DNp63 Regulates Homeostasis, Stemness, and Suppression of Inflammation in the Adult Epidermis
The Journal of Investigative Dermatology (JID)
Abstract
The p63 transcription factor is critical for epidermis formation in embryonic development, but its role in the adult epidermis is poorly understood. In this study, we show that acute genetic ablation of ΔNp63, the main p63 isoform, in adult epidermis disrupts keratinocyte proliferation and self-maintenance and, unexpectedly, triggers an inflammatory psoriasis-like condition. Mechanistically, single-cell RNA sequencing revealed the downregulation of cell cycle genes, upregulation of differentiation markers, and induction of several proinflammatory pathways in ΔNp63-ablated keratinocytes. Intriguingly, ΔNp63-ablated cells disappear by 3 weeks after ablation, at the expense of the remaining nonablated cells. This is not associated with active cell death and is likely due to reduced self-maintenance and enhanced differentiation. Indeed, in vivo wound healing, a physiological readout of the epidermal stem cell function, is severely impaired upon ΔNp63 ablation. We found that the Wnt signaling pathway (Wnt10A, Fzd6, Fzd10) and the activator protein 1 (JunB, Fos, FosB) factors are the likely ΔNp63 effectors responsible for keratinocyte proliferation/stemness and suppression of differentiation, respectively, whereas IL-1a, IL-18, IL-24, and IL-36γ are the likely negative effectors responsible for suppression of inflammation. These data establish ΔNp63 as a critical node that coordinates epidermal homeostasis, stemness, and suppression of inflammation, upstream of known regulatory pathways.
Download PDF
July 2023
Six-Year Study of Emails Sent to Unverified Addresses
The IFIP International Symposium on Human Aspects of Information Security & Assurance (HAISA 2023)
Abstract
In addition to a username and password, more and more websites are requiring an email address during account creation. But often, users are granted full access before email verification, allowing them to create accounts using others’ email addresses. As a result, emails sent to such users will instead end up in the true owners’ inboxes. These emails can contain private data ranging from personally identifiable information to banking details and social security numbers. Additionally, the true owner can reset the password and access the account directly. But regardless of potential malicious action, both the user and the true owner face negative consequences.
In this paper, we enumerate the prevalence of this shortcoming by manually analyzing account accessibility before email verification on leading United States websites—72% of them failed to restrict potentially harmful actions. Then, we used our rare opportunity to use a short, dictionaryword Gmail address to analyze unverified emails over the course of six years. We categorize the exposed private data and reveal user risks. We aim to bring attention to the dangers of this security flaw and call for the development of new privacy policies.
Download PDF
June 2023