Modelling response strategies for controlling gonorrhoea outbreaks in men who have sex with men in Australia

The ability to treat gonorrhoea with current first-line drugs is threatened by the global spread of extensively drug resistant (XDR) Neisseria gonorrhoeae (NG) strains. In Australia, urban transmission is high among men who have sex with men (MSM) and importation of an XDR NG strain in this population could result in an epidemic that would be difficult and costly to control. An individual-based, anatomical site-specific mathematical model of NG transmission among Australian MSM was developed and used to evaluate the potential for elimination of an imported NG strain under a range of case-based and population-based test-and-treat strategies. When initiated upon detection of the imported strain, these strategies enhance the probability of elimination and reduce the outbreak size compared with current practice (current testing levels and no contact tracing). The most effective strategies combine testing targeted at regular and casual partners with increased rates of population testing. However, even with the most effective strategies, outbreaks can persist for up to 2 years post-detection. Our simulations suggest that local elimination of imported NG strains can be achieved with high probability using combined case-based and population-based test-and-treat strategies. These strategies may be an effective means of preserving current treatments in the event of wider XDR NG emergence.     

Uptake of Rhodnius heme-binding protein (RHBP) by the ovary of Rhodnius prolixus

The uptake of RHBP (Rhodnius heme-binding protein) by the ovaries of Rhodnius prolixus was characterized. RHBP purified from oocyte was labeled with ¹²⁵I and used to study the process of uptake by the ovary in vivo and in vitro. After injection, the [¹²⁵I]RHBP was readily removed from the hemolymph and accumulated especially in the ovary. The capacity of the ovary to take up [¹²⁵I]RHBP from the hemolymph varied during the days following blood meal. It increased up to day 2, remained stable until day 5, and then decreased up to the end of oogenesis. In vitro, the uptake of [¹²⁵I]RHBP was linear at least up to 60 min. The uptake was dependent on [¹²⁵I]RHBP concentration and showed to be a saturable process. The addition of a molar excess of non-related proteins such as Vitellin (Vt), Lipophorin (Lp), and Bovine Serum Albumin (BSA) did not reduce [¹²⁵I]RHBP uptake. Using immunogold technique the RHBP was localized at the microvilli, coated pits, and yolk granules. The main yolk protein, Vt, did not compete with RHBP for the uptake. Thus, it is discussed here that they bind to independent binding sites of the oocytes, and are directed later on to the same compartment. The need of both proteins for the completion of mature oocyte was verified in vivo. The reduction of heme-RHBP in the hemolymph, by changing the diet, decreased the number of eggs laid. Increasing the concentration of heme-RHBP in the hemolymph, the number of eggs produced increased in a dose dependent manner. In vitro, both apo-RHBP and heme-RHBP can be taken up by the oocyte. Since the mature oocyte contains only heme-saturated RHBP, the possible fate of apo-RHBP is also discussed. Arch. Insect Biochem. Physiol. 39:133–143, 1998. © 1998 Wiley-Liss, Inc.     

Biological and conformational studies on analogues of a synthetic peptide enhancing HIV-1 infection

We have previously demonstrated that a 23-amino acid peptide derived from the V3 loop of the surface glycoprotein of the HIV-1 strain MN is able to bind CD4 and to enhance HIV-1 infection. Further studies have suggested that the peptide/CD4 interaction induces an increase in both CD4 expression and CD4/gp120 binding affinity. This paper describes the biological and physico-chemical characterization of three analogues of reduced sequence that have been designed in order to identify the minimum active sequence of this peptide corresponding to the MN-HIV-1 principal neutralizing domain. Biological studies indicate that the entire sequence is required for biological activity and that the sequence 1–18 presents an inhibitory activity. CD and FT-IR absorption data are discussed here in order to identify possible structure-function correlations. © 1998 European Peptide Society and John Wiley & Sons, Ltd.     

Effects of enhanced productivity of resources shared by predators in a food‐web module: Comparing results of a field experiment to predictions of mathematical models of intra‐guild predation

