BIOMECHANICAL LOADING OF THE LOWER EXTREMITIES DURING NORDIC WALKING – A FIELD STUDY

The purpose of this study was to analyse under field conditions the loading of the lower extremities during nordic walking compared to walking. For that purpose 14 experienced, middle aged nordic walkers and 6 nordic walking instructors have been asked to walk a 1575m field track in randomised sequence, once with and once without poles. The mean vertical ground reaction forces are not different between nordic walking and walking. The present results are showing that the common opinion of a load reduction of the lower extremities by 30-50 % during Nordic Walking has to be rejected

Activation of the Kynurenine Pathway in Human Malignancies Can Be Suppressed by the Cyclin-Dependent Kinase Inhibitor Dinaciclib

Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO2) are the key enzymes of tryptophan (TRP) metabolism in the kynurenine pathway (KP). Both enzymes function as indicators of immunosuppression and poor survival in cancer patients. Direct or indirect targeting of either of these substances seems thus reasonable to improve therapy options for patients. In this study, glioblastoma multiforme (GBM) as well as head and neck squamous cell carcinomas (HNSCC) were examined because of their different mechanisms of spontaneous and treatment-induced immune escape. Effects on gene expression and protein levels were examined. Accompanying assessment of TRP metabolites from treated GBM cell culture supernatants was conducted. Our results show a heterogeneous and inversely correlated expression profile of TRP-metabolizing genes among GBM and HNSCC cells, with low, but inducible IDO1 expression upon IFNγ treatment. TDO2 expression was higher in GBM cells, while genes encoding kynurenine aminotransferases were mainly confined to HNSCC cells. These data indicate that the KP is active in both entities, with however different enzymes involved in TRP catabolism. Upon treatment with Temozolomide, the standard of care for GBM patients, IDO1 was upregulated. Comparable, although less pronounced effects were seen in HNSCC upon Cetuximab and conventional drugs (i.e., 5-fluorouracil, Gemcitabine). Here, IDO1 and additional genes of the KP (KYAT1, KYAT2, and KMO) were induced. Vice versa, the novel yet experimental cyclin-dependent kinase inhibitor Dinaciclib suppressed KP in both entities. Our comprehensive data imply inhibition of the TRP catabolism by Dinaciclib, while conventional chemotherapeutics tend to activate this pathway. These data point to limitations of conventional therapy and highlight the potential of targeted therapies to interfere with the cells' metabolism more than anticipated

IgG1 B cell receptor signaling is inhibited by CD22 and promotes the development of B cells whose survival is less dependent on Igα/β

We describe a mouse strain in which B cell development relies either on the expression of membrane-bound immunoglobulin (Ig) γ1 or μ heavy chains. Progenitor cells expressing γ1 chains from the beginning generate a peripheral B cell compartment of normal size with all subsets, but a partial block is seen at the pro– to pre–B cell transition. Accordingly, γ1-driven B cell development is disfavored in competition with developing B cells expressing a wild-type (WT) IgH locus. However, the mutant B cells display a long half-life and accumulate in the mature B cell compartment, and even though partial truncation of the Igα cytoplasmic tail compromises their development, it does not affect their maintenance, as it does in WT cells. IgG1-expressing B cells showed an enhanced Ca2+ response upon B cell receptor cross-linking, which was not due to a lack of inhibition by CD22. The enhanced Ca2+ response was also observed in mature B cells that had been switched from IgM to IgG1 expression in vivo. Collectively, these results suggest that the γ1 chain can exert a unique signaling function that can partially replace that of the Igα/β heterodimer in B cell maintenance and may contribute to memory B cell physiology

Prevention of DNA Replication Stress by CHK1 Leads to Chemoresistance Despite a DNA Repair Defect in Homologous Recombination in Breast Cancer

Chromosomal instability not only has a negative effect on survival in triple-negative breast cancer, but also on the well treatable subgroup of luminal A tumors. This suggests a general mechanism independent of subtypes. Increased chromosomal instability (CIN) in triple-negative breast cancer (TNBC) is attributed to a defect in the DNA repair pathway homologous recombination. Homologous recombination (HR) prevents genomic instability by repair and protection of replication. It is unclear whether genetic alterations actually lead to a repair defect or whether superior signaling pathways are of greater importance. Previous studies focused exclusively on the repair function of HR. Here, we show that the regulation of HR by the intra-S-phase damage response at the replication is of overriding importance. A damage response activated by Ataxia telangiectasia and Rad3 related-checkpoint kinase 1 (ATR-CHK1) can prevent replication stress and leads to resistance formation. CHK1 thus has a preferred role over HR in preventing replication stress in TNBC. The signaling cascade ATR-CHK1 can compensate for a double-strand break repair error and lead to resistance of HR-deficient tumors. Established methods for the identification of HR-deficient tumors for Poly(ADP-Ribose)-Polymerase 1 (PARP1) inhibitor therapies should be extended to include analysis of candidates for intra-S phase damage response

Integrative medicine during the intensive phase of chemotherapy in pediatric oncology in Germany: a randomized controlled trial with 5-year follow up

