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Various Pathways (various + pathway)
Selected AbstractsMultiple pathways for invasion of anurans on a Pacific islandDIVERSITY AND DISTRIBUTIONS, Issue 5 2007Michelle T. Christy ABSTRACT Since 1937, thirteen species of non-indigenous anurans have made their way to Guam. Of these, at least six have established breeding populations. Various pathways led to the introduction of these species to the island. The only anuran intentionally introduced was Chaunus marinus (formerly Bufo marinus), which was brought to Guam as a biocontrol agent. Kaloula picta, K. pulchra, Polypedates leucomystax, and probably Litoria fallax arrived as stowaways via maritime or air-transport vessels. Eleutherodactylus coqui and Euhyas (formerly Eleutherodactylus) planirostris appear to have entered Guam through the horticultural trade. Specimens of Pseudacris regilla were found among agricultural products and Christmas trees. Five species have been transported to Guam via the aquacultural trade. The importation of tilapia, milkfish, and white shrimp from China, Hong Kong, Taiwan, and the Philippines was associated with the introduction to Guam of Fejervarya cancrivora, F. limnocharis sensu lato, Microhyla pulchra, Polypedates megacephalus, and Sylvirana guentheri (formerly Rana guentheri). Presently, no quarantine or containment guidelines have been established for Guam's aquacultural industry. [source] Glucuronidation of olanzapine by cDNA-expressed human UDP-glucuronosyltransferases and human liver microsomesHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 5 2002Kristian Linnet Abstract Olanzapine is a widely used, newer antipsychotic agent, which is metabolized by various pathways: hydroxylation and N -demethylation by cytochrome P450, N -oxidation by flavin monooxygenase and direct glucuronidation. In vivo studies have pointed towards the latter pathway as being of major importance. Accordingly, the glucuronidation reaction was studied in vitro using cDNA-expressed human UDP-glucuronosyltransferase (UGT) enzymes and a pooled human liver microsomal preparation (HLM). Glucuronidated olanzapine was determined by HPLC after acid or enzymatic hydrolysis. The following UGT-isoenzymes were screened for their ability to glucuronidate olanzapine: 1A1, 1A3, 1A4, 1A6, 1A9, 2B7 and 2B15. Only UGT1A4 was able to glucuronidate olanzapine obeying saturation kinetics. The Km value was 227,,mol/l (SE 43), i.e. of the same order of magnitude as for other psychotropic drugs, and the Vmax value was 2370,pmol/(min,mg) (SE 170). Glucuronidation was also mediated by the HLM preparation, but a saturation level was not reached. The olanzapine glucuronidation reaction was inhibited by several drugs known as substrates for UGT1A4, e.g. amitriptyline, trifluoperazine and lamotrigine. Thus, competition for glucuronidation by UGT1A4 represents a possibility for drug,drug interactions in subjects receiving several of these psychotropic drugs at the same time. Whether such possible interactions are of any clinical importance may await further studies in patients. Copyright © 2002 John Wiley & Sons, Ltd. [source] Multi-variable and multi-site calibration and validation of SWAT in a large mountainous catchment with high spatial variabilityHYDROLOGICAL PROCESSES, Issue 5 2006Wenzhi Cao Abstract Many methods developed for calibration and validation of physically based distributed hydrological models are time consuming and computationally intensive. Only a small set of input parameters can be optimized, and the optimization often results in unrealistic values. In this study we adopted a multi-variable and multi-site approach to calibration and validation of the Soil Water Assessment Tool (SWAT) model for the Motueka catchment, making use of extensive field measurements. Not only were a number of hydrological processes (model components) in a catchment evaluated, but also a number of subcatchments were used in the calibration. The internal variables used were PET, annual water yield, daily streamflow, baseflow, and soil moisture. The study was conducted using an 11-year historical flow record (1990,2000); 1990,94 was used for calibration and 1995,2000 for validation. SWAT generally predicted well the PET, water yield and daily streamflow. The predicted daily streamflow matched the observed values, with a Nash,Sutcliffe coefficient of 0·78 during calibration and 0·72 during validation. However, values for subcatchments ranged from 0·31 to 0·67 during calibration, and 0·36 to 0·52 during validation. The