We compared the response to resource enhancement of a simple empirical model of intra‐guild predation (IGP) to the predictions of published, simple mathematical models of asymmetric IGP (a generalist IG Predator that feeds both on a specialist IG Prey and a Resource that it shares with the IG Prey). The empirical model was a food‐web module created by pooling species abundances across many families in a speciose community of soil micro‐arthropods into three categories: IG Predator (large predatory mites), IG Prey (small predatory mites), and a shared Resource (fungivorous mites and springtails). By pooling abundances of species belonging to broadly defined functional groups, we tested the hypothesis that IGP is a dominant organizing principle in this community. Simple mathematical models of asymmetric IGP predict that increased input of nutrients and energy to the shared Resource will increase the equilibrium density of Resource and IG Predator, but will decrease that of IG Prey. In a field experiment, we observed how the three categories of the empirical model responded to two rates of addition of artificial detritus, which enhanced the food of fungivores, the Resource of the IGP module. By the experiment''s end, fungivore densities had increased ~1.5× (ratio of pooled fungivore densities in the higher‐input treatment to plots with no addition of detritus), and densities of IG Predators had increased ~4×. Contrary to the prediction of mathematical models, IG Prey had not decreased, but instead had increased ~1.5×. We discuss possible reasons for the failure of the empirical model to agree with IGP theory. We then explore analogies between the behavior of the empirical model and another mathematical model of trophic interactions as one way to gain insights into the trophic connections in this community. We also propose one way forward for reporting comparisons of simple empirical and mathematical models.     

Negative-sense RNA viruses: An underexplored platform for examining virus–host lipid interactions

Viruses are pathogenic agents that can infect all varieties of organisms, including plants, animals, and humans. These microscopic particles are genetically simple as they encode a limited number of proteins that undertake a wide range of functions. While structurally distinct, viruses often share common characteristics that have evolved to aid in their infectious life cycles. A commonly underappreciated characteristic of many deadly viruses is a lipid envelope that surrounds their protein and genetic contents. Notably, the lipid envelope is formed from the host cell the virus infects. Lipid-enveloped viruses comprise a diverse range of pathogenic viruses, which often lead to high fatality rates and many lack effective therapeutics and/or vaccines. This perspective primarily focuses on the negative-sense RNA viruses from the order Mononegavirales, which obtain their lipid envelope from the host plasma membrane. Specifically, the perspective highlights the common themes of host cell lipid and membrane biology necessary for virus replication, assembly, and budding.     

Molecular insights into substrate recognition and catalysis by phthalate dioxygenase from Comamonas testosteroni

Phthalate, a plasticizer, endocrine disruptor, and potential carcinogen, is degraded by a variety of bacteria. This degradation is initiated by phthalate dioxygenase (PDO), a Rieske oxygenase (RO) that catalyzes the dihydroxylation of phthalate to a dihydrodiol. PDO has long served as a model for understanding ROs despite a lack of structural data. Here we purified PDO_KF1 from Comamonas testosteroni KF1 and found that it had an apparent k_cat/K_m for phthalate of 0.58 ± 0.09 μM⁻¹s⁻¹, over 25-fold greater than for terephthalate. The crystal structure of the enzyme at 2.1 Å resolution revealed that it is a hexamer comprising two stacked α₃ trimers, a configuration not previously observed in RO crystal structures. We show that within each trimer, the protomers adopt a head-to-tail configuration typical of ROs. The stacking of the trimers is stabilized by two extended helices, which make the catalytic domain of PDO_KF1 larger than that of other characterized ROs. Complexes of PDO_KF1 with phthalate and terephthalate revealed that Arg207 and Arg244, two residues on one face of the active site, position these substrates for regiospecific hydroxylation. Consistent with their roles as determinants of substrate specificity, substitution of either residue with alanine yielded variants that did not detectably turnover phthalate. Together, these results provide critical insights into a pollutant-degrading enzyme that has served as a paradigm for ROs and facilitate the engineering of this enzyme for bioremediation and biocatalytic applications.     

Decomposition and nitrogen dynamics of turtle grass (<Emphasis Type="Italic">Thalassia testudinum</Emphasis>) in a subtropical estuarine system

Seagrass beds are pivotal in the functioning of coastal ecosystems in terms of productivity, organic matter turnover and nutrient cycling. Aiming to document decay and nitrogen (N) dynamics of turtle grass (Thalassia testudinum) in a subtropical estuarine system, decomposition patterns of leaves and rhizomes were characterized and compared. Nitrogen usage during decomposition of tissues, and of live tissues and epiphytes growing on live leaves, was also quantified and compared. Stable isotope ratios allowed tracing N within the seagrass bed, following N incorporation into seagrass tissues from the surrounding media (water, sediment). Leaves had a higher N content and decomposed at a faster rate (~6.4 times) compared to rhizomes. Leaching of soluble materials explain the rapid (0–3 days) initial mass loss of leaves (20%) and rhizomes (18%); with a loss of 85 and 56%, respectively, by the end of the study (77 days). Overall, leaves released N while rhizomes immobilized it. Nitrogen concentration was significantly different among live tissues. The main source of N for both seagrass tissues was the sediment, and water column for epiphytes. Differences in decomposition rates among seagrass tissues can be explained by the quality of the substrate and its susceptibility to microbial use. Seagrass leaves and rhizomes are equally important in taking up nutrients from either the water column or the sediments. This study provides a platform to study energy and matter transfers through detrital foodwebs linked to seagrass meadows.