Background: Integrative medicine is used frequently alongside chemotherapy treatment in pediatric oncology, but little is known about the influence on toxicity. This German, multi-center, open-label, randomized controlled trial assessed the effects of complementary treatments on toxicity related to intensive-phase chemotherapy treatment in children aged 1-18 with the primary outcome of the toxicity sum score. Secondary outcomes were chemotherapy-related toxicity, overall and event-free survival after 5 years in study patients. Methods: Intervention and control were given standard chemotherapy according to malignancy & tumor type. The intervention arm was provided with anthroposophic supportive treatment (AST); given as anthroposophic base medication (AMP), as a base medication for all patients and additional on-demand treatment tailored to the intervention malignancy groups. The control was given no AMP. The toxicity sum score (TSS) was assessed using NCI-CTC scales. Results: Data of 288 patients could be analyzed. Analysis did not reveal any statistically significant differences between the AST and the control group for the primary endpoint or the toxicity measures (secondary endpoints). Furthermore, groups did not differ significantly in the five-year overall and event-free survival follow up. Discussion: In this trial findings showed that AST was able to be safely administered in a clinical setting, although no beneficial effects of AST between group toxicity scores, overall or event-free survival were shown

Beyond the black box: promoting mathematical collaborations for elucidating interactions in soil ecology

This work is licensed under a Creative Commons Attribution 4.0 International License.Understanding soil systems is critical because they form the structural and nutritional foundation for plants and thus every terrestrial habitat and agricultural system. In this paper, we encourage increased use of mathematical models to drive forward understanding of interactions in soil ecological systems. We discuss several distinctive features of soil ecosystems and empirical studies of them. We explore some perceptions that have previously deterred more extensive use of models in soil ecology and some advances that have already been made using models to elucidate soil ecological interactions. We provide examples where mathematical models have been used to test the plausibility of hypothesized mechanisms, to explore systems where experimental manipulations are currently impossible, or to determine the most important variables to measure in experimental and natural systems. To aid in the development of theory in this field, we present a table describing major soil ecology topics, the theory previously used, and providing key terms for theoretical approaches that could potentially address them. We then provide examples from the table that may either contribute to important incremental developments in soil science or potentially revolutionize our understanding of plant–soil systems. We challenge scientists and mathematicians to push theoretical explorations in soil systems further and highlight three major areas for the development of mathematical models in soil ecology: theory spanning scales and ecological hierarchies, processes, and evolution

Beyond the black box: Promoting mathematical collaborations for elucidating interactions in soil ecology

© 2019 The Authors. Understanding soil systems is critical because they form the structural and nutritional foundation for plants and thus every terrestrial habitat and agricultural system. In this paper, we encourage increased use of mathematical models to drive forward understanding of interactions in soil ecological systems. We discuss several distinctive features of soil ecosystems and empirical studies of them. We explore some perceptions that have previously deterred more extensive use of models in soil ecology and some advances that have already been made using models to elucidate soil ecological interactions. We provide examples where mathematical models have been used to test the plausibility of hypothesized mechanisms, to explore systems where experimental manipulations are currently impossible, or to determine the most important variables to measure in experimental and natural systems. To aid in the development of theory in this field, we present a table describing major soil ecology topics, the theory previously used, and providing key terms for theoretical approaches that could potentially address them. We then provide examples from the table that may either contribute to important incremental developments in soil science or potentially revolutionize our understanding of plant-soil systems. We challenge scientists and mathematicians to push theoretical explorations in soil systems further and highlight three major areas for the development of mathematical models in soil ecology: Theory spanning scales and ecological hierarchies, processes, and evolution

Potential of Airborne LiDAR Derived Vegetation Structure for the Prediction of Animal Species Richness at Mount Kilimanjaro

The monitoring of species and functional diversity is of increasing relevance for the development of strategies for the conservation and management of biodiversity. Therefore, reliable estimates of the performance of monitoring techniques across taxa become important. Using a unique dataset, this study investigates the potential of airborne LiDAR-derived variables characterizing vegetation structure as predictors for animal species richness at the southern slopes of Mount Kilimanjaro. To disentangle the structural LiDAR information from co-factors related to elevational vegetation zones, LiDAR-based models were compared to the predictive power of elevation models. 17 taxa and 4 feeding guilds were modeled and the standardized study design allowed for a comparison across the assemblages. Results show that most taxa (14) and feeding guilds (3) can be predicted best by elevation with normalized RMSE values but only for three of those taxa and two of those feeding guilds the difference to other models is significant. Generally, modeling performances between different models vary only slightly for each assemblage. For the remaining, structural information at most showed little additional contribution to the performance. In summary, LiDAR observations can be used for animal species prediction. However, the effort and cost of aerial surveys are not always in proportion with the prediction quality, especially when the species distribution follows zonal patterns, and elevation information yields similar results

Embodied viewing and Degas’s Little Dancer Aged Fourteen: a multi-disciplinary experiment in eye-tracking and motion capture

This paper presents a cross-disciplinary project based on an experiment in eye-tracking and motion capture (Sainsbury’s Centre for Visual Arts), which aimed to study viewers’ movements around an iconic sculpture: Edgar Degas’s Little Dancer Aged Fourteen. The experiment studies how viewers respond to this three-dimensional artwork not only by looking at it but also through their own bodily reactions to it, such as by unconsciously mimicking a represented attitude or gesture. We compared two groups of viewers: classically trained dancers and non-dancers. Our hypothesis was that the skills and embodied experiences of the dancers would alter the ways in which they engage bodily with the work compared to the non-dancers. Our underlying research question was: how are vision and the body interlinked in esthetic and kinesthetic experience? This paper does not give results, which are forthcoming. It focuses on methodology and provides a commentary on the design and development of the interdisciplinary collaboration behind the project. It explores an interdisciplinary collaboration that bridges the humanities and experimental sciences and asks how being confronted with unfamiliar methodologies forces researchers in a given field to critically self-examine the limits and presuppositions of their practices