Embryonic control of epidermal cell patterning in the root and hypocotyl of Arabidopsis.

PubMed

Lin, Y; Schiefelbein, J

2001-10-01

A position-dependent pattern of epidermal cell types is produced during the development of the Arabidopsis seedling root and hypocotyl. To understand the origin and regulation of this patterning mechanism, we have examined the embryonic expression of the GLABRA2 (GL2) gene, which encodes a cell-type-specific transcription factor. Using in situ RNA hybridization and a sensitive GL2::GFP reporter, we discovered that a position-dependent pattern of GL2 expression is established within protodermal cells at the heart stage and is maintained throughout the remainder of embryogenesis. In addition, we show that an exceptional GL2 expression character and epidermal cell pattern arises during development of the root-hypocotyl junction, which represents an anatomical transition zone. Furthermore, we find that two of the genes regulating seedling epidermal patterning, TRANSPARENT TESTA GLABRA (TTG) and WEREWOLF (WER), also control the embryonic GL2 pattern, whereas the CAPRICE (CPC) and GL2 genes are not required to establish this pattern. These results indicate that position-dependent patterning of epidermal cell types begins at an early stage of embryogenesis, before formation of the apical meristems and shortly after the cellular anatomy of the protoderm and outer ground tissue layer is established. Thus, epidermal cell specification in the Arabidopsis seedling relies on the embryonic establishment of a patterning mechanism that is perpetuated postembryonically.

Could tight junctions regulate the barrier function of the aged skin?

PubMed

Svoboda, Marek; Bílková, Zuzana; Muthný, Tomáš

2016-03-01

The skin is known to be the largest organ in human organism creating interface with outer environment. The skin provides protective barrier against pathogens, physical and chemical insults, and against uncontrolled loss of water. The barrier function was primarily attributed to the stratum corneum (SC) but recent studies confirmed that epidermal tight junctions (TJs) also play important role in maintaining barrier properties of the skin. Independent observations indicate that barrier function and its recovery is impaired in aged skin. However, trans-epidermal water loss (TEWL) values remains rather unchanged in elderly population. UV radiation as major factor of photoageing impairs TJ proteins, but TJs have great self-regenerative potential. Since it may be possible that TJs can compensate TEWL in elderly due to its regenerative and compensatory capabilities, important question remains to be answered: how are TJs regulated during skin ageing? This review provides an insight into TJs functioning as epidermal barrier and summarizes current knowledge about the impact of ageing on the barrier function of the skin and epidermal TJs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

LEAF UV OPTICAL PROPERTIES OF 'RUMEX PATIENTIA' L. AND 'RUMEX OBTUSIFOLIUS L. IN REGARD TO A PROTECTIVE MECHANISM AGAINST SOLAR UV-B RADIATION INJURY

EPA Science Inventory

Effective UV attenuation in the outer leaf layers may represent an important protective mechanism against potentially damaging solar UV-B radiation. Epidermal optical properties for Rumex patientia and Rumex obtusifolius were examined on field collected and greenhouse grown plant...

Mechanism regulating nuclear calcium signaling.

PubMed

Malviya, Anant N; Klein, Christian

2006-01-01

Although the outer nuclear membrane is continuous with the endoplasmic reticulum, it is possible to isolate nuclei both intact and free from endoplasmic reticulum contaminants. The outer and the inner nuclear membranes can be purified free from cross-contamination. Evidence in support of autonomous regulation of nuclear calcium signaling relies upon the investigations with isolated nuclei. Mechanisms for generating calcium signaling in the nucleus have been identified. Two calcium transporting systems, an ATP-dependant nuclear Ca(2+)-ATPase and an IP4-mediated inositol 1,3,4,5-tetrakisphosphate receptor, are located on the outer nuclear membrane. Thus, ATP and IP4, depending on external free calcium concentrations, are responsible for filling the nuclear envelope calcium pool. The inositol 1,4,5-trisphosphate receptor is located on the inner nuclear membrane with its ligand binding domain facing toward the nucleoplasm. Likewise, the ryanodine receptor is located on the inner nuclear membrane and its ligand cADP-ribose is generated within the nucleus. A 120 kDa protein fragment of nuclear PLC-gamma1 is stimulated in vivo by epidermal growth factor nuclear signaling coincident with the time course of nuclear membrane epidermal growth factor receptor activation. Stimulated 120 kDa protein fragment interacts with PIKE, a nuclear GTPase, and together they form a complex with PI[3]kinase serving as a module for nuclear PI[3]K stimulation. Thus, the nucleus has its own IP(3) generating system.

Human papillomavirus E6/E7 oncogenes promote mouse ear regeneration by increasing the rate of wound re-epithelization and epidermal growth.

PubMed

Valencia, Concepción; Bonilla-Delgado, José; Oktaba, Katarzyna; Ocádiz-Delgado, Rodolfo; Gariglio, Patricio; Covarrubias, Luis

2008-12-01

Mammals have limited regeneration capacity. We report here that, in transgenic mice (Tg(bK6-E6/E7)), the expression of the E6/E7 oncogenes of human papilloma virus type 16 (HPV16) under the control of the bovine keratin 6 promoter markedly improves the mouse's capacity to repair portions of the ear after being wounded. Increased repair capacity correlates with an increased number of epidermal proliferating cells. In concordance with the expected effects of the E6 and E7 oncogenes, levels of p53 decreased and those of p16 in epidermal cells increased. In addition, we observed that wound re-epithelization proceeded faster in transgenic than in wild-type animals. After the initial re-epithelization, epidermal cell migration from the intact surrounding tissue appears to be a major contributor to the growing epidermis, especially in the repairing tissue of transgenic mice. We also found that there is a significantly higher number of putative epidermal stem cells in Tg(bK6-E6/E7) than in wild-type mice. Remarkably, hair follicles and cartilage regenerated within the repaired ear tissue, without evidence of tumor formation. We propose that the ability to regenerate ear portions is limited by the capacity of the epidermis to repair itself and grow.

Penile epidermal inclusion cyst: a late complication of penile girth enhancement surgery.

PubMed

Park, Hyun Jun; Park, Nam Cheol; Park, Sung Woo; Jern, Tae Kyung; Choi, Kyung-Un

2008-09-01

Epidermal inclusion cysts are benign lesions that can develop in any part of the body. However, the finding of an epidermal inclusion cyst in the penis is rare. The aim of this article was to present the management of a case of a penile epidermal inclusion cyst that occurred because of late complications of a penile girth enhancement surgery. A 52-year-old man presented with a painless, slowly growing mass in the penis, which was first noted after a penile girth enhancement surgery 20 years ago. A cystic mobile mass about 2 cm in depth was found surrounding the coronal sulcus. Excision of the mass was performed for diagnosis and treatment. There was no communication with the urethra. The pathological diagnosis was an epidermal inclusion cyst of the penis. A penile epidermal inclusion cyst in adult men is rare. It can develop after an inadequate procedure for penile girth enhancement, and should be treated by complete resection.

The Tomato MIXTA-Like Transcription Factor Coordinates Fruit Epidermis Conical Cell Development and Cuticular Lipid Biosynthesis and Assembly1

PubMed Central

Lotan, Orfa; Alkan, Noam; Tsimbalist, Tatiana; Rechav, Katya; Fernandez-Moreno, Josefina-Patricia; Widemann, Emilie; Grausem, Bernard; Pinot, Franck; Costa, Fabrizio; Aharoni, Asaph

2015-01-01

The epidermis of aerial plant organs is the primary source of building blocks forming the outer surface cuticular layer. To examine the relationship between epidermal cell development and cuticle assembly in the context of fruit surface, we investigated the tomato (Solanum lycopersicum) MIXTA-like gene. MIXTA/MIXTA-like proteins, initially described in snapdragon (Antirrhinum majus) petals, are known regulators of epidermal cell differentiation. Fruit of transgenically silenced SlMIXTA-like tomato plants displayed defects in patterning of conical epidermal cells. They also showed altered postharvest water loss and resistance to pathogens. Transcriptome and cuticular lipids profiling coupled with comprehensive microscopy revealed significant modifications to cuticle assembly and suggested SlMIXTA-like to regulate cutin biosynthesis. Candidate genes likely acting downstream of SlMIXTA-like included cytochrome P450s (CYPs) of the CYP77A and CYP86A subfamilies, LONG-CHAIN ACYL-COA SYNTHETASE2, GLYCEROL-3-PHOSPHATE SN-2-ACYLTRANSFERASE4, and the ATP-BINDING CASSETTE11 cuticular lipids transporter. As part of a larger regulatory network of epidermal cell patterning and L1-layer identity, we found that SlMIXTA-like acts downstream of SlSHINE3 and possibly cooperates with homeodomain Leu zipper IV transcription factors. Hence, SlMIXTA-like is a positive regulator of both cuticle and conical epidermal cell formation in tomato fruit, acting as a mediator of the tight association between fruit cutin polymer formation, cuticle assembly, and epidermal cell patterning. PMID:26443676

Why intra-epidermal electrical stimulation achieves stimulation of small fibres selectively: a simulation study

NASA Astrophysics Data System (ADS)

Motogi, Jun; Sugiyama, Yukiya; Laakso, Ilkka; Hirata, Akimasa; Inui, Koji; Tamura, Manabu; Muragaki, Yoshihiro

2016-06-01

The in situ electric field in the peripheral nerve of the skin is investigated to discuss the selective stimulation of nerve fibres. Coaxial planar electrodes with and without intra-epidermal needle tip were considered as electrodes of a stimulator. From electromagnetic analysis, the tip depth of the intra-epidermal electrode should be larger than the thickness of the stratum corneum, the electrical conductivity of which is much lower than the remaining tissue. The effect of different radii of the outer ring electrode on the in situ electric field is marginal. The minimum threshold in situ electric field (rheobase) for free nerve endings is estimated to be 6.3 kV m-1. The possible volume for electrostimulation, which can be obtained from the in situ electric field distribution, becomes deeper and narrower with increasing needle depth, suggesting that possible stimulation sites may be controlled by changing the needle depth. The injection current amplitude should be adjusted when changing the needle depth because the peak field strength also changes. This study shows that intra-epidermal electrical stimulation can achieve stimulation of small fibres selectively, because Aβ-, Aδ-, and C-fibre terminals are located at different depths in the skin.

Integrin Beta 1 Suppresses Multilayering of a Simple Epithelium

PubMed Central

Chen, Jichao; Krasnow, Mark A.

2012-01-01

Epithelia are classified as either simple, a single cell layer thick, or stratified (multilayered). Stratified epithelia arise from simple epithelia during development, and transcription factor p63 functions as a key positive regulator of epidermal stratification. Here we show that deletion of integrin beta 1 (Itgb1) in the developing mouse airway epithelium abrogates airway branching and converts this monolayer epithelium into a multilayer epithelium with more than 10 extra layers. Mutant lung epithelial cells change mitotic spindle orientation to seed outer layers, and cells in different layers become molecularly and functionally distinct, hallmarks of normal stratification. However, mutant lung epithelial cells do not activate p63 and do not switch to the stratified keratin profile of epidermal cells. These data, together with previous data implicating Itgb1 in regulation of epidermal stratification, suggest that the simple-versus-stratified developmental decision may involve not only stratification inducers like p63 but suppressors like Itgb1 that prevent simple epithelia from inappropriately activating key steps in the stratification program. PMID:23285215

Evolution and genetics of root hair stripes in the root epidermis.

PubMed

Dolan, L; Costa, S

2001-03-01

Root hair pattern develops in a number of different ways in angiosperm. Cells in the epidermis of some species undergo asymmetric cell divisions to form a smaller daughter cell from which a hair grows, and a larger cell that forms a non-hair epidermal cell. In other species any cell in the epidermis can form a root hair. Hair cells are arranged in files along the Arabidopsis root, located in the gaps between underlying cortical cell files. Epidermal cells overlying a single cortical cell file develop as non-hair epidermal cells. Genetic analysis has identified a transcription factor cascade required for the formation of this pattern. WEREWOLF (WER) and GLABRA2 (GL2) are required for the formation of non-hair epidermal cells while CAPRICE (CPC) is required for hair cell development. Recent analyses of the pattern of epidermal cells among the angiosperms indicate that this striped pattern of cell organization evolved from non-striped ancestors independently in a number of diverse evolutionary lineages. The genetic basis for the evolution of epidermal pattern in angiosperms may now be examined.

Perforator Flaps after Excision of Large Epidermal Cysts in the Buttocks

PubMed Central

Kim, Sang Wha; Yang, Seong Hyeok; Kim, Jeong Tae

2014-01-01

Background Epidermal cysts are commonly occurring masses usually less than 5 cm in diameter, but in predisposed patients, epidermal cysts can grow relatively large due to chronic infection. Methods From June 2002 to July 2010, 17 patients received 19 regional perforator-based island flaps to cover defects due to the excision of large epidermal cysts (diameter >5 cm) in the buttocks. Eight patients had diabetes, and seven had rheumatoid arthritis. The pedicles were not fully isolated to prevent spasms or twisting. Results All the flaps survived completely, except for one case with partial necrosis of the flap, which necessitated another perforator-based island flap for coverage. There were two cases of wound dehiscence, which were re-closed after meticulous debridement. There were no recurrences of the masses during follow-up periods of 8.1 months (range, 6-12 months). Conclusions In patients with large epidermal cysts and underlying medical disorders, regional perforator-based island flaps can be the solution to coverage of the defects after excision. PMID:24665422

ACR4, a putative receptor kinase gene of Arabidopsis thaliana, that is expressed in the outer cell layers of embryos and plants, is involved in proper embryogenesis.

PubMed

Tanaka, Hirokazu; Watanabe, Masaru; Watanabe, Daisuke; Tanaka, Toshihiro; Machida, Chiyoko; Machida, Yasunori

2002-04-01

The surfaces of higher plants are characterized by epidermis, which usually consists of a single layer of cells. The epidermis is derived from the outer cell layer of the embryo or protoderm, which arises as a result of periclinal cell division. After seed germination, most of the epidermal cells of the aerial parts of plants are derived from the outer cell layer of the shoot apical meristem (the L1 layer). Thus, knowledge of how the protoderm and/or L1 layer is established is fundamental to understanding the morphogenesis of higher plants. Here, we report the isolation of a gene encoding an Arabidopsis homologue (ACR4) of the maize putative receptor kinase CRINKLY4 (CR4), which is involved in epidermal differentiation. The domain organization of the predicted amino acid sequence of ACR4 is essentially identical to that of CR4. ACR4-GFP fusion protein localized to the cell surface when expressed in tobacco cell (BY-2) culture. ACR4 transcripts were detected in all the organs of the Arabidopsis plant. In developing embryos and shoot apices, ACR4 transcripts accumulated in protoderm and epidermis at relatively higher levels than in the inner tissues. Over-expression of antisense ACR4 in Arabidopsis plants resulted in malformation of embryos to varying degrees. These results suggest that ACR4 is, at a minimum, involved in the normal morphogenesis of embryos, most likely through properly differentiating protoderm cells.

Structural Interaction Between GFP-Labeled Diazotrophic Endophytic Bacterium Herbaspirillum seropedicae RAM10 and Pineapple Plantlets ‘VitóRia’

PubMed Central

Estrela Borges Baldotto, Lílian; Lopes Olivares, Fábio; Bressan-Smith, Ricardo

2011-01-01

The events involved in the structural interaction between the diazotrophic endophytic bacterium Herbaspirillum seropedicae, strain RAM10, labeled with green fluorescent protein, and pineapple plantlets ‘Vitória’ were evaluated by means of bright-field and fluorescence microscopy, combined with scanning electron microscopy for 28 days after inoculation. After 6 hours of inoculation, H. seropedicae was already adhered to the roots, colonizing mainly root hair surface and bases, followed by epidermal cell wall junctions. Bacteria adherence in the initial periods occurred mainly in the form of solitary cells and small aggregates with pleomorphic cells. Bacteria infection of root tissue occurred through the cavities caused by the disruption of epidermal cells during the emergence of lateral roots and the endophytic establishment by the colonization of intercellular spaces of the cortical parenchyma. Moreover, within 1 day after inoculation the bacteria were colonizing the shoots. In this region, the preferred sites of epiphytic colonization were epidermal cell wall junctions, peltate scutiform trichomes and non-glandular trichomes. Subsequently, the bacteria occupied the outer periclinal walls of epidermal cells and stomata. The penetration into the shoot occurred passively through stoma aperture followed by the endophytic establishment on the substomatal chambers and spread to the intercellular spaces of spongy chlorenchyma. After 21 days of inoculation, bacterial biofilm were seen at the root hair base and on epidermal cell wall surface of root and leaf, also confirming the epiphytic nature of H. seropedicae. PMID:24031612

Structural Interaction Between GFP-Labeled Diazotrophic Endophytic Bacterium Herbaspirillum seropedicae RAM10 and Pineapple Plantlets 'VitóRia'.

PubMed

Estrela Borges Baldotto, Lílian; Lopes Olivares, Fábio; Bressan-Smith, Ricardo

2011-01-01

The events involved in the structural interaction between the diazotrophic endophytic bacterium Herbaspirillum seropedicae, strain RAM10, labeled with green fluorescent protein, and pineapple plantlets 'Vitória' were evaluated by means of bright-field and fluorescence microscopy, combined with scanning electron microscopy for 28 days after inoculation. After 6 hours of inoculation, H. seropedicae was already adhered to the roots, colonizing mainly root hair surface and bases, followed by epidermal cell wall junctions. Bacteria adherence in the initial periods occurred mainly in the form of solitary cells and small aggregates with pleomorphic cells. Bacteria infection of root tissue occurred through the cavities caused by the disruption of epidermal cells during the emergence of lateral roots and the endophytic establishment by the colonization of intercellular spaces of the cortical parenchyma. Moreover, within 1 day after inoculation the bacteria were colonizing the shoots. In this region, the preferred sites of epiphytic colonization were epidermal cell wall junctions, peltate scutiform trichomes and non-glandular trichomes. Subsequently, the bacteria occupied the outer periclinal walls of epidermal cells and stomata. The penetration into the shoot occurred passively through stoma aperture followed by the endophytic establishment on the substomatal chambers and spread to the intercellular spaces of spongy chlorenchyma. After 21 days of inoculation, bacterial biofilm were seen at the root hair base and on epidermal cell wall surface of root and leaf, also confirming the epiphytic nature of H. seropedicae.

Identification of a Population of Epidermal Squamous Cell Carcinoma Cells with Enhanced Potential for Tumor Formation

PubMed Central

Adhikary, Gautam; Grun, Dan; Kerr, Candace; Balasubramanian, Sivaprakasam; Rorke, Ellen A.; Vemuri, Mohan; Boucher, Shayne; Bickenbach, Jackie R.; Hornyak, Thomas; Xu, Wen; Fisher, Matthew L.; Eckert, Richard L.

2013-01-01

Epidermal squamous cell carcinoma is among the most common cancers in humans. These tumors are comprised of phenotypically diverse populations of cells that display varying potential for proliferation and differentiation. An important goal is identifying cells from this population that drive tumor formation. To enrich for tumor-forming cells, cancer cells were grown as spheroids in non-attached conditions. We show that spheroid-selected cells form faster growing and larger tumors in immune-compromised mice as compared to non-selected cells. Moreover, spheroid-selected cells gave rise to tumors following injection of as few as one hundred cells, suggesting these cells have enhanced tumor-forming potential. Cells isolated from spheroid-selected tumors retain an enhanced ability to grow as spheroids when grown in non-attached culture conditions. Thus, these tumor-forming cells retain their phenotype following in vivo passage as tumors. Detailed analysis reveals that spheroid-selected cultures are highly enriched for expression of epidermal stem cell and embryonic stem cell markers, including aldehyde dehydrogenase 1, keratin 15, CD200, keratin 19, Oct4, Bmi-1, Ezh2 and trimethylated histone H3. These studies indicate that a subpopulation of cells that possess stem cell-like properties and express stem cell markers can be derived from human epidermal cancer cells and that these cells display enhanced ability to drive tumor formation. PMID:24376802

Ultrastructure and chemical composition of the proboscis hooks of Acanthocephalus lucii (Müller, 1776) (Acanthocephala: Palaeacanthocephala) using X-ray elemental analysis.

PubMed

Brázová, Tímea; Poddubnaya, Larisa G; Miss, Noemí Ramírez; Hanzelová, Vladimíra

2014-12-01

The ultrastructure and chemical composition of the proboscis hooks and surrounding tegument of Acanthocephalus lucii (Müller, 1776), a parasite of European perch, Perca fluviatilis Linnaeus, were examined using scanning (SEM) and transmission (TEM) electron microscopy and X-ray microanalysis (EDXA). The blade of middle hooks consists of three layers: an outer homogeneous layer, an inner heterogeneous layer and a central core. TEM observation revealed the presence of hollow tubes, which spaced the central core; fibrous inner hook layer surrounded by an electron-dense margin and the basal tegumental layer filled with electron-dense bodies and outer layer. We found for the first time that the so-called 'epidermal covering' surrounding of the exposed hook blade (outer hook layer) is a modified striped portion of the tegumental layer and there are no special contact sites between these two morphologically different structures, i.e. striped layer of the syncytial tegument and following proper outer hook layer, which is a homogeneous, moderately electron-dense layer of -0.3 μm in thickness. The hook root is embedded into subtegumental fibrous layer. X-ray microanalysis of both the surface and internal parts of A. lucii hooks demonstrated the presence of calcium, magnesium, phosphorus and sulphur. The highest concentration of sulphur was recorded at the tip of hooks, whereas the middle part of the hooks was most rich in calcium, phosphorus and magnesium. The proximal part of the hooks contained lower concentrations of sulphur, calcium and phosphorus. In the proboscis tegument, only two elements, calcium and silicon, were found. The differences observed in the chemical composition of the hook 'epidermal covering' and the proboscis tegument support our ultrastructural findings that the hook tegumental covering is a modified structure compared with that of the general proboscis tegument.

Epidermal Cell Death in Rice Is Regulated by Ethylene, Gibberellin, and Abscisic Acid

PubMed Central

Steffens, Bianka; Sauter, Margret

2005-01-01

Programmed cell death (PCD) of epidermal cells that cover adventitious root primordia in deepwater rice (Oryza sativa) is induced by submergence. Early suicide of epidermal cells may prevent injury to the growing root that emerges under flooding conditions. Induction of PCD is dependent on ethylene signaling and is further promoted by gibberellin (GA). Ethylene and GA act in a synergistic manner, indicating converging signaling pathways. Treatment of plants with GA alone did not promote PCD. Treatment with the GA biosynthesis inhibitor paclobutrazol resulted in increased PCD in response to ethylene and GA presumably due to an increased sensitivity of epidermal cells to GA. Abscisic acid (ABA) was shown to efficiently delay ethylene-induced as well as GA-promoted cell death. The results point to ethylene signaling as a target of ABA inhibition of PCD. Accumulation of ethylene and GA and a decreased ABA level in the rice internode thus favor induction of epidermal cell death and ensure that PCD is initiated as an early response that precedes adventitious root growth. PMID:16169967

Protoplasmic Swelling as a Symptom of Freezing Injury in Onion Bulb Cells 1

PubMed Central

Arora, Rajeev; Palta, Jiwan P.

1986-01-01

Freezing injury, in onion bulb tissue, is known to cause enhanced K+ efflux accompanied by a small but significant loss of Ca2+ following incipient freezing injury and swelling of protoplasm during the postthaw secondary injury. The protoplasmic swelling of the cell is thought to be caused by the passive influx of extracellular K+ into the cell followed by water uptake. Using outer epidermal layer of unfrozen onion bulb scales (Allium cepa L. cv Big Red), we were able to stimulate the irreversible freezing injury symptoms, by bathing epidermal cells in 50 millimolar KCl. These symptoms were prevented by adding 20 millimolar CaCl2 to the extracellular KCl solution. Our results provide evidence that loss of cellular Ca2+ plays an important role in the initiation and the progression of freezing injury. Images Fig. 1 PMID:16665083

Fingerprint-Inspired Flexible Tactile Sensor for Accurately Discerning Surface Texture.

PubMed

Cao, Yudong; Li, Tie; Gu, Yang; Luo, Hui; Wang, Shuqi; Zhang, Ting

2018-04-01

Inspired by the epidermal-dermal and outer microstructures of the human fingerprint, a novel flexible sensor device is designed to improve haptic perception and surface texture recognition, which is consisted of single-walled carbon nanotubes, polyethylene, and polydimethylsiloxane with interlocked and outer micropyramid arrays. The sensor shows high pressure sensitivity (-3.26 kPa -1 in the pressure range of 0-300 Pa), and it can detect the shear force changes induced by the dynamic interaction between the outer micropyramid structure on the sensor and the tested material surface, and the minimum dimension of the microstripe that can be discerned is as low as 15 µm × 15 µm (interval × width). To demonstrate the texture discrimination capability, the sensors are tested for accurately discerning various surface textures, such as the textures of different fabrics, Braille characters, the inverted pyramid patterns, which will have great potential in robot skins and haptic perception, etc. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Interactions Between Epidermal Keratinocytes, Dendritic Epidermal T-Cells, and Hair Follicle Stem Cells.

PubMed

Badarinath, Krithika; Dutta, Abhik; Hegde, Akshay; Pincha, Neha; Gund, Rupali; Jamora, Colin

2018-06-13

The interplay of immune cells and stem cells in maintaining skin homeostasis and repair is an exciting new frontier in cutaneous biology. With the growing appreciation of the importance of this new crosstalk comes the requirement of methods to interrogate the molecular underpinnings of these leukocyte-stem cell interactions. Here we describe how a combination of FACS, cellular coculture assays, and conditioned media treatments can be utilized to advance our understanding of this emerging area of intercellular communication between immune cells and stem cells.

Squamous cell cancer (image)

MedlinePlus

Squamous cell cancer involves cancerous changes to the cells of the middle portion of the epidermal skin layer. It is ... malignant tumor, and is more aggressive than basal cell cancer, but still may be relatively slow-growing. It ...

Self-assembled polyhydroxy fatty acids vesicles: a mechanism for plant cutin synthesis.

PubMed

Heredia-Guerrero, José A; Benítez, José J; Heredia, Antonio

2008-03-01

Despite its biological importance, the mechanism of formation of cutin, the polymeric matrix of plant cuticles, has not yet been fully clarified. Here, for the first time, we show the participation in the process of lipid vesicles formed by the self-assembly of endogenous polyhydroxy fatty acids. The accumulation and fusion of these vesicles (cutinsomes) at the outer part of epidermal cell wall is proposed as the mechanism for early cuticle formation.

Polarization of IRON-REGULATED TRANSPORTER 1 (IRT1) to the plant-soil interface plays crucial role in metal homeostasis.

PubMed

Barberon, Marie; Dubeaux, Guillaume; Kolb, Cornelia; Isono, Erika; Zelazny, Enric; Vert, Grégory

2014-06-03

In plants, the controlled absorption of soil nutrients by root epidermal cells is critical for growth and development. IRON-REGULATED TRANSPORTER 1 (IRT1) is the main root transporter taking up iron from the soil and is also the main entry route in plants for potentially toxic metals such as manganese, zinc, cobalt, and cadmium. Previous work demonstrated that the IRT1 protein localizes to early endosomes/trans-Golgi network (EE/TGN) and is constitutively endocytosed through a monoubiquitin- and clathrin-dependent mechanism. Here, we show that the availability of secondary non-iron metal substrates of IRT1 (Zn, Mn, and Co) controls the localization of IRT1 between the outer polar domain of the plasma membrane and EE/TGN in root epidermal cells. We also identify FYVE1, a phosphatidylinositol-3-phosphate-binding protein recruited to late endosomes, as an important regulator of IRT1-dependent metal transport and metal homeostasis in plants. FYVE1 controls IRT1 recycling to the plasma membrane and impacts the polar delivery of this transporter to the outer plasma membrane domain. This work establishes a functional link between the dynamics and the lateral polarity of IRT1 and the transport of its substrates, and identifies a molecular mechanism driving polar localization of a cell surface protein in plants.

Human dermal papilla cells and outer root sheath cells: no follicular differentiation in nude mice and chicken embryos.

PubMed

Chiu, H C; Chang, C H; Jee, S H; Chang, C C; Wu, Y C

1994-09-01

Human scalp specimens were incubated in 5 U/ml dispase solution at 4 degrees C overnight before the isolation of dermal papillae and follicle epithelium. This pretreatment not only facilitated the attachment and cell outgrowth of dermal papillae but also made it easier to pluck out hairs with intact follicle epithelium. The outer root sheath cells were released from the follicle epithelium and grown on a feeder layer of mitomycin C-treated human dermal fibroblasts. The subcultured outer root sheath cells were grown in a serum-free medium. When the mixtures of early-passage dermal papilla cells and outer root sheath cells were injected into the subcutis of nude mice, an epidermal cyst surrounded by layers of fibrous tissue was found in three weeks. No hair follicles were found when the mixtures were implanted onto the chorioallantoic membrane of nine-day-old chicken embryos. A keratinized mass lying on the chorionic epithelium with or without smaller similar masses in the chorioallantoic membrane was found in eight days. No hair follicle-like structure could be found. Possible factors contributing to the failure to undergo follicular differentiation in this study are discussed.

Rotating Vessels for Growing Protein Crystals

NASA Technical Reports Server (NTRS)

Cottingham, Paul

2005-01-01

Rotating vessels have been proposed as means of growing larger, more nearly uniform protein crystals than would otherwise be possible in the presence of normal Earth gravitation. Heretofore, nonrotating vessels have been used. It is difficult to grow high-quality protein crystals in the terrestrial gravitational field because of convection plumes created by the interaction between gravitation and density gradients in protein-solution depletion layers around growing crystals. The density gradients and the associated convection plumes cause the surfaces of growing crystals to be exposed to nonuniform solution densities, thereby causing the crystals to form in irregular shapes. The microgravitational environment of outer space has been utilized to eliminate gravitation-induced convection, but this approach is generally not favorable because of the high cost and limited availability of space flight. The use of a rotating vessel according to the proposal is intended to ameliorate the effects of gravitation and the resultant convection, relative to the corresponding effects in a non-rotating vessel. The rotation would exert an averaging effect over time, distributing the convective force on the depletion layer. Therefore, the depletion layer would be more nearly uniform and, as a result, the growing crystal would be more nearly perfect. The proposal admits of variations (see figure), including the following: The growing crystal could be rotated about its own central axis or an external axis. The crystal-growth vessel could be of any of various shapes, including cylindrical, hemispherical, conical, and combinations thereof. The crystal-growth vessel could be suspended in a viscous fluid in an outer vessel to isolate the growing crystal from both ambient vibrations and vibrations induced by a mechanism that drives the rotation. The rotation could be coupled to the crystal-growth vessel by viscous or magnetic means. The crystal-growth vessel could be supported within the outer vessel by use of a magnetic field. The crystal-growth vessel and the outer vessel could be configured in a variety of ways to facilitate heat transfer, instrumentation, and rotation.

Automated measurement of epidermal thickness from optical coherence tomography images using line region growing

NASA Astrophysics Data System (ADS)

Delacruz, Jomer; Weissman, Jesse; Gossage, Kirk

2010-02-01

Optical Coherence Tomography (OCT) is a non-invasive imaging modality that acquires cross sectional images of tissue in-vivo. It accelerates skin diagnosis by eliminating invasive biopsy and laborious histology in the process. Dermatologists have widely used it for looking at morphology of skin diseases such as psoriasis, dermatitis, basal cell carcinoma etc. Skin scientists have also successfully used it for looking at differences in epidermal thickness and its underlying structure with respect to age, body sites, ethnicity, gender, and other related factors. Similar to other in-vivo imaging systems, OCT images suffer from a high degree of speckle and noise content, which hinders examination of tissue structures. Most of the previous work in OCT segmentation of skin was done manually. This compromised the quality of the results by limiting the analyses to a few frames per area. In this paper, we discuss a region growing method for automatic identification of the upper and lower boundaries of the epidermis in living human skin tissue. This image analysis method utilizes images obtained from a frequency-domain OCT. This system is high-resolution and high-speed, and thus capable of capturing volumetric images of the skin in short time. The three-dimensional (3D) data provides additional information that is used in the segmentation process to help compensate for the inherent noise in the images. This method not only provides a better estimation of the epidermal thickness, but also generates a 3D surface map of the epidermal-dermal junction, from which underlying topography can be visualized and further quantified.

Eradication of damaged keratinocytes in cutaneous lichen planus forms demonstrated by evaluation of epidermal and follicular expression of CK15, indices of apoptosis and regulatory protein S100.

PubMed

Upeniece, Ilze; Groma, Valerie; Skuja, Sandra; Cauce, Vinita

The study of cytoskeleton arrangement and its contribution to survival of cell-to-cell contacts appears to be essential for understanding of numerous cellular and tissue processes. Applying CK15, S100 labeling and TUNEL reaction to cutaneous lichen planus subtypes, we found CK15 expression in the outer and inner root sheath of hair follicles, the basal epidermal layer, and eccrine glands. Its follicular expression was decreased in nearby inflammatory infiltrates. The CK15 immunopositivity was mostly described as weak (92.3%) for lichen planus but equally subdivided into weak, moderate and strong in lichen planopilaris (2 = 32.514; df = 4; p < 0.001). The greatly varying apoptotic index was the highest in the lichen planopilaris involving the scalp: 81.2 ±10.7; 87.8 ±10.7 and 88.0 ±10.5 for the basal, spinous and upper epidermal layers, respectively. S100 positive epidermal and follicular cells did not differ in the lesions demonstrated in the study groups; still immunoreactivity was more pronounced in the scalp region of lichen planopilaris. Damage of cell-to-cell contacts was confirmed by electron microscopy. Apart from immunocyte-mediated keratinocyte death, cytoskeleton-based injury and loss of cell-to-cell and matrix contacts may be of great importance, leading to eradication of degrading cells and thus contributing to the pathogenesis of lichen planus.

Effects of heparin-binding epidermal growth factor-like growth factor on cell repopulation and signal transduction in periodontal ligament cells after scratch wounding in vitro.

PubMed

Lee, J S; Kim, J M; Hong, E K; Kim, S-O; Yoo, Y-J; Cha, J-H

2009-02-01

A growing amount of attention has been placed on periodontal regeneration and wound healing for periodontal therapy. This study was conducted in an effort to determine the effects of heparin-binding epidermal growth factor-like growth factor on cell repopulation and signal transduction in periodontal ligament cells after scratch wounding in vitro. Human periodontal ligament cells were acquired from explant tissue of human healthy periodontal ligament. After the wounding of periodontal ligament cells, the change in expression of heparin-binding epidermal growth factor-like growth factor and epidermal growth factor receptors 1-4 mRNA was assessed. The effects of heparin-binding epidermal growth factor-like growth factor on periodontal ligament cell proliferation and repopulation were assessed in vitro via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and by photographing the injuries, respectively. Extracellular signal-regulated kinase (Erk)1/2, p38 and Akt phosphorylation was characterized via western blotting. Scratch wounding resulted in a significant up-regulation of heparin-binding epidermal growth factor-like growth factor mRNA expression, whereas wounding had no effect on the expression levels of epidermal growth factor receptors 1-4. Interestingly, no expression of epidermal growth factor receptors 2 and 4 was detectable prior to or after wounding. Heparin-binding epidermal growth factor-like growth factor treatment promoted the proliferation and repopulation of periodontal ligament cells. The scratch wounding also stimulated the phosphorylation of Erk1/2 and p38, but not of Akt, in periodontal ligament cells, and heparin-binding epidermal growth factor-like growth factor treatment applied after wounding amplified and extended the activations of Erk1/2 and p38, but not of Akt. Furthermore, Erk1/2 inhibition blocked the process of cell repopulation induced by heparin-binding epidermal growth factor-like growth factor, whereas the inhibition of p38 delayed the process. These results indicate that heparin-binding epidermal growth factor-like growth factor may constitute a critical factor in the wound healing of human periodontal ligament cells by a mechanism that requires the activation of Erk1/2 via specific interaction with epidermal growth factor receptor 1.

[Changes of lastids in virus-infected cells of the attraction-zone from Sarracenia purpurea L].

PubMed

Barckhaus, R H; Weinert, H

1975-01-01

Viruslike particles 300-350 nm long and 70 nm in diameter were found in ultrathin sections of attraction-zone from Sarracenia purpurea. Epidermal- and mesophyll cells contained the bacilliform particles. The membrane-bound particles-most virions occured within ER-like membranes-consisted of an outer coat 70-90 A thick, an inner membrane and an axial core. The plastids of infected cells in which virus particles were localized show morphologicals changes of the organells.

Escherichia coli mutants impaired in maltodextrin transport.

PubMed

Wandersman, C; Schwartz, M; Ferenci, T

1979-10-01

Wild-type Escherichia coli K-12 was found to grow equally well on maltose and on maltodextrins containing up to seven glucose residues. Three classes of mutants unable to grow on maltodextrins, but still able to grow on maltose, were investigated in detail. The first class, already known, was composed of phage lambda-resistant mutants, which lack the outer membrane protein coded by gene lamB. These mutants grow on maltose and maltotriose but not at all on maltotetraose and longer maltodextrins which cannot cross the outer membrane. A second class of mutants were affected in malE, the structural gene of the periplasmic maltose binding protein. The maltose binding proteins isolated from the new mutants were altered in their substrate binding properties, but not in a way that could account for the mutant phenotypes. Rather, the results of growth experiments and transport studies suggest that these malE mutants are impaired in their ability to transport maltodextrins across the outer membrane. This implies that the maltose binding protein (in wild-type strains) cooperates with the lambda receptor in permeation through the outer membrane. The last class of mutants described in this paper were affected in malG, or perhaps in an as yet undetected gene close to malG. They were defective in the transfer of maltodextrins from the periplasmic space to the cytoplasm but only slightly affected in the transport of maltose.

Myosin II activity is required for functional leading-edge cells and closure of epidermal sheets in fish skin ex vivo.

PubMed

Morita, Toshiyuki; Tsuchiya, Akiko; Sugimoto, Masazumi

2011-09-01

Re-epithelialization in skin wound healing is a process in which epidermal sheets grow and close the wound. Although the actin-myosin system is thought to have a pivotal role in re-epithelialization, its role is not clear. In fish skin, re-epithelialization occurs around 500 μm/h and is 50 times faster than in mammalian skin. We had previously reported that leading-edge cells of the epidermal outgrowth have both polarized large lamellipodia and "purse string"-like actin filament cables in the scale-skin culture system of medaka fish, Oryzias latipes (Cell Tissue Res, 2007). The actin purse-string (APS) is a supracellular contractile machinery in which adherens junctions (AJs) link intracellular myosin II-including actin cables between neighboring cells. In this study, we developed a modified "face-to-face" scale-skin culture system as an ex vivo model to study epidermal wound healing, and examined the role of the actin-myosin system in the rapid re-epithelialization using a myosin II ATPase inhibitor, blebbistatin. A low level of blebbistatin suppressed the formation of APS and induced the dissociation of keratocytes from the leading edge without attenuating the growth of the epidermal sheet or the migration rate of solitary keratocytes. AJs in the superficial layer showed no obvious changes elicited by blebbistatin. However, two epidermal sheets without APSs did not make a closure with each other, which was confirmed by inhibiting the connecting AJs between the superficial layers. These results suggest that myosin II activity is required for functional leading-edge cells and for epidermal closure.

Ultrastructural studies of regenerating spines of the sea urchin Strongylocentrotus purpuratus. I. Cell types without spherules.

PubMed

Heatfield, B M; Travis, D F

1975-01-01

The fine structure of regenerating tips of spines of the sea urchin Strongylocentrotus purpuratus was investigated. Each conical tip consisted of an inner dermis, which deposits and contains the calcite skeleton, and an external layer of epidermis. Although cell types termed spherulecytes containing large, intracellular membrane bound spherules were also present in spine tissues, only epidermal and dermal cell types lacking such spherules are described in this paper. The epidermis was composed largely of free cells representing several functional types. Over the apical portion of the tip these cells occurred in groups, while proximally they were distributed within longitudinal grooves present along the periphery of the spine from the base to the tip. The terminal portions of apical processes extending from some of the epidermal cells formed a thin, contiguous outer layer consisting of small individual islands of cytoplasm bearing microvilli. Adjacent islands were connected around the periphery by a junctional complex extending roughly 200 A in depth in which the opposing plasma membranes were separated by a narrow gap about 145 A in width bridged by amorphous material. Other epidermal cells were closely associated with the basal lamina, which was 900 A in thickness and delineated the dermoepidermal junction; some of these cells appeared to synthesize the lamina, while others may be sensory nerve cells. The dermis at the spine tip also consisted of several functional types of free cells; the most interesting of these was the calcoblast, which deposits the skeleton. Calcoblasts extended a thin, cytoplasmic skeletal sheath which surrounded the tips and adjacent proximal portions of each of the longitudinally oriented microspines comprising the regenerating skeleton, and distally, formed a conical extracellular channel ahead of the mineralizing tip. The intimate relationship between calcoblasts and the growing mineral surface strongly suggests that these cells directly control both the kinetics of mineral deposition and morphogenesis of the skeleton. Other cell types in the dermis were precalcoblasts and phagocytes. Precalcoblasts may function as fibroblasts and are possible precursors of calcoblasts. Closely associated with the basal lamina at the dermoepidermal junction were extracellular unbanded anchoring fi0rils 150 A to 200 A51 in diameter. Scattered proximally among dermal cells were other extracellular fibrils, presumably collagenous, about 300 A in diameter wit

Reduced growth factor requirement of keloid-derived fibroblasts may account for tumor growth

DOE Office of Scientific and Technical Information (OSTI.GOV)

Russell, S.B.; Trupin, K.M.; Rodriguez-Eaton, S.

Keloids are benign dermal tumors that form during an abnormal wound-healing process is genetically susceptible individuals. Although growth of normal and keloid cells did not differ in medium containing 10% (vol/vol) fetal bovine serum, keloid culture grew to significantly higher densities than normal cells in medium containing 5% (vol/vol) fetal bovine serum, keloid cultures grew to significantly higher densities than normal cells in medium containing 5% (vol/vol) plasma or 1% fetal bovine serum. Conditioned medium from keloid cultures did not stimulate growth of normal cells in plasma nor did it contain detectable platelet-derived growth factor or epidermal growth factor. Keloidmore » fibroblasts responded differently than normal adult fibroblasts to transforming growth factor ..beta... Whereas transforming growth factor ..beta.. reduced growth stimulation by epidermal growth factor in cells from normal adult skin or scars, it enhanced the activity of epidermal growth factor in cells from normal adult skin or scars, it enhanced the activity of epidermal growth factor in cells from keloids. Normal and keloid fibroblasts also responded differently to hydrocortisone: growth was stimulated in normal adult cells and unaffected or inhibited in keloid cells. Fetal fibroblasts resembled keloid cells in their ability to grow in plasma and in their response to hydrocortisone. The ability of keloid fibroblasts to grow to higher cell densities in low-serum medium than cells from normal adult skin or from normal early or mature scars suggests that a reduced dependence on serum growth factors may account for their prolonged growth in vivo. Similarities between keloid and fetal cells suggest that keloids may result from the untimely expression of growth-control mechanism that is developmentally regulated.« less

A Naturally Occurring Mutation in an Arabidopsis Accession Affects a β-d-Galactosidase That Increases the Hydrophilic Potential of Rhamnogalacturonan I in Seed Mucilage[W

PubMed Central

Macquet, Audrey; Ralet, Marie-Christine; Loudet, Olivier; Kronenberger, Jocelyne; Mouille, Gregory; Marion-Poll, Annie; North, Helen M.

2007-01-01

The Arabidopsis thaliana accession Shahdara was identified as a rare naturally occurring mutant that does not liberate seed mucilage on imbibition. The defective locus was found to be allelic to the mum2-1 and mum2-2 mutants. Map-based cloning showed that MUCILAGE-MODIFIED2 (MUM2) encodes the putative β-d-galactosidase BGAL6. Activity assays demonstrated that one of four major β-d-galactosidase activities present in developing siliques is absent in mum2 mutants. No difference was observed in seed coat epidermal cell structure between wild-type and mutant seed; however, weakening of the outer tangential cell wall by chemical treatment resulted in the release of mucilage from mum2 seed coat epidermal cells, and the mum2 mucilage only increased slightly in volume, relative to the wild type. Consistent with the absence of β-d-galactosidase activity in the mutant, the inner layer of mucilage contained more Gal. The allocation of polysaccharides between the inner and outer mucilage layers was also modified in mum2. Mass spectrometry showed that rhamnogalacturonan I in mutant mucilage had more branching between rhamnose and hexose residues relative to the wild type. We conclude that the MUM2/BGAL6 β-d-galactosidase is required for maturation of rhamnogalacturonan I in seed mucilage by the removal of galactose/galactan branches, resulting in increased swelling and extrusion of the mucilage on seed hydration. PMID:18165330

VLF Wave Local Acceleration & ULF Wave Radial Diffusion: The Importance of K-Dependent PSD Analysis for Diagnosing the cause of Radiation Belt Acceleration.

NASA Astrophysics Data System (ADS)

Ozeke, L.; Mann, I. R.; Claudepierre, S. G.; Morley, S.; Henderson, M. G.; Baker, D. N.; Kletzing, C.; Spence, H. E.

2017-12-01

We present results showing the temporal evolution of electron Phase Space Density (PSD) in the outer radiation belt during the most intense geomagnetic storm of the last decade which occurred on March 17th 2015. Based on observations of growing local PSD peaks at fixed first and second adiabatic invariants of M=1000 MeV/G and K=0.18 G1/2Re respectively, previous studies argued that the outer radiation belt flux enhancement that occurred during this storm resulted from local acceleration driven by VLF waves. Here we show that the vast majority of the outer radiation belt consisted of electrons with much lower K-values than 0.18 G1/2Re, and that at these lower K-values there is no clear evidence of growing local PSD peaks consistent with that expected from local acceleration. Contrary to prior studies we show that the outer radiation belt flux enhancement is consistent with inward radial diffusion driven by ULF waves and present evidence that the growing local PSD peaks at K=0.18 G1/2Re and M=1000 MeV/G result from pitch-angle scattering of lower-K electrons to K=0.18 G1/2Re. In addition, we also show that the observed outer radiation belt flux enhancement during this geomagnetic storm can be reproduced using a radial diffusion model driven by measured ULF waves without including any local acceleration. These results highlight the importance of careful analysis of the electron PSD profiles as a function of L* over a range of fixed first, M and second K, adiabatic invariants to correctly determine the mechanism responsible for the electron flux enhancements observed in the outer radiation belt.

Immunohistochemical demonstration of keratins in the epidermal layers of the Malayan pangolin (Manis javanica), with remarks on the evolution of the integumental scale armour.

PubMed

Meyer, W; Liumsiricharoen, M; Suprasert, A; Fleischer, L G; Hewicker-Trautwein, M

2013-09-16

Using immunohistochemistry, the study demonstrates the distribution of keratins (pan-keratin with CK1-8, 10, 14-16, 19; keratins CK1, 5, 6, 9, 10; hair keratins AE13, AE14) in the epidermis of the Malayan pangolin (Manis javanica). A varying reaction spectrum was observed for pan-keratin, with body region-dependent negative to very strong reaction intensities. The dorsolateral epidermis exhibited positive reactions only in its vital layers, whereas the abdominal epidermis showed strong positive reactions in the soft two outer strata. The single acidic and basic-to-neutral (cyto)keratins produced clear variations compared to the pan-keratin tinging. E.g., CK1 appeared in all epidermal layers of both body regions, except for the ventral stratum corneum, whereas CK5, 6, 9, 10 were restricted to the soft ventral epidermis. Here, distinctly positive reactions were confined to the stratum granulosum, except for CK6 that appeared in the soft stratum corneum. A different staining pattern was obvious for the hair keratins, i.e., positive reactions of AE13 concentrated only in the granular layer of the dorsal epidermis. In the abdominal epidermis, remarkable tinging for AE14 was visible in the stratum basale, decreasing toward the corneal layer, but was also found in the outer root sheath cells of the hair follicles in the ventral body part. Our findings are discussed related to the evolution of the horny dorsal scales of the pangolin, which may have started from the tail root, projecting forward to the head.

De novo activating epidermal growth factor mutations (EGFR) in small-cell lung cancer.

PubMed

Thai, Alesha; Chia, Puey L; Russell, Prudence A; Do, Hongdo; Dobrovic, Alex; Mitchell, Paul; John, Thomas

2017-09-01

In Australia, mutations in epidermal growth factor mutations (EGFR) occur in 15% of patients diagnosed with non-small-cell lung cancer and are found with higher frequency in female, non-smokers of Asian ethnicity. Activating mutations in the EGFR gene are rarely described in SCLC. We present two cases of de novo EGFR mutations in patients with SCLC detected in tissue and in plasma cell free DNA, both of whom were of Asian ethnicity and never-smokers. These two cases add to the growing body of evidence suggesting that screening for EGFR mutations in SCLC should be considered in patients with specific clinical features. © 2017 Royal Australasian College of Physicians.

Solid-State (13)C NMR Delineates the Architectural Design of Biopolymers in Native and Genetically Altered Tomato Fruit Cuticles.

PubMed

Chatterjee, Subhasish; Matas, Antonio J; Isaacson, Tal; Kehlet, Cindie; Rose, Jocelyn K C; Stark, Ruth E

2016-01-11

Plant cuticles on outer fruit and leaf surfaces are natural macromolecular composites of waxes and polyesters that ensure mechanical integrity and mitigate environmental challenges. They also provide renewable raw materials for cosmetics, packaging, and coatings. To delineate the structural framework and flexibility underlying the versatile functions of cutin biopolymers associated with polysaccharide-rich cell-wall matrices, solid-state NMR spectra and spin relaxation times were measured in a tomato fruit model system, including different developmental stages and surface phenotypes. The hydrophilic-hydrophobic balance of the cutin ensures compatibility with the underlying polysaccharide cell walls; the hydroxy fatty acid structures of outer epidermal cutin also support deposition of hydrophobic waxes and aromatic moieties while promoting the formation of cell-wall cross-links that rigidify and strengthen the cuticle composite during fruit development. Fruit cutin-deficient tomato mutants with compromised microbial resistance exhibit less efficient local and collective biopolymer motions, stiffening their cuticular surfaces and increasing their susceptibility to fracture.

A Homozygous Missense Mutation in TGM5 Abolishes Epidermal Transglutaminase 5 Activity and Causes Acral Peeling Skin Syndrome

PubMed Central

Cassidy, Andrew J.; van Steensel, Maurice A. M.; Steijlen, Peter M.; van Geel, Michel; Velden, Jaap van der; Morley, Susan M.; Terrinoni, Alessandro; Melino, Gerry; Candi, Eleonora; McLean, W. H. Irwin

2005-01-01

Peeling skin syndrome is an autosomal recessive genodermatosis characterized by the shedding of the outer epidermis. In the acral form, the dorsa of the hands and feet are predominantly affected. Ultrastructural analysis has revealed tissue separation at the junction between the granular cells and the stratum corneum in the outer epidermis. Genomewide linkage analysis in a consanguineous Dutch kindred mapped the gene to 15q15.2 in the interval between markers D15S1040 and D15S1016. Two homozygous missense mutations, T109M and G113C, were found in TGM5, which encodes transglutaminase 5 (TG5), in all affected persons in two unrelated families. The mutation was present on the same haplotype in both kindreds, indicating a probable ancestral mutation. TG5 is strongly expressed in the epidermal granular cells, where it cross-links a variety of structural proteins in the terminal differentiation of the epidermis to form the cornified cell envelope. An established, in vitro, biochemical cross-linking assay revealed that, although T109M is not pathogenic, G113C completely abolishes TG5 activity. Three-dimensional modeling of TG5 showed that G113C lies close to the catalytic domain, and, furthermore, that this glycine residue is conserved in all known transglutaminases, which is consistent with pathogenicity. Other families with more-widespread peeling skin phenotypes lacked TGM5 mutations. This study identifies the first causative gene in this heterogeneous group of skin disorders and demonstrates that the protein cross-linking function performed by TG5 is vital for maintaining cell-cell adhesion between the outermost layers of the epidermis. PMID:16380904

Biochemical and Ultrastructural Changes in Sida cordifolia L. and Catharanthus roseus L. to Auto Pollution.

PubMed

Verma, Vijeta; Chandra, Neelam

2014-01-01

Auto pollution is the by-product of our mechanized mobility, which adversely affects both plant and human life. However, plants growing in the urban locations provide a great respite to us from the brunt of auto pollution by absorbing the pollutants at their foliar surface. Foliar surface configuration and biochemical changes in plant species, namely, Sida cordifolia L. and Catharanthus roseus L. grown at roadside (polluted site 1, Talkatora; polluted site 2, Charbagh) in Lucknow city and in the garden of the university campus, which has been taken as reference site, were investigated. It was observed that air pollution caused by auto exhaust showed marked alterations in photosynthetic pigments (chlorophyll, carotenoid, and phaeophytin), and relative water content was reduced while antioxidative enzymes like catalase and peroxidase were found to be enhanced. The changes in the foliar configuration reveal marked alteration in epidermal traits, with decreased number of stomata, stomatal indices, and epidermal cells per unit area, while length and breadth of stomata and epidermal cells were found to be increased in leaves samples wich can be used as biomarkers of auto pollution.

Biochemical and Ultrastructural Changes in Sida cordifolia L. and Catharanthus roseus L. to Auto Pollution

PubMed Central

Verma, Vijeta; Chandra, Neelam

2014-01-01

Auto pollution is the by-product of our mechanized mobility, which adversely affects both plant and human life. However, plants growing in the urban locations provide a great respite to us from the brunt of auto pollution by absorbing the pollutants at their foliar surface. Foliar surface configuration and biochemical changes in plant species, namely, Sida cordifolia L. and Catharanthus roseus L. grown at roadside (polluted site 1, Talkatora; polluted site 2, Charbagh) in Lucknow city and in the garden of the university campus, which has been taken as reference site, were investigated. It was observed that air pollution caused by auto exhaust showed marked alterations in photosynthetic pigments (chlorophyll, carotenoid, and phaeophytin), and relative water content was reduced while antioxidative enzymes like catalase and peroxidase were found to be enhanced. The changes in the foliar configuration reveal marked alteration in epidermal traits, with decreased number of stomata, stomatal indices, and epidermal cells per unit area, while length and breadth of stomata and epidermal cells were found to be increased in leaves samples wich can be used as biomarkers of auto pollution. PMID:27355010

De novo epidermal regeneration using human eccrine sweat gland cells: higher competence of secretory over absorptive cells.

PubMed

Pontiggia, Luca; Biedermann, Thomas; Böttcher-Haberzeth, Sophie; Oliveira, Carol; Braziulis, Erik; Klar, Agnieszka S; Meuli-Simmen, Claudia; Meuli, Martin; Reichmann, Ernst

2014-06-01

In our previous work, we showed that human sweat gland-derived epithelial cells represent an alternative source of keratinocytes to grow a near normal autologous epidermis. The role of subtypes of sweat gland cells in epidermal regeneration and maintenance remained unclear. In this study, we compare the regenerative potential of both secretory and absorptive sweat gland cell subpopulations. We demonstrate the superiority of secretory over absorptive cells in forming a new epidermis on two levels: first, the proliferative and colony-forming efficiencies in vitro are significantly higher for secretory cells (SCs), and second, SCs show a higher frequency of successful epidermis formation as well as an increase in the thickness of the formed epidermis in the in vitro and in vivo functional analyses using a 3D dermo-epidermal skin model. However, the ability of forming functional skin substitutes is not limited to SCs, which supports the hypothesis that multiple subtypes of sweat gland epithelial cells hold regenerative properties, while the existence and exact localization of a keratinocyte stem cell population in the human eccrine sweat gland remain elusive.

Legal Consequences of the Pollution of Outer Space with Space Debris

NASA Astrophysics Data System (ADS)

Stubbe, Peter

2017-07-01

Space debris has grown to be a significant problem for outer space activities. The remnants of human activities in space are very diverse; they can be tiny paint flakes, all sorts of fragments, or entirely intact—but otherwise nonfunctional spacecraft and rocket bodies. The amount of debris is increasing at a growing pace, thus raising the risk of collision with operational satellites. Due to the relative high velocities involved in on-orbit collisions, their consequences are severe; collisions lead to significant damage or the complete destruction of the affected spacecraft. Protective measures and collision avoidance have thus become a major concern for spacecraft operators. The pollution of space with debris must, however, not only be seen as an unfavorable circumstance that accompanies space activities and increases the costs and complexity of outer space activities. Beyond this rather technical perspective, the presence of man-made, nonfunctional objects in space represents a global environmental concern. Similar to the patterns of other environmental problems on Earth, debris generation appears to have surpassed the absorption capacity of the space environment. Studies indicate that the evolution of the space object environment has crossed the tipping point to a runaway situation in which an increasing number of collisions―mostly among debris―leads to an uncontrolled population growth. It is thus in the interest of all mankind to address the debris problem in order to preserve the space environment for future generations. International space law protects the space environment. Article IX of the Outer Space Treaty obligates States to avoid the harmful contamination of outer space. The provision corresponds to the obligation to protect the environment in areas beyond national jurisdiction under the customary "no harm" rule of general environmental law. These norms are applicable to space debris and establish the duty not to pollute outer space by limiting the generation of debris. They become all the more effective when the principles of sustainable development are taken into account, which infuse considerations of intra- as well as inter-generational justice into international law. In view of the growing debris pollution and its related detrimental effects, it is obvious that questions of liability and responsibility will become increasingly relevant. The Liability Convention offers a remedy for victims having suffered damage caused by space debris. The launching State liability that it establishes is even absolute for damage occurring on the surface of the Earth. The secondary rules of international responsibility law go beyond mere compensation: States can also be held accountable for the environmental pollution event itself, entailing a number of consequential obligations, among them―under certain circumstances―a duty to active debris removal. While international law is, therefore, generally effective in addressing the debris problem, growing use and growing risks necessitate the establishment of a comprehensive traffic management regime for outer space. It would strengthen the rule of law in outer space and ensure the sustainability of space utilization.

Evolution of space food in Nostoc sp. HK-01

NASA Astrophysics Data System (ADS)

Tomita-Yokotani, Kaori; Yamashita, Masamichi; Hashimoto, Hirofumi; Sato, Seigo; Kimura, Yasuko; Katoh, Hiroshi; Arai, Mayumi

2012-07-01

Habitation in outer space is one of our challenges. We have been studying future space agriculture to provide food and oxygen for the habitation area in the space environment, on Mars. A cyanobacteria, Nostoc sp. HK-01, has high several outer space environmental tolerance. We have already confirmed that Nostoc sp.HK-01 had an ability to grow for over several years on the Martian regolith simulant in a laboratory experiment. Nostoc sp HK-01 would have high contribution to change the atmosphere in Mars as a photosynthetic creature. In outer environment, all of materials have to circulate for all of creature living in artificial eco-systems on Mars. This material has several functions as the utilization in space agriculture. Here, we are proposing using them as a food after its growing on Mars. We are trying to determine the best conditions and evolution for space food using Nostoc sp.HK-01 and studying the proposal of utilization of cyanobacteria, Nostoc sp HK-01, for the variation of meal as space agriculture.

Root growth regulation and gravitropism in maize roots does not require the epidermis

NASA Technical Reports Server (NTRS)

Bjorkman, T.; Cleland, R. E.

1991-01-01

We have earlier published observations showing that endogenous alterations in growth rate during gravitropism in maize roots (Zea mays L.) are unaffected by the orientation of cuts which remove epidermal and cortical tissue in the growing zone (Bjorkman and Cleland, 1988, Planta 176, 513-518). We concluded that the epidermis and cortex are not essential for transporting a growth-regulating signal in gravitropism or straight growth, nor for regulating the rate of tissue expansion. This conclusion has been challenged by Yang et al. (1990, Planta 180, 530-536), who contend that a shallow girdle around the entire perimeter of the root blocks gravitropic curvature and that this inhibition is the result of a requirement for epidermal cells to transport the growth-regulating signal. In this paper we demonstrate that the entire epidermis can be removed without blocking gravitropic curvature and show that the position of narrow girdles does not affect the location of curvature. We therefore conclude that the epidermis is not required for transport of a growth-regulating substance from the root cap to the growing zone, nor does it regulate the growth rate of the elongating zone of roots.

Blockade of epidermal growth factor receptor signaling in tumor cells and tumor-associated endothelial cells for therapy of androgen-independent human prostate cancer growing in the bone of nude mice.

PubMed

Kim, Sun-Jin; Uehara, Hisanori; Karashima, Takashi; Shepherd, David L; Killion, Jerald J; Fidler, Isaiah J

2003-03-01

We determined whether blockade of the epidermal growth factor receptor (EGF-R) signaling pathway by oral administration of the EGF-R tyrosine kinase inhibitor (PKI 166) alone or in combination with injectable Taxol inhibits the growth of PC-3MM2 human prostate cancer cells in the bone of nude mice. Male nude mice implanted with PC-3MM2 cells in the tibia were treated with oral administrations of PKI 166 or PKI 166 plus injectable Taxol beginning 3 days after implantation. The incidence and size of bone tumors and destruction of bone were determined by digitalized radiography. Expression of epidermal growth factor (EGF), EGF-R, and activated EGF-R in tumor cells and tumor-associated endothelial cells was determined by immunohistochemistry. Oral administration of PKI 166 or PKI 166 plus injectable Taxol reduced the incidence and size of bone tumors and destruction of bone. Immunohistochemical analysis revealed that PC-3MM2 cells growing adjacent to the bone expressed high levels of EGF and activated EGF-R, whereas tumor cells in the adjacent musculature did not. Moreover, endothelial cells within the bone tumor lesions, but not in uninvolved bone or tumors in the muscle, expressed high levels of activated EGF-R. Treatment with PKI 166 and more so with PKI 166 plus Taxol significantly inhibited phosphorylation of EGF-R on tumor and endothelial cells and induced significant apoptosis and endothelial cells within tumor lesions. These data indicate that endothelial cells exposed to EGF produced by tumor cells express activated EGF-R and that targeting EGF-R can produce significant therapeutic effects against prostate cancer bone metastasis.

On the role of stress anisotropy in the growth of stems.

PubMed

Baskin, Tobias I; Jensen, Oliver E

2013-11-01

We review the role of anisotropic stress in controlling the growth anisotropy of stems. Instead of stress, growth anisotropy is usually considered in terms of compliance. Anisotropic compliance is typical of cell walls, because they contain aligned cellulose microfibrils, and it appears to be sufficient to explain the growth anisotropy of an isolated cell. Nevertheless, a role for anisotropic stress in the growth of stems is indicated by certain growth responses that appear too rapid to be accounted for by changes in cell-wall compliance and because the outer epidermal wall of most growing stems has microfibrils aligned axially, an arrangement that would favour radial expansion based on cell-wall compliance alone. Efforts to quantify stress anisotropy in the stem have found that it is predominantly axial, and large enough in principle to explain the elongation of the epidermis, despite its axial microfibrils. That the epidermis experiences a stress deriving from the inner tissue, the so-called 'tissue stress', has been widely recognized; however, the origin of the dominant axial direction remains obscure. Based on geometry, an isolated cylindrical cell should have an intramural stress anisotropy favouring the transverse direction. Explanations for tissue stress have invoked differential elastic moduli, differential plastic deformation (so-called differential growth), and a phenomenon analogous to the maturation stress generated by secondary cell walls. None of these explanations has been validated. We suggest that understanding the role of stress anisotropy in plant growth requires a deeper understanding of the nature of stress in hierarchical, organic structures.

A Structurally Specialized Uniform Wall Layer is Essential for Constructing Wall Ingrowth Papillae in Transfer Cells

PubMed Central

Xia, Xue; Zhang, Hui-Ming; Offler, Christina E.; Patrick, John W.

2017-01-01

Transfer cells are characterized by wall labyrinths with either a flange or reticulate architecture. A literature survey established that reticulate wall ingrowth papillae ubiquitously arise from a modified component of their wall labyrinth, termed the uniform wall layer; a structure absent from flange transfer cells. This finding sparked an investigation of the deposition characteristics and role of the uniform wall layer using a Vicia faba cotyledon culture system. On transfer of cotyledons to culture, their adaxial epidermal cells spontaneously trans-differentiate to a reticulate architecture comparable to their abaxial epidermal transfer cell counterparts formed in planta. Uniform wall layer construction commenced once adaxial epidermal cell expansion had ceased to overlay the original outer periclinal wall on its inner surface. In contrast to the dense ring-like lattice of cellulose microfibrils in the original primary wall, the uniform wall layer was characterized by a sparsely dispersed array of linear cellulose microfibrils. A re-modeled cortical microtubule array exerted no influence on uniform wall layer formation or on its cellulose microfibril organization. Surprisingly, formation of the uniform wall layer was not dependent upon depositing a cellulose scaffold. In contrast, uniform wall cellulose microfibrils were essential precursors for constructing wall ingrowth papillae. On converging to form wall ingrowth papillae, the cellulose microfibril diameters increased 3-fold. This event correlated with up-regulated differential, and transfer-cell specific, expression of VfCesA3B while transcript levels of other cellulose biosynthetic-related genes linked with primary wall construction were substantially down-regulated. PMID:29259611

A Structurally Specialized Uniform Wall Layer is Essential for Constructing Wall Ingrowth Papillae in Transfer Cells.

PubMed

Xia, Xue; Zhang, Hui-Ming; Offler, Christina E; Patrick, John W

2017-01-01

Transfer cells are characterized by wall labyrinths with either a flange or reticulate architecture. A literature survey established that reticulate wall ingrowth papillae ubiquitously arise from a modified component of their wall labyrinth, termed the uniform wall layer; a structure absent from flange transfer cells. This finding sparked an investigation of the deposition characteristics and role of the uniform wall layer using a Vicia faba cotyledon culture system. On transfer of cotyledons to culture, their adaxial epidermal cells spontaneously trans -differentiate to a reticulate architecture comparable to their abaxial epidermal transfer cell counterparts formed in planta . Uniform wall layer construction commenced once adaxial epidermal cell expansion had ceased to overlay the original outer periclinal wall on its inner surface. In contrast to the dense ring-like lattice of cellulose microfibrils in the original primary wall, the uniform wall layer was characterized by a sparsely dispersed array of linear cellulose microfibrils. A re-modeled cortical microtubule array exerted no influence on uniform wall layer formation or on its cellulose microfibril organization. Surprisingly, formation of the uniform wall layer was not dependent upon depositing a cellulose scaffold. In contrast, uniform wall cellulose microfibrils were essential precursors for constructing wall ingrowth papillae. On converging to form wall ingrowth papillae, the cellulose microfibril diameters increased 3-fold. This event correlated with up-regulated differential, and transfer-cell specific, expression of VfCesA3B while transcript levels of other cellulose biosynthetic-related genes linked with primary wall construction were substantially down-regulated.

Cell Geometry Guides the Dynamic Targeting of Apoplastic GPI-Linked Lipid Transfer Protein to Cell Wall Elements and Cell Borders in Arabidopsis thaliana

PubMed Central

Wasteneys, Geoffrey

2013-01-01

During cellular morphogenesis, changes in cell shape and cell junction topology are fundamental to normal tissue and organ development. Here we show that apoplastic Glycophosphatidylinositol (GPI)-anchored Lipid Transfer Protein (LTPG) is excluded from cell junctions and flat wall regions, and passively accumulates around their borders in the epidermal cells of Arabidopsis thaliana. Beginning with intense accumulation beneath highly curved cell junction borders, this enrichment is gradually lost as cells become more bulbous during their differentiation. In fully mature epidermal cells, YFP-LTPG often shows a fibrous cellulose microfibril-like pattern within the bulging outer faces. Physical contact between a flat glass surface and bulbous cell surface induces rapid and reversible evacuation from contact sites and accumulation to the curved wall regions surrounding the contact borders. Thus, LTPG distribution is dynamic, responding to changes in cell shape and wall curvature during cell growth and differentiation. We hypothesize that this geometry-based mechanism guides wax-carrying LTPG to functional sites, where it may act to “seal” the vulnerable border surrounding cell-cell junctions and assist in cell wall fortification and cuticular wax deposition. PMID:24260561

Microsurgical removal of epidermal and cortical cells: evidence that the gravitropic signal moves through the outer cell layers in primary roots of maize

NASA Technical Reports Server (NTRS)

Yang, R. L.; Evans, M. L.; Moore, R.

1990-01-01

There is general agreement that during root gravitropism some sort of growth-modifying signal moves from the cap to the elongation zone and that this signal ultimately induces the curvature that leads to reorientation of the root. However, there is disagreement regarding both the nature of the signal and the pathway of its movement from the root cap to the elongation zone. We examined the pathway of movement by testing gravitropism in primary roots of maize (Zea mays L.) from which narrow (0.5 mm) rings of epidermal and cortical tissue were surgically removed from various positions within the elongation zone. When roots were girdled in the apical part of the elongation zone gravitropic curvature occurred apical to the girdle but not basal to the girdle. Filling the girdle with agar allowed curvature basal to the girdle to occur. Shallow girdles, in which only two or three cell layers (epidermis plus one or two cortical cell layers) were removed, prevented or greatly delayed gravitropic curvature basal to the girdle. The results indicate that the gravitropic signal moves basipetally through the outermost cell layers, perhaps through the epidermis itself.

Ultraviolet Radiation-Induced Skin Aging: The Role of DNA Damage and Oxidative Stress in Epidermal Stem Cell Damage Mediated Skin Aging

PubMed Central

Panich, Uraiwan; Sittithumcharee, Gunya; Rathviboon, Natwarath

2016-01-01

Skin is the largest human organ. Skin continually reconstructs itself to ensure its viability, integrity, and ability to provide protection for the body. Some areas of skin are continuously exposed to a variety of environmental stressors that can inflict direct and indirect damage to skin cell DNA. Skin homeostasis is maintained by mesenchymal stem cells in inner layer dermis and epidermal stem cells (ESCs) in the outer layer epidermis. Reduction of skin stem cell number and function has been linked to impaired skin homeostasis (e.g., skin premature aging and skin cancers). Skin stem cells, with self-renewal capability and multipotency, are frequently affected by environment. Ultraviolet radiation (UVR), a major cause of stem cell DNA damage, can contribute to depletion of stem cells (ESCs and mesenchymal stem cells) and damage of stem cell niche, eventually leading to photoinduced skin aging. In this review, we discuss the role of UV-induced DNA damage and oxidative stress in the skin stem cell aging in order to gain insights into the pathogenesis and develop a way to reduce photoaging of skin cells. PMID:27148370

Role of Homeodomain leucine zipper (HD-Zip) IV transcription factors in plant development and plant protection from deleterious environmental factors.

PubMed

Chew, William; Hrmova, Maria; Lopato, Sergiy

2013-04-12

Homeobox genes comprise an important group of genes that are responsible for regulation of developmental processes. These genes determine cell differentiation and cell fate in all eukaryotic organisms, starting from the early stages of embryo development. Homeodomain leucine zipper (HD-Zip) transcription factors are unique to the plant kingdom. Members of the HD-Zip IV subfamily have a complex domain topology and can bind several cis-elements with overlapping sequences. Many of the reported HD-Zip IV genes were shown to be specifically or preferentially expressed in plant epidermal or sub-epidermal cells. HD-Zip IV TFs were found to be associated with differentiation and maintenance of outer cell layers, and regulation of lipid biosynthesis and transport. Insights about the role of these proteins in plant cuticle formation, and hence their possible involvement in plant protection from pathogens and abiotic stresses has just started to emerge. These roles make HD-Zip IV proteins an attractive tool for genetic engineering of crop plants. To this end, there is a need for in-depth studies to further clarify the function of each HD-Zip IV subfamily member in commercially important plant species.

Role of Homeodomain Leucine Zipper (HD-Zip) IV Transcription Factors in Plant Development and Plant Protection from Deleterious Environmental Factors

PubMed Central

Chew, William; Hrmova, Maria; Lopato, Sergiy

2013-01-01

Homeobox genes comprise an important group of genes that are responsible for regulation of developmental processes. These genes determine cell differentiation and cell fate in all eukaryotic organisms, starting from the early stages of embryo development. Homeodomain leucine zipper (HD-Zip) transcription factors are unique to the plant kingdom. Members of the HD-Zip IV subfamily have a complex domain topology and can bind several cis-elements with overlapping sequences. Many of the reported HD-Zip IV genes were shown to be specifically or preferentially expressed in plant epidermal or sub-epidermal cells. HD-Zip IV TFs were found to be associated with differentiation and maintenance of outer cell layers, and regulation of lipid biosynthesis and transport. Insights about the role of these proteins in plant cuticle formation, and hence their possible involvement in plant protection from pathogens and abiotic stresses has just started to emerge. These roles make HD-Zip IV proteins an attractive tool for genetic engineering of crop plants. To this end, there is a need for in-depth studies to further clarify the function of each HD-Zip IV subfamily member in commercially important plant species. PMID:23584027

Skin Barrier and Calcium.

PubMed

Lee, Sang Eun; Lee, Seung Hun

2018-06-01

Epidermal barrier formation and the maintenance of barrier homeostasis are essential to protect us from the external environments and organisms. Moreover, impaired keratinocytes differentiation and dysfunctional skin barrier can be the primary causes or aggravating factors for many inflammatory skin diseases including atopic dermatitis and psoriasis. Therefore, understanding the regulation mechanisms of keratinocytes differentiation and skin barrier homeostasis is important to understand many skin diseases and establish an effective treatment strategy. Calcium ions (Ca 2+ ) and their concentration gradient in the epidermis are essential in regulating many skin functions, including keratinocyte differentiation, skin barrier formation, and permeability barrier homeostasis. Recent studies have suggested that the intracellular Ca 2+ stores such as the endoplasmic reticulum (ER) are the major components that form the epidermal calcium gradient and the ER calcium homeostasis is crucial for regulating keratinocytes differentiation, intercellular junction formation, antimicrobial barrier, and permeability barrier homeostasis. Thus, both Ca 2+ release from intracellular stores, such as the ER and Ca 2+ influx mechanisms are important in skin barrier. In addition, growing evidences identified the functional existence and the role of many types of calcium channels which mediate calcium flux in keratinocytes. In this review, the origin of epidermal calcium gradient and their role in the formation and regulation of skin barrier are focused. We also focus on the role of ER calcium homeostasis in skin barrier. Furthermore, the distribution and role of epidermal calcium channels, including transient receptor potential channels, store-operated calcium entry channel Orai1, and voltage-gated calcium channels in skin barrier are discussed.

Profiling the outer membrane proteome during growth and development of the social bacterium Myxococcus xanthus by selective biotinylation and analyses of outer membrane vesicles.

PubMed

Kahnt, Jörg; Aguiluz, Kryssia; Koch, Jürgen; Treuner-Lange, Anke; Konovalova, Anna; Huntley, Stuart; Hoppert, Michael; Søgaard-Andersen, Lotte; Hedderich, Reiner

2010-10-01

Social behavior in the bacterium Myxococcus xanthus relies on contact-dependent activities involving cell-cell and cell-substratum interactions. To identify outer membrane proteins that have a role in these activities, we profiled the outer membrane proteome of growing and starving cells using two strategies. First, outer membrane proteins were enriched by biotinylation of intact cells using the reagent NHS (N-hydroxysuccinimide)-PEO(12) (polyethylene oxide)-biotin with subsequent membrane solubilization and affinity chromatography. Second, the proteome of outer membrane vesicles (OMV) was determined. Comparisons of detected proteins show that these methods have different detection profiles and together provide a comprehensive view of the outer membrane proteome. From 362 proteins identified, 274 (76%) were cell envelope proteins including 64 integral outer membrane proteins and 85 lipoproteins. The majority of these proteins were of unknown function. Among integral outer membrane proteins with homologues of known function, TonB-dependent transporters comprise the largest group. Our data suggest novel functions for these transporters. Among lipoproteins with homologues of known function, proteins with hydrolytic functions comprise the largest group. The luminal load of OMV was enriched for proteins with hydrolytic functions. Our data suggest that OMV have functions in predation and possibly in transfer of intercellular signaling molecules between cells.

[Effects of soil wetting pattern on the soil water-thermal environment and cotton root water consumption under mulched drip irrigation].

PubMed

Li, Dong-wei; Li, Ming-si; Liu, Dong; Lyu, Mou-chao; Jia, Yan-hui

2015-08-01

Abstract: To explore the effects of soil wetting pattern on soil water-thermal environment and water consumption of cotton root under mulched drip irrigation, a field experiment with three drip intensities (1.69, 3.46 and 6.33 L · h(-1)), was carried out in Shihezi, Xinjiang Autonomous Region. The soil matric potential, soil temperature, cotton root distribution and water consumption were measured during the growing period of cotton. The results showed that the main factor influencing the soil temperature of cotton under plastic mulch was sunlight. There was no significant difference in the soil temperature and root water uptake under different treatments. The distribution of soil matrix suction in cotton root zone under plastic mulch was more homogeneous under ' wide and shallow' soil wetting pattern (W633). Under the 'wide and shallow' soil wetting pattern, the average difference of cotton root water consumption between inner row and outer row was 0.67 mm · d(-1), which was favorable to the cotton growing trimly at both inner and outer rows; for the 'narrow and deep' soil wetting pattern (W169), the same index was 0.88 mm · d(-1), which was unfavorable to cotton growing uniformly at both inner and outer rows. So, we should select the broad-shallow type soil wetting pattern in the design of drip irrigation under mulch.