predicted soil moisture remained wet compared with the measurement. About 50% of the extra soil water storage predicted by the model can be ascribed to overprediction of precipitation; the remaining 50% discrepancy was likely to be a result of poor representation of soil properties. Hydrological compensations in the modelling results are derived from water balances in the various pathways and storage (evaporation, streamflow, surface runoff, soil moisture and groundwater) and the contributions to streamflow from different geographic areas (hill slopes, variable source areas, sub-basins, and subcatchments). The use of an integrated multi-variable and multi-site method improved the model calibration and validation and highlighted the areas and hydrological processes requiring greater calibration effort. Copyright © 2005 John Wiley & Sons, Ltd. [source] CNTO 859, a humanized anti-tissue factor monoclonal antibody, is a potent inhibitor of breast cancer metastasis and tumor growth in xenograft modelsINTERNATIONAL JOURNAL OF CANCER, Issue 6 2007Cam V. Ngo Abstract Thromboembolic complications are frequently associated with advanced cancer. Interestingly, one of the major initiators of blood coagulation, tissue factor (TF), is reported to be overexpressed in several tumor types and can be found on both tumor cells and tumor vasculature. Although the exact mechanisms have yet to be elucidated, TF expressed on tumor cells can trigger intracellular signaling events through various pathways that can lead to tumor angiogenesis, proliferation, and metastasis. There exists preclinical evidence that disruption of TF dependent signaling can effectively inhibit tumor cell migration, metastasis, and angiogenesis. Here, we report for the first time that an antibody to tissue factor can also prevent tumor growth in vivo. Prophylactic administration of CNTO 859, a humanized anti-human TF antibody, was shown to inhibit experimental lung metastasis of MDA-MB-231 human breast carcinoma cells by over 99% compared to a control antibody. Furthermore, therapeutic doses of CNTO 859 were shown to reduce tumor incidence and growth of orthotopically implanted MDA-MB-231 cells. © 2006 Wiley-Liss, Inc. [source] The Role of DNA Recombination in Herpes Simplex Virus DNA ReplicationIUBMB LIFE, Issue 8 2003Dianna Wilkinson Abstract In many organisms the processes of DNA replication and recombination are closely linked. For instance, in bacterial and eukaryotic systems, replication forks can become stalled or damaged, in many cases leading to the formation of double stranded breaks. Replication restart is an essential mechanism in which the recombination and repair machinery can be used to continue replication after such a catastrophic event. DNA viruses of bacteria such as lambda and T4 also rely heavily on DNA recombination to replicate their genomes and both viruses encode specialized gene products which are required for recombination-dependent replication. In this review, we examine the linkage between replication and recombination in the eukaryotic pathogen, Herpes Simplex Virus Type 1 (HSV-1). The evidence that recombination plays an intrinsic role in HSV-1 DNA replication and the infection process will be reviewed. We have recently demonstrated that HSV-1 encodes two proteins which may be analogous to the lambda phage recombination system, Red ,and ,. The HSV-1 alkaline nuclease, a 5' to 3' exonuclease, and ICP8, a single stranded DNA binding protein, can carry out strand annealing reactions similar to those carried out by the lambda Red system. In addition, evidence suggesting that host recombination proteins may also be important for HSV-1 replication will be reviewed. In summary, it is likely that HSV-1 infection will require both viral and cellular proteins which participate in various pathways of recombination and that recombination-dependent replication is essential for the efficient replication of viral genomes. IUBMB Life, 55: 451-458, 2003 [source] Redox Photochemistry of Thiouredopyrenetrisulfonate,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 6 2004Alexander B. Kottyar ABSTRACT 1-Thiouredopyrene-3,6,8-trisulfonate (TUPS) has recently been used as a photoinduced covalent redox label capable of reducing various cofactors of proteins. A new reaction of this dye, whereby its excited triplet state oxidizes suitable electron donors, is now reported. The characteristic difference spectrum of the reduced radical of TUPS is determined. We also observe the self-exchange electron transfer between two TUPS molecules in their