Recent years have seen the rise of historical trauma as a construct to describe the impact of colonization, cultural suppression, and historical oppression of Indigenous peoples in North America (e.g., Native Americans in the United States, Aboriginal peoples in Canada). The discourses of psychiatry and psychology contribute to the conflation of disparate forms of violence by emphasizing presumptively universal aspects of trauma response. Many proponents of this construct have made explicit analogies to the Holocaust as a way to understand the transgenerational effects of genocide. However, the social, cultural, and psychological contexts of the Holocaust and of post-colonial Indigenous "survivance" differ in many striking ways. Indeed, the comparison suggests that the persistent suffering of Indigenous peoples in the Americas reflects not so much past trauma as ongoing structural violence. The comparative study of genocide and other forms of massive, organized violence can do much to illuminate both common mechanisms and distinctive features, and trace the looping effects from political processes to individual experience and back again. The ethics and pragmatics of individual and collective healing, restitution, resilience, and recovery can be understood in terms of the self-vindicating loops between politics, structural violence, public discourse, and embodied experience.

Key Points Blockmirs are designed against the miR-27 binding site in VE-cadherin and display restricted specificity. Blockmirs regulate VE-cadherin and endothelial cell junctions, inhibit edema, and promote angiogenesis associated with ischemia.

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Fibrosis is characterized by the excessive deposition of extracellular matrix and crosslinked proteins, in particular collagen and elastin, leading to tissue stiffening and disrupted organ function. Lysyl oxidases are key players during this process, as they initiate collagen crosslinking through the oxidation of the ε‐amino group of lysine or hydroxylysine on collagen side‐chains, which subsequently dimerize to form immature, or trimerize to form mature, collagen crosslinks. The role of LOXL2 in fibrosis and cancer is well documented, however the specific enzymatic function of LOXL2 and LOXL3 during disease is less clear. Herein, we describe the development of PXS‐5153A, a novel mechanism based, fast‐acting, dual LOXL2/LOXL3 inhibitor, which was used to interrogate the role of these enzymes in models of collagen crosslinking and fibrosis. PXS‐5153A dose‐dependently reduced LOXL2‐mediated collagen oxidation and collagen crosslinking in vitro. In two liver fibrosis models, carbon tetrachloride or streptozotocin/high fat diet‐induced, PXS‐5153A reduced disease severity and improved liver function by diminishing collagen content and collagen crosslinks. In myocardial infarction, PXS‐5153A improved cardiac output. Taken together these results demonstrate that, due to their crucial role in collagen crosslinking, inhibition of the enzymatic activities of LOXL2/LOXL3 represents an innovative therapeutic approach for the treatment of fibrosis.