Ectodysplasin-A (Ectodermal dysplasia protein) (EDA protein) [Contains: Ectodysplasin-A, membrane form; Ectodysplasin-A, secreted form] [ED1] [EDA2]

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Interplay between aging, lung inflammation/remodeling, and fibronectin EDA in lung cancer progression.

Lung cancer remains the leading cause of cancer death in the United States. Since most lung cancers occur in aged individuals with chronic lung disorders characterized by inflammation and/or fibrosis, we hypothesized that aging and tissue inflammation/remodeling act in concert to promote lung cancer progression. To test this, we engaged in studies using young and aged C57BL/6 mice in conjunction with bleomycin treatment in a syngeneic model of lung cancer. Wildtype young (3 months) and aged (9 months) C57BL/6 mice were injected with Lewis Lung Carcinoma (LLC) cells at day 14 after injection with phosphate-buffered saline or bleomycin. Untreated aged mice were found to develop more lung metastases than young mice. Bleomycin induced weight loss and lung inflammation/remodeling in both young and aged mice, and it increased the number of lung metastases in aged lungs, but not in young lungs. Since aged lungs show alterations in the expression of fibronectin EDA, we repeated studies in aged WT and aged FN EDA KO mice. In the absence of tissue remodeling/inflammation, WT and FN EDA KO mice developed the same number of metastases when injected with LLC cells. However, the increase in lung metastasis due to bleomycin treatment was abolished in FN EDA KO mice, but only in aged and injured lungs. Together, these studies show increased lung cancer metastasis in aging animals and point to the influence of FN EDA and injury in this process.


Keywords

  • Lung cancer
  • aging
  • fibronectin EDA
  • fibrosis
  • inflammation
  • lewis lung carcinoma
  • metastasis


Arousal Detection in Elderly People from Electrodermal Activity Using Musical Stimuli.

The detection of emotions is fundamental in many areas related to health and well-being. This paper presents the identification of the level of arousal in older people by monitoring their electrodermal activity (EDA) through a commercial device. The objective was to recognize arousal changes to create future therapies that help them to improve their mood, contributing to reduce possible situations of depression and anxiety. To this end, some elderly people in the region of Murcia were exposed to listening to various musical genres (flamenco, Spanish folklore, Cuban genre and rock/jazz) that they heard in their youth. Using methods based on the process of deconvolution of the EDA signal, two different studies were carried out. The first, of a purely statistical nature, was based on the search for statistically significant differences for a series of temporal, morphological, statistical and frequency features of the processed signals. It was found that Flamenco and Spanish Folklore presented the highest number of statistically significant parameters. In the second study, a wide range of classifiers was used to analyze the possible correlations between the detection of the EDA-based arousal level compared to the participants' responses to the level of arousal subjectively felt. In this case, it was obtained that the best classifiers are support vector machines, with 87% accuracy for flamenco and 83.1% for Spanish Folklore, followed by K-nearest neighbors with 81.4% and 81.5% for Flamenco and Spanish Folklore again. These results reinforce the notion of familiarity with a musical genre on emotional induction.


Keywords

  • aging adults
  • arousal
  • electrodermal activity
  • musical genres


The structure of agricultural microplastics (PT, PU and UF) and their sorption capacities for PAHs and PHE derivates under various salinity and oxidation treatments.

Microplastic (MP) pollution and its potential to concentrate and transport organic contaminants in environments have recently gained widespread attention. Compared to traditional nonpolar plastics such as polypropylene (PP) and polyethylene (PE), study about the environmental behavior of polyurethane (PT), polyuria (PU) and urea-formaldehyde resin (UF), which are typically used as shell materials for pesticide microcapsules and have polar structure is scarce. In the present study, we investigated the sorption capacities and binding mechanisms of PT, PU and UF for three polycyclic aromatic hydrocarbons (PAHs, naphthalene, phenanthrene (PHE), and pyrene) and two PHE derivates (ethylphenanthrene-2-carboxylate (2-CPHE) and 2-methylphenathrene (2-MPHE)) selected as the model compounds, and the effects of salinity and UV and/or H O aging treatments on PHE sorption to MPs. The results showed that PT, PU and UF had negative surface charges, micron-scaled sizes and abundant polar functional groups containing O and N elements. PT, PU and UF could sorb PAHs efficiently with sorption coefficients (K ) being in the range of 8.11 × 10 -9.53 × 10 (L/Kg) and partitioning was the main sorption mechanism with polar interactions (H-boning and p/π-π EDA interactions) also contributing. The sorption capacity of the three MPs changed mainly depending on their glass transition temperatures (T ). Furthermore, high salinity decreased the surface zeta-potential of the MPs and enhanced PHE sorption to MPs. In addition, aging treatments with UV and/or H O markedly decreased the T of PT and enhanced its sorption capacity for PHE, while opposite results were obtained for PU. The findings on the sorption mechanisms of PAHs to agricultural MPs are useful for predicting the transport, fate and persistence of the co-existing HOCs in agricultural ecosystems and provide a scientific basis for the comprehensive risk assessment of agricultural MPs.

