Characterization of Skin Interfollicular Stem Cells and Early Transit Amplifying Cells during the Transition from Infants to Young Children.

In the interfollicular epidermis, keratinocyte stem cells (KSC) generate a short-lived population of transit amplifying (TA) cells that undergo terminal differentiation after several cell divisions. Recently, we isolated and characterized a highly proliferative keratinocyte cell population, named "early" TA (ETA) cell, representing the first KSC progenitor with exclusive features. This work aims to evaluate epidermis, with a focus on KSC and ETA cells, during transition from infancy to childhood. Reconstructed human epidermis (RHE) generated from infant keratinocytes is more damaged by UV irradiation, as compared to RHE from young children. Moreover, the expression of several differentiation and barrier genes increases with age, while the expression of genes related to stemness is reduced from infancy to childhood. The proliferation rate of KSC and ETA cells is higher in cells derived from infants' skin samples than of those derived from young children, as well as the capacity of forming colonies is more pronounced in KSC derived from infants than from young children's skin samples. Finally, infants-KSC show the greatest regenerative capacity in skin equivalents, while young children ETA cells express higher levels of differentiation markers, as compared to infants-ETA. KSC and ETA cells undergo substantial changes during transition from infancy to childhood. The study presents a novel insight into pediatric skin, and sheds light on the correlation between age and structural maturation of the skin.

The first balloon-borne sample analysis of atmospheric carbonaceous components reveals new insights into formation processes.

Atmospheric aerosol optical, physical, and chemical properties play a fundamental role in the Earth's climate system. A better understanding of the processes involved in their formation, evolution, and interaction with radiation and the water cycle is critical. We report the analysis of atmospheric molecules/particles collected with a new sampling system that flew under regular weather balloons for the first time. The flight took place on January 18, 2022 from Reims (France). The samples were subsequently analyzed by high-resolution mass spectrometry (Orbitrap) to specifically infer hundreds of organic components present in 4 different layers from the troposphere to the stratosphere (up to 20 km). Additional measurements of O3, CO, and aerosol concentrations a few hours before this flight took place to contextualize the sampling. After separating common species found on each filter that might be common to atmospheric layers or residuals for contaminations, we found that each sample yields significant differences in the number and size of organic species detected that should reflect the unique composition of atmospheric layers. While tropospheric samples yield significantly oxidized and saturated components, with carbon numbers below 30 that might be explained by complex organics chemistry from local and distant source emissions, the upper tropospheric and stratospheric samples were associated with increased carbon numbers (C > 30), with a significantly reduced unsaturation number for the stratosphere, that might be induced by strong UV radiations. The multimodal distributions of carbon numbers in chemical formulas observed between 15 and 20 km suggest that oligomerization and growth of organic molecules may take place in aged air masses of tropical origin that are known to carry organic compounds even several km above the tropopause where their lifetime significantly increases. In addition, the presence of organics may also reflect the extended influence of wildfires smoke injected during the spring and summer in the NH hemisphere before the in situ observations and their long-lifetime in the upper troposphere and stratosphere.

IL-17 and IL-22 are pivotal cytokines to delay wound healing of S. aureus and P. aeruginosa infected skin.

Introduction: Although the presence of pathogens in skin wounds is known to delay the wound healing process, the mechanisms underlying this delay remain poorly understood. In the present study, we have investigated the regulatory role of proinflammatory cytokines on the healing kinetics of infected wounds. Methods: We have developed a mouse model of cutaneous wound healing, with or without wound inoculation with Staphylococcus aureus and Pseudomonas aeruginosa, two major pathogens involved in cutaneous wound bacterial infections. Results: Aseptic excision in C57BL/6 mouse skin induced early expression of IL-1ß, TNFα and Oncostatin M (OSM), without detectable expression of IL-22 and IL-17A/F. S. aureus and P. aeruginosa wound inoculation not only increased the expression of IL-1ß and OSM, but also induced a strong cutaneous expression of IL-22, IL-17A and IL-17F, along with an increased number of infiltrating IL-17A and/or IL-22-producing γδ T cells. The same cytokine expression pattern was observed in infected human skin wounds. When compared to uninfected wounds, mouse skin infection delayed the wound healing process. Injection of IL-1α, TNFα, OSM, IL-22 and IL-17 together in the wound edges induced delayed wound healing similar to that induced by the bacterial infection. Wound healing experiments in infected Rag2KO mice (deficient in lymphocytes) showed a wound healing kinetic similar to uninfected Rag2KO mice or WT mice. Rag2KO infected-skin lesions expressed lower levels of IL-17 and IL-22 than WT, suggesting that the expression of these cytokines is mainly dependent on γδ T cells in this model. Wound healing was not delayed in infected IL-17R/IL-22KO, comparable to uninfected control mice. Injection of recombinant IL-22 and IL-17 in infected wound edges of Rag2KO mice re-establish the delayed kinetic of wound healing, as in infected WT mice. Conclusion: These results demonstrate the synergistic and specific effects of IL-22 and IL-17 induced by bacterial infection delay the wound healing process, regardless of the presence of bacteria per se. Therefore, these cytokines play an unexpected role in delayed skin wound healing.

