bluuebunny/crossref_metadata_2025 huggingface dataset:
Ovulation-selective genes: the generation and characterization of an ovulatory-selective cDNA library
Authors: Hourvitz A , Gershon E , Hennebold J D , Elizur S , Maman E , Brendle C , Adashi E Y , Dekel N
Published: March 2006

Ovulation-selective/specific genes, that is, genes preferentially or exclusively expressed during the ovulatory process, have been the subject of growing interest. We report herein studies on the use of suppression subtractive hybridization (SSH) to construct a ‘forward’ ovulation-selective/specific cDNA library. In toto, 485 clones were sequenced and analyzed for homology to known genes with the basic local alignment tool (BLAST). Of those, 252 were determined to be nonredundant. Of these 252 nonredundant clones, 98 were analyzed by probing mouse preovulatory and postovulatory ovarian cDNA. Twenty-five clones (26%) failed to show any signal, and 43 cDNAs tested thus far display a true ovulation-selective/specific expression pattern. In this communication, we focus on one such ovulation-selective gene, the fatty acid elongase 1 (FAE-1) homolog, found to be localized to the inner periantral granulosa and to the cumulus granulosa cells of antral follicles. The FAE-1 gene is a β-ketoacyl-CoA synthase belonging to the fatty acid elongase (ELO) family, which catalyzes the initial step of very long-chain fatty acid synthesis. All in all, the present study accomplished systematic identification of those hormonally regulated genes that are expressed in the ovary in an ovulation-selective/specific manner. These ovulation-selective/specific genes may have significant implications for the understanding of ovarian function in molecular terms and for the development of innovative strategies for both the promotion of fertility and its control.
Acute and chronic leptin reduces food intake and body weight in goldfish (Carassius auratus)
Authors: de Pedro N , Martínez-Álvarez R , Delgado M J
Published: March 2006

The purpose of the present study was to elucidate the possible role of leptin in food intake and body weight regulation in goldfish. We examined the effects of i.c.v. or i.p. acute leptin administration on food intake in food-deprived goldfish at different time intervals post-injection (0–2, 2–8 and 0–8 h). Food intake was reduced by i.p. administered leptin (1 μg) at 8 h post-injection, without statistically significant differences after i.c.v. treatment. The present study shows for the first time in a teleost that chronic (10 days) leptin treatment (i.p.) reduces food intake, body weight gain, specific growth rate and food efficiency ratio. Moreover, lipid and carbohydrate metabolism seems to be regulated by leptin in fish. Chronic leptin treatment increased lipid mobilization and carbohydrate storage as hepatic and muscle glycogen. Finally, leptin could mediate its actions on energy homeostasis in fish, at least in part, through interactions with hypothalamic catecholamines, since chronic leptin treatment reduced both hypothalamic noradrenergic and dopaminergic turnover without significant modifications in hypothalamic serotoninergic and neuropeptide Y (NPY) systems. In summary, our results suggest that leptin can regulate feeding behaviour and body weight homeostasis in fish.
Rodent adrenocortical cells display high affinity binding sites and proteins for inhibin A, and express components required for autocrine signalling by activins and bone morphogenetic proteins
Authors: Farnworth Paul G , Wang Yao , Leembruggen Pauline , Ooi Guck T , Harrison Craig , Robertson David M , Findlay Jock K
Published: March 2006

Inhibins are expressed in the adrenal cortex, but little is known of their binding or role in the adrenal. The aims of the present study were, first, to establish whether a mouse adrenocortical (AC) cell line expresses inhibins/activins and bone morphogenetic proteins (BMP), along with proteins required for inhibin to antagonise activin and BMP actions and, secondly, to characterise and compare inhibin binding sites and proteins in the rat adrenal gland and AC cells. AC cells were found to: (1) express mRNA for multiple BMPs (BMP-2, -3, -4, -6, -8a), growth/differentiation factors (GDF-1, -3, -5, -9), Lefty A and B, and the inhibin α, βA and βB subunits (2) secrete inhibin A and inhibin B and (3) express mRNA encoding the inhibin co-receptor, betaglycan, along with activin and BMP type I (ALK2–7) and type II (ActRII, ActRIIB, BMPRII) receptors, and binding proteins (follistatin, BAMBI, gremlin). When applied to sections of rat adrenal glands, [125I]inhibin A specifically bound to cells of the adrenal cortex, mainly in the zona reticularis. Scatchard analyses of in vitro [125I]inhibin A binding to dispersed rat adrenal cells and AC cells revealed sites of high affinity (Kd(1) of 0.18 and 0.15 nM, respectively) and low affinity (Kd(2) of 2.6 and 1.3 nM, respectively. Competition for [125I]inhibin A binding by activin A or B (30 nM) was negligible, whereas BMP-2, -6 and -7 competed for between 21 and 33% of specific inhibin A binding (IC50 between 0.2 and 0.3 nM). Inhibin B crossreaction with inhibin A binding sites was < 8%. Multiple binding protein complexes (molecular weight ranging from 35 to > 220 kDa) were affinity labelled by [125I]inhibin A on both the primary rat adrenal and AC cells. The species of > 220 kDa were shown by immunoprecipitation to include betaglycan, the species of 105 kDa is consistent in size with type II receptors for activin/BMP, and that of 62 kDa co-migrates with the inhibin-follistatin complex.