MeSH Terms

  • Adsorption
  • Agriculture
  • Ecosystem
  • Environmental Pollutants
  • Hydrogen Peroxide
  • Microplastics
  • Models, Chemical
  • Naphthalenes
  • Organic Chemicals
  • Phenanthrenes
  • Plastics
  • Polycyclic Aromatic Hydrocarbons
  • Polyethylene
  • Polypropylenes
  • Polyurethanes
  • Polyuria
  • Pyrenes
  • Salinity

Keywords

  • Aging
  • Microplastics
  • Polycyclic aromatic hydrocarbons
  • Salinity
  • Sorption


Effect of storage on quality parameters and phenolic content of Italian extra-virgin olive oils.

The quality of extra virgin olive oils is affected mainly by hydrolytic and oxidative reactions. The present paper investigated the changes of major and minor components and oxidation indices of three monovarietal extra virgin olive oils after 18 months of storage at room temperature and in dark glass bottles conditions. After storage, the basic quality parameters such as free acidity, peroxide values, extinction coefficients, fatty acids composition, chlorophyll and carotenoid content, did not exceed the upper limits set by European Community Regulations for extra-virgin olive oils. Given the importance of the phenolic fraction, UHPLC-HESI-MS metodology was used. A decrease in 3,4-DHPEA-EDA (oleacin) and p-HPEA-EDA (oleochantal) was detected whereas, an increase of tyrosol and hydroxytyrosol was measured as a consequence of degradation of ligstroside and oleuropein derivatives. Based on the results it is possible to observe the high nutritional value of the studied oils even after 18 months of conservation.

MeSH Terms

  • Fatty Acids
  • Food Quality
  • Food Storage
  • Glucosides
  • Iridoids
  • Italy
  • Olive Oil
  • Oxidation-Reduction
  • Phenols
  • Pyrans

Keywords

  • Oleacin
  • UHPLC-HESI-MS
  • hydroxytyrosol
  • oil aging
  • oleochantal


Fibronectin Containing Extra Domain A Induces Plaque Destabilization in the Innominate Artery of Aged Apolipoprotein E-Deficient Mice.

Fibronectin containing extra domain A (Fn-EDA) is an endogenous ligand of TLR4 (toll-like receptor 4) and is abundant in the extracellular matrix of advanced atherosclerotic lesions in human and mice. Irrespective of sex, deletion of Fn-EDA reduces early atherosclerosis in apolipoprotein E-deficient (Apoe ) mice. However, the contribution of Fn-EDA in advanced atherosclerosis remains poorly characterized. We determined the contribution of Fn-EDA in advanced atherosclerotic lesions of aged (1-year-old) Apoe mice. Plaque composition was determined in the innominate artery, a plaque instability site that is known to mimic several histological features of vulnerable human plaques. Female Apoe , Fn-EDA Apoe , TLR4 Apoe , and Fn-EDA TLR4 Apoe mice were fed a high-fat Western diet for 44 weeks. Fn-EDA Apoe mice exhibited reduced plaque size characterized by smaller necrotic cores, thick fibrous caps containing abundant vascular smooth muscle cells and collagen, reduced CD68/MMP9 (matrix metalloproteinase 9)-positive content, less accumulation of MMP-cleaved extracellular matrix aggrecan, and decreased vascular smooth muscle cell and macrophage apoptosis ([i]P[/i]<0.05 versus Apoe mice). Together these findings suggest that Fn-EDA induces plaque destabilization. Deletion of TLR4 reduced histological features of plaque instability in Apoe mice but did not further reduce features of plaque destabilization in Fn-EDA Apoe mice, suggesting that TLR4 may contribute to Fn-EDA-induced plaque destabilization. Fn-EDA potentiated TLR4-dependent MMP9 expression in bone marrow-derived macrophages, suggesting that macrophage TLR4 may contribute to Fn-EDA-mediated plaque instability. Fn-EDA induces histological features of plaque instability in established lesions of aged Apoe mice. The abundance of Fn-EDA in advanced atherosclerotic lesions may increase the risk of plaque destabilization.

