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

Efficient multiscale imaging of subsurface resistivity with uncertainty quantification using ensemble Kalman inversion

Electrical resistivity tomography (ERT) is widely used to image the Earth's subsurface and has proven to be an extremely useful tool in application to hydrological problems. Conventional smoothness-constrained inversion of ERT data is efficient and robust, and consequently very popular. However, it does not resolve well sharp interfaces of a resistivity field and tends to reduce and smooth resistivity variations. These issues can be problematic in a range of hydrological or near-surface studies, for example mapping regolith-bedrock interfaces. While fully Bayesian approaches, such as those using Markov chain Monte Carlo sampling, can address the above issues, their very high computation cost makes them impractical for many applications. Ensemble Kalman inversion (EKI) offers a computationally efficient alternative by approximating the Bayesian posterior distribution in a derivative-free manner, which means only a relatively small number of 'black-box' model runs are required. Although common limitations for ensemble Kalman filter-type methods apply to EKI, it is both efficient and generally captures uncertainty patterns correctly. We propose the use of a new EKI-based framework for ERT which estimates a resistivity model and its uncertainty at a modest computational cost. Our EKI framework uses a level-set parametrization of the unknown resistivity to allow efficient estimation of discontinuous resistivity fields. Instead of estimating level-set parameters directly, we introduce a second step to characterize the spatial variability of the resistivity field and infer length scale hyperparameters directly. We demonstrate these features by applying the method to a series of synthetic and field examples. We also benchmark our results by comparing them to those obtained from standard smoothness-constrained inversion. Resultant resistivity images from EKI successfully capture arbitrarily shaped interfaces between resistivity zones and the inverted resistivities are close to the true values in synthetic cases. We highlight its readiness and applicability to similar problems in geophysics

Deep roots and soil structure

In this opinion article we examine the relationship between penetrometer resistance and soil depth in the field. Assuming that root growth is inhibited at penetrometer resistances > 2.5 MPa, we conclude that in most circumstances the increases in penetrometer resistance with depth are sufficiently great to confine most deep roots to elongating in existing structural pores. We suggest that deep rooting is more likely related to the interaction between root architecture and soil structure than it is to the ability of a root to deform strong soil. Although the ability of roots to deform strong soil is an important trait, we propose it is more closely related to root exploration of surface layers than deep rooting

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

A novel grass hybrid to reduce flood generation in temperate regions

We report on the evaluation of a novel grass hybrid that provides efficient forage production and could help mitigate flooding. Perennial ryegrass (Lolium perenne) is the grass species of choice for most farmers, but lacks resilience against extremes of climate. We hybridised L. perenne onto a closely related and more stress-resistant grass species, meadow fescue Festuca pratensis. We demonstrate that the L. perenne × F. pratensis cultivar can reduce runoff during the events by 51% compared to a leading UK nationally recommended L. perenne cultivar and by 43% compared to F. pratensis over a two year field experiment. We present evidence that the reduced runoff from this Festulolium cultivar was due to intense initial root growth followed by rapid senescence, especially at depth. Hybrid grasses of this type show potential for reducing the likelihood of flooding, whilst providing food production under conditions of changing climate