The value of decreasing the duration of the infectious period of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection

Finding medications or vaccines that may decrease the infectious period of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could potentially reduce transmission in the broader population. We developed a computational model of the U.S. simulating the spread of SARS-CoV-2 and the potential clinical and economic impact of reducing the infectious period duration. Simulation experiments found that reducing the average infectious period duration could avert a median of 442,852 [treating 25% of symptomatic cases, reducing by 0.5 days, reproductive number (R₀) 3.5, and starting treatment when 15% of the population has been exposed] to 44.4 million SARS-CoV-2 cases (treating 75% of all infected cases, reducing by 3.5 days, R₀ 2.0). With R₀ 2.5, reducing the average infectious period duration by 0.5 days for 25% of symptomatic cases averted 1.4 million cases and 99,398 hospitalizations; increasing to 75% of symptomatic cases averted 2.8 million cases. At $500/person, treating 25% of symptomatic cases saved $209.5 billion (societal perspective). Further reducing the average infectious period duration by 3.5 days averted 7.4 million cases (treating 25% of symptomatic cases). Expanding treatment to 75% of all infected cases, including asymptomatic infections (R₀ 2.5), averted 35.9 million cases and 4 million hospitalizations, saving $48.8 billion (societal perspective and starting treatment after 5% of the population has been exposed). Our study quantifies the potential effects of reducing the SARS-CoV-2 infectious period duration.     

Transforming growth factor beta induces the production of interleukin 6 by human peripheral blood mononuclear cells

Previous studies have indicated that the cytokine transforming growth factor beta 1 (TGF beta 1) has immunosuppressive properties and can inhibit the production of tumor necrosis factor (TNF) and Interleukin 1 (IL 1) by human peripheral blood mononuclear cells. In this study, we have examined the effects of TGF beta 1 on the production of Interleukin 6 (IL 6) by human peripheral blood mononuclear cells. Treatment with only TGF beta 1 leads to the induction of IL 6, and this was both dose- and time-dependent. The effect of TGF beta 1 was evident at the level of IL 6 mRNA, suggesting TGF beta 1-induced de novo synthesis of IL 6. Induction of IL 6 by TGF beta 1 was specific, as other cytokines made by mononuclear cells (TNF and IL 1) were not induced by TGF beta 1. Furthermore, when a panel of stimuli were compared for their ability to induce IL 1, TNF and IL 6 in the presence or absence of TGF beta 1, IL 6 levels were augmented in the presence of TGF beta 1, while the induction of IL 1 and TNF was inhibited significantly. These results indicate that TGF beta 1 has complex effects on the production of cytokines by peripheral blood mononuclear cells and that TGF beta 1 is not inhibitory for all cytokine production. The ability of TGF beta 1 to induce IL 6 suggests that IL 6 may mediate some of the effects of TGF beta 1.     

Pre-exposure affects the olfactory response of Drosophila melanogaster to menthol

A modification of the trap assay (Woodard et al., 1989) was used to evaluate the response of Drosophila melanogaster (Meigen) to food media containing menthol. Dose-response curves for flies to mentholic foods were produced for flies that had been pre-exposed to menthol, during development and adult life, and flies that had not been exposed to menthol before the assay. Mentholic food media were less attractive to Drosophila than plain food medium. Rearing flies on a medium containing menthol reduced their aversion to some concentrations of menthol. The rearing effect was not simply due to lowered general activity levels resulting from developing in a medium containing menthol. There was a threshold concentration of menthol in the rearing medium below which we found no induced behavioural change.     

Activation of AMPK by Bitter Melon Triterpenoids Involves CaMKKβ

We recently showed that bitter melon-derived triterpenoids (BMTs) activate AMPK and increase GLUT4 translocation to the plasma membrane in vitro, and improve glucose disposal in insulin resistant models in vivo. Here we interrogated the mechanism by which these novel compounds activate AMPK, a leading anti-diabetic drug target. BMTs did not activate AMPK directly in an allosteric manner as AMP or the Abbott compound (A-769662) does, nor did they activate AMPK by inhibiting cellular respiration like many commonly used anti-diabetic medications. BMTs increased AMPK activity in both L6 myotubes and LKB1-deficient HeLa cells by 20–35%. Incubation with the CaMKKβ inhibitor, STO-609, completely attenuated this effect suggesting a key role for CaMKKβ in this activation. Incubation of L6 myotubes with the calcium chelator EGTA-AM did not alter this activation suggesting that the BMT-dependent activation was Ca²⁺-independent. We therefore propose that CaMKKβ is a key upstream kinase for BMT-induced activation of AMPK.     

