Tenofovir treatment augments anti-viral immunity against drug-resistant SIV challenge in chronically infected rhesus macaques

BACKGROUND: Emergence of drug-resistant strains of human immunodeficiency virus type 1 (HIV-1) is a major obstacle to successful antiretroviral therapy (ART) in HIV-infected patients. Whether antiviral immunity can augment ART by suppressing replication of drug-resistant HIV-1 in humans is not well understood, but can be explored in non-human primates infected with simian immunodeficiency virus (SIV). Rhesus macaques infected with live, attenuated SIV develop robust SIV-specific immune responses but remain viremic, often at low levels, for periods of months to years, thus providing a model in which to evaluate the contribution of antiviral immunity to drug efficacy. To investigate the extent to which SIV-specific immune responses augment suppression of drug-resistant SIV, rhesus macaques infected with live, attenuated SIVmac239Δnef were treated with the reverse transcriptase (RT) inhibitor tenofovir, and then challenged with pathogenic SIVmac055, which has a five-fold reduced sensitivity to tenofovir. RESULTS: Replication of SIVmac055 was detected in untreated macaques infected with SIVmac239Δnef, and in tenofovir-treated, naïve control macaques. The majority of macaques infected with SIVmac055 experienced high levels of plasma viremia, rapid CD4(+ )T cell loss and clinical disease progression. By comparison, macaques infected with SIVmac239Δnef and treated with tenofovir showed no evidence of replicating SIVmac055 in plasma using allele-specific real-time PCR assays with a limit of sensitivity of 50 SIV RNA copies/ml plasma. These animals remained clinically healthy with stable CD4(+ )T cell counts during three years of follow-up. Both the tenofovir-treated and untreated macaques infected with SIVmac239Δnef had antibody responses to SIV gp130 and p27 antigens and SIV-specific CD8(+ )T cell responses prior to SIVmac055 challenge, but only those animals receiving concurrent treatment with tenofovir resisted infection with SIVmac055. CONCLUSION: These results support the concept that anti-viral immunity acts synergistically with ART to augment drug efficacy by suppressing replication of viral variants with reduced drug sensitivity. Treatment strategies that seek to combine immunotherapeutic intervention as an adjunct to antiretroviral drugs may therefore confer added benefit by controlling replication of HIV-1, and reducing the likelihood of treatment failure due to the emergence of drug-resistant virus, thereby preserving treatment options

Limitations and considerations for electrical resistivity and induced polarization imaging of riverbed sediments:Observations from laboratory, field, and synthetic experiments

Characterization of riverbed sediments is important for understanding groundwater (GW) and surface water (SW) interactions, and their consequent implications for ecological and environmental health. There have been numerous studies using geoelectrical methods for GW-SW interaction studies; however, most applications have not focused on obtaining quantitative information. For instance, although numerous laboratory studies highlight the relationship between geoelectrical properties and relevant parameters (e.g. specific surface area, hydraulic conductivity, and cation exchange capacity), such relationships are not commonly applied to field-scale studies. Furthermore, in addition to the spatial resolution obstacles typically present when applying petrophysical models to field data, geoelectrical data from aquatic environments have complications arising from the presence of a conductive water column overlying a resistive bed. Inadequate consideration of these complications may further preclude the reliable use of such petrophysical models. In this work, laboratory measurements, synthetic modeling, and field measurements were conducted in a third-order river where the riverbed comprises alluvial gravel and underlying red sand. A strong relationship (R2 = 0.72) between imaginary conductivity and specific surface area was observed, and laboratory results were comparable to previous studies. It was demonstrated through synthetic modeling that river stage and channel width, regularization across the river-riverbed interface, and incorrect constraints of both the river conductivity and river stage can have varying influence on inverted geoelectrical images. Reliable geoelectrical images require a priori definition of river stage and conductivity, however inversion constraints using incorrect a priori values result in misleading artifacts. The conductivity image obtained from the field data in this work appeared to reflect the geoelectrical structure anticipated from the laboratory data; however, the phase angle image did not. Although this study focused on riverbed characterization, findings here demonstrate common pitfalls of inversion of aquatic-based geoelectrical data. Primarily, they highlight that synthetic modeling ought to be used to alleviate any uncertainty in the interpretation of geoelectrical models before predictions about GW-SW interactions can be made

Time-intensive geoelectrical monitoring under winter wheat

Several studies have explored the potential of electrical resistivity tomography to monitor changes in soil moisture associated with the root water uptake of different crops. Such studies usually use a set of limited below-ground measurements throughout the growth season but are often unable to get a complete picture of the dynamics of the processes. With the development of high-throughput phenotyping platforms, we now have the capability to collect more frequent above-ground measurements, such as canopy cover, enabling the comparison with below-ground data. In this study hourly DC resistivity data were collected under the Field Scanalyzer platform at Rothamsted Research with different winter wheat varieties and nitrogen treatments in 2018 and 2019. Results from both years demonstrate the importance of applying the temperature correction to interpret hourly electrical conductivity (EC) data. Crops which received larger amounts of nitrogen showed larger canopy cover and more rapid changes in EC, especially during large rainfall events. The varieties showed contrasted heights although this does not appear to have influenced EC dynamics. The daily cyclic component of the EC signal was extracted by decomposing the time series. A shift in this daily component was observed during the growth season. For crops with appreciable difference in canopy cover, high frequency DC resistivity monitoring was able to distinguish the different below-ground behaviors. The results also highlight how coarse temporal sampling may affect interpretation of resistivity data from crop monitoring studies