Visual and functional demonstration of growing Bax-induced pores in mitochondrial outer membranes

PubMed Central

Gillies, Laura A; Du, Han; Peters, Bjoern; Knudson, C. Michael; Newmeyer, Donald D.; Kuwana, Tomomi

2015-01-01

Bax induces mitochondrial outer membrane permeabilization (MOMP), a critical step in apoptosis in which proteins are released into the cytoplasm. To resolve aspects of the mechanism, we used cryo-electron microscopy (cryo-EM) to visualize Bax-induced pores in purified mitochondrial outer membranes (MOMs). We observed solitary pores that exhibited negative curvature at their edges. Over time, the pores grew to ∼100–160 nm in diameter after 60–90 min, with some pores measuring more than 300 nm. We confirmed these results using flow cytometry, which we used to monitor the release of fluorescent dextrans from isolated MOM vesicles. The dextran molecules were released gradually, in a manner constrained by pore size. However, the release rates were consistent over a range of dextran sizes (10–500 kDa). We concluded that the pores were not static but widened dramatically to release molecules of different sizes. Taken together, the data from cryo-EM and flow cytometry argue that Bax promotes MOMP by inducing the formation of large, growing pores through a mechanism involving membrane-curvature stress. PMID:25411335

Physical State of Ices in the Outer Solar System. Revised

NASA Technical Reports Server (NTRS)

Roush, Ted L.; DeVincenzi, Donald (Technical Monitor)

2001-01-01

Comparison of the identity and abundances of ices observed around protostars and those associated with comets clearly suggests that comets preserve the heritage of the interstellar materials that aggregated to form them. However, the ability to identify these same species on icy satellites in the outer solar system is a complex function of the composition of the original ices, their subsequent thermal histories, and their exposure to various radiation environments. Our ability to identify the ices currently present on objects in the outer solar system relies upon observational and laboratory, and theoretical efforts. To date there is ample observational evidence for crystalline water ice throughout the outer solar system. In addition, there is growing evidence that amorphous ice may be present on some bodies. More volatile ices, e.g. N2, CH4. CO, and other species, e.g. ammonia hydrate, are identified on objects lying at and beyond Uranus. Both photolysis and radiolysis play important roles in altering the original surfaces due to chemical reactions and erosion of the surface. Ultraviolet photolysis appears to dominate alteration of the upper few hundred Angstroms, although sputtering the surface can sometimes be a significantly competitative process; dominating on icy surfaces embedded in a strong planetary magnetospheric field. There is growing observational evidence that the by-products of photolysis and radiolysis, suggested on a theoretical basis, are present on icy surfaces.

Switch from intracellular to intercellular invasion during water stress-tolerant legume nodulation

PubMed Central

Goormachtig, Sofie; Capoen, Ward; James, Euan K.; Holsters, Marcelle

2004-01-01

Rhizobia colonize their legume hosts by different modes of entry while initiating symbiotic nitrogen fixation. Most legumes are invaded via growing root hairs by the root hair-curl mechanism, which involves epidermal cell responses. However, invasion of a number of tropical legumes happens through fissures at lateral root bases by cortical, intercellular crack entry. In the semiaquatic Sesbania rostrata, the bacteria entered via root hair curls under nonflooding conditions. Upon flooding, root hair growth was prevented, invasion on accessible root hairs was inhibited, and intercellular invasion was recruited. The plant hormone ethylene was involved in these processes. The occurrence of both invasion pathways on the same host plant enabled a comparison to be made of the structural requirements for the perception of nodulation factors, which were more stringent for the epidermal root hair invasion than for the cortical intercellular invasion at lateral root bases. PMID:15079070

Parents׳ experiences of raising pre-school aged children in an outer-Melbourne growth corridor.

PubMed

Andrews, Fiona Jane; Rich, Stephanie; Stockdale, Rebecca; Shelley, Julia

2014-05-01

There is growing concern about the outer-suburbs in Australia as healthy places to raise children. This paper aimed to explore this from the perspectives of parents raising preschool-age children in an outer-Melbourne municipality. Findings showed that parents were positive about the natural environment as well as the provision of recreation areas and generally felt their neighbourhoods were a safe place for raising children. However, car-dependency, housing estate design and limited local job opportunities all appeared to contribute to social isolation amongst families. Using the Environments for Health Framework, this paper makes suggestions to improve liveability for families in this municipality. Copyright © 2014 Elsevier Ltd. All rights reserved.

Apple cuticle: the perfect interface

NASA Astrophysics Data System (ADS)

Curry, Eric; Arey, Bruce

2010-06-01

The domestic apple might well be called an 'extreme' fruit. In the arid Northwest United States, the fruit often tolerates surface temperatures ranging from -2 °C in the early spring to 50 °C in the heat of summer, and again to -2 °C during controlled postharvest storage for up to 12 months. During its 18-month existence, the apple maintains a cuticle that is dynamic and environmentally responsive to protect against 1) cellular water loss during desiccation stress and 2) excessive uptake of standing surface moisture. Physiological disorders of the peel such as russeting, cracking, splitting, flecking and lenticel marking, develop as epidermal cells respond to rapid changes in ambient conditions at specific developmental stages during the growing season. Resultant market losses underlie research investigating the nature of apple cuticle growth and development. Ultrastructural analysis of the pro-cuticle using scanning electron microscopy indicates an overlapping network of lipid-based distally-elongating microtubules--produced by and connected to epidermal cells--which co-polymerize to form an organic solvent-insoluble semi-permeable cutin matrix. Microtubule elongation, aggregation, and polymerization function together as long as the fruit continues to enlarge. The nature of lipid transport from the epidermal cells through the cell wall to become part of the cuticular matrix was explored using an FEI Helios NanoLabTM DualBeamTM focused ion beam/scanning electron microscope on chemically- and cryo-fixed peel tissue from mature or freshly harvested apples. Based on microtubule dimensions, regular projections found at the cell/cuticle interface suggest an array of microtubule-like structures associated with the epidermal cell.

University of Texas MD Anderson: Phenotypic Examination of PIK3CA Allelic Series using In Vitro/In Vivo Sensor Platforms | Office of Cancer Genomics

Cancer.gov

The CTD2 Center at the University of Texas MD Anderson Cancer Center utilized an established and operational MCF10A normal breast epithelial cell model to assess the ability of candidate driver aberrations to promote cell grow in anchorage-independent conditions (soft agar assay) and proliferate in the absence of insulin and epidermal growth factor (EGF).

University of Texas MD Anderson Cancer Center: Phenotypic Examination of PIK3CA Allelic Series using In Vitro/In Vivo Sensor Platforms | Office of Cancer Genomics

Cancer.gov

The CTD2 Center at the University of Texas MD Anderson Cancer Center utilized an established and operational MCF10A normal breast epithelial cell model to assess the ability of candidate driver aberrations to promote cell grow in anchorage-independent conditions (soft agar assay) and proliferate in the absence of insulin and epidermal growth factor (EGF).

Whole organ, venation and epidermal cell morphological variations are correlated in the leaves of Arabidopsis mutants.

PubMed

Pérez-Pérez, José Manuel; Rubio-Díaz, Silvia; Dhondt, Stijn; Hernández-Romero, Diana; Sánchez-Soriano, Joaquín; Beemster, Gerrit T S; Ponce, María Rosa; Micol, José Luis

2011-12-01

Despite the large number of genes known to affect leaf shape or size, we still have a relatively poor understanding of how leaf morphology is established. For example, little is known about how cell division and cell expansion are controlled and coordinated within a growing leaf to eventually develop into a laminar organ of a definite size. To obtain a global perspective of the cellular basis of variations in leaf morphology at the organ, tissue and cell levels, we studied a collection of 111 non-allelic mutants with abnormally shaped and/or sized leaves, which broadly represent the mutational variations in Arabidopsis thaliana leaf morphology not associated with lethality. We used image-processing techniques on these mutants to quantify morphological parameters running the gamut from the palisade mesophyll and epidermal cells to the venation, whole leaf and rosette levels. We found positive correlations between epidermal cell size and leaf area, which is consistent with long-standing Avery's hypothesis that the epidermis drives leaf growth. In addition, venation parameters were positively correlated with leaf area, suggesting that leaf growth and vein patterning share some genetic controls. Positional cloning of the genes affected by the studied mutations will eventually establish functional links between genotypes, molecular functions, cellular parameters and leaf phenotypes. © 2011 Blackwell Publishing Ltd.

Emodin suppresses maintenance of stemness by augmenting proteosomal degradation of epidermal growth factor receptor/epidermal growth factor receptor variant III in glioma stem cells.

PubMed

Kim, Jeongyub; Lee, Jong-Seon; Jung, Jieun; Lim, Inhye; Lee, Ji-Yun; Park, Myung-Jin

2015-02-01

There is a growing body of evidence that small subpopulations of cells with stem cell-like characteristics within most solid tumors are responsible for the malignancy of aggressive cancer cells and that targeting these cells might be a good therapeutic strategy to reduce the risk of tumor relapse after therapy. Here, we examined the effects of emodin (1,3,8-trihydroxy-6-methylanthraquinone), an active component of the root and rhizome of Rheum palmatum that has several biological activities, including antitumor effects, on primary cultured glioma stem cells (GSCs). Emodin inhibited the self-renewal activity of GSCs in vitro as evidenced by neurosphere formation, limiting dilution, and soft agar clonogenic assays. Emodin inhibited the maintenance of stemness by suppressing the expression of Notch intracellular domain, nonphosphorylated β-catenin, and phosphorylated STAT3 proteins. In addition, treatment with emodin partially induced apoptosis, reduced cell invasiveness, and sensitized GSCs to ionizing radiation. Intriguingly, emodin induced proteosomal degradation of epidermal growth factor receptor (EGFR)/EGFR variant III (EGFRvIII) by interfering with the association of EGFR/EGFRvIII with heat shock protein 90, resulting in the suppression of stemness pathways. Based on these data, we propose that emodin could be considered as a potent therapeutic adjuvant that targets GSCs.

Fluorescence fibre-optic confocal microscopy of skin in vivo: microscope and fluorophores.

PubMed

Suihko, Christian; Swindle, Lucinda D; Thomas, Steven G; Serup, Jørgen

2005-11-01

Fibre-optic confocal imaging in vivo is a new approach in the assessment of human skin. The objective is to describe a novel instrument and its operation and use in combination with fluorophores. The Stratum is a fibre-optic fluorescence confocal microscope especially developed for the study of skin and mucous membranes. The system is flexible and any body site can be studied with a hand-held scanner. The light source is a 488 nm argon ion laser. Horizontal (en face) images of the epidermis and outer dermis are produced with cellular resolution. Magnification is approximately 1000 x . Fluorescein sodium is routinely used as fluorophore (intradermal injection or application to the skin surface). This fluorophore is safe for human use in vivo, but other substances (rhodamine B, Acridine Orange, green fluorescent protein, curcumin) have also been studied. The instrument produces sharp images of epidermal cell layers from the epidermal surface to the sub-papillary dermis, with sub-cellular resolution. The scanner is flexible in use. The technique of intradermal fluorophore injection requires some skill. We consider this fibre-optic instrument a potentially important tool in skin research for non-invasive optical biopsy of primarily the epidermis. Present use is focussed on research applications, where the fluorophore distribution in the skin may illustrate morphological changes in the epidermis.

Silicification in Grasses: Variation between Different Cell Types

PubMed Central

Kumar, Santosh; Soukup, Milan; Elbaum, Rivka

2017-01-01

Plants take up silicon as mono-silicic acid, which is released to soil by the weathering of silicate minerals. Silicic acid can be taken up by plant roots passively or actively, and later it is deposited in its polymerized form as amorphous hydrated silica. Major silica depositions in grasses occur in root endodermis, leaf epidermal cells, and outer epidermal cells of inflorescence bracts. Debates are rife about the mechanism of silica deposition, and two contrasting scenarios are often proposed to explain it. According to the passive mode of silicification, silica deposition is a result of silicic acid condensation due to dehydration, such as during transpirational loss of water from the aboveground organs. In general, silicification and transpiration are positively correlated, and continued silicification is sometimes observed after cell and tissue maturity. The other mode of silicification proposes the involvement of some biological factors, and is based on observations that silicification is not necessarily coupled with transpiration. Here, we review evidence for both mechanisms of silicification, and propose that the deposition mechanism is specific to the cell type. Considering all the cell types together, our conclusion is that grass silica deposition can be divided into three modes: spontaneous cell wall silicification, directed cell wall silicification, and directed paramural silicification in silica cells. PMID:28400787

Channel catfish response to ultraviolet-B radiation

USGS Publications Warehouse

Ewing, M.S.; Blazer, V.S.; Fabacher, D.L.; Little, E.E.; Kocan, K.M.

1999-01-01

Fingerling channel catfish Ictalurus punctatus exposed to simulated ultraviolet-B radiation at an average daily dose of 2.9 J/cm2 were quite sensitive to the radiation. After a 24-h exposure, thinning of the most dorsal epidermis frequently was accompanied by edema. Compared with epidermis of unexposed fish, mucous cells in exposed fish were less superficial and club cells were less numerous both dorsally and high on the lateral surface of the body. Sunburn cells with pyknotic nuclei were evident in the epidermis of exposed fish. Among fish exposed for 48 h, focal necrosis and sloughing of the outer epidermal layer were widespread. A methanol-extractable skin substance that is associated with resistance to sunburn in other fish species was not detected in channel catfish.

Colonization and Intrusive Invasion of Potato Psyllid by 'Candidatus Liberibacter solanacearum'.

PubMed

Cicero, Joseph M; Fisher, Tonja W; Qureshi, Jawwad A; Stansly, Philip A; Brown, Judith K

2017-01-01

Previous studies have shown that the fastidious bacterial plant pathogen 'Candidatus Liberibacter solanacearum' (CLso) is transmitted circulatively and propagatively by the potato psyllid (PoP) Bactericera cockerelli. In this study, the temporal and spatial interrelationships between CLso PoP were investigated by scanning electron microscopy of the digestive system of PoP immature and adult instars and salivary glands of adults post CLso ingestion. CLso biofilms were not detectable on the outer midgut surface of the first and second instars; however, for third to fifth instars and teneral and mature adults, biofilms were observed in increasing numbers in each successive developmental stage. In adult PoP midguts, CLso cells were observed between the basal lamina and basal epithelial cell membranes; in basal laminar perforations, on the outer basal laminar surface, and in the ventricular lumen, epithelial cytosol, and filter chamber periventricular space. CLso were also abundantly visible in the salivary gland pericellular spaces and in the epidermal cell cytosol of the head. Collectively, these results point to an intrusive, systemic invasion of PoP by CLso that employs an endo/exocytosis-like mechanism, in the context of a propagative, circulative mode of transmission.

Onion epidermis as a new model to study the control of growth anisotropy in higher plants.

PubMed

Suslov, Dmitry; Verbelen, Jean-Pierre; Vissenberg, Kris

2009-01-01

To elucidate the role of cellulose microfibrils in the control of growth anisotropy, a link between their net orientation, in vitro cell wall extensibility, and anisotropic cell expansion was studied during development of the adaxial epidermis of onion (Allium cepa) bulb scales using polarization confocal microscopy, creep tests, and light microscopy. During growth the net cellulose alignment across the whole thickness of the outer epidermal wall changed from transverse through random to longitudinal and back to transverse relative to the bulb axis. Cell wall extension in vitro was always higher transverse than parallel to the net cellulose alignment. The direction of growth anisotropy was perpendicular to the net microfibril orientation and changed during development from longitudinal to transverse to the bulb axis. The correlation between the degree of growth anisotropy and the net cellulose alignment was poor. Thus the net cellulose microfibril orientation across the whole thickness of the outer periclinal epidermis wall defines the direction but not the degree of growth anisotropy. Strips isolated from the epidermis in the directions perpendicular and transverse to a net cellulose orientation can be used as an extensiometric model to prove a protein involvement in the control of growth anisotropy.

University of Texas MD Anderson Cancer Center (UT-MDACC): Phenotypic Examination of PIK3CA Allelic Series using In Vitro/In Vivo Sensor Platforms | Office of Cancer Genomics

Cancer.gov

The CTD2 Center at the University of Texas MD Anderson Cancer Center utilized an established and operational MCF10A normal breast epithelial cell model to assess the ability of candidate driver aberrations to promote cell grow in anchorage-independent conditions (soft agar assay) and proliferate in the absence of insulin and epidermal growth factor (EGF).

Diurnal changes in epidermal UV transmittance of plants in naturally high UV environments.

PubMed

Barnes, Paul W; Flint, Stephan D; Slusser, James R; Gao, Wei; Ryel, Ronald J

2008-06-01

Studies were conducted on three herbaceous plant species growing in naturally high solar UV environments in the subalpine of Mauna Kea, Hawaii, USA, to determine if diurnal changes in epidermal UV transmittance (T(UV)) occur in these species, and to test whether manipulation of the solar radiation regime could alter these diurnal patterns. Additional field studies were conducted at Logan, Utah, USA, to determine if solar UV was causing diurnal T(UV) changes and to evaluate the relationship between diurnal changes in T(UV) and UV-absorbing pigments. Under clear skies, T(UV), as measured with a UV-A-pulse amplitude modulation fluorometer for leaves of Verbascum thapsus and Oenothera stricta growing in native soils and Vicia faba growing in pots, was highest at predawn and sunset and lowest at midday. These patterns in T(UV) closely tracked diurnal changes in solar radiation and were the result of correlated changes in fluorescence induced by UV-A and blue radiation but not photochemical efficiency (F(v)/F(m)) or initial fluorescence yield (F(o)). The magnitude of the midday reduction in T(UV) was greater for young leaves than for older leaves of Verbascum. Imposition of artificial shade eliminated the diurnal changes in T(UV) in Verbascum, but reduction in solar UV had no effect on diurnal T(UV) changes in Vicia. In Vicia, the diurnal changes in T(UV) occurred without detectable changes in the concentration of whole-leaf UV-absorbing compounds. Results suggest that plants actively control diurnal changes in UV shielding, and these changes occur in response to signals other than solar UV; however, the underlying mechanisms responsible for rapid changes in T(UV) remain unclear.

Cellular interactions of a lipid-based nanocarrier model with human keratinocytes: Unravelling transport mechanisms.

PubMed

Silva, Elisabete; Barreiros, Luísa; Segundo, Marcela A; Costa Lima, Sofia A; Reis, Salette

2017-04-15

Knowledge of delivery system transport through epidermal cell monolayer is vital to improve skin permeation and bioavailability. Recently, nanostructured lipid carriers (NLCs) have gained great attention for transdermal delivery due to their biocompatibility, high drug payload, occlusive properties and skin hydration effect. However, the nanocarriers transport related mechanisms in epidermal epithelial cells are not yet understood. In this research, the internalization and transport pathways of the NLCs across the epidermal epithelial cell monolayer (HaCaT cells) were investigated. The 250nm sized witepsol/miglyol NLCs, prepared by hot homogenization had reduced cytotoxicity and no effect on the integrity of cell membrane in human HaCaT keratinocytes. The internalization was time-, concentration- and energy-dependent, and the uptake of NLCs was a vesicle-mediated process by macropinocytosis and clathrin-mediated pathways. 3% of NLCs were found at the apical membrane side of the HaCaT monolayer through exocytosis mechanism. Additionally, the endoplasmic reticulum, Golgi apparatus and microtubules played crucial roles in the transport of NLCs out of HaCaT cells. NLCs were transported intact across the human keratinocytes monolayer, without disturbing the tight junction's structure. From the transcytosis data only approximately 12% of the internalized NLCs were passed from the apical to the basolateral side. The transcytosis of NLCs throughout the HaCaT cell monolayer towards the basolateral membrane side requires the involvement of the endoplasmic reticulum, Golgi apparatus and microtubules. Our findings may contribute to a systematic understanding of NLCs transport across epidermal epithelial cell monolayers and their optimization for clinical transdermal application. Transdermal drug delivery is a challenging and growing area of clinical application. Lipid nanoparticles such as nanostructured lipid carriers (NLCs) have gained wide interest for transdermal drug delivery. However these nanocarriers' interactions with epidermal epithelial barrier are yet unknown. Unveiling the mechanisms involved in NLCs transport across the epidermal epithelial monolayers will contribute with valuable information to achieve enhanced skin permeability, superior bioavailability and consequently improved therapeutic effect. With our present work we could certainly provide researchers and clinicians guidance for the design of optimized transdermal delivery systems, based on the nanomaterials and biological interactions. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Harnessing Integrative Omics to Facilitate Molecular Imaging of the Human Epidermal Growth Factor Receptor Family for Precision Medicine.

PubMed

Pool, Martin; de Boer, H Rudolf; Hooge, Marjolijn N Lub-de; van Vugt, Marcel A T M; de Vries, Elisabeth G E

2017-01-01

Cancer is a growing problem worldwide. The cause of death in cancer patients is often due to treatment-resistant metastatic disease. Many molecularly targeted anticancer drugs have been developed against 'oncogenic driver' pathways. However, these treatments are usually only effective in properly selected patients. Resistance to molecularly targeted drugs through selective pressure on acquired mutations or molecular rewiring can hinder their effectiveness. This review summarizes how molecular imaging techniques can potentially facilitate the optimal implementation of targeted agents. Using the human epidermal growth factor receptor (HER) family as a model in (pre)clinical studies, we illustrate how molecular imaging may be employed to characterize whole body target expression as well as monitor drug effectiveness and the emergence of tumor resistance. We further discuss how an integrative omics discovery platform could guide the selection of 'effect sensors' - new molecular imaging targets - which are dynamic markers that indicate treatment effectiveness or resistance.

MicroFilament Analyzer identifies actin network organizations in epidermal cells of Arabidopsis thaliana roots

PubMed Central

Jacques, Eveline; Lewandowski, Michal; Buytaert, Jan; Fierens, Yves; Verbelen, Jean-Pierre; Vissenberg, Kris

2013-01-01

The plant cytoskeleton plays a crucial role in the cells’ growth and development during different developmental stages and it undergoes many rearrangements. In order to describe the arrangements of the F-actin cytoskeleton in root epidermal cells of Arabidopsis thaliana, the recently developed software MicroFilament Analyzer (MFA) was exploited. This software enables high-throughput identification and quantification of the orientation of filamentous structures on digital images in a highly standardized and fast way. Using confocal microscopy and transgenic GFP-FABD2-GFP plants the actin cytoskeleton was visualized in the root epidermis. MFA analysis revealed that during the early stages of cell development F-actin is organized in a mainly random pattern. As the cells grow, they preferentially adopt a longitudinal organization, a pattern that is also preserved in the largest cells. In the evolution from young to old cells, an approximately even distribution of transverse, oblique or combined orientations is always present besides the switch from random to a longitudinal oriented actin cytoskeleton. PMID:23656865

Emodin Suppresses Maintenance of Stemness by Augmenting Proteosomal Degradation of Epidermal Growth Factor Receptor/Epidermal Growth Factor Receptor Variant III in Glioma Stem Cells

PubMed Central

Kim, Jeongyub; Lee, Jong-Seon; Jung, Jieun; Lim, Inhye; Lee, Ji-Yun

2015-01-01

There is a growing body of evidence that small subpopulations of cells with stem cell-like characteristics within most solid tumors are responsible for the malignancy of aggressive cancer cells and that targeting these cells might be a good therapeutic strategy to reduce the risk of tumor relapse after therapy. Here, we examined the effects of emodin (1,3,8-trihydroxy-6-methylanthraquinone), an active component of the root and rhizome of Rheum palmatum that has several biological activities, including antitumor effects, on primary cultured glioma stem cells (GSCs). Emodin inhibited the self-renewal activity of GSCs in vitro as evidenced by neurosphere formation, limiting dilution, and soft agar clonogenic assays. Emodin inhibited the maintenance of stemness by suppressing the expression of Notch intracellular domain, nonphosphorylated β-catenin, and phosphorylated STAT3 proteins. In addition, treatment with emodin partially induced apoptosis, reduced cell invasiveness, and sensitized GSCs to ionizing radiation. Intriguingly, emodin induced proteosomal degradation of epidermal growth factor receptor (EGFR)/EGFR variant III (EGFRvIII) by interfering with the association of EGFR/EGFRvIII with heat shock protein 90, resulting in the suppression of stemness pathways. Based on these data, we propose that emodin could be considered as a potent therapeutic adjuvant that targets GSCs. PMID:25229646

A mitosis block links active cell cycle with human epidermal differentiation and results in endoreplication.

PubMed

Zanet, Jennifer; Freije, Ana; Ruiz, María; Coulon, Vincent; Sanz, J Ramón; Chiesa, Jean; Gandarillas, Alberto

2010-12-20

How human self-renewal tissues co-ordinate proliferation with differentiation is unclear. Human epidermis undergoes continuous cell growth and differentiation and is permanently exposed to mutagenic hazard. Keratinocytes are thought to arrest cell growth and cell cycle prior to terminal differentiation. However, a growing body of evidence does not satisfy this model. For instance, it does not explain how skin maintains tissue structure in hyperproliferative benign lesions. We have developed and applied novel cell cycle techniques to human skin in situ and determined the dynamics of key cell cycle regulators of DNA replication or mitosis, such as cyclins E, A and B, or members of the anaphase promoting complex pathway: cdc14A, Ndc80/Hec1 and Aurora kinase B. The results show that actively cycling keratinocytes initiate terminal differentiation, arrest in mitosis, continue DNA replication in a special G2/M state, and become polyploid by mitotic slippage. They unambiguously demonstrate that cell cycle progression coexists with terminal differentiation, thus explaining how differentiating cells increase in size. Epidermal differentiating cells arrest in mitosis and a genotoxic-induced mitosis block rapidly pushes epidermal basal cells into differentiation and polyploidy. These observations unravel a novel mitosis-differentiation link that provides new insight into skin homeostasis and cancer. It might constitute a self-defence mechanism against oncogenic alterations such as Myc deregulation.

Arbuscular Mycorrhizal Fungi Elicit a Novel Intracellular Apparatus in Medicago truncatula Root Epidermal Cells before InfectionW⃞

PubMed Central

Genre, Andrea; Chabaud, Mireille; Timmers, Ton; Bonfante, Paola; Barker, David G.

2005-01-01

The penetration of arbuscular mycorrhizal (AM) fungi through the outermost root tissues of the host plant is a critical step in root colonization, ultimately leading to the establishment of this ecologically important endosymbiotic association. To evaluate the role played by the host plant during AM infection, we have studied in vivo cellular dynamics within Medicago truncatula root epidermal cells using green fluorescent protein labeling of both the plant cytoskeleton and the endoplasmic reticulum. Targeting roots with Gigaspora hyphae has revealed that, before infection, the epidermal cell assembles a transient intracellular structure with a novel cytoskeletal organization. Real-time monitoring suggests that this structure, designated the prepenetration apparatus (PPA), plays a central role in the elaboration of the apoplastic interface compartment through which the fungus grows when it penetrates the cell lumen. The importance of the PPA is underlined by the fact that M. truncatula dmi (for doesn't make infections) mutants fail to assemble this structure. Furthermore, PPA formation in the epidermis can be correlated with DMI-dependent transcriptional activation of the Medicago early nodulin gene ENOD11. These findings demonstrate how the host plant prepares and organizes AM infection of the root, and both the plant–fungal signaling mechanisms involved and the mechanistic parallels with Rhizobium infection in legume root hairs are discussed. PMID:16284314

A Mitosis Block Links Active Cell Cycle with Human Epidermal Differentiation and Results in Endoreplication

PubMed Central

Zanet, Jennifer; Freije, Ana; Ruiz, María; Coulon, Vincent; Sanz, J. Ramón; Chiesa, Jean; Gandarillas, Alberto

2010-01-01

How human self-renewal tissues co-ordinate proliferation with differentiation is unclear. Human epidermis undergoes continuous cell growth and differentiation and is permanently exposed to mutagenic hazard. Keratinocytes are thought to arrest cell growth and cell cycle prior to terminal differentiation. However, a growing body of evidence does not satisfy this model. For instance, it does not explain how skin maintains tissue structure in hyperproliferative benign lesions. We have developed and applied novel cell cycle techniques to human skin in situ and determined the dynamics of key cell cycle regulators of DNA replication or mitosis, such as cyclins E, A and B, or members of the anaphase promoting complex pathway: cdc14A, Ndc80/Hec1 and Aurora kinase B. The results show that actively cycling keratinocytes initiate terminal differentiation, arrest in mitosis, continue DNA replication in a special G2/M state, and become polyploid by mitotic slippage. They unambiguously demonstrate that cell cycle progression coexists with terminal differentiation, thus explaining how differentiating cells increase in size. Epidermal differentiating cells arrest in mitosis and a genotoxic-induced mitosis block rapidly pushes epidermal basal cells into differentiation and polyploidy. These observations unravel a novel mitosis-differentiation link that provides new insight into skin homeostasis and cancer. It might constitute a self-defence mechanism against oncogenic alterations such as Myc deregulation. PMID:21187932

Gravitational tides in the outer planets. I - Implications of classical tidal theory. II - Interior calculations and estimation of the tidal dissipation factor

NASA Technical Reports Server (NTRS)

Ioannou, Petros J.; Lindzen, Richard S.

1993-01-01

Classical tidal theory is applied to the atmospheres of the outer planets. The tidal geopotential due to satellites of the outer planets is discussed, and the solution of Laplace's tidal equation for Hough modes appropriate to tides on the outer planets is examined. The vertical structure of tidal modes is described, noting that only relatively high-order meridional mode numbers can propagate vertically with growing amplitude. Expected magnitudes for tides in the visible atmosphere of Jupiter are discussed. The classical theory is extended to planetary interiors taking the effects of spherically and self-gravity into account. The thermodynamic structure of Jupiter is described and the WKB theory of the vertical structure equation is presented. The regions for which inertial, gravity, and acoustic oscillations are possible are delineated. The case of a planet with a neutral interior is treated, discussing the various atmospheric boundary conditions and showing that the tidal response is small.

The Arabidopsis SOS5 Locus Encodes a Putative Cell Surface Adhesion Protein and Is Required for Normal Cell Expansion

PubMed Central

Shi, Huazhong; Kim, YongSig; Guo, Yan; Stevenson, Becky; Zhu, Jian-Kang

2003-01-01

Cell surface proteoglycans have been implicated in many aspects of plant growth and development, but genetic evidence supporting their function has been lacking. Here, we report that the Salt Overly Sensitive5 (SOS5) gene encodes a putative cell surface adhesion protein and is required for normal cell expansion. The sos5 mutant was isolated in a screen for Arabidopsis salt-hypersensitive mutants. Under salt stress, the root tips of sos5 mutant plants swell and root growth is arrested. The root-swelling phenotype is caused by abnormal expansion of epidermal, cortical, and endodermal cells. The SOS5 gene was isolated through map-based cloning. The predicted SOS5 protein contains an N-terminal signal sequence for plasma membrane localization, two arabinogalactan protein–like domains, two fasciclin-like domains, and a C-terminal glycosylphosphatidylinositol lipid anchor signal sequence. The presence of fasciclin-like domains, which typically are found in animal cell adhesion proteins, suggests a role for SOS5 in cell-to-cell adhesion in plants. The SOS5 protein was present at the outer surface of the plasma membrane. The cell walls are thinner in the sos5 mutant, and those between neighboring epidermal and cortical cells in sos5 roots appear less organized. SOS5 is expressed ubiquitously in all plant organs and tissues, including guard cells in the leaf. PMID:12509519

Hair follicle defects and squamous cell carcinoma formation in Smad4 conditional knockout mouse skin.

PubMed

Qiao, W; Li, A G; Owens, P; Xu, X; Wang, X-J; Deng, C-X

2006-01-12

Smad4 is the common mediator for TGFbeta signals, which play important functions in many biological processes. To study the role of Smad4 in skin development and epidermal tumorigenesis, we disrupted this gene in skin using the Cre-loxP approach. We showed that absence of Smad4 blocked hair follicle differentiation and cycling, leading to a progressive hair loss of mutant (MT) mice. MT hair follicles exhibited diminished expression of Lef1, and increased proliferative cells in the outer root sheath. Additionally, the skin of MT mice exhibited increased proliferation of basal keratinocytes and epidermal hyperplasia. Furthermore, we provide evidence that the absence of Smad4 resulted in a block of both TGFbeta and bone morphogenetic protein (BMP) signaling pathways, including p21, a well-known cyclin-dependent kinase inhibitor. Consequently, all MT mice developed spontaneous malignant skin tumors from 3 months to 13 months of age. The majority of tumors are malignant squamous cell carcinomas. A most notable finding is that tumorigenesis is accompanied by inactivation of phosphatase and tensin homolog deleted on chromosome 10 (Pten), activation of AKT, fast proliferation and nuclear accumulation of cyclin D1. These observations revealed the essential functions of Smad4-mediated signals in repressing skin tumor formation through the TGFbeta/BMP pathway, which interacts with the Pten signaling pathway.

Phage as a template to grow bone mineral nanocrystals.

PubMed

Cao, Binrui; Xu, Hong; Mao, Chuanbin

2014-01-01

Phage display is a biotechnique that fuses functional peptides on the outer surface of filamentous phage by inserting DNA encoding the peptides into the genes of its coat proteins. The resultant peptide-displayed phage particles have been widely used as biotemplates for the synthesis of functional hybrid nanomaterials. Here, we describe the bioengineering of M13 filamentous phage to surface-display bone mineral (hydroxyapatite (HAP))-nucleating peptides derived from dentin matrix protein-1 and using the engineered phage as a biotemplate to grow HAP nanocrystals.

The merger of small and large black holes

NASA Astrophysics Data System (ADS)

Mösta, P.; Andersson, L.; Metzger, J.; Szilágyi, B.; Winicour, J.

2015-12-01

We present simulations of binary black-hole mergers in which, after the common outer horizon has formed, the marginally outer trapped surfaces (MOTSs) corresponding to the individual black holes continue to approach and eventually penetrate each other. This has very interesting consequences according to recent results in the theory of MOTSs. Uniqueness and stability theorems imply that two MOTSs which touch with a common outer normal must be identical. This suggests a possible dramatic consequence of the collision between a small and large black hole. If the penetration were to continue to completion, then the two MOTSs would have to coalesce, by some combination of the small one growing and the big one shrinking. Here we explore the relationship between theory and numerical simulations, in which a small black hole has halfway penetrated a large one.

Protective role of p53 in skin cancer: Carcinogenesis studies in mice lacking epidermal p53.

PubMed

Page, Angustias; Navarro, Manuel; Suarez-Cabrera, Cristian; Alameda, Josefa P; Casanova, M Llanos; Paramio, Jesús M; Bravo, Ana; Ramirez, Angel

2016-04-12

p53 is a protein that causes cell cycle arrest, apoptosis or senescence, being crucial in the process of tumor suppression in several cell types. Different in vitro and animal models have been designed for the study of p53 role in skin cancer. These models have revealed opposing results, as in some experimental settings it appears that p53 protects against skin cancer, but in others, the opposite conclusion emerges. We have generated cohorts of mice with efficient p53 deletion restricted to stratified epithelia and control littermates expressing wild type p53 and studied their sensitivity to both chemically-induced and spontaneous tumoral transformation, as well as the tumor types originated in each experimental group. Our results indicate that the absence of p53 in stratified epithelia leads to the appearance, in two-stage skin carcinogenesis experiments, of a higher number of tumors that grow faster and become malignant more frequently than tumors arisen in mice with wild type p53 genotype. In addition, the histological diversity of the tumor type is greater in mice with epidermal p53 loss, indicating the tumor suppressive role of p53 in different epidermal cell types. Aging mice with p53 inactivation in stratified epithelia developed spontaneous carcinomas in skin and other epithelia. Overall, these results highlight the truly protective nature of p53 functions in the development of cancer in skin and in other stratified epithelia.

Colonization of epidermal tissue by Staphylococcus aureus produces localized hypoxia and stimulates secretion of antioxidant and caspase-14 proteins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lone , Abdul G.; Atci, Erhan; Renslow, Ryan S.

A partial-thickness epidermal explant model was colonized with GFP-expressing S. aureus and the pattern of S. aureus biofilm growth was characterized using electron and confocal laser scanning microscopy. Oxygen concentration in explants was quantified using microelectrodes. The relative effective diffusivity and porosity of the epidermis were determined using magnetic resonance imaging, while hydrogen peroxide (H2O2) concentration in explant media was measured by using microelectrodes. Secreted proteins were identified and quantified using MSE mass spectrometry. We found that S. aureus biofilm grows predominantly in sebum-rich areas around hair follicles and associated skin folds. Dissolved oxygen was selectively depleted (2-3 fold) inmore » these locations, but the relative effective diffusivity and porosity did not change between colonized and control epidermis. Histological analysis revealed keratinocyte damage across all the layers of colonized epidermis after four days of culture. The colonized explants released significantly (P< 0.01) more anti-oxidant proteins of both epidermal and S. aureus origin, consistent with elevated H2O2 concentration found in the media from the colonized explants (P< 0.001). Caspase-14 was also elevated significantly in media from infected explants. While H2O2 induces primary keratinocyte differentiation, caspase-14 is required for terminal keratinocyte differentiation and desquamation. These results are consistent with a localized biological impact from S. aureus in response to colonization of the skin surface.« less

A Method for the Immortalization of Newborn Mouse Skin Keratinocytes

PubMed Central

Hammiller, Brianna O.; El-Abaseri, Taghrid Bahig; Dlugosz, Andrzej A.; Hansen, Laura A.

2015-01-01

Isolation and culture of mouse primary epidermal keratinocytes is a common technique that allows for easy genetic and environmental manipulation. However, due to their limited lifespan in culture, experiments utilizing primary keratinocytes require large numbers of animals, and are time consuming and expensive. To avoid these issues, we developed a method for the immortalization of primary mouse epidermal keratinocytes. Upon isolation of newborn epidermal keratinocytes according to established methods, the cells were cultured long-term in keratinocyte growth factor-containing medium. The cells senesced within a few weeks and eventually, small, slowly growing colonies emerged. After they regained confluency, the cells were passaged and slowly refilled the dish. With several rounds of subculture, the cells adapted to culture conditions, were easily subcultured, maintained normal morphology, and were apparently immortal. The immortalized cells retained the ability to differentiate with increased calcium concentrations, and were maintained to high passage numbers while maintaining a relatively stable karyotype. Analysis of multiple immortalized cell lines as well as primary keratinocyte cultures revealed increased numbers of chromosomes, especially in the primary keratinocytes, and chromosomal aberrations in most of the immortalized cultures and in the primary keratinocytes. Orthotopic grafting of immortalized keratinocytes together with fibroblasts onto nude mouse hosts produced skin while v-rasHa infection of the immortalized keratinocytes prior to grafting produced squamous cell carcinoma. In summary, this method of cell line generation allows for decreased use of animals, reduces the expense and time involved in research, and provides a useful model for cutaneous keratinocyte experimentation. PMID:26284198

Compartmentation of Mitochondrial and Oxidative Metabolism in Growing Hair Follicles: A Ring of Fire.

PubMed

Lemasters, John J; Ramshesh, Venkat K; Lovelace, Gregory L; Lim, John; Wright, Graham D; Harland, Duane; Dawson, Thomas L

2017-07-01

Little is known about the energetics of growing hair follicles, particularly in the mitochondrially abundant bulb. Here, mitochondrial and oxidative metabolism was visualized by multiphoton and light sheet microscopy in cultured bovine hair follicles and plucked human hairs. Mitochondrial membrane potential (ΔΨ), cell viability, reactive oxygen species (ROS), and secretory granules were assessed with parameter-indicating fluorophores. In growing follicles, lower bulb epithelial cells had high viability, and mitochondria were polarized. Most epithelially generated ROS co-localized with polarized mitochondria. As the imaging plane captured more central and distal cells, ΔΨ disappeared abruptly at a transition to a nonfluorescent core continuous with the hair shaft. Approaching the transition, ΔΨ and ROS increased, and secretory granules disappeared. ROS and ΔΨ were strongest in a circumferential paraxial ring at putative sites for formation of the outer cortex/cuticle of the hair shaft. By contrast, polarized mitochondria in dermal papillar fibroblasts produced minimal ROS. Plucked hairs showed a similar abrupt transition of degranulation/depolarization near sites of keratin deposition, as well as an ROS-generating paraxial ring of fire. Hair movement out of the follicle appeared to occur independently of follicular bulb bioenergetics by a tractor mechanism involving the inner and outer root sheaths. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Temporal variation in leaf nitrogen partitioning of a broad-leaved evergreen tree, Quercus myrsinaefolia.

PubMed

Yasumura, Yuko; Ishida, Atsushi

2011-01-01

We examined temporal changes in the amount of nitrogenous compounds in leaves from the outer and inner parts of the crown of Quercus myrsinaefolia growing in a seasonal climate. Throughout the leaf life span, metabolic protein and Rubisco content closely correlated with total nitrogen content, while structural protein content was relatively stable after full leaf expansion. Chlorophyll content was affected by shading as well as total nitrogen content in outer leaves that were overtopped by new shoots in the second year. Outer leaves showed a large seasonal variation in photosynthetic nitrogen-use efficiency (PNUE; the light-saturated photosynthetic rate per unit leaf nitrogen content) during the first year of their life, with PNUE decreasing from the peak in summer towards winter. Outer and inner leaves both showed age-related decline in PNUE in the second year. There were no such drastic changes in leaf nitrogen partitioning that could explain seasonal and yearly variations in PNUE. Nitrogen resorption occurred in overwintering leaves in spring. Metabolic protein explained the majority of nitrogen being resorbed, whereas structural protein, which was low in degradability, contributed little to nitrogen resorption.

QATAR-2: A K DWARF ORBITED BY A TRANSITING HOT JUPITER AND A MORE MASSIVE COMPANION IN AN OUTER ORBIT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bryan, Marta L.; Alsubai, Khalid A.; Latham, David W.

We report the discovery and initial characterization of Qatar-2b, a hot Jupiter transiting a V = 13.3 mag K dwarf in a circular orbit with a short period, P{sub b} = 1.34 days. The mass and radius of Qatar-2b are M{sub P} = 2.49 M{sub J} and R{sub P} = 1.14 R{sub J}, respectively. Radial-velocity monitoring of Qatar-2 over a span of 153 days revealed the presence of a second companion in an outer orbit. The Systemic Console yielded plausible orbits for the outer companion, with periods on the order of a year and a companion mass of at leastmore » several M{sub J}. Thus, Qatar-2 joins the short but growing list of systems with a transiting hot Jupiter and an outer companion with a much longer period. This system architecture is in sharp contrast to that found by Kepler for multi-transiting systems, which are dominated by objects smaller than Neptune, usually with tightly spaced orbits that must be nearly coplanar.« less

Sound generated by instability waves of supersonic flows. I Two-dimensional mixing layers. II - Axisymmetric jets

NASA Technical Reports Server (NTRS)

Tam, C. K. W.; Burton, D. E.

1984-01-01

An investigation is conducted of the phenomenon of sound generation by spatially growing instability waves in high-speed flows. It is pointed out that this process of noise generation is most effective when the flow is supersonic relative to the ambient speed of sound. The inner and outer asymptotic expansions corresponding to an excited instability wave in a two-dimensional mixing layer and its associated acoustic fields are constructed in terms of the inner and outer spatial variables. In matching the solutions, the intermediate matching principle of Van Dyke and Cole is followed. The validity of the theory is tested by applying it to an axisymmetric supersonic jet and comparing the calculated results with experimental measurements. Very favorable agreements are found both in the calculated instability-wave amplitude distribution (the inner solution) and the near pressure field level contours (the outer solution) in each case.

Pavement cells and the topology puzzle.

PubMed

Carter, Ross; Sánchez-Corrales, Yara E; Hartley, Matthew; Grieneisen, Verônica A; Marée, Athanasius F M

2017-12-01

D'Arcy Thompson emphasised the importance of surface tension as a potential driving force in establishing cell shape and topology within tissues. Leaf epidermal pavement cells grow into jigsaw-piece shapes, highly deviating from such classical forms. We investigate the topology of developing Arabidopsis leaves composed solely of pavement cells. Image analysis of around 50,000 cells reveals a clear and unique topological signature, deviating from previously studied epidermal tissues. This topological distribution is established early during leaf development, already before the typical pavement cell shapes emerge, with topological homeostasis maintained throughout growth and unaltered between division and maturation zones. Simulating graph models, we identify a heuristic cellular division rule that reproduces the observed topology. Our parsimonious model predicts how and when cells effectively place their division plane with respect to their neighbours. We verify the predicted dynamics through in vivo tracking of 800 mitotic events, and conclude that the distinct topology is not a direct consequence of the jigsaw piece-like shape of the cells, but rather owes itself to a strongly life history-driven process, with limited impact from cell-surface mechanics. © 2017. Published by The Company of Biologists Ltd.

Pavement cells and the topology puzzle

PubMed Central

2017-01-01

D'Arcy Thompson emphasised the importance of surface tension as a potential driving force in establishing cell shape and topology within tissues. Leaf epidermal pavement cells grow into jigsaw-piece shapes, highly deviating from such classical forms. We investigate the topology of developing Arabidopsis leaves composed solely of pavement cells. Image analysis of around 50,000 cells reveals a clear and unique topological signature, deviating from previously studied epidermal tissues. This topological distribution is established early during leaf development, already before the typical pavement cell shapes emerge, with topological homeostasis maintained throughout growth and unaltered between division and maturation zones. Simulating graph models, we identify a heuristic cellular division rule that reproduces the observed topology. Our parsimonious model predicts how and when cells effectively place their division plane with respect to their neighbours. We verify the predicted dynamics through in vivo tracking of 800 mitotic events, and conclude that the distinct topology is not a direct consequence of the jigsaw piece-like shape of the cells, but rather owes itself to a strongly life history-driven process, with limited impact from cell-surface mechanics. PMID:29084800

The Need for Maintaining CLT in Indonesia

ERIC Educational Resources Information Center

Ariatna

2016-01-01

Recent decades have shown growing interest among outer circle language researchers and practitioners in the discussion of communicative language teaching (CLT), as both a leading teaching model and a frequently disputed dimension of language pedagogy. Repeatedly, the debate returns to the question of how to best implement CLT as a Western product…

Laboratory Experiments to Study Spherical, Iron Oxide Concretion Growth Without Solid Nuclei: Implications for Understanding Meridiani "Blueberries"

NASA Astrophysics Data System (ADS)

Ormö, J.; Souza-Egipsy, V.; Chan, M. A.; Park, A. J.; Stich, M.; Komatsu, G.

2006-03-01

Spherical hematite concretions can form without a nucleus. Self-organized zones of super-saturated solution cause spherical precipitates of amorphous iron-hydroxide. Diffusion of Fe ions towards the outer perimeter of the amorphous sphere forms a rind, which then grows inwards.

Novel insights on the structure and composition of pseudostomata of Sphagnum.

PubMed

Merced, Amelia

2015-03-01

The occurrence of stomata on sporophytes of mosses and hornworts is congruent with a single origin in land plants. Although true stomata are absent in early-divergent mosses, Sphagnum has specialized epidermal cells, pseudostomata, that partially separate but do not open to the inside. This research examined two competing hypotheses that explain the origin of pseudostomata: (1) they are modified stomata, or (2) they evolved from epidermal cells independently from stomata.• Capsule anatomy and ultrastructure of pseudostomata were studied using light and electron microscopy, including immunolocalization of pectins.• Cell walls in pseudostomata are thin, two-layered, and rich in pectins, similar to young moss stomata, including the presence of cuticle on exterior walls. Outer and ventral walls have a thick cuticle that suggests that initial separation of ventral walls involves cuticle deposition as in true stomata. Further mechanical separation between ventral walls does not form a pore and occurs as the capsule dries.• As in moss stomata, pseudostomata wall architecture and behavior facilitate capsule dehydration, shape change, and dehiscence, supporting a common function. The divergent structure and fate of pseudostomata may be explained by the retention of Sphagnum sporophytes within protective leaves until nearly mature. Ultrastructural and immunocytological data suggest that pseudostomata are related to stomata but do not conclusively support either hypothesis. Solving the relationship of early land plants is critical to understanding stomatal evolution. Pseudostomata are structurally and anatomically unique, but their relationship to true stomata remains to be determined. © 2015 Botanical Society of America, Inc.

A Ca2+-dependent remodelled actin network directs vesicle trafficking to build wall ingrowth papillae in transfer cells.

PubMed

Zhang, Hui-Ming; Colyvas, Kim; Patrick, John W; Offler, Christina E

2017-10-13

The transport function of transfer cells is conferred by an enlarged plasma membrane area, enriched in nutrient transporters, that is supported on a scaffold of wall ingrowth (WI) papillae. Polarized plumes of elevated cytosolic Ca2+ define loci at which WI papillae form in developing adaxial epidermal transfer cells of Vicia faba cotyledons that are induced to trans-differentiate when the cotyledons are placed on culture medium. We evaluated the hypothesis that vesicle trafficking along a Ca2+-regulated remodelled actin network is the mechanism that underpins this outcome. Polarized to the outer periclinal cytoplasm, a Ca2+-dependent remodelling of long actin bundles into short, thin bundles was found to be essential for assembling WI papillae but not the underlying uniform wall layer. The remodelled actin network directed polarized vesicle trafficking to sites of WI papillae construction, and a pharmacological study indicated that both exo- and endocytosis contributed to assembly of the papillae. Potential candidates responsible for the Ca2+-dependent actin remodelling, along with those underpinning polarized exo- and endocyotosis, were identified in a transcriptome RNAseq database generated from the trans-differentiating epidermal cells. Of most significance, endocytosis was controlled by up-regulated expression of a dynamin-like isoform. How a cycle of localized exo- and endocytosis, regulated by Ca2+-dependent actin remodelling, assembles WI papillae is discussed. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

The coordination of ploidy and cell size differs between cell layers in leaves

PubMed Central

Katagiri, Yohei; Hasegawa, Junko; Fujikura, Ushio; Hoshino, Rina; Matsunaga, Sachihiro; Tsukaya, Hirokazu

2016-01-01

Growth and developmental processes are occasionally accompanied by multiple rounds of DNA replication, known as endoreduplication. Coordination between endoreduplication and cell size regulation often plays a crucial role in proper organogenesis and cell differentiation. Here, we report that the level of correlation between ploidy and cell volume is different in the outer and inner cell layers of leaves of Arabidopsis thaliana using a novel imaging technique. Although there is a well-known, strong correlation between ploidy and cell volume in pavement cells of the epidermis, this correlation was extremely weak in palisade mesophyll cells. Induction of epidermis cell identity based on the expression of the homeobox gene ATML1 in mesophyll cells enhanced the level of correlation between ploidy and cell volume to near that of wild-type epidermal cells. We therefore propose that the correlation between ploidy and cell volume is regulated by cell identity. PMID:26903507

Quantifying Hydrostatic Pressure in Plant Cells by Using Indentation with an Atomic Force Microscope

PubMed Central

Beauzamy, Léna; Derr, Julien; Boudaoud, Arezki

2015-01-01

Plant cell growth depends on a delicate balance between an inner drive—the hydrostatic pressure known as turgor—and an outer restraint—the polymeric wall that surrounds a cell. The classical technique to measure turgor in a single cell, the pressure probe, is intrusive and cannot be applied to small cells. In order to overcome these limitations, we developed a method that combines quantification of topography, nanoindentation force measurements, and an interpretation using a published mechanical model for the pointlike loading of thin elastic shells. We used atomic force microscopy to estimate the elastic properties of the cell wall and turgor pressure from a single force-depth curve. We applied this method to onion epidermal peels and quantified the response to changes in osmolality of the bathing solution. Overall our approach is accessible and enables a straightforward estimation of the hydrostatic pressure inside a walled cell. PMID:25992723

Acquired Brachial Cutaneous Dyschromatosis in a Middle Aged Male

PubMed Central

Choi, Min Jung; Byun, Ji Yeon; Choi, Hae Young

2018-01-01

Acquired brachial cutaneous dyschromatosis (ABCD) is an acquired disorder of pigmentary change that presents as chronic, asymptomatic, geographic-shaped, gray-brown patches, consisting of mixed hyper and hypopigmented macules on the dorsal aspect of the forearms. We report a case of a 40-year-old male who presented with asymptomatic, multiple brown-colored macules on the outer aspects of both arms. He had no history of hypertension and had never taken angiotensin converting enzyme inhibitors. He also denied chronic sun exposure history. Histologic examination demonstrated epidermal atrophy, increased basal layer pigmentation, and several telangiectatic vessels in the upper dermis. Solar elastosis was not remarkable. The patient's clinical and histopathologic features were consistent with a diagnosis of ABCD. Poikiloderma of Civatte, melasma, acquired bilateral telangiectatic macules and other pigmentary disorders should be considered in the differential diagnosis of ABCD. Herein, we report a case of ABCD in a middle-aged male without hypertension and medication. PMID:29853750

Inhibition of Epidermal Growth Factor Receptor and Vascular Endothelial Growth Factor Receptor Phosphorylation on Tumor-Associated Endothelial Cells Leads to Treatment of Orthotopic Human Colon Cancer in Nude Mice1

PubMed Central

Sasaki, Takamitsu; Kitadai, Yasuhiko; Nakamura, Toru; Kim, Jang-Seong; Tsan, Rachel Z; Kuwai, Toshio; Langley, Robert R; Fan, Dominic; Kim, Sun-Jin; Fidler, Isaiah J

2007-01-01

The purpose of our study was to determine whether the dual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) signaling pathways in tumor-associated endothelial cells can inhibit the progressive growth of human colon carcinoma in the cecum of nude mice. SW620CE2 human colon cancer cells growing in culture and orthotopically in the cecum of nude mice expressed a high level of transforming growth factor alpha (TGF-α) and vascular endothelial growth factor (VEGF) but were negative for EGFR, human epidermal growth factor receptor 2 (HER2), and VEGFR. Double immunofluorescence staining revealed that tumor-associated endothelial cells expressed EGFR, VEGFR2, phosphorylated EGFR (pEGFR), and phosphorylated VEGFR (pVEGFR). Treatment of mice with either 7H-pyrrolo [2,3-d]-pyrimidine lead scaffold (AEE788; an inhibitor of EGFR and VEGFR tyrosine kinase) or CPT-11 as single agents significantly inhibited the growth of cecal tumors (P < .01); this decrease was even more pronounced with AEE788 combined with CPT-11 (P < .001). AEE788 alone or combined with CPT-11 also inhibited the expression of pEGFR and pVEGFR on tumor-associated endothelial cells, significantly decreased vascularization and tumor cell proliferation, and increased the level of apoptosis in both tumor-associated endothelial cells and tumor cells. These data demonstrate that targeting EGFR and VEGFR signaling on tumor-associated endothelial cells provides a viable approach for the treatment of colon cancer. PMID:18084614

Establishment and characterization of a new human functional cell line from a choriocarcinoma.

PubMed

Okabe, T; Sasaki, N; Matsuzaki, M; Imai, Y; Kaneko, Y; Matsuzaki, F; Takaku, F; Tsushima, T

1983-10-01

A new human functional tumor cell line, designated as T3M-3, has been established from a xenotransplanted choriocarcinoma grown in nude mice. One of the biggest problems of the in vitro culture of these tumor cells using the xenotransplanted tumors had been the dense contamination of fibroblasts of host nude mouse origin. In the present study, these fibroblasts were completely removed by incubating the cells with antiserum raised against nude mouse spleen cells. The cell line established from the remaining tumor cells has been successfully propagated in vitro for as long as 4 years. These cells show the morphology of epithelioid cells containing a prominent nucleus with one or two large nucleoli. The cells grow in a monolayered sheet with the population-doubling time of 19 hr. The cells show perfect tumor takes when they are reinoculated into nude mice. Chromosomal analysis revealed that the cell is a human aneuploid one with a hypotriploid mode. These cultured cells maintained well the function of secreting large amounts of human chorionic gonadotropin, progesterone, and estrogen. The secretion of human chorionic gonadotropin and progesterone by these cells is enhanced by stimulation with tumor promoters, such as 12-O-tetradecanoylphorbol-13-acetate and teleocidin B, or with epidermal growth factor in a dose-and time-dependent manner. Interestingly, however, the tumor promoters did not exert a marked effect on the cellular binding of epidermal growth factor, indicating that the receptors for these reagents in T3M-3 cells are not shared by epidermal growth factor.

Highly expressed EGFR in pearl sac may facilitate the pearl formation in the pearl oyster, Pinctada fucata.

PubMed

Zhu, Wenjie; Fan, Sigang; Huang, Guiju; Zhang, Dongling; Liu, Baosuo; Bi, Xiaomin; Yu, Dahui

2015-07-25

Epidermal growth factor receptor (EGFR) plays an important role in cell growth, proliferation, differentiation and migration. Yet whether it functions in pearl formation or not is not reported. In this study, EGFR was cloned from the pearl oyster Pinctada fucata (named as Pf-EGFR) and its expression profiles were investigated. The cDNA was 2156bp long with an ORF of 1017bp encoding 338 amino acid residues. The deduced polypeptide contained an L domain and a cysteine-rich domain, consistent with the characteristics of ErbB family. The sequence of Pf-EGFR shared 22.78-56.71% identity with other EGFRs. The genomic sequence of Pf-EGFR consisted of six exons and five introns, being 5190bp in total length, and expressed in all the tested tissues with a higher expression level in the pearl sac (P<0.05). In situ hybridization showed that Pf-EGFR was specifically expressed on both the inner side of the outer fold and the outer side of the inner fold of the mantle, as well as on the whole pearl sac including the connective tissues. In addition, Pf-EGFR was markedly increased at larval metamorphosis, significantly higher than other development periods (P<0.05). These results indicated that the Pf-EGFR may facilitate pearl formation as well as larval metamorphosis. Copyright © 2015 Elsevier B.V. All rights reserved.

Live imaging of β-1,3-glucan synthase FKS-1 in Neurospora crassa hyphae.

PubMed

Sánchez-León, Eddy; Riquelme, Meritxell

2015-09-01

The subcellular localization and dynamics of FKS-1, the putative catalytic subunit of the β-1,3-glucan synthase complex, was analyzed in growing hyphae of Neurospora crassa by live confocal microscopy. GFP-tagged FKS-1 accumulated at the outer layer of the Spitzenkörper (Spk), and at the apical plasma membrane (PM). Fluorescence recovery after photobleaching analysis revealed arrival of FKS-1-containing carriers first at the immediate surroundings of the core region of the Spk, and thereafter to the Spk most outer region. The results obtained here and previous data suggest that FKS-1 is transported to the Spk in macrovesicles. Copyright © 2015 Elsevier Inc. All rights reserved.

Engaging space: extraterrestrial architecture and the human psyche

NASA Astrophysics Data System (ADS)

Marie Seguin, Angel

2005-05-01

The human fascination with exploring and inhabiting the space that lies beyond Earth's atmosphere continues to grow. Nevertheless, 40 years of experience to date have clearly established that humans in outer space routinely suffer significant psychological impairment arising from their stressful extraterrestrial living conditions. This paper explores those extraterrestrial conditions through the interactions between the extraordinarily harsh environment of outer space, the sensations that humans encounter in space, and the qualities of a habitat that physically interposes itself between the two. The objective of this paper is to develop a habitat that expresses the extraterrestrial condition while supporting the mental health of its inhabitants, so as to augment the success of prolonged extraterrestrial residence and interplanetary travel.

Detoxifying Escherichia coli for endotoxin-free production of recombinant proteins.

PubMed

Mamat, Uwe; Wilke, Kathleen; Bramhill, David; Schromm, Andra Beate; Lindner, Buko; Kohl, Thomas Andreas; Corchero, José Luis; Villaverde, Antonio; Schaffer, Lana; Head, Steven Robert; Souvignier, Chad; Meredith, Timothy Charles; Woodard, Ronald Wesley

2015-04-16

Lipopolysaccharide (LPS), also referred to as endotoxin, is the major constituent of the outer leaflet of the outer membrane of virtually all Gram-negative bacteria. The lipid A moiety, which anchors the LPS molecule to the outer membrane, acts as a potent agonist for Toll-like receptor 4/myeloid differentiation factor 2-mediated pro-inflammatory activity in mammals and, thus, represents the endotoxic principle of LPS. Recombinant proteins, commonly manufactured in Escherichia coli, are generally contaminated with endotoxin. Removal of bacterial endotoxin from recombinant therapeutic proteins is a challenging and expensive process that has been necessary to ensure the safety of the final product. As an alternative strategy for common endotoxin removal methods, we have developed a series of E. coli strains that are able to grow and express recombinant proteins with the endotoxin precursor lipid IVA as the only LPS-related molecule in their outer membranes. Lipid IVA does not trigger an endotoxic response in humans typical of bacterial LPS chemotypes. Hence the engineered cells themselves, and the purified proteins expressed within these cells display extremely low endotoxin levels. This paper describes the preparation and characterization of endotoxin-free E. coli strains, and demonstrates the direct production of recombinant proteins with negligible endotoxin contamination.

PVOL: The Planetary Virtual Observatory & Laboratory. An online database of the Outer Planets images.

NASA Astrophysics Data System (ADS)

Morgado, A.; Sánchez-Lavega, A.; Rojas, J. F.; Hueso, R.

2005-08-01

The collaboration between amateurs astronomers and the professional community has been fruitful on many areas of astronomy. The development of the Internet has allowed a better than ever capability of sharing information worldwide and access to other observers data. For many years now the International Jupiter Watch (IJW) Atmospheric discipline has coordinated observational efforts for long-term studies of the atmosphere of Jupiter. The International Outer Planets Watch (IOPW) has extended its labours to the four Outer Planets. Here we present the Planetary Virtual Observatory & Laboratory (PVOL), a website database where we integer IJW and IOPW images. At PVOL observers can submit their data and professionals can search for images under a wide variety of useful criteria such as date and time, filters used, observer, or central meridian longitude. PVOL is aimed to grow as an organized easy to use database of amateur images of the Outer Planets. The PVOL web address is located at http://www.pvol.ehu.es/ and coexists with the traditional IOPW site: http://www.ehu.es/iopw/ Acknowledgements: This work has been funded by Spanish MCYT PNAYA2003-03216, fondos FEDER and Grupos UPV 15946/2004. R. Hueso acknowledges a post-doc fellowship from Gobierno Vasco.

Human corpus luteum: presence of epidermal growth factor receptors and binding characteristics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ayyagari, R.R.; Khan-Dawood, F.S.

Epidermal growth factor receptors are present in many reproductive tissues but have not been demonstrated in the human corpus luteum. To determine the presence of epidermal growth factor receptors and its binding characteristics, we carried out studies on the plasma cell membrane fraction of seven human corpora lutea (days 16 to 25) of the menstrual cycle. Specific epidermal growth factor receptors were present in human corpus luteum. Insulin, nerve growth factor, and human chorionic gonadotropin did not competitively displace epidermal growth factor binding. The optimal conditions for corpus luteum-epidermal growth factor receptor binding were found to be incubation for 2more » hours at 4 degrees C with 500 micrograms plasma membrane protein and 140 femtomol /sup 125/I-epidermal growth factor per incubate. The number (mean +/- SEM) of epidermal growth factor binding sites was 12.34 +/- 2.99 X 10(-19) mol/micrograms protein; the dissociation constant was 2.26 +/- 0.56 X 10(-9) mol/L; the association constant was 0.59 +/- 0.12 X 10(9) L/mol. In two regressing corpora lutea obtained on days 2 and 3 of the menstrual cycle, there was no detectable specific epidermal growth factor receptor binding activity. Similarly no epidermal growth factor receptor binding activity could be detected in ovarian stromal tissue. Our findings demonstrate that specific receptors for epidermal growth factor are present in the human corpus luteum. The physiologic significance of epidermal growth factor receptors in human corpus luteum is unknown, but epidermal growth factor may be involved in intragonadal regulation of luteal function.« less

The Characteristics of Fatigue Damage in the Fuselage Riveted Lap Splice Joint

NASA Technical Reports Server (NTRS)

Piascik, Robert S.; Willard, Scott A.

1997-01-01

An extensive data base has been developed to form the physical basis for new analytical methodology to predict the onset of widespread fatigue damage in the fuselage lap splice joint. The results of detailed destructive examinations have been cataloged to describe the physical nature of MSD in the lap splice joint. ne catalog includes a detailed description, e.g., crack initiation, growth rates, size, location, and fracture morphology, of fatigue damage in the fuselage lap splice joint structure. Detailed examinations were conducted on a lap splice joint panel removed from a full scale fuselage test article after completing a 60,000 cycle pressure test. The panel contained a four bay region that exhibited visible outer skin cracks and regions of crack link-up along the upper rivet row. Destructive examinations revealed undetected fatigue damage in the outer skin, inner skin, and tear strap regions. Outer skin fatigue cracks were found to initiate by fretting damage along the faying surface. The cracks grew along the faying surface to a length equivalent to two to three skin thicknesses before penetrating the outboard surface of the outer skin. Analysis of fracture surface marker bands produced during full scale testing revealed that all upper rivet row fatigue cracks contained in a dim bay region grow at similar rates; this important result suggests that fracture mechanics based methods can be used to predict the growth of outer skin fatigue cracks in lap splice structure. Results are presented showing the affects of MSD and out-of-plane pressure loads on outer skin crack link-up.

Efficacy of Epidermal Skin Grafts Over Complex, Chronic Wounds in Patients With Multiple Comorbidities.

PubMed

Fearmonti, Regina M

2016-07-01

Epidermal skin grafting presents an alternative to traditional autografts since only epidermal skin is harvested from the donor site. Split-thickness skin grafts are associated with difficulties at the donor site, including excessive pain, delayed healing, fluid loss, and unsatisfactory cosmetic results - all exacerbated in patients with comorbidities. A new automated epidermal harvesting tool (CelluTome Epidermal Harvesting System, KCI, an Acelity company, San Antonio, TX) involves concurrent application of heat and suction to normal skin to produce epidermal grafts. This article outlines the author's experience using this automated epidermal harvesting tool to harvest epidermal grafts and apply them on 23 chronic lower extremity wounds of patients with multiple comorbidities. Vacuum and heat were applied until epidermal microdomes were formed (30-45 minutes); an epidermal microdome array was collected onto a transfer dressing and applied over the wound. The automated harvesting tool yielded viable epithelium with every use. In addition to the epidermal skin graft, 16 of 23 wounds (70%) received adjunctive wound treatment, including negative pressure wound therapy, hyperbaric oxygen therapy, and/or regenerative tissue matrix. The average reepithelialization rate was 88.1% during a mean follow-up period of 76.4 days; no use of an anesthetic/operating room was required for the procedure. All donor sites were completely healed within 2 weeks without complications or scarring. Epidermal skin grafting provided a simplified, office-based grafting option with no donor site morbidity, and assisted in closure or size reduction of chronic wounds in this series.

Morphometrics and structure of complete baleen racks in gray whales (Eschrichtius robustus) from the Eastern North Pacific Ocean.

PubMed

Young, Samantha; DeméRé, Thomas A; Ekdale, Eric G; Berta, Annalisa; Zellmer, Nicholas

2015-04-01

Mysticetes have evolved a novel filter feeding apparatus-baleen-an epidermal keratinous tissue composed of keratin that grows as a serial arrangement of transverse cornified laminae from the right and left sides of the palate. The structure and function of baleen varies among extant mysticete clades and this variation likely can be viewed as adaptations related to different filter feeding strategies. In one of the first morphometric studies of the full baleen apparatus, we describe the morphology of complete baleen racks in neonate, yearling and adult gray whales (Eschrichtius robustus), and note morphometric variations between age groups as well as within individual racks. Morphometric data and detailed descriptions were collected from the full baleen apparatus of three frozen specimens of E. robustus using previously derived ecologically significant and broad scale measurements of baleen. Additionally, characters of the baleen apparatus were described based on visible patterns of baleen laminae and plates on the dorsal root of the rack. Results indicate that the longest, widest, and thickest plates and laminae are found toward the posterior half of the rack, resulting in the greatest surface area for filtration of prey occurring in this region. Ontogenetic changes were also documented that reveal a progressive increase in the filter surface area of the developing baleen apparatus as baleen laminae and main plates grow in length and width. Also noted was a progressive posterior shift in the position of greatest filtration area. Histological examination of the epithelial base (Zwischensubstanz) and laminae showed basic epidermal layers, as well as gapping between layers and vacuoles. © 2015 Wiley Periodicals, Inc.

The mathematics of tanning

PubMed Central

Thingnes, Josef; Øyehaug, Leiv; Hovig, Eivind; Omholt, Stig W

2009-01-01

Background The pigment melanin is produced by specialized cells, called melanocytes. In healthy skin, melanocytes are sparsely spread among the other cell types in the basal layer of the epidermis. Sun tanning results from an UV-induced increase in the release of melanin to neighbouring keratinocytes, the major cell type component of the epidermis as well as redistribution of melanin among these cells. Here we provide a mathematical conceptualization of our current knowledge of the tanning response, in terms of a dynamic model. The resolution level of the model is tuned to available data, and its primary focus is to describe the tanning response following UV exposure. Results The model appears capable of accounting for available experimental data on the tanning response in different skin and photo types. It predicts that the thickness of the epidermal layer and how far the melanocyte dendrites grow out in the epidermal layers after UV exposure influence the tanning response substantially. Conclusion Despite the paucity of experimental validation data the model is constrained enough to serve as a foundation for the establishment of a theoretical-experimental research programme aimed at elucidating the more fine-grained regulatory anatomy underlying the tanning response. PMID:19505344

Genetics Home Reference: Stevens-Johnson syndrome/toxic epidermal necrolysis

MedlinePlus

... Conditions Stevens-Johnson syndrome/toxic epidermal necrolysis Stevens-Johnson syndrome/toxic epidermal necrolysis Printable PDF Open All ... to view the expand/collapse boxes. Description Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a ...

Expression of epidermal fatty acid binding protein (E-FABP) in septoclasts in the growth plate cartilage of mice.

PubMed

Bando, Yasuhiko; Yamamoto, Miyuki; Sakiyama, Koji; Inoue, Katsuyuki; Takizawa, Shota; Owada, Yuji; Iseki, Shoichi; Kondo, Hisatake; Amano, Osamu

2014-10-01

n-3 Polyunsaturated fatty acids play a role in regulating the growth of the long bones. Fatty acid-binding proteins (FABPs) bind and transport hydrophobic long-chain fatty acids intracellularly, and epidermal-type FABP (E-FABP) has an affinity for n-3 fatty acids. This study aimed to clarify the localization of E-FABP in the growth plate of the mouse tibia. At the chondro-osseous junction (COJ) of the growth plate, E-FABP-immunoreactivity was exclusively localized in mononuclear, spindle-shaped cells with several long processes. These E-FABP-immunoreactive cells were identified as being septoclasts, i.e., cells that resorb uncalcified transverse septa. The processes of these immunoreactive septoclasts terminated between the longitudinal and transverse septa. E-FABP-immunoreactivity was found in the entire cytoplasm and on the mitochondrial outer membrane. In ontogeny, immunoreactive septoclasts were observed immediately after emergence of the primary ossifying center and were distributed not only at the COJ but also in the metaphysis near the COJ. The number of septoclasts increased at the postnatal age of 1 week (P1w)-P2w, and thereafter gradually decreased; and the cells became concentrated at the COJ after P3w-P4w. The immunoreactivity for peroxisome proliferator-activated receptor (PPAR)β/δ was detected in these E-FABP-immunoreactive septoclasts. The present results suggest that fatty acids, preferably n-3 ones, are intracellularly transported by E-FABP to various targets, including mitochondria and nucleus, in which PPARβ/δ may play functional roles in the transcriptional regulation of genes involved in the endochondral ossification.

Engineering human cell spheroids to model embryonic tissue fusion in vitro

PubMed Central

Wolf, Cynthia J.; Wood, Carmen; Ren, Hongzu; Grindstaff, Rachel; Padgett, William; Swank, Adam; MacMillan, Denise; Fisher, Anna; Winnik, Witold; Abbott, Barbara D.

2017-01-01

Epithelial-mesenchymal interactions drive embryonic fusion events during development, and perturbations of these interactions can result in birth defects. Cleft palate and neural tube defects can result from genetic defects or environmental exposures during development, yet very little is known about the effect of chemical exposures on fusion events during human development because of a lack of relevant and robust human in vitro assays of developmental fusion behavior. Given the etiology and prevalence of cleft palate and the relatively simple architecture and composition of the embryonic palate, we sought to develop a three-dimensional culture system that mimics the embryonic palate and could be used to study fusion behavior in vitro using human cells. We engineered size-controlled human Wharton’s Jelly stromal cell (HWJSC) spheroids and established that 7 days of culture in osteogenesis differentiation medium was sufficient to promote an osteogenic phenotype consistent with embryonic palatal mesenchyme. HWJSC spheroids supported the attachment of human epidermal keratinocyte progenitor cells (HPEKp) on the outer spheroid surface likely through deposition of collagens I and IV, fibronectin, and laminin by mesenchymal spheroids. HWJSC spheroids coated in HPEKp cells exhibited fusion behavior in culture, as indicated by the removal of epithelial cells from the seams between spheroids, that was dependent on epidermal growth factor signaling and fibroblast growth factor signaling in agreement with palate fusion literature. The method described here may broadly apply to the generation of three-dimensional epithelial-mesenchymal co-cultures to study developmental fusion events in a format that is amenable to predictive toxicology applications. PMID:28898253

Light, genotype, and abscisic acid affect chloroplast positioning in guard cells of Arabidopsis thaliana leaves in distinct ways.

PubMed

Königer, Martina; Jessen, Brita; Yang, Rui; Sittler, Dorothea; Harris, Gary C

2010-09-01

The goal of this study was to investigate the effects of light intensity, genotype, and various chemical treatments on chloroplast movement in guard cells of Arabidopsis thaliana leaves. After treatment at various light intensities (dark, low, and high light), leaf discs were fixed with glutaraldehyde, and imaged using confocal laser microscopy. Each chloroplast was assigned a horizontal (close to pore, center, or epidermal side) and vertical (outer, middle, inner) position. White light had a distinct effect on chloroplast positioning, most notably under high light (HL) when chloroplasts on the upper leaf surface of wild-type (WT) moved from epidermal and center positions toward the pore. This was not the case for phot1-5/phot2-1 or phot2-1 plants, thus phototropins are essential for chloroplast positioning in guard cells. In npq1-2 mutants, fewer chloroplasts moved to the pore position under HL than in WT plants, indicating that white light can affect chloroplast positioning also in a zeaxanthin-dependent way. Cytochalasin B inhibited the movement of chloroplasts to the pore under HL, while oryzalin did not, supporting the idea that actin plays a role in the movement. The movement along actin cables is dependent on CHUP1 since chloroplast positioning in chup1 was significantly altered. Abscisic acid (ABA) caused most chloroplasts in WT and phot1-5/phot2-1 to be localized in the center, middle part of the guard cells irrespective of light treatment. This indicates that not only light but also water stress influences chloroplast positioning.

Sprouty / FGF signaling regulates the proximal-distal feather morphology and the size of dermal papillae

PubMed Central

Yue, Zhicao; Jiang, Ting Xin; Wu, Ping; Widelitz, Randall B; Chuong, Cheng Ming

2013-01-01

In a feather, there are distinct morphologies along the proximal-distal axis. The proximal part is a cylindrical stalk (calamus), whereas the distal part has barb and barbule branches. Here we focus on what molecular signaling activity can modulate feather stem cells to generate these distinct morphologies. We demonstrate the drastic tissue remodeling during feather cycling which includes initiation, growth and resting phases. In the growth phase, epithelial components undergo progressive changes from the collar growth zone to the ramogenic zone, to maturing barb branches along the proximal- distal axis. Mesenchymal components also undergo progressive changes from the dermal papilla, to the collar mesenchyme, to the pulp along the proximal- distal axis. Over-expression of Spry4, a negative regulator of receptor tyrosine kinases, promotes barb branch formation at the expense of the epidermal collar. It even induces barb branches from the follicle sheath (equivalent to the outer root sheath in hair follicles). The results are feathers with expanded feather vane regions and small or missing proximal feather shafts (the calamus). Spry4 also expands the pulp region while reducing the size of dermal papillae, leading to a failure to regenerate. In contrast, over-expressing Fgf10 increases the size of the dermal papillae, expands collar epithelia and mesenchyme, but also prevents feather branch formation and feather keratin differentiation. These results suggest that coordinated Sprouty/FGF pathway activity at different stages is important to modulate feather epidermal stem cells to form distinct feather morphologies along the proximal-distal feather axis. PMID:23000358

On the role of VDAC in apoptosis: fact and fiction.

PubMed

Rostovtseva, Tatiana K; Tan, Wenzhi; Colombini, Marco

2005-06-01

Research on VDAC has accelerated as evidence grows of its importance in mitochondrial function and in apoptosis. New investigators entering the field are often confounded by the VDAC literature and its many apparent conflicts and contradictions. This review is an effort to shed light on the situation and identify reliable information from more questionable claims. Our views on the most important controversial issues are as follows: VDAC is only present in the mitochondrial outer membrane. VDAC functions as a monomer. VDAC functions normally with or without Ca(2+). It does not form channels that mediate the flux of proteins through membranes (peptides and unfolded proteins are excluded from this statement). Closure of VDAC, not VDAC opening, leads to mitochondria outer membrane permeabilization and apoptosis.

Engaging space: extraterrestrial architecture and the human psyche.

PubMed

Sequin, Angel Marie

2005-01-01

The human fascination with exploring and inhabiting the space that lies beyond Earth's atmosphere continues to grow. Nevertheless, 40 years of experience to date have clearly established that humans in outer space routinely suffer significant psychological impairment arising from their stressful extraterrestrial living conditions. This paper explores those extraterrestrial conditions through the interactions between the extraordinarily harsh environment of outer space, the sensations that humans encounter in space, and the qualities of a habitat that physically interposes itself between the two. The objective of this paper is to develop a habitat that expresses the extraterrestrial condition while supporting the mental health of its inhabitants, so as to augment the success of prolonged extraterrestrial residence and interplanetary travel. c2005 Elsevier Ltd. All rights reserved.

