bluuebunny/crossref_metadata_2025 huggingface dataset:
Mouse pregnancy-specific glycoproteins: tissue-specific expression and evidence of association with maternal vasculature
Authors: Wynne Freda , Ball Melanie , McLellan Andrew S , Dockery Peter , Zimmermann Wolfgang , Moore Tom
Published: April 2006

The pregnancy-specific glycoproteins (Psg) are secreted hormones encoded by multiple genes in rodents and primates, and are thought to act as immune modulators. The only Psg receptor identified is CD9, through which Psg17 induces cytokine production from macrophages cultured in vitro. We examined temporal and spatial aspects of Psg and CD9 expression during mouse pregnancy to determine whether their expression patterns support a role in immune modulation. Using in situ hybridisation, immunohistochemistry and RT-PCR we found Psg expression in trophoblast giant cells and in the spongiotrophoblast. Psg22 is the predominant Psg family member expressed in giant cells. Detectable Psg is associated predominantly with endothelial cells lining vascular channels in the decidua, rather than with maternal immune cell markers. CD9 expression exhibited partial overlap with Psg, but without exclusive co-localisation. CD9 was observed in decidual cells surrounding early implantation sites, and in the endometrium. However, embryo transfer of wild-type embryos to CD9-deficient females indicates that maternal CD9 is not essential for successful pregnancy.
Short photoperiod-induced ovarian regression is mediated by apoptosis in Siberian hamsters (Phodopus sungorus)
Authors: Moffatt-Blue C S , Sury J J , Young Kelly A
Published: April 2006

Siberian hamster reproduction is mediated by photoperiod-induced changes in gonadal activity. However, little is known about how photoperiod induces cellular changes in ovarian function. We hypothesized that exposing female hamsters to short (inhibitory) as opposed to long (control) photoperiods would induce an apoptosis-mediated disruption of ovarian function. Ovaries and plasma from hamsters exposed to either long (LD, 16 h light:8 h darkness) or short (SD, 8 h light:16 h darkness) days were collected during diestrus II after 3, 6, 9 and 12 weeks and processed for histology or RIA respectively. Apoptosis was assessed by in situ TUNEL and active caspase-3 protein immunolabeling. No significant differences were observed among LD hamsters for any parameter; therefore, these control data were pooled. SD exposure induced a decline in preantral follicles (P < 0.05), early antral/antral follicles (P < 0.01) and corpora lutea (P < 0.01) by week 12 as compared with LD. Terminal atretic follicles appeared by SD week 9; by week 12, these had become the predominant ovarian structures. Estradiol concentrations decreased by weeks 9 and 12 SD when compared with both LD and week-3 SD hamsters (P < 0.05); however, no changes were observed for progesterone. TUNEL-positive follicles in SD ovaries increased at week 3 and subsequently declined by week 12 as compared with LD ovaries (P < 0.01). Active capsase-3 protein immunostaining peaked at SD week 3 as compared with all other groups (P < 0.01). TUNEL and capsase-3 immunolabeling were localized to granulosa cells of late-preantral and early-antral/antral follicles. These data indicate that SD exposure rapidly induces follicular apoptosis in Siberian hamsters, which ultimately disrupts both estradiol secretion and folliculogenesis, resulting in the seasonal loss of ovarian function.
The effects of sex steroid hormones and interleukin-1-beta on MUC1 expression in endometrial epithelial cell lines
Authors: Horne A W , Lalani E-N , Margara R A , White J O
Published: April 2006

Oestrogen, progesterone and paracrine signals from the embryo have been associated with the overall control of implantation. Changes in the expression of the heavily glycosylated transmembrane glycoprotein MUC1 mucin on the endometrial epithelium are also thought to be important for embryo attachment. Increased MUC1 expression has been correlated with elevated progesterone levels in the secretory phase of the menstrual cycle. Embryonic control of endometrial receptivity through changes in MUC1 expression could be achieved through the interleukin-1 system. Four endometrial epithelial cell lines (HEC1A, HEC1B, Ishikawa and RL592) were treated with oestrogen and progesterone (with or without interleukin-1-beta) and were subjected to immunocytochemistry and flow cytometric analysis to determine MUC1 production using MUC1 antibodies. HEC1A (oestrogen receptor (ER) and progesterone receptor (PR) positive) and HEC1B (ER positive and PR negative) were transfected with the MUC1 promoter, underwent similar treatment regimes and the activity of the MUC1 promoter relative to their untreated controls was determined using a chloramphenicol acetyltransferase (CAT) enzyme-linked immunoassay. Using the cell lines, we determined that endometrial MUC1 expression is up-regulated by progesterone, consistent with the in vivo increases in MUC1 related to high progesterone levels. We also revealed that neither oestrogen, nor interleukin-1-beta, appear to modulate MUC1. Progesterone-dependent regulation of MUC1 is likely to be an important factor in determining endometrial receptivity.
Presence and regulation of messenger ribonucleic acids encoding components of the class II major histocompatibility complex-associated antigen processing pathway in the bovine corpus luteum
Authors: Cannon Matthew J , Davis John S , Pate Joy L
Published: April 2006

