It can be an alternative to other castration techniques in equines.Regenerative medicine applications require cells that are not inflicted with senescence after in vitro culture for an optimal in vivo outcome. Methods to overcome replicative senescence include genomic modifications which have their own disadvantages. We have evaluated a three-dimensional (3D) thermo-reversible gelation polymer (TGP) matrix environment for its capabilities to reverse cellular senescence. The expression of senescence-associated beta-galactosidase (SA-βgal) by human chondrocytes from osteoarthritis-affected cartilage tissue, grown in a conventional two-dimensional (2D) monolayer culture versus in 3D-TGP were compared. In 2D, the cells de-differentiated into fibroblasts, expressed higher SA-βgal and started degenerating at 25 days. SA-βgal levels decreased when the chondrocytes were transferred from the 2D to the 3D-TGP culture, with cells exhibiting a tissue-like growth until 42-45 days. Other senescence associated markers such as p16INK4a and p21 were also expressed only in 2D cultured cells but not in 3D-TGP tissue engineered cartilage. This is a first-of-its-kind report of a chemically synthesized and reproducible in vitro environment yielding an advantageous reversal of aging of human chondrocytes without any genomic modifications. The method is worth consideration as an optimal method for growing cells for regenerative medicine applications.When probed at nanometer and picosecond scales, the properties of a liquid present striking analogies with the ones of the corresponding solid, one of the most surprising is the ability of supporting shear wave propagation, as a rigid medium. Although this evidence is being reported by a growing number of terahertz scattering measurements, it remains an open question whether it is universal or rather typical of some liquids only. Furthermore, given its elusive signatures in the scattering signal, the detection of this effect appears as a typical case where an unintentional „bias of confirmation” can mislead experimentalists. We thus decided to use a Bayesian inference approach to achieve a probabilistically grounded and evidence-based lineshape modeling of the inelastic neutron scattering spectra from liquid silver, whose simulated density autocorrelations bear evidence of a shear mode propagation over very short distances. The result of our analysis indicates that the observation of any additional, non-longitudinal, acoustic modes in this simple system goes beyond the accuracy of the used scattering method.Exceptional performance is present in various human activities but its origins are debated and challenging to study. We report evidence of exceptional performance and qualitative variation in learning object-names in dogs. 34 naïve family dogs and 6 knowledgeable individuals that knew multiple toy names, found in 2 years of search around the Globe, were exposed to 3 months of training to learn two novel toy-names and were tested in two-way choice tests. Only 1 naïve and all 6 knowledgeable dogs passed the tests. Additionally, only these dogs learned at least 10 new toy names over the 3 months, showing qualitative variation in this capacity. Although previous object-name knowledge could provide an explanation for the superior performance of the knowledgeable dogs, their rarity and the absence of previous training of this skill point to exceptional giftedness in these individuals, providing the basis to establish dogs as a model-species for studying talent.Growth rates importantly determine developmental time and are, therefore, a key variable of a species’ life history. A widely used method to reconstruct growth rates and to estimate age at death in extant and particularly in fossil vertebrates is the analysis of bone tissue apposition rates. Lines of arrested growth (LAGs) are of special interest here, as they indicate a halt in bone growth. However, although of great importance, the time intervals between, and particularly the reason of growth arrests remains unknown. Therefore, experiments are increasingly called for to calibrate growth rates with tissue types and life history events, and to provide reliable measurements of the time involved in the formation of LAGs. Based on in vivo bone labelling, we calibrated periods of bone tissue apposition, growth arrest, drift and resorption over the period from birth to post-weaning in a large mammal, the red deer. We found that bone growth rates tightly matched the daily weight gain curve, i.e. decreased with age, with two discrete periods of growth rate disruption that coincided with the life history events birth and weaning, that were visually recognisable in bone tissue as either partial LAGs or annuli. Our study identified for the first time in a large mammal a general pattern for juvenile bone growth rates, including periods of growth arrest. The tight correlation between daily weight gain and bone tissue apposition suggests that the red deer bone growth model is valid for ruminants in general where the daily weight gain curve is comparable.In sepsis-associated coagulopathies and disseminated intravascular coagulation, relative platelet reductions may reflect coagulopathy severity. However, limited evidence supports their clinical significance and most sepsis-associated coagulopathy criteria focus on the absolute platelet counts. To estimate the impact of relative platelet reductions and absolute platelet counts on sepsis outcomes. A multicenter retrospective observational study was performed using the eICU Collaborative Research Database, comprising 335 intensive care units (ICUs) in the United States. Patients with sepsis and an ICU stay > 2 days were included. Estimated effects of relative platelet reductions and absolute platelet counts on mortality and coagulopathy-related complications were evaluated. Overall, 26,176 patients were included. Multivariate mixed-effect logistic regression analysis revealed marked in-hospital mortality risk with larger platelet reductions between days one and two, independent from the resultant absolute platelet counts. The adjusted odds ratio (OR) [95% confidence intervals (CI)] for in-hospital mortality was 1.28[1.23-1.32], 1.86[1.75-1.97], 2.99[2.66-3.36], and 6.05[4.40-8.31] for 20-40%, 40-60%, 60-80%, and > 80% reductions, respectively, when compared with a  less then  20% decrease in platelets (P  less then  0.001 for each). In the multivariate logistic regression analysis, platelet reductions ≥ 11% and platelet counts ≤ 100,000/μL on day 2 were associated with high coagulopathy-related complications (OR [95%CI], 2.03 and 1.18; P  less then  0.001 and P  less then  0.001), while only platelet reduction was associated with thromboembolic complications (OR [95%CI], 1.43 [1.03-1.98], P  less then  0.001). The magnitude of platelet reductions represent mortality risk and provides a better signature of coagulopathies in sepsis; therefore, it is a plausible criterion for sepsis-associated coagulopathies.Medulloblastoma is the most common high-grade brain tumor in childhood. Medulloblastomas with c-myc amplification, classified as group 3, are the most aggressive among the four disease subtypes resulting in a 5-year overall survival of just above 50%. Despite current intensive therapy regimens, patients suffering from group 3 medulloblastoma urgently require new therapeutic options. Using a recently established c-myc amplified human medulloblastoma cell line, we performed an in-vitro-drug screen with single and combinatorial drugs that are either already clinically approved or agents in the advanced stage of clinical development. Candidate drugs were identified in vitro and then evaluated in vivo. Tumor growth was closely monitored by BLI. Vessel development was assessed by 3D light-sheet-fluorescence-microscopy. We identified the combination of gemcitabine and axitinib to be highly cytotoxic, requiring only low picomolar concentrations when used in combination. In the orthotopic model, gemcitabine and axitinib showed efficacy in terms of tumor control and survival. In both models, gemcitabine and axitinib were better tolerated than the standard regimen comprising of cisplatin and etoposide phosphate. 3D light-sheet-fluorescence-microscopy of intact tumors revealed thinning and rarefication of tumor vessels, providing one explanation for reduced tumor growth. Thus, the combination of the two drugs gemcitabine and axitinib has favorable effects on preventing tumor progression in an orthotopic group 3 medulloblastoma xenograft model while exhibiting a favorable toxicity profile. The combination merits further exploration as a new approach to treat high-risk group 3 medulloblastoma.Despite its paramount importance for manifold use cases (e.g., in the health care industry, sports, rehabilitation and fitness assessment), sufficiently valid and reliable gait parameter measurement is still limited to high-tech gait laboratories mostly. Here, we demonstrate the excellent validity and test-retest repeatability of a novel gait assessment system which is built upon modern convolutional neural networks to extract three-dimensional skeleton joints from monocular frontal-view videos of walking humans. The validity study is based on a comparison to the GAITRite pressure-sensitive walkway system. All measured gait parameters (gait speed, cadence, step length and step time) showed excellent concurrent validity for multiple walk trials at normal and fast gait speeds. The test-retest-repeatability is on the same level as the GAITRite system. In conclusion, we are convinced that our results can pave the way for cost, space and operationally effective gait analysis in broad mainstream applications. Most sensor-based systems are costly, must be operated by extensively trained personnel (e.g., motion capture systems) or-even if not quite as costly-still possess considerable complexity (e.g., wearable sensors). In contrast, a video sufficient for the assessment method presented here can be obtained by anyone, without much training, via a smartphone camera.Cleavage and dissociation of a large N-terminal fragment and the consequent unmasking of a short sequence (Stachel) remaining on the N-terminus have been proposed as mechanisms of activation of some members of the adhesion G protein-coupled receptor (aGPCR) family. However, the identity of residues that play a role in the activation of aGPCRs by the cognate Stachel remains largely unknown. Protein sequence alignments revealed a conserved stretch of residues in the extracellular loop 2 (ECL2) of all 33 members of the aGPCR family. ADGRG2, an orphan aGPCR, plays a major role in male fertility, Ewing sarcoma cell proliferation, and parathyroid cell function. We used ADGRG2 as a model aGPCR and generated mutants of the conserved residues in the ECL2 via site-directed mutagenesis. We show that tryptophan and isoleucine in the ECL2 are essential for receptor stability and surface expression in the HEK293 cells. By adjusting the receptor surface expression levels, we show that mutation of these residues of ECL2 ablates the Stachel-mediated activation of multiple signaling pathways of ADGRG2. This study provides a novel understanding of the role of the ECL2 in Stachel-mediated signaling and degradation of ADGRG2, which may lay the foundation for the rational design of therapeutics to target aGPCRs.