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Search Results: 1 - 10 of 464503 matches for " Sophie A. Matthews "
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Mutational and Topological Analysis of the Escherichia coli BamA Protein
Douglas F. Browning, Sophie A. Matthews, Amanda E. Rossiter, Yanina R. Sevastsyanovich, Mark Jeeves, Jessica L. Mason, Timothy J. Wells, Catherine A. Wardius, Timothy J. Knowles, Adam F. Cunningham, Vassiliy N. Bavro, Michael Overduin, Ian R. Henderson
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0084512
Abstract: The multi-protein β-barrel assembly machine (BAM) of Escherichia coli is responsible for the folding and insertion of β-barrel containing integral outer membrane proteins (OMPs) into the bacterial outer membrane. An essential component of this complex is the BamA protein, which binds unfolded β-barrel precursors via the five polypeptide transport-associated (POTRA) domains in its N-terminus. The C-terminus of BamA contains a β-barrel domain, which tethers BamA to the outer membrane and is also thought to be involved in OMP insertion. Here we mutagenize BamA using linker scanning mutagenesis and demonstrate that all five POTRA domains are essential for BamA protein function in our experimental system. Furthermore, we generate a homology based model of the BamA β-barrel and test our model using insertion mutagenesis, deletion analysis and immunofluorescence to identify β-strands, periplasmic turns and extracellular loops. We show that the surface-exposed loops of the BamA β-barrel are essential.
Scattering Theory for Quantum Hall Anyons in a Saddle Point Potential
A. Matthews,N. R. Cooper
Physics , 2009, DOI: 10.1103/PhysRevB.80.165309
Abstract: We study the theory of scattering of two anyons in the presence of a quadratic saddle-point potential and a perpendicular magnetic field. The scattering problem decouples in the centre-of-mass and the relative coordinates. The scattering theory for the relative coordinate encodes the effects of anyon statistics in the two-particle scattering. This is fully characterized by two energy-dependent scattering phase shifts. We develop a method to solve this scattering problem numerically, using a generalized lowest Landau level approximation.
Taking a chance on epigenetics
Sophie A. Lelievre
Frontiers in Genetics , 2014, DOI: 10.3389/fgene.2014.00205
Abstract: Epigenetics has become the indispensable science for understanding the gene-environment relationships that control risk exposure, therapeutic response and disease progression. Despite the importance of the field, not all scientists agree on how even to define epigenetics (Dupont et al., 2009); some, like me, restrict epigenetics to events that happen at the gene level, such as DNA methylation and histone modifications that constitute epigenetic marks, and the binding of proteins and RNAs involved in transcription control. Others also include miRNAs that interact with messenger RNAs. My purpose here is not to discuss semantics, but rather to consider the enormous expectations that we have placed upon epigenetics for its potential to provide quantifiable markers of risk. The notion of risk itself is a matter of significant debate in public health. It relies on our capacity to determine when a cell or tissue has become altered to the point where a disease might have a chance of onset, recurrence, progression or resistance to treatment. Risk is also linked to statistics; individuals who display a known marker of risk are placed in an “at risk” group from which, usually, only some people will actually develop the disorder. Therefore, to address uncertainty associated with risk assessment, the individual “at risk” should be monitored, and we should prioritize the search for underlying mechanisms in order to develop prevention strategies. Next-generation sequencing is currently the basis for large scale epigenetic analyses. But the balance between the investment of large amounts of funds in genetic sequencing and the paucity of resulting new information for cancer knowledge has raised doubt about the overall efficiency of this approach (Yaffe 2013). With the epigenetic code consisting of more than two-dozen different epigenetic marks, the gathering of data for risk assessment would require an exponential use of such costly technologies. Nonetheless, in my opinion, epigenetics is likely to enable great strides in risk assessment because epigenetic marks are rapidly, and sometimes sustainably, modified in response to risk variations. The highly specific nature of the mechanisms that control epigenetic marks might even provide targets for strategies designed to reduce individual risk. Indeed, our query should not be merely whether epigenetics can contribute to risk assessment, but how the information that we learn can and will be used to provide meaningful measures of risk. However, as developed in the next paragraphs, epigenetic information is unlikely to
