The effects of membrane cholesterol and simvastatin on red blood cell deformability and ATP release

It is known that deformation of red blood cells (RBCs) is linked to ATP release from the cells. Further, membrane cholesterol has been shown to alter properties of the cell membrane such as fluidity and bending stiffness. Membrane cholesterol content is increased in some cardiovascular diseases, for example, in individuals with acute coronary syndromes and chronic stable angina, and therefore, because of the potential clinical relevance, we investigated the influence of altered RBC membrane cholesterol levels on ATP release. Because of the correlation between statins and reduced membrane cholesterol in vivo, we also investigated the effects of simvastatin on RBC deformation and ATP release. We found that reducing membrane cholesterol increases cell deformability and ATP release. We also found that simvastatin increases deformability by acting directly on the membrane in the absence of the liver, and that ATP release was increased for cells with enriched cholesterol after treatment with simvastatin.     

Importance of Ca(2+) modifications for osseointegration of smooth and moderately rough anodized titanium implants - a removal torque and histological evaluation in rabbit

Background: Incorporation of Ca²⁺ into the titania of anodized titanium surfaces has been found to enhance osseointegration. It provides a stable surface when the ions are incorporated into the oxide layer during the anodizing process. The Ca²⁺ may suggestively be prominent sites for mineral induction, attract proteins, and catalyze intracellular cascades. Purpose: The aim of the present study was to evaluate the osseointegration of smooth (S_a < 0.5 µm) and moderately rough (S_a 1.0–2.0 µm) commercially pure titanium implants, with and without Ca²⁺, in order to reflect on the importance of surface chemistry in relation to topography. Materials and Methods: Anodized implants with (OxCa) or without Ca²⁺ (Ox), blasted implants (Bl), and blasted anodized implants, with (BlOxCa) or without Ca²⁺ (BlOx), were inserted in rabbit femur and tibia. The implant surfaces were characterized using interferometry, scanning electron microscopy, and X‐ray photoelectron spectroscopy prior to implant installation. Removal torque (RTQ) measurements were executed on all implants after a healing period of 12 weeks. The implants were, thereafter, removed en bloc with surrounding tissues and prepared for histological evaluations. Results: RTQ measurements of tibial implants revealed significantly higher values for BlOxCa implants (90.7 ± 23.3 Ncm) compared to OxCa (64.6 ± 18.2 Ncm) and BlOx implants (69.7 ± 17.5 Ncm) (p = 0.029). Ca²⁺ modification of smooth implants placed in the femur did not reveal any differences. Conclusion: Ca²⁺ modification of smooth implants resulted in similar interfacial shear strength as moderately rough implants and Ca²⁺ modification of moderately rough implants demonstrated the significantly strongest interfacial shear strength when placed in rabbit tibia. This possibly demonstrated surface chemistry compensating for lesser roughness.     

Prediagnostic circulating carotenoid levels and the risk of non-Hodgkin lymphoma: the Multiethnic Cohort

This analysis examined the association of non-Hodgkin lymphoma (NHL) with prediagnostic carotenoid levels, a marker for a diet rich in fruits and vegetables. We conducted a nested case-control study within the Multiethnic Cohort with 271 NHL cases and 538 controls matched on sex, ethnicity, location (Hawaii or Los Angeles), birth year, date and time of blood draw, and hours fasting before blood draw. Serum carotenoid levels were obtained by high-pressure liquid chromatography with photodiode array detection. Conditional logistic regression was used to calculate odds ratios (ORs) according to tertiles of serum carotenoids and trend tests using continuous variables. Higher total serum carotenoids (OR(T3 vs T1) = 0.66 [0.46-0.96]; P(trend) = .02), lycopene (OR = 0.54 [0.38-0.78]; P(trend) = .003), and α-cryptoxanthin (OR = 0.53 [0.36-0.78]; P(trend) = .003) were associated with a lower risk of NHL. For retinol (OR = 0.90 [0.61-1.33]; P(trend) = .04), a statistically significant inverse linear trend was detected. Risk estimates remained unchanged with adjustment for NHL risk factors and were similar in analyses stratified by sex and ethnicity; heterogeneity with NHL subtype was detected only for β-carotene. Other carotenoids, including α-carotene, β-carotene, lutein, β-cryptoxanthin, and zeaxanthin, showed no association with risk. These data provide support for a protective role of carotenoid-rich fruits and vegetables in the etiology of NHL.     

On the symmetry of siblings: automated single-cell tracking to quantify the behavior of hematopoietic stem cells in a biomimetic setup

The interplay between hematopoietic stem and progenitor cells (HSPC) and their local microenvironment is a key mechanism for the organization of hematopoiesis. To quantitatively study this process, a time-resolved analysis of cellular dynamics at the single-cell level is an essential prerequisite. One way to generate sufficient amounts of appropriate data is automatic single-cell tracking using time-lapse video microscopy. We describe and apply newly developed computational algorithms that allow for an automated generation of high-content data of single-cell characteristics at high temporal and spatial resolution, together with the reconstruction and statistical evaluation of complete genealogical histories. This methodology has been applied to the particular example of purified primary human HSPCs in bioengineered culture conditions. The combination of genealogical information and dynamic profiles of cellular properties identified a marked symmetry between sibling HSPCs regarding cell cycle time, but also migration speed and growth kinetics. Furthermore, we demonstrate that this symmetry of HSPC siblings can be altered by exogenous cues of the local biomimetic microenvironment. Using the example of HSPC growth in biomimetic culture systems, we show that our approach provides a valuable tool for the quantitative analysis of dynamic single-cell features under defined in?vitro conditions, allowing for integration of functional and genealogical data. The efficiency and accuracy of our approach pave the way for new and intriguing insights into the organizational principles of developmental patterns and the respective influence of exogenous cues not limited to the study of primary HSPCs.     