Adult epidermal Notch activity induces dermal accumulation of T cells and neural crest derivatives through upregulation of jagged 1.

PubMed

Ambler, Carrie A; Watt, Fiona M

2010-11-01

Notch signalling regulates epidermal differentiation and tumour formation via non-cell autonomous mechanisms that are incompletely understood. This study shows that epidermal Notch activation via a 4-hydroxy-tamoxifen-inducible transgene caused epidermal thickening, focal detachment from the underlying dermis and hair clumping. In addition, there was dermal accumulation of T lymphocytes and stromal cells, some of which localised to the blisters at the epidermal-dermal boundary. The T cell infiltrate was responsible for hair clumping but not for other Notch phenotypes. Notch-induced stromal cells were heterogeneous, expressing markers of neural crest, melanocytes, smooth muscle and peripheral nerve. Although Slug1 expression was expanded in the epidermis, the stromal cells did not arise through epithelial-mesenchymal transition. Epidermal Notch activation resulted in upregulation of jagged 1 in both epidermis and dermis. When Notch was activated in the absence of epidermal jagged 1, jagged 1 was not upregulated in the dermis, and epidermal thickening, blister formation, accumulation of T cells and stromal cells were inhibited. Gene expression profiling revealed that epidermal Notch activation resulted in upregulation of several growth factors and cytokines, including TNFα, the expression of which was dependent on epidermal jagged 1. We conclude that jagged 1 is a key mediator of non-cell autonomous Notch signalling in skin.

Effects of UV-B radiation on phenolic composition and deposition patterns and leaf physiology in three Eastern tree species

NASA Astrophysics Data System (ADS)

Sullivan, Joseph H.; Gitz, Dennis C.; Peek, Michael S.; McElrone, Andrew J.

2002-01-01

Quantitative changes in foliar chemistry in response to UVB radiation are frequently reported but less is known about the qualitative changes in putative UV-screening compounds. It has also not been conclusively shown whether qualitative differences in screening compounds or differences in localization patterns influences the sensitivity of plants to damage from UVB radiation. In this study we evaluated the chemical composition and deposition patterns of UV-absorbing compounds in three tree species and assayed these species for possible effects on gas exchange and photosynthetic carbon assimilation. Branches of mature trees of sweetgum (Liquidambar styraciflua), tulip poplar (Liriodendron tulipifera) and red maple (Acer rubrum) were exposed to supplemental levels of UVB radiation over three growing seasons. Controls for UVA were also measured by exposing branches to supplemental UVA only, and additional branches not irradiated were also used for controls. These species demonstrated contrasting chemical composition and deposition patterns with poplar being the most responsive in terms of epidermal accumulation of phenolics including flavonols and chlorogenic acid and hydroxycinnamates. Sweetgum and red maple showed increases primarily in hydroxycinnamates, particularly in the mesophyll in red maple. Leaf area was marginally influenced by UV exposure level. Assimilation was generally not reduced by UVB radiation in these species and was enhanced in red maple by both UVB and UVA and by UVA in sweetgum. These finding are consistent with a hypothesis that epidermal attenuation of UVB would only be reduced in poplar, which accumulated the additional epidermal screening compounds. It is possible that photosynthetic efficiency was enhanced in red maple by the increased absorption of blue light within the mesophyll. Stomatal conductance was generally reduced, and this led to an increase in water use efficiency in red maple and poplar.

Role of Epidermal Growth Factor Receptor (EGFR) Inhibitors and Radiation in the Management of Brain Metastases from EGFR Mutant Lung Cancers.

PubMed

Khandekar, Melin J; Piotrowska, Zofia; Willers, Henning; Sequist, Lecia V

2018-04-27

The growth of genotype-directed targeted therapies, such as inhibitors of the epidermal growth factor receptor (EGFR), has revolutionized treatment for some patients with oncogene-addicted lung cancer. However, as systemic control for these patients has improved, brain metastases remain an important source of morbidity and mortality. Traditional treatment for brain metastases has been radiotherapy, either whole-brain radiation or stereotactic radiosurgery. The growing availability of drugs that can cross the blood-brain barrier and have activity in the central nervous system (CNS) has led to many studies investigating whether targeted therapy can be used in combination with or in lieu of radiation. In this review, we summarize the key literature about the incidence and nature of EGFR-mutant brain metastases (EGFR BMs), the data about the activity of EGFR inhibitors in the CNS, and whether they can be used as front-line therapy for brain metastases. Although initial use of tyrosine kinase inhibitors for EGFR BMs can often be an effective treatment strategy, multidisciplinary evaluation is critical, and prospective studies are needed to clarify which patients may benefit from early radiotherapy. Management of brain metastases in epidermal growth factor receptor (EGFR) mutant lung cancer is a common clinical problem. The question of whether to start initial therapy with an EGFR inhibitor or radiotherapy (either whole-brain radiotherapy or stereotactic radiosurgery) is controversial. The development of novel EGFR inhibitors with enhanced central nervous system (CNS) penetration is an important advance in the treatment of CNS disease. Multidisciplinary evaluation and evaluation of extracranial disease status are critical to choosing the best treatment option for each patient. © AlphaMed Press 2018.

On the growth and form of cortical convolutions

NASA Astrophysics Data System (ADS)

Tallinen, Tuomas; Chung, Jun Young; Rousseau, François; Girard, Nadine; Lefèvre, Julien; Mahadevan, L.

2016-06-01

The rapid growth of the human cortex during development is accompanied by the folding of the brain into a highly convoluted structure. Recent studies have focused on the genetic and cellular regulation of cortical growth, but understanding the formation of the gyral and sulcal convolutions also requires consideration of the geometry and physical shaping of the growing brain. To study this, we use magnetic resonance images to build a 3D-printed layered gel mimic of the developing smooth fetal brain; when immersed in a solvent, the outer layer swells relative to the core, mimicking cortical growth. This relative growth puts the outer layer into mechanical compression and leads to sulci and gyri similar to those in fetal brains. Starting with the same initial geometry, we also build numerical simulations of the brain modelled as a soft tissue with a growing cortex, and show that this also produces the characteristic patterns of convolutions over a realistic developmental course. All together, our results show that although many molecular determinants control the tangential expansion of the cortex, the size, shape, placement and orientation of the folds arise through iterations and variations of an elementary mechanical instability modulated by early fetal brain geometry.

Posttraumatic epidermal inclusion cyst of the deep infratemporal fossa.

PubMed

Acarturk, T O; Stofman, G M

2001-01-01

The authors report a case of an epidermal inclusion cyst found in the deep infratemporal fossa 12 years after the patient sustained blunt trauma to that region. Posttraumatic epidermal inclusion cysts are rare and occur mainly in the fingers, palms, and soles. Introduction of the epidermal elements into the dermis during the trauma is thought to be the cause. This case is rare in presentation, with few reports in the English literature that describe an epidermal inclusion cyst in the deep infratemporal fossa. Review of the English literature disclosed no other cases of epidermal inclusion cyst after blunt trauma involving the deep infratemporal region.

Carbon Dioxide Metabolism in Leaf Epidermal Tissue 1

PubMed Central

Willmer, C. M.; Pallas, J. E.; Black, C. C.

1973-01-01

A number of plant species were surveyed to obtain pure leaf epidermal tissue in quantity. Commelina communis L. and Tulipa gesnariana L. (tulip) were chosen for further work. Chlorophyll a/b ratios of epidermal tissues were 2.41 and 2.45 for C. communis and tulip, respectively. Phosphoenolpyruvate carboxylase, ribulose-1,5-diphosphate carboxylase, malic enzyme, and NAD+ and NADP+ malate dehydrogenases were assayed with epidermal tissue and leaf tissue minus epidermal tissue. In both species, there was less ribulose 1,5-diphosphate than phosphoenolpyruvate carboxylase activity in epidermal tissue whether expressed on a protein or chlorophyll basis whereas the reverse was true for leaf tissue minus epidermal tissue. In both species, malic enzyme activities were higher in epidermal tissue than in the remaining leaf tissue when expressed on a protein or chlorophyll basis. In both species, NAD+ and NADP+ malate dehydrogenase activities were higher in the epidermal tissue when expressed on a chlorophyll basis; however, on a protein basis, the converse was true. Microautoradiography of C. communis epidermis and histochemical tests for keto acids suggested that CO2 fixation occurred predominantly in the guard cells. The significance and possible location of the enzymes are discussed in relation to guard cell metabolism. Images PMID:16658581

Adult epidermal Notch activity induces dermal accumulation of T cells and neural crest derivatives through upregulation of jagged 1

PubMed Central

Ambler, Carrie A.; Watt, Fiona M.

2010-01-01

Notch signalling regulates epidermal differentiation and tumour formation via non-cell autonomous mechanisms that are incompletely understood. This study shows that epidermal Notch activation via a 4-hydroxy-tamoxifen-inducible transgene caused epidermal thickening, focal detachment from the underlying dermis and hair clumping. In addition, there was dermal accumulation of T lymphocytes and stromal cells, some of which localised to the blisters at the epidermal-dermal boundary. The T cell infiltrate was responsible for hair clumping but not for other Notch phenotypes. Notch-induced stromal cells were heterogeneous, expressing markers of neural crest, melanocytes, smooth muscle and peripheral nerve. Although Slug1 expression was expanded in the epidermis, the stromal cells did not arise through epithelial-mesenchymal transition. Epidermal Notch activation resulted in upregulation of jagged 1 in both epidermis and dermis. When Notch was activated in the absence of epidermal jagged 1, jagged 1 was not upregulated in the dermis, and epidermal thickening, blister formation, accumulation of T cells and stromal cells were inhibited. Gene expression profiling revealed that epidermal Notch activation resulted in upregulation of several growth factors and cytokines, including TNFα, the expression of which was dependent on epidermal jagged 1. We conclude that jagged 1 is a key mediator of non-cell autonomous Notch signalling in skin. PMID:20940224

Arctigenin induced gallbladder cancer senescence through modulating epidermal growth factor receptor pathway.

PubMed

Zhang, Mingdi; Cai, Shizhong; Zuo, Bin; Gong, Wei; Tang, Zhaohui; Zhou, Di; Weng, Mingzhe; Qin, Yiyu; Wang, Shouhua; Liu, Jun; Ma, Fei; Quan, Zhiwei

2017-05-01

Gallbladder cancer has poor prognosis and limited therapeutic options. Arctigenin, a representative dibenzylbutyrolactone lignan, occurs in a variety of plants. However, the molecular mechanisms involved in the antitumor effect of arctigenin on gallbladder cancer have not been fully elucidated. The expression levels of epidermal growth factor receptor were examined in 100 matched pairs of gallbladder cancer tissues. A positive correlation between high epidermal growth factor receptor expression levels and poor prognosis was observed in gallbladder cancer tissues. Pharmacological inhibition or inhibition via RNA interference of epidermal growth factor receptor induced cellular senescence in gallbladder cancer cells. The antitumor effect of arctigenin on gallbladder cancer cells was primarily achieved by inducing cellular senescence. In gallbladder cancer cells treated with arctigenin, the expression level of epidermal growth factor receptor significantly decreased. The analysis of the activity of the kinases downstream of epidermal growth factor receptor revealed that the RAF-MEK-ERK signaling pathway was significantly inhibited. Furthermore, the cellular senescence induced by arctigenin could be reverted by pcDNA-epidermal growth factor receptor. Arctigenin also potently inhibited the growth of tumor xenografts, which was accompanied by the downregulation of epidermal growth factor receptor and induction of senescence. This study demonstrates arctigenin could induce cellular senescence in gallbladder cancer through the modulation of epidermal growth factor receptor pathway. These data identify epidermal growth factor receptor as a key regulator in arctigenin-induced gallbladder cancer senescence.

[Progress in epidermal stem cells].

PubMed

Wang, Li-Juan; Wang, You-Liang; Yang, Xiao

2010-03-01

Mammalian skin epidermis contains different epidermal stem cell pools which contribute to the homeostasis and repair of skin epithelium. Epidermal stem cells possess two essential features common to all stem cells: self-renewal and differentiation. Disturbing the balance between self-renewal and differentiation of epidermal stem cell often causes tumors or other skin diseases. Epidermal stem cell niches provide a special microenvironment that maintains a balance of stem cell quiescence and activity. This review primarily concentrates on the following points of the epidermal stem cells: the existing evidences, the self-renewal and differentiation, the division pattern, the signal pathways regulating self-renewal and differentiation, and the microenvironment (niche) and macroenvironment maintaining the homeostasis of stem cells.

A TRANSPLANTABLE RABBIT CARCINOMA ORIGINATING IN A VIRUS-INDUCED PAPILLOMA AND CONTAINING THE VIRUS IN MASKED OR ALTERED FORM

PubMed Central

Kidd, John G.; Rous, Peyton

1940-01-01

A squamous cell carcinoma derived from a virus-induced rabbit papilloma has been propagated in fourteen successive groups of animals. It grows rapidly now in most individuals to which it is transplanted, killing early and metastasizing frequently. The original cancer was the outcome of alterations in epidermal cells already rendered neoplastic by the virus, and the latter, or an agent nearly related to it, has persisted and increased in the malignant tissue, as a study of the blood of the first ten groups of cancerous animals has shown. An antibody capable of specifically neutralizing the virus in vitro appeared in the blood of every new host in which the tumor enlarged progressively, and reached a titer comparable with that obtaining in animals which had long carried large papillomas. The antibody was absent from normal rabbits and those in which the cancer failed to grow. The implications of these facts are considered. PMID:19871000

Global Modeling of Spur Formation in Spiral Galaxies

NASA Astrophysics Data System (ADS)

Shetty, Rahul; Ostriker, Eve C.

2006-08-01

We investigate the formation of substructure in spiral galaxies using global MHD simulations, including gas self-gravity. Local modeling by Kim & Ostriker previously showed that self-gravity and magnetic fields cause rapid growth of overdensities in spiral arms; differential compression of gas flowing through the arms then results in the formation of sheared structures in the interarms. These sheared structures resemble features described as spurs or feathers in optical and IR observations of many spiral galaxies. Global modeling extends previous local models by including the full effects of curvilinear coordinates, a realistic log-spiral perturbation, self-gravitational contribution from five radial wavelengths of the spiral shock, and variation of density and epicyclic frequency with radius. We show that with realistic Toomre Q-values self-gravity and galactic differential rotation produce filamentary gaseous structures with kiloparsec-scale separations, regardless of the strength-or even presence-of a stellar spiral potential. However, a sufficiently strong spiral potential is required to produce true spurs, consisting of interarm structures emerging from gas concentrations in the main spiral arms. In models where Q is initially constant, filaments due to interarm self-gravity grow mainly in the outer regions, whereas true arm spurs grow only in the inner regions. For models with Q~R, outer regions are intrinsically more stable, so background interarm filaments do not grow, but arm spurs can develop if the spiral potential is strong. Unlike independently growing background filaments, the orientation of arm spurs depends on galactic location. Inside corotation, spurs emanate outward, on the convex side of the arm; outside corotation, spurs grow inward, on the concave side of the arm. Based on orientation and the relation to arm clumps, it is possible to distinguish true spurs that originate as instabilities in the arms from independently growing background filaments. We measure spur spacings of ~3-5 times the Jeans length in the arm and arm clump masses of ~107 Msolar. Finally, we have also studied models without self-gravity, finding that magnetic fields suppress a purely hydrodynamic instability recently proposed by Wada & Koda as a means of growing interarm spurs and feathers. Our models also suggest that magnetic fields are important in preserving grand-design spiral structure when gas in the arms fragments via self-gravity into GMCs.

Esterase Activity and Intracellular Localization in Reconstructed Human Epidermal Cultured Skin Models.

PubMed

Tokudome, Yoshihiro; Katayanagi, Mishina; Hashimoto, Fumie

2015-06-01

Reconstructed human epidermal culture skin models have been developed for cosmetic and pharmaceutical research. This study evaluated the total and carboxyl esterase activities (i.e., Km and Vmax , respectively) and localization in two reconstructed human epidermal culture skin models (LabCyte EPI-MODEL [Japan Tissue Engineering] and EpiDerm [MatTek/Kurabo]). The usefulness of the reconstruction cultured epidermis was also verified by comparison with human and rat epidermis. Homogenized epidermal samples were fractioned by centrifugation. p-nitrophenyl acetate and 4-methylumbelliferyl acetate were used as substrates of total esterase and carboxyl esterase, respectively. Total and carboxyl esterase activities were present in the reconstructed human epidermal culture skin models and were localized in the cytosol. Moreover, the activities and localization were the same as those in human and rat epidermis. LabCyte EPI-MODEL and EpiDerm are potentially useful for esterase activity prediction in human epidermis.

Esterase Activity and Intracellular Localization in Reconstructed Human Epidermal Cultured Skin Models

PubMed Central

Katayanagi, Mishina; Hashimoto, Fumie

2015-01-01

Background Reconstructed human epidermal culture skin models have been developed for cosmetic and pharmaceutical research. Objective This study evaluated the total and carboxyl esterase activities (i.e., Km and Vmax, respectively) and localization in two reconstructed human epidermal culture skin models (LabCyte EPI-MODEL [Japan Tissue Engineering] and EpiDerm [MatTek/Kurabo]). The usefulness of the reconstruction cultured epidermis was also verified by comparison with human and rat epidermis. Methods Homogenized epidermal samples were fractioned by centrifugation. p-nitrophenyl acetate and 4-methylumbelliferyl acetate were used as substrates of total esterase and carboxyl esterase, respectively. Results Total and carboxyl esterase activities were present in the reconstructed human epidermal culture skin models and were localized in the cytosol. Moreover, the activities and localization were the same as those in human and rat epidermis. Conclusion LabCyte EPI-MODEL and EpiDerm are potentially useful for esterase activity prediction in human epidermis. PMID:26082583

Skin problems and EGFR-tyrosine kinase inhibitor

PubMed Central

Kozuki, Toshiyuki

2016-01-01

Epidermal growth factor receptor inhibition is a good target for the treatment of lung, colon, pancreatic and head and neck cancers. Epidermal growth factor receptor-tyrosine kinase inhibitor was first approved for the treatment of advanced lung cancer in 2002. Epidermal growth factor receptor-tyrosine kinase inhibitor plays an essential role in the treatment of cancer, especially for patients harbouring epidermal growth factor receptor activating mutation. Hence, skin toxicity is the most concerning issue for the epidermal growth factor receptor-tyrosine kinase inhibitor treatment. Skin toxicity is bothersome and sometimes affects the quality of life and treatment compliance. Thus, it is important for physicians to understand the background and how to manage epidermal growth factor receptor-tyrosine kinase inhibitor-associated skin toxicity. Here, the author reviewed the mechanism and upfront preventive and reactive treatments for epidermal growth factor receptor inhibitor-associated skin toxicities. PMID:26826719

Epidermal stem cells: location, potential and contribution to cancer.

PubMed

Ambler, C A; Määttä, A

2009-01-01

Epidermal stem cells have been classically characterized as slow-cycling, long-lived cells that reside in discrete niches in the skin. Gene expression studies of niche-resident cells have revealed a number of stem cell markers and regulators, including the Wnt/beta-catenin, Notch, p63, c-Myc and Hedgehog pathways. A new study challenges the traditional developmental paradigm of slow-cycling stem cells and rapid-cycling transit amplifying cells in some epidermal regions, and there is mounting evidence to suggest that multi-lineage epidermal progenitors can be isolated from highly proliferative, non-niche regions. Whether there is a unique microenvironment surrounding these progenitors remains to be determined. Interestingly, cancer stem cells derived from epidermal tumours exist independent of the classic skin stem cell niche, yet also have stem cell properties, including multi-lineage differentiation. This review summarizes recent studies identifying the location and regulators of mouse and human epidermal stem cells and highlights the strategies used to identify cancer stem cells, including expression of normal epidermal stem cell markers, expression of cancer stem cell markers identified in other epidermal tumours and characterization of side-population tumour cells.

An Automated and Minimally Invasive Tool for Generating Autologous Viable Epidermal Micrografts

PubMed Central

Osborne, Sandra N.; Schmidt, Marisa A.; Harper, John R.

2016-01-01

ABSTRACT OBJECTIVE: A new epidermal harvesting tool (CelluTome; Kinetic Concepts, Inc, San Antonio, Texas) created epidermal micrografts with minimal donor site damage, increased expansion ratios, and did not require the use of an operating room. The tool, which applies both heat and suction concurrently to normal skin, was used to produce epidermal micrografts that were assessed for uniform viability, donor-site healing, and discomfort during and after the epidermal harvesting procedure. DESIGN: This study was a prospective, noncomparative institutional review board–approved healthy human study to assess epidermal graft viability, donor-site morbidity, and patient experience. SETTING: These studies were conducted at the multispecialty research facility, Clinical Trials of Texas, Inc, San Antonio. PATIENTS: The participants were 15 healthy human volunteers. RESULTS: The average viability of epidermal micrografts was 99.5%. Skin assessment determined that 76% to 100% of the area of all donor sites was the same in appearance as the surrounding skin within 14 days after epidermal harvest. A mean pain of 1.3 (on a scale of 1 to 5) was reported throughout the harvesting process. CONCLUSIONS: Use of this automated, minimally invasive harvesting system provided a simple, low-cost method of producing uniformly viable autologous epidermal micrografts with minimal patient discomfort and superficial donor-site wound healing within 2 weeks. PMID:26765157

An Automated and Minimally Invasive Tool for Generating Autologous Viable Epidermal Micrografts.

PubMed

Osborne, Sandra N; Schmidt, Marisa A; Harper, John R

2016-02-01

A new epidermal harvesting tool (CelluTome; Kinetic Concepts, Inc, San Antonio, Texas) created epidermal micrografts with minimal donor site damage, increased expansion ratios, and did not require the use of an operating room. The tool, which applies both heat and suction concurrently to normal skin, was used to produce epidermal micrografts that were assessed for uniform viability, donor-site healing, and discomfort during and after the epidermal harvesting procedure. This study was a prospective, noncomparative institutional review board-approved healthy human study to assess epidermal graft viability, donor-site morbidity, and patient experience. These studies were conducted at the multispecialty research facility, Clinical Trials of Texas, Inc, San Antonio. The participants were 15 healthy human volunteers. The average viability of epidermal micrografts was 99.5%. Skin assessment determined that 76% to 100% of the area of all donor sites was the same in appearance as the surrounding skin within 14 days after epidermal harvest. A mean pain of 1.3 (on a scale of 1 to 5) was reported throughout the harvesting process. Use of this automated, minimally invasive harvesting system provided a simple, low-cost method of producing uniformly viable autologous epidermal micrografts with minimal patient discomfort and superficial donor-site wound healing within 2 weeks.

Bearing Restoration by Grinding

DTIC Science & Technology

1976-05-21

lIng of bearings prior to installation, installing a contaminated bearing, manufacturing defects, ring growth in service, and corrosion. Nonmetallic...operation of rolling-elemsnt bearings is growth of the bearing race rings. As an example, the inner or outer races, can grow due to metallurgical...transformations or due to hoop stresses during operation This growth results in the bearing being not reusable after removal from its application. For aircraft

Dynamics of the outer radiation belts in relation to polar substorms and hot plasma injections at geostationary altitude

NASA Technical Reports Server (NTRS)

Sauvaud, J. A.; Winckler, J. R.

1981-01-01

Geostationary satellite and ground measurements of dynamic variations of the outer radiation belts and their relations with the development of auroral structures during magnetospheric substorms are analyzed. A comparison of measurements of the H or X geomagnetic field components made by seven auroral stations with ATS-6 low-energy and high-energy particle measurements during the multiple-onset substorm of Aug. 16, 1974 is presented which demonstrates that while the decrease in energetic particle fluxed ends only at the time of a strong substorm onset, rapid motions of the outer radiation belts may occur during the flux decrease. All-sky photographs of auroral phenomena taken at Fort Yukon and College, Alaska are then compared with ATS-1 energetic particle flux measurements in order to demonstrate the relation between flux decreases and increases and distinct substorm phases. Results support the hypothesis of a magnetospheric substorm precursor which appears to be an instability growing at the inner boundary of the plasma layer and approaching the earth, and underline the importance of current and magnetic field variations in charged particle dynamics.

The coordination of ploidy and cell size differs between cell layers in leaves.

PubMed

Katagiri, Yohei; Hasegawa, Junko; Fujikura, Ushio; Hoshino, Rina; Matsunaga, Sachihiro; Tsukaya, Hirokazu

2016-04-01

Growth and developmental processes are occasionally accompanied by multiple rounds of DNA replication, known as endoreduplication. Coordination between endoreduplication and cell size regulation often plays a crucial role in proper organogenesis and cell differentiation. Here, we report that the level of correlation between ploidy and cell volume is different in the outer and inner cell layers of leaves of Arabidopsis thaliana using a novel imaging technique. Although there is a well-known, strong correlation between ploidy and cell volume in pavement cells of the epidermis, this correlation was extremely weak in palisade mesophyll cells. Induction of epidermis cell identity based on the expression of the homeobox gene ATML1 in mesophyll cells enhanced the level of correlation between ploidy and cell volume to near that of wild-type epidermal cells. We therefore propose that the correlation between ploidy and cell volume is regulated by cell identity. © 2016. Published by The Company of Biologists Ltd.

Rumen Bacterial Degradation of Forage Cell Walls Investigated by Electron Microscopy

PubMed Central

Akin, Danny E.; Amos, Henry E.

1975-01-01

The association of rumen bacteria with specific leaf tissues of the forage grass Kentucky-31 tall fescue (Festuca arundinacea Schreb.) during in vitro degradation was investigated by transmission and scanning electron microscopy. Examination of degraded leaf cross-sections revealed differential rates of tissue degradation in that the cell walls of the mesophyll and pholem were degraded prior to those of the outer bundle sheath and epidermis. Rumen bacteria appeared to degrade the mesophyll, in some cases, and phloem without prior attachment to the plant cell walls. The degradation of bundle sheath and epidermal cell walls appeared to be preceded by attachment of bacteria to the plant cell wall. Ultrastructural features apparently involved in the adhesion of large cocci to plant cells were observed by transmission and scanning electron microscopy. The physical association between plant and rumen bacterial cells during degradation apparently varies with tissue types. Bacterial attachment, by extracellular features in some microorganisms, is required prior to degradation of the more resistant tissues. Images PMID:16350017

Quantifying hydrostatic pressure in plant cells by using indentation with an atomic force microscope.

PubMed

Beauzamy, Léna; Derr, Julien; Boudaoud, Arezki

2015-05-19

Plant cell growth depends on a delicate balance between an inner drive-the hydrostatic pressure known as turgor-and an outer restraint-the polymeric wall that surrounds a cell. The classical technique to measure turgor in a single cell, the pressure probe, is intrusive and cannot be applied to small cells. In order to overcome these limitations, we developed a method that combines quantification of topography, nanoindentation force measurements, and an interpretation using a published mechanical model for the pointlike loading of thin elastic shells. We used atomic force microscopy to estimate the elastic properties of the cell wall and turgor pressure from a single force-depth curve. We applied this method to onion epidermal peels and quantified the response to changes in osmolality of the bathing solution. Overall our approach is accessible and enables a straightforward estimation of the hydrostatic pressure inside a walled cell. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

The goat mammary glandular epithelial (GMGE) cell line promotes polyfucosylation and N,N'-diacetyllactosediaminylation of N-glycans linked to recombinant human erythropoietin.

PubMed

Sánchez, O; Montesino, R; Toledo, J R; Rodríguez, E; Díaz, D; Royle, L; Rudd, P M; Dwek, R A; Gerwig, G J; Kamerling, J P; Harvey, D J; Cremata, J A

2007-08-15

We have established a continuous, non-transformed cell line from primary cultures from Capra hircus mammary gland. Low-density cultures showed a homogeneous epithelial morphology without detectable fibroblastic or myoepithelial cells. The culture was responsive to contact inhibition of proliferation and its doubling time was dependent on the presence of insulin and epidermal growth factor (EGF). GMGE cells secrete caseins regardless of the presence or absence of lactogenic hormones in the culture media. Investigation of the total N-glycan pool of human erythropoietin (rhEPO) expressed in GMGE cells by monosaccharide analysis, HPLC profiling, and mass spectrometry, indicated significant differences with respect to the same protein expressed in Chinese hamster ovary (CHO) cells. N-Glycans of rhEPO-GMGE are core-fucosylated, but fucosylation of outer arms was also found. Our results also revealed the presence of low levels of sialylation (>95% Neu5Ac), N,N'-diacetyllactosediamine units, and possibly Gal-Gal non-reducing terminal elements.

The Stone Cold Truth: The Effect of Concrete Encasement on the Rate and Pattern of Soft Tissue Decomposition.

PubMed

Martin, D C; Dabbs, Gretchen R; Roberts, Lindsey G; Cleary, Megan K

2016-03-01

This study provides a descriptive analysis of taphonomic changes observed in the soft tissue of ten pigs (Sus scrofa) after being encased in Quickrete (®) concrete and excavated at monthly or bimonthly intervals over the course of 2 years. The best method of subject excavation was investigated. Rate and pattern of decomposition were compared to a nonencased control subject. Results demonstrate subjects interred in concrete decomposed significantly slower than the control subject (p < 0.01), the difference being observable after 1 month. After 1 year, the encased subject was in the early stage of decomposition with purging fluids and intact organs present, versus complete skeletonization of the control subject. Concrete subjects also display a unique decomposition pattern, exhibiting a chemically burned outer layer of skin and a common separation of the dermal and epidermal layers. Results suggest using traditional methods to estimate postmortem interval on concrete subjects may result in underestimation. © 2015 American Academy of Forensic Sciences.

A bio-ballistic micro-jet for drug injection into animal skin using a Nd:YAG laser

NASA Astrophysics Data System (ADS)

Yoh, J. J.; Jang, H.; Park, M.; Han, T.; Hah, J.

2016-01-01

Imaging of the abdominal skin of a guinea pig after injecting a fluorescent probe and biotin via the laser-induced ballistic technique revealed the epidermal and dermal layers which were stained well below 60 \\upmu m underneath the outer layer of the skin. An extensive network of cells was evident in the deeper layer of the stained dermis as the distributed fluorescein isothiocyanate dose was administered by repeated injection using a laser-based micro-jet. We performed optically controlled release of the drug by breaching the guinea pig's skin tissue targeting the region 10-400 \\upmu m beneath the outermost layer. Tissue damage was minimized by reducing the injection volume to approximately 100 nl per pulse. This was done using a micro-jet diameter equal to half of that of a conventional 200 \\upmu m syringe needle. Thus, the optimally controlled delivery of liquid drugs using an irradiated laser pulse was shown to be possible.

Epidermal cyst mimicking incision line metastasis.

PubMed

Gündoğdu, Ramazan; Ayhan, Erhan; Çolak, Tahsin

2017-01-01

Epidermal cysts are cystic tumors lined with keratinized squamous layer and filled with keratin debris. Epidermal cysts may develop by implantation of surface epidermal layer into the dermis or subcutaneous tissue after trauma or surgical procedures. Cervix cancer spreads either directly or via the vascular and lymphatic systems. Distant skin metastasis of endometrium or cervix cancer is very rare. In this case report, a patient who had a history of cervix cancer operation 11 years ago and presented with a mass that mimicked incision line metastasis and was histopathologically diagnosed with epidermal cyst is presented.

Epidermal cyst mimicking incision line metastasis

PubMed Central

Gündoğdu, Ramazan; Ayhan, Erhan; Çolak, Tahsin

2017-01-01

Epidermal cysts are cystic tumors lined with keratinized squamous layer and filled with keratin debris. Epidermal cysts may develop by implantation of surface epidermal layer into the dermis or subcutaneous tissue after trauma or surgical procedures. Cervix cancer spreads either directly or via the vascular and lymphatic systems. Distant skin metastasis of endometrium or cervix cancer is very rare. In this case report, a patient who had a history of cervix cancer operation 11 years ago and presented with a mass that mimicked incision line metastasis and was histopathologically diagnosed with epidermal cyst is presented. PMID:28740968

Two Cases of Giant Epidermal Cyst Occurring in the Neck

PubMed Central

Kang, Sang-Gue; Kim, Chul-Han; Cho, Hong-Ki; Park, Mi-Youn; Lee, Yoon-Jin

2011-01-01

Epidermal cysts are the most common cysts of the skin. Aconventional epidermal cyst rarely reaches a size of more than 5 cm in diameter. We report on two cases of giant epidermal cyst occurring in the neck. One patient had a cyst measuring 12×9×9 cm and the other patient had a non-pulsatile, dome-shaped lesion in the neck, which measured 6×5×3 cm. The lesions were totally excised. Histopathologically, both were confirmed as giant epidermal cysts. PMID:22028561

Hypocotyls of Lepidium meyenii (maca), a plant of the Peruvian highlands, prevent ultraviolet A-, B-, and C-induced skin damage in rats.

PubMed

Gonzales-Castañeda, Cynthia; Gonzales, Gustavo F

2008-02-01

Lepidium meyenii (maca) is a plant that grows exclusively in the Peruvian Central Andes, where ultraviolet radiation (UVR) is predominant. Determine if two extracts of maca can provide dermal protection against UVR. We have administered two maca extracts (0.13 mg/ml), one obtained after boiling and the other without boiling, on the dorsal surface of male Holtzman rats exposed to UVC radiation once a week during 3 consecutive weeks. A dose-response effect of an aqueous extract of maca after a boiling process under exposure of rats to UVA, UVB, or UVC was also studied. A commercial sunscreen was used as a positive control. UVR caused significant increase in skin epidermal thickness. The epidermal height in animals treated with maca was similar to those who did not receive UVR. The aqueous extract of maca after a boiling process had better effect than maca extract without a boiling process. A dose-response effect was observed with increasing doses of aqueous extract of maca after a boiling process. Maca extract had benzyl glucosinolates and polyphenols. Maca extracts protect the skin of rats against UV irradiations and can be suggested as an alternative means of solar protection.

Skin manifestations of growth hormone-induced diseases.

PubMed

Kanaka-Gantenbein, Christina; Kogia, Christina; Abdel-Naser, Mohamed Badawy; Chrousos, George P

2016-09-01

The human skin is a well-organized organ bearing different types of cells in a well-structured interference to each other including epidermal and follicular keratinocytes, sebocytes, melanocytes, dermal papilla cells and fibroblasts, endothelial cells, sweat gland cells as well as nerves. Several hormones act on different cell types of the skin, while it is also considered an endocrine organ secreting hormones that act at several sites of the organism. GH receptors are found in almost all cell types forming the skin, while IGF-1 receptors' expression is restricted to the epidermal keratinocytes. Both Growth Hormone (GH) excess, as in the case of Acromegaly in adults, or Gigantism in growing children, and GH deficiency states lead to skin manifestations. In case of GH excess the main dermatological findings are skin thickening, coarsening of facial features, acrochordons, puffy hands and feet, oily skin and hyperhidrosis, while GH deficiency, on the contrary, is characterized by thin, dry skin and disorder of normal sweating. Moreover, special disorders associated with GH excess may have specific characteristics, as is the case of café-au-lait spots in Neurofibromatosis, or big café-au-lait skin hyperpigmented regions with irregular margins, as is the case in McCune-Albright syndrome. Meticulous examination of the skin may therefore contribute to the final diagnosis in cases of GH-induced disorders.

Effects of epidermal growth factor on bone formation and resorption in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marie, P.J.; Hott, M.; Perheentupa, J.

1990-02-01

The effects of mouse epidermal growth factor (EGF) on bone formation and resorption were examined in male mice. EGF administration (2-200 ng.g-1.day-1 ip for 7 days) induced a dose-dependent rise in plasma EGF levels that remained within physiological range. Histomorphometric analysis of caudal vertebrae showed that EGF (20 and 200 ng.g-1.day-1) reduced the endosteal matrix and mineral appositional rates after 5 days of treatment as measured by double (3H)proline labeling and double tetracycline labeling, respectively. This effect was transitory and was not observed after 7 days of EGF administration. EGF administered for 7 days induced a dose-dependent increase in themore » periosteal osteoblastic and tetracycline double-labeled surfaces. At high dosage (200 ng.g-1.day-1) EGF administration increased the osteoclastic surface and the number of acid phosphatase-stained osteoclasts, although plasma calcium remained normal. The results show that EGF administration at physiological doses induces distinct effects on endosteal and periosteal bone formation and that the effects are dependent on EGF dosage and duration of treatment. This study indicates that EGF at physiological dosage stimulates periosteal bone formation and increases endosteal bone resorption in the growing mouse.« less

Diagnosis of ambient air pollution injury to red maple leaves

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krause, C.R.

1981-01-01

Ramets of red maple, Acer rubrum L. (cv 'Scarlet Sentinel') were grown under ambient field conditions for 5 months (May-Sept) in either clean air (i.e. minimum background of ozone (O/sub 3/) and sulfur dioxide (SO/sub 2/)) or were grown in polluted air containing phytotoxic combinations of O/sub 3/ and SO/sub 2/. At the end of the growing season leaf samples from each site were fixed in glutaraldehyde, washed in buffer (3X) post-fixed in O/sub s/O/sub 4/, dehydrated in ethanol and critically-point-dried. Samples were fractured with a razor blade, mounted either abaxially or adaxially or in cross-section, and sputter-coated with Au.more » While plants from either site failed to exhibit macroscopic air pollutant-induced symptoms, SEM examination revealed significant microscopic differences between prepared samples from different sites. Epidermal cells of leaves grown in clean air were uniformly turgid with fluffy epicuticular wax. Leaf samples from ramets that were grown in polluted air exhibited collapsed epidermal cells and lacked fluffy epicuticular wax. Cross-sections revealed increased vesicular activity in leaf mesophyll cells of plants exposed to high ambient pollution while cells of plants grown in clean air appeared normal. 10 references, 6 figures.« less

E- and P-cadherin expression during murine hair follicle morphogenesis and cycling.

PubMed

Müller-Röver, S; Tokura, Y; Welker, P; Furukawa, F; Wakita, H; Takigawa, M; Paus, R

1999-08-01

The role of adhesion molecules in the control of hair follicle (HF) morphogenesis, regression and cycling is still rather enigmatic. Since the adhesion molecules E- and P-cadherin (Ecad and Pcad) are functionally important, e.g. during embryonic pattern formation, we have studied their expression patterns during neonatal HF morphogenesis and cycling in C57/BL6 mice by immunohistology and semi-quantitative RT-PCR. The expression of both cadherins was strikingly hair cycle-dependent and restricted to distinct anatomical HF compartments. During HF morphogenesis, hair bud keratinocytes displayed strong Ecad and Pcad immunoreactivity (IR). While neonatal epidermis showed Ecad IR in all epidermal layers, Pcad IR was restricted to the basal layer. During later stages of HF morphogenesis and during anagen IV-VI of the adolescent murine hair cycle, the outer root sheath showed strong E- and Pcad IR. Instead, the outermost portion of the hair matrix and the inner root sheath displayed isolated Ecad IR, while the innermost portion of the hair matrix exhibited isolated Pcad IR. During telogen, all epidermal and follicular keratinocytes showed strong Ecad IR. This is in contrast to Pcad, whose IR was stringently restricted to matrix and secondary hair germ keratinocytes which are in closest proximity to the dermal papilla. These findings suggest that isolated or combined E- and/or Pcad expression is involved in follicular pattern formation by segregating HF keratinocytes into functionally distinct subpopulations; most notably, isolated Pcad expression may segregate those hair matrix keratinocytes into one functional epithelial tissue unit, which is particularly susceptible to growth control by dermal papilla-derived morphogens. The next challenge is to define which secreted agents implicated in hair growth control modulate these follicular cadherin expression patterns, and to define how these basic parameters of HF topobiology are altered during common hair growth disorders.

Characterization of xenobiotic metabolizing enzymes of a reconstructed human epidermal model from adult hair follicles.

PubMed

Bacqueville, Daniel; Jacques, Carine; Duprat, Laure; Jamin, Emilien L; Guiraud, Beatrice; Perdu, Elisabeth; Bessou-Touya, Sandrine; Zalko, Daniel; Duplan, Hélène

2017-08-15

In this study, a comprehensive characterization of xenobiotic metabolizing enzymes (XMEs) based on gene expression and enzyme functionality was made in a reconstructed skin epidermal model derived from the outer root sheath (ORS) of hair follicles (ORS-RHE). The ORS-RHE model XME gene profile was consistent with native human skin. Cytochromes P450 (CYPs) consistently reported to be detected in native human skin were also present at the gene level in the ORS-RHE model. The highest Phase I XME gene expression levels were observed for alcohol/aldehyde dehydrogenases and (carboxyl) esterases. The model was responsive to the CYP inducers, 3-methylcholanthrene (3-MC) and β-naphthoflavone (βNF) after topical and systemic applications, evident at the gene and enzyme activity level. Phase II XME levels were generally higher than those of Phase I XMEs, the highest levels were GSTs and transferases, including NAT1. The presence of functional CYPs, UGTs and SULTs was confirmed by incubating the models with 7-ethoxycoumarin, testosterone, benzo(a)pyrene and 3-MC, all of which were rapidly metabolized within 24h after topical application. The extent of metabolism was dependent on saturable and non-saturable metabolism by the XMEs and on the residence time within the model. In conclusion, the ORS-RHE model expresses a number of Phase I and II XMEs, some of which may be induced by AhR ligands. Functional XME activities were also demonstrated using systemic or topical application routes, supporting their use in cutaneous metabolism studies. Such a reproducible model will be of interest when evaluating the cutaneous metabolism and potential toxicity of innovative dermo-cosmetic ingredients. Copyright © 2017 Elsevier Inc. All rights reserved.

Transient Proliferation of Proanthocyanidin-Accumulating Cells on the Epidermal Apex Contributes to Highly Aluminum-Resistant Root Elongation in Camphor Tree1[W

PubMed Central

Osawa, Hiroki; Endo, Izuki; Hara, Yukari; Matsushima, Yuki; Tange, Takeshi

2011-01-01

Aluminum (Al) is a harmful element that rapidly inhibits the elongation of plant roots in acidic soils. The release of organic anions explains Al resistance in annual crops, but the mechanisms that are responsible for superior Al resistance in some woody plants remain unclear. We examined cell properties at the surface layer of the root apex in the camphor tree (Cinnamomum camphora) to understand its high Al resistance mechanism. Exposure to 500 μm Al for 8 d, more than 20-fold higher concentration and longer duration than what soybean (Glycine max) can tolerate, only reduced root elongation in the camphor tree to 64% of the control despite the slight induction of citrate release. In addition, Al content in the root apices was maintained at low levels. Histochemical profiling revealed that proanthocyanidin (PA)-accumulating cells were present at the adjacent outer layer of epidermis cells at the root apex, having distinctive zones for cell division and the early phase of cell expansion. Then the PA cells were gradually detached off the root, leaving thin debris behind, and the root surface was replaced with the elongating epidermis cells at the 3- to 4-mm region behind the tip. Al did not affect the proliferation of PA cells or epidermis cells, except for the delay in the start of expansion and the accelerated detachment of the former. In soybean roots, the innermost lateral root cap cells were absent in both PA accumulation and active cell division and failed to protect the epidermal cell expansion at 25 μm Al. These results suggest that transient proliferation and detachment of PA cells may facilitate the expansion of epidermis cells away from Al during root elongation in camphor tree. PMID:21045123

Transient proliferation of proanthocyanidin-accumulating cells on the epidermal apex contributes to highly aluminum-resistant root elongation in camphor tree.

PubMed

Osawa, Hiroki; Endo, Izuki; Hara, Yukari; Matsushima, Yuki; Tange, Takeshi

2011-01-01

Aluminum (Al) is a harmful element that rapidly inhibits the elongation of plant roots in acidic soils. The release of organic anions explains Al resistance in annual crops, but the mechanisms that are responsible for superior Al resistance in some woody plants remain unclear. We examined cell properties at the surface layer of the root apex in the camphor tree (Cinnamomum camphora) to understand its high Al resistance mechanism. Exposure to 500 μm Al for 8 d, more than 20-fold higher concentration and longer duration than what soybean (Glycine max) can tolerate, only reduced root elongation in the camphor tree to 64% of the control despite the slight induction of citrate release. In addition, Al content in the root apices was maintained at low levels. Histochemical profiling revealed that proanthocyanidin (PA)-accumulating cells were present at the adjacent outer layer of epidermis cells at the root apex, having distinctive zones for cell division and the early phase of cell expansion. Then the PA cells were gradually detached off the root, leaving thin debris behind, and the root surface was replaced with the elongating epidermis cells at the 3- to 4-mm region behind the tip. Al did not affect the proliferation of PA cells or epidermis cells, except for the delay in the start of expansion and the accelerated detachment of the former. In soybean roots, the innermost lateral root cap cells were absent in both PA accumulation and active cell division and failed to protect the epidermal cell expansion at 25 μm Al. These results suggest that transient proliferation and detachment of PA cells may facilitate the expansion of epidermis cells away from Al during root elongation in camphor tree.

Expression of ZO-1 and claudin-1 in a 3D epidermal equivalent using canine progenitor epidermal keratinocytes.

PubMed

Teramoto, Keiji; Asahina, Ryota; Nishida, Hidetaka; Kamishina, Hiroaki; Maeda, Sadatoshi

2018-05-21

Previous studies indicate that tight junctions are involved in the pathogenesis of canine atopic dermatitis (cAD). An in vitro skin model is needed to elucidate the specific role of tight junctions in cAD. A 3D epidermal equivalent model using canine progenitor epidermal keratinocytes (CPEK) has been established; the expression of tight junctions within this model is uncharacterized. To investigate the expression of tight junctions in the 3D epidermal equivalent. Two normal laboratory beagle dogs served as donors of full-thickness skin biopsy samples for comparison to the in vitro model. Immunohistochemical techniques were employed to investigate the expression of tight junctions including zonula occludens (ZO)-1 and claudin-1 in normal canine skin, and in the CPEK 3D epidermal equivalent. Results demonstrated the expression of ZO-1 and claudin-1 in the CPEK 3D epidermal equivalent, with staining patterns that were similar to those in normal canine skin. The CPEK 3D epidermal equivalent has the potential to be a suitable in vitro research tool for clarifying the specific role of tight junctions in cAD. © 2018 ESVD and ACVD.

Immunohistochemical distribution of Ki67 in epidermis of thick glabrous skin of human digits.

PubMed

Petrovic, Aleksandar; Petrovic, Vladimir; Milojkovic, Bobana; Nikolic, Ivan; Jovanovic, Dragan; Antovic, Aleksandra; Milic, Miroslav

2018-01-01

The glabrous skin on the flexor sides of hands and feet, compared to other integument regions, has thicker epidermis and more complex pattern of epidermal ridges, wherefore in microscopy is denominated as thick skin. The epidermis of this skin type has individually unique and permanent superficial patterns, called dermatoglyphics, which are maintained by regenerative potential of deep epidermal rete ridges, that interdigitate with adjacent dermis. Using light microscopy, we analyzed cadaveric big toes thick skin samples, described histology of deep epidermal ridges (intermediate, limiting, and transverse), and quantitatively evidenced their pattern of proliferation by immunohistochemical assessment of Ki67. Immunohistochemical distribution of Ki67 was confined to basal and suprabasal layers, with pattern of distribution specific for intermediate, limiting and transverse ridges that gradually transform within epidermal height. Deep epidermal ridges, interdigitating with dermal papillae, participate in construction of intricate epidermal base, whose possible role in epidermal regeneration was also discussed. Having a prominent morphology, this type of epidermis offers the best morphological insight in complexities of skin organization, and its understanding could challenge and improve currently accepted models of epidermal organization.

Dynamic FtsA and FtsZ localization and outer membrane alterations during polar growth and cell division in Agrobacterium tumefaciens

PubMed Central

Zupan, John R.; Cameron, Todd A.; Anderson-Furgeson, James; Zambryski, Patricia C.

2013-01-01

Growth and cell division in rod-shaped bacteria have been primarily studied in species that grow predominantly by peptidoglycan (PG) synthesis along the length of the cell. Rhizobiales species, however, predominantly grow by PG synthesis at a single pole. Here we characterize the dynamic localization of several Agrobacterium tumefaciens components during the cell cycle. First, the lipophilic dye FM 4-64 predominantly stains the outer membranes of old poles versus growing poles. In cells about to divide, however, both poles are equally labeled with FM 4-64, but the constriction site is not. Second, the cell-division protein FtsA alternates from unipolar foci in the shortest cells to unipolar and midcell localization in cells of intermediate length, to strictly midcell localization in the longest cells undergoing septation. Third, the cell division protein FtsZ localizes in a cell-cycle pattern similar to, but more complex than, FtsA. Finally, because PG synthesis is spatially and temporally regulated during the cell cycle, we treated cells with sublethal concentrations of carbenicillin (Cb) to assess the role of penicillin-binding proteins in growth and cell division. Cb-treated cells formed midcell circumferential bulges, suggesting that interrupted PG synthesis destabilizes the septum. Midcell bulges contained bands or foci of FtsA-GFP and FtsZ-GFP and no FM 4-64 label, as in untreated cells. There were no abnormal morphologies at the growth poles in Cb-treated cells, suggesting unipolar growth uses Cb-insensitive PG synthesis enzymes. PMID:23674672

[Enhanced lymphocyte proliferation in the presence of epidermal cells of HIV-infected patients in vitro].

PubMed

Kappus, R P; Berger, S; Thomas, C A; Ottmann, O G; Ganser, A; Stille, W; Shah, P M

1992-07-01

Clinical observations show that the HIV infection is often associated with affections of the skin. In order to examine the involvement of the epidermal immune system in the HIV infection, we determined accessory cell function of epidermal cells from HIV-1-infected patients. For this we measured the proliferative response of enriched CD(4+)-T-lymphocytes from HIV-infected patients and noninfected controls to stimulation with anti-CD3 and IL-2 in the presence of epidermal cells; the enhancement of the response is dependent on the presence of functionally intact accessory cells. The capacity of epidermal cells to increase the anti-CD3-stimulated T-cell proliferative response was significantly enhanced in HIV patients (CDC III/IVA) as compared with noninfected donors. It is discussed, whether the increased activity of epidermal cells from HIV-infected patients may be responsible for several of the dermal lesions in the course of an HIV infection as due to an enhanced production and release of epidermal cell-derived cytokines.

Morphological and functional studies on the epidermal cells of amphioxus ( Branchiostoma belcheri tsingtauense) at different developmental stages

NASA Astrophysics Data System (ADS)

Mao, Bing-Yu; Sun, Xiao-Yang; Zhang, Hong-Wei; Zhang, Shi-Cui; Wu, Xian-Han

1997-09-01

Epidermal cells of amphioxus at different developmental stages were investigated by electron microscopy and colloidal carbon tracing experiments. Amphioxus epidermal cells showed different ultrastructural characteristics at larval and adult stages. The epidermal cells at all larval stages studied (24 96 h) had numerous vesicles containing electron dense materials in their apical cytoplasm. In tracing experiments, carbon particles were found in apical vesicles and interoellular spaces. Under scanning electron microscope, many crater-like protrusions were observed on the surface of the cells. These results indicated that amphioxus larval epidermal cells may be capable of endocytosis. The epidermal cells of 3-month and adult amphioxus were obviously secretory ones characterized by well-developed peripheral filaments, a prominent Golgi apparatus and abundant apical secretory vesicles. This study also showed that adult amphioxus body surface mucus contained lectin that could agglutinate human red blood cells. The authors propose that the epidermal cells of amphioxus larva and adult may contribute to the immune defense of the amimal by different means.

Skin problems and EGFR-tyrosine kinase inhibitor.

PubMed

Kozuki, Toshiyuki

2016-04-01

Epidermal growth factor receptor inhibition is a good target for the treatment of lung, colon, pancreatic and head and neck cancers. Epidermal growth factor receptor-tyrosine kinase inhibitor was first approved for the treatment of advanced lung cancer in 2002. Epidermal growth factor receptor-tyrosine kinase inhibitor plays an essential role in the treatment of cancer, especially for patients harbouring epidermal growth factor receptor activating mutation. Hence, skin toxicity is the most concerning issue for the epidermal growth factor receptor-tyrosine kinase inhibitor treatment. Skin toxicity is bothersome and sometimes affects the quality of life and treatment compliance. Thus, it is important for physicians to understand the background and how to manage epidermal growth factor receptor-tyrosine kinase inhibitor-associated skin toxicity. Here, the author reviewed the mechanism and upfront preventive and reactive treatments for epidermal growth factor receptor inhibitor-associated skin toxicities. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Bronchoalveolar carcinoma: current treatment and future trends.

PubMed

Laskin, Janessa J

2004-12-01

Bronchoalveolar carcinoma (BAC) is a subtype of non-small-cell lung cancer (NSCLC) with unique clinical and pathologic characteristics. The most recent classification system defines BAC as a primary lung cancer that tends to be peripheral and grow in a lepedic fashion along the alveolar septae without parenchymal invasion. Most of the clinical information on BAC comes from retrospective institutional reviews; however, recent studies have focused more specifically on BAC. In particular, clinical trials of molecular-targeted anticancer therapies against the epidermal growth factor receptor have led to a deeper understanding of the distinct features of this cancer and suggest that BAC may require a therapeutic paradigm different from that of other NSCLCs.

Periplasmic orientation of nascent lipid A in the inner membrane of an Escherichia coli LptA mutant

PubMed Central

Ma, Bing; Reynolds, C. Michael; Raetz, Christian R. H.

2008-01-01

The core-lipid A domain of Escherichia coli lipopolysaccharide (LPS) is synthesized on the inner surface of the inner membrane (IM) and flipped to its outer surface by the ABC transporter MsbA. Recent studies with deletion mutants implicate the periplasmic protein LptA, the cytosolic protein LptB, and the IM proteins LptC, LptF, and LptG in the subsequent transport of nascent LPS to the outer membrane (OM), where the LptD/LptE complex flips LPS to the outer surface. We have isolated a temperature-sensitive mutant (MB1) harboring the S22C and Q111P substitutions in LptA. MB1 stops growing after 30 min at 42°C. 32Pi and [35S]methionine labeling show that export of newly synthesized phospholipids and proteins is not severely impaired, but export of LPS is defective. Using the lipid A 1-phosphatase LpxE as a periplasmic IM marker and the lipid A 3-O-deacylase PagL as an OM marker, we show that core-lipid A reaches the periplasmic side of the IM at 42°C in MB1 but not the outer surface of the OM. Electron microscopy of MB1 reveals dense periplasmic material and a smooth OM at 42°C, consistent with a role for LptA in shuttling LPS across the periplasm. PMID:18768814

Periplasmic orientation of nascent lipid A in the inner membrane of an Escherichia coli LptA mutant.

PubMed

Ma, Bing; Reynolds, C Michael; Raetz, Christian R H

2008-09-16

The core-lipid A domain of Escherichia coli lipopolysaccharide (LPS) is synthesized on the inner surface of the inner membrane (IM) and flipped to its outer surface by the ABC transporter MsbA. Recent studies with deletion mutants implicate the periplasmic protein LptA, the cytosolic protein LptB, and the IM proteins LptC, LptF, and LptG in the subsequent transport of nascent LPS to the outer membrane (OM), where the LptD/LptE complex flips LPS to the outer surface. We have isolated a temperature-sensitive mutant (MB1) harboring the S22C and Q111P substitutions in LptA. MB1 stops growing after 30 min at 42 degrees C. (32)P(i) and [(35)S]methionine labeling show that export of newly synthesized phospholipids and proteins is not severely impaired, but export of LPS is defective. Using the lipid A 1-phosphatase LpxE as a periplasmic IM marker and the lipid A 3-O-deacylase PagL as an OM marker, we show that core-lipid A reaches the periplasmic side of the IM at 42 degrees C in MB1 but not the outer surface of the OM. Electron microscopy of MB1 reveals dense periplasmic material and a smooth OM at 42 degrees C, consistent with a role for LptA in shuttling LPS across the periplasm.

The Aviation Accident Experience of Civilian Airmen With Refractive Surgery

DTIC Science & Technology

2002-06-01

such as photorefractive keratec- tomy (PRK) and laser-assisted in situ keratomileusis ( LASIK ), are being performed on a rapidly growing number of...stable, healing is complete, and no glare intolerance is present (4). RK, PRK, and LASIK procedures are similar only in that the goal is to improve...called photoablation, which utilizes the excimer laser to vaporize the cornea’s outer tissue. LASIK uses a specially designed surgical scalpel

Effects of adenosine 5'-monophosphate on epidermal turnover.

PubMed

Furukawa, Fukumi; Kanehara, Shoko; Harano, Fumiki; Shinohara, Shigeo; Kamimura, Junko; Kawabata, Shigekatsu; Igarashi, Sachiyo; Kawamura, Mitsuaki; Yamamoto, Yuki; Miyachi, Yoshiki

2008-10-01

The structure and function of the epidermis is maintained by cell renewal based on epidermal turnover. Epidermal turnover is delayed by aging, and it is thought that the delay of the epidermal turnover is a cause of aging alternation of skin. The epidermal turnover is related to the energy metabolism of epidermal basal cells. Adenosine 5'-triphosphate (ATP) is needed for cell renewal: cell division, and adenosine 5'-monophosphate (AMP) increases the amount of intracellular ATP. These findings suggest that AMP accelerates the epidermal turnover delayed by aging. This study investigated whether AMP and adenosine 5'-monophosphate disodium salt (AMP2Na) accelerates the epidermal turnover. An effect of AMP2Na on cell proliferation was examined by our counting of keratinocytes. An effect of AMP2Na on cell cycle was examined by our counting of basal cells in DNA synthetic period of hairless rats. The effects of AMP2Na (or AMP) on the epidermal turnover were examined by our measuring stratum corneum transit time by use of guinea pigs, and by our measuring stratum corneum surface area by use of hairless rats and in a clinical pharmacological study. The AMP2Na showed two different profiles on the proliferation of primary cultured keratinocytes. At a low concentration it induced cell growth, whereas at a high concentration it inhibited cell growth. The number of basal cells in the DNA synthetic period of AMP2Na was significantly higher than that of the vehicle in hairless rats. The stratum corneum transit time of AMP2Na was significantly shorter than that of the vehicle in guinea pigs. The corneocyte surface area of emulsion containing AMP2Na was significantly smaller than that of the vehicle in volunteers. We conclude that AMP promotes the cell proliferation and the cell cycle progression of epidermal basal cells and accelerates epidermal turnover safely. In addition, AMP is useful for skin rejuvenation in dermatology and aesthetic dermatology.

New procedure for epidermal cell isolation using kiwi fruit actinidin, and improved culture of melanocytes in the presence of leukaemia inhibitory factor and forskolin.

PubMed

Yarani, Reza; Mansouri, Kamran; Mohammadi-Motlagh, Hamid Reza; Bakhtiari, Mitra; Mostafaie, Ali

2013-06-01

Conventional isolation of epidermis from the dermis and disruption of epidermal sheets to liberate the cells, are performed using proteolytic enzymes such as thermolysin or collagenase. Selective population expansion of melanocytes is achieved by suppressing proliferation of keratinocytes and fibroblasts in epidermal cell suspensions, using phorbol esters and cholera toxin. Here, we introduce a new procedure for isolation of epidermal cells, using proteolytic activity of kiwi fruit actinidin, and also an improved growth medium for melanocytes in the presence of leukaemia inhibitory factor (LIF) and forskolin. Dermo-epidermal separation and epidermal sheet cell dispersion were performed using actinidin compared to conventional proteases including collagenase, thermolysin or trypsin. Thereafter, melanocyte culture was performed in two common media and one modified medium to discover optimization for these cells. We found that dermo-epidermal separation and epidermal sheet cell dispersion using kiwi fruit actinidin were considerably better than previously used methods, both from the aspect of less fibroblast and keratinocyte contamination, and of more viable native cells. Also, melanocytes proliferated better in phorbol ester- and cholera toxin-free proliferation medium supplemented with LIF and forskolin. Less contamination and higher numbers of viable cells were actinidin preferential for separation of epidermis and isolation of epidermal cells. Supplementation of LIF and forskolin to new medium increased proliferation potential of melanocytes in comparison to exogenous mitogens. © 2013 Blackwell Publishing Ltd.

Regenerative and reparative effects of human chorion-derived stem cell conditioned medium on photo-aged epidermal cells

PubMed Central

Li, Qiankun; Chen, Yan; Ma, Kui; Zhao, Along; Zhang, Cuiping; Fu, Xiaobing

2016-01-01

ABSTRACT Epidermal cells are an important regenerative source for skin wound healing. Aged epidermal cells have a low ability to renew themselves and repair skin injury. Ultraviolet (UV) radiation, particularly UVB, can cause photo-aging of the skin by suppressing the viability of human epidermal cells. A chorion-derived stem cell conditioned medium (CDSC-CNM) is thought to have regenerative properties. This study aimed to determine the regenerative effects of CDSC-CNM on UVB-induced photo-aged epidermal cells. Epidermal cells were passaged four times and irradiated with quantitative UVB, and non-irradiated cells served as a control group. Cells were then treated with different concentrations of CDSC-CNM. Compared to the non-irradiated group, the proliferation rates and migration rates of UVB-induced photo-aged epidermal cells significantly decreased (p < 0.05) with increasing intracellular radical oxygen species (ROS) generation and DNA damage. After treatment with CDSC-CNM, photo-aged epidermal cells significantly improved their viability, and their ROS generation and DNA damage decreased. The secretory factors in CDSC-CNM, including epidermal growth factor (EGF), transforming growth factor-β (TGF-β), interleukin (IL)-6, and IL-8 and the related signaling pathway protein levels, increased compared to the control medium (CM). The potential regenerative and reparative effects of CDSC-CNM indicate that it may be a candidate material for the treatment of prematurely aged skin. The functions of the secretory factors and the mechanisms of CDSC-CNM therapy deserve further attention. PMID:27097375

Differentiated epidermal cells regain the ability to regenerate a skin equivalent by increasing the level of β-catenin in the cells.

PubMed

Zhao, Zhili; Zhang, Cuiping; Fu, Xiaobing; Yang, Rongya; Peng, Chen; Gu, Tingmin; Sui, Zhifu; Wang, Congmin; Liu, Chang

2012-01-01

Epidermal stem cells are of major importance for skin regeneration and tissue engineering, but differentiated epidermal cells lost their proliferative capacity and are no longer able to regenerate a skin equivalent. Here, we investigated the role of β-catenin in regulating regenerative functions of differentiated epidermal cells. Lithium chloride and a highly specific glycogen synthase kinase (GSK)-3β inhibitor were applied to induce the expression of β-catenin in differentiated epidermal cells. After a 6-day induction, the large flat-shaped cells with a small nuclear-cytoplasmic ratio had changed into small round-shaped cells with a large nuclear-cytoplasmic ratio. Phenotypic assays showed a remarkably higher expression of CK19, β(1)-integrin, Oct4 and Nanog in induced cells than in the control group (p < 0.01). In addition, the results of growth and functional investigations demonstrated that the induced epidermal cells exhibited a high colony-forming ability, a long-term proliferative potential and the ability to regenerate a skin equivalent, which were regarded as the most important features of epidermal stem cells. These results suggest that the activation of β-catenin favors the reversion or dedifferentiation of differentiated epidermal cells to an immature or a less differentiated state. This study may also offer a new approach to yield enough epidermal stem cells for skin regeneration and tissue engineering. Copyright © 2012 S. Karger AG, Basel.

Polymeric membranes modulate human keratinocyte differentiation in specific epidermal layers.

PubMed

Salerno, Simona; Morelli, Sabrina; Giordano, Francesca; Gordano, Amalia; Bartolo, Loredana De

2016-10-01

In vitro models of human bioengineered skin substitutes are an alternative to animal experimentation for testing the effects and toxicity of drugs, cosmetics and pollutants. For the first time specific and distinct human epidermal strata were engineered by using membranes and keratinocytes. To this purpose, biodegradable membranes of chitosan (CHT), polycaprolactone (PCL) and a polymeric blend of CHT-PCL were prepared by phase-inversion technique and characterized in order to evaluate their morphological, physico-chemical and mechanical properties. The capability of membranes to modulate keratinocyte differentiation inducing specific interactions in epidermal membrane systems was investigated. The overall results demonstrated that the membrane properties strongly influence the cell morpho-functional behaviour of human keratinocytes, modulating their terminal differentiation, with the creation of specific epidermal strata or a fully proliferative epidermal multilayer system. In particular, human keratinocytes adhered on CHT and CHT-PCL membranes, forming the structure of the epidermal top layers, such as the corneum and granulosum strata, characterized by withdrawal or reduction from the cell cycle and cell proliferation. On the PCL membrane, keratinocytes developed an epidermal basal lamina, with high proliferating cells that stratified and migrated over time to form a complete differentiating epidermal multilayer system. Copyright © 2016 Elsevier B.V. All rights reserved.

Procedure to prepare transparent silica gels

NASA Technical Reports Server (NTRS)

Barber, Patrick G. (Inventor); Simpson, Norman R. (Inventor)

1987-01-01

This invention relates to the production of silica gels and in particular to a process for the preparation of silica gels which can be used as a crystal growth medium that simulates the convectionless environment of space to produce structurally perfect crystals. Modern utilizations of substances in electronics, such as radio transmitters and high frequency microphones, often require single crystals with controlled purity and structural perfection. The near convectionless environment of silica gel suppresses nucleation, thereby reducing the competitive nature of crystal growth. This competition limits the size and perfection of the crystal; and it is obviously desirable to suppress nucleation until, ideally, only one crystal grows in a predetermined location. A silica gel is not a completely convectionless environment like outer space, but is the closest known environment to that of outer space that can be created on Earth.

Pigmented epidermal cyst with dense collection of melanin: A rare entity – Report of a case with review of the literature

PubMed Central

Jayalakshmy, P. S.; Subitha, K.; Priya, P. V.; Johnson, Gerald

2012-01-01

Epidermal cyst is a very common benign cystic lesion of the skin. It is usual to find ulceration of the lining epithelium, rupture of the cyst wall with chronic inflammation and foreign body giant cell reaction. But, it is very rare to see an epidermal cyst with marked accumulation of melanin pigment. Only a few cases of pigmented epidermal cyst with dense collection of melanin pigment have been published in the literature. Here, we are reporting a case of ruptured epidermal cyst with keratin granuloma formation and showing dense collection of melanin pigment. PMID:23130289

Stromal cell-derived factor 1 (SDF-1) accelerated skin wound healing by promoting the migration and proliferation of epidermal stem cells.

PubMed

Guo, Rui; Chai, Linlin; Chen, Liang; Chen, Wenguang; Ge, Liangpeng; Li, Xiaoge; Li, Hongli; Li, Shirong; Cao, Chuan

2015-06-01

Epidermal stem cells could contribute to skin repair through the migration of cells from the neighboring uninjured epidermis, infundibulum, hair follicle, or sebaceous gland. However, little is known about the factors responsible for the complex biological processes in wound healing. Herein, we will show that the attracting chemokine, SDF-1/CXCR4, is a major regulator involved in the migration of epidermal stem cells during wound repair. We found that the SDF-1 levels were markedly increased at the wound margins following injury and CXCR4 expressed in epidermal stem cells and proliferating epithelial cells. Blocking the SDF-1/CXCR4 axis resulted in a significant reduction in epidermal stem cell migration toward SDF-1 in vitro and delayed wound healing in vivo, while an SDF-1 treatment enhanced epidermal stem cell migration and proliferation and accelerated wound healing. These results provide direct evidence that SDF-1 promotes epidermal stem cell migration, accelerates skin regeneration, and makes the development of new regenerative therapeutic strategies for wound healing possible.

Loss of EGF binding and cation transport response during differentiation of mouse neuroblastoma cells.

PubMed

Mummery, C L; van der Saag, P T; de Laat, S W

1983-01-01

Mouse neuroblastoma cells (clone N1E-115) differentiate in culture upon withdrawal of serum growth factors and acquire the characteristics of neurons. We have shown tht exponentially growing N1E-115 cells possess functional epidermal growth factor (EGF) receptors but that the capacity for binding EGF and for stimulation of DNA synthesis is lost as the cells differentiate. Furthermore, in exponentially growing cells, EGF induces a rapid increase in amiloride-sensitive Na+ influx, followed by stimulation of the (Na+-K+)ATPase, indicating that activation of the Na+/H+ exchange mechanism in N1E-115 cells [1] may be induced by EGF. The ionic response is also lost during differentiation, but we have shown that the stimulation of both Na+ and K+ influx is directly proportional to the number of occupied receptors in all cells whether exponentially growing or differentiating, thus only indirectly dependent on the external EGF concentration. The linearity of the relationships indicates that there is no rate-limiting step between EGF binding and the ionic response. Our data would suggest that as neuroblastoma cells differentiate and acquire neuronal properties, their ability to respond to mitogens, both biologically and in the activation of cation transport processes, progressively decreases owing to the loss of the appropriate receptors.

Arap1 Deficiency Causes Photoreceptor Degeneration in Mice.

PubMed

Moshiri, Ala; Humpal, Devin; Leonard, Brian C; Imai, Denise M; Tham, Addy; Bower, Lynette; Clary, Dave; Glaser, Thomas M; Lloyd, K C Kent; Murphy, Christopher J

2017-03-01

Small guanosine triphosphatase (GTPase) ADP-ribosylation factors (Arfs) regulate membrane traffic and actin reorganization under the control of GTPase-activating proteins (GAPs). Arap1 is an Arf-directed GAP that inhibits the trafficking of epidermal growth factor receptor (EGFR) to the early endosome, but the diversity of its functions is incompletely understood. The aim of this study was to determine the role of Arap1 in the mammalian retina. Genetically engineered Arap1 knockout mice were screened for ocular abnormalities in the National Institutes of Health Knockout Mouse Production and Phenotyping (KOMP2) Project. Arap1 knockout and wild-type eyes were imaged using optical coherence tomography and fundus photography, and analyzed by immunohistochemistry. Arap1-/- mice develop a normal appearing retina, but undergo photoreceptor degeneration starting at 4 weeks postnatal age. The fundus appearance of mutants is notable for pigmentary changes, optic nerve pallor, vascular attenuation, and outer retinal thinning, reminiscent of retinitis pigmentosa in humans. Immunohistochemical studies suggest the cell death is predominantly in the outer nuclear layer. Functional evaluation of the retina by electroretinography reveals amplitudes are reduced. Arap1 is detected most notably in Müller glia, and not in photoreceptors, implicating a role for Müller glia in photoreceptor survival. Arap1 is necessary for normal photoreceptor survival in mice, and may be a novel gene relevant to human retinal degenerative processes, although its mechanism is unknown. Further studies in this mouse model of retinal degeneration will give insights into the cellular functions and signaling pathways in which Arap1 participates.

Localization and pattern of graviresponse across the pulvinus of barley Hordeum vulgare

NASA Technical Reports Server (NTRS)

Brock, T. G.; Lu, C. R.; Ghosheh, N. S.; Kaufman, P. B.

1989-01-01

Pulvini of excised stem segments from barley (Hordeum vulgare cv Larker') were pretreated with 1 millimolar coumarin before gravistimulation to reduce longitudinal cell expansion and exaggerate radial cell enlargement. The cellular localization and pattern of graviresponse across individual pulvini were then evaluated by cutting the organ in cross-section, photographing the cross-section, and then measuring pulvinus thickness and the radial width of cortical and epidermal cells in enlargements of the photomicrographs. With respect to orientation during gravistimulation, we designated the uppermost point of the cross-section 0 degrees and the lowermost point 180 degrees. A gravity-induced increase in pulvinus thickness was observable within 40 degrees of the vertical in coumarin-treated pulvini. In upper halves of coumarin-treated gravistimulated pulvini, cells in the inner cortex and inner epidermis had increased radial widths, relative to untreated gravistimulated pulvini. In lower halves of coumarin-treated pulvini, cells in the central and outer cortex and in the outer epidermis showed the greatest increase in radial width. Cells comprising the vascular bundles also increased in radial width, with this pattern following that of the central cortex. These results indicate (a) that all cell types are capable of showing a graviresponse, (b) that the graviresponse occurs in both the top and the bottom of the responding organ, and (c) that the magnitude of the response increases approximately linearly from the uppermost point to the lowermost. These results are also consistent with models of gravitropism that link the pattern and magnitude of the graviresponse to graviperception via statolith sedimentation.

Elaiophores in Gomesa bifolia (Sims) M.W. Chase & N.H. Williams (Oncidiinae: Cymbidieae: Orchidaceae): structure and oil secretion

PubMed Central

Aliscioni, Sandra S.; Torretta, Juan P.; Bello, Mariano E.; Galati, Beatriz G.

2009-01-01

Background and Aims Oils are an unusual floral reward in Orchidaceae, being produced by specialized glands called elaiophores. Such glands have been described in subtribe Oncidiinae for a few species. The aims of the present study were to identify the presence of elaiophores in Gomesa bifolia, to study their structure and to understand how the oil is secreted. Additionally, elaiophores of G. bifolia were compared with those of related taxa within the Oncidiinae. Methods Elaiophores were identified using Sudan III. Their structure was examined by using light, scanning electron and transmission electron microscopy. Key Results Secretion of oils was from the tips of callus protrusions. The secretory cells each had a large, centrally located nucleus, highly dense cytoplasm, abundant plastids containing lipid globules associated with starch grains, numerous mitochondria, an extensive system of rough and smooth endoplasmatic reticulum, and electron-dense dictyosomes. The outer tangential walls were thick, with a loose cellulose matrix and a few, sparsely distributed inconspicuous cavities. Electron-dense structures were observed in the cell wall and formed a lipid layer that covered the cuticle of the epidermal cells. The cuticle as viewed under the scanning electron microscope was irregularly rugose. Conclusions The elaiophores of G. bifolia are of the epithelial type. The general structure of the secretory cells resembles that described for other species of Oncidiinae, but some unique features were encountered for this species. The oil appears to pass through the outer tangential wall and the cuticle, covering the latter without forming cuticular blisters. PMID:19692391

Genetic analysis of Ras genes in epidermal development and tumorigenesis

PubMed Central

Drosten, Matthias; Lechuga, Carmen G; Barbacid, Mariano

2013-01-01

Proliferation and differentiation of epidermal keratinocytes are tightly controlled to ensure proper development and homeostasis of the epidermis. The Ras family of small GTPases has emerged as a central node in the coordination of cell proliferation in the epidermis. Recent genetic evidence from mouse models has revealed that the intensity of Ras signaling modulates the proliferative capacity of epidermal keratinocytes. Interfering with Ras signaling either by combined elimination of the 3 Ras genes from the basal layer of the epidermis or by overexpression of dominant-negative Ras isoforms caused epidermal thinning due to hypoproliferation of keratinocytes. In contrast, overexpression of oncogenic Ras mutants in different epidermal cell layers led to hyperproliferative phenotypes including the development of papillomas and squamous cell carcinomas. Here, we discuss the value of loss- and gain-of-function studies in mouse models to assess the role of Ras signaling in the control of epidermal proliferation. PMID:24150175

Phacomatosis pigmentokeratotica: another epidermal nevus syndrome and a distinctive type of twin spotting.

PubMed

Boente, M C; Pizzi de Parra, N; Larralde de Luna, M; Bonet, H B; Santos Muñoz, A; Parra, V; Gramajo, P; Moreno, S; Asial, R A

2000-01-01

The name epidermal nevus syndrome could be applied to a group of clinically and histopathologically different entities as has been pointed out by Happle. Phacomatosis pigmentokeratotica is a further type of epidermal nevus syndrome distinguished by the presence of a sebaceous nevus and a contralateral speckled lentiginous nevus of the papular type, associated with skeletal or neurological abnormalities. Three new cases of this recently delineated syndrome are presented. A common origin may account for the temporal and spatial relationship between the epidermal and the speckled lentiginous nevus. The concept of melanocytic-epidermal twin spotting similar to the interpretation of vascular twin spotting could explain the pathogenesis of this entity.

Paired dating of pith and outer edge (terminus) samples from prehispanic Caribbean wooden sculptures

Treesearch

Fiona Brock; Joanna Ostapkowicz; Christopher Bronk Ramsey; Alex Wiedenhoeft; Caroline Cartwright

2012-01-01

Radiocarbon dating of historical and archaeological wood can be complicated, sometimes involving issues of “inbuilt” age in slow-growing woods, and/or the possibility of reuse or long delays between felling and use of the wood. Terminus dates can be provided by dating the sapwood, or the outermost edge of heartwood, while a date from the pith can give an indication of...

The targeted overexpression of a Claudin mutant in the epidermis of transgenic mice elicits striking epidermal and hair follicle abnormalities.

PubMed

Troy, Tammy-Claire; Turksen, Kursad

2007-06-01

Skin is one of the largest organs of the body, and is formed during development through a highly orchestrated process involving mesenchymal-epithelial interactions, cell commitment, and terminal differentiation. It protects against microorganism invasion and UV irradiation, inhibits water loss, regulates body temperature, and is an important part of the immune system. Using transgenic mouse technology, we have demonstrated that Claudin (Cldn)-containing tight junctions (TJs) are intricately involved in cell signaling during epidermal differentiation and that an epidermal suprabasal overexpression of Cldn6 results in a perturbed epidermal terminal differentiation program with distinct phenotypic abnormalities. To delineate the role of the Cldn cytoplasmic tail domain in epidermal differentiation, we engineered transgenic mice targeting the overexpression of a Cldn6 cytoplasmic tail-truncation mutant in the epidermis. Transgenic mice were characterized by a lethal barrier dysfunction in addition to the existence of hyperproliferative squamous invaginations/cysts replacing hair follicles. Immunohistochemical analysis revealed an epidermal cytoplasmic accumulation of Cldn6, Cldn11, Cldn12, and Cldn18, downregulation of Cldn1 and aberrant expression of various classical markers of epidermal differentiation; namely the basal keratins as well as K1, involucrin, loricrin, and filaggrin. Collectively these studies suggest an important role for Cldns in epidermal/hair follicle differentiation programs likely involving cross talk to signaling pathways (e.g., Notch) directing cell fate selection and differentiation.