In summary, the results show that inhibin A binds selectively and with both high and low affinity to AC cells via multiple binding proteins, including a single betaglycan-like species. The results support the role of glycosylated betaglycan in the high affinity binding of inhibin A, but provide consistent evidence from two independent sources of adrenal cells that inhibin A interacts with several membrane proteins in addition to those currently understood to mediate the anti-activin/BMP actions of inhibin.
Inositol triphosphate participates in an oestradiol nongenomic signalling pathway involved in accelerated oviductal transport in cycling rats
Authors: Orihuela Pedro A , Parada-Bustamante Alexis , Zuñiga Lidia M , Croxatto Horacio B
Published: March 2006

Oestradiol (E2) accelerates oviductal transport of oocytes in cycling rats through a nongenomic pathway that involves the cAMP–PKA signalling cascade. Here we examined the role of the inositol triphosphate (IP3) and mitogen-activated protein kinase (MAPK) signalling cascades in this nongenomic pathway. Oestrous rats were injected with E2 s.c. and intrabursally (i.b) with the selective inhibitors of phospholipase C (PLC) ET-18-OCH3 or MAPK PD98059. The number of eggs in the oviduct assessed 24 h later showed that ET-18-OCH3 blocked E2-induced egg transport acceleration, whereas PD98059 had no effect. Other oestrous rats were treated with E2 s.c. and 1, 3 or 6 h later oviducts were excised and the levels of IP3 and phosphorylated MAPK p44/42 (activated) were determined by radioreceptor assay and western blot, respectively. Oestradiol administration increased IP3 level at 1 and 6 h after treatment, whereas activated MAPK p44/42 level was unchanged. Finally, we explored whether cAMP-PKA and PLC-IP3 signalling cascades are coupled. Inhibition of adenylyl cyclase by i.b. injection of SQ 22536 blocked the increase of IP3 levels induced by E2, while inhibition of PLC by ET-18-OCH3 had no effect on E2-induced PKA activity. Furthermore, activation of adenylyl cylase by Forskolin increased oviductal IP3 levels. Thus, activation of PLC-IP3 by E2 requires previous stimulation of cAMP-PKA. We conclude that the nongenomic pathway utilised by E2 to accelerate oviductal transport of oocytes in cycling rats involves successive activation of the cAMP-PKA and PLC-IP3 signalling cascades and does not require activation of MAPK. These findings clearly illustrate a non-genomic pathway triggered by E2 that regulates a complex physiologic process accomplished by an entire organ.
Effect of the oestrous cycle, pregnancy and uterine region on the responsiveness of the isolated mouse uterus to prostaglandin F2α and the thromboxane mimetic U46619
Authors: Griffiths A L , Marshall K M , Senior J , Fleming C , Woodward D F
Published: March 2006

Previous studies in this laboratory have suggested that the isolated uterus from non-pregnant mice has a prostaglandin F and a thromboxane receptor population similar to that found in human myometrium. The aim of this study was to investigate any regional variation in myogenic activity ) and the and responsiveness to prostaglandin F2α (PGF2α thromboxane mimetic U46619 in the mouse uterus taken during different stages of the oestrous cycle and during pregnancy. Uterine samples from BKW mice were taken from different anatomical segments along the length of each uterine horn and set up for superfusion at 2 ml/min with Krebs solution (containing 1 μM indometacin) at 37 °C, and gassed with 95%O2/5%CO2. Responses (area under the curve) are expressed as a percentage of the final contraction induced by hypotonic shock. Data are expressed as the means ± s.e.m. of n=5–12 and were analysed using Student’s paired t-test or two-way ANOVA with a Bonferroni post hoc test. Regional variation in myogenic activity was observed in all tissues studied except those taken during labour. These tissues displayed significantly greater myogenic activity than tissues taken at late gestation and at all stages of the oestrous cycle. Tissues from pregnant animals were generally more responsive to U46619 and PGF2α than tissues taken from non-pregnant animals. Tissues taken from the upper segment of the uterine horn were more responsive to both agonists during the oestrous cycle. The findings demonstrated that the hormonal milieu and site of excision are important for myogenic activity and responsiveness.
Novel fish hypothalamic neuropeptides stimulate the release of gonadotrophins and growth hormone from the pituitary of sockeye salmon
Authors: Amano Masafumi , Moriyama Shunsuke , Iigo Masayuki , Kitamura Shoji , Amiya Noriko , Yamamori Kunio , Ukena Kazuyoshi , Tsutsui Kazuyoshi
Published: March 2006

We recently identified a cDNA encoding three novel fish hypothalamic neuropeptides, having LPXRF-NH2 from the goldfish brain. In this study, to clarify the physiological functions of these three LPXRFamide peptides (gfLPXRFa-1, -2, and -3), we analysed the localisation and hypophysiotrophic activity of these peptides using sockeye salmon, Oncorhynchus nerka, in which immunoassay systems for several anterior pituitary hormones have been developed. gfLPXRFa-immunoreactive cell bodies were detected in the nucleus posterioris periventricularis of the hypothalamus and immunoreactive fibres were distributed in various brain regions and the pituitary. We also detected gfLPXRFa-immunoreactivity in the pituitary by competitive enzyme-linked immunosorbent assay combined with reversed-phase HPLC. These three gfLPXRFamide peptides stimulated the release of FSH, LH and GH, but did not affect the release of prolactin (PRL) and somatolactin (SL) from cultured pituitary cells. These results suggest that novel fish hypothalamic LPXR-Famide peptides exist in the brain and pituitary of sockeye salmon and stimulate the release of gonadotrophins and GH from the pituitary.
Altered vascular contractility in adult female rats with hypertension programmed by prenatal glucocorticoid exposure
Authors: Hadoke P W F , Lindsay R S , Seckl J R , Walker B R , Kenyon C J
Published: March 2006

