136 research outputs found
Reproduction Files for the Paper "Comparing Access to US Marine and Terrestrial Protected Areas"
No full textRelated Publication:
"Comparing Access to US Marine and Terrestrial Protected Areas"
Authors:
Anna Lou Abatayo (*,a), Madelon van Adrichem (a), and John Lynham (b,c)
*Corresponding Author. Email: [email protected]
(a) Environmental Economics and Natural Resources Group, Wageningen University and Research
(b) Department of Economics, University of Hawaii at Manoa
(c) UHERO, University of Hawaii at Manoa
Details on the uploaded reproduction files and how to use them can be found in "~ReadMe.txt"
Molecular regulation and pharmacological targeting of the β-catenin destruction complex
No full textThe β-catenin destruction complex is a dynamic cytosolic multiprotein assembly that provides a key node in Wnt signalling regulation. The core components of the destruction complex comprise the scaffold proteins axin and adenomatous polyposis coli and the Ser/Thr kinases casein kinase 1 and glycogen synthase kinase 3. In unstimulated cells, the destruction complex efficiently drives degradation of the transcriptional coactivator β-catenin, thereby preventing the activation of the Wnt/β-catenin pathway. Mutational inactivation of the destruction complex is a major pathway in the pathogenesis of cancer. Here, we review recent insights in the regulation of the β-catenin destruction complex, including newly identified interaction interfaces, regulatory elements and post-translationally controlled mechanisms. In addition, we discuss how mutations in core destruction complex components deregulate Wnt signalling via distinct mechanisms and how these findings open up potential therapeutic approaches to restore destruction complex activity in cancer cells. Linked Articles: This article is part of a themed section on WNT Signalling: Mechanisms and Therapeutic Opportunities. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.24/issuetoc
Wnt Signaling in 3D: Recent Advances in the Applications of Intestinal Organoids
Get PDFIntestinal organoids grown from adult stem cells have emerged as prototype 3D organotypic models for studying tissue renewal and homeostasis. Owing to their strict dependence on Wnt signaling, intestinal organoids offer an unprecedented opportunity to examine Wnt pathway regulation in normal physiology and cancer. We review how alterations in growth factor dependency and organoid morphology can be exploited to identify Wnt signaling mechanisms, characterize mutated pathway components, and predict responses of patient-derived tumors to targeted therapy. We discuss current deficits in the understanding of genotype–phenotype relationships that are to be considered when interpreting mutation-induced changes in organoid morphology
Mutations and mechanisms of WNT pathway tumour suppressors in cancer
No full textMutation-induced activation of WNT-β-catenin signalling is a frequent driver event in human cancer. Sustained WNT-β-catenin pathway activation endows cancer cells with sustained self-renewing growth properties and is associated with therapy resistance. In healthy adult stem cells, WNT pathway activity is carefully controlled by core pathway tumour suppressors as well as negative feedback regulators. Gene inactivation experiments in mouse models unequivocally demonstrated the relevance of WNT tumour suppressor loss-of-function mutations for cancer growth. However, in human cancer, a far more complex picture has emerged in which missense or truncating mutations mediate stable expression of mutant proteins, with distinct functional and phenotypic ramifications. Herein, we review recent advances and challenges in our understanding of how different mutational subsets of WNT tumour suppressor genes link to distinct cancer types, clinical outcomes and treatment strategies
Publisher Correction: Mutations and mechanisms of WNT pathway tumour suppressors in cancer
No full textNature Reviews Cancer (2020) https://doi.org/10.1038/s41568-020-00307-z Published online 23 October 2020 Figure 3 of the article as originally published contained a graphic editing error, whereby the publisher’s redrawn figure wrongly indicated the length of the MCR in the APC protein structure. This has been corrected in the HTML and PDF versions of the manuscript
Organoid-based modeling of intestinal development, regeneration, and repair
