Nonresponse of native Cottonwood trees to water additions during summer drought

Studies have demonstrated that some riparian trees may switch their reliance on surface soil water (unsaturated or vadose zone) to groundwater (saturated zone) sources during the growing season in association with changes in moisture availability. A closely related question is: How do these trees respond to pulse increases in water availability in previously dry zones? We tested the whole-tree physiological response of 6 natural Populus genotypes to water additions during the peak of summer drought in northern Utah, USA. We found clear evidence that trees were insensitive to water additions to the surface soil that were twice the magnitude of whole-tree transpiration rates. Our results suggest that some cottonwoods may have little immediate transpiration of leaf conductance response to pulse soil moisture increases. This lack of response may be related to water-use strategy associated with regional climate patterns (i.e. genetic or environmental programming), cavitation recovery, or other physical determinants of water use such as depth to groundwater. Our data suggest that it is important to consider potential nonresponsiveness to changes in soil water availability when evaluating the impact of climate change on these important and productive ecosystems

Forest gene diversity is correlated with the composition and function of soil microbial communities

The growing field of community and ecosystem genetics indicates that plant genotype and genotypic variation are important for structuring communities and ecosystem processes. Little is known, however, regarding the effects of stand gene diversity on soil communities and processes under field conditions. Utilizing natural genetic variation occurring in Populus spp. hybrid zones, we tested the hypothesis that stand gene diversity structures soil microbial communities and influences soil nutrient pools. We found significant unimodal patterns relating gene diversity to soil microbial community composition, microbial exoenzyme activity of a carbon‐acquiring enzyme, and availability of soil nitrogen. Multivariate analyses indicate that this pattern is due to the correlation between gene diversity, plant secondary chemistry, and the composition of the microbial community that impacts the availability of soil nitrogen. Together, these data from a natural system indicate that stand gene diversity may affect soil microbial communities and soil processes in ways similar to species diversity (i.e., unimodal patterns). Our results further demonstrate that the effects of plant genetic diversity on other organisms may be mediated by plant functional trait variation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147191/1/pope0035.pd

Leaf-level physiology in four subalpine plants in tephra-impacted forests during drought

Ecological impacts of climate change in the Pacific Northwest may hinge on acclimation to drier summers, highlighting the importance of plant physiological studies in forests. Evaluating dominant forest plant species under old-growth and managed forest conditions is similarly important as timber harvest might change microclimates and alter drought effects on plants. We examined water potential and gas exchange rates of four dominant plant species in understories of subalpine forests of the Pacific Northwest region of the United States during 2015 - a year with drought conditions representative of future climate projections. We examined two conifer species (Abies amabilis Douglas ex J. Forbes and Tsuga heterophylla (Raf.) Sarg.) and two huckleberry species (Vaccinium membranaceum Douglas ex Torr. and Vaccinium ovalifolium Sm.) in old-growth and formerly clear-cut forests at two elevations. Contrary to expectations, we found no evidence of hydraulic stress, and there were no significant differences between old-growth and clear-cut stands, consistent with an edaphic buffering effect in this volcanic landscape. Variation in stem elongation rates among years also indicated the lack of a strong drought response in 2015. Water potential, photosynthesis, and stomatal conductance varied among species and among elevations. In combination, our results help constrain expected physiological activity of understory species in subalpine forests and emphasize the importance of the edaphic context (e.g., tephra deposits) in framing expectations for the responses to drought

Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1.

The endogenous metabolite itaconate has recently emerged as a regulator of macrophage function, but its precise mechanism of action remains poorly understood. Here we show that itaconate is required for the activation of the anti-inflammatory transcription factor Nrf2 (also known as NFE2L2) by lipopolysaccharide in mouse and human macrophages. We find that itaconate directly modifies proteins via alkylation of cysteine residues. Itaconate alkylates cysteine residues 151, 257, 288, 273 and 297 on the protein KEAP1, enabling Nrf2 to increase the expression of downstream genes with anti-oxidant and anti-inflammatory capacities. The activation of Nrf2 is required for the anti-inflammatory action of itaconate. We describe the use of a new cell-permeable itaconate derivative, 4-octyl itaconate, which is protective against lipopolysaccharide-induced lethality in vivo and decreases cytokine production. We show that type I interferons boost the expression of Irg1 (also known as Acod1) and itaconate production. Furthermore, we find that itaconate production limits the type I interferon response, indicating a negative feedback loop that involves interferons and itaconate. Our findings demonstrate that itaconate is a crucial anti-inflammatory metabolite that acts via Nrf2 to limit inflammation and modulate type I interferons

