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Terms modified by F3 Selected AbstractsConditional expression of a myocardium-specific transgene in zebrafish transgenic linesDEVELOPMENTAL DYNAMICS, Issue 4 2005Chiu-Ju Huang Abstract To develop the first heart-specific tetracycline (Tet)-On system in zebrafish, we constructed plasmids in which the cardiac myosin light chain 2 promoter of zebrafish was used to drive the reverse Tet-controlled transactivator (rtTA) and the green fluorescent protein (GFP) reporter gene was preceded by an rtTA-responsive element. In the zebrafish fibroblast cell-line, rtTA-M2, one of rtTA's derivatives, demonstrated the highest increase in luciferase activity upon doxycycline (Dox) induction. We then generated two germ lines of transgenic zebrafish: line T03 was derived from microinjection of a plasmid containing rtTA-M2 and a plasmid containing a responsive reporter gene, whereas line T21 was derived from microinjection of a single dual plasmid. Results showed that line T21 was superior to line T03 in terms of greater GFP intensity after induction and with of minimal leakiness before induction. The photographic images of induced GFP in the heart of F2 larvae showed that the fluorescent level of GFP was dose-responsive. The level of GFP expressed in the F3 3 days postfertilization larvae that were treated with Dox for 1 hr decreased gradually after the withdrawal of the inducer; and the fluorescent signal disappeared after 5 days. The GFP induction and reduction were also tightly controlled by Dox in the F3 adult fish from line T21. This Tet-On system developed in zebrafish shows much promise for the study of the gene function in a specific tissue at the later developmental stage. Developmental Dynamics 233:1294,1303, 2005. © 2005 Wiley-Liss, Inc. [source] Exposure of three generations of the estuarine sheepshead minnow (Cyprinodon variegatus) to the androgen, 17,-trenbolone: Effects on survival, development, and reproductionENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 9 2010Geraldine M. Cripe Abstract Estimating long-term effects of endocrine-disrupting chemicals on a species is important to assessing the overall risk to the populations. The present study reports the results of a 42-week exposure of estuarine sheepshead minnows (Cyprinodon variegatus) to the androgen, 17,-trenbolone (Tb) conducted to determine if partial-(F0) or single-generation (F1) fish exposures identify multigenerational (F0,F3) effects of androgens on fish. Adult F0 fish were exposed to 0.007, 0.027, 0.13, 0.87,and 4.1,µg Tb/L, the F1 generation to ,0.87,µg Tb/L, the F2 fish to ,0.13,µg Tb/L, and the F3 fish to ,0.027,µg Tb/L. The highest concentrations with reproducing populations at the end of the F0, F1, and F2 generations were 4.1, 0.87, and 0.027,µg Tb/L, respectively. Reproduction in the F0, F1, and F2 generations was significantly reduced at 0.87, 0.027, and 0.027,µg Tb/L, respectively. Fish were significantly masculinized in the F1 generation exposed to 0.13 µg Tb/L or greater. Female plasma vitellogenin was significantly reduced in F0 fish exposed to ,0.87,µg Tb/L. Gonadosomatic indices of the F0 and F1 generations were significantly increased at 0.87 and 0.13 µg Tb/L in the F0 and F1 generation, respectively, and were accompanied by ovarian histological changes. Reproduction was the most consistently sensitive measure of androgen effects and, after a life-cycle exposure, the daily reproductive rate predicted concentrations affecting successive generations. The present study provides evidence that a multiple generation exposure of fish to some endocrine-disrupting chemicals can result in developmental and reproductive changes that have a much greater impact on the success of a species than was indicated from shorter term exposures. Environ. Toxicol. Chem. 2010;29:2079,2087. © 2010 SETAC [source] Effects of unilateral laser-assisted ventriculocordectomy in horses with laryngeal hemiplegiaEQUINE VETERINARY JOURNAL, Issue 6 2006P. ROBINSON Summary Reasons for performing study: Recent studies have evaluated surgical techniques aimed at reducing noise and improving airway function in horses with recurrent laryngeal neuropathy (RLN). These techniques require general anaesthesia and are invasive. A minimally invasive transnasal surgical technique for treatment of RLN that may be employed in the standing, sedated horse would be advantageous. Objective: To determine whether unilateral laser-assisted ventriculocordectomy (LVC) improves upper airway function and reduces noise during inhalation in exercising horses with laryngeal hemiplegia (LH). Methods: Six Standardbred horses were used; respiratory sound and inspiratory transupper airway pressure (Pui) measured before and after induction of LH, and 60, 90 and 120 days after LVC. Inspiratory sound level (SL) and the sound intensities of formants 1, 2 and 3 (F1, F2 and F3, respectively), were measured using computer-based sound analysis programmes. In addition, upper airway endoscopy was performed at each time interval, at rest and during treadmill exercise. Results: In LH-affected horses, Pui, SL and the sound intensity of F2 and F3 were increased significantly from baseline values. At 60 days after LVC, Pui and SL had returned to baseline, and F2 and F3 values had improved partially compared to LH values. At 90 and 120 days, however, SL increased again to LH levels. Conclusions: LVC decreases LH-associated airway obstruction by 60 days after surgery, and reduces inspiratory noise but not as effectively as bilateral ventriculocordectomy. Potential relevance: LVC may be recommended as a treatment of LH, where reduction of upper airway obstruction and respiratory noise is desired and the owner wishes to avoid risks associated with a laryngotomy incision or general anaesthesia. [source] Synthesis and Structure Determination of Selenium(IV) CyanidesEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 30 2008Stefanie Fritz Abstract The reaction of SeF4 with Me3SiCN did not result in thepreparation of the designated Se(CN)4 but Se(CN)F3 and Se(CN)2F2 were obtained as first known selenium(IV)cyanide compounds and characterized by their NMR spectra. Se(CN)2F2 was crystallized as 1,2-dimethoxyethane solvate as well as the corresponding tellurium compound Te(CN)2F2 with very similar structures. NMR spectroscopic data of some more miscellaneous tellurium cyanides and the crystal structures of solvates of Se(CN)2 and oxygen-bridged TeO(CN)2 are presented. