Utilisation of CO2 as "Structure Modifier" of Inorganic Solids.

Utilisation of CO2 as a chemical reagent is challenging, due to the molecule's inherent chemical stability. However, CO2 reacts promptly at high temperature (∼1000 °C) with alkaline-earth oxides to form carbonates and such reactions are used towards capture and re-utilisation. In this work, this concept is extended and CO2 is utilised as a reagent to modify the crystal structure of mixed-metal inorganic solids. Modification of the crystal structure is a "tool" used by materials scientists to tailor the physical property of solids. CO2 gas was reacted with several isostructural mixed-metal oxides Sr2 CuO3 , Sr1.8 Ba0.2 CuO3 and Ba2 PdO3 . These oxides are carefully selected to show anion vacancies in their crystal structure, to act as host sites for CO2 molecules, leading to the formation of carbonate anions, (CO3 )2- . The corresponding oxide carbonates were formed successfully and the favourable formation of SrCO3 as secondary phase was minimised via an innovative, yet simple synthetic procedure involving alternating of CO2 and air. We also derived a simple model to predict the kinetics of the reactions for the cuprates, using first-principles density functional theory and assimilating the reaction to a gas-surface process.

The impact of haemodilution and bypass pump flow on cerebral oxygen desaturation during cardiopulmonary bypass--A comparison of two systems of cardiopulmonary bypass.

OBJECTIVE: To determine the influence of haemodilution, bypass flow rates and calculated oxygen delivery during cardiopulmonary bypass (CPB) with either a conventional CPB (C-CPB) circuit or a miniaturised (Mini-CPB) circuit on cerebral oxygen desaturation. The effect of minimal haemodilution with a Mini-CPB was investigated. PARTICIPANTS: Eighty patients scheduled for elective cardiac surgery. INTERVENTION: Oxygenated haemoglobin (O2Hb) and tissue oxygenation index (TOI) were measured with near-infrared spectroscopy (NIRS). RESULTS: The average indexed bypass pump flow was significantly lower with Mini-CPB. When combined with haemoglobin concentration, the average oxygen delivery was the same between groups. Patients in the C-CPB group had a greater duration and severity of cerebral desaturation to a level <20% below baseline values, but none reached the depth and duration of the cerebral desaturation associated with poor outcome. Cerebral oxygen desaturation with C-CPB was significantly associated with low flows during bypass, whereas desaturation with Mini-CPB was associated with low perioperative haemoglobin concentration.

Taccalonolide binding to tubulin imparts microtubule stability and potent in vivo activity.

The taccalonolides are highly acetylated steroids that stabilize cellular microtubules and overcome multiple mechanisms of taxane resistance. Recently, two potent taccalonolides, AF and AJ, were identified that bind to tubulin directly and enhance microtubule polymerization. Extensive studies were conducted to characterize these new taccalonolides. AF and AJ caused aberrant mitotic spindles and bundling of interphase microtubules that differed from the effects of either paclitaxel or laulimalide. AJ also distinctly affected microtubule polymerization in that it enhanced the rate and extent of polymerization in the absence of any noticeable effect on microtubule nucleation. In addition, the resulting microtubules were found to be profoundly cold stable. These data, along with studies showing synergistic antiproliferative effects between AJ and either paclitaxel or laulimalide, suggest a distinct binding site. Direct binding studies demonstrated that AJ could not be displaced from microtubules by paclitaxel, laulimalide, or denaturing conditions, suggesting irreversible binding of AJ to microtubules. Mass spectrometry confirmed a covalent interaction of AJ with a peptide of ß-tubulin containing the cyclostreptin-binding sites. Importantly, AJ imparts strong inter-protofilament stability in a manner different from other microtubule stabilizers that covalently bind to tubulin, consistent with the distinct effects of the taccalonolides as compared with other stabilizers. AF was found to be a potent and effective antitumor agent that caused tumor regression in the MDA-MB-231 breast cancer xenograft model. The antitumor efficacy of some taccalonolides, which stabilize microtubules in a manner different from other microtubule stabilizers, provides the impetus to explore the therapeutic potential of this site.