Luteal cells express class II major histocompatibility complex (MHC) molecules and can stimulate T lymphocyte proliferation in vitro. However, it is unknown whether luteal cells express the intracellular components necessary to process the peptides presented by class II MHC molecules. The objective of the present study was to examine the expression and regulation of three major class II-associated antigen processing components – class II MHC-associated invariant chain (Ii), DMα and DMβ – in luteal tissue. Corpora lutea were collected early in the estrous cycle, during midcycle and late in the estrous cycle, and at various times following administration of a luteolytic dose of prostaglandin F2α (PGF2α) to the cow. Northern analysis revealed the presence of mRNA encoding each of the class II MHC-associated antigen processing proteins in luteal tissue. Ii mRNA concentrations did not change during the estrous cycle, whereas DMα and DMβ mRNA concentrations were highest in midcycle luteal tissue compared with either early or late luteal tissue. Tumor necrosis factor-α (TNF-α) reduced DMα mRNA concentrations in cultured luteal cells in the presence of LH or PGF2α. DMα and DMβ mRNA were also present in highly enriched cultures of luteal endothelial (CLENDO) cells, and DMα mRNA concentrations were greater in CLENDO cultures compared with mixed luteal cell cultures. Expression of invariant chain, DMα and DMβ genes indicates that cells within the corpus luteum express the minimal requirements to act as functional antigen-presenting cells, and the observation that CLENDO cells are a source of DMα and DMβ mRNA indicates that non-immune cells within the corpus luteum may function as antigen-presenting cells.
Selective expression of the scaffold protein JSAP1 in spermatogonia and spermatocytes
Authors: Bayarsaikhan Munkhuu , Shiratsuchi Akiko , Gantulga Davaakhuu , Nakanishi Yoshinobu , Yoshioka Katsuji
Published: April 2006

Scaffold proteins of mitogen-activated protein kinase (MAPK) intracellular signal transduction pathways mediate the efficient and specific activation of the relevant MAPK signaling modules. Previously, our group and others have identified c-Jun NH2-terminal kinase (JNK)/stress-activated protein kinase-associated protein 1 (JSAP1, also known as JNK-interacting protein 3) as a scaffold protein for JNK MAPK pathways. Although JSAP1 is expressed in the testis in adults, its expression during development has not been investigated. In addition, it is unknown which types of cells in the testis express the scaffold protein. Here, we examined the expression of JSAP1 in the testis of mice aged 14 days, 20 days, 6 weeks, and 12 weeks by immunohistochemistry and Western blotting. The specificity of the anti-JSAP1 antibody was evaluated from its reactivity to exogenously expressed JSAP1 and a structurally related protein, and by antigen-absorption experiments. The immunohistochemical analyses with the specific antibody showed that the JSAP1 protein was selectively expressed in the spermatogonia and spermatocytes, but not in other cell types, including spermatids and somatic cells, during development. However, not all spermatogonia and spermatocytes were immunopositive either, especially in the 12-week-old mouse testis. Furthermore, we found by Western blotting that the expression levels of JSAP1 protein vary during development; there is high expression until 6 weeks after birth, which approximately corresponds to the end of the first wave of spermatogenesis. Collectively, these results suggest that JSAP1 function may be important in spermatogenic cells during early postnatal development.
Disruption of sexual function, FSH secretion, and spermiogenesis in rabbits following developmental exposure to vinclozolin, a fungicide
Authors: Veeramachaneni D N R , Palmer J S , Amann R P , Kane C M , Higuchi T T , Pau K-Y F
Published: April 2006

We studied sequelae of prenatal plus infantile exposure of male rabbits to vinclozolin, because it is ingested by women and children. Female Dutch-Belted rabbits (7–10/group) were treated daily per orum from gestation day 15 through post-natal week 4 to provide 0, 7.2, or 72 mg vinclozolin/kg dam’s body weight/day. Vinclozolin had no effect on maintenance of pregnancy, growth of pups, age at testicular descent or weight of organs. Concentrations of serum LH or testosterone at 6, 12, or 24 weeks of age were unaffected. However, FSH was lower (P < 0.05) in both vinclozolin groups at all three ages. Following injection of GnRH at 12 or 24 weeks, the increase in FSH was less (P < 0.05) in both vinclozolin groups, as was testosterone at 12 weeks of age. After full sexual maturity, 2 of 7 low dose rabbits were uninterested in female or male teasers and never achieved erection or ejaculation. Overall, rates of ejaculation failure were: control 0% (0/48), low dose 29% (12/42), and high dose 5% (3/60). Daily sperm production per gram of testis and total number of sperm per ejaculate in both vinclozolin groups were similar (P > 0.1) to controls. However, semen from vinclozolin rabbits contained over two times more (P < 0.05) morphologically abnormal spermatozoa, mostly nuclear and acrosomal defects, than semen from controls. Seminiferous tubules with degenerative changes were more frequent (P < 0.05) in vinclozolin rabbits than in controls. Lesions included syncytia of spherical spermatids and desquamation of germ cells. Hence, developmental exposure to vinclozolin caused presumably permanent changes in copulatory ability, secretion of FSH, and spermiogenesis.
Multiple-Interval Mapping for Ordinal Traits
Authors: Li Jian , Wang Shengchu , Zeng Zhao-Bang
Published: April 2006

Many statistical methods have been developed to map multiple quantitative trait loci (QTL) in experimental cross populations. Among these methods, multiple-interval mapping (MIM) can map QTL with epistasis simultaneously. However, the previous implementation of MIM is for continuously distributed traits. In this study we extend MIM to ordinal traits on the basis of a threshold model. The method inherits the properties and advantages of MIM and can fit a model of multiple QTL effects and epistasis on the underlying liability score. We study a number of statistical issues associated with the method, such as the efficiency and stability of maximization and model selection. We also use computer simulation to study the performance of the method and compare it to other alternative approaches. The method has been implemented in QTL Cartographer to facilitate its general usage for QTL mapping data analysis on binary and ordinal traits.
Cri du Chat Syndrome and Congenital Heart Disease: A Review of Previously Reported Cases and Presentation of an Additional 21 Cases From the Pediatric Cardiac Care Consortium
Authors: Hills Christine , Moller James H. , Finkelstein Marsha , Lohr Jamie , Schimmenti Lisa
Published: April 2006

OBJECTIVES. To analyze the cases submitted to the Pediatric Cardiac Care Consortium (PCCC) database from 1982 to 2002 to determine the frequency and distribution of congenital heart disease (CHD) found in this population, to review the literature for previously published accounts of CHD in this population, and to review current genotype-phenotype associations for cri du chat (CDC) syndrome with CHD.