Excessive exposure to glucocorticoids during gestation reduces birth weight and induces permanent hypertension in adulthood. The mechanisms underlying this programmed elevation of blood pressure have not been established. We hypothesised that prenatal glucocorticoid exposure may lead to vascular dysfunction in adulthood. Pregnant rats received dexamethasone (Dex) (100 μg/kg, s.c.) or vehicle (control) daily throughout pregnancy. Blood pressure was elevated (students t-test, unpaired; P < 0.05) in adult female offspring (aged 12–16 weeks) of Dex-treated mothers (148.0 ± 3.6 mmHg, n=10) compared with the control group (138.0 ± 2.5 mmHg, n=8). Vascular responsiveness in aortae and mesenteric arteries was differentially affected by prenatal Dex: aortae were less responsive to angiotensin II, whereas mesenteric arteries were more responsive to norepinephrine, vasopressin and potassium (mesenteric arteries respond poorly to angiotensin II in vitro). Acetylcholine-mediated, endothelium-dependent relaxation was similar in both groups. Prenatal exposure to Dex had no effect on blood pressure or aldosterone response to acute (15 min, i.v.) infusion of angiotensin II (75 ng/kg per min). In contrast, chronic (2-week, s.c.) infusion of angiotensin II (100 ng/kg per min) produced a greater elevation (P < 0.05) of blood pressure in Dex-treated rats (150.0 ± 3.6 mmHg) than in controls (135.3 ± 5.4 mmHg), and aldosterone levels were higher in Dex-treated animals. There was no angiotensin II-induced medial hypertrophy/hyperplasia in mesenteric arteries from Dex-treated rats. These results indicate that vascular function is altered in a region-specific manner in rats with glucocorticoid-programmed hypertension. Despite a striking increase in mesenteric artery contraction in Dex-treated rats, in vivo studies suggest that abnormalities of the renin-angiotensin-aldosterone system, rather than enhanced vascular contractility, may be responsible for the elevation of blood pressure in these animals.
Renal effects of a neutralising RAGE-antibody in long-term streptozotocin-diabetic mice
Authors: Jensen Louise J N , Denner Larry , Schrijvers Bieke F , Tilton Ronald G , Rasch Ruth , Flyvbjerg Allan
Published: March 2006

Advanced glycation endproducts (AGEs) have been implicated in the pathogenesis of diabetic kidney disease. The actions of AGEs are mediated both through a non-receptor mediated pathway and through specific receptors for AGEs (e.g. RAGE). To explore a potentially specific role for RAGE in renal changes in type 1 diabetes, we examined the renal effects of a neutralising murine RAGE-antibody (ab) in streptozotocin (STZ)-diabetic mice, a model of type 1 diabetes. One group of STZ-diabetic mice was treated for two months with the RAGE-ab, while another STZ-diabetic group was treated for the same period with an irrelevant immunoglobulin G (IgG). Two groups of non-diabetic NMRI mice were treated with either RAGE-ab or isotype-matched IgG for two months. Placebo-treated STZ-diabetic mice showed an increase in kidney weight, glomerular volume, basement membrane thickness (BMT), urinary albumin excretion (UAE) and creatinine clearance (CrCl), when compared with non-diabetic controls. In RAGE-ab-treated STZ-diabetic mice, the increase in kidney weight and UAE was reduced, while the increase in CrCl was abolished. RAGE-ab administration in NMRI mice caused a reduction in liver weight and an increase in BMT. Renal messenger RNA (mRNA) for connective tissue growth factor and collagen IVα1 was increased in placebo-treated diabetic animals. RAGE-ab treatment had no impact on the expression of these factors. The renal effects of RAGE-ab administration in STZ-diabetic mice were seen without impact on body weight, blood glucose or food consumption. In conclusion, the present data support the hypothesis that RAGE is an important pathogenic factor in the renal changes in an animal model of type 1 diabetes.
Developmental regulation of the lung in preparation for life after birth: hormonal and nutritional manipulation of local glucocorticoid action and uncoupling protein–2
Authors: Gnanalingham M G , Mostyn A , Gardner D S , Stephenson T , Symonds M E
Published: March 2006

Glucocorticoid action has a major role in regulating fetal and postnatal lung development, although its impact on mitochondrial development is less well understood. Critically, the consequences of any change in glucocorticoid action and mitochondrial function in early life may not be limited to the postnatal period, but may extend into later life. This paper focuses on more recent findings on the impact of ontogeny, fetal cortisol status, maternal nutrient restriction and postnatal leptin administration on mitochondrial uncoupling protein (UCP)-2, glucocorticoid receptor (GR) and 11 β-hydroxysteroid dehydrogenase type 1 (11βHSD1) isoform abundance in the lung. For example, in sheep, GR and 11βHSD1 mRNA are maximal at 140 days’ gestation (term ~147 days), while UCP2 mRNA peaks at 1 day after birth and then decreases with advancing age. In the fetus, chronic umbilical cord compression enhances the abundance of these genes, an outcome that can also be produced after birth following chronic, but not acute, leptin administration. Irrespective of the timing of maternal nutrient restriction in pregnancy, glucocorticoid sensitivity and UCP2 abundance are both upregulated in the lungs of the resulting offspring. In conclusion, prenatal and postnatal endocrine challenges have distinct effects on mitochondrial development in the lung resulting from changes in glucocorticoid action, which can persist into later life. As a consequence, changes in glucocorticoid sensitivity and mitochondrial protein abundance have the potential to be used to identify those at greatest risk of developing later lung disease.
Human prolactin receptors are insensitive to mouse prolactin: implications for xenotransplant modeling of human breast cancer in mice
Authors: Utama F E , LeBaron M J , Neilson L M , Sultan A S , Parlow A F , Wagner K-U , Rui H
Published: March 2006

