Assessing the potential for managed aquifer recharge (MAR) of the Cape Flats Aquifer

This paper discusses the potential use of ‘managed aquifer recharge’ (MAR) in Cape Town to provide additional water supplies to the city that are fit-for-purpose. The paper investigates the feasibility of implementing MAR by simulating the artificial recharge of winter stormwater into the Cape Flats Aquifer (CFA), an extensive sandy, unconfined aquifer that covers most of metropolitan Cape Town’s urban landscape. The objective is to assess the storage capacity and supply potential of two MAR sites by modelling various scenarios in order to determine the feasibility of MAR as a viable strategy for achieving improved water security by augmenting groundwater water supply. The selected scenarios demonstrated that MAR could be used to minimise the risk of seawater intrusion and maximise the amount of water available for abstraction from the CFA. Six MAR scenarios provided strong evidence to suggest that there is sufficient storage capacity within the CFA for using stormwater to improve the wellfield yield in two regions of the CFA and which can sustainably yield approximately 18 Mm3per year. The study concluded that the use of stormwater or treated wastewater could be deliberately used to recharge the CFA and as a viable option in support of the City of Cape Town’s intention to establish a water-resilient city by 2030

Evidence of Local Adaptation in Plant Virus Effects on Host-Vector Interactions

Recent research suggests that plant viruses, and other pathogens, frequently alter host-plant phenotypes in ways that facilitate transmission by arthropod vectors. However, many viruses infect multiple hosts, raising questions about whether these pathogens are capable of inducing transmission-facilitating phenotypes in phylogenetically divergent host plants and the extent to which evolutionary history with a given host or plant community influences such effects. To explore these issues, we worked with two newly acquired field isolates of cucumber mosaic virus (CMV)—a widespread multi-host plant pathogen transmitted in a non-persistent manner by aphids—and explored effects on the phenotypes of different host plants and on their subsequent interactions with aphid vectors. An isolate collected from cultivated squash fields (KVPG2-CMV) induced in the native squash host (Cucurbita pepo) a suite of effects on host-vector interactions suggested by previous work to be conducive to transmission (including reduced host-plant quality for aphids, rapid aphid dispersal from infected to healthy plants, and enhanced aphid attraction to the elevated emission of a volatile blend similar to that of healthy plants). A second isolate (P1-CMV) collected from cultivated pepper (Capsicum annuum) induced more neutral effects in its native host (largely exhibiting non-significant trends in the direction of effects seen for KVPG2-CMV in squash). When we attempted cross-host inoculations of these two CMV isolates (KVPG2-CMV in pepper and P1-CMV in squash), P1-CMV was only sporadically able to infect the novel host; KVPG2-CMV infected the novel pepper host with somewhat reduced success compared with its native host and reached virus titers significantly lower than those observed for either strain in its native host. Furthermore, KVPG2-CMV induced changes in the phenotype of the novel host, and consequently in host-vector interactions, dramatically different than those observed in the native host and apparently maladaptive with respect to virus transmission (e.g., host plant quality for aphids was significantly improved in this instance, and aphid dispersal was reduced). Taken together, these findings provide evidence of adaption by CMV to local hosts (including reduced infectivity and replication in novel versus native hosts) and further suggest that such adaptation may extend to effects on host-plant traits mediating interactions with aphid vectors. Thus, these results are consistent with the hypothesis that virus effects on host-vector interactions can be adaptive, and they suggest that multi-host pathogens may exhibit adaptation with respect to these and other effects on host phenotypes, perhaps especially in homogeneous monoculture

Correlation between compartmental tenofovir concentrations and an ex vivo rectal biopsy model of tissue infectibility in the RMP-02/MTN-006 phase 1 study

Design: Phase 1, randomized, two-site (US), double-blind, placebo-controlled study of sexually-abstinent males and females

A multi-compartment single and multiple dose pharmacokinetic comparison of rectally applied tenofovir 1% gel and oral tenofovir disoproxil fumarate

This Phase 1, randomized, two-site (United States), double-blind, placebo-controlled study enrolled 18 sexually abstinent men and women. All received a single 300-mg dose of oral tenofovir disoproxil fumarate (TDF) and were then randomized 2:1 to receive single and then seven daily rectal exposures of vaginally-formulated tenofovir (TFV) 1% gel or a hydroxyethyl cellulose (HEC) placebo gel. Blood, colonic biopsies and rectal and vaginal mucosal fluids were collected after the single oral TDF, the single topical TFV gel dose, and after 7 days of topical TFV gel dosing for extracellular analysis of TFV and intracellular analysis of the active metabolite tenofovir diphosphate (TFVdp) in peripheral blood mononuclear cells (PBMCs) and isolated mucosal mononuclear cells (MMC), including CD4+ and CD4- cell subsets. With a single rectal dose, TFV plasma concentrations were 24-33 fold lower and half-life was 5 h shorter compared to a single oral dose (p = 0.02). TFVdp concentrations were also undetectable in PBMCs with rectal dosing. Rectal tissue exposure to both TFV and TFVdp was 2 to 4-log10 higher after a single rectal dose compared to a single oral dose, and after 7 daily doses, TFVdp accumulated 4.5 fold in tissue. TFVdp in rectal tissue homogenate was predictive (residual standard error, RSE = 0.47) of tissue MMC intracellular TFVdp concentration, with the CD4+ cells having a 2-fold higher TFVdp concentration than CD4- cells. TFV concentrations from rectal sponges was a modest surrogate indicator for both rectal tissue TFV and TFVdp (RSE = 0.67, 0.66, respectively) and plasma TFV (RSE = 0.38). TFV penetrates into the vaginal cavity after oral and rectal dosing, with rectal dosing leading to higher vaginal TFV concentrations (p<0.01)

