• Rossen Moesgaard posted an update 6 months ago

    We further combined IF analyses with microfluorimetric Ca2+ measurements to address the functionality of these ion channels in iDNs. Thus, we provide a detailed morphological and functional characterization of iDNs, thereby, underpinning their enormous potential as an animal-free alternative for human specific research in the pain field for unveiling pathophysiological mechanisms and for unbiased, disease-specific personalized drug development.The combination of work and family roles can lead to work-to-family conflict (WTFC), which may have consequences for the parents’ health. We examined the association between WTFC and self-reported general health among working parents in Germany over time. Data were drawn from wave 6 (2013) and wave 8 (2015) of the German family and relationship panel. It included working persons living together with at least one child in the household (791 mothers and 723 fathers). Using logistic regressions, we estimated the longitudinal effects of WTFC in wave 6 and 8 on self-reported general health in wave 8. Moderating effects of education were also considered. The odds ratio for poor self-reported general health for mothers who developed WTFC in wave 8 compared to mothers who never reported conflicts was 2.4 (95% CI 1.54-3.68). For fathers with newly emerged WTFC in wave 8, the odds ratio was 1.8 (95% CI 1.03-3.04). Interactions of WTFC with low education showed no significant effects on self-reported general health, although tendencies show that fathers with lower education are more affected. It remains to be discussed how health-related consequences of WTFC can be reduced e.g., through workplace interventions and reconciliation policies.A compelling body of research demonstrates that exposure to nature, especially trees, is beneficial to human health. We know little, however, about the extent to which understory vegetation that does not reach the height of trees, impacts human health. An additional gap in our knowledge concerns the extent to which daily variations in exposure to various forms of vegetation are related to human health outcomes. Many previous findings describing such connections were achieved in laboratory settings or through semi-controlled experiments, which do not reflect the dynamic variations of people’s daily exposure to nature. Thus, we conducted an online survey to address these questions. We used the National Land Cover Dataset 2011 and Google Street View images to estimate participants’ daily exposure to nature, and two standard questionnaires (General Health SF-12 and the Perceived Stress Scale) to assess health. Results show that greater exposure to trees in daily life is associated with better health outcomes. Specifically, higher neighborhood concentrations of tree canopy are related to better physical health, overall health and an increased capacity to control stress. In contrast, the results exploring the health associations of understory vegetation were inconsistent. In most cases, understory vegetation had a negative relationship with stress and mental health measures.DSCAM-AS1 is a cancer-related long noncoding RNA with higher expression levels in Luminal A, B, and HER2-positive Breast Carcinoma (BC), where its expression is strongly dependent on Estrogen Receptor Alpha (ERα). DSCAM-AS1 expression is analyzed in 30 public datasets and, additionally, by qRT-PCR in tumors from 93 BC patients, to uncover correlations with clinical data. Moreover, the effect of DSCAM-AS1 knockdown on gene expression and alternative splicing is studied by RNA-Seq in MCF-7 cells. We confirm DSCAM-AS1 overexpression in high grade Luminal A, B, and HER2+ BCs and find a significant correlation with disease relapse. In total, 908 genes are regulated by DSCAM-AS1-silencing, primarily involved in the cell cycle and inflammatory response. Noteworthily, the analysis of alternative splicing and isoform regulation reveals 2085 splicing events regulated by DSCAM-AS1, enriched in alternative polyadenylation sites, 3’UTR (untranslated region) shortening and exon skipping events. Finally, the DSCAM-AS1-interacting splicing factor heterogeneous nuclear ribonucleoprotein L (hnRNPL) is predicted as the most enriched RBP for exon skipping and 3’UTR events. The relevance of DSCAM-AS1 overexpression in BC is confirmed by clinical data and further enhanced by its possible involvement in the regulation of RNA processing, which is emerging as one of the most important dysfunctions in cancer.Cancer stem cells (CSCs) are the main culprits involved in therapy resistance and disease recurrence in colorectal carcinoma (CRC). Results using cell culture, animal models and tissues from patients with CRC suggest the indispensable roles of colorectal CSCs in therapeutic failure. Pyridostatin modulator Conventional therapies target proliferating and mature cancer cells, while CSCs are mostly quiescent and poorly differentiated, thereby they can easily survive chemotherapeutic insults. The aberrant activation of Wnt/β-catenin, Notch, Hedgehog, Hippo/YAP (Yes-associated protein) and phosphatidylinositol 3-kinase/protein kinase B facilitates CSCs with excessive self-renewal and therapy resistance property in CRC. CSCs survive the chemo-radiotherapies by escaping therapy mediated DNA damage via altering the cell cycle checkpoints, increasing DNA damage repair capacity and by an efficient scavenging of reactive oxygen species. Furthermore, dysregulations of miRNAs e.g., miR-21, miR-93, miR-203, miR-215, miR-497 etc., modulate the therapeutic sensitivity of colorectal CSCs by regulating growth and survival signalling. In addition, a reversible quiescent G0 state and the re-entering cell cycle capacity of colorectal CSCs can accelerate tumour regeneration after treatment. Moreover, switching to favourable metabolic signatures during a therapeutic regimen will add more complexity in therapeutic outcomes against CSCs. Therapeutic strategies targeting these underlying mechanisms of CSCs’ therapy resistance could provide a promising outcome, however, deep understanding and concerted research are necessary to design novel therapies targeting CSCs. To conclude, the understanding of these mechanisms of CSC in CRC could lead to the improved management of patients with CRC.

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