vignette|Le repas familial (gravure sur bois, ). vignette|La famille de Philippe V d'Espagne (en 1723). vignette|Le portrait de famille est une des formes picturales répandues d'abord dans les familles nobles puis chez les familles bourgeoises (ici la famille Souchay vers 1805). vignette|Un peu de conversation, huile sur toile de Lilly Martin Spencer, vers 1851-1852 vignette|Peinture à l'huile de Jean de Francqueville intitulée . thumb|Portrait d'un chef camerounais et de sa famille (entre 1910 et 1930). vignette|Famille inuit (1917). vignette|Famille européenne photographiée au début du (1912). vignette|Famille congolaise (2007). vignette|Repas de famille au Japon (1980). La famille est :

au sens large : l'ensemble des personnes ayant avec le sujet un lien de parenté ou d'alliance ;

au sens strict : une personne ou un couple et leurs enfants vivant sous le même toit.

C'est une communauté de personnes existant dans toutes les sociétés humaines, selon l'anthropologue Claude Lév

HER receptor dimerization controlled with bivalent ligands

Seymour de Picciotto

In this thesis, I show the ability of engineered bivalent ligands to control HER signaling by taking advantage of the dimerization-dependent mechanism of the four different receptors in the HER (EGFR) family. While monovalent wild-type ligands form HER homoe- and hetero-dimers according to the different members' relative expression levels, I hypothesize that bivalent ligands are able to drive dimerization of specific family members, independently of the cell's HER receptor composition. Using human telomerase reverse transcriptase (hTERT)-immortalized human mesenchymal stem cells (hTMSC), this study first confirms the bioactivity of the bivalent ligands: they exhibit an EC50 one order of magnitude lower than wild-type monomeric ligands and shown an avidity effect as shown from dose-response analysis of the pERK and pY-EGFR nodes. Then, I take advantage of known differences between EGFR hetero- and homodimer to investigate the bivalent ligands' ability to form selective dimers. I demonstrate that bivalent EGF is capable of inducing greater EGFR phosphorylation while preventing HER2 phosphorylation compared to wild-type EGF stimulation. Furthermore, the kinetics of EGFR activation by bivalent EGF differs from wild-type EGF with the appearance of a second activation peak at 20 minutes. Controlling the HER signaling network with these bivalent ligands has potential applications in tissue engineering, cancer therapy and in fundamental studies of the ErbB receptors activation mechanism

2009

Where is my place? Native home and culture in Iranian immigrants' homemaking

Maryam Jafarbegloo

This research investigates homemaking of culturally diverse groups. Homemaking is a process, which is created by residents through the understanding of forms and belongings to represent and celebrate events throughout new structures and objects. Homemaking also is influenced by residents¿ domestic traditions. The investigation of this phenomenon is the focus of this study. Several questions are discussed, partly related to understanding the meaning of home among immigrants, and partly aiming to discover the relation between homemaking and immigrants¿ previous home in their house country. In order to answer the research questions, the present study examines the tensions of immigrants to change different parts of their houses to understand how their homemaking is affected by their domestic culture and memories of their house in their native country. The research contains two main parts. The first part explains a theoretical framework and the bodies of knowledge, while the second part focuses on the analysis of findings and conclusions. In the second part of the research, a study on transformation of domestic traditions on modern house architecture in Tehran aims at discovering respective achievements related to the use of space based on cultural values. In addition, similarities and differences between immigrants¿ current houses in two different host countries and their previous houses in their native countries are observed and examined. Throughout this part, those aspects of domestic tradition, which are transferred by immigrants in the settling process, are investigated. The city of Tehran is considered as a benchmark to achieve all documents from the immigrant houses in their native country during the second Pahlavi period. In addition, as the host cities, Hamburg from Germany and Zürich from Switzerland are studied to answer the research questions with a comparative analysis from Iranian families. In addition, four types of modern houses, including detached houses, row houses, high-rise apartments, and slum houses (Alunak), built in 1940-1979 in Tehran, are examined to understand the immigrants¿ previous houses. The results of this research reveal that homemaking among immigrants serves the creation of the feeling of being at home pursued by immigrants¿ culture in order to recall their houses in Tehran. Results unravel a strong relationship between the immigrants¿ domestic traditions in Iran and their homemaking in Zürich and Hamburg. The Iranian traditional aspects commonly introduce influential factors in homemaking of Iranian immigrants. Some common findings of homemaking process, which are the results of the transformation of Iranian immigrants¿ domestic culture to Zürich and Hamburg, introduce an adaptation of the original Iranian house according to several common factors as follows: ¿ Renovation of the interior arrangement of spaces like living room and kitchen based on their houses in Tehran. ¿ The importance of privacy forces the families to make their home by covering the windows with curtains, covering the yards by tall greenery walls, and separating the interior plans into public and private sections. ¿ Owing to guest hospitality, the houses are furnished to offer sufficient space for guests same as the houses in Tehran, thereby providing different daily and nightly functions for the rooms.

