Young Individuals Are More Stable and Stand More Upright When Using Rollator Assistance During Standing up and Sitting Down

Copyright \ua9 2022 Krafft, Herzog, Stein and Sloot.Four-wheeled walkers or rollators are often used to assist older individuals in maintaining an independent life by compensating for muscle weakness and reduced movement stability. However, limited biomechanical studies have been performed to understand how rollator support affects posture and stability, especially when standing up and sitting down. Therefore, this study examined how stability and posture change with varying levels of rollator support and on an unstable floor. The aim was to collect comprehensive baseline data during standing up and sitting down in young participants. In this study, 20 able-bodied, young participants stood up and sat down both 1) unassisted and assisted using a custom-made robot rollator simulator under 2) full support and 3) touch support. Unassisted and assisted performances were analyzed on normal and unstable floors using balance pads with a compliant surface under each foot. Using 3D motion capturing and two ground-embedded force plates, we compared assistive support and floor conditions for movement duration, the relative timing of seat-off, movement stability (center of pressure (COP) path length and sway area), and posture after standing up (lower body sagittal joint angles) using ANOVA analysis. The relative event of seat-off was earliest under full support compared to touch and unassisted conditions under normal but not under unstable floor conditions. The duration of standing up and sitting down did not differ between support conditions on normal or unstable floors. COP path length and sway area during both standing up and sitting down were lowest under full support regardless of both floor conditions. Hip and knee joints were least flexed under full support, with no differences between touch and unassisted in both floor conditions. Hence, full rollator support led to increased movement stability, while not slowing down the movement, during both standing up and sitting down. During standing up, the full support led to an earlier seat-off and a more upright standing posture when reaching a stable stance. These results indicate that rollator support when handles are correctly aligned does not lead to the detrimental movement alterations of increased forward-leaning. Future research aims to verify these findings in older persons with stability and muscle weakness deficiencies

Young Individuals Are More Stable and Stand More Upright When Using Rollator Assistance During Standing up and Sitting Down

Four-wheeled walkers or rollators are often used to assist older individuals in maintaining an independent life by compensating for muscle weakness and reduced movement stability. However, limited biomechanical studies have been performed to understand how rollator support affects posture and stability, especially when standing up and sitting down. Therefore, this study examined how stability and posture change with varying levels of rollator support and on an unstable floor. The aim was to collect comprehensive baseline data during standing up and sitting down in young participants. In this study, 20 able-bodied, young participants stood up and sat down both 1) unassisted and assisted using a custom-made robot rollator simulator under 2) full support and 3) touch support. Unassisted and assisted performances were analyzed on normal and unstable floors using balance pads with a compliant surface under each foot. Using 3D motion capturing and two ground-embedded force plates, we compared assistive support and floor conditions for movement duration, the relative timing of seat-off, movement stability (center of pressure (COP) path length and sway area), and posture after standing up (lower body sagittal joint angles) using ANOVA analysis. The relative event of seat-off was earliest under full support compared to touch and unassisted conditions under normal but not under unstable floor conditions. The duration of standing up and sitting down did not differ between support conditions on normal or unstable floors. COP path length and sway area during both standing up and sitting down were lowest under full support regardless of both floor conditions. Hip and knee joints were least flexed under full support, with no differences between touch and unassisted in both floor conditions. Hence, full rollator support led to increased movement stability, while not slowing down the movement, during both standing up and sitting down. During standing up, the full support led to an earlier seat-off and a more upright standing posture when reaching a stable stance. These results indicate that rollator support when handles are correctly aligned does not lead to the detrimental movement alterations of increased forward-leaning. Future research aims to verify these findings in older persons with stability and muscle weakness deficiencies

Rollator usage lets young individuals switch movement strategies in sit-to-stand and stand-to-sit tasks