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] Mu-35: A Fluorogallophosphate Obtained by In Situ Generation of the TemplateEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 25 2007Louwanda Lakiss Abstract A two-dimensional microporous fluorogallophosphate, named Mu-35, closely related to ULM-8, was hydrothermally synthesized by in situ generation of the structure-directing agent. The precursor of the structure-directing agent is ethylformamide, which is generated in situ by decomposition, and goes on to form ethylamine molecules that act as templates in the medium used for the synthesis. The fluorogallophosphate Mu-35 (Mu is Mulhouse), Ga3(PO4)2(HPO4)F3(C2H8N)2(C2H7N)0.5 (Z = 8), crystallizes in the orthorhombic space group Pbcn with the following unit cell parameters: a = 22.117(1), b = 17.3740(8), c = 10.1550(4) Å. The structure of fluorogallophosphate Mu-35 was determined from single-crystal XRD data. It exhibits anionic layers composed of an unusual arrangement of three-, five-, and eight-membered rings (MR) [Ga2PO2F, Ga3P2O4F, and Ga3P3O8, respectively], and intercalated by protonated and nonprotonated ethylamine molecules. Mu-35 was also characterized by powder XRD, SEM, elemental and thermal analyses, and solid-state NMR spectroscopy (1H, 13C, 19F, and 31P MAS and 1H- 31P HETCOR experiments). (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] Myristyl and palmityl acylation of pI 5.1 carboxylesterase from porcine intestine and liverFEBS JOURNAL, Issue 4 2002Tissue, subcellular distribution Immunoblotting analyses revealed the presence of carboxylesterase in the porcine small intestine, liver, submaxillary and parotid glands, kidney cortex, lungs and cerebral cortex. In the intestinal mucosa, the pI 5.1 enzyme was detected in several subcellular fractions including the microvillar fraction. Both fatty monoacylated and diacylated monomeric (F1), trimeric (F3) and tetrameric (F4) forms of the intestinal protein were purified here for the first time by performing hydrophobic chromatography and gel filtration. The molecular mass of these three enzymatic forms was,estimated to be 60, 180 and 240 kDa, respectively, based on size-exclusion chromatography and SDS/PAGE analysis. The existence of a covalent attachment linking palmitate and myristate to porcine intestinal carboxylesterase (PICE), which was suggested by the results of gas-liquid chromatography (GLC) experiments in which the fatty acids resulting from alkali treatment of the protein forms were isolated, was confirmed here by the fact that [3H]palmitic and [3H]myristic acids were incorporated into porcine enterocytes and hepatocytes in cell primary cultures. Besides these two main fatty acids, the presence of oleic, stearic, and arachidonic acids was also detected by GLC and further confirmed by performing radioactivity counts on the 3H-labelled PICE forms after an immunoprecipitation procedure using specific polyclonal antibodies, followed by a SDS/PAGE separation step. Unlike the F1 and F4 forms, which were both myristoylated and palmitoylated, the F3 form was only palmitoylated. The monomeric, trimeric and tetrameric forms of PICE were all able to hydrolyse short chain fatty acids containing glycerides, as well as phorbol esters. The broad specificity of fatty acylated carboxylesterase is discussed in terms of its possible involvement in the metabolism of ester-containing xenobiotics and signal transduction. [source] Estimation of stage-specific fibrosis progression rates in chronic hepatitis C virus infection: A meta-analysis and meta-regression,HEPATOLOGY, Issue 2 2008Hla-Hla Thein Published estimates of liver fibrosis progression in individuals with chronic hepatitis C virus (HCV) infection are heterogeneous. We aimed to estimate stage-specific fibrosis progression rates and their determinants in these individuals. A systematic review of published prognostic studies was undertaken. Study inclusion criteria were as follows: (1) presence of HCV infection determined by serological assays; (2) available information about age at assessment of liver disease or HCV acquisition; (3) duration of HCV infection; and (4) histological and/or clinical diagnosis of cirrhosis. Annual stage-specific transition probabilities (F0,F1, , , F3,F4) were derived using the Markov maximum likelihood estimation method and a meta-analysis was performed. The impact of potential covariates was evaluated using meta-regression. A total of 111 studies of individuals with chronic HCV infection (n = 33,121) were included. Based on the random effects model, the estimated annual mean (95% confidence interval) stage-specific transition probabilities were: F0,F1 0.117 (0.104,0.130); F1,F2 0.085 (0.075,0.096); F2,F3 0.120 (0.109,0.133); and F3,F4 0.116 (0.104,0.129). The estimated prevalence of cirrhosis at 20 years after the infection was 16% (14%,19%) for all studies, 18% (15%,21%) for cross-sectional/retrospective studies, 7% (4%,14%) for retrospective-prospective studies, 18% (16%,21%) for studies conducted in clinical settings, and 7% (4%,12%) for studies conducted in nonclinical settings. Duration of infection was the most consistent factor significantly associated with progression of fibrosis. Conclusion: Our large systematic review provides increased precision in estimating fibrosis progression in chronic HCV infection and supports nonlinear disease progression. Estimates of progression to cirrhosis from studies conducted in clinical settings were lower than previous estimates. (HEPATOLOGY 2008.) [source] Reversibility of hepatic fibrosis in treated genetic hemochromatosis: A study of 36 cases,HEPATOLOGY, Issue 2 2006Ludivine Falize The current study was undertaken to assess whether fibrosis could regress under venesection therapy in patients with C282Y homozygous genetic hemochromatosis. The 36 patients studied were recruited from a subfile of our database consisting of 125 C282Y homozygotes with either severe fibrosis or cirrhosis (F3 or F4 fibrosis stage, respectively, according to the METAVIR grading system). The second liver biopsy was performed for management of liver cancer, extrahepatic surgery, or assessment of liver fibrosis. All paired biopsies were reviewed by two pathologists without knowledge of clinical data. Among the 13 patients who had F3 fibrosis on their initial liver biopsy, 3 had F0, 6 had F1, and 2 had F2 on their second liver biopsy. Among the 23 patients with cirrhosis on their initial liver biopsy, 1 had F0, 4 had F1, 3 had F2, and 2 had F3 on their second liver biopsy. When defining regression of fibrosis as a decrease of at least 2 METAVIR units, fibrosis regressed in 9 of 13 (69%) F3 and in 8 of 23 (35%) F4. When the ratio of gammaglobulins (g/L) to (platelets [n/mm3] × prothrombin activity [%]) was greater than 7.5, fibrosis never regressed. In conclusion, these data extend the concept of regression of fibrosis to patients with treated genetic hemochromatosis and suggest that some simple biochemical tests would be predictive of further regression of fibrosis as a result of venesection therapy. If