Cholestatic Jaundice Associated with Carnitine Palmitoyltransferase IA Deficiency.

Liver dysfunction usually accompanies metabolic decompensation in fatty acid oxidation disorders, including carnitine palmitoyltransferase (CPT) Ia deficiency. Typically, the liver is enlarged with raised plasma transaminase activities and steatosis on histological examination. In contrast, cholestatic jaundice is rare, having only been reported in long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency. We report a 3-year-old boy with CPT Ia deficiency who developed hepatomegaly and cholestatic jaundice following a viral illness. No cause for the jaundice could be found, apart from the fatty acid oxidation disorder. Liver histology showed diffuse, predominately macrovesicular steatosis, hepatocellular and canalicular cholestasis but no bile duct paucity or evidence of large duct obstruction. The liver dysfunction resolved in 4-7 weeks.

Modelling auxin efflux carrier phosphorylation and localization.

Regulation of the activity and localization of PIN-FORMED (PIN) membrane proteins, which facilitate efflux of the plant hormone auxin from cells, is important for plants to respond to environmental stimuli and to develop new organs. The protein kinase PINOID (PID) is involved in regulating PIN phosphorylation, and this is thought to affect PIN localization by biasing recycling towards shootwards (apical) (rather than rootwards (basal)) membrane domains. PID has been observed to undergo transient internalization following auxin treatment, and it has been suggested that this may be a result of calcium-dependent sequestration of PID by the calcium-binding protein TOUCH3 (TCH3). We present a mathematical formulation of these processes and examine the resulting steady-state and time-dependent behaviours in response to transient increases in cytosolic calcium. We further combine this model with one for the recycling of PINs in polarized cells and also examine its behaviour. The results provide insight into the behaviour observed experimentally and provide the basis for subsequent studies of the tissue-level implications of these subcellular processes for phenomena such as gravitropism.

Pathophysiology of fatty acid oxidation disorders.

Mitochondrial fatty acid oxidation represents an important pathway for energy generation during periods of increased energy demand such as fasting, febrile illness and muscular exertion. In liver, the primary end products of the pathway are ketone bodies, which are released into the circulation and provide energy to tissues that are not able to oxidize fatty acids such as brain. Other tissues, such as cardiac and skeletal muscle are capable of direct utilization of the fatty acids as sources of energy. This article provides an overview of the pathogenesis of fatty acid oxidation disorders. It describes the different tissue involvement with the disease processes and correlates disease phenotype with the nature of the genetic defect for the known disorders of the pathway.

Mathematical modelling of the Aux/IAA negative feedback loop.

The hormone auxin is implicated in regulating a diverse range of developmental processes in plants. Auxin acts in part by inducing the Aux/IAA genes. The associated pathway comprises multiple negative feedback loops (whereby Aux/IAA proteins can repress Aux/IAA genes) that are disrupted by auxin mediating the turnover of Aux/IAA protein. In this paper, we develop a mathematical model of a single Aux/IAA negative feedback loop in a population of identical cells. The model has a single steady-state. We explore parameter space to uncover a number of dynamical regimes. In particular, we identify the ratio between the Aux/IAA protein and mRNA turnover rates as a key parameter in the model. When this ratio is sufficiently small, the system can evolve to a stable limit cycle, corresponding to an oscillation in Aux/IAA expression levels. Otherwise, the steady-state is either a stable-node or a stable-spiral. These observations may shed light on recent experimental results.

[Hyperinsulinism in infancy and childhood: when an insulin level is not always enough]. / Hyperinsulinisme de l'enfant et de l'adolescent: quand la détermination de la concentration en insuline n'est pas toujours suffisante.

