576 research outputs found
A functional description of CymA, an electron-transfer hub supporting anaerobic respiratory flexibility in Shewanella
CymA (tetrahaem cytochrome c) is a member of the NapC/NirT family of quinol dehydrogenases. Essential for the anaerobic respiratory flexibility of shewanellae, CymA transfers electrons from menaquinol to various dedicated systems for the reduction of terminal electron acceptors including fumarate and insoluble minerals of Fe(III). Spectroscopic characterization of CymA from Shewanella oneidensis strain MR-1 identifies three low-spin His/His co-ordinated c-haems and a single high-spin c-haem with His/H2O co-ordination lying adjacent to the quinol-binding site. At pHĀ 7, binding of the menaquinol analogue, 2-heptyl-4-hydroxyquinoline-N-oxide, does not alter the mid-point potentials of the high-spin (approximately ā240 mV) and low-spin (approximately ā110, ā190 and ā265 mV) haems that appear biased to transfer electrons from the high- to low-spin centres following quinol oxidation. CymA is reduced with menadiol (Em=ā80 mV) in the presence of NADH (Em=ā320 mV) and an NADHāmenadione (2-methyl-1,4-naphthoquinone) oxidoreductase, but not by menadiol alone. In cytoplasmic membranes reduction of CymA may then require the thermodynamic driving force from NADH, formate or H2 oxidation as the redox poise of the menaquinol pool in isolation is insufficient. Spectroscopic studies suggest that CymA requires a non-haem co-factor for quinol oxidation and that the reduced enzyme forms a 1:1 complex with its redox partner Fcc3 (flavocytochrome c3 fumarate reductase). The implications for CymA supporting the respiratory flexibility of shewanellae are discussed.</jats:p
Determination of suitable housekeeping genes for normalisation of quantitative real time PCR analysis of cells infected with human immunodeficiency virus and herpes viruses
The choice of an appropriate housekeeping gene for normalisation purposes has now become an essential requirement when designing QPCR experiments. This is of particular importance when using QPCR to measure viral and cellular gene transcription levels in the context of viral infections as viruses can significantly interfere with host cell pathways, the components of which traditional housekeeping genes often encode. In this study we have determined the reliability of 10 housekeeping genes in context of four heavily studied viral infections; human immunodeficiency virus type 1, herpes simplex virus type 1, cytomegalovirus and varicella zoster virus infections using a variety of cell types and virus strains. This provides researchers of these viruses with a shortlist of potential housekeeping genes to use as normalisers for QPCR experiments
PPARĪ³ agonists negatively regulate Ī±IIbĪ²3 integrin outside-in signalling and platelet function through upregulation of protein kinase A activity
BACKGROUND:
Agonists for the peroxisome proliferator activated receptor PPARĪ³, have been shown to have inhibitory effects on platelet activity following stimulation by GPVI and GPCR agonists.
OBJECTIVES:
Profound effects on thrombus formation led us to suspect a role for PPARĪ³ agonists in the regulation of integrin Ī±IIbĪ²3 mediated signalling. Both GPVI and GPCR signalling pathways lead to Ī±IIbĪ²3 activation, and signalling through Ī±IIbĪ²3 plays a critical role in platelet function and normal haemostasis.
METHODS:
The effects of PPARĪ³ agonists on the regulation of Ī±IIbĪ²3 outside-in signalling was determined by monitoring the ability of platelets to adhere and spread on fibrinogen and undergo clot retraction. Effects on signalling components downstream of Ī±IIbĪ²3 activation were also determined following adhesion to fibrinogen by western blotting.
RESULTS:
Treatment of platelets with PPARĪ³ agonists inhibited platelet adhesion and spreading on fibrinogen and diminished clot retraction. A reduction in phosphorylation of several components of Ī±IIbĪ²3 signalling, including the integrin Ī²3 subunit, Syk, PLCĪ³2, FAK and Akt was also observed as a result of reduced interaction of the integrin Ī²3 subunit with GĪ±13. Studies of VASP phosphorylation revealed that this was a due to an increase in PKA activity following treatment with PPARĪ³ receptor agonists.
