Composition in the Interface between Clay Mineral Surfaces and Divalent Cation Electrolytes.

The interfacial free energy of a solid, which determines its adsorption properties, depends on interactions between the surface and the fluid. A change in surface composition can completely change the behavior of the solid. Decades of work have explored adsorption and its effects at solid-fluid interfaces from the macroscopic perspective and using molecular modeling, so the concept of the electric double layer (EDL) is well established in the community. However, direct, molecular level, experimental observations of the composition within the interface region, and its change with time and conditions, are not abundant. We used cryogenic X-ray photoelectron spectroscopy (cryoXPS) to observe the composition in the clay mineral-solution interface region as a function of bulk solution composition, on illite and chlorite in MgCl2 and CaCl2 electrolytes, over a range of concentrations (1-125 mM), in situ, on vitrified samples. These samples were prepared from very thin smears of centrifuged wet paste that were instantaneously chilled to liquid N2 temperature. They preserved the adsorbed solution in its amorphous state, maintaining the location of the ions and water with respect to the solid, without the disruption that occurs during drying or the rearrangement that results as water crystallizes during freezing. With decreasing ionic strength, we could directly monitor the loss of negative charge in the interface region, producing an anion deficiency, as predicted by theory. The Cl-/Me2+ ratio dropped below 1 for chlorite at 12-25 mM MeCl2 and for illite at 75-100 mM. In addition to better understanding of clay mineral behavior in solution, this work demonstrates that only those clay minerals where surface charge density is the same or lower than that for chlorite contribute to a low salinity enhanced oil recovery response (LS EOR). This explains many of the contradictory results from studies about the role of clay minerals in LS EOR.

A cross-sectional study of tetanus and diphtheria antibody concentrations post vaccination among lung transplant patients compared with healthy individuals.

BACKGROUND: Lung transplant (LuTx) patients are routinely immunized against tetanus and diphtheria. However, few studies have been done to measure serologic immunity in the transplant population. OBJECTIVES: The primary objective of this study was to compare tetanus and diphtheria antibody concentrations in LuTx vs. healthy subjects. METHODS: Serum was used from an available sample of 111 total individuals (n = 36 healthy; n = 75 LuTx). Tetanus and diphtheria antibody concentrations were measured using an enzyme-linked immunosorbant assay method. RESULTS: A statistically significant difference in both tetanus and diphtheria antibody concentrations was found between the groups. The median concentration of tetanus antibody was higher for healthy individuals compared with the LuTx group (3.2 IU/mL [1.2-5.2 interquartile range {IQR}] vs. 1.3 IU/mL [0.4-2.6 IQR], respectively; P = 0.0001). No difference in time was found since the last tetanus-diphtheria vaccine or tetanus-diphtheria-pertussis vaccine dose between the groups (healthy 76.5 months [16-114 IQR] vs. LuTx 74.5 months [45-118 IQR]; P = 0.44). CONCLUSIONS: Tetanus and diphtheria immunizations are recommended for LuTx patients to reduce the risk of infection. Because the LuTx group has lower antibody concentrations, further studies should investigate the possible need for more frequent tetanus and diphtheria boosters.

Soluble CD163: a biomarker linking macrophages and insulin resistance.

AIMS/HYPOTHESIS: Soluble CD163 (sCD163) was recently identified as a strong risk marker for developing type 2 diabetes. We hypothesised that sCD163 independently associates with insulin resistance. METHODS: This cross-sectional study includes 234 participants: 96 with type 2 diabetes, 34 with impaired glucose tolerance (IGT) and 104 with normal glucose tolerance (NGT), matched for sex and BMI. Glucose-lowering medication was paused for 1 week before plasma samples were obtained for determination of sCD163 and other inflammatory and metabolic variables. Insulin resistance was estimated by homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Concentrations of sCD163 were 1.95 mg/l (0.63-6.97) in individuals with type 2 diabetes, 1.64 mg/l (0.58-4.19) in those with IGT, and 1.48 mg/l (0.48-4.11) (median [range]) in those with NGT (p < 0.0001). In univariate analyses, sCD163 correlated significantly with HOMA-IR (R = 0.44), insulin (R = 0.41), glucose (R = 0.30), triacylglycerol (R = 0.29) and HDL-cholesterol (R = -0.34) (all p < 0.0001). All but glucose remained significant when adjusting for age, sex, BMI and glycaemic group. In univariate regression analyses, HOMA-IR was associated with sCD163, C-reactive protein (CRP), TNF-α and IL-6 (all p ≤ 0.0001). An increase of 50% in sCD163 resulted in an estimated increase in HOMA-IR of 36% (95% CI 26, 48; p < 0.0001). In multiple linear regression analyses, sCD163 (p = 0.001) and CRP (p = 0.01) remained independent predictors of HOMA-IR, whereas TNF-α and IL-6 did not. CONCLUSIONS/INTERPRETATION: Macrophage-specific sCD163 was strongly associated with insulin resistance independently of TNF-α and other predictors. Moreover, sCD163 was associated with well-known variables of the metabolic syndrome.

