Variety in the USP deubiquitinase catalytic mechanism.

The ubiquitin-specific protease (USP) family of deubiquitinases (DUBs) controls cellular ubiquitin-dependent signaling events. This generates therapeutic potential, with active-site inhibitors in preclinical and clinical studies. Understanding of the USP active site is primarily guided by USP7 data, where the catalytic triad consists of cysteine, histidine, and a third residue (third critical residue), which polarizes the histidine through a hydrogen bond. A conserved aspartate (fourth critical residue) is directly adjacent to this third critical residue. Although both critical residues accommodate catalysis in USP2, these residues have not been comprehensively investigated in other USPs. Here, we quantitatively investigate their roles in five USPs. Although USP7 relies on the third critical residue for catalysis, this residue is dispensable in USP1, USP15, USP40, and USP48, where the fourth critical residue is vital instead. Furthermore, these residues vary in importance for nucleophilic attack. The diverging catalytic mechanisms of USP1 and USP7 are independent of substrate and retained in cells for USP1. This unexpected variety of catalytic mechanisms in this well-conserved protein family may generate opportunities for selective targeting of individual USPs.

Who Called Team Europe? The European Union's Development Policy Response During the First Wave of COVID-19.

The COVID-19 pandemic is a critical juncture for global development. Under the label of "Team Europe", the EU has sought to mobilize rapid development assistance to support partners in addressing the impacts of the crisis, while promoting joined-up approaches among European actors to assert itself in a changing and competitive geopolitical context. This article assesses how substantive and process-oriented EU development policy norms are reflected in the Union's global COVID-19 response. Focusing on the EU's response during the first wave of the COVID-19 pandemic in the first half of 2020, the article shows that the EU's response to this extraordinary crisis consisted of a deepening of EU integration. In so doing, the EU emphasized process-oriented over substantive norms in its development policy.

La pandémie de COVID-19 représente un moment de transition critique pour le développement international. En utilisant l'étiquette « Équipe Europe ¼, l'UE a cherché à mobiliser une aide au développement rapide pour aider ses partenaires à faire face aux impacts de la crise, tout en favorisant des approches conjointes entre les acteurs européens pour s'affirmer dans un contexte géopolitique changeant et concurrentiel. Cet article évalue la façon dont les normes de la politique de développement de l'UE, qui portent sur le fond et sont axées sur les processus, se reflètent dans la riposte de l'Union à la COVID-19 à l'échelle mondiale. En se concentrant sur la réponse de l'UE lors de la première vague de pandémie de COVID-19 durant le premier semestre 2020, l'article démontre que la riposte de l'UE à cette crise sans précédent a consisté en un renforcement de l'intégration européenne. Ce faisant, dans sa politique de développement, l'UE a mis l'accent sur les normes axées sur les processus plutôt que sur les normes qui portent sur le fond.

When 'unintended effects' reveal hidden intentions: Implications of 'mutual benefit' discourses for evaluating development cooperation.

This article's starting point is that the dichotomy between intended and unintended effects is linked to official policy discourse on the overall purpose and objectives of development cooperation. It describes and discusses recent policy trends that move away from emphasizing developing country benefits toward the pursuit of 'mutual benefit' as the key motivating factor and aim for development cooperation as an area of public policy. A mix of motivations has always driven development cooperation, yet the current policy trend differs in that such motivations are made explicit. As a consequence, recent policies suggest that these different interests represent 'win-wins' rather than trade-offs and conceptualize a common development agenda for the donor and recipient countries. Given that political discourse promotes and prepares legal and accountability systems, public scrutiny and independent evaluation are a few steps behind and largely restricted to analyzing benefits for developing countries. The article argues that articulating all goals of development cooperation can facilitate evaluation practice in this changed setting, as effects considered to be 'unintended' from the perspective of promoting development goals may, in fact, be intentional or anticipated from a mutual benefit perspective.