METHODS. We performed a retrospective review of the 98422 CHD cases submitted to the PCCC between 1982 and 2002, to find patients who had a noncardiac diagnosis of CDC syndrome.

RESULTS. A total of 21 patients (15 female and 6 male patients) were identified. Although some patients had multiple cardiac anomalies, they were categorized according to primary diagnoses on the basis of the most hemodynamically significant component. The patient groups were ventricular septal defect (n = 6), patent ductus arteriosus (n = 6), tetralogy of Fallot (n = 5), pulmonary valve atresia with ventricular septal defect (n = 2), pulmonary valve stenosis (n = 1), and double-outlet right ventricle (n = 1). Eighteen of the 21 patients underwent surgical repair of their defects. There was 1 late operative death. To determine whether the observed frequency of these cardiac defects among patients with CDC syndrome was comparable to that of the general population of patients with CHD, data for all cases submitted to the PCCC from 1982 to 2002 were used. Use of these numbers to determine expected frequencies for these defects showed significantly greater proportions of patients with these specific lesions among the patients with CDC syndrome.

CONCLUSIONS. Currently there is no clear understanding of the genomic cause of the prevalence of these defects in the population with CDC syndrome, although CHD has been noted among patients with other deletion syndromes.
Human androgen receptor gene ligand-binding-domain mutations leading to disrupted interaction between the N- and C-terminal domains
Authors: Jääskeläinen J , Deeb A , Schwabe J W , Mongan N P , Martin H , Hughes I A
Published: April 2006

Most mutations in the androgen receptor (AR) ligand-binding domain (LBD) disrupt binding of the natural ligands: dihydrotestosterone and testosterone. Some AR LBD mutations do not affect ligand binding but they disrupt androgen-induced interaction of the N-terminal motif FXXLF and C-terminal activation function 2 (AF2). As N-/C-terminal interaction requires binding of agonists that have androgen activity in vivo, it correlates well with the phenotype. To study this further, we searched the Cambridge intersex database for patients with a detected missense mutation in the AR LBD presenting with normal ligand binding. Six mutations (D695N, Y763C, R774H, Q798E, R855H and L907F) were selected and introduced by site-directed mutagenesis into the pSVAR and pM-LBD plasmids. The transactivational potential of the wild-type and mutant androgen receptors (pSVAR) was examined by dual-luciferase assay using pGRE-LUC as a reporter vector. N-/C-terminal interaction was studied by mammalian two-hybrid assay using wild-type and mutated AR LBD (pM-LBD), pVP16-rAR-(5–538) (encoding rat amino-terminal AR) and pCMX-UAS-TK-LUC as a reporter. AR LBD mutations D695N, R774H and L907F presented with minimal transactivational capacity and N-/C-terminal interaction was totally disrupted. Mutations Y763C and R885H had some residual dose-dependent transactivational potential and minimal N-/C-terminal interaction. Q798E presented with good transactivational potential and it showed only mild reduction in N-/C-terminal interaction. With the selected mutations, N-/C-terminal interaction correlated well with AR transactivation and the phenotype. Disrupted N-/C-terminal interaction is capable of providing the mechanism for androgen-insensitivity syndrome in most cases where the mutation in the LBD does not disrupt ligand binding. Furthermore, mutations leading to the disrupted N-/C-terminal interaction can be localized to certain critical regions in the three-dimensional structure of the AR LBD. Our study shows that apart from the previously reported regions, regions just before helix 3, between helices 5 and 6, and at helix 10 are also important for AR N-/C-terminal interaction.
Evaluation of denaturing high performance liquid chromatography for the mutational analysis of the MEN1 gene
Authors: Crépin Michel , Pigny Pascal , Escande Fabienne , Bauters Catherine Cardot , Calender Alain , Lefevre Sylvain , Buisine Marie-Pierre , Porchet Nicole , Odou Marie-Françoise
Published: April 2006

The identification of mutations in the MEN1 gene causing MEN1 has represented a challenge since the cloning of the gene in 1997 because of the lack of mutation hot-spots in the gene and the lack of phenotype–genotype correlations. The use of denaturing high performance liquid chromatography (DHPLC), a high throughput, reliable and automated heteroduplex-based technique, is the ideal for mutation detection in MEN1. In this work, DHPLC was optimised for the screening of the nine coding exons and splice junctions of MEN1. Thanks to collaboration between two French laboratories recognised as reference centres for genotypic MEN1 diagnosis (Lyon and Lille), a blind retrospective study conducted in a cohort of 160 unrelated MEN1 probands with (or without) known germline mutations was undertaken to evaluate the sensitivity of DHPLC. We were able to detect 101 different sequence variations by DHPLC, distributed in the 10 analysed DNA fragments and corresponding to 100% of mutation detection compared with direct sequencing. 1·2% of samples were considered as false positive, exhibiting a heterogenous profile. DHPLC did not detect five cases of deletion or duplication of complete exons, neither did direct sequencing, showing the limits of the technique. Nevertheless, the method appeared to allow automated, rapid and low-cost mutation detection with high accuracy. Direct sequencing can be then applied to identify the sequence variations on the targeted DNA fragments showing heterozygous profile by DHPLC. In conclusion, genotypic diagnosis of MEN1 can benefit from DHPLC in terms of efficacy, rapidity and cost.
Steroid 5α-reductase isozymes in the adult female rat brain: central role of dihydrotestosterone
Authors: Torres J M , Ortega E
Published: April 2006