Sonographic findings of ruptured epidermal inclusion cysts in superficial soft tissue: emphasis on shapes, pericystic changes, and pericystic vascularity.

PubMed

Jin, Wook; Ryu, Kyung Nam; Kim, Gou Young; Kim, Hyun Cheol; Lee, Jae Hoon; Park, Ji Seon

2008-02-01

The purpose of this study was to retrospectively evaluate the sonographic findings of ruptured epidermal inclusion cysts in superficial soft tissue, with an emphasis on shapes, pericystic changes, and pericystic vascularity. The cases of 61 patients with surgically confirmed epidermal inclusion cysts were reviewed, and 13 patients were found to have ruptured cysts. The Ethics Committees of our institutions did not require patient approval or informed patient consent for this retrospective study. We evaluated the shapes, sizes, locations, pericystic changes, and pericystic vascularity for the 13 cases. The shapes of the ruptured epidermal inclusion cysts were classified into 3 types: with lobulations (type I, 2 cases), with protrusions (type II, 8 cases), and with abscess pocket formations (type III, 3 cases). The mean long diameter of the cysts was 3 cm. Common sites of ruptured epidermal inclusion cysts were the plantar surface of the metatarsophalangeal joint (4 cases) and buttocks (3 cases). Pericystic changes were noted in all of the type II and III cysts. Increased vascularity on color Doppler sonography was prominent in 3 type II cysts and 3 type III cysts. Deep abscess formation was noted in the epidermal inclusion cysts, especially for the type III cysts. A ruptured epidermal inclusion cyst visualized by sonography had variable shapes; the sonographic findings can be useful for obtaining a correct diagnosis of a ruptured epidermal inclusion cyst.

Comprehensive Analysis of Transport Proteins Encoded Within the Genome of Bdellovibrio bacteriovorus

PubMed Central

Barabote, Ravi D.; Rendulic, Snjezana; Schuster, Stephan C.; Saier, Milton H.

2012-01-01

Bdellovibrio bacteriovorus is a bacterial parasite with an unusual lifestyle. It grows and reproduces in the periplasm of a host prey bacterium. The complete genome sequence of B. bacteriovorus has recently been reported. We have reanalyzed the transport proteins encoded within the B. bacteriovorus genome according to the current content of the transporter classification database (TCDB). A comprehensive analysis is given on the types and numbers of transport systems that B. bacteriovorus has. In this regard, the potential protein secretory capabilities of at least 4 types of inner membrane secretion systems and 5 types for outer membrane secretion are described. Surprisingly, B. bacteriovorus has a disproportionate percentage of cytoplasmic membrane channels and outer membrane porins. It has far more TonB/ExbBD-type systems and MotAB-type systems for energizing outer membrane transport and motility than does E. coli. Analysis of probable substrate specificities of its transporters provides clues to its metabolic preferences. Interesting examples of gene fusions and of potentially overlapping genes were also noted. Our analyses provide a comprehensive, detailed appreciation of the transport capabilities of B. bacteriovorus. They should serve as a guide for functional experimental analyses. PMID:17706914

Hairpin vortices in the outer and near wall regions of the canonical turbulent boundary layer

NASA Astrophysics Data System (ADS)

Wallace, James; Wu, Xiaohua; Moin, Parviz

2016-11-01

While the dominance of hairpin vortices and their significance for transport processes in the transitional and early turbulent regions of the canonical turbulent boundary layer has been widely accepted, opinion is divided about the developed flow downstream. Here we investigate the representative vortical structures in the outer and near wall regions for the momentum thickness Reynolds number, Reθ , of up to 3000 using the DNS database described in. This boundary layer grows spatially from a laminar state at Reθ = 80 beneath a freestream of continuous and nearly isotropic turbulence decaying from an intensity of 3 to 0.8%. The vortical structures are visualized with the swirling strength, λci. In the outer region hairpin vortices appear and are advected over distances corresponding to about 300 - 400 in Reθ within the fully turbulent region, demonstrating that they are not remnants of transitional structures. The near wall vortical structures are more difficult to visualize and require careful tuning of the swirling strength and making invisible the flow above the near wall region of the flow. The hairpins in this region occur in intermittent clusters that have features remarkably similar to transitional turbulent spots.

Gloss, colour and grip: multifunctional epidermal cell shapes in bee- and bird-pollinated flowers.

PubMed

Papiorek, Sarah; Junker, Robert R; Lunau, Klaus

2014-01-01

Flowers bear the function of filters supporting the attraction of pollinators as well as the deterrence of floral antagonists. The effect of epidermal cell shape on the visual display and tactile properties of flowers has been evaluated only recently. In this study we quantitatively measured epidermal cell shape, gloss and spectral reflectance of flowers pollinated by either bees or birds testing three hypotheses: The first two hypotheses imply that bee-pollinated flowers might benefit from rough surfaces on visually-active parts produced by conical epidermal cells, as they may enhance the colour signal of flowers as well as the grip on flowers for bees. In contrast, bird-pollinated flowers might benefit from flat surfaces produced by flat epidermal cells, by avoiding frequent visitation from non-pollinating bees due to a reduced colour signal, as birds do not rely on specific colour parameters while foraging. Moreover, flat petal surfaces in bird-pollinated flowers may hamper grip for bees that do not touch anthers and stigmas while consuming nectar and thus, are considered as nectar thieves. Beside this, the third hypothesis implies that those flower parts which are vulnerable to nectar robbing of bee- as well as bird-pollinated flowers benefit from flat epidermal cells, hampering grip for nectar robbing bees. Our comparative data show in fact that conical epidermal cells are restricted to visually-active parts of bee-pollinated flowers, whereas robbing-sensitive parts of bee-pollinated as well as the entire floral surface of bird-pollinated flowers possess on average flat epidermal cells. However, direct correlations between epidermal cell shape and colour parameters have not been found. Our results together with published experimental studies show that epidermal cell shape as a largely neglected flower trait might act as an important feature in pollinator attraction and avoidance of antagonists, and thus may contribute to the partitioning of flower-visitors.

The organization of human epidermis: functional epidermal units and phi proportionality.

PubMed

Hoath, Steven B; Leahy, D G

2003-12-01

The concept that mammalian epidermis is structurally organized into functional epidermal units has been proposed on the basis of stratum corneum (SC) architecture, proliferation kinetics, melanocyte:keratinocyte ratios (1:36), and, more recently, Langerhans cell: epidermal cell ratios (1:53). This article examines the concept of functional epidermal units in human skin in which the maintenance of phi (1.618034) proportionality provides a central organizing principle. The following empirical measurements were used: 75,346 nucleated epidermal cells per mm2, 1394 Langerhans cells per mm2, 1999 melanocytes per mm2, 16 (SC) layers, 900-microm2 corneocyte surface area, 17,778 corneocytes per mm2, 14-d (SC) turnover time, and 93,124 per mm2 total epidermal cells. Given these empirical data: (1) the number of corneocytes is a mean proportional between the sum of the Langerhans cell + melanocyte populations and the number of epidermal cells, 3393/17,778-17,778/93,124; (2) the ratio of nucleated epidermal cells over corneocytes is phi proportional, 75,346/17,778 approximately phi3; (3) assuming similar 14-d turnover times for the (SC) and Malpighian epidermis, the number of corneocytes results from subtraction of a cellular fraction equal to approximately 2/phi2 x the number of living cells, 75,436 - (2/phi2 x 75,346) approximately 17,778; and (4) if total epidermal turnover time equals (SC) turnover time x the ratio of living/dead cells, then compartmental turnover times are unequal (14 d for (SC) to 45.3 d for nucleated epidermis approximately 1/2phi) and cellular replacement rates are 52.9 corneocytes/69.3 keratinocytes per mm2 per h approximately 2/phi2. These empirically derived equivalences provide logicomathematical support for the presence of functional epidermal units in human skin. Validation of a phi proportional unit architecture in human epidermis will be important for tissue engineering of skin and the design of instruments for skin measurement.

Multiple Roles of Integrin-Linked Kinase in Epidermal Development, Maturation and Pigmentation Revealed by Molecular Profiling

PubMed Central

Judah, David; Rudkouskaya, Alena; Wilson, Ryan; Carter, David E.; Dagnino, Lina

2012-01-01

Integrin-linked kinase (ILK) is an important scaffold protein that mediates a variety of cellular responses to integrin stimulation by extracellular matrix proteins. Mice with epidermis-restricted inactivation of the Ilk gene exhibit pleiotropic phenotypic defects, including impaired hair follicle morphogenesis, reduced epidermal adhesion to the basement membrane, compromised epidermal integrity, as well as wasting and failure to thrive leading to perinatal death. To better understand the underlying molecular mechanisms that cause such a broad range of alterations, we investigated the impact of Ilk gene inactivation on the epidermis transcriptome. Microarray analysis showed over 700 differentially regulated mRNAs encoding proteins involved in multiple aspects of epidermal function, including keratinocyte differentiation and barrier formation, inflammation, regeneration after injury, and fundamental epidermal developmental pathways. These studies also revealed potential effects on genes not previously implicated in ILK functions, including those important for melanocyte and melanoblast development and function, regulation of cytoskeletal dynamics, and homeobox genes. This study shows that ILK is a critical regulator of multiple aspects of epidermal function and homeostasis, and reveals the previously unreported involvement of ILK not only in epidermal differentiation and barrier formation, but also in melanocyte genesis and function. PMID:22574216

Multiple roles of integrin-linked kinase in epidermal development, maturation and pigmentation revealed by molecular profiling.

PubMed

Judah, David; Rudkouskaya, Alena; Wilson, Ryan; Carter, David E; Dagnino, Lina

2012-01-01

Integrin-linked kinase (ILK) is an important scaffold protein that mediates a variety of cellular responses to integrin stimulation by extracellular matrix proteins. Mice with epidermis-restricted inactivation of the Ilk gene exhibit pleiotropic phenotypic defects, including impaired hair follicle morphogenesis, reduced epidermal adhesion to the basement membrane, compromised epidermal integrity, as well as wasting and failure to thrive leading to perinatal death. To better understand the underlying molecular mechanisms that cause such a broad range of alterations, we investigated the impact of Ilk gene inactivation on the epidermis transcriptome. Microarray analysis showed over 700 differentially regulated mRNAs encoding proteins involved in multiple aspects of epidermal function, including keratinocyte differentiation and barrier formation, inflammation, regeneration after injury, and fundamental epidermal developmental pathways. These studies also revealed potential effects on genes not previously implicated in ILK functions, including those important for melanocyte and melanoblast development and function, regulation of cytoskeletal dynamics, and homeobox genes. This study shows that ILK is a critical regulator of multiple aspects of epidermal function and homeostasis, and reveals the previously unreported involvement of ILK not only in epidermal differentiation and barrier formation, but also in melanocyte genesis and function.

Epidermal carbonic anhydrase activity and exoskeletal metal content during the molting cycle of the blue crab, Callinectes sapidus.

PubMed

Calhoun, Stacy; Zou, Enmin

2016-03-01

During the crustacean molting cycle, the exoskeleton is first mineralized in postmolt and intermolt and then presumably demineralized in premolt in order for epidermal retraction to occur. The mineralization process calls for divalent metal ions, such as Ca(2+) and Mg(2+) , and bicarbonate ions whereas protons are necessary for dissolution of carbonate salts. Carbonic anhydrase (CA) has been suggested to be involved in exoskeletal mineralization by providing bicarbonate ions through catalyzing the reaction of carbon dioxide hydration. However, results of earlier studies on the role of epidermal CA in metal incorporation in crustacean exoskeleton are not consistent. This study was aimed to provide further evidence to support the notion that epidermal CA is involved in exoskeletal mineralization using the blue crab, Callinectes sapidus (Rathbun 1896), as the model crustacean. Significant increases first in calcium and magnesium then in manganese post-ecdysis indicate significant metal deposition during postmolt and intermolt. Significant positive correlation between calcium or magnesium content and epidermal CA activity in postmolt and intermolt constitutes evidence that CA is involved in the mineralization of the crustacean exoskeleton. Additionally, we proposed a hypothetical model to describe the role of epidermal CA in both mineralization and demineralization of the exoskeleton based on the results of epidermal CA activity and exoskeletal metal content during the molting cycle. Furthermore, we found that the pattern of epidermal CA activity during the molting cycle of C. sapidus is similar to that of ecdysteroids reported for the same species, suggesting that epidermal CA activity may be under control of the molting hormones. © 2016 Wiley Periodicals, Inc.

Serine Proteolytic Pathway Activation Reveals an Expanded Ensemble of Wound Response Genes in Drosophila

PubMed Central

Patterson, Rachel A.; Juarez, Michelle T.; Hermann, Anita; Sasik, Roman; Hardiman, Gary; McGinnis, William

2013-01-01

After injury to the animal epidermis, a variety of genes are transcriptionally activated in nearby cells to regenerate the missing cells and facilitate barrier repair. The range and types of diffusible wound signals that are produced by damaged epidermis and function to activate repair genes during epidermal regeneration remains a subject of very active study in many animals. In Drosophila embryos, we have discovered that serine protease function is locally activated around wound sites, and is also required for localized activation of epidermal repair genes. The serine protease trypsin is sufficient to induce a striking global epidermal wound response without inflicting cell death or compromising the integrity of the epithelial barrier. We developed a trypsin wounding treatment as an amplification tool to more fully understand the changes in the Drosophila transcriptome that occur after epidermal injury. By comparing our array results with similar results on mammalian skin wounding we can see which evolutionarily conserved pathways are activated after epidermal wounding in very diverse animals. Our innovative serine protease-mediated wounding protocol allowed us to identify 8 additional genes that are activated in epidermal cells in the immediate vicinity of puncture wounds, and the functions of many of these genes suggest novel genetic pathways that may control epidermal wound repair. Additionally, our data augments the evidence that clean puncture wounding can mount a powerful innate immune transcriptional response, with different innate immune genes being activated in an interesting variety of ways. These include puncture-induced activation only in epidermal cells in the immediate vicinity of wounds, or in all epidermal cells, or specifically in the fat body, or in multiple tissues. PMID:23637905

Differential activity of 2-methylene-19-nor vitamin D analogs on growth factor gene expression in rhino mouse skin and comparison to all-trans retinoic acid.

PubMed

Ahrens, Jamie M; Jones, James D; Nieves, Nirca J; Mitzey, Ann M; DeLuca, Hector F; Clagett-Dame, Margaret

2017-01-01

While all 2-methylene-19-nor analogs of 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) tested produce an increase in epidermal thickness in the rhino mouse, only a subset reduce utricle size (comedolysis). All-trans retinoic acid (atRA) also causes epidermal thickening and a reduction in utricle size in the rhino mouse. We now report that 2-methylene-19-nor-(20S)-1α-hydroxybishomopregnacalciferol (2MbisP), a comedolytic analog, increases epidermal thickening more rapidly than does atRA, while both reduce utricle area at an equal rate. Whereas unlike atRA, 2MbisP does not alter the epidermal growth factor receptor ligand, heparin-binding epidermal growth factor-like growth factor, it does increase the expression of both amphiregulin and epigen mRNA, even after a single dose. In situ hybridization reveals an increase in these transcripts throughout the closing utricle as well as in the interfollicular epidermis. The mRNAs for other EGFR ligands including betacellulin and transforming growth factor-α, as well as the epidermal growth factor receptor are largely unaffected by 2MbisP. Another analog, 2-methylene-19-nor-(20S)-26,27-dimethylene-1α,25-dihydroxyvitamin D3 (CAGE-3), produces epidermal thickening but fails to reduce utricle size or increase AREG mRNA levels. CAGE-3 modestly increases epigen mRNA levels, but only after 5 days of dosing. Thus, 2-MbisP produces unique changes in epidermal growth factor receptor ligand mRNAs that may be responsible for both epidermal proliferation and a reduction in utricle size.

rhEGF-containing thermosensitive and mucoadhesive polymeric sol-gel for endoscopic treatment of gastric ulcer and bleeding.

PubMed

Maeng, Jin Hee; So, Jung Won; Kim, Jungju; Kim, In Ae; Jung, Ji Hoon; Min, Kyunghyun; Lee, Don Haeng; Yang, Su-Geun

2014-03-01

Gastrointestinal endoscopy is a standard diagnostic tool for gastrointestinal ulcers and cancer. In this study, we have developed recombinant human epidermal growth factor-containing ulcer-coating polymeric sol-gel for endoscopic application. Chitosan and pluronic F127 were employed for their thermoresponsive and bioadhesive properties. At temperatures below 21, polymeric sol-gel remains liquid during endoscopic application and transforms to gel at body temperature after application on ulcers. In an in vitro cellular wounding assay, recombinant human epidermal growth factor sol-gel significantly enhanced the cell migration and decreased the wounding area (68%) compared to nontreated, recombinant human epidermal growth factor solution, and sol-gel without recombinant human epidermal growth factor (42, 49, and 32 % decreased at day 1). The in vivo ulcer-healing study was performed in an acetic acid-induced gastric ulcer rat model and proved that our recombinant human epidermal growth factor endoscopic sol-gel facilitated the ulcer-healing process more efficiently than the other treatments. Ulcer sizes in the recombinant human epidermal growth factor sol-gel group were decreased 2.9- and 2.1-fold compared with those in the nontreated group on days 1 and 3 after ulceration, respectively. The mucosal thickness in the recombinant human epidermal growth factor sol-gel group was significantly increased compared to that in the nontreated group (3.2- and 6.9-fold on days 1 and 3 after ulceration, respectively). In a gastric retention study, recombinant human epidermal growth factor sol-gel stayed on the gastric mucosa more than 2 h after application. The present study suggests that recombinant human epidermal growth factor sol-gel is a prospective candidate for treating gastric ulcers via endoscopic application.

Planar cell polarity pathway in vertebrate epidermal development, homeostasis and repair

PubMed Central

Dworkin, Sebastian; Jane, Stephen M

2011-01-01

The planar cell polarity (PCP) pathway plays a critical role in diverse developmental processes that require coordinated cellular movement, including neural tube closure and renal tubulogenesis. Recent studies have demonstrated that this pathway also has emerging relevance to the epidermis, as PCP signaling underpins many aspects of skin biology and pathology, including epidermal development, hair orientation, stem cell division and cancer. Coordinated cellular movement required for epidermal repair in mammals is also regulated by PCP signaling, and in this context, a new PCP gene encoding the developmental transcription factor Grainyhead-like 3 (Grhl3) is critical. This review focuses on the role that PCP signaling plays in the skin across a variety of epidermal functions and highlights perturbations that induce epidermal pathologies. PMID:22041517

Increasing the efficiency of designing hemming processes by using an element-based metamodel approach

NASA Astrophysics Data System (ADS)

Kaiser, C.; Roll, K.; Volk, W.

2017-09-01

In the automotive industry, the manufacturing of automotive outer panels requires hemming processes in which two sheet metal parts are joined together by bending the flange of the outer part over the inner part. Because of decreasing development times and the steadily growing number of vehicle derivatives, an efficient digital product and process validation is necessary. Commonly used simulations, which are based on the finite element method, demand significant modelling effort, which results in disadvantages especially in the early product development phase. To increase the efficiency of designing hemming processes this paper presents a hemming-specific metamodel approach. The approach includes a part analysis in which the outline of the automotive outer panels is initially split into individual segments. By doing a para-metrization of each of the segments and assigning basic geometric shapes, the outline of the part is approximated. Based on this, the hemming parameters such as flange length, roll-in, wrinkling and plastic strains are calculated for each of the geometric basic shapes by performing a meta-model-based segmental product validation. The metamodel is based on an element similar formulation that includes a reference dataset of various geometric basic shapes. A random automotive outer panel can now be analysed and optimized based on the hemming-specific database. By implementing this approach into a planning system, an efficient optimization of designing hemming processes will be enabled. Furthermore, valuable time and cost benefits can be realized in a vehicle’s development process.

21 CFR 358.703 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-04-01

... increased rate of shedding of dead epidermal cells of the scalp. (c) Psoriasis. A condition of the scalp or body characterized by irritation, itching, redness, and extreme excess shedding of dead epidermal cells..., redness, and excess shedding of dead epidermal cells. (e) Selenium sulfide, micronized. Selenium sulfide...

21 CFR 358.703 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-04-01

... increased rate of shedding of dead epidermal cells of the scalp. (c) Psoriasis. A condition of the scalp or body characterized by irritation, itching, redness, and extreme excess shedding of dead epidermal cells..., redness, and excess shedding of dead epidermal cells. (e) Selenium sulfide, micronized. Selenium sulfide...

21 CFR 358.703 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-04-01

... increased rate of shedding of dead epidermal cells of the scalp. (c) Psoriasis. A condition of the scalp or body characterized by irritation, itching, redness, and extreme excess shedding of dead epidermal cells..., redness, and excess shedding of dead epidermal cells. (e) Selenium sulfide, micronized. Selenium sulfide...

21 CFR 358.703 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... increased rate of shedding of dead epidermal cells of the scalp. (c) Psoriasis. A condition of the scalp or body characterized by irritation, itching, redness, and extreme excess shedding of dead epidermal cells..., redness, and excess shedding of dead epidermal cells. (e) Selenium sulfide, micronized. Selenium sulfide...

21 CFR 358.703 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... increased rate of shedding of dead epidermal cells of the scalp. (c) Psoriasis. A condition of the scalp or body characterized by irritation, itching, redness, and extreme excess shedding of dead epidermal cells..., redness, and excess shedding of dead epidermal cells. (e) Selenium sulfide, micronized. Selenium sulfide...

Genomic determinants of epidermal appendage patterning and structure in domestic birds

PubMed Central

Boer, Elena F.; Van Hollebeke, Hannah F.; Shapiro, Michael D.

2017-01-01

Variation in regional identity, patterning, and structure of epidermal appendages contributes to skin diversity among many vertebrate groups, and is perhaps most striking in birds. In pioneering work on epidermal appendage patterning, John Saunders and his contemporaries took advantage of epidermal appendage diversity within and among domestic chicken breeds to establish the importance of mesoderm-ectoderm signaling in determining skin patterning. Diversity in chickens and other domestic birds, including pigeons, is driving a new wave of research to dissect the molecular genetic basis of epidermal appendage patterning. Domestic birds are not only outstanding models for embryonic manipulations, as Saunders recognized, but they are also ideal genetic models for discovering the specific genes that control normal development and the mutations that contribute to skin diversity. Here, we review recent genetic and genomic approaches to uncover the basis of epidermal macropatterning, micropatterning, and structural variation. We also present new results that confirm expression changes in two limb identity genes in feather-footed pigeons, a case of variation in appendage structure and identity. PMID:28347644

Developmental patterning of the sub-epidermal integument cell layer in Arabidopsis seeds

PubMed Central

Coen, Olivier; Fiume, Elisa; Xu, Wenjia; De Vos, Delphine; Lu, Jing; Pechoux, Christine; Lepiniec, Loïc

2017-01-01

Angiosperm seed development is a paradigm of tissue cross-talk. Proper seed formation requires spatial and temporal coordination of the fertilization products – embryo and endosperm – and the surrounding seed coat maternal tissue. In early Arabidopsis seed development, all seed integuments were thought to respond homogenously to endosperm growth. Here, we show that the sub-epidermal integument cell layer has a unique developmental program. We characterized the cell patterning of the sub-epidermal integument cell layer, which initiates a previously uncharacterized extra cell layer, and identified TRANSPARENT TESTA 16 and SEEDSTICK MADS box transcription factors as master regulators of its polar development and cell architecture. Our data indicate that the differentiation of the sub-epidermal integument cell layer is insensitive to endosperm growth alone and to the repressive mechanism established by FERTILIZATION INDEPENDENT ENDOSPERM and MULTICOPY SUPPRESSOR OF IRA1 Polycomb group proteins. This work demonstrates the different responses of epidermal and sub-epidermal integument cell layers to fertilization. PMID:28348169

Altered epidermal lipid processing and calcium distribution in the KID syndrome mouse model Cx26S17F.

PubMed

Bosen, Felicitas; Celli, Anna; Crumrine, Debra; vom Dorp, Katharina; Ebel, Philipp; Jastrow, Holger; Dörmann, Peter; Winterhager, Elke; Mauro, Theodora; Willecke, Klaus

2015-07-08

The keratitis-ichthyosis-deafness (KID) syndrome is caused by mutations in the gap junctional channel protein connexin 26 (Cx26), among them the mutation Cx26S17F. Heterozygous Cx26S17F mice resemble the human KID syndrome, i.e. exhibiting epidermal hyperplasia and hearing impairments. Newborn Cx26S17F mice show a defective epidermal water barrier as well as altered epidermal lipid secretion and location. Linoleoyl ω-esterified ceramides are strongly decreased on the skin surface of Cx26S17F mice. Moreover, the epidermal calcium gradient is altered in the mutant mice. These alterations may be caused by an abnormal Cx26S17F channel function that leads to a defective epidermal water barrier, which in turn may trigger the hyperproliferation seen in the KID syndrome. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Apoptosis as a Mechanism for Keratinocyte Death in Canine Toxic Epidermal Necrolysis.

PubMed

Banovic, F; Dunston, S; Linder, K E; Rakich, P; Olivry, T

2017-03-01

In humans and dogs, toxic epidermal necrolysis (TEN) is a life-threatening dermatosis characterized by sudden epidermal death resulting in extensive skin detachment. There is little information on the pathogenesis of keratinocyte cell death in canine TEN. We studied the occurrence of apoptosis in skin lesions of dogs with TEN to determine if apoptosis contributes to the pathogenesis of this disease. Immunostaining with antibodies to activated caspase-3 and the terminal deoxynucleotidyl-transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end labeling technique revealed positive apoptotic keratinocytes in basal and suprabasal epidermal compartments in 17 biopsy specimens collected from 3 dogs with TEN and 16 from 3 dogs with erythema multiforme (EM). There was no significant difference in the number of positively stained epidermal cells between TEN and EM. These results suggest that apoptosis of epidermal keratinocytes and lymphocytic satellitosis represent one of the early steps in the pathogenesis of canine TEN, as in the human disease counterpart.

Cardiolipin Synthesis and Outer Membrane Localization Are Required for Shigella flexneri Virulence.

PubMed

Rossi, Rachael M; Yum, Lauren; Agaisse, Hervé; Payne, Shelley M

2017-08-29

Cardiolipin, an anionic phospholipid that resides at the poles of the inner and outer membranes, is synthesized primarily by the putative cardiolipin synthase ClsA in Shigella flexneri An S. flexneri clsA mutant had no cardiolipin detected within its membrane, grew normally in vitro , and invaded cultured epithelial cells, but it failed to form plaques in epithelial cell monolayers, indicating that cardiolipin is required for virulence. The clsA mutant was initially motile within the host cell cytoplasm but formed filaments and lost motility during replication and failed to spread efficiently to neighboring cells. Mutation of pbgA , which encodes the transporter for cardiolipin from the inner membrane to the outer membrane, also resulted in loss of plaque formation. The S. flexneri pbgA mutant had normal levels of cardiolipin in the inner membrane, but no cardiolipin was detected in the outer membrane. The pbgA mutant invaded and replicated normally within cultured epithelial cells but failed to localize the actin polymerization protein IcsA properly on the bacterial surface and was unable to spread to neighboring cells. The clsA mutant, but not the pbgA mutant, had increased phosphatidylglycerol in the outer membrane. This appeared to compensate partially for the loss of cardiolipin in the outer membrane, allowing some IcsA localization in the outer membrane of the clsA mutant. We propose a dual function for cardiolipin in S. flexneri pathogenesis. In the inner membrane, cardiolipin is essential for proper cell division during intracellular growth. In the outer membrane, cardiolipin facilitates proper presentation of IcsA on the bacterial surface. IMPORTANCE The human pathogen Shigella flexneri causes bacterial dysentery by invading colonic epithelial cells, rapidly multiplying within their cytoplasm, and then spreading intercellularly to neighboring cells. Worldwide, Shigella spp. infect hundreds of millions of people annually, with fatality rates up to 15%. Antibiotic treatment of Shigella infections is compromised by increasing antibiotic resistance, and there is no approved vaccine to prevent future infections. This has created a growing need to understand Shigella pathogenesis and identify new targets for antimicrobial therapeutics. Here we show a previously unknown role of phospholipids in S. flexneri pathogenesis. We demonstrate that cardiolipin is required in the outer membrane for proper surface localization of IcsA and in the inner membrane for cell division during growth in the host cell cytoplasm. Copyright © 2017 Rossi et al.

Splash control of drop impacts with geometric targets.

PubMed

Juarez, Gabriel; Gastopoulos, Thomai; Zhang, Yibin; Siegel, Michael L; Arratia, Paulo E

2012-02-01

Drop impacts on solid and liquid surfaces exhibit complex dynamics due to the competition of inertial, viscous, and capillary forces. After impact, a liquid lamella develops and expands radially, and under certain conditions, the outer rim breaks up into an irregular arrangement of filaments and secondary droplets. We show experimentally that the lamella expansion and subsequent breakup of the outer rim can be controlled by length scales that are of comparable dimension to the impacting drop diameter. Under identical impact parameters (i.e., fluid properties and impact velocity) we observe unique splashing dynamics by varying the target cross-sectional geometry. These behaviors include (i) geometrically shaped lamellae and (ii) a transition in splashing stability, from regular to irregular splashing. We propose that regular splashes are controlled by the azimuthal perturbations imposed by the target cross-sectional geometry and that irregular splashes are governed by the fastest-growing unstable Plateau-Rayleigh mode.

Intranasal epidermal growth factor treatment rescues neonatal brain injury.

PubMed

Scafidi, Joseph; Hammond, Timothy R; Scafidi, Susanna; Ritter, Jonathan; Jablonska, Beata; Roncal, Maria; Szigeti-Buck, Klara; Coman, Daniel; Huang, Yuegao; McCarter, Robert J; Hyder, Fahmeed; Horvath, Tamas L; Gallo, Vittorio

2014-02-13

There are no clinically relevant treatments available that improve function in the growing population of very preterm infants (less than 32 weeks' gestation) with neonatal brain injury. Diffuse white matter injury (DWMI) is a common finding in these children and results in chronic neurodevelopmental impairments. As shown recently, failure in oligodendrocyte progenitor cell maturation contributes to DWMI. We demonstrated previously that the epidermal growth factor receptor (EGFR) has an important role in oligodendrocyte development. Here we examine whether enhanced EGFR signalling stimulates the endogenous response of EGFR-expressing progenitor cells during a critical period after brain injury, and promotes cellular and behavioural recovery in the developing brain. Using an established mouse model of very preterm brain injury, we demonstrate that selective overexpression of human EGFR in oligodendrocyte lineage cells or the administration of intranasal heparin-binding EGF immediately after injury decreases oligodendroglia death, enhances generation of new oligodendrocytes from progenitor cells and promotes functional recovery. Furthermore, these interventions diminish ultrastructural abnormalities and alleviate behavioural deficits on white-matter-specific paradigms. Inhibition of EGFR signalling with a molecularly targeted agent used for cancer therapy demonstrates that EGFR activation is an important contributor to oligodendrocyte regeneration and functional recovery after DWMI. Thus, our study provides direct evidence that targeting EGFR in oligodendrocyte progenitor cells at a specific time after injury is clinically feasible and potentially applicable to the treatment of premature children with white matter injury.

Intranasal epidermal growth factor treatment rescues neonatal brain injury

NASA Astrophysics Data System (ADS)

Scafidi, Joseph; Hammond, Timothy R.; Scafidi, Susanna; Ritter, Jonathan; Jablonska, Beata; Roncal, Maria; Szigeti-Buck, Klara; Coman, Daniel; Huang, Yuegao; McCarter, Robert J.; Hyder, Fahmeed; Horvath, Tamas L.; Gallo, Vittorio

2014-02-01

There are no clinically relevant treatments available that improve function in the growing population of very preterm infants (less than 32 weeks' gestation) with neonatal brain injury. Diffuse white matter injury (DWMI) is a common finding in these children and results in chronic neurodevelopmental impairments. As shown recently, failure in oligodendrocyte progenitor cell maturation contributes to DWMI. We demonstrated previously that the epidermal growth factor receptor (EGFR) has an important role in oligodendrocyte development. Here we examine whether enhanced EGFR signalling stimulates the endogenous response of EGFR-expressing progenitor cells during a critical period after brain injury, and promotes cellular and behavioural recovery in the developing brain. Using an established mouse model of very preterm brain injury, we demonstrate that selective overexpression of human EGFR in oligodendrocyte lineage cells or the administration of intranasal heparin-binding EGF immediately after injury decreases oligodendroglia death, enhances generation of new oligodendrocytes from progenitor cells and promotes functional recovery. Furthermore, these interventions diminish ultrastructural abnormalities and alleviate behavioural deficits on white-matter-specific paradigms. Inhibition of EGFR signalling with a molecularly targeted agent used for cancer therapy demonstrates that EGFR activation is an important contributor to oligodendrocyte regeneration and functional recovery after DWMI. Thus, our study provides direct evidence that targeting EGFR in oligodendrocyte progenitor cells at a specific time after injury is clinically feasible and potentially applicable to the treatment of premature children with white matter injury.

OsSNDP1, a Sec14-nodulin domain-containing protein, plays a critical role in root hair elongation in rice.

PubMed

Huang, Jin; Kim, Chul Min; Xuan, Yuan-hu; Park, Soon Ju; Piao, Hai Long; Je, Byoung Il; Liu, Jingmiao; Kim, Tae Ho; Kim, Bo-Kyeong; Han, Chang-Deok

2013-05-01

Rice is cultivated in water-logged paddy lands. Thus, rice root hairs on the epidermal layers are exposed to a different redox status of nitrogen species, organic acids, and metal ions than root hairs growing in drained soil. To identify genes that play an important role in root hair growth, a forward genetics approach was used to screen for short-root-hair mutants. A short-root-hair mutant was identified and isolated by using map-based cloning and sequencing. The mutation arose from a single amino acid substitution of OsSNDP1 (Oryza sativa Sec14-nodulin domain protein), which shows high sequence homology with Arabidopsis COW1/AtSFH1 and encodes a phosphatidylinositol transfer protein (PITP). By performing complementation assays with Atsfh1 mutants, we demonstrated that OsSNDP1 is involved in growth of root hairs. Cryo-scanning electron microscopy was utilized to further characterize the effect of the Ossndp1 mutation on root hair morphology. Aberrant morphogenesis was detected in root hair elongation and maturation zones. Many root hairs were branched and showed irregular shapes due to bulged nodes. Many epidermal cells also produced dome-shaped root hairs, which indicated that root hair elongation ceased at an early stage. These studies showed that PITP-mediated phospholipid signaling and metabolism is critical for root hair elongation in rice.

Epidermal growth factor receptor (EGFR) transactivation by estrogen via the G-protein-coupled receptor, GPR30: a novel signaling pathway with potential significance for breast cancer.

PubMed

Filardo, Edward J

2002-02-01

The biological and biochemical effects of estrogen have been ascribed to its known receptors, which function as ligand-inducible transcription factors. However, estrogen also triggers rapid activation of classical second messengers (cAMP, calcium, and inositol triphosphate) and stimulation of intracellular signaling cascades mitogen-activated protein kinase (MAP K), PI3K and eNOS. These latter events are commonly activated by membrane receptors that either possess intrinsic tyrosine kinase activity or couple to heterotrimeric G-proteins. We have shown that estrogen transactivates the epidermal growth factor receptor (EGFR) to MAP K signaling axis via the G-protein-coupled receptor (GPCR), GPR30, through the release of surface-bound proHB-EGF from estrogen receptor (ER)-negative human breast cancer cells [Molecular Endocrinology 14 (2000) 1649]. This finding is consistent with a growing body of evidence suggesting that transactivation of EGFRs by GPCRs is a recurrent theme in cell signaling. GPCR-mediated transactivation of EGFRs by estrogen provides a previously unappreciated mechanism of cross-talk between estrogen and serum growth factors, and explains prior data reporting the EGF-like effects of estrogen. This novel mechanism by which estrogen activates growth factor-dependent signaling and its implications for breast cancer biology are discussed further in this review.

Light-stimulated cell expansion in bean (Phaseolus vulgaris L.) leaves. I. Growth can occur without photosynthesis

NASA Technical Reports Server (NTRS)

Van Volkenburgh, E.; Cleland, R. E.

1990-01-01

Cell expansion in dicotyledonous leaves is strongly stimulated by bright white light (WL), at least in part as a result of light-induced acidification of the cell walls. It has been proposed that photosynthetic reactions are required for light-stimulated transport processes across plasma membranes of leaf cells, including proton excretion. The involvement of photosynthesis in growth and wall acidification of primary leaves of bean has been tested by inhibiting photosynthesis in two ways: by reducing chlorophyll content of intact plants with tentoxin (TX) and by treating leaf discs with 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU). Exposure to bright WL stimulated growth of intact leaves of TX-treated plants. Discs excised from green as well as from TX-or DCMU-treated leaves also responded by growing faster in WL, as long as exogenous sucrose was supplied to the photosynthetically inhibited tissues. The WL caused acidification of the epidermal surface of intact TX-leaves, but acidification of the incubation medium by mesophyll cells only occurred when photosynthesis was not inhibited. It is concluded that light-stimulated cell enlargement of bean leaves, and the necessary acidification of epidermal cell walls, are mediated by a pigment other than chlorophyll. Light-induced proton excretion by mesophyll cells, on the other hand, may require both a photosynthetic product (or exogenous sugars) and a non-photosynthetic light effect.

Phosphorylation of hepatocyte growth factor receptor and epidermal growth factor receptor of human hepatocytes can be maintained in a (3D) collagen sandwich culture system.

PubMed

Engl, Tobias; Boost, Kim A; Leckel, Kerstin; Beecken, Wolf-Dietrich; Jonas, Dietger; Oppermann, Elsie; Auth, Marcus K H; Schaudt, André; Bechstein, Wolf-Otto; Blaheta, Roman A

2004-08-01

In vitro culture models that employ human liver cells could be potent tools for predictive studies on drug toxicity and metabolism in the pharmaceutical industry. However, an adequate receptor responsiveness is necessary to allow intracellular signalling and metabolic activity. We tested the ability of three-dimensionally arranged human hepatocytes to respond to the growth factors hepatocyte growth factor (HGF) or epidermal growth factor (EGF). Isolated adult human hepatocytes were cultivated within a three-dimensional collagen gel (sandwich) or on a two-dimensional collagen matrix. Cells were treated with HGF or EGF and expression and phosphorylative activity of HGF receptors (HGFr, c-met) or EGF receptors (EGFr) were measured by flow cytometry and Western blot. Increasing HGFr and EGFr levels were detected in hepatocytes growing two-dimensionally. However, both receptors were not activated in presence of growth factors. In contrast, when hepatocytes were plated within a three-dimensional matrix, HGFr and EGFr levels remained constantly low. However, both receptors became strongly phosphorylated by soluble HGF or EGF. We conclude that cultivation of human hepatocytes in a three-dimensionally arranged in vitro system allows the maintenance of specific functional activities. The necessity of cell dimensionality for HGFr and EGFr function should be considered when an adequate in vitro system has to be introduced for drug testing.

Ontogenetic characterization of sporangium and spore of Huperzia serrata: an anti-aging disease fern.

PubMed

Long, Hua; Li, Jing; Li, You-You; Xie, De-Yu; Peng, Qing-Zhong; Li, Li

2016-12-01

Huperzia serrata is a medicinal plant used in Traditional Chinese Medicine, which has been used to prevent against aging diseases. It is mainly propagated by spores and grows extremely slowly. Due to severe harvest, it is a highly endangered species. In this report, we characterize ontogenesis of sporangia and spores that are associated with propagation. A wild population of H. serrata plants is localized in western Hunan province, China and protected by Chinese Government to study its development (e.g. sporangia and spores) and ecology. Both field and microscopic observations were conducted for a few of years. The development of sporangia from their initiation to maturation took nearly 1 year. Microscopic observations showed that the sporangial walls were developed from epidermal cells via initiation, cell division, and maturation. The structure of the mature sporangial wall is composed of one layer of epidermis, two middle layers of cells, and one layer of tapetum. Therefore, the sporangium is the eusporangium type. Spore development is characterized into six stages, initiation from epidermal cell and formation of sporogenous cells, primary sporogenous cell, secondary sporogenous cell, spore mother cell, tetrad, and maturation. The sporangial development of H. serrata belongs to the eusporangium type. The development takes approximately 1 year period from the initiation to the maturation. These data are useful for improving propagation of this medicinal plant in the future.

The group of epidermal nevus syndromes Part I. Well defined phenotypes.

PubMed

Happle, Rudolf

2010-07-01

The epidermal nevus syndromes represent a group of distinct disorders that can be distinguished by the type of associated epidermal nevus and by the criterion of presence or absence of heritability. Well defined syndromes characterized by organoid epidermal nevi include Schimmelpenning syndrome, phacomatosis pigmentokeratotica, nevus comedonicus syndrome, angora hair nevus syndrome, and Becker nevus syndrome. The molecular basis of these disorders has so far not been identified. By contrast, the group of syndromes characterized by keratinocytic nevi comprises three phenotypes with a known molecular etiology in the form of CHILD (congenital hemidysplasia with ichthyosiform nevus and limb defects) syndrome, type 2 segmental Cowden disease, and fibroblast growth factor receptor 3 epidermal nevus syndrome (García-Hafner-Happle syndrome), whereas Proteus syndrome is still of unknown origin. From this overview, it is clear that a specific type of these disorders cannot be classified by the name "epidermal nevus syndrome" nor by the terms "organoid nevus syndrome" or "keratinocytic nevus syndrome." After completing this learning activity, participants should be able to distinguish nine different epidermal nevus syndromes by their characteristic features, understand the practical significance of avoiding terms like "epidermal nevus syndrome" or "keratinocytic nevus syndrome" to define any specific entity within this group of disorders, and differentiate between nonhereditary traits and those bearing a genetic risk because of either Mendelian or non-Mendelian inheritance. Copyright (c) 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

The temporal and spatial expression of Claudins in epidermal development and the accelerated program of epidermal differentiation in K14-CaSR transgenic mice.

PubMed

Troy, Tammy-Claire; Li, Yuhua; O'Malley, Lauren; Turksen, Kursad

2007-02-01

The importance of the epidermal permeability barrier (EPB) in protecting the mammalian species against harmful UV irradiation, microorganism invasion and water loss is well recognized, as is the role of calcium (Ca(2+)) in keratinocyte differentiation, cell-cell contact and the EPB. In a previous study, we reported that the overexpression of the Ca(2+)-sensing receptor (CaSR) in the undifferentiated basal cells of the epidermis induced a modified epidermal differentiation program including an accelerated EPB formation in transgenic mice, suggesting a role for CaSR signaling in the differentiation of embryonic epidermal cells during development. We now describe the expression profile of claudins (Cldns) and keratin markers in the accelerated EPB formation of K14-CaSR transgenic mice during development as compared to the wild type from E12.5 to newborn stages. Our data show that the transgenic epidermis undergoes an advanced epidermal differentiation program as compared to the wild type as evidenced morphologically as well as by the expression of K14, K1, loricrin, Cldn6, Cldn18 and Cldn11. In addition, we report for the first time the sequential expression of Cldns in epidermal development and describe that the localization of some Cldns change within the epidermis as it matures. Furthermore, we demonstrate that Cldn6 is expressed very early in epidermal morphogenesis, followed by Cldn18, Cldn11 and Cldn1.

Epidermal electronic systems for sensing and therapy

NASA Astrophysics Data System (ADS)

Lu, Nanshu; Ameri, Shideh K.; Ha, Taewoo; Nicolini, Luke; Stier, Andrew; Wang, Pulin

2017-04-01

Epidermal electronic system is a class of hair thin, skin soft, stretchable sensors and electronics capable of continuous and long-term physiological sensing and clinical therapy when applied on human skin. The high cost of manpower, materials, and photolithographic facilities associated with its manufacture limit the availability of disposable epidermal electronics. We have invented a cost and time effective, completely dry, benchtop "cut-and-paste" method for the green, freeform and portable manufacture of epidermal electronics within minutes. We have applied the "cut-and-paste" method to manufacture epidermal electrodes, hydration and temperature sensors, conformable power-efficient heaters, as well as cuffless continuous blood pressure monitors out of metal thin films, two-dimensional (2D) materials, and piezoelectric polymer sheets. For demonstration purpose, we will discuss three examples of "cut-and-pasted" epidermal electronic systems in this paper. The first will be submicron thick, transparent epidermal graphene electrodes that can be directly transferred to human skin like a temporary transfer tattoo and can measure electrocardiogram (ECG) with signal-to-noise ratio and motion artifacts on par with conventional gel electrodes. The second will be a chest patch which houses both electrodes and pressure sensors for the synchronous measurements of ECG and seismocardiogram (SCG) such that beat-to-beat blood pressure can be inferred from the time interval between the R peak of the ECG and the AC peak of the SCG. The last example will be a highly conformable, low power consumption epidermal heater for thermal therapy.

Transcriptional switch of dormant tumors to fast-growing angiogenic phenotype.

PubMed

Almog, Nava; Ma, Lili; Raychowdhury, Raktima; Schwager, Christian; Erber, Ralf; Short, Sarah; Hlatky, Lynn; Vajkoczy, Peter; Huber, Peter E; Folkman, Judah; Abdollahi, Amir

2009-02-01

Tumor dormancy has important implications for early detection and treatment of cancer. Lack of experimental models and limited clinical accessibility constitute major obstacles to the molecular characterization of dormant tumors. We have developed models in which human tumors remain dormant for a prolonged period of time (>120 days) until they switch to rapid growth and become strongly angiogenic. These angiogenic tumors retain their ability to grow fast once injected in new mice. We hypothesized that dormant tumors undergo a stable genetic reprogramming during their switch to the fast-growing phenotype. Genome-wide transcriptional analysis was done to dissect the molecular mechanisms underlying the switch of dormant breast carcinoma, glioblastoma, osteosarcoma, and liposarcoma tumors. A consensus expression signature distinguishing all four dormant versus switched fast-growing tumors was generated. In alignment with our phenotypic observation, the angiogenesis process was the most significantly affected functional gene category. The switch of dormant tumors was associated with down-regulation of angiogenesis inhibitor thrombospondin and decreased sensitivity of angiogenic tumors to angiostatin. The conversion of dormant tumors to exponentially growing tumors was also correlated with regulation and activation of pathways not hitherto linked to tumor dormancy process, such as endothelial cell-specific molecule-1, 5'-ecto-nucleotidase, tissue inhibitor of metalloproteinase-3, epidermal growth factor receptor, insulin-like growth factor receptor, and phosphatidylinositol 3-kinase signaling. Further, novel dormancy-specific biomarkers such as H2BK and Eph receptor A5 (EphA5) were discovered. EphA5 plasma levels in mice and mRNA levels in tumor specimens of glioma patients correlated with diseases stage. These data will be instrumental in identifying novel early cancer biomarkers and could provide a rationale for development of dormancy-promoting tumor therapy strategies.

Replenishable food supply on Mars

NASA Technical Reports Server (NTRS)

1990-01-01

The design team's present objective is to design a facility which will provide an environment to grow plants on the surface of Mars for a continuous supply of food for a ten-man crew. The main focus of the project is the design of a greenhouse. Concentration of the current design effort is on the outer structure, internal layout, and construction methods. The project was conducted by undergraduate students at Prairie View A&M University during Fall 1989 and Spring 1990.

Cross-immunoreactivity between the LH1 antibody and cytokeratin epitopes in the differentiating epidermis of embryos of the grass snake Natrix natrix L. during the end stages of embryogenesis.

PubMed

Swadźba, Elwira; Rupik, Weronika

2012-01-01

The monoclonal anti-cytokeratin 1/10 (LH1) antibody recognizing K1/K10 keratin epitopes that characterizes a keratinized epidermis of mammals cross-reacts with the beta and Oberhäutchen layers covering the scales and gastrosteges of grass snake embryos during the final period of epidermis differentiation. The immunolocalization of the anti-cytokeratin 1/10 (LH1) antibody appears in the beta layer of the epidermis, covering the outer surface of the gastrosteges at the beginning of developmental stage XI, and in the beta layer of the epidermis, covering the outer surface of the scales at the end of developmental stage XI. This antibody cross-reacts with the Oberhäutchen layers in the epidermis covering the outer surface of both scales and gastrosteges at developmental stages XI and XII just before its fusion with the beta layers. After fusion of the Oberhäutchen and beta layers, LH1 immunolabeling is weaker than before. This might suggest that alpha-keratins in these layers of the epidermis are masked by beta-keratins, modified, or degraded. The anti-cytokeratin 1/10 (LH1) antibody stains the Oberhäutchen layer in the epidermis covering the inner surface of the gastrosteges and the hinge regions between gastrosteges at the end of developmental stage XI. However, the Oberhäutchen of the epidermis covering the inner surfaces of the scales and the hinge regions between scales does not show cytokeratin 1/10 (LH1) immunolabeling until hatching. This cross-reactivity suggests that the beta and Oberhäutchen layers probably contain some alpha-keratins that react with the LH1 antibody. It is possible that these alpha-keratins create specific scaffolding for the latest beta-keratin deposition. It is also possible that the LH1 antibody cross-reacts with other epidermal proteins such as filament-associated proteins, i.e., filaggrin-like. The anti-cytokeratin 1/10 (LH1) antibody does not stain the alpha and mesos layers until hatching. We suppose that the differentiation of these layers will begin just after the first postnatal sloughing.

Elemental analysis of tissue pellets for the differentiation of epidermal lesion and normal skin by laser-induced breakdown spectroscopy

PubMed Central

Moon, Youngmin; Han, Jung Hyun; Shin, Sungho; Kim, Yong-Chul; Jeong, Sungho

2016-01-01

By laser induced breakdown spectroscopy (LIBS) analysis of epidermal lesion and dermis tissue pellets of hairless mouse, it is shown that Ca intensity in the epidermal lesion is higher than that in dermis, whereas Na and K intensities have an opposite tendency. It is demonstrated that epidermal lesion and normal dermis can be differentiated with high selectivity either by univariate or multivariate analysis of LIBS spectra with an intensity ratio difference by factor of 8 or classification accuracy over 0.995, respectively. PMID:27231610

Toxic epidermal necrolysis: a paradigm of critical illness

PubMed Central

Estrella-Alonso, Alfonso; Aramburu, José Antonio; González-Ruiz, Mercedes Yolanda; Cachafeiro, Lucía; Sánchez, Manuel Sánchez; Lorente, José A.

2017-01-01

Toxic epidermal necrolysis is an adverse immunological skin reaction secondary in most cases to the administration of a drug. Toxic epidermal necrolysis, Stevens-Johnson syndrome, and multiform exudative erythema are part of the same disease spectrum. The mortality rate from toxic epidermal necrolysis is approximately 30%. The pathophysiology of toxic epidermal necrolysis is similar in many respects to that of superficial skin burns. Mucosal involvement of the ocular and genital epithelium is associated with serious sequelae if the condition is not treated early. It is generally accepted that patients with toxic epidermal necrolysis are better treated in burn units, which are experienced in the management of patients with extensive skin loss. Treatment includes support, elimination, and coverage with biosynthetic derivatives of the skin in affected areas, treatment of mucosal involvement, and specific immunosuppressive treatment. Of the treatments tested, only immunoglobulin G and cyclosporin A are currently used in most centers, even though there is no solid evidence to recommend any specific treatment. The particular aspects of the treatment of this disease include the prevention of sequelae related to the formation of synechiae, eye care to prevent serious sequelae that can lead to blindness, and specific immunosuppressive treatment. Better knowledge of the management principles of toxic epidermal necrolysis will lead to better disease management, higher survival rates, and lower prevalence of sequelae. PMID:29340540

JACKDAW controls epidermal patterning in the Arabidopsis root meristem through a non-cell-autonomous mechanism.

PubMed

Hassan, Hala; Scheres, Ben; Blilou, Ikram

2010-05-01

In Arabidopsis, specification of the hair and non-hair epidermal cell types is position dependent, in that hair cells arise over clefts in the underlying cortical cell layer. Epidermal patterning is determined by a network of transcriptional regulators that respond to an as yet unknown cue from underlying tissues. Previously, we showed that JACKDAW (JKD), a zinc finger protein, localizes in the quiescent centre and the ground tissue, and regulates tissue boundaries and asymmetric cell division by delimiting SHORT-ROOT movement. Here, we provide evidence that JKD controls position-dependent signals that regulate epidermal-cell-type patterning. JKD is required for appropriately patterned expression of the epidermal cell fate regulators GLABRA2, CAPRICE and WEREWOLF. Genetic interaction studies indicate that JKD operates upstream of the epidermal patterning network in a SCRAMBLED (SCM)-dependent fashion after embryogenesis, but acts independent of SCM in embryogenesis. Tissue-specific induction experiments indicate non-cell-autonomous action of JKD from the underlying cortex cell layer to specify epidermal cell fate. Our findings are consistent with a model where JKD induces a signal in every cortex cell that is more abundant in the hair cell position owing to the larger surface contact of cells located over a cleft.

Relationship between Endopolyploidy and Cell Size in Epidermal Tissue of Arabidopsis.

PubMed Central

Melaragno, JE; Mehrotra, B; Coleman, AW

1993-01-01

Relative quantities of DNA in individual nuclei of stem and leaf epidermal cells of Arabidopsis were measured microspectrofluorometrically using epidermal peels. The relative ploidy level in each nucleus was assessed by comparison to root tip mitotic nuclei. A clear pattern of regular endopolyploidy is evident in epidermal cells. Guard cell nuclei contain levels of DNA comparable to dividing root cells, the 2C level (i.e., one unreplicated copy of the nuclear DNA). Leaf trichome nuclei had elevated ploidy levels of 4C, 8C, 16C, 32C, and 64C, and their cytology suggested that the polyploidy represents a form of polyteny. The nuclei of epidermal pavement cells were 2C, 4C, and 8C in stem epidermis, and 2C, 4C, 8C, and 16C in leaf epidermis. Morphometry of epidermal pavement cells revealed a direct proportionality between nuclear DNA level and cell size. A consideration of the development process suggests that the cells of highest ploidy level are developmentally oldest; consequently, the developmental pattern of epidermal tissues can be read from the ploidy pattern of the cells. This observation is relevant to theories of stomate spacing and offers opportunities for genetic analysis of the endopolyploidy/polyteny phenomenon. PMID:12271050

Peeling off the genetics of atopic dermatitis-like congenital disorders.

PubMed

Samuelov, Liat; Sprecher, Eli

2014-10-01

The epidermis forms during the course of a complex differentiation process known as cornification, which culminates with the formation of the epidermal barrier. The epidermal barrier serves as a vital line of defense against the environment and mainly consists of 3 elements: intracellular keratin filaments, intercellular lipids, and the cornified cell envelope. Adequate epidermal barrier function is also critically dependent on normal shedding of terminally differentiated keratinocytes, a process termed desquamation, which requires the dissolution of cell-cell junctions in the upper granular layers. Although much has been learned about epidermal differentiation through the deciphering of the molecular basis of various cornification disorders, less is currently known about the mechanisms regulating epidermal desquamation and disorders resulting from disruption of this process. Netherton syndrome, peeling skin syndrome type B, and skin dermatitis--multiple severe allergies--metabolic wasting syndrome are 3 autosomal recessive conditions resulting from aberrant regulation of epidermal desquamation. The deciphering of their pathogenesis has not only broadened our understanding of this process but has also shed new light on clinical and mechanistic links between allergic reactions and abnormal desquamation, substantiating the notion that allergic manifestations might, under some circumstances, be the sole consequence of a primary epidermal defect. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Use of a novel epidermal harvesting system in resource-poor countries.

PubMed

Serena, Thomas; Francius, Adler; Taylor, Cristin; MacDonald, John

2015-03-01

The 2010 earthquake in Port-au-Prince, Haiti, highlighted the need for wound care in resource-poor countries. Subsequently, the University of Miami in Florida established one of the first interprofessional wound care centers located at Bernard Mevs Hospital in the central portion of Port-au-Prince, caring for patients with acute and chronic wounds. In 2012, the authors used a novel epidermal harvesting system (CelluTome Epidermal Harvesting System; Kinetic Concepts Inc, San Antonio, Texas) to harvest epithelium to be grafted on 7 patients at the Mevs Hospital with longstanding wounds. Epidermal microblisters were obtained from each patient's thigh using the CelluTome Epidermal Harvesting System. After 35 minutes, microblisters were raised using the device harvester, and an adhesive dressing was inserted into the harvester for transfer to the wound site. In patients with lower-extremity wounds, a 2-layer compression dressing was placed over epidermal grafts. Six of the 7 wounds improved or achieved complete closure in 4 weeks. One of the patients with a 2-year-old thigh wound failed to demonstrate improvement; this may have been secondary to an inability to adequately secure the graft. All donor sites healed without any visible scarring. The authors were able to conclude that epidermal grafting may represent a viable reconstructive option for patients in resource-poor countries.

Real-time three-dimensional imaging of epidermal splitting and removal by high-definition optical coherence tomography.

PubMed

Boone, Marc; Draye, Jean Pierre; Verween, Gunther; Pirnay, Jean-Paul; Verbeken, Gilbert; De Vos, Daniel; Rose, Thomas; Jennes, Serge; Jemec, Gregor B E; Del Marmol, Véronique

2014-10-01

While real-time 3-D evaluation of human skin constructs is needed, only 2-D non-invasive imaging techniques are available. The aim of this paper is to evaluate the potential of high-definition optical coherence tomography (HD-OCT) for real-time 3-D assessment of the epidermal splitting and decellularization. Human skin samples were incubated with four different agents: Dispase II, NaCl 1 M, sodium dodecyl sulphate (SDS) and Triton X-100. Epidermal splitting, dermo-epidermal junction, acellularity and 3-D architecture of dermal matrices were evaluated by High-definition optical coherence tomography before and after incubation. Real-time 3-D HD-OCT assessment was compared with 2-D en face assessment by reflectance confocal microscopy (RCM). (Immuno) histopathology was used as control. HD-OCT imaging allowed real-time 3-D visualization of the impact of selected agents on epidermal splitting, dermo-epidermal junction, dermal architecture, vascular spaces and cellularity. RCM has a better resolution (1 μm) than HD-OCT (3 μm), permitting differentiation of different collagen fibres, but HD-OCT imaging has deeper penetration (570 μm) than RCM imaging (200 μm). Dispase II and NaCl treatments were found to be equally efficient in the removal of the epidermis from human split-thickness skin allografts. However, a different epidermal splitting level at the dermo-epidermal junction could be observed and confirmed by immunolabelling of collagen type IV and type VII. Epidermal splitting occurred at the level of the lamina densa with dispase II and above the lamina densa (in the lamina lucida) with NaCl. The 3-D architecture of dermal papillae and dermis was more affected by Dispase II on HD-OCT which corresponded with histopathologic (orcein staining) fragmentation of elastic fibres. With SDS treatment, the epidermal removal was incomplete as remnants of the epidermal basal cell layer remained attached to the basement membrane on the dermis. With Triton X-100 treatment, the epidermis was not removed. In conclusion, HD-OCT imaging permits real-time 3-D visualization of the impact of selected agents on human skin allografts. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Assessing the value of silicone and hydrocolloid products in stoma care.

PubMed

Berry, Jeanette; Black, Pat; Smith, Rory; Stuchfield, Barbara

Intact skin among many other functions provides a protective barrier between the body and its environment, which is critical in regulating transepidermal water loss (Wilkinson and Moor, 1982). The frequent application and removal of adhesives can damage skin by stripping away the outer epidermal layers. Older people, very young children and those with an underlying skin disorder may be particularly at risk (Gibelli et al, 1999; Lyons and Smith, 2003). Hydrocolloid adhesives, which hold moisture in the adhesive mass, are more skin friendly than the acrylic adhesives they now replace and have now become the material of choice for ostomy flanges and flange extenders (Smith et al, 2007). To understand stoma care nurses' awareness of the value of technologically advanced silicone and hydrocolloid products, the authors undertook a nationwide postal survey. The survey, commissioned by four companies in the United Kingdom, who make silicone and hydrocolloid products that can be used in stoma care, were keen to evaluate the awareness of these products to confirm their importance to the patient and why they should be appropriately categorized for reimbursement by the Department of Health.

Influence of DMPS on the water retention capacity of electroporated stratum corneum: ATR-FTIR study.

PubMed

Sckolnick, Maria; Hui, Sek-Wen; Sen, Arindam

2008-02-28

Anionic lipids like phosphatidylserine are known to significantly enhance electroporation mediated transepidermal transport of polar solutes of molecular weights up to 10kDa. The underlying mechanism of the effect of anionic lipids on transdermal transport is not fully understood. The main barrier to transdermal transport lies within the intercellular lipid matrix (ILM) of the stratum corneum (SC) and our previous studies indicate that dimyristoyl phosphatidylserine (DMPS) can perturb the packing of this lipid matrix. Here we report on our investigation on water retention in the SC following electroporation in the presence and the absence of DMPS. The water content in the outer most layers of the SC of full thickness porcine skin was determined using ATR-FTIR-spectroscopy. The results show that in the presence of DMPS, the SC remains in a state of enhanced hydration for longer periods after electroporation. This increase in water retention in the SC by DMPS is likely to play an important role in trans-epidermal transport, since improved hydration of the skin barrier can be expected to increase the partitioning of polar solutes and possibly the permeability.

A laser syringe aimed at delivering drug into the outer layer of human skin

NASA Astrophysics Data System (ADS)

Yoh, Jack J.; Jang, Hun-jae; Park, Mi-ae; Han, Tae-hee; Hah, Jung-moo

2012-07-01

A desire to eliminate hypodermic needle in transdermal drug delivery may now be realized. Imaging of the skin after injection of fluorescent probe and biotin via the bio-ballistic technique revealed the epidermal and dermal layers which were stained well below 60 μm underneath the abdominal skin of the guinea-pig. An extensive network of cells are shown in the deeper layer of the stained dermis as the distributed fluorescein isothiocyanate (FITC) dose is administered by repeated injection via the laser-based microjet. Here, we show our method of laser-based microjet drug delivery is capable of breaching guinea-pig's skin tissue and then delivering controlled dose of drug to the targeted region between 10 to 400 μm underneath the outermost layer of the skin. While minimizing pain and tissue damage by reducing the injection volume to ˜100 nl per pulse and the microjet diameter of half the conventional syringe needle in 100 μm, the optimally controlled delivery of liquid drug by the irradiated laser pulse is shown possible.

The Roles of Vitamin C in Skin Health.

PubMed

Pullar, Juliet M; Carr, Anitra C; Vissers, Margreet C M

2017-08-12

The primary function of the skin is to act as a barrier against insults from the environment, and its unique structure reflects this. The skin is composed of two layers: the epidermal outer layer is highly cellular and provides the barrier function, and the inner dermal layer ensures strength and elasticity and gives nutritional support to the epidermis. Normal skin contains high concentrations of vitamin C, which supports important and well-known functions, stimulating collagen synthesis and assisting in antioxidant protection against UV-induced photodamage. This knowledge is often used as a rationale for the addition of vitamin C to topical applications, but the efficacy of such treatment, as opposed to optimising dietary vitamin C intake, is poorly understood. This review discusses the potential roles for vitamin C in skin health and summarises the in vitro and in vivo research to date. We compare the efficacy of nutritional intake of vitamin C versus topical application, identify the areas where lack of evidence limits our understanding of the potential benefits of vitamin C on skin health, and suggest which skin properties are most likely to benefit from improved nutritional vitamin C intake.

Analysis of Effluent Gases During the CCVD Growth of Multi Wall Carbon Nanotubes from Acetylene

NASA Technical Reports Server (NTRS)

Schmitt, T. C.; Biris, A. S.; Miller, D. W.; Biris, A. R.; Lupu, D.; Trigwell, S.; Rahman, Z. U.

2005-01-01

Catalytic chemical vapor deposition was used to grow multi-walled carbon nanotubes on a Fe:Co:CaCO3 catalyst from acetylene. The influent and effluent gases were analyzed by gas chromatography and mass spectrometry at different time intervals during the nanotubes growth process in order to better understand and optimize the overall reaction. A large number of byproducts were identified and it was found that the number and the level for some of the carbon byproducts significantly increased over time. The CaCO3 catalytic support thermally decomposed into CaO and CO2 resulting in a mixture of two catalysts for growing the nanotubes, which were found to have outer diameters belonging to two main groups 8 to 35 nm and 40 to 60 nm, respectively.

Genomic determinants of epidermal appendage patterning and structure in domestic birds.

PubMed

Boer, Elena F; Van Hollebeke, Hannah F; Shapiro, Michael D

2017-09-15

Variation in regional identity, patterning, and structure of epidermal appendages contributes to skin diversity among many vertebrate groups, and is perhaps most striking in birds. In pioneering work on epidermal appendage patterning, John Saunders and his contemporaries took advantage of epidermal appendage diversity within and among domestic chicken breeds to establish the importance of mesoderm-ectoderm signaling in determining skin patterning. Diversity in chickens and other domestic birds, including pigeons, is driving a new wave of research to dissect the molecular genetic basis of epidermal appendage patterning. Domestic birds are not only outstanding models for embryonic manipulations, as Saunders recognized, but they are also ideal genetic models for discovering the specific genes that control normal development and the mutations that contribute to skin diversity. Here, we review recent genetic and genomic approaches to uncover the basis of epidermal macropatterning, micropatterning, and structural variation. We also present new results that confirm expression changes in two limb identity genes in feather-footed pigeons, a case of variation in appendage structure and identity. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

A STUDY OF THE COMPONENTS OF THE CORNIFIED EPITHELIUM OF HUMAN SKIN

PubMed Central

Matoltsy, A. Gedeon; Balsamo, Constance A.

1955-01-01

Pulverized cornified epithelium of human skin was divided into a "soluble fraction" and a "residue." About half of the "soluble fraction" proved to be soluble epidermal keratin (keratin A); the remainder, dialyzable substances of low molecular weight. The "residue" contained epidermal keratin and resistant cell membranes of cornified cells. Epidermal keratin was found to form an oriented and dense submicroscopic structure in the cornified cells. It showed high resistance toward strong acid and moderately strong alkali solutions as well as concentrated urea. In strong alkali, reducing substances, alkaline urea, and mixtures of reducing substance with alkali, epidermal keratin dissociated and yielded a non-dialyzable derivative of high molecular weight (keratin B) which resembled true proteins. The cell membranes of cornified cells showed higher resistance toward strong alkali and reducing substance than did epidermal keratin. PMID:13242598

Duox, Flotillin-2, and Src42A Are Required to Activate or Delimit the Spread of the Transcriptional Response to Epidermal Wounds in Drosophila

PubMed Central

Juarez, Michelle T.; Patterson, Rachel A.; Sandoval-Guillen, Efren; McGinnis, William

2011-01-01

The epidermis is the largest organ of the body for most animals, and the first line of defense against invading pathogens. A breach in the epidermal cell layer triggers a variety of localized responses that in favorable circumstances result in the repair of the wound. Many cellular and genetic responses must be limited to epidermal cells that are close to wounds, but how this is regulated is still poorly understood. The order and hierarchy of epidermal wound signaling factors are also still obscure. The Drosophila embryonic epidermis provides an excellent system to study genes that regulate wound healing processes. We have developed a variety of fluorescent reporters that provide a visible readout of wound-dependent transcriptional activation near epidermal wound sites. A large screen for mutants that alter the activity of these wound reporters has identified seven new genes required to activate or delimit wound-induced transcriptional responses to a narrow zone of cells surrounding wound sites. Among the genes required to delimit the spread of wound responses are Drosophila Flotillin-2 and Src42A, both of which are transcriptionally activated around wound sites. Flotillin-2 and constitutively active Src42A are also sufficient, when overexpressed at high levels, to inhibit wound-induced transcription in epidermal cells. One gene required to activate epidermal wound reporters encodes Dual oxidase, an enzyme that produces hydrogen peroxide. We also find that four biochemical treatments (a serine protease, a Src kinase inhibitor, methyl-ß-cyclodextrin, and hydrogen peroxide) are sufficient to globally activate epidermal wound response genes in Drosophila embryos. We explore the epistatic relationships among the factors that induce or delimit the spread of epidermal wound signals. Our results define new genetic functions that interact to instruct only a limited number of cells around puncture wounds to mount a transcriptional response, mediating local repair and regeneration. PMID:22242003

A Mixture of Extracts of Kochia scoparia and Rosa multiflora with PPAR α/γ Dual Agonistic Effects Prevents Photoaging in Hairless Mice

PubMed Central

Jeon, Hyerin; Kim, Dong Hye; Nho, Youn-Hwa; Park, Ji-Eun; Kim, Su-Nam; Choi, Eung Ho

2016-01-01

Activation of peroxisome proliferator-activated receptors (PPAR) α/γ is known to inhibit the increases in matrix metalloproteinase (MMP) and reactive oxygen species (ROS) induced by ultraviolet light (UV). Extracts of natural herbs, such as Kochia scoparia and Rosa multiflora, have a PPAR α/γ dual agonistic effect. Therefore, we investigated whether and how they have an antiaging effect on photoaging skin. Eighteen-week-old hairless mice were irradiated with UVA 14 J/cm2 and UVB 40 mJ/cm2 three times a week for 8 weeks. A mixture of extracts of Kochia scoparia and Rosa multiflora (KR) was topically applied on the dorsal skin of photoaging mice twice a day for 8 weeks. Tesaglitazar, a known PPAR α/γ agonist, and vehicle (propylene glycol:ethanol = 7:3, v/v) were applied as positive and negative controls, respectively. Dermal effects (including dermal thickness, collagen density, dermal expression of procollagen 1 and collagenase 13) and epidermal effects (including skin barrier function, epidermal proliferation, epidermal differentiation, and epidermal cytokines) were measured and compared. In photoaging murine skin, KR resulted in a significant recovery of dermal thickness as well as dermal fibroblasts, although it did not change dermal collagen density. KR increased the expression of dermal transforming growth factor (TGF)-β. The dermal effects of KR were explained by an increase in procollagen 1 expression, induced by TGF-β, and a decrease in MMP-13 expression. KR did not affect basal transepidermal water loss (TEWL) or stratum corneum (SC) integrity, but did decrease SC hydration. It also did not affect epidermal proliferation or epidermal differentiation. KR decreased the expression of epidermal interleukin (IL)-1α. Collectively, KR showed possible utility as a therapeutic agent for photoaging skin, with few epidermal side effects such as epidermal hyperplasia or poor differentiation. PMID:27854351

A Mixture of Extracts of Kochia scoparia and Rosa multiflora with PPAR α/γ Dual Agonistic Effects Prevents Photoaging in Hairless Mice.

PubMed

Jeon, Hyerin; Kim, Dong Hye; Nho, Youn-Hwa; Park, Ji-Eun; Kim, Su-Nam; Choi, Eung Ho

2016-11-16

Activation of peroxisome proliferator-activated receptors (PPAR) α/γ is known to inhibit the increases in matrix metalloproteinase (MMP) and reactive oxygen species (ROS) induced by ultraviolet light (UV). Extracts of natural herbs, such as Kochia scoparia and Rosa multiflora , have a PPAR α/γ dual agonistic effect. Therefore, we investigated whether and how they have an antiaging effect on photoaging skin. Eighteen-week-old hairless mice were irradiated with UVA 14 J/cm² and UVB 40 mJ/cm² three times a week for 8 weeks. A mixture of extracts of Kochia scoparia and Rosa multiflora (KR) was topically applied on the dorsal skin of photoaging mice twice a day for 8 weeks. Tesaglitazar, a known PPAR α/γ agonist, and vehicle (propylene glycol:ethanol = 7:3, v / v ) were applied as positive and negative controls, respectively. Dermal effects (including dermal thickness, collagen density, dermal expression of procollagen 1 and collagenase 13) and epidermal effects (including skin barrier function, epidermal proliferation, epidermal differentiation, and epidermal cytokines) were measured and compared. In photoaging murine skin, KR resulted in a significant recovery of dermal thickness as well as dermal fibroblasts, although it did not change dermal collagen density. KR increased the expression of dermal transforming growth factor (TGF)-β. The dermal effects of KR were explained by an increase in procollagen 1 expression, induced by TGF-β, and a decrease in MMP-13 expression. KR did not affect basal transepidermal water loss (TEWL) or stratum corneum (SC) integrity, but did decrease SC hydration. It also did not affect epidermal proliferation or epidermal differentiation. KR decreased the expression of epidermal interleukin (IL)-1α. Collectively, KR showed possible utility as a therapeutic agent for photoaging skin, with few epidermal side effects such as epidermal hyperplasia or poor differentiation.

Oral mucosa: an alternative epidermic cell source to develop autologous dermal-epidermal substitutes from diabetic subjects

PubMed Central

GUZMÁN-URIBE, Daniela; ALVARADO-ESTRADA, Keila Neri; PIERDANT-PÉREZ, Mauricio; TORRES-ÁLVAREZ, Bertha; SÁNCHEZ-AGUILAR, Jesus Martin; ROSALES-IBÁÑEZ, Raúl

2017-01-01

Abstract Oral mucosa has been highlighted as a suitable source of epidermal cells due to its intrinsic characteristics such as its higher proliferation rate and its obtainability. Diabetic ulcers have a worldwide prevalence that is variable (1%-11%), meanwhile treatment of this has been proven ineffective. Tissue-engineered skin plays an important role in wound care focusing on strategies such autologous dermal-epidermal substitutes. Objective The aim of this study was to obtain autologous dermal-epidermal skin substitutes from oral mucosa from diabetic subjects as a first step towards a possible clinical application for cases of diabetic foot. Material and Methods Oral mucosa was obtained from diabetic and healthy subjects (n=20 per group). Epidermal cells were isolated and cultured using autologous fibrin to develop dermal-epidermal in vitro substitutes by the air-liquid technique with autologous human serum as a supplement media. Substitutes were immunocharacterized with collagen IV and cytokeratin 5-14 as specific markers. A Student´s t- test was performed to assess the differences between both groups. Results It was possible to isolate epidermal cells from the oral mucosa of diabetic and healthy subjects and develop autologous dermal-epidermal skin substitutes using autologous serum as a supplement. Differences in the expression of specific markers were observed and the cytokeratin 5-14 expression was lower in the diabetic substitutes, and the collagen IV expression was higher in the diabetic substitutes when compared with the healthy group, showing a significant difference. Conclusion Cells from oral mucosa could be an alternative and less invasive source for skin substitutes and wound healing. A difference in collagen production of diabetic cells suggests diabetic substitutes could improve diabetic wound healing. More research is needed to determine the crosstalk between components of these skin substitutes and damaged tissues. PMID:28403359

Toxic epidermal necrolysis successfully treated with etanercept.

PubMed

Gubinelli, Emanuela; Canzona, Flora; Tonanzi, Tiziano; Raskovic, Desanka; Didona, Biagio

2009-03-01

Toxic epidermal necrolysis (TEN) is a rare and acute severe adverse reaction to drugs, characterised by massive apoptosis and widespread epidermal and mucosal detachment. Although no gold standard therapy exists, human i.v. immunoglobulins have recently been described as an effective treatment for this disease. We report a case of phenobarbital-induced TEN in a 59-year-old white woman where the epidermal detachment stopped 48 h after beginning the etanercept treatment with complete healing after 20 days. To the best of our knowledge, this is only the second reported case of TEN successfully treated with etanercept.

A case of epidermal cyst with pilomatrical differentiation.

PubMed

Ikoma, Norihiro; Iwashita, Kenichi; Umezawa, Yoshinori; Matsuyama, Takashi; Ohta, Yukinori; Ozawa, Akira; Umemura, Shinobu; Ueyama, Yoshito; Yamazaki, Hitoshi

2004-09-01

A 20-year-old Japanese woman with an epidermal cyst on the back is described. Physical examination revealed a deep blue and round shaped cystic lesion measuring 10 min in diameter. A comedo-like keratotic plug also could be seen at the center. Histologically, the inner surface of the cyst was clearly separated of two types of the cells. The one was layers of epidermal keratinocytes and the other looked like a basal layer of epidermis, which immunohistochemically stained by S-100, HMB-45, cytokeratin (CK19) and Fontana-Masson staining. We diagnosed this case as epidermal cyst with pilomatrical differentiation.

Spatial organization of cellulose microfibrils and matrix polysaccharides in primary plant cell walls as imaged by multichannel atomic force microscopy.

