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The authors uncover a role for the proteostasis modulator AIRAPL as a tumor suppressor in myeloproliferative malignancies, through its regulation of IGFR stability. The results ascribe a biological function to AIRAPL, and they implicate prosteostatic deregulation as an oncogenic mechanism in myeloid transformation, thus suggesting potential novel therapeutic strategies.
A small-molecule inducer of apoptosis is able to kill senescent cells in the bone marrow of irradiated or aged mice, thereby improving hematopoietic stem cell function.
The details of the GIP signaling pathway are murky, but new data identify a downstream pathway involving Tcf7 that regulates beta cell survival and activity.
Ralph Baric, Vineet Menachery and colleagues characterize a SARS-like coronavirus circulating in Chinese horseshoe bats to determine its potential to infect primary human airway epithelial cells, cause disease in mice and respond to available therapeutics.
The authors identify EZH2 as a general underlying dependency of tumors with mutations in the SWI/SNF chromatin regulator complex, and they show that EZH2's pro-tumorigenic role may be dependent on non-catalytic activities. This may pose new opportunities and challenges for using EZH2 as a cancer therapy target.
Kenzo Tokunaga and colleagues report that MARCH8 inhibits the incorporation of the HIV-1 envelope glycoprotein into virus particles, thereby reducing viral infectivity.
Toll-like receptor 5 (TLR5) expression is found to be enriched in mouse dorsal root ganglion (DRG) A-fiber neurons known to mediate mechanical allodynia, a form of chronic neuropathic pain. Selective silencing of both mouse and human DRG A-fiber neurons is achieved by co-application of the TLR5 ligand flagellin and the lidocaine derivative QX-314, which is also sufficient to reverse mechanical allodynia in three different mouse models of chronic neuropathic pain.
Blocking alternative activation of p38 in tumor-infiltrating CD4+ T cells reduces proinflammatory cytokine production and inhibits pancreatic cancer growth in mice.
Penny Moore and colleagues identify viral variants from an HIV-1 infected individual that drove maturation of the antibody response from an unmutated common ancestor, ultimately resulting in both broadly neutralizing and strain-specific antibody sublineages.
MALDI mass spectrometry shows distinct patterns of drug distribution in tuberculosis lesions in human lungs that provide insight into treatment efficacy.
Barney Graham and colleagues have developed a hemagglutinin stem–based nanoparticle as a vaccine that confers protection against different influenza strains in mice and ferrets.
The cytokine TNF-α, typically considered to have deleterious effects on the heart, can also have cardioprotective effects by inducing formation of a keratin cytoskeletal network in cardiomyocytes.
The intracellular domain of amyloid precursor protein (AICD), generated during the processing of APP along the amyloidogenic pathway, is shown to repress transcription of the Wasf1 gene, encoding the WAVE1 protein. The reduction in WAVE1 levels inhibits cell surface trafficking of APP, thereby creating a homeostatic negative feedback circuit to limit further production of amyloid-β.
PCSK6 is identified as the protease that cleaves and activates the zymogen form of corin, a protease that in turn activates the natriuretic peptides that control salt balance and blood pressure.