The enzyme 5α-reductase (5α-R) (EC 1.3.99.5) exists as two isoforms, 5α-R type 1 (5α-R1) and 5α-R type 2 (5α-R2). 5α-R1 has been associated with catabolic functions whereas 5α-R2 has been associated with sexually dimorphic functions of the male. We recently demonstrated that both 5α-R isozymes are present in the central nervous system (CNS) of the adult male rat and are regulated in an opposing way by androgens. This finding raises the question as to whether both isozymes play a role in the sexual dimorphism of the CNS, besides other functions. To test this hypothesis, it is essential to study the regulation of both isozymes by androgens in the female. In this work, we studied the effects of testosterone (T) and dihydrotestosterone (DHT) on mRNA levels of both 5α-R isoforms in the prefrontal cortex of the adult female rat by one-step quantitative RT-PCR coupled with laser-induced fluorescence capillary electrophoresis. Our results demonstrate for the first time that 5α-R2 mRNA is slightly regulated by T and DHT in females. Surprisingly, 5α-R1 mRNA is not regulated by T in the intact female, whereas it is very positively regulated by DHT, a more potent androgen than T. These data indicate the great sexual dimorphism in the CNS with respect to both 5α-R isozymes, and suggest a crucial role of DHT in the sexual dimorphism of the CNS in the female. These results open up a new research line that may lead to a better understanding of the physiology of the CNS.
Effects of dihydrotestosterone on skeletal muscle transcriptome in mice measured by serial analysis of gene expression
Authors: Yoshioka M , Boivin A , Ye P , Labrie F , St-Amand J
Published: April 2006

In order to characterize the action of androgen in skeletal muscle, we have investigated the effects of castration (GDX) and dihydrotestosterone (DHT) on global gene expression in mice. The serial analysis of gene expression method was performed in the muscle of male mice in six experimental groups: intact, GDX and GDX+DHT injection 1, 3, 6 or 24 h before they were killed. A total of 780 822 sequenced tags quantified the expression level of 80 142 tag species. Thirteen and seventy-nine transcripts were differentially expressed in GDX and DHT respectively (P < 0.05), including eight partially characterized and 21 potential novel transcripts. The induced transcripts within 3 h after DHT injection were involved in the following functions: transcription, protein synthesis, modification and degradation, muscle contraction and relaxation, cell signaling, polyamine biosynthesis, cell cycle progression and arrest, angiogenesis, energy metabolism and immunity. However, the inductions of transcripts related to cell cycle arrest and angiogenesis were no longer significant 24 h after DHT injection. The current study might suggest that DHT promotes protein synthesis, cell signaling, cell proliferation and ATP production, as well as muscle contraction and relaxation at the transcriptional level in skeletal muscle in vivo.
Glucose-induced repression of PPARα gene expression in pancreatic β-cells involves PP2A activation and AMPK inactivation
Authors: Ravnskjaer Kim , Boergesen Michael , Dalgaard Louise T , Mandrup Susanne
Published: April 2006

Tight regulation of fatty acid metabolism in pancreatic β-cells is important for β-cell viability and function. Chronic exposure to elevated concentrations of fatty acid is associated with β-cell lipotoxicity. Glucose is known to repress fatty acid oxidation and hence to augment the toxicity of fatty acids. The peroxisome proliferator activated receptor α (PPARα) is a key activator of genes involved in β-cell fatty acid oxidation, and transcription of the PPARα gene has been shown to be repressed by increasing concentrations of glucose in β-cells. However, the mechanism underlying this transcriptional repression by glucose remains unclear. Here we report that glucose-induced repression of PPARα gene expression in INS-1E cells is independent of β-cell excitation and insulin secretion but requires activation of protein phosphatase 2A in a process involving inactivation of the AMP-activated protein kinase (AMPK). Pharmacological activation of AMPK at high glucose concentrations interferes with glucose repression of PPARα and PPARα target genes in INS-1E cells as well as in rat islets. Specific knock-down of the catalytic AMPK-subunit AMPKα2 but not AMPKα1 using RNAi suppressed PPARα expression, thereby mimicking the effect of glucose. These results indicate that activation of protein phosphatase 2A and subsequent inactivation of AMPK is necessary for glucose repression of PPARα expression in pancreatic β-cells.
Overexpression of the insulin-like growth factor I receptor in human pheochromocytomas
Authors: Fottner Christian , Minnemann Timo , Kalmbach Sarah , Weber Matthias M
Published: April 2006