Experimental testing of growth, metastatic progression and drug responsiveness of human breast cancer in vivo is performed in immunodeficient mice. Drug candidates need to show promise against human breast cancer in mice before being allowed into clinical trials. Breast cancer growth is under endocrine control by ovarian steroids and the pituitary peptide hormone prolactin. While it is recognized that the most relevant biologic effects of prolactin are achieved with prolactin from the matching species, the biologic efficacy of mouse prolactin for human prolactin receptors has not been recorded. Thus, it is unclear whether the mouse endocrine environment adequately reflects the hormonal environment in breast cancer patients with regard to prolactin. We now show both recombinant and natural pituitary-derived mouse prolactin to be a poor agonist for human prolactin receptors. Mouse prolactin failed to induce human prolactin receptor-mediated biologic responses of cell clustering, proliferation, gene induction and signal transduction, including activation of Stat5, Stat3, Erk1/2 and Akt pathways. Consistent data were derived from human breast cancer lines T-47D, MCF-7 and ZR-75.1, as well as human prolactin receptor-transfected COS-7 and 32D cells. Failure of mouse prolactin to activate human prolactin receptors uncovers a key deficiency of the mouse endocrine environment for human xenotransplant studies. Since most human breast cancers express prolactin receptors, human breast cancer transferred into mice is unnaturally selected for growth in the absence of circulating prolactin. The new insight raises concerns about the validity of analyzing biology and drug responsiveness of human breast cancer in existing mouse xenotransplant models.
Involvement of brain-derived neurotrophic factor in the regulation of hypothalamic somatostatin in vivo
Authors: Givalois Laurent , Naert Gaëlle , Tapia-Arancibia Lucia , Arancibia Sandor
Published: March 2006

Brain-derived neurotrophic factor (BDNF) has been extensively studied in the central nervous system as a survival and differentiation factor and in plasticity processes. In vitro, BDNF has been shown to stimulate cellular differentiation and neurohormones synthesis and release. We demonstrated that BDNF is a potent and specific stimulatory agent of somatostatin (SRIH) synthesis in primary cultures of hypothalamic neurons. However, less information is available about its function on SRIH neurons in vivo. In the present study, we examined the effect of in vivo intracerebroventricular BDNF administration in adult non-anesthetized male rats. Two distinct experimental approaches were used: acute intracerebroventricular injection and long-term (14 days) continuous infusion (Alzet micro-pumps). We demonstrate that single intracerebroventricular BDNF injections (5 μg/rat) induce an early (60 and 180 min) decrease in the SRIH mRNA signal in the hypothalamic periventricular nucleus (PeVN) accompanied by a decrease of the hypothalamic SRIH content. 48 h after the acute injection, SRIH mRNA levels and peptide content strongly and significantly increased. After continuous intracerebroventricular BDNF administration (12 μg/day for 14 days), a significant increase in the SRIH hypothalamic content was observed. Nevertheless, the increase in peptide content was not correlated with a similar increase in the PeVN messenger level. These findings show the involvement of BDNF in the in vivo regulation of somatostatinergic neurons in adult rats, which clearly differs according to the BDNF administration mode.
In vitro evidence that hyperglycemia stimulates tumor necrosis factor-α release in obese women with polycystic ovary syndrome
Authors: González F , Rote N S , Minium J , Kirwan J P
Published: March 2006

Women with polycystic ovary syndrome (PCOS) are often insulin resistant and have chronic low-level inflammation. The purpose of this study was to determine the effects of hyperglycemia in vitro on tumor necrosis factor (TNF)-α release from mononuclear cells (MNC) in PCOS. Twelve reproductive-age women with PCOS (six lean, six obese) and 12 age-matched controls (six lean, six obese) were studied. Insulin sensitivity (ISHOMA) was estimated from fasting levels of glucose and insulin and percent truncal fat was determined by dual energy absorptiometry (DEXA). TNFα release was measured from MNC cultured under euglycemic and hyperglycemic conditions. ISHOMA was higher in obese women with PCOS than in lean women with PCOS (student’s t-test; 73.7 ± 14.8 vs 43.1 ± 8.6, P < 0.05), but similar to that of obese controls. ISHOMA was positively correlated with percent truncal fat (r=0.57, P < 0.04). Obese women with PCOS exhibited an increase in the percent change in TNFα release from MNC in response to hyperglycemia compared with obese controls (10 mM, 649 ± 208% vs 133 ± 30%, P < 0.003; 15 mM, 799 ± 347% vs 183 ± 59%, P < 0.04). The TNFα response directly correlated with percent truncal fat (r=0.45, P < 0.03) and ISHOMA (r=0.40, P < 0.05) for the combined groups, and with plasma testosterone (r=0.60, P < 0.05) for women with PCOS. MNC of obese women with PCOS exhibit an increased TNFα response to in vitro physiologic hyperglycemia. MNC-derived TNFα release may contribute to insulin resistance and hyperandrogenism, particularly when the combination of PCOS and increased adiposity is present.
Inactivation of Kupffer cells by gadolinium administration prevents lipopolysaccharide-induced decrease in liver insulin-like growth factor-I and IGF-binding protein-3 gene expression
Authors: Granado M , Martín A I , Priego T , Villanúa M A , López-Calderón A
Published: March 2006

