90,065 results

  • Synthetic studies towards the B,C,D,E fragment of antibiotic CP44, 161

    Allen, PA; Brimble, Margaret; Prabaharan, H (1999)

    Journal article
    The University of Auckland Library

    The synthesis of polyethers 32 and 33 from tricyclic bis-spiroacetal aldehyde 27 and E-bromide 7 are described. A key step in the synthetic strategy involved the oxidative cyclisation of a bicyclic hydroxyspiroacetal 22a,b to a cis bis-spiroacetal un

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  • The Influence of Microwave Irradiation on Lipase-Catalyzed Kinetic Resolution of Racemic Secondary Alcohols

    Bachu, P; Gibson, J; Sperry, Jonathan; Brimble, Margaret (2007)

    Journal article
    The University of Auckland Library

    The influence of microwave irradiation on the Novozyme 435?? (Candida antarctica lipase) catalyzed kinetic resolution of secondary alcohols with different functional groups was studied in comparison to the use of conventional heating at 60 ??C. p-Chlorophenyl acetate was used as an acyl donor and toluene as the solvent. (??)-1-Phenyl-1-propanol 1, (??)-1-(4-bromophenyl)-propan-1-ol 3, (??)-1-phenylbut-3-en-1-ol 5 and (??)-3-bromo-2-(2-hydroxypropyl)-1,4-dimethoxynaphthalene 7 were successfully resolved into their (S)-alcohols and (R)-esters, respectively, in good enantiomeric excess. Resolution of (??)-ethyl-5-(4-methoxybenyloxy)-3-hydroxypentanoate 9 afforded its (R)-alcohol and (S)-ester using this method. In addition, microwave-assisted lipase transesterification of meso-symmetric diol 11 effected desymmetrization to ester 12 with high enantiomeric excess. In all cases studied, the conversion value for the microwave-assisted lipase kinetic resolution of secondary alcohols was higher than that obtained using conventional heating.

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  • Use of Bis(aminol) Ethers derived from N-(S)-(-)-a-Methylbenzylamine in Reactions with Resorcinarenes and Double Mannich Reactions

    Brimble, MA; Buckley, BR; Bulman Page, PC; Heaney, H; Sampler, EP; Carley, Sarah; Brocke, Constanze (2005)

    Journal article
    The University of Auckland Library

    The synthesis of some chiral bis-(aminol)ethers are described. Reaction of a solution of the resorcin[4]arene derived from propanal with N,N-bis(methoxymethyl)-N-(S)-(???)-??-methylbenzylamine in toluene at 85 ??C initially afforded a 1:1 mixture of two diastereoisomeric tetrakis(benzoxazines). Further, heating of this mixture under reflux in ethanol for 24 h afforded the crystalline (??S),(S)-diastereoisomer in 77% yield. N,N-bis(ethoxymethyl)-N-(S)-(???)-??-methylbenzylamine and N,N-bis(ethoxymethyl)-N-(R)-(+)-??-methylbenzylamine were reacted with ?? keto esters to afford a 1:1 mixture of the diastereoisomeric double Mannich adducts. Two of the double Mannich adducts were converted into tricyclic ABE analogues of the alkaloid methyllycaconitine 1.

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  • Pharmacological prevention of prematurity.

    Groom, Katie (2007-10)

    Journal article
    The University of Auckland Library

    The acute treatment of premature labour is successful for delaying delivery for short periods of time. Acute tocolysis does not have a significant impact on perinatal outcome. This is likely to be because the process leading to labour occurs over a longer timeframe and therefore therapies instigated as preventative measures are more likely to be successful in delaying delivery. Identification of women at risk of preterm birth is essential to ensure therapies are targeted appropriately. Risk assessments for prediction include previous obstetric history, previous episode of threatened preterm labour, fetal fibronectin status and cervical length. Several groups of pharmacological agents have been studied for the prophylactic treatment of preterm labour. There is no evidence to support the use of tocolytics such as beta-mimetics and oxytocin receptor antagonists. Current studies of calcium channel blockers are too small to draw final conclusions. Non-steroidal anti-inflammatory drugs are associated with side effects on the fetal renal system and ductus arteriosus, making them suitable only for long term use in pregnancy with close ultrasound surveillance. Antibiotics used early in pregnancy in women with abnormal vaginal flora may reduce the risk of preterm birth; however, in women with other risk factors for preterm birth, metronidazole may be associated with an increased risk. The use of progesterone in women with a history of very early preterm labour is likely to be beneficial for preventing preterm labour.

