The measurement of regional rates of cerebral protein synthesis in vivo

Special issue dedicated to Dr. Louis Sokoloff.     

Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions

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Inflammation-associated S100 proteins: new mechanisms that regulate function

This review focuses on new aspects of extracellular roles of the calgranulins. S100A8, S100A9 and S100A12 are constitutively expressed in neutrophils and induced in several cell types. The S100A8 and S100A9 genes are regulated by pro- and anti-inflammatory mediators and their functions may depend on cell type, mediators within a particular inflammatory milieu, receptors involved in their recognition and their post-translational modification. The S100A8 gene induction in macrophages is dependent on IL-10 and potentiated by immunosuppressive agents. S100A8 and S100A9 are oxidized by peroxide, hypochlorite and nitric oxide (NO). HOCl generates intra-chain sulfinamide bonds; stronger oxidation promotes cross-linked forms that are seen in human atheroma. S100A8 is >200-fold more sensitive to oxidative cross-linking than low-density lipoprotein and may reduce oxidative damage. S100A8 and S100A9 can be S-nitrosylated. S100A8–SNO suppresses mast cell activation and inflammation in the microcirculation and may act as an NO transporter to regulate vessel tone in inflammatory lesions. S100A12 activates mast cells and is a monocyte and mast cell chemoattractant; a G-protein-coupled mechanism may be involved. Structure–function studies are discussed in relation to conservation and divergence of functions in S100A8. S100A12 induces cytokines in mast cells, but not monocytes/macrophages. It forms complexes with Zn²⁺ and, by chelating Zn²⁺, S100A12 significantly inhibits MMPs. Zn²⁺ in S100A12 complexes co-localize with MMP-9 in foam cells in atheroma. In summary, S100A12 has pro-inflammatory properties that are likely to be stable in an oxidative environment, because it lacks Cys and Met residues. Conversely, S100A8 and S100A9 oxidation and S-nitrosylation may have important protective mechanisms in inflammation.     

Final Remarks

The author replies to the comments of Drs Blanchard and McGrady, urging that researchers reinvigorate their research efforts in complementary and alternative treatments for hypertension. In subsequent research there is a need to assess treatment adherence, to use more rigorous outcome measures, and to develop new outcome measures that assess impact and improvement in quality of life.     

Inferring patterns of aggression from red howler monkey injuries

Venezuelan red howler monkeys in a semideciduous habitat typically survive injuries and disabilities. Intraspecific physical aggression was the most frequently observed and inferred cause of injury. Thirty-eight percent of 119 howlers of all ages examined during capture had scars or other evidence of “damage.” Overall, the sexes did not differ significantly in total number of injuries or number of individuals classified as “damaged.” The incidence of injury was not independent of age-sex class. The subadult male class had the highest percentage of “damaged” individuals. However, when total injuries per age class were examined for each sex separately, only females showed a pattern that was significantly different than expected based on age (i.e., exposure to injury factors). Subadult females experienced more injuries than expected, whereas adult females had fewer injuries. Troop status (resident troop, natal troop, or extratroop) was not significantly related to the number of injuries in adult and subadult males. Thin finding was not surprising, because adult and subadult males of all status classes are involved in aggression related to breeding competition. Extratroop females had more injuries than expected, and natal females had the fewest injuries. The higher incidence of injuries on subadult females and extratroop females is consistent with aggression-mediated emigration of some females and observed resistance to female immigration by resident females. Overall, 74% of injuries were located on anterior-ventral portions of the body, consistent with the face-to-face fighting observed in howlers. Sociobiological costs of aggression in red howlers are difficult to assess because many howlers, despite frequent and severe injury, subsequently survive and reproduce. We recommend caution in inferring mortality from injuries, especially when social mobility and emigration out of the study area are common.