Model Studies of Catechol Dioxygenases. Important Role of Monodentate Catecholate-Iron(III) Intermediate

1993 ◽  
Vol 66 (5) ◽  
pp. 1408-1419 ◽  
Author(s):  
Satoshi Fujii ◽  
Hiroaki Ohya-Nishiguchi ◽  
Noboru Hirota ◽  
Akira Nishinaga
Keyword(s):  
Model Studies ◽  
Catechol Dioxygenases

scholarly journals From animal models to patients: the role of placental microRNAs, miR-210, miR-126, and miR-148a/152 in preeclampsia

2020 ◽  
Vol 134 (8) ◽  
pp. 1001-1025 ◽  
Author(s):  
Sonya Frazier ◽  
Martin W. McBride ◽  
Helen Mulvana ◽  
Delyth Graham
Keyword(s):  
Animal Models ◽  
Cell Types ◽  
Rodent Model ◽  
Hypertensive Disorder ◽  
Model Studies ◽  
Genetic Components ◽  
Immune Mediated ◽  
Hypertensive Disorder Of Pregnancy

Abstract Placental microRNAs (miRNAs) regulate the placental transcriptome and play a pathological role in preeclampsia (PE), a hypertensive disorder of pregnancy. Three PE rodent model studies explored the role of placental miRNAs, miR-210, miR-126, and miR-148/152 respectively, by examining expression of the miRNAs, their inducers, and potential gene targets. This review evaluates the role of miR-210, miR-126, and miR-148/152 in PE by comparing findings from the three rodent model studies with in vitro studies, other animal models, and preeclamptic patients to provide comprehensive insight into genetic components and pathological processes in the placenta contributing to PE. The majority of studies demonstrate miR-210 is upregulated in PE in part driven by HIF-1α and NF-κBp50, stimulated by hypoxia and/or immune-mediated processes. Elevated miR-210 may contribute to PE via inhibiting anti-inflammatory Th2-cytokines. Studies report an up- and downregulation of miR-126, arguably reflecting differences in expression between cell types and its multifunctional capacity. MiR-126 may play a pro-angiogenic role by mediating the PI3K-Akt pathway. Most studies report miR-148/152 family members are upregulated in PE. Evidence suggests they may inhibit DNA methylation of genes involved in metabolic and inflammatory pathways. Given the genetic heterogeneity of PE, it is unlikely that a single placental miRNA is a suitable therapeutic target for all patients. Investigating miRNAs in PE subtypes in patients and animal models may represent a more appropriate approach going forward. Developing methods for targeting placental miRNAs and specific placental cell types remains crucial for research seeking to target placental miRNAs as a novel treatment for PE.

The Boger Synthesis of (+)-Complestatin

2013 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Nitro Group ◽  
The Other ◽  
Aryl Ether ◽  
Silyl Group ◽  
Model Studies ◽  
La Jolla ◽  
Indole Synthesis ◽  
Modular Nature

(+)-Complestatin 3 shows promising activity against HIV infectivity. Dale L. Boger of Scripps/La Jolla described (J. Am. Chem. Soc. 2010, 132, 7776) an elegant multicomponent assembly of 3, the key step of which was the atropisomer-selective intramolecular Larock cyclization of 1 to 2. The preparation of 1 began with the protected phenethylamine 5, prepared by Sharpless asymmetric aminohydroxylation of the styrene 4. Conversion of 5 to the areneboronic acid followed by coupling with 6 delivered 7. Acylation led to 8, with the stage set for nitro-assisted addition-elimination, to form the first bis-aryl ether of 3. The product was a mixture of atropisomers, subsequently symmetrized to 9 by removal of the nitro group. Acylation of 9 led to 1. The role of the silyl group on the alkyne of 1 was to direct the regioselectivity of the intramolecular Larock indole synthesis. Again, two atropisomers were possible from the cyclization. Earlier model studies had suggested some preference for one over the other. As it turned out, in this case the desired atropisomer was the only one observed. It is particularly striking that the coupling was efficient even in the presence of the readily reduced and unprotected chlorophenols. The modular nature of this route to (+)-complestatin 3 will make it possible to prepare a variety of analogues. As long as only the substituents on the periphery are changed, the atropisomer selectivity in the Larock cyclization should be maintained.