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  • What is the recurrence rate of postmenopausal bleeding in women who have a thin endometrium during a first episode of postmenopausal bleeding?

    Van Doorn, HC; Timmermans, A; Opmeer, BC; Kruitwagen, RF; Dijkhuizen, FP; Kooi, GS; van de Weijer, Petrus; Mol, BW; Dupomeb, F (2008)

    Journal article
    The University of Auckland Library

    Objective. To determine the incidence and significance of recurrent postmenopausal bleeding among women diagnosed with an endometrial thickness ???4 mm after a first episode of postmenopausal bleeding. Methods. Consecutive patients not using hormone replacement therapy (HRT) presenting with a first episode of postmenopausal bleeding and an endometrial thickness ???4 mm at transvaginal ultrasonography (TVU) were managed expectantly. In case of recurrent bleeding, the patient was evaluated according to the hospital's local policy with TVU, office endometrial sampling, hysteroscopy or dilatation and curettage (D&C) or a combination of these tests. We evaluated the incidence of recurrent bleeding, potential risk factors for recurrent bleeding, and the diagnosis made after recurrent bleeding. Results. A total of 607 patients were registered with a first episode of postmenopausal bleeding, of whom 249 had an endometrial thickness ???4 mm. Follow-up took place with a median of 174 weeks (range: 4???250 weeks). During follow-up, 25 of the 249 patients (10%; 95% CI: 6.6???14%) had recurrent bleeding. Median time until recurrence of bleeding was 49 weeks (range: 9???186 weeks). Two patients with recurrent bleeding turned out to have an endometrial carcinoma (8%; 95% CI: 2.2???25%), and 1 patient had a malignant melanoma. Time since menopause, age, body mass index, hypertension, diabetes and anticoagulants were not predictive for recurrent bleeding. Conclusion. The recurrence rate after a first episode of postmenopausal bleeding managed expectantly is low and cannot be predicted by patient characteristics. Patients with recurrent bleeding should be re-evaluated, as they bear a considerable risk of carcinoma.

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  • Intranasal continuous combined 17 beta-estradiol/norethisterone therapy improves the lipid profile in healthy postmenopausal women.

    Hemelaar, M; Kenemans, P; de Bie, L; van de Weijer, Petrus; van der Mooren, MJ (2006-04)

    Journal article
    The University of Auckland Library

    Objective: To compare the effects of continuous combined 17 -estradiol (E2) plus norethisterone (acetate) [NET(A)] therapy by either intranasal or oral administration on the lipid profile in postmenopausal women. Design: Randomized, double-blind, multicenter trial. Setting: Gynecologic outpatient department. Patient(s): Two-hundred thirty-three healthy postmenopausal women. Intervention(s): Women received continuous combined hormone therapy, either intranasal E2/NET (175 g/275 g) as a spray (n 117) or oral E2/NETA (1 mg/0.5 mg) as a capsule (n 116), for 1 year. Main Outcome Measure(s): Fasting plasma concentrations of lipids and (apo)lipoproteins; and atherogenic indices at baseline and after 12, 24, and 52 weeks of treatment. Result(s): We found a significant (P .001) decrease from baseline in both treatment groups in total, low-density lipoprotein- (LDL), high-density lipoprotein- (HDL), and HDL2-cholesterol, in triglycerides, apolipoprotein B (apoB), and lipoprotein(a). Levels of HDL3-cholesterol and apolipoprotein A1 (apoA1) were transiently decreased in the intranasal group. In the oral group, compared with the intranasal group, the decrease was larger for ratio total and LDL-cholesterol and lipoprotein(a) and smaller for triglycerides and apoA1. In the oral group, the ratios total/HDL cholesterol and LDL/HDL cholesterol were lowered, and the ratio apoB/LDL was increased, more than in the intranasal group. Conclusion(s): Both intranasal and oral E2/NET(A) therapy improved the lipid profile of healthy postmenopausal women, with some effects being more pronounced after oral administration. (Fertil Steril 2006;85:979???88. ?? 2006 by American Society for Reproductive Medicine.)