confirmed on larger series, this could modify the ultrasound screening policy of hepatocellular carcinoma in genetic hemochromatosis. (HEPATOLOGY 2006;44:472,477.) [source] Usefulness of transient elastography for assessment of liver fibrosis in chronic hepatitis B: Regression of liver stiffness during entecavir therapyHEPATOLOGY RESEARCH, Issue 9 2010Masaru Enomoto Aim:, The usefulness of transient elastography remains to be validated in chronic hepatitis B, particularly as a tool for monitoring the degree of liver fibrosis during treatment. Methods:, The subjects were 50 patients with chronic hepatitis B virus infection. Liver biopsy was performed in 38 patients, and in 12 patients with platelet counts of 50 × 109/L or less, cirrhosis was clinically diagnosed on the basis of specific signs of portal hypertension. Liver stiffness was measured by transient elastography at baseline and after 12 months of treatment in 20 nucleos(t)ide-naïve patients who started entecavir within 3 months after study entry. Results:, Twenty (40%) patients were classified as F1, 10 (20%) as F2, 5 (10%) as F3, and 15 (30%) as F4 (cirrhosis). Median liver stiffness (interquartile range) was 7.0 kPa (5.6,9.4), 9.8 kPa (5.6,14.7), 9.8 kPa (7.6,12.9), and 17.3 kPa (8.2,27.6) in fibrosis stages F1 to F4, respectively. Liver stiffness significantly correlated with fibrosis stage (r = 0.46; P = 0.0014). Of the patients who started entecavir, median liver stiffness significantly decreased from 11.2 kPa (7.0,15.2) to 7.8 kPa (5.1,11.9; P = 0.0090) during 12 months of treatment. Median levels of amino-terminal peptide of type III procollagen and type IV collagen 7S domain in serum significantly decreased from 0.9 (0.6,1.3) to 0.6 (0.5,0.7) U/mL (P = 0.0010) and from 5.0 (4.4,6.7) to 3.9 (3.2,4.4) ng/mL (P = 0.015), respectively. Conclusion:, Liver stiffness measurement can be useful for monitoring regression of liver fibrosis during entecavir treatment in patients with chronic hepatitis B virus infection. [source] Neuropsychiatric dysfunction in patients with chronic hepatitis and liver cirrhosisHEPATOLOGY RESEARCH, Issue 11 2008Kojiro Michitaka Aim:, The aim of this study is to clarify the cerebral functions in patients with chronic hepatitis (CH) as well as those with liver cirrhosis (LC). Methods:, We studied 58 patients with CH (20 in fibrosis stage F1, 20 in F2, 18 in F3), 77 with LC (46 rated as Child,Pugh class A, 24 as B, 7 as C), and 20 healthy volunteers (HV). Computer-aided quantitative neuropsychiatric function test systems, including eight neuropsychiatric tests were performed. Results:, Subjects with results over the cut-off value for healthy subjects ranged from 11.1,28.6% in CH and 19.5,36.4% in LC. The percentages with abnormality in at least one test in CH and LC were 72.4% and 80.6%, respectively, which were significantly higher than that in the HV group (35.0%) (P = 0.003, P = 0.0003, respectively). Among CH subjects, those with three or more abnormal results in the F1, F2 and F3 subgroups were 15.0%, 20.0% and 38.9%, respectively. Among LC subjects, those with three or more abnormal results in the Child,Pugh class A, B and C subgroups comprised 30.4%, 50.0% and 57.1%, respectively. The rate in the CH F3 subgroup (P = 0.011) and in all three LC subgroups (P = 0.023, P = 0.001, P = 0.002, respectively) were significantly higher than that in the HV group. Conclusion:, The percentage of patients with neuropsychiatric function impairment was high in both LC and CH, especially in stage F3. Neuropsychiatric dysfunction may initiate in CH in a considerable number of patients. [source] SEM evaluation of root canal debridement with Sonicare CanalBrush irrigationINTERNATIONAL ENDODONTIC JOURNAL, Issue 5 2010M. I. Salman Salman MI, Baumann MA, Hellmich M, Roggendorf MJ, Termaat S. SEM evaluation of root canal debridement with Sonicare CanalBrush irrigation. International Endodontic Journal, 43, 363,369, 2010. Abstract Aim, To determine the efficacy of Sonicare CanalBrush irrigation for root canal cleaning. Methodology, Fifty human molar root canals were shaped with sequential NiTi rotary instruments up to size F3 (size 30, 0.09 taper; ProTaper system) and then enlarged apically with a Profile size 40, 0.04 taper. Five different irrigation protocols were tested (n = 10 canals per group) with 2 mL of distilled water (control, group I) or 2.5% NaOCl (control group II and test groups III, IV and V) between instrument size changes. Group III,IV received a final rinse with 17% EDTA for one min. This was extended by 30 s in group IV, whereas group V received this additional 30 s of 17% EDTA sonically dispersed with a Sonicare CanalBrush. For cleanliness evaluations, roots were split longitudinally, examined with scanning electron microscopy and scored according to Hülsmann et al. (1997) for debris and smear layer on the surface of the root canal wall. Walls were assessed at the coronal, middle and apical thirds. Data were analysed with the Kruskal,Wallis and Mann,Whitney tests. Results, Irrigation with 17% EDTA significantly reduced debris and smear layer scores (P < 0.05) compared to controls. The coronal and middle thirds had lower debris and smear layer scores than the apical third (P < 0.05). In all thirds, sonic agitation of the irrigant with a CanalBrush (group V) resulted in significantly cleaner canal walls compared to all other groups (P < 0.05). Conclusions, Irrigation by agitation with the Sonicare CanalBrush improved root canal debridement in the coronal, middle and particularly the apical thirds of the root canal. [source] Changes in compaction stress distributions in roots resulting from canal preparationINTERNATIONAL ENDODONTIC JOURNAL, Issue 12 2006A. Versluis Abstract Aim, To examine if canal enlargement with instruments of controlled taper leads to more uniform stress distributions within a root, thereby reducing fracture susceptibility. Methodology, Finite element models of a mandibular incisor were constructed with round and oval canal profiles, based on measurements from extracted teeth. The shapes of rotary nickel,titanium instruments (ProTaper F1, F2, and F3 and ProFile size 30, 0.04 taper and size 30, 0.06 taper; Dentsply Maillefer) were superimposed on the canals. Equivalent stresses and circumferential stresses in the root were calculated for a compaction load. Results, The highest stresses were found at the canal wall. Round canals showed lower uniform distributions, whilst oval canals showed uneven distributions with high concentrations at the buccal and lingual canal extensions and greater stresses in the coronal and middle thirds than in the apical third. Preparation of round canals introduced only small circumferential stress increases in the apical half; preparation of oval canals produced