Gram-negative bacterial infection or treatment of animals with bacterial lipopolysaccharide (LPS) induces a catabolic state with proteolysis, liver injury and an inhibition of the insulin-like growth factor-I (IGF-I) system. The purpose of this work was to elucidate the role of Kupffer cells in LPS-induced inhibition of the IGF-I/IGF-binding protein-3 (IGFBP-3) system. Adult male Wistar rats were either pretreated with the Kupffer cell inhibitor gadolinium chloride (10 mg/kg, i.v., 24 h prior to LPS exposure) or saline vehicle. Rats received two i.p. injections of 1 mg/kg LPS (at 17:30 and 08:30 h the following day) and were killed 4 h after the second injection. LPS administration induced a significant decrease in body weight and in serum concentrations of IGF-I and IGFBP-3 (P < 0.01), as well as in their gene expression in the liver. LPS-injected rats had increased serum concentrations of ACTH, corticosterone (P < 0.05), tumour necrosis factor-α (TNF-α) and nitrites (P < 0.01). Pretreatment of the animals with gadolinium chloride blocked the inhibitory effect of LPS on body weight, and on serum concentrations of IGF-I, IGFBP-3 and nitrites, as well as growth hormone receptor (GHR), IGF-I and IGFBP-3 gene expression in the liver. In contrast, gadolinium chloride administration did not modify the stimulatory effect of LPS on serum concentrations of ACTH, corticosterone and TNF-α. These results suggest that Kupffer cells are important mediators in the inhibitory effect of LPS on GHR, IGF-I and IGFBP-3 gene expression in the liver, leading to a decrease in serum concentrations of IGF-I and IGFBP-3.
Follicle-stimulating hormone increases primordial follicle reserve in mature female hypogonadal mice
Authors: Allan C M , Wang Y , Jimenez M , Marshan B , Spaliviero J , Illingworth P , Handelsman D J
Published: March 2006

Ovarian primordial follicle reserve is considered hormonally independent or subject to depletion by FSH-driven follicle recruitment. To explore specific in vivo effects of FSH on early follicle populations in the absence of luteinizing hormone (LH) activity, we examined mature hypogonadal (hpg), gonadotrophin-deficient mice expressing transgenic (tg) human FSH. Sustained expression of tg-FSH (5.3 ± 0.3 IU/l) increased ovary weights fourfold and significantly elevated total primordial follicle numbers twofold in tg-FSH hpg (4209 ± 457) relative to non-tg hpg (2079 ± 391) and wild-type (2043 ± 195) age-matched ovaries. Absolute primary follicle numbers in tg-FSH hpg ovaries were similar to non-tg hpg and wild-type ovaries. Furthermore, tg-FSH quantitatively increased secondary and antral follicles in hpg ovaries to numbers equivalent to wild-type, but did not induce ovulation, indicating a selective FSH response without LH. Circulating inhibin B and inhibin A levels were significantly increased in tg-FSH hpg females compared with hpg controls, and inhibin B correlated with antral number, consistent with FSH-driven antral follicle formation. These findings revealed that sustained pituitary-independent FSH activity, in the absence of endogenous gonadotrophins, promotes an increase in primordial follicle reserve despite also stimulating follicular growth in mature females. Therefore, the tg-FSH hpg ovary presents a novel paradigm to evaluate specific gonadotrophin effects on follicle reserve and recruitment.
Intrinsic biological activity of the thrombospondin structural homology repeat in connective tissue growth factor
Authors: Tong Zhen-Yue , Brigstock David R
Published: March 2006

Connective tissue growth factor (CCN2) is a 349-residue mosaic protein that contains four structural modules (modules 1–4), which are presumptive domains for interactions with regulatory binding proteins and receptors. Module 3, corresponding to residues 199–243, is a thrombospondin structural homology repeat (TSR) and is flanked by regions that are highly susceptible to proteolytic cleavage. To test whether CCN2 module 3 (CCN23) has intrinsic biological properties, it was produced recombinantly in Escherichia coli (E. coli) and examined for its effects on the function of hepatic stellate cells (HSC), the principal fibrogenic cell type in the liver. CCN23 stimulated dose-dependent HSC adhesion and activity of p42/p44 mitogen activated protein kinase, the latter of which was antagonized by blocking the activity of focal adhesion kinase. HSC adhesion to immobilized CCN23 was attributed to binding interactions with cell surface integrin α6β1. As assessed by RT-PCR or Western blotting, CCN23 stimulated production of fibronectin and pro-collagen type IV(α5), both of which are downstream components of HSC-mediated fibrogenesis and which are constituents of high density matrix in fibrotic lesions. These data show that while the full length CCN2 protein is strongly associated with fibrosis and stellate cell function, key integrinbinding properties, signaling, and fibrogenic pathways are exhibited by module 3 alone. These data indicate that module 3 of CCN2 is intrinsically active and suggest that liberation of module 3 following CCN2 proteolysis may contribute to HSC-mediated fibrogenesis, as well as other CCN2-dependent processes.
Development of in situ joints for pre-cast bridge deck units
Authors: Gordon S. R. , May I. M.
Published: March 2006

