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Cells and organisms adapt to mitochondrial dysfunction by activating the mitochondrial unfolded protein response (UPRmt), which is regulated by mitochondrial-to-nuclear communication; and UPRmt activation can also be transmitted between different cell types suggesting a role in tissue coordination. Shao and colleagues now identify a neuronal circuit and a secreted neuropeptide required for cell non-autonomous UPRmt regulation.
Studying the immune response against infection with hepatitis viruses is hampered by the lack of suitable preclinical model systems. A recent publication in Science identifies the cytosolic adapter molecule MAVS as being responsible for species restriction of infection with hepatitis A virus as well as linking cytosolic immune sensing in infected hepatocytes with innate effector functions and protective adaptive immunity.
A recent paper published in Nature reports that the immunosuppressive activity of tumor-associated macrophages is regulated via PI3Kγ signaling. Small-molecule inhibitors targeting PI3Kγ stimulate T cell activity against tumor alone and add additional effects for clinically proven PD1 immunotherapy.
Despite major advances in understanding the genetics and epigenetics of acute myelogenous leukemia, there is still a great need to develop more specific and effective therapies. High throughput approaches involving either genetic approaches or small molecule inhibitor screens are beginning to identify promising new therapeutic targets.
Recent evidence indicates that codon optimality is a broad determinant of mRNA stability. A study by Radhakrishnan et al. in Cell raises the possibility that the conserved DEAD-box protein Dhh1 underlies the phenomenon.
A near-atomic resolution structure of a mammalian voltage-gated calcium channel (Cav) has been determined. This first fully-assembled Cav structure illuminates mechanisms of Cav properties and functions and ushers in a new era in Cav research and beyond.