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In multiple sclerosis and experimental autoimmune encephalomyelitis, astrocytes produce lactosylceramide, a glycolipid that promotes astrocyte and microglial activation and immune cell infiltration into the CNS.
An in vivo RNAi dropout screen identifies Mapk14 as a new mediator of sorafenib resistance in hepatocellular carcinoma, and Mapk14 inhibition both improves sorafenib therapy and restores sensitivity to sorafenib-resistant tumors.
Activation of the insulin-like growth factor 1 receptor may underlie clinical resistance to inhibition of the anaplastic lymphoma receptor kinase in lung cancer.
Deficiency in Gnas, encoding the Gs protein α subunit, is sufficient to induce medulloblastoma in mice due to derepression of the Sonic hedgehog pathway.
A novel internal ribosomal entry site in the 5' end of the dystrophin gene allows for expression of a form of the protein that could be therapeutic for certain forms of Duchenne muscular dystrophy.
Manipulation of acetate levels in mice can affect the activity of the hypoxia-responsive transcription factor HIF-2α and facilitate recovery from anemia.
Stanley Lemon and colleagues show that the HCV replicase is sensitive to lipid peroxidation, which may restrict viral replication in vitro and in vivo.
Notch signaling is shown to regulate the browning of adipocytes and whole-body energy expenditure, with inhibition leading to protection from diet-induced obesity in mice.
In Alzheimer's disease, increased MAOB activity in reactive astrocytes leads to enhanced GABA release, and blockage of this pathway ameliorates memory dysfunction in mouse models.
Mounia Tannour-Louet and her colleagues show that 1–3% of cases of male genitourinary tract malformations are associated with increased copy number variations of the VAMP7 gene, which encodes a SNARE protein involved in vesicular transport. They show that overexpression of human VAMP7 in mice is sufficient to replicate the condition in this species and that the phenotype is due to alterations in the balance between androgen and estrogen signaling.
Neisseria meningitidis is the causative agent of potentially fatal meningitis and septic shock, induced by bacterial colonization of blood vessels in the brain and the periphery. The endothelial cell receptor mediating meningococcal adhesion to blood vessels has previously been unknown. Here Sandrine Bourdoulous and colleagues report that CD147 expressed on human endothelial cells is a crucial mediator of N. meningitidis vascular colonization, providing new insight into some of the mechanisms that give rise to meningococcal disease.
Circulating tumor cells from patients with small-cell lung cancer can form tumors in mice, and their derived explants recapitulate the patients' response to chemotherapy.