substantial reductions where the canal was enlarged to a smooth round shape. Even where fins were not completely eliminated, the maximum stresses were still reduced by up to 15%. External distal and mesial surfaces of roots with oval canals showed moderate stress concentrations that were minimally affected by preparations, whilst stress concentrations emerged on roots with round canals when preparation sizes increased. Conclusions, The potential for reducing fracture susceptibility exists as a result of round canal profiles achieved and smooth canal taper. Even when fins were not contacted by the instrument, stresses within the root were lower and more evenly distributed than before preparation. [source] Quetiapine indication shift in the elderly: diagnosis and dosage in 208 psychogeriatric patients from 2000 to 2006INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 5 2007Lorenz Hilwerling Abstract Rationale Quetiapine was approved in Germany as an atypical antipsychotic for treatment of schizophrenia in 2000, followed by the approval as an antipsychotic for treatment of bipolar mania in 2003. The approval of quetiapine for treatment of bipolar depression is expected. We hypothesized that the psychogeriatric prescription pattern for quetiapine shifts from the psychotic to the affective spectrum. Methods Retrospectively we screened discharge reports of all geriatric inpatients of the psychiatric department of the Ruhr-University of Bochum in the period from January 2001 until March 2006 and identified 208 individual patients aged over 60 years, who had received quetiapine as final medication. Age, gender, daily drug dose, year of treatment and diagnosis (according to ICD-10) were recorded and analyzed. Results Over the six-year time span, the proportion of affective disorders (F3) as indication for quetiapine in the elderly increased, whereas the proportion of dementia (F0) as indication for quetiapine decreased significantly. The proportion of schizophrenic disorders (F2) treated with quetiapine did not change significantly. Discussion Since the decision of the German Federal Court in 2002 ,off label' use goes to the expenses of the prescriber. So the decrease of quetiapine in dementia is probably due to its ,off label' status in dementia. The psychogeriatric indication shift for quetiapine towards affective disorders could be the consequence of good clinical experiences with the drug and growing evidence for its antidepressant effect. Conclusion In addition to controlled pharmacological trials prospective clinical research is needed to evaluate the prescription attitudes of clinicians. Copyright © 2006 John Wiley & Sons, Ltd. [source] Validity of FibroScan values for predicting hepatic fibrosis stage in patients with chronic HCV infectionJOURNAL OF DIGESTIVE DISEASES, Issue 2 2009Ryosuke TAKEMOTO OBJECTIVE: The aim of this study was to validate the FibroScan system compared with liver histology and serum markers for the diagnosis of hepatic fibrosis. We also tried to determine the cut-off levels and assess the feasibility of using FibroScan values to predict the fibrosis stage. METHODS: In 44 patients with HCV infection, liver stiffness was evaluated by FibroScan, serum fibrosis markers and a liver biopsy. Associations between these indices were also analyzed. RESULTS: FibroScan values showed a good correlation with serum levels of type IV collagen, hyaluronic acid and procollagen-III-peptide, and with the platelet count. Compared with liver histology, the FibroScan values increased proportionally with the progression of the histological fibrosis stage. Advanced fibrosis (F3 or F4) could be efficiently predicted by a FibroScan cut-off value of 15 kPa. The FibroScan sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 100%, 73.9%, 77.8%, 100%, and 86.4%, respectively. CONCLUSION: FibroScan values gave a good correlation with various markers of fibrosis and increased proportionally with the progression of the hepatic fibrosis stage. A FibroScan value of 15 kPa was found to be a significant separation limit for differentiating advanced fibrosis stages (F3 and F4) from the milder stages (F0,F2). FibroScan values are clinically useful for predicting the fibrosis stages and helpful in managing interferon therapy in patients with chronic hepatitis C. [source] A disaggregated empirical analysis of the determinants of IMF arrangements: Does one model fit all?JOURNAL OF INTERNATIONAL DEVELOPMENT, Issue 7 2009Graham Bird JEL: F33, F3 Abstract Does one model fit all when it comes to the determinants of IMF programs? Certainly claims have been made by the IMF that capital account crisis (CAC) countries are discernibly different in terms of the characteristics that lead them to borrow from it, while other research has claimed that it is only Asian economies that are different from the rest. This paper sets out to examine these issues. It tests various forms of a fairly conventional model to see whether some forms better fit certain groups of countries than others. It then uses the favoured models to estimate the probability of countries having an IMF arrangement. In particular it examines countries that have been identified by the Fund as CAC countries, but it also looks at a number of comparator countries. The findings suggest that there are some differences between low income and middle income countries. Pressures in the foreign exchange market are significant for the latter but not for the former. The paper also discusses differences between regions and within regions. Broadly speaking the findings confirm that Asian economies around the time of the 1997/1998 crisis tended to turn to the IMF for financial support more quickly than would have been anticipated on the basis of the existing best-fitting models. The paper also discusses the implications of the findings for policy and for the reform of the IMF. Copyright © 2008 John Wiley & Sons, Ltd. [source] Molecular dynamics simulation of human neurohypophyseal hormone receptors complexed with oxytocin,modeling of an activated stateJOURNAL OF PEPTIDE SCIENCE, Issue 3 2006Magdalena J., lusarz Abstract The neurohypophyseal hormone oxytocin (CYIQNCPLG-NH2, OT) is involved in the control of labor, secretion of milk and many social and behavioral functions via interaction with its receptors (OTR) located in the uterus, mammary glands and peripheral tissues, respectively. In this paper we propose the interactions responsible for OT binding and selectivity to OTR versus vasopressin ([F3,R8]OT, AVP) receptors: V1aR and V2R, all three belonging to the Class A G protein-coupled receptors (GPCRs). Three-dimensional models of the activated receptors were constructed using a multiple sequence alignment and the activated rhodopsin,transducin (MII,Gt) prototype [,lusarz and Ciarkowski, 2004] as a template. The 1 ns unconstrained molecular dynamics (MD) of three pairs of receptor,OT complexes (two complexes per each receptor) immersed in the fully hydrated 1-palmitoyl-2-oleoyl- sn -glycero-3-phosphatidylcholine (POPC) lipid bilayer was conducted in the AMBER 7.0 force field. The relaxed models of ligand,receptor complexes were used to identify the putative binding sites of OT. The stabilizing interactions with conserved Gln residues in all complexes were identified. The nonconserved hydrophobic residues were proposed as responsible for OTR,OT selectivity and ligand recognition. These results provide guidelines for experimental site-directed mutagenesis and if confirmed, they may be helpful in designing new selective OT analogs with both agonistic or antagonistic properties. Copyright © 2005 European Peptide Society and John Wiley & Sons, Ltd. [source] Genetic Analysis of Tolerance to Rice Tungro Bacilliform Virus in Rice (Oryza sativa L.) Through AgroinoculationJOURNAL OF PHYTOPATHOLOGY, Issue 4 2006N. S. Zenna Abstract Balimau Putih [an Indonesian cultivar tolerant to rice tungro bacilliform virus (RTBV)] was crossed with IR64 (RTBV, susceptible variety) to produce the three filial generations F1, F2 and F3. Agroinoculation was used to introduce RTBV into the test plants. RTBV tolerance was based on the RTBV level in plants by analysis of coat protein using enzyme-linked immunosorbent assay. The level of RTBV in cv. Balimau Putih was significantly lower than that of IR64 and the susceptible control, Taichung Native 1. Mean RTBV levels of the F1, F2 and F3 populations were comparable with one another and with the average of the parents. Results indicate that there was no dominance and an additive gene action may control the expression of tolerance to RTBV. Tolerance based on the level of RTBV coat protein was highly heritable (0.67) as estimated using the mean values of F3 lines, suggesting that selection for tolerance to RTBV can be performed in the early selfing generations using the technique employed in this study. The RTBV level had a negative correlation with plant height, but positive relationship with disease index value. [source] Synthesis and characterization of poly[styrene- b -methyl(3,3,3-trifluoropropyl)siloxane] diblock copolymers via anionic polymerizationJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 19 2005Lingmin Yi Abstract A series of narrow molecular weight distribution (MWD) polystyrene- b -poly[methyl(3,3,3-trifluoropropyl)siloxane] (PS- b -PMTFPS) diblock copolymers were synthesized by the sequential anionic polymerization of styrene and trans -1,3,5-trimethyl-1,3,5-tris(3,,3,,3,-trifluoropropyl)cyclotrisiloxane in tetrahydrofuran (THF) with n -butyllithium as the initiator. The diblock copolymers had narrow MWDs ranging from 1.06 to 1.20 and number-average molecular weights ranging from 8.2 × 103 to 37.1 × 103. To investigate the properties of the copolymers, diblock copolymers with different weight fractions of poly[methyl(3,3,3-trifluoropropyl)siloxane] (15.4,78.8 wt %) were prepared. The compositions of the diblock copolymers were calculated from the characteristic proton integrals of 1H NMR spectra. For the anionic ring-opening polymerization (ROP) of 1,3,5-trimethyl-1,3,5-tris(3,,3,,3,-trifluoropropyl)cyclotrisiloxane (F3) initiated by polystyryllithium, high monomer concentrations could give high polymer yields and good control of MWDs when THF was used as the polymerization solvent. It was speculated that good control of the block copolymerization under the condition of high monomer concentrations was due to the slowdown of the anionic ROP rate of F3 and the steric hindrance of the polystyrene precursors. There was enough time to terminate the ROP of F3 when the polymer yield was high, and good control of block copolymerization could be achieved thereafter. The thermal properties (differential scanning calorimetry and thermogravimetric analysis) were also investigated for the PS- b -PMTFPS diblock copolymers. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 4431,4438, 2005 [source] Factors that affect the diagnostic accuracy of liver fibrosis measurement by Fibroscan in patients with chronic hepatitis BALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2010S. U. Kim Aliment Pharmacol Ther 2010; 32: 498,505 Summary Background, Interquartile range/median value (IQR/M) of liver stiffness measurement (LSM) is a factor in chronic hepatitis C (CHC) leading to over estimation of fibrosis by Fibroscan. Aim, To investigate factors that affect the accuracy of LSM in chronic hepatitis B (CHB). Methods, One hundred and ninety-nine patients were enrolled. Only procedures yielding ,10 valid measurements were considered reliable. Liver fibrosis was evaluated using the Batts and Ludwig system. Liver biopsy (LB) specimens <15 mm were considered ineligible. Results, The mean age (142 men and 57 women) was 40.1 years. A significant discordance (discordance of at least two stages between LB and LSM) was identified in 38 (19.1%) and 47 (23.6%) patients respectively, according to Marcellin et al. and Chan et al.'s cutoff values. In multivariate analyses, BMI and fibrosis stage (F0,2 vs. F3,4) were identified as independent predictors for significant discordance (P = 0.040; hazard ratio [HR], 1.126; 95% confidence interval [CI], 1.005,1.261 and P = 0.036; HR, 0.450; 95% CI, 0.213,0.949 respectively) with Marcellin et al.'s cutoffs, whereas fibrosis stage was the only independent predictor (P = 0.004; HR, 0.300; 95% CI, 0.131,0.685) with Chan's cutoffs. Conclusions, Success rate and IQR/M were not predictive factors of the accuracy for diagnosing liver fibrosis by Fibroscan in CHB. Fibrosis stage (F0-2) was the only factor to predict significant discordance between LB and LSM. [source] Development of a non-invasive algorithm with transient elastography (Fibroscan) and serum test formula for advanced liver fibrosis in chronic hepatitis BALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2010G. L. H. WONG Aliment Pharmacol Ther,31, 1095,1103 Summary Background, Non-invasive assessments of liver fibrosis in chronic hepatitis B were well established. Aim, To develop a combined algorithm of liver stiffness measurement (LSM) and serum test formula to predict advanced liver fibrosis in chronic hepatitis B. Methods, We reported an alanine aminotransferase (AST)-based LSM algorithm for liver fibrosis in 156 chronic hepatitis B patients, which formed the training cohort to evaluate the performance of APRI (AST-to-platelet-ratio-index), Forns index, FIB-4 and Fibroindex against liver histology. The best combined LSM-serum formula algorithm would be validated in another cohort of 82 chronic hepatitis B patients. Results, In the