MeSH Terms

  • Age Factors
  • Aging
  • Animals
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Apoptosis
  • Atherosclerosis
  • Brachiocephalic Trunk
  • Cells, Cultured
  • Disease Models, Animal
  • Female
  • Fibronectins
  • Fibrosis
  • Macrophages
  • Matrix Metalloproteinase 9
  • Mice, Inbred C57BL
  • Mice, Knockout, ApoE
  • Necrosis
  • Plaque, Atherosclerotic
  • Rupture, Spontaneous
  • Toll-Like Receptor 4

Keywords

  • apolipoproteins E
  • extracellular matrix
  • fibronectins
  • mice
  • toll-like receptor 4


An Extract from the Plant [i]Deschampsia antarctica[/i] Protects Fibroblasts from Senescence Induced by Hydrogen Peroxide.

The Antarctic plant [i]Deschampsia antarctica[/i] (DA) is able to survive in extreme conditions thanks to its special mechanism of protection against environmental aggressions. In this work, we investigated whether an aqueous extract of the plant (EDA) retains some of its defensive properties and is able to protect our skin against common external oxidants. We evaluated EDA over young human fibroblasts and exposed to H O , and we measured cell proliferation, viability, and senescence-associated [i]β[/i]-galactosidase (SA-[i]β[/i]-Gal). We also tested the expression of several senescence-associated proteins including sirtuin1, lamin A/C, the replicative protein PCNA, and the redox protein thioredoxin 2. We found that EDA promoted [i]per se[/i] cell proliferation and viability and increased the expression of anti-senescence-related markers. Then, we selected a dose of H O as an inductor of senescence in human fibroblasts, and we found that an EDA treatment 24 h prior H O exposure increased fibroblast proliferation. EDA significantly inhibited the increase in SA-[i]β[/i]-Gal levels induced by H O and promoted the expression of sirtuin 1 and lamin A/C proteins. Altogether, these results suggest that EDA protects human fibroblasts from cellular senescence induced by H O , pointing to this compound as a potential therapeutic agent to treat or prevent skin senescence.

MeSH Terms

  • Aging
  • Cell Proliferation
  • Cellular Senescence
  • Fibroblasts
  • Humans
  • Hydrogen Peroxide
  • Plant Extracts


Occurrence of fibronectin-fibrin complexes in plasma of patients with multimorbidity due to the inflamm-aging phenomenon.

Multimorbidity is the co-occurrence of chronic diseases associated with low-grade chronic inflammation of connective tissue. Frequency of occurrence and relative amounts of fibronectin (FN) complexes with fibrin (FN-fibrin) and FN monomer were analyzed in 130 plasma samples of 18 to 94-year-old multimorbid patients in relation to concentrations of FN and extra domain A (EDA)-FN, and C-reactive protein (CRP) as well as to age, number of coexisting chronic diseases and presence of specified diseases. Immunoblotting revealed, besides FN dimer, the presence of FN monomer, and 750-, 1000-, and 1300-kDa FN-fibrin complexes in the multimorbid plasmas. The FN-fibrin complexes appeared more frequently and in higher relative amounts, but FN monomer less frequently and in a lower relative amount in the groups of elderly multimorbid patients, with a higher number of coexisting diseases and with dominance of cardiovascular diseases and osteoarthrosis, and with CRP concentration of 3-5mg/l. In contrast, the normal plasma contained only the FN-fibrin complex of 750 kDa in a lower relative amount, but with an increasing amount with normal aging. Moreover, FN concentration increased and EDA-FN decreased with the number of co-existing diseases and aging of patients, although both concentration values were lower than in the age-matched normal groups. FN concentration was the lowest in the exacerbation of a chronic disease and EDA-FN in the stable chronic disease groups. The alterations in plasma FN molecular status were associated with micro-inflammation and micro-coagulation, as well as multimorbidity of subjects and their physiological aging.