Twice-daily application of HIV microbicides alters the vaginal microbiota

Vaginal HIV microbicides offer great promise in preventing HIV transmission, but failures of phase 3 clinical trials, in which microbicide-treated subjects had an increased risk of HIV transmission, raised concerns about endpoints used to evaluate microbicide safety. A possible explanation for the increased transmission risk is that the agents shifted the vaginal bacterial community, resulting in loss of natural protection and enhanced HIV transmission susceptibility. We characterized vaginal microbiota, using pyrosequencing of bar-coded 16S rRNA gene fragments, in samples from 35 healthy, sexually abstinent female volunteer subjects (ages 18 to 50 years) with regular menses in a repeat phase 1 study of twice-daily application over 13.5 days of 1 of 3 gel products: a hydroxyethylcellulose (HEC)-based “universal” placebo (10 subjects), 6% cellulose sulfate (CS; 13 subjects), and 4% nonoxynol-9 (N-9; 12 subjects). We used mixed effects models inferred using Bayesian Markov chain Monte Carlo methods, which showed that treatment with active agents shifted the microbiota toward a community type lacking significant numbers of Lactobacillus spp. and dominated by strict anaerobes. This state of the vaginal microbiota was associated with a low or intermediate Nugent score and was not identical to bacterial vaginosis, an HIV transmission risk factor. The placebo arm contained a higher proportion of communities dominated by Lactobacillus spp., particularly L. crispatus, throughout treatment. The data suggest that molecular evaluation of microbicide effects on vaginal microbiota may be a critical endpoint that should be incorporated in early clinical assessment of microbicide candidates. IMPORTANCE Despite large prevention efforts, HIV transmission and acquisition rates remain unacceptably high. In developing countries, transmission mainly occurs through heterosexual intercourse, where women are significantly more vulnerable to infection than men. Vaginal microbicides are considered to be one of the most promising female-controlled products, in that women themselves insert the microbicides into the vagina to prevent HIV transmission during sexual intercourse. The failure of several microbicides in clinical trials has raised questions concerning the low in vivo efficacy of such anti-HIV molecules. This study was designed to gain insights into the failures of two microbicides by testing the hypothesis that the microbicides negatively affect a critical line of defense against HIV, the vaginal microbiota. The results suggest that in the early assessment of candidate microbicides, culture-independent evaluation of their effect on the vaginal microbiota should be considered and may constitute a critical endpoint

Preconditioning of mesenchymal stromal cells with low-intensity ultrasound: influence on chondrogenesis and directed SOX9 signaling pathways

Background: Continuous low-intensity ultrasound (cLIUS) facilitates the chondrogenic differentiation of human mesenchymal stromal cells (MSCs) in the absence of exogenously added transforming growth factor-beta (TGFβ) by upregulating the expression of transcription factor SOX9, a master regulator of chondrogenesis. The present study evaluated the molecular events associated with the signaling pathways impacting SOX9 gene and protein expression under cLIUS. Methods: Human bone marrow-derived MSCs were exposed to cLIUS stimulation at 14 kPa (5 MHz, 2.5 Vpp) for 5 min. The gene and protein expression of SOX9 was evaluated. The specificity of SOX9 upregulation under cLIUS was determined by treating the MSCs with small molecule inhibitors of select signaling molecules, followed by cLIUS treatment. Signaling events regulating SOX9 expression under cLIUS were analyzed by gene expression, immunofluorescence staining, and western blotting. Results: cLIUS upregulated the gene expression of SOX9 and enhanced the nuclear localization of SOX9 protein when compared to non-cLIUS-stimulated control. cLIUS was noted to enhance the phosphorylation of the signaling molecule ERK1/2. Inhibition of MEK/ERK1/2 by PD98059 resulted in the effective abrogation of cLIUS-induced SOX9 expression, indicating that cLIUS-induced SOX9 upregulation was dependent on the phosphorylation of ERK1/2. Inhibition of integrin and TRPV4, the upstream cell-surface effectors of ERK1/2, did not inhibit the phosphorylation of ERK1/2 and therefore did not abrogate cLIUS-induced SOX9 expression, thereby suggesting the involvement of other mechanoreceptors. Consequently, the effect of cLIUS on the actin cytoskeleton, a mechanosensitive receptor regulating SOX9, was evaluated. Diffused and disrupted actin fibers observed in MSCs under cLIUS closely resembled actin disruption by treatment with cytoskeletal drug Y27632, which is known to increase the gene expression of SOX9. The upregulation of SOX9 under cLIUS was, therefore, related to cLIUS-induced actin reorganization. SOX9 upregulation induced by actin reorganization was also found to be dependent on the phosphorylation of ERK1/2. Conclusions: Collectively, preconditioning of MSCs by cLIUS resulted in the nuclear localization of SOX9, phosphorylation of ERK1/2 and disruption of actin filaments, and the expression of SOX9 was dependent on the phosphorylation of ERK1/2 under cLIUS

