The mouse major urinary proteins (Mups) are encoded by a large family of highly related genes clustered on chromosome 4. Mups, synthesized primarily and abundantly in the liver and secreted through the kidneys, exhibit male-biased expression. Mups bind a variety of volatile ligands; these ligands, and Mup proteins themselves, influence numerous behavioral traits. Although urinary Mup protein levels vary between inbred mouse strains, this difference is most pronounced in BALB/cJ mice, which have dramatically low urinary Mup levels; this BALB/cJ trait had been mapped to a locus on chromosome 15. We previously identified Zhx2 (zinc fingers and homeoboxes 2) as a regulator of numerous liver-enriched genes. is located on chromosome 15, and a natural hypomorphic mutation in the BALB/cJ allele dramatically reduces Zhx2 expression. Based on these data, we hypothesized that reduced Zhx2 levels are responsible for lower Mup expression in BALB/cJ mice. Using both transgenic and knock-out mice along with assays, our data show that Zhx2 binds Mup promoters and is required for high levels of Mup expression in the adult liver. In contrast to previously identified Zhx2 targets that appear to be repressed by Zhx2, Mup genes are positively regulated by Zhx2. These data identify Zhx2 as a novel regulator of Mup expression and indicate that Zhx2 activates as well as represses expression of target genes.
Analogues of the compound 2,5-di-tert-butylhydroquinone (BHQ) are capable of inhibiting the enzyme sarco/endoplasmic reticulum ATPase (SERCA) in the low micromolar and submicromolar concentration ranges. Not only are SERCA inhibitors valuable research tools, but they also have potential medicinal value as agents against prostate cancer. This study describes the synthesis of thirteen compounds representing several classes of BHQ analogues, such as hydroquinones with a single aromatic substituent, symmetrically and unsymmetrically disubstituted hydroquinones, and hydroquinones with ω-amino acid tethers attached to their hydroxyl groups. Structure-activity relationships were established by measuring the inhibitory potencies of all synthesized compounds in bioassays. The assays were complemented by computational ligand docking for an analysis of the relevant ligand/receptor interactions.
Background: Hobbies may be used on the residency application to communicate similarity to other members of their desired specialty or uniqueness. Objectives: This study aimed to determine the most common hobbies among emergency medicine (EM) applicants and whether they differ from the reported hobbies of other applicants. Methods: This was a two-center retrospective application review study at large U.S. midwestern academic institutions with a 3- and a 4-year EM residency program. Data from the “hobbies and interests” field of the Electronic Residency Application Service (ERAS) application from 2015 - 2019 were reviewed. Hobbies data were individually coded by two independent physician coders into 19 defined hobby types. EM applicants were compared to plastic surgery and psychiatry applicants. Results: A total of 2675 individual hobbies were initially identified, with strong agreement between raters (κ = 0.92). The most commonly listed EM hobbies were sports (25.0%), outdoor (19.3%), and fitness (9.6%). Sports and outdoor hobbies were also listed most frequently by applicants to psychiatry and plastic surgery. While there were several significant differences between EM and other specialties, these differences were minimal overall. Conclusions: Active hobbies appeared most prominently for all applicants. Less stereotypical EM hobbies, including literary arts and cooking, were also frequently noted, suggesting that applicants may have motivations beyond communicating similarity when listing hobbies.
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