Cutting Edge: Differential inhibition of TLR signaling pathways by cell-permeable peptides representing BB loops of TLRs

We designed cell-penetrating peptides comprised of the translocating segment of Drosophila antennapedia homeodomain fused with BB loop sequences of TLR2, TLR4, and TLR1/6. TLR2- and TLR4-BB peptides (BBPs) inhibited NF-kappaB translocation and early IL-1beta mRNA expression induced by LPS, and the lipopeptides S-[2,3-bis(palmitoyloxy)-(2-RS)-propyl]-N-palmitoyl-(R)-Cys-Ser-Lys(4)-OH (P3C) and S-[2,3-bis(palmitoyloxy)-(2-RS)-propyl]-Cys-Ser-Lys(4)-OH (P2C). TLR4- and TLR2-BBPs also strongly inhibited LPS-induced activation of ERK. Only TLR2-BBP significantly inhibited ERK activation induced by P3C, which acts via TLR2/1 heterodimers. BBPs did not inhibit activation of ERK induced by P2C, a TLR2/6 agonist. The TLR2-BBP induced weak activation of p38, but not ERK or cytokine mRNA. The TLR1/6-BBP failed to inhibit NF-kappaB or MAPK activation induced by any agonist. Our results suggest that the receptor BBPs selectively affect different TLR signaling pathways, and that the BB loops of TLR1/6 and TLR2 play distinct roles in formation of receptor heterodimers and recruitment of adaptor proteins.     

Characteristics of papers that affect citations in the Journal of Fish Biology

Identifying the factors that influence the citation of articles helps authors improve the impact and reach of their research. Analysis of publications in the Journal of Fish Biology between 2008 and 2021 revealed that variables such as the number of keywords, abstract length, number of authors, and page length were associated with higher impact papers. These trends applied to both review and regular papers. These findings suggest that papers that are more informative, have higher numbers of authors, and have more keywords are more likely to be cited. Adoption of some simple “best-practice” behaviors can improve the likelihood that a paper is cited.     

Effect of a zinc-deficient diet on lipid peroxidation in liver and tumor subcellular membranes

The effect of a zinc-deficient diet on lipid peroxidation in liver and tumor mitochondrial and microsomal membrane preparations from BALB/c mice was investigated. Mitochondrial and microsomal membranes from both tissues displayed increased rates of in vitro peroxidation, both enzymatic and nonenzymatic. Measurement of in vivo peroxidation, using diene conjugation as an index of measurement revealed slight increases in tissues from zinc-deficient animals that were not statistically significant. Serum lipoperoxides analyzed from all three groups revealed no significant differences. The results point to an alteration in the peroxidation potential of mitochondrial and microsomal membranes due to zinc deficiency which may be related to an alteration in fatty acid composition.     

Optimal infection strategies: should macroparasites hedge their bets?

Despite considerable research into the mechanisms that lead to the persistence of parasites, the huge diversity of macroparasite transmission strategies observed both within and among species has yet to be explained. This may be because questions of parasite persistence are typically addressed at the population level, even though observed transmission rates are determined by infection events at the level of the individual parasite. To help overcome this disparity, a simple model is developed to explore the optimal infection strategy for a macroparasite under a range of selection pressures. The model calculates the fitness of the parasite by considering explicitly the probability of the individual infective stages surviving and infecting. The optimal strategy is highly sensitive to the rate of host availability and, considering the parasite's fitness, it is often preferable to have sub-maximal infectivity to maximise survival during periods of host absence. An important finding is that when parasites are faced with unpredictable conditions such as the time of host availability, the optimum strategy may be to produce offspring that differ in their infection strategies. By spreading the risk in this way, known as bet hedging, parasites can increase the chances that at least some of their offspring will infect successfully. This potential for variation in infection strategies has not been considered explicitly before and may have wide reaching implications for current epidemiology theory.