The role of cholesterol in membrane activity of digitonin: Experimental and theoretical model studies

2020 ◽  
pp. 114598
Author(s):  
Beata Korchowiec ◽  
Maria Janikowska-Sagan ◽  
Klaudia Kwiecińska ◽  
Anna Stachowicz-Kuśnierz ◽  
Jacek Korchowiec
Keyword(s):  
Theoretical Model ◽  
Membrane Activity ◽  
Model Studies

scholarly journals THE ROLE OF SURFACE TENSION IN BREAKING WAVES

1972 ◽  
Vol 1 (13) ◽  
pp. 22 ◽  
Author(s):  
Robert L. Miller
Keyword(s):  
Surface Tension ◽  
Natural Waters ◽  
Experimental Studies ◽  
Breaking Waves ◽  
Engineering Model ◽  
Constant Depth ◽  
Model Studies ◽  
Limit Form ◽  
Satisfactory Theory

Breaking criteria in the vicinity of the crest, such as limit crest angle and limit form, and larger dimensions such as limit height (H/L) and breaker height (Hb/db)» are found experimentally to be significantly affected by change in surface tension. A number of wave types were examined, including periodic waves, solitary waves, and standing waves, over both constant depth and uniform slopes. Variations in natural waters in some cases were found to be of equivalent magnitude to those induced for the experiments. The conclusion is drawn that surface tension should be taken into account in development of a satisfactory theory of breakers. It is also an important factor in experimental studies, particularly engineering model studies involving breaking waves.

Chemoprevention of Tumors: The Role of RAR-Beta

2003 ◽  
Vol 18 (1) ◽  
pp. 78-81 ◽  
Author(s):  
S. Toma ◽  
L. Emionite ◽  
G. Fabia ◽  
N. Spadini ◽  
L. Vergani
Keyword(s):  
Animal Model ◽  
Invasive Cancer ◽  
Model Studies ◽  
Chemical Agents ◽  
Different Types ◽  
Scientific Rationale ◽  
Cellular Alterations

Chemoprevention can be defined as the use of specific natural or synthetic chemical agents to reverse, suppress, or prevent carcinogenic progression to invasive cancer. The knowledge of carcinogenic mechanisms provides the scientific rationale for chemoprevention. Epithelial carcinogenesis proceeds through multiple discernible stages of molecular and cellular alterations. Understanding of the multistep nature of carcinogenesis has evolved through highly controlled animal carcinogenesis studies, and these studies have identified three distinct phases: initiation, promotion and progression. Animal model studies have provided evidence that the development of cancer involves many different factors, including alterations in the structures and functions of different genes. Transitions between successive stages can be enhanced or inhibited in the laboratory by different types of agents, such activities providing the fundamental basis for chemoprevention.

The role of glucagon in the regulation of blood glucose: Model studies

1978 ◽  
Vol 40 (1) ◽  
pp. 59-77 ◽  
Author(s):  
Ruby Celeste ◽  
Eugene Ackerman ◽  
Laël C. Gatewood ◽  
Clayton Reynolds ◽  
George D. Molnar
Keyword(s):  
Blood Glucose ◽  
Model Studies

scholarly journals Conversion of 19-oxo[2β-2H]androgens into oestrogens by human placental aromatase. An unexpected stereochemical outcome

1990 ◽  
Vol 268 (3) ◽  
pp. 553-561 ◽  
Author(s):  
P A Cole ◽  
C H Robinson
Keyword(s):  
Active Site ◽  
Extended Period ◽  
Direct Role ◽  
Methyl Group ◽  
Enzyme Active Site ◽  
Model Studies ◽  
The Third ◽  
Intensive Investigation ◽  
Cytochrome P 450

Aromatase is a cytochrome P-450 enzyme that catalyzes the conversion of androgens into oestrogens via sequential oxidations at the 19-methyl group. Despite intensive investigation, the mechanism of the third step, conversion of the 19-aldehydes into oestrogens, has remained unsolved. We have previously found that a pre-enolized 19-al derivative undergoes smooth aromatization in non-enzymic model studies, but the role of enolization by the enzyme in transformations of 19-oxoandrogens has not been previously investigated. The compounds 19-oxo[2 beta-2H]testosterone and 19-oxo[2 beta-2H]androstenedione have now been synthesized. Exposure of either of these compounds to microsomal aromatase, in the absence of NADPH, for an extended period led to no significant 2H loss or epimerization at C-2, leaving open the importance of an active-site base. However, in the presence of NADPH there was an unexpected substrate-dependent difference in the stereoselectivity of H loss at C-2 in the enzyme-induced aromatization of 19-oxo[2 beta-2H]-testosterone versus 19-oxo[2 beta-2H]androstenedione. The aromatization results for 17 beta-ol derivative 19-oxo[2 beta-2H]-testosterone correspond to about 1.2:1 2 beta-H/2 alpha-H loss from unlabelled 19-oxotestosterone. In contrast, aromatization results for 19-oxo[2 beta-2H]androstenedione correspond to at least 11:1 2 beta-H/2 alpha-H loss from unlabelled 19-oxoandrostenedione. This substrate-dependent stereoselectivity implies a direct role for an enzyme active-site base in 2-H removal. Furthermore, these results argue against the proposal that 2 beta-hydroxylation is the obligatory third step in aromatase action.