\ua9 2023, Springer Nature Limited.The transitions between sitting and standing have a high physical and coordination demand, frequently causing falls in older individuals. Rollators, or four-wheeled walkers, are often prescribed to reduce lower-limb load and to improve balance but have been found a fall risk. This study investigated how rollator support affects sit-to-stand and stand-to-sit movements. Twenty young participants stood up and sat down under three handle support conditions (unassisted, light touch, and full support). As increasing task demands may affect coordination, a challenging floor condition (balance pads) was included. Full-body kinematics and ground reaction forces were recorded, reduced in dimensionality by principal component analyses, and clustered by k-means into movement strategies. Rollator support caused the participants to switch strategies, especially when their balance was challenged, but did not lead to support-specific strategies, i.e., clusters that only comprise light touch or full support trials. Three strategies for sit-to-stand were found: forward leaning, hybrid, and vertical rise; two in the challenging condition (exaggerated forward and forward leaning). For stand-to-sit, three strategies were found: backward lowering, hybrid, and vertical lowering; two in the challenging condition (exaggerated forward and forward leaning). Hence, young individuals adjust their strategy selection to different conditions. Future studies may apply this methodology to older individuals to recommend safe strategies and ultimately reduce falls

A full-body motion capture gait dataset of 138 able-bodied adults across the life span and 50 stroke survivors

\ua9 2023, The Author(s).This reference dataset contains biomechanical data of 138 able-bodied adults (21–86 years) and 50 stroke survivors walking bare-footed at their preferred speed. It is unique due to its size, and population, including adults across the life-span and over 70 years, as well as stroke survivors. Full-body kinematics (PiG-model), kinetics and muscle activity of 14 back and lower limbs muscles was collected with a Vicon motion capture system, ground-embedded force plates, and a synchronized surface EMG system. The data is reliable to compare within and between groups as the same methodology and infrastructure were used to gather all data. Both source files (C3D) and post-processed ready-to-use stride-normalized kinematics, kinetics and EMG data (MAT-file, Excel file) are available, allowing high flexibility and accessibility of analysis for both researchers and clinicians. These records are valuable to examine ageing, typical and hemiplegic gait, while also offering a wide range of reference data which can be utilized for age-matched controls during normal walking

Interplay between thyroid cancer cells and macrophages: effects on IL-32 mediated cell death and thyroid cancer cell migration

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Male Accessory Gland Protein Reduces Egg Laying in a Simultaneous Hermaphrodite

Seminal fluid is an important part of the ejaculate of internally fertilizing animals. This fluid contains substances that nourish and activate sperm for successful fertilization. Additionally, it contains components that influence female physiology to further enhance fertilization success of the sperm donor, possibly beyond the recipient's optimum. Although evidence for such substances abounds, few studies have unraveled their identities, and focus has been exclusively on separate-sex species. We present the first detailed study into the seminal fluid composition of a hermaphrodite (Lymnaea stagnalis). Eight novel peptides and proteins were identified from the seminal-fluid-producing prostate gland and tested for effects on oviposition, hatching and consumption. The gene for the protein found to suppress egg mass production, Ovipostatin, was sequenced, thereby providing the first fully-characterized seminal fluid substance in a simultaneous hermaphrodite. Thus, seminal fluid peptides and proteins have evolved and can play a crucial role in sexual selection even when the sexes are combined

Yang-Lee Zeros of the Q-state Potts Model on Recursive Lattices

The Yang-Lee zeros of the Q-state Potts model on recursive lattices are studied for non-integer values of Q. Considering 1D lattice as a Bethe lattice with coordination number equal to two, the location of Yang-Lee zeros of 1D ferromagnetic and antiferromagnetic Potts models is completely analyzed in terms of neutral periodical points. Three different regimes for Yang-Lee zeros are found for Q>1 and 0<Q<1. An exact analytical formula for the equation of phase transition points is derived for the 1D case. It is shown that Yang-Lee zeros of the Q-state Potts model on a Bethe lattice are located on arcs of circles with the radius depending on Q and temperature for Q>1. Complex magnetic field metastability regions are studied for the Q>1 and 0<Q<1 cases. The Yang-Lee edge singularity exponents are calculated for both 1D and Bethe lattice Potts models. The dynamics of metastability regions for different values of Q is studied numerically.Comment: 15 pages, 6 figures, with correction

Identification of a possible role of thymine DNA glycosylase (TDG) in epigenome maintenance

