The objective of this study was to test the hypothesis that large cortical cell size (CCS) would improve drought tolerance by reducing root metabolic costs. Maize (Zea mays) lines contrasting in root ...CCS measured as cross-sectional area were grown under well-watered and water-stressed conditions in greenhouse mesocosms and in the field in the United States and Malawi. CCS varied among genotypes, ranging from 101 to 533 μm². In mesocosms, large CCS reduced respiration per unit of root length by 59%. Under water stress in mesocosms, lines with large CCS had between 21% and 27% deeper rooting (depth above which 95% of total root length is located in the soil profile), 50% greater stomatal conductance, 59% greater leaf CO₂ assimilation, and between 34% and 44% greater shoot biomass than lines with small CCS. Under water stress in the field, lines with large CCS had between 32% and 41% deeper rooting (depth above which 95% of total root length is located in the soil profile), 32% lighter stem water isotopic ratio of ¹⁸O to ¹⁶O signature, signifying deeper water capture, between 22% and 30% greater leaf relative water content, between 51% and 100% greater shoot biomass at flowering, and between 99% and 145% greater yield than lines with small cells. Our results are consistent with the hypothesis that large CCS improves drought tolerance by reducing the metabolic cost of soil exploration, enabling deeper soil exploration, greater water acquisition, and improved growth and yield under water stress. These results, coupled with the substantial genetic variation for CCS in diverse maize germplasm, suggest that CCS merits attention as a potential breeding target to improve the drought tolerance of maize and possibly other cereal crops.
The health threat posed by the novel coronavirus that caused the COVID-19 pandemic has particular implications for people with disabilities, including vulnerability to exposure and complications, and ...concerns about the role of ableism in access to treatment and medical rationing decisions. Shortages of necessary medical equipment to treat COVID-19 have prompted triage guidelines outlining the ways in which lifesaving equipment, such as mechanical ventilators and intensive care unit beds, may need to be rationed among affected individuals. In this article, we explore the realities of medical rationing, and various approaches to triage and prioritization. We discuss the psychology of ableism, perceptions about quality of life, social determinants of health, and how attitudes toward disability can affect rationing decisions and access to care. In addition to the grassroots advocacy and activism undertaken by the disability community, psychology is rich in its contributions to the role of attitudes, prejudice, and discriminatory behavior on the social fabric of society. We call on psychologists to advocate for social justice in pandemic preparedness, promote disability justice in health care settings, call for transparency and accountability in rationing approaches, and support policy changes for macro- and microallocation strategies to proactively reduce the need for rationing.
Public Significance Statement
This article explains barriers faced by disabled people in obtaining access to healthcare, including lifesaving treatment during the COVID-19 pandemic. Ableism can affect quality of life determinations and result in discriminatory behavior, unfairly costing disabled lives. Psychologists are positioned to advocate for social justice alongside the disability community by including disability in research, promoting meaningful inclusion in training and education, and leveraging roles in health care practice and leadership.
At the genus and species level, variation in root anatomy and architecture may interact to affect strategies of drought avoidance. To investigate this idea, root anatomy and architecture of the ...drought‐sensitive common bean (Phaseolus vulgaris) and drought‐adapted tepary bean (Phaseolus acutifolius) were analyzed in relation to water use under terminal drought. Intraspecific variation for metaxylem anatomy and axial conductance was found in the roots of both species. Genotypes with high‐conductance root metaxylem phenotypes acquired and transpired more water per unit leaf area, shoot mass, and root mass than genotypes with low‐conductance metaxylem phenotypes. Interspecific variation in root architecture and root depth was observed where P. acutifolius has a deeper distribution of root length than P. vulgaris. In the deeper‐rooted P. acutifolius, genotypes with high root conductance were better able to exploit deep soil water than genotypes with low root axial conductance. Contrastingly, in the shallower‐rooted P. vulgaris, genotypes with low root axial conductance had improved water status through conservation of soil moisture for sustained water capture later in the season. These results indicate that metaxylem morphology interacts with root system depth to determine a strategy of drought avoidance and illustrate synergism among architectural and anatomical phenotypes for root function.