Virus effects on plant quality and vector behavior are species specific and do not depend on host physiological phenotype

There is growing evidence that plant viruses manipulate host plants to increase transmission-conducive behaviors by vectors. Reports of this phenomenon frequently include only highly susceptible, domesticated annual plants as hosts, which constrains our ability to determine whether virus effects are a component of an adaptive strategy on the part of the pathogen or simply by-products of pathology. Here, we tested the hypothesis that transmission-conducive effects of a virus (Turnip yellows virus [TuYV]) on host palatability and vector behavior (Myzus persicae) are linked with host plant tolerance and physiological phenotype. Our study system consisted of a cultivated crop, false flax (Camelina sativa) (Brassicales: Brassicaceae), a wild congener (C. microcarpa), and a viable F1 hybrid of these two species. We found that the most tolerant host (C. microcarpa) exhibited the most transmission-conducive changes in phenotype relative to mock-inoculated healthy plants: Aphids preferred to settle and feed on TuYV-infected C. microcarpa and did not experience fitness changes due to infection—both of which will increase viruliferous aphid numbers. In contrast, TuYV induced transmission-limiting phenotypes in the least tolerant host (C. sativa) and to a greater degree in the F1 hybrid, which exhibited intermediate tolerance to infection. Our results provide no evidence that virus effects track with infection tolerance or physiological phenotype. Instead, vector preferences and performance are driven by host-specific changes in carbohydrates under TuYV infection. These results provide evidence that induction of transmission-enhancing phenotypes by plant viruses is not simply a by-product of general pathology, as has been proposed as an explanation for putative instances of parasite manipulation by viruses and many other taxa

Tension-Compression Loading with Chemical Stimulation Results in Additive Increases to Functional Properties of Anatomic Meniscal Constructs

Objective: This study aimed to improve the functional properties of anatomically-shaped meniscus constructs through simultaneous tension and compression mechanical stimulation in conjunction with chemical stimulation. Methods: Scaffoldless meniscal constructs were subjected to simultaneous tension and compressive stimulation and chemical stimulation. The temporal aspect of mechanical loadingwas studied by employing two separate five day stimulation periods. Chemical stimulation consisted of the application of a catabolic GAG-depleting enzyme, chondroitinase ABC (C-ABC), and an anabolic growth factor, TGF-b1. Mechanical and chemical stimulation combinations were studied through a full-factorial experimental design and assessed for histological, biochemical, and biomechanical properties following 4 wks of culture. Results: Mechanical loading applied from days 10–14 resulted in significant increases in compressive, tensile, and biochemical properties of meniscal constructs. When mechanical and chemical stimuliwere combined significant additive increases in collagen per wet weight (4-fold), compressive instantaneous (3-fold) and relaxation (2-fold) moduli, and tensile moduli in the circumferential (4-fold) and radial (6-fold) directions were obtained. Conclusions: This study demonstrates that a stimulation regimen of simultaneous tension and compression mechanical stimulation, C-ABC, and TGF-b1 is able to create anatomic meniscus constructs replicating the compressive mechanica

Only the best? Exploring cross-border investor preferences in US gateway cities

Despite heady growth in cross-border investment into commercial real estate over recent decades, there are few studies that examine differences in investment preferences between domestic and cross-border investors at a micro level. We address the gap by examining the characteristics of assets acquired by cross border investors in six major US metro areas, comparing them with the purchases made by US investors in those same areas. Our study uses data on more than 67 500 transactions recorded by Real Capital Analytics (RCA) over the period from Q1 2003 to Q3 2016. As well as examining cross-border investors in aggregate, we isolate and examine purchases by investors from each of the four principal source nations for cross-border real estate investment in these cities. This is important since treating cross-border investors as a single group may obscure important differences between them. We employ multilevel logit techniques and we find across a number of specifications that cross-border investors prefer larger assets, newer assets and CBD locations regardless of nationality. However, temporal and sectoral patterns of investment, as well as evidence for return chasing behavior, vary with the nationality of investor being studied