Resilience and Resistance in Sagebrush Ecosystems Are Associated With Seasonal Soil Temperature and Water Availability

Invasion and dominance of exotic grasses and increased fire frequency threaten native ecosystems worldwide. In the Great Basin region of the western United States, woody and herbaceous fuel treatments are implemented to decrease the effects of wildfire and increase sagebrush (Artemisia spp.) ecosystem resilience to disturbance and resistance to exotic annual grasses. High cover of the exotic annual cheatgrass (Bromus tectorum) after treatments increases fine fuels, which in turn increases the risk of passing over a biotic threshold to a state of increased wildfire frequency and conversion to cheatgrass dominance. Sagebrush ecosystem resilience to wildfire and resistance to cheatgrass depend on climatic conditions and abundance of perennial herbaceous species that compete with cheatgrass. In this study, we used longer‐term data to evaluate the relationships among soil climate conditions, perennial herbaceous cover, and cheatgrass cover following fuel management treatments across the environmental gradients that characterize sagebrush ecosystems in the Great Basin. We examined the effects of woody and herbaceous fuel treatments on soil temperature, soil water availability (13–30 and 50 cm depths), and native and exotic plant cover on six sagebrush sites lacking piñon (Pinus spp.) or juniper (Juniperus spp.) tree expansion and 11 sagebrush sites with tree expansion. Both prescribed fire and mechanical treatments increased soil water availability on woodland sites and perennial herbaceous cover on some woodland and sagebrush sites. Prescribed fire also slightly increased soil temperatures and especially increased cheatgrass cover compared to no treatment and mechanical treatments on most sites. Non‐metric dimensional scaling ordination and decision tree partition analysis indicated that sites with warmer late springs and warmer and wetter falls had higher cover of cheatgrass. Sites with wetter winters and early springs (March–April) had higher cover of perennial herbs. Our findings suggest that site resistance to cheatgrass after fire and fuel control treatments decreases with a warmer and drier climate. This emphasizes the need for management actions to maintain and enhance perennial herb cover, such as implementing appropriate grazing management, and revegetating sites that have low abundance of perennial herbs in conjunction with fuel control treatments

Resilience and resistance in sagebrush ecosystems are associated with seasonal soil temperature and water availability

Invasion and dominance of exotic grasses and increased fire frequency threaten native ecosystems worldwide. In the Great Basin region of the western United States, woody and herbaceous fuel treatments are implemented to decrease the effects of wildfire and increase sagebrush (Artemisia spp.) ecosystem resilience to disturbance and resistance to exotic annual grasses. High cover of the exotic annual cheatgrass (Bromus tectorum) after treatments increases fine fuels, which in turn increases the risk of passing over a biotic threshold to a state of increased wildfire frequency and conversion to cheatgrass dominance. Sagebrush ecosystem resilience to wildfire and resistance to cheatgrass depend on climatic conditions and abundance of perennial herbaceous species that compete with cheatgrass. In this study, we used longer-term data to evaluate the relationships among soil climate conditions, perennial herbaceous cover, and cheatgrass cover following fuel management treatments across the environmental gradients that characterize sagebrush ecosystems in the Great Basin. We examined the effects of woody and herbaceous fuel treatments on soil temperature, soil water availability (13-30 and 50 cm depths), and native and exotic plant cover on six sagebrush sites lacking pinon (Pinus spp.) or juniper (Juniperus spp.) tree expansion and 11 sagebrush sites with tree expansion. Both prescribed fire and mechanical treatments increased soil water availability on woodland sites and perennial herbaceous cover on some woodland and sagebrush sites. Prescribed fire also slightly increased soil temperatures and especially increased cheatgrass cover compared to no treatment and mechanical treatments on most sites. Non-metric dimensional scaling ordination and decision tree partition analysis indicated that sites with warmer late springs and warmer and wetter falls had higher cover of cheatgrass. Sites with wetter winters and early springs (March-April) had higher cover of perennial herbs. Our findings suggest that site resistance to cheatgrass after fire and fuel control treatments decreases with a warmer and drier climate. This emphasizes the need for management actions to maintain and enhance perennial herb cover, such as implementing appropriate grazing management, and revegetating sites that have low abundance of perennial herbs in conjunction with fuel control treatments

Novel highly potent CD4bs bNAb with restricted pathway to HIV-1 escape

Purpose: Broadly HIV-1 neutralizing antibodies (bNAbs) can suppress viremia in humans and represent a novel approach for effective immunotherapy. However, bNAb monotherapy selects for antibody-resistant viral variants. Thus, we focused on the identification of new antibody combinations and/or novel bNAbs that restrict pathways of HIV-1 escape. Methods: We screened HIV-1 positive patients for their neutralizing capacities. Following, we performed single cell sorting and PCR of HIV-1 Env-reactive mature B cells of identified elite neutralizers. Found antibodies were tested for neutralization and binding capacities in vitro. Further, their antiviral activity was tested in an HIV-1 infected humanized mouse model. Results: Here we report the isolation of antibody 1–18, a VH1–46-encoded CD4 binding site (CD4bs) bNAb identified in an individual ranking among the top 1% neutralizers of 2,274 HIV-1-infected subjects. Tested on a 119-virus panel, 1–18 showed to be exceptionally broad and potent with a coverage of 97% and a mean IC50 of 0.048 lg/mL, exceeding the activity of most potent CD4bs bNAbs described to-date. A 2.4 Å cryo-EM structure of 1–18 bound to a native-like Env trimer revealed that it interacts with HIV-1 env similar to other CD4bs bNAbs, but includes additional contacts to the V3 loop of the adjacent protomer. Notably, in vitro, 1–18 maintained activity against viruses carrying mutations associated with escape from VRC01-class bNAbs. Further, its HIV-1 env wide escape profile differed critically from other CD4bs bNAbs. In humanized mice, monotherapy with 1–18 was sufficient to prevent the development of viral escape variants that rapidly emerged during treatment with other CD4bs bNAbs. Finally, 1–18 overcame classical HIV-1 mutations that are driven by VRC01-like bNAbs in vivo. Conclusion: 1–18 is a highly potent and broad bNAb that restricts escape and overcomes frequent CD4bs escape pathways, providing new options for bNAb combinations to prevent and treat HIV-1 infection

