Viscoelastic behaviour of human mesenchymal stem cells

Background  

In this study, we have investigated the viscoelastic behaviour of individual human adult bone marrow-derived mesenchymal stem cells (hMSCs) and the role of F-actin filaments in maintaining these properties, using micropipette aspiration technique together with a standard linear viscoelastic solid model.     

Use of quasi-least squares to adjust for two levels of correlation

This article considers data with two levels of association. Our motivating example is an international intervention trial with repeated observations on subjects who reside within geographically defined clusters. To account for the potential correlation within clusters and within the repeated measurements that pertain to each subject, we apply a method based on generalized estimating equations for a correlation structure proposed by Lefkopoulou, Moore, and Ryan (1989, Journal of the American Statistical Association 84, 810-815).     

Mitochondrial dysfunction and possible treatments in Parkinson's disease--a review

Mitochondria are central not only to the bioenergetics of the cell but also to the process of apoptotic cell death. Substantial data indicate mitochondrial dysfunction, particularly of complex I of the electron transport chain, in some patients with Parkinson's disease (PD), and it appears likely that mitochondria contribute to the pathogenic processes that occurs in this disorder. Treatments targeted at mitochondrial function hold promise to slow the progression of PD.     

Dynamic RNA Fitness Landscapes of a Group I Ribozyme during Changes to the Experimental Environment

Fitness landscapes of protein and RNA molecules can be studied experimentally using high-throughput techniques to measure the functional effects of numerous combinations of mutations. The rugged topography of these molecular fitness landscapes is important for understanding and predicting natural and experimental evolution. Mutational effects are also dependent upon environmental conditions, but the effects of environmental changes on fitness landscapes remains poorly understood. Here, we investigate the changes to the fitness landscape of a catalytic RNA molecule while changing a single environmental variable that is critical for RNA structure and function. Using high-throughput sequencing of in vitro selections, we mapped a fitness landscape of the Azoarcus group I ribozyme under eight different concentrations of magnesium ions (1–48 mM MgCl₂). The data revealed the magnesium dependence of 16,384 mutational neighbors, and from this, we investigated the magnesium induced changes to the topography of the fitness landscape. The results showed that increasing magnesium concentration improved the relative fitness of sequences at higher mutational distances while also reducing the ruggedness of the mutational trajectories on the landscape. As a result, as magnesium concentration was increased, simulated populations evolved toward higher fitness faster. Curve-fitting of the magnesium dependence of individual ribozymes demonstrated that deep sequencing of in vitro reactions can be used to evaluate the structural stability of thousands of sequences in parallel. Overall, the results highlight how environmental changes that stabilize structures can also alter the ruggedness of fitness landscapes and alter evolutionary processes.     

A Note on the Use of Unbiased Estimating Equations to Estimate Correlation in Analysis of Longitudinal Trials

Longitudinal trials can yield outcomes that are continuous, binary (yes/no), or are realizations of counts. In this setting we compare three approaches that have been proposed for estimation of the correlation in the framework of generalized estimating equations (GEE): quasi‐least squares (QLS), pseudo‐likelihood (PL), and an approach we refer to as Wang–Carey (WC). We prove that WC and QLS are identical for the first‐order autoregressive AR(1) correlation structure. Using simulations, we then develop guidelines for selection of an appropriate method for analysis of data from a longitudinal trial. In particular, we argue that no method is uniformly superior for analysis of unbalanced and unequally spaced data with a Markov correlation structure. Choice of the best approach will depend on the degree of imbalance and variability in the temporal spacing of measurements, value of the correlation, and type of outcome, e.g. binary or continuous. Finally, we contrast the methods in analysis of a longitudinal study of obesity following renal transplantation in children (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Obesity‐related Comorbidities in Obese African Americans in an Outpatient Weight Loss Program

Objective: To identify, among obese African‐American enrollees in an outpatient weight loss program, differences between those with and without obesity‐related comorbidities (ORCMs). Research Methods and Procedures: Data were from 237 obese African Americans (BMI, 30 to 50 kg/m²; 90% women) who enrolled in a 10‐week lifestyle weight loss program. Analyses compared subgroups defined by ORCM status (from medical history) on baseline characteristics, program attendance, and postprogram weight change. Results: Most participants (76%) had one or more ORCMs. Those with versus without ORCMs, respectively, were older (mean age, 45.6 vs. 37.1 years; p < 0.001), were less educated (59.2% vs. 76.6% with >12 years; p = 0.031), were more likely to perceive a physical limitation affecting activity (22.2% vs. 1.8%; p < 0.001), and had higher waist circumference (mean, 113.7 vs. 106.9 cm; p < 0.001) but not BMI (38.3 vs. 37.0 kg/m²; p = 0.095). Logistic regression analyses confirmed the independence of these associations. Having ORCMs was not associated with class attendance or return for data collection after the 10‐week program. Postprogram weight change (n = 134) was unrelated to ORCMs, but better weight loss was seen among those without perceived physical limitations (1.9 vs. 0.4 kg in those without versus with limitations; p = 0.069). Conclusion: Data from this clinical sample of obese African Americans suggest that waist circumference is relevant to ORCM status at BMI levels up to 50 kg/m². Clear indications for tailoring of treatment based on ORCM status were not identified, although the possible influence of ORCM‐related activity limitations warrants further study.     

Study of skin anti-ageing and anti-inflammatory effects of dihydroquercetin, natural triterpenoinds, and their synthetic derivatives

Accessible triterpenoids of ursane and lupane series, the flavonoid dihydroquercetin and their synthetic derivatives with polar substituents were tested in vitro for inhibition of collagenase 1 (MMP-1) in UVB irradiation assay. Ursolic acid and uvaol disuccinate were the most active inhibitors in the ursane series. In the lupane series, the best inhibition was manifested by carboxymethyl ester of betulonic acid and betulin succinates. Down- regulation of MMP-1 by dihydroquercetin and its synthetic derivatives surpassed the activity of a standard (retinoic acid).