Signaling diversity and subsequent complexity in higher eukaryotes is partially explained by one gene encoding a polypeptide with multiple biochemical functions in different cellular contexts. For example, mouse double minute 2 (MDM2) is functionally characterized as both an oncogene and tumor suppressor, yet this dual classification confounds the cell biology and clinical literatures. Identified via complementary biochemical, organellar, and cellular approaches, we report that MDM2 negatively regulates NADH:ubiquinone oxidoreductase 75 kDa Fe-S protein 1 (NDUFS1), leading to decreased mitochondrial respiration, marked oxidative stress, and commitment to the mitochondrial pathway of apoptosis. MDM2 directly binds and sequesters NDUFS1 preventing its mitochondrial localization, ultimately causing Complex I and supercomplex destabilization, and inefficiency of oxidative phosphorylation. The amino terminal region of MDM2 is sufficient to bind NDUFS1, alter supercomplex assembly, and induce apoptosis. Finally, this pathway is independent of p53, and several mitochondrial phenotypes are observed in Drosophila and murine models expressing transgenic Mdm2.
The COVID‐19 mRNA vaccines not only provide remarkable protection but also have been characterized by an overall safe and well‐tolerated side effect profile. Herein, we discuss a rare but manageable cutaneous reaction to COVID vaccination in order to further characterize dermatologic reactions and stress the continued vaccination of eligible patients.
Prior to transplantation, the transplant team is responsible for transplant education and posttransplant expectations. The majority of outcomes research focuses on 1-and 3-year graft survival, with a lack of literature focused upon whether patients have a realistic understanding of how many years deceased donor kidneys can be expected to function after transplant. Objective: To determine whether potential kidney transplant patients' expectations for how long a deceased donor kidney will function after transplantation differs from transplant surgeons, using quantitative analysis. Design: A cross-sectional survey was used with potential adult kidney transplant recipients and transplant surgeons. Patient surveys included demographics, quality-oflife questions, and questions of expectations of kidney function for deceased donor kidneys from the Kidney Donor Profile Index. The survey categorized donor organ risk as 0% to 20%, 21% to 85%, and 86% to 100%, and results were compared to responses from US Transplant Surgeons. Surgeons were contacted via e-mail using an online survey program. Results: Responses included 154 transplant surgeons and 172 patients. Surgeon and patient responses were compared using Fisher exact test, showing a significant difference in each of the donor organ categories. We found that 47% of patient respondents did not correctly interpret the Kidney Donor Profile Index continuum. Conclusion: In every organ donor category, patients had a significantly different expectation for how long a transplanted kidney will last after transplant when compared to transplant surgeons. More study is required to determine why 47% of patients did not correctly interpret the Kidney Donor Profile continuum.
Obesity is currently considered a low-grade chronic inflammatory condition that has well-documented associations with heart disease, hypertension, diabetes mellitus, and metabolic syndrome. In addition to these conditions, there is growing evidence that the inflammatory cytokines produced in obesity may play contributory roles in other inflammatory phenomena. Notably, numerous studies over the last several decades have shed light on the genetic, mechanistic, and epidemiologic links between obesity and psoriasis, with implications for the treatment of these patients. This article reviews the current literature regarding the relationship of obesity and psoriasis, with exploration of their common mechanistic etiology and the necessary considerations in the management, both pharmacological and otherwise, of this patient population.
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