Mapping the stem cell state: eight novel human embryonic stem and embryonal carcinoma cell antibodies.

The antigenic profile of human embryonic stem (ES) and embryonal carcinoma (EC) cells has served as a key element of their characterization, with a common panel of surface and intracellular markers now widely used. Such markers have been used to identify cells within the 'undifferentiated state', yet it appears that this categorization may be an oversimplification, because a number of sub-states appear to exist within this state. To increase the resolution of the undifferentiated state, we have generated eight novel monoclonal antibodies, all capable of recognizing undifferentiated human ES and EC cells, and herein describe their characterization. The reactivity of these antibodies against a range of cell lines is reported, as well as their developmental regulation, basic biochemistry and reactivity in immunohistochemistry of testicular germ cell tumours. Our data reveal a range of reactivity for all antibodies against both ES and EC cells, suggesting that these markers will afford recognition of unique sub-states within the undifferentiated stem cell compartment.

Genomic variants at the PINK1 locus are associated with transcript abundance and plasma nonesterified fatty acid concentrations in European whites.

The purpose of this study was to characterize associations between PINK1 genotypes, PINK1 transcript levels, and metabolic phenotypes in healthy adults and those with type 2 diabetes (T2D). We measured PINK1 skeletal muscle transcript levels and 8 independent PINK1 single nucleotide polymorphisms (SNPs) in a cohort of 208 Danish whites and in a cohort of 1701 British whites (SNPs and metabolic phenotypes only). Furthermore, we assessed the effects of PINK1 transcript ablation in primary adipocytes using RNA interference (RNAi). Six PINK1 SNPs were associated with PINK1 transcript levels (P<0.04 to P<0.0001). Obesity modified the association between PINK1 transcript levels and T2D risk (interaction P=0.005); transcript levels were inversely related with T2D in obese (n=105) [odds ratio (OR) per sd increase in expression levels=0.44; 95% confidence interval (CI): 0.23, 0.84; P=0.013] but not in nonobese (n=103) (OR=1.20; 95% CI: 0.82, 1.76; P=0.34) individuals. In the British cohort, several PINK1 SNPs were associated with plasma nonesterified fatty acid concentrations. Nominal genotype associations were also observed for fasting glucose, 2-h glucose, and maximal oxygen consumption, although these were not statistically significant after correcting for multiple testing. In primary adipocytes, Pink1 knockdown affected fatty acid binding protein 4 (Fabp4) expression, indicating that PINK1 may influence substrate metabolism. We demonstrate that PINK1 polymorphisms are associated with PINK1 transcript levels and measures of fatty acid metabolism in a concordant manner, whereas our RNAi data imply that PINK1 may indirectly influence lipid metabolism.

RBP-to-retinol ratio, but not total RBP, is elevated in patients with type 2 diabetes.

AIM: It was recently reported that serum retinol-binding protein (RBP), also known as retinol-binding protein 4 (RBP4), was positively associated with systemic insulin resistance. We hypothesized that an imbalance between RBP and retinol might be the underlying cause for this association. METHODS: We studied the ratio between RBP and retinol in 233 humans divided into groups depending on normal glucose tolerance (NGT), impaired glucose tolerance (IGT), type 2 diabetes (T2DM) and presence or absence of obesity. RESULTS: Plasma RBP and retinol levels were lower in patients with T2DM than in individuals with NGT (p < 0.05 and p < 0.0001 respectively). In contrast, RBP-to-retinol ratio was higher in individuals with T2DM (p < 0.0001) and IGT (p < 0.05). Following multivariate adjustment, RBP and retinol correlated positively with low-density lipoprotein (LDL) and triglycerides (p < 0.0001, except retinol and LDL: p < 0.001). RBP-to-retinol ratio correlated positively with glucose 2 h after an oral glucose tolerance test (p < 0.0001) and with C-reactive protein (p < 0.001). Retinol, RBP and adipose tissue RBP messenger RNA (mRNA) levels shared an inverse relationship with plasma interleukin-6, and adipose tissue RBP mRNA levels correlated positively with plasma tumour necrosis factor-alpha (TNF-alpha) and skeletal muscle TNF-alpha mRNA levels. CONCLUSIONS: Our results suggest that the excess of RBP relative to retinol, assessed as the RBP-to-retinol ratio, is more indicative of T2DM than RBP itself. Hence, the previously reported insulin resistance in mice induced by overexpression or injection of RBP could be because of higher levels of RBP relative to retinol rather than higher total levels of RBP. Moreover, TNF-alpha may have a role in RBP-mediated adipose to muscle crosstalk.

