Many targets of the Wnt/β-catenin signaling pathway are regulated by TCF transcription factors, which play important roles in animal development, stem cell biology, and oncogenesis. TCFs can regulate Wnt targets through a “transcriptional switch,” repressing gene expression in unstimulated cells and promoting transcription upon Wnt signaling. However, it is not clear whether this switch mechanism is a general feature of Wnt gene regulation or limited to a subset of Wnt targets. Co-repressors of the TLE family are known to contribute to (...) the repression of Wnt targets in the absence of signaling, but how they are inactivated or displaced by Wnt signaling is poorly understood. In this mini-review, we discuss several recent reports that address the prevalence and molecular mechanisms of the Wnt transcription switch, including the finding of Wnt-dependent ubiquitination/inactivation of TLEs. Together, these findings highlight the growing complexity of the regulation of gene expression by the Wnt pathway. Wnt targets are regulated by a “switch” where TLE co-repressors are displaced from TCFs by β-catenin, leading to activation of transcription. Recent reports challenge this view and suggest that additional processes, including exchange of specific TCF proteins and Wnt-dependent ubiquitination of TLEs, play important roles in the Wnt transcriptional switch. (shrink)

This article is a theoretical treatment of feminist epistemology of crime, which advocates the centrality of gender as a theoretical starting point for the investigating of digital crimes. It does so by exploring the synergy between the feminist perspectives and the Tripartite Cybercrime Framework (TCF) (which argues that three possible factors motivate cybercrimes – socioeconomic, psychosocial, and geopolitical) to critique mainstream criminology and the meaning of the term “cybercrime”. Additionally, the article examines gender gaps in online harassment, cyber‐bullying, cyber‐fraud, revenge (...) porn, and cyber‐stalking to demonstrate that who is victimised, why, and to what effect are the critical starting points for the analysis of the connections between gender and crimes. In turn, it uses the lens of intersectionality to acknowledge that, while conceptions of gender and crime interact, they intersect with other categories (e.g., sexuality) to provide additional layers of explanation. To nuance the utilitarian value of the synergy between the TCF and the feminist perspectives, the focus shifts to a recent case study (which compared socioeconomic and psychosocial cybercrimes). The article concludes that, while online and offline lives are inextricably intertwined, the victimisations in psychosocial cybercrimes may be more gendered than in socioeconomic cybercrimes. These contributions align the TCF to the feminist epistemology of crime in their attempt to move gender analysis of digital crimes “from margin to centre”. (shrink)

Driven by the question, 'What is the computational content of a (formal) proof?', this book studies fundamental interactions between proof theory and computability. It provides a unique self-contained text for advanced students and researchers in mathematical logic and computer science. Part I covers basic proof theory, computability and Gödel's theorems. Part II studies and classifies provable recursion in classical systems, from fragments of Peano arithmetic up to Π11-CA0. Ordinal analysis and the (Schwichtenberg-Wainer) subrecursive hierarchies play a central role and are (...) used in proving the 'modified finite Ramsey' and 'extended Kruskal' independence results for PA and Π11-CA0. Part III develops the theoretical underpinnings of the first author's proof assistant MINLOG. Three chapters cover higher-type computability via information systems, a constructive theory TCF of computable functionals, realizability, Dialectica interpretation, computationally significant quantifiers and connectives and polytime complexity in a two-sorted, higher-type arithmetic with linear logic. (shrink)

This thesis, which is based on six peer-reviewed publications, is a theoretical and qualitative treatment of the ways in which social and contextual factors serve as a resource for understanding the particularities of ‘cybercrime’ that emanates from Nigeria. The thesis illuminates how closer attention to Nigerian society aids the understanding of Nigerian cybercriminals (known as Yahoo Boys), their actions and what constitutes ‘cybercrime’ in a Nigerian context. ‘Cybercrime’ is used in everyday parlance as a simple acronym for all forms of (...) crimes on the internet, whereas ‘cybercrime’ in a Nigerian context is rooted in socioeconomics and determined by it. In particular, the defrauding of victims for monetary benefit is the most significant theme that emerged from the analysis of Yahoo Boys. While all six publications are situated at the intersections of multiple fields of study, they all share a common endorsement of the constructionist/interpretivist position. The six published works comprise: [a] three conceptual publications; and [b] three empirical publications. The conceptual publications deconstruct the meanings of multiple taken-for-granted concepts in cybercrime scholarship and develop more robust conceptual lenses, namely: (1) ‘Digital Spiritualization’; (2) ‘The Tripartite Cybercrime Framework – TCF’; and (3) ‘The Synergy between Feminist Criminology and the TCF’. These new conceptual lenses represent the candidate’s contribution to developing theory in the field. Alongside this, the empirical section includes three sets of qualitative data, which include: (1) interviews with seventeen Nigerian parents; (2) lyrics from eighteen Nigerian musicians; and (3) interviews with forty Nigerian law enforcement officers. These diverse sources of qualitative data provide a more fully-developed understanding of ‘cybercrime’ in the Nigerian context (and elsewhere). All six-published works, while individually contributing to knowledge, collectively shed clearer light on the centrality of cultural context in the explanation of ‘cybercrime’. (shrink)

