SHP2 promotes sarcoidosis severity by inhibiting SKP2-targeted ubiquitination of TBET in CD8 T cells.

Sarcoidosis is an interstitial lung disease (ILD) characterized by interferon-γ (IFN-γ) and T-box expressed in T cells (TBET) dysregulation. Although one-third of patients progress from granulomatous inflammation to severe lung damage, the molecular mechanisms underlying this process remain unclear. Here, we found that pharmacological inhibition of phosphorylated SH2-containing protein tyrosine phosphatase-2 (pSHP2), a facilitator of aberrant IFN-γ abundance, decreased large granuloma formation and macrophage infiltration in the lungs of mice with sarcoidosis-like disease.

The Role of Bronchoalveolar Lavage in the Diagnosis of COVID-19 Pneumonia: A Report of Three Cases.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) initially infects and replicates in epithelial cells of the nasopharynx where there are relatively high levels of angiotensin-converting enzyme 2 receptor, which correlates with the highest sensitivity time point of the nasopharyngeal swab (NPS) real-time polymerase chain reaction (RT-PCR) during the first week, with subsequent decline thereafter. As viral shedding progresses throughout the respiratory tract, the virus can be detectable for up to 30 days in bronchoalveolar fluids. This report presents three cases of acute respiratory distress in the setting of multifocal pneumonia, with multiple false-negative NPS SARS-CoV-2/RT-PCR but positive SARS-CoV-2/RT-PCR in bronchoalveolar lavage (BAL) samples.

Intrinsic Dynamics of the ClpXP Proteolytic Machine Using Elastic Network Models.

ClpXP complex is an ATP-dependent mitochondrial matrix protease that binds, unfolds, translocates, and subsequently degrades specific protein substrates. Its mechanisms of operation are still being debated, and several have been proposed, including the sequential translocation of two residues (SC/2R), six residues (SC/6R), and even long-pass probabilistic models. Therefore, it has been suggested to employ biophysical-computational approaches that can determine the kinetics and thermodynamics of the translocation.