Get PDFThe intestinal epithelium harbors a remarkable adaptability to undergo injury-induced repair. A key part of the regenerative response is the transient reprogramming of epithelial cells into a fetal-like state, which drives uniform proliferation, tissue remodeling, and subsequent restoration of the homeostatic state. In this review, we discuss how Wnt and YAP signaling pathways control the intestinal repair response and the transitioning of cell states, in comparison with the process of intestinal development. Furthermore, we highlight how organoid-based applications have contributed to the characterization of the mechanistic principles and key players that guide these developmental and regenerative events
Building a complex for destruction
No full textRanes et al. (2021) report on an in vitro reconstituted β-catenin destruction complex and elucidate the contributions of full-length and cancer-related mutated core components to β-catenin turnover, thereby advancing our understanding of the inner workings of this tumor suppressor complex
Tales from the crypt: intestinal niche signals in tissue renewal, plasticity and cancer
Get PDFRapidly renewing tissues such as the intestinal epithelium critically depend on the activity of small-sized stem cell populations that continuously generate new progeny to replace lost and damaged cells. The complex and tightly regulated process of intestinal homeostasis is governed by a variety of signalling pathways that balance cell proliferation and differentiation. Accumulating evidence suggests that stem cell control and daughter cell fate determination is largely dictated by the microenvironment. Here, we review recent developments in the understanding of intestinal stem cell dynamics, focusing on the roles, mechanisms and interconnectivity of prime signalling pathways that regulate stem cell behaviour in intestinal homeostasis. Furthermore, we discuss how mutational activation of these signalling pathways endows colorectal cancer cells with niche-independent growth advantages during carcinogenesis
CHANSONS TRICOLORES ET CHANTS PATRIOTIQUES
No full textTitre uniforme : [Fleur de Paris]Titre uniforme : [La Marseillaise]Titre uniforme : [La Madelon]Titre uniforme : [Le chant du départ]Titre uniforme : [Chant des Partisans]Titre uniforme : [Ce que c'est qu'un drapeau / adapt. Dupont]Titre uniforme : [Chant des partisans]Titre uniforme : [Le Rêve passe]Titre uniforme : [Fleur de Paris]Collection : Les Belles années du music-hall ; 15Collection : Les Belles années du music-hall ; 15Comprend : LA MARSEILLAISE / ROUGET DE L'ISLE - LE CHANT DU DEPART / M.J. CHENIER et MEHUL ; Marthe CHENAL, de l'Opéra-Comique, avec accompagnement d'orchestre - POUR NOS MORTS, SONNEZ CLAIRONS ! / Th. BOTREL ; poème dit par Th. BOTREL avec clairons de la Garde Républicaine - LEUR JOUR DE GLOIRE (14 juillet 1919) / Th. BOTREL ; Poème dit par Th. BOTREL - LE REVE PASSE / FOUCHER - HELMER et KRIER ; ELVAL, avec accomp d'orchestre et choeurs - QUAND MADELON / BOUSQUET et C. ROBERT ; MARCELLY, avec accomp. d'orchestre - CE QUE C'EST QU'UN DRAPEAU / E. FAVART et LA MAREILLE ; arrang. P. DUPO ; Georges THILL et la Musique de la Garde Républicaine dir. P. DUPONT - LE CLAIRON / Paul DEROULEDE et E. ANDRE ; André GORDON, avec accompagnement d'orchestre dir. BERVILLY - LA GARDE DE NUIT A L'YSER / GENVAL et Lucien BOYER ; DAMIA, avec accompagnement d'orchestre dir. Pierre CHAGNON - LA MALEDICTION / A. GOIZET et L. IZOIRD ; DAMIA, avec accompagnement d'orchestre dir. WAL-BERG - CA FAIT D'EXCELLENTS FRANCAIS / J. BOYER et G. Van PARYS ; Maurice CHEVALIER, avec orchestre dir. Marcel CARIVEN - CHANT DES PARTISANS / J. KESSEL - M. DRUON et Anna MARLY ; Germaine SABLON avec orchestre dir. G. LUYPAERTS - FLEUR DE PARIS / Maurice VANDAIR et Henry BOURTAYRE ; Maurice CHEVALIER, avec orchestre dir. Jacques HELIANBnF-Partenariats, Collection sonore - BelieveContient une table des matière
Large extent of disorder in Adenomatous Polyposis Coli offers a strategy to guard Wnt signalling against point mutations.
Get PDFMutations in the central region of the signalling hub Adenomatous Polyposis Coli (APC) cause colorectal tumourigenesis. The structure of this region remained unknown. Here, we characterise the Mutation Cluster Region in APC (APC-MCR) as intrinsically disordered and propose a model how this structural feature may contribute to regulation of Wnt signalling by phosphorylation. APC-MCR was susceptible to proteolysis, lacked α-helical secondary structure and did not display thermal unfolding transition. It displayed an extended conformation in size exclusion chromatography and was accessible for phosphorylation by CK1ε in vitro. The length of disordered regions in APC increases with species complexity, from C. elegans to H. sapiens. We speculate that the large disordered region harbouring phosphorylation sites could be a successful strategy to stabilise tight regulation of Wnt signalling against single missense mutations
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