training cohort, LSM has the best performance of diagnosing advanced (,F3) fibrosis [area under the receiver operating characteristics curve (AUROC) 0.88, 95% confidence interval (CI) 0.85,0.91], while Forns index has the best performance among the various serum test formulae (AUROC 0.70, 95% CI 0.62,0.78). In the combined algorithm, low LSM or low Forns index could be used to exclude advanced fibrosis as both of them had high sensitivity (>90%). To confirm advanced fibrosis, agreement between high LSM and high Forns index could improve the specificity (from 99% to 100% and from 87% to 98% in the training and validation cohorts respectively). Conclusion, A combined LSM,Forns algorithm can improve the accuracy to predict advanced liver fibrosis in chronic hepatitis B. [source] Insulin resistance is a major determinant of liver stiffness in nondiabetic patients with HCV genotype 1 chronic hepatitisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2009S. PETTA Summary Background, In patients with chronic hepatitis C (CHC), liver stiffness measurement (LSM) by transient elastography (TE), is closely related to the stage of fibrosis, but may be affected by necroinflammation. Other factors, such as insulin resistance (IR), might influence the performance of LSM. Aims, To evaluate in a cohort of nondiabetic patients with genotype 1 CHC, whether IR and other anthropometric, biochemical, metabolic and histological factors contribute to LSM and to identify the best cut-off values of LSM for predicting different stages of fibrosis. Methods, Nondiabetic patients with genotype 1 CHC (n = 156) were evaluated by liver biopsy (Metavir score), anthropometric, biochemical and metabolic features including IR. Furthermore, all subjects underwent LSM by TE. Results, Severe fibrosis (F3,F4) was associated with LSM (OR 1.291; 95%CI 1.106,1.508). LSM was also independently correlated with low platelets (P = 0.03), high ,GT (P < 0.001) and high HOMA (P = 0.004) levels. A stiffness value ,8 KPa was identified as the best cut-off for predicting severe fibrosis (AUC 0.870); yet this cut-off still failed to rule out F3,F4 fibrosis in 22.7% of patients (false-negative rate) or rule in F3,F4 in 19.6% (false-positive rate). Platelets <200 × 103/mmc and a HOMA of >2.7 were the major determinants of these diagnostic errors in predicting severe fibrosis. Conclusions, In nondiabetic patients with genotype 1 CHC, insulin resistance, ,GT and platelet levels contribute to LSM independently of liver fibrosis. The identification of these three factors contributes to a more correct interpretation of LSM. [source] Response to pegylated interferon plus ribavirin in HIV-infected patients with chronic hepatitis C due to genotype 4JOURNAL OF VIRAL HEPATITIS, Issue 10 2008L. Martín-Carbonero Summary., Hepatitis C virus (HCV) genotypes 1 and 4 respond less well to pegylated interferon (pegIFN) plus ribavirin (RBV) therapy. For this reason most studies merge these two genotypes when assessing virological response. However, in most trials the HCV genotype 4 population is rather small, and conclusions are mainly derived from what occurs in HCV-1 patients. All HCV-4 patients coinfected with HIV who received pegIFN plus RBV in two different multicentre studies, PRESCO and ROMANCE, conducted respectively in Spain and Italy, were retrospectively analyzed. Baseline plasma HCV-RNA, proportion of patients with HCV-RNA <10 IU,/,mL at week 4 (rapid virological response), and HCV-RNA declines >2 logs at week 12 (early virological response, EVR) were all assessed as predictors of sustained virological response (SVR). Overall, 75 patients (60 men) were evaluated. Median age was 40 years and median CD4 count 598 cells,/,mm3; 49% had plasma HIV-RNA <50 copies,,/,,mL; 71% had elevated liver enzymes and 31% had advanced liver fibrosis (Metavir F3,F4). Median serum HCV-RNA was 5.7 log IU,/,mL. Rapid virological response was attained by 10 (20%) patients and EVR by 26 (42%). Using intention-to-treat and on-treatment (OT) analyses, SVR was achieved by 21,/,75 (28%) and 21,/,62 (34%) of HCV-4 patients, respectively. In the multivariate analysis (OT), baseline HCV-RNA (OR 0.09 for every log increment; 95% CI: 0.01,0.7) and EVR (OR: 7.08; 95% CI: 1.8,27.2) were significantly and independently associated with SVR. This is the largest series of HIV-infected patients with chronic hepatitis C due to HCV-4 treated with pegIFN plus RBV examined so far and the results show that HCV-4 behaves similarly to HCV-1. Therefore, these patients should be considered as difficult to treat population. Baseline serum HCV-RNA and EVR are the best predictors of SVR in HCV-4,/,HIV-coinfected patients. [source] Insulin resistance is a major determinant of sustained virological response in genotype 1 chronic hepatitis C patients receiving peginterferon ,-2b plus ribavirinALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2009C.-J. CHU Summary Background, Cross-sectional studies suggest insulin resistance is strongly associated with hepatic steatosis and fibrosis in patients with chronic hepatitis C (CHC), which might affect the efficacy of antiviral therapy. Aim, To investigate retrospectively the impact of insulin resistance on treatment response in Chinese genotype 1 CHC patients receiving a 24-week course therapy with peginterferon ,-2b/ribavirin. Methods, A total of 133 biopsy-proven CHC patients were enrolled for analyses. Insulin resistance was evaluated by homeostasis model assessment of insulin resistance (HOMA-IR). Hepatic fibrosis was graded by the METAVIR scoring system. Results, Mean HOMA-IR progressively elevated along with the severity of hepatic fibrosis (F1,F2 fibrosis: 2.55 ± 0.16 vs. F3,F4 fibrosis: 3.61 ± 0.20, P < 0.001). Compared with patients with sustained virological response (SVR), patients without SVR had significantly higher percentages of F3,F4 fibrosis (62.2% vs. 21.6%, P < 0.001) and baseline high viral load (,600 000 IU/mL; 64.4% vs. 35.6%, P = 0.038). In addition, patients without SVR had significantly higher plasma levels of insulin (15.03 ± 0.89 vs. 10.19 ± 0.55 ,U/mL, P < 0.001) and HOMA-IR values (3.76 ± 0.23 vs. 2.50 ± 0.15, P < 0.001). Multivariate analyses showed that F1,F2 fibrosis (odds ratio: 4.49, P = 0.001), HOMA-IR < 2 (odds ratio: 7.15, P = 0.005) and pre-treatment hepatitis C virus RNA < 600 000 IU/mL (odds ratio: 3.26, P = 0.012) were the independent factors associated with SVR. Conclusions, Insulin resistance is a major determinant of SVR in genotype 1 CHC patients receiving peginterferon ,-2b/ribavirin. Strategies to modify insulin resistance may be effective in enhancing SVR before or during anti-viral therapy. [source] Prevalence, risk factors and causes of discordance in fibrosis staging by transient elastography and liver biopsyLIVER