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  • Differential expression of group I metabotropic glutamate receptors in human motoneurons at low and high risk of degeneration in amyotrophic lateral sclerosis

    Ma, Li; Ostrovsky, Helena; Miles, Gareth; Lipski, Janusz; Funk, Gregory; Nicholson, Louise (2006-11-17)

    Journal article
    The University of Auckland Library

    Glutamate excitotoxicity has been suggested to play a role in amyotrophic lateral sclerosis, since overstimulation of post-synaptic glutamate receptors by accumulated extracellular glutamate leads to motoneuron cell death. It is however unclear as to why some groups of motoneurons degenerate in this disease while other groups remain relatively intact even during terminal stages of the disease. Our previous studies in the rat showed differential expression of group I metabotropic glutamate receptors in motoneurons at low and high risk of degeneration in amyotrophic lateral sclerosis. Here we have extended this study to normal human brains. In situ hybridization showed that transcripts of both metabotropic glutamate receptor (mGluR) 1 and mGluR5 were expressed in motoneurons in both the resistant motor nucleus III and the vulnerable motor nucleus XII. Immunolabeling of mGluR1?? and mGluR5 was found in both motoneurons and glia-like cells in all the motor nuclei and the ventral horn of the cervical spinal cord studied. Quantitative analysis of optical density measurements showed higher levels of mGluR1?? protein expression but lower levels of mGluR5 protein expression in the vulnerable motoneuron pool (VII, XII and spinal cord) than in the resistant motoneuron pool (III, IV and VI). This differential expression of group I metabotropic glutamate receptor proteins within vulnerable motoneuron pools may predispose these neurons to degeneration as seen in amyotrophic lateral sclerosis.

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  • Optimization of Tet-on system for inducible expression of RAGE

    Shaikh, Shamim; Nicholson, Louise (2006)

    Journal article
    The University of Auckland Library

    We have optimized a two-plasmid Tet-On system, the regulatory plasmid and the response plasmid, to produce tightly controlled inducible expression of the gene RAGE in cell-culture models. Two sets of plasmids were constructed: set 1 (universal; for broad range of cell types) and set 2 (neuron specific). For the response plasmid, the gene RAGE was cloned in pIRES2-EGFP plasmid (Clontech) and the CMV promoter replaced with TREtight (modified seven copies of Tet-operon fused with CMVm promoter). For the regulatory plasmid, rtTA (reverse tetracycline transactivator) was placed under either the CMV promoter or the cell-specific promoter neuronal specific enolase. Both plasmids have the mammalian selection marker neomycine; the EGFP reporter gene is only in the response plasmid and IRES is between the gene and EGFP. Following induction with doxycycline, cells expressing RAGE showed neomycine resistance and green fluorescence (EGFP). Our system has been tested in two different cell lines and showed negligible basal leakiness, high induction of the gene RAGE (142-fold), dose-dependent response to doxycycline, and strict cell-type specificity. This system is highly suitable for cell-specific expression of any gene of interest in primary cultures and mixed cell populations.

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  • Cell type-specific, topoisomerase II-dependent inhibition of hypoxia-inducible factor-1α protein accumulation by NSC 644221

    Creighton-Gutteridge, M; Cardinella, JH; Stephen, AG; Rapisarda, U; Uranchimeg, B; Hite, K; Denny, William; Shoemaker, RH; Melillo, G (2007)

