Bacteria help norovius infect B cells: Stomach ache, nausea, diarrhea—many people know the sort of gastrointestinal havoc norovirus can wreak. Despite this, norovirus biology remains unclear, because human norovirus cannot be grown in culture. Jones et al. now report that with the help of bacteria, human norovirus can infect cultured B cells (see the Perspective by Robinson and Pfeiffer). To infect B cells, human norovirus required the presence of gut bacteria that expressed proteins involved in determining blood type. Mouse norovirus also infected B cells, and the treatment of mice with antibiotics protected them from norovirus infection. Science , this issue p. 755 ; see also p. 700

Significance: Human susceptibility to gout is driven by the fact that we have a pseudogene for uricase that prevents a functional enzyme from being produced. Our inability to convert highly insoluble uric acid into a more soluble molecule makes us vulnerable to disease and other health complications. We have exploited ancestral sequence reconstruction to better understand how and why apes lost this functional enzyme. Our ancient proteins support one hypothesis that the progressive loss of uricase activity allowed our ancestors to readily accumulate fat via the metabolism of fructose from fruits. This adaptation may have provided our ancestors with an advantage when the energy-rich rainforests of Europe and Asia were displaced by temperate forests by the end of the Oligocene.

The gut microbiota is strongly influenced by environmental factors, although host contribution is far less understood. We leveraged macrophage-deficient interferon regulatory factor irf8 zebrafish mutants to investigate the role of macrophages in this process. In conventionally raised adult irf8-deficient mutants, we found a significant loss of intestinal macrophages associated with a strikingly altered gut microbiota when compared to co-housed siblings. The destabilization of the gut commensal microbiota was associated with a severe reduction in complement C1q genes and outgrowth of a rare bacterial species. Consistent with a critical function of irf8 in adult intestinal macrophages, irf8 is abundantly expressed in these cells normally, and restoring macrophage irf8 expression in irf8 mutants was sufficient to recover commensal microbes and C1q genes expression. This study reports an important subpopulation of intestinal macrophages that requires irf8 to establish in the gut, ensure normal colonization of gut microbes, and prevent immune dysregulation.

Background: Resolution of inflammation is an emerging new strategy to reduce damage following ischemic stroke. Lipoxin A₄ (LXA₄) is an anti‐inflammatory, pro‐resolution lipid mediator that reduces neuroinflammation in stroke. Since LXA₄ is rapidly inactivated, potent analogs have been synthesized, including BML‐111. We hypothesized that post‐ischemic, intravenous treatment with BML‐111 for 1 week would provide neuroprotection and reduce neurobehavioral deficits at 4 weeks after ischemic stroke in rats. Additionally, we investigated the potential protective mechanisms of BML‐111 on the post‐stroke molecular and cellular profile.Methods: A total of 133 male Sprague‐Dawley rats were subjected to 90 min of transient middle cerebral artery occlusion (MCAO) and BML‐111 administration was started at the time of reperfusion. Two methods of week‐long BML‐111 intravenous administration were tested: continuous infusion via ALZET^® osmotic pumps (1.25 and 3.75 μg μl⁻¹ hr⁻¹), or freshly prepared daily single injections (0.3, 1, and 3 mg/kg). We report for the first time on the stability of BML‐111 and characterized an optimal dose and a dosing schedule for the administration of BML‐111.Results: One week of BML‐111 intravenous injections did not reduce infarct size or improve behavioral deficits 4 weeks after ischemic stroke. However, post‐ischemic treatment with BML‐111 did elicit early protective effects as demonstrated by a significant reduction in infarct volume and improved sensorimotor function at 1 week after stroke. This protection was associated with reduced pro‐inflammatory cytokine and chemokine levels, decreased M1 CD40+ macrophages, and increased alternatively activated, anti‐inflammatory M2 microglia/macrophage cell populations in the post‐ischemic brain.Conclusion: These data suggest that targeting the endogenous LXA₄ pathway could be a promising therapeutic strategy for the treatment of ischemic stroke. More work is necessary to determine whether a different dosing regimen or more stable LXA₄ analogs could confer long‐term protection.