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The chordoid glioma PRKCA D463H mutation is a kinase inactive, gain-of-function allele that induces early-onset chondrosarcoma in mice
No full textThe penetrant D463H mutation in PRKCA, which encodes the kinase PKCα, is a biomarker and driver of chordoid glioma, a type of brain cancer. Here, we found that heterozygous knock-in expression of the D463H mutant in mice elicited the development of chondrosarcomas. The mutant protein kinase was catalytically inactive, but no such oncogenic phenotype was observed for the related inactivating mutation D463N, indicating that the lack of activity per se was not the cause of the oncogenicity of the D463H mutant. In cultured glioma cells, the behavior of the D463H mutant closely mirrored that of wild-type PKCα and retained ATP binding, unlike the related D463N mutant. Mechanistically, PKCα D463H displayed quantitative alterations in its interactome compared with that of the wild-type kinase, with enhanced association with epigenetic regulators. This change in the interactome aligned with transcriptomic changes that resembled an increased PKCα-induced expression program, with enhanced gene signatures mediated by BRD4, MYC, and TGF-β. D463H expression reduced the sensitivity of cells to the BET inhibitors JQ1 and AZD5153, indicating the functional importance of these pathways. The findings indicate that D463H is a dominant gain-of-function oncogenic mutant that operates through a noncatalytic allosteric mechanism
“I could have done otherwise”: the neural bases of counterfactual representations
Get PDFCounterfactual thinking, the ability to mentally represent how events might have unfolded differently, plays a central role in decision-making, memory, learning, and emotional regulation, and has even been described as a foundation of human cognition itself. Yet the neural systems supporting this capacity remain debated. Here, we present a quantitative meta-analysis of 20 fMRI studies, synthesising evidence across tasks involving both counterfactual generation, where individuals voluntarily and constructively imagine alternative self-referential scenarios, and counterfactual evaluation, where the brain assess externally provided or rapidly inferred unchosen outcomes during decision-making. This analysis identified a specific set of regions encompassing the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), hippocampus, striatum, and amygdala. Within this set, the OFC emerged as a hub for representing counterfactual options and their value, while the ACC, particularly its dorsal subdivision, linked these representations to behavioural control. The hippocampus supported constructive aspects of counterfactual thought, overlapping with episodic memory processes, and the amygdala contributed to the affective responses, particularly regret. Separate analyses for counterfactual generation and counterfactual evaluation revealed partial dissociations. Counterfactual generation prominently recruited the superior frontal gyrus, involved in constructive memory processes. Counterfactual evaluation engaged, among other regions, the striatum, where fictive error signals encoded the value of unchosen outcomes and predicted subsequent behaviour. These findings indicate that counterfactual thinking relies on distinct but interacting set of regions for valuation, control, memory, and emotion, highlighting its multifaceted role in adaptive human cognition
Reflecting on social inclusion through philosophical discussion: a sustainable partnership framework
Get PDFThe 17 sustainable development goals advocated by the United Nations have played a big role in focusing the minds of policy makers in terms of sustainability issues and have also highlighted the issue of social inclusion and the need to make society more equitable. As well as referencing the sustainable development goals, attention is given to the planetary health concept as it is known to deepen our understanding of the ecological interdependence brought about by cultural, environmental and socio-economic factors, which have relevance in terms of mankind achieving the sustainable development goals. This paper addresses the following question: How can a framework to foster global partnerships leading to sustainable development be underpinned by a philosophical argument that strengthens the case for social inclusion? Consequently, a wide body of literature is reviewed, with key concepts such as collaboration being placed in context and reinforced through stakeholder theory. A philosophical discussion is entered into embracing Moore’s open question argument regarding the reliance on Intuitionism to explain how actions can be coined as immoral or moral. Such arguments are useful for raising moral issues that often end in moral disagreements, and which raise and help solve ethical problems. To effectively deal with the complexity involved, policy makers should support the use of frameworks that can be used to support and encourage social inclusion. In adopting this viewpoint, we put forward a sustainable partnership framework that provides guidance to policy makers and their advisors in terms of tackling the issue of social inclusion. In order to achieve social inclusion, policy makers need to understand the role that symbolic representation plays and how the influence of major influencers generates collaborative knowledge that is reappraised through philosophical argument. The outcome of the philosophical argument is a change in a nation’s cultural value system and the implementation of social inclusion policy
A concurrent validity study of the Mullen Scales of Early Learning (MSEL) and the MacArthur‐Bates Communicative Developmental Inventory (CDI) in infants with an elevated likelihood or diagnosis of Autism