Fields and Flares: Understanding the Complex Magnetic Topologies of Solar Active Regions
Sophie A. Murray
Physics , 2013,
Abstract: Sunspots are regions of decreased brightness on the visible surface of the Sun (photosphere) that are associated with strong magnetic fields. They have been found to be locations associated with solar flares, which occur when energy stored in sunspot magnetic fields is suddenly released. The processes involved in flaring and the link between sunspot magnetic fields and flares is still not fully understood, and this thesis aims to gain a better understanding of these topics. The magnetic field evolution of a number of sunspot regions is examined using high spatial resolution data from the Hinode spacecraft. The research presented in this thesis gives insight into both photospheric and coronal magnetic field evolution of flaring regions. Significant increases in vertical field strength, current density, and field inclination angle towards the vertical are observed in the photosphere just hours before a flare occurs, which is on much shorter timescales than previously studied. First observations of spatial changes in field inclination across a magnetic neutral line (generally believed to be a typical source region of flares) are also discovered. 3D magnetic field extrapolation methods are used to study the coronal magnetic field, using the photospheric magnetic field data as a boundary condition. Magnetic energy and free magnetic energy are observed to increase significantly a few hours before a flare, and decrease afterwards, which is a similar trend to the photospheric field parameter changes observed. Evidence of partial Taylor relaxation is also detected after a flare, as predicted by several previous studies. The results outlined in this thesis show that this particular field of research is vital in furthering our understanding of the magnetic nature of sunspots and its link to flare processes.
Pro-Inflammatory Cytokine Regulation of P-glycoprotein in the Developing Blood-Brain Barrier
Majid Iqbal, Hay Lam Ho, Sophie Petropoulos, Vasilis G. Moisiadis, William Gibb, Stephen G. Matthews
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0043022
Abstract: Placental P-glycoprotein (P-gp) acts to protect the developing fetus from exogenous compounds. This protection declines with advancing gestation leaving the fetus and fetal brain vulnerable to these compounds and potential teratogens in maternal circulation. This vulnerability may be more pronounced in pregnancies complicated by infection, which is common during pregnancy. Pro-inflammatory cytokines (released during infection) have been shown to be potent inhibitors of P-gp, but nothing is known regarding their effects at the developing blood-brain barrier (BBB). We hypothesized that P-gp function and expression in endothelial cells of the developing BBB will be inhibited by pro-inflammatory cytokines. We have derived brain endothelial cell (BEC) cultures from various stages of development of the guinea pig: gestational day (GD) 50, 65 (term ~68 days) and postnatal day (PND) 14. Once these cultures reached confluence, BECs were treated with various doses (100–104 pg/mL) of pro-inflammatory cytokines: interleukin-1β (IL-1β), interleukin-6 (IL-6) or tumor necrosis factor- α (TNF-α). P-gp function or abcb1 mRNA (encodes P-gp) expression was assessed following treatment. Incubation of GD50 BECs with IL-1β, IL-6 or TNF-α resulted in no change in P-gp function. GD65 BECs displayed a dose-dependent decrease in function with all cytokines tested; maximal effects at 42%, 65% and 34% with IL-1β, IL-6 and TNF-α treatment, respectively (P<0.01). Inhibition of P-gp function by IL-1β, IL-6 and TNF-α was even greater in PND14 BECs; maximal effects at 36% (P<0.01), 84% (P<0.05) and 55% (P<0.01), respectively. Cytokine-induced reductions in P-gp function were associated with decreased abcb1 mRNA expression. These data suggest that BBB P-gp function is increasingly responsive to the inhibitory effects of pro-inflammatory cytokines, with increasing developmental age. Thus, women who experience infection and take prescription medication during pregnancy may expose the developing fetal brain to greater amounts of exogenous compounds – many of which are considered potentially teratogenic.