This paper, which extends research described in a previous paper, describes and discusses tests carried out to develop in situ joints suitable for pre-cast reinforced concrete deck units, for the decks of steel concrete composite bridges, in negative moment areas. The results of 18 tests of symmetric and non-symmetric arrangements of straight and looped bars are given together with comparisons to the theoretical strengths. The behaviour of the joints at serviceability and ultimate loads and beyond, are discussed. The tests show that the failure loads of joints containing looped bars can be accurately predicted based on the ultimate strength of the reinforcement provided there are adequate transverse lacer bars. Crack widths were measured in a number of specimens and it was concluded that they would be unlikely to impose a limitation at the serviceability limit state.
The replacement of Heath Town footbridge
Authors: Mordey A. G.
Published: March 2006

Heath Town footbridge was constructed in 1999–2000 to replace an existing concrete bridge that was in poor condition and had failed its assessment. The existing bridge had performed two functions, one as a footbridge over an urban dual carriageway and service road between high-level walkways in Heath Town, Wolverhampton, the other being to carry district heating pipes from the boiler house on one side of the road to flats and other premises on the other side of the road. The new bridge is a parabolic arch in steel, on piled foundations. It was originally designed to carry the district heating pipes in the same way as the previous one, but permission was given to bury these permanently beneath the dual carriageway, which prompted a redesign of the deck, making it simpler in detail.
Calculating an influence line from direct measurements
Authors: OBrien E. J. , Quilligan M. J. , Karoumi R.
Published: March 2006

The response of a bridge to a pre-weighed truck can be measured on site. This paper describes a mathematical method for converting the measured response of a load effect into an influence line for that effect. One influence ordinate is calculated for each scan of the data acquisition system. The vector of ordinates is found by solving a large set of simultaneous equations expressed in matrix form. The general form of the matrices is described, and the particular matrices for a three-axle truck are given. The technique is demonstrated using measured strain on two bridges using pre-weighed trucks with different numbers of axles.
Heat-straightening repairs to a steel road bridge
Authors: Clubley S. K. , Winter S. N. , Turner K. W.
Published: March 2006

On 16 July 2002 a low-loader lorry carrying heavy machinery travelling eastbound on the A27 struck the underside of Brockhampton Road new bridge. The bridge suffered structural damage to the main beams and bracing. From an initial emergency inspection, the damage was found to be located close to the point of contraflexure in an area where the bottom flange was in tension. It was not considered necessary to impose immediate closures or traffic restrictions. A heat-straightening repair of the damaged beams was proposed. Detailed analysis using both hand calculations and the finite-element method confirmed the structural adequacy of the bridge to undergo the heat-straightening process. These checks encompassed the temporary conditions prior to, during and after the heating. The major heat-straightening process was successfully completed on site in ten days. Impact damage to the beams was repaired within acceptable tolerances and the straightened steel was subjected to hardness and magnetic particle investigation testing. The repairs to Brockhampton Road new bridge were concluded without undue disruption to the travelling public or local residents.
A fuzzy optimum model to assess bridge design options
Authors: Wang H.-L. , Zhang Z. , Huang C.-L. , Shi L.
Published: March 2006

In the process of bridge design, it is necessary to select the best from a number of feasible alternatives by comparison and selection or elimination. The set of criteria used to evaluate and select the satisfactory alternative consists of many qualitative and quantitative factors. Therefore, the selection is a problem of multi-criteria and semi-structural decision making. A new framework and methodology for evaluation of bridge alternatives, which differs from the traditional methods used in semi-structural decision making, is presented in this paper. First the set of criteria for the evaluation of alternatives is established. Next, the method of construction of the relative membership degree matrix, in which both qualitative and quantitative factors are consistent with the uniform calculating standard, is studied. A new weight-assessing method is then developed for calculation of the weightings, based on the relative membership degree matrix and finally a fuzzy optimum model is adopted to select the various alternative bridge designs that satisfy the criteria. A case study is then presented, to show the efficiency and robustness of the new framework and methodology.
Sustainability evaluation for brownfield redevelopment
Authors: Pediaditi K. , Wehrmeyer W. , Chenoweth J.
Published: March 2006

Redevelopment of brownfield land has been identified as an essential component to the achievement of sustainable urban regeneration. However, in some cases, brownfield redevelopment has been characterised by a lack of long-term consideration of impacts, as well as the failure to holistically examine the environmental, economic and social issues, which form the basis of sustainability. It is therefore important to develop and implement a new approach that can be used to address and monitorcc sustainability throughout the life cycle of land-use, thus addressing the intergenerational principle of sustainable development. This paper describes a new Redevelopment Assessment Framework that will enable the use of sustainability indicators to monitor holistically the long-term sustainability of brownfield redevelopments. The framework's key characteristics are that it is dynamic in nature, allowing for sustainability monitoring through the land-use life cycle of a brownfield project, as well as being participatory and transparent as a process. The framework incorporates consideration of the risk perception and risk communication issues that are typical of brownfield projects. By design, the new framework is aimed at developing site-specific indicators within the overall context of the existing monitoring and planning processes that brownfield redevelopment projects are required to undergo.
Integrating 1D and 2D hydrodynamic models for flood simulation
Authors: Lin B. , Wicks J. M. , Falconer R. A. , Adams K.
Published: March 2006