triplet excited states and determine the reaction scheme and the rate constants of the various pathways in the process of triplet depletion. The ability of photoexcited TUPS to withdraw an electron from reduced cytochrome-c is also observed. It is thus demonstrated that TUPS is an appropriate photoinduced covalent redox label for initiating both the oxidative and reductive phases of electron transfer processes in biological macromolecules. [source] Mechanisms of stretch-induced muscle damage in normal and dystrophic muscle: role of ionic changesTHE JOURNAL OF PHYSIOLOGY, Issue 3 2005D. G. Allen Muscle damage, characterized by prolonged weakness and delayed onset of stiffness and soreness, is common following contractions in which the muscles are stretched. Stretch-induced damage of this sort is more pronounced in the muscular dystrophies and the profound muscle damage observed in these conditions may involve similar pathways. It has been known for many years that damaged muscles accumulate calcium and that elevating calcium in normal muscles simulates many aspects of muscle damage. The changes in intracellular calcium, sodium and pH following stretched contractions are reviewed and the various pathways which have been proposed to allow ion entry are discussed. One possibility is that TRPC1 (transient receptor potential, canonical), a protein which seems to form both a stretch-activated channel and a store-operated channel, is the main source of Ca2+ entry. The mechanisms by which the changes in intracellular ions contribute to reduced force production, to increased protein breakdown and to increased membrane permeability are considered. A hypothetical scheme for muscle damage which incorporates these ideas is presented. [source] Understanding Disparities in Transplantation: Do Social Networks Provide the Missing Clue?AMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2010K. Ladin Although the National Organ Transplant Act calls for equity in access to transplantation, scarcity and racial disparities persist. To date, even the most comprehensive models have been unable to adequately explain these racial disparities, leaving policymakers unsure how best to intervene. Previous individual-level analyses, which have implicated risk factors such as race, financial status, cultural beliefs, unemployment, lack of commitment to surgery and lack of continuous access to care, overlook contextual and social network exposures. Social networks present a compelling way to examine cumulative risk clustered across individuals. Social networks have been shown to influence health outcomes and health behaviors through various pathways, including shared social capital, engaging in similar or group risky behaviors, diffusion of information and adopting or propagating social norms. Precursors to chronic kidney disease, including obesity, have been shown to spread through social networks. Social network analysis can reveal shared risks between potential donors and recipients in a given network, clarifying the likelihood of finding an appropriate match through either direct donation or paired exchanges. This paper presents a novel application of social network analysis to transplantation, illustrating implications for disparities and future clinical interventions. [source] Human adipose-derived stem cells: isolation, characterization and applications in surgeryANZ JOURNAL OF SURGERY, Issue 4 2009Michelle Locke Abstract The ideal stem cell for use in functional tissue engineering needs to be abundantly available, harvested with minimal morbidity, differentiated reliably down various pathways and able to be transplanted safely and efficaciously. Adult human adipose tissue contains a population of mesenchymal stem cells, termed ,adipose-derived stem cells' (ASC), which seem to fulfil most, if not all, of these criteria. ASC can be harvested readily, safely, and in relative abundance by modern liposuction techniques. They are capable of differentiating into other mesenchymal tissue types, including adipocytes, chondrocytes, myocytes and osteoblasts. They also show angiogenic properties, with recent evidence of a potential role in healing radiotherapy-damaged tissue, possibly due to their secretion of vascular endothelial growth factor. Similarly, they may have a role in healing chronic wounds, and as such are being investigated in phase 1 trials for their ability to aid healing of recurrent Crohn's fistulae. Subsequently they have a wide range of potential clinical uses in all fields of surgery. This article reviews the current