Dermal fibroblasts are the key sensors of aseptic skin inflammation through interleukin 1 release by lesioned keratinocytes.

IL-1 plays a crucial role in triggering sterile inflammation following tissue injury. Although most studies associate IL-1 release by injured cells to the recruitment of neutrophils for tissue repair, the inflammatory cascade involves several molecular and cellular actors whose role remains to be specified. In the present study, we identified dermal fibroblasts among the IL-1R1-expressing skin cells as key sensors of IL-1 released by injured keratinocytes. After in vitro stimulation by recombinant cytokines or protein extracts of lysed keratinocytes containing high concentrations of IL-1, we show that dermal fibroblasts are by far the most IL-1-responsive cells compared to keratinocytes, melanocytes and endothelial cells. Fibroblasts have the property to respond to very low concentrations of IL-1 (from 10 fg/ml), even in the presence of 100-fold higher concentrations of IL-1RA, by increasing their expression of chemokines such as IL-8 for neutrophil recruitment. The capacity of IL-1-stimulated fibroblasts to attract neutrophils has been demonstrated both in vitro using cell migration assay and in vivo using a model of superficial epidermal lesion in IL-1R1-deficient mice which harbored reduced expression of inflammatory mediators and neutrophil skin infiltration. Together, our results shed a light on dermal fibroblasts as key relay cells in the chain of sterile inflammation induced after epidermal lesion.

Enhanced In Vitro Expression of Filaggrin and Antimicrobial Peptides Following Application of Glycosaminoglycans and a Sphingomyelin-Rich Lipid Extract.

Filaggrin is an epidermal protein involved in skin barrier formation and hydration, whose expression is altered in canine atopic dermatitis (CAD). CAD patients also present an abnormal immune response with an altered expression of antimicrobial peptides (AMPs), such as ß-defensins and cathelicidins. Sphingolipids and glycosaminoglycans (GAGs) have been reported to improve the skin barrier in several animal species, including dogs. Our objective was to evaluate the in vitro effects of a sphingomyelin-rich lipid extract (LE), a hyaluronic acid-rich GAG matrix, and their combination, on the expression of filaggrin and human ß-defensin 2 (hBD-2). Filaggrin expression was quantified in a reconstructed human epidermis (RHE), and hBD-2 in normal human epidermal keratinocyte (NHEK) cultures. LE and GAGs were tested at 0.02 mg/mL, with or without adding a cytokine mix. A significant increase in mean hBD-2, compared to the control (99 pg/mL) was achieved with LE (138 pg/mL) and LE+GAGs (165 pg/mL). Filaggrin increased with GAGs (202% ± 83) and LE (193% ± 44) vs. the stimulated control, but this difference was statistically significant (p < 0.05) only with LE+GAGs (210% ± 39). In conclusion, the tested GAGs and LE enhance filaggrin and AMP expression in vitro, which might benefit CAD patients if applied in vivo.