CONCLUSIONS:
This study provides further evidence for anti-platelet actions of PPARĪ³ agonists, identifies a negative regulatory role for PPARĪ³ agonists in the control of integrin Ī±IIbĪ²3 outside-in signalling, and provides a molecular basis by which the PPARĪ³ agonists negatively regulate platelet activation and thrombus formation
Vascular Health in American Football Players: Cardiovascular Risk Increased in Division III Players
Studies report that football players have high blood pressure (BP) and increased cardiovascular risk. There are over 70,000 NCAA football players and 450 Division III schools sponsor football programs, yet limited research exists on vascular health of athletes. This study aimed to compare vascular and cardiovascular health measures between football players and nonathlete controls. Twenty-three athletes and 19 nonathletes participated. Vascular health measures included flow-mediated dilation (FMD) and carotid artery intima-media thickness (IMT). Cardiovascular measures included clinic and 24 hr BP levels, body composition, VO2 max, and fasting glucose/cholesterol levels. Compared to controls, football players had a worse vascular and cardiovascular profile. Football players had thicker carotid artery IMT (0.49 Ā± 0.06 mm versus 0.46 Ā± 0.07 mm) and larger brachial artery diameter during FMD (4.3 Ā± 0.5 mm versus 3.7 Ā± 0.6 mm), but no difference in percent FMD. Systolic BP was significantly higher in football players at all measurements: resting (128.2 Ā± 6.4 mmHg versus 122.4 Ā± 6.8 mmHg), submaximal exercise (150.4 Ā± 18.8 mmHg versus 137.3 Ā± 9.5 mmHg), maximal exercise (211.3 Ā± 25.9 mmHg versus 191.4 Ā± 19.2 mmHg), and 24-hour BP (124.9 Ā± 6.3 mmHg versus 109.8 Ā± 3.7 mmHg). Football players also had higher fasting glucose (91.6 Ā± 6.5 mg/dL versus 86.6 Ā± 5.8 mg/dL), lower HDL (36.5Ā±11.2 mg/dL versus 47.1Ā±14.8 mg/dL), and higher body fat percentage (29.2Ā±7.9% versus 23.2Ā±7.0%). Division III collegiate football players remain an understudied population and may be at increased cardiovascular risk
A Transiting Planet of a Sun-like Star
A planet transits an 11th magnitude, G1V star in the constellation Corona
Borealis. We designate the planet XO-1b, and the star, XO-1, also known as GSC
02041-01657. XO-1 lacks a trigonometric distance; we estimate it to be 200+-20
pc. Of the ten stars currently known to host extrasolar transiting planets, the
star XO-1 is the most similar to the Sun in its physical characteristics: its
radius is 1.0+-0.08 R_Sun, its mass is 1.0+-0.03 M_Sun, V sini < 3 km/s, and
its metallicity [Fe/H] is 0.015+-0.04. The orbital period of the planet XO-1b
is 3.941534+-0.000027 days, one of the longer ones known. The planetary mass is
0.90+-0.07 M_Jupiter, which is marginally larger than that of other transiting
planets with periods between 3 and 4 days. Both the planetary radius and the
inclination are functions of the spectroscopically determined stellar radius.
If the stellar radius is 1.0+-0.08 R_Sun, then the planetary radius is
1.30+-0.11 R_Jupiter and the inclination of the orbit is 87.7+-1.2 degrees. We
have demonstrated a productive international collaboration between professional
and amateur astronomers that was important to distinguishing this planet from
many other similar candidates.Comment: 31 pages, 9 figures, accepted for part 1 of Ap
Recommended from our members
Lessons Learned on Benchmarking from the International Human Reliability Analysis Empirical Study
The International Human Reliability Analysis (HRA) Empirical Study is a comparative benchmark of the prediction of HRA methods to the performance of nuclear power plant crews in a control room simulator. There are a number of unique aspects to the present study that distinguish it from previous HRA benchmarks, most notably the emphasis on a method-to-data comparison instead of a method-to-method comparison. This paper reviews seven lessons learned about HRA benchmarking from conducting the study: (1) the dual purposes of the study afforded by joining another HRA study; (2) the importance of comparing not only quantitative but also qualitative aspects of HRA; (3) consideration of both negative and positive drivers on crew performance; (4) a relatively large sample size of crews; (5) the use of multiple methods and scenarios to provide a well-rounded view of HRA performance; (6) the importance of clearly defined human failure events; and (7) the use of a common comparison language to ātranslateā the results of different HRA methods. These seven lessons learned highlight how the present study can serve as a useful template for future benchmarking studies
Three Stages of Lysozyme Thermal Stabilization by High and Medium Charge Density Anions
Addition of high and medium charge density anions (phosphate, sulfate, and chloride) to lysozyme in pure water demonstrates three stages for stabilization of the protein structure. The first two stages have a minor impact on lysozyme stability and are probably associated with direct interaction of the ions with charged and partial charges on the proteinās surface. There is a clear transition between the second and third stages; in the case of sodium chloride, disodium sulfate and disodium hydrogen phosphate this is at 550, 210, and 120 mM, respectively. Stabilization of lysozyme can be explained by the free energy required to hydrate the protein as it unfolds. At low ion concentrations, the proteinās hydration layer is at equilibrium with the bulk water. After the transition, bulk water is depleted and the protein is competing for water with the ions. With competition for water between the protein and the ions at higher salt concentrations, the free energy required to hydrate the interior of the protein rises and it is this that stabilizes the protein structure
Dynamical scaling and isotope effect in temporal evolution of mesoscopic structure during hydration of cement
The evolution of mesoscopic structure for cement-water mixtures turning into
colloidal gels remains far from being understood. Recent neutron scattering
investigations (Phys. Rev. Lett. 93, 255704 (2004); Phys. Rev. B. 72, 224208
(2005); Phys. Rev. B. 82, 064203 (2010)),, reveal the role of hydrogen bond in
temporal evolution of the mesoscopic structure during hydration of cement which
is the most consumed synthetic material. The present neutron scattering
investigation on hydration of cement with a mixture of light and heavy water
points to incomprehensibility of the temporal evolution of the mesoscopic
structure in terms of earlier observations on hydration with pure light or
heavy water. Unlike in the case of hydration with light water, disagreement has
been observed with the hypothesis of dynamical scaling for hydration of cement
with a mixture of the two types of water. The dynamics of evolution of the
mesoscopic structure has been observed to be nonlinear in regard to the
composition of hydration medium.Comment: 16 Pages, 5 Figure
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