Restriction of HIV-1 Escape by a Highly Broad and Potent Neutralizing Antibody

Broadly neutralizing antibodies (bNAbs) represent a promising approach to prevent and treat HIV-1 infection. However, viral escape through mutation of the HIV-1 envelope glycoprotein (Env) limits clinical applications. Here we describe 1-18, a new V_H1-46-encoded CD4 binding site (CD4bs) bNAb with outstanding breadth (97%) and potency (GeoMean IC₅₀ = 0.048 μg/mL). Notably, 1-18 is not susceptible to typical CD4bs escape mutations and effectively overcomes HIV-1 resistance to other CD4bs bNAbs. Moreover, mutational antigenic profiling uncovered restricted pathways of HIV-1 escape. Of most promise for therapeutic use, even 1-18 alone fully suppressed viremia in HIV-1-infected humanized mice without selecting for resistant viral variants. A 2.5-Å cryo-EM structure of a 1-18-BG505_(SOSIP.664) Env complex revealed that these characteristics are likely facilitated by a heavy-chain insertion and increased inter-protomer contacts. The ability of 1-18 to effectively restrict HIV-1 escape pathways provides a new option to successfully prevent and treat HIV-1 infection

Field drift correction of proton resonance frequency shift temperature mapping with multichannel fast alternating nonselective free induction decay readouts

Purpose To demonstrate that proton resonance frequency shift MR thermometry (PRFS-MRT) acquisition with nonselective free induction decay (FID), combined with coil sensitivity profiles, allows spatially resolved B-0 drift-corrected thermometry. Methods Phantom experiments were performed at 1.5T and 3T. Acquisition of PRFS-MRT and FID were performed during MR-guided high-intensity focused ultrasound heating. The phase of the FIDs was used to estimate the change in angular frequency delta omega(drift) per coil element. Two correction methods were investigated: (1) using the average delta omega(drift) over all coil elements (0th-order) and (2) using coil sensitivity profiles for spatially resolved correction. Optical probes were used for independent temperature verification. In-vivo feasibility of the methods was evaluated in the leg of 1 healthy volunteer at 1.5T. Results In 30 minutes, B-0 drift led to an apparent temperature change of up to -18 degrees C and -98 degrees C at 1.5T and 3T, respectively. In the sonicated area, both corrections had a median error of 0.19 degrees C at 1.5T and -0.54 degrees C at 3T. At 1.5T, the measured median error with respect to the optical probe was -1.28 degrees C with the 0th-order correction and improved to 0.43 degrees C with the spatially resolved correction. In vivo, without correction the spatiotemporal median of the apparent temperature was at -4.3 degrees C and interquartile range (IQR) of 9.31 degrees C. The 0th-order correction had a median of 0.75 degrees C and IQR of 0.96 degrees C. The spatially resolved method had the lowest median at 0.33 degrees C and IQR of 0.80 degrees C. Conclusion FID phase information from individual receive coil elements allows spatially resolved B-0 drift correction in PRFS-based MRT

Model predictive control for MR-HIFU-mediated, uniform hyperthermia

Purpose: In local hyperthermia, precise temperature control throughout the entire target region is key for swift, safe, and effective treatment. In this article, we present a model predictive control (MPC) algorithm providing voxel-level temperature control in magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) and assess the improvement in performance it provides over the current state of the art. Materials and methods: The influence of model detail on the prediction quality and runtime of the controller is evaluated and a tissue mimicking phantom is characterized using the resulting model. Next, potential problems arising from modeling errors are evaluated in silico and in the characterized phantom. Finally, the controller?s performance is compared to the current state-of-the-art hyperthermia controller in side-by-side experiments. Results: Modeling diffusion by heat exchange between four neighboring voxels achieves high predictive performance and results in runtimes suited for real-time control. Erroneous model parameters deteriorate the MPC?s performance. Using models derived from thermometry data acquired during low powered test sonications, however, high control performance is achieved. In a direct comparison with the state-of-the-art hyperthermia controller, the MPC produces smaller tracking errors and tighter temperature distributions, both in a homogeneous target and near a localized heat sink. Conclusion: Using thermal models deduced from low-powered test sonications, the proposed MPC algorithm provides good performance in phantoms. In direct comparison to the current state-of-the-art hyperthermia controller, MPC performs better due to the more finely tuned heating patterns and therefore constitutes an important step toward stable, uniform hyperthermia