MeSH Terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging
  • C-Reactive Protein
  • Chronic Disease
  • Comorbidity
  • Connective Tissue Diseases
  • Female
  • Fibrin
  • Fibronectins
  • Humans
  • Inflammation
  • Male
  • Middle Aged
  • Poland
  • Young Adult

Keywords

  • C-reactive protein
  • EDA-fibronectin
  • FN agarose-immunoblotting
  • FN–fibrin complexes
  • Fibronectin
  • Multimorbidity


Autonomic changes following generalized tonic clonic seizures: An analysis of adult and pediatric patients with epilepsy.

Sudden unexpected death in epilepsy (SUDEP) is the most common cause of mortality directly related to epilepsy. Its incidence is higher in adult patients and its pathophysiology remains poorly understood, but likely involves autonomic dysregulation following generalized tonic clonic seizures (GTCS). In the current study, we aimed to analyze post-ictal autonomic changes following GTCS in adult and pediatric patients. Patients admitted to the epilepsy monitoring unit were prospectively recruited, and wore an electrodermal activity (EDA) wrist sensor that continuously measured sympathetic activity while being monitored with EEG and EKG electrodes. Peri-ictal EDA parameters were assessed as a measure of sympathetic activity. Peri-ictal parasympathetic activity was determined through the high frequency component (HF) analysis of heart rate variability (HRV). The duration of post-ictal generalized EEG suppression (PGES) was also documented. Twenty patients with GTCS were included in the study on whom 30 GTCS were recorded. PGES duration strongly correlated with age (r=0.62, p=0.004) and measures of the EDA response. After controlling for PGES duration, we found pediatric patients had greater sympathetic activation measured as log rising portion of the area under the curve of the EDA response (β= 0.67, p=0.034) and a higher degree of vagal suppression measured as maximal percentage change of HF power (β=-12.65, p=0.0036). Sympathetic activity can be measured in the peri-ictal period, and directly correlates with PGES duration. Age is a significant determinant of the sympathetic and parasympathetic response following a GTCS; given the same PGES duration, pediatric patients demonstrate stronger sympathetic activation and higher vagal suppression. However, the increase in PGES duration with age and the associated autonomic dysregulation may provide clues as to why there is a variable vulnerability to SUDEP across age groups.

MeSH Terms

  • Adolescent
  • Adult
  • Aged
  • Aging
  • Brain
  • Child
  • Electrocardiography
  • Electroencephalography
  • Epilepsy, Generalized
  • Female
  • Galvanic Skin Response
  • Heart Rate
  • Humans
  • Male
  • Middle Aged
  • Monitoring, Physiologic
  • Prospective Studies
  • Seizures
  • Time Factors
  • Young Adult

Keywords

  • Autonomic nervous system
  • Electrodermal activity
  • Generalized tonic clonic seizures
  • Post-ictal generalized EEG suppression
  • Sudden unexpected death in epilepsy


Error detection and error memory in spatial navigation as reflected by electrodermal activity.

The study investigated spatial navigation by means of electrodermal activity (EDA). Two groups of healthy subjects (group 1, age <38; group 2, age ≥ 38) were recorded during navigation through two 3-D virtual mazes differing in difficulty, that is, Maze Simple (MazeS) and Maze Complex (MazeC). Our results show (1) an effect of difficulty, that is, larger skin conductance responses (SCRs) and slower velocity profiles while navigating through MazeC as compared to MazeS. (2) An effect of age, that is, larger SCRs and faster velocity profiles in younger subjects (group 1) compared to older subjects (group 2). (3) An effect of maze region, that is, SCRs increased when subjects entered dead ends with group 1 (young group) decreasing in velocity, whereas group 2 (old group) increased in velocity. (4) And an error memory effect, that is, subjects who remembered an error at a given decision point (crossroads preceding dead ends in MazeC) from previous trials, and then if they did not repeat that error, elicited decreased SCRs as compared to subjects who did not remember and subsequently repeated an error. The latter aspect is the most impactful as it shows that EDA is able to reflect error detection and memory during spatial navigation. Our data designate EDA as suitable monitoring tool for identification and differentiation of the affective correlates underlying spatial navigation, which has recently attracted researchers' attention due to its increased use in 3-D virtual environments.

MeSH Terms

  • Adult
  • Aging
  • Analysis of Variance
  • Female
  • Galvanic Skin Response
  • Humans
  • Male
  • Memory
  • Middle Aged
  • Multivariate Analysis
  • Psychomotor Performance
  • Space Perception
  • User-Computer Interface


Regulated splicing of the fibronectin EDA exon is essential for proper skin wound healing and normal lifespan.