In order to determine the role of the IGF-I receptor (IGF-IR) in human pheochromocytomas we have compared the expression of the IGF-IR in normal tissues and in pheochromocytomas with regard to the IGF-IR mRNA levels and ligand binding. By semiquantitative reverse transcription polymerase chain reaction (RT-PCR), the mRNA of the IGF-IR could be detected in all samples of normal adrenomedullary cells (n=13) and pheochromocytomas (n=16). However, pheochromocytomas exhibited 2.8-fold higher mean IGF-IR mRNA levels than normal adrenomedullary cells (2.8±0.5×105 molecules/μg RNA vs 7.8±1.2×105 molecules/μg RNA; P < 0.001). This overexpression of the IGF-IR in pheochromocytomas could be confirmed at the protein level by binding studies. Radioligand assays and Scatchard analysis revealed a single class of high affinity IGF-IR binding sites with a similar dissociation constant (Kd: 0.32±0.1 nmol/l vs 0.22±0.08 nmol/l) for both normal adrenomedullary cells and pheochromocytomas. However, specific 125I-labeled IGF-I binding and the calculated receptor concentration were significantly elevated in pheochromocytomas as compared with normal adrenomedullary cells (58.3±5 vs 24.3±12 nmol/kg protein; P < 0.05). In summary, our results demonstrate significant overexpression of the IGF-IR in human pheochromocytomas. This suggests a possible role of the IGF system in the pathogenesis of adrenal neoplasia and thus IGF-IR may be a target for future therapeutic approaches.
CCAAT enhancer binding protein β and hepatocyte nuclear factor 3β are necessary and sufficient to mediate dexamethasone-induced up-regulation of alpha2HS-glycoprotein/fetuin-A gene expression
Authors: Wöltje Michael , Tschöke Beate , von Bülow Verena , Westenfeld Ralf , Denecke Bernd , Gräber Steffen , Jahnen-Dechent Willi
Published: April 2006

Alpha2HS-glycoprotein/fetuin-A (Ahsg) is a serum protein preventing soft tissue calcification. In trauma and inflammation, Ahsg is down-regulated and therefore considered a negative acute phase protein. Enhancement of Ahsg expression as a protective serum protein is desirable in several diseases including tissue remodelling after trauma and infection, kidney and heart failure, and cancer. Using reporter gene assays in hepatoma cells combined with electrophoretic mobility shift assays we determined that dexamethasone up-regulates hepatic Ahsg. A steroid response unit at position −146/−119 within the mouse Ahsg promoter mediates the glucocorticoid-induced increase of Ahsg mRNA. It binds the hepatocyte nuclear factor 3β and CCAAT enhancer binding protein β (C/EBP-β). The up-regulation is mediated indirectly via glucocorticoid hormone-induced transcriptional up-regulation in C/EBP-β protein. A high degree of sequence identity in mouse, rat and human Ahsg promoters suggests that the promoter is similarly up-regulated by dexamethasone in all three species. Therefore, our findings suggest that glucocorticoids may be used to enhance the level of Ahsg protein circulating in serum.
Angiotensin II stimulates the synthesis of vascular endothelial growth factor through the p38 mitogen activated protein kinase pathway in cultured mouse podocytes
Authors: Kang Young Sun , Park Yun Gyu , Kim Bo Kyung , Han Sang Youb , Jee Yi Hwa , Han Kum Hyun , Lee Mi Hwa , Song Hye Kyoung , Cha Dae Ryong , Kang Shin Wook , Han Dae Suk
Published: April 2006

Angiotensin II (Ang-II) and vascular endothelial growth factor (VEGF) have an important role in the pathogenesis of diabetic nephropathy, but the signaling cascade of VEGF regulation in response to Ang-II in podocytes is largely unknown. In these experiments, we looked at the effect of Ang-II on the production of VEGF, and investigated whether VEGF production depends on the p38 mitogen activated protein kinase (MAPK) pathway in cultured mouse podocytes. Incubation of podocytes with Ang-II induced a rapid increase in VEGF mRNA expression and protein synthesis as well as its transcriptional activity in an Ang-II dose-dependent manner. To further define the role of angiotensin type 1 (AT1) and type 2 (AT2) receptors involved in Ang-II-mediated VEGF synthesis, the effects of selective AT1 and AT2 receptor antagonists were evaluated. Prior treatment with losartan significantly inhibited VEGF mRNA and protein synthesis induced by Ang-II, which suggests that the AT1 receptor is involved in Ang-II-mediated VEGF synthesis. Furthermore, stimulation of the cells with Ang-II increased both phosphorylation of p38 MAPK and MAP kinase kinase 3/6 (MKK3/6). Additionally, Ang-II enhanced the DNA binding activity to cAMP response element binding protein (CREB) and phosphorylation of CREB. In addition, to investigate the role of p38 MAPK in Ang-II-induced VEGF synthesis, podocytes were pretreated with or without the p38 MAPK inhibitor, SB203580 for 24 h to observe whether Ang-II-mediated VEGF synthesis was inhibited by blocking p38 MAPK. The addition of SB203580 led to a marked inhibition of the increased VEGF mRNA and protein production induced by Ang-II in a dose-dependent manner. Taken together, these results suggest that Ang-II stimulates the synthesis of VEGF in podocytes and the production of VEGF induced by Ang-II is mediated, in part, through the activation of the p38 MAPK pathway.
Briefing: I. K. Brunel: Engineer of the Great Western Railway
Authors: Bailey M. R.
Published: April 2006

Brunel challenged the conventional ‘Stephenson’ railway when he introduced the broad gauge and novel forms of track and locomotives. When multiple problems arose in service his engineering authority was challenged. His tenacity in responding to independent reports influenced sufficient opinion to vindicate his decisions and restore his authority
Nottingham Express Transit Line 1: geometrical aspects
Authors: Leighton K. , Gillespy M.
Published: April 2006

The Nottingham Express Transit Line 1 was opened in March 2004. It consists of 14 route-km, of which 4 km are on-street. This paper describes the design of the on-street alignment and some of the technical issues, such as effects of combining horizontal and vertical geometry, associated with reintroducing tram track into the streets of the city of Nottingham.
Rail ballast: conclusions from a historical perspective
Authors: Claisse P. , Calla C.
Published: April 2006

Although it is now universally accepted that good-quality hard angular stone of nominal size 40–50 mm is the best material for ballast, historically track has been for longer on non-stone ballast than on stone ballast. Even the stone ballast specified up until the 1980s was of a smaller average size than present ballast.