Atmospheric Chemistry of c-C5HF7 and c-C5F8: Temperature-Dependent OH Reaction Rate Coefficients, Degradation Products, Infrared Spectra, and Global Warming Potentials.

c-C5HF7 (1H-heptafluorocyclopentene) and c-C5F8 (perfluorocyclopentene) are potent greenhouse gases presently used as replacement compounds in Si etching. A thorough understanding of their potential impact on climate and air quality necessitates studies of their atmospheric reactivity, radiative properties, and atmospheric degradation pathways. The predominant atmospheric removal process for these compounds is expected to be via reaction with the OH radical. In this study, rate coefficients, k, for the gas-phase reaction of the OH radical with c-C5HF7 and c-C5F8 were measured over a range of temperatures (242-370 K) and pressures (50-100 Torr, He) using a pulsed laser photolysis-laser-induced fluorescence technique. In addition, a complementary relative rate technique, employing multiple reference compounds, was used to study the reactions between 273 and 372 K at 100 Torr (He) total pressure. Reaction rate coefficients were found to be independent of pressure over this range of conditions with k1(296 K) = (4.59 ± 0.10) × 10-14 cm3 molecule-1 s-1 and k1(T) = (4.00 ± 0.40) × 10-13 exp(-(631 ± 30)/T) cm3 molecule-1 s-1 for c-C5HF7 and k2(296 K) = (4.90 ± 0.14) × 10-14 cm3 molecule-1 s-1 and k2(T) = (3.59 ± 0.4) × 10-13 exp(-(591 ± 25)/T) cm3 molecule-1 s-1 for c-C5F8. Stable end-products were measured following the OH radical-initiated degradation of c-C5HF7 and c-C5F8 in the presence of O2. F(O)CCF2CF2CF2CH(O), CF2O, and CO2 were observed as the major end-products in the oxidation of c-C5HF7 with molar yields of 0.64, 1.27, and 0.53, respectively. For c-C5F8, F(O)CCF2CF2CF2CF(O), CF2O, and CO2 were observed with molar yields of 0.66, 0.63, and 0.43, respectively. The total carbon mass balance in both systems was 1.0 ± 0.15. The high yield of a C5-dicarbonyl end-product is consistent with a ring opening at the carbon-carbon double bond site for both c-C5HF7 and c-C5F8. A comparison of the present kinetic and degradation product results with previously published studies is presented. A rate coefficient upper limit for the gas-phase reaction of O3 with c-C5HF7 and c-C5F8 of 1 × 10-21 cm3 molecule-1 s-1 was measured as part of this work. Atmospheric lifetimes for c-C5HF7 and c-C5F8 are estimated to be 252 and 236 days, respectively. Infrared absorption spectra of c-C5HF7 and c-C5F8 were also measured and found to agree, to within 5%, with results from previous studies. The well-mixed and lifetime adjusted radiative efficiencies (RE, W m-2 ppb-1) and 100 year time horizon global warming potential (GWP) for c-C5HF7 are 0.35, 0.24, and 46.7 and for c-C5F8 are 0.38, 0.25, and 46.2, respectively.

Alzheimer's disease disrupts domain-specific and domain-general processes in numerosity estimation.

INTRODUCTION: This study investigated how Alzheimer's Disease (AD) affects numerosity estimation abilities (e.g., finding the approximate number of items in a collection). METHOD: Across two experiments, performance from HOA (i.e., Healthy Older Adults; N = 48) and AD patients (N = 50) was compared on dot comparison tasks. Participants were presented with two dot arrays and had to select the more numerous dot array in comparison tasks. They also took a Simon task and a number-line tasks (i.e., number-line tasks in which they had to indicate the position of a number on a line 0 to 100 or on a line 0 to 1,000 in the number-line task). RESULTS: In Experiment 1, (a) AD patients obtained significantly poorer performance while comparing collections of dots, especially harder (small-ratio) collections, (b) these deficits correlated with poorer performance on the number-line task for larger numerosities (i.e., 0 to 1,000), and (c) AD patients showed poorer performance on incongruent (where numerosity and area occupied by dots mismatched) than on congruent items (where both features matched), while HOA showed no congruency effects. Experiment 2 showed (a) congruency effects in both groups when convex hull was tested as an incongruent feature, and (b) comparable sequential modulations of congruency effects in both groups. CONCLUSIONS: Our findings showed that numerosity abilities decline in AD patients, and that this decline results from impaired domain-specific processes (i.e., numerosity processing) and domain-general processes (i.e., inhibition). These findings have important implications to further our understanding of how specific and general cognitive processes contribute to numerosity estimation/comparison performance, and how such contributions change during Alzheimer's disease.

Type-1 cytokines regulate MMP-9 production and E-cadherin disruption to promote melanocyte loss in vitiligo.

Loss of melanocytes is the pathological hallmark of vitiligo, a chronic inflammatory skin depigmenting disorder induced by exaggerated immune response, including autoreactive CD8 T cells producing high levels of type 1 cytokines. However, the interplay between this inflammatory response and melanocyte disappearance remains to be fully characterized. Here, we demonstrate that vitiligo skin contains a significant proportion of suprabasal melanocytes, associated with disruption of E-cadherin expression, a major protein involved in melanocyte adhesion. This phenomenon is also observed in lesional psoriatic skin. Importantly, apoptotic melanocytes were mainly observed once cells were detached from the basal layer of the epidermis, suggesting that additional mechanism(s) could be involved in melanocyte loss. The type 1 cytokines IFN-γ and TNF-α induce melanocyte detachment through E-cadherin disruption and the release of its soluble form, partly due to MMP-9. The levels of MMP-9 are increased in the skin and sera of patients with vitiligo, and MMP-9 is produced by keratinocytes in response to IFN-γ and TNF-α. Inhibition of MMP-9 or the JAK/STAT signaling pathway prevents melanocyte detachment in vitro and in vivo. Therefore, stabilization of melanocytes in the basal layer of the epidermis by preventing E-cadherin disruption appears promising for the prevention of depigmentation occurring in vitiligo and during chronic skin inflammation.

Impact of mild traumatic brain injury on cingulate functions.

Mild traumatic brain injury (mTBI) is a condition of normal neuroimaging, because conventional MRI is not sensitive to brain lesions. Neurocognitive deficits persist for years after injury in 15% of patients. Persistent TAI can continue after the trauma and contribute to progressive disability. Neuropathologic studies underestimate the total axonal damage, by failure to identify fine-caliber unmyelinated fiber. Swollen axons represent the "tip of the iceberg" of damage. Progression of molecular changes, including mitochondrial dysfunction, leads to secondary injuries. Primary low-intensity "invisible injury" is solely detectable at ultrastructural levels. Over the long term, mTBI is not a static event but a progressive injury, increasing risk of neurodegenerative diseases. Lack of evidence of brain injury has led to the development of more sensitive methods: morphometric MRI (VBM, DTI) and functional techniques (fMRI, PET, SPECT). By deformation of the surface of gray matter cingulate gyrus and disruption of long-coursing WM of CB structures, striking the falx, mTBI causes alteration of cingulate functions. Postconcussion, blast, and whiplash-associated disorders are the main mechanisms providing behavior and cognitive symptoms after mTBI.

Cingulate cortex in pre-MCI cognition.

Studies of Alzheimer's disease over the years have focused on the prodromal stage, or mild cognitive impairment (MCI), in order to understand its evolution and to diagnose this pathology early. More recently, research has focused on an even earlier stage (pre-MCI) characterized in particular by a cognitive complaint. The purpose of this chapter is, first, to describe the different concepts defining pre-MCI, which refers to cognitive or memory complaint, and to define this concept based on biologic markers (abnormal proteins and neuroimaging). In the second part of the chapter, we describe the cognitive performance of these subjects (pre-MCI), and, finally, in the third part we describe the correlations linking cognitive performance of pre-MCI subjects to cingulate cortex, cingulate gyrus, and cingulum bundle.

Atmospheric Fate and Impact of Perfluorinated Butanone and Pentanone.

Perfluoroketones, used as replacement to halons and CFCs, are excluded from the Montreal Protocol because they are considered as nonozone depleting substances. However, their chemical structure makes them possible greenhouse gases if their atmospheric lifetimes are long enough. To assess that possibility, we investigated the photolysis of perfluoro-2-methyl-3-pentanone (PF-2M3P), and perfluoro-3-methyl-2-butanone (PF-3M2B) using outdoor atmospheric simulation chambers. In addition, the photolysis of a non fluorinated pentanone (2-methyl-3-pentanone, 2M3P) was studied. The results showed that photolysis is the dominant loss pathway of PF-2M3P and PF-3M2B in the troposphere whereas 2M3P is lost by both photolysis and gas phase reaction with atmospheric oxidants. The photolysis effective quantum yields of PF-2M3P, PF-3M2B, and 2M3P were estimated and some of the main products identified. The photolysis of PF-2M3P and PF-3M2B was found to have a minor impact on the atmospheric burden of fluorinated acids. The atmospheric lifetimes of PF-2M3P, PF-3M2B, and 2M3P were estimated to 3-11 days, ∼13 days, and 1-2 days, respectively. Combining the obtained data, it has been concluded that with 100-year time horizon global warming potentials (GWP100) equivalent to <0.21, ∼0.29, and ≤1.3 × 10-7 for PF-2M3P, PF-3M2B, and 2M3P, respectively, these compounds will have a negligible impact on global warming.