Degradation of GSPT1 causes TP53-independent cell death in leukemia whilst sparing normal hematopoietic stem cells

Targeted protein degradation is a rapidly advancing and expanding therapeutic approach. Drugs that degrade GSPT1 via the CRL4CRBN ubiquitin ligase are a new class of cancer therapy in active clinical development with evidence of activity against acute myeloid leukemia in early phase trials. However, other than activation of the integrated stress response, the downstream effects of GSPT1 degradation leading to cell death are largely undefined, and no murine models are available to study these agents. We identified the domains of GSPT1 essential for cell survival and show that GSPT1 degradation leads to impaired translation termination, activation of the integrated stress response pathway, and TP53-independent cell death. CRISPR-Cas9 screens implicated decreased translation initiation as protective to GSPT1 degradation, suggesting that cells with higher levels of translation are more susceptible to GSPT1 degradation. We defined two Crbn amino acids that prevent Gspt1 degradation in mice, generated a knock-in mouse with alteration of these residues, and demonstrated the efficacy of GSPT1-degrading drugs in vivo with relative sparing of numbers and function of long-term hematopoietic stem cells. Our results provide a mechanistic basis for the use of GSPT1 degraders for the treatment of cancer, including TP53-mutant AML

Current Opinions on Optimal Management of Basilar Artery Occlusion: After the BEST of BASICS Survey

Background The best management of basilar artery occlusion (BAO) remains uncertain. The BASICS (Basilar Artery International Cooperation Study) and the BEST (Basilar Artery Occlusion Endovascular Intervention Versus Standard Medical Treatment) trials reported neutral results. We sought to understand physicians’ approaches to BAOs and whether further BAO randomized controlled trials were warranted. Methods We conducted an online international survey from January to March 2022 to stroke neurologists and neurointerventionalists. Survey questions were designed to examine clinical and imaging parameters under which clinicians would offer (or rescind) a patient with BAO to endovascular therapy (EVT) or best medical management versus enrollment into a randomized clinical trial. Results Of >3002 invited participants, 1245 responded (41.4% response rate) from 73 countries, including 54.7% stroke neurologists and 43.6% neurointerventionalists. More than 95% of respondents would offer EVT to patients with BAO, albeit in various clinical circumstances. There were 70.0% of respondents who indicated that the BASICS and BEST trials did not change their practice. Only 22.1% of respondents would perform EVT according to anterior circulation occlusion criteria. The selection of patients for BAO EVT by clinical severity, timing, and imaging modality differed according to geography, specialty, and country income level. Over 80% of respondents agreed that further randomized clinical trials for BAO were warranted. Moreover, 45.6% of respondents indicated they would find it acceptable to enroll all trial‐eligible patients into the medical arm of a BAO trial, whereas 26.3% would not enroll. Conclusion Most stroke physicians continue to believe in the efficacy of EVT in selected patients with BAO in spite of BEST and BASICS. There is no consensus on which selection criteria to use, and few clinicians would use anterior circulation occlusion criteria for BAOs. Further randomized clinical trials for BAO are warranted

NeuroBench:A Framework for Benchmarking Neuromorphic Computing Algorithms and Systems

Neuromorphic computing shows promise for advancing computing efficiency and capabilities of AI applications using brain-inspired principles. However, the neuromorphic research field currently lacks standardized benchmarks, making it difficult to accurately measure technological advancements, compare performance with conventional methods, and identify promising future research directions. Prior neuromorphic computing benchmark efforts have not seen widespread adoption due to a lack of inclusive, actionable, and iterative benchmark design and guidelines. To address these shortcomings, we present NeuroBench: a benchmark framework for neuromorphic computing algorithms and systems. NeuroBench is a collaboratively-designed effort from an open community of nearly 100 co-authors across over 50 institutions in industry and academia, aiming to provide a representative structure for standardizing the evaluation of neuromorphic approaches. The NeuroBench framework introduces a common set of tools and systematic methodology for inclusive benchmark measurement, delivering an objective reference framework for quantifying neuromorphic approaches in both hardware-independent (algorithm track) and hardware-dependent (system track) settings. In this article, we present initial performance baselines across various model architectures on the algorithm track and outline the system track benchmark tasks and guidelines. NeuroBench is intended to continually expand its benchmarks and features to foster and track the progress made by the research community