DBH −1021C>T and COMT Val108/158Met genotype are not associated with the P300 ERP in an auditory oddball task

ObjectiveThe amplitude and latency of the P300 may be associated by variations in dopaminergic genes. The current study was conducted to determine whether functional variants of the catechol-O-methyltransferase (COMT) and dopamine beta-hydroxylase (DBH) gene were associated with P300 amplitude and latency in an auditory oddball task.MethodsThe P300 ERP was assessed by a two-tone auditory oddball paradigm in a large sample of 320 healthy volunteers. The Val108/158Met polymorphism (rs4680) of the COMT gene and the ?1021C>T polymorphism (rs1611115) of the DBH gene were genotyped. P300 amplitude and latency were compared across genotype groups using analysis of variance.ResultsThere were no differences in demographic characteristics in subjects for genotypic subgroups. No genotype associations were observed for the P300 amplitude and latency on frontal, central and parietal electrode positions.ConclusionsCOMT Val108/158Met and DBH ?1021C>T polymorphisms do not show evidence of association with characteristics of the P300 ERP in an auditory oddball paradigm in healthy volunteers.SignificanceWe failed to find evidence for the association between dopaminergic enzymatic polymorphisms and the P300 ERP in healthy volunteers, in the largest study undertaken to date.     

Macro-AST: misleading finding in an adolescent with MCAD-deficiency

ABSTRACT: BACKGROUND: MCAD-deficiency is the most common inborn error of fatty acid oxidation now included in many newborn screening programms using MS/MS. During prolonged catabolic episodes, patients may suffer from metabolic decompensation with dysfunction of liver, skeletal- and heart muscle as well as brain. In anabolism, neither clinical symptoms nor biochemical signs of organ dysfunction occur. CASE PRESENTATION: We report a female patient with MCAD-deficiency in whom at the age of 11 years isolated AST-elevation was found without any clinical or biochemical signs of organ dysfunction. We showed by polyethylene glycol precipitation that macro-AST formation was responsible for this biochemical finding. AST was probably complexed with immunoglobulins possibly related to an allergic disposition. Macro-AST formation is not a special feature of MCAD-deficiency but rather a non-specific, coincidental finding which also occurs in healthy individuals. The general practitioner consulted by the patient before coming to our outpatient clinic for inborn errors of metabolism was worried that isolated AST-elevation indicated cell damage in MCAD-deficiency. He ordered further diagnostic tests like ultrasound, ECG and echocardiography without any pathology. CONCLUSION: In isolated AST-elevation, macro-AST has to be considered in order to avoid unnecessary, costly and invasive evaluation. This is not only true for healthy persons but for patients with chronic diseases like MCAD as well.     

Muscle architecture adaptations to knee extensor eccentric training: Rectus femoris vs. vastus lateralis

Introduction: Changes in muscle architecture induced by eccentric knee extensor training remain unclear, as well the adaptive responses of synergistic knee extensor muscles with different geometrical designs. Methods: Ultrasonography images were taken from rectus femoris (RF) and vastus lateralis (VL) of 20 male volunteers before and after a non‐training control period of 4 weeks, and additional evaluations were performed after 4, 8, and 12 weeks of isokinetic eccentric training. Results: RF and VL had significant changes in muscle architecture within the first 4 training weeks, and the adaptive response throughout the intervention was similar. Muscle thickness increased by around 7–10%, fascicle length increased 17–19%, and pennation angle was unchanged. Conclusions: Increased muscle thickness due to eccentric training was related to increased fascicle length and not to pennation angle changes. Although RF and VL have a different fascicular geometry, they had similar morphological adaptations to eccentric training. Muscle Nerve 48 : 498–506, 2013     

Ten years of enhancing neuro-imaging genetics through meta-analysis: An overview from the ENIGMA Genetics Working Group

Here we review the motivation for creating the enhancing neuroimaging genetics through meta-analysis (ENIGMA) Consortium and the genetic analyses undertaken by the consortium so far. We discuss the methodological challenges, findings, and future directions of the genetics working group. A major goal of the working group is tackling the reproducibility crisis affecting “candidate gene” and genome-wide association analyses in neuroimaging. To address this, we developed harmonized analytic methods, and support their use in coordinated analyses across sites worldwide, which also makes it possible to understand heterogeneity in results across sites. These efforts have resulted in the identification of hundreds of common genomic loci robustly associated with brain structure. We have found both pleiotropic and specific genetic effects associated with brain structures, as well as genetic correlations with psychiatric and neurological diseases.