Secondary Organic Aerosol Formation from Aromatic Alkene Ozonolysis: Influence of the Precursor Structure on Yield, Chemical Composition, and Mechanism.

The influence of the precursor chemical structure on secondary organic aerosol (SOA) formation was investigated through the study of the ozonolysis of two anthropogenic aromatic alkenes: 2-methylstyrene and indene. Experiments were carried out in three different simulation chambers: ICARE 7300L FEP Teflon chamber (ICARE, Orléans, France), EUPHORE FEP Teflon chamber (CEAM, Valencia, Spain), and CESAM evacuable stainless steel chamber (LISA, Créteil, France). For both precursors, SOA yield and growth were studied on a large range of initial concentrations (from ∼60 ppbv to 1.9 ppmv) and the chemical composition of both gaseous and particulate phases was investigated at a molecular level. Gas phase was described using FTIR spectroscopy and online gas chromatography coupled to mass spectrometry, and particulate chemical composition was analyzed (i) online by thermo-desorption coupled to chemical ionization mass spectrometry and (ii) offline by supercritical fluid extraction coupled to gas chromatography and mass spectrometry. The results obtained from a large set of experiments performed in three different chambers and using several complementary analytical techniques were in very good agreement. SOA yield was up to 10 times higher for indene ozonolysis than for 2-methylstyrene ozonolysis at the same reaction advancement. For 2-methylstyrene ozonolysis, formaldehyde and o-tolualdehyde were the two main gaseous phase products while o-toluic acid was the most abundant among six products detected within the particulate phase. For indene ozonolysis, traces of formic and phthalic acids as well as 11 species were detected in the gaseous phase and 11 other products were quantified in the particulate phase, where phthaldialdehyde was the main product. On the basis of the identified products, reaction mechanisms were proposed that highlight specific pathways due to the precursor chemical structure. These mechanisms were finally compared and discussed regarding SOA formation. In the case of 2-methylstyrene ozonolysis, ozone adds mainly on the external and monosubstituted double bond, yielding only one C8- and monofunctionalized Criegee intermediate and hence more volatile products as well as lower SOA mass than indene ozonolysis in similar experimental conditions. In the case of indene, ozone adds mainly on the five-carbon-ring and disubstituted C═C double bond, leading to the formation of two C9- and bifunctionalized Criegee intermediates, which then evolve via different pathways including the hydroperoxide channel and form highly condensable first-generation products.

Oncostatin M is overexpressed in skin squamous-cell carcinoma and promotes tumor progression.

Cutaneous squamous cell carcinoma (cSCC) is the second most common keratinocyte malignancy and accounts for 20% of skin cancer deaths. Cancer is closely related to inflammation, but the contribution of the tumor microenvironment to cSCC development is poorly understood. We previously showed that oncostatin M (OSM), a cytokine belonging to the IL-6 family, promotes normal keratinocyte proliferation and migration, skin inflammation, and epidermal hyperplasia, both in vitro and in vivo. Here, we show that OSM is overexpressed in human cSCC and is associated with type 1 immune polarization. In vitro, OSM induced STAT-3 and ERK signaling, modified the expression of genes involved in cytokine signaling, proliferation, inhibition of apoptosis, and immune responses, and promoted proliferation and migration of malignant keratinocyte PDVC57 cells. PDVC57 cells grafted in the skin of mice led to rapid cSCC development, associated with OSM expression by tumor-infiltrating neutrophils. Finally, the absence of OSM (OSM-KO mice) led to a 30% reduction of tumor size and reduced M2 polarization in the tumor microenvironment. Globally, these results support a pro-tumoral role of OSM in cSCC development and suggest that a new therapeutic approach targeting this cytokine could be considered.

Pseudomonas aeruginosa flagellum is critical for invasion, cutaneous persistence and induction of inflammatory response of skin epidermis.