Thymine DNA glycosylase (TDG) was discovered as an enzyme capable of removing uracil (U) and thymine (T) from G/U and G/T mispairs, respectively. Owing to this ability, TDG was proposed to initiate restoration of C/G pairs at sites of cytosine or 5-methycytosine (5-meC) deamination. In addition to products of base deamination, the substrate spectrum of TDG covers a wide range of DNA base damages resulting from base oxidation and alkylation. TDG was also found to engage in physical and functional interactions with transcription factors, and more recent evidence supports additional interactions with the de novo DNA methyltransferases Dnmt3a and 3b in the context of gene transcription. Together with its biochemical properties, these observations suggest that TDG might be targeted to gene regulatory sequences as part of a macromolecular assembly to control their functional integrity. TDG may counteract the mutagenic effects of C and 5-meC deamination in CG-rich regions and/or be involved in the maintenance of CpG promoter methylation patterns. A tight regulation of CpG methylation at gene regulatory regions is critical for accurate gene expression, proper cellular differentiation and embryonic development. A somewhat surprising but in this context consistent finding was that, in contrast to other DNA glycosylases, TDG is essential for proper fetal development since a targeted knockout of the gene leads to embryonic lethality. To gain insights into the biological functions of TDG, we aimed to establish and apply biochemical fractionation procedures for high affinity purification and structural and functional characterization of TDG containing proteins complexes. The first part of the thesis was concerned with biochemical characterization of the protein interaction network of TDG in living mammalian cells. To this end, I applied different approaches allowing high affinity isolation of protein complexes from mammalian cells, such as the tandem affinity purification (TAP) method as well as immunoprecipitation of endogenous protein and of the TDGa isoform from TdgA overexpressing embryonic stem (ES) cells. These efforts, however, did not reveal any TDG interacting partners in subsequent mass spectrometry (MS) analyses. These results were surprising, as TDG was previously reported to interact with transcription factors and DNA methyltransferases. Remarkably, however, all previously identified protein interactors of TDG were discovered in screen with the respective partner proteins, and under conditions of simultaneous overexpression of both interacting proteins. The only proteins ever identified in screen with TDG were Sumo1 and Sumo3, which turned out to covalently modify the glycosylase. For this reason, we decided to pursue our search with classical cell fractionation experiments. We first did gel filtration experiments from total cell lysates and showed that TDG is indeed able to form distinct multiprotein complexes in undifferentiated mouse embryonic stem cells that may also contain the RNA helicase p68. Further subcellular fractionation experiments then revealed that TDG is present in all cell compartments, with a significant fraction of nuclear TDG being associated with chromatin, together with p68 and de novo DNA methyltransferases. Together with published findings, these results suggested that protein complexes containing TDG might act in a chromatin-associated context, at gene regulatory regions. The developmental phenotype of Tdg-/- knockout mice and the interactions of TDG with factors involved in developmental gene regulation (e.g. retinoic acid receptors RAR/RXR) implicate a function of TDG during early development and cell differentiation, at times governed by dynamic changes in gene expression, DNA methylation and histone modifications. Such changes have been studied using a well-established during in vitro differentiation of ES cells to lineage committed neuronal progenitors (NPs). We thus aimed to address the function of TDG as part of chromatin associated protein complexes during the process of retinoic acid induced differentiation of ES cells to NPs. In the second part of the thesis we made use of a this well-established in vitro differentiation system to examine the genome-wide localization of TDG to chromatin by TDG chromatin immunoprecipitation (ChIP) and to correlate TDG association to chromatin with gene expression and DNA methylation changes linked to cellular differentiation. TDG ChIP combined with high throughput sequencing showed that TDG associates with high preference to CpG islands in promoters of actively transcribed genes or genes poised for transcriptional activation. Such CpG rich sequences are normally unmethylated in mammalian genomes. Interestingly, we found TDG to localize to promoters of many genes controlling pluripotency (e.g. Oct4, Nanog) and developmental processes (e.g. Sfrp2, Tgfb2, Gata6), thus, supporting a function of TDG in cell differentiation and/or embryonic development. As different lines of circumstantial evidence have associated TDG with changes in CpG methylation following activation of hormone responsive gene promoters, we went on to further test genome-wide promoter methylation in Tdg+/- and Tdg-/- NPs making use of a combination of methylated DNA immunoprecipitation (MeDIP) and microarray technology. This showed that the loss of TDG does not affect global promoter DNA methylation. Nevertheless, there were a number of significant differences, suggesting that TDG might affect the CpG methylation pattern at some promoters. Also, owing to the limited resolution of the MeDIP method, however, we could not exclude an involvement of TDG in the control of DNA methylation of specific promoter CpGs. Additional bisulfite sequencing of promoters of TDG bound developmental genes (e.g. Sfrp2, Tgfb2) in NPs and differentiated mouse embryonic fibroblasts (MEFs) have indeed proved that loss of TDG affects local changes in DNA methylation at particular CpGs. Subsequent analysis of genome-wide gene expression profiles of ES cells and differentiated Tdg+/- and Tdg-/- NPs revealed that a limited number of genes (229) are differentially regulated in ES, whereas substantial differences in gene expression in were observed in NPs (1022 genes). This implicated a specific function of TDG in the regulation of cell differentiation triggered gene expression changes. Detailed analysis of the expression of the Pax6 gene, accurate regulation of which is essential for proper neuron development, showed that its promoter is bound by TDG and that its transcription is inappropriately regulated upon further differentiation of Tdg-/- NPs into the neuronal lineage. Whereas Tdg+/- NPs efficiently downregulated Pax6 (50x) and further differentiated into neuron-like cells, Tdg-/- NPs only partially downregulated Pax6 gene expression (6x) and underwent apoptosis at day 2 after plating in neuronal medium. This phenotype was complemented by expression of TDGa, clearly implicating TDG in the regulation of Pax6 expression during differentiation of ES cells to terminal neurons. We further observed misregulation of pluripotency genes (e.g. Oct4) regulated by TDG bound promoters during early differentiation of ES cells. In the absence of TDG, ES cells showed the tendency to enter spontaneous and/or RA induced differentiation, suggesting a role for TDG in the regulation of pluripotency. During RA induced differentiation we further observed the activation of the neuron specific gene Lrrtm2 exclusively in TDG proficient cells. In addition, ChIP experiments showed that transcription factors involved in the activation of the Lrrtm2 gene (e.g. COUP-TFI, RAR) are not recruited to the respective promoter in Tdg-/- cells, suggesting that TDG might act passively as a scaffold factor important for the recruitment of transcription factors to promoter regions. I set out to clarify the biological function of TDG by investigating its molecular interactions in mammalian cells. I found that TDG, as a DNA repair enzyme, associates tightly with chromatin, where it localizes with high preference to CpG island promoters of active genes and genes poised to be expressed. I also found that the loss of TDG causes misregulation of genes during cell differentiation and that this appears to be related to a function of TDG in establishing and/or maintaining CpG methylation pattern in gene regulatory sequences. These discoveries implicate a novel function of DNA repair, in the maintenance not only of the genome, but also the epigenome