    Journal article
    The University of Auckland Library

    Purpose: The discovery and development of small-molecule inhibitors of hypoxia-inducible factor-1 (HIF-1) is an attractive, yet challenging, strategy for the development of new cancer therapeutic agents. Here, we report on a novel tricyclic carboxamide inhibitor of HIF-1??, NSC 644221. Experimental Design: We investigated the mechanism by which the novel compound NSC 644221 inhibited HIF-1??. Results: NSC 644221 inhibited HIF-1???dependent, but not constitutive, luciferase expression in U251-HRE and U251-pGL3 cells, respectively, as well as hypoxic induction of vascular endothelial growth factor mRNA expression in U251 cells. HIF-1??, but not HIF-1??, protein expression was inhibited by NSC 644221 in a time- and dose-dependent fashion. Interestingly, NSC 644221 was unable to inhibit HIF-1?? protein accumulation in the presence of the proteasome inhibitors MG132 or PS341, yet it did not directly affect the degradation of HIF-1?? as shown by experiments done in the presence of cyclohexamide or pulse-chase labeling using [35S]methionine. In contrast, NSC 644221 decreased the rate of HIF-1?? translation relative to untreated controls. Silencing of topoisomerase (topo) II??, but not topo I, by specific small interfering RNA completely blocked the ability of NSC 644221 to inhibit HIF-1??. The data presented show that topo II is required for the inhibition of HIF-1?? by NSC 644221. Furthermore, although NSC 644221 induced p21 expression, ??H2A.X, and G2-M arrest in the majority of cell lines tested, it only inhibited HIF-1?? in a distinct subset of cells, raising the possibility of pathway-specific ???resistance??? to HIF-1 inhibition in cancer cells. Conclusions: NSC 644221 is a novel HIF-1 inhibitor with potential for use as both an analytic tool and a therapeutic agent. Our data provide a strong rationale for pursuing the preclinical development of NSC 644221 as a HIF-1 inhibitor.

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  • Clomiphene citrate for unexplained subfertility in women

    Hughes, E; Brown, Julie; Collins, JJ; Vanderkerchove, P (2010)

    Journal article
    The University of Auckland Library

    Background The effectiveness of clomiphene citrate has been demonstrated in the treatment of subfertility associated with infrequent or irregular ovulation. The physiologic effects and clinical benefits in ovulatory women with unexplained subfertility are less clear. The drug is associated with an increased risk of multiple pregnancy and a suggestion of potentially increased ovarian cancer risks. In light of these concerns, defining the effectiveness of clomiphene citrate for ovulatory women with unexplained subfertility is extremely important. Objectives To determine the effectiveness of clomiphene citrate in improving pregnancy outcomes in women with unexplained subfertility, used in a dose range of 50 to 250 mg for up to 10 days. The primary outcome was live births. Search strategy We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register (June 2009), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 2), MEDLINE (1966 to June 2009), EMBASE (1980 to June 2009) and reference lists of articles. Selection criteria Only randomised controlled trials were included. Quasi-randomised designs were excluded. Data collection and analysis Fourteen potentially relevant trials were identified of which seven were included in this review. All trials were assessed for risk of bias using standardised Menstrual Disorders and Subfertility Group methodology. Main results Data relating to 1159 participants from seven trials were collated. There was no evidence that clomiphene citrate was more effective than no treatment or placebo for live birth (odds ratio (OR) 0.79, 95% CI 0.45 to 1.38; P = 0.41) or for clinical pregnancy per woman randomised both with intrauterine insemination (IUI) (OR 2.40, 95% CI 0.70 to 8.19; P = 0.16), without IUI (OR 1.03, 95% CI 0.64 to 1.66; P = 0.91) and without IUI but using human chorionic gonadotropin (hCG) (OR 1.66, 95% CI 0.56 to 4.80; P = 0.35). It should be noted that heterogeneity between studies ranged from 34% to 58% using the I2 statistic. Authors' conclusions There is no evidence of clinical benefit of clomiphene citrate for unexplained fertility. When making this treatment choice, potential side effects should be discussed. These include the increased risk of multiple pregnancy and the concern that use for more that 12 cycles has been associated with a three-fold increase in risk of ovarian cancer.

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  • Energetic consequences of mechanical loads.

