Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model

Background

Different patterns of drug resistance are observed in treated and therapy naïve HIV-1 infected populations. Especially the NRTI-related M184I/V variants, which are among the most frequently encountered mutations in treated patients, are underrepresented in the antiretroviral naïve population. M184I/V mutations are known to have a profound effect on viral replication and tend to revert over time in the new host. However it is debated whether a diminished transmission efficacy of HIV variants with a reduced replication capacity can also contribute to the observed discrepancy in genotypic patterns.As dendritic cells (DCs) play a pivotal role in HIV-1 transmission, we used a model containing primary human Langerhans cells (LCs) and DCs to compare the transmission efficacy M184 variants (HIV-M184V/I/T) to HIV wild type (HIV-WT). As control, we used HIV harboring the NNRTI mutation K103N (HIV-K103N) which has a minor effect on replication and is found at a similar prevalence in treated and untreated individuals.

Results

In comparison to HIV-WT, the HIV-M184 variants were less efficiently transmitted to CCR5⁺ Jurkat T cells by both LCs and DCs. The transmission rate of HIV-K103N was slightly reduced to HIV-WT in LCs and even higher than HIV-WT in DCs. Replication experiments in CCR5⁺ Jurkat T cells revealed no apparent differences in replication capacity between the mutant viruses and HIV-WT. However, viral replication in LCs and DCs was in concordance with the transmission results; replication by the HIV-M184 variants was lower than replication by HIV-WT, and the level of replication of HIV-K103N was intermediate for LCs and higher than HIV-WT for DCs.

Conclusions

Our data demonstrate that drug resistant M184-variants display a reduced replication capacity in LCs and DCs which directly impairs their transmission efficacy. As such, diminished transmission efficacy may contribute to the lower prevalence of drug resistant variants in therapy naive individuals.

     

The role of snail aestivation in transmission of schistosomiasis in changing climatic conditions

Schistosomiasis vector snails are subjected to extreme seasonal changes, particularly in ephemeral rivers and lentic waterbodies. In the tropics, aestivation is one of the adaptive strategies for survival and is used by snails in times of extremely high temperatures and desiccation. Aestivation therefore plays an important role in maintaining the transmission of schistosomiasis. This review assesses the possible impacts of climate change on the temporal and spatial distribution of schistosomiasis-transmitting snails with special emphasis on aestivation, and discusses the effect of schistosome infection on aestivation ability. The impacts of parasite development on snails, as well as physiological changes, are discussed with reference to schistosomiasis transmission. This review shows that schistosome-infected snails have lower survival rates during aestivation, and that those that survive manage to get rid of the infection. In general, snail aestivation ability is poor and survival chances diminish with time. Longer dry periods result in fewer, as well as uninfected, snails. However, the ability of the surviving snails to repopulate the habitats is high.     

Growth and Cadmium Phytoextraction by Swiss Chard,Maize, Rice,Noccaea caerulescens,and Alyssum murale in pH Adjusted Biosolids Amended Soils

Past applications of biosolids to soils at some locations added higher Cd levels than presently permitted. Cadmium phytoextraction would alleviate current land use constraints. Unamended farm soil, and biosolids amended farm and mine soils were obtained from a Fulton Co., IL biosolids management facility. Soils contained 0.16, 22.8, 45.3 mg Cd kg^–1 and 43.1, 482, 812 mg Zn kg^–1 respectively with initial pH 6.0, 6.1, 6.4. In greenhouse studies, Swiss chard (Beta vulgaris var. cicla), a Cd-accumulator maize (inbred B37 Zea mays) and a southern France Cd-hyperaccumulator genotype of Noccaea caerulescens were tested for Cd accumulation and phytoextraction. Soil pH was adjusted from ～5.5–7.0. Additionally 100 rice (Oryza sativa) genotypes and the Ni-hyperaccumulator Alyssum murale were screened for potential phytoextraction use.

Chard suffered phytotoxicity at low pH and accumulated up to 90 mg Cd kg^–1 on the biosolids amended mine soil. The maize inbred accumulated up to 45 mg Cd kg^–1 with only mild phytotoxicity symptoms during early growth at pH > 6.0. N. caerulescens did not exhibit phytotoxicity symptoms at any pH, and accumulated up to 235 mg Cd kg^–1 in 3 months. Reharvested N. caerulescens accumulated up to 900 mg Cd kg^–1 after 10 months. Neither Alyssum nor 90% of rice genotypes survived acceptably.

Both N. caerulescens and B37 maize show promise for Cd phytoextraction in IL and require field evaluation; both plants could be utilized for nearly continuous Cd removal. Other maize inbreds may offer higher Cd phytoextraction at lower pH, and mono-cross hybrids higher shoot biomass yields. Further, maize grown only for biomass Cd maximum removal could be double-cropped.     

