Cardiovascular Endurance Among College Students: How is it Related to Overall Fitness?

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Characterization of non‑linear mechanical behavior of the cornea

The objective of this study was to evaluate which hyperelastic model could best describe the nonlinear mechanical behavior of the cornea, in order to characterize the capability of the non-linear model parameters to discriminate structural changes in a damaged cornea. Porcine corneas were used, establishing two diferent groups: control (non-treated) and NaOH-treated (damaged) corneas (n= 8). NaOH causes a chemical burn to the corneal tissue, simulating a disease associated to structural damage of the stromal layer. Quasi-static uniaxial tensile tests were performed in nasaltemporal direction immediately after preparing corneal strips from the two groups. Three non-linear hyperelastic models (i.e. Hamilton-Zabolotskaya model, Ogden model and Mooney-Rivlin model) were ftted to the stress–strain curves obtained in the tensile tests and statistically compared. The corneas from the two groups showed a non-linear mechanical behavior that was best described by the Hamilton-Zabolotskaya model, obtaining the highest coefcient of determination (R2 > 0.95). Moreover, Hamilton-Zabolotskaya model showed the highest discriminative capability of the nonlinear model parameter (Parameter A) for the tissue structural changes between the two sample groups (p= 0.0005). The present work determines the best hyperelastic model with the highest discriminative capability in description of the non-linear mechanical behavior of the cornea.Ministry of Education DPI2017-83859-R DPI2014-51870-R EQC2018004508-P UNGR15-CE-3664Ministry of Health - Turkey DTS15/00093Junta de Andalucia PI16/00339 PI-0107-2017 PIN-0030-201

Modeling of the Influence of Operational Parameters on Tire Lateral Dynamics

Tires play a critical role in vehicle safety. Proper modeling of tire–road interaction is essential for optimal performance of active safety systems. This work studies the influence of temperature, longitudinal vehicle speed, steering frequency, vertical load, and inflation pressure on lateral tire dynamics. To this end, a tire test bench that allows the accurate control of these parameters and the measurement of the variables of interest was used. The obtained results made it possible to propose a simple model that allowed the determination of relaxation length as a function of tire vertical load and vehicle linear speed, and the determination of a representative tread temperature. Additionally, a model has been proposed to determine the lateral friction coefficient from the aforementioned temperature. Finally, results also showed that some variables had little influence on the parameters that characterize lateral dynamicsThis work is partly supported partly by the Spanish Ministry of Science and Innovation under grant PID2019-105572RB-I00, partly by the Economy, Knowledge, Enterprise and Universities Council of the Andalusian Regional Government under grant UMA18-FEDERJA-109, partly by the Spanish Ministry of Education, Culture and Sport under grant FPU18/00450, and partly by the University of Malaga.Partial funding for open access charge: Universidad de Málag

Regenerative Therapies in Dry Eye Disease: From Growth Factors to Cell Therapy

Dry eye syndrome is a complex and insidious pathology with a high level of prevalence among the human population and with a consequently high impact on quality of life and economic cost. Currently, its treatment is symptomatic, mainly based on the control of lubrication and inflammation, with significant limitations. Therefore, the latest research is focused on the development of new biological strategies, with the aim of regenerating affected tissues, or at least restricting the progression of the disease, reducing scar tissue, and maintaining corneal transparency. Therapies range from growth factors and cytokines to the use of different cell sources, in particular mesenchymal stem cells, due to their multipotentiality, trophic, and immunomodulatory properties. We will review the state of the art and the latest advances and results of these promising treatments in this pathology

SMARCA4 deficient tumours are vulnerable to KDM6A/UTX and KDM6B/JMJD3 blockade

Cancer therapyTeràpia del càncerTerapia del cáncerDespite the genetic inactivation of SMARCA4, a core component of the SWI/SNF-complex commonly found in cancer, there are no therapies that effectively target SMARCA4-deficient tumours. Here, we show that, unlike the cells with activated MYC oncogene, cells with SMARCA4 inactivation are refractory to the histone deacetylase inhibitor, SAHA, leading to the aberrant accumulation of H3K27me3. SMARCA4-mutant cells also show an impaired transactivation and significantly reduced levels of the histone demethylases KDM6A/UTX and KDM6B/JMJD3, and a strong dependency on these histone demethylases, so that its inhibition compromises cell viability. Administering the KDM6 inhibitor GSK-J4 to mice orthotopically implanted with SMARCA4-mutant lung cancer cells or primary small cell carcinoma of the ovary, hypercalcaemic type (SCCOHT), had strong anti-tumour effects. In this work we highlight the vulnerability of KDM6 inhibitors as a characteristic that could be exploited for treating SMARCA4-mutant cancer patients