INTERNATIONAL, Issue 10 2010Robert P. Myers Abstract Background and aims: Liver stiffness measurement (LSM) by transient elastography (TE) is widely used for the noninvasive assessment of fibrosis. Our objectives were to examine the prevalence, risk factors and causes of discordance between fibrosis estimated by TE and liver biopsy. Methods: Two hundred and fifty-one patients with hepatitis B, C and nonalcoholic fatty liver disease underwent LSM by TE and liver biopsy. Predictors of discordance (,2 fibrosis stages) between measures, which occurred in 14% of patients (n=35), were identified by comparing patient, TE and biopsy characteristics of discordant and nondiscordant cases. Results: According to predefined criteria, 40% of discordances were attributed to TE error and 23% to biopsy error; 37% were indeterminate. In multivariate analysis, mild fibrosis (F0,2 vs. F3,4), and higher body mass index (BMI), ALT and LSM variability [assessed by the ratio of the interquartile range to median LSM (IQR/M)] were independently associated with discordance. Discordance was three-fold more common in patients with obesity (28 vs. 9%), ALT,60 U/L (20 vs. 7%) and IQR/M ,0.17 (22 vs. 7%; all P<0.005). Based on these variables, a discordance risk score assigning 1 point to each factor was developed. The prevalence of discordance in patients with 0, 1, 2 and 3 factors were 2, 7, 20, and 55% respectively (P<0.0005). Conclusions: Discordance between liver fibrosis estimated by TE and biopsy occurs in one in seven patients. In assessing the validity of TE results, clinicians must recognize risk factors for discordance and in at-risk patients, consider alternative measures including biomarkers and possibly biopsy. [source] Worse recent efficacy of antiviral therapy in liver transplant recipients with recurrent hepatitis C: Impact of donor age and baseline cirrhosis,LIVER TRANSPLANTATION, Issue 7 2009Marina Berenguer We hypothesized that antiviral efficacy [sustained virologic response (SVR)] has improved in recent years in the transplant setting. Our aim was to assess whether the efficacy of pegylated interferon (PegIFN),ribavirin (Rbv) has improved over time. One hundred seven liver transplant patients [74% men, 55.5 years old (range: 37.5,69.5), 86% genotype 1a or 1b] were treated with PegIFN-Rbv for 355 (16,623) days at 20.1 (1.7,132.6) months after transplantation. Tacrolimus was used in 61%. Sixty-seven percent had baseline F3,F4 (cirrhosis: 20.5%). Donor age was 49 (12,78) years. SVR was achieved in 39 (36.5%) patients, with worse results achieved in recent years (2001,2003: n = 27, 46.5%; 2004: n = 23, 43.5%; 2005: n = 21, 35%; 2006 to January 2007: n = 36, 24%; P = 0.043). Variables associated with SVR in the univariate analysis included donor age, baseline viremia and cirrhosis, bilirubin levels, rapid virologic response and early virologic response (EVR), premature discontinuation of PegIFN or Rbv, and accumulated Rbv dose. In the multivariate analysis, the variables in the model were EVR [odds ratio (OR): 0.08, 95% confidence interval (CI): 0.016,0.414, P = 0.002] and donor age (OR: 1.039, 95% CI: 1.008,1.071, P = 0.01). Variables that had changed over time included donor age, baseline viremia, disease severity (cirrhosis, baseline bilirubin, and leukocyte and platelet counts), interval between transplantation and therapy, and use of growth factors. In the multivariate analysis, variables independently changing were donor age (OR: 1.041, 95% CI: 1.013,1.071, P = 0.004), duration from transplantation to antiviral therapy (OR: 1.001, 95% CI: 1.000,1.001, P = 0.013), and baseline leukocyte count (OR: 1.000, 95% CI: 1.000,1.000, P = 0.034). In conclusion, the efficacy of antiviral therapy with PegIFN-Rbv has worsened over time, at least in our center. The increase in donor age and greater proportion of patients treated at advanced stages of disease are potential causes. Liver Transpl 15:738,746, 2009. © 2009 AASLD. [source] Theoretical investigation on multinuclear NMR chemical shifts of some tris(trifluoromethyl)boron complexesMAGNETIC RESONANCE IN CHEMISTRY, Issue 8 2009Jun Zhang Abstract Tris(trifluoromethyl)boron complexes have unusual properties and may find applications in many fields of chemistry, biology, and physics. To gain insight into their NMR properties, the isotropic 11B, 13C, and 19F NMR chemical shifts of a series of tris(trifluoromethyl)boron complexes were systematically studied using the gauge-included atomic orbitals (GIAO) method at the levels of B3LYP/6-31 + G(d,p)//B3LYP/6-31G* and B3LYP/6-311 + G(d,p)//B3LYP/6-311 + G(d,p). Solvent effects were taken into account by polarizable continuum models (PCM). The calculated results were compared with the experimental values. The reason that the structurally inequivalent fluorine atoms in a specific species give a same chemical shift in experimental measurements is attributed to the fast rotation of CF3 group around the BC(F3) bond because of the low energy barrier. The calculated 11B, 13C(F3), and 19F chemical shifts are in good agreement with the experimental measurements, while the deviations of calculated 13C(X, X = O, N) chemical shifts are slightly large. For the latter, the average absolute deviations of the results from B3LYP/6-311 + G(d,p)//B3LYP/6-311 + G(d,p) are smaller than those from B3LYP/6-31 + G(d,p)//B3LYP/6-31G*, and the inclusion of PCM reduces the deviation values. The calculated 19F and 11B chemical shieldings of (CF3)3BCO are greatly dependent on the optimized structures, while the influence of structural parameters on the calculated 13C chemical shieldings is minor. Copyright © 2009 John Wiley & Sons, Ltd. [source] Heterogeneous agglutinitic glass and the fusion of the finest fraction (F3) modelMETEORITICS & PLANETARY SCIENCE, Issue 12 2002Abhijit Basu They include (1) theoretical expectations that shock pulses should engulf and melt smaller grains more efficiently than larger grains, (2) experimental results of impact shock, albeit at lower than presumed hypervelocity impacts of micrometeorites on the lunar regolith, and (3) new analyses confirming previous results that average compositions of agglutinitic glass are biased towards that of the finest fraction of lunar soils from which they had formed. We add another reason in support of the F3 model. Finer grains of lunar soils are also much more abundant. Hence, electrostatic forces associated with the rotating terminator region bring the finest grains that are obviously much lighter than courser grains to the surface of the Moon. This further contributes to the preferential melting of the finest fraction upon micrometeoritic impacts. New backscattered electron imaging shows that agglutinitic glass is inhomogeneous at submicron scale. Composition ranges of agglutinitic