High-performance liquid chromatography as a technique to measure the competitive adsorption of plasma proteins onto latices

Isotherms of human serum albumin (HSA), human immunoglobulin G (HIgG), and human fibrinogen (HFb) onto a polystyrene (PS)-latex were determined by depletion of protein in the solution, which was either followed by radioactivity measurements or by UV spectroscopy. Different adsorption isotherms for the same protein were obtained when either radioactivity measurements or UV spectroscopy was used as a detection technique. In order to obtain reliable results from competitive protein adsorption experiments, a method based on the use of high-performance liquid chromatography was developed. A strong preferential adsorption of HFb was observed when adsorption studies were carried out with mixtures of HSA, HFb, and HIgG. When adsorption studies were carried out with solutions containing HSA monomer and dimer, a strong preferential adsorption of HSA dimer was also observed

Dimensional Effects on Densities of States and Interactions in Nanostructures

We consider electrons in the presence of interfaces with different effective electron mass, and electromagnetic fields in the presence of a high-permittivity interface in bulk material. The equations of motion for these dimensionally hybrid systems yield analytic expressions for Green’s functions and electromagnetic potentials that interpolate between the two-dimensional logarithmic potential at short distance, and the three-dimensional r−1 potential at large distance. This also yields results for electron densities of states which interpolate between the well-known two-dimensional and three-dimensional formulas. The transition length scales for interfaces of thickness L are found to be of order Lm/2m* for an interface in which electrons move with effective mass m*, and for a dielectric thin film with permittivity in a bulk of permittivity . We can easily test the merits of the formalism by comparing the calculated electromagnetic potential with the infinite series solutions from image charges. This confirms that the dimensionally hybrid models are excellent approximations for distances r ≳ L/2

Association between TNF Receptors and KIM-1 with Kidney Outcomes in Early-Stage Diabetic Kidney Disease

Background and objectives: Clinical trials in nephrology are enriched for patients with micro- or macroalbuminuria to enroll patients at risk of kidney failure. However, patients with normoalbuminuria can also progress to kidney failure. Tumor Necrosis Factor Receptor (TNFR)-1, TNFR-2 and Kidney Injury Marker (KIM)-1 are known to be associated with kidney disease progression in patients with micro- or macroalbuminuria. We assessed the value of TNFR-1, TNFR-2 and KIM-1 as prognostic biomarkers for CKD progression in patients with type 2 diabetes and normoalbuminuria. Design, setting, participants and measurements: TNFR-1, TNFR-2, and KIM-1 were measured using immunoassays in plasma samples from patients with type 2 diabetes at high cardiovascular risk participating in the CANVAS trial. We used multivariable adjusted Cox proportional hazards analyses to estimate hazard ratios per doubling of each biomarker for the kidney outcome and stratified the population by the 4th quartile of each biomarker distribution and assessed the number of events and event rates. Results: In patients with normoalbuminuria (N=2,553), 51 kidney outcomes were recorded during a median follow-up of 6.1 (IQR 5.8 to 6.4) years (event rate 3.5 [95%CI 2.6-4.6] per 1,000-patient-years). Each doubling of baseline TNFR-1 (HR 4.16; 95%CI 1.80-9.61) and TNFR-2 (HR 2.35; 95%CI 1.51-3.63) was associated with a higher risk for the kidney outcome. Baseline KIM-1, UACR and eGFR were not associated with kidney outcomes. The event rates in the highest quartile of the TNFR-1 (≥2,992 ng/ml) or TNFR-2 (≥11,394 ng/ml) were 5.6 and 7.0 events per 1000-patient-years compared to 2.4 and 2.8 in the lower three quartiles. Conclusion: TNFR-1 and TNFR-2 are associated with kidney outcomes in patients with type 2 diabetes and normoalbuminuria

Non-Minimal Warm Inflation and Perturbations on the Warped DGP Brane with Modified Induced Gravity

We construct a warm inflation model with inflaton field non-minimally coupled to induced gravity on a warped DGP brane. We incorporate possible modification of the induced gravity on the brane in the spirit of $f(R)$-gravity. We study cosmological perturbations in this setup. In the case of two field inflation such as warm inflation, usually entropy perturbations are generated. While it is expected that in the case of one field inflation these perturbations to be removed, we show that even in the absence of the radiation field, entropy perturbations are generated in our setup due to non-minimal coupling and modification of the induced gravity.Comment: 29 pages, 7 figures, Accepted by Gen. Rel Gravi

Brane Big-Bang Brought by Bulk Bubble

We propose an alternative inflationary universe scenario in the context of Randall-Sundrum braneworld cosmology. In this new scenario the existence of extra-dimension(s) plays an essential role. First, the brane universe is initially in the inflationary phase driven by the effective cosmological constant induced by small mismatch between the vacuum energy in the 5-dimensional bulk and the brane tension. This mismatch arises since the bulk is initially in a false vacuum. Then, the false vacuum decay occurs, nucleating a true vacuum bubble with negative energy inside the bulk. The nucleated bubble expands in the bulk and consequently hits the brane, bringing a hot big-bang brane universe of the Randall-Sundrum type. Here, the termination of the inflationary phase is due to the change of the bulk vacuum energy. The bubble kinetic energy heats up the universe. As a simple realization, we propose a model, in which we assume an interaction between the brane and the bubble. We derive the constraints on the model parameters taking into account the following requirements: solving the flatness problem, no force which prohibits the bubble from colliding with the brane, sufficiently high reheating temperature for the standard nucleosynthesis to work, and the recovery of Newton's law up to 1mm. We find that a fine tuning is needed in order to satisfy the first and the second requirements simultaneously, although, the other constraints are satisfied in a wide range of the model parameters.Comment: 20pages, 5figures, some references added, the previous manuscript has been largely improve

Cardiomyocytes from human pluripotent stem cells: from laboratory curiosity to industrial biomedical platform

Cardiomyocytes from human pluripotent stem cells (hPSCs-CMs) could revolutionise biomedicine. Global burden of heart failure will soon reach USD $90bn, while unexpected cardiotoxicity underlies 28% of drug withdrawals. Advances in hPSC isolation, Cas9/CRISPR genome engineering and hPSC-CM differentiation have improved patient care, progressed drugs to clinic and opened a new era in safety pharmacology. Nevertheless, predictive cardiotoxicity using hPSC-CMs contrasts from failure to almost total success. Since this likely relates to cell immaturity, efforts are underway to use biochemical and biophysical cues to improve many of the ~ 30 structural and functional properties of hPSC-CMs towards those seen in adult CMs. Other developments needed for widespread hPSC-CM utility include subtype specification, cost reduction of large scale differentiation and elimination of the phenotyping bottleneck. This review will consider these factors in the evolution of hPSC-CM technologies, as well as their integration into high content industrial platforms that assess structure, mitochondrial function, electrophysiology, calcium transients and contractility. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele