Empirical and anecdotal evidence has associated stress with accelerated hair greying (formation of unpigmented hairs)
, but so far there has been little scientific validation of this link. Here we ...report that, in mice, acute stress leads to hair greying through the fast depletion of melanocyte stem cells. Using a combination of adrenalectomy, denervation, chemogenetics
, cell ablation and knockout of the adrenergic receptor specifically in melanocyte stem cells, we find that the stress-induced loss of melanocyte stem cells is independent of immune attack or adrenal stress hormones. Instead, hair greying results from activation of the sympathetic nerves that innervate the melanocyte stem-cell niche. Under conditions of stress, the activation of these sympathetic nerves leads to burst release of the neurotransmitter noradrenaline (also known as norepinephrine). This causes quiescent melanocyte stem cells to proliferate rapidly, and is followed by their differentiation, migration and permanent depletion from the niche. Transient suppression of the proliferation of melanocyte stem cells prevents stress-induced hair greying. Our study demonstrates that neuronal activity that is induced by acute stress can drive a rapid and permanent loss of somatic stem cells, and illustrates an example in which the maintenance of somatic stem cells is directly influenced by the overall physiological state of the organism.
The prevalence of chronic skin wounds in humans is high, and treatment is often complicated by the presence of pathogenic bacteria. Therefore, safe and innovative treatments to reduce the bacterial ...load in cutaneous wounds are needed. Mesenchymal stromal cells (MSC) are known to provide paracrine signals that act on resident skin cells to promote wound healing, but their potential antibacterial activities are not well described. The present study was designed to examine the antibacterial properties of MSC from horses, as this animal model offers a readily translatable model for MSC therapies in humans. Specifically, we aimed to (i) evaluate the in vitro effects of equine MSC on the growth of representative gram-negative and gram-positive bacterial species commonly found in skin wounds and (ii) define the mechanisms by which MSC inhibit bacterial growth.
MSC were isolated from the peripheral blood of healthy horses. Gram-negative E. coli and gram-positive S. aureus were cultured in the presence of MSC and MSC conditioned medium (CM), containing all factors secreted by MSC. Bacterial growth was measured by plating bacteria and counting viable colonies or by reading the absorbance of bacterial cultures. Bacterial membrane damage was detected by incorporation of N-phenyl-1-naphthylamine (NPN). Antimicrobial peptide (AMP) gene and protein expression by equine MSC were determined by RT-PCR and Western blot analysis, respectively. Blocking of AMP activity of MSC CM was achieved using AMP-specific antibodies.
We found that equine MSC and MSC CM inhibit the growth of E. coli and S. aureus, and that MSC CM depolarizes the cell membranes of these bacteria. In addition, we found that equine MSC CM contains AMPs, and blocking these AMPs with antibodies reduces the effects of MSC CM on bacteria.
Our results demonstrate that equine MSC inhibit bacterial growth and secrete factors that compromise the membrane integrity of bacteria commonly found in skin wounds. We also identified four specific AMPs produced by equine MSC. The secretion of AMPs may contribute to the value of MSC as a therapy for cutaneous wounds in both horses and humans.
Epigenetic fun(ction) in the sun He, Megan; Raftrey, Brian; Hsu, Ya-Chieh
Developmental cell,
09/2021, Letnik:
56, Številka:
18
Journal Article
Recenzirano
Odprti dostop
Tanning, or increased epidermal pigmentation, protects organisms from ultraviolet radiation (UV)-induced damages. In this issue of Development Cell, Li et al. demonstrate a key role for a chromatin ...regulator—the Polycomb complex—in epidermal stem cells (EpSCs) in mediating UV-induced tanning responses and epidermal pigmentation.
Tanning, or increased epidermal pigmentation, protects organisms from ultraviolet radiation (UV)-induced damages. In this issue of Development Cell, Li et al. demonstrate a key role for a chromatin regulator—the Polycomb complex—in epidermal stem cells (EpSCs) in mediating UV-induced tanning responses and epidermal pigmentation.
Laboratory and field observations of organic compound emissions reveal a previously unknown source of reactive pollution precursors.
Asphalt-based materials are abundant and a major nontraditional ...source of reactive organic compounds in urban areas, but their emissions are essentially absent from inventories. At typical temperature and solar conditions simulating different life cycle stages (i.e., storage, paving, and use), common road and roofing asphalts produced complex mixtures of organic compounds, including hazardous pollutants. Chemically speciated emission factors using high-resolution mass spectrometry reveal considerable oxygen and reduced sulfur content and the predominance of aromatic (~30%) and intermediate/semivolatile organic compounds (~85%), which together produce high overall secondary organic aerosol (SOA) yields. Emissions rose markedly with moderate solar exposure (e.g., 300% for road asphalt) with greater SOA yields and sustained SOA production. On urban scales, annual estimates of asphalt-related SOA precursor emissions exceed those from motor vehicles and substantially increase existing estimates from noncombustion sources. Yet, their emissions and impacts will be concentrated during the hottest, sunniest periods with greater photochemical activity and SOA production.
Highlights • Equine MSCs secrete PAI-1 and tenascin-C. • PAI-1 and tenascin-C secreted by equine MSCs promote fibroblast migration in vitro. • PAI-1 and tenascin-C secreted by equine MSCs decrease ...fibroblast adhesion in vitro. • Equine MSC-derived tenascin-C reduces anisotropy of fibroblast actin in vitro. • PAI-1 and tenascin-C secreted by equine MSCs improve wound closure in vivo.
Stress is a risk factor for many skin conditions, but the cellular and molecular mechanisms of its impacts have only begun to be revealed. In mice, acute stress induces loss of melanocyte stem cells ...(MeSCs) and premature hair greying. Our previous work demonstrated that the loss of MeSCs upon acute stress is caused by the hyperactivation of the sympathetic nervous system. Stress also induces the secretion of stress hormones from the hypothalamic–pituitary–adrenal (HPA) axis; however, whether stress hormones are involved in the hair greying process has not been fully examined. In particular, the adrenocorticotropic hormone (ACTH) is released from the pituitary glands upon stress. ACTH is a ligand for the melanocortin 1 receptor (MC1R), which plays critical roles in regulating MeSC migration and skin pigmentation. We investigated whether the MC1R pathway is required for the stress‐induced hair greying. We confirmed that MC1R is the major melanocortin receptor expressed in MeSCs. However, induction of acute stress via resiniferatoxin (RTX) injection still leads to hair greying in Mc1r mutant mice, suggesting that the ACTH–MC1R pathway is not a major contributor in acute stress‐induced premature hair greying.
Anthropogenic organic carbon emissions reporting has been largely limited to subsets of chemically speciated volatile organic compounds. However, new aircraft-based measurements revealed total ...gas-phase organic carbon emissions that exceed oil sands industry-reported values by 1900% to over 6300%, the bulk of which was due to unaccounted-for intermediate-volatility and semivolatile organic compounds. Measured facility-wide emissions represented approximately 1% of extracted petroleum, resulting in total organic carbon emissions equivalent to that from all other sources across Canada combined. These real-world observations demonstrate total organic carbon measurements as a means of detecting unknown or underreported carbon emissions regardless of chemical features. Because reporting gaps may include hazardous, reactive, or secondary air pollutants, fully constraining the impact of anthropogenic emissions necessitates routine, comprehensive total organic carbon monitoring as an inherent check on mass closure.
Forest fires are major contributors of reactive gas- and particle-phase organic compounds to the atmosphere. We used offline high-resolution tandem mass spectrometry to perform a molecular-level ...speciation of gas- and particle-phase compounds sampled via aircraft from an evolving boreal forest fire smoke plume in Saskatchewan, Canada. We observed diverse multifunctional compounds containing oxygen, nitrogen, and sulfur (CHONS), whose structures, formation, and impacts are understudied. The dilution-corrected absolute ion abundance of particle-phase CHONS compounds increased with plume age by a factor of 6.4 over the first 4 h of downwind transport, and their relative contribution to the observed functionalized organic aerosol (OA) mixture increased from 19 % to 40 %. The dilution-corrected absolute ion abundance of particle-phase compounds with sulfide functional groups increased by a factor of 13 with plume age, and their relative contribution to observed OA increased from 4 % to 40 %. Sulfides were present in up to 75 % of CHONS compounds and the increases in sulfides were accompanied by increases in ring-bound nitrogen; both increased together with CHONS prevalence. A complex mixture of intermediate- and semi-volatile gas-phase organic sulfur species was observed in emissions from the fire and depleted downwind, representing potential precursors to particle-phase CHONS compounds. These results demonstrate CHONS formation from nitrogen- and oxygen-containing biomass burning emissions in the presence of reduced sulfur species. In addition, they highlight chemical pathways that may also be relevant in situations with elevated emissions of nitrogen- and sulfur-containing organic compounds from residential biomass burning and fossil fuel use (e.g., coal), respectively.
Wildfire impacts on air quality and climate are expected to be exacerbated
by climate change with the most pronounced impacts in the boreal biome.
Despite the large geographic coverage, there is ...limited information on
boreal forest wildfire emissions, particularly for organic compounds, which
are critical inputs for air quality model predictions of downwind impacts.
In this study, airborne measurements of 193 compounds from 15 instruments,
including 173 non-methane organics compounds (NMOG), were used to provide
the most detailed characterization, to date, of boreal forest wildfire
emissions. Highly speciated measurements showed a large diversity of
chemical classes highlighting the complexity of emissions. Using
measurements of the total NMOG carbon (NMOGT), the ΣNMOG was
found to be 50 % ± 3 % to 53 % ± 3 % of NMOGT, of which, the
intermediate- and semi-volatile organic compounds (I/SVOCs) were estimated
to account for 7 % to 10 %. These estimates of I/SVOC emission factors
expand the volatility range of NMOG typically reported. Despite extensive
speciation, a substantial portion of NMOGT remained unidentified
(47 % ± 15 % to 50 % ± 15 %), with expected contributions from more
highly-functionalized VOCs and I/SVOCs. The emission factors derived in this
study improve wildfire chemical speciation profiles and are especially
relevant for air quality modelling of boreal forest wildfires. These
aircraft-derived emission estimates were further linked with those derived
from satellite observations demonstrating their combined value in assessing
variability in modelled emissions. These results contribute to the
verification and improvement of models that are essential for reliable
predictions of near-source and downwind pollution resulting from boreal
forest wildfires.
Empirical and anecdotal evidence have associated stress with accelerated hair greying (formation of unpigmented hairs)
1
,
2
, but the scientific evidence linking the two is scant. Here, we report ...that acute stress leads to hair greying through fast depletion of melanocyte stem cells (MeSCs). Combining adrenalectomy, denervation, chemogenetics
3
,
4
, cell ablation, and MeSC-specific adrenergic receptor knockout, we found that stress-induced MeSC loss is independent of immune attack or adrenal stress hormones. Rather, hair greying results from activation of the sympathetic nerves that innervate the MeSC niche. Upon stress, sympathetic nerve activation leads to burst release of the neurotransmitter norepinephrine, which drives quiescent MeSCs into rapid proliferation, followed by differentiation, migration, and permanent depletion from the niche. Transient suppression of MeSC proliferation prevents stress-induced hair greying. Our studies demonstrate that acute stress-induced neuronal activity can drive rapid and permanent loss of somatic stem cells, and illustrate an example in which somatic stem cell maintenance is directly influenced by the overall physiological state of the organism.