Pseudomonas aeruginosa, an opportunistic pathogen involved in skin and lung diseases, possesses numerous virulence factors, including type 2 and 3 secretion systems (T2SS and T3SS) and its flagellum, whose functions remain poorly known during cutaneous infection. Using isogenic mutants deleted from genes encoding each or all of these three virulence factors, we investigated their role in induction of inflammatory response and in tissue invasiveness in human primary keratinocytes and reconstructed epidermis. Our results showed that flagellum, but not T2SS and T3SS, is involved in induction of a large panel of cytokine, chemokine, and antimicrobial peptide (AMP) mRNA in the infected keratinocytes. Chemokine secretion and AMP tissular production were also dependent on the presence of the bacterial flagellum. This pro-inflammatory effect was significantly reduced in keratinocytes infected in presence of anti-toll-like receptor 5 (TLR5) neutralizing antibody. Bacterial invasion of human epidermis and persistence in a mouse model of sub-cutaneous infection were dependent on the P. aeruginosa flagellum. We demonstrated that flagellum constitutes the main virulence factor of P. aeruginosa involved not only in early induction of the epidermis inflammatory response but also in bacterial invasion and cutaneous persistence. P. aeruginosa is mainly sensed by TLR5 during the early innate immune response of human primary keratinocytes.

Temperature Dependent Rate Coefficients for the Gas-Phase Reaction of the OH Radical with Linear (L2, L3) and Cyclic (D3, D4) Permethylsiloxanes.

Permethylsiloxanes are emitted into the atmosphere during production and use as personal care products, lubricants, and cleaning agents. The predominate atmospheric loss process for permethylsiloxanes is expected to be via gas-phase reaction with the OH radical. In this study, rate coefficients, k(T), for the OH radical gas-phase reaction with the two simplest linear and cyclic permethylsiloxanes were measured using a pulsed laser photolysis-laser induced fluorescence technique over the temperature range of 240-370 K and a relative rate method at 294 K: hexamethyldisiloxane ((CH3)3SiOSi(CH3)3, L2), k1; octamethyltrisiloxane ([(CH3)3SiO]2Si(CH3)2, L3), k2; hexamethylcyclotrisiloxane ([-Si(CH3)2O-]3, D3), k3; and octamethylcyclotetrasiloxane ([-Si(CH3)2O-]4, D4), k4. The obtained k(294 K) values and temperature-dependence expressions for the 240-370 K temperature range are (cm3 molecule-1 s-1, 2σ absolute uncertainties): k1(294 K) = (1.28 ± 0.08) × 10-12, k1( T) = (1.87 ± 0.18) × 10-11 exp(-(791 ± 27)/ T); k2(294 K) = (1.72 ± 0.10) × 10-12, k2( T) = 1.96 × 10-13 (T/298)4.34 exp(657/ T); k3(294 K) = (0.82 ± 0.05) × 10-12, k3( T) = (1.29 ± 0.19) × 10-11 exp(-(805 ± 43)/ T); and k4(294 K) = (1.12 ± 0.10) × 10-12, k4( T) = (1.80 ± 0.26) × 10-11 exp(-(816 ± 43)/ T). The cyclic molecules were found to be less reactive than the analogous linear molecule with the same number of -CH3 groups, while the linear and cyclic permethylsiloxane reactivity both increase with the increasing number of CH3- groups. The present results are compared with previous rate coefficient determinations where available. The permethylsiloxanes included in this study are atmospherically short-lived compounds with estimated atmospheric lifetimes of 11, 8, 17, and 13 days, respectively.

Diurnal Variability and Emission Pattern of Decamethylcyclopentasiloxane (D5) from the Application of Personal Care Products in Two North American Cities.

Decamethylcyclopentasiloxane (D5) is a cyclic volatile methyl siloxane (cVMS) that is widely used in consumer products and commonly observed in urban air. This study quantifies the ambient mixing ratios of D5 from ground sites in two North American cities (Boulder, CO, USA, and Toronto, ON, CA). From these data, we estimate the diurnal emission profile of D5 in Boulder, CO. Ambient mixing ratios were consistent with those measured at other urban locations; however, the diurnal pattern exhibited similarities with those of traffic-related compounds such as benzene. Mobile measurements and vehicle experiments demonstrate that emissions of D5 from personal care products are coincident in time and place with emissions of benzene from motor vehicles. During peak commuter times, the D5/benzene ratio (w/w) is in excess of 0.3, suggesting that the mass emission rate of D5 from personal care product usage is comparable to that of benzene due to traffic. The diurnal emission pattern of D5 is estimated using the measured D5/benzene ratio and inventory estimates of benzene emission rates in Boulder. The hourly D5 emission rate is observed to peak between 6:00 and 7:00 AM and subsequently follow an exponential decay with a time constant of 9.2 h. This profile could be used by models to constrain temporal emission patterns of personal care products.