Research into the two-layered ballast system and a study of development of ballast specification from the early 1900s suggests that current ballast specifications should be changed to ballast of smaller size. This would: cause substantial reduction in maintenance requirements for ballasted railway track; reduce track noise levels; provide better ride quality; and increase ballast life.
Investigation of railway track subgrade. Part 2: Case study
Authors: Brough M. J. , Ghataora G. , Stirling A. B. , Madelin K. B. , Rogers C. D. F. , Chapman D. N.
Published: April 2006

Track quality indices, continued track component performance and subsequent maintenance are highly dependent upon trackbed stiffness. This is exacerbated by consolidation and settlement of subgrade and the subsequent differential track geometry. Consequently, any site investigation to diagnose the causes of track geometry deterioration should include an assessment of stiffness parameters. In addition to stiffness assessment, a trackbed investigation should comprise a full assessment of ballast, sub-ballast and subgrade condition. If information about any of these layers is omitted, a complete diagnosis is not feasible, and consequently appropriate ground improvement schemes may not be implemented. Test devices suitable for trackbed investigation to assess the causes of track settlement have been identified in a previous paper in this series. This paper summarises the staged trackbed investigation performed at a site historically requiring high maintenance, suspected as being caused by poor subgrade. The paper concludes with a diagnosis of the site and suggested remedial schemes deemed suitable for generic treatment of poor subgrade sites.
An analytical study of road pavement fatigue
Authors: Evdorides H. T. , Snaith M. S. , Anyala M.
Published: April 2006

The structural evaluation of road pavements is an integral part of any modern pavement management system. Emphasis has been given to the structural analysis of road pavements with methodologies that seek to quantify the key parameters of pavement behavioural modelling to facilitate the prediction of the remaining life of pavements. These parameters are associated with major distresses such as cracking, and their magnitude is determined using appropriate analytical models. The most advanced, which enable an insight into the pavement structure, are based on finite-element analysis. This paper deals with such models, and first presents the fundamental issues associated with the fatigue behaviour of bituminous layers. Thereafter it presents model forms used to tackle crack initiation and propagation, and discusses how finite elements could provide a better insight into the effect of cracking on falling weight deflectometer induced deflections and their associated analysis. This is demonstrated by an example that shows the effect of bottom-up and top-down cracking on the stress distribution within the bituminous layer.
Environmental Impact of Irrigation in La Violada District (Spain)
Authors: Isidoro D. , Quílez D. , Aragüés R.
Published: April 2006

Salt loading in irrigation return flows contributes to the salinization of the receiving water bodies, particularly when originated in salt‐affected areas as frequently found in the middle Ebro River basin (Spain). We determined the salt loading in La Violada Gully from the total dissolved solids (TDS) and flows (Q) during the 1995 to 1998 hydrological years. Since this gully collects flows from various sources, an end‐member mixing analysis (EMMA) was performed to quantify the drainage flow from La Violada Irrigation District (VID). Three flow components were identified in La Violada Gully: drainage waters from VID (Qd); tail‐waters from irrigation ditches, spill‐over, and seepage from the Monegros Canal (Qo); and ground water inflows (Qg) originating in the dryland watershed. Gypsum in the soils of VID was the main source for salts in La Violada Gully (flow‐weighted mean TDS = 1720 mg L−1, dominated by sulfate and calcium). The contribution of Qg to the total gully flow during the 1996 irrigation season was low (6.5% of the total flow). The 1995 to 1998 annual salt load average in La Violada Gully was 78 628 Mg, 71% of which was exported during the irrigation season. The 1995 to 1998 irrigation season salt load average in Qd was 43 015 Mg (77% of the total load). Thus, irrigated agriculture in VID was the main source of salt loading in this gully, with a yield of 11.1 Mg of salts per hectare of irrigated land for the irrigation season. Efficient irrigation systems and irrigation management practices that reduce Qd are key factors for controlling off‐site salt pollution of these gypsum‐rich irrigated areas.
Environmental Impact of Irrigation in La Violada District (Spain)
Authors: Isidoro D. , Quílez D. , Aragüés R.
Published: April 2006

Fertilizer leaching affects farm profitability and contributes to nonpoint‐source pollution of receiving waters. This work aimed to establish nitrate nitrogen export from La Violada Gully in relation to nitrogen fertilization practices in its basin (La Violada Gully watershed, VGW, 19 637 ha) and especially in La Violada Irrigation District (VID, 5282 ha). Nitrogen (N) fertilization in VID (and VGW) was determined through interviews with local farmers for the hydrologic years 1995 and 1996 and NO3‐N load in the gully was monitored from 1995 to 1998. The N fertilizer applied in VGW was 2175 Mg in 1995 and 2795 Mg in 1996. About 43% was applied in VID (945 Mg in 1995 and 1161 Mg in 1996). The most fertilized crop was corn: 398 kg N ha−1(665 Mg) in 1995 and 453 kg N ha−1(911 Mg) in 1996. Nitrogen fertilization was higher than N uptake for irrigated crops, especially for corn and rice. Nitrate N load in La Violada Gully averaged 427.4 Mg yr−1Seventy‐five percent of the exports took place during the irrigation season (321.8 Mg). During the non‐irrigation season maximum NO3‐N loads (3.1 Mg NO3‐N d−1) were found after heavy rains following the N side‐dressing of wheat in the rain‐fed area of VGW (February). During the irrigation season NO3‐N load was determined by outflow from the district (caused by irrigation) and to a lesser extent by changes in NO3concentration (caused by fertilization), showing peaks in April (pre‐sowing corn N fertilization and first irrigations) and June to August (highest irrigation months and corn side‐dress N applications, maximum 6.3 Mg NO3‐N d−1in July). Adjusting N fertilization to crops' needs, improving irrigation efficiencies, and better scheduling N fertilization and irrigation in corn could reduce N export from VID.
Sediment and Phosphorus Transport in Irrigation Furrows
Authors: Bjorneberg D. L. , Westermann D. T. , Aase J. K. , Clemmens A. J. , Strelkoff T. S.
Published: April 2006

