Using three-point bending to evaluate tibia bone strength in ovariectomized young mice

It is well known that estrogen deficiency induces a deterioration of bone strength in aged females. The aim of this study is to determine the effect of estrogen depletion on tibia bone strength in sexually mature mice that are still undergoing skeletal maturation. At 8 weeks of age, C57BL/6 female mice underwent an ovariectomy (OVX) or sham (SHAM) surgery. Mice were killed at 2, 4, or 8 weeks post-surgery. Tibia length and cross-sectional area continued to increase in both treatment groups until 4 weeks post-surgery. Compared to SHAM mice, OVX mice demonstrated a significant reduction in uterine weight and plasma estrogen levels. Three-point bending was used to quantify the mechanical properties (breaking point, stress, stiffness, and elasticity) of the tibia. The tibias from the SHAM mice had a higher breaking point than all the age-matched OVX mice. At 8 weeks post-surgery, the tibias from the SHAM mice demonstrated higher elasticity, stress, and stiffness than the younger SHAM mice and the age-matched OVX mice. Compared to the SHAM mice, our study suggests that (1) there is a reduction in the mechanical strength of tibias from young OVX mice, and (2) the greatest decline in tibia strength of the OVX mice was once they reached skeletal maturity.     

Persistence length of collagen molecules based on nonlocal viscoelastic model

Persistence length is one of the most interesting properties of a molecular chain, which is used to describe the stiffness of a molecule. The experimentally measured values of the persistence length of the collagen molecule are widely scattered from 14 to 180 nm. Therefore, an alternative approach is highly desirable to predict the persistence length of a molecule and also to explain the experimental results. In this paper, a nonlocal viscoelastic model is developed to obtain the persistence length of the collagen molecules in solvent. A new explicit formula is proposed for the persistence length of the molecule with the consideration of the small-scale effect, viscoelastic properties of the molecule, loading frequency, and viscosity of the solvent. The presented model indicates that there exists a range of molecule lengths in which the persistence length strongly depends on the frequency and spatial mode of applied loads, small-scale effect, and viscoelastic properties of the collagen.     

The Effect of Post-Exercise Cryotherapy on Recovery Characteristics: A Systematic Review and Meta-Analysis

The aim of this review and meta-analysis was to critically determine the possible effects of different cooling applications, compared to non-cooling, passive post-exercise strategies, on recovery characteristics after various, exhaustive exercise protocols up to 96 hours (hrs). A total of n = 36 articles were processed in this study. To establish the research question, the PICO-model, according to the PRISMA guidelines was used. The Cochrane’s risk of bias tool, which was used for the quality assessment, demonstrated a high risk of performance bias and detection bias. Meta-analyses of subjective characteristics, such as delayed-onset muscle soreness (DOMS) and ratings of perceived exertion (RPE) and objective characteristics like blood plasma markers and blood plasma cytokines, were performed. Pooled data from 27 articles revealed, that cooling and especially cold water immersions affected the symptoms of DOMS significantly, compared to the control conditions after 24 hrs recovery, with a standardized mean difference (Hedges’ g) of -0.75 with a 95% confidence interval (CI) of -1.20 to -0.30. This effect remained significant after 48 hrs (Hedges’ g: -0.73, 95% CI: -1.20 to -0.26) and 96 hrs (Hedges’ g: -0.71, 95% CI: -1.10 to -0.33). A significant difference in lowering the symptoms of RPE could only be observed after 24 hrs of recovery, favouring cooling compared to the control conditions (Hedges’ g: -0.95, 95% CI: -1.89 to -0.00). There was no evidence, that cooling affects any objective recovery variable in a significant way during a 96 hrs recovery period.     

O-GlcNAcylation: key regulator of glycolytic pathways

Elevated O-GlcNAcylation is emerging as a general characteristic of most cancers. Although O-GlcNAcylation can regulate many cell biological pathways, recent evidence suggests that it is a key regulator of metabolic pathways including glycolysis in cancer cells. This review summarizes our current understanding of how O-GlcNAcylation regulates glycolytic pathways and contributes to alterations in cancer cell metabolism.     

Using variation partitioning techniques to quantify the effects of invasive alien species on native urban bird assemblages

Quantifying the impacts that invasive alien species (IAS) cause on affected systems is not an easy task. Here, we explore the application of variation partitioning techniques to measure and control for the effects of possible confounding factors when studying the impact that feral pigeons, European starlings, and house sparrows cause on native urban bird communities in Mexico. We argue that these IAS are provoking a severe impact on whole assemblages of native passerines only if (a) their marginal effect is statistically significant, (b) it remains so after partialling out other explanatory variables, and (c) is larger than (or similar to) the conditional effect of these covariates. We censused passerine bird assemblages and measured habitat variables in a number of greenspaces in three replicate study areas. Then, by means of partial redundancy analyses, we decomposed the total variability in bird data as a function of IAS, physical variables and vegetation data. In one of the study areas the marginal effect of IAS on native assemblages was significant, but the conditional effect was not. We conclude that this IAS effect was confounded with other explanatory variables. In the other study areas, no (marginal or partial) significant effect was found. Without invoking interspecific competition, our results support the opportunistic hypothesis, according to which IAS can exploit ecological conditions in modern cities that native species cannot even tolerate. Finally, apart from the Precautionary Principle, we found no scientific justification to control the abundance of the three IAS in our study areas.     

