The effect of walking speed on local dynamic stability is sensitive to calculation methods

Local dynamic stability has been assessed by the short-term local divergence exponent (λ_S), which quantifies the average rate of logarithmic divergence of infinitesimally close trajectories in state space. Both increased and decreased local dynamic stability at faster walking speeds have been reported. This might pertain to methodological differences in calculating λ_S. Therefore, the aim was to test if different calculation methods would induce different effects of walking speed on local dynamic stability. Ten young healthy participants walked on a treadmill at five speeds (60%, 80%, 100%, 120% and 140% of preferred walking speed) for 3 min each, while upper body accelerations in three directions were sampled. From these time-series, λ_S was calculated by three different methods using: (a) a fixed time interval and expressed as logarithmic divergence per stride-time (λ_S−a), (b) a fixed number of strides and expressed as logarithmic divergence per time (λ_S−b) and (c) a fixed number of strides and expressed as logarithmic divergence per stride-time (λ_S−c). Mean preferred walking speed was 1.16±0.09 m/s. There was only a minor effect of walking speed on λ_S−a. λ_S−b increased with increasing walking speed indicating decreased local dynamic stability at faster walking speeds, whereas λ_S−c decreased with increasing walking speed indicating increased local dynamic stability at faster walking speeds. Thus, the effect of walking speed on calculated local dynamic stability was significantly different between methods used to calculate local dynamic stability. Therefore, inferences and comparisons of studies employing λ_S should be made with careful consideration of the calculation method.     

Dynamic stability of superior vs. inferior body segments in individuals with transtibial amputation walking in destabilizing environments

Interestingly, young and highly active people with lower limb amputation appear to maintain a similar trunk and upper body stability during walking as able-bodied individuals. Understanding the mechanisms underlying how this stability is achieved after lower-leg amputation is important to improve training regimens for improving walking function in these patients. This study quantified how superior (i.e., head, trunk, and pelvis) and inferior (i.e., thigh, shank, and feet) segments of the body respond to continuous visual or mechanical perturbations during walking. Nine persons with transtibial amputation (TTA) and 12 able-bodied controls (AB) walked on a 2 m×3 m treadmill in a Computer Assisted Rehabilitation Environment (CAREN). Subjects were perturbed by continuous pseudo-random mediolateral movements of either the treadmill platform or the visual scene. TTA maintained a similar local and orbital stability in their superior body segments as AB throughout both perturbation types. However, for their inferior body segments, TTA subjects exhibited greater dynamic instability during perturbed walking. In TTA subjects, these increases in instability were even more pronounced in their prosthetic limb compared to their intact leg. These findings demonstrate that persons with unilateral lower leg amputation maintain upper body stability in spite of increased dynamic instability in their impaired lower leg. Thus, transtibial amputation does significantly impair sensorimotor function, leading to substantially altered dynamic movements of their lower limb segments. However, otherwise relatively healthy patients with unilateral transtibial amputation appear to retain sufficient remaining sensorimotor function in their proximal and contralateral limbs to adequately compensate for their impairment.     

Alteration of LncRNA expression in mice placentae after frozen embryo transfer is associated with increased fetal weight

The birthweight after frozen embryo transfer (FET) was significantly higher compared with fresh embryo transfer (fresh ET), while the mechanism remains unclear. In this study, we transferred vitrified-warmed or fresh mice blastocysts into pseudopregnant recipients (n = 11 each group) produced by natural mating to avoid the influence of superovulation. The fetal weight, placental weight, placental efficiency and placental architecture were studied at E18.5. Placental RNA-Seq analysis was used to identify candidate different lncRNAs and mRNAs between the FET group and the fresh ET group. We found that the fetal weight was increased in the FET group, with increased placental efficiency and the proportion of placental function related labyrinth zone area. 554 lncRNAs and 1012 mRNAs were differentially expressed. KEGG and GO enrichment analyses showed these differentially expressed lncRNAs and their targeted mRNAs might be related to placental morphogenesis. Furthermore, the most differentially expressed 15 lncRNAs and 15 mRNAs were validated by qRT-PCR, we found the LncRNA embryonic stem cells expressed 1 (Lncenc1) was significantly decreased, and Gjb5, which played an important role in labyrinth zone development, was increased. Gjb5 protein increase was further confirmed by Western blot. Lncenc1 and Gjb5 had 48 predicted co-targeted miRNAs, while the correlation analysis of Lncenc1 and Gjb5 mRNA showed a significant inverse correlation. The results showed that FET treatment might enhance the placental function to increase mouse fetal weight via the network diagram of Lncenc1-miRNA-Gjb5.     