    Loiselle, Denis; Crampin, Edmund; Niederer, SA; Smith, NP; Barclay, CJ (2008)

    Journal article
    The University of Auckland Library

    n this brief review, we have focussed largely on the well-established, but essentially phenomenological, linear relationship between the energy expenditure of the heart (commonly assessed as the oxygen consumed per beat, oxygen consumption (VO2)) and the pressure-volume-area (PVA, the sum of pressure???volume work and a specified ???potential energy??? term). We raise concerns regarding the propriety of ignoring work done during ???passive??? ventricular enlargement during diastole as well as the work done against series elasticity during systole. We question the common assumption that the rate of basal metabolism is independent of ventricular volume, given the equally well-established Feng- or stretch-effect. Admittedly, each of these issues is more of conceptual than of quantitative import. We point out that the linearity of the enthalpy???PVA relation is now so well established that observed deviations from linearity are often ignored. Given that a one-dimensional equivalent of the linear VO2???PVA relation exists in papillary muscles, it seems clear that the phenomenon arises at the cellular level, rather than being a property of the intact heart. This leads us to discussion of the classes of crossbridge models that can be applied to the study of cardiac energetics. An admittedly superficial examination of the historical role played by Hooke's Law in theories of muscle contraction foreshadows deeper consideration of the thermodynamic constraints that must, in our opinion, guide the development of any mathematical model. We conclude that a satisfying understanding of the origin of the enthalpy???PVA relation awaits the development of such a model.

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  • Successful but limited use of external cephalic version in Auckland

    Wise, Michelle; Sadler, Lynn; Ansell, D (2008-10)

    Journal article
    The University of Auckland Library

    Background: External cephalic version (ECV) can effectively reduce the chance of non-cephalic presentation at birth and reduce caesarean section rate for breech presentation at term. It is recommended in New Zealand to offer ECV to all eligible women with breech presentation at term. Aim: This study aims to determine the ECV success rate at our hospital, factors that predict ECV success, and perinatal outcomes for women who had ECV, and to estimate the ECV attempt rate at our hospital. Methods: A prospective audit was performed of all women with singleton non-cephalic presentation ??? 36 weeks who attended the ECV clinic at National Women's Health in Auckland from July 2002 to January 2006. Results: Two hundred and fifty five women presented for ECV during the study period, and the ECV success rate was 59%. The strongest predictor of ECV success was an unengaged presenting part. Women with successful ECV had a vaginal birth rate of 67%. Three women needed to have an ECV attempt in order to prevent one caesarean section. We estimated that 26% of women with term breech presentation had an ECV attempt. Conclusions: ECV at National Women's Health is effective at reducing beech presentation at term and at restoring a caesarean section rate equivalent to that of cephalic singleton pregnancy at term. However, the low rate of referral should be addressed.

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  • Early differences in epithalamic left-right asymmetry influence lateralization and personality of adult zebrafish

    Dadda, M; Domenichini, Alice; Piffer, L; Argenton, F; Bisazza, A (2010-01)

    Journal article
    The University of Auckland Library

    The habenulae are part of an evolutionary conserved conduction system that connects the limbic forebrain areas with midbrain structures and is implicated in important functions such as feeding, mating, avoidance learning, and hormonal response to stress. Very early during zebrafish neurogenesis the parapineal organ migrates near to one habenula, commonly the left, inducing wide left???right habenular asymmetries in gene expression and connectivity. It was posited that this initial symmetry-breaking event determines the development of lateralized brain functions and early differences in epithalamic left???right asymmetry give rise to individual variation in coping styles and personality. We tested these two hypotheses by sorting zebrafish with left or right parapineal at birth using a foxD3:GFP marker and by measuring visual and motor laterality and three personality dimensions as they become adults. Significant differences between fish with opposite parapineal position were found in all laterality tests while the influence of asymmetry of the habenulae on personality was more complex. Fish with atypical right parapineal position, tended to be bolder when inspecting a predator, spent less time in the peripheral portion of an open field and covered a shorter distance when released in the dark. Activity in the open field was not associated to anatomical asymmetry but correlated with laterality of predator inspection that in turn was influenced by parapineal position. One personality dimension, sociality, appeared uncorrelated to both anatomical and functional asymmetries and was instead influenced by the sex of the fish, thus suggesting that other factors, i.e. hormonal, may be implicated in its development.