PubMed

Zhang, Tian; Zheng, Yunzhen; Cosgrove, Daniel J

2016-01-01

We used atomic force microscopy (AFM), complemented with electron microscopy, to characterize the nanoscale and mesoscale structure of the outer (periclinal) cell wall of onion scale epidermis - a model system for relating wall structure to cell wall mechanics. The epidermal wall contains ~100 lamellae, each ~40 nm thick, containing 3.5-nm wide cellulose microfibrils oriented in a common direction within a lamella but varying by ~30 to 90° between adjacent lamellae. The wall thus has a crossed polylamellate, not helicoidal, wall structure. Montages of high-resolution AFM images of the newly deposited wall surface showed that single microfibrils merge into and out of short regions of microfibril bundles, thereby forming a reticulated network. Microfibril direction within a lamella did not change gradually or abruptly across the whole face of the cell, indicating continuity of the lamella across the outer wall. A layer of pectin at the wall surface obscured the underlying cellulose microfibrils when imaged by FESEM, but not by AFM. The AFM thus preferentially detects cellulose microfibrils by probing through the soft matrix in these hydrated walls. AFM-based nanomechanical maps revealed significant heterogeneity in cell wall stiffness and adhesiveness at the nm scale. By color coding and merging these maps, the spatial distribution of soft and rigid matrix polymers could be visualized in the context of the stiffer microfibrils. Without chemical extraction and dehydration, our results provide multiscale structural details of the primary cell wall in its near-native state, with implications for microfibrils motions in different lamellae during uniaxial and biaxial extensions. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

Epidermal differentiation in embryos of the tuatara Sphenodon punctatus (Reptilia, Sphenodontidae) in comparison with the epidermis of other reptiles.

PubMed

Alibardi, L; Gill, B J

2007-07-01

Studying the epidermis in primitive reptiles can provide clues regarding evolution of the epidermis during land adaptation in vertebrates. With this aim, the development of the skin of the relatively primitive reptile Sphenodon punctatus in representative embryonic stages was studied by light and electron microscopy and compared with that of other reptiles previously studied. The dermis organizes into a superficial and deep portion when the epidermis starts to form the first layers. At embryonic stages comparable with those of lizards, only one layer of the inner periderm is formed beneath the outer periderm. This also occurs in lizards and snakes so far studied. The outer and inner periderm form the embryonic epidermis and accumulate thick, coarse filaments (25-30 nm thick) and sparse alpha-keratin filaments as in other reptiles. Beneath the embryonic epidermis an oberhautchen and beta-cells form small horny tips that represent overlapping borders along the margin of beta-cells that overlap other beta-cells (in a tile-like arrangement). The tips resemble those of agamine lizards but at a small scale, forming a lamellate-spinulated pattern as previously described in adult epidermis. The embryonic epidermis matures by the dispersion of coarse filaments among keratin at the end of embryonic development and is shed around hatching. The presence of these matrix organelles in the embryonic epidermis of this primitive reptile further indicates that amniote epidermis acquired interkeratin matrix proteins early for land adaptation. Unlike the condition in lizards and snakes, a shedding complex is not formed in the epidermis of embryonic S. punctatus that is like that of the adult. Therefore, as in chelonians and crocodilians, the epidermis of S. punctatus also represents an initial stage that preceded the evolution of the shedding complex for moulting.

Epidermal differentiation in embryos of the tuatara Sphenodon punctatus (Reptilia, Sphenodontidae) in comparison with the epidermis of other reptiles

PubMed Central

Alibardi, L; Gill, B J

2007-01-01

Studying the epidermis in primitive reptiles can provide clues regarding evolution of the epidermis during land adaptation in vertebrates. With this aim, the development of the skin of the relatively primitive reptile Sphenodon punctatus in representative embryonic stages was studied by light and electron microscopy and compared with that of other reptiles previously studied. The dermis organizes into a superficial and deep portion when the epidermis starts to form the first layers. At embryonic stages comparable with those of lizards, only one layer of the inner periderm is formed beneath the outer periderm. This also occurs in lizards and snakes so far studied. The outer and inner periderm form the embryonic epidermis and accumulate thick, coarse filaments (25–30 nm thick) and sparse alpha-keratin filaments as in other reptiles. Beneath the embryonic epidermis an oberhautchen and beta-cells form small horny tips that represent overlapping borders along the margin of beta-cells that overlap other beta-cells (in a tile-like arrangement). The tips resemble those of agamine lizards but at a small scale, forming a lamellate-spinulated pattern as previously described in adult epidermis. The embryonic epidermis matures by the dispersion of coarse filaments among keratin at the end of embryonic development and is shed around hatching. The presence of these matrix organelles in the embryonic epidermis of this primitive reptile further indicates that amniote epidermis acquired interkeratin matrix proteins early for land adaptation. Unlike the condition in lizards and snakes, a shedding complex is not formed in the epidermis of embryonic S. punctatus that is like that of the adult. Therefore, as in chelonians and crocodilians, the epidermis of S. punctatus also represents an initial stage that preceded the evolution of the shedding complex for moulting. PMID:17532799

α-Xylosidase plays essential roles in xyloglucan remodelling, maintenance of cell wall integrity, and seed germination in Arabidopsis thaliana

PubMed Central

Shigeyama, Takuma; Watanabe, Asuka; Tokuchi, Konatsu; Toh, Shigeo; Sakurai, Naoki; Shibuya, Naoto; Kawakami, Naoto

2016-01-01

Regulation and maintenance of cell wall physical properties are crucial for plant growth and environmental response. In the germination process, hypocotyl cell expansion and endosperm weakening are prerequisites for dicot seeds to complete germination. We have identified the Arabidopsis mutant thermoinhibition-resistant germination 1 (trg1), which has reduced seed dormancy and insensitivity to unfavourable conditions for germination owing to a loss-of-function mutation of TRG1/XYL1, which encodes an α-xylosidase. Compared to those of wild type, the elongating stem of trg1 showed significantly lower viscoelasticity, and the fruit epidermal cells were longitudinally shorter and horizontally enlarged. Actively growing tissues of trg1 over-accumulated free xyloglucan oligosaccharides (XGOs), and the seed cell wall had xyloglucan with a greatly reduced molecular weight. These observations suggest that XGOs reduce xyloglucan size by serving as an acceptor in transglycosylation and eventually enhancing cell wall loosening. TRG1/XYL1 gene expression was abundant in growing wild-type organs and tissues but relatively low in cells at most actively elongating part of the tissues, suggesting that α-xylosidase contributes to maintaining the mechanical integrity of the primary cell wall in the growing and pre-growing tissues. In germinating seeds of trg1, expression of genes encoding specific abscisic acid and gibberellin metabolism enzymes was altered in accordance with the aberrant germination phenotype. Thus, cell wall integrity could affect seed germination not only directly through the physical properties of the cell wall but also indirectly through the regulation of hormone gene expression. PMID:27605715

Extracellular Matrix as a Regulator of Epidermal Stem Cell Fate.

PubMed

Chermnykh, Elina; Kalabusheva, Ekaterina; Vorotelyak, Ekaterina

2018-03-27

Epidermal stem cells reside within the specific anatomic location, called niche, which is a microenvironment that interacts with stem cells to regulate their fate. Regulation of many important processes, including maintenance of stem cell quiescence, self-renewal, and homeostasis, as well as the regulation of division and differentiation, are common functions of the stem cell niche. As it was shown in multiple studies, extracellular matrix (ECM) contributes a lot to stem cell niches in various tissues, including that of skin. In epidermis, ECM is represented, primarily, by a highly specialized ECM structure, basement membrane (BM), which separates the epidermal and dermal compartments. Epidermal stem cells contact with BM, but when they lose the contact and migrate to the overlying layers, they undergo terminal differentiation. When considering all of these factors, ECM is of fundamental importance in regulating epidermal stem cells maintenance, proper mobilization, and differentiation. Here, we summarize the remarkable progress that has recently been made in the research of ECM role in regulating epidermal stem cell fate, paying special attention to the hair follicle stem cell niche. We show that the destruction of ECM components impairs epidermal stem cell morphogenesis and homeostasis. A deep understanding of ECM molecular structure as well as the development of in vitro system for stem cell maintaining by ECM proteins may bring us to developing new approaches for regenerative medicine.

Periostin contributes to epidermal hyperplasia in psoriasis common to atopic dermatitis

PubMed Central

Arima, Kazuhiko; Ohta, Shoichiro; Takagi, Atsushi; Shiraishi, Hiroshi; Masuoka, Miho; Ontsuka, Kanako; Suto, Hajime; Suzuki, Shoichi; Yamamoto, Ken-ichi; Ogawa, Masahiro; Simmons, Olga; Yamaguchi, Yukie; Toda, Shuji; Aihara, Michiko; Conway, Simon J.; Ikeda, Shigaku; Izuhara, Kenji

2016-01-01

Background Epidermal hyperplasia is a histological hallmark observed in both atopic dermatitis (AD) and psoriasis, although the clinical features and the underlying immunological disorders of these diseases are different. We previously showed that periostin, a matricellular protein, plays a critical role in epidermal hyperplasia in AD, using a mouse model and a 3-dimensional organotypic coculture system. In this study, we explore the hypothesis that periostin is involved in epidermal hyperplasia in psoriasis. Methods To examine expression of periostin in psoriasis patients, we performed immunohistochemical analysis on skin biopsies from six such patients. To investigate periostin’s role in the pathogenesis of psoriasis, we evaluated periostin-deficient mice in a psoriasis mouse model induced by topical treatment with imiquimod (IMQ). Results Periostin was substantially expressed in the dermis of all investigated psoriasis patients. Epidermal hyperplasia induced by IMQ treatment was impaired in periostin-deficient mice, along with decreased skin swelling. However, upon treatment with IMQ, periostin deficiency did not alter infiltration of inflammatory cells such as neutrophils; production of IL-17, –22, or –23; or induction/expansion of IL-17– and IL-22–producing group 3 innate lymphoid cells. Conclusions Periostin plays an important role during epidermal hyperplasia in IMQ-induced skin inflammation, independently of the IL-23–IL-17/IL-22 axis. Periostin appears to be a mediator for epidermal hyperplasia that is common to AD and psoriasis. PMID:25572557

Epidermal ADAM17 maintains the skin barrier by regulating EGFR ligand–dependent terminal keratinocyte differentiation

PubMed Central

Cobzaru, Cristina; Triantafyllopoulou, Antigoni; Löffek, Stefanie; Horiuchi, Keisuke; Threadgill, David W.; Kurz, Thomas; van Rooijen, Nico; Bruckner-Tuderman, Leena

2012-01-01

ADAM17 (a disintegrin and metalloproteinase 17) is ubiquitously expressed and cleaves membrane proteins, such as epidermal growth factor receptor (EGFR) ligands, l-selectin, and TNF, from the cell surface, thus regulating responses to tissue injury and inflammation. However, little is currently known about its role in skin homeostasis. We show that mice lacking ADAM17 in keratinocytes (A17ΔKC) have a normal epidermal barrier and skin architecture at birth but develop pronounced defects in epidermal barrier integrity soon after birth and develop chronic dermatitis as adults. The dysregulated expression of epidermal differentiation proteins becomes evident 2 d after birth, followed by reduced transglutaminase (TGM) activity, transepidermal water loss, up-regulation of the proinflammatory cytokine IL-36α, and inflammatory immune cell infiltration. Activation of the EGFR was strongly reduced in A17ΔKC skin, and topical treatment of A17ΔKC mice with recombinant TGF-α significantly improved TGM activity and decreased skin inflammation. Finally, we show that mice lacking the EGFR in keratinocytes (EgfrΔKC) closely resembled A17ΔKC mice. Collectively, these results identify a previously unappreciated critical role of the ADAM17–EGFR signaling axis in maintaining the homeostasis of the postnatal epidermal barrier and suggest that this pathway could represent a good target for treatment of epidermal barrier defects. PMID:22565824

Oral mucosa: an alternative epidermic cell source to develop autologous dermal-epidermal substitutes from diabetic subjects.

PubMed

Guzmán-Uribe, Daniela; Alvarado-Estrada, Keila Neri; Pierdant-Pérez, Mauricio; Torres-Álvarez, Bertha; Sánchez-Aguilar, Jesus Martin; Rosales-Ibáñez, Raúl

2017-01-01

The aim of this study was to obtain autologous dermal-epidermal skin substitutes from oral mucosa from diabetic subjects as a first step towards a possible clinical application for cases of diabetic foot. Oral mucosa was obtained from diabetic and healthy subjects (n=20 per group). Epidermal cells were isolated and cultured using autologous fibrin to develop dermal-epidermal in vitro substitutes by the air-liquid technique with autologous human serum as a supplement media. Substitutes were immunocharacterized with collagen IV and cytokeratin 5-14 as specific markers. A Student´s t- test was performed to assess the differences between both groups. It was possible to isolate epidermal cells from the oral mucosa of diabetic and healthy subjects and develop autologous dermal-epidermal skin substitutes using autologous serum as a supplement. Differences in the expression of specific markers were observed and the cytokeratin 5-14 expression was lower in the diabetic substitutes, and the collagen IV expression was higher in the diabetic substitutes when compared with the healthy group, showing a significant difference. Cells from oral mucosa could be an alternative and less invasive source for skin substitutes and wound healing. A difference in collagen production of diabetic cells suggests diabetic substitutes could improve diabetic wound healing. More research is needed to determine the crosstalk between components of these skin substitutes and damaged tissues.

Epidermal Dysfunction Leads to an Age-Associated Increase in Levels of Serum Inflammatory Cytokines.

PubMed

Hu, Lizhi; Mauro, Theodora M; Dang, Erle; Man, George; Zhang, Jing; Lee, Dale; Wang, Gang; Feingold, Kenneth R; Elias, Peter M; Man, Mao-Qiang

2017-06-01

Even though elderly populations lack visible or other clinical signs of inflammation, their serum cytokine and C-reactive protein levels typically are elevated. However, the origin of age-associated systemic inflammation is unknown. Our previous studies showed that abnormalities in epidermal function provoke cutaneous inflammation, and because intrinsically aged skin displays compromised permeability barrier homeostasis and reduced stratum corneum hydration, we hypothesized here that epidermal dysfunction could contribute to the elevations in serum cytokines in the elderly. Our results show first that acute disruption of the epidermal permeability barrier in young mice leads not only to a rapid increase in cutaneous cytokine mRNA expression but also an increase in serum cytokine levels. Second, cytokine levels in both the skin and serum increase in otherwise normal, aged mice (>12 months). Third, expression of tumor necrosis factor-α and amyloid A mRNA levels increased in the epidermis, but not in the liver, in parallel with a significant elevation in serum levels of cytokines. Fourth, disruption of the permeability barrier induced similar elevations in epidermal and serum cytokine levels in normal and athymic mice, suggesting that T cells play a negligible role in the elevations in cutaneous and serum inflammatory cytokines induced by epidermal dysfunction. Fifth, correction of epidermal function significantly reduced cytokine levels not only in the skin but also in the serum of aged mice. Together, these results indicate that the sustained abnormalities in epidermal function in chronologically aged skin contribute to the elevated serum levels of inflammatory cytokines, potentially predisposing the elderly to the subsequent development or exacerbation of chronic inflammatory disorders. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Epidermal and dermal integumentary structures of ankylosaurian dinosaurs.

PubMed

Arbour, Victoria M; Burns, Michael E; Bell, Phil R; Currie, Philip J

2014-01-01

Ankylosaurian dinosaurs are most notable for their abundant and morphologically diverse osteoderms, which would have given them a spiky appearance in life. Isolated osteoderms are relatively common and provide important information about the structure of the ankylosaur dermis, but fossilized impressions of the soft-tissue epidermis of ankylosaurs are rare. Nevertheless, well-preserved integument exists on several ankylosaur fossils that shows osteoderms were covered by a single epidermal scale, but one or many millimeter-sized ossicles may be present under polygonal, basement epidermal scales. Evidence for the taxonomic utility of ankylosaurid epidermal scale architecture is presented for the first time. This study builds on previous osteological work that argues for a greater diversity of ankylosaurids in the Dinosaur Park Formation of Alberta than has been traditionally recognized and adds to the hypothesis that epidermal skin impressions are taxonomically relevant across diverse dinosaur clades. Copyright © 2013 Wiley Periodicals, Inc.

Comparative SEM and LM foliar epidermal and palyno-morphological studies of Amaranthaceae and its taxonomic implications.

PubMed

Hussain, Amara Noor; Zafar, Muhammad; Ahmad, Mushtaq; Khan, Raees; Yaseen, Ghulam; Khan, Muhammad Saleem; Nazir, Abdul; Khan, Amir Muhammad; Shaheen, Shabnum

2018-05-01

Palynological features as well as comparative foliar epidermal using light and scanning electron microscope (SEM) of 17 species (10genera) of Amaranthaceae have been studied for its taxonomic significance. Different foliar and palynological micro-morphological characters were examined to explain their value in resolving the difficulty in identification. All species were amphistomatic but stomata on abaxial surface were more abundant. Taxonomically significant epidermal character including stomata type, trichomes (unicellular, multicellular, and capitate) and epidermal cells shapes (polygonal and irregular) were also observed. Pollens of this family are Polypantoporate, pores large, spheroidal, mesoporous region is sparsely to scabrate, densely psilate, and spinulose. All these characters can be active at species level for identification purpose. This study indicates that at different taxonomic levels, LM and SEM pollen and epidermal morphology is explanatory and significant to identify species and genera. © 2018 Wiley Periodicals, Inc.

Cellular, ultrastructural and molecular analyses of epidermal cell development in the planarian Schmidtea mediterranea.

PubMed

Cheng, Li-Chun; Tu, Kimberly C; Seidel, Chris W; Robb, Sofia M C; Guo, Fengli; Sánchez Alvarado, Alejandro

2018-01-15

The epidermis is essential for animal survival, providing both a protective barrier and cellular sensor to external environments. The generally conserved embryonic origin of the epidermis, but the broad morphological and functional diversity of this organ across animals is puzzling. We define the transcriptional regulators underlying epidermal lineage differentiation in the planarian Schmidtea mediterranea, an invertebrate organism that, unlike fruitflies and nematodes, continuously replaces its epidermal cells. We find that Smed-p53, Sox and Pax transcription factors are essential regulators of epidermal homeostasis, and act cooperatively to regulate genes associated with early epidermal precursor cell differentiation, including a tandemly arrayed novel gene family (prog) of secreted proteins. Additionally, we report on the discovery of distinct and previously undescribed secreted organelles whose production is dependent on the transcriptional activity of soxP-3, and which we term Hyman vesicles. Copyright © 2017 Elsevier Inc. All rights reserved.

Cytoplasmic poly (A)-binding protein critically regulates epidermal maintenance and turnover in the planarian Schmidtea mediterranea.

PubMed

Bansal, Dhiru; Kulkarni, Jahnavi; Nadahalli, Kavana; Lakshmanan, Vairavan; Krishna, Srikar; Sasidharan, Vidyanand; Geo, Jini; Dilipkumar, Shilpa; Pasricha, Renu; Gulyani, Akash; Raghavan, Srikala; Palakodeti, Dasaradhi

2017-09-01

Identifying key cellular events that facilitate stem cell function and tissue organization is crucial for understanding the process of regeneration. Planarians are powerful model system to study regeneration and stem cell (neoblast) function. Here, using planaria, we show that the initial events of regeneration, such as epithelialization and epidermal organization are critically regulated by a novel cytoplasmic poly A-binding protein, SMED-PABPC2. Knockdown of smed-pabpc2 leads to defects in epidermal lineage specification, disorganization of epidermis and ECM, and deregulated wound healing, resulting in the selective failure of neoblast proliferation near the wound region. Polysome profiling suggests that epidermal lineage transcripts, including zfp-1 , are translationally regulated by SMED-PABPC2 . Together, our results uncover a novel role for SMED-PABPC2 in the maintenance of epidermal and ECM integrity, critical for wound healing and subsequent processes for regeneration. © 2017. Published by The Company of Biologists Ltd.

"Cut-and-paste" manufacture of multiparametric epidermal electronic systems

NASA Astrophysics Data System (ADS)

Lu, Nanshu; Yang, Shixuan; Wang, Pulin

2016-05-01

Epidermal electronics is a class of noninvasive and unobstructive skin-mounted, tattoo-like sensors and electronics capable of vital sign monitoring and establishing human-machine interface. The high cost of manpower, materials, vacuum equipment, and photolithographic facilities associated with its manufacture greatly hinders the widespread use of disposable epidermal electronics. Here we report a cost and time effective, completely dry, benchtop "cut-and-paste" method for the freeform and portable manufacture of multiparametric epidermal sensor systems (ESS) within minutes. This versatile method works for all types of thin metal and polymeric sheets and is compatible with any tattoo adhesives or medical tapes. The resulting ESS are multimaterial and multifunctional and have been demonstrated to noninvasively but accurately measure electrophysiological signals, skin temperature, skin hydration, as well as respiratory rate. In addition, planar stretchable coils exploiting double-stranded serpentine design have been successfully applied as wireless, passive epidermal strain sensors.

Intracellular processing of epidermal growth factor. I. Acidification of 125I-epidermal growth factor in intracellular organelles.

PubMed

Matrisian, L M; Planck, S R; Magun, B E

1984-03-10

We previously reported that 125I-labeled epidermal growth factor is processed intracellularly to acidic macromolecules in Rat-1 fibroblasts. The present study defines the precursor-product relationship and localization of the processing steps to subcellular organelles by the use of a single isoelectric species of 125I-epidermal growth factor and Percoll gradient fractionation. The native pI 4.55 125I-epidermal growth factor was rapidly processed to a pI 4.2 species on or near the cell surface and in organelles corresponding to clathrin-coated vesicles, Golgi, and endoplasmic reticulum. This species was then processed to a pI 4.35 species in similar organelles. The pI 4.2 and 4.35 species were converted to a pI 4.0 species in dense, lysosome-like organelles. This species was ultimately degraded and exocytosed from the cell as low molecular weight products.

Cytoplasmic poly (A)-binding protein critically regulates epidermal maintenance and turnover in the planarian Schmidtea mediterranea

PubMed Central

Bansal, Dhiru; Kulkarni, Jahnavi; Nadahalli, Kavana; Lakshmanan, Vairavan; Krishna, Srikar; Sasidharan, Vidyanand; Dilipkumar, Shilpa; Gulyani, Akash; Raghavan, Srikala

2017-01-01

Identifying key cellular events that facilitate stem cell function and tissue organization is crucial for understanding the process of regeneration. Planarians are powerful model system to study regeneration and stem cell (neoblast) function. Here, using planaria, we show that the initial events of regeneration, such as epithelialization and epidermal organization are critically regulated by a novel cytoplasmic poly A-binding protein, SMED-PABPC2. Knockdown of smed-pabpc2 leads to defects in epidermal lineage specification, disorganization of epidermis and ECM, and deregulated wound healing, resulting in the selective failure of neoblast proliferation near the wound region. Polysome profiling suggests that epidermal lineage transcripts, including zfp-1, are translationally regulated by SMED-PABPC2. Together, our results uncover a novel role for SMED-PABPC2 in the maintenance of epidermal and ECM integrity, critical for wound healing and subsequent processes for regeneration. PMID:28807897

Clinical Experience and Best Practices Using Epidermal Skin Grafts on Wounds.

PubMed

Kirsner, Robert S; Bernstein, Brent; Bhatia, Animesh; Lantis, John; Le, Lam; Lincoln, Katherine; Liu, Paul; Rodgers, Lee; Shaw, Mark; Young, David

2015-11-01

Over the years, autologous skin grafting has been used extensively to achieve wound closure, optimize a functional scar, and improve aesthetic outcomes for the patient. Although a vast majority of the literature is on the use of full-thickness and split-thickness skin grafts, epidermal skin grafts (ESGs) have emerged as a viable option in the reconstructive ladder when only the epidermal layer is needed. These grafts are distinct from other types of autologous skin grafts in that they can be harvested without anesthesia and leave minimal or no scarring at the donor site. In order to explore the use of ESGs in the continuum of primary wound closure, a multidisciplinary expert panel convened in October 2014, in Las Vegas, NV, to review the scientific basis and clinical uses of epidermal grafting. This publication provides an overview of epidermal grafting, recommendations for graft application, and potential roles for its use in wound care and closure.

An unusual cause of intractable heel pain.

PubMed

Ghani, Samuel; Fazal, Muhammad Ali

2011-01-01

We report a case of severe heel pain that did not respond to noninvasive measures. Magnetic resonance imaging scans revealed a soft tissue mass that after complete surgical excision was found to be an epidermal cyst. The patient experienced full resolution of the symptoms after excision of the epidermal cyst. To our knowledge, intractable heel pain due to an epidermal cyst is rare. We were unable to identify a previous publication describing the presence of an epidermal cyst localized to the heel without a history of previous trauma. From our experience with the present case, we believe that clinicians should consider the possibility of an epidermal inclusion cyst and should have a low threshold for obtaining magnetic resonance imaging scans, in particular, before the initiation of invasive treatment, in the case of intractable heel pain. Copyright © 2011 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

The Flare/CME Connection

NASA Technical Reports Server (NTRS)

Moore, Ron; Falconer, David; Sterling, Alphonse

2008-01-01

We present evidence supporting the view that, while many flares are produced by a confined magnetic explosion that does not produce a CME, every CME is produced by an ejective magnetic explosion that also produces a flare. The evidence is that the observed heliocentric angular width of the full-blown CME plasmoid in the outer corona (at 3 to 20 solar radii) is about that predicted by the standard model for CME production, from the amount of magnetic flux covered by the co-produced flare arcade. In the standard model, sheared and twisted sigmoidal field in the core of an initially closed magnetic arcade erupts. As it erupts, tether-cutting reconnection, starting between the legs of the erupting sigmoid and continuing between the merging stretched legs of the enveloping arcade, simultaneously produces a growing flare arcade and unleashes the erupting sigmoid and arcade to become the low-beta plasmoid (magnetic bubble) that becomes the CME. The flare arcade is the downward product of the reconnection and the CME plasmoid is the upward product. The unleashed, expanding CME plasmoid is propelled into the outer corona and solar wind by its own magnetic field pushing on the surrounding field in the inner and outer corona. This tether-cutting scenario predicts that the amount of magnetic flux in the full-blown CME plasmoid nearly equals that covered by the full-grown flare arcade. This equality predicts (1) the field strength in the flare region from the ratio of the angular width of the CME in the outer corona to angular width of the full-grown flare arcade, and (2) an upper bound on the angular width of the CME in the outer corona from the total magnetic flux in the active region from which the CME explodes. We show that these predictions are fulfilled by observed CMEs. This agreement validates the standard model. The model explains (1) why most CMEs have much greater angular widths than their co-produced flares, and (2) why the radial path of a CME in the outer corona can be laterally far offset from the co-produced flare.

How do the medial olivocochlear efferents influence the biomechanics of the outer hair cells and thereby the cochlear amplifier? Simulation results

NASA Astrophysics Data System (ADS)

Saremi, Amin; Stenfelt, Stefan; Verhulst, Sarah

2015-12-01

The bottom-up signal pathway, which starts from the outer ear and leads to the brain cortices, gives the classic image of the human sound perception. However, there have been growing evidences in the last six decades for existence of a functional descending network whereby the central auditory system can modulate the early auditory processing, in a top-down manner. The medial olivocochlear efferent fibers project from the superior olivary complex at the brainstem into the inner ear. They are linked to the basal poles of the hair cells by forming synaptic cisterns. This descending network can activate nicotinic cholinergic receptors (nAChR) that increase the membrane conductance of the outer hair cells and thereby modify the magnitude of the active force generated inside the cochlea. The aim of the presented work is to quantitatively investigate how the changes in the biomechanics of the outer hair cells, caused by the efferent activation, manipulate the cochlear responses. This is done by means of a frequency-domain biophysical model of the cochlea [12] where the parameters of the model convey physiological interpretations of the human cochlear structures. The simulations manifest that a doubling of the outer hair cell conductance, due to efferent activation, leads to a frequency-dependent gain reduction along the cochlear duct with its highest effect at frequencies between 1 kHz and 3.5 kHz and a maximum of approximately 10 dB gain reduction at 2 kHz. This amount of the gain inhibition and its frequency dependence reasonably agrees with the experimental data recorded from guinea pig, cat and human cochleae where the medial olivococlear efferents had been elicited by broad-band stimuli. The simulations also indicate that the efferent-induced increase of the outer hair cell conductance increases the best frequency of the cochlear responses, in the basal region. The presented simulations quantitatively confirm that activation of the medial olivocochlear efferents can biomechanically manipulate the cochlear responses, in a top-down manner, by inhibiting the gain of the cochlear amplifier as well as altering the frequency-position map (tuning pattern) of the cochlea.

Epidermal differentiation during ontogeny and after hatching in the snake Liasis fuscus (Pythonidae, Serpentes, Reptilia), with emphasis on the formation of the shedding complex.

PubMed

Alibardi, L; Thompson, M B

2003-04-01

Differentiation and localization of keratin in the epidermis during embryonic development and up to 3 months posthatching in the Australian water python, Liasis fuscus, was studied by ultrastructural and immunocytochemical methods. Scales arise from dome-like folds in the skin that produce tightly imbricating scales. The dermis of these scales is completely differentiated before any epidermal differentiation begins, with a loose dermis made of mesenchymal cells beneath the differentiating outer scale surface. At this stage (33) the embryo is still unpigmented and two layers of suprabasal cells contain abundant glycogen. At Stage 34 (beginning of pigmentation) the first layers of cells beneath the bilayered periderm (presumptive clear and oberhautchen layers) have not yet formed a shedding complex, within which prehatching shedding takes place. At Stage 35 the shedding complex, consisting of the clear and oberhautchen layers, is discernible. The clear layer contains a fine fibrous network that faces the underlying oberhautchen, where the spinulae initially contain a core of fibrous material and small beta-keratin packets. Differentiation continues at Stage 36 when the beta-layer forms and beta-keratin packets are deposited both on the fibrous core of the oberhautchen and within beta-cells. Mesos cells are produced from the germinal layer but remain undifferentiated. At Stage 37, before hatching, the beta-layer is compact, the mesos layer contains mesos granules, and cells of the alpha-layer are present but are not yet keratinized. They are still only partially differentiated a few hours after hatching, when a new shedding complex is forming underneath. Using antibodies against chick scale beta-keratin resolved at high magnification with immunofluorescent or immunogold conjugates, we offer the first molecular confirmation that in snakes only the oberhautchen component of the shedding complex and the underlying beta cells contain beta-keratin. Initially, there is little immunoreactivity in the small beta-packets of the oberhautchen, but it increases after fusion with the underlying cells to produce the syncytial beta layer. The beta-keratin packets coalesce with the tonofilaments, including those attached to desmosomes, which rapidly disappear in both oberhautchen and beta-cells as differentiation progresses. The labeling is low to absent in forming mesos-cells beneath the beta-layer. This study further supports the hypothesis that the shedding complex in lepidosaurian reptiles evolved after there was a segregation between alpha-keratogenic cells from beta-keratogenic cells during epidermal renewal. Copyright 2003 Wiley-Liss, Inc.

Epidermal nevus syndrome and didymosis aplasticosebacea.

PubMed

Demerdjieva, Zdravka; Kavaklieva, Svetlana; Tsankov, Nikolay

2007-01-01

The epidermal nevus syndrome is a disease complex consisting of the association of an epidermal nevus with various developmental abnormalities of the skin, eyes, nervous, skeletal, cardiovascular, and urogenital systems. The epidermal nevi are classified according to their predominant component; nevus sebaceus (sebaceous glands), nevus comedonicus (hair follicles), and nevus verrucosus (keratinocytes). We report a neonate who presented with a nevus sebaceus on the scalp and face as well as a coloboma and dermoid on his left eye. Within the sebaceous nevus on the scalp, circumscribed lesions of aplasia cutis congenita were detected, which is consistent with the recently proposed term in the literature didymosis aplasticosebacea.

Epidermal Notch signalling: differentiation, cancer and adhesion.

PubMed

Watt, Fiona M; Estrach, Soline; Ambler, Carrie A

2008-04-01

The Notch pathway plays an important role in regulating epidermal differentiation. Notch ligands, receptors and effectors are expressed in a complex and dynamic pattern in embryonic and adult skin. Genetic ablation or activation of the pathway reveals that Notch signalling promotes differentiation of the hair follicle, sebaceous gland and interfollicular epidermal lineages and that Notch acts as an epidermal tumour suppressor. Notch signalling interacts with a range of other pathways to fulfil these functions and acts via RBP-Jkappa dependent and independent mechanisms. The effects on differentiation can be cell autonomous and non-autonomous, and Notch contributes to stem cell clustering via modulation of cell adhesion.

Evaluation of Carbon Dioxide Laser in the Treatment of Epidermal Nevi.

PubMed

Bhat, Yasmeen Jabeen; Hassan, Iffat; Sajad, Peerzada; Yaseen, Atiya; Mubashir, Syed; Akhter, Saniya; Wani, Roohi

2016-01-01

Epidermal naevi are benign hamartomatous growths of the skin which are generally asymptomatic with a benign course but are cosmetically disagreeable. Topical treatments such as steroids, calcipotriol, 5 fluorouracil, podophyllin, retinoids and cryotherapy are ineffective and surgical excision results in scar formation. Therapy is often challenging. To study the response of carbon dioxide (CO 2 ) laser in the management of epidermal naevi. We conducted a study of CO 2 laser treatment on 15 patients of epidermal naevi, eight with verrucous epidermal naevi and seven with sebaceous naevi. A thorough history and examination was done to rule out any epidermal naevus syndrome. The diagnosis was confirmed by histopathology. The number of treatment sessions varied from 1 to 8. Response was excellent (>90% reduction in lesion size) in three patients, very good (>75% reduction) in five, good (>50% reduction in lesion size) in five and poor (<50% reduction in lesion size) in two patients. The side effects were hyperpigmentation and scarring. Long-term follow-up over a period of 10 months showed a recurrence rate of 20%. We conclude that CO 2 laser treatment might be an effective option with long-term safety, minimal discomfort and rapid recovery.

Terminal epidermal differentiation is regulated by the interaction of Fra-2/AP-1 with Ezh2 and ERK1/2

PubMed Central

Wurm, Stefanie; Zhang, Jisheng; Guinea-Viniegra, Juan; García, Fernando; Muñoz, Javier; Bakiri, Latifa; Ezhkova, Elena

2015-01-01

Altered epidermal differentiation characterizes numerous skin diseases affecting >25% of the human population. Here we identified Fra-2/AP-1 as a key regulator of terminal epidermal differentiation. Epithelial-restricted, ectopic expression of Fra-2 induced expression of epidermal differentiation genes located within the epidermal differentiation complex (EDC). Moreover, in a papilloma-prone background, a reduced tumor burden was observed due to precocious keratinocyte differentiation by Fra-2 expression. Importantly, loss of Fra-2 in suprabasal keratinocytes is sufficient to cause skin barrier defects due to reduced expression of differentiation genes. Mechanistically, Fra-2 binds and transcriptionally regulates EDC gene promoters, which are co-occupied by the transcriptional repressor Ezh2. Fra-2 remains transcriptionally inactive in nondifferentiated keratinocytes, where it was found monomethylated and dimethylated on Lys104 and interacted with Ezh2. Upon keratinocyte differentiation, Fra-2 is C-terminally phosphorylated on Ser320 and Thr322 by ERK1/2, leading to transcriptional activation. Thus, the induction of epidermal differentiation by Fra-2 is controlled by a dual mechanism involving Ezh2-dependent methylation and activation by ERK1/2-dependent phosphorylation. PMID:25547114

Overexpression of cyclin D1 induces the reprogramming of differentiated epidermal cells into stem cell-like cells.

PubMed

Zhao, Along; Yang, Leilei; Ma, Kui; Sun, Mengli; Li, Lei; Huang, Jin; Li, Yang; Zhang, Cuiping; Li, Haihong; Fu, Xiaobing

2016-01-01

It has been reported that Wnt/β-catenin is critical for dedifferentiation of differentiated epidermal cells. Cyclin D1 (CCND1) is a β-catenin target gene. In this study, we provide evidence that overexpression of CCND1 induces reprogramming of epidermal cells into stem cell-like cells. After introducing CCND1 gene into differentiated epidermal cells, we found that the large flat-shaped cells with a small nuclear-cytoplasmic ratio changed into small round-shaped cells with a large nuclear-cytoplasmic ratio. The expressions of CK10, β1-integrin, Oct4 and Nanog in CCND1 induced cells were remarkably higher than those in the control group (P < 0.01). In addition, the induced cells exhibited a high colony-forming ability and a long-term proliferative potential. When the induced cells were implanted into a wound of laboratory animal model, the wound healing was accelerated. These results suggested that overexpression of CCND1 induced the reprogramming of differentiated epidermal cells into stem cell-like cells. This study may also offer a new approach to yield epidermal stem cells for wound repair and regeneration.

Psoriatic T cells reduce epidermal turnover time and affect cell proliferation contributed from differential gene expression.

PubMed

Li, Junqin; Li, Xinhua; Hou, Ruixia; Liu, Ruifeng; Zhao, Xincheng; Dong, Feng; Wang, Chunfang; Yin, Guohua; Zhang, Kaiming

2015-09-01

Psoriasis is mediated primarily by T cells, which reduce epidermal turnover time and affect keratinocyte proliferation. We aimed to identify differentially expressed genes (DEG) in T cells from normal, five pairs of monozygotic twins concordant or discordant for psoriasis, to determine whether these DEG may account for the influence to epidermal turnover time and keratinocyte proliferation. The impact of T cells on keratinocyte proliferation and epidermal turnover time were investigated separately by immunohistochemistry and cultured with (3) H-TdR. mRNA expression patterns were investigated by RNA sequencing and verified by real-time reverse transcription polymerase chain reaction. After co-culture with psoriatic T cells, the expression of Ki-67, c-Myc and p53 increased, while expression of Bcl-2 and epidermal turnover time decreased. There were 14 DEG which were found to participate in the regulation of cell proliferation or differentiation. Psoriatic T cells exhibited the ability to decrease epidermal turnover time and affect keratinocyte proliferation because of the differential expression of PPIL1, HSPH1, SENP3, NUP54, FABP5, PLEKHG3, SLC9A9 and CHCHD4. © 2015 Japanese Dermatological Association.

Biological interactions of quantum dot nanoparticles in skin and in human epidermal keratinocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Leshuai W.; Yu, William W.; Colvin, Vicki L.

2008-04-15

Quantum dots nanoparticles have novel optical properties for biomedical applications and electronics, but little is known about their skin permeability and interaction with cells. QD621 are nail-shaped nanoparticles that contain a cadmium/selenide core with a cadmium sulfide shell coated with polyethylene glycol (PEG) and are soluble in water. QD were topically applied to porcine skin flow-through diffusion cells to assess penetration at 1 {mu}M, 2 {mu}M and 10 {mu}M for 24 h. QD were also studied in human epidermal keratinocytes (HEK) to determine cellular uptake, cytotoxicity and inflammatory potential. Confocal microscopy depicted the penetration of QD621 through the uppermost stratummore » corneum (SC) layers of the epidermis and fluorescence was found primarily in the SC and near hair follicles. QD were found in the intercellular lipid bilayers of the SC by transmission electron microscopy (TEM). Inductively coupled plasma-optical emission spectroscopy (ICP-OES) analysis for cadmium (Cd) and fluorescence for QD both did not detect Cd nor fluorescence signal in the perfusate at any time point or concentration. In HEK, viability decreased significantly (p < 0.05) from 1.25 nM to 10nM after 24 h and 48 h. There was a significant increase in IL-6 at 1.25 nM to 10 nM, while IL-8 increased from 2.5nM to 10nM after 24 h and 48 h. TEM of HEK treated with 10 nM of QD621 at 24 h depicted QD in cytoplasmic vacuoles and at the periphery of the cell membranes. These results indicate that porcine skin penetration of QD621 is minimal and limited primarily to the outer SC layers, yet if the skin were damaged allowing direct QD exposure to skin or keratinocytes, an inflammatory response could be initiated.« less

Skin lesions on yellowfin tuna Thunnus albacares from Gulf of Mexico outer continental shelf: Morphological, molecular, and histological diagnosis of infection by a capsalid monogenoid.

PubMed

Bullard, Stephen A; Womble, Matthew R; Maynard, Margaret K; Orélis-Ribeiro, Raphael; Arias, Cova R

2015-12-01

We characterize lesion-associated capsaline infections on yellowfin tuna, Thunnus albacares, in the Gulf of Mexico by comparing our specimens with published descriptions and museum specimens ascribed to Capsala biparasiticum and its synonyms: vouchers of C. biparasiticum from parasitic copepods; the holotype of Capsala neothunni; and vouchers of Capsala abidjani. Those from parasitic copepods differed by having a small, rounded body, large anterior attachment organs, closely spaced dorsomarginal body sclerites, small testes, and a short and wide testicular field. No morphometric feature in the holotype of C. neothunni ranged outside of that reported for the newly-collected specimens, indicating conspecificity of our specimens. The specimens of C. abidjani differed by having a large anterior attachment organ, few and dendritic testes, and a short, wide testicular field. Large subunit ribosomal DNA (28S) sequences grouped our specimens and Capsala sp. as sister taxa and indicated a phylogenetic affinity of Nasicola klawei. The haptoral attachment site comprised a crater-like depression surrounded by a blackish-colored halo of extensively rugose skin, with abundant pockmarked-like, irregularly-shaped oblong or semi-circular epidermal pits surrounding these attachment sites. Histology confirmed extensive folding of epidermis and underlying stratum laxum, likely epidermal hyperplasia, foci of weak cell-to-cell adhesions among apical malpighian cells as well as that between stratum germinativum and stratum laxum, myriad goblet cells in epidermis, rodlet cells in apical layer of epidermis, and lymphocytic infiltrates and melanin in dermis. The present study comprises (i) the first published report of this parasite from yellowfin tuna captured in the Gulf of Mexico-NW Atlantic Ocean Basin, (ii) confirmation of its infection on the skin (rather than on a parasitic copepod), (iii) the first molecular data for this capsaline, and (iv) the first observations of histopathological changes associated with a capsalid infection on a wild-caught epipelagic fish. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Evaluation of Epidermal Skin Grafts for the Treatment of Complex Wounds in a Wound Care Center: A 94-Patient Case Series.

PubMed

Lincoln, Katherine; Hyde, Jessica

2016-10-01

In recent years, a new technology for autologous epidermal harvesting has been developed to produce epidermal skin grafts (ESGs) for use over wounds. This technology employs negative pressure and heat to raise the epidermal skin layer, allowing for consistent and reproducible epidermal harvesting. The aim of this case series is to present the authors' experience using an automated, epidermal harvesting system to produce ESGs to treat wounds of patients with multiple comorbidities. This case series was conducted between January 1, 2013 and December 31, 2014. Patients with wounds (≤ 25 cm2) that failed to heal were treated with ESGs by a group of 3 wound care physicians in 2 outpatient wound care centers in a community health center setting. A total of 94 patients with 102 wounds were identified. Of the 94 patients, 3 were noncompliant and 9 were lost to follow-up. Therefore, 82 patients with 90 wounds were included in the analysis. The majority of wounds demonstrated epithelialization (83/90, 92.2%). Of the 90 wounds, 75 (83.3%) healed following epidermal grafting, 4 (4.4%) wounds displayed improvement, and 11 (12.2%) did not heal. Minimal or no pain at the donor site was reported by the patients, and all donor sites healed without complications. This case series provides additional evidence for the use of ESGs for the treatment of wounds that fail to heal.

Intralaboratory and interlaboratory evaluation of the EpiDerm 3D human reconstructed skin micronucleus (RSMN) assay.

PubMed

Hu, Ting; Kaluzhny, Yulia; Mun, Greg C; Barnett, Brenda; Karetsky, Viktor; Wilt, Nathan; Klausner, Mitchell; Curren, Rodger D; Aardema, Marilyn J

2009-03-17

A novel in vitro human reconstructed skin micronucleus (RSMN) assay has been developed using the EpiDerm 3D human skin model [R. D. Curren, G. C. Mun, D. P. Gibson, and M. J. Aardema, Development of a method for assessing micronucleus induction in a 3D human skin model EpiDerm, Mutat. Res. 607 (2006) 192-204]. The RSMN assay has potential use in genotoxicity assessments as a replacement for in vivo genotoxicity assays that will be banned starting in 2009 according to the EU 7th Amendment to the Cosmetics Directive. Utilizing EpiDerm tissues reconstructed with cells from four different donors, intralaboratory and interlaboratory reproducibility of the RSMN assay were examined. Seven chemicals were evaluated in three laboratories using a standard protocol. Each chemical was evaluated in at least two laboratories and in EpiDerm tissues from at least two different donors. Three model genotoxins, mitomycin C (MMC), vinblastine sulfate (VB) and methyl methanesulfonate (MMS) induced significant, dose-related increases in cytotoxicity and MN induction in EpiDerm tissues. Conversely, four dermal non-carcinogens, 4-nitrophenol (4-NP), trichloroethylene (TCE), 2-ethyl-1,3-hexanediol (EHD), and 1,2-epoxydodecane (EDD) were negative in the RSMN assay. Results between tissues reconstructed from different donors were comparable. These results indicate the RSMN assay using the EpiDerm 3D human skin model is a promising new in vitro genotoxicity assay that allows evaluation of chromosome damage following "in vivo-like" dermal exposures.

Identification of Candidate Transcriptional Regulators of Epidermal Transfer Cell Development in Vicia faba Cotyledons

PubMed Central

Arun-Chinnappa, Kiruba S.; McCurdy, David W.

2016-01-01

Transfer cells (TCs) are anatomically-specialized cells formed at apoplasmic-symplasmic bottlenecks in nutrient transport pathways in plants. TCs form invaginated wall ingrowths which provide a scaffold to amplify plasma membrane surface area and thus increase the density of nutrient transporters required to achieve enhanced nutrient flow across these bottlenecks. Despite their importance to nutrient transport in plants, little is known of the transcriptional regulation of wall ingrowth formation. Here, we used RNA-Seq to identify transcription factors putatively involved in regulating epidermal TC development in cotyledons of Vicia faba. Comparing cotyledons cultured for 0, 3, 9, and 24 h to induce trans-differentiation of epidermal TCs identified 43 transcription factors that showed either epidermal-specific or epidermal–enhanced expression, and 10 that showed epidermal-specific down regulation. Members of the WRKY and ethylene-responsive families were prominent in the cohort of transcription factors showing epidermal-specific or epidermal–enhanced expression, consistent with the initiation of TC development often representing a response to stress. Members of the MYB family were also prominent in these categories, including orthologs of MYB genes involved in localized secondary wall deposition in Arabidopsis thaliana. Among the group of transcription factors showing down regulation were various homeobox genes and members of the MADs-box and zinc-finger families of poorly defined functions. Collectively, this study identified several transcription factors showing expression characteristics and orthologous functions that indicate likely participation in transcriptional regulation of epidermal TC development in V. faba cotyledons. PMID:27252730

Geographic Variations and Time Trends in Cancer Treatments in Taiwan.

PubMed

Hsu, Jason C; Chang, Sheng-Mao; Lu, Christine Y

2017-08-02

Targeted therapies have become important treatment options for cancer care in many countries. This study aimed to examine recent trends in utilization of antineoplastic drugs, particularly the use of targeted therapies for treatment of cancer, by geographic region in Taiwan (northern, midwestern, southern, and eastern regions and the outer islands). This was a retrospective observational study of antineoplastic agents using 2009-2012 quarterly claims data from Taiwan's National Health Insurance Research Database. Yearly market shares by prescription volume and costs for targeted therapies among total antineoplastic agents by region were estimated. We used multivariate regression model and ANOVA to examine variations in utilization of targeted therapies between geographic regions and used ARIMA models to estimate longitudinal trends. Population-adjusted use and costs of antineoplastic drugs (including targeted therapies) were highest in the southern region of Taiwan and lowest in the outer islands. We found a 4-fold difference in use of antineoplastic drugs and a 49-fold difference in use of targeted therapies between regions if the outer islands were included. There were minimal differences in use of antineoplastic drugs between other regions with about a 2-fold difference in use of targeted therapies. Without considering the outer islands, the market share by prescription volume and costs of targeted therapies increased almost 2-fold (1.84-1.90) and 1.5-fold (1.26-1.61) respectively between 2009 and 2012. Furthermore, region was not significantly associated with use of antineoplastic agents or use of targeted therapies after adjusting for confounders. Region was associated with costs of antineoplastic agents but it was not associated with costs of targeted therapies after confounding adjustments. Use of antineoplastic drugs overall and use of targeted therapies for treatment of cancer varied somewhat between regions in Taiwan; use was notably low in the outer islands. Strategies might be needed to ensure access to cancer care in each region as economic burden of cancer care increase due to growing use of targeted therapies.

SOX2 plays a critical role in EGFR-mediated self-renewal of human prostate cancer stem-like cells.

PubMed

Rybak, Adrian P; Tang, Damu

2013-12-01

SOX2 is an essential transcription factor for stem cells and plays a role in tumorigenesis, however its role in prostate cancer stem cells (PCSCs) remains unclear. We report here a significant upregulation of SOX2 at both mRNA and protein levels in DU145 PCSCs propagated as suspension spheres in vitro. The expression of SOX2 in DU145 PCSCs is positively regulated by epidermal growth factor receptor (EGFR) signaling. Activation of EGFR signaling, following the addition of epidermal growth factor (EGF) or ectopic expression of a constitutively-active EGFR mutant (EGFRvIII), increased SOX2 expression and the self-renewal of DU145 PCSCs. Conversely, a small molecule EGFR inhibitor (AG1478) blocked EGFR activation, reduced SOX2 expression and inhibited PCSC self-renewal activity, implicating SOX2 in mediating EGFR-dependent self-renewal of PCSCs. In line with this notion, ectopic SOX2 expression enhanced EGF-induced self-renewal of DU145 PCSCs, while SOX2 knockdown reduced PCSC self-renewal with EGF treatment no longer capable of enhancing their propagation. Furthermore, SOX2 knockdown reduced the capacity of DU145 PCSCs to grow under anchorage-independent conditions. Finally, DU145 PCSCs generated xenograft tumors more aggressively with elevated levels of SOX2 expression compared to xenograft tumors derived from non-PCSCs. Collectively, we provide evidence that SOX2 plays a critical role in EGFR-mediated self-renewal of DU145 PCSCs. © 2013.

Evidence for a role of SNX16 in regulating traffic between the early and later endosomal compartments.

PubMed

Hanson, Brendon J; Hong, Wanjin

2003-09-05

Sorting nexins (SNXs) are a growing family of proteins characterized by the presence of a PX domain. The PX domain mediates membrane association by interaction with phosphoinositides. The SNXs are generally believed to participate in membrane trafficking, but information regarding the function of individual proteins is limited. In this report, we describe the major characteristics of one member, SNX16. SNX16 is a novel 343-amino acid protein consisting of a central PX domain followed by a potential coiled-coil domain and a C-terminal region. Like other sorting nexins, SNX16 associates with the membrane via the PX domain which interacts with the phospholipid phosphatidylinositol 3-phosphate. We show via biochemical and cellular studies that SNX16 is distributed in both early and late endosome/lysosome structures. The coiled-coil domain is necessary for localization to the later endosomal structures, as mutant SNX16 lacking this domain was found only in early endosomes. Trafficking of internalized epidermal growth factor was also delayed by this SNX16 mutant, as these cells showed a delay in the segregation of epidermal growth factor in the early endosome for its delivery to later compartments. In addition, the coiled-coil domain is shown here to be important for homo-oligomerization of SNX16. Taken together, these results suggest that SNX16 is a sorting nexin that may function in the trafficking of proteins between the early and late endosomal compartments.

Uranus and Neptune: Refugees from the Jupiter-Saturn zone?

NASA Astrophysics Data System (ADS)

Thommes, E. W.; Duncan, M. J.; Levison, H. F.

1999-09-01

Plantesimal accretion models of planet formation have been quite successful at reproducing the terrestrial region of the Solar System. However, in the outer Solar System these models run into problems, and it becomes very difficult to grow bodies to the current mass of the ``ice giants," Uranus and Neptune. Here we present an alternative scenario to in-situ formation of the ice giants. In addition to the Jupiter and Saturn solid cores, several more bodies of mass ~ 10 MEarth or more are likely to have formed in the region between 4 and 10 AU. As Jupiter's core, and perhaps Saturn's, accreted nebular gas, the other nearby bodies must have been scattered outward. Dynamical friction with the trans-Saturnian part of the planetesimal disk would have acted to decouple these ``failed cores" from their scatterer, and to circularize their orbits. Numerical simulations presented here show that systems very similar to our outer Solar System (including Uranus, Neptune, the Kuiper belt, and the scattered disk) are a natural product of this process.

The role of volatiles and lithology in the impact cratering process

NASA Technical Reports Server (NTRS)

Kieffer, S. W.; Simonds, C. H.

1980-01-01

A survey of published descriptions of 32 of the largest, least eroded terrestrial impact structures shows that the amount of melt at craters in crystalline rocks is approximately two orders of magnitude greater than that at craters in sedimentary rocks. A model is proposed for the impact process, and it is examined whether the difference in melt abundance is due to differences in the amount of melt generated in various target materials or due to differences in the fate of the melt during late stages of the impact. The model accounts semiquantitatively for the effects of porosity and water and volatile content on the cratering process. Important features of the model are noted. Even if the recondensation of released volatiles is very efficient, the cumulative effect of repeated impacts on accreting planets would be to continually transfer volatiles toward the outer surface. By this process, volatiles might be enriched toward the outer layer of a growing planet.

Systematic Analysis of mRNA and miRNA Expression of 3D-Cultured Neural Stem Cells (NSCs) in Spaceflight.

PubMed

Cui, Yi; Han, Jin; Xiao, Zhifeng; Qi, Yiduo; Zhao, Yannan; Chen, Bing; Fang, Yongxiang; Liu, Sumei; Wu, Xianming; Dai, Jianwu

2017-01-01

Recently, with the development of the space program there are growing concerns about the influence of spaceflight on tissue engineering. The purpose of this study was thus to determine the variations of neural stem cells (NSCs) during spaceflight. RNA-Sequencing (RNA-Seq) based transcriptomic profiling of NSCs identified many differentially expressed mRNAs and miRNAs between space and earth groups. Subsequently, those genes with differential expression were subjected to bioinformatic evaluation using gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) and miRNA-mRNA network analyses. The results showed that NSCs maintain greater stemness ability during spaceflight although the growth rate of NSCs was slowed down. Furthermore, the results indicated that NSCs tended to differentiate into neuron in outer space conditions. Detailed genomic analyses of NSCs during spaceflight will help us to elucidate the molecular mechanisms behind their differentiation and proliferation when they are in outer space.

Process for depositing epitaxial alkaline earth oxide onto a substrate and structures prepared with the process

DOEpatents

McKee, Rodney A.; Walker, Frederick J.

1996-01-01

A process and structure involving a silicon substrate utilize molecular beam epitaxy (MBE) and/or electron beam evaporation methods and an ultra-high vacuum facility to grow a layup of epitaxial alkaline earth oxide films upon the substrate surface. By selecting metal constituents for the oxides and in the appropriate proportions so that the lattice parameter of each oxide grown closely approximates that of the substrate or base layer upon which oxide is grown, lattice strain at the film/film or film/substrate interface of adjacent films is appreciably reduced or relieved. Moreover, by selecting constituents for the oxides so that the lattice parameters of the materials of adjacent oxide films either increase or decrease in size from one parameter to another parameter, a graded layup of films can be grown (with reduced strain levels therebetween) so that the outer film has a lattice parameter which closely approximates that of, and thus accomodates the epitaxial growth of, a pervoskite chosen to be grown upon the outer film.

Investigation of growth features in several hydraulic fractures

NASA Astrophysics Data System (ADS)

Bykov, Alexander; Galybin, Alexander; Evdokimov, Alexander; Zavialova, Natalia; Zavialov, Ivan; Negodiaev, Sergey; Perepechkin, Ilia

2017-04-01

In this paper we simulate the growth of three or more interacting hydraulic fractures in the horizontal well with a cross flow of fluid between them. Calculation of the dynamics of cracks is performed in three dimensional space. The computation of the movement of fracturing fluid with proppant is performed in the two-dimensional space (the flow was averaged along crack aperture). For determining the hydraulic pipe resistance coefficient we used a generalization of the Reynolds number for fluids with power rheology and a generalization of the von Karman equation made by Dodge and Meiner. The calculations showed that the first crack was developing faster than the rest in homogeneous medium. During the steady loading the outer cracks pinch the inner cracks and it was shown that only the first and last fracture develop in extreme case. It is also possible to simulate the parameters at which the two developing outer cracks pinch the central one in the horizontal direction. In this case, the central crack may grow in the vertical direction.

Comparative effect of gromwell (Lithospermum erythrorhizon) extract and borage oil on reversing epidermal hyperproliferation in guinea pigs.

PubMed

Kim, Juyoung; Kim, Hyunae; Jeong, Do Hyeon; Kim, Sung Han; Park, Seong Kyu; Cho, Yunhi

2006-09-01

To compare the systemic efficacy of borage oil (Borago officinalis: BO) and gromwell (Lithospermum erythrorhizon), two plant species of the Boraginaceae family, epidermal hyperproliferation was induced in guinea pigs by a hydrogenated coconut oil diet for 8 weeks. Subsequently, guinea pigs were fed diets of BO (group HBO), organic extract (group HGO), or water extract (group HGW) of gromwell for 2 weeks. In groups HGO and HGW, proliferation scores and the level of ceramides, the major lipid maintaining epidermal barrier, were similar with those in normal control group BO fed BO diet for 10 weeks. Despite accumulation of 15-hydroxyeicosatrienoic acid (15-HETrE), the potent anti-proliferative metabolite of gamma-linolenic acid (GLA: major polyunsaturated fatty acid in BO), the reversal of epidermal hyperproliferation and the ceramide level of group HBO were less than those of groups HGO and HGW. Taken together, our data demonstrate that gromwell is more effective in reversing epidermal hyperproliferation with a marked increase in ceramides.

Egr-5 is a post-mitotic regulator of planarian epidermal differentiation

PubMed Central

Tu, Kimberly C; Cheng, Li-Chun; TK Vu, Hanh; Lange, Jeffrey J; McKinney, Sean A; Seidel, Chris W; Sánchez Alvarado, Alejandro

2015-01-01

Neoblasts are an abundant, heterogeneous population of adult stem cells (ASCs) that facilitate the maintenance of planarian tissues and organs, providing a powerful system to study ASC self-renewal and differentiation dynamics. It is unknown how the collective output of neoblasts transit through differentiation pathways to produce specific cell types. The planarian epidermis is a simple tissue that undergoes rapid turnover. We found that as epidermal progeny differentiate, they progress through multiple spatiotemporal transition states with distinct gene expression profiles. We also identified a conserved early growth response family transcription factor, egr-5, that is essential for epidermal differentiation. Disruption of epidermal integrity by egr-5 RNAi triggers a global stress response that induces the proliferation of neoblasts and the concomitant expansion of not only epidermal, but also multiple progenitor cell populations. Our results further establish the planarian epidermis as a novel paradigm to uncover the molecular mechanisms regulating ASC specification in vivo. DOI: http://dx.doi.org/10.7554/eLife.10501.001 PMID:26457503

Cellular pattern formation by SCRAMBLED, a leucine-rich repeat receptor-like kinase in Arabidopsis.

PubMed

Kwak, Su-Hwan; Schiefelbein, John

2008-02-01

The appropriate specification of distinct cell types is important for generating the proper tissues and bodies of multicellular organisms. In the root epidermis of Arabidopsis, cell fate determination is accomplished by a transcriptional regulatory circuit that is influenced by positional signaling. A leucine-rich repeat receptor-like kinase, SCRAMBLED (SCM), has been shown to be responsible for the position-dependent aspect of this epidermal pattern. In a recent report, we find that SCM affects the transcriptional regulatory network by down-regulating the WEREWOLF (WER) MYB gene expression in a set of epidermal cells located in a specific position. We also find that SCM and the SCM-related SRF1 and SRF3 are not required for embryonic epidermal patterning and that SRF1 and SRF3 do not act redundantly with SCM. This suggests that distinct positional signaling mechanisms exist for embryonic and post-embryonic epidermal patterning. In this addendum, we discuss the implications of our recent findings and extend our working model for epidermal cell pattering.

Cellular pattern formation by SCRAMBLED, a leucine-rich repeat receptor-like kinase in Arabidopsis

PubMed Central

Kwak, Su-Hwan

2008-01-01

The appropriate specification of distinct cell types is important for generating the proper tissues and bodies of multicellular organisms. In the root epidermis of Arabidopsis, cell fate determination is accomplished by a transcriptional regulatory circuit that is influenced by positional signaling. A leucine-rich repeat receptor-like kinase, SCRAMBLED (SCM), has been shown to be responsible for the position-dependent aspect of this epidermal pattern. In a recent report, we find that SCM affects the transcriptional regulatory network by down-regulating the WEREWOLF (WER) MYB gene expression in a set of epidermal cells located in a specific position. We also find that SCM and the SCM-related SRF1 and SRF3 are not required for embryonic epidermal patterning and that SRF1 and SRF3 do not act redundantly with SCM. This suggests that distinct positional signaling mechanisms exist for embryonic and post-embryonic epidermal patterning. In this addendum, we discuss the implications of our recent findings and extend our working model for epidermal cell pattering. PMID:19704725

Multiple transcription factor codes activate epidermal wound–response genes in Drosophila

PubMed Central

Pearson, Joseph C.; Juarez, Michelle T.; Kim, Myungjin; Drivenes, Øyvind; McGinnis, William

2009-01-01

Wounds in Drosophila and mouse embryos induce similar genetic pathways to repair epidermal barriers. However, the transcription factors that transduce wound signals to repair epidermal barriers are largely unknown. We characterize the transcriptional regulatory enhancers of 4 genes—Ddc, ple, msn, and kkv—that are rapidly activated in epidermal cells surrounding wounds in late Drosophila embryos and early larvae. These epidermal wound enhancers all contain evolutionarily conserved sequences matching binding sites for JUN/FOS and GRH transcription factors, but vary widely in trans- and cis-requirements for these inputs and their binding sites. We propose that the combination of GRH and FOS is part of an ancient wound–response pathway still used in vertebrates and invertebrates, but that other mechanisms have evolved that result in similar transcriptional output. A common, but largely untested assumption of bioinformatic analyses of gene regulatory networks is that transcription units activated in the same spatial and temporal patterns will require the same cis-regulatory codes. Our results indicate that this is an overly simplistic view. PMID:19168633

Photoacoustic measurement of epidermal melanin

NASA Astrophysics Data System (ADS)

Viator, John A.; Svaasand, Lars O.; Aguilar, Guillermo; Choi, Bernard; Nelson, J. Stuart

2003-06-01

Most dermatologic laser procedures must consider epidermal melanin, as it is a broadband optical absorber which affects subsurface fluence, effectively limiting the amount of light reaching the dermis and targeted chromophores. An accurate method for quantifying epidermal melanin content would aid clinicians in determining proper light dosage for therapeutic laser procedures. While epidermal melanin content has been quantified non-invasively using optical methods, there is currently no way to determine the melanin distribution in the epidermis. We have developed a photoacoustic probe that uses a Q-switched, frequency doubled Nd:YAG laser operating at 532nm to generate acoustic pulses in skin in vivo. The probe contained a piezoelectric element that detected photoacoustic waves which were then analyzed for epidermal melanin content, using a photoacoustic melanin index (PAMI). We tested 15 human subjects with skin types I--VI using the photoacoustic probe. We also present photoacoustic data for a human subject with vitiligo. Photoacoustic measurement showed melanin in the vitiligo subject was almost completely absent.

Woolly hair nevus with an ipsilateral associated epidermal nevus and additional findings of a white sponge nevus.

PubMed

Legler, Allison; Thomas, Tracy; Zlotoff, Barrett

2010-01-01

We report a case of a 16-year-old male with a woolly hair nevus, an associated ipsilateral epidermal nevus who also had a white plaque on his tongue, clinically diagnosed as a white sponge nevus. The concurrent findings of a white sponge nevus, a woolly hair nevus, and an ipsilateral epidermal nevus, to our knowledge, have not been previously reported.

Epidermal lipid in several cetacean species: ultrastructural observations.

PubMed

Pfeiffer, C J; Jones, F M

1993-09-01

The ultrastructure of the skin of four cetacean species, bottlenose dolphin (Tursiops truncatus) long-finned pilot whale (Globicephala melaena), humpback whale (Megaptera novaeangliae), and fin whale (Balaenoptera physalus) was investigated with particular reference to epidermal lipid. It has already been established that massive lipid reservoirs exist in whales, that the biochemical structures of cetacean lipids are unique, and that unusual intracellular lipid droplets appear in the epidermis. We report here some novel findings on scanning electron microscopic morphology of epidermal lipid, and on its ultrastructural morphology in general and specialized integumentary sites, including species not previously investigated. The intracellular epidermal lipid droplets were more extensive than lamellar body-derived intercellular lipid which is within the interstices of stratum externum cells. The intracellular droplets were spherical, highly variable in size ranging from 0.24 micron to 3.0 microns in diameter, appeared singly or were aggregated in cytoplasmic cavitations, and often were closely associated with epidermal cell nuclei. Evidence for exocytosis of the intracellular droplets was not observed. Significant numbers of intracellular lipid droplets are not observed in the epidermis of terrestrial mammals, so their presence is one of several aquatic specializations of the cetacean integument. Its full significance remains obscure, but it is more probably associated with epidermal cell metabolism than with secretion of lipid.

Evaluation of Carbon Dioxide Laser in the Treatment of Epidermal Nevi

PubMed Central

Bhat, Yasmeen Jabeen; Hassan, Iffat; Sajad, Peerzada; Yaseen, Atiya; Mubashir, Syed; Akhter, Saniya; Wani, Roohi

2016-01-01

Background: Epidermal naevi are benign hamartomatous growths of the skin which are generally asymptomatic with a benign course but are cosmetically disagreeable. Topical treatments such as steroids, calcipotriol, 5 fluorouracil, podophyllin, retinoids and cryotherapy are ineffective and surgical excision results in scar formation. Therapy is often challenging. Aim of the Study: To study the response of carbon dioxide (CO2) laser in the management of epidermal naevi. Subjects and Methods: We conducted a study of CO2 laser treatment on 15 patients of epidermal naevi, eight with verrucous epidermal naevi and seven with sebaceous naevi. A thorough history and examination was done to rule out any epidermal naevus syndrome. The diagnosis was confirmed by histopathology. The number of treatment sessions varied from 1 to 8. Results: Response was excellent (>90% reduction in lesion size) in three patients, very good (>75% reduction) in five, good (>50% reduction in lesion size) in five and poor (<50% reduction in lesion size) in two patients. The side effects were hyperpigmentation and scarring. Long-term follow-up over a period of 10 months showed a recurrence rate of 20%. Conclusion: We conclude that CO2 laser treatment might be an effective option with long-term safety, minimal discomfort and rapid recovery. PMID:27761089

The role of the SCRAMBLED receptor-like kinase in patterning the Arabidopsis root epidermis.

PubMed

Kwak, Su-Hwan; Schiefelbein, John

2007-02-01

Cell-type patterning in the Arabidopsis root epidermis is achieved by a network of transcription factors and influenced by a position-dependent mechanism. The SCRAMBLED receptor-like kinase is required for the normal pattern to arise, but its precise role is not understood. Here we describe genetic and molecular studies to define the spatial and temporal role of SCM in epidermal patterning and its relationship to the transcriptional network. Our results suggest that SCM helps unspecified epidermal cells interpret their position in relation to the underlying cortical cells and establish distinct cell identities. Furthermore, SCM loss-of-function and overexpression analyses suggest that SCM influences cell fate through its negative transcriptional regulation of the WEREWOLF MYB gene in epidermal cells at the H position. We also find that SCM function is specifically required for patterning the post-embryonic root epidermis and not for the analogous epidermal cell-type patterning during embryogenesis or hypocotyl development. In addition, we show that two closely related SCM-like genes in Arabidopsis (SRF1 and SRF3) are not required alone or together with SCM for proper epidermal patterning. These findings help define the developmental and mechanistic role of SCM and suggest a new model for its action in root epidermal cell patterning.

Immortalized N/TERT keratinocytes as an alternative cell source in 3D human epidermal models.

PubMed

Smits, Jos P H; Niehues, Hanna; Rikken, Gijs; van Vlijmen-Willems, Ivonne M J J; van de Zande, Guillaume W H J F; Zeeuwen, Patrick L J M; Schalkwijk, Joost; van den Bogaard, Ellen H

2017-09-19

The strong societal urge to reduce the use of experimental animals, and the biological differences between rodent and human skin, have led to the development of alternative models for healthy and diseased human skin. However, the limited availability of primary keratinocytes to generate such models hampers large-scale implementation of skin models in biomedical, toxicological, and pharmaceutical research. Immortalized cell lines may overcome these issues, however, few immortalized human keratinocyte cell lines are available and most do not form a fully stratified epithelium. In this study we compared two immortalized keratinocyte cell lines (N/TERT1, N/TERT2G) to human primary keratinocytes based on epidermal differentiation, response to inflammatory mediators, and the development of normal and inflammatory human epidermal equivalents (HEEs). Stratum corneum permeability, epidermal morphology, and expression of epidermal differentiation and host defence genes and proteins in N/TERT-HEE cultures was similar to that of primary human keratinocytes. We successfully generated N/TERT-HEEs with psoriasis or atopic dermatitis features and validated these models for drug-screening purposes. We conclude that the N/TERT keratinocyte cell lines are useful substitutes for primary human keratinocytes thereby providing a biologically relevant, unlimited cell source for in vitro studies on epidermal biology, inflammatory skin disease pathogenesis and therapeutics.

Epidermal skin grafting in vitiligo: a pilot study.

PubMed

Janowska, Agata; Dini, Valentina; Panduri, Salvatore; Macchia, Michela; Oranges, Teresa; Romanelli, Marco

2016-09-01

Vitiligo is a multifactorial acquired dermatosis characterised by achromic or hypochromic macules and by the absence of functioning melanocytes. Treatment depends on the extent of the affected areas and on disease activity. Surgical techniques have proven to be effective in stable cases but can be time-consuming and, in some cases, aesthetically unsatisfying or painful for the patients. The aim of the study was to assess the clinical safety and effectiveness of a new automatic epidermal skin harvesting device in patients with stable localised vitiligo over a minimum 12-month period. This new system (CELLUTOME™ Epidermal Harvesting System, KCI, an ACELITY Company, San Antonio, TX) is a commercially available epidermal skin harvesting system that can be used without local anaesthesia or other pre-treatments and has been shown to have low rates of donor site morbidity. Epidermal skin grafts can used in patients with acute and hard to heal chronic wounds, burns and stable vitiligo. The use of advanced therapies may improve the quality of life, have cost benefits and accelerate re-pigmentation of patients with vitiligo. In our preliminary study, this system was seen to be a safe and efficacious means of harvesting epidermal micrografts containing melanocytes for use in patients with stable vitiligo unresponsive to standard therapies. © 2016 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Postzygotic HRAS mutation causing both keratinocytic epidermal nevus and thymoma and associated with bone dysplasia and hypophosphatemia due to elevated FGF23.

PubMed

Avitan-Hersh, Emily; Tatur, Sameh; Indelman, Margarita; Gepstein, Vardit; Shreter, Roni; Hershkovitz, Dov; Brick, Riva; Bergman, Reuven; Tiosano, Dov

2014-01-01

Epidermal nevus syndrome is a rare group of disorders characterized by the combination of congenital epidermal nevi and extracutaneous features, including skeletal, neurological, ocular, and other systemic findings. We report a case of keratinocytic epidermal nevus syndrome that includes a thymoma, bone dysplasia, and hypophosphatemia with elevated fibroblast growth factor 23 (FGF23) levels associated with postzygotic HRAS mutation. A 14-year-old boy was admitted due to recent limping. The physical examination revealed multiple right-sided linear epidermal nevi along Blaschko's lines. Magnetic resonance imaging showed cystic lesions in cervical bones and thymoma, and x-ray examination showed cystic lesions in the hands. Biochemical studies demonstrated severe hypophosphatemia, normocalcemia, high normal PTH, low 25-hydroxyvitamin D and low 1,25-dihydroxyvitamin D levels. The serum FGF23 C-terminal level was normal, but the intact FGF23 level was found to be elevated. Genetic evaluation revealed a heterozygote mutation in the HRAS gene in both the keratinocytic epidermal nevus and thymoma but not in DNA extracted from blood lymphocytes, thus establishing the mutation as postzygotic. Postzygotic mutations in HRAS lead to elevation of FGF23 levels, as found in mutated PHEX, FGF23, DMP1, and ENPP1 genes, which lead to hypophosphatemia. An identical postzygotic HRAS mutation was shown to be present in both keratinocytic epidermal nevus and thymoma and to be associated with bone lesions and hypophosphatemia due to elevated FGF23 levels. These may all be related to the HRAS mutation.

Epidermal growth factor- and hepatocyte growth factor-receptor activity in serum-free cultures of human hepatocytes.

PubMed

Runge, D M; Runge, D; Dorko, K; Pisarov, L A; Leckel, K; Kostrubsky, V E; Thomas, D; Strom, S C; Michalopoulos, G K

1999-02-01

Serum-free primary cultures of hepatocytes are a useful tool to study factors triggering hepatocyte proliferation and regeneration. We have developed a chemically defined serum-free system that allows human hepatocyte proliferation in the presence of epidermal growth factor and hepatocyte growth factor. DNA synthesis and accumulation were determined by [3H]thymidine incorporation and fluorometry, respectively. Western blot analyses and co-immunoprecipitations were used to investigate the association of proteins involved in epidermal growth factor and hepatocyte growth factor activation and signaling: epidermal growth factor receptor, hepatocyte growth factor receptor (MET), urokinase-type plasminogen activator and its receptor, and a member of the signal transducer and activator of transcription family, STAT-3. Primary human hepatocytes proliferated under serum-free conditions in a chemically defined medium for up to 12 days. Epidermal growth factor-receptor and MET were present and functional, decreasing over time. MET, urokinase-type plasminogen activator and urokinase-type plasminogen activator receptor co-precipitated to varying degrees during the culture period. STAT-3 co-precipitated with epidermal growth factor-receptor and MET to varying degrees. Proliferation of human hepatocytes can improve by modification of a chemically defined medium originally used for rat hepatocyte cultures. In these long-term cultures of human hepatocytes, hepatocyte growth factor and epidermal growth factor can stimulate growth and differentiation by interacting with their receptors and initiating downstream signaling. This involves complex formation of the receptors with other plasma membrane components for MET (urokinase-type plasminogen activator in context of its receptor) and activation of STAT-3 for both receptors.

Simple preparation of plant epidermal tissue for laser microdissection and downstream quantitative proteome and carbohydrate analysis

PubMed Central

Falter, Christian; Ellinger, Dorothea; von Hülsen, Behrend; Heim, René; Voigt, Christian A.

2015-01-01

The outwardly directed cell wall and associated plasma membrane of epidermal cells represent the first layers of plant defense against intruding pathogens. Cell wall modifications and the formation of defense structures at sites of attempted pathogen penetration are decisive for plant defense. A precise isolation of these stress-induced structures would allow a specific analysis of regulatory mechanism and cell wall adaption. However, methods for large-scale epidermal tissue preparation from the model plant Arabidopsis thaliana, which would allow proteome and cell wall analysis of complete, laser-microdissected epidermal defense structures, have not been provided. We developed the adhesive tape – liquid cover glass technique (ACT) for simple leaf epidermis preparation from A. thaliana, which is also applicable on grass leaves. This method is compatible with subsequent staining techniques to visualize stress-related cell wall structures, which were precisely isolated from the epidermal tissue layer by laser microdissection (LM) coupled to laser pressure catapulting. We successfully demonstrated that these specific epidermal tissue samples could be used for quantitative downstream proteome and cell wall analysis. The development of the ACT for simple leaf epidermis preparation and the compatibility to LM and downstream quantitative analysis opens new possibilities in the precise examination of stress- and pathogen-related cell wall structures in epidermal cells. Because the developed tissue processing is also applicable on A. thaliana, well-established, model pathosystems that include the interaction with powdery mildews can be studied to determine principal regulatory mechanisms in plant–microbe interaction with their potential outreach into crop breeding. PMID:25870605

Simple preparation of plant epidermal tissue for laser microdissection and downstream quantitative proteome and carbohydrate analysis.

PubMed

Falter, Christian; Ellinger, Dorothea; von Hülsen, Behrend; Heim, René; Voigt, Christian A

2015-01-01

The outwardly directed cell wall and associated plasma membrane of epidermal cells represent the first layers of plant defense against intruding pathogens. Cell wall modifications and the formation of defense structures at sites of attempted pathogen penetration are decisive for plant defense. A precise isolation of these stress-induced structures would allow a specific analysis of regulatory mechanism and cell wall adaption. However, methods for large-scale epidermal tissue preparation from the model plant Arabidopsis thaliana, which would allow proteome and cell wall analysis of complete, laser-microdissected epidermal defense structures, have not been provided. We developed the adhesive tape - liquid cover glass technique (ACT) for simple leaf epidermis preparation from A. thaliana, which is also applicable on grass leaves. This method is compatible with subsequent staining techniques to visualize stress-related cell wall structures, which were precisely isolated from the epidermal tissue layer by laser microdissection (LM) coupled to laser pressure catapulting. We successfully demonstrated that these specific epidermal tissue samples could be used for quantitative downstream proteome and cell wall analysis. The development of the ACT for simple leaf epidermis preparation and the compatibility to LM and downstream quantitative analysis opens new possibilities in the precise examination of stress- and pathogen-related cell wall structures in epidermal cells. Because the developed tissue processing is also applicable on A. thaliana, well-established, model pathosystems that include the interaction with powdery mildews can be studied to determine principal regulatory mechanisms in plant-microbe interaction with their potential outreach into crop breeding.

Selective Matrix (Hyaluronan) Interaction with CD44 and RhoGTPase Signaling Promotes Keratinocyte Functions and Overcomes Age-related Epidermal Dysfunction

PubMed Central

Bourguignon, Lilly Y.W.; Wong, Gabriel; Xia, Weiliang; Man, Mao-Qiang; Holleran, Walter M.; Elias, Peter M.