Delivery of sTRAIL variants by MSCs in combination with cytotoxic drug treatment leads to p53-independent enhanced antitumor effects

Mesenchymal stem cells (MSCs) are able to infiltrate tumor tissues and thereby effectively deliver gene therapeutic payloads. Here, we engineered murine MSCs (mMSCs) to express a secreted form of the TNF-related apoptosis-inducing ligand (TRAIL), which is a potent inducer of apoptosis in tumor cells, and tested these MSCs, termed MSC.sTRAIL, in combination with conventional chemotherapeutic drug treatment in colon cancer models. When we pretreated human colorectal cancer HCT116 cells with low doses of 5-fluorouracil (5-FU) and added MSC.sTRAIL, we found significantly increased apoptosis as compared with single-agent treatment. Moreover, HCT116 xenografts, which were cotreated with 5-FU and systemically delivered MSC.sTRAIL, went into remission. Noteworthy, this effect was protein 53 (p53) independent and was mediated by TRAIL-receptor 2 (TRAIL-R2) upregulation, demonstrating the applicability of this approach in p53-defective tumors. Consequently, when we generated MSCs that secreted TRAIL-R2-specific variants of soluble TRAIL (sTRAIL), we found that such engineered MSCs, labeled MSC.sTRAIL DR5, had enhanced antitumor activity in combination with 5-FU when compared with MSC.sTRAIL. In contrast, TRAIL-resistant pancreatic carcinoma PancTu1 cells responded better to MSC.sTRAIL DR4 when the antiapoptotic protein XIAP (X-linked inhibitor of apoptosis protein) was silenced concomitantly. Taken together, our results demonstrate that TRAIL-receptor selective variants can potentially enhance the therapeutic efficacy of MSC-delivered TRAIL as part of individualized and tumor-specific combination treatments. © 2013 Macmillan Publishers Limited All rights reserved