Accounting for heterogeneity in θ-σ relationship:application to wheat phenotyping using ΕMI

Geophysical methods, such as electromagnetic induction (EMI), can be effective for monitoring changes in soil moisture at the field scale, particularly in agricultural applications. The electrical conductivity (σ) inferred from EMI needs to be converted to soil moisture content (θ) using an appropriate relationship. Typically, a single global relationship is applied to an entire agricultural field, however, soil heterogeneity at the field scale may limit the effectiveness of such an approach. One application area that may suffer from such an effect is crop phenotyping. Selecting crop varieties based on their root traits is important for crop breeding and maximizing yield. Hence, high throughput tools for phenotyping the root system architecture and activity at the field-scale are needed. Water uptake is a major root activity and, under appropriate conditions, can be approximated by measuring changes in soil moisture from time-lapse geophysical surveys. We examine here the effect of heterogeneity in the θ-σ relationship using a crop phenotyping study for illustration. In this study, the θ-σ relationship was found to vary substantially across a field site. To account for this, we propose a range of local (plot specific) θ-σ models. We show that the large number of parameters required for these models can be estimated from baseline σ and θ measurements. Finally, we compare the use of global (field scale) and local (plot scale) models with respect to ranking varieties based on the estimated soil moisture content change

Use of small scale electrical resistivity tomography to identify soil-root interactions during deficit irrigation

Plant roots activity affect the exchanges of mass and energy between the soil and atmosphere. However, it is challenging to monitor the activity of the root-zone because roots are not visible from the soil surface, and root systems undergo spatial and temporal variations in response to internal and external conditions. Therefore, measurements of the activity of root systems are interesting to ecohydrologists in general, and are especially important for specific applications, such as irrigation water management. This study demonstrates the use of small scale three-dimensional (3-D) electrical resistivity tomography (ERT) to monitor the root-zone of orange trees irrigated by two different regimes: (i) full rate, in which 100% of the crop evapotranspiration (ETc) is provided; and (ii) partial root-zone drying (PRD), in which 50% of ETc is supplied to alternate sides of the tree. We performed time-lapse 3-D ERT measurements on these trees from 5 June to 24 September 2015, and compared the long-term and short-term changes before, during, and after irrigation events. Given the small changes in soil temperature and pore water electrical conductivity, we interpreted changes of soil electrical resistivity from 3-D ERT data as proxies for changes in soil water content. The ERT results are consistent with measurements of transpiration flux and soil temperature. The changes in electrical resistivity obtained from ERT measurements in this case study indicate that root water uptake (RWU) processes occur at the 0.1 m scale, and highlight the impact of different irrigation schemes. (C) 2017 Elsevier B.V. All rights reserved

Electrical resistivity imaging of the architecture of substream sediments

The modeling of fluvial systems is constrained by a lack of spatial information about the continuity and structure of streambed sediments. There are few methods for noninvasive characterization of streambeds. Invasive methods using wells and cores fail to provide detailed spatial information on the prevailing architecture and its continuity. Geophysical techniques play a pivotal role in providing spatial information on subsurface properties and processes across many other environments, and we have applied the use of one of those techniques to streambeds. We demonstrate, through two examples, how electrical resistivity imaging can be utilized for characterization of subchannel architecture. In the first example, electrodes installed in riparian boreholes and on the streambed are used for imaging, under the river bed, the thickness and continuity of a highly permeable alluvial gravel layer overlying chalk. In the second example, electrical resistivity images, determined from data collected using electrodes installed on the river bed, provide a constrained estimate of the sediment volume behind a log jam, vital to modeling biogeochemical exchange, which had eluded measurement using conventional drilling methods owing to the boulder content of the stream. The two examples show that noninvasive electrical resistivity imaging is possible in complex stream environments and provides valuable information about the subsurface architecture beneath the stream channels

Derivation of lowland riparian wetland deposit architecture using geophysical image analysis and interface detection

For groundwater-surface water interactions to be understood in complex wetland settings, the architecture of the underlying deposits requires investigation at a spatial resolution sufficient to characterize significant hydraulic pathways. Discrete intrusive sampling using conventional approaches provides insufficient sample density and can be difficult to deploy on soft ground. Here a noninvasive geophysical imaging approach combining three-dimensional electrical resistivity tomography (ERT) and the novel application of gradient and isosurface-based edge detectors is considered as a means of illuminating wetland deposit architecture. The performance of three edge detectors were compared and evaluated against ground truth data, using a lowland riparian wetland demonstration site. Isosurface-based methods correlated well with intrusive data and were useful for defining the geometries of key geological interfaces (i.e., peat/gravels and gravels/Chalk). The use of gradient detectors approach was unsuccessful, indicating that the assumption that the steepest resistivity gradient coincides with the associated geological interface can be incorrect. These findings are relevant to the application of this approach in settings with a broadly layered geology with strata of contrasting resistivities. In addition, ERT revealed substantial structures in the gravels related to the depositional environment (i.e., braided fluvial system) and a complex distribution of low-permeability putty Chalk at the bedrock surface—with implications for preferential flow and variable exchange between river and groundwater systems. These results demonstrate that a combined approach using ERT and edge detectors can provide valuable information to support targeted monitoring and inform hydrological modeling of wetlands