2013-01-01

Background Mouse epidermal chronologic aging is closely associated with aberrant matrix (hyaluronan, HA) -size distribution/production and impaired keratinocyte proliferation/differentiation, leading to a marked thinning of the epidermis with functional consequence that causes a slower recovery of permeability barrier function. Objective The goal of this study is to demonstrate mechanism-based, corrective therapeutic strategies using topical applications of small HA (HAS) and/or large HA (HAL) [or a sequential small HA (HAS) and large HA(HAL) (HAs-»HAL) treatment] as well as RhoGTPase signaling perturbation agents to regulate HA/CD44-mediated signaling, thereby restoring normal epidermal function, and permeability barrier homeostasis in aged mouse skin. Methods A number of biochemical, cell biological/molecular, pharmacological and physiological approaches were used to investigate matrix HA-CD44-mediated RhoGTPase signaling in regulating epidermal functions and skin aging. Results In this study we demonstrated that topical application of small HA (HAS) promotes keratinocyte proliferation and increases skin thickness, while it fails to upregulate keratinocyte differentiation or permeability barrier repair in aged mouse skin. In contrast, large HA (HAL) induces only minimal changes in keratinocyte proliferation and skin thickness, but restores keratinocyte differentiation and improves permeability barrier function in aged epidermis. Since neither HAS nor HAL corrects these epidermal defects in aged CD44 knock-out mice, CD44 likely mediates HA-associated epidermal functions in aged mouse skin. Finally, blockade of Rho-kinase activity with Y27632 or protein kinase-Nγ activity with Ro31-8220 significantly decreased the HA (HAS or HAL)-mediated changes in epidermal function in aged mouse skin. Conclusion The results of our study show first that HA application of different sizes regulates epidermal proliferation, differentiation and barrier function in aged mouse skin. Second, manipulation of matrix (HA) interaction with CD44 and RhoGTPase signaling could provide further novel therapeutic approaches that could be targeted for the treatment of various aging-related skin disorders. PMID:23790635

The effect of distant metastases sites on survival in de novo stage-IV breast cancer: A SEER database analysis.

PubMed

Wu, San-Gang; Li, Hui; Tang, Li-Ying; Sun, Jia-Yuan; Zhang, Wen-Wen; Li, Feng-Yan; Chen, Yong-Xiong; He, Zhen-Yu

2017-06-01

To investigate the effect of distant metastases sites on survival in patients with de novo stage-IV breast cancer. From 2010 to 2013, patients with a diagnosis of de novo stage-IV breast cancer were identified using the Surveillance, Epidemiology, and End Results database. Univariate and multivariate Cox regression analyses were performed to analyze the effect of distant metastases sites on breast cancer-specific survival and overall survival. A total of 7575 patients were identified. The most common metastatic sites were bone, followed by lung, liver, and brain. Patients with hormone receptor+/human epidermal growth factor receptor 2- and hormone receptor+/human epidermal growth factor receptor 2+ status were more prone to bone metastases. Lung and brain metastases were common in hormone receptor-/human epidermal growth factor receptor 2+ and hormone receptor-/human epidermal growth factor receptor 2- subtypes, and patients with hormone receptor+/ human epidermal growth factor receptor 2+ and hormone receptor-/human epidermal growth factor receptor 2+ subtypes were more prone to liver metastases. Patients with liver and brain metastases had unfavorable prognosis for breast cancer-specific survival and overall survival, whereas bone and lung metastases had no effect on patient survival in multivariate analyses. The hormone receptor-/human epidermal growth factor receptor 2- subtype conferred a significantly poorer outcome in terms of breast cancer-specific survival and overall survival. hormone receptor+/human epidermal growth factor receptor 2+ disease was associated with the best prognosis in terms of breast cancer-specific survival and overall survival. Patients with liver and brain metastases were more likely to experience poor prognosis for breast cancer-specific survival and overall survival by various breast cancer subtypes. Distant metastases sites have differential impact on clinical outcomes in stage-IV breast cancer. Follow-up screening for brain and liver metastases might be effective in improving breast cancer-specific survival and overall survival.

Epidermal Hydration Is Improved by Enhanced Ceramide Metabolism in Aged C57BL/6J Mice After Dietary Supplementation of Royal Jelly.

PubMed

Jeon, Sanghun; Cho, Yunhi

2015-09-01

Epidermal hydration is maintained by the epidermal lipid barrier, of which ceramide (Cer) is the major constituent. We examined the dietary effect of royal jelly (RJ) on epidermal hydration in aged mice. Altered Cer metabolism was further determined by measuring epidermal levels of individual Cer, glucosylceramide (GC), and sphingomyelin (SM) species, and of Cer-metabolizing enzymes. Aged C57BL/6J mice were fed a control diet (group AGED) or diets with 1% RJ harvested from two different areas (groups AGED+RJ1:AGED + RJ2) for 16 weeks. Aged C57BL/6J mice with no dietary intervention (the control group: group C) represented the onset of aging. In group AGED, epidermal levels of hydration, Cer1/2/5/6/7, GC-A/B/C/D, SM1/2/3, and β-glucocerebrosidase (GCase) protein, an enzyme of GC hydrolysis for Cer generation, were lower than in group C; these levels, as well as those of Cer3/4 and acidic sphingomyelinase (aSMase) protein, an enzyme of SM hydrolysis for Cer generation, were higher in group AGED + RJ1 than in group AGED. Despite increases in GC-B, SM1/2/3, and serine palmitoyltransferase2 protein, an enzyme of de novo Cer synthesis, in group AGED + RJ2 to levels higher than in group AGED, epidermal levels of hydration, Cer1-7, GC-A/C/D, GCase, and aSMase proteins were similar in these two groups. Expression of GCase and aSMase mRNAs, and of Cer synthase3 and ceramidase proteins, enzymes of de novo Cer synthesis and degradation, did not differ among groups. Dietary RJ1 improved epidermal hydration by enhancing Cer metabolism with increased levels of all Cer, GC, and SM species, and of GCase and aSMase proteins.

SU-E-I-16: Scan Length Dependency of the Radial Dose Distribution in a Long Polyethylene Cylinder

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bakalyar, D; McKenney, S; Feng, W

Purpose: The area-averaged dose in the central plane of a long cylinder following a CT scan depends upon the radial dose distribution and the length of the scan. The ICRU/TG200 phantom, a polyethylene cylinder 30 cm in diameter and 60 cm long, was the subject of this study. The purpose was to develop an analytic function that could determine the dose for a scan length L at any point in the central plane of this phantom. Methods: Monte Carlo calculations were performed on a simulated ICRU/TG200 phantom under conditions of cylindrically symmetric conditions of irradiation. Thus, the radial dose distributionmore » function must be an even function that accounts for two competing effects: The direct beam makes its weakest contribution at the center while the scatter begins abruptly at the outer radius and grows as the center is approached. The scatter contribution also increases with scan length with the increase approaching its limiting value at the periphery faster than along the central axis. An analytic function was developed that fit the data and possessed these features. Results: Symmetry and continuity dictate a local extremum at the center which is a minimum for the ICRU/TG200 phantom. The relative depth of the minimum decreases as the scan length grows and an absolute maximum can occur between the center and outer edge of the cylinders. As the scan length grows, the relative dip in the center decreases so that for very long scan lengths, the dose profile is relatively flat. Conclusion: An analytic function characterizes the radial and scan length dependency of dose for long cylindrical phantoms. The function can be integrated with the results expressed in closed form. One use for this is to help determine average dose distribution over the central cylinder plane for any scan length.« less

α-Xylosidase plays essential roles in xyloglucan remodelling, maintenance of cell wall integrity, and seed germination in Arabidopsis thaliana.

PubMed

Shigeyama, Takuma; Watanabe, Asuka; Tokuchi, Konatsu; Toh, Shigeo; Sakurai, Naoki; Shibuya, Naoto; Kawakami, Naoto

2016-10-01

Regulation and maintenance of cell wall physical properties are crucial for plant growth and environmental response. In the germination process, hypocotyl cell expansion and endosperm weakening are prerequisites for dicot seeds to complete germination. We have identified the Arabidopsis mutant thermoinhibition-resistant germination 1 (trg1), which has reduced seed dormancy and insensitivity to unfavourable conditions for germination owing to a loss-of-function mutation of TRG1/XYL1, which encodes an α-xylosidase. Compared to those of wild type, the elongating stem of trg1 showed significantly lower viscoelasticity, and the fruit epidermal cells were longitudinally shorter and horizontally enlarged. Actively growing tissues of trg1 over-accumulated free xyloglucan oligosaccharides (XGOs), and the seed cell wall had xyloglucan with a greatly reduced molecular weight. These observations suggest that XGOs reduce xyloglucan size by serving as an acceptor in transglycosylation and eventually enhancing cell wall loosening. TRG1/XYL1 gene expression was abundant in growing wild-type organs and tissues but relatively low in cells at most actively elongating part of the tissues, suggesting that α-xylosidase contributes to maintaining the mechanical integrity of the primary cell wall in the growing and pre-growing tissues. In germinating seeds of trg1, expression of genes encoding specific abscisic acid and gibberellin metabolism enzymes was altered in accordance with the aberrant germination phenotype. Thus, cell wall integrity could affect seed germination not only directly through the physical properties of the cell wall but also indirectly through the regulation of hormone gene expression. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Circus Family of Stars (Artist's Concept)

NASA Technical Reports Server (NTRS)

2005-01-01

[figure removed for brevity, see original site] Quick Time Movie for PIA03521 Circus Family of Stars

This artist's animation shows the clockwork-like orbits of a triple-star system called HD 188753, which was discovered to harbor a gas giant, or 'hot Jupiter,' planet. The planet zips around the system's main star (yellow, center) every 3.3 days, while the main star is circled every 25.7 years by a dancing duo of stars (yellow and orange, outer orbit). The star pair is locked in a 156-day orbit.

This eccentric star family is a cramped bunch; the distance between the main star and the outer pair of stars is about the same as that between the Sun and Saturn. Though multiple-star systems like this one are common in the universe, astronomers were surprised to find a planet living in such tight quarters.

One reason for the surprise has to do with theories of hot Jupiter formation. Astronomers believe that these planets begin life at the outer fringes of their stars, in thick dusty disks called protoplanetary disks, before migrating inward. The discovery of a world under three suns throws this theory into question. As seen in this animation, there is not much room at this system's outer edges for a hot Jupiter to grow.

The discovery was made using the Keck I telescope atop Mauna Kea mountain in Hawaii. The triple-star system is located 149 light-years away in the constellation Cygnus.

The sizes and orbital periods in the animation are not shown to scale. The relative motions are shown with respect to the main star.

The early evolution of protostellar disks

NASA Technical Reports Server (NTRS)

Stahler, Steven W.; Korycansky, D. G.; Brothers, Maxwell J.; Touma, Jihad

1994-01-01

We consider the origin and intital growth of the disks that form around protostars during the collapse of rotating molecular cloud cores. These disks are assumed to be inviscid and pressure free, and to have masses small compared to those of their central stars. We find that there exist three distinct components-an outer disk, in which shocked gas moves with comparable azimuthal and radical velocities; and inner disk, where material follows nearly circular orbits, but spirals slowly toward the star because of the drag exerted by adjacent onfalling matter, and a turbulent ring adjoining the first two regions. Early in the evolution, i.e., soon after infalling matter begins to miss the star, only the outer disk is present, and the total mass acceration rate onto the protostar is undiminished. Once the outer disk boundary grows to more than 2.9 times the stellar radius, first the ring, and then the inner disk appear. Thereafter, the radii of all three components expand as t(exp 3). The mass of the ring increase with time and is always 13% of the total mass that has fallen from the cloud. Concurrently with the buildup of the inner disk and ring, the accretion rate onto the star falls off. However, the protostellar mass continue to rise, asymptotically as t(exp 1/4). We calculated the radiated flux from the inner and outer disk components due to the release of gravitational potential energy. The flux from the inner disk is dominant and rises steeply toward the stellar surface. We also determine the surface temperature of the inner disk as a function of radius. The total disk luminosity decreases slowly with time, while the contributions from the ring and inner disk both fall as t(exp -2).

Ultrathin epidermal strain sensor based on an elastomer nanosheet with an inkjet-printed conductive polymer

NASA Astrophysics Data System (ADS)

Tetsu, Yuma; Yamagishi, Kento; Kato, Akira; Matsumoto, Yuya; Tsukune, Mariko; Kobayashi, Yo; Fujie, Masakatsu G.; Takeoka, Shinji; Fujie, Toshinori

2017-08-01

To minimize the interference that skin-contact strain sensors cause natural skin deformation, physical conformability to the epidermal structure is critical. Here, we developed an ultrathin strain sensor made from poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) inkjet-printed on a polystyrene-polybutadiene-polystyrene (SBS) nanosheet. The sensor, whose total thickness and gauge factor were ˜1 µm and 0.73 ± 0.10, respectively, deeply conformed to the epidermal structure and successfully detected the small skin strain (˜2%) while interfering minimally with the natural deformation of the skin. Such an epidermal strain sensor will open a new avenue for precisely detecting the motion of human skin and artificial soft-robotic skin.

Multiple Sub-Epidermal Calcified Nodule Mimicking Eruptive Xanthoma: A Case Report and Review of the Literature

PubMed Central

Ozuguz, Pinar; Balta, Ilknur; Bozkurt, Ozlem; Unverdi, Hatice; Dostbil, Ahmet

2013-01-01

Sub-epidermal calcified nodule (SCN) is an uncommon form of idiopathic calcinosis. It usually occurs in children, particularly in the head and neck region, presenting as a solitary, painless, yellow-white nodule with papillomatous features. These lesions occur twice as common in males compared with females. The pathogenesis is uncertain, but the clinical and histological features of this lesion are distinctive. We report a case of 22-year-old man with multiple nodules bilaterally located on the dorsum of hands simulating eruptive xanthoma. Histopathological examination of one of the excised lesion confirmed the diagnosis showing epidermal and sub-epidermal deposition of calcium. This paper presents a review of the literature and adds a new case of SCN. PMID:24082201

A novel cream formulation containing nicotinamide 4%, arbutin 3%, bisabolol 1%, and retinaldehyde 0.05% for treatment of epidermal melasma.

PubMed

Crocco, Elisete I; Veasey, John V; Boin, Maria F; Lellis, Rute F; Alves, Renata O

2015-11-01

Epidermal melasma is a common hyperpigmentation disorder that can be challenging to treat. Although current treatment options for melasma are limited, topical skin-lightening preparations have widely been used as alternatives to hydroquinone. In this prospective, single-arm, open-label study, treatment of epidermal melasma with a novel cream formulation containing nicotinamide 4%, arbutin 3%, bisabolol 1%, and retinaldehyde 0.05% was associated with reductions in Melasma Area and Severity Index (MASI) scores as well as total melasma surface area as measured by medical imaging software. Treatment outcomes including tolerance and safety profiles as well as patient satisfaction and product appreciation showed this novel cosmetic compound may be valuable in the treatment of epidermal melasma.

Management of Patients with Atopic Dermatitis: The Role of Emollient Therapy

PubMed Central

Catherine Mack Correa, M.; Nebus, Judith

2012-01-01

Atopic dermatitis is a common inflammatory skin disorder that afflicts a growing number of young children. Genetic, immune, and environmental factors interact in a complex fashion to contribute to disease expression. The compromised stratum corneum found in atopic dermatitis leads to skin barrier dysfunction, which results in aggravation of symptoms by aeroallergens, microbes, and other insults. Infants—whose immune system and epidermal barrier are still developing—display a higher frequency of atopic dermatitis. Management of patients with atopic dermatitis includes maintaining optimal skin care, avoiding allergic triggers, and routinely using emollients to maintain a hydrated stratum corneum and to improve barrier function. Flares of atopic dermatitis are often managed with courses of topical corticosteroids or calcineurin inhibitors. This paper discusses the role of emollients in the management of atopic dermatitis, with particular emphasis on infants and young children. PMID:23008699

Root Hairs

PubMed Central

Grierson, Claire; Nielsen, Erik; Ketelaarc, Tijs; Schiefelbein, John

2014-01-01

Roots hairs are cylindrical extensions of root epidermal cells that are important for acquisition of nutrients, microbe interactions, and plant anchorage. The molecular mechanisms involved in the specification, differentiation, and physiology of root hairs in Arabidopsis are reviewed here. Root hair specification in Arabidopsis is determined by position-dependent signaling and molecular feedback loops causing differential accumulation of a WD-bHLH-Myb transcriptional complex. The initiation of root hairs is dependent on the RHD6 bHLH gene family and auxin to define the site of outgrowth. Root hair elongation relies on polarized cell expansion at the growing tip, which involves multiple integrated processes including cell secretion, endomembrane trafficking, cytoskeletal organization, and cell wall modifications. The study of root hair biology in Arabidopsis has provided a model cell type for insights into many aspects of plant development and cell biology. PMID:24982600

[Acceptance and Commitment Therapy in the Treatment of Chronic Disease].

PubMed

Kuba, Katharina; Weißflog, Gregor

2017-12-01

Acceptance and Commitment Therapy (ACT) is an intervention representing a transdiagnostic and contextual approach that assumes that psychological suffering is caused by experiential avoidance. The primary intention of ACT is not to eliminate symptoms and to treat mental disorders. Instead, ACT aims to increase psychological flexibility, i. e. to broaden the repertoire of cognitions and behaviors when facing inner and outer aversive events or experiences. Psychological flexibility can be enhanced by working with the 6 core components of the ACT model. Experience-focused methods like metaphors and exercises for acceptance play a crucial role in the therapeutic work. In short, with ACT patients can learn: ▪ that rigid and inflexible attempts to fight aversive experience are problematic ▪ a mindful experience of inner and outer experience ▪ to differentiate between unchangeable and changeable events (acceptance) ▪ to identify values or respectively life goals and to behave in a way that is consistent with them (commitment)The therapeutic focus of ACT is to create a balance between acceptance and behavioral change consistent with chosen values. Chronic diseases are often associated with aversive inner and outer experiences. A growing number of studies support the efficacy of ACT. There is evidence that ACT can increase psychological flexibility and potentially also lead to better self-management within the context of chronic somatic diseases. © Georg Thieme Verlag KG Stuttgart · New York.

Effect of extrusion rate on morphology of Kaolin/PolyEtherSulfone (PESf) membrane precursor

NASA Astrophysics Data System (ADS)

Misaran, M. S.; Sarbatly, R.; Bono, A.; Rahman, M. M.

2016-11-01

This study aims to investigate the influence of apparent viscosity induced by spinneret geometry and extrusion rate on morphology of Kaolin/PESf hollow fiber membranes. Different extrusion rates at two different rheology properties were introduced on a straight and conical spinneret resulting in various shear rates. The hollow fiber membrane precursors were spun using the wet spinning method to decouple the effect of shear and elongation stress due to gravity stretched drawing. The morphology of the spun hollow fiber was observed under Scanning Electron Microscope (SEM) and the overall porosity were measured using mercury intrusion porosimeter. Shear rate and apparent viscosity at the tip of the spinneret annulus were simulated using a computational fluid dynamics package; solidworks floworks. Simulation data shows that extrusion rate increment increases the shear rate at the spinneret wall which in turn reduce the apparent viscosity; consistent with a non Newtonian shear thinning fluid behavior. Thus, the outer finger-like region grows as the shear rate increases. Also, overall porosity of hollow fiber membrane decreases with extrusion rate increment which is caused by better molecular orientation; resulting in denser hollow fiber membrane. Thin outer finger-like region is achieved at low shear experience of 109.55 s-1 via a straight spinneret. Increasing the extrusion rate; thus shear rate will cause outer finger-like region growth which is not desirable in a separation process.

Shifting baselines in the Ems Dollard estuary: A comparison across three decades reveals changing benthic communities

NASA Astrophysics Data System (ADS)

Compton, Tanya J.; Holthuijsen, Sander; Mulder, Maarten; van Arkel, Maarten; Schaars, Loran Kleine; Koolhaas, Anita; Dekinga, Anne; ten Horn, Job; Luttikhuizen, Pieternella C.; van der Meer, Jaap; Piersma, Theunis; van der Veer, Henk W.

2017-09-01

At a time when there is a growing discussion about the natural state of estuaries, a comparison of macrozoobenthos communities from two surveys conducted 30 years apart in the Ems Dollard estuary, in the eastern Wadden Sea, The Netherlands, provides a unique opportunity to compare changes over time. As expected, our comparison revealed a gradient in species composition from land (the Dollard) to sea (the Outer Ems) at both points in time, with brackish species in the Dollard and more marine species in the Outer Ems (Wadden Sea). Total richness increased over time; however, this mainly reflected the immigration of new species and sampling differences. In the Dollard, total biomass declined over time, most likely reflecting de-eutrophication in this area. Strikingly, at the meeting point between the sea and the brackish Dollard, i.e. the Inner Ems, the community composition changed from one dominated by bivalves (1970s) to one dominated by worms (since 2009). This change involved a reduction in total biomass, mainly of Mya arenaria, and immigration of polychaete worms (Marenzellaria viridis and Alitta succinea). In the Outer Ems, an increase in total biomass was observed, associated with the recent successful recruitment of Cerastoderma edule. This comparison highlights that historical data provides useful insights at large spatial scales. However, a full understanding of the complex dynamics of estuaries requires an analysis of continuous long-term monitoring series.

A theoretical approach to the relationship between wettability and surface microstructures of epidermal cells and structured cuticles of flower petals

PubMed Central

Taneda, Haruhiko; Watanabe-Taneda, Ayako; Chhetry, Rita; Ikeda, Hiroshi

2015-01-01

Background and Aims The epidermal surface of a flower petal is composed of convex cells covered with a structured cuticle, and the roughness of the surface is related to the wettability of the petal. If the surface remains wet for an excessive amount of time the attractiveness of the petal to floral visitors may be impaired, and adhesion of pathogens may be promoted. However, it remains unclear how the epidermal cells and structured cuticle contribute to surface wettability of a petal. Methods By considering the additive effects of the epidermal cells and structured cuticle on petal wettability, a thermodynamic model was developed to predict the wetting mode and contact angle of a water droplet at a minimum free energy. Quantitative relationships between petal wettability and the geometries of the epidermal cells and the structured cuticle were then estimated. Measurements of contact angles and anatomical traits of petals were made on seven herbaceous species commonly found in alpine habitats in eastern Nepal, and the measured wettability values were compared with those predicted by the model using the measured geometries of the epidermal cells and structured cuticles. Key Results The model indicated that surface wettability depends on the height and interval between cuticular steps, and on a height-to-width ratio for epidermal cells if a thick hydrophobic cuticle layer covers the surface. For a petal epidermis consisting of lenticular cells, a repellent surface results when the cuticular step height is greater than 0·85 µm and the height-to-width ratio of the epidermal cells is greater than 0·3. For an epidermis consisting of papillate cells, a height-to-width ratio of greater than 1·1 produces a repellent surface. In contrast, if the surface is covered with a thin cuticle layer, the petal is highly wettable (hydrophilic) irrespective of the roughness of the surface. These predictions were supported by the measurements of petal wettability made on flowers of alpine species. Conclusions The results indicate that surface roughness caused by epidermal cells and a structured cuticle produces a wide range of petal wettability, and that this can be successfully modelled using a thermodynamic approach. PMID:25851137

Indirubin, an acting component of indigo naturalis, inhibits EGFR activation and EGF-induced CDC25B gene expression in epidermal keratinocytes.

PubMed

Hsieh, Wan-Ling; Lin, Yin-Ku; Tsai, Chi-Neu; Wang, Ta-Min; Chen, Tzu-Ya; Pang, Jong-Hwei S

2012-08-01

Topical indigo naturalis ointment is clinically proved to be an effective therapy for plaque-type psoriasis. Indirubin, as the active component of indigo naturalis, inhibits cell proliferation of epidermal keratinocytes. However, the detailed underlying mechanism is not fully understood. To further investigate the anti-proliferating effects of indigo naturalis and indirubin on epidermal keratinocytes. The decreased expression of CDC25B in indigo naturalis- or indirubin-treated epidermal keratinocytes, as revealed by cDNA microarray analysis, was studied. The CDC25B expression was examined under different serum concentrations and compared between primary and immortalized keratinocytes. The activation of EGFR and the effect of EGF on the cell proliferation and CDC25B expression were also investigated in epidermal keratinocytes. RT/real-time PCR and western blot method were used to analyze the CDC25B expression at the mRNA and protein levels, respectively. Indigo naturalis and indirubin were confirmed to down-regulate CDC25B expression significantly at both the mRNA and protein levels. The growth-dependent expression of CDC25B was demonstrated by the increased expression in serum-stimulated and immortalized keratinocytes. The activation of EGF receptor, known to be highly expressed in psoriatic lesions, was inhibited by indigo naturalis or indirubin. The cell proliferation and CDC25B expression of epidermal keratinocytes were induced by EGF alone and confirmed to be inhibited by indigo naturalis or indirubin. Except being a common therapeutic target in various cancers, CDC25B also plays an important role in the hyper-proliferation of epidermal keratinocytes which can be suppressed by anti-psoriatic drug indigo naturalis and its component, indirubin. Copyright © 2012 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Delphinidin, a dietary antioxidant, induces human epidermal keratinocyte differentiation but not apoptosis: studies in submerged and three-dimensional epidermal equivalent models.

PubMed

Chamcheu, Jean Christopher; Afaq, Farrukh; Syed, Deeba N; Siddiqui, Imtiaz A; Adhami, Vaqar M; Khan, Naghma; Singh, Sohinderjit; Boylan, Brendan T; Wood, Gary S; Mukhtar, Hasan

2013-05-01

Delphinidin (Del), [3,5,7,3'-,4'-,5'-hexahydroxyflavylium], an anthocyanidin and a potent antioxidant abundantly found in pigmented fruits and vegetables exhibits proapoptotic effects in many cancer cells. Here, we determined the effect of Del on growth, apoptosis and differentiation of normal human epidermal keratinocytes (NHEKs) in vitro in submerged cultures and examined its effects in a three-dimensional (3D) epidermal equivalent (EE) model that permits complete differentiation reminiscent of in vivo skin. Treatment of NHEKs with Del (10-40 μm; 24-48 h) significantly enhanced keratinocyte differentiation. In Del-treated cells, there was marked increase in human involucrin (hINV) promoter activity with simultaneous increase in the mRNA and protein expressions of involucrin and other epidermal differentiation markers including procaspase-14 and transglutaminase-1 (TGM1), but without any effect on TGM2. Del treatment of NHEKs was associated with minimal decrease in cell viability, which was not associated with apoptosis as evident by lack of modulation of caspases, apoptosis-related proteins including Bcl-2 family of proteins and poly(ADP-ribose) polymerase cleavage. To establish the in vivo relevance of our observations in submerged cultures, we then validated these effects in a 3D EE model, where Del was found to significantly enhance cornification and increase the protein expression of cornification markers including caspase-14 and keratin 1. For the first time, we show that Del induces epidermal differentiation using an experimental system that closely mimics in vivo human skin. These observations suggest that Del could be a useful agent for dermatoses associated with epidermal barrier defects including aberrant keratinization, hyperproliferation or inflammation observed in skin diseases like psoriasis and ichthyoses. © 2013 John Wiley & Sons A/S.

The DP-1 transcription factor is required for keratinocyte growth and epidermal stratification.

PubMed

Chang, Wing Y; Bryce, Dawn M; D'Souza, Sudhir J A; Dagnino, Lina

2004-12-03

The epidermis is a stratified epithelium constantly replenished through the ability of keratinocytes in its basal layer to proliferate and self-renew. The epidermis arises from a single-cell layer ectoderm during embryogenesis. Large proliferative capacity is central to ectodermal cell and basal keratinocyte function. DP-1, a heterodimeric partner of E2F transcription factors, is highly expressed in the ectoderm and all epidermal layers during embryogenesis. To investigate the role of DP-1 in epidermal morphogenesis, we inhibited DP-1 activity through exogenous expression of a dominant-negative mutant (dnDP-1). Expression of the dnDP-1 mutant interferes with binding of E2F/DP-1 heterodimers to DNA and inhibits DNA replication, as well as cyclin A mRNA and protein expression. Chromatin immunoprecipitation analysis demonstrated that the cyclin A promoter is predominantly bound in proliferating keratinocytes by complexes containing E2F-3 and E2F-4. Thus, the mechanisms of decreased expression of cyclin A in the presence of dnDP-1 seem to involve inactivation of DP-1 complexes containing E2F-3 and E2F-4. To assess the consequences on epidermal morphogenesis of inhibiting DP-1 activity, we expressed dnDP-1 in rat epithelial keratinocytes in organotypic culture and observed that DP-1 inhibition negatively affected stratification of these cells. Likewise, expression of dnDP-1 in embryonic ectoderm explants produced extensive disorganization of subsequently formed epidermal basal and suprabasal layers, interfering with normal epidermal formation. We conclude that DP-1 activity is required for normal epidermal morphogenesis and ectoderm-to-epidermis transition.

Epidermal Th22 and Tc17 cells form a localized disease memory in clinically healed psoriasis.

PubMed

Cheuk, Stanley; Wikén, Maria; Blomqvist, Lennart; Nylén, Susanne; Talme, Toomas; Ståhle, Mona; Eidsmo, Liv

2014-04-01

Psoriasis is a common and chronic inflammatory skin disease in which T cells play a key role. Effective treatment heals the skin without scarring, but typically psoriasis recurs in previously affected areas. A pathogenic memory within the skin has been proposed, but the nature of such site-specific disease memory is unknown. Tissue-resident memory T (TRM) cells have been ascribed a role in immunity after resolved viral skin infections. Because of their localization in the epidermal compartment of the skin, TRM may contribute to tissue pathology during psoriasis. In this study, we investigated whether resolved psoriasis lesions contain TRM cells with the ability to maintain and potentially drive recurrent disease. Three common and effective therapies, narrowband-UVB treatment and long-term biologic treatment systemically inhibiting TNF-α or IL-12/23 signaling were studied. Epidermal T cells were highly activated in psoriasis and a high proportion of CD8 T cells expressed TRM markers. In resolved psoriasis, a population of cutaneous lymphocyte-associated Ag, CCR6, CD103, and IL-23R expressing epidermal CD8 T cells was highly enriched. Epidermal CD8 T cells expressing the TRM marker CD103 responded to ex vivo stimulation with IL-17A production and epidermal CD4 T cells responded with IL-22 production after as long as 6 y of TNF-α inhibition. Our data suggest that epidermal TRM cells are retained in resolved psoriasis and that these cells are capable of producing cytokines with a critical role in psoriasis pathogenesis. We provide a potential mechanism for a site-specific T cell-driven disease memory in psoriasis.

Transgenic expression of human amphiregulin in mouse skin: inflammatory epidermal hyperplasia and enlarged sebaceous glands.

PubMed

Li, Yong; Stoll, Stefan W; Sekhon, Sahil; Talsma, Caroline; Camhi, Maya I; Jones, Jennifer L; Lambert, Sylviane; Marley, Hue; Rittié, Laure; Grachtchouk, Marina; Fritz, Yi; Ward, Nicole L; Elder, James T

2016-03-01

To explore the role of amphiregulin in inflammatory epidermal hyperplasia, we overexpressed human AREG (hAREG) in FVB/N mice using a bovine K5 promoter. A construct containing AREG coding sequences flanked by 5' and 3' untranslated region sequences (AREG-UTR) led to a >10-fold increase in hAREG expression compared to an otherwise-identical construct containing only the coding region (AREG-CDR). AREG-UTR mice developed tousled, greasy fur as well as elongated nails and thickened, erythematous tail skin. No such phenotype was evident in AREG-CDR mice. Histologically, AREG-UTR mice presented with marked epidermal hyperplasia of tail skin (2.1-fold increase in epidermal thickness with a 9.5-fold increase in Ki-67(+) cells) accompanied by significantly increased CD4+ T-cell infiltration. Dorsal skin of AREG-UTR mice manifested lesser but still significant increases in epidermal thickness and keratinocyte hyperplasia. AREG-UTR mice also developed marked and significant sebaceous gland enlargement, with corresponding increases in Ki-67(+) cells. To determine the response of AREG-UTR animals to a pro-inflammatory skin challenge, topical imiquimod (IMQ) or vehicle cream was applied to dorsal and tail skin. IMQ increased dorsal skin thickness similarly in both AREG-UTR and wild type mice (1.7- and 2.2-fold vs vehicle, P < 0.001 each), but had no such effect on tail skin. These results confirm that keratinocyte expression of hAREG elicits inflammatory epidermal hyperplasia, and are consistent with prior reports of tail epidermal hyperplasia and increased sebaceous gland size in mice expressing human epigen. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Caenorhabditis elegans anillin (ani-1) regulates neuroblast cytokinesis and epidermal morphogenesis during embryonic development.

PubMed

Fotopoulos, N; Wernike, D; Chen, Y; Makil, N; Marte, A; Piekny, A

2013-11-01

The formation of tissues is essential for metazoan development. During Caenorhabditis elegans embryogenesis, ventral epidermal cells migrate to encase the ventral surface of the embryo in a layer of epidermis by a process known as ventral enclosure. This process is regulated by guidance cues secreted by the underlying neuroblasts. However, since the cues and their receptors are differentially expressed in multiple cell types, the role of the neuroblasts in ventral enclosure is not fully understood. Furthermore, although F-actin is required for epidermal cell migration, it is not known if nonmuscle myosin is also required. Anillin (ANI-1) is an actin and myosin-binding protein that coordinates actin-myosin contractility in the early embryo. Here, we show that ANI-1 localizes to the cleavage furrows of dividing neuroblasts during mid-embryogenesis and is required for their division. Embryos depleted of ani-1 display a range of ventral enclosure phenotypes, where ventral epidermal cells migrate with similar speeds to control embryos, but contralateral neighbors often fail to meet and are misaligned. The ventral enclosure phenotypes in ani-1 RNAi embryos suggest that the position or shape of neuroblasts is important for directing ventral epidermal cell migration, although does not rule out an autonomous requirement for ani-1 in the epidermal cells. Furthermore, we show that rho-1 and other regulators of nonmuscle myosin activity are required for ventral epidermal cell migration. Interestingly, altering nonmuscle myosin contractility alleviates or strengthens ani-1's ventral enclosure phenotypes. Our findings suggest that ventral enclosure is a complex process that likely relies on inputs from multiple tissues. © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Malignant Change in an Epidermal Cyst Over Gluteal Region

PubMed Central

Kshirsagar, Ashok Y; Sulhyan, Sanjitsingh R; Deshpande, Shradha; Jagtap, SV

2011-01-01

A 72-year-old male presented with a large ulceroproliferative lesion over left gluteal region. After histopathological confirmation of squamous cell carcinoma, the lesion was excised with wide margins. Further histopathological study of the excised specimen revealed the growth arising from an epidermal cyst. Malignant change is a rare, but wellknown complication occurring in an epidermal cyst. The mainstay of treatment consists of wide excision of cancerous lesion with primary reconstruction of the defect. PMID:21572684

Heterotrimeric G Protein Signaling Is Required for Epidermal Cell Death in Rice[W][OA

PubMed Central

Steffens, Bianka; Sauter, Margret

2009-01-01

In rice (Oryza sativa) adventitious root primordia are formed at the nodes as part of normal development. Upon submergence of rice plants, adventitious roots emerge from the nodes preceded by death of epidermal cells above the root primordia. Cell death is induced by ethylene and mediated by hydrogen peroxide (H2O2). Pharmacological experiments indicated that epidermal cell death was dependent on signaling through G proteins. Treatment with GTP-γ-S induced epidermal cell death, whereas GDP-β-S partially inhibited ethylene-induced cell death. The dwarf1 (d1) mutant of rice has repressed expression of the Gα subunit RGA1 of heterotrimeric G protein. In d1 plants, cell death in response to ethylene and H2O2 was nearly completely abolished, indicating that signaling through Gα is essential. Ethylene and H2O2 were previously shown to alter gene expression in epidermal cells that undergo cell death. Transcriptional regulation was not generally affected in the d1 mutant, indicating that altered gene expression is not sufficient to trigger cell death in the absence of Gα. Analysis of genes encoding proteins related to G protein signaling revealed that four small GTPase genes, two GTPase-activating protein genes, and one GDP dissociation inhibitor gene but not RGA1 were differentially expressed in epidermal cells above adventitious roots, indicating that Gα activity is regulated posttranscriptionally. PMID:19656904

Skin Barrier Development Depends on CGI-58 Protein Expression during Late-Stage Keratinocyte Differentiation

PubMed Central

Grond, Susanne; Radner, Franz P.W.; Eichmann, Thomas O.; Kolb, Dagmar; Grabner, Gernot F.; Wolinski, Heimo; Gruber, Robert; Hofer, Peter; Heier, Christoph; Schauer, Silvia; Rülicke, Thomas; Hoefler, Gerald; Schmuth, Matthias; Elias, Peter M.; Lass, Achim; Zechner, Rudolf; Haemmerle, Guenter

2017-01-01

Adipose triglyceride lipase (ATGL) and its coactivator comparative gene identification-58 (CGI-58) are limiting in cellular triglyceride catabolism. Although ATGL deficiency is compatible with normal skin development, mice globally lacking CGI-58 die postnatally and exhibit a severe epidermal permeability barrier defect, which may originate from epidermal and/or peripheral changes in lipid and energy metabolism. Here, we show that epidermis-specific disruption of CGI-58 is sufficient to provoke a defect in the formation of a functional corneocyte lipid envelope linked to impaired ω-O-acylceramide synthesis. As a result, epidermis-specific CGI-58-deficient mice show severe skin dysfunction, arguing for a tissue autonomous cause of disease development. Defective skin permeability barrier formation in global CGI-58-deficient mice could be reversed via transgenic restoration of CGI-58 expression in differentiated but not basal keratinocytes suggesting that CGI-58 is essential for lipid metabolism in suprabasal epidermal layers. The compatibility of ATGL deficiency with normal epidermal function indicated that CGI-58 may stimulate an epidermal triglyceride lipase beyond ATGL required for the adequate provision of fatty acids as a substrate for ω-O-acylceramide synthesis. Pharmacological inhibition of ATGL enzyme activity similarly reduced triglyceride-hydrolytic activities in wild-type and CGI-58 overexpressing epidermis implicating that CGI-58 participates in ω-O-acylceramide biogenesis independent of its role as a coactivator of epidermal triglyceride catabolism. PMID:27725204

Bioengineering a Human Plasma-Based Epidermal Substitute With Efficient Grafting Capacity and High Content in Clonogenic Cells

PubMed Central

Alexaline, Maia M.; Trouillas, Marina; Nivet, Muriel; Bourreau, Emilie; Leclerc, Thomas; Duhamel, Patrick; Martin, Michele T.; Doucet, Christelle; Fortunel, Nicolas O.

2015-01-01

Cultured epithelial autografts (CEAs) produced from a small, healthy skin biopsy represent a lifesaving surgical technique in cases of full-thickness skin burn covering >50% of total body surface area. CEAs also present numerous drawbacks, among them the use of animal proteins and cells, the high fragility of keratinocyte sheets, and the immaturity of the dermal-epidermal junction, leading to heavy cosmetic and functional sequelae. To overcome these weaknesses, we developed a human plasma-based epidermal substitute (hPBES) for epidermal coverage in cases of massive burn, as an alternative to traditional CEA, and set up critical quality controls for preclinical and clinical studies. In this study, phenotypical analyses in conjunction with functional assays (clonal analysis, long-term culture, or in vivo graft) showed that our new substitute fulfills the biological requirements for epidermal regeneration. hPBES keratinocytes showed high potential for cell proliferation and subsequent differentiation similar to healthy skin compared with a well-known reference material, as ascertained by a combination of quality controls. This work highlights the importance of integrating relevant multiparameter quality controls into the bioengineering of new skin substitutes before they reach clinical development. Significance This work involves the development of a new bioengineered epidermal substitute with pertinent functional quality controls. The novelty of this work is based on this quality approach. PMID:25848122

Bioengineering a human plasma-based epidermal substitute with efficient grafting capacity and high content in clonogenic cells.

PubMed

Alexaline, Maia M; Trouillas, Marina; Nivet, Muriel; Bourreau, Emilie; Leclerc, Thomas; Duhamel, Patrick; Martin, Michele T; Doucet, Christelle; Fortunel, Nicolas O; Lataillade, Jean-Jacques

2015-06-01

Cultured epithelial autografts (CEAs) produced from a small, healthy skin biopsy represent a lifesaving surgical technique in cases of full-thickness skin burn covering >50% of total body surface area. CEAs also present numerous drawbacks, among them the use of animal proteins and cells, the high fragility of keratinocyte sheets, and the immaturity of the dermal-epidermal junction, leading to heavy cosmetic and functional sequelae. To overcome these weaknesses, we developed a human plasma-based epidermal substitute (hPBES) for epidermal coverage in cases of massive burn, as an alternative to traditional CEA, and set up critical quality controls for preclinical and clinical studies. In this study, phenotypical analyses in conjunction with functional assays (clonal analysis, long-term culture, or in vivo graft) showed that our new substitute fulfills the biological requirements for epidermal regeneration. hPBES keratinocytes showed high potential for cell proliferation and subsequent differentiation similar to healthy skin compared with a well-known reference material, as ascertained by a combination of quality controls. This work highlights the importance of integrating relevant multiparameter quality controls into the bioengineering of new skin substitutes before they reach clinical development. This work involves the development of a new bioengineered epidermal substitute with pertinent functional quality controls. The novelty of this work is based on this quality approach. ©AlphaMed Press.

Functions of Vγ4 T Cells and Dendritic Epidermal T Cells on Skin Wound Healing

PubMed Central

Li, Yashu; Wu, Jun; Luo, Gaoxing; He, Weifeng

2018-01-01

Wound healing is a complex and dynamic process that progresses through the distinct phases of hemostasis, inflammation, proliferation, and remodeling. Both inflammation and re-epithelialization, in which skin γδ T cells are heavily involved, are required for efficient skin wound healing. Dendritic epidermal T cells (DETCs), which reside in murine epidermis, are activated to secrete epidermal cell growth factors, such as IGF-1 and KGF-1/2, to promote re-epithelialization after skin injury. Epidermal IL-15 is not only required for DETC homeostasis in the intact epidermis but it also facilitates the activation and IGF-1 production of DETC after skin injury. Further, the epidermal expression of IL-15 and IGF-1 constitutes a feedback regulatory loop to promote wound repair. Dermis-resident Vγ4 T cells infiltrate into the epidermis at the wound edges through the CCR6-CCL20 pathway after skin injury and provide a major source of IL-17A, which enhances the production of IL-1β and IL-23 in the epidermis to form a positive feedback loop for the initiation and amplification of local inflammation at the early stages of wound healing. IL-1β and IL-23 suppress the production of IGF-1 by DETCs and, therefore, impede wound healing. A functional loop may exist among Vγ4 T cells, epidermal cells, and DETCs to regulate wound repair.

Characterizing the microcirculation of atopic dermatitis using angiographic optical coherence tomography

NASA Astrophysics Data System (ADS)

Byers, R. A.; Maiti, R.; Danby, S. G.; Pang, E. J.; Mitchell, B.; Carré, M. J.; Lewis, R.; Cork, M. J.; Matcher, S. J.

2017-02-01

Background and Aim: With inflammatory skin conditions such as atopic dermatitis (AD), epidermal thickness is mediated by both pathological hyperplasia and atrophy such as that resulting from corticosteroid treatment. Such changes are likely to influence the depth and shape of the underlying microcirculation. Optical coherence tomography (OCT) provides a non-invasive view into the tissue, however structural measures of epidermal thickness are made challenging due to the lack of a delineated dermal-epidermal junction in AD patients. Instead, angiographic extensions to OCT may allow for direct measurement of vascular depth, potentially presenting a more robust method of estimating the degree of epidermal thickening. Methods and results: To investigate microcirculatory changes within AD patients, volumes of angiographic OCT data were collected from 5 healthy volunteers and compared to that of 5 AD patients. Test sites included the cubital and popliteal fossa, which are commonly affected by AD. Measurements of the capillary loop and superficial arteriolar plexus (SAP) depth were acquired and used to estimate the lower and upper bounds of the undulating basement membrane of the dermal-epidermal junction. Furthermore, quantitative parameters such as vessel density and diameter were derived from each dataset and compared between groups. Capillary loop depth increased slightly for AD patients at the poplitial fossa and SAP was found to be measurably deeper in AD patients at both sites, likely due to localized epidermal hyperplasia.

Protein-protein interactions between SWCNT/chitosan/EGF and EGF receptor: a model of drug delivery system.

PubMed

Rungnim, Chompoonut; Rungrotmongkol, Thanyada; Kungwan, Nawee; Hannongbua, Supot

2016-09-01

Epidermal growth factor (EGF) was used as the targeting ligand to enhance the specificity of a cancer drug delivery system (DDS) via its specific interaction with the EGF receptor (EGFR) that is overexpressed on the surface of some cancer cells. To investigate the intermolecular interaction and binding affinity between the EGF-conjugated DDS and the EGFR, 50 ns molecular dynamics simulations were performed on the complex of tethered EGFR and EGF linked to single-wall carbon nanotube (SWCNT) through a biopolymer chitosan wrapping the tube outer surface (EGFR·EGF-CS-SWCNT-Drug complex), and compared to the EGFR·EGF complex and free EGFR. The binding pattern of the EGF-CS-SWCNT-Drug complex to the EGFR was broadly comparable to that for EGF, but the binding affinity of the EGF-CS-SWCNT-Drug complex was predicted to be somewhat better than that for EGF alone. Additionally, the chitosan chain could prevent undesired interactions of SWCNT at the binding pocket region. Therefore, EGF connected to SWCNT via a chitosan linker is a seemingly good formulation for developing a smart DDS served as part of an alternative cancer therapy.

Immobilized Subpopulations of Leaf Epidermal Mitochondria Mediate PENETRATION2-Dependent Pathogen Entry Control in Arabidopsis

PubMed Central

Klapprodt, Christine; Hause, Gerd; Lipka, Volker

2016-01-01

The atypical myrosinase PENETRATION2 (PEN2) is required for broad-spectrum invasion resistance to filamentous plant pathogens. Previous localization studies suggested PEN2-GFP association with peroxisomes. Here, we show that PEN2 is a tail-anchored protein with dual-membrane targeting to peroxisomes and mitochondria and that PEN2 has the capacity to form homo-oligomer complexes. We demonstrate pathogen-induced recruitment and immobilization of mitochondrial subpopulations at sites of attempted fungal invasion and show that mitochondrial arrest is accompanied by peripheral accumulation of GFP-tagged PEN2. PEN2 substrate production by the cytochrome P450 monooxygenase CYP81F2 is localized to the surface of the endoplasmic reticulum, which focally reorganizes close to the immobilized mitochondria. Exclusive targeting of PEN2 to the outer membrane of mitochondria complements the pen2 mutant phenotype, corroborating the functional importance of the mitochondrial PEN2 protein subpool for controlled local production of PEN2 hydrolysis products at subcellular plant-microbe interaction domains. Moreover, live-cell imaging shows that mitochondria arrested at these domains exhibit a pathogen-induced redox imbalance, which may lead to the production of intracellular signals. PMID:26721862

Nanoparticle orientation to control RNA loading and ligand display on extracellular vesicles for cancer regression

NASA Astrophysics Data System (ADS)

Pi, Fengmei; Binzel, Daniel W.; Lee, Tae Jin; Li, Zhefeng; Sun, Meiyan; Rychahou, Piotr; Li, Hui; Haque, Farzin; Wang, Shaoying; Croce, Carlo M.; Guo, Bin; Evers, B. Mark; Guo, Peixuan

2018-01-01

Nanotechnology offers many benefits, and here we report an advantage of applying RNA nanotechnology for directional control. The orientation of arrow-shaped RNA was altered to control ligand display on extracellular vesicle membranes for specific cell targeting, or to regulate intracellular trafficking of small interfering RNA (siRNA) or microRNA (miRNA). Placing membrane-anchoring cholesterol at the tail of the arrow results in display of RNA aptamer or folate on the outer surface of the extracellular vesicle. In contrast, placing the cholesterol at the arrowhead results in partial loading of RNA nanoparticles into the extracellular vesicles. Taking advantage of the RNA ligand for specific targeting and extracellular vesicles for efficient membrane fusion, the resulting ligand-displaying extracellular vesicles were capable of specific delivery of siRNA to cells, and efficiently blocked tumour growth in three cancer models. Extracellular vesicles displaying an aptamer that binds to prostate-specific membrane antigen, and loaded with survivin siRNA, inhibited prostate cancer xenograft. The same extracellular vesicle instead displaying epidermal growth-factor receptor aptamer inhibited orthotopic breast cancer models. Likewise, survivin siRNA-loaded and folate-displaying extracellular vesicles inhibited patient-derived colorectal cancer xenograft.

Anticancer β-hairpin peptides: membrane-induced folding triggers activity

PubMed Central

Sinthuvanich, Chomdao; Veiga, Ana Salomé; Gupta, Kshitij; Gaspar, Diana; Blumenthal, Robert; Schneider, Joel P.

2012-01-01

Several cationic antimicrobial peptides (AMPs) have recently been shown to display anticancer activity via a mechanism that usually entails the disruption of cancer cell membranes. In this work, we designed an 18-residue anticancer peptide, SVS-1, whose mechanism of action is designed to take advantage of the aberrant lipid composition presented on the outer leaflet of cancer cell membranes, which makes the surface of these cells relatively electronegative relative to non-cancerous cells. SVS-1 is designed to remain unfolded and inactive in aqueous solution but preferentially fold at the surface of cancer cells, adopting an amphiphilic β-hairpin structure capable of membrane disruption. Membrane-induced folding is driven by electrostatic interaction between the peptide and the negatively charge membrane surface of cancer cells. SVS-1 is active against a variety of cancer cell lines such as A549 (lung carcinoma), KB (epidermal carcinoma), MCF-7 (breast carcinoma) and MDA-MB-436 (breast carcinoma). However, the cytotoxicity towards non-cancerous cells having typical membrane compositions, such as HUVEC and erythrocytes, is low. CD spectroscopy, appropriately designed peptide controls, cell-based studies, liposome leakage assays and electron microscopy support the intended mechanism of action, which leads to preferential killing of cancerous cells. PMID:22413859

Differential Growth in Periclinal and Anticlinal Walls during Lobe Formation in Arabidopsis Cotyledon Pavement Cells

PubMed Central

Barton, Deborah A.; Law, Andrew M.K.; Overall, Robyn L.

2015-01-01

Lobe development in the epidermal pavement cells of Arabidopsis thaliana cotyledons and leaves is thought to take place via tip-like growth on the concave side of lobes driven by localized concentrations of actin filaments and associated proteins, with a predicted role for cortical microtubules in establishing the direction of restricted growth at the convex side. We used homologous landmarks fixed to the outer walls of pavement cells and thin-plate spline analysis to demonstrate that lobes form by differential growth of both the anticlinal and periclinal walls. Most lobes formed within the first 24 h of the cotyledons unfurling, during the period of rapid cell expansion. Cortical microtubules adjacent to the periclinal wall were persistently enriched at the convex side of lobes during development where growth was anisotropic and were less concentrated or absent at the concave side where growth was promoted. Alternating microtubule-enriched and microtubule-free zones at the periclinal wall in neighboring cells predicted sites of new lobes. There was no particular arrangement of cortical actin filaments that could predict where lobes would form. However, drug studies demonstrate that both filamentous actin and microtubules are required for lobe formation. PMID:26296967

The Roles of Vitamin C in Skin Health

PubMed Central

Pullar, Juliet M.; Carr, Anitra C.; Vissers, Margreet C. M.

2017-01-01

The primary function of the skin is to act as a barrier against insults from the environment, and its unique structure reflects this. The skin is composed of two layers: the epidermal outer layer is highly cellular and provides the barrier function, and the inner dermal layer ensures strength and elasticity and gives nutritional support to the epidermis. Normal skin contains high concentrations of vitamin C, which supports important and well-known functions, stimulating collagen synthesis and assisting in antioxidant protection against UV-induced photodamage. This knowledge is often used as a rationale for the addition of vitamin C to topical applications, but the efficacy of such treatment, as opposed to optimising dietary vitamin C intake, is poorly understood. This review discusses the potential roles for vitamin C in skin health and summarises the in vitro and in vivo research to date. We compare the efficacy of nutritional intake of vitamin C versus topical application, identify the areas where lack of evidence limits our understanding of the potential benefits of vitamin C on skin health, and suggest which skin properties are most likely to benefit from improved nutritional vitamin C intake. PMID:28805671

ZNF750 is a p63 Target Gene that Induces KLF4 to Drive Terminal Epidermal Differentiation

PubMed Central

Sen, George L.; Boxer, Lisa D.; Webster, Dan E.; Bussat, Rose T.; Qu, Kun; Zarnegar, Brian J.; Johnston, Danielle; Siprashvili, Zurab; Khavari, Paul A.

2012-01-01

SUMMARY Disrupted epidermal differentiation characterizes numerous diseases that impact >25% of the population. In a search for dominant mediators of differentiation, we defined a requirement for ZNF750 in terminal epidermal differentiation. ZNF750 controlled genes mutated in numerous human skin diseases, including FLG, LOR, LCE3B, ALOXE3, and SPINK5. ZNF750 induced progenitor differentiation via an evolutionarily conserved C2H2 zinc finger motif. The epidermal master regulator, p63, bound the ZNF750 promoter and was necessary for its induction. ZNF750 restored differentiation to p63-deficient tissue, suggesting it acts downstream of p63. A search for functionally important ZNF750 targets via analysis of ZNF750-regulated genes identified KLF4, a transcription factor that activates late epidermal differentiation. ZNF750 binds to KLF4 at multiple sites flanking the transcriptional start site and controls its expression. ZNF750 thus directly links a tissue-specifying factor, p63, to an effector of terminal differentiation, KLF4, and represents a potential future target for disorders of this process. PMID:22364861

Neonatal hyperthyroidism impairs epinephrine-provoked secretion of nerve growth factor and epidermal growth factor in mouse saliva.

PubMed

Lakshmanan, J; Landel, C P

1986-07-01

We examined long-term effects of neonatal hyperthyroidism on salivary secretions of nerve growth factor and epidermal growth factor in male and female mice at the age of 31 days. Hyperthyroidism was induced by thyroxine (T4) injections (0.4 microgram/g body weight/day) during days 0-6. Littermate control mice were treated with vehicle. T4 treatment did not alter the amounts of protein secreted into saliva but hormone administration induced alteration in the types of protein secreted. T4 treatment decreased the contents of both nerve growth factor and epidermal growth factor secreted into the saliva. A Sephadex G-200 column chromatographic profile revealed the presence of two distinct nerve growth factor immunoreactive peaks, while epidermal growth factor immunoreactivity predominantly eluted as a single low molecular weight form. T4 treatment did not alter the molecular nature of their secretion, but the treatment decreased their contents. These results indicate an impairment in salivary secretion of nerve growth factor and epidermal growth factor long after T4 treatment has been discontinued.

Leaf Epidermis of the Rheophyte Dyckia brevifolia Baker (Bromeliaceae)

PubMed Central

Lobo, Ghislaine Maria; de Souza, Thaysi Ventura; Voltolini, Caroline Heinig; Reis, Ademir

2013-01-01

Some species of Dyckia Schult. f., including Dyckia brevifolia Baker, are rheophytes that live in the fast-moving water currents of streams and rivers which are subject to frequent flooding, but also period of low water. This study aimed to analyze the leaf epidermis of D. brevifolia in the context of epidermal adaptation to this aquatic plant's rheophytic habitat. The epidermis is uniseriate, and the cuticle is thickened. The inner periclinal and anticlinal walls of the epidermal cells are thickened and lignified. Stomata are tetracytic, located in the depressions in relation to the surrounding epidermal cells, and covered by peltate trichomes. While the epidermal characteristics of D. brevifolia are similar to those of Bromeliaceae species, this species has made particular adaptations of leaf epidermis in response to its rheophytic environment. PMID:23864825

p63 Adjusts Sugar Taste of Epidermal Layers.

PubMed

Amelio, Ivano; Melino, Gerry; Candi, Eleonora

2017-06-01

p63 is a master regulator of epidermal biology, sustaining stemness and renewal capacity of the proliferating keratinocyte compartment. Hamanaka and Mutlu propose that p63 regulates the keratinocyte proliferation/differentiation switch by affecting the cellular glycolic rate through a direct transcriptional regulation of the metabolic enzyme PFKFB3. This finding sheds light on mechanisms underlining p63 function in the skin and suggests a role for energetic metabolism in epidermal biology. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

In Vitro and In Vivo Measurement of Percutaneous Penetration of Low Molecular Weight Toxins of Military Interest

DTIC Science & Technology

1989-12-15

epidermal surfaces were exposed to ambient air (220C) during the entire length of the experiment. Penetration of [3H]PbTx-3 into skin layers and receptor...bathed by the receptor fluid and the epidermal surface was exposed to ambient conditions in an en- vironmental chamber. Temperature and relative...DMSO or water. The epidermal surfaces were exposed to ambient conditions in the environmental chamber. In order to determine if constituents leaching

Treatment and prognosis of breast cancer patients with brain metastases according to intrinsic subtype.

PubMed

Kuba, Sayaka; Ishida, Mayumi; Nakamura, Yoshiaki; Yamanouchi, Kosho; Minami, Shigeki; Taguchi, Kenichi; Eguchi, Susumu; Ohno, Shinji

2014-11-01

How breast cancer subtypes should affect treatment decisions for breast cancer patients with brain metastases is unclear. We analyzed local brain metastases treatments and their outcomes according to subtype in patients with breast cancer and brain metastases. We reviewed records and database information for women treated at the National Kyushu Cancer Center between 2001 and 2010. Patients were divided into three breast cancer subtype groups: Luminal (estrogen receptor positive and/or progesterone receptor positive, but human epidermal growth factor receptor 2 negative); human epidermal growth factor receptor 2 positive and triple negative (estrogen receptor negative, progesterone receptor negative and human epidermal growth factor receptor 2 negative). Of 524 advanced breast cancer patients, we reviewed 65 (12%) with brain metastases and records showing estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status, as well as outcome data; there were 26 (40%) Luminal, 26 (40%) had human epidermal growth factor receptor 2 and 13 (20%) had triple negative subtypes. There was no statistical difference in the number of brain metastases among subtypes; however, rates of stereotactic radiosurgery or surgery for brain metastases differed significantly by subtype (human epidermal growth factor receptor 2: 81%, Luminal: 42% and triple negative: 47%; P = 0.03). Patients having the human epidermal growth factor receptor 2 subtype, a performance status of ≤1 and ≤4 brain metastases, who underwent systemic therapy after brain metastases and underwent stereotactic radiosurgery or surgery, were predicted to have longer overall survival after brain metastases. Multivariate analysis demonstrated that not having systemic therapy and not having the human epidermal growth factor receptor 2 subtype were independent factors associated with an increased risk of death (hazard ratio 2.4, 95% confidence interval 1.01-5.6; P = 0.05 and hazard ratio 2.9, 95% confidence interval 1.5-5.8; P = 0.003, respectively). Our study showed that local brain treatments and prognosis differed by subtype in breast cancer patients with brain metastases. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Selective Ablation of Ctip2/Bcl11b in Epidermal Keratinocytes Triggers Atopic Dermatitis-Like Skin Inflammatory Responses in Adult Mice

PubMed Central

Guha, Gunjan; Li, Shan; Kyrylkova, Kateryna; Kioussi, Chrissa; Leid, Mark; Ganguli-Indra, Gitali; Indra, Arup K.

2012-01-01

Background Ctip2 is crucial for epidermal homeostasis and protective barrier formation in developing mouse embryos. Selective ablation of Ctip2 in epidermis leads to increased transepidermal water loss (TEWL), impaired epidermal proliferation, terminal differentiation, as well as altered lipid composition during development. However, little is known about the role of Ctip2 in skin homeostasis in adult mice. Methodology/Principal Findings To study the role of Ctip2 in adult skin homeostasis, we utilized Ctip2ep−/− mouse model in which Ctip2 is selectively deleted in epidermal keratinocytes. Measurement of TEWL, followed by histological, immunohistochemical, and RT-qPCR analyses revealed an important role of Ctip2 in barrier maintenance and in regulating adult skin homeostasis. We demonstrated that keratinocytic ablation of Ctip2 leads to atopic dermatitis (AD)-like skin inflammation, characterized by alopecia, pruritus and scaling, as well as extensive infiltration of immune cells including T lymphocytes, mast cells, and eosinophils. We observed increased expression of T-helper 2 (Th2)-type cytokines and chemokines in the mutant skin, as well as systemic immune responses that share similarity with human AD patients. Furthermore, we discovered that thymic stromal lymphopoietin (TSLP) expression was significantly upregulated in the mutant epidermis as early as postnatal day 1 and ChIP assay revealed that TSLP is likely a direct transcriptional target of Ctip2 in epidermal keratinocytes. Conclusions/Significance Our data demonstrated a cell-autonomous role of Ctip2 in barrier maintenance and epidermal homeostasis in adult mice skin. We discovered a crucial non-cell autonomous role of keratinocytic Ctip2 in suppressing skin inflammatory responses by regulating the expression of Th2-type cytokines. It is likely that the epidermal hyperproliferation in the Ctip2-lacking epidermis may be secondary to the compensatory response of the adult epidermis that is defective in barrier functions. Our results establish an initiating role of epidermal TSLP in AD pathogenesis via a novel repressive regulatory mechanism enforced by Ctip2. PMID:23284675

Phospholipase D inhibition by hexanal is associated with calcium signal transduction events in raspberry

PubMed Central

Kayal, Walid El; Paliyath, Gopinadhan; Sullivan, J Alan; Subramanian, Jayasankar

2017-01-01

Raspberry (Rubus spp.) is an economically important crop with a restricted growing season and very limited fruit shelf-life due to its extreme tenderness. In order to prolong its shelf life, an aqueous composition containing hexanal as the key active ingredient (HC) was applied as a preharvest spray during fruit development. The effects of HC were assessed using physiological, biochemical and anatomical parameters on the treated fruits and compared with the effects of mock inoculation which lacked hexanal. Sugars and acidity did not show a significant change in response to HC treatment, while the pulling force (the tension required to detach the berry from the receptacle) significantly improved in the HC-treated fruits, compared to control. Scanning electron microscope (SEM) analysis revealed a high correlation between the presence of rigid epidermal hairs and a stronger degree of attachment between berries and their receptacle in the HC treated fruits. Further, electron micrographs also showed abnormal crystalline depositions on the epidermal drupelets of the treated berries. Energy Dispersive X-ray Spectroscopy (EDS) analysis showed those crystals to be largely composed of calcium. HC treatment also resulted in the reduction of transcript level of three phospholipase D genes, as well as altered expression pattern of five members of the annexin gene family, and four calmodulin-binding transcription activators. Quantification of PLD activity showed that hexanal inhibited PLD activity in treated berries. The potential crosstalk between hexanal, phospholipase D activity and calcium and this crosstalk’s role in delaying fruit softening and in prolonging storage life of fruits shelf life is discussed. PMID:29114390

Novel targeted approaches to treating biliary tract cancer: the dual epidermal growth factor receptor and ErbB-2 tyrosine kinase inhibitor NVP-AEE788 is more efficient than the epidermal growth factor receptor inhibitors gefitinib and erlotinib.

PubMed

Wiedmann, Marcus; Feisthammel, Jürgen; Blüthner, Thilo; Tannapfel, Andrea; Kamenz, Thomas; Kluge, Annett; Mössner, Joachim; Caca, Karel

2006-08-01

Aberrant activation of the epidermal growth factor receptor is frequently observed in neoplasia, notably in tumors of epithelial origin. Attempts to treat such tumors with epidermal growth factor receptor antagonists resulted in remarkable success in recent studies. Little is known, however, about the efficacy of this therapy in biliary tract cancer. Protein expression of epidermal growth factor receptor, ErbB-2, and vascular endothelial growth factor receptor-2 was assessed in seven human biliary tract cancer cell lines by immunoblotting. In addition, histological sections from 19 patients with extrahepatic cholangiocarcinoma were analyzed for epidermal growth factor receptor, ErbB-2 and vascular endothelial growth factor receptor-2 expression by immunohistochemistry. Moreover, we sequenced the cDNA products representing the entire epidermal growth factor receptor coding region of the seven cell lines, and searched for genomic epidermal growth factor receptor amplifications and polysomy by fluorescence in-situ hybridization. Cell growth inhibition by gefitinib erlotinib and NVP-AEE788 was studied in vitro by automated cell counting. In addition, the anti-tumoral effect of erlotinib and NVP-AEE788 was studied in a chimeric mouse model. The anti-tumoral drug mechanism in this model was assessed by MIB-1 antibody staining, terminal deoxynucleotidyl transfer-mediated dUTP nick end-labelling assay, von Willebrand factor staining, and immunoblotting for p-p42/44 (p-Erk1/2, p-MAPK) and p-AKT. Immunoblotting revealed expression of epidermal growth factor receptor, ErbB-2, and vascular endothelial growth factor receptor-2 in all biliary tract cancer cell lines. EGFR was detectable in six of 19 (32%) extrahepatic human cholangiocarcinoma tissue samples, ErbB-2 in 16 of 19 (84%), and vascular endothelial growth factor receptor-2 in nine of 19 (47%). Neither epidermal growth factor receptor mutations nor amplifications or polysomy were found in the seven biliary tract cancer cell lines. Gefitinib, erlotinib and NVP-AEE788 caused a significant growth inhibition in vitro; however, there was a significant difference in efficacy (NVP-AEE788>erlotinib>gefitinib). After 14 days of in-vivo treatment, using the chimeric mouse model, tumors had a significantly reduced volume and mass after NVP-AEE788, but not after erlotinib treatment, as compared with placebo. Reduction of proliferation (signalling via the mitogen-activated protein kinase pathway), induction of apoptosis and inhibition of angiogenesis were the main mechanisms of drug action. No significant reduction of anti-apoptotic AKT phosphorylation, however, occurred, which may be a possible counter mechanism of the tumor. Epidermal growth factor receptor, ErbB-2, and vascular endothelial growth factor receptor-2 expression was detectable in biliary tract cancer, and receptor inhibition exerts marked effects on tumor growth in vitro and in vivo, which was strongest for the dual EGFR/ErbB-2 inhibitor NVP-AEE788. Therefore, further clinical evaluation of this new drug for the treatment of biliary tract cancer is recommended.

Toxic epidermal necrolysis and hemophagocytic lymphohistiocytosis: a case report and literature review

PubMed Central

Sniderman, Jonathan D S; Cuvelier, Geoff D E; Veroukis, Stasa; Hansen, Gregory

2015-01-01

Key Clinical Message Diagnostic criteria for hemophagocytic lymphohistiocytosis should be reviewed early in critically ill patients with toxic epidermal necrolysis, multisystem dysfunction, and a deteriorating clinical trajectory. PMID:25767712

Stomatal Opening in Isolated Epidermal Strips of Vicia faba. I. Response to Light and to CO2-free Air 1

PubMed Central

Fischer, R. A.

1968-01-01

This paper reports a consistent and large opening response to light + CO2-free air in living stomata of isolated epidermal strips of Vicia faba. The response was compared to that of non-isolated stomata in leaf discs floating on water; stomatal apertures, guard cell solute potentials and starch contents were similar in the 2 situations. To obtain such stomatal behavior, it was necessary to float epidermal strips on dilute KCl solutions. This suggests that solute uptake is necessary for stomatal opening. The demonstration of normal stomatal behavior in isolated epidermal strips provides a very useful system in which to investigate the mechanism of stomatal opening. It was possible to show independent responses in stomatal aperture to light and to CO2-free air. PMID:16656995

Keratinocytes at the uppermost layer of epidermis might act as sensors of atmospheric pressure change.

PubMed

Denda, Mitsuhiro

2016-01-01

It has long been suggested that climate, especially atmospheric pressure change, can cause health problems ranging from migraine to myocardial infarction. Here, I hypothesize that the sensory system of epidermal keratinocytes mediates the influence of atmospheric pressure change on the human physiological condition. We previously demonstrated that even subtle changes of atmospheric pressure (5-20 hPa) induce elevation of intracellular calcium level in cultured human keratinocytes (excitation of keratinocytes). It is also established that communication occurs between epidermal keratinocytes and peripheral nerve systems. Moreover, various neurotransmitters and hormones that influence multiple systems (nervous, cardiovascular, endocrine, and immune systems) are generated and released from epidermal keratinocytes in response to various external stimuli. Thus, I suggest that pathophysiological phenomena induced by atmospheric pressure changes might be triggered by epidermal keratinocytes.

Production and emission of volatile compounds by petal cells.

PubMed

Baudino, Sylvie; Caissard, Jean-Claude; Bergougnoux, Véronique; Jullien, Frédéric; Magnard, Jean-Louis; Scalliet, Gabriel; Cock, J Mark; Hugueney, Philippe

2007-11-01

We localized the tissues and cells that contribute to scent biosynthesis in scented and non-scented Rosa x hybrida cultivars as part of a detailed cytological analysis of the rose petal. Adaxial petal epidermal cells have a typical conical, papillate shape whereas abaxial petal epidermal cells are flat. Using two different techniques, solid/liquid phase extraction and headspace collection of volatiles, we showed that, in roses, both epidermal layers are capable of producing and emitting scent volatiles, despite the different morphologies of the cells of these two tissues. Moreover, OOMT, an enzyme involved in scent molecule biosynthesis, was localized in both epidermal layers. These results are discussed in view of results found in others species such as Antirrhinum majus, where it has been shown that the adaxial epidermis is the preferential site of scent production and emission.

Production and Emission of Volatile Compounds by Petal Cells

PubMed Central

Caissard, Jean-Claude; Bergougnoux, Véronique; Jullien, Frédéric; Magnard, Jean-Louis; Scalliet, Gabriel; Cock, J Mark; Hugueney, Philippe

2007-01-01

We localized the tissues and cells that contribute to scent biosynthesis in scented and non-scented Rosa × hybrida cultivars as part of a detailed cytological analysis of the rose petal. Adaxial petal epidermal cells have a typical conical, papillate shape whereas abaxial petal epidermal cells are flat. Using two different techniques, solid/liquid phase extraction and headspace collection of volatiles, we showed that, in roses, both epidermal layers are capable of producing and emitting scent volatiles, despite the different morphologies of the cells of these two tissues. Moreover, OOMT, an enzyme involved in scent molecule biosynthesis, was localized in both epidermal layers. These results are discussed in view of results found in others species such as Antirrhinum majus, where it has been shown that the adaxial epidermis is the preferential site of scent production and emission. PMID:19704548

Specific binding of Clostridium perfringens enterotoxin fragment to Claudin-b and modulation of zebrafish epidermal barrier.

PubMed

Zhang, Jingjing; Ni, Chen; Yang, Zhenguo; Piontek, Anna; Chen, Huapu; Wang, Sijie; Fan, Yiming; Qin, Zhihai; Piontek, Joerg

2015-08-01

Claudins (Cldn) are the major components of tight junctions (TJs) sealing the paracellular cleft in tissue barriers of various organs. Zebrafish Cldnb, the homolog of mammalian Cldn4, is expressed at epithelial cell-cell contacts and is important for regulating epidermal permeability. The bacterial toxin Clostridium perfringens enterotoxin (CPE) has been shown to bind to a subset of mammalian Cldns. In this study, we used the Cldn-binding C-terminal domain of CPE (194-319 amino acids, cCPE 194-319 ) to investigate its functional role in modulating zebrafish larval epidermal barriers. In vitro analyses show that cCPE 194-319 removed Cldn4 from epithelial cells and disrupted the monolayer tightness, which could be rescued by the removal of cCPE 194-319. Incubation of zebrafish larvae with cCPE 194-319 removed Cldnb specifically from the epidermal cell membrane. Dye diffusion analysis with 4-kDa fluorescent dextran indicated that the permeability of the epidermal barrier increased due to cCPE 194-319 incubation. Electron microscopic investigation revealed reversible loss of TJ integrity by Cldnb removal. Collectively, these results suggest that cCPE 194-319 could be used as a Cldnb modulator to transiently open the epidermal barrier in zebrafish. In addition, zebrafish might be used as an in vivo system to investigate the capability of cCPE to enhance drug delivery across tissue barriers. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Blunted epidermal L-tryptophan metabolism in vitiligo affects immune response and ROS scavenging by Fenton chemistry, part 1: Epidermal H2O2/ONOO(-)-mediated stress abrogates tryptophan hydroxylase and dopa decarboxylase activities, leading to low serotonin and melatonin levels.

PubMed

Schallreuter, Karin U; Salem, Mohamed A E L; Gibbons, Nick C J; Martinez, Aurora; Slominski, Radomir; Lüdemann, Jürgen; Rokos, Hartmut

2012-06-01

Vitiligo is characterized by a progressive loss of inherited skin color. The cause of the disease is still unknown. To date, there is accumulating in vivo and in vitro evidence for massive oxidative stress via hydrogen peroxide (H(2)O(2)) and peroxynitrite (ONOO(-)) in the skin of affected individuals. Autoimmune etiology is the favored theory. Since depletion of the essential amino acid L-tryptophan (Trp) affects immune response mechanisms, we here looked at epidermal Trp metabolism via tryptophan hydroxylase (TPH) with its downstream cascade, including serotonin and melatonin. Our in situ immunofluorescence and Western blot data reveal significantly lower TPH1 expression in patients with vitiligo. Expression is also low in melanocytes and keratinocytes under in vitro conditions. Although in vivo Fourier transform-Raman spectroscopy proves the presence of 5-hydroxytryptophan, epidermal TPH activity is completely absent. Regulation of TPH via microphthalmia-associated transcription factor and L-type calcium channels is severely affected. Moreover, dopa decarboxylase (DDC) expression is significantly lower, in association with decreased serotonin and melatonin levels. Computer simulation supports H(2)O(2)/ONOO(-)-mediated oxidation/nitration of TPH1 and DDC, affecting, in turn, enzyme functionality. Taken together, our data point to depletion of epidermal Trp by Fenton chemistry and exclude melatonin as a relevant contributor to epidermal redox balance and immune response in vitiligo.

Proposal for an in vivo histopathologic scoring system for skin aging by means of confocal microscopy.

PubMed

Longo, Caterina; Casari, Alice; De Pace, Barbara; Simonazzi, Silvia; Mazzaglia, Giovanna; Pellacani, Giovanni

2013-02-01

Many instrumental devices have been testing in analysing and quantifying the skin aging signs. However, histopathology still remains the only methods that allow a microscopic assessment of the skin. However, a skin biopsy is not feasible in aesthetically critical areas such as the face. Recently, confocal microscopy has been discovered as a noninvasive tool with a nearly histologic resolution. Distinct morphologic confocal aspects on facial skin have been described and correlated with the histopathologic counterparts. In our study we aim to develop an easy to use confocal aging score to quantify the skin aging related signs. A sample of facial skin of fifty volunteers has been subjected to confocal imaging. Combining the previously identified confocal features, three different semi-quantitative scores were calculated: - epidermal disarray score (irregular honeycombed pattern + epidermal thickness + furrow pattern); - epidermal hyperplasia score (mottled pigmentation + extent of polycyclic papillary + epidermal thickness; - collagen score (curled fibers, 2 for huddles of collagen, 1 for coarse collagen structures, and 0 for thin reticulated collagen) The epidermal disarray score showed a stable trend up to 65 years and a dramatic increase in the elderly subjects epidermal. Hyperplasia score was characterized by an ascending trend from younger subjects to middle age. The total collagen score showed a progressive trend with age with a different proportion of distinct collagen type. RCM is a powerful, noninvasive technique that could permit to microscopically quantify the aging signs and to test cosmetic efficacy. © 2012 John Wiley & Sons A/S.

Epidermal protection with cryogen spray cooling during high fluence pulsed dye laser irradiation: an ex vivo study.

PubMed

Tunnell, J W; Nelson, J S; Torres, J H; Anvari, B

2000-01-01

Higher laser fluences than currently used in therapy (5-10 J/cm(2)) are expected to result in more effective treatment of port wine stain (PWS) birthmarks. However, higher incident fluences increase the risk of epidermal damage caused by absorption of light by melanin. Cryogen spray cooling offers an effective method to reduce epidermal injury during laser irradiation. The objective of this study was to determine whether high laser incident fluences (15-30 J/cm(2)) could be used while still protecting the epidermis in ex vivo human skin samples. Non-PWS skin from a human cadaver was irradiated with a Candela ScleroPlus Laser (lambda = 585 nm; pulse duration = 1.5 msec) by using various incident fluences (8-30 J/cm(2)) without and with cryogen spray cooling (refrigerant R-134a; spurt durations: 40-250 msec). Assessment of epidermal damage was based on histologic analysis. Relatively short spurt durations (40-100 msec) protected the epidermis for laser incident fluences comparable to current therapeutic levels (8-10 J/cm(2)). However, longer spurt durations (100-250 msec) increased the fluence threshold for epidermal damage by a factor of three (up to 30 J/cm(2)) in these ex vivo samples. Results of this ex vivo study show that epidermal protection from high laser incident fluences can be achieved by increasing the cryogen spurt duration immediately before pulsed laser exposure. Copyright 2000 Wiley-Liss, Inc.

SABRE is required for stabilization of root hair patterning in Arabidopsis thaliana.