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  • Structure and properties of melt-processed PVDF/PMMA/polyaniline blends.

    Edmonds, Neil; Easteal, AJ; Cooney, Ralph; Ray, Sudip (2009)

    Journal article
    The University of Auckland Library

    Ternary blends composed of the matrix polymer poly(vinylidene fluoride) (PVDF) and poly(methyl methacrylate) (PMMA) with different proportions of thermally doped polyaniline (PAni) using an alkylated dopant (dodecylbenzenesulfonic acid) (DBSA) were prepared by melt mixing. The effectiveness of these blends was compared with the corresponding binary blends of PVDF or PMMA with PAni???DBSA complex. Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD) measurements, thermal analysis by differential scanning calorimetry (DSC) and morphological studies by optical microscopy and scanning electron microscopy (SEM) were carried out to characterize the blends in light of the interactions between their components and on the resulting electrical conductivity. Though a notable dispersion of PAni???DBSA in the PMMA matrix was incurred along with better conductivity with respect to PVDF/PAni???DBSA and PVDF/PMMA/PAni???DBSA blends, the thin films based on PMMA/PAni???DBSA were found to be fragile in nature. However, the presence of PMMA in the ternary blends of PVDF/PMMA/PAni???DBSA provided improved dispersion of PAni???DBSA in the PVDF/PMMA host matrix as compared to PVDF/PAni???DBSA binary blends. An enhancement in the conductivity by about two orders of magnitude at >5 wt% PAni???DBSA was witnessed in the ternary blends than that of PVDF/PAni???DBSA binary blends. Thin films made of ternary blends of PVDF/PMMA/PAni???DBSA also offered superior mechanical properties and flexibility than that of PMMA/PAni???DBSA binary blends due to the contribution of PVDF in the blend.

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  • Developing a grounded theory to explain the practices of self-organizing Agile teams

    Hoda, R; Noble, J; Marshall, S (2011)

    Journal article
    The University of Auckland Library

    Software Engineering researchers are constantly looking to improve the quantity and quality of their research findings through the use of an appropriate research methodology. Over the last decade, there has been a sustained increase in the number of researchers exploring the human and social aspects of Software Engineering, many of whom have used Grounded Theory. We have used Grounded Theory as a qualitative research method to study 40 Agile practitioners across 16 software organizations in New Zealand and India and explore how these Agile teams self-organize. We use our study to demonstrate the application of Grounded Theory to Software Engineering. In doing so, we present (a) a detailed description of the Grounded Theory methodology in general and its application in our research in particular; (b) discuss the major challenges we encountered while performing Grounded Theory???s various activities and our strategies for overcoming these challenges; and (c) we present a sample of our data and results to illustrate the artifacts and outcomes of Grounded Theory research.

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  • Is there an indication for embolic protection in renal artery intervention?

    Holden, Andrew (2011-06)

    Journal article
    The University of Auckland Library

    The role of endovascular treatment of atherosclerotic renal artery disease is uncertain, particularly after the publication of the Angioplasty and Stenting for Renal Artery Lesions trial and other randomized trials. These trials have shown that nonselective treatment of patients with renal artery stenosis does not result in a benefit when compared with best medical therapy. However, all trials have identified a subgroup of patients who do respond favorably to revascularization. In particular, patients with a degree of chronic renal insufficiency, critical renal artery stenosis, and a recent decline in renal function are likely to respond positively to revascularization. Endovascular treatment of renal artery stenosis must be performed safely, particularly in the high-risk patient group with background chronic renal insufficiency. Atheroembolization occurs during renal artery revascularization, as demonstrated by ex vivo studies and the high embolic yield obtained in published series of protected renal artery revascularization. The evidence supporting embolic protection includes single-center series wherein excellent results for renal function preservation have been reported. One small, randomized, controlled trial demonstrated a significant benefit if both embolic protection and abciximab were used. There are unique demands on an embolic protection device in the renal artery circulation and a dedicated device has not been developed. Both distal filters and occlusion balloons have been successfully used. Both devices can normally be primarily passed through the stenosis, allowing the remainder of the procedure to be protected. Filters have the advantage of maintaining renal perfusion throughout the procedure. Distal occlusion balloons can capture embolic particles of all sizes although the clinical advantage is uncertain.