Get PDFInfants at elevated likelihood for or later diagnosed with autism typically have smaller vocabularies than their peers, as shown by the Mullen Scales of Early Learning (MSEL) and the MacArthur-Bates Communicative Developmental Inventory (CDI). However, the extent to which MSEL and CDI scores align remains unclear, especially across clinical and non-clinical popu- lations. This study examined whether the concurrent validity of the MSEL and CDI differs based on autism likelihood and diagnosis. Data from 720 14-month-old infants were analysed, grouped by likelihood (elevated vs. typical) and diagnosis at 36 months (diagnosed vs. not diagnosed). Vocabulary scores were compared across both likelihood and diagnostic groups. Moderate correlations were observed between the MSEL and CDI in most groups (rs range = [.34–.58]). One exception was that the expressive scores of elevated likelihood infants on the MSEL and CDI were more closely associated than the expres- sive scores of typical likelihood infants. Diagnosed infants had lower vocabulary scores than non-diagnosed peers on both the MSEL and CDI. The elevated likelihood group showed lower scores on the MSEL but not the CDI compared to typical likelihood infants. The moderate correlations suggest that the MSEL and CDI assess different aspects of language in infancy. These associations were weaker than previously reported in autistic children. Differences in vocabulary scores across likeli- hood and diagnostic groups highlight the need for further research to understand the association between these measures
Transfer dynamics of litter: introduction to new vectors in the mobility of terrestrial litter
Get PDFRivers are the primary contributor to marine plastics, transporting litter from inland sources through natural drainage systems. Despite an agreement among researchers that waste littered on land has the potential to enter river systems, there lacks specific quantification of the forces that facilitate transport. Although meteorological conditions (e.g. wind, rain) are considered factors, this exploratory study theorises that the influence of movement of individuals through an urban environment deserves investigation. To illustrate this hypothesis, litter items fitted with Global Positioning System (GPS) were released in an area of high foot traffic along the river Thames in Central London during a time of low meteorological influence. Point data were analysed through a Standard Deviational Ellipse (SDE) to quantify distance, speed and direction of travel of litter items under the sole influence of human movement. Of the 9 bottles distributed, 5 remained in the test site undisturbed by street cleansing staff. During this time, bottles travelled an average distance of 2.4 metres in directions consistent with the flow of foot traffic; two of which ultimately entering the river as a result of these forces. Although the study is limited, results imply proof of concept that passive anthropogenic forces contribute to riverine litter loads, calling into question public complicity when ignoring or kicking litter. It is suggested that packaging be designed with qualities that reduce transportability and the use of physical barriers along river edges be implemented as means to reduce the contribution of terrestrial litter to marine plastics
Lenin and the image in time
Get PDFLenin has been represented in photographs, film, paintings
and in other modes. Beginning from some of the discussions about
adequate portrayals of Lenin, whether in time-based or more ‘auratic’
media, the politics of aesthetics and concomitant aesthetics of politics is
here investigated as standing in broader relation to the politics of time,
dialectics and mobility and what genius means. After some observations
on various considerations of Lenin in relation to Western Marxism and
avant garde aesthetics, another context, derived from a short review by
Walter Benjamin of Lenin’s letters to Gorky, excavates the constrasting
dialectical context of ‘Creative Indifference’ (Salomo Friedlaender/Myona).
Benjamin’s review attempts to place Lenin in relation to post-Nietzschean
and absurdist strands of thinking that transform both the assumptions
conveyed by the Westernness of Western Marxism and the modes of
avant gardism typically associated with Bolshevism. Conclusions about
the reactionary nature of a demand for genius and the collapse of public
and private life into something prior to both are what Walter Benjamin
draws from his Lenin lessons.
Keywords: Image; Walter Benjamin; Dialectics; Trotsky; Stalin; air-Brushing, Friedlaende
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Blood and animal character in Aristotle's Parts of Animals
No full textOn the Parts of Animals (PA) is our main source for Aristotle’s explanations of animal character. This he locates in the qualities of an animal’s blood (or it’s analogue), whether it is hot, cold, thick, then, turbid or pure (PA II.2, 651a16). This chapter sets out the main debate about character in Aristotle’s biological writings, whether it is formal or material, and argues that it is part of an animals’ material nature. While the materials existing in the blood vessels are not put there for the purpose of underlying character, they are often utilised for this end, displaying a complex coordination of material and formal natures. The chapter ends with a detailed analysis of which fluid elements in the body are responsible for underlying character and at which point they emerge in the digestive process. This further clarifies the relationship between animal bodies, nutritive processes, and the character potentials animals possess
Against conferencing-as-usual in times of genocide: criminology, complicity, and sexual violence in Palestine
Get PDFThis reflection stems from a roundtable convened at the European Society of Criminology Conference (EUROCRIM) in September 2025. Originally proposed as a discussion on expertise and sexual violence research, the session was reconfigured in response to a call by the Palestinian Campaign for the Academic and Cultural Boycott of Israel (PACBI) to boycott the conference. In place of the planned roundtable, we delivered a collective statement addressing sexual violence within the context of settler colonialism in Palestine, situating our interventions through reflections on our
own positionalities and the broader complicities of Criminology as a discipline and the European Society of Criminology as a disciplinary body. The statement brings together individual reflections grounded in a shared commitment to feminist, anticolonial, and abolitionist praxis
Profit, cost, price, learned societies; further thoughts on Samuel A. Moore's Publishing Beyond the Market
Get PDFSince I last wrote, I have had a few more thoughts on Samuel Moore’s book. Again, these are not necessarily things that he does not discuss or things that he should have discussed. They are merely thoughts that occurred to me in response to reading his work
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