The apical anion exchanger Slc26a6 promotes oxalate secretion by murine submandibular gland acinar cells.

The solute carrier family 26 (SLC26) gene family encodes at least 10 different anion exchangers. SLC26 member 6 (SLC26A6 or CFEX/PAT-1) and the cystic fibrosis transmembrane conductance regulator (CFTR) co-localize to the apical membrane of pancreatic duct cells, where they act in concert to drive HCO3- and fluid secretion. In contrast, in the small intestine, SLC26A6 serves as the major pathway for oxalate secretion. However, little is known about the function of Slc26a6 in murine salivary glands. Here, RNA sequencing-based transcriptional profiling and Western blots revealed that Slc26a6 is highly expressed in mouse submandibular and sublingual salivary glands. Slc26a6 localized to the apical membrane of salivary gland acinar cells with no detectable immunostaining in the ducts. CHO-K1 cells transfected with mouse Slc26a6 exchanged Cl- for oxalate and HCO3-, whereas two other anion exchangers known to be expressed in salivary gland acinar cells, Slc4a4 and Slc4a9, mediated little, if any, Cl-/oxalate exchange. Of note, both Cl-/oxalate exchange and Cl-/HCO3- exchange were significantly reduced in acinar cells isolated from the submandibular glands of Slc26a6-/- mice. Oxalate secretion in submandibular saliva also decreased significantly in Slc26a6-/- mice, but HCO3- secretion was unaffected. Taken together, our findings indicate that Slc26a6 is located at the apical membrane of salivary gland acinar cells, where it mediates Cl-/oxalate exchange and plays a critical role in the secretion of oxalate into saliva.

Autoantibodies against the Immunoglobulin-Binding Region of Ro52 Link its Autoantigenicity with Pathogen Neutralization.

Ro52/TRIM21 plays a key role in antibody-dependent pathogen neutralization and is a major autoantigen in systemic lupus erythematosus, Sjögren's syndrome (SS), and other autoimmune diseases. Here we evaluated immunoreactivity against Ro52-related molecules in SS and healthy volunteers. Although most proteins examined were not antigenic, several TRIM paralogs, including TRIM22, and TRIM38, showed sporadic immunoreactivity in SS. In contrast, the murine Ro52 ortholog with limited linear homology demonstrated high levels of autoantibodies implicating the importance of shared conformational epitopes. To further explore the autoantigencity of Ro52, deletion and point mutant analyses were employed revealing previously hidden, robust autoantibodies directed against its C-terminal immunoglobulin-binding domain. Another autoantibody, rheumatoid factor, targeting the Fc region of IgG, strongly overlapped with Ro52 seropositivity (odds ratio 14; P < 0.0001). These convergent mechanistic findings support a model whereby intracellular Ro52-bound antibody-coated pathogen complexes, released or misprocessed from infected cells, drive autoantigenicity against Ro52 and the Fc region of IgG.

Reinterpreting features of the advertisement call of Dermatonotus muelleri (Boettger, 1885; Anura, Microhylidae).

The advertisement call of Dermatonotus muelleri was originally described by Nelson (1973) in a brief section of a review on the mating calls of the Microhylinae. He used two calls from São Leopoldo, state of Minas Gerais, in Brazil to determine that they have i) dominant frequency between 1.500-2.200 kHz (mean 1.854 + 0.216 kHz), and ii) harmonic intervals between 0.140 and 0.150 kHz (0.146 +/- 0.005 kHz). Nelson (1973) based his description on an audiospectrogram produced with high frequency resolution and did not quantify the pulse structure of the calls. More recently, Giaretta and colleagues (2013) expanded on the original description using a larger set of calls recorded from Gurinhat, state of Minas Gerais, in Brazil. They quantified the temporal structure of the call and confirmed that the dominant frequency is around 1.8 kHz. In addition, they identified a secondary low frequency band at 667 Hz.