Prenatal Endotoxemia and Placental Drug Transport in The Mouse: Placental Size-Specific Effects
Enrrico Bloise, Manzerul Bhuiyan, Melanie C. Audette, Sophie Petropoulos, Mohsen Javam, William Gibb, Stephen G. Matthews
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0065728
Abstract: Lipopolysaccharide (LPS) in high doses inhibits placental multidrug resistance P-glycoprotein (P-gp - Abcb1a/b) and breast cancer resistance protein (BCRP - Abcg2). This potentially impairs fetal protection against harmful factors in the maternal circulation. However, it is unknown whether LPS exposure, at doses that mimic sub-lethal clinical infection, alters placental multidrug resistance. We hypothesized that sub-lethal (fetal) LPS exposure reduces placental P-gp activity. Acute LPS (n = 19;150 μg/kg; ip) or vehicle (n = 19) were given to C57BL/6 mice at E15.5 and E17.5. Placentas and fetal-units were collected 4 and 24 h following injection. Chronic LPS (n = 6; 5 μg/kg/day; ip) or vehicle (n = 5) were administered from E11.5–15.5 and tissues were collected 4 h after final treatment. P-gp activity was assessed by [3H]digoxin accumulation. Placental Abcb1a/b, Abcg2, interleukin-6 (Il-6), Tnf-α, Il-10 and toll-like receptor-4 (Tlr-4) mRNA were measured by qPCR. Maternal plasma IL-6 was determined. At E15.5, maternal IL-6 was elevated 4 h after single (p<0.001) and chronic (p<0.05) LPS, but levels had returned to baseline by 24 h. Placental Il-6 mRNA was also increased after acute and chronic LPS treatments (p<0.05), whereas Abcb1a/b and Abcg2 mRNA were unaffected. However, fetal [3H]digoxin accumulation was increased (p<0.05) 4 h after acute LPS, and maternal [3H]digoxin myocardial accumulation was increased (p<0.05) in mice exposed to chronic LPS treatments. There was a negative correlation between fetal [3H]digoxin accumulation and placental size (p<0.0001). Acute and chronic sub-lethal LPS exposure resulted in a robust inflammatory response in the maternal systemic circulation and placenta. Acute infection decreased placental P-gp activity in a time- and gestational age-dependent manner. Chronic LPS decreased P-gp activity in the maternal myocardium and there was a trend for fetuses with smaller placentas to accumulate more P-gp substrate than their larger counterparts. Collectively, we demonstrate that acute sub-lethal LPS exposure during pregnancy impairs fetal protection against potentially harmful xenobiotics in the maternal circulation.
Effects of Sertraline and Fluoxetine on P-Glycoprotein at Barrier Sites: In Vivo and In Vitro Approaches
Amita Kapoor, Majid Iqbal, Sophie Petropoulos, Hay Lam Ho, William Gibb, Stephen G. Matthews
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0056525
Abstract: Background and Purpose Retention of substances from systemic circulation in the brain and testes are limited due to high levels of P-glycoprotein (P-gp) in the luminal membranes of brain and testes capillary endothelial cells. From a clinical perspective, P-gp rapidly extrudes lipophilic therapeutic agents, which then fail to reach efficacious levels. Recent studies have demonstrated that acute administration of selective serotonin reuptake inhibitors (SSRI) can affect P-gp function, in vitro and in vivo. However, little is known concerning the time-course of these effects or the effects of different SSRI in vivo. Experimental Approach The P-gp substrate, tritiated digoxin ([3H] digoxin), was co-administered with fluoxetine or sertraline to determine if either compound increased drug accumulation within the brains and testes of mice due to inhibition of P-gp activity. We undertook parallel studies in endothelial cells derived from brain microvessels to determine the dose-response and time-course of effects. Key Results In vitro, sertraline resulted in rapid and potent inhibition of P-gp function in brain endothelial cells, as determined by cellular calcein accumulation. In vivo, a biphasic effect was demonstrated. Brain accumulation of [3H] digoxin was increased 5 minutes after treatment with sertraline, but by 60 minutes after sertraline treatment, brain accumulation of digoxin was reduced compared to control. By 240 minutes after sertraline treatment brain digoxin accumulation was elevated compared to control. A similar pattern of results was obtained in the testes. There was no significant effect of fluoxetine on P-gp function, in vitro or in vivo. Conclusions and Implications Acute sertraline administration can modulate P-gp activity in the blood-brain barrier and blood-testes barrier. This clearly has implications for the ability of therapeutic agents that are P-gp substrates, to enter the brain when co-administered with SSRI.
