitationally dependent reaches of the body to dorsally located lymph hearts. EMG activity of M. piriformis, M. gracilis minor, M. abdominal crenator, M. tensor fasciae latae, M. sphincter ani cloacalis, M. cutaneous pectoris and M. cutaneous dorsi was synchronous with pressure changes in their associated lymph sacs. These muscles contracted synchronously, and the pressures generated within the lymph sacs were sufficient to move lymph vertically against gravity to the lymph hearts. The pressure relationships were complex; both negative and positive pressures were recorded during a contractile event, a pattern consistent with the addition and loss of lymphatic fluid to the lymph sacs. Severing the tendons of some of the muscles led to lymph pooling in gravitationally dependent lymph sacs. These data are the first to: (1)describe a function for many of these skeletal muscles; (2) document the role of skeletal muscles in vertical lymph movement in anurans; and (3) reinterpret the role of the urostyle, a bony element of the anuran pelvic girdle.
Nitric oxide modulation of the electrically excitable skin ofXenopus laevisfrog tadpoles
Authors: Alpert Michael H. , Zhang HongYan , Molinari Micol , Heitler William J. , Sillar Keith T.
Published: November 2007

Nitric oxide (NO) is a highly diffusible signalling molecule with widespread effects on the integrative electrical properties of a variety of neuronal and muscle cells. We have explored the effects of NO on the cardiac-like impulse generated by skin cells of the hatchling Xenopustadpole. Skin cell impulses propagate from cell to cell via gap junctions and form an unusual sensory system, which triggers escape behaviour at early stages of amphibian development. We show that the NO donor S-nitroso-N-acetylpenicillamine (SNAP) increases the duration of the skin impulse and slows the rate of impulse propagation across the skin, and also produces a significant depolarization of the membrane potential of skin cells. Each of these effects of SNAP is significantly reversed by the NO scavenger, C-PTIO. Possible sources of NO have been investigated using both NADPH-diaphorase histochemistry and nNOS immunocytochemistry to label the enzyme nitric oxide synthase (NOS), and DAF-2 to label NO itself. In each case a punctate distribution of skin cells is labelled, indicating that the endogenous production of NO may regulate the properties of the skin impulse.
Area postrema, a brain circumventricular organ, is the site of antidipsogenic action of circulating atrial natriuretic peptide in eels
Authors: Tsukada Takehiro , Nobata Shigenori , Hyodo Susumu , Takei Yoshio
Published: November 2007

Accumulating evidence indicates that circulating atrial natriuretic peptide(ANP) potently reduces excess drinking to ameliorate hypernatremia in seawater(SW) eels. However, the cerebral mechanism underlying the antidipsogenic effect is largely unknown. To localize the ANP target site in the brain, we examined the distribution of ANP receptors (NPR-A) in eel brain immunohistochemically using an antiserum specific for eel NPR-A. The immunoreactive NPR-A was localized in the capillaries of various brain regions. In addition, immunoreactive neurons were observed mostly in the medulla oblongata, including the reticular formation, glossopharyngeal-vagal motor complex, commissural nucleus of Cajal, and area postrema (AP). Trypan Blue, which binds serum albumin and does not cross the blood–brain barrier, was injected peripherally and stained the neurons in the AP but not other NPR-A immunopositive neurons. These histological data indicate that circulating ANP acts on the AP, which was further confirmed by physiological experiments. To this end, the AP in SW eels was topically destroyed by electric cauterization or were by chemical lesion of its neurons by kainic acid, and ANP (100 pmol kg–1) was then injected into the circulation. Both heat-coagulative and chemical lesions to the AP greatly reduced an antidipsogenic effect of ANP, but the ANP effect was retained in sham-operated eels and in those with lesions outside the AP. These results strongly suggest that the AP, a circumventricular organ without a blood–brain barrier, serves as a functional window of access for the circulating ANP to inhibit drinking in eels.
Estimation of transient wall and flow temperature distributions in a circular duct using an inverse approach
Authors: Masouros S D , Mathioudakis K
Published: November 2007

Inverse methods have become a useful tool for estimating parameters that cannot be measured or calculated directly in engineering applications. Parameters characterizing unsteady heat convection in circular duct flows are associated with numerous uncertainties. This fact renders the inverse approach appropriate for the determination of these parameters.