Fibronectins (FNs) are multifunctional high molecular weight glycoproteins present in the blood plasma and in the ECMs of tissues. The FN primary transcript undergoes alternative splicing in three regions generating up to 20 main different variants in humans. However, the precise role of the FN isoforms is poorly understood. One of the alternatively spliced exons is the extra domain A (EDA) or extra type III homology that is regulated spatially and temporally during development and aging. To study its in vivo function, we generated mice devoid of EDA exon-regulated splicing. Constitutive exon inclusion was obtained by optimizing the splice sites, whereas complete exclusion was obtained after in vivo CRE-loxP-mediated deletion of the exon. Homozygous mouse strains with complete exclusion or inclusion of the EDA exon were viable and developed normally, indicating that the alternative splicing at the EDA exon is not necessary during embryonic development. Conversely, mice without the EDA exon in the FN protein displayed abnormal skin wound healing, whereas mice having constitutive inclusion of the EDA exon showed a major decrease in the FN levels in all tissues. Moreover, both mutant mouse strains have a significantly shorter lifespan than the control mice, suggesting that EDA splicing regulation is necessary for efficient long-term maintenance of biological functions.

MeSH Terms

  • Aging
  • Alternative Splicing
  • Animals
  • Cells, Cultured
  • Down-Regulation
  • Exons
  • Fetus
  • Fibroblasts
  • Fibronectins
  • Gene Deletion
  • Gene Expression Regulation, Developmental
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mutation
  • Protein Isoforms
  • Protein Structure, Tertiary
  • RNA, Messenger
  • Skin
  • Survival Rate
  • Wound Healing


In vitro erythrocidal activity of activated spleen cells from young and old mice.

We have recently reported that activated mouse spleen mononuclear cells (MNCs) efficiently lyse autologous erythrocytes in vitro (Saxena and Chandrasekhar, 2000). In the present study, we have investigated erythrocyte-depleting ability (EDA) of spleen MNCs from young and old mice. Time kinetics of survival of erythrocytes in mitogen-activated spleen cell cultures indicated that the erythrocyte depletion was significantly faster in young spleen cell cultures than in the old. Poorer EDA of old MNCs was in spite of the fact that the susceptibility to lysis actually increased in erythrocytes from old mice. Erythrocytes opsonized by a hamster anti mouse Fas monoclonal antibody, were destroyed with a much greater efficiency by young MNCs, whereas the corresponding effect of opsonization was only moderate for old MNCs. Depletion of macrophages from MNC preparations by plastic adherence as well as carbonyl-iron and magnet treatment had a marginal if any effect on EDA of young and old mouse MNCs, indicating that a lower lymphocyte-associated erythrocidal activity as one of the factors responsible for overall lower EDA associated with spleen derived MNCs of old mice.

MeSH Terms

  • Aging
  • Animals
  • Antibodies, Monoclonal
  • Cell Survival
  • Concanavalin A
  • Cricetinae
  • Cytotoxicity, Immunologic
  • Erythrocytes
  • In Vitro Techniques
  • Kinetics
  • Leukocytes, Mononuclear
  • Macrophages
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Opsonin Proteins
  • Spleen


Electrodermal activity in nonmedicated hyperthyroid patients having no depressive symptoms.

The aim of the present study was to investigate whether the alteration in hypothalamic-pituitary-thyroid axis function results in electrodermal abnormality without causing marked psychiatric manifestations or not. Electrodermal activity was recorded with the skin conductance unit and IBM-AT computer. Basal levels of electrodermal activity (EDA), as well as responsivity to repeated insignificant acoustic stimulation were studied in 24 nonmedicated hyperthyroid patients and 35 healthy controls. The outcome of psychiatric rating scores indicated that patients had low anxiety scores and normal depression scores. The basal levels of thyroid hormones were higher in patients, when compared with the control group. On the analysis of EDA, we found lower onset latency and duration of the skin conductance response and higher skin conductance level in nonmedicated patients than healthy controls. The results above provide supporting evidence that the change of hypothalamic-pituitary-thyroid axis function results in abnormal EDA, without causing marked psychiatric manifestations.

MeSH Terms

  • Acoustic Stimulation
  • Adult
  • Aging
  • Depression
  • Female
  • Galvanic Skin Response
  • Humans
  • Hyperthyroidism
  • Male
  • Middle Aged
  • Psychiatric Status Rating Scales
  • Sex Characteristics
  • Thyroid Function Tests
  • Thyroid Hormones