The Misregulation of Cell Adhesion Components during Tumorigenesis: Overview and Commentary

Cell adhesion complexes facilitate attachment between cells or the binding of cells to the extracellular matrix. The regulation of cell adhesion is an important step in embryonic development and contributes to tissue homeostasis allowing processes such as differentiation and cell migration. Many mechanisms of cancer progression are reminiscent of embryonic development, for example, epithelial-mesenchymal transition, and involve the disruption of cell adhesion and expression changes in components of cell adhesion structures. Tight junctions, adherens junctions, desmosomes, and focal adhesion besides their roles in cell-cell or cell-matrix interaction also possess cell signaling function. Perturbations of such signaling pathways can lead to cancer. This article gives an overview of the common structures of cell adhesion and summarizes the impact of their loss on cancer development and progression with articles highlighted from the present issue

William F. Ogburn im Blickwinkel der Informatisierung

Das Ziel dieser Arbeit, ist die Aktualitätsprüfung der Theorie des sozialen Wandels und des Cultural Lags von William F. Ogburn. Dazu wird Ogburns Theorie dargestellt und die nachfolgenden techniksoziologischen Strömungen formuliert. Im aktuellen technischen Teil werden ausgewählte Meilensteine der Informations- und Kommunikationstechnologie und verschiedene Tendenzen durch Studien präsentiert. Daraufhin soll Ogburns Theorie auf die Entwicklungen im IT Bereich angewandt werden, um zu sehen ob seine Aussagen immer noch Erklärungspotential bieten und auch noch auf die heutigen technischen Entwicklungen anwendbar bleiben

DKK1 Mediated Inhibition of Wnt Signaling in Postnatal Mice Leads to Loss of TEC Progenitors and Thymic Degeneration

Thymic epithelial cell (TEC) microenvironments are essential for the recruitment of T cell precursors from the bone marrow, as well as the subsequent expansion and selection of thymocytes resulting in a mature self-tolerant T cell repertoire. The molecular mechanisms, which control both the initial development and subsequent maintenance of these critical microenvironments, are poorly defined. Wnt signaling has been shown to be important to the development of several epithelial tissues and organs. Regulation of Wnt signaling has also been shown to impact both early thymocyte and thymic epithelial development. However, early blocks in thymic organogenesis or death of the mice have prevented analysis of a role of canonical Wnt signaling in the maintenance of TECs in the postnatal thymus.Here we demonstrate that tetracycline-regulated expression of the canonical Wnt inhibitor DKK1 in TECs localized in both the cortex and medulla of adult mice, results in rapid thymic degeneration characterized by a loss of DeltaNP63(+) Foxn1(+) and Aire(+) TECs, loss of K5K8DP TECs thought to represent or contain an immature TEC progenitor, decreased TEC proliferation and the development of cystic structures, similar to an aged thymus. Removal of DKK1 from DKK1-involuted mice results in full recovery, suggesting that canonical Wnt signaling is required for the differentiation or proliferation of TEC populations needed for maintenance of properly organized adult thymic epithelial microenvironments.Taken together, the results of this study demonstrate that canonical Wnt signaling within TECs is required for the maintenance of epithelial microenvironments in the postnatal thymus, possibly through effects on TEC progenitor/stem cell populations. Downstream targets of Wnt signaling, which are responsible for maintenance of these TEC progenitors may provide useful targets for therapies aimed at counteracting age associated thymic involution or the premature thymic degeneration associated with cancer therapy and bone marrow transplants

Identification of signaling pathways in early mammary gland development by mouse genetics

The mammary gland develops as an appendage of the ectoderm. The prenatal stage of mammary development is hormone independent and is regulated by sequential and reciprocal signaling between the epithelium and the mesenchyme. A number of recent studies using human and mouse genetics, in particular targeted gene deletion and transgenic expression, have identified some of the signals that control specific steps in development. This process involves cell specification and proliferation, reciprocal tissue interactions and cell migration. Since some of these events are recapitulated during tumorigenesis, an understanding of these signaling pathways may contribute to the development of targeted therapies and novel drugs