Sediment and phosphorus (P) in agricultural runoff can impair water quality in streams, lakes, and rivers. We studied the factors affecting P transfer and transport in irrigated furrows in six freshly tilled fallow fields, 110 to 180 m long with 0.007 to 0.012 m m−1 slopes without the interference of raindrops or sheet flow that occur during natural or simulated rain. The soil on all fields was Portneuf silt loam (coarse‐silty, mixed, superactive, mesic Durinodic Xeric Haplocalcids). Flow rate, sediment concentration, and P concentrations were monitored at four, equally spaced locations in each furrow. Flow rate decreased with distance down the furrow as water infiltrated. Sediment concentration varied with distance and time with no set pattern. Total P concentrations related directly to sediment concentrations (r2 = 0.75) because typically >90% of the transported P was particulate P, emphasizing the need to control erosion to reduce P loss. Dissolved reactive phosphorus (DRP) concentrations decreased with time at a specific furrow site but increased with distance down the furrow as contact time with soil and suspended sediment increased. The DRP concentration correlated better with sediment concentration than extractable furrow soil P concentration. However, suspended sediment concentration tended to not affect DRP concentration later in the irrigation (>2 h). These results indicate that the effects of soil P can be overshadowed by differences in flow hydraulics, suspended sediment loads, and non‐equilibrium conditions.
SignificantEscherichia coliAttenuation by Vegetative Buffers on Annual Grasslands
Authors: Tate Kenneth W. , Atwill Edward R. , Bartolome James W. , Nader Glenn
Published: April 2006

A study was conducted to estimate the retention efficiency of vegetative buffers forEscherichia colideposited on grasslands in cattle fecal deposits and subject to natural rainfall‐runoff conditions. The study was conducted on annual grasslands in California's northern Sierra Nevada foothills, a region with a distinct wet–dry season Mediterranean climate. We used 48, 2.0‐ by 3.0‐m runoff plots to examine the efficacy of 0.1‐, 1.1‐, and 2.1‐m buffers at three land slopes (5, 20, and 35%) and four dry vegetation matter levels (225, 560, 900, and 4500 kg/ha) across 27 rainfall‐runoff events during two rainfall seasons. Buffer width treatments were implemented by placement of cattle fecal material containing known loads ofE. coli0.1, 1.1, or 2.1 m upslope of the plot runoff collector. Mean total runoff to total rainfall ratio per plot ranged from 0.014:1 to 0.019:1 and reflected the high infiltration capacity of these soils. Approximately 94.8 to 99.995% of totalE. coliload applied to each plot appears to be either retained in the fecal pat and/or attenuated within 0.1 m downslope of the fecal pat, irrespective of the presence of a wider vegetated buffer. Relative to a 0.1‐m buffer, we found 0.3 to 3.1 log10reduction inE. colidischarge per additional meter of vegetative buffer across the range of residual dry vegetation matter levels, land slope, and rainfall and runoff conditions experienced during this project. Buffer efficiency was significantly reduced as runoff increased. These results support the assertion that grassland buffers are an effective method for reducing animal agricultural inputs of waterborneE. coliinto surface waters.
Peat Fire Effects on Some Properties of an Artificially Drained Peatland
Authors: Dikici Huseyin , Yilmaz C. Hakan
Published: April 2006

The management of artificially drained organic soils is a very important issue, since the accelerated mineralization and sometimes peat fires alter physical and chemical properties of soils and the availability of plant nutrients. This study was performed to determine relatively short‐ and long‐term effects of peat fires on some physical and chemical properties of soils in the artificially drained Gavur Lake Peatland of Turkey. To achieve this objective, measured properties of soils burned in 2001, burned in 1965, and unburned were compared. The results indicated that soil bulk density, pH, amounts of soluble salts, CaCO3, and concentrations of ammonium acetate–extractable (AAE) Ca, Mg, K, and Na were significantly higher for both sampling depths in the burned areas. The areas burned in 2001 had higher pH, soluble salts, and the concentrations of AAE Ca, Mg, and K compared with sites burned in 1965, and this was reasoned with leaching losses and plant uptake of these basic cations for four decades in the latter. Percent saturation and organic carbon contents of soils, however, were significantly lower in the burned areas for both sampling depths. Olsen P levels were not significantly different between the sites. This work clearly shows that alterations in soils properties with peat fires do not recover in the long term.
Behavior of an Aerated Submerged Fixed‐Film Reactor (ASFFR) under Simultaneous Organic and Ammonium Loading
Authors: Nabizadeh R. , Mesdaghinia A.
Published: April 2006