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  • Novel core promoter elements and a cognate transcription factor in the divergent unicellular eukaryote Trichomonas vaginalis.

    Smith, AJ; Chudnovsky, L; Barbosa, Augusto; Delgadillo-Correa, MG; Jonsson, ZO; Wohlschlegel, JA; Johnson, PJ (2011-04)

    Journal article
    The University of Auckland Library

    A highly conserved DNA initiator (Inr) element has been the only core promoter element described in the divergent unicellular eukaryote Trichomonas vaginalis, although genome analyses reveal that only ???75% of protein-coding genes appear to contain an Inr. In search of another core promoter element(s), a nonredundant database containing 5' untranslated regions of expressed T. vaginalis genes was searched for overrepresented DNA motifs and known eukaryotic core promoter elements. In addition to identifying the Inr, two elements that lack sequence similarity to the known protein-coding gene core promoter, motif 3 (M3) and motif 5 (M5), were identified. Mutational and functional analyses demonstrate that both are novel core promoter elements. M3 [(A/G/T)(A/G)C(G/C)G(T/C)T(T/A/G)] resembles a Myb recognition element (MRE) and is bound specifically by a unique protein with a Myb-like DNA binding domain. The M5 element (CCTTT) overlaps the transcription start site and replaces the Inr as an alternative, gene-specific initiator element. Transcription specifically initiates at the second cytosine within M5, in contrast to characteristic initiation by RNA polymerase II at an adenosine. In promoters that combine M3 with either M5 or Inr, transcription initiation is regulated by the M3 motif.

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  • A Genomics approach reveals that aroma production in apple is controlled by ethylene predominantly at the final step in each biosynthetic pathway([w])

    Schaffer, Robert; Friel, EN; Souleyre, EJF; Bolitho, K; Thodey, K; Ledger, S; Bowen, JH; Ma, JH; Nain, B; Cohen, D; Gleave, AP; Crowhurst, RN; Janssen, BJ; Yao, JL; Newcomb, Richard (2007-08)

    Journal article
    The University of Auckland Library

    Ethylene is the major effector of ripening in many fleshy fruits. In apples (Malus x domestica) the addition of ethylene causes a climacteric burst of respiration, an increase in aroma, and softening of the flesh. We have generated a transgenic line of ???Royal Gala??? apple that produces no detectable levels of ethylene using antisense ACC OXIDASE, resulting in apples with no ethyleneinduced ripening attributes. In response to external ethylene these antisense fruits undergo a normal climacteric burst and produced increasing concentrations of ester, polypropanoid, and terpene volatile compounds over an 8-d period. A total of 186 candidate genes that might be involved in the production of these compounds were mined from expressed sequence tags databases and full sequence obtained. Expression patterns of 179 of these were assessed using a 15,720 oligonucleotide apple microarray. Based on sequence similarity and gene expression patterns we identified 17 candidate genes that are likely to be ethylene control points for aroma production in apple. While many of the biosynthetic steps in these pathways were represented by gene families containing two or more genes, expression patterns revealed that only a single member is typically regulated by ethylene. Only certain points within the aroma biosynthesis pathways were regulated by ethylene. Often the first step, and in all pathways the last steps, contained enzymes that were ethylene regulated. This analysis suggests that the initial and final enzymatic steps with the biosynthetic pathways are important transcriptional regulation points for aroma production in apple.