Self-organizing & stochastic behaviors during the regeneration of hair stem cells

Stem cells cycle through active and quiescent states. Large populations of stem cells in an organ may cycle randomly or in a coordinated manner. Although stem cell cycling within single hair follicles has been studied, less is known about regenerative behavior in a hair follicle population. By combining predictive mathematical modeling with in vivo studies in mice and rabbits, we show that a follicle progresses through cycling stages by continuous integration of inputs from intrinsic follicular and extrinsic environmental signals based on universal patterning principles. Signaling from the WNT/bone morphogenetic protein activator/inhibitor pair is coopted to mediate interactions among follicles in the population. This regenerative strategy is robust and versatile because relative activator/inhibitor strengths can be modulated easily, adapting the organism to different physiological and evolutionary needs

Regisztráció, körzethatár, előnyben részesítés

Jelen tanulmány egy 2008 tavaszán, 27 magyarországi többiskolás településen, illetve fővárosi kerületben megvalósított hatásvizsgálat eredményeit mutatja be. A vizsgálat arra irányult, hogy a körzethatárokra vonatkozó, a többiskolás települések deszegregációja érdekében hozott rendelkezések milyen mértékben érvényesültek a gyakorlatban. A kutatás rámutat arra, hogy a körzethatárok jogszabály szerinti kialakításánál olyan mutatót kell használniuk az önkormányzatoknak, ami egzakt módon nem megállapítható. A halmozott an hátrányos helyzet megállapításához szükséges szülői nyilatkozatok megtétele önkéntes, így a „halmozott an hátrányos helyzetű” státusz megállapítása nagyon könnyen manipulálható és szinte ellenőrizhetetlen. A kutatási eredmények fényében egyértelmű, hogy a beiskolázási körzethatárok módosítása önmagában nem oldja meg a szegregáció problémáját. A törvény által kifejezett szándék a hétköznapi gyakorlatban csak akkor realizálódhat a megfelelő mértékben, ha az önkormányzat valóban elkötelezett deszegregációs oktatáspolitikát folytat, és képes hatékony együtt működést kialakítani a nem önkormányzati fenntartókkal, civil szervezetekkel, szülői csoportokkal

Cancer-Associated Fibroblasts Build and Secure the Tumor Microenvironment

Tumor cells reside in a highly complex and heterogeneous tumor microenvironment (TME), which is composed of a myriad of genetically stable non-cancer cells, including fibroblasts, immune cells, endothelial cells, and epithelial cells, and a tumor-specific extracellular matrix (ECM). Cancer-associated fibroblasts (CAFs), as an abundant and active stromal cell population in the TME, function as the signaling center and remodeling machine to aid the creation of a desmoplastic tumor niche. Although there is no denial that the TME and CAFs may have anti-tumor effects as well, a great deal of findings reported in recent years have convincingly revealed the tumor-promoting effects of CAFs and CAF-derived ECM proteins, enzymes, chemical factors and other downstream effectors. While there is growing enthusiasm for the development of CAF-targeting therapies, a better understanding of the complexities of CAF-ECM and CAF-cancer cell interactions is necessary before novel therapeutic strategies targeting the malignant tumor “soil” can be successfully implemented in the clinic

β-catenin Initiates Tooth Neogenesis in Adult Rodent Incisors

β-catenin signaling is required for embryonic tooth morphogenesis and promotes continuous tooth development when activated in embryos. To determine whether activation of this pathway in the adult oral cavity could promote tooth development, we induced mutation of epithelial β-catenin to a stabilized form in adult mice. This caused increased proliferation of the incisor tooth cervical loop, outpouching of incisor epithelium, abnormal morphology of the epithelial-mesenchymal junction, and enhanced expression of genes associated with embryonic tooth development. Ectopic dental-like structures were formed from the incisor region following implantation into immunodeficient mice. Thus, forced activation of β-catenin signaling can initiate an embryonic-like program of tooth development in adult rodent incisor teeth