Development of a new model of reconstituted mouse epidermis and characterization of its response to proinflammatory cytokines.

The development of three-dimensional models of reconstituted mouse epidermis (RME) has been hampered by the difficulty to maintain murine primary keratinocyte cultures and to achieve a complete epidermal stratification. In this study, a new protocol is proposed for the rapid and convenient generation of RME, which reproduces accurately the architecture of a normal mouse epidermis. During RME morphogenesis, the expression of differentiation markers such as keratins, loricrin, filaggrin, E-cadherin and connexins was followed, showing that RME structure at day 5 was similar to those of a normal mouse epidermis, with the acquisition of the natural barrier function. It was also demonstrated that RME responded to skin-relevant proinflammatory cytokines by increasing the expression of antimicrobial peptides and chemokines, and inhibiting epidermal differentiation markers, as in the human system. This new model of RME is therefore suitable to investigate mouse epidermis physiology further and opens new perspectives to generate reconstituted epidermis from transgenic mice.

Health-Promoting Home and Workplace Neighborhoods: Associations With Multiple Facets of Men's Health.

Despite the importance of healthy settings for health promotion, little is known about how neighborhood characteristics affect men's health. The present study aims to explore the associations between perceptions of home and workplace neighborhoods with diverse health outcomes, and to examine mediating mechanisms. A sample of 669 men members of labor unions in Quebec, Canada, completed a questionnaire assessing social and physical aspects of their work and home neighborhoods (the Health-Promoting Neighborhood Questionnaire) as well as subjective and objective health outcomes (perceived health, positive mental health, body mass index) and potential mediators (health behaviors, self-efficacy). Structural equation modeling (path analysis) revealed that the Health-Promoting Neighborhood Questionnaire was associated with all three health outcomes, either directly or indirectly through health behaviors and self-efficacy. Both home and workplace neighborhoods were associated with men's health, home neighborhood being more strongly associated. The findings suggest that physical and social aspects of neighborhood might contribute to men's health. The study highlights positive environmental levers for urban planners, policy makers, and health professionals to promote men's health.

Interleukin-17A-induced production of acute serum amyloid A by keratinocytes contributes to psoriasis pathogenesis.

BACKGROUND: Acute-serum Amyloid A (A-SAA), one of the major acute-phase proteins, is mainly produced in the liver but extra-hepatic synthesis involving the skin has been reported. Its expression is regulated by the transcription factors NF-κB, C/EBPß, STAT3 activated by proinflammatory cytokines. OBJECTIVES: We investigated A-SAA synthesis by resting and cytokine-activated Normal Human Epidermal Keratinocytes (NHEK), and their inflammatory response to A-SAA stimulation. A-SAA expression was also studied in mouse skin and liver in a model mimicking psoriasis and in the skin and sera of psoriatic and atopic dermatitis (AD) patients. METHODS: NHEK were stimulated by A-SAA or the cytokines IL-1α, IL-17A, IL-22, OSM, TNF-α alone or in combination, previously reported to reproduce features of psoriasis. Murine skins were treated by imiquimod cream. Human skins and sera were obtained from patients with psoriasis and AD. A-SAA mRNA was quantified by RT qPCR. A-SAA proteins were dosed by ELISA or immunonephelemetry assay. RESULTS: IL-1α, TNF-α and mainly IL-17A induced A-SAA expression by NHEK. A-SAA induced its own production and the synthesis of hBD2 and CCL20, both ligands for CCR6, a chemokine receptor involved in the trafficking of Th17 lymphocytes. A-SAA expression was increased in skins and livers from imiquimod-treated mice and in patient skins with psoriasis, but not significantly in those with AD. Correlations between A-SAA and psoriasis severity and duration were observed. CONCLUSION: Keratinocytes could contribute to psoriasis pathogenesis via A-SAA production, maintaining a cutaneous inflammatory environment, activating innate immunity and Th17 lymphocyte recruitment.