EPFL2017

Immunosuppressive roles of Activin-A in melanoma and characterization of its precursor cleavage

Katarina Pinjusic

Activin-A, a transforming growth factor êµ family member, is a pleiotropic cytokine with diverse functions in development, fertility, adult tissue homeostasis, and aging. Accordingly, deregulation of Activin-A signaling has been associated with many pathological conditions, including cancer and cancer-associated muscle wasting (cachexia). Activin-A was shown to signal in endocrine, but also local autocrine and paracrine manner. Its secretion in many cancer types is associated with a poor prognosis. Previous studies suggest that Activin-A expression in melanoma promotes tumor growth and metastasis indirectly by inhibiting adaptive anti-tumor immunity, leading to a decrease in the intratumoral frequency of cytotoxic CD8+ T cells (CTLs). However, the underlying mechanisms and the relevant direct target cells of Activin-A and their significance for cancer therapies remained unknown. Similar to other TGFêµ-related ligands, proActivin-A is cleaved by proprotein convertases (PCs) to release mature ligands. However, unlike other family members whose signaling is tightly regulated, Activin-A apparently does not have latency.In this thesis, I characterize proActivin-A cleavage and show that one prodomain can be cleaved independently of known PCs. The resulting hemi-cleaved Activin-A can bind activin type II receptors and induce SMAD3 signaling in reporter cells. A protein interactome screen and analysis of cleavage intermediates in plasma revealed that the hemi-cleaved Activin-A likely interacts with extracellular matrix proteins via the remaining prodomain where it promotes local signaling and regulates trafficking. Luciferase reporter assay showed that hemi-cleaved Activin-A can avoid, at least partially, inhibition by endogenous inhibitors FSTL3 and FST, and enable parallel activation of BMP and Activin signaling pathways. Finally, analysis of B16-F1 melanoma models revealed that only fully cleaved Activin-A in source cells increased tumor growth by acting locally in the tumor microenvironment suggesting that the context of Activin-A precursor processing regulates its tumor growth-promoting effect.The second part of this thesis addresses the mechanisms of Activin-induced immunosuppression in melanoma. We found that Activin-A impairs CTL function indirectly and independently of CD4+ T cell, CSF1R+ macrophages, and IL4 signaling. At least in part, anti-tumor CTL responses are impaired by the inhibitory effects of Activin-A on the secretion of critical CTL-recruiting chemokines CXCL9 and CXCL10 by macrophages and dendritic cells (DCs). Furthermore, Activin-A conferred resistance to immune checkpoint blockade therapy. Characterization of Activin-induced changes in the gene expression of tumor-infiltrating cells by Single cell RNA sequencing revealed that INHBA expression induced the most changes in DCs and least in T cells. Interestingly, the most prominently induced hallmark in Activin-secreting tumors across cell types was the IFN signature. In vitro analyses showed that Activin-A increases IFNÎ³-induced activation of STAT1 and confers resistance to cytostatic IFN signaling in cancer cells.Altogether, the findings of this thesis expand our knowledge on the regulation of Activin-A signaling by precursor cleavage and offer insights into mechanisms of Activin-induced immunosuppression in melanoma. Inhibition of Activin-A maturation thus emerges as a potential new strategy to improve responses to immunotherapies in melanoma and likely other cancers

EPFL2022