Hypoglycemia in infants and children can lead to seizures, developmental delay, and permanent brain damage. Hyperinsulinism (HI) is the most common cause of both transient and permanent disorders of hypoglycemia. HI is characterized by dysregulated insulin secretion, which results in persistent mild to severe hypoglycemia. The various forms of HI represent a group of clinically, genetically, and morphologically heterogeneous disorders. Congenital hyperinsulinism is associated with mutations of SUR-1 and Kir6.2, glucokinase, glutamate dehydrogenase, short-chain 3-hydroxyacyl-CoA dehydrogenase, and ectopic expression on beta-cell plasma membrane of SLC16A1. Hyperinsulinism can be associated with perinatal stress such as birth asphyxia, maternal toxemia, prematurity, or intrauterine growth retardation, resulting in prolonged neonatal hypoglycemia. Mimickers of hyperinsulinism include neonatal panhypopituitarism, drug-induced hypoglycemia, insulinoma, antiinsulin and insulin-receptor stimulating antibodies, Beckwith-Wiedemann Syndrome, and congenital disorders of glycosylation. Laboratory testing for hyperinsulinism may include quantification of blood glucose, plasma insulin, plasma beta-hydroxybutyrate, plasma fatty acids, plasma ammonia, plasma acylcarnitine profile, and urine organic acids. Genetic testing is available through commercial laboratories for genes known to be associated with hyperinsulinism. Acute insulin response (AIR) tests are useful in phenotypic characterization. Imaging and histologic tools are also available for diagnosing and classifying hyperinsulinism. The goal of treatment in infants with hyperinsulinism is to prevent brain damage from hypoglycemia by maintaining plasma glucose levels above 700 mg/L (70 mg/dL) through pharmacologic or surgical therapy. The management of hyperinsulinism requires a multidisciplinary approach that includes pediatric endocrinologists, radiologists, surgeons, and pathologists who are trained in diagnosing, identifying, and treating hyperinsulinism.

The Arabidopsis thaliana/Myzus persicae model system demonstrates that a single gene can influence the interaction between a plant and a sap-feeding insect.

We have developed an Arabidopsis thaliana/Myzus persicae model system to allow the dissection of plant/insect interactions at a molecular genetic level. This allows the examination of the role of single plant genes in the interaction between the plant and an aphid. Our initial studies have exploited an Arabidopsis genotype in which the function of the amino acid transporter ANT1 has been abolished. This mutation results in a change in the proportions of several amino acids within the phloem sieve elements (SEs) resulting in an increase in the proportion of essential amino acids. This has been measured using aphid stylectomy to collect SE samples, followed by a novel micellar electrokinetic chromatography method for amino acid analysis. The SE content represents the aphid's diet, and use of electrical penetration graph technology and honeydew clocks have demonstrated that this altered diet results in a change in the feeding rate of the aphid. Balance sheets can be produced to show the amount (nmoles/24 h) of each of 18 amino acids taken up and excreted by aphids feeding on wild type and ant1 mutant plants. The data show that aphids feeding on the ant1 mutant take up larger amounts of amino acids. However, we could not detect any effect on the reproductive rate of the aphids. The results show that, under experimental conditions, this model system can be used to identify plant genes that control the behaviour and fecundity of an insect pest.

AXR4 is required for localization of the auxin influx facilitator AUX1.

The AUX1 and PIN auxin influx and efflux facilitators are key regulators of root growth and development. For root gravitropism to occur, AUX1 and PIN2 must transport auxin via the lateral root cap to elongating epidermal cells. Genetic studies suggest that AXR4 functions in the same pathway as AUX1. Here we show that AXR4 is a previously unidentified accessory protein of the endoplasmic reticulum (ER) that regulates localization of AUX1 but not of PIN proteins. Loss of AXR4 resulted in abnormal accumulation of AUX1 in the ER of epidermal cells, indicating that the axr4 agravitropic phenotype is caused by defective AUX1 trafficking in the root epidermis.