The dietary compound capsaicin is responsible for the “hot and spicy” taste of chili peppers and pepper extracts. It is a valuable pharmacological agent with several therapeutic applications in ...controlling pain and inflammation. Emerging studies show that it displays potent anti-tumor activity in several human cancers. On a more basic research level, capsaicin has been used as a ligand to activate several types of ion-channel receptors. The pharmacological activity of capsaicin-like compounds is dependent on several factors like the dose, the route of administration and most importantly on its concentration at target tissues. The present review describes the current knowledge involving the metabolism and bioavailability of capsaicinoids in rodents and humans. Novel drug delivery strategies used to improve the bioavailability and therapeutic index of capsaicin are discussed in detail. The generation of novel capsaicin-mimetics and improved drug delivery methods will foster the hope of innovative applications of capsaicin in human disease.
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The use of flavored e-liquids in electronic nicotine delivery systems (ENDS) has become very popular in recent years, but effects of these products have not been well characterized outside the lung. ...In this study, acute exposure to the popular flavoring vanillin (VAN) was performed on human proximal tubule (HK-2) kidney cells. Cells were exposed to 0–1000 μM VAN for 24 or 48 h and cellular stress responses were determined. Mitochondrial viability using MTT assay showed a significant decrease between the control and 1000 μM group by 48 h. Seahorse XFp analysis showed significantly increased basal respiration, ATP production, and proton leak after 24 h exposure. By 48 h exposure, these parameters remained significantly increased in addition to non-mitochondrial respiration and maximal respiration. Glycolytic activity after 24 h exposure showed significant decreases in glycolysis, glycolytic capacity, glycolytic reserve, and non-glycolytic acidification. The autophagy markers microtubule-associated protein 1A/1B light chain 3 (LC3B–I and LC3B-II) were probed via western blotting. The ratio of LC3B-II/LC3B–I was significantly increased after 24 h exposure to VAN, but by 48 h this ratio significantly decreased. The mitophagy marker PINK1 showed an increasing trend at 24 h, and its downstream target Parkin was significantly increased between the control and 750 μM group only. Finally, the oxidative stress marker 4-HNE was significantly decreased after 48 h exposure to VAN. These results indicate that acute exposure to VAN in the kidney HK-2 model can induce energy and autophagic changes within the cell.
•E-Liquid flavoring agent vanillin was cytotoxic at 24 h to renal HK-2 cells.•Vanillin (1000 μM) increased the autophagy biomarker LC3BII/I ratio at 24 h.•Vanillin impaired glycolysis and glycolytic capacity.•Vanillin (750 and 1000 μM) reduced the oxidative stress marker 4-HNE at 48 h.•Vanillin increased mitophagy marker PINK exclusively at 24 h.
The National Lung Screening Trial (NLST) has provided compelling evidence of the efficacy of lung cancer screening using low-dose helical computed tomography (LDCT) to reduce lung cancer mortality. ...The NLST randomized 53,454 older current or former heavy smokers to receive LDCT or chest radiography (CXR) for three annual screens. Participants were observed for a median of 6.5 years for outcomes. Vital status was available in more than 95% of participants. LDCT was positive in 24.2% of screens, compared with 6.9% of CXRs; more than 95% of all positive LDCT screens were not associated with lung cancer. LDCT detected more than twice the number of early-stage lung cancers and resulted in a stage shift from advanced to early-stage disease. Complications of LDCT screening were minimal. Lung cancer-specific mortality was reduced by 20% relative to CXR; all-cause mortality was reduced by 6.7%. The major harms of LDCT are radiation exposure, high false-positive rates, and the potential for overdiagnosis. This review discusses the risks and benefits of LDCT screening as well as an approach to LDCT implementation that incorporates systematic screening practice with smoking cessation programs and offers opportunities for better determination of appropriate risk cohorts for screening and for better diagnostic prediction of lung cancer in the setting of screen-detected nodules. The challenges of implementation are considered for screening programs, for primary care clinicians, and across socioeconomic strata. Considerations for future research to complement imaging-based screening to reduce the burden of lung cancer are discussed.
