SALSA: a novel flow cytometry assay to detect ascorbate at the single-cell level.

Ascorbate (AA) is an essential antioxidant and enzymatic cofactor with emerging roles in epigenetic regulation, redox biology, and immune function. However, single-cell quantification of intracellular AA has remained technically challenging. Here, we present SALSA (Single-cell Ascorbate Level Sensing Assay), a novel flow cytometry-based method that enables sensitive, specific detection of intracellular AA at the single-cell level.

Hypoxia and IL-15 Cooperate to Induce Perforin Expression by CD8 T Cells and Promote Damage to the Skin in Murine Cutaneous Leishmaniasis.

Cutaneous leishmaniasis is a disease caused by protozoan parasites of the genus Leishmania, and although parasites influence disease severity, cytotoxic CD8 T-cell responses mediate damage to the infected skin. We found that the cytotoxic protein perforin was expressed in CD8 T cells only upon recruitment to Leishmania-infected skin, suggesting that lesional inflammatory cues induced perforin. In this study, using a mouse model of Leishmania major infection, we demonstrated that the expression of perforin was driven by a combination of hypoxia and IL-15, both of which are microenvironmental signals present within Leishmania-infected skin.

How to Advise Medical Students Interested in Dermatology: A Survey of Academic Dermatology Mentors.

Dermatology residency programs are among the most competitive residencies of medical specialties. To navigate this competitive process, students seek advice from dermatology mentors who provide a range of responses depending on their experience or preferences. To consolidate this range of advice, we surveyed members of the Association of Professors of Dermatology (APD) on their responses to common questions from medical students regarding quantity of program applications, research gap year, internship year, letters of intent, away rotations, letters of recommendation (LORs), and the new Electronic Residency Application Service (ERAS) supplemental application.

Re-examination of MAGE-A3 as a T-cell Therapeutic Target.

In 2013, an innovative MAGE-A3-directed cancer therapeutic of great potential value was terminated in the clinic because of neurotoxicity. The safety problems were hypothesized to originate from off-target T-cell receptor activity against a closely related MAGE-A12 peptide. A combination of published and new data led us to test this hypothesis with current technology.

Free-Floating Bikeshare and Helmet Use in Seattle, WA.

Wearing a helmet when bicycling prevents traumatic brain injury in the event of a crash. Most cyclists nationwide use helmets when riding. However, the growth of free-floating bike sharing systems, which offer short-term access to bicycles but not helmets, may erode helmet-wearing norms among cyclists.

Autoimmune Th2-mediated dacryoadenitis in MRL/MpJ mice becomes Th1-mediated in IL-4 deficient MRL/MpJ mice.

Purpose: MRL/MpJ mice of substrains MRL/MpJ-fas(+)/fas(+) (MRL/+) and MRL/MpJ-fas(lpr)/fas(lpr) (MRL/lpr) spontaneously develop autoimmune dacryoadenitis and sialadenitis and are a model for the human disorder Sjögren syndrome. The dacryoadenitis in both substrains appears to be Th2 in nature, with little IFN-gamma and substantial IL-4 at the site of lacrimal gland inflammation.

Methods: MRL/MpJ mice with a defective IL-4 gene-both MRL/+-IL-4(tm)/IL-4(tm) (MRL/+/IL-4(tm)) and MRL/lpr-IL-4(tm)/IL-4(tm) (MRL/lpr-IL-4(tm))-that resulted in a loss of IL-4 production were bred and evaluated for dacryoadenitis.

Inflammatory mediators in autoimmune lacrimal gland disease in MRL/Mpj mice.

Purpose: MRL/MpJ-fas(+)/fas(+) (MRL/+) and MRL/MpJ-fas(lpr)/fas(lpr) (MRL/lpr) mice are congenic substrains of mice that have spontaneously developing lacrimal and salivary gland inflammation and are models for the human disorder Sjögren's syndrome. Nitric oxide (NO) and tumor necrosis factor (TNF)-alpha are proinflammatory and potential mediators of tissue damage. The presence of the inducible form of nitric oxide synthase (iNOS), which catalyzes the production of NO, and the presence TNF-alpha in the lacrimal glands of MRL/MpJ mice were assessed.

Chemokines in autoimmune lacrimal gland disease in MRL/MpJ mice.

Purpose: MRL/MpJ-fas+/fas+ (MRL/+) and MRL/MpJ-fas(lpr)/fas(lpr) (MRL/lpr) mice undergo spontaneous development of inflammation of the lacrimal and salivary glands, similar to that in the human disorder Sjögren's syndrome. Previous work has shown that these lesions appear to be largely T helper (Th)-2-driven, as evidenced by the substantially greater expression of IL-4 than interferon-gamma. The relative contributions of selected chemokines associated with Th1 and Th2 immune responses were assessed.