Longitudinal assessment of ovarian perifollicular and endometrial vascularity by power Doppler ultrasound in pregnant and non-pregnant cycles in the IVF setting.

PURPOSE: This longitudinal study aimed to compare ovarian perifollicular and endometrial blood flow (PFBF and EBF, respectively) during the follicular phase in pregnant and non-pregnant IVF cycles. METHODS: Serial transvaginal scans were performed in 15 subjects undergoing IVF treatment. Both PFBF and EBF were subjectively graded (grades 0-4 for PFBF and grades 1-3 for EBF). After confirmation of clinical pregnancy, the treatment cycles were grouped into 'Pregnant' and 'Non-pregnant' cycles. Ovarian PFBF and EBF were retrospectively compared between the two groups. RESULTS: In pregnant cycles, the proportion of large (> or = 15 mm) follicles with high (24) grade PFBF increased with time throughout the follicular phase, and the proportion of large follicles with poor (0-1) grade PFBF decreased. In non-pregnant cycles these trends were reversed. There was no difference in EBF between the two groups. CONCLUSION: The pattern of ovarian PFBF but not EBF may be predictive of treatment outcome.

Enhanced systemic transgene expression after nonviral salivary gland transfection using a novel endonuclease inhibitor/DNA formulation.

Gene transfer to the major salivary glands is an attractive method for the systemic delivery of therapeutic proteins. To date, nonviral gene transfer to these glands has resulted in inadequate systemic protein concentrations. We believe that identification of the barriers responsible for this inefficient transfection will enable the development of enhanced nonviral gene transfer in salivary glands and other tissues. One potential barrier is the degradation of plasmid DNA by endonucleases. To test this hypothesis, we coadministered two endonuclease inhibitors ((zinc and aurintricarboxylic acid (ATA)) with plasmid DNA, containing the secreted alkaline phosphatase gene (SEAP), to the submandibular glands of rats. The effect of zinc and ATA on SEAP expression, tissue accumulation of plasmid DNA, and plasmid DNA stability was then characterized. We observed that mixtures containing zinc/DNA, ATA/DNA, and zinc/ATA/DNA significantly enhanced both systemic transgene expression and the amount of plasmid DNA associated with treated tissues. The relative endonuclease inhibitory activity of zinc, ATA, and zinc/ATA correlated with the observed effects on transfection efficacy. The use of zinc/ATA enhanced the efficacy of salivary gland transfection by at least 1000-fold versus DNA alone. Importantly, this improved performance resulted in robust systemic secretion of an exogenous protein (SEAP), thus demonstrating the potential this nonviral gene transfer technology has as a method to treat systemic protein deficiencies.

The effect of childbirth on pelvic organ mobility.

OBJECTIVE: To study the effect of child birth on pelvic organ mobility in a prospective observational study. METHODS: A total of 200 women were recruited early in their first ongoing pregnancy and examined by translabial ultrasound in the first/early second trimester, the late third trimester, and 2-5 months postpartum. Peripartal changes in the mobility of urethra, bladder, cervix, and rectal ampulla were correlated with labor and delivery data. RESULTS: A total of 169 women returned postpartum (84.5%). Highly significant increases in organ mobility on Valsalva were found after vaginal delivery (P <.001), with forceps causing the most marked changes. Length of second stage, especially active second stage, correlated with an increase in pelvic organ descent (P =.03 to P <.001). The influence of gestational age, length of first stage, and birth weight did not reach significance. CONCLUSION: Vaginal birth, in particular operative delivery, negatively affects pelvic organ support. This appears to be true for all three vaginal compartments. All forms of cesarean delivery were associated with relatively less pelvic organ descent. These findings may partly explain the protective effect of elective cesarean delivery for future symptoms of pelvic floor disorders.