How reliable are the Powell–Wetherall plot method and the maximum-length approach? Implications for length-based studies of growth and mortality

Length-based methods are the cornerstone of many population studies and stock assessments. This study tested two widely used methods: the Powell–Wetherall (P–W) plot and the L_max approach (i.e., estimating L_∞ directly from L_max). In most simulations, P–W estimates of the ratio total mortality/growth (Z/K ratio) were biased beyond acceptable limits (bias?>?30%). Bias in Z/K showed a complex behavior, without possible corrections. Estimates of asymptotic length (L_∞) were less biased than Z/K, but were very sensitive to intra-cohort variability in growth and to changes in the occurrence of large individuals in the sample. Exclusion of the largest size classes during the regression procedure or weighing by abundance does not solve these issues. Perfect linearization of the data and extremely narrow confidence intervals for Z/K will lead users to erroneous overconfidence in outputs. Clearly, the P–W method is not suitable for the assessment of Z/K ratios of natural populations. Estimation of L_∞ may be tentatively possible under very specific conditions, with necessary external verifications. Also, this study demonstrates that there is no way to estimate L_∞ directly from L_max, since there is no particular relationship to expect a priori between L_∞ and L_max. Errors in estimating L_∞ directly affect the estimate of the growth constant K and all other subsequent calculations in population studies, stock assessments and ecosystem models. New approaches are urgently needed for length-based studies of body growth (e.g., unconstrained curve fit with subsequent bootstrapping), that consider the inherent uncertainty regarding the underlying data and processes.     

High-speed broadband monitoring of cell viscoelasticity in real time shows myosin-dependent oscillations

Study of the dynamic evolutions of cell viscoelasticity is important as during cell activities such as cell metastasis and invasion, the rheological behaviors of the cells also change dynamically, reflecting the biophysical and biochemical connections between the outer cortex and the intracellular structures. Although the time variations of the static modulus of cells have been investigated, few studies have been reported on the dynamic variations of the frequency-dependent viscoelasticity of cells. Measuring and monitoring such dynamic evolutions of cells at nanoscale can be challenging as the measurement needs to meet two objectives inherently contradictory to each other—the measurement must be broadband (to cover a large frequency spectrum) but also rapid (to capture the time-elapsed changes). In this study, we exploited a recently developed control-based nanomechanical protocol of atomic force microscope to monitor in real time the dynamic evolutions of the viscoelasticity of live human prostate cancer cells (PC-3 cells) and study its dependence on myosin activities. We found that the viscoelasticity of PC-3 cells, followed the power law, and oscillated at a period of about 200 s. Both the amplitude and the frequency of the oscillation strongly depended on the intracellular calcium and blebbistatin-sensitive motor proteins.     

Notch pathway plays a novel and critical role in regulating responses of T and antigen-presenting cells in aGVHD

Graft-versus-host disease (GVHD) induced by host antigen-presenting cells (APCs) and donor-derived T cells remains the major limitation of allogeneic bone marrow transplantation (allo-BMT). Notch signaling pathway is a highly conserved cell-cell communication that is important in T cell development. Recently, Notch signaling pathway is reported to be involved in regulating GVHD. To investigate the role of Notch inhibition in modulating GVHD, we established MHC-mismatched murine allo-BMT model. We found that inhibition of Notch signaling pathway by γ-secretase inhibitor in vivo could reduce aGVHD, which was shown by the onset time of aGVHD, body weight, clinical aGVHD scores, pathology aGVHD scores, and survival. Inhibition of Notch signaling pathway by DAPT ex vivo only reduced pathology aGVHD scores in the liver and intestine and had no impact on the onset time and clinical aGVHD scores. We investigated the possible mechanism by analyzing the phenotype of host APCs and donor-derived T cells. Notch signaling pathway had a broad effect on both host APCs and donor-derived T cells. The expressions of CD11c, CD40, and CD86 as the markers of activated dendritic cells (DCs) were decreased. The proliferative response of CD8+ T cell decreased, while CD4⁺ Notch-deprived T cells had preserved expansion with increased expressions of CD25 and Foxp3 as markers of regulatory T cells (Tregs). In conclusion, Notch inhibition may minimize aGVHD by decreasing proliferation and activation of DCs and CD8⁺ T cells while preserving Tregs expansion.