Search results for "way"

Advanced mechanotherapy: Biotensegrity  for governing metastatic tumor cell fate via modulating the extracellular matrix.

2021

Mechano-transduction is the procedure of mechanical stimulus translation via cells, among substrate shear flow, topography, and stiffness into a biochemical answer. TAZ and YAP are transcriptional coactivators which are recognized as relay proteins that promote mechano-transduction within the Hippo pathway. With regard to healthy cells in homeostasis, mechano-transduction regularly restricts proliferation, and TAZ and YAP are totally inactive. During cancer development a YAP/TAZ - stimulating positive response loop is formed between the growing tumor and the stiffening ECM. As tumor developments, local stromal and cancerous cells take advantage of mechanotransduction to enhance proliferatio…

Interfering with MIF-CD74 signalling on macrophages and dendritic cells with a peptide-based approach restores the immune response against metastatic…

2018

ABSTRACTMounting an effective immune response against cancer requires the activation of innate and adaptive immune cells. Metastatic melanoma is the most aggressive form of skin cancer. Immunotherapies that boost the activity of effector T cells have shown a remarkable success in melanoma treatment. Patients, however, can develop resistance to such therapies by mechanisms that include the establishment of an immune suppressive tumour microenvironment. Understanding how metastatic melanoma cells suppress the immune system is vital to develop effective immunotherapies against this disease. In this study, we find that the innate immune cells, macrophages and dendritic cells are suppressed in m…

Mast cells as initiators of immunity and host defense

2001

Until recently, mast cells have been viewed primarily as harmful because of their key role as effector cells of allergic and potentially lethal anaphylactic reactions. Their contribution to human health appeared instead to be limited to the elimination of parasites. There is, however, growing evidence for additional beneficial functions of mast cells, particularly regarding the initiation of acquired immune reactions. Thus, mast cells can phagocytize diverse particles, take up antigens, and express a number of receptors, particularly MHC class I and II antigens, ICAM-1 and -3, CD43, CD80, CD86 and CD40L which allow them to interact with T and B lymphocytes. They can also secrete numerous cy…

2021

The CMS4 mesenchymal subtype of colorectal cancer (CRC) is associated with poor prognosis and resistance to treatment. The cellular prion protein PrPC is overexpressed in CMS4 tumors and controls the expression of a panel of CMS4-specific genes in CRC cell lines. Here, we sought to investigate PrPC downstream pathways that may underlie its role in CMS4 CRC. By combining gene set enrichment analyses and gain and loss of function approaches in CRC cell lines, we identify the integrin-linked kinase ILK as a proximal effector of PrPC that mediates its control on the CMS4 phenotype. We further leveraged three independent large CRC cohorts to assess correlations in gene expression pattern with pa…

Self-organised symmetry breaking in zebrafish reveals feedback from morphogenesis to pattern formation

2019

A fundamental question in developmental biology is how the early embryo breaks initial symmetry to establish the spatial coordinate system later important for the organisation of the embryonic body plan. In zebrafish, this is thought to depend on the inheritance of maternal mRNAs [1–3], cortical rotation to generate a dorsal pole of beta-catenin activity [4–8] and the release of Nodal signals from the yolk syncytial layer (YSL) [9–12]. Recent work aggregating mouse embryonic stem cells has shown that symmetry breaking can occur in the absence of extra-embryonic tissue [19,20]. To test whether this is also true in zebrafish, we separated embryonic cells from the yolk and allowed them to deve…

Analysis of metabolic pathways by the growth of cells in the presence of organic solvents

1996

A new approach to the analysis of metabolic pathways involving poorly water-soluble intermediates is proposed. It relies upon the ability of the hydrophobic intermediates formed by a sequence of intracellular reactions to cross the membrane(s) and partition between aqueous and organic phases, when cells are incubated in the presence of a nonpolar and nontoxic organic solvent. As a result of this thermodynamically driven efflux of the formed intermediates from the cell, they accumulate in the organic medium in sufficient quantities for GC-MS analysis and identification. This enables direct determination of the sequence of chemical reactions involved with no requirement for the isolation of e…

SORT-CC: A procedure for the statistical treatment of free sorting data

2008

International audience; A statistical approach for the analysis of free sorting data is discussed. In a first stage, the sorting data from each subject are arranged into a dataset consisting of indicator variables which reflect the memberships of the stimuli to the groups formed by the subject under consideration. Thereafter, an appropriate standardization is applied on these data and a three way statistical method, namely Common Components and Specific Weights Analysis, is performed on the datasets thus obtained. This makes it possible to take account of the individual differences among the subjects and to depict graphical displays showing the relationships among the stimuli on the one han…

Differential PI3K signal transduction in obesity-associated cardiac hypertrophy and response to ischemia

2014

Objective Elevated insulin and inflammatory cytokine levels in obesity may chronically activate signaling pathways regulating cardiac growth and contractility. Our aim was to examine the effect of obesity on cardiac PI3K isoform and Akt activation during left ventricular (LV) hypertrophy and heart failure. Methods Wild-type mice were fed normal chow or high-fat diet (HFD) for 2, 4, or 6 months. A subset of mice was subjected to chronic myocardial ischemia (MI). Results Echocardiography revealed a progressive increase in LV mass, wall thickness, and diameters in obese mice. Systolic pump function was not impaired. Increased cardiac levels of PI3Kγ, phosphorylated Akt, GSK3β, and Epac were ob…

Reviving the lost spaces under urban highways and bridges: an empirical study

2019

Purpose The fast development of urban movement infrastructures has created neglected urban places in cities. This study aims to provide users’ preferences for designing lost spaces that are a by-product of elevated urban highways (UHs) and bridges to develop a conceptual model for better environmental design. Design/methodology/approach This research is conducted by a combination of both qualitative and quantitative methods. In the first phase, to explore the citizen’s environmental preferences based on the Q-sort technique and in-depth interviews, the ideas of 50 users were considered up to data saturation. The preferences of people for designs under urban bridges were extracted by conten…

Don't Think That Kids Aren't Noticing: Indirect Pathways to Children's Fear of COVID-19

2021

The present study is couched within Rachman's three-pathway theory of fear acquisition (Rachman, 1977, 1991). Besides the direct contact with the objects of fear, this model also includes two indirect pathways to fear acquisition: negative information transmission and modeling. The study aims to explore the contribution of these three factors to the level of children's fear of COVID-19. The sample consisted of 376 children (59.6% girls), aged 7–19 (Mage = 12.77, SDage = 3.57), and one of their parents (Mage = 42.88, SDage = 6.00). The survey was conducted online during the COVID-19 national state of emergency in the Republic of Serbia. The children assessed their fear of COVID-19, general f…