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Abstract The HIV reservoir consists of infected cells in which the HIV-1 genome persists as provirus despite effective antiretroviral therapy (ART). Studies exploring HIV cure therapies often measure intact proviral DNA levels, time to rebound after ART interruption, or ex vivo stimulation assays of latently infected cells. This study utilizes barcoded HIV to analyze the reservoir in humanized mice. Using bulk PCR and deep sequencing methodologies, we retrieve 890 viral RNA barcodes and 504 proviral barcodes linked to 15,305 integration sites at the single RNA or DNA molecule in vivo. We track viral genetic diversity throughout early infection, ART, and rebound. The proviral reservoir retains genetic diversity despite cellular clonal proliferation and viral seeding by rebounding virus. Non-proliferated cell clones are likely the result of elimination of proviruses associated with transcriptional activation and viremia. Elimination of proviruses associated with viremia is less prominent among proliferated cell clones. Proliferated, but not massively expanded, cell clones contribute to proviral expansion and viremia, suggesting they fuel viral persistence. This approach enables comprehensive assessment of viral levels, lineages, integration sites, clonal proliferation and proviral epigenetic patterns in vivo. These findings highlight complex reservoir dynamics and the role of proliferated cell clones in viral persistence. 

The increase of tree canopy cover due to woody plant encroachment and tree plantations modifies both carbon and water dynamics. The tradeoffs between ecosystem net primary productivity (NPP) and water use with increasing tree cover in different climate conditions, particularly under future climate scenarios, are not well understood. Within the climate transition zone of the southern Great Plains, USA, we used the Soil and Water Assessment Tool+ (SWAT+) to investigate the combined impacts of increasing tree cover and climate change on carbon and water dynamics in three watersheds representing semiarid, subhumid, and humid climates. Model simulations incorporated two land use modifications (Baseline: existing tree cover; Forest +: increasing evergreen tree cover), in conjunction with two climate change projections (the RCP45 and the RCP85), spanning two time periods (historic: 1991-2020; future: 2070-2099). With climate change, the subhumid and humid watersheds exhibited a greater increase in evapotranspiration (ET) and a corresponding reduction in runoff compared to the semi-arid watershed, while the semi-arid and subhumid watersheds encountered pronounced losses in water availability for streams (>200 mm/year) due to increasing tree cover and climate change. With every 1 % increase in tree cover, both NPP and water use efficiency were projected to increase in all three watersheds under both climate change scenarios, with the subhumid watershed demonstrating the largest increases (>0.16 Mg/ha/year and 170 %, respectively). Increasing tree cover within grasslands, either through woody plant expansion or afforestation, boosts ecosystem NPP, particularly in subhumid regions. Nevertheless, this comes with a notable decrease in water resources, a concern made worse by future climate change. While afforestation offers the potential for greater NPP, it also brings heightened water scarcity concerns, highlighting the importance of tailoring carbon sequestration strategies within specific regions to mitigate unintended repercussions on water availability. 

Quantifying the relationship of different grass functional groups to increasing woody plant cover is necessary to better understand the effects of woody plant encroachment on grasslands. This study explored biomass production responses of three perennial grass groups based on photosynthetic pathway and potential canopy height (C4 short-grasses, C3 midgrasses, and C4 midgrasses) to different percent canopy covers of the surrounding deciduous woody legume, honey mesquite (Prosopis glandulosa). Two methods were used to determine mesquite canopy cover, line-intercept and geospatial analysis of aerial images, and both were used to predict production of the three grass groups. Five years of grass production data were included in the mesquite cover/grass production regressions. Two yr had extreme grass production responses, one due to drought and the other to high rainfall. Of the 3 remaining yr, best-fit curves were negative linear for C4 short-grasses and C3 midgrasses and negative sigmoidal for C4 midgrasses using both cover determination methods, although slopes of the curves differed between cover determination methods. C4 midgrasses were more sensitive than the other grass groups to increasing mesquite cover. Loss of production potential when mesquite cover increased from 0% to 35% was 75.5%, 28.7%, and 23.2% for C4 midgrasses, C3 midgrasses, and C4 short-grasses, respectively. Moreover, production potential of C4 midgrasses under no mesquite cover was 3 and 6 times greater than C3 midgrasses or C4 short-grasses, respectively. Spatial settings of the different grass groups in relation to mesquite tree size and size of intercanopy areas provided indirect evidence that the process of mesquite encroachment in the past 50−100 yr may have negatively impacted C4 midgrasses more than the other grass groups. Results suggest that gains in grass production following mesquite treatment would be limited if the system has degraded to where only C3 midgrasses and C4 short-grasses dominate. 