Flight loss linked to faster molecular evolution in insects

The loss of flight ability has occurred thousands of times independently during insect evolution. Flight loss may be linked to higher molecular evolutionary rates because of reductions in effective population sizes (N_e) and relaxed selective constraints. Reduced dispersal ability increases population subdivision, may decrease geographical range size and increases (sub)population extinction risk, thus leading to an expected reduction in N_e. Additionally, flight loss in birds has been linked to higher molecular rates of energy-related genes, probably owing to relaxed selective constraints on energy metabolism. We tested for an association between insect flight loss and molecular rates through comparative analysis in 49 phylogenetically independent transitions spanning multiple taxa, including moths, flies, beetles, mayflies, stick insects, stoneflies, scorpionflies and caddisflies, using available nuclear and mitochondrial protein-coding DNA sequences. We estimated the rate of molecular evolution of flightless (FL) and related flight-capable lineages by ratios of non-synonymous-to-synonymous substitutions (dN/dS) and overall substitution rates (OSRs). Across multiple instances of flight loss, we show a significant pattern of higher dN/dS ratios and OSRs in FL lineages in mitochondrial but not nuclear genes. These patterns may be explained by relaxed selective constraints in FL ectotherms relating to energy metabolism, possibly in combination with reduced N_e.     

The XcpR protein of Pseudomonas aeruginosa dimerizes via its N-terminus

Extracellular protein secretion by the main terminal branch of the general secretory pathway in Pseudomonas aeruginosa requires a secretion machinery comprising the products of at least 12 genes. One of the components of this machinery, the XcpR protein, belongs to a large family of related proteins distinguished by the presence of a highly conserved nucleotide binding domain (Walker box A). The XcpR protein is essential for the process of extracellular secretion and amino acid substitutions within the Walker A sequence result in inactive XcpR. The same mutations exert a dominant negative effect on protein secretion when expressed in wild-type bacteria. Transdominance of XcpR mutants suggests that this protein is involved in interactions with other components of the secretion machinery or that it functions as a multimer. In this study, the amino-terminal portion of the cI repressor protein of phage λ was used as a reporter of dimerization in Escherichia coli following fusion to full-length as well as a truncated form of XcpR. The cI–XcpR hybrid proteins were able to dimerize, as demonstrated by the immunity of bacteria expressing them to killing by λ phage. The full-length XcpR as well as several deletion mutants of XcpR were able to disrupt the dimerization of the chimeric cI–XcpR protein. The disruption of cI–XcpR dimers using the deletion mutants of XcpR, combined with the analysis of their dominant negative effects on protein secretion, was used to map the minimal dimerization domain of XcpR, which is located within an 85 amino acid region in its N-terminal domain. Taken together, the data presented in this paper suggest that the XcpR protein dimerizes via its N-terminus and that this dimerization is essential for extracellular protein secretion.     

Competition for nectar resources does not affect bee foraging tactic constancy

1. Competition alters animal foraging, including promoting the use of alternative resources. It may also impact how animals feed when they are able to handle the same food with more than one tactic. Competition likely impacts both consumers and their resources through its effects on food handling, but this topic has received little attention. 2. Bees often use two tactics for extracting nectar from flowers: they can visit at the flower opening, or rob nectar from holes at the base of flowers. Exploitative competition for nectar is thought to promote nectar robbing. If so, higher competition among floral visitors should reduce constancy to a single foraging tactic as foragers will seek food using all possible tactics. To test this prediction, field observations and two experiments involving bumble bees visiting three montane Colorado plant species (Mertensia ciliata, Linaria vulgaris, Corydalis caseana) were used under various levels of inter- and intra-specific competition for nectar. 3. In general, individual bumble bees remained constant to a single foraging tactic, independent of competition levels. However, bees that visited M. ciliata in field observations decreased their constancy and increased nectar robbing rates as visitation rates by co-visitors increased. 4. While tactic constancy was high overall regardless of competition intensity, this study highlights some intriguing instances in which competition and tactic constancy may be linked. Further studies investigating the cognitive underpinnings of tactic constancy should provide insight on the ways in which animals use alternative foraging tactics to exploit resources.     

Crime or affliction? Rape in an African community

Amongst the Gush of southwestern Kenya instances of rape are frequently reported; this was true also in the colonial period and yet it seems that those cases which come to the notice of the authorities are few compared with the numbers which actually occur. While certain features of the traditional culture seem to have encouraged violent sexual assault, because in a patrilocal society miscreants are likely to victimize their relatives, that is women who are sexually taboo, the crime is considered a sacrilegious matter to be dealt with in the family, not by the secular authorities. Given the sacrilegious nature of the act the Gush are convinced that such behavior is involuntary and that the criminal is not a criminal but an afflicted person, motivated by the malevolence of the ancestral spirits or of jealous neighbors and kin. The author uses case material to illustrate various aspects of the Gush belief system in regard to criminal behavior in general and rape in particular.