No abstract

Primary cilia are hairlike extensions of the plasma membrane of most mammalian cells that serve specialized signaling functions. To traffic properly to cilia, multiple cilia proteins rely on palmitoylation, the post-translational attachment of a saturated 16-carbon lipid. However, details regarding the mechanism of how palmitoylation affects cilia protein localization and function are unknown. Herein, we investigated the protein ADP-ribosylation factor-like GTPase 13b (ARL13b) as a model palmitoylated ciliary protein. Using biochemical, cellular, and studies, we found that ARL13b palmitoylation occurs in mouse kidneys and that it is required for trafficking to and function within cilia. Myristoylation, a 14-carbon lipid, is shown to largely substitute for palmitoylation with regard to cilia localization of ARL13b, but not with regard to its function within cilia. The functional importance of palmitoylation results in part from a dramatic increase in ARL13b stability, which is not observed with myristoylation. Additional results show that blockade of depalmitoylation slows the degradation of ARL13b that occurs during cilia resorption, raising the possibility that the sensitivity of ARL13b stability to palmitoylation may be exploited by the cell to accelerate degradation of ARL13b by depalmitoylating it. Together, the results show that palmitoylation plays a unique and critical role in controlling the localization, stability, abundance, and thus function of ARL13b. Pharmacological manipulation of protein palmitoylation may be a strategy to alter cilia function.

Background: The present study assesses training characteristics, scholastic achievements, and traditional career accomplishments of ethnically underrepresented in medicine (UIM) plastic and reconstructive surgery (PRS) faculty relative to non-UIM PRS faculty. Method: A cross-sectional analysis of core PRS faculty appointed to accredited United States residency training programs (n = 99) was performed. Results: Of the 949 US PRS faculty, a total of 51 (5.4%) were identified as UIM. Compared with non-UIM faculty, there were few differences when evaluating medical education, residency training, pursuit of advanced degrees, and attainment of subspecialty fellowship training. UIM faculty were more likely than non-UIM faculty to have graduated from a medical school outside the United States (25% versus 13%, P = 0.014). In addition, UIM faculty did not differ from non-UIM counterparts in traditional career accomplishments, including promotion to full professor, obtaining NIH funding, serving as program director, receiving an endowed professorship, appointment to a peer-reviewed editorial board, scholarly contributions (H-index and number of publications), and appointment to chief/ chair of their division/department. Conclusions: The historical lack of ethnic diversity that comprise US academic PRS faculty persists. This study reveals that those UIM faculty who are able to obtain faculty appointments are equally successful in achieving scholastic success and traditional career accomplishments as their non-UIM counterparts. As we strive toward increasing representation of UIM physicians in academic plastic surgery, the field will benefit from efforts that promote a pipeline for underrepresented groups who traditionally face barriers to entry.

Central centrifugal cicatricial alopecia (CCCA) is a scarring alopecia that primarily affects women of African descent. Although histopathological features of CCCA have been described, the pathophysiology of this disease remains unclear. To better understand the components of CCCA pathophysiology, we evaluated the composition of the inflammatory infiltrate, the distribution of Langerhans cells (LCs), and the relationship between fibrosis and perifollicular vessel distribution. Our data indicate that CCCA is associated with a CD4-predominant T-cell infiltrate with increased LCs extending into the lower hair follicle. Fibroplasia associated with follicular scarring displaces blood vessels away from the outer root sheath epithelium. These data indicate that CCCA is an inflammatory scarring alopecia with unique pathophysiologic features that differentiate it from other lymphocytic scarring processes.

Background: Successful strategies to improve the representation of female and ethnically underrepresented in medicine (UIM) physicians among US plastic and reconstructive surgery (PRS) faculty have not been adequately explored. Accordingly, we aimed to identify programs that have had success, and in parallel gather PRS program directors’ and chiefs/chairs’ perspectives on diversity recruitment intentionality and strategies. Methods: We conducted a cross-sectional analysis of the demographic composition of female and UIM faculty of PRS residency training programs. Separate lists of programs in the top quartile for female and UIM faculty representation were collated. Additionally, a 14-question survey was administered to program directors and chiefs/chairs of all 99 Accreditation Council for Graduate Medical Education-accredited PRS residency programs. The questions comprised three domains: (1) demographic information; (2) perceptions about diversity; and (3) recruitment strategies utilized to diversify faculty. Results: Female and UIM faculty representation ranged from 0% to 63% and 0% to 50%, respectively. Survey responses were received from program directors and chiefs/chairs of 55 institutions (55% response rate). Twenty-five (43%) respondents felt their program was diverse. Fifty-one (80%) respondents felt diversity was important to the composition of PRS faculty. Active recruitment of diverse faculty and the implementation of a diversity, equity, and inclusion committee were among the most frequently cited strategies to establish a culturally sensitive and inclusive environment. Conclusions: These findings reveal that female and UIM representation among US PRS faculty remains insufficient; however, some programs have had success through deliberate and intentional implementation of diversity, equity, and inclusion strategies.