Flow measurements via two-particle azimuthal correlations in Au + Au collisions at sqrt [s(NN)]=130 GeV.

Two-particle azimuthal correlation functions are presented for charged hadrons produced in Au+Au collisions at the Relativistic Heavy Ion Collider (sqrt [s(NN)]=130 GeV). The measurements permit determination of elliptic flow without event-by-event estimation of the reaction plane. The extracted elliptic flow values (v2) show significant sensitivity to both the collision centrality and the transverse momenta of emitted hadrons, suggesting rapid thermalization and relatively strong velocity fields. When scaled by the eccentricity of the collision zone epsilon, the scaled elliptic flow shows little or no dependence on centrality for charged hadrons with relatively low p(T). A breakdown of this epsilon scaling is observed for charged hadrons with pT >1.0 GeV/c.

Measurement of Lambda and Lambda(macro) particles in Au+Au collisions at the square root of S(NN) = 130 GeV.

We present results on the measurement of Lambda and Lambda(macro) production in Au+Au collisions at square root of (S (NN) = 130 GeV with the PHENIX detector at the Relativistic Heavy Ion Collider. The transverse momentum spectra were measured for minimum bias and for the 5% most central events. The Lambda;/Lambda ratios are constant as a function of p(T) and the number of participants. The measured net Lambda density is significantly larger than predicted by models based on hadronic strings (e.g., HIJING) but in approximate agreement with models which include the gluon-junction mechanism.

Net charge fluctuations in Au + Au interactions at sqrt[s(NN)]=130 GeV.

Data from Au + Au interactions at sqrt[s(NN)]=130 GeV, obtained with the PHENIX detector at the Relativistic Heavy-Ion Collider, are used to investigate local net charge fluctuations among particles produced near midrapidity. According to recent suggestions, such fluctuations may carry information from the quark-gluon plasma. This analysis shows that the fluctuations are dominated by a stochastic distribution of particles, but are also sensitive to other effects, like global charge conservation and resonance decays.

Centrality dependence of pi(+/-), K(+/-), p, and (-)p production from sqrt[s(NN)] = 130 GeV Au + Au collisions at RHIC.

Identified pi(+/-), K(+/-), p, and (-)p transverse momentum spectra at midrapidity in sqrt[s(NN)] = 130 GeV Au+Au collisions were measured by the PHENIX experiment at RHIC as a function of collision centrality. Average transverse momenta increase with the number of participating nucleons in a similar way for all particle species. Within errors, all midrapidity particle yields per participant are found to be increasing with the number of participating nucleons. There is an indication that K(+/-), p, and (-)p yields per participant increase faster than the pi(+/-) yields. In central collisions at high transverse momenta (p(T) > or =2 GeV/c), (-)p and p yields are comparable to the pi(+/-) yields.

Evidence for fatty acid oxidation in human placenta, and the relationship of fatty acid oxidation enzyme activities with gestational age.

Fetal disorders of mitochondrial fatty acid oxidation have recently been associated with obstetric complications including pre-eclampsia, Hemolysis, Elevated Liver enzymes, Low Platelets (HELLP) syndrome, placental floor infarct, and Acute Fatty Liver of Pregnancy (AFLP). These diseases occur in about a third of the mothers who are heterozygous for a defect in long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) enzyme and who bear a fetus homozygous for the defect. The mechanism of this association is not clearly understood. In this study, we provide evidence that the placenta may be the site of production of toxic intermediates of fatty acid metabolism, which accumulate to cause liver damage in the mother. We show that two critical enzymes of long chain fatty acid metabolism, long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) and short chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD), are active in the normal human placenta. There is an inverse correlation between the enzyme activity of both the enzymes and maternal gestational age during the second and third trimesters. We believe that the demonstration of fatty acid oxidation enzyme activity by the placenta is the first step towards assessing a possible role for fetal/placental fatty acid oxidation defects in the pathogenesis of a subset of pregnancy complications.