Overexpression of the urokinase receptor splice variant uPAR-del4/5 in breast cancer cells affects cell adhesion and invasion in a dose-dependent manner and modulates transcription of tumor-associated genes

mRNA levels of the urokinase receptor splice variant uPAR-del4/5 are associated with prognosis in breast cancer. Its overexpression in cancer cells affects tumor biologically relevant processes. In the present study, individual breast cancer cell clones displaying low vs. high uPAR-del4/5 expression were analyzed demonstrating that uPAR-del4/5 leads to reduced cell adhesion and invasion in a dose-dependent manner. Additionally, matrix metalloproteinase-9 (MMP-9) was found to be strongly upregulated in uPAR-del4/5 overexpressing compared to vector control cells. uPAR-del4/5 may thus play an important role in the regulation of the extracellular proteolytic network and, by this, influence the metastatic potential of breast cancer cells

Mobile eye tracking applied as a tool for customer experience research in a crowded train station

Train stations have increasingly become crowded, necessitating stringent requirements in the design of stations and commuter navigation through these stations. In this study, we explored the use of mobile eye tracking in combination with observation and a survey to gain knowledge on customer experience in a crowded train station. We investigated the utilization of mobile eye tracking in ascertaining customers’ perception of the train station environment and analyzed the effect of a signalization prototype (visual pedestrian flow cues), which was intended for regulating pedestrian flow in a crowded underground passage. Gaze behavior, estimated crowd density, and comfort levels (an individual’s comfort level in a certain situation), were measured before and after the implementation of the prototype. The results revealed that the prototype was visible in conditions of low crowd density. However, in conditions of high crowd density, the prototype was less visible, and the path choice was influenced by other commuters. Hence, herd behavior appeared to have a stronger effect than the implemented signalization prototype in conditions of high crowd density. Thus, mobile eye tracking in combination with observation and the survey successfully aided in understanding customers’ perception of the train station environment on a qualitative level and supported the evaluation of the signalization prototype the crowded underground passage. However, the analysis process was laborious, which could be an obstacle for its practical use in gaining customer insights

IGF1R expression by adult oligodendrocytes is not required in the steady-state but supports neuroinflammation.

In the central nervous system (CNS), insulin-like growth factor 1 (IGF-1) regulates myelination by oligodendrocyte (ODC) precursor cells and shows anti-apoptotic properties in neuronal cells in different in vitro and in vivo systems. Previous work also suggests that IGF-1 protects ODCs from cell death and enhances remyelination in models of toxin-induced and autoimmune demyelination. However, since evidence remains controversial, the therapeutic potential of IGF-1 in demyelinating CNS conditions is unclear. To finally shed light on the function of IGF1-signaling for ODCs, we deleted insulin-like growth factor 1 receptor (IGF1R) specifically in mature ODCs of the mouse. We found that ODC survival and myelin status were unaffected by the absence of IGF1R until 15 months of age, indicating that IGF-1 signaling does not play a major role in post-mitotic ODCs during homeostasis. Notably, the absence of IGF1R did neither affect ODC survival nor myelin status upon cuprizone intoxication or induction of experimental autoimmune encephalomyelitis (EAE), models for toxic and autoimmune demyelination, respectively. Surprisingly, however, the absence of IGF1R from ODCs protected against clinical neuroinflammation in the EAE model. Together, our data indicate that IGF-1 signaling is not required for the function and survival of mature ODCs in steady-state and disease

Understanding the relations between crowd density, safety perception and risk-taking behavior on train station platforms: A case study from Switzerland

Railway platforms are becoming increasingly crowded, especially at peak hours. In this observational study, we investigated how the density of people is perceived by passengers and how this perceived density correlates with safety perception and risk-taking behavior. Risk-taking behavior here means stepping into the danger zone, the area of the platform bordering the tracks where individuals are at risk to their physical integrity by a train passing through, arriving at or leaving the station. The investigation of perceived density and actual behavior on the platform poses methodological challenges. Therefore, we used a stereo sensor technology to collect anonymized behavioral data on a train station platform over two months. Data regarding passenger density and oversteps into the danger zone was collected during rush hours and analyzed for this study. Additionally, subjective data, such as estimation and perception of passenger density and safety perception were collected in a survey with 179 participants. Survey links were distributed during rush hours in three different train stations on platforms over two weeks. While distributing the links for the online survey in the field (two-hour sessions during rush hours), an observation was conducted (i.e., oversteps into the danger zone, general passenger behavior). The results indicate that increased measured passenger density is related to more oversteps. Subjective perception of crowd density, regarding how comfortable someone feels in the given situation, correlates with safety perception and also significantly predicts overstepping into the danger zone. Increased estimated density also correlates with reduced safety perception but is not a predictor of oversteps. We suggest optimizing the passenger distribution on the platform by motivating passengers to move to less crowded areas, e.g. with approaches such as “nudging” so that passengers feel more comfortable on the platform. This can both improve both safety and the customer experience on the platform

Modulation of protein expression levels and DNA methylation status of breast cancer metastasis genes by anthracycline-based chemotherapy and the demethylating agent decitabine

Epigenetic drugs are promising add-ons to cancer treatment; still, adverse effects concerning tumour promotion have been reported occasionally. In this in vitro study, we investigated the effect of combination treatment of decitabine with anthracycline-based chemotherapy [5-fluorouracil plus epirubicine plus cyclophosphamide (FEC)] on viability and metastatic activity of breast cancer cell lines, MDA-MB-231 (estrogen receptor-negative) and MCF-7 (estrogen receptor-positive). The effect of decitabine and its combined treatment with FEC on viability of both cancer cell lines was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide and adenosine triphosphate (ATP) cell survival assays. DNA methylation specific real-time polymerase chain reaction (PCR) (Methylight (R)) was employed to document the methylation status of the metastasis-relevant urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-I (PAI-1) genes. Additionally, protein expression levels of uPA and PAI-1 were determined using enzyme-linked immunosorbent assays. Invasion capacity of cells was assayed using Matrigel (R) invasion assay. Decitabine lowered the viability of MCF-7 cells, although MDA-MB-231 cells were not affected. Decitabine did not augment FEC-mediated cytotoxicity in both cell lines. In MCF-7 cells, methylation of the uPA and PAI-1 gene promoter was significantly reduced by decitabine or decitabine plus FEC. Protein levels of uPA and PAI-1 were induced by all treatments. Decitabine significantly induced the invasion capacity of MCF-7 cells, whereas all of the drugs resulted in decreased invasion capacity of MDA-MB-231. Our results suggest differential effects of single-dose decitabine and its combination with FEC on the metastatic capacity and survival of breast cancer cell lines endowed with different metastatic behaviour.Seventh Framework Programme (201279)UK Research & Innovation (UKRI) Science & Technology Facilities Council (STFC) (ST/I005912/1) (ST/I002200/1) (ST/G502347/1) (ST/F006748/1