and potential clinical applications of ASC in relation to surgery, as well as methods for their isolation, differentiation and molecular characterization. [source] The cost-effectiveness of cervical screening in Australia: what is the impact of screening at different intervals or over a different age range?AUSTRALIAN AND NEW ZEALAND JOURNAL OF PUBLIC HEALTH, Issue 1 2008Rob Anderson Abstract Objective: To estimate the cost-effectiveness of altering the currently recommended interval and age range for cervical screening of Australian women. Methods: The cost and effectiveness estimates of alternative screening strategies were generated using an established decision model. This model incorporated a Markov model (of the natural history of cervical cancer and pre-cancerous lesions) and decision trees which: ,mapped' the various pathways to cervical cancer screening; the follow-up of abnormal Pap test results; and the management of confirmed lesions. The model simulated a hypothetical large cohort of Australian women from age 15 to age 85 and calculated the accumulated costs and life-years under each screening strategy. Results: Our model estimated that moving from the current two-yearly screening strategy to annual screening (over the same age range) would cost $379,300 per additional life-year saved. Moving from the current strategy to three-yearly screening would yield $117,100 of savings per life-year lost (costs and effects both discounted at 5% per year), with a relatively modest (<5%) reduction in the total number of life-years saved by the program. Conclusions: Although moving to annual screening would save some additional lives, it is not a cost-effective strategy. Consideration should be given to increasing the recommended interval for cervical screening. However, the net value of any such shift to less effective (e.g. less frequent) and less costly screening strategies will require better evidence about the cost-effectiveness of strategies that encourage non-screeners or irregular screeners to have a Pap test more regularly. [source] Prostate carcinoma tissue proteomics for biomarker discoveryCANCER, Issue 12 2003Yaxin Zheng M.D. Abstract BACKGROUND The advent of the prostate-specific antigen (PSA) test has had a profound impact on the diagnosis and treatment of prostate carcinoma. However, the use of PSA levels alone for screening for prostate carcinoma was compromised by the variations in the amount of PSA produced by the benign prostatic tissue specimens. Proteins were involved in various pathways that determine the behavior of a cell. Therefore, information regarding proteins may reveal drug targets and/or markers for early detection. METHODS The authors used surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to determine the protein profiles from fresh tissues of the prostate. Laser capture microdissection was performed to isolate pure populations of cells. RESULTS The authors identified a protein with an average m/Z of 24,782.56 ± 107.27 that was correlated with the presence of prostate carcinoma. Furthermore, using laser capture microdissection, they demonstrated that the origin of this protein, which the authors designated PCa-24, was derived from the epithelial cells of the prostate. PCa-24 expression was detected in 16 of 17 (94%) prostate carcinoma specimens but not in paired normal cells. In addition, this protein was not expressed in any of the 12 benign prostatic hyperplasia specimens that were assayed. CONCLUSIONS PCa-24 may be useful a marker for prostate carcinoma. Cancer 2003;98:2576,82. © 2003 American Cancer Society. [source] Carbonic Anhydrase Inhibitors: Inhibition of Cytosolic Carbonic Anhydrase Isozymes II and VII with Simple Aromatic Sulfonamides and Some Azo DyesCHEMICAL BIOLOGY & DRUG DESIGN, Issue 2 2009Fabrizio Carta Several substituted benzenesulfonamides were synthesized by various pathways starting from sulfanilamide. The sulfanilamide diazonium salt was reacted with copper (I) halides, potassium iodide and/or aromatic derivatives, leading to 4-halogeno-, and 4-hydroxy-benzenesulfonamides as well as diazo dyes incorporating sulfamoyl moieties. These sulfonamides were assayed as inhibitors of two physiologically relevant isoforms of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), i.e., the cytosolic CA II (ubiquitous), and CA VII (brain-specific enzyme). Good CA inhibitory activity was detected for some of these derivatives, with inhibition constants (Ki) in the range of 17.5,863 nm against CA II; and 30,4200 nm against CA VII. [source] | |||||||||||||