The one-dimensional (1D) hydrodynamic model ISIS has been extensively used for designing river engineering and irrigation schemes and mapping flood risks. This paper presents the integration of a two-dimensional (2D) model with ISIS to enhance its capability for simulating floodplain flows. The 2D model is based on the DIVAST model, a research model widely used for predicting flows and water quality indicators in estuarine and coastal waters. One of the main advantages of using DIVAST is that the model has a very robust subroutine for simulating flooding and drying processes. In this study DIVAST is dynamically linked to the ISIS model and the linked model is used to predict overland flood flows. In order to increase the flexibility of the DIVAST model for dealing with complex flow situations while minimising the computational time, several modelling options were considered. These options include the so-called hydrodynamic approach, gravity wave approach and flood wave approach. A series of numerical tests were undertaken to assess the accuracy and efficacy of these approaches for simulating flows over initially dried land and dam-break flows. The model was then used to predict the flood flow in an urban area for an assumed extreme flood flow condition.
Briefing: Introducing the Flood Risk Management Research Consortium
Authors: Pender G.
Published: March 2006

This paper reports on the formation of the Flood Risk Management Research Consortium and the research that is under way within the ‘towards whole systems modelling’ (WSM) priority area. Funding for the consortium is provided from a wide range of research funders in the UK including the national research councils, government departments and agencies with responsibility for flood risk management. The research portfolio has been formulated to address key research needs identified by the funders. This briefing note explains the relationship between the planned research in the WSM area and the UK Environment Agency's Strategy for Flood Risk Management. Additionally, it provides an introduction to the companion research papers in this issue by Villanueva and Wright, Hunter et al., Lin et al., and Néelz et al. The research reported in these companion papers focuses on flood inundation modelling and is an important subset of the work to be undertaken within WSM.
Using remotely sensed data to support flood modelling
Authors: Néelz S. , Pender G. , Villanueva I. , Wilson M. , Wright N. G. , Bates P. , Mason D. , Whitlow C.
Published: March 2006

Recent severe flooding in the UK has highlighted the need for better information on flood risk, increasing the pressure on engineers to enhance the capabilities of computer models for flood prediction. This paper evaluates the benefits to be gained from the use of remotely sensed data to support flood modelling. The remotely sensed data available can be used either to produce high-resolution digital terrain models (DTMs) (light detection and ranging (Lidar) data), or to generate accurate inundation mapping of past flood events (airborne synthetic aperture radar (SAR) data and aerial photography). The paper reports on the modelling of real flood events that occurred at two UK sites on the rivers Severn and Ouse. At these sites a combination of remotely sensed data and recorded hydrographs was available. It is concluded first that light detection and ranging Lidar generated DTMs support the generation of considerably better models and enhance the visualisation of model results and second that flood outlines obtained from airborne SAR or aerial images help develop an appreciation of the hydraulic behaviour of important model components, and facilitate model validation. The need for further research is highlighted by a number of limitations, namely: the difficulties in obtaining an adequate representation of hydraulically important features such as embankment crests and walls; uncertainties in the validation data; and difficulties in extracting flood outlines from airborne SAR images in urban areas.
Application of 3D hydrodynamic model to flood risk assessment
Authors: Li B. , Phillips M. , Fleming C. A.
Published: March 2006

In this paper a newly developed three-dimensional hydrodynamic model has been used to investigate the consequences of the site redevelopment of Llanwern and flooding prevention measures. The 3D model includes hydrodynamic pressure without static pressure assumption. Two possible flooding risks have been analysed—tidal flooding from the south and fluvial flooding from the River Usk. Modelling results show that the consequences of the redevelopment and flood prevention measures are minimal on the surrounding area.
Marcuse, Bloch and Freire: Reinvigorating a Pedagogy of Hope
Authors: Van Heertum Richard
Published: March 2006

Critique of the current order of things is a necessary starting point for any project for radical change. Without an analysis of what is wrong, it is hard to convince anyone that change is necessary. And yet critique alone rarely inspires people to act. We need something to fight for as well as against. The article looks at the centrality of hope as a necessary complement to critique. Combining insights from Freire, Bloch and Marcuse, it argues that critical pedagogy needs to seriously engage methods to create an environment amenable to resistance and struggle for change, founded on a belief that a better world is possible. Marcuse, in particular, offers three key insights that can be instrumental in moving beyond the overly negative discourse and cynicism that prevail today – including a trenchant analysis of capitalism and desire, a program for aesthetic education and a model for utopian dreaming and embodied hope. It is argued that critical pedagogy must move beyond consciousness raising and identity formation alone to foster the belief that change is possible. We need to move toward a discourse and action that can capitalize on repressed desires and provide a provisional alternative vision that can galvanize people to act toward its realization.
On Marcuse and Caring in Education
Authors: Shel Tammy
Published: March 2006