Evolution of Base Excision Repair in Entamoeba histolytica is shaped by gene loss,gene duplication,and lateral gene transfer

During its life cycle, the protist parasite Entamoeba histolytica encounters reactive oxygen and nitrogen species that alter its genome. Base excision repair (BER) is one of the most important pathways for the repair of DNA base lesions. Analysis of the E. histolytica genome revealed the presence of most of the BER components. Surprisingly, this included a gene encoding an apurinic/apyrimidinic (AP) endonuclease that previous studies had assumed was absent. Indeed, our analysis showed that the genome of E. histolytica harbors the necessary genes needed for both short and long-patch BER sub-pathways. These genes include DNA polymerases with predicted 5′-dRP lyase and strand-displacement activities and a sole DNA ligase. A distinct feature of the E. histolytica genome is the lack of several key damage-specific BER glycosylases, such as OGG1/MutM, MDB4, Mag1, MPG, SMUG, and TDG. Our evolutionary analysis indicates that several E. histolytica DNA glycosylases were acquired by lateral gene transfer (LGT). The genes that encode for MutY, AlkD, and UDG (Family VI) are included among these cases. Endonuclease III and UNG (family I) are the only DNA glycosylases with a eukaryotic origin in E. histolytica. A gene encoding a MutT 8-oxodGTPase was also identified that was acquired by LGT. The mixed composition of BER genes as a DNA metabolic pathway shaped by LGT in E. histolytica indicates that LGT plays a major role in the evolution of this eukaryote. Sequence and structural prediction of E. histolytica DNA glycosylases, as well as MutT, suggest that the E. histolytica DNA repair proteins evolved to harbor structural modifications that may confer unique biochemical features needed for the biology of this parasite.     

Selective accumulation of alpha-tocopherol in Drosophila is associated with cytochrome P450 tocopherol-omega-hydroxylase activity but not alpha-tocopherol transfer protein

Humans and other mammals actively discriminate among the various forms of vitamin E to selectively retain alpha-tocopherol, but the phylogenetic breadth of this trait is unknown. We sought to determine if the fruit fly, Drosophila melanogaster, similarly discriminates and if so by what mechanism. Larvae and adult flies fed diets containing predominantly gamma- and delta-tocopherols were enriched in alpha-tocopherol. Inclusion in the diet of piperonyl butoxide (PBO), an insect cytochrome P450 inhibitor and inhibitor of tocopherol-omega-hydroxylase activity, greatly elevated tissue levels of delta-tocopherol but not alpha-tocopherol. Drosophila microsomes exhibited tocopherol-omega-hydroxylase activity in the order of delta-T > gamma-T > alpha-T, a pattern consistent with the effect of PBO in vivo. To determine if selectivity involved alpha-tocopherol transfer protein (alpha-TTP), adult flies were fed an equimolar mixture of d3-RRR- and d6-all-racemic alpha-tocopherol. Flies exhibited a d3/d6 ratio of 1.03, demonstrating an inability to discriminate on the basis of phytyl tail stereochemistry, a hallmark of alpha-TTP activity. We conclude that Drosophila preferentially accumulates alpha-tocopherol via a mechanism involving cytochrome P450 tocopherol-omega-hydroxylase-mediated catabolism of other tocopherols, but not a mammalian-like alpha-TTP. The selective pressure favoring this trait and its remarkable conservation from insects to humans requires elucidation.