PubMed

Pietra, Stefano; Lang, Patricia; Grebe, Markus

2015-03-01

Patterned differentiation of distinct cell types is essential for the development of multicellular organisms. The root epidermis of Arabidopsis thaliana is composed of alternating files of root hair and non-hair cells and represents a model system for studying the control of cell-fate acquisition. Epidermal cell fate is regulated by a network of genes that translate positional information from the underlying cortical cell layer into a specific pattern of differentiated cells. While much is known about the genes of this network, new players continue to be discovered. Here we show that the SABRE (SAB) gene, known to mediate microtubule organization, anisotropic cell growth and planar polarity, has an effect on root epidermal hair cell patterning. Loss of SAB function results in ectopic root hair formation and destabilizes the expression of cell fate and differentiation markers in the root epidermis, including expression of the WEREWOLF (WER) and GLABRA2 (GL2) genes. Double mutant analysis reveal that wer and caprice (cpc) mutants, defective in core components of the epidermal patterning pathway, genetically interact with sab. This suggests that SAB may act on epidermal patterning upstream of WER and CPC. Hence, we provide evidence for a role of SAB in root epidermal patterning by affecting cell-fate stabilization. Our work opens the door for future studies addressing SAB-dependent functions of the cytoskeleton during root epidermal patterning. © 2014 The Authors. Physiologia Plantarum published by John Wiley & Sons Ltd on behalf of Scandinavian Plant Physiology Society.

Dynamics of keratinocytes in vivo using HO labeling: a sensitive marker of epidermal proliferation state.

PubMed

Hsieh, Elaine A; Chai, Christine M; de Lumen, Benito O; Neese, Richard A; Hellerstein, Marc K

2004-09-01

A heavy water ((2)H(2)O) labeling method recently developed to measure cell proliferation in vivo is applied here to the measurement of murine epidermal cell turnover and to investigate conditions in which keratinocyte proliferation is either inhibited or stimulated. The technique is based on incorporation of (2)H(2)O into the deoxyribose moiety of deoxyribonucleotides in dividing cells. Label incorporation and die-away studies in cells isolated from C57BL/6J mouse epidermis revealed the replacement rate to be 34%-44% per wk (half-life of 1.6-2 wk). The kinetics provided evidence of a non-proliferative subpopulation of cells (10%-15% of the total) within the epidermis. Topical administration of 7,12-dimethylbenz(a)anthracene and 12-O-tetradecanoylphorbol-13-acetate for 3 wk increased epidermal cell proliferation by 55% in SENCAR mice. Topical addition of lunasin, an anti-mitotic agent from soy, decreased epidermal cell proliferation modestly though significantly (16% given alone, 9% given with carcinogens). Caloric restriction (by 33% of energy intake) for 4 wk decreased the epidermal cell proliferation rate by 45% in C57BL/6J mice. In summary, epidermal cell proliferation can be measured in vivo using (2)H(2)O labeling in normal, hyper- and hypo-proliferative conditions. Potential applications of this inherently safe method in humans might include studies of psoriasis, wound healing, chemopreventive agents, and caloric intake.

Nicotinic Acid Receptor Abnormalities in Human Skin Cancer: Implications for a Role in Epidermal Differentiation

PubMed Central

Bermudez, Yira; Benavente, Claudia A.; Meyer, Ralph G.; Coyle, W. Russell; Jacobson, Myron K.; Jacobson, Elaine L.

2011-01-01

Background Chronic UV skin exposure leads to epidermal differentiation defects in humans that can be largely restored by pharmacological doses of nicotinic acid. Nicotinic acid has been identified as a ligand for the human G-protein-coupled receptors GPR109A and GPR109B that signal through Gi-mediated inhibition of adenylyl cyclase. We have examined the expression, cellular distribution, and functionality of GPR109A/B in human skin and skin derived epidermal cells. Results Nicotinic acid increases epidermal differentiation in photodamaged human skin as judged by the terminal differentiation markers caspase 14 and filaggrin. Both GPR109A and GPR109B genes are transcribed in human skin and in epidermal keratinocytes, but expression in dermal fibroblasts is below limits of detection. Receptor transcripts are greatly over-expressed in squamous cell cancers. Receptor protein in normal skin is prominent from the basal through granular layers of the epidermis, with cellular localization more dispersive in the basal layer but predominantly localized at the plasma membrane in more differentiated epidermal layers. In normal human primary and immortalized keratinocytes, nicotinic acid receptors show plasma membrane localization and functional Gi-mediated signaling. In contrast, in a squamous cell carcinoma derived cell line, receptor protein shows a more diffuse cellular localization and the receptors are nearly non-functional. Conclusions The results of these studies justify future genetic and pharmacological intervention studies to define possible specific role(s) of nicotinic acid receptors in human skin homeostasis. PMID:21655214

Difference in light-induced increase in ploidy level and cell size between adaxial and abaxial epidermal pavement cells of Phaseolus vulgaris primary leaves.

PubMed

Kinoshita, Isao; Sanbe, Akiko; Yokomura, E-iti

2008-01-01

Changes in nuclear DNA content and cell size of adaxial and abaxial epidermal pavement cells were investigated using bright light-induced leaf expansion of Phaseolus vulgaris plants. In primary leaves of bean plants grown under high (sunlight) or moderate (ML; photon flux density, 163 micromol m(-2) s(-1)) light, most adaxial epidermal pavement cells had a nucleus with the 4C amount of DNA, whereas most abaxial pavement cells had a 2C nucleus. In contrast, plants grown under low intensity white light (LL; 15 micromol m(-2) s(-1)) for 13 d, when cell proliferation of epidermal pavement cells had already finished, had a 2C nuclear DNA content in most adaxial pavement cells. When these LL-grown plants were transferred to ML, the increase in irradiance raised the frequency of 4C nuclei in adaxial but not in abaxial pavement cells within 4 d. On the other hand, the size of abaxial pavement cells increased by 53% within 4 d of transfer to ML and remained unchanged thereafter, whereas adaxial pavement cells continuously enlarged for 12 d. This suggests that the increase in adaxial cell size after 4 d is supported by the nuclear DNA doubling. The different responses between adaxial and abaxial epidermal cells were not induced by the different light intensity at both surfaces. It was shown that adaxial epidermal cells have a different property than abaxial ones.

microRNA-184 Induces a Commitment Switch to Epidermal Differentiation.

PubMed

Nagosa, Sara; Leesch, Friederike; Putin, Daria; Bhattacharya, Swarnabh; Altshuler, Anna; Serror, Laura; Amitai-Lange, Aya; Nasser, Waseem; Aberdam, Edith; Rouleau, Matthieu; Tattikota, Sudhir G; Poy, Matthew N; Aberdam, Daniel; Shalom-Feuerstein, Ruby

2017-12-12

miR-184 is a highly evolutionary conserved microRNA (miRNA) from fly to human. The importance of miR-184 was underscored by the discovery that point mutations in miR-184 gene led to corneal/lens blinding disease. However, miR-184-related function in vivo remained unclear. Here, we report that the miR-184 knockout mouse model displayed increased p63 expression in line with epidermal hyperplasia, while forced expression of miR-184 by stem/progenitor cells enhanced the Notch pathway and induced epidermal hypoplasia. In line, miR-184 reduced clonogenicity and accelerated differentiation of human epidermal cells. We showed that by directly repressing cytokeratin 15 (K15) and FIH1, miR-184 induces Notch activation and epidermal differentiation. The disease-causing miR-184 C57U mutant failed to repress K15 and FIH1 and to induce Notch activation, suggesting a loss-of-function mechanism. Altogether, we propose that, by targeting K15 and FIH1, miR-184 regulates the transition from proliferation to early differentiation, while mis-expression or mutation in miR-184 results in impaired homeostasis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Silicone sheet containing all-trans retinoic acid and hydroquinone for the treatment of epidermal melanosis.

PubMed

Iida, Shoko; Takushima, Akihiko; Ohura, Norihiko; Sato, Suguru; Kurita, Masakazu; Harii, Kiyonori

2013-08-01

Although bleaching treatment using all-trans retinoic acid (RA) and hydroquinone (HQ) improves epidermal melanosis, the application of two medications and the irritant dermatitis induced by RA inconvenience patients. To overcome these problems, we developed a silicone sheet containing RA and HQ. To compare the efficacy of a silicone sheet containing RA and HQ with that of conventional bleaching treatment. Silicone sheets containing 1% RA and 5% HQ were applied at night during the bleaching phase of 4 weeks, followed by application of sheets containing 5% HQ during the healing phase of 4 weeks. Hemifacial epidermal melanosis, for which the sheets were applied, was compared with a contralateral face which was treated conventionally using RA and HQ. Twenty-four Japanese women who were enrolled in this study and followed up for more than 6 months were analyzed. RA/HQ sheets improved epidermal melanosis, as did the conventional bleaching method, but irritant dermatitis occurred less in patients treated using silicone sheets. RA/HQ sheets, which are easily applied to face skin, can improve epidermal melanosis to the same extent as conventional bleaching. © 2013 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

Epidermal growth factor induction of front–rear polarity and migration in keratinocytes is mediated by integrin-linked kinase and ELMO2

PubMed Central

Ho, Ernest; Dagnino, Lina

2012-01-01

Epidermal growth factor (EGF) is a potent chemotactic and mitogenic factor for epidermal keratinocytes, and these properties are central for normal epidermal regeneration after injury. The involvement of mitogen-activated protein kinases as mediators of the proliferative effects of EGF is well established. However, the molecular mechanisms that mediate motogenic responses to this growth factor are not clearly understood. An obligatory step for forward cell migration is the development of front–rear polarity and formation of lamellipodia at the leading edge. We show that stimulation of epidermal keratinocytes with EGF, but not with other growth factors, induces development of front–rear polarity and directional migration through a pathway that requires integrin-linked kinase (ILK), Engulfment and Cell Motility-2 (ELMO2), integrin β1, and Rac1. Furthermore, EGF induction of front–rear polarity and chemotaxis require the tyrosine kinase activity of the EGF receptor and are mediated by complexes containing active RhoG, ELMO2, and ILK. Our findings reveal a novel link between EGF receptor stimulation, ILK-containing complexes, and activation of small Rho GTPases necessary for acquisition of front–rear polarity and forward movement. PMID:22160594

Epidermal growth factor induction of front-rear polarity and migration in keratinocytes is mediated by integrin-linked kinase and ELMO2.

PubMed

Ho, Ernest; Dagnino, Lina

2012-02-01

Epidermal growth factor (EGF) is a potent chemotactic and mitogenic factor for epidermal keratinocytes, and these properties are central for normal epidermal regeneration after injury. The involvement of mitogen-activated protein kinases as mediators of the proliferative effects of EGF is well established. However, the molecular mechanisms that mediate motogenic responses to this growth factor are not clearly understood. An obligatory step for forward cell migration is the development of front-rear polarity and formation of lamellipodia at the leading edge. We show that stimulation of epidermal keratinocytes with EGF, but not with other growth factors, induces development of front-rear polarity and directional migration through a pathway that requires integrin-linked kinase (ILK), Engulfment and Cell Motility-2 (ELMO2), integrin β1, and Rac1. Furthermore, EGF induction of front-rear polarity and chemotaxis require the tyrosine kinase activity of the EGF receptor and are mediated by complexes containing active RhoG, ELMO2, and ILK. Our findings reveal a novel link between EGF receptor stimulation, ILK-containing complexes, and activation of small Rho GTPases necessary for acquisition of front-rear polarity and forward movement.

Inactivated Wnt signaling in resveratrol-treated epidermal squamous cancer cells and its biological implication

PubMed Central

Liu, Zhi-Li; Li, Hong; Liu, Jia; Wu, Mo-Li; Chen, Xiao-Yan; Liu, Li-Hong; Wang, Qian

2017-01-01

Squamous cell carcinoma (SCC) is the most common epidermal malignancy, and Wnt/β-catenin signaling is frequently activated in SCC. Resveratrol prevents rodent epidermal carcinogenesis, while its effect on human epidermal cancer remains unknown. To address this issue, the impact of resveratrol on the growth and Wnt signaling of skin SCC Colo16 cells were investigated at the cellular and molecular biology levels by flow cytometry, immunocytochemistry, reverse transcription-polymerase chain reaction, western blotting and β-catenin-specific small interfering RNA (siRNA) transfection. Resveratrol (100 µM) suppressed cell growth and induced apoptosis in Colo16 cells. Wnt2 and its downstream genes were downregulated, which was accompanied by increased expression of the Wnt signaling inhibitor Axin2. Transfection with a β-catenin-specific siRNA did not affect cell growth but enhanced the resveratrol susceptibility of Colo16 transfectants. The present results suggest the inhibitory effects of resveratrol on epidermal SCCs and inactivation of Wnt signaling as one of the resveratrol-caused molecular events in Colo16 cells. β-catenin oriented siRNA is insufficient to induce cell crisis, implicating the presence of more critical cancer-associated element(s) as the target in Colo16 cells. PMID:28781663

Modeling the Morphogenesis of Epidermal Tissues on the Surface of a 3D Last

NASA Astrophysics Data System (ADS)

McCleery, W. Tyler; Crews, Sarah M.; Mashburn, David N.; Veldhuis, Jim; Brodland, G. Wayne; Hutson, M. Shane

2014-03-01

Embryogenesis in the fruit fly Drosophila melanogaster is coordinated by the interaction of cells in adjacent tissues. For some events of embryogenesis, e.g., dorsal closure, two-dimensional models have been sufficient to elucidate the relevant cell and tissue mechanics. Here, we describe a new three-dimensional cell-level finite element model for investigating germ band retraction - a morphogenetic event where one epidermal tissue, the germ band, initially wraps around the posterior end of the ellipsoidal embryo. This tissue then retracts with a mechanical assist from contraction of cells in a second epidermal tissue, the amnioserosa. To speed simulation run times and focus on the relevant tissues, we only model epidermal tissue interactions. Epidermal cells are defined as polygons constrained to lie on the surface of the ellipsoidal last, but have adjustable parameters such as edge tensions and cell pressures. Tissue movements are simulated by balancing these dynamic cell-level forces with viscous resistance and allowing cells to exchange neighbors. Our choice of modeling parameters is informed by in vivo measurements of cell-level forces using laser microsurgery. We use this model to investigate the multicellular stress fields in normal and aberrant development.

Role of fibroblast-derived factors in the pathogenesis of melasma.

PubMed

Byun, J W; Park, I S; Choi, G S; Shin, J

2016-08-01

The hyperactive melanocytes present in melasma skin are confined to the epidermis, but epidermal ablation to treat melasma pigmentation may lead to disease recurrence and aggravation. Melanocyte function is regulated by interactions between melanocytes and neighbouring cells such as keratinocytes and fibroblasts. Because melasma skin usually shows dermal changes after exposure to sunlight, we hypothesized that sun-damaged fibroblasts might play a crucial role in the pathogenesis of melasma. In this study, the melanogenic role of primary cultured fibroblasts from human melasma skin was investigated. We explored whether primary cultured fibroblasts from melasma tissue have a melanogenic function on cultured human epidermal melanocytes and artificial skin. The cytokine profile derived from fibroblasts and their effect on the pigmented epidermal equivalents were investigated. Fibroblasts from the melasma lesion and perilesional skin increased melanogenesis in cultured human epidermal melanocytes and in artificial skin. Fibroblasts from the melasma lesion and perilesional skin secreted more nerve growth factor (NGF)-β than those in normal buttock skin, and also increased melanogenesis and the expression level of NGF-β in cultured human epidermal melanocytes and artificial skin. These results suggest that fibroblasts may play a role in melanogenesis and the pathogenesis of melasma. © 2016 British Association of Dermatologists.

Human eccrine sweat gland cells turn into melanin-uptaking keratinocytes in dermo-epidermal skin substitutes.

PubMed

Böttcher-Haberzeth, Sophie; Biedermann, Thomas; Pontiggia, Luca; Braziulis, Erik; Schiestl, Clemens; Hendriks, Bart; Eichhoff, Ossia M; Widmer, Daniel S; Meuli-Simmen, Claudia; Meuli, Martin; Reichmann, Ernst

2013-02-01

Recently, Biedermann et al. (2010) have demonstrated that human eccrine sweat gland cells can develop a multilayered epidermis. The question still remains whether these cells can fulfill exclusive and very specific functional properties of epidermal keratinocytes, such as the incorporation of melanin, a feature absent in sweat gland cells. We added human melanocytes to eccrine sweat gland cells to let them develop into an epidermal analog in vivo. The interaction between melanocytes and sweat gland-derived keratinocytes was investigated. The following results were gained: (1) macroscopically, a pigmentation of the substitutes was seen 2-3 weeks after transplantation; (2) we confirmed the development of a multilayered, stratified epidermis with melanocytes distributed evenly throughout the basal layer; (3) melanocytic dendrites projected to suprabasal layers; and (4) melanin was observed to be integrated into former eccrine sweat gland cells. These skin substitutes were similar or equal to skin substitutes cultured from human epidermal keratinocytes. The only differences observed were a delay in pigmentation and less melanin uptake. These data suggest that eccrine sweat gland cells can form a functional epidermal melanin unit, thereby providing striking evidence that they can assume one of the most characteristic keratinocyte properties.

Immunohistochemical expression of AQP-3 in vitiligo: a new potential guide for disease activity.

PubMed

Hodeib, Abeer; Hegab, Doaa; Rizk, Omnia; Mohammed, Shahdan

2017-08-01

Vitiligo is a depigmenting skin disorder, with disappearance of functioning epidermal melanocytes. Aquaporin-3 (AQP-3) is an aquaglyceroporin expressed in epidermal keratinocytes, where it shares in regulating their proliferation and differentiation, and so it might affect melanocytes indirectly. So far, little is known regarding its possible role in vitiligo. This work aimed to study the changes in immunohistochemical expression of AQP-3 protein in vitiligo to detect its possible role in disease pathogenesis. Skin biopsies were taken from lesional skin of 30 vitiligo patients in addition to 20 normal controls. Epidermal immunohistochemical expression of AQP-3 was assessed as: +3 = strong expression, +2 = moderate, +1= weak and 0= negative expression. AQP-3 was significantly less expressed in vitiligo epidermis than control (P<0.001) with an inverse correlation with Vitiligo Index of Disease Activity (r =-0.505, P=0.004). Reduced epidermal AQP-3 may have a role in impaired melanocyte survival in vitiligo, and might be a potential negative biological marker for vitiligo activity. Larger trials should further elucidate the effect of changes in epidermal AQP-3 expression in development of vitiligo, and that might pave the road for discovering new therapeutic modalities for the disease.

Integration and scaling of UV-B radiation effects on plants: from molecular interactions to whole plant responses.

PubMed

Suchar, Vasile Alexandru; Robberecht, Ronald

2016-07-01

A process based model integrating the effects of UV-B radiation to molecular level processes and their consequences to whole plant growth and development was developed from key parameters in the published literature. Model simulations showed that UV-B radiation induced changes in plant metabolic and/or photosynthesis rates can result in plant growth inhibitions. The costs of effective epidermal UV-B radiation absorptive compounds did not result in any significant changes in plant growth, but any associated metabolic costs effectively reduced the potential plant biomass. The model showed significant interactions between UV-B radiation effects and temperature and any factor leading to inhibition of photosynthetic production or plant growth during the midday, but the effects were not cumulative for all factors. Vegetative growth were significantly delayed in species that do not exhibit reproductive cycles during a growing season, but vegetative growth and reproductive yield in species completing their life cycle in one growing season did not appear to be delayed more than 2-5 days, probably within the natural variability of the life cycles for many species. This is the first model to integrate the effects of increased UV-B radiation through molecular level processes and their consequences to whole plant growth and development.

Hypophosphatemic rickets associated with epidermal nevus syndrome and giant hairy nevus.

PubMed

Chou, Yen-Yin; Chao, Sheau-Chiou; Shiue, Chiou-Nan; Tsai, Wen-Hui; Lin, Shio-Jean

2005-01-01

The association of hypophosphatemic rickets and epidermal nevus or giant hairy nevus is rare. We report two patients with hypophosphatemic rickets, one associated with epidermal nevus syndrome and the other with giant hairy nevus, and describe their clinical features and variable response to treatment. The abnormal nevus tissue may have contributed to the pathogenesis of hypophosphatemic rickets. We did not find a PHEX gene mutation in these two patients, and the mechanism for their rickets may be different from that in X-linked hypophosphatemic rickets.

Mycobacterium longobardum Infection in the Hand.

PubMed

Lekic, Nikola; Rosenberg, Andrew E; Askari, Morad

2018-05-01

Mycobacterium longobardum is a slow-growing, nontuberculous mycobacterium that was first characterized in 2012. We report a case of M. longobardum infection in the right middle finger of a diabetic man. He underwent surgery for a presumed diagnosis of an epidermal inclusion cyst. Molecular diagnosis of the surgical specimens demonstrated M. longobardum through RNA polymerase β-subunit encoding gene sequencing. After surgery, the patient was treated with antibiotics and eventually cured of the infection. To the best of our knowledge, this is only the second reported case of a pathogenic M. longobardum infection worldwide and the first such case in the hand. The purposes of this case study are to alert treating providers to consider nontuberculous mycobacterium infection when an inflammatory process persists, discuss signs and symptoms of the disease, and provide general treatment guidelines. Copyright © 2018 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Analysis of interlaminar stresses in thick composite laminates with and without edge delamination

NASA Technical Reports Server (NTRS)

Whitcomb, J. D.; Raju, I. S.

1984-01-01

The effect of laminate thickness on the interlaminar stresses in rectangular quasi-isotropic laminates under uniform axial strain was studied. Laminates from 8-ply to infinitely thick were analyzed. Thick laminates were synthesized by stacking (45/0/-45/90) ply groups, rather than grouping like plies. Laminates with and without delaminations were studied. In laminates without delaminations, the free-edge interlaminar normal stress distribution in the outer ply groups was insensitive to total laminate thickness. The interlaminar normal stress distribution for the interior ply groups was nearly the same as for an infinitely thick laminate. In contrast, the free-edge inter-laminar shear stress distribution was nearly the same for inner and outer ply groups and was insensitive to laminate thickness. In laminates with delaminations those delaminations near the top and bottom surfaces of a thick laminate have much larger total strain-energy-release rates (G sub t) and mode I-to-total (G sub t/G sub t) ratios than delaminations deep in the interior. Therefore, delaminations can be expected to grow more easily near the surfaces of a laminate than in the interior.

Aligning leadership across systems and organizations to develop a strategic climate for evidence-based practice implementation.

PubMed

Aarons, Gregory A; Ehrhart, Mark G; Farahnak, Lauren R; Sklar, Marisa

2014-01-01

There has been a growing impetus to bridge the gap between basic science discovery, development of evidence-based practices (EBPs), and the availability and delivery of EBPs in order to improve the public health impact of such practices. To capitalize on factors that support implementation and sustainment of EBPs, it is important to consider that health care is delivered within the outer context of public health systems and the inner context of health care organizations and work groups. Leaders play a key role in determining the nature of system and organizational contexts. This article addresses the role of leadership and actions that leaders can take at and across levels in developing a strategic climate for EBP implementation within the outer (i.e., system) and inner (i.e., organization, work group) contexts of health care. Within the framework of Edgar Schein's "climate embedding mechanisms," we describe strategies that leaders at the system, organization, and work group levels can consider and apply to develop strategic climates that support the implementation and sustainment of EBP in health care and allied health care settings.

Biomineral repair of abalone shell apertures.

PubMed

Cusack, Maggie; Guo, Dujiao; Chung, Peter; Kamenos, Nicholas A

2013-08-01

The shell of the gastropod mollusc, abalone, is comprised of nacre with an outer prismatic layer that is composed of either calcite or aragonite or both, depending on the species. A striking characteristic of the abalone shell is the row of apertures along the dorsal margin. As the organism and shell grow, new apertures are formed and the preceding ones are filled in. Detailed investigations, using electron backscatter diffraction, of the infill in three species of abalone: Haliotis asinina, Haliotis gigantea and Haliotis rufescens reveals that, like the shell, the infill is composed mainly of nacre with an outer prismatic layer. The infill prismatic layer has identical mineralogy as the original shell prismatic layer. In H. asinina and H. gigantea, the prismatic layer of the shell and infill are made of aragonite while in H. rufescens both are composed of calcite. Abalone builds the infill material with the same high level of biological control, replicating the structure, mineralogy and crystallographic orientation as for the shell. The infill of abalone apertures presents us with insight into what is, effectively, shell repair. Copyright © 2013 Elsevier Inc. All rights reserved.

Aligning Leadership Across Systems and Organizations to Develop Strategic Climate to for Evidence-Based Practice Implementation

PubMed Central

Aarons, Gregory A.; Farahnak, Lauren R.; Ehrhart, Mark G.; Sklar, Marisa

2015-01-01

There has been a growing impetus to bridge the gap between basic science discovery, development of evidence-based practices (EBPs) and their availability and delivery in order to improve public health impact of such practices. In seeking to capitalize on factors that support implementation and sustainment of EBPs, it is important to consider that healthcare is delivered within the outer context of public health systems, and the inner context of healthcare organizations and workgroups. Leaders have a key role in determining the nature of system and organizational context. This article will addresses the role of leadership across levels in developing strategic climate for EBP implementation within the outer (i.e., system) and inner (i.e., organization, work group) contexts of healthcare. Within the framework of Edgar Schein’s “climate embedding mechanisms,” we describe strategies that leaders at the system, organization, and work group levels can consider and apply to develop a strategic climates that support the implementation and sustainment of EBP in healthcare and allied healthcare settings. PMID:24641560

A Pseudomonas T6SS effector recruits PQS-containing outer membrane vesicles for iron acquisition

PubMed Central

Lin, Jinshui; Zhang, Weipeng; Cheng, Juanli; Yang, Xu; Zhu, Kaixiang; Wang, Yao; Wei, Gehong; Qian, Pei-Yuan; Luo, Zhao-Qing; Shen, Xihui

2017-01-01

Iron sequestration by host proteins contributes to the defence against bacterial pathogens, which need iron for their metabolism and virulence. A Pseudomonas aeruginosa mutant lacking all three known iron acquisition systems retains the ability to grow in media containing iron chelators, suggesting the presence of additional pathways involved in iron uptake. Here we screen P. aeruginosa mutants defective in growth in iron-depleted media and find that gene PA2374, proximal to the type VI secretion system H3 (H3-T6SS), functions synergistically with known iron acquisition systems. PA2374 (which we have renamed TseF) appears to be secreted by H3-T6SS and is incorporated into outer membrane vesicles (OMVs) by directly interacting with the iron-binding Pseudomonas quinolone signal (PQS), a cell–cell signalling compound. TseF facilitates the delivery of OMV-associated iron to bacterial cells by engaging the Fe(III)-pyochelin receptor FptA and the porin OprF. Our results reveal links between type VI secretion, cell–cell signalling and classic siderophore receptors for iron acquisition in P. aeruginosa. PMID:28348410

Epidermal keratinocytes initiate wound healing and pro-inflammatory immune responses following percutaneous schistosome infection

PubMed Central

Bourke, Claire D.; Prendergast, Catriona T.; Sanin, David E.; Oulton, Tate E.; Hall, Rebecca J.; Mountford, Adrian P.

2015-01-01

Keratinocytes constitute the majority of cells in the skin’s epidermis, the first line of defence against percutaneous pathogens. Schistosome larvae (cercariae) actively penetrate the epidermis to establish infection, however the response of keratinocytes to invading cercariae has not been investigated. Here we address the hypothesis that cercariae activate epidermal keratinocytes to promote the development of a pro-inflammatory immune response in the skin. C57BL/6 mice were exposed to Schistosoma mansoni cercariae via each pinna and non-haematopoietic cells isolated from epidermal tissue were characterised for the presence of different keratinocyte sub-sets at 6, 24 and 96 h p.i. We identified an expansion of epidermal keratinocyte precursors (CD45−, CD326−, CD34+) within 24 h of infection relative to naïve animals. Following infection, cells within the precursor population displayed a more differentiated phenotype (α6integrin−) than in uninfected skin. Parallel immunohistochemical analysis of pinnae cryosections showed that this expansion corresponded to an increase in the intensity of CD34 staining, specifically in the basal bulge region of hair follicles of infected mice, and a higher frequency of keratinocyte Ki67+ nuclei in both the hair follicle and interfollicular epidermis. Expression of pro-inflammatory cytokine and stress-associated keratin 6b genes was also transiently upregulated in the epidermal tissue of infected mice. In vitro exposure of keratinocyte precursors isolated from neonatal mouse skin to excretory/secretory antigens released by penetrating cercariae elicited IL-1α and IL-1β production, supporting a role for keratinocyte precursors in initiating cutaneous inflammatory immune responses. Together, these observations indicate that S.mansoni cercariae and their excretory/secretory products act directly upon epidermal keratinocytes, which respond by initiating barrier repair and pro-inflammatory mechanisms similar to those observed in epidermal wound healing. PMID:25575749

Genetic Ablation of CCAAT/Enhancer Binding Protein α in Epidermis Reveals Its Role in Suppression of Epithelial Tumorigenesis

PubMed Central

Loomis, Kari D.; Zhu, Songyun; Yoon, Kyungsil; Johnson, Peter F.; Smart, Robert C.

2013-01-01

CCAAT/enhancer binding protein y (C/EBPα) is a basic leucine zipper transcription factor that inhibits cell cycle progression and regulates differentiation in various cell types. C/EBPα is inactivated by mutation in acute myeloid leukemia (AML) and is considered a human tumor suppressor in AML. Although C/EBPα mutations have not been observed in malignancies other than AML, greatly diminished expression of C/EBPα occurs in numerous human epithelial cancers including lung, liver, endometrial, skin, and breast, suggesting a possible tumor suppressor function. However, direct evidence for C/EBPα as an epithelial tumor suppressor is lacking due to the absence of C/EBPα mutations in epithelial tumors and the lethal effect of C/EBPα deletion in mouse model systems. To examine the function of C/EBPα in epithelial tumor development, an epidermal-specific C/EBPα knockout mouse was generated. The epidermal-specific C/EBPα knockout mice survived and displayed no detectable abnormalities in epidermal keratinocyte proliferation, differentiation, or apoptosis, showing that C/EBPα is dispensable for normal epidermal homeostasis. In spite of this, the epidermal-specific C/EBPα knockout mice were highly susceptible to skin tumor development involving oncogenic Ras. These mice displayed decreased tumor latency and striking increases in tumor incidence, multiplicity, growth rate, and the rate of malignant progression. Mice hemizygous for C/EBPα displayed an intermediate-enhanced tumor phenotype. Our results suggest that decreased expression of C/EBPα contributes to deregulation of tumor cell proliferation. C/EBPα had been proposed to block cell cycle progression through inhibition of E2F activity. We observed that C/EBPα blocked Ras-induced and epidermal growth factor-induced E2F activity in keratinocytes and also blocked Ras-induced cell transformation and cell cycle progression. Our study shows that C/EBPα is dispensable for epidermal homeostasis and provides genetic evidence that C/EBPα is a suppressor of epithelial tumorigenesis. PMID:17638888

A novel DLX3-PKC integrated signaling network drives keratinocyte differentiation.

PubMed

Palazzo, Elisabetta; Kellett, Meghan D; Cataisson, Christophe; Bible, Paul W; Bhattacharya, Shreya; Sun, Hong-Wei; Gormley, Anna C; Yuspa, Stuart H; Morasso, Maria I

2017-04-01

Epidermal homeostasis relies on a well-defined transcriptional control of keratinocyte proliferation and differentiation, which is critical to prevent skin diseases such as atopic dermatitis, psoriasis or cancer. We have recently shown that the homeobox transcription factor DLX3 and the tumor suppressor p53 co-regulate cell cycle-related signaling and that this mechanism is functionally involved in cutaneous squamous cell carcinoma development. Here we show that DLX3 expression and its downstream signaling depend on protein kinase C α (PKCα) activity in skin. We found that following 12-O-tetradecanoyl-phorbol-13-acetate (TPA) topical treatment, DLX3 expression is significantly upregulated in the epidermis and keratinocytes from mice overexpressing PKCα by transgenic targeting (K5-PKCα), resulting in cell cycle block and terminal differentiation. Epidermis lacking DLX3 (DLX3cKO), which is linked to the development of a DLX3-dependent epidermal hyperplasia with hyperkeratosis and dermal leukocyte recruitment, displays enhanced PKCα activation, suggesting a feedback regulation of DLX3 and PKCα. Of particular significance, transcriptional activation of epidermal barrier, antimicrobial peptide and cytokine genes is significantly increased in DLX3cKO skin and further increased by TPA-dependent PKC activation. Furthermore, when inhibiting PKC activity, we show that epidermal thickness, keratinocyte proliferation and inflammatory cell infiltration are reduced and the PKC-DLX3-dependent gene expression signature is normalized. Independently of PKC, DLX3 expression specifically modulates regulatory networks such as Wnt signaling, phosphatase activity and cell adhesion. Chromatin immunoprecipitation sequencing analysis of primary suprabasal keratinocytes showed binding of DLX3 to the proximal promoter regions of genes associated with cell cycle regulation, and of structural proteins and transcription factors involved in epidermal differentiation. These results indicate that Dlx3 potentially regulates a set of crucial genes necessary during the epidermal differentiation process. Altogether, we demonstrate the existence of a robust DLX3-PKCα signaling pathway in keratinocytes that is crucial to epidermal differentiation control and cutaneous homeostasis.

A novel DLX3–PKC integrated signaling network drives keratinocyte differentiation

PubMed Central

Palazzo, Elisabetta; Kellett, Meghan D; Cataisson, Christophe; Bible, Paul W; Bhattacharya, Shreya; Sun, Hong-wei; Gormley, Anna C; Yuspa, Stuart H; Morasso, Maria I

2017-01-01

Epidermal homeostasis relies on a well-defined transcriptional control of keratinocyte proliferation and differentiation, which is critical to prevent skin diseases such as atopic dermatitis, psoriasis or cancer. We have recently shown that the homeobox transcription factor DLX3 and the tumor suppressor p53 co-regulate cell cycle-related signaling and that this mechanism is functionally involved in cutaneous squamous cell carcinoma development. Here we show that DLX3 expression and its downstream signaling depend on protein kinase C α (PKCα) activity in skin. We found that following 12-O-tetradecanoyl-phorbol-13-acetate (TPA) topical treatment, DLX3 expression is significantly upregulated in the epidermis and keratinocytes from mice overexpressing PKCα by transgenic targeting (K5-PKCα), resulting in cell cycle block and terminal differentiation. Epidermis lacking DLX3 (DLX3cKO), which is linked to the development of a DLX3-dependent epidermal hyperplasia with hyperkeratosis and dermal leukocyte recruitment, displays enhanced PKCα activation, suggesting a feedback regulation of DLX3 and PKCα. Of particular significance, transcriptional activation of epidermal barrier, antimicrobial peptide and cytokine genes is significantly increased in DLX3cKO skin and further increased by TPA-dependent PKC activation. Furthermore, when inhibiting PKC activity, we show that epidermal thickness, keratinocyte proliferation and inflammatory cell infiltration are reduced and the PKC-DLX3-dependent gene expression signature is normalized. Independently of PKC, DLX3 expression specifically modulates regulatory networks such as Wnt signaling, phosphatase activity and cell adhesion. Chromatin immunoprecipitation sequencing analysis of primary suprabasal keratinocytes showed binding of DLX3 to the proximal promoter regions of genes associated with cell cycle regulation, and of structural proteins and transcription factors involved in epidermal differentiation. These results indicate that Dlx3 potentially regulates a set of crucial genes necessary during the epidermal differentiation process. Altogether, we demonstrate the existence of a robust DLX3–PKCα signaling pathway in keratinocytes that is crucial to epidermal differentiation control and cutaneous homeostasis. PMID:28186503

Monoclonal Antibody Analysis of Keratin Expression in the Central Nervous System

NASA Astrophysics Data System (ADS)

Franko, Maryellen C.; Gibbs, Clarence J.; Rhoades, Dorothy A.; Carleton Gajdusek, D.

1987-05-01

A monoclonal antibody directed against a 65-kDa brain protein demonstrates an epitope found in keratin from human epidermis. By indirect immunofluorescence, the antibody decorates intracytoplasmic filaments in a subclass of astrocytes and Purkinje cells of adult hamster brain. Double-label immunofluorescence study using antibody to glial fibrillary acidic protein and this antibody reveals the 65-kDa protein to be closely associated with glial filaments in astrocytes of fetal mouse brain cultures. Immunoblot analysis of purified human epidermal keratin and hamster brain homogenate confirms the reactivity of this antibody to epidermal keratin polypeptides. All the major epidermal keratins were recognized by this antibody. It did not bind to the remaining major intermediate filament proteins. These findings suggest that monoclonal antibody 34C9 recognizes a cytoskeletal structure connected with intermediate filaments. In addition, the monoclonal antibody demonstrates that epidermal keratins share an epitope not only among themselves but also with a ``neural keratin.''

Linear Cowden nevus: a new distinct epidermal nevus.

PubMed

Happle, Rudolf

2007-01-01

Within the group of epidermal nevi, a so far nameless disorder is described under the term "linear Cowden nevus". This non-organoid epidermal nevus is caused by loss of heterozygosity, occurring at an early developmental stage in an embryo with a germline PTEN mutation, giving rise to Cowden disease. Hence, linear Cowden nevus can be categorized as a characteristic feature of type 2 segmental Cowden disease. Until now, several authors had mistaken this epidermal nevus as a manifestation of Proteus syndrome. The concept of linear Cowden nevus implies that Proteus syndrome is by no means caused by PTEN mutations. As a clinical difference, linear Cowden nevus is markedly papillomatous and thick, whereas linear Proteus nevus tends to be rather flat. Moreover, the spectrum of possibly associated cutaneous or extracutaneous anomalies differs in the two types of nevi. In conclusion, linear Cowden nevus, that may also be called "linear PTEN nevus", represents a distinct clinicogenetic entity.

Acquired drug resistance conferred by a KRAS gene mutation following the administration of cetuximab: a case report

PubMed Central

2013-01-01

Background Although a number of studies have reported acquired drug resistance due to administration of epidermal growth factor receptor antibody inhibitors, the underlying causes of this phenomenon remain unclear. Case presentation Here we report a case of a 75-year-old man with liver metastasis at 3 years after a successful transverse colectomy to treat KRAS wild-type colorectal cancer. While initial administration of epidermal growth factor receptor inhibitors proved effective, continued use of the same treatment resulted in new peritoneal seeding. An acquired KRAS mutation was found in a resected tissue specimen from one such area. This mutation, possibly caused by administration of epidermal growth factor receptor inhibitors, appears to have conferred drug resistance. Conclusion The present findings suggest that administration of epidermal growth factor receptor inhibitors results in an acquired KRAS mutation that confers drug resistance. PMID:24304820

Particles Growing in Solutions: Depletion Forces and Instability of Homogeneous Particle Distribution

NASA Technical Reports Server (NTRS)

Chernov, A. A.

2004-01-01

Crystallites, droplets and amorphous precipitates growing from supersaturated solution are surrounded by zones, which are depleted with respect to the molecules they are built of. If two such particles of colloidal size are separated by a distance comparable to their diameters, then the depletion within the gap between particles is deeper than that at the outer portion of the particles. This will cause depletion attraction between the particles should appear. It may cause particle coagulation and decay of the originally homogeneous particle distribution into a system of clouds within which the particle number density is higher, separated by the region of the lower number density. Stability criterion, Q = 4 pi R(exp 3)c/3 >> 1, was analytically found along with typical particle density distribution wavevector q = (Q/I)(exp 1/2)(a/R)(exp 1/4). Here, R and a are the particle and molecular radii, respectively, c is the average molecular number density in solution and I is the squared diffusion length covered by a molecule during a typical time characterizing decay of molecular concentration in solution due to consumption of the molecules by the growing particles.

Development of an Advanced Aidman Vision Screener (AVS) for selective assessment of outer and inner laser induced retinal injury

NASA Astrophysics Data System (ADS)

Boye, Michael W.; Zwick, Harry; Stuck, Bruce E.; Edsall, Peter R.; Akers, Andre

2007-02-01

The need for tools that can assist in evaluating visual function is an essential and a growing requirement as lasers on the modern battlefield mature and proliferate. The requirement for rapid and sensitive vision assessment under field conditions produced the USAMRD Aidman Vision Screener (AVS), designed to be used as a field diagnostic tool for assessing laser induced retinal damage. In this paper, we describe additions to the AVS designed to provide a more sensitive assessment of laser induced retinal dysfunction. The AVS incorporates spectral LogMar Acuity targets without and with neural opponent chromatic backgrounds. Thus, it provides the capability of detecting selective photoreceptor damage and its functional consequences at the level of both the outer and inner retina. Modifications to the original achromatic AVS have been implemented to detect selective cone system dysfunction by providing LogMar acuity Landolt rings associated with the peak spectral absorption regions of the S (short), M (middle), and L (long) wavelength cone photoreceptor systems. Evaluation of inner retinal dysfunction associated with selective outer cone damage employs LogMar spectral acuity charts with backgrounds that are neurally opponent. Thus, the AVS provides the capability to assess the effect of selective cone dysfunction on the normal neural balance at the level of the inner retinal interactions. Test and opponent background spectra have been optimized by using color space metrics. A minimal number of three AVS evaluations will be utilized to provide an estimate of false alarm level.

Kozai-Lidov disc instability

NASA Astrophysics Data System (ADS)

Lubow, Stephen H.; Ogilvie, Gordon I.

2017-08-01

Recent results by Martin et al. showed in 3D smoothed particle hydrodynamics simulations that tilted discs in binary systems can be unstable to the development of global, damped Kozai-Lidov (KL) oscillations in which the discs exchange tilt for eccentricity. We investigate the linear stability of KL modes for tilted inviscid discs under the approximations that the disc eccentricity is small and the disc remains flat. By using 1D equations, we are able to probe regimes of large ratios of outer to inner disc edge radii that are realistic for binary systems of hundreds of astronomical unit separations and are not easily probed by multidimensional simulations. For order unity binary mass ratios, KL instability is possible for a window of disc aspect ratios H/r in the outer parts of a disc that roughly scale as (nb/n)2 ≲ H/r ≲ nb/n, for binary orbital frequency nb and orbital frequency n at the disc outer edge. We present a framework for understanding the zones of instability based on the determination of branches of marginally unstable modes. In general, multiple growing eccentric KL modes can be present in a disc. Coplanar apsidal-nodal precession resonances delineate instability branches. We determine the range of tilt angles for unstable modes as a function of disc aspect ratio. Unlike the KL instability for free particles that involves a critical (minimum) tilt angle, disc instability is possible for any non-zero tilt angle depending on the disc aspect ratio.

Dermal penetration and metabolism of p-aminophenol and p-phenylenediamine: application of the EpiDerm human reconstructed epidermis model.

PubMed

Hu, Ting; Bailey, Ruth E; Morrall, Stephen W; Aardema, Marilyn J; Stanley, Lesley A; Skare, Julie A

2009-07-24

To address the provision of the 7th Amendment to the EU Cosmetics Directive banning the use of in vivo genotoxicity assays for testing cosmetic ingredients in 2009, the 3D EpiDerm reconstructed human skin micronucleus assay has been developed. To further characterise the EpiDerm tissue for potential use in genotoxicity testing, we have evaluated the dermal penetration and metabolism of two hair dye ingredients, p-aminophenol (PAP) and p-phenylenediamine (PPD) in this reconstructed epidermis model. When EpiDerm tissue was topically exposed to PAP or PPD for 30 min (typical for a hair dye exposure), the majority (80->90%) of PAP or PPD was excluded from skin tissue and removed by rinsing. After a 23.5h recovery period, the PAP fraction that did penetrate was completely N-acetylated to acetaminophen (APAP). Similarly, 30 min topical application of PPD resulted in the formation of the N-mono- and N,N'-diacetylated metabolites of PPD. These results are consistent with published data on the dermal metabolism of these compounds from other in vitro systems as well as from in vivo studies. When tissue was exposed topically (PAP) or via the culture media (PPD) for 24h, there was good batch-to-batch and donor-to-donor reproducibility in the penetration and metabolism of PAP and PPD. Overall, the results demonstrate that these two aromatic amines are biotransformed in 3D EpiDerm tissue via N-acetylation. Characterising the metabolic capability of EpiDerm tissue is important for the evaluation of this model for use in genotoxicity testing.

Angiopoietin-Like 4 Regulates Epidermal Differentiation

PubMed Central

Huang, Royston-Luke; Goh, Yan Yih; Wang, Xiao Ling; Tang, Mark Boon Yang; Tan, Nguan Soon

2011-01-01

The nuclear hormone receptor PPARβ/δ is integral to efficient wound re-epithelialization and implicated in epidermal maturation. However, the mechanism underlying the latter process of epidermal differentiation remains unclear. We showed that ligand-activated PPARβ/δ indirectly stimulated keratinocyte differentiation, requiring de novo gene transcription and protein translation. Using organotypic skin cultures constructed from PPARβ/δ- and angiopoietin-like 4 (ANGPTL4)-knockdown human keratinocytes, we showed that the expression of ANGPTL4, a PPARβ/δ target gene, is essential for the receptor mediated epidermal differentiation. The pro-differentiation effect of PPARβ/δ agonist GW501516 was also abolished when keratinocytes were co-treated with PPARβ/δ antagonist GSK0660 and similarly in organotypic skin culture incubated with blocking ANGPTL4 monoclonal antibody targeted against the C-terminal fibrinogen-like domain. Our focused real-time PCR gene expression analysis comparing the skin biopsies from wildtype and ANGPTL4-knockout mice confirmed a consistent down-regulation of numerous genes involved in epidermal differentiation and proliferation in the ANGPTL4-knockout skin. We further showed that the deficiency of ANGPTL4 in human keratinocytes and mice skin have diminished expression of various protein kinase C isotypes and phosphorylated transcriptional factor activator protein-1, which are well-established for their roles in keratinocyte differentiation. Chromatin immunoprecipitation confirmed that ANGPTL4 stimulated the activation and binding of JUNB and c-JUN to the promoter region of human involucrin and transglutaminase type 1 genes, respectively. Taken together, we showed that PPARβ/δ regulates epidermal maturation via ANGPTL4-mediated signalling pathway. PMID:21966511

Signalling in the epidermis: the E2F cell cycle regulatory pathway in epidermal morphogenesis, regeneration and transformation.

PubMed

Ivanova, Iordanka A; D'Souza, Sudhir J A; Dagnino, Lina

2005-01-01

The epidermis is the outermost layer in the skin, and it is the first line of defence against the environment. The epidermis also provides a barrier against loss of fluids and electrolytes, which is crucial for life. Essential in the maintenance of this tissue is its ability to continually self-renew and regenerate after injury. These two characteristics are critically dependent on the ability of the principal epidermal cell type, the keratinocyte, to proliferate and to respond to differentiation cues. Indeed, the epidermis is a multilayered tissue composed of keratinocyte stem cells and their differentiated progeny. Central for the control of cell proliferation is the E2F transcription factor regulatory network. This signaling network also includes cyclins, cdk, cdk inhibitors and the retinoblastoma (pRb) family of proteins. The biological importance of the E2F/pRb pathway is emphasized by the fact that a majority of human tumours exhibit alterations that disrupt the ability of pRb proteins to inhibit E2F, leading to permanent activation of the latter. Further, E2F is essential for normal epidermal regeneration after injury. Other member of the E2F signaling pathway are also involved in epidermal development and pathophysiology. Thus, whereas the pRb family of proteins is essential for epidermal morphogenesis, abnormal regulation of cyclins and E2F proteins results in tumorgenesis in this tissue. In this review, we discuss the role of each member of this important growth regulatory network in epidermal formation, homeostasis and carcinogenesis.

Signalling In The Epidermis: The E2f Cell Cycle Regulatory Pathway In Epidermal Morphogenesis, Regeneration And Transformation

PubMed Central

2005-01-01

The epidermis is the outermost layer in the skin, and it is the first line of defence against the environment. The epidermis also provides a barrier against loss of fluids and electrolytes, which is crucial for life. Essential in the maintenance of this tissue is its ability to continually self-renew and regenerate after injury. These two characteristics are critically dependent on the ability of the principal epidermal cell type, the keratinocyte, to proliferate and to respond to differentiation cues. Indeed, the epidermis is a multilayered tissue composed of keratinocyte stem cells and their differentiated progeny. Central for the control of cell proliferation is the E2F transcription factor regulatory network. This signaling network also includes cyclins, cdk, cdk inhibitors and the retinoblastoma (pRb) family of proteins. The biological importance of the E2F/pRb pathway is emphasized by the fact that a majority of human tumours exhibit alterations that disrupt the ability of pRb proteins to inhibit E2F, leading to permanent activation of the latter. Further, E2F is essential for normal epidermal regeneration after injury. Other member of the E2F signaling pathway are also involved in epidermal development and pathophysiology. Thus, whereas the pRb family of proteins is essential for epidermal morphogenesis, abnormal regulation of cyclins and E2F proteins results in tumorgenesis in this tissue. In this review, we discuss the role of each member of this important growth regulatory network in epidermal formation, homeostasis and carcinogenesis. PMID:15951853

Assessment of the human epidermal model LabCyte EPI-MODEL for In vitro skin corrosion testing according to the OECD test guideline 431.

PubMed

Katoh, Masakazu; Hamajima, Fumiyasu; Ogasawara, Takahiro; Hata, Ken-Ichiro

2010-06-01

A new OECD test guideline 431 (TG431) for in vitro skin corrosion tests using human reconstructed skin models was adopted by OECD in 2004. TG431 defines the criteria for the general function and performance of applicable skin models. In order to confirm that the new reconstructed human epidermal model, LabCyte EPI-MODEL is applicable for the skin corrosion test according to TG431, the predictability and repeatability of the model for the skin corrosion test was evaluated. The test was performed according to the test protocol described in TG431. Based on the knowledge that LabCyte EPI-MODEL is an epidermal model as well as EpiDerm, we decided to adopt the the Epiderm prediction model of skin corrosion for the LabCyte EPI-MODEL, using twenty test chemicals (10 corrosive chemicals and 10 non-corrosive chemicals) in the 1(st) stage. The prediction model results showed that the distinction of non-corrosion to corrosion corresponded perfectly. Therefore, it was judged that the prediction model of EpiDerm could be applied to the LabCyte EPI-MODEL. In the 2(nd) stage, the repeatability of this test protocol with the LabCyte EPI-MODEL was examined using twelve chemicals (6 corrosive chemicals and 6 non-corrosive chemicals) that are described in TG431, and these results recognized a high repeatability and accurate predictability. It was concluded that LabCyte EPI-MODEL is applicable for the skin corrosive test protocol according to TG431.

Burn Injury Alters Epidermal Cholinergic Mediators and Increases HMGB1 and Caspase 3 in Autologous Donor Skin and Burn Margin

PubMed Central

Holmes, Casey J.; Plichta, Jennifer K.; Gamelli, Richard L.; Radek, Katherine A.

2016-01-01

Burn wound healing complications, such as graft failure or infection, are a major source of morbidity and mortality in burn patients. The mechanisms by which local burn injury alters epidermal barrier function in autologous donor skin and surrounding burn margin are largely undefined. We hypothesized that defects in the epidermal cholinergic system may impair epidermal barrier function and innate immune responses. The objective was to identify alterations in the epidermal cholinergic pathway, and their downstream targets, associated with inflammation and cell death. We established that protein levels, but not gene expression, of the α7 nicotinic acetylcholine receptor (CHRNA7) were significantly reduced in both donor and burn margin skin. Furthermore, the gene and protein levels of an endogenous allosteric modulator of CHRNA7, secreted mammalian Ly-6/urokinase-type plasminogen activator receptor-related protein-1 (SLURP1) and acetylcholine were significantly elevated in donor and burn margin skin. As downstream proteins of inflammatory and cell death targets of nAChR activation, we found significant elevations in epidermal High Mobility Group Box Protein 1 (HMGB1) and caspase 3 in donor and burn margin skin. Lastly, we employed a novel in vitro keratinocyte burn model to establish that burn injury influences the gene expression of these cholinergic mediators and their downstream targets. These results indicate that defects in cholinergic mediators and inflammatory/apoptotic molecules in donor and burn margin skin may directly contribute to graft failure or infection in burn patients. PMID:27648692

The retention and distribution of parent, alkylated, and N/O/S-containing polycyclic aromatic hydrocarbons on the epidermal tissue of mangrove seedlings.

PubMed

Li, Ruilong; Tan, Huadong; Zhu, Yaxian; Zhang, Yong

2017-07-01

The polycyclic aromatic hydrocarbons (PAHs) located on the epidermal tissues showed distinctive toxic effects to root, while the retention and distribution of PAHs on mangrove seedlings poorly understood. Our results confirmed that the partition coefficients (K f ) of the PAHs retained on the epidermal tissue of mangrove roots, such as Kandelia obovata, Avicennia marina and Aegiceras corniculatum, were much higher than the Poaceae plants roots, for example wheat and maize (Wild et al., 2005). Moreover, to the parent and alkyl PAHs, a well negative correlation was observed between the surface polarity of these three species of mangrove root and the K f values (p < 0.05). To the N/O/S containing PAHs, these relationships were not obviously due to existing of the π-π, n-π interactions and hydrogen bonding between the N/O/S-containing PAHs and epidermal tissues. The PAHs retained on these three species of mangrove root epidermal tissues formed larger clusters than that of on Poaceae plants, such as wheat and maize (Wild et al., 2005) due to the limitation of the suberization of the root exodermis and endodermis. After exposure of 30 d, rhizo- and endophytic bacteria degraded parts of the N/O/S-containing PAHs to medium-lifetime fluorescence substances. To our knowledge, this is the first time to assess the retention of PAHs on the epidermal tissue of mangrove root, which will improve our understanding of the root uptake PAHs process. Copyright © 2017 Elsevier Ltd. All rights reserved.

Protocol for a systematic review of the efficacy of epidermal grafting for wound healing.

PubMed

Kanapathy, Muholan; Smith, Oliver J; Hachach-Haram, Nadine; Bystrzonowski, Nicola; Mosahebi, Afshin; Richards, Toby

2016-06-03

Autologous skin grafting is an important modality for wound coverage; however, it can result in donor site morbidity. Epidermal grafting is an emerging option to overcome this challenge. Furthermore, it can be done in an outpatient setting with minimal or no pain. To date, the evidence on the efficacy of this technique for wound healing has yet to be outlined. We aim to synthesise the current evidence on epidermal grafting for wound healing to establish the efficacy of this technique. We will conduct a comprehensive search in the MEDLINE, EMBASE, and CENTRAL databases (up to May 2016) to identify studies on epidermal grafting for wound healing. We will include any primary studies (excluding case reports or case series lesser than three patients) or systematic reviews of such studies to assess the outcome of epidermal grafting for wound healing either on its own or compared to other methods. The expected primary outcome measures are the efficacy of epidermal grafting for wound healing (measured by the proportion of wounds healed at 6 weeks) and the mean wound-healing time (time for complete re-epithelialisation). Secondary outcome measures are the mean donor site-healing time, need for anaesthesia, costs associated with resource use, health-related quality of life, and proportion of patients with adverse event. Subgroup analysis will be performed for the proportions of wounds healed based on wound aetiology. This is a timely systematic review, and the finding of this systematic review is expected to guide research and clinical practice aimed at improving wound care. PROSPERO CRD42016033051.

DEFECTIVE KERNEL1 (DEK1) Regulates Cell Walls in the Leaf Epidermis1

PubMed Central

Amanda, Dhika; Ingram, Gwyneth C.

2016-01-01

The plant epidermis is crucial to survival, regulating interactions with the environment and controlling plant growth. The phytocalpain DEFECTIVE KERNEL1 (DEK1) is a master regulator of epidermal differentiation and maintenance, acting upstream of epidermis-specific transcription factors, and is required for correct cell adhesion. It is currently unclear how changes in DEK1 lead to cellular defects in the epidermis and the pathways through which DEK1 acts. We have combined growth kinematic studies, cell wall analysis, and transcriptional analysis of genes downstream of DEK1 to determine the cause of phenotypic changes observed in DEK1-modulated lines of Arabidopsis (Arabidopsis thaliana). We reveal a novel role for DEK1 in the regulation of leaf epidermal cell wall structure. Lines with altered DEK1 activity have epidermis-specific changes in the thickness and polysaccharide composition of cell walls that likely underlie the loss of adhesion between epidermal cells in plants with reduced levels of DEK1 and changes in leaf shape and size in plants constitutively overexpressing the active CALPAIN domain of DEK1. Calpain-overexpressing plants also have increased levels of cellulose and pectins in epidermal cell walls, and this is correlated with the expression of several cell wall-related genes, linking transcriptional regulation downstream of DEK1 with cellular effects. These findings significantly advance our understanding of the role of the epidermal cell walls in growth regulation and establish a new role for DEK1 in pathways regulating epidermal cell wall deposition and remodeling. PMID:27756823

Glucose transporter member 1 is involved in UVB-induced epidermal hyperplasia by enhancing proliferation in epidermal keratinocytes.

PubMed

Tochio, Takumi; Tanaka, Hiroshi; Nakata, Satoru

2013-03-01

Glucose transporter member 1 (GLUT-1) is one of the major facilitated glucose transporters and contributes to the promotion of keratinocyte proliferation in psoriasis and carcinogenic lesions. In this study, we postulate that GLUT-1 is involved in ultraviolet B (UVB)-induced epidermal hyperplasia. The purpose of this study is to investigate the possible role of GLUT-1 in UVB-induced hyperplasia. The effects of UVB on GLUT-1 expression levels were investigated in in vitro and in vivo studies. In addition, the involvement of epidermal growth factor (EGF) and hypoxia inducible factor-1 alpha (HIF-1α), transcriptional factors for GLUT-1, in GLUT-1-related events were investigated. GLUT-1 mRNA and its protein levels were markedly increased by UVB irradiation in HaCaT cells. In in vivo studies, a strong immunofluorescence signal of GLUT-1 was clearly observed around the basal layer of the epidermis, which proliferated excessively by UVB irradiation. In HaCaT cells, EGF mRNA and its protein levels were markedly increased by UVB irradiation, and then the GLUT-1 mRNA level was significantly increased by treatment with EGF. Additionally, the upregulation of GLUT-1 by both UVB irradiation and treatment with EGF was significantly suppressed by transfection with HIF-1α siRNA. We conclude that GLUT-1 is involved in UVB-induced epidermal hyperplasia by enhancing proliferation of epidermal basal cells, and the GLUT-1-related event might be regulated by an increase in HIF-1α stimulated by EGF. © 2013 The International Society of Dermatology.

Fractional sunburn threshold UVR doses generate equivalent vitamin D and DNA damage in skin types I-VI, but with epidermal DNA damage gradient correlated to skin darkness.

PubMed

Shih, Barbara B; Farrar, Mark D; Cooke, Marcus S; Osman, Joanne; Langton, Abigail K; Kift, Richard; Webb, Ann R; Berry, Jacqueline L; Watson, Rachel E B; Vail, Andy; de Gruijl, Frank R; Rhodes, Lesley E

2018-05-03

Public health guidance recommends limiting sun-exposure to sub-sunburn levels, but it's unknown whether these can gain vitamin D (for musculoskeletal health) whilst avoiding epidermal DNA damage (initiates skin cancer). Well-characterised healthy humans of all skin types (I-VI; lightest to darkest skin) were exposed to a low dose-series of solar simulated UVR of 20-80% their individual sunburn threshold dose (minimal erythemal dose, MED). Significant UVR dose-responses were seen for serum 25(OH)D and whole epidermal CPD, with as little as 0.2 MED concurrently producing 25(OH)D and CPD. Notably, fractional MEDs generated equivalent levels of whole epidermal CPD and 25(OH)D across all skin types. Crucially, we demonstrated an epidermal gradient of CPD formation strongly correlated with skin darkness (r=0.74; P<0.0001), which reflected melanin content and revealed increasing protection across the skin types, ranging from darkest skin, where high CPD levels occurred superficially with none in the germinative basal layer, through to lightest skin where CPD were induced evenly across the epidermal depth. Darker skin people can be encouraged to utilise sub-sunburn UVR-exposure to enhance their vitamin D. In lighter skin people, basal cell damage occurs concurrent with vitamin D synthesis at exquisitely low UVR levels, providing an explanation for their high skin cancer incidence; greater caution is required. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Biaxially stretchable supercapacitors based on the buckled hybrid fiber electrode array

NASA Astrophysics Data System (ADS)

Zhang, Nan; Zhou, Weiya; Zhang, Qiang; Luan, Pingshan; Cai, Le; Yang, Feng; Zhang, Xiao; Fan, Qingxia; Zhou, Wenbin; Xiao, Zhuojian; Gu, Xiaogang; Chen, Huiliang; Li, Kewei; Xiao, Shiqi; Wang, Yanchun; Liu, Huaping; Xie, Sishen

2015-07-01

In order to meet the growing need for smart bionic devices and epidermal electronic systems, biaxial stretchability is essential for energy storage units. Based on porous single-walled carbon nanotube/poly(3,4-ethylenedioxythiophene) (SWCNT/PEDOT) hybrid fiber, we designed and fabricated a biaxially stretchable supercapacitor, which possesses a unique configuration of the parallel buckled hybrid fiber array. Owing to the reticulate SWCNT film and the improved fabrication technique, the hybrid fiber retained its porous architecture both outwardly and inwardly, manifesting a superior capacity of 215 F g-1. H3PO4-polyvinyl alcohol gel with an optimized component ratio was introduced as both binder and stretchable electrolyte, which contributed to the regularity and stability of the buckled fiber array. The buckled structure and the quasi one-dimensional character of the fibers endow the supercapacitor with 100% stretchability along all directions. In addition, the supercapacitor exhibited good transparency, as well as excellent electrochemical properties and stability after being stretched 5000 times.In order to meet the growing need for smart bionic devices and epidermal electronic systems, biaxial stretchability is essential for energy storage units. Based on porous single-walled carbon nanotube/poly(3,4-ethylenedioxythiophene) (SWCNT/PEDOT) hybrid fiber, we designed and fabricated a biaxially stretchable supercapacitor, which possesses a unique configuration of the parallel buckled hybrid fiber array. Owing to the reticulate SWCNT film and the improved fabrication technique, the hybrid fiber retained its porous architecture both outwardly and inwardly, manifesting a superior capacity of 215 F g-1. H3PO4-polyvinyl alcohol gel with an optimized component ratio was introduced as both binder and stretchable electrolyte, which contributed to the regularity and stability of the buckled fiber array. The buckled structure and the quasi one-dimensional character of the fibers endow the supercapacitor with 100% stretchability along all directions. In addition, the supercapacitor exhibited good transparency, as well as excellent electrochemical properties and stability after being stretched 5000 times. Electronic supplementary information (ESI) available: SEM images of the twist-first hybrid fiber, TEM images of SWCNT/PEDOT hybrid bundles, Raman spectra and FTIR spectra of the hybrid electrodes, CVs of the pristine, bended and wound supercapacitor, transmittance spectra of the pristine and stretched supercapacitor, demo video of the supercapacitor. See DOI: 10.1039/c5nr03027g

Severe Acneiform Eruption Induced by Cetuximab (Erbitux®)

PubMed Central

Lee, Jung Eun; Lee, Sang Ju; Lee, Hee Jung; Lee, Ju Hee

2008-01-01

Epidermal growth factor has an important role in the regulation of proliferation and differentiation in epidermal keratinocytes, as well as in the survival, angiogenesis and metastasis of cancer cells. Cetuximab is a chimeric monoclonal antibody selective for the epidermal growth factor receptor that induces a broad range of cellular responses that enhance tumor sensitivity to radiotherapy and chemotherapeutic agents. However, it can cause adverse events in the patient including acneiform eruption, asthenia, abdominal pain and nausea/vomiting. We report a case of severe acneiform eruption induced by cetuximab in a 56-year-old man with colorectal cancer and liver metastases. PMID:18972607

Remodelling of three-dimensional organization of the nucleus during terminal keratinocyte differentiation in the epidermis

PubMed Central

Gdula, Michal R.; Poterlowicz, Krzysztof; Mardaryev, Andrei N.; Sharov, Andrey A.; Peng, Y.; Fessing, Michael Y.; Botchkarev, Vladimir A.

2014-01-01

The nucleus of epidermal keratinocytes is a complex and highly compartmentalized organelle, whose structure is markedly changed during terminal differentiation and transition of the genome from a transcriptionally active state seen in the basal and spinous epidermal cells to a fully inactive state in the keratinized cells of the cornified layer. Here, using multi-color confocal microscopy, followed by computational image analysis and mathematical modelling, we demonstrate that in normal mouse foot-pad epidermis transition of keratinocytes from basal epidermal layer to the granular layer is accompanied by marked differences in nuclear architecture and micro-environment including: i) decrease of the nuclear volume, ii) decrease in expression of the markers of transcriptionally-active chromatin; iii) internalization and decrease in the number of nucleoli; iv) increase in the number of pericentromeric heterochromatic clusters; v) increase in the frequency of associations between pericentromeric clusters, chromosomal territory 3, and nucleoli. These data suggest a role for nucleoli and pericentromeric heterochromatin clusters as organizers of nuclear micro-environment required for proper execution of gene expression programs in differentiating keratinocytes and provide important background information for further analyses of alterations in the topological genome organization seen in pathological skin conditions including disorders of epidermal differentiation and epidermal tumors. PMID:23407401

Genetic and pharmacological analysis identifies a physiological role for the AHR in epidermal differentiation

PubMed Central

van den Bogaard, Ellen; Podolsky, Michael; Smits, Jos; Cui, Xiao; John, Christian; Gowda, Krishne; Desai, Dhimant; Amin, Shantu; Schalkwijk, Joost; Perdew, Gary H.

2015-01-01

Stimulation of the aryl hydrocarbon receptor (AHR) by xenobiotics is known to affect epidermal differentiation and skin barrier formation. The physiological role of endogenous AHR signaling in keratinocyte differentiation is not known. We used murine and human skin models to address the hypothesis that AHR activation is required for normal keratinocyte differentiation. Using transcriptome analysis of Ahr-/- and Ahr+/+ murine keratinocytes, we found significant enrichment of differentially expressed genes linked to epidermal differentiation. Primary Ahr-/- keratinocytes showed a significant reduction in terminal differentiation gene and protein expression, similar to Ahr+/+ keratinocytes treated with AHR antagonists GNF351 and CH223191, or the selective AHR modulator (SAhRM), SGA360. In vitro keratinocyte differentiation led to increased AHR levels and subsequent nuclear translocation, followed by induced CYP1A1 gene expression. Monolayer cultured primary human keratinocytes treated with AHR antagonists also showed an impaired terminal differentiation program. Inactivation of AHR activity during human skin equivalent development severely impaired epidermal stratification, terminal differentiation protein expression and stratum corneum formation. As disturbed epidermal differentiation is a main feature of many skin diseases, pharmacological agents targeting AHR signaling or future identification of endogenous keratinocyte-derived AHR ligands should be considered as potential new drugs in dermatology. PMID:25602157

Epidermal electronics for electromyography: An application to swallowing therapy.

PubMed

Constantinescu, Gabriela; Jeong, Jae-Woong; Li, Xinda; Scott, Dylan K; Jang, Kyung-In; Chung, Hyun-Joong; Rogers, John A; Rieger, Jana

2016-08-01

Head and neck cancer treatment alters the anatomy and physiology of patients. Resulting swallowing difficulties can lead to serious health concerns. Surface electromyography (sEMG) is used as an adjuvant to swallowing therapy exercises. sEMG signal collected from the area under the chin provides visual biofeedback from muscle contractions and is used to help patients perform exercises correctly. However, conventional sEMG adhesive pads are relatively thick and difficult to effectively adhere to a patient's altered chin anatomy, potentially leading to poor signal acquisition in this population. Here, the emerging technology of epidermal electronics is introduced, where ultra-thin geometry allows for close contouring of the chin. The two objectives of this study were to (1) assess the potential of epidermal electronics technology for use with swallowing therapy and (2) assess the significance of the reference electrode placement. This study showed comparative signals between the new epidermal sEMG patch and the conventional adhesive patches used by clinicians. Furthermore, an integrated reference yielded optimal signal for clinical use; this configuration was more robust to head movements than when an external reference was used. Improvements for future iterations of epidermal sEMG patches specific to day-to-day clinical use are suggested. Copyright © 2016 IPEM. Published by Elsevier Ltd. All rights reserved.

Beneficial Effects of the Genus Aloe on Wound Healing, Cell Proliferation, and Differentiation of Epidermal Keratinocytes

PubMed Central

Uda, Junki; Kubo, Hirokazu; Nakajima, Yuka; Goto, Arisa; Akaki, Junji; Yoshida, Ikuyo; Matsuoka, Nobuya; Hayakawa, Takao

2016-01-01

Aloe has been used as a folk medicine because it has several important therapeutic properties. These include wound and burn healing, and Aloe is now used in a variety of commercially available topical medications for wound healing and skin care. However, its effects on epidermal keratinocytes remain largely unclear. Our data indicated that both Aloe vera gel (AVG) and Cape aloe extract (CAE) significantly improved wound healing in human primary epidermal keratinocytes (HPEKs) and a human skin equivalent model. In addition, flow cytometry analysis revealed that cell surface expressions of β1-, α6-, β4-integrin, and E-cadherin increased in HPEKs treated with AVG and CAE. These increases may contribute to cell migration and wound healing. Treatment with Aloe also resulted in significant changes in cell-cycle progression and in increases in cell number. Aloe increased gene expression of differentiation markers in HPEKs, suggesting roles for AVG and CAE in the improvement of keratinocyte function. Furthermore, human skin epidermal equivalents developed from HPEKs with medium containing Aloe were thicker than control equivalents, indicating the effectiveness of Aloe on enhancing epidermal development. Based on these results, both AVG and CAE have benefits in wound healing and in treatment of rough skin. PMID:27736988

Study of the incidence and nature of "very subtle epidermal melasma" in relation to intense pulsed light treatment.

PubMed

Negishi, Kei; Kushikata, Nobuharu; Tezuka, Yukiko; Takeuchi, Kaori; Miyamoto, Eiko; Wakamatsu, Shingo

2004-06-01

Skin rejuvenation with intense pulsed light (IPL) is effective for clearing epidermal pigment disorders. Complications are mild and limited to epidermal burns caused by excessive settings. Some patients, however, experience IPL-induced melasma-like hyperpigmentation despite the appearance of normal skin. These patients seem to have very subtle epidermal melasma not visible to the naked eye. Ultraviolet photography has been useful in identifying these patients and preventing complications. The study investigated the incidence of very subtle melasma in patients using UV photography, and assessed this tool in identifying high-risk patients. 223 Japanese women, 30-69 years old, participated in the study. Very subtle melasma invisible to the naked eye under normal light was diagnosed by UV photography by two physicians, and any relationship among the disease incidence, age, and regular sunscreen use was examined. Sixty-three cases of very subtle melasma (28.3%) were identified among the 223 subjects, with a significantly lower incidence in sunscreen users. Patients diagnosed with subtle epidermal melasma and treated with mild IPL parameters did not suffer induced secondary hyperpigmentaion. To help avoid complications after treatment, IPL users should be aware of the age and sunscreen-related incidence of this phenomenon in Asian patients.

Eosinophils in biopsy specimens of lichen sclerosus: a not uncommon finding.

PubMed

Lester, Elizabeth B; Swick, Brian L

2015-01-01

Evolving lesions of lichen sclerosus (LS) pose a diagnostic challenge owing to an absence of classic findings of epidermal atrophy, dermal sclerosis, a band-like lymphocytic infiltrate and the presence of eosinophils. Retrospective specimens of LS were reviewed. Demographic information, biopsy vs. excision and the following histopathological characteristics were noted: presence and number of eosinophils, epidermal hyperplasia, spongiosis, early/transitional LS, well-developed LS and coexisting squamous cell carcinoma (SCC). Linear regression analysis was performed. The data consisted of 66 biopsies (36 male [M], 30 female [F]), from 53 individuals (33M, 20F), including 57 genital and 9 extragenital biopsies. Seven biopsies showed SCC, 28 showed epidermal hyperplasia and 14 exhibited spongiosis. Thirty-five specimens were early/transitional LS and commonly exhibited epidermal hyperplasia (57%), epidermotropism of lymphocytes (97%) and basement membrane thickening (97%). Thirty-five biopsies (53%) contained eosinophils (23 early/transitional lesions). Male gender (p = 0.074) was associated with increased eosinophils. The presence of SCC (p = 0.014) was a significant predictors of eosinophil number. Epidermal hyperplasia, epidermotropism of lymphocytes and basement membrane thickening are helpful features in identifying early LS. Eosinophils are not an uncommon finding in LS and are most common in male genital lesions and in LS associated with SCC. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Vibrational spectroscopy and microscopic imaging: novel approaches for comparing barrier physical properties in native and human skin equivalents.

PubMed

Yu, Guo; Zhang, Guojin; Flach, Carol R; Mendelsohn, Richard

2013-06-01

Vibrational spectroscopy and imaging have been used to compare barrier properties in human skin, porcine skin, and two human skin equivalents, Epiderm 200X with an enhanced barrier and Epiderm 200 with a normal barrier. Three structural characterizations were performed. First, chain packing and conformational order were compared in isolated human stratum corneum (SC), isolated porcine SC, and in the Epiderm 200X surface layers. The infrared (IR) spectrum of isolated human SC revealed a large proportion of orthorhombically packed lipid chains at physiological temperatures along with a thermotropic phase transition to a state with hexagonally packed chains. In contrast, the lipid phase at physiological temperatures in both porcine SC and in Epiderm 200X, although dominated by conformationally ordered chains, lacked significant levels of orthorhombic subcell packing. Second, confocal Raman imaging of cholesterol bands showed extensive formation of cholesterol-enriched pockets within the human skin equivalents (HSEs). Finally, IR imaging tracked lipid barrier dimensions as well as the spatial disposition of ordered lipids in human SC and Epiderm 200X. These approaches provide a useful set of experiments for exploring structural differences between excised human skin and HSEs, which in turn may provide a rationale for the functional differences observed among these preparations.

Cellular responses to disruption of the permeability barrier in a three-dimensional organotypic epidermal model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ajani, Gati; Sato, Nobuyuki; Mack, Judith A.

2007-08-15

Repeated injury to the stratum corneum of mammalian skin (caused by friction, soaps, or organic solvents) elicits hyperkeratosis and epidermal thickening. Functionally, these changes serve to restore the cutaneous barrier and protect the organism. To better understand the molecular and cellular basis of this response, we have engineered an in vitro model of acetone-induced injury using organotypic epidermal cultures. Rat epidermal keratinocytes (REKs), grown on a collagen raft in the absence of any feeder fibroblasts, developed all the hallmarks of a true epidermis including a well-formed cornified layer. To induce barrier injury, REK cultures were treated with intermittent 30-s exposuresmore » to acetone then were fixed and paraffin-sectioned. After two exposures, increased proliferation (Ki67 and BrdU staining) was observed in basal and suprabasal layers. After three exposures, proliferation became confined to localized buds in the basal layer and increased terminal differentiation was observed (compact hyperkeratosis of the stratum corneum, elevated levels of K10 and filaggrin, and heightened transglutaminase activity). Thus, barrier disruption causes epidermal hyperplasia and/or enhances differentiation, depending upon the extent and duration of injury. Given that no fibroblasts are present in the model, the ability to mount a hyperplastic response to barrier injury is an inherent property of keratinocytes.« less

UV fluorescence excitation spectroscopy as a non-invasive predictor of epidermal proliferation and clinical performance of cosmetic formulations

NASA Astrophysics Data System (ADS)

Maidhof, Robert; Liebel, Frank; Hwang, Cheng; Ruvolo, Eduardo; Lyga, John

2017-02-01

The epidermis is the outermost layer of skin and is composed of cells primarily containing keratin. It consists of about ten layers of living cells (keratinocytes) and ten layers of dead cells (corneocytes). These cells are continually shed from the outside and replaced from the inside in a process called desquamation which is controlled by two biological events - proliferation and differentiation. One method to non-invasively study biological changes in the skin is using fluorescence excitation spectroscopy. Several characteristic excitation-emission peaks occur in skin that have been related to the epidermal and dermal composition. The magnitude of the peak that occurs at 295nm excitation (F295) has been linked to changes in skin proliferation, cell turnover, epidermal thickening, and skin aging. We hypothesize that changes in this fluorescent signal could be used to assess the potential activity of cosmetic anti-aging compounds to deliver a benefit to skin. Previous work with retinol and glycolic acid, two commonly used actives that effect epidermal proliferation and exfoliation, has demonstrated an increase in F295 (attributed to tryptophan excitation fluorescence). In this study we present the results of a placebo controlled study that aims to correlate changes in F295 with biological performance (epidermal thickening and Ki67 expression).

The excimer lamp induces cutaneous nerve degeneration and reduces scratching in a dry-skin mouse model.

PubMed

Kamo, Atsuko; Tominaga, Mitsutoshi; Kamata, Yayoi; Kaneda, Kazuyuki; Ko, Kyi C; Matsuda, Hironori; Kimura, Utako; Ogawa, Hideoki; Takamori, Kenji

2014-12-01

Epidermal hyperinnervation, which is thought to underlie intractable pruritus, has been observed in patients with atopic dermatitis (AD). The epidermal expression of axonal guidance molecules has been reported to regulate epidermal hyperinnervation. Previously, we showed that the excimer lamp has antihyperinnervative effects in nonpruritic dry-skin model mice, although epidermal expression of axonal guidance molecules was unchanged. Therefore, we investigated the antipruritic effects of excimer lamp irradiation and its mechanism of action. A single irradiation of AD model mice significantly inhibited itch-related behavior 1 day later, following improvement in the dermatitis score. In addition, irradiation of nerve fibers formed by cultured dorsal root ganglion neurons increased bleb formation and decreased nerve fiber expression of nicotinamide mononucleotide adenylyl transferase 2, suggesting degenerative changes in these fibers. We also analyzed whether attaching a cutoff excimer filter (COF) to the lamp, thus decreasing cytotoxic wavelengths, altered hyperinnervation and the production of cyclobutane pyrimidine dimer (CPD), a DNA damage marker, in dry-skin model mice. Irradiation with COF decreased CPD production in keratinocytes, as well as having an antihyperinnervative effect, indicating that the antipruritic effects of excimer lamp irradiation with COF are due to induction of epidermal nerve degeneration and reduced DNA damage.