Do men and women perceive cybercrime types differently? This article draws on the distinction between socio-economic and psychosocial cybercrime proposed by Lazarus (2019) to investigate whether men and women hold different perceptions of digital crimes across these two dimensions. Informed by the synergy between feminist theory and the Tripartite Cybercrime Framework (TCF), our survey examined respondents’ differential perceptions of socio-economic cybercrime (online fraud) and psychosocial cybercrime (cyberbullying, revenge porn, cyberstalking, online harassment) among men and women in the United Kingdom. The (...) results revealed that women considered psychosocial cybercrime worse than men. Conversely, we found no differences between men and women with regard to socio-economic cybercrime. The article concludes that psychosocial cybercrimes are more gendered than socio-economic cybercrime, suggesting problems with the meaning of ‘cyber-enabled crimes’, and substantiating the synergy between the TCF and feminist perspectives. (shrink)

Wnt glycoproteins are signaling molecules that control a wide range of developmental processes in organisms ranging from the simple metazoan Hydra to vertebrates. Wnt signaling also plays a key role in the development of the nematode C. elegans, and is involved in cell fate specification and determination of cell polarity and cell migration. Surprisingly, the first genetic studies of Wnt signaling in C. elegans revealed major differences with the established (canonical) Wnt signaling pathways of Drosophila and vertebrates. Thus, the Wnt-dependent (...) induction of endoderm in the early embryo and the specification of several asymmetric cell divisions during larval development are mediated by as yet novel Wnt signaling pathways that repress, rather than activate the TCF/LEF-1 transcription factor POP-1. Recently, however, it has been shown that, in addition to these divergent Wnt pathways, C. elegans also has a canonical Wnt pathway that converts POP-1 into an activator and controls the expression of several homeobox genes. Interestingly, these different Wnt pathways use distinct beta-catenins to control POP-1 function: the endoderm induction pathway requires the beta-catenin WRM-1 and parallel input from a mitogen-activated kinase (MAPK) pathway to downregulate POP-1, whereas the canonical Wnt pathway employs the beta-catenin BAR-1 to activate Wnt target gene expression. (shrink)

Wnt proteins are involved in a large number of events during development and disease. The crucial element in the transduction of the signal elicited by Wnt is the state and activity of β-catenin. There are two pools of β-catenin, one associated with cadherins at the cell surface and a soluble one in the cytolasm, whose state and concentration are critical for Wnt signalling. In the absence of Wnt, the cytoplasmic pool is low due to targetted degradation of β-catenin. Upon Wnt (...) signalling, β-catenin is stabilized. As a consequence, it can access the nucleus where it interacts with members of the Tcf family of transcription factors to modulate the expression of defined targets. Recent reports indicate that, in addition to Tcfs, β-catenin can interact with other nuclear proteins raising the possibility that Wnt signalling has a wider modulatory effect on transcription than is mediated by its interactions with Tcfs. BioEssays 23:311–318, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Recent studies indicate that plakoglobin may have a similar function to that of β-catenin within the Wnt signaling pathway. β-catenin is known to be an oncogene in many forms of human cancer, following acquisition of stabilizing mutations in amino terminal sequences. Kolligs1 and coworkers show, however, that unlike β-catenin, plakoglobin induces neoplastic transformation of rat epithelial cells in the absence of such stabilizing mutations. Cellular transformation by plakoglobin also appears to be distinct from that of β-catenin in that it requires (...) activation of the proto-oncogene c-myc. Surprisingly, c-myc is activated more efficiently by plakoglobin than β-catenin, despite its previous identification as a target of Tcf/β-catenin.2 In contrast, a synthetic Tcf reporter gene is activated to a much greater extent by β-catenin than plakoglobin. Plakoglobin and β-catenin may therefore have different roles in Wnt signaling and cancer, which reflect their differential effects on target gene activity. BioEssays 22:961–965, 2000. © 2000 John Wiley & Sons, Inc. (shrink)

Cadherins are a large family of single‐pass transmembrane proteins principally involved in Ca2+‐dependent homotypic cell adhesion. The cadherin molecules comprise three domains, the intracellular domain, the transmembrane domain and the extracellular domain, and form large complexes with a vast array of binding partners (including cadherin molecules of the same type in homophilic interactions and cellular protein catenins), orchestrating biologically essential extracellular and intracellular signalling processes. While current, contrasting models for classic cadherin homophilic interaction involve varying numbers of specific repeats found (...) in the extracellular domain, the structure of the domain itself clearly remains the main determinant of cell stability and binding specificity. Through intracellular interactions, cadherin enhances its adhesive properties binding the cytoskeleton via cytoplasmic associated factors α‐ catenin, β‐catenin and p120ctn. Recent structural studies on classic cadherins and these catenin molecules have provided new insight into the essential mechanisms underlying cadherin‐mediated cell interaction and catenin‐mediated cellular signalling. Remarkable structural diversity has been observed in β‐catenin recognition of other cellular factors including APC, Tcf and ICAT, proteins that contribute to or compete with cadherin/catenin functioning. BioEssays 26:497–511, 2004. © 2004 Wiley Periodicals, Inc. (shrink)