An inverse problem for transient turbulent thermally developing and thermally developed forced-convection flow in a circular duct is formulated and discussed, and a simplified direct thermal model is presented. Parameters of the model are estimated by solving a minimization problem, using temperature data from the wall surface and/or the flow. A multivariable optimization algorithm is employed for this purpose. Furthermore, a model for the forced-convection heat-transfer coefficient is proposed and its effect on the results is discussed.

The validity of the proposed method is assessed using data from two different circular duct flows. The method is shown to provide a good prediction capability in computationally demanding transient heat-data sequences of different duct flows, both in terms of duct and of flow characteristics. Results show that a hyperbolic axial distribution of the forced-convection heat-transfer coefficient in the developing region of the flow is essential for good adaptation of the method to the test data.
Exergy analysis: Parametric study on lithium bromide—water absorption refrigeration systems
Authors: Sedighi K , Farhadi M , Liaghi M
Published: November 2007

In the current study, an exergy analysis of a single-effect absorption refrigeration cycle using lithium bromide-water solution is carried out. The cycle has been analysed by considering the mass and energy conservation based on the first and second laws of thermodynamics. This analysis provides a detailed information on the effect of different parameters on the system performance. The coefficient of performance (COP), exergetic efficiency (ECOP), and exergy destruction are determined. The results show that a reduction in cooling water temperature caused an improvement in the COP and ECOP. Increasing the evaporator temperature has also improved the COP, but it caused a reduction in the ECOP of the system. Also it can be seen that the parameters' variation at the solution side has a more significant effect on cycle performances.
Buckling analysis of circular functionally graded material plate having variable thickness under uniform compression by finite-element method
Authors: Naei M H , Masoumi A , Shamekhi A
Published: November 2007

The current study presents the buckling analysis of radially-loaded circular plate with variable thickness made of functionally graded material. The boundary conditions of the plate is either simply supported or clamped. The stability equations were obtained using energy method based on Love-Kichhoff hypothesis and Sander's non-linear strain-displacement relation for thin plates. The finite-element method is used to determine the critical buckling load. The results obtained show good agreement with known analytical and numerical data. The effects of thickness variation and Poisson's ratio are investigated by calculating the buckling load. These effects are found not to be the same for simply supported and clamped plates.
Precise account of frictional loads in motor current-based compensation system of cutting force-induced error
Authors: Turyagyenda G , Yang J , Wu H
Published: November 2007

The balance between precision and its cost implications is a major determining factor for the competitiveness in the contemporary machining industry. The current paper presents an inexpensive compensation system for cutting force induced error based on current sensory system for indirect monitoring of cutting force. Based on machining parameters and online sensor signal, a dedicated model predicts the corresponding error. The model precisely accounts for the complex phenomena of coulomb and viscous frictions in the transmission system. Finally, the predicted error is compensated by means of external shifting of respective coordinate system origins in real-time. This system is convenient and reliable and, in addition, precise and easy to repair. The experimental evaluation of the system demonstrated robustness and great enhancement of machine accuracy.
Influence of unequal air-gap thickness in servo valve torque motors
Authors: Urata E
Published: November 2007

The current paper considers servo valve torque motors having four air-gaps. An ideal for these types of torque motors is to have four equal air-gaps at free state. However, real servo valve torque motors have unequal air-gaps due to production errors. Because the influence of the inequality of air-gaps is not clear, servo valve manufacturers have made great efforts to establish the equality of the air-gaps. The current paper gives a prospect on how an imbalance of air-gaps changes the flux densities in the air-gaps and the resultant torque characteristic. An important result of the paper is that some of the air-gap imbalance induces a torque change of magnitude of second- or higher-powers of the imbalance. The imbalance of the air-gaps due to different pole heights results in an offset proportional to the magnitude of the imbalance. These results can be used for setting a tolerance limit for air-gap thickness.
Advanced finite-element modelling of a 32-panel soccer ball
Authors: Price D S , Jones R , Harland A R
Published: November 2007

The current paper details the development of a finite-element model of a manually stitched, textile reinforced 32-panel soccer ball used in elite competition. The model included material anisotropy, a stiffer region representative of the polyester fibre based stitching, and a latex bladder membrane which was pressurized through inflation. A stiffness proportional damping coefficient was included within the material model to describe kinetic energy loss characteristics. The model was validated through experimental impact testing at speeds representative of play. It was found that the combined effects of material anisotropy, panel stitching, and panel configuration had a profound effect on the impact characteristics of the ball.