Flowers are critical for successful reproduction and have been a major axis of diversification among angiosperms. As the frequency and severity of droughts are increasing globally, maintaining water balance of flowers is crucial for food security and other ecosystem services that rely on flowering. Yet remarkably little is known about the hydraulic strategies of flowers. We characterized hydraulic strategies of leaves and flowers of ten species by combining anatomical observations using light and scanning electron microscopy with measurements of hydraulic physiology (minimum diffusive conductance ( g min ) and pressure-volume (PV) curves parameters). We predicted that flowers would exhibit higher g min and higher hydraulic capacitance than leaves, which would be associated with differences in intervessel pit traits because of their different hydraulic strategies. We found that, compared to leaves, flowers exhibited: 1) higher g min , which was associated with higher hydraulic capacitance ( C T ); 2) lower variation in intervessel pit traits and differences in pit membrane area and pit aperture shape; and 3) independent coordination between intervessel pit traits and other anatomical and physiological traits; 4) independent evolution of most traits in flowers and leaves, resulting in 5) large differences in the regions of multivariate trait space occupied by flowers and leaves. Furthermore, across organs intervessel pit trait variation was orthogonal to variation in other anatomical and physiological traits, suggesting that pit traits represent an independent axis of variation that have as yet been unquantified in flowers. These results suggest that flowers, employ a drought-avoidant strategy of maintaining high capacitance that compensates for their higher g min to prevent excessive declines in water potentials. This drought-avoidant strategy may have relaxed selection on intervessel pit traits and allowed them to vary independently from other anatomical and physiological traits. Furthermore, the independent evolution of floral and foliar anatomical and physiological traits highlights their modular development despite being borne from the same apical meristem. 

Introduction Amyotrophic Lateral Sclerosis (ALS) is a paralyzing, multifactorial neurodegenerative disease with limited therapeutics and no known cure. The study goal was to determine which pathophysiological treatment targets appear most beneficial. Methods A big data approach was used to analyze high copy SOD1 G93A experimental data. The secondary data set comprised 227 published studies and 4,296 data points. Treatments were classified by pathophysiological target: apoptosis, axonal transport, cellular chemistry, energetics, neuron excitability, inflammation, oxidative stress, proteomics, or systemic function. Outcome assessment modalities included onset delay, health status (rotarod performance, body weight, grip strength), and survival duration. Pairwise statistical analysis (two-tailed t -test with Bonferroni correction) of normalized fold change (treatment/control) assessed significant differences in treatment efficacy. Cohen’s d quantified pathophysiological treatment category effect size compared to “all” (e.g., all pathophysiological treatment categories combined). Results Inflammation treatments were best at delaying onset ( d = 0.42, p > 0.05). Oxidative stress treatments were significantly better for prolonging survival duration ( d = 0.18, p < 0.05). Excitability treatments were significantly better for prolonging overall health status ( d = 0.22, p < 0.05). However, the absolute best pathophysiological treatment category for prolonging health status varied with disease progression: oxidative stress was best for pre-onset health ( d = 0.18, p > 0.05); excitability was best for prolonging function near onset ( d = 0.34, p < 0.05); inflammation was best for prolonging post-onset function ( d = 0.24, p > 0.05); and apoptosis was best for prolonging end-stage function ( d = 0.49, p > 0.05). Finally, combination treatments simultaneously targeting multiple pathophysiological categories (e.g., polytherapy) performed significantly ( p < 0.05) better than monotherapies at end-stage. Discussion In summary, the most effective pathophysiological treatments change as function of assessment modality and disease progression. Shifting pathophysiological treatment category efficacy with disease progression supports the homeostatic instability theory of ALS disease progression.