Biology subjects

Kozlowska, K.

Publications and source records attributed to Kozlowska, K..

4 recordsLinked to original sources

bioRxiv2021

Persistence and anti-persistence in treadmill walking

BackgroundLong-range persistent correlations in stride time (ST) and length (SL) are the fundamental traits of treadmill gait. Our recent work showed that the ST and SL time series statistical properties originated from the superposition of large-scale trends and small-scale fluctuations (residuals). Trends served as the control manifolds about which ST and SL fluctuated. The scaling exponents of the residuals were slightly smaller than 0.5. Research questionDo random changes in treadmill belt speed affect the trend properties and scaling exponents of ST/SL residuals? MethodsWe used Multivariate Adaptive Regression Splines (MARS) to determine gait trends during a walk on a treadmill whose belt speed was perturbed by a strong random noise. Then, we calculated the scaling exponents of MARS residuals with the madogram estimator. ResultsExcept for the ST at the lowest treadmill speed v = 0.8 m/s, the normalized trend duration was at least three times greater than that for the unperturbed walk. The Cauchy distribution scale parameter, which served as a measure of the width of SL and ST trend slope distributions, was at v = 1.2 m/s, almost 50% and 25% smaller than the unperturbed values. The differences were even greater at v = 1.6 m/s: 73% and 83%. For all speeds, the ST and SL MARS residuals were strongly anti-persistent. At v = 1.2 m/s, the corresponding scaling exponents were equal to 0.37{+/-}0.10 and 0.25{+/-}0.09. Apart from ST at v = 0.8 m/s, the ST/SL scaling indices were close to 0.5. SignificancePersistence of gait parameters is closely related to the properties of their trends. Longer trends with a gentle slope and strong anti-persistence of ST/SL residuals are the manifestations or tight control required during the perturbed treadmill walk.

physiology↗

bioRxiv2019

Significance of trends in gait dynamics

Trends in time series generated by physiological control systems are ubiquitous. Determining whether trends arise from intrinsic system dynamics or originate outside of the system is a fundamental problem of fractal series analysis. In the latter case, it is necessary to filter out the trends before attempting to quantify correlations in the noise (residuals). For over two decades, detrended fluctuation analysis (DFA) has been used to calculate scaling exponents of stride time (ST), stride length (SL), and stride speed (SS) of human gait. Herein, rather than relying on the very specific form of detrending characteristic of DFA, we adopt Multivariate Adaptive Regression Splines (MARS) to explicitly determine trends in spatio-temporal gait parameters during treadmill walking. Then, we use the madogram estimator to calculate the scaling exponent of the corresponding MARS residuals. The durations of ST and SL trends are determined to be independent of treadmill speed and have distributions with exponential tails. At all speeds considered, the trends of ST and SL are strongly correlated and are statistically independent of their corresponding residuals. The group-averaged values of scaling exponents of ST and ST MARS residuals are slightly smaller than 0.5, indicating weak anti-persistence. Thus, contrary to the interpretation prevalent in the literature, the statistical properties of ST and SL time series originate from the superposition of large scale trends and small scale fluctuations. We show that trends serve as the control manifolds about which ST and SL fluctuate. Moreover, the trend speed, defined as the ratio of instantaneous values of SL and ST trends, is tightly controlled about the treadmill speed. The strong coupling between the ST and SL trends ensures that the concomitant changes of their values correspond to movement along the constant speed goal equivalent manifold as postulated by Dingwell et al. doi:10.1371/journal.pcbi.1000856. Author summaryDuring treadmill walking, the subjects stride time (ST) and stride length (SL) must yield a stride speed which can fluctuate over a narrow range centered on the treadmill belts speed. The fact that both ST and SL are persistent is an intriguing property of human gait. For persistent fluctuations any deviation from the mean value is likely to be followed by a deviation in the same direction. To trace the origin of such persistence, we used a novel approach to determine trends in spatio-temporal gait parameters. We find that the trends of ST and SL of a subject are strongly correlated and are statistically independent of their corresponding residuals. Moreover, the trend speed, defined as the ratio of instantaneous values of SL and ST trends, is tightly controlled about the treadmill speed. The persistence of gait parameters stems from superposition of large scale trends and small scale fluctuations.

physiology↗

bioRxiv2018

Global increase in circRNA levels in myotonic dystrophy

Splicing aberrations induced as a consequence of the sequestration of MBNL splicing factors on the DMPK transcript, which contains expanded CUG repeats, present a major pathomechanism of myotonic dystrophy type 1 (DM1). As MBNLs may also be important factors involved in the biogenesis of circular RNAs (circRNAs), we hypothesized that the level of circRNAs would be decreased in DM1. To test this hypothesis, we selected twenty well-validated circRNAs and analyzed their levels in several experimental systems (e.g., cell lines, DM muscle tissues, and a mouse model of DM1) using droplet digital PCR assays. We also explored the global level of circRNAs using two RNA-Seq datasets of DM1 muscle samples. Contrary to our original hypothesis, our results consistently showed a global increase in circRNA levels in DM1 and we identified numerous circRNAs that were increased in DM1. We also identified many genes (including muscle-specific genes) giving rise to numerous (>10) circRNAs. Thus, this study is the first to show an increase in global circRNA levels in DM1. We also provided preliminary results showing the association of circRNA level with muscle weakness and alternative splicing changes that are biomarkers of DM1 severity. Author SummaryRecently, a great deal of interest has been focused on a new class of RNA molecules called circular RNAs (circRNAs). To date, thousands of circRNAs have been found in different human cells/tissues. Although the function of circRNAs remains mostly unknown, circRNAs have emerged as an important component of the RNA-RNA and RNA-protein interactome. Thus, intensive efforts are being made to fully understand the biology and function of circRNAs, especially their role in human diseases. As an important role in the biogenesis of circRNA may be played by MBNL splicing factors, in this study we used DM1 (to a lesser extent, DM2) as a natural model in which the level of MBNLs is decreased. In contrast to the expected effect, our results consistently showed a global increase in circRNA levels in DM1. As a consequence, whole genome transcriptome analysis revealed dozens of circRNAs with significantly altered (mostly increased) levels in DM1. Furthermore, we observed that the circRNA levels were in many cases strongly associated with DM1 severity.

molecular biology↗

bioRxiv2018

Decreased IgG core fucosylation, a player in antibody-dependent cell-mediated cytotoxicity, is associated with autoimmune thyroid diseases

Autoimmune thyroid diseases (AITD) are the most common group of autoimmune diseases, associated with lymphocyte infiltration and the production of thyroid autoantibodies, like thyroid peroxidase antibodies (TPOAb), in the thyroid gland. Immunoglobulins (Igs) and cell-surface receptors are glycoproteins with distinctive glycosylation patterns that play a structural role in maintaining and modulating their functions. We investigated associations of total circulating IgG and peripheral blood mononuclear cells (PBMCs) glycosylation with AITD and the influence of genetic background. The study revealed an inverse association of IgG core fucosylation with TPOAb and PBMCs antennary 1,2 fucosylation with AITD, but no shared genetic variance between AITD and glycosylation. These data suggest that the decreased level of IgG core fucosylation is a risk factor for AITD that promotes antibody-dependent cell-mediated cytotoxicity (ADCC) associated with TPOAb levels.

immunology↗