Ligand and membrane-binding behavior of the phosphatidylinositol transfer proteins PITPα and β

Phosphatidylinositol transfer proteins (PITPs) are believed to be lipid transfer proteins due to their ability to transfer either PI or PC between membrane compartments in vitro. However, the detailed mechanism of this transfer process is not fully established. To further understand the transfer mechanism of PITPs we examined the interaction of PITPs with membranes using dual polarization interferometry (DPI) which measures protein binding affinity on a flat immobilized lipid surface. In addition, a fluorescence resonance energy transfer (FRET)-based assay was also employed to monitor how quickly PITPs transfer their ligands to lipid vesicles. DPI analysis revealed that PITPβ had a higher affinity to membranes compared to PITPα. Furthermore, the FRET-based transfer assay revealed that PITPβ has a higher ligand transfer rate compared to PITPα. However, both PITPα and PITPβ demonstrated a preference for highly curved membrane surfaces during ligand transfer. In other words, ligand transfer rate was higher when the accepting vesicles were highly curved

Association of antihypertensive monotherapy with serum sodium and potassium levels in Chinese patients

<b>Background</b> International guidelines on management of hypertension recommend any major classes of antihypertensive drugs. However, the low prescribing rate of thiazides has been attributed to concerns about electrolyte disturbances and studies between antihypertensive drug classes and hyponatremia/hypokalemia among Chinese patients were scarce. <p></p> <b>Methods</b> From clinical databases we included 2,759 patients who received their first-ever antihypertensive monotherapy from January 2004 to June 2007 in a large territory of Hong Kong. We studied the plasma sodium and potassium levels 8 weeks after prescriptions and factors associated with hyponatremia and hypokalemia by multivariable regression analyses. <p></p> <b>Results</b> Among major antihypertensive drug classes, thiazide users had the lowest sodium level (139.6 mEq/l, 95% confidence interval (CI) 139.3, 140.0, P < 0.001) and patients-prescribed calcium channel blockers (CCBs; 3.92 mEq/l, 95% CI 3.89, 3.95) or thiazide diuretics (3.99 mEq/l, 95% CI 3.93, 4.04) had the lowest potassium levels (P < 0.001). Multivariate analysis reported that advanced age (>/=70 years, odds ratio (OR) 7.49, 95% CI 2.84, 19.8, P < 0.001), male gender (OR 2.38, 95% CI 1.45, 3.91, P < 0.001), and thiazide users (OR 2.42, 95% CI 1.29, 4.56, P = 0.006) were significantly associated with hyponatremia, while renin-angiotensin system (RAS) (OR 0.31, 95% CI 0.13, 0.73, P = 0.008) and beta-blockers (BBs) (OR 0.35, 95% CI 0.23, 0.54, P < 0.001) users were less likely to present with hypokalemia. However, the proportions having normonatremic (95.1%) and normokalemic (89.4%) levels were high. <p></p> <b>Conclusions</b> In view of the low prevalence of hyponatremia and hypokalemia associated with thiazides, physicians should not be deterred from prescribing thiazide diuretics as first-line antihypertensive agents as recommended by most international guidelines

Feeling of knowing and restudy choices

Feeling-of-knowing judgments (FOK-Js) reflect people’s confidence that they would be able to recognize a currently unrecallable item. Although much research has been devoted to the factors determining the magnitude and accuracy of FOK-Js, much less work has addressed the issue of whether FOK-Js are related to any form of metacognitive control over memory processes. In the present study, we tested the hypothesis that FOK-Js are related to participants’ choices of which unrecallable items should be restudied. In three experiments, we showed that participants tend to choose for restudy items with high FOK-Js, both when they are explicitly asked to choose for restudy items that can be mastered in the restudy session (Exps. 1a and 2) and when such specific instructions are omitted (Exp. 1b). The study further demonstrated that increasing FOK-Js via priming cues affects restudy choices, even though it does not affect recall directly. Finally, Experiment 2 showed the strategy of restudying unrecalled items with high FOK-Js to be adaptive, because the efficacy of restudy is greater for these items than for items with low FOK-Js. Altogether, the present findings underscore an important role of FOK-Js for the metacognitive control of study operations

