Vegetation processes are fundamentally limited by nutrient and water availability, the uptake of which is mediated by plant roots in terrestrial ecosystems. While tropical forests play a central role ...in global water, carbon, and nutrient cycling, we know very little about tradeoffs and synergies in root traits that respond to resource scarcity. Tropical trees face a unique set of resource limitations, with rock-derived nutrients and moisture seasonality governing many ecosystem functions, and nutrient versus water availability often separated spatially and temporally. Root traits that characterize biomass, depth distributions, production and phenology, morphology, physiology, chemistry, and symbiotic relationships can be predictive of plants’ capacities to access and acquire nutrients and water, with links to aboveground processes like transpiration, wood productivity, and leaf phenology. In this review, we identify an emerging trend in the literature that tropical fine root biomass and production in surface soils are greatest in infertile or sufficiently moist soils. We also identify interesting paradoxes in tropical forest root responses to changing resources that merit further exploration. For example, specific root length, which typically increases under resource scarcity to expand the volume of soil explored, instead can increase with greater base cation availability, both across natural tropical forest gradients and in fertilization experiments. Also, nutrient additions, rather than reducing mycorrhizal colonization of fine roots as might be expected, increased colonization rates under scenarios of water scarcity in some forests. Efforts to include fine root traits and functions in vegetation models have grown more sophisticated over time, yet there is a disconnect between the emphasis in models characterizing nutrient and water uptake rates and carbon costs versus the emphasis in field experiments on measuring root biomass, production, and morphology in response to changes in resource availability. Closer integration of field and modeling efforts could connect mechanistic investigation of fine-root dynamics to ecosystem-scale understanding of nutrient and water cycling, allowing us to better predict tropical forest-climate feedbacks.
Transcriptional mediators of cell stress pathways, including HIF1α, ATF4, and p53, are key to normal development and play critical roles in disease, including ischemia and cancer. Despite their ...importance, mechanisms by which pathways mediated by these transcription factors interact with one another are not fully understood. In addressing the controversial role of HIF1α in cardiomyocytes (CMs) during heart development, we discovered a mid-gestational requirement for HIF1α for proliferation of hypoxic CMs, involving metabolic switching and a complex interplay among HIF1α, ATF4, and p53. Loss of HIF1α resulted in activation of ATF4 and p53, the latter inhibiting CM proliferation. Bioinformatic and biochemical analyses revealed unexpected mechanisms by which HIF1α intersects with ATF4 and p53 pathways. Our results highlight previously undescribed roles of HIF1α and interactions among major cell stress pathways that could be targeted to enhance proliferation of CMs in ischemia and may have relevance to other diseases, including cancer.
•HIF1α is required for proliferation of a subset of cardiomyocytes at mid-gestation•HIF1α targets genes regulating both energy metabolism and the cell cycle•HIF1α promotes Mif expression to prevent p53 activation•HIF1α represses ATF4 signaling
Guimarães-Camboa et al. demonstrate that before completion of cardiac angiogenesis, subsets of highly proliferative fetal cardiomyocytes display nuclear accumulation of HIF1α. Cardiac ablation of HIF1α and subsequent mechanistic analyses suggest that this transcription factor promotes proliferation of hypoxic fetal cardiomyocytes by regulating multiple cellular functions, including ATF4 and p53 signaling.
Much of our understanding of the regulatory mechanisms governing the cell cycle in mammals has relied heavily on methods that measure the aggregate state of a population of cells. While instrumental ...in shaping our current understanding of cell proliferation, these approaches mask the genetic signatures of rare subpopulations such as quiescent (G
) and very slowly dividing (SD) cells. Results described in this study and those of others using single-cell analysis reveal that even in clonally derived immortalized cancer cells, ∼1-5% of cells can exhibit G
and SD phenotypes. Therefore to enable the study of these rare cell phenotypes we established an integrated molecular, computational, and imaging approach to track, isolate, and genetically perturb single cells as they proliferate. A genetically encoded cell-cycle reporter (K67
-FUCCI) was used to track single cells as they traversed the cell cycle. A set of R-scripts were written to quantify K67
-FUCCI over time. To enable the further study G
and SD phenotypes, we retrofitted a live cell imaging system with a micromanipulator to enable single-cell targeting for functional validation studies. Single-cell analysis revealed HT1080 and MCF7 cells had a doubling time of ∼24 and ∼48 h, respectively, with high duration variability in G
and G
phases. Direct single-cell microinjection of mRNA encoding (GFP) achieves detectable GFP fluorescence within ∼5 h in both cell types. These findings coupled with the possibility of targeting several hundreds of single cells improves throughput and sensitivity over conventional methods to study rare cell subpopulations.
Quality improvement (QI) efforts can improve guideline-recommended asthma care processes in the pediatric office setting. We sought to assess whether practice participation in an asthma QI ...collaborative was associated with decreased asthma-related emergency department (ED) visits.
A statewide network of practices participated in a pediatric asthma QI collaborative from 2015 to 2016. We evaluated asthma-related ED visit rates per 100 child-years for children ages 3 to 21 years with asthma, using the state's all-payer claims database. We used a difference-in-differences approach, with mixed-effects negative binomial regression models to control for practice and patient covariates. Our main analysis measured the outcome before (2014) and after (2017) the QI collaborative at fully participating and control practices. Additional analyses assessed (1) associations during the intervention period (2016) and (2) associations including practices partially participating in QI collaborative activities.
In the postintervention year (2017), participating practices' (
= 20) asthma-related ED visit rate decreased by 5.8 per 100 child-years, compared to an increase of 1.8 per 100 child-years for control practices (
= 15; difference in differences = -7.3;
= .002). Within the intervention year (2016), we found no statistically significant differences in asthma-related ED visit rates compared to controls (difference in differences = -4.3;
= .17). The analysis including partially participating practices yielded similar results and inferences to our main analysis.
Participation in an asthma-focused QI collaborative was associated with decreased asthma-related ED visit rates. For those considering implementing this type of QI collaborative, our findings indicate that it takes time to see measurable improvements in ED visit rates. Further study is warranted regarding QI elements contributing to success for partial participants.
To perform a systematic review of biomechanical and clinical studies to determine whether the iliopsoas is a femoral head stabilizer.
A systematic review was conducted using Preferred Reporting Items ...for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Inclusion criteria were any human clinical (Levels I-IV evidence) or laboratory studies that investigated the role of the iliopsoas as a stabilizer of the hip. Exclusion criteria included studies that investigated patients undergoing spine surgery or those with a total hip arthroplasty or hip hemiarthroplasty. Study methodologic quality for clinical-outcomes studies were analyzed using the Modified Coleman Methodology Score. Because of the heterogeneity in the participants and interventions, no quantitative assimilative meta-analysis was performed.
Eight articles were analyzed (3 biomechanical 35 cadavers and 18 healthy subjects; 5 clinical outcomes studies 537 subjects, 207 arthroscopic iliopsoas tenotomies). Two in vivo biomechanical studies identified the iliopsoas as an anterior hip stabilizer. One cadaveric study identified the iliopsoas as a femoral head stabilizer at 0o-15o of hip flexion. Two clinical studies demonstrated the role of the iliopsoas as a dynamic hip stabilizer, particularly in patients with increased femoral version (greater than 15˚-25˚). Two studies reported cases of atraumatic anterior hip dislocations after arthroscopic iliopsoas tenotomies.
Evidence from biomechanical and clinical studies may suggest that the iliopsoas is a dynamic anterior femoral head stabilizer.
Level IV, systematic review of Level III and IV plus biomechanical studies.