Epigenetic Silencing of Tumor Suppressor miR-124 Directly Supports STAT3 Activation in Cutaneous T-Cell Lymphoma

Increasing evidence supports a potential role for STAT3 as a tumor driver in cutaneous T-cell lymphomas (CTCL). The mechanisms leading to STAT3 activation are not fully understood; however, we recently found that miR-124, a known STAT3 regulator, is robustly silenced in MF tumor-stage and CTCL cells. OBJECTIVE: We studied here whether deregulation of miR-124 contributes to STAT3 pathway activation in CTCL. METHODS: We measured the effect of ectopic mir-124 expression in active phosphorylated STAT3 (p-STAT3) levels and evaluated the transcriptional impact of miR-124-dependent STAT3 pathway regulation by expression microarray analysis. RESULTS: We found that ectopic expression of miR-124 results in massive downregulation of activated STAT3 in different CTCL lines, which resulted in a significant alteration of genetic signatures related with gene transcription and proliferation such as MYC and E2F. CONCLUSIONS: Our study highlights the importance of the miR-124/STAT3 axis in CTCL and demonstrates that the STAT3 pathway is regulated through epigenetic mechanisms in these cells. Since deregulated STAT3 signaling has a major impact on CTCL initiation and progression, a better understanding of the molecular basis of the miR-124/STAT3 axis may provide useful information for future personalized therapies

Community-curated and standardised metadata of published ancient metagenomic samples with AncientMetagenomeDir

Ancient DNA and RNA are valuable data sources for a wide range of disciplines. Within the field of ancient metagenomics, the number of published genetic datasets has risen dramatically in recent years, and tracking this data for reuse is particularly important for large-scale ecological and evolutionary studies of individual microbial taxa, microbial communities, and metagenomic assemblages. AncientMetagenomeDir (archived at https://doi.org/10.5281/zenodo.3980833) is a collection of indices of published genetic data deriving from ancient microbial samples that provides basic, standardised metadata and accession numbers to allow rapid data retrieval from online repositories. These collections are community-curated and span multiple sub-disciplines in order to ensure adequate breadth and consensus in metadata definitions, as well as longevity of the database. Internal guidelines and automated checks to facilitate compatibility with established sequence-read archives and term-ontologies ensure consistency and interoperability for future meta-analyses. This collection will also assist in standardising metadata reporting for future ancient metagenomic studies.Competing Interest StatementThe authors have declared no competing interest.Background & Summary Methods - Repository Structure - Data Acquisition - Data Validation Data Records Technical Validation Usage Note

RGD-Dendrimer-Poly(L-lactic) Acid Nanopatterned Substrates for the Early Chondrogenesis of Human Mesenchymal Stromal Cells Derived from Osteoarthritic and Healthy Donors

Aiming to address a stable chondrogenesis derived from mesenchymal stromal cells (MSCs) to be applied in cartilage repair strategies at the onset of osteoarthritis (OA), we analyzed the effect of arginine-glycine-aspartate (RGD) density on cell condensation that occurs during the initial phase of chondrogenesis. For this, we seeded MSC-derived from OA and healthy (H) donors in RGD-dendrimer-poly(L-lactic) acid (PLLA) nanopatterned substrates (RGD concentrations of 4 × 10−9, 10−8, 2.5 × 10−8, and 10−2 w/w), during three days and compared to a cell pellet conventional three-dimensional culture system. Molecular gene expression (collagens type-I and II-COL1A1 and COL2A1, tenascin-TNC, sex determining region Y-box9-SOX9, and gap junction protein alpha 1-GJA1) was determined as well as the cell aggregates and pellet size, collagen type-II and connexin 43 proteins synthesis. This study showed that RGD-tailored first generation dendrimer (RGD-Cys-D1) PLLA nanopatterned substrates supported the formation of pre-chondrogenic condensates from OA- and H-derived human bone marrow-MSCs with enhanced chondrogenesis regarding the cell pellet conventional system (presence of collagen type-II and connexin 43, both at the gene and protein level). A RGD-density dependent trend was observed for aggregates size, in concordance with previous studies. Moreover, the nanopatterns' had a higher effect on OA-derived MSC morphology, leading to the formation of bigger and more compact aggregates with improved expression of early chondrogenic markers