The performance of an aerated submerged fixed‐film reactor (ASFFR) under simultaneous organic and ammonium loading and its effect on nitrification was studied. Organic loadings varied in the range of 1.93 to 5.29 g chemical oxygen demand (COD) m−2 d−1 and NH4–N loadings were in the range of 116 to 318 mg NH4–N m−2 d−1 Increments of loading rates were obtained both by increasing the flow rate and increasing the influent substrate in individual pilot runs. Results showed that with organic loading rates up to 3.97 g COD m−2 d−1, complete nitrification was achievable. Although high organic loading such as 5.29 g COD m−2 d−1 could cause nitrification to stop, shifting to lower organic loadings made nitrification start and set rapidly to its previous steady‐state concentrations. Comparison of results showed that in the ASFFR, nitrification would be severely affected by an organic loading rate of 5.29 g COD m−2 d−1 by increasing either the flow or the influent substrate. It should be noted that the average value of dissolved oxygen was 3.4 mg L−1 with an air supply of 15 L min−1, and there was no indication of oxygen limitation. The results of this study show the flexibility of ASFFRs under changing organic loads. Furthermore, for achieving complete nitrification and optimum application of these reactors for protecting receiving water from the environmental hazards of ammonium, the maximum organic loading that would present complete nitrification should be considered.
Lead Transport into Bayou Trepagnier Wetlands in Louisiana, USA
Authors: Devall Margaret S. , Thien Leonard B. , Ellgaard Erik , Flowers George
Published: April 2006

Establishment of a petroleum refinery in 1916 near the headwaters of Bayou Trepagnier with subsequent dredging of the bayou resulted in spoil banks containing high levels of Pb. A large swamp abuts the eastern bank of the bayou. Cores were taken from 15 baldcypress [Taxodium distichum(L.) Richard] trees growing in the swamp along a 610‐m transect (nine trees) and a 183‐m transect (six trees) running perpendicular from the spoil bank. The cores were crossdated, annual rings were measured, and 5‐yr segments of the cores were prepared and analyzed for heavy metals. Soil samples were collected along one transect and analyzed for metals. Levels of Pb in Bayou Trepagnier swamp trees were compared to levels in nine baldcypress trees growing along Stinking Bayou, a reference area. During the last 100 yr, Pb in growth rings of swamp baldcypress trees averaged 8.6 mg/kg (SD 4.88) along one transect and 7.9 mg/kg (SD 5.39) along the other. Lead in the soil along the first transect dropped from >2700 mg/kg (spoil bank) to 10 mg/kg at 420 m into the swamp. Baldcypress trees growing near the refinery on the spoil bank along Bayou Trepagnier (covered in an earlier study) averaged 4.5 mg/kg Pb, and trees along Stinking Bayou averaged 2.1 mg/kg. Trees in the swamp soil with 10 to 425 mg/kg Pb concentrated much more Pb than trees growing on the heavily polluted bank. Greater uptake of Pb by trees in the swamp is discussed in terms of soil dynamics and Pb sources.
Measuring Runoff‐Suspended Solids Using an Improved Turbidometer Method
Authors: Ginting Daniel , Mamo Martha
Published: April 2006

Differences in particle size distribution between runoff standards and unknown samples affect the accuracy of estimation of total suspended solids (TSS) concentration using the nephelometric turbidity (NTU) method. The objective was to quantify the effects of a sucrose solution as suspending medium and contrasting particle size distribution on nephelometric turbidity and accuracy of TSS estimation. Nineteen benchmark soils varying in texture and color were divided into particle size distribution of <250 and <2000 μm. Soils from these two aggregate classes were then made into suspension ranging from 0.2 to 15 g L−1 using distilled deionized water. Runoff suspensions ranging from 0.2 to 21 g L−1 were also collected from different watersheds. Turbidity of soil and runoff suspensions was measured in sucrose solution and in distilled deionized water. The sucrose solution density ranged from 1.10 to 1.30 kg L−1 Increasing sucrose solution density decreased turbidity. The TSS concentration was most sensitive to changes in turbidity with the 1.30 kg L−1 sucrose solution. Using the 1.30 kg L−1 sucrose solution, particle size bias and error of TSS estimates were decreased by at least 20% compared to distilled deionized water. Reduction in refraction index differences between the suspended particles and sucrose solution combined with reduced particle settling and reduced Brownian motion resulted in dampening the effects of particle size distribution. We propose a sucrose solution of 1.30 kg L−1 as a better suspending medium to dampen the effect of particle size distribution and thus improve suspension TSS concentration estimation.
Transport of Giardia and Manure Suspensions in Saturated Porous Media
Authors: Bradford Scott A. , Tadassa Yadata F. , Pachepsky Yakov
Published: April 2006

Experiments were conducted to elucidate the transport behavior of cysts of Giardia and manure suspensions through several aquifer sands. Decreasing the median grain size of the sand resulted in lower peak effluent concentrations and increased deposition of the Giardia and manure particles in the sand near the column inlet. The effluent concentration curves for the manure suspensions also exhibited asymmetric shapes that tended to include larger particle sizes as the manure suspension was continuously added. Simulations of the transport of Giardia and manure particles using a simple and flexible power law model for the solid‐water mass exchange term provided a satisfactory description of the effluent and spatial distribution data. The cumulative size distribution (CSD) of manure particles in the suspension initially and after passage through the packed columns was used to identify the mechanisms that were controlling the deposition of manure particles and Giardia The CSD data indicated that manure particles were completely removed at early times by mechanical filtration and/or straining when the ratio of the particle to the median grain diameter was greater than 0.003 to 0.017. However, the CSD changed with increasing time due to deposition‐induced filling of straining sites. The Giardia transport was controlled by straining. For a given sand, higher effluent concentrations of Giardia were observed in the presence than in the absence of manure suspension. The relative increase of Giardia in the effluent concentrations varied from 75 to 172%. Hence, pathogen transport studies conducted in the absence of manure suspension may underestimate transport potential in manure‐contaminated environments.