To test the hypothesis that multiple integrated root phenotypes would co-optimize drought tolerance, we phenotyped the root anatomy and architecture of 400 mature maize (
) genotypes under ...well-watered and water-stressed conditions in the field. We found substantial variation in all 23 root phenes measured. A phenotypic bulked segregant analysis revealed that bulks representing the best and worst performers in the field displayed distinct root phenotypes. In contrast to the worst bulk, the root phenotype of the best bulk under drought consisted of greater cortical aerenchyma formation, more numerous and narrower metaxylem vessels, and thicker nodal roots. Partition-against-medians clustering revealed several clusters of unique root phenotypes related to plant performance under water stress. Clusters associated with improved drought tolerance consisted of phene states that likely enable greater soil exploration by reallocating internal resources to greater root construction (increased aerenchyma content, larger cortical cells, fewer cortical cell files), restrict uptake of water to conserve soil moisture (reduced hydraulic conductance, narrow metaxylem vessels), and improve penetrability of hard, dry soils (thick roots with a larger proportion of stele, and smaller distal cortical cells). We propose that the most drought-tolerant-integrated phenotypes merit consideration as breeding ideotypes.
Flavored e-liquid use has become popular among e-cigarette users recently, but the effects of such products outside the lung are not well characterized. In this work, acute exposure to the popular ...flavoring cinnamaldehyde (CIN) was performed on human proximal tubule (HK-2) kidney cells. Cells were exposed to 0–100 µM CIN for 24–48 h and cellular stress responses were assessed. Mitochondrial viability via MTT assay was significantly decreased at 20 µM for 24 and 48 h exposure. Seahorse XFp analysis showed significantly decreased mitochondrial energy output at 20 µM by 24 h exposure, in addition to significantly reduced ATP Synthase expression. Seahorse analysis also revealed significantly decreased glycolytic function at 20 µM by 24 h exposure, suggesting inability of glycolytic processes to compensate for reduced mitochondrial energy output. Cleaved caspase-3 expression, a mediator of apoptosis, was significantly increased at the 24 h mark. C/EBP homologous protein (CHOP) expression, a mediator of ER-induced apoptosis, was induced by 48 h and subsequently lost at the highest concentration of 100 µM. This decrease was accompanied by a simultaneous decrease in its downstream target cleaved caspase-3 at the 48 h mark. The autophagy marker microtubule-associated protein 1 A/1B light chain 3 (LC3B-I and LC3B-II) expression was significantly increased at 100 µM by 24 h. Autophagy-related 7 (ATG7) protein and mitophagy-related proteins PTEN-induced putative kinase 1 (PINK1) and PARKIN expression were significantly reduced at 24 and 48 h exposure. These results indicate acute exposure to CIN in the kidney HK-2 model induces mitochondrial dysfunction and cellular stress responses.
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SARS-CoV-2 has infected over 340 million people, prompting therapeutic research. While genetic studies can highlight potential drug targets, understanding the heritability of SARS-CoV-2 ...susceptibility and COVID-19 severity can contextualize their results. To date, loci from meta-analyses explain 1.2% and 5.8% of variation in susceptibility and severity respectively. Here we estimate the importance of shared environment and additive genetic variation to SARS-CoV-2 susceptibility and COVID-19 severity using pedigree data, PCR results, and hospitalization information. The relative importance of genetics and shared environment for susceptibility shifted during the study, with heritability ranging from 33% (95% CI: 20%-46%) to 70% (95% CI: 63%-74%). Heritability was greater for days hospitalized with COVID-19 (41%, 95% CI: 33%-57%) compared to shared environment (33%, 95% CI: 24%-38%). While our estimates suggest these genetic architectures are not fully understood, the shift in susceptibility estimates highlights the challenge of estimation during a pandemic, given environmental fluctuations and vaccine introduction.
Nicotinic acetylcholine receptors (nAChRs) constitute a heterogeneous family of ion channels that mediate fast synaptic transmission in neurons. They have also been found on non-neuronal cells such ...as bronchial epithelium and keratinocytes, underscoring the idea that they have functions well beyond neurotransmission. Components of cigarette smoke, including nicotine and NNK 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, are agonists of nAChRs. Given the association of tobacco use with several diseases, the non-neuronal nAChR signaling pathway has considerable implications for cancer and cardiovascular disease. Recent studies have shown that α7 is the main nAChR subunit that mediates the proliferative effects of nicotine in cancer cells. As a result, α7 nAChR might be a valuable molecular target for therapy of cancers such as lung cancer and mesothelioma. Future studies involving the design of nAChR antagonists with improved selectivity might identify novel strategies for the treatment of tobacco-related cancers. Here we review the cellular roles of non-neuronal nAChRs, including regulation of cell proliferation, angiogenesis, apoptosis, migration, invasion and secretion.
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