Tolerance Study for Standardized Macleaya cordata Extract Added to Chicken Layer Diet  [PDF]
Ray A. Matulka, Sophie von Alvensleben, Mauro Morlacchini, Giorgio Fusconi
Open Journal of Animal Sciences (OJAS) , 2018, DOI: 10.4236/ojas.2018.81008
Abstract: The objective of this study was to assess the effects of Sangrovit?, a standardized preparation of Macleaya cordata extract (MCE), on the health status and egg laying parameters of layer chickens. Layer chickens (N = 360) were randomly divided into four groups (90 birds/treatment, 10 birds/pen) and fed either a standard basal feed (T1) or a basal diet that was supplemented with 100 mg/kg (T2), 500 mg/kg (T3) or 1000 mg/kg (T4) Sangrovit? (providing 0, 3.7, 18.5, and 37.0 mg MCE/kg feed, respectively) for 56 consecutive days. Live Weight (LW), Average Daily Feed Intake (ADFI) and the Feed Conversion Ratios (FCR) were calculated during the study, and biochemical and hematological endpoints were obtained at the end of the study (Day 56). Eggs were analyzed for the isoquinoline alkaloids sanguinarine and chelerythrine. No statistically significant (P > 0.05) differences were found between control and treatment groups for LW, ADFI and FCR. There was a significant increase in the % laying in groups T3 and T4 for the study overall, but no significant differences in egg size during the study. Blood biochemical analyses showed a near-significant trend for decreased bilirubin in the T2 and T4 groups, but this was not dose-dependent and not considered treatment-related. The percent hemoglobin was significantly decreased in the high dose group, but was not considered treatment-related as it was not a dose-dependent effect. No treatment-related changes were found after necropsy of the selected organs. No quantifiable sanguinarine or chelerythrine was found in the eggs after 56 days administration of the MCE preparation to the hens. The results of this study show that consumption of a standardized MCE preparation at up to 1000 mg/kg feed in laying hens had no adverse effect on the hen or eggs, and no residual sanguinarine or chelerythrine was transferred to the eggs.
Bioavailability of Soy Protein and Corn Zein Films  [PDF]
Laura B. Matthews, M. Elizabeth Kunkel, James C. Acton, Amod A. Ogale, Paul L. Dawson
Food and Nutrition Sciences (FNS) , 2011, DOI: 10.4236/fns.2011.210148
Abstract: The in vivo bioavailability of soy protein isolates and corn zein film material before and after film formation by heat/ pressure was determined. The In vitro digestibility of corn zein before and after film formation was also measured. Films were produced from anhydrous protein with 30% glycerol added using a heat-press method with no use of casting solvents or cross-linking agents. Corn zein raw and film material were ground under liquid nitrogen then digested in two enzyme-acid cocktails with free amino acid analysis before and after digestion. The protein efficiency ratio and net protein ratio were determined for both zein and soy protein using a weanling Sprague-Dawley descended rat feeding study. The In vitro digestibility study indicated that the non-heat pressed corn zein was more digestible than the heat pressed zein. However, the in vivo results indicated that corn and soy protein were equally bioavailable whether they were derived from film mixture prior to or after film formation. Both corn zein and soy protein material had lower protein efficiency ratio than the control diet. Furthermore, soy protein films materials had a higher protein efficiency ratio than corn zein.
Ecological Life History, IncludingLaboratory Investigation,of the Mayfly, Ameletus Tarteri (Ephemeroptera: Siphloneuridae)
Kimberly A. Matthews,Donald C. Tarter
Psyche , 1989, DOI: 10.1155/1989/53971
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