Can caring and standardized testing coincide? Marcuse criticized the misuse of science because it also legitimizes social and economic hierarchy. By the same token, scholars develop standardized testing, claiming these tests are scientific and can measure objectively individuals’ learning and intelligence capabilities. However, if inclusive caring embraces human beings’ diversity and recognizes diverse learning styles and intelligences, the concept of standards promotes the opposite agenda. Standardized testing aims toward what Marcuse called a one-dimensional human being and social stratification. Can standardized testing promote learning and tolerance? The public and academic debate on this issue also needs to address the moral and social ramifications on society. If the emphasis in education is primarily on quantity, then society devalues human life and narrows it down, as Horkheimer & Adorno claimed, to zero. Such an agenda serves mostly those in power. Marcuse criticized the social ramifications and the portrayal and use of science as an accurate and neutral academic discipline. In a world that copes with violence, poverty, and intolerance domestically, nationally, and internationally, one needs to contemplate the danger that lies in the excessive quantitative measurement of human beings where there is scant qualitative value.
Utopia and Education in Critical Theory
Authors: Lewis Tyson
Published: March 2006

In this article the author examines the intimate connections between utopia and education in Frankfurt School critical theory. Although substantial links have been made in the critical pedagogy tradition between education, critique, and utopian dreaming, an in-depth analysis of the utopia–education matrix in the works of Herbert Marcuse, Theodor Adorno, and Fredric Jameson enriches our current understanding of this topic in several key ways. Marcuse enables us to envision play as a possible praxis for revitalizing utopian longings while Adorno's focus on anxiety offers a sound corrective to the overemphasis on hope in utopian scholarship. Finally, Jameson mediates many of the differences arising between Marcuse and Adorno to fashion a post-utopian utopianism for late capitalism.
Fumbling toward a Critical Legal Pedagogy and Practice
Authors: Matambanadzo Saru
Published: March 2006

This article argues that the culture and practice of legal education in the United States functions to dehumanize law students and potentially produce one-dimensional lawyers in the service of corporate interests and the capitalist status quo. These lawyers are trained to serve not only as the guardians of legal rights, social entitlements and privileges of citizenship but also as the vested producers and protectors of the unjust institutions and systems that deny these rights, entitlements and privileges to certain groups and ensure them to others. Drawing on the work of Freire, Gramsci, and Marcuse, critical legal scholars like Lani Guinier and the history of legal education and the legal profession in the United States, this article uses theory and critical scholarship to read and interrogate the ways in which the current practices and the historical evolution of legal education have functioned and continue to function in the service of capitalism and to the disservice of many of its clients. It also proposes Freirean reforms to the structure of legal education that utilize mandatory clinical education as a means to ensure that legal education and lawyers are multidimensional in their orientation to law and social justice.
The Potential of Vacuum Brazing – State of the Art and Developments from the Perspective of a Service Contractor
Authors: Boretius M.
Published: March 2006

Vacuum brazing is widely used to join sophisticated components for a broad range of industrial applications. Combining different materials by brazing offers new opportunities to design engineers to improve existing or to create new functions.
Performant Clay/Carbon Nanotube Polymer Nanocomposites
Authors: Dubois Ph. , Alexandre M.
Published: March 2006

This contribution aims at reviewing on very recent developments in syntheses, properties and (future) applications of polymer‐based nanocomposites filled with either organoclays and/or carbon nanotubes. Undoubtedly, the key‐challenge remains to reach a high level of nanoparticle dissociation (i.e., either to delaminate the silicate nanoplatelets or to break down the bundles of aggregated carbon nanotubes) and their fine dispersion upon melt blending within the selected polymer matrix. In that context, the in situ polymerization/grafting process as catalyzed directly from the nanofiller (organoclay or carbon nanotube) surface proved highly efficient allowing for the complete destructuration of the native filler aggregates. Dissociated nanoparticles were accordingly recovered, their surface was homogeneously coated/grafted by the in situ grown polymer chains as generated by this so‐called “Polymerization‐filling technique” (PFT). Interestingly enough, such surface‐coated organoclays and/or carbon nanotubes were further added as “masterbatch” in commercial polymeric matrices by twin‐screw extrusion. As a result of the pre‐destructuration of the nanofillers by PFT, it comes out that the resulting polymer nanocomposites displayed much higher thermo‐mechanical properties even with a nanofiller loading as tiny as 1wt%.
Relationship between Condition of Deposition and Properties of W‐Ti‐N Thin Films Prepared by Reactive Magnetron Sputtering
Authors: Kuchuk A. V. , Kladko V. P. , Lytvyn O. S. , Piotrowska A. , Minikayev R. A. , Ratajczak R.
Published: March 2006

A correlation between the film properties of nitrides, oxides etc., and their structure, is of fundamental importance – not only for thin solid films physics but also for practical applications. The structure of the films depends on deposition methods and their parameters. The relationship between properties (chemical and phase compositions, surface morphology, and electrical resistivity) and nitrogen partial pressure of reactive magnetron sputtered W‐Ti‐N thin films has been discussed here in detail.
Mechanical Properties and Processing of Low‐Temperature Diffusion‐Welded Hybrid Joints
Authors: Wilden J. , Bergmann J. P. , Jahn S.
Published: March 2006

Diffusion welding represents an attractive joining technology. This paper deals with joining Al to Ti. Initial investigations were performed on Al99.5 and cp‐Ti in order to understand the diffusion process for technically pure materials. In further investigations AA5xxx and AA6xxx were joined with cp‐Ti in order to show the effect of alloying elements. The results concerning the mechanical behaviour of joints confirm the suitability of the process for high‐strength applications.