Effects of Modified Handling on the Physiological Stress of Trawled-and-Discarded Yellowfin Bream (Acanthopagrus australis)

Modified handling is often claimed to reduce (sub-)lethal impacts among organisms caught-and-released in fisheries. Improving welfare of discarded fish warrants investigation, when their survival is of both economic and ecological importance. In this study, juvenile yellowfin bream (Acanthopagrus australis) were trawled in an Australian penaeid fishery and then discarded after on-board sorting in either dry or water-filled (modified) trays and with delays in starting sorting of either 2 or 15 mins. Blood plasma cortisol, glucose and potassium were sampled immediately from some yellowfin bream, while others were placed into cages (with controls) and sampled after five days. Irrespective of their on-board handling, all trawled fish incurred a relatively high acute stress response (i.e. an increase in Mean ± SE cortisol from a baseline of <4 to 122.0 ± 14.9 ng/mL) that was mostly attributed to the trawling process, and exacerbated by variation in key parameters (low salinity, changes in water temperature and the presence of jellyfish Catostylus mosaicus in catches). When C. mosaicus was present, the potassium concentrations of fish sampled immediately after sorting were significantly elevated, possibly due to nematocyst contact and subsequent inhibition of ion pumps or cytolysis. Stress also increased during handling in response to warmer air temperatures and longer exposure. While most fish had substantially recovered by 120 hours after discarding, deploying selective trawls (to reduce jellyfish) for short periods and then quickly sorting catches in water would benefit discard welfare.     

A graphical method for detecting recombination in phylogenetic data sets

Current phylogenetic tree reconstruction methods assume that there is a single underlying tree topology for all sites along the sequence. The presence of mosaic sequences due to recombination violates this assumption and will cause phylogenetic methods to give misleading results due to the imposition of a single tree topology on all sites. The detection of mosaic sequences caused by recombination is therefore an important first step in phylogenetic analysis. A graphical method for the detection of recombination, based on the least squares method of phylogenetic estimation, is presented here. This method locates putative recombination breakpoints by moving a window along the sequence. The performance of the method is assessed by simulation and by its application to a real data set.      

Variation of physico-chemical parameters along a river transect through the Okavango Delta,Botswana

The Okavango Delta depends on water quantity and quality to sustain its ecosystem services. Whereas many studies have been carried out on its hydrology, few have been done on water quality in the delta. Water pH, electrical conductivity (EC), dissolved oxygen (DO), turbidity, total suspended solids (TSS) and dissolved organic carbon (DOC) were monitored at 10 sites along the Okavango–Boro–Thamalakane–Lake Ngami system almost fortnightly from June 2008 to June 2010. Water quality in the delta was generally good, despite high evapotranspiration rates which would normally produce very saline waters. Electrical conductivity and water temperature increased with distance from Mohembo to Lake Ngami, the former most likely due to evapoconcentration. In contrast, pH, DO, turbidity and TSS decreased with distance from Mohembo to Boro at the lower end of the seasonal floodplain, before increasing again to Lake Ngami. Dissolved oxygen and TSS most likely declined due to biological uptake and particle sedimentation, respectively. Strong and significant relationships were observed between TSS and turbidity and between DOC and EC, indicating that turbidity and EC could be useful proxies for routine estimations of TSS and DOC, respectively, in the delta.     

The merits of artificial selection for the development of restoration‐ready plant materials of native perennial grasses

Although seed harvested from remnant, wildland perennial‐grass populations can be used for restoration in humid and subhumid temperate regions, seed harvested in semiarid and arid environments is often of low quality and highly variable in quantity. In addition, ongoing harvest of indigenous populations can be unsustainable, especially for those that are small. In such environments, dependable and repeatable broad‐scale restoration of degraded grasslands requires sufficient and consistent supplies of reliable, cost‐effective seed sources that can only result from intensively managed cultivated stands. But does the harvest of intensively managed seed‐production fields inadvertently compromise genetic diversity, thereby adversely affecting the restoration outcome? That is, are seed‐production systems a part of the solution for restoration, or do they create new unintended management issues? This article discusses the potential impacts of cultivated seed‐production systems and recurrent artificial selection for specific traits on genetic integrity and performance of native‐species perennial‐grass populations. Although genetic shift resulting from cultivated perennial‐grass seed production may be inevitable, genetic shifts that change phenological expression may be limited in genotypes that exhibit high seed retention. Artificial selection can improve plant material performance on the often‐harsh conditions of restoration sites, but sufficiently high‐effective population sizes (N_e) must be maintained to conserve genetic diversity, thereby precluding the inbreeding depression that can compromise plant performance. Potentially useful traits of native perennial‐grass species that respond to artificial selection include seed production, seed retention, seedling establishment, competitive ability against weeds, and herbicide tolerance. Potential trade‐offs between traits should also be considered to avoid undesirable inadvertent responses to selection.