glass are extreme and deviate from that of the finest fraction, even by more than an order of magnitude for some components. Additionally, we show how an ilmenite grain upon impact would produce TiO2 -rich agglutinitic glass in complete disregard to the requirements of fusion of the finest fraction. We propose an addition to the F3 model to accommodate these observations (i.e., that micrometeorite impacts indiscriminately melt the immediate target regardless of grain size or grain composition). We, therefore, suggest that (1) agglutinitic glass is the sum of (a) the melt produced by the fusion of the finest fraction of lunar soils and (b) the microvolume of the indiscriminate target, which melts at high-shock pressures from micrometeoritic impacts, and that (2) because of the small volume of the melt and incorporating cold soil grains, the melt quenched so rapidly that it did not mix and homogenize to represent any preferential composition, for example, that of the finest fraction. [source] Epidermal growth factor (EGF) induces motility and upregulates MMP-9 and TIMP-1 in bovine trophoblast cellsMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 7 2010M. Dilly Differentiation and restricted invasion/migration of trophoblast cells are crucial for feto-maternal communication in the synepitheliochorial placenta of cattle. EGF is expressed in the bovine placenta and likely regulates these cell properties. As cell migration and motility rely on the degradation of extracellular matrix we hypothesize that EGF is involved in the regulation of the MMP-9/TIMP-1 balance and thus could influence trophoblast migration, tissue remodeling, and the release of the fetal membranes after parturition. The aim of this in vitro study was to examine EGF-mediated effects on cell motility, proliferation, and MMP-9 and TIMP-1 expression in cultured bovine trophoblast cells. We used a trophoblast cell line (F3) derived from bovine placentomes to examine the influence of EGF on MMP-9 and TIMP-1 expression by semiquantitative RT-PCR and MMP activity by zymography. Migration assays were performed using a Boyden chamber and cell motility was measured by time-lapse analyses. To identify the involved signaling cascades, phosphorylation of mitogen-activated protein kinase (MAPK) 42/44 and Akt was detected by Western blot. EGF treatment increased both the abundance of MMP-9 and TIMP-1 mRNAs and the proteolytic activity of MMP-9. Furthermore, EGF stimulated proliferation and migration of F3 cells. Addition of specific inhibitors of MAPK (PD98059) and/or PI3K (LY294002) activation abolished or reduced EGF-induced effects in all experiments. In conclusion, EGF-mediated effects stimulate migration and proliferation of bovine trophoblast cells and may be involved in bovine placental tissue remodeling and postpartum release of fetal membranes. Mol. Reprod. Dev. 77: 622,629, 2010. © 2010 Wiley-Liss, Inc. [source] Technical Note: Effect of contact lenses on measurement of the accommodation microfluctuationsOPHTHALMIC AND PHYSIOLOGICAL OPTICS, Issue 1 2008Mhairi Day Abstract Aim:, Dynamic measurement of accommodation in subjects with myopia usually involves recording through soft contact lenses (CLs) to correct the refractive error. Conversely, dynamic accommodation measurement in emmetropic control subjects is generally undertaken without any corrective lenses. The aim of this experiment was to determine whether CL correction affects the measurement of accommodation microfluctuations using infrared refractometry, and whether this needs to be considered in studies which attempt to compare accommodation responses between the two groups. Methods:, Ten young emmetropic subjects viewed a high contrast Maltese cross target monocularly using the right eye at a target vergence of 0 D. The subjects viewed the target under two conditions: with CL condition and without CL condition, where the subjects viewed the target with the eye only. Accommodation responses of the right eye were recorded continuously for 2 min at a sampling rate of 52 Hz using the Shin-Nippon SRW-5000 autorefractor. Results:, No significant difference (two-tailed paired t -test, t9 = ,1.499, p = 0.168) was found in mean accommodation response between the with CL (mean ± S.D. = ,0.02 ± 0.24 D) and without CL conditions (mean ± S.D. = +0.01 ± 0.25 D). No significant (two-tailed paired t -test, t9 = 0.151, p = 0.883) difference in the magnitude of the accommodation microfluctuations was found between the with CL (mean ± S.D. = 0.162 ± 0.04 D) and without CL condition (mean ± S.D. = 0.169 ± 0.04 D). Power spectrum analysis revealed no differences in the characteristics of the microfluctuations waveform between the two conditions. A control experiment carried out on a subgroup of five subjects using a negative (,3 D) CL demonstrated that there was no significant effect of the dioptric power of the CL on the magnitude of the accommodation microfluctuations (anova: F3,15 = 0.254, p = 0.782). Conclusion:, Thin soft CLs do not affect the magnitude or frequency characteristics of accommodation microfluctuations when measured using the Shin-Nippon SRW-5000. [source] Engineered native pathways for high kaempferol and caffeoylquinate production in potatoPLANT BIOTECHNOLOGY JOURNAL, Issue 9 2008Caius M. Rommens Summary Flavonols and caffeoylquinates represent important groups of phenolic antioxidants with health-promoting activities. The genetic potential of potato (Solanum tuberosum) to produce high levels of these dietary compounds has not been realized in currently available commodity varieties. In this article, it is demonstrated that tuber-specific expression of the native and slightly modified MYB transcription factor gene StMtf1M activates the phenylpropanoid biosynthetic pathway. Compared with untransformed controls, transgenic tubers contained fourfold increased levels of caffeoylquinates, including chlorogenic acid (CGA) (1.80 mg/g dry weight), whilst also accumulating various flavonols and anthocyanins. Subsequent impairment of anthocyanin biosynthesis through silencing of the flavonoid-3,,5,-hydroxylase (F3,5,h) gene resulted in the accumulation of kaempferol-rut (KAR) to levels that were approximately 100-fold higher than in controls (0.12 mg/g dry weight). The biochemical changes were associated with increased expression of both the CGA biosynthetic hydroxycinnamoyl-CoA quinate hydroxycinnamoyl transferase (Hqt) gene and the upstream chorismate mutase (Cm) and prephenate dehydratase (Pdh) genes. Field trials indicated that transgenic lines produced similar tuber yields to the original potato variety Bintje. Processed products of these lines retained most of their phenylpropanoids and were indistinguishable from untransformed controls in texture and taste. [source] |