Less Fuel for the Next Fire? Short-Interval Fire Delays Forest Recovery and Interacting Drivers Amplify Effects

As 21st-century climate and disturbance dynamics depart from historic baselines, ecosystem resilience is uncertain. Multiple drivers are changing simultaneously, and interactions among drivers could amplify ecosystem vulnerability to change. Subalpine forests in Greater Yellowstone (Northern Rocky Mountains, USA) were historically resilient to infrequent (100–300 year), severe fire. We sampled paired short-interval (\u3c30-year) and long-interval (\u3e125-year) post-fire plots most recently burned between 1988 and 2018 to address two questions: (1) How do short-interval fire, climate, topography, and distance to unburned live forest edge interact to affect post-fire forest regeneration? (2) How do forest biomass and fuels vary following short-interval versus long-interval severe fires? Mean post-fire live tree stem density was an order of magnitude lower following short-interval versus long-interval fires (3240 vs. 28,741 stems ha-1, respectively). Differences between paired plots were amplified at longer distances to live forest edge. Surprisingly, warmer–drier climate was associated with higher seedling densities even after short-interval fire, likely relating to regional variation in serotiny of lodgepole pine (Pinus contorta var. latifolia). Unlike conifers, density of aspen (Populus tremuloides), a deciduous resprouter, increased with short-interval versus long-interval fires (mean 384 vs. 62 stems ha-1, respectively). Live biomass and canopy fuels remained low nearly 30 years after short-interval fire, in contrast with rapid recovery after long-interval fire, suggesting that future burn severity may be reduced for several decades following reburns. Short-interval plots also had half as much dead woody biomass compared with long-interval plots (60 vs. 121 Mg ha-1), primarily due to the absence of large snags. Our results suggest differences in tree regeneration following short-interval versus long-interval fires will be especially pronounced where serotiny was high historically. Propagule limitation will also interact with short-interval fires to diminish tree regeneration but lessen subsequent burn severity. Amplifying driver interactions are likely to threaten forest resilience under expected trajectories of a future fire

CD81 Is Essential for the Re-entry of Hematopoietic Stem Cells to Quiescence following Stress-Induced Proliferation Via Deactivation of the Akt Pathway

A protein that is thought to orchestrate the distribution of other signaling molecules on the cell membrane, CD81, is critical to maintaining the functional integrity of hematopoietic stem cells during their regeneration

Fisetin for COVID- 19 in skilled nursing facilities: Senolytic trials in the COVID era

The burden of senescent cells (SnCs), which do not divide but are metabolically active and resistant to death by apoptosis, is increased in older adults and those with chronic diseases. These individuals are also at the greatest risk for morbidity and mortality from SARS- CoV- 2 infection. SARS- CoV- 2 complications include cytokine storm and multiorgan failure mediated by the same factors as often produced by SnCs through their senescence- associated secretory phenotype (SASP). The SASP can be amplified by infection- related pathogen- associated molecular profile factors. Senolytic agents, such as Fisetin, selectively eliminate SnCs and delay, prevent, or alleviate multiple disorders in aged experimental animals and animal models of human chronic diseases, including obesity, diabetes, and respiratory diseases. Senolytics are now in clinical trials for multiple conditions linked to SnCs, including frailty; obesity/diabetes; osteoporosis; and cardiovascular, kidney, and lung diseases, which are also risk factors for SARS- CoV- 2 morbidity and mortality. A clinical trial is underway to test if senolytics decrease SARS- CoV- 2 progression and morbidity in hospitalized older adults. We describe here a National Institutes of Health- funded, multicenter, placebo- controlled clinical trial of Fisetin for older adult skilled nursing facility (SNF) residents who have been, or become, SARS- CoV- 2 rtPCR- positive, including the rationale for targeting fundamental aging mechanisms in such patients. We consider logistic challenges of conducting trials in long- term care settings in the SARS- CoV- 2 era, including restricted access, consent procedures, methods for obtaining biospecimens and clinical data, staffing, investigational product administration issues, and potential solutions for these challenges. We propose developing a national network of SNFs engaged in interventional clinical trials.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/171033/1/jgs17416_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171033/2/jgs17416-sup-0001-Supinfo.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171033/3/jgs17416.pd

Regional-Specific Effects of Ovarian Hormone Loss on Synaptic Plasticity in Adult Human APOE Targeted Replacement Mice

The human apolipoprotein ε4 allele (APOE4) has been implicated as one of the strongest genetic risk factors associated with Alzheimer’s disease (AD) and in influencing normal cognitive functioning. Previous studies have demonstrated that mice expressing human apoE4 display deficits in behavioral and neurophysiological outcomes compared to those with apoE3. Ovarian hormones have also been shown to be important in modulating synaptic processes underlying cognitive function, yet little is known about how their effects are influenced by apoE. In the current study, female adult human APOE targeted replacement (TR) mice were utilized to examine the effects of human APOE genotype and long-term ovarian hormone loss on synaptic plasticity in limbic regions by measuring dendritic spine density and electrophysiological function. No significant genotype differences were observed on any outcomes within intact mice. However, there was a significant main effect of genotype on total spine density in apical dendrites in the hippocampus, with post-hoc t-tests revealing a significant reduction in spine density in apoE3 ovariectomized (OVX) mice compared to sham operated mice. There was also a significant main effect of OVX on the magnitude of LTP, with post-hoc t-tests revealing a decrease in apoE3 OVX mice relative to sham. In contrast, apoE4 OVX mice showed increased synaptic activity relative to sham. In the lateral amygdala, there was a significant increase in total spine density in apoE4 OVX mice relative to sham. This increase in spine density was consistent with a significant increase in spontaneous excitatory activity in apoE4 OVX mice. These findings suggest that ovarian hormones differentially modulate synaptic integrity in an apoE-dependent manner within brain regions that are susceptible to neurophysiological dysfunction associated with AD