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  • A canine model of inherited myopia: Familial aggregation of refractive error in Labrador Retrievers

    Black, Joanna; Browning, Sharon; Collins, Andrew; Phillips, John (2008)

    Journal article
    The University of Auckland Library

    PURPOSE. To determine whether the distribution of naturally occurring myopia in Labrador Retrievers has a genetic component. METHODS. Pedigree records of a large canine family were analyzed. Pure Labrador Retrievers, 1 to 8 years of age, free of ocular disease, and available for testing were studied. Refractive error was measured by cycloplegic retinoscopy in both eyes. The family included mating loops, and so an expectation maximization (EM) algorithm (multivar program, MORGAN software; University of Washington, Seattle) was used to calculate log likelihoods of refractive error with environmental and additive genetic models. The fixed effects of coat color, sex, and litter size were also tested. RESULTS. In our sample of 116 dogs from this one family, the average spherical equivalent refraction (SER) was 0.41 D (range, 5.38 to 1.65 D, mean of both eyes, n 116): 31% were myopic (SER 0.50 D), 60% were emmetropic (SER 0.49 to 0.99 D), and 9% were hyperopic (SER 1.00 D). The significance of fixed and genetic effects was tested by comparing the full model (including genetic and all fixed effects) to models with one effect removed. Litter size and additive genetic effects were significant (P 0.0013 and P 0.000093, respectively), whereas sex and coat color were not. The overall variance in SER was accounted for approximately equally by additive genetic variance and residual/environmental variance. Narrow sense heritability of SER was 0.506. CONCLUSIONS. The distribution of refractive error within this family of Labrador Retrievers had a significant genetic component, but was also influenced by other factors (litter size, and undefined residual/environmental effects). The dog represents a unique model for the study of naturally occurring, heritable, high-prevalence, low-degree myopia. methods. Pedigree records of a large canine family were analyzed. Pure Labrador Retrievers, 1 to 8 years of age, free of ocular disease, and available for testing were studied. Refractive error was measured by cycloplegic retinoscopy in both eyes. The family included mating loops, and so an expectation maximization (EM) algorithm (multivar program, MORGAN software; University of Washington, Seattle) was used to calculate log likelihoods of refractive error with environmental and additive genetic models. The fixed effects of coat color, sex, and litter size were also tested. results. In our sample of 116 dogs from this one family, the average spherical equivalent refraction (SER) was ???0.41 D (range, ???5.38 to +1.65 D, mean of both eyes, n = 116): 31% were myopic (SER ??? ???0.50 D), 60% were emmetropic (SER = ???0.49 to +0.99 D), and 9% were hyperopic (SER ??? +1.00 D). The significance of fixed and genetic effects was tested by comparing the full model (including genetic and all fixed effects) to models with one effect removed. Litter size and additive genetic effects were significant (P = 0.0013 and P = 0.000093, respectively), whereas sex and coat color were not. The overall variance in SER was accounted for approximately equally by additive genetic variance and residual/environmental variance. Narrow sense heritability of SER was 0.506. conclusions. The distribution of refractive error within this family of Labrador Retrievers had a significant genetic component, but was also influenced by other factors (litter size, and undefined residual/environmental effects). The dog represents a unique model for the study of naturally occurring, heritable, high-prevalence, low-degree myopia.

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  • Yang-Mills detour complexes and conformal geometry

    Gover, Ashwin; Somberg, P; Soucek, V (2008)

    Journal article
    The University of Auckland Library

    Working over a pseudo-Riemannian manifold, for each vector bundle with connection we construct a sequence of three differential operators which is a complex (termed a Yang-Mills detour complex) if and only if the connection satisfies the full Yang-Mills equations. A special case is a complex controlling the deformation theory of Yang-Mills connections. In the case of Riemannian signature the complex is elliptic. If the connection respects a metric on the bundle then the complex is formally self-adjoint. In dimension 4 the complex is conformally invariant and generalises, to the full Yang-Mills setting, the composition of (two operator) Yang-Mills complexes for (anti-)self-dual Yang-Mills connections. Via a prolonged system and tractor connection a diagram of differential operators is constructed which, when commutative, generates differential complexes of natural operators from the Yang-Mills detour complex. In dimension 4 this construction is conformally invariant and is used to yield two new sequences of conformal operators which are complexes if and only if the Bach tensor vanishes everywhere. In Riemannian signature these complexes are elliptic. In one case the first operator is the twistor operator and in the other sequence it is the operator for Einstein scales. The sequences are detour sequences associated to certain Bernstein-Gelfand-Gelfand sequences.

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