Traditional and emerging indicators of cardiovascular risk in chronic obstructive pulmonary disease

With the increased cardiovascular (CV) morbidity and mortality in subjects with chronic obstructive pulmonary disease (COPD), there is a priority to identify those patients at increased risk of cardiovascular disease. Stable patients with COPD (n = 185) and controls with a smoking history (n = 106) underwent aortic pulse wave velocity (PWV), blood pressure (BP) and skin autofluorescence (AF) at clinical stability. Blood was sent for fasting lipids, soluble receptor for advanced glycation end products (sRAGE) and CV risk prediction scores were calculated. More patients (18%) had a self-reported history of CV disease than controls (8%), p = 0.02, whilst diabetes was similar (14% and 10%), p = 0.44. Mean (SD) skin AF was greater in patients: 3.1 (0.5) AU than controls 2.8 (0.6) AU, p < 0.001. Aortic PWV was greater in patients: 10.2 (2.3) m/s than controls: 9.6 (2.0) m/s, p = 0.02 despite similar BP. The CV risk prediction scores did not differentiate between patients and controls nor were the individual components of the scores different. The sRAGE levels were not statistically different. We present different indicators of CV risk alongside each other in well-defined subjects with and without COPD. Two non-invasive biomarkers associated with future CV burden: skin AF and aortic PWV are both significantly greater in patients with COPD compared to the controls. The traditional CV prediction scores used in the general population were not statistically different. We provide new data to suggest that alternative approaches for optimal CV risk detection should be employed in COPD management

Mathematically gifted and talented learners: Theory and practice

This is an Author's Accepted Manuscript of an article published in International Journal of Mathematical Education in Science and Technology, 40(2), 213-228, 2009, copyright Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/00207390802566907.There is growing recognition of the special needs of mathematically gifted learners. This article reviews policy developments and current research and theory on giftedness in mathematics. It includes a discussion of the nature of mathematical ability as well as the factors that make up giftedness in mathematics. The article is set in the context of current developments in Mathematics Education and Gifted Education in the UK and their implications for Science and Technology. It argues that early identification and appropriate provision for younger mathematically promising pupils capitalizes on an intellectual resource which could provide future mathematicans as well as specialists in Science or Technology. Drawing on a Vygotskian framework, it is suggested that the mathematically gifted require appropriate cognitive challenges as well as attitudinally and motivationally enhancing experiences. In the second half of this article we report on an initiative in which we worked with teachers to identify mathematically gifted pupils and to provide effective enrichment support for them, in a number of London Local Authorities. A number of significant issues are raised relating to the identification of mathematical talent, enrichment provision for students and teachers’ professional development

The M33 Globular Cluster System with PAndAS Data: The Last Outer Halo Cluster?

We use CFHT/MegaCam data to search for outer halo star clusters in M33 as part of the Pan-Andromeda Archaeological Survey (PAndAS). This work extends previous studies out to a projected radius of 50 kpc and covers over 40 square degrees. We find only one new unambiguous star cluster in addition to the five previously known in the M33 outer halo (10 kpc <= r <= 50 kpc). Although we identify 2440 cluster candidates of various degrees of confidence from our objective image search procedure, almost all of these are likely background contaminants, mostly faint unresolved galaxies. We measure the luminosity, color and structural parameters of the new cluster in addition to the five previously-known outer halo clusters. At a projected radius of 22 kpc, the new cluster is slightly smaller, fainter and redder than all but one of the other outer halo clusters, and has g' ~ 19.9, (g'-i') ~ 0.6, concentration parameter c ~ 1.0, a core radius r_c ~ 3.5 pc, and a half-light radius r_h ~ 5.5 pc. For M33 to have so few outer halo clusters compared to M31 suggests either tidal stripping of M33's outer halo clusters by M31, or a very different, much calmer accretion history of M33.Comment: 37 pages, 9 figures. Accepted by the Astrophysical Journa