Systematic and quantitative analysis of protein phosphorylation is revealing dynamic regulatory networks underlying cellular responses to environmental cues. However, matching these sites to the kinases that phosphorylate them and the phosphorylation-dependent binding domains that may subsequently bind to them remains a challenge. NetPhorest is an atlas of consensus sequence motifs that covers 179 kinases and 104 phosphorylation-dependent binding domains [Src homology 2 (SH2), phosphotyrosine binding (PTB), BRCA1 C-terminal (BRCT), WW, and 14–3–3]. The atlas reveals new aspects of signaling systems, including the observation that tyrosine kinases mutated in cancer have lower specificity than their non-oncogenic relatives. The resource is maintained by an automated pipe line, which uses phylogenetic trees to structure the currently available in vivo and in vitro data to derive probabilistic sequence models of linear motifs. The atlas is available as a community resource (http://netphorest.info).

New therapies that target chronic inflammation with fibrosis are urgently required. Increasing evidence points to innate activation of inflammatory cells in driving chronic organ fibrosis. Serum amyloid P is a naturally circulating soluble pattern recognition receptor, a member of the family of pentraxin proteins. It links danger-associated molecular pattern recognition to Fcγ receptor-mediated phagocytosis. Here we show that fibrosis progression in the mouse kidney is significantly inhibited by therapeutic administration of human serum amyloid P, regulated by activating Fcγ receptors, and dependent on inflammatory monocytes and macrophages, but not fibrocytes. Human serum amyloid P-mediated inhibition of mouse kidney fibrosis correlated with specific binding of human serum amyloid P to cell debris and with subsequent suppression of inflammatory monocytes and kidney macrophages in vitro and in vivo, and was dependent on regulated binding to activating Fcγ receptors and interleukin-10 expression. These studies uncover previously unidentified roles for Fcγ receptors in sterile inflammation and highlight serum amyloid P as a potential antifibrotic therapy through local generation of interleukin-10.

The IPEMs found on all otolaryngology association websites exceed the recommended fourth- to sixth-grade reading level.

SARS-CoV-2, and its clinical manifestation as COVID-19, is an ongoing global pandemic. Patients with COVID-19 can present with numerous otolaryngologic conditions, such as Bell palsy (BP). Bell palsy is a unilateral peripheral facial nerve palsy of sudden onset. Several case reports and series have described peripheral facial nerve palsies associated with COVID-19. 1 In addition, since the US Food and Drug Administration's (FDA) emergency use authorization of several COVID-19 vaccines, there have been media reports of BP associated with vaccination. 2 Such concerns could erode vaccine confidence and exacerbate public hesitancy to obtain a COVID-19 vaccine. We used data from a large health research network to estimate the incidence of BP in patients with COVID-19 vs individuals vaccinated against the disease.Methods | The institutional review board at Case Western Reserve University deemed this cohort study exempt from review and waived the requirement for patient informed consent because deidentified information, aggregated counts, and statistical summaries of electronic medical records were used. These data were collected from 41 health care organizations worldwide and accessed through TriNetX, a global federated research network. Queries were made on April 7, 2021, to identify patients diagnosed with COVID-19 (January 1, 2020, to December 31, 2020) with or without a diagnosis code of BP within 8 weeks of the COVID-19 diagnosis. Among these patients, we identified those with a history of BP. To account for vaccination, the queries were restricted from January 1, 2021, to March 31, 2021. Using TriNetX to evaluate BP as our outcome, we matched 63 551 non-vaccinated patients with COVID-19 to those who were vaccinated against the disease and had no history of COVID-19 infection.