Molecular dissection of Meis1 reveals 2 domains required for leukemia induction and a key role for Hoxa gene activation

The Hoxa9 and Meis1 genes represent important oncogenic collaborators activated in a significant proportion of human leukemias with genetic alterations in the MLL gene. In this study, we show that the transforming property of Meis1 is modulated by 3 conserved domains, namely the Pbx interaction motif (PIM), the homeodomain, and the C-terminal region recently described to possess transactivating properties. Meis1 and Pbx1 interaction domain-swapping mutants are dysfunctional separately, but restore the full oncogenic activity of Meis1 when cotransduced in primary cells engineered to overexpress Hoxa9, thus implying a modular nature for PIM in Meis1-accelerated transformation. Moreover, we show that the transactivating domain of VP16 can restore, and even enhance, the oncogenic potential of the Meis1 mutant lacking the C-terminal 49 amino acids. In contrast to Meis1, the fusion VP16-Meis1 is spontaneously oncogenic, and all leukemias harbor genetic activation of endogenous Hoxa9 and/or Hoxa7, suggesting that Hoxa gene activation represents a key event required for the oncogenic activity of VP16-Meis1.

A Transition Study to Support Curriculum Reform

This paper presents details of a project to support the transition from school to university for engineering students in the UK. The initial phases have already been disseminated by the project collaborators. The background, rationale, objectives and outcomes of this latter phase of the project are presented and specific data from a web-based transition diagnostic is discussed which verifies specific learning issues amongst engineering students enrolling in their first year of study. This prompted further investigations into these specific learning issues, which produced relevant data pertinent to enhancing learning through curriculum reform with the ultimate goal of accommodating the transition from school to university, improving the learning experience and increasing retention.

Partial Cooperation in Strategic Decision Situations

We consider a normal form game in which there is a single exogenously given coalition of cooperating players that can write a binding agreement on pre-selected actions. These collective actions typically represent a certain number of dimensions in the players’ strategy space. The actions represented by the other dimensions of the strategy space remain under the complete, individual control of the players.
We consider a standard extension of the Nash equilibrium concept denoted as a partial cooperative equilibrium as well as an equilibrium concept in which the coalition of cooperators has a leadership position. Existence results are developed for these new equilibrium concepts. We identify conditions on these partial cooperative games under which the various equilibrium concepts are equivalent.
We apply this game theoretic framework to existing models of multi-market oligopolies and international pollution abatement. In a multi-market oligopoly typically a merger paradox emerges in the partial cooperative equilibrium, which vanishes if the cartel of collaborators exploits its leadership position. Our application to international pollution abatement treaties shows that cooperation by a sufficiently large group of countries results in a Pareto improvement over the standard tragedy of the commons outcome described by the Nash equilibrium.

Civilianizing Civil Conflict: Civilian Defense Militias and the Logic of Violence in Intra-State Conflict

This article examines how civilian defense militias shape violence during civil war. We define civilian defense forces as a sedentary and defensive form of pro-government militia that incumbents often use to harness the participation of civilians during a counterinsurgency campaign. We argue that civilian defense forces reduce the problem of insurgent identification. This leads to a reduction in state violence against civilians. However, we also claim that these actors undermine civilian support for insurgents, which leads to an increase in rebel violence against civilians and overall intensification of conflict. A statistical analysis of government and rebel violence against civilians from 1981 to 2005, and a qualitative assessment of a civilian defense force operating in Iraq from 2005 to 2009, offer strong support for our theoretical claims. These findings provide further insight into pro-government militias and their effects on violence. They also have wider ethical implications for the use of civilian collaborators during civil war.

Enlivening, Invigorating & Enhancing Science:This session explores learning from a range of Primary Science Teaching Trust projects focused on invigorating the experience of children, teachers and whole school communities with primary science.

This session will provide you with opportunity to find out what is being achieved and explore the implications for your own practice.