Imaging and quantitative data acquisition of biological cell walls with Atomic Force Microscopy and Scanning Acoustic Microscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tittmann, B. R.; Xi, X.

This chapter demonstrates the feasibility of Atomic Force Microscopy (AFM) and High Frequency Scanning Acoustic Microscopy (HF-SAM) as tools to characterize biological tissues. Both the AFM and the SAM have shown to provide imaging (with different resolution) and quantitative elasticity measuring abilities. Plant cell walls with minimal disturbance and under conditions of their native state have been examined with these two kinds of microscopy. After descriptions of both the SAM and AFM, their special features and the typical sample preparation is discussed. The sample preparation is focused here on epidermal peels of onion scales and celery epidermis cells which weremore » sectioned for the AFM to visualize the inner surface (closest to the plasma membrane) of the outer epidermal wall. The nm-wide cellulose microfibrils orientation and multilayer structure were clearly observed. The microfibril orientation and alignment tend to be more organized in older scales compared with younger scales. The onion epidermis cell wall was also used as a test analog to study cell wall elasticity by the AFM nanoindentation and the SAM V(z) feature. The novelty in this work was to demonstrate the capability of these two techniques to analyze isolated, single layered plant cell walls in their natural state. AFM nanoindentation was also used to probe the effects of Ethylenediaminetetraacetic acid (EDTA), and calcium ion treatment to modify pectin networks in cell walls. The results suggest a significant modulus increase in the calcium ion treatment and a slight decrease in EDTA treatment. To complement the AFM measurements, the HF-SAM was used to obtain the V(z) signatures of the onion epidermis. These measurements were focused on documenting the effect of pectinase enzyme treatment. The results indicate a significant change in the V(z) signature curves with time into the enzyme treatment. Thus AFM and HF-SAM open the door to a systematic nondestructive structure and mechanical property study of complex biological cell walls. A unique feature of this approach is that both microscopes allow the biological samples to be examined in their natural fluid (water) environment.« less

Expression and distribution patterns of spermine, spermidine, and putrescine in rat hair follicle.

PubMed

Yamamoto, Yutaro; Makino, Takamitsu; Kudo, Hideo; Ihn, Hironobu; Murakami, Yasuko; Matsufuji, Senya; Fujiwara, Kunio; Shin, Masashi

2018-02-01

No expression and distribution patterns of polyamines (PAs), spermine, spermidine, and their precursor putrescine in mammalian hair follicle are available, although polyamines are known to correlate well with hair growth and epidermal tumor genesis. Immunohistochemistry (IHC) using our original two monoclonal antibodies (mAbs) ASPM-29 specific for spermine or spermidine, and APUT-32 specific for putrescine allowed us to detect immunoreactivity for polyamines in hair follicles from normal adult rats. A wide range of immunoreactivity for the total spermine and spermidine was observed in the compartments of hair follicle: The highest degree of immunoreactivity for polyamines was observed in the matrix, in the Huxley's layer, in the deeper Henle's layer, and in the cuticle of the inner root sheath/the hair cuticle, while moderate immunoreactivity existed in the lower-to-mid cortex and the companion layer, followed by lower immunoreactivity in the outer root sheath, including the bulge region and in the deeper medulla, in which the immunoreactivity was also evident in their nuclei. In addition, somewhat surprisingly, with IHC by APUT-32 mAb, we detected significant levels of putrescine in the compartments, in which the immunostaining pattern was the closely similar to that of the total spermine and spermidine. Thus, among these compartments, the cell types of the matrix, the Huxley's layer, the deeper Henle's layer, and the cuticle of the inner root sheath/the hair cuticle seem to have the biologically higher potential in compartments of anagen hair follicle, maybe suggesting that they are involved more critically in the biological event of hair growth. In addition, we noted sharp differences of immunostaining by IHCs between ASPM-29 mAb and APUT-32 mAb in the epidermis cells and fibroblast. ASPM-29 mAb resulted in strong staining in both the cell types, but APUT-32 mAb showed only very light staining in both types. Consequently, the use of the two IHCs could be extremely useful in further studies on hair cycle and epidermal tumor genesis experimentally or clinically.

Engineering sucrose metabolism in Pseudomonas putida highlights the importance of porins.

PubMed

Löwe, Hannes; Sinner, Peter; Kremling, Andreas; Pflüger-Grau, Katharina

2018-05-28

Using agricultural wastes as a substrate for biotechnological processes is of great interest in industrial biotechnology. A prerequisite for using these wastes is the ability of the industrially relevant microorganisms to metabolize the sugars present therein. Therefore, many metabolic engineering approaches are directed towards widening the substrate spectrum of the workhorses of industrial biotechnology like Escherichia coli, yeast or Pseudomonas putida. For instance, neither xylose or arabinose from cellulosic residues, nor sucrose, the main sugar in waste molasses, can be metabolized by most E. coli and P. putida wild types. We evaluated a new, so far uncharacterized gene cluster for sucrose metabolism from Pseudomonas protegens Pf-5 and showed that it enables P. putida to grow on sucrose as the sole carbon and energy source. Even when integrated into the genome of P. putida, the resulting strain grew on sucrose at rates similar to the rate of the wild type on glucose - making it the fastest growing, plasmid-free P. putida strain known so far using sucrose as substrate. Next, we elucidated the role of the porin, an orthologue of the sucrose porin ScrY, in the gene cluster and found that in P. putida, a porin is needed for sucrose transport across the outer membrane. Consequently, native porins were not sufficient to allow unlimited growth on sucrose. Therefore, we concluded that the outer membrane can be a considerable barrier for substrate transport, depending on strain, genotype and culture conditions, all of which should be taken into account in metabolic engineering approaches. We additionally showed the potential of the engineered P. putida strains by growing them on molasses with efficiencies twice as high as obtained with the wild-type P. putida. This can be seen as a further step towards the production of low-value chemicals and biofuels with P. putida from alternative and more affordable substrates in the future. © 2018 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

Species profiles: Life history and environmental requirements of coastal fishes and invertebrates (South Florida): King mackerel and Spanish mackerel. [Scomberomorus cavalla; Scomberomorus maculatus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Godcharles, M.F.; Murphy, M.D.

1986-06-01

This Species Profile on king and Spanish mackerel summarizes the taxonomy, morphology, distribution, life history, fishery descriptions, ecological role, and environmental requirements of these coastal pelagic fish to assist environmental impact assessment. King and Spanish mackerel support major commercial and sport fisheries in south Florida. In 1974 to 1983, Gulf of Mexico and Atlantic commercial landings of king mackerel declined from 10.4 to 4.3 million lb.; Spanish mackerel have fluctuated between 4.9 to 17.4 million lb. Both inhabit coastal waters, but Spanish mackerel are generally found closer to beaches and in outer estuarine waters. Both species feed principally on estuarine-dependentmore » species. They are highly migratory, exhibiting seasonal migrations to winter feeding grounds off south Florida and summer spawning/feeding grounds in the northern Gulf of Mexico and off the Atlantic coast of the Southeastern US. Spawning occurs from March/April through September/October between the middle and Outer Continental Shelf (35 to 183 mi) for king mackerel and the inner shelf (12 to 34 mi) for Spanish mackerel. King mackerel reach sexual maturity in their 3rd and 4th years and Spanish, between their 2nd and 3rd. Female king mackerel live longer and grow larger and faster than males. Spanish mackerel live to 8 years; females also grow faster than males. King and Spanish mackerel feed principally on schooling fishes. Larvae and juveniles of both species are prey to little tunny and dolphin; adults are prey for sharks and bottlenose dolphin. Temperature and salinity are important factors regulating mackerel distribution.« less

76 FR 40381 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-08

... applications. Breakthrough Immunotherapy for Brain Cancer: Epidermal Growth Factor Receptor Variant III... receptor variant III (EGFRvIII) to use as a promising immunotherapy for aggressive brain cancer... immunotherapy targeting type III variant epidermal growth factor receptor, a glioma-associated antigen. Cancer...

A Case of Epidermal Nervous Syndrome with a Novel Association of Congenital Cystic Dysplastic Kidney with Numerous Nephroblastic Proliferations

DTIC Science & Technology

2016-04-19

syndrome. We present a unique case of a female neonate with a medical history significant for seizure -like activity, a hyperplastic thryoid nodelue. aortic coarctaction, patent ductus arterlosus, and epidermal nevus syndrome.

Onset and Cessation of Thermal Convection within Titan's Ice Shell

NASA Astrophysics Data System (ADS)

Mitri, G.; Tobie, G.; Choblet, G.

2015-12-01

The onset of thermal convection within the outer ice shell of Titan is believed to be at the origin of methane outgassing on Titan (Tobie et al., 2006), a possible factor in Titan's resurfacing processes (Mitri et al., 2008), and to have a major role in the evolution and tectonic activity of this Saturnian icy satellite (Tobie et al., 2005; Mitri and Showman, 2008; Mitri et al., 2010). Recent measurements of the gravity field (Iess et al., 2010, 2012) and the modeling of the shape and topography (Zebker et al., 2009; Mitri et al., 2014) have recently improved our knowledge of the thermal state and structure of Titan's outer ice shell. Mitri et al. (2014) found that Titan's surface topography is consistent with an isostatically compensated ice shell of variable thickness, likely at the present in a thermally conductive state (see also Nimmo and Bills, 2010; Hemingway et al., 2013), overlying a relatively dense (~1200-1350 kg m-3) subsurface ocean. As Titan's ice shell is not currently experiencing thermal convection it is likely that the ice shell could have experienced during its history both the onset and the cessation of thermal convection; thermal convection could be present within the ice shell for limited times or in fact be episodic. We investigate the evolution of Titan's outer ice shell from the crystallization of the underlying ocean with a focus on the onset and cessation of thermal convection. To simulate convection in a growing ice shell, we numerically solve the thermal convection equations for a Newtonian rheology in a two dimensional Cartesian domain using finite element method, with a moving bottom boundary to ocean crystallization. We discuss how the crystallization process affects the onset of convection and in which conditions the cessation of thermal convection may occur. The geological consequences of the changes of the thermal state and structure of the outer ice shell will also be discussed.

Delayed Geodynamo in Hadean

NASA Astrophysics Data System (ADS)

Arkani-Hamed, J.

2014-12-01

Paleointensity measurements of Archean rocks reveal a strong geodynamo at ~3.45 Ga, while excess nitrogen content of lunar soil samples implies no geodynamo at ~3.9 Ga. Here I propose that initiation of a strong geodynamo is delayed due to accretion style of Earth, involving collision and merging of a few dozen Moon to Mars size planetary embryos. Two accretion scenarios consisting of 25 and 50 embryos are investigated. The collision of an embryo heats the proto-Earth's core differentially and the rotating low-viscosity core stably stratifies, creating a spherically symmetric and radially increasing temperature distribution. Convection starts in the outer core after each impact but is destroyed by the next impact. The iron core of an impacting embryo descends in the mantle and merges to the proto-Earth's core. Both adiabatic and non-adiabatic merging cases are studied. A major part of the gravitational energy released due to core merging is used to lift up the upper portion of the core to emplace the impactor core material at the neutrally buoyant level in the proto-Earth's core. The remaining energy is converted to heat. In the adiabatic case the merging embryo's core retains all of the remaining energy, while in the non-adiabatic merging 50% of the remaining energy is shared with the outer part of the proto-Earth's core where the embryo's core descends. The two merging models result in significantly different temperature distributions in the core at the end of accretion. After the accretion, the convecting shell in the outer core grows monotonically and generates geodynamo gradually. It takes about 50-100 Myr for the convecting shell to generate a strong dipole field at the surface, 50,000 to 100,000 nT, in the presence of a large stably stratified liquid inner core when the convecting outer core thickness exceeds about one half the radius of the Earth's core.

NagA-dependent uptake of N-acetyl-glucosamine and N-acetyl-chitin oligosaccharides across the outer membrane of Caulobacter crescentus.

PubMed

Eisenbeis, Simone; Lohmiller, Stefanie; Valdebenito, Marianne; Leicht, Stefan; Braun, Volkmar

2008-08-01

Among the 67 predicted TonB-dependent outer membrane transporters of Caulobacter crescentus, NagA was found to be essential for growth on N-acetyl-beta-D-glucosamine (GlcNAc) and larger chitin oligosaccharides. NagA (93 kDa) has a predicted typical domain structure of an outer membrane transport protein: a signal sequence, the TonB box EQVVIT, a hatch domain of 147 residues, and a beta-barrel composed of 22 antiparallel beta-strands linked by large surface loops and very short periplasmic turns. Mutations in tonB1 and exbBD, known to be required for maltose transport via MalA in C. crescentus, and in two additional predicted tonB genes (open reading frames cc2327 and cc3508) did not affect NagA-mediated GlcNAc uptake. nagA is located in a gene cluster that encodes a predicted PTS sugar transport system and two enzymes that convert GlcNAc-6-P to fructose-6-P. Since a nagA insertion mutant did not grow on and transport GlcNAc, diffusion of GlcNAc through unspecific porins in the outer membrane is excluded. Uptake of GlcNAc into tonB and exbBD mutants and reduction but not abolishment of GlcNAc transport by agents which dissipate the electrochemical potential of the cytoplasmic membrane (0.1 mM carbonyl cyanide 3-chlorophenylhydrazone and 1 mM 2,4-dinitrophenol) suggest diffusion of GlcNAc through a permanently open pore of NagA. Growth on (GlcNAc)(3) and (GlcNAc)(5) requires ExbB and ExbD, indicating energy-coupled transport by NagA. We propose that NagA forms a small pore through which GlcNAc specifically diffuses into the periplasm and functions as an energy-coupled transporter for the larger chitin oligosaccharides.

Niclosamide inhibits epithelial-mesenchymal transition and tumor growth in lapatinib-resistant human epidermal growth factor receptor 2-positive breast cancer.

PubMed

Liu, Junjun; Chen, Xiaosong; Ward, Toby; Mao, Yan; Bockhorn, Jessica; Liu, Xiaofei; Wang, Gen; Pegram, Mark; Shen, Kunwei

2016-02-01

Acquired resistance to lapatinib, a human epidermal growth factor receptor 2 kinase inhibitor, remains a clinical problem for women with human epidermal growth factor receptor 2-positive advanced breast cancer, as metastasis is commonly observed in these patients. Niclosamide, an anti-helminthic agent, has recently been shown to exhibit cytotoxicity to tumor cells with stem-like characteristics. This study was designed to identify the mechanisms underlying lapatinib resistance and to determine whether niclosamide inhibits lapatinib resistance by reversing epithelial-mesenchymal transition. Here, two human epidermal growth factor receptor 2-positive breast cancer cell lines, SKBR3 and BT474, were exposed to increasing concentrations of lapatinib to establish lapatinib-resistant cultures. Lapatinib-resistant SKBR3 and BT474 cells exhibited up-regulation of the phenotypic epithelial-mesenchymal transition markers Snail, vimentin and α-smooth muscle actin, accompanied by activation of nuclear factor-кB and Src and a concomitant increase in stem cell marker expression (CD44(high)/CD24(low)), compared to naive lapatinib-sensitive SKBR3 and BT474 cells, respectively. Interestingly, niclosamide reversed epithelial-mesenchymal transition, induced apoptosis and inhibited cell growth by perturbing aberrant signaling pathway activation in lapatinib-resistant human epidermal growth factor receptor 2-positive cells. The ability of niclosamide to alleviate stem-like phenotype development and invasion was confirmed. Collectively, our results demonstrate that lapatinib resistance correlates with epithelial-mesenchymal transition and that niclosamide inhibits lapatinib-resistant cell viability and epithelial-mesenchymal transition. These findings suggest a role of niclosamide or derivatives optimized for more favorable bioavailability not only in reversing lapatinib resistance but also in reducing metastatic potential during the treatment of human epidermal growth factor receptor 2-positive breast cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evolution of petal epidermal micromorphology in Leguminosae and its use as a marker of petal identity.

PubMed

Ojeda, Isidro; Francisco-Ortega, Javier; Cronk, Quentin C B

2009-11-01

The legume flower is highly variable in symmetry and differentiation of petal types. Most papilionoid flowers are zygomorphic with three types of petals: one dorsal, two lateral and two ventral petals. Mimosoids have radial flowers with reduced petals while caesalpinioids display a range from strongly zygomorphic to nearly radial symmetry. The aims are to characterize the petal micromorphology relative to flower morphology and evolution within the family and assess its use as a marker of petal identity (whether dorsal, lateral or ventral) as determined by the expression of developmental genes. Petals were analysed using the scanning electron microscope and light microscope. A total of 175 species were studied representing 26 tribes and 89 genera in all three subfamilies of the Leguminosae. The papilionoids have the highest degree of variation of epidermal types along the dorsiventral axis within the flower. In Loteae and genistoids, in particular, it is common for each petal type to have a different major epidermal micromorphology. Papillose conical cells are mainly found on dorsal and lateral petals. Tabular rugose cells are mainly found on lateral petals and tabular flat cells are found only in ventral petals. Caesalpinioids lack strong micromorphological variation along this axis and usually have only a single major epidermal type within a flower, although the type maybe either tabular rugose cells, papillose conical cells or papillose knobby rugose cells, depending on the species. Strong micromorphological variation between different petals in the flower is exclusive to the subfamily Papilionoideae. Both major and minor epidermal types can be used as micromorphological markers of petal identity, at least in papilionoids, and they are important characters of flower evolution in the whole family. The molecular developmental pathway between specific epidermal micromorphology and the expression of petal identity genes has yet to be established.

Lupus erythematosus tumidus: a series of 26 cases.

PubMed

Vieira, Vanessa; Del Pozo, Jesús; Yebra-Pimentel, Maria Teresa; Martínez, Walter; Fonseca, Eduardo

2006-05-01

To study 26 cases of lupus erythematosus tumidus (LET), a subset of chronic cutaneous lupus erythematosus (CCLE), referred to in the literature as a rare entity. A retrospective study was conducted of 26 patients diagnosed with LET between 1996 and 2002. The clinical characteristics, histopathologic and laboratory findings, response to treatment, association with other subsets of lupus, course, and diagnostic criteria were analyzed. The incidence by sex was similar. The mean age of presentation was 49.19 years. The clinical presentation usually involved erythematous, edematous plaques located on the face, chest, back, or extremities, related to sun exposure. A dermal lymphocytic infiltrate with a perivascular disposition and differing degrees of mucin deposition was observed in all cases. Minimal epidermal changes were present in 18 cases, and 11 of these also showed minimal dermal-epidermal changes. Only one case showed dermal-epidermal changes without any epidermal alteration. Direct immunofluorescence test was performed in 15 patients, and 11 were negative. All cases showed a benign course without systemic manifestations. The response to topical steroids or antimalarial treatment was excellent, but a seasonal recurrence was usually observed. Discussion No defined criteria for LET are universally accepted. The main controversies are the acceptance of LET as a separate subset of CCLE, and the histopathologic diagnostic features, mainly the presence or absence of epidermal and dermal-epidermal changes in these lesions. No inflexible histologic criteria should be employed for the diagnosis of LET. This subset of lupus erythematosus is characterized by intense photosensitivity, definite clinical lesions, a benign course, the absence of systemic disease, good response to antimalarial treatment, and a tendency to recur. More studies should be performed in order to establish the true incidence of LET because this subset of CCLE is probably underestimated.

Dermal matrix proteins initiate re-epithelialization but are not sufficient for coordinated epidermal outgrowth in a new fish skin culture model.

PubMed

Matsumoto, Reiko; Sugimoto, Masazumi

2007-02-01

We have established a new culture system to study re-epithelialization during fish epidermal wound healing. In this culture system, fetal bovine serum (FBS) stimulates the epidermal outgrowth of multi-cellular layers from scale skin mounted on a coverslip, even when cell proliferation is blocked. The rate of outgrowth is about 0.4 mm/h, and at 3 h after incubation, the area occupied by the epidermal sheet is nine times larger than the area of the original scale skin. Cells at the bottom of the outgrowth show a migratory phenotype with lamellipodia, and "purse string"-like actin bundles have been found over the leading-edge cells with polarized lamellipodia. In the superficial cells, re-development of adherens junctions and microridges has been detected, together with the appearance and translocation of phosphorylated p38 MAPK into nuclear areas. Thus, this culture system provides an excellent model to study the mechanisms of epidermal outgrowth accompanied by migration and re-differentiation. We have also examined the role of extracellular matrix proteins in the outgrowth. Type I collagen or fibronectin stimulates moderate outgrowth in the absence of FBS, but development of microridges and the distribution of phosphorylated p38 MAPK are attenuated in the superficial cells. In addition, the leading-edge cells do not have apparent "purse string"-like actin bundles. The outgrowth stimulated by FBS is inhibited by laminin. These results suggest that dermal substrates such as type I collagen and fibronectin are able to initiate epidermal outgrowth but require other factors to enhance such outgrowth, together with coordinated alterations in cellular phenotype.

Histone deacetylases inhibitor Trichostatin A ameliorates DNFB-induced allergic contact dermatitis and reduces epidermal Langerhans cells in mice

PubMed Central

Shi, Yu-Ling; Gu, Jun; Park, Jun-Yang; Xu, Ying-Ping; Yu, Fu-Shin; Zhou, Li; Mi, Qing-Sheng

2012-01-01

Background Histone deacetylases (HDACs) influence chromatin organization, representing a key epigenetic regulatory mechanism in cells. Trichostatin A (TSA), a potent HDAC inhibitor, has anti-tumor and anti-inflammatory effects. Allergic contact dermatitis (ACD) is a T-cell-mediated inflammatory reaction in skin and is regulated by epidermal Langerhans cells (LCs). Objective The aim of this study was to investigate if TSA treatment prevents 2,4-dinitrofluorobenzene (DNFB)-induced ACD in mice and regulates epidermal LCs and other immune cells during ACD development. Methods ACD was induced by sensitizing and challenging with DNFB topically. Mice were treated intraperitoneally with TSA or vehicle DMSO as a control every other day before and during induction of ACD. The ear swelling response was measured and skin biopsies from sensitized skin areas were obtained for histology. Epidermal cells, thymus, spleens and skin draining lymph nodes were collected for immune staining. Results TSA treatment ameliorated skin lesion severity of DNFB-induced ACD. The percentages of epidermal LCs and splenic DCs as well as LC maturation were significantly reduced in TSA-treated mice. However, TSA treatment did not significantly affect the homeostasis of conventional CD4+ and CD8+ T cells, Foxp3+CD4+ regulatory T cells, iNKT cells, and γδ T cells in thymus, spleen and draining lymph nodes (dLNs). Furthermore, there were no significant differences in IL-4 and IFN-γ-producing T cells and iNKT cells between TSA- and DMSO-treated mice. Conclusion Our findings suggest that TSA may ameliorate ACD through the regulation of epidermal LCs and HDACs could serve as potential therapeutic targets for ACD and other LCs-related skin diseases. PMID:22999682

Cervi cornus Colla (deer antler glue) induce epidermal differentiation in the reconstruction of skin equivalents.

PubMed

Choi, H-R; Nam, K-M; Kim, D-S; Huh, C-H; Na, J-I; Park, K-C

2013-06-01

In the reconstruction of skin equivalents (SEs), keratinocyte differentiation is important because epidermal differentiation is closely related with barrier function. The aim of this study was to investigate the effects of Cervi cornus Colla (CCC) on the stem cell activity and epidermal differentiation in the reconstruction of skin equivalent. Four different models were constructed according to different composition of dermal substitute. Results showed similar morphologic findings when hyaluronic acid (HA) and/or CCC was added. But, immunohistochemical staining showed that p63 was significantly increased by addition of HA and/or CCC. Increased staining of integrin α6 and β1 was variably observed when HA and/or CCC was added to make dermal substitute. These finding showed that addition of HA and/or CCC may affect the stem cell activity in the reconstruction of skin. Furthermore, filaggrin expression was much increased when CCC was added. It showed that epidermal differentiation was significantly improved by addition of CCC. In conclusion, simultaneous presence of HA and CCC contributed to the stem cell activity and epidermal differentiation in the reconstruction of SE. Legislation in the EU prohibits marketing cosmetics and personal care products that contain constituents that have been examined through animal experiments. To avoid these limitations, SEs can be used for testing the safety or the efficacy of cosmetic ingredients. Therefore, our results showed that combined use of HA and CCC can be helpful for the reconstruction of SE with good stem cell activity and epidermal differentiation. © 2013 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Building a flagellum in biological outer space.

PubMed

Evans, Lewis D B; Hughes, Colin; Fraser, Gillian M

2014-02-01

Flagella, the rotary propellers on the surface of bacteria, present a paradigm for how cells build and operate complex molecular 'nanomachines'. Flagella grow at a constant rate to extend several times the length of the cell, and this is achieved by thousands of secreted structural subunits transiting through a central channel in the lengthening flagellum to incorporate into the nascent structure at the distant extending tip. A great mystery has been how flagella can assemble far outside the cell where there is no conventional energy supply to fuel their growth. Recent work published by Evans et al. [ Nature (2013) 504: 287-290], has gone some way towards solving this puzzle, presenting a simple and elegant transit mechanism in which growth is powered by the subunits them selves as they link head-to-tail in a chain that is pulled through the length of the growing structure to the tip. This new mechanism answers an old question and may have resonance in other assembly processes.

SELF-SUSTAINED RECYCLING IN THE INNER DUST RING OF PRE-TRANSITIONAL DISKS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Husmann, T.; Loesche, C.; Wurm, G., E-mail: tim.jankowski@uni-due.de

Observations of pre-transitional disks show a narrow inner dust ring and a larger outer one. They are separated by a cavity with no or only little dust. We propose an efficient recycling mechanism for the inner dust ring which keeps it in a steady state. No major particle sources are needed for replenishment. Dust particles and pebbles drift outwards by radiation pressure and photophoresis. The pebbles grow during outward drift until they reach a balanced position where residual gravity compensates photophoresis. While still growing larger they reverse their motion and drift inward. Eventually, their speed is fast enough for themmore » to be destroyed in collisions with other pebbles and drift outward again. We quantify the force balance and drift velocities for the disks LkCa15 and HD 135344B. We simulate single-particle evolution and show that this scenario is viable. Growth and drift timescales are on the same order and a steady state can be established in the inner dust ring.« less

Mesophyll distribution of 'antioxidant' flavonoid glycosides in Ligustrum vulgare leaves under contrasting sunlight irradiance.

PubMed

Agati, Giovanni; Stefano, Giovanni; Biricolti, Stefano; Tattini, Massimiliano

2009-10-01

Flavonoids have the potential to serve as antioxidants in addition to their function of UV screening in photoprotective mechanisms. However, flavonoids have long been reported to accumulate mostly in epidermal cells and surface organs in response to high sunlight. Therefore, how leaf flavonoids actually carry out their antioxidant functions is still a matter of debate. Here, the distribution of flavonoids with effective antioxidant properties, i.e. the orthodihydroxy B-ring-substituted quercetin and luteolin glycosides, was investigated in the mesophyll of Ligustrum vulgare leaves acclimated to contrasting sunlight irradiance. In the first experiment, plants were grown at 20 % (shade) or 100% (sun) natural sunlight. Plants were exposed to 100 % sunlight irradiance in the presence or absence of UV wavelengths, in a second experiment. Fluorescence microspectroscopy and multispectral fluorescence microimaging were used in both cross sections and intact leaf pieces to visualize orthodihydroxy B-ring-substituted flavonoids at inter- and intracellular levels. Identification and quantification of individual hydroxycinnamates and flavonoid glycosides were performed via HPLC-DAD. Quercetin and luteolin derivatives accumulated to a great extent in both the epidermal and mesophyll cells in response to high sunlight. Tissue fluorescence signatures and leaf flavonoid concentrations were strongly related. Monohydroxyflavone glycosides, namely luteolin 4'-O-glucoside and two apigenin 7-O-glycosides were unresponsive to changes in sunlight irradiance. Quercetin and luteolin derivatives accumulated in the vacuoles of mesophyll cells in leaves growing under 100 % natural sunlight in the absence of UV wavelengths. The above findings lead to the hypothesis that flavonoids play a key role in countering light-induced oxidative stress, and not only in avoiding the penetration of short solar wavelengths in the leaf.

Mesophyll distribution of ‘antioxidant’ flavonoid glycosides in Ligustrum vulgare leaves under contrasting sunlight irradiance

PubMed Central

Agati, Giovanni; Stefano, Giovanni; Biricolti, Stefano; Tattini, Massimiliano

2009-01-01

Background and Aims Flavonoids have the potential to serve as antioxidants in addition to their function of UV screening in photoprotective mechanisms. However, flavonoids have long been reported to accumulate mostly in epidermal cells and surface organs in response to high sunlight. Therefore, how leaf flavonoids actually carry out their antioxidant functions is still a matter of debate. Here, the distribution of flavonoids with effective antioxidant properties, i.e. the orthodihydroxy B-ring-substituted quercetin and luteolin glycosides, was investigated in the mesophyll of Ligustrum vulgare leaves acclimated to contrasting sunlight irradiance. Methods In the first experiment, plants were grown at 20 % (shade) or 100% (sun) natural sunlight. Plants were exposed to 100 % sunlight irradiance in the presence or absence of UV wavelengths, in a second experiment. Fluorescence microspectroscopy and multispectral fluorescence microimaging were used in both cross sections and intact leaf pieces to visualize orthodihydroxy B-ring-substituted flavonoids at inter- and intracellular levels. Identification and quantification of individual hydroxycinnamates and flavonoid glycosides were performed via HPLC-DAD. Key Results Quercetin and luteolin derivatives accumulated to a great extent in both the epidermal and mesophyll cells in response to high sunlight. Tissue fluorescence signatures and leaf flavonoid concentrations were strongly related. Monohydroxyflavone glycosides, namely luteolin 4′-O-glucoside and two apigenin 7-O-glycosides were unresponsive to changes in sunlight irradiance. Quercetin and luteolin derivatives accumulated in the vacuoles of mesophyll cells in leaves growing under 100 % natural sunlight in the absence of UV wavelengths. Conclusions The above findings lead to the hypothesis that flavonoids play a key role in countering light-induced oxidative stress, and not only in avoiding the penetration of short solar wavelengths in the leaf. PMID:19633310

Dynamics of virus shedding and in situ confirmation of chelonid herpesvirus 5 in Hawaiian green turtles with Fibropapillomatosis

USGS Publications Warehouse

Work, Thierry M.; Dagenais, Julie; Balazs, George H.; Schettle, Nelli; Ackermann, Mathias

2015-01-01

Cancers in humans and animals can be caused by viruses, but virus-induced tumors are considered to be poor sites for replication of intact virions (lytic replication). Fibropapillomatosis (FP) is a neoplastic disease associated with a herpesvirus, chelonid herpesvirus 5 (ChHV5), that affects green turtles globally. ChHV5 probably replicates in epidermal cells of tumors, because epidermal intranuclear inclusions (EIIs) contain herpesvirus-like particles. However, although EIIs are a sign of herpesvirus replication, they have not yet been firmly linked to ChHV5. Moreover, the dynamics of viral shedding in turtles are unknown, and there are no serological reagents to confirm actual presence of the specific ChHV5 virus in tissues. The investigators analyzed 381 FP tumors for the presence of EIIs and found that overall, about 35% of green turtles had lytic replication in skin tumors with 7% of tumors showing lytic replication. A few (11%) turtles accounted for more than 30% cases having lytic viral replication, and lytic replication was more likely in smaller tumors. To confirm that turtles were actively replicating ChHV5, a prerequisite for shedding, the investigators used antiserum raised against F-VP26, a predicted capsid protein of ChHV5 that localizes to the host cell nucleus during viral replication. This antiserum revealed F-VP26 in EIIs of tumors, thus confirming the presence of replicating ChHV5. In this light, it is proposed that unlike other virus-induced neoplastic diseases, FP is a disease that may depend on superspreaders, a few highly infectious individuals growing numerous small tumors permissive to viral production, for transmission of ChHV5.

Phosphorylation of Glutathione S-Transferase P1 (GSTP1) by Epidermal Growth Factor Receptor (EGFR) Promotes Formation of the GSTP1-c-Jun N-terminal kinase (JNK) Complex and Suppresses JNK Downstream Signaling and Apoptosis in Brain Tumor Cells*

PubMed Central

Okamura, Tatsunori; Antoun, Gamil; Keir, Stephen T.; Friedman, Henry; Bigner, Darell D.; Ali-Osman, Francis

2015-01-01

Under normal physiologic conditions, the glutathione S-transferase P1 (GSTP1) protein exists intracellularly as a dimer in reversible equilibrium with its monomeric subunits. In the latter form, GSTP1 binds to the mitogen-activated protein kinase, JNK, and inhibits JNK downstream signaling. In tumor cells, which frequently are characterized by constitutively high GSTP1 expression, GSTP1 undergoes phosphorylation by epidermal growth factor receptor (EGFR) at tyrosine residues 3, 7, and 198. Here we report on the effect of this EGFR-dependent GSTP1 tyrosine phosphorylation on the interaction of GSTP1 with JNK, on the regulation of JNK downstream signaling by GSTP1, and on tumor cell survival. Using in vitro and in vivo growing human brain tumors, we show that tyrosine phosphorylation shifts the GSTP1 dimer-monomer equilibrium to the monomeric state and facilitates the formation of the GSTP1-JNK complex, in which JNK is functionally inhibited. Targeted mutagenesis and functional analysis demonstrated that the increased GSTP1 binding to JNK results from phosphorylation of the GSTP1 C-terminal Tyr-198 by EGFR and is associated with a >2.5-fold decrease in JNK downstream signaling and a significant suppression of both spontaneous and drug-induced apoptosis in the tumor cells. The findings define a novel mechanism of regulatory control of JNK signaling that is mediated by the EGFR/GSTP1 cross-talk and provides a survival advantage for tumors with activated EGFR and high GSTP1 expression. The results lay the foundation for a novel strategy of dual EGFR/GSTP1 for treating EGFR+ve, GSTP1 expressing GBMs. PMID:26429914

Origin of the color of Cv. rhapsody in blue rose and some other so-called "blue" roses.

PubMed

Gonnet, Jean-François

2003-08-13

Flowers of the rose cultivar Rhapsody in Blue display unusual colors, changing as they age, from a vivid red-purple to a lighter and duller purple, which are based on tonalities corresponding to hue angles between 340 and 320 degrees in the CIELAB scale. Unexpectedly, the chemical basis of these colors is among the simplest, featuring cyanin (cyanidin 3,5-di-O-glucoside), the most frequent anthocyanin in flowers, as the sole pigment and quercetin kaempferol glycosides as copigments at a relatively low copigment/pigment ratio (about 3/1), which usually produces magenta or red shades in roses. This color shift to bluer shades is coupled with the progressive accumulation of cyanin into vacuolar anthocyanic inclusions (AVIs), the occurrence of which increases as the petals grow older. In addition to the normal lambda(max) of cyanin at approximately 545 nm, the transmission spectra of live petals and of epidermal cells exhibit a second lambda(max) in the 620-625 nm range, the relative importance increasing with the presence of AVIs. In petals of fully opened flowers, the only pigmented structures in the vacuoles of epidermal cells are AVIs; their intense and massive absorption in the 520-640 nm area produces a much darker and bluer color than measured for the vacuolar solution present at the very first opening stage. Cyanin is probably "trapped" into AVIs at higher concentrations than would be possible in a vacuolar solution and in quinonoidal form, appearing purple-blue because of additional absorption in the 580-630 nm area. Quite similar pigmentation features were found in very ancient rose cultivars (cv. L'Evêque or Bleu Magenta), also displaying this type of so-called "blue" color.

Insulin and heparin-binding epidermal growth factor-like growth factor synergistically promote astrocyte survival and proliferation in serum-free medium.

PubMed

Jia, Mei; Shi, Zhongfang; Yan, Xu; Xu, Lixin; Dong, Liping; Li, Jiaxin; Wang, Yujiao; Yang, Shaohua; Yuan, Fang

2018-06-08

In vitro systems allowing maintenance and experimentation on primary astrocyte cultures have been used for decades. Astrocyte cultures are most maintained in serum-containing medium which has been found to alter the morphology and gene profiles of astrocytes. Here, we reported a new serum-free medium for astrocyte culture, which consisted of DMEM and NB media supplemented with insulin and heparin-binding epidermal growth factor-like growth factor (HB-EGF) (SF-I-H medium). Meanwhile FBS-containing (FBS) medium composed of DMEM medium containing 10% FBS were used for comparison study. Cerebral cortex was harvested from postnatal day 1 Wistar rats and brain cells were isolated and seeded to poly-L-lysine coated culture dishes after 15 min differential velocity adherence. Compared with FBS medium, astrocytes in SF-I-H medium are smaller and exhibited process bearing morphologies. MTT assays showed that cell density and proliferation rate were higher in SF-I-H medium than in FBS medium all the time, and flow cytometry analysis revealed that SF-I-H medium promoted cell mitosis in a manner comparable to FBS medium. Consistently, western blot analysis further revealed that insulin and HB-EGF synergistically activated the PI3K-AKT and MAPK-ERK1/2 signaling cascades as FBS. Astrocytes cultured in SF-I-H medium grow faster than FBS medium. Taken together, our results indicated that SF-I-H medium, in which cell morphology was similar with astrocytes in brain, was more effective for astrocyte survival and proliferation than FBS medium, providing a new cell model to study astrocyte functions without the interference of serum. Copyright © 2018. Published by Elsevier B.V.

Optimization for the blockade of epidermal growth factor receptor signaling for therapy of human pancreatic carcinoma.

PubMed

Solorzano, C C; Baker, C H; Tsan, R; Traxler, P; Cohen, P; Buchdunger, E; Killion, J J; Fidler, I J

2001-08-01

We determined the optimal administration schedule of a novel epidermal growth factor receptor (EGFR) protein tyrosine kinase inhibitor (PKI), PKI 166 (4-(R)-phenethylamino-6-(hydroxyl)phenyl-7H-pyrrolo[2.3-d]-pyrimidine), alone or in combination with gemcitabine (administered i.p.) for therapy of L3.6pl human pancreatic carcinoma growing in the pancreas of nude mice. Seven days after orthotopic implantation of L3.6pl cells, the mice received daily oral doses of PKI 166. PKI 166 therapy significantly inhibited phosphorylation of the EGFR without affecting EGFR expression. EGFR phosphorylation was restored 72 h after cessation of therapy. Seven days after orthotopic injection of L3.6pl cells, groups of mice received daily or thrice weekly oral doses of PKI 166 alone or in combination with gemcitabine. Treatment with PKI 166 (daily), PKI 166 (3 times/week), or gemcitabine alone produced a 72%, 69%, or 70% reduction in the volume of pancreatic tumors in mice, respectively. Daily oral PKI 166 or thrice weekly oral PKI 166 in combination with injected gemcitabine produced 97% and 95% decreases in volume of pancreatic cancers and significant inhibition of lymph node and liver metastasis. Daily oral PKI 166 produced a 20% decrease in body weight, whereas treatment 3 times/week did not. Decreased microvessel density, decreased proliferating cell nuclear antigen staining, and increased tumor cell and endothelial cell apoptosis correlated with therapeutic success. Collectively, our results demonstrate that three weekly oral administrations of an EGFR tyrosine kinase inhibitor in combination with gemcitabine are sufficient to significantly inhibit primary and metastatic human pancreatic carcinoma.

Dynamics of Virus Shedding and In Situ Confirmation of Chelonid Herpesvirus 5 in Hawaiian Green Turtles With Fibropapillomatosis.

PubMed

Work, T M; Dagenais, J; Balazs, G H; Schettle, N; Ackermann, M

2015-11-01

Cancers in humans and animals can be caused by viruses, but virus-induced tumors are considered to be poor sites for replication of intact virions (lytic replication). Fibropapillomatosis (FP) is a neoplastic disease associated with a herpesvirus, chelonid herpesvirus 5 (ChHV5), that affects green turtles globally. ChHV5 probably replicates in epidermal cells of tumors, because epidermal intranuclear inclusions (EIIs) contain herpesvirus-like particles. However, although EIIs are a sign of herpesvirus replication, they have not yet been firmly linked to ChHV5. Moreover, the dynamics of viral shedding in turtles are unknown, and there are no serological reagents to confirm actual presence of the specific ChHV5 virus in tissues. The investigators analyzed 381 FP tumors for the presence of EIIs and found that overall, about 35% of green turtles had lytic replication in skin tumors with 7% of tumors showing lytic replication. A few (11%) turtles accounted for more than 30% cases having lytic viral replication, and lytic replication was more likely in smaller tumors. To confirm that turtles were actively replicating ChHV5, a prerequisite for shedding, the investigators used antiserum raised against F-VP26, a predicted capsid protein of ChHV5 that localizes to the host cell nucleus during viral replication. This antiserum revealed F-VP26 in EIIs of tumors, thus confirming the presence of replicating ChHV5. In this light, it is proposed that unlike other virus-induced neoplastic diseases, FP is a disease that may depend on superspreaders, a few highly infectious individuals growing numerous small tumors permissive to viral production, for transmission of ChHV5. © The Author(s) 2014.

Problem-Solving Test: The Role of Ubiquitination in Epidermal Growth Factor Receptor Trafficking

ERIC Educational Resources Information Center

Szeberenyi, Jozsef

2012-01-01

Terms to be familiar with before you start to solve the test: growth factor signaling, epidermal growth factor, tyrosine protein kinase, tyrosine phosphorylation, ubiquitin, monoubiquitination, polyubiquitination, site-directed mutagenesis, transfection, expression vector, cDNA, immunoprecipitation, SDS-polyacrylamide gel electrophoresis, Western…

A severe form of epidermal nevus syndrome associated with brainstem and cerebellar malformations and neonatal medulloblastoma.

PubMed

Okumura, Akihisa; Lee, Tsubasa; Ikeno, Mitsuru; Shimojima, Keiko; Kajino, Kazunori; Inoue, Yuka; Yoshikawa, Naomi; Suganuma, Hiroki; Suzuki, Mitsuyoshi; Hisata, Ken; Shoji, Hiromichi; Takanashi, Jun-ichi; Barkovich, A James; Shimizu, Toshiaki; Yamamoto, Toshiyuki; Hayashi, Masaharu

2012-11-01

Here we report a boy with epidermal nevus syndrome associated with brainstem and cerebellar malformations and neonatal medulloblastoma. The patient had epidermal nevi and complicated brain malformations including macrocephaly with polymicrogyria, dysmorphic and enlarged midbrain tectum, enlarged cerebellar hemispheres with small and maloriented folia. The patient died after surgical resection of medulloblastoma which was newly recognized on MRI at 51 days of age. Postmortem pathological examinations showed very unique and bizarre malformation of the midbrain and hindbrain. The cerebellar cortex exhibited a coarse, irregular and bumpy surface, blurred border between the Purkinje cell layer and internal granule cell layer, and many foci of heterotopia in the cerebellar white matter. The brainstem showed multiple anomalies, including enlargement of superior colliculi, hypoplasia of pyramidal tracts and dysplasia of inferior olivary nuclei. The unusual constellation of brain malformations of our patient will widen the spectrum of epidermal nevus syndrome. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

The structure and function of the epidermal barrier in patients with atopic dermatitis – treatment options. Part two

PubMed Central

Czarnecka-Operacz, Magdalena; Adamski, Zygmunt

2018-01-01

Atopic dermatitis (AD) is a chronic and recurrent disease induced by underlying defects of the epidermal barrier and immunological disorders, typical of atopic diseases. The genetic and immunological mechanisms (outlined in the previous paper) affecting the dysfunction of the barrier are intensified by environmental factors, e.g. airborne and food allergens, infections and stress. For this reason, proper skin care, which prevents further damage and restores the epidermal barrier is of such importance in the field of AD therapy. Appropriate therapy is based on emollients which, coupled with anti-inflammatory and antipruritic treatment, should be used as the first-line therapy. The aim of the present paper is to outline the effects of the abovementioned factors on the dysfunction of the epidermal barrier as well as to emphasize the importance of proper atopic skin care in maintaining the integrity of the barrier and preventing exacerbation of the disease. PMID:29760610

Epidermal Notch1 recruits RORγ(+) group 3 innate lymphoid cells to orchestrate normal skin repair.

PubMed

Li, Zhi; Hodgkinson, Tom; Gothard, Elizabeth J; Boroumand, Soulmaz; Lamb, Rebecca; Cummins, Ian; Narang, Priyanka; Sawtell, Amy; Coles, Jenny; Leonov, German; Reboldi, Andrea; Buckley, Christopher D; Cupedo, Tom; Siebel, Christian; Bayat, Ardeshir; Coles, Mark C; Ambler, Carrie A

2016-04-21

Notch has a well-defined role in controlling cell fate decisions in the embryo and the adult epidermis and immune systems, yet emerging evidence suggests Notch also directs non-cell-autonomous signalling in adult tissues. Here, we show that Notch1 works as a damage response signal. Epidermal Notch induces recruitment of immune cell subsets including RORγ(+) ILC3s into wounded dermis; RORγ(+) ILC3s are potent sources of IL17F in wounds and control immunological and epidermal cell responses. Mice deficient for RORγ(+) ILC3s heal wounds poorly resulting from delayed epidermal proliferation and macrophage recruitment in a CCL3-dependent process. Notch1 upregulates TNFα and the ILC3 recruitment chemokines CCL20 and CXCL13. TNFα, as a Notch1 effector, directs ILC3 localization and rates of wound healing. Altogether these findings suggest that Notch is a key stress/injury signal in skin epithelium driving innate immune cell recruitment and normal skin tissue repair.

Roles of CONSTITUTIVE PHOTOMORPHOGENIC 10 in Arabidopsis stomata development

PubMed Central

Delgado, Dolores; Ballesteros, Isabel; Mena, Montaña; Fenoll, Carmen

2012-01-01

Stomata are epidermal bi-celled structures that differentiate within special cell lineages initiated by a subset of protodermal cells. Recently, we showed that the Arabidopsis photomorphogenic repressor COP10 controls specific cell-lineage and cell-signaling developmental mechanisms in stomatal lineages. Loss-of-function cop10-1 mutant cotyledons and leaves produced (in the light and in the dark) abundant stomatal clusters, but nonlineage epidermal cells were not affected. Here we examine COP10 role in hypocotyls, cylindrical organs displaying a distinct epidermal organization with alternate files of protruding and non-protruding cells, with the latter producing a limited number of stomata. COP10 prevents stomatal clusters and restricts stomata production in hypocotyls; these roles are specific to lineage cells as in cotyledons, since COP10 loss of function does not elicit stomatal fate in nonlineage cells; COP10 also sustains the directional cell expansion of all hypocotyl epidermal cell types, and seems necessary for the differentiation between protruding and non-protruding cell files. PMID:22836493

Ephrin-Bs Drive Junctional Downregulation and Actin Stress Fiber Disassembly to Enable Wound Re-epithelialization

PubMed Central

Nunan, Robert; Campbell, Jessica; Mori, Ryoichi; Pitulescu, Mara E.; Jiang, Wen G.; Harding, Keith G.; Adams, Ralf H.; Nobes, Catherine D.; Martin, Paul

2015-01-01

Summary For a skin wound to successfully heal, the cut epidermal-edge cells have to migrate forward at the interface between scab and healthy granulation tissue. Much is known about how lead-edge cells migrate, but very little is known about the mechanisms that enable active participation by cells further back. Here we show that ephrin-B1 and its receptor EphB2 are both upregulated in vivo, just for the duration of repair, in the first 70 or so rows of epidermal cells, and this signal leads to downregulation of the molecular components of adherens and tight (but not desmosomal) junctions, leading to loosening between neighbors and enabling shuffle room among epidermal cells. Additionally, this signaling leads to the shutdown of actomyosin stress fibers in these same epidermal cells, which may act to release tension within the wound monolayer. If this signaling axis is perturbed, then disrupted healing is a consequence in mouse and man. PMID:26549443

Detection of single-molecule H2O2 signalling from epidermal growth factor receptor using fluorescent single-walled carbon nanotubes

NASA Astrophysics Data System (ADS)

Jin, Hong; Heller, Daniel A.; Kalbacova, Marie; Kim, Jong-Ho; Zhang, Jingqing; Boghossian, Ardemis A.; Maheshri, Narendra; Strano, Michael S.

2010-04-01

An emerging concept in cell signalling is the natural role of reactive oxygen species such as hydrogen peroxide (H2O2) as beneficial messengers in redox signalling pathways. The nature of H2O2 signalling is confounded, however, by difficulties in tracking it in living systems, both spatially and temporally, at low concentrations. Here, we develop an array of fluorescent single-walled carbon nanotubes that can selectively record, in real time, the discrete, stochastic quenching events that occur as H2O2 molecules are emitted from individual human epidermal carcinoma cells stimulated by epidermal growth factor. We show mathematically that such arrays can distinguish between molecules originating locally on the cell membrane from other contributions. We find that epidermal growth factor induces 2 nmol H2O2 locally over a period of 50 min. This platform promises a new approach to understanding the signalling of reactive oxygen species at the cellular level.

Vγ4 T Cells Inhibit the Pro-healing Functions of Dendritic Epidermal T Cells to Delay Skin Wound Closure Through IL-17A

PubMed Central

Li, Yashu; Wang, Yangping; Zhou, Lina; Liu, Meixi; Liang, Guangping; Yan, Rongshuai; Jiang, Yufeng; Hao, Jianlei; Zhang, Xiaorong; Hu, Xiaohong; Huang, Yong; Wang, Rupeng; Yin, Zhinan; Wu, Jun; Luo, Gaoxing; He, Weifeng

2018-01-01

Dendritic epidermal T cells (DETCs) and dermal Vγ4 T cells engage in wound re-epithelialization and skin inflammation. However, it remains unknown whether a functional link between Vγ4 T cell pro-inflammation and DETC pro-healing exists to affect the outcome of skin wound closure. Here, we revealed that Vγ4 T cell-derived IL-17A inhibited IGF-1 production by DETCs to delay skin wound healing. Epidermal IL-1β and IL-23 were required for Vγ4 T cells to suppress IGF-1 production by DETCs after skin injury. Moreover, we clarified that IL-1β rather than IL-23 played a more important role in inhibiting IGF-1 production by DETCs in an NF-κB-dependent manner. Together, these findings suggested a mechanistic link between Vγ4 T cell-derived IL-17A, epidermal IL-1β/IL-23, DETC-derived IGF-1, and wound-healing responses in the skin. PMID:29483920

The relationship between skin aging and steady state ultraweak photon emission as an indicator of skin oxidative stress in vivo.

PubMed

Gabe, Y; Osanai, O; Takema, Y

2014-08-01

Ultraweak photon emission (UPE) is one potential method to evaluate the oxidative status of the skin in vivo. However, little is known about how the daily oxidative stress of the skin is related to skin aging-related alterations in vivo. We characterized the steady state UPE and performed a skin survey. We evaluated the skin oxidative status by UPE, skin elasticity, epidermal thickness and skin color on the inner upper arm, the outer forearm, and the buttock of 70 Japanese volunteers. The steady state UPE at the three skin sites increased with age. Correlation analysis revealed that the steady state UPE only from the buttock was related to skin elasticity, which showed age-dependent changes. Moreover, analysis by age group indicated that b* values of the inner upper arm of subjects in their 20s were inversely correlated with UPE as occurred in buttock skin. In contrast, photoaged skin did not show a clear relationship with steady state UPE because the accumulation of sun-exposure might influence the sensitivity to oxidative stress. These results suggest that steady state UPE reflects not only intrinsic skin aging and cutaneous color but also the current oxidative status independent of skin aging. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Vesicles between plasma membrane and cell wall prior to visible senescence of Iris and Dendrobium flowers.

PubMed

Kamdee, Channatika; Kirasak, Kanjana; Ketsa, Saichol; van Doorn, Wouter G

2015-09-01

Cut Iris flowers (Iris x hollandica, cv. Blue Magic) show visible senescence about two days after full opening. Epidermal cells of the outer tepals collapse due to programmed cell death (PCD). Transmission electron microscopy (TEM) showed irregular swelling of the cell walls, starting prior to cell collapse. Compared to cells in flowers that had just opened, wall thickness increased up to tenfold prior to cell death. Fibrils were visible in the swollen walls. After cell death very little of the cell wall remained. Prior to and during visible wall swelling, vesicles (paramural bodies) were observed between the plasma membrane and the cell walls. The vesicles were also found in groups and were accompanied by amorphous substance. They usually showed a single membrane, and had a variety of diameters and electron densities. Cut Dendrobium hybrid cv. Lucky Duan flowers exhibited visible senescence about 14 days after full flower opening. Paramural bodies were also found in Dendrobium tepal epidermis and mesophyll cells, related to wall swelling and degradation. Although alternative explanations are well possible, it is hypothesized that paramural bodies carry enzymes involved in cell wall breakdown. The literature has not yet reported such bodies in association with senescence/PCD. Copyright © 2015 Elsevier GmbH. All rights reserved.

Temporal and spatial characteristics of male cone development in Metasequoia glyptostroboides Hu et Cheng

PubMed Central

Jin, Biao; Tang, Liang; Lu, Yan; Wang, Di; Zhang, Min; Ma, Jiuxia

2012-01-01

Metasequoia glyptostroboides, a famous relic species of conifer that survived in China, has been successfully planted in large numbers across the world. However, limited information on male cone development in the species is available. In this study, we observed the morphological and anatomical changes that occur during male cone development in M. glyptostroboides using semi-thin sections and scanning electron microscopy. The male cones were borne oppositely on one-year-old twigs that were mainly located around the outer and sunlit parts of crown. Male cones were initiated from early September and shed pollen in the following February. Each cone consisted of spirally arranged microsporophylls subtended by decussate sterile scales, and each microsporophyll commonly consisted of three microsporangia and a phylloclade. The microsporangial wall was composed of an epidermis, endothecium, and tapetum. In mid-February, the endothecium and tapetum layers disintegrated, and in the epidermal layer the cell walls were thickened with inner protrusions. Subsequently, dehiscence of the microsporangia occurred through rupturing of the microsporangial wall along the dehiscence line. These results suggest that the structure, morphology, architecture and arrangement of male cones of M. glyptostroboides are mainly associated with the production, protection and dispersal of pollen for optimization of wind pollination. PMID:23221679

Temporal and spatial characteristics of male cone development in Metasequoia glyptostroboides Hu et Cheng.

PubMed

Jin, Biao; Tang, Liang; Lu, Yan; Wang, Di; Zhang, Min; Ma, Jiuxia

2012-12-01

Metasequoia glyptostroboides, a famous relic species of conifer that survived in China, has been successfully planted in large numbers across the world. However, limited information on male cone development in the species is available. In this study, we observed the morphological and anatomical changes that occur during male cone development in M. glyptostroboides using semi-thin sections and scanning electron microscopy. The male cones were borne oppositely on one-year-old twigs that were mainly located around the outer and sunlit parts of crown. Male cones were initiated from early September and shed pollen in the following February. Each cone consisted of spirally arranged microsporophylls subtended by decussate sterile scales, and each microsporophyll commonly consisted of three microsporangia and a phylloclade. The microsporangial wall was composed of an epidermis, endothecium, and tapetum. In mid-February, the endothecium and tapetum layers disintegrated, and in the epidermal layer the cell walls were thickened with inner protrusions. Subsequently, dehiscence of the microsporangia occurred through rupturing of the microsporangial wall along the dehiscence line. These results suggest that the structure, morphology, architecture and arrangement of male cones of M. glyptostroboides are mainly associated with the production, protection and dispersal of pollen for optimization of wind pollination.

Differential Growth in Periclinal and Anticlinal Walls during Lobe Formation in Arabidopsis Cotyledon Pavement Cells.

PubMed

Armour, William J; Barton, Deborah A; Law, Andrew M K; Overall, Robyn L

2015-09-01

Lobe development in the epidermal pavement cells of Arabidopsis thaliana cotyledons and leaves is thought to take place via tip-like growth on the concave side of lobes driven by localized concentrations of actin filaments and associated proteins, with a predicted role for cortical microtubules in establishing the direction of restricted growth at the convex side. We used homologous landmarks fixed to the outer walls of pavement cells and thin-plate spline analysis to demonstrate that lobes form by differential growth of both the anticlinal and periclinal walls. Most lobes formed within the first 24 h of the cotyledons unfurling, during the period of rapid cell expansion. Cortical microtubules adjacent to the periclinal wall were persistently enriched at the convex side of lobes during development where growth was anisotropic and were less concentrated or absent at the concave side where growth was promoted. Alternating microtubule-enriched and microtubule-free zones at the periclinal wall in neighboring cells predicted sites of new lobes. There was no particular arrangement of cortical actin filaments that could predict where lobes would form. However, drug studies demonstrate that both filamentous actin and microtubules are required for lobe formation. © 2015 American Society of Plant Biologists. All rights reserved.

Efficacy of chemotherapy after first-line gefitinib therapy in EGFR mutation-positive advanced non-small cell lung cancer-data from a randomized Phase III study comparing gefitinib with carboplatin plus paclitaxel (NEJ002).

PubMed

Miyauchi, Eisaku; Inoue, Akira; Kobayashi, Kunihiko; Maemondo, Makoto; Sugawara, Shunichi; Oizumi, Satoshi; Isobe, Hiroshi; Gemma, Akihiko; Saijo, Yasuo; Yoshizawa, Hirohisa; Hagiwara, Koichi; Nukiwa, Toshihiro

2015-07-01

Epidermal growth factor receptor tyrosine kinase inhibitors are effective as first-line therapy for advanced non-small cell lung cancer patients harboring epidermal growth factor receptor mutations. However, it is unknown whether second-line platinum-based chemotherapy after epidermal growth factor receptor tyrosine kinase inhibitor therapy could lead to better outcomes. We evaluated the efficacy of second-line platinum-based chemotherapy after gefitinib for advanced non-small cell lung cancers harboring epidermal growth factor receptor mutations (the NEJ002 study). Seventy-one non-small cell lung cancers, treated with gefitinib as first-line therapy and then receiving platinum-based chemotherapy as second-line therapy were evaluated in NEJ002. Patients were evaluated for antitumor response to second-line chemotherapy by computed tomography according to the criteria of the Response Evaluation Criteria in Solid Tumors group (version 1.0). Of the 71 patients receiving platinum-based chemotherapy after first-line gefitinib, a partial response was documented in 25.4% (18/71), stable disease in 43.7% (31/71) and progression of disease in 21.1% (15/71). The objective response and disease control rates were 25.4% (18/71) and 69% (49/71), respectively. There was no significant difference between first- and second-line chemotherapy in objective response and disease control rates for advanced non-small cell lung cancer harboring activating epidermal growth factor receptor mutations. In the analysis of epidermal growth factor receptor mutation types, the objective responses of deletions in exon 19 and a point mutation in exon 21 (L858R) were 27.3% (9/33) and 28.1% (9/32), respectively, but these differences between objective response rates were not significant. The efficacy of second-line platinum-based chemotherapy followed at progression by gefitinib was similar to first-line platinum-based chemotherapy, and epidermal growth factor receptor mutation types did not influence the efficacy of second-line platinum-based chemotherapy. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Induction of a chloracne phenotype in an epidermal equivalent model by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is dependent on aryl hydrocarbon receptor activation and is not reproduced by aryl hydrocarbon receptor knock down.

PubMed

Forrester, Alison R; Elias, Martina S; Woodward, Emma L; Graham, Mark; Williams, Faith M; Reynolds, Nick J

2014-01-01

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent activator of the aryl hydrocarbon receptor (AhR) and causes chloracne in humans. The pathogenesis and role of AhR in chloracne remains incompletely understood. To elucidate the mechanisms contributing to the development of the chloracne-like phenotype in a human epidermal equivalent model and identify potential biomarkers. Using primary normal human epidermal keratinocytes (NHEK), we studied AhR activation by XRE-luciferase, AhR degradation and CYP1A1 induction. We treated epidermal equivalents with high affinity TCDD or two non-chloracnegens: β-naphthoflavone (β-NF) and 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE). Using Western blotting and immunochemistry for filaggrin (FLG), involucrin (INV) and transglutaminase-1 (TGM-1), we compared the effects of the ligands on keratinocyte differentiation and development of the chloracne-like phenotype by H&E. In NHEKs, activation of an XRE-luciferase and CYP1A1 protein induction correlated with ligand binding affinity: TCDD>β-NF>ITE. AhR degradation was induced by all ligands. In epidermal equivalents, TCDD induced a chloracne-like phenotype, whereas β-NF or ITE did not. All three ligands induced involucrin and TGM-1 protein expression in epidermal equivalents whereas FLG protein expression decreased following treatment with TCDD and β-NF. Inhibition of AhR by α-NF blocked TCDD-induced AhR activation in NHEKs and blocked phenotypic changes in epidermal equivalents; however, AhR knock down did not reproduce the phenotype. Ligand-induced CYP1A1 and AhR degradation did not correlate with their chloracnegenic potential, indicating that neither CYP1A1 nor AhR are suitable biomarkers. Mechanistic studies showed that the TCDD-induced chloracne-like phenotype depends on AhR activation whereas AhR knock down did not appear sufficient to induce the phenotype. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Aridification as a driver of biodiversity: a case study for the cycad genus Dioon (Zamiaceae).

PubMed

Said Gutiérrez-Ortega, José; Yamamoto, Takashi; Vovides, Andrew P; Angel Pérez-Farrera, Miguel; Martínez, José F; Molina-Freaner, Francisco; Watano, Yasuyuki; Kajita, Tadashi

2018-01-25

Aridification is considered a selective pressure that might have influenced plant diversification. It is suggested that plants adapted to aridity diversified during the Miocene, an epoch of global aridification (≈15 million years ago). However, evidence supporting diversification being a direct response to aridity is scarce, and multidisciplinary evidence, besides just phylogenetic estimations, is necessary to support the idea that aridification has driven diversification. The cycad genus Dioon (Zamiaceae), a tropical group including species occurring from humid forests to arid zones, was investigated as a promising study system to understand the associations among habitat shifts, diversification times, the evolution of leaf epidermal adaptations, and aridification of Mexico. A phylogenetic tree was constructed from seven chloroplast DNA sequences and the ITS2 spacer to reveal the relationships among 14 Dioon species from habitats ranging from humid forests to deserts. Divergence times were estimated and the habitat shifts throughout Dioon phylogeny were detected. The epidermal anatomy among Dioon species was compared and correlation tests were performed to associate the epidermal variations with habitat parameters. Events of habitat shifts towards arid zones happened exclusively in one of the two main clades of Dioon. Such habitat shifts happened during the species diversification of Dioon, mainly during the Miocene. Comparative anatomy showed epidermal differences between species from arid and mesic habitats. The variation of epidermal structures was found to be correlated with habitat parameters. Also, most of the analysed epidermal traits showed significant phylogenetic signals. The diversification of Dioon has been driven by the aridification of Mexico. The Miocene timing corresponds to the expansion of arid zones that embedded the ancestral Dioon populations. As response, species in arid zones evolved epidermal traits to counteract aridity stress. This case study provides a robust body of evidence supporting the idea that aridification is an important driver of biodiversity. © The Authors 2017. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Induction of a chloracne phenotype in an epidermal equivalent model by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is dependent on aryl hydrocarbon receptor activation and is not reproduced by aryl hydrocarbon receptor knock down

PubMed Central

Forrester, Alison R.; Elias, Martina S.; Woodward, Emma L.; Graham, Mark; Williams, Faith M.; Reynolds, Nick J.

2014-01-01

Background 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent activator of the aryl hydrocarbon receptor (AhR) and causes chloracne in humans. The pathogenesis and role of AhR in chloracne remains incompletely understood. Objective To elucidate the mechanisms contributing to the development of the chloracne-like phenotype in a human epidermal equivalent model and identify potential biomarkers. Methods Using primary normal human epidermal keratinocytes (NHEK), we studied AhR activation by XRE-luciferase, AhR degradation and CYP1A1 induction. We treated epidermal equivalents with high affinity TCDD or two non-chloracnegens: β-naphthoflavone (β-NF) and 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE). Using Western blotting and immunochemistry for filaggrin (FLG), involucrin (INV) and transglutaminase-1 (TGM-1), we compared the effects of the ligands on keratinocyte differentiation and development of the chloracne-like phenotype by H&E. Results In NHEKs, activation of an XRE-luciferase and CYP1A1 protein induction correlated with ligand binding affinity: TCDD > β-NF > ITE. AhR degradation was induced by all ligands. In epidermal equivalents, TCDD induced a chloracne-like phenotype, whereas β-NF or ITE did not. All three ligands induced involucrin and TGM-1 protein expression in epidermal equivalents whereas FLG protein expression decreased following treatment with TCDD and β-NF. Inhibition of AhR by α-NF blocked TCDD-induced AhR activation in NHEKs and blocked phenotypic changes in epidermal equivalents; however, AhR knock down did not reproduce the phenotype. Conclusion Ligand-induced CYP1A1 and AhR degradation did not correlate with their chloracnegenic potential, indicating that neither CYP1A1 nor AhR are suitable biomarkers. Mechanistic studies showed that the TCDD-induced chloracne-like phenotype depends on AhR activation whereas AhR knock down did not appear sufficient to induce the phenotype. PMID:24161567

Masquerading as self? Endoparasitic Strepsiptera (Insecta) enclose themselves in host-derived epidermal bag

PubMed Central

Kathirithamby, Jeyaraney; Ross, Larry D.; Johnston, J. Spencer

2003-01-01

We report here the case of a metazoan parasite, a strepsipteran, that manipulates host epidermal tissue and wraps itself within it; which probably camouflages the endoparasite and is recognized as ``self'' by the host. This mechanism is one of immune avoidance among parasitoid insects. The host-derived epidermal ``bag'' might have enabled Strepsiptera to radiate to disparate hosts compared with the relatively few taxa (596 species) described so far. They have been recorded as parasitizing 34 families belonging to seven orders of Insecta. We also report a mechanism of insect ecdysis between the first- and second-instar larva, while enclosed in the bag. PMID:12788973

Human Papilloma Viral DNA Replicates as a Stable Episome in Cultured Epidermal Keratinocytes

NASA Astrophysics Data System (ADS)

Laporta, Robert F.; Taichman, Lorne B.

1982-06-01

Human papilloma virus (HPV) is poorly understood because systems for its growth in tissue culture have not been developed. We report here that cultured human epidermal keratinocytes could be infected with HPV from plantar warts and that the viral DNA persisted and replicated as a stable episome. There were 50-200 copies of viral DNA per cell and there was no evidence to indicate integration of viral DNA into the cellular genome. There was also no evidence to suggest that viral DNA underwent productive replication. We conclude that cultured human epidermal keratinocytes may be a model for the study of certain aspects of HPV biology.

MECHANISMS OF ZN-INDUCED SIGNAL INITIATION THROUGH THE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR)

EPA Science Inventory

MECHANISMS OF Zn-INDUCED SIGNAL INITIATION THROUGH THE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR)
James M. Samet*, Lee M. Graves? and Weidong Wu?. *Human Studies Division, NHEERL, ORD, Research Triangle Park, NC 27711, and ?Center for Environmental Medicine, University of North C...

United theory of planet formation (i): Tandem regime

NASA Astrophysics Data System (ADS)

Ebisuzaki, Toshikazu; Imaeda, Yusuke

2017-07-01

The present paper is the first one of a series of papers that present the new united theory of planet formation, which includes magneto-rotational instability and porous aggregation of solid particles in an consistent way. We here describe the ;tandem; planet formation regime, in which a solar system like planetary systems are likely to be produced. We have obtained a steady-state, 1-D model of the accretion disk of a protostar taking into account the magneto-rotational instability (MRI) and and porous aggregation of solid particles. We find that the disk is divided into an outer turbulent region (OTR), a MRI suppressed region (MSR), and an inner turbulent region (ITR). The outer turbulent region is fully turbulent because of MRI. However, in the range, rout(= 8 - 60 AU) from the central star, MRI is suppressed around the midplane of the gas disk and a quiet area without turbulence appears, because the degree of ionization of gas becomes low enough. The disk becomes fully turbulent again in the range rin(= 0.2 - 1 AU), which is called the inner turbulent region, because the midplane temperature become high enough (>1000 K) due to gravitational energy release. Planetesimals are formed through gravitational instability at the outer and inner MRI fronts (the boundaries between the MRI suppressed region (MSR) and the outer and inner turbuent regions) without particle enhancement in the original nebula composition, because of the radial concentration of the solid particles. At the outer MRI front, icy particles grow through low-velocity collisions into porous aggregates with low densities (down to ∼10-5 gcm-3). They eventually undergo gravitational instability to form icy planetesimals. On the other hand, rocky particles accumulate at the inner MRI front, since their drift velocities turn outward due to the local maximum in gas pressure. They undergo gravitational instability in a sub-disk of pebbles to form rocky planetesimals at the inner MRI front. They are likely to be volatile-free because of the high temperature (>1000 K) at this formation site. Such water-free rocky particles may explain the formation of enstatite chondrites, of which the Earth is likely to be primarily composed of. It is also consistent with the model in which the Earth was initially formed as a completely volatile-free planet. The water and other volatile elements came later through the accretion of icy particles by the occasional scatterings in the outer regions. Our new proposed tandem planet formation regime shows that planetesimals are formed at two distinct sites (outer and inner edges of the MRI suppressed region). The former is likely to be the source of outer gas giants and the latter inner rocky planets. The tandem regime also explains the gap in the distribution of solid components (2-4 AU), which is necessary to form a ;solar-system-like; planetary system, which has a relatively small Mars and a very small mass in the main asteroid belt. We found that this tandem regime dose not take place when the vertical magnetic field of the disk five times weaker compared with that we assumed in the present paper, since the outer MRI front shift outward beyond 100 AU. This suggests that yet other regimes exists in our united theory. It may explain the variation observed in exsoplanetary systems by variations in magnetic field and probably angular momentum of the parent molecular cloud.

Epidermal PPARγ influences subcutaneous tumor growth and acts through TNF-α to regulate contact hypersensitivity and the acute photoresponse

PubMed Central

Konger, Raymond L.; Derr-Yellin, Ethel; Travers, Jeffrey B.; Ocana, Jesus A.; Sahu, Ravi P.

2017-01-01

It is known that ultraviolet B (UVB) induces PPARγ ligand formation while loss of murine epidermal PPARγ (Pparg-/-epi) promotes UVB-induced apoptosis, inflammation, and carcinogenesis. PPARγ is known to suppress tumor necrosis factor-α (TNF-α) production. TNF-α is also known to promote UVB-induced inflammation, apoptosis, and immunosuppression. We show that Pparg-/-epi mice exhibit increased baseline TNF-α expression. Neutralizing Abs to TNF-α block the increased photo-inflammation and photo-toxicity that is observed in Pparg-/-epi mouse skin. Interestingly, the increase in UVB-induced apoptosis in Pparg-/-epi mice is not accompanied by a change in cyclobutane pyrimidine dimer clearance or in mutation burden. This suggests that loss of epidermal PPARγ does not result in a significant alteration in DNA repair capacity. However, loss of epidermal PPARγ results in marked immunosuppression using a contact hypersensitivity (CHS) model. This impaired CHS response was significantly alleviated using neutralizing TNF-α antibodies or loss of germline Tnf. In addition, the PPARγ agonist rosiglitazone reversed UVB-induced systemic immunosuppression (UV-IS) as well as UV-induced growth of B16F10 melanoma tumor cells in syngeneic mice. Finally, increased B16F10 tumor growth was observed when injected subcutaneously into Pparg-/-epi mice. Thus, we provide novel evidence that epidermal PPARγ is important for cutaneous immune function and the acute photoresponse. PMID:29228682

Epidermal E-Cadherin Dependent β-Catenin Pathway Is Phytochemical Inducible and Accelerates Anagen Hair Cycling.

PubMed

Ahmed, Noha S; Ghatak, Subhadip; El Masry, Mohamed S; Gnyawali, Surya C; Roy, Sashwati; Amer, Mohamed; Everts, Helen; Sen, Chandan K; Khanna, Savita

2017-11-01

Unlike the epidermis, which regenerates continually, hair follicles anchored in the subcutis periodically regenerate by spontaneous repetitive cycles of growth (anagen), degeneration (catagen), and rest (telogen). The loss of hair follicles in response to injuries or pathologies such as alopecia endangers certain inherent functions of the skin. Thus, it is of interest to understand mechanisms underlying follicular regeneration in adults. In this work, a phytochemical rich in the natural vitamin E tocotrienol (TRF) served as a productive tool to unveil a novel epidermal pathway of hair follicular regeneration. Topical TRF application markedly induced epidermal hair follicle development akin to that during fetal skin development. This was observed in the skin of healthy as well as diabetic mice, which are known to be resistant to anagen hair cycling. TRF suppressed epidermal E-cadherin followed by 4-fold induction of β-catenin and its nuclear translocation. Nuclear β-catenin interacted with Tcf3. Such sequestration of Tcf3 from its otherwise known function to repress pluripotent factors induced the plasticity factors Oct4, Sox9, Klf4, c-Myc, and Nanog. Pharmacological inhibition of β-catenin arrested anagen hair cycling by TRF. This work reports epidermal E-cadherin/β-catenin as a novel pathway capable of inducing developmental folliculogenesis in the adult skin. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

A new system for cultivation of human keratinocytes on acellular dermal matrix substitute with the use of human fibroblast feeder layer.

PubMed

Xiao, S; Zhu, S; Ma, B; Xia, Z-F; Yang, J; Wang, G

2008-01-01

To improve the proliferative potential of human keratinocytes (HK) cultured on acellular dermal matrix (ADM), HK and mitomycin C-treated human fibroblasts (MMC-HF) were seeded onto ADM to form four types of composite skin: type I, HK were seeded onto the epidermal side of ADM; type II, both HK and MMC-HF were seeded onto the epidermal side; type III, MMC-HF were preseeded onto the dermal side of ADM, and then HK were seeded onto the epidermal side, and type IV, where MMC-HF were preseeded onto both sides, and then HK were seeded onto the epidermal side. Compared with type I and III, the proliferative potential of HK of type II and IV was significantly higher on day 3, 5, 7 and 9 in vitro. In type I and III, HK grew into one layer on day 7-9, while in type II and IV keratinocytes grew into a confluent monolayer by day 4-6. The adherence to ADM of HK in types II and IV was stronger than that in type I and III. The take rate of type II and IV composite skin was also significantly higher. In conclusion, when MMC-HF and HK were cocultured on the epidermal side of ADM, MMC-HF could serve as excellent feeder cells. Copyright 2007 S. Karger AG, Basel.

Role of epidermal stem cells in repair of partial-thickness burn injury after using Moist Exposed Burn Ointment (MEBO(®)) histological and immunohistochemical study.

PubMed

El-Hadidy, M R; El-Hadidy, A R; Bhaa, A; Asker, S A; Mazroa, S A

2014-04-01

Moist Exposed Burn Ointment (MEBO(®)) is widely used topical agent applied on skin burn. This study investigated the effect of MEBO topical application on activation and proliferation of epidermal stem cells through the immunohistochemical localization of cytokeratin 19 (CK19) as a known marker expressed in epidermal stem cells. Biopsies from normal skin and burn wounds were taken from 21 patients with partial thickness burn 1, 4, 7, 14, 21, and 28 days after treatment with MEBO. Tissue sections were prepared for histological study and for CK19 immunohistochemical localization. In control skin, only few cells showed a positive CK19 immune-reaction. Burned skin showed necrosis of full thickness epidermis that extended to dermis. Gradual regeneration of skin accompanied with an enhancement in CK19 immune-reactivity was noted 4, 7, 14 and 21 days after treatment with MEBO. On day 28, a complete regeneration of skin was observed with a return of CK19 immune-reactivity to the basal pattern again. In conclusion, the enhancement of epidermal stem cell marker CK19 after treatment of partial thickness burn injuries with MEBO suggested the role of MEBO in promoting epidermal stem cell activation and proliferation during burn wound healing. Copyright © 2014 Elsevier Ltd. All rights reserved.

Delineation of Matriptase Protein Expression by Enzymatic Gene Trapping Suggests Diverging Roles in Barrier Function, Hair Formation, and Squamous Cell Carcinogenesis

PubMed Central

List, Karin; Szabo, Roman; Molinolo, Alfredo; Nielsen, Boye Schnack; Bugge, Thomas H.

2006-01-01

The membrane serine protease matriptase is required for epidermal barrier function, hair formation, and thymocyte development in mice, and dysregulated matriptase expression causes epidermal squamous cell carcinoma. To elucidate the specific functions of matriptase in normal and aberrant epidermal differentiation, we used enzymatic gene trapping combined with immunohistochemical, ultrastructural, and barrier function assays to delineate the spatio-temporal expression and function of matriptase in mouse keratinized tissue development, homeostasis, and malignant transformation. In the interfollicular epidermis, matriptase expression was restricted to postmitotic transitional layer keratinocytes undergoing terminal differentiation. Matriptase was also expressed in keratinizing oral epithelium, where it was required for oral barrier function, and in thymic epithelium. In all three tissues, matriptase colocalized with profilaggrin. In staged embryos, the onset of epidermal matriptase