The Displacement of Residual Crude Oil by CO2 and Nitrogen in Gravity Stabilized Systems

1984 ◽  
Vol 24 (06) ◽  
pp. 593-596 ◽  
Author(s):  
T.M. Doscher ◽  
R.O. Oyekan ◽  
M. El Arabi
Keyword(s):  
High Pressure ◽  
Crude Oil ◽  
Physical Model ◽  
Low Permeability ◽  
Residual Oil ◽  
Fluid Displacement ◽  
Effect Of Pressure ◽  
Model Studies ◽  
Miscible Fluid

Abstract Physical model studies of the displacement of residual oil Physical model studies of the displacement of residual oil by CO2 have led to the conclusion that the driving mechanism for the process is that of a gas drive of the swollen crude. In this final phase of the study, the fluid/fluid displacement process was gravity-stabilized; mixing of the CO2 with the residual crude oil was minimized. As a result, the performance of CO2 was only marginally better than that of relatively insoluble nitrogen. Introduction The work described herein concludes the scaled physical model study of the displacement of residual crude by CO2 that had been sponsored by the U.S. DOE and the U. of Southern California. The overall goal of the work was to elucidate the mechanism of the process and to gain insight into its ultimate efficiency in recovering the crude oil remaining in a reservoir after completing an efficient water flood. The conclusions drawn from the work are limited to the displacement and recovery of residual, nonmobile crude oil. The general applicability of these conclusions to the recovery of higher saturations of mobile crude oil by CO2 is still moot. In the first phase of this work the role of CO2 was simulated by using fluids that were both liquid and completely miscible with the residual crude oil in scaled models of a linear reservoir. The results were consistent with expectations based on the basic laws for fluid flow in porous media.1. After a water flood, the water is the first phase to be displaced by the injected oil-miscible fluid. This can be accounted for readily by the water being the only mobile phase in the reservoir after water flooding has been concluded.2. The first appearance of the injected oil-miscible fluid in the effluent and the volumetric efficiency of the fluid displacement process are functions of the density and viscosity of the injected oil-miscible fluid. These observations can be related to the injected oil-miscible fluids being less dense and less viscous than the continuous, mobile water: therefore the injected fluids both segregate as a result of gravitational instability and finger through the water as a result of viscous instability.3. The residual crude oil was found to be produced along with the injected oil-miscible fluid. It was then inferred that the mechanism of the recovery of the residual crude required solution of the CO2 in the crude, swelling (saturation increase), and, ultimately, displacement of the swollen crude by the injected fluid. The scaled model studies, in which the role of CO2 was simulated by low-viscosity miscible fluids, was followed by high-pressure studies in which CO2 itself was used. However, the geometry was still restricted to that of a linear low-permeability reservoir having a circular cross section. The low permeability of the prototype, 25 md, was chosen since the earlier work already prototype, 25 md, was chosen since the earlier work already had indicated the highly pernicious effect of gravity segregation on the performance of CO2 in displacing and recovering residual crude oil. The circularity and linearity of the reservoir were dictated by the cost of a more realistic three-dimensional model. However, it was easy to show that the linearity and circularity of the prototype led to, if anything, a more optimistic performance being deduced for the recovery process. The results of the high-pressure study duplicated those in which the role of CO2 had been simulated. In addition, however, specific effects of pressure, temperature, and slug size were revealed.1. The efficiency of the displacement process in terms of oil produced per 1,000 scf of CO2 injected (bbl/10 scf) increases rapidly with pressure, but the effect of pressure becomes smaller and smaller as the pressure pressure becomes smaller and smaller as the pressure approaches 1,000 to 1,200 psi [6895 to 8274 kPa] (at temperatures in the range of 100 to 150 degrees F 138 to 66 degrees C]). The reduced effect of pressure on efficiency occurs when the density also becomes less sensitive to further increases in pressure-i.e., when the behavior of the density suggests the CO2 is liquid rather than gaseous.2. Increasing temperature reduces the efficiency of the process and the experiments showed that the negative process and the experiments showed that the negative effect of temperature could be offset by an increase in pressure. The efficiency of the CO2 was the same as long pressure. The efficiency of the CO2 was the same as long as the pressure and temperature of the experiment resulted in an identical density of the CO2.3. The efficiency increases with residual oil saturation (ROS). SPEJ P. 593

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