Intravascular infusion of PEGylated Au nanoparticles affects cardiovascular function in healthy mice.

Recent advances of nanotechnology in clinical settings have spurred the development of various complex engineered nanoparticles (NPs). NPs share characteristics with ultrafine particles (UFPs; <1 µm) that can cross the pulmonary epithelium and disturb cardiovascular functions. Since these particles are injected directly into the blood stream, it is imperative to clarify whether NPs disrupt cardiovascular functions similar to UFPs. Therefore, we investigated whether engineered polyethylene glycol (PEG)-coated aluminum NPs for biomedical uses disturb cardiovascular functions in healthy mice. Mean arterial blood pressure (MAP) was measured in mice chronically instrumented with telemetric blood pressure transducers, and NPs were administered intravenously (10 mg kg(-1)). The NPs caused a prolonged lowering of MAP 7 days after injection (119.3 ± 3.3 vs. 97.4 ± 7.5 min(-1)), with no effect on the endothelial function as revealed by normal endothelial function of small vessels mounted in a myograph.

Associations between insulin resistance and TNF-alpha in plasma, skeletal muscle and adipose tissue in humans with and without type 2 diabetes.

AIMS/HYPOTHESIS: Clear evidence exists that TNF-alpha inhibits insulin signalling and thereby glucose uptake in myocytes and adipocytes. However, conflicting results exist with regard to the role of TNF-alpha in type 2 diabetes. METHODS: We obtained blood and biopsy samples from skeletal muscle and subcutaneous adipose tissue in patients with type 2 diabetes (n = 96) and healthy controls matched for age, sex and BMI (n = 103). RESULTS: Patients with type 2 diabetes had higher plasma levels of fasting insulin (p < 0.0001) and glucose (p < 0.0001) compared with controls, but there was no difference between groups with regard to fat mass. Plasma levels of TNF-alpha (p = 0.0009) and soluble TNF receptor 2 (sTNFR2; p = 0.002) were elevated in diabetic patients. Insulin sensitivity was correlated with quartiles of plasma TNF-alpha after adjustment for age, sex, obesity, WHR, neutrophils, IL-6 and maximum O(2) uptake (VO2/kg) in the diabetes group (p < 0.05). The TNF mRNA content of adipose or muscle tissue did not differ between the groups, whereas muscle TNF-alpha protein content, evaluated by western blotting, was higher in type 2 diabetic patients. Immunohistochemistry revealed more TNF-alpha protein in type 2 than in type 1 muscle fibres. CONCLUSIONS/INTERPRETATION: After adjustment for multiple confounders, plasma TNF-alpha is associated with insulin resistance. This supports the idea that TNF-alpha plays a significant role in the pathogenesis of chronic insulin resistance in humans. However, findings on the TNF-alpha protein levels in plasma and skeletal muscle indicate that measurement of TNF mRNA content in adipose or muscle tissue provides no information with regard to the degree of insulin resistance.

Brain-derived neurotrophic factor (BDNF) and type 2 diabetes.

AIMS/HYPOTHESIS: Decreased levels of brain-derived neurotrophic factor (BDNF) have been implicated in the pathogenesis of Alzheimer's disease and depression. These disorders are associated with type 2 diabetes, and animal models suggest that BDNF plays a role in insulin resistance. We therefore explored whether BDNF plays a role in human glucose metabolism. SUBJECTS AND METHODS: We included (Study 1) 233 humans divided into four groups depending on presence or absence of type 2 diabetes and presence or absence of obesity; and (Study 2) seven healthy volunteers who underwent both a hyperglycaemic and a hyperinsulinaemic-euglycaemic clamp. RESULTS: Plasma levels of BDNF in Study 1 were decreased in humans with type 2 diabetes independently of obesity. Plasma BDNF was inversely associated with fasting plasma glucose, but not with insulin. No association was found between the BDNF G196A (Val66Met) polymorphism and diabetes or obesity. In Study 2 an output of BDNF from the human brain was detected at basal conditions. This output was inhibited when blood glucose levels were elevated. In contrast, when plasma insulin was increased while maintaining normal blood glucose, the cerebral output of BDNF was not inhibited, indicating that high levels of glucose, but not insulin, inhibit the output of BDNF from the human brain. CONCLUSIONS/INTERPRETATION: Low levels of BDNF accompany impaired glucose metabolism. Decreased BDNF may be a pathogenetic factor involved not only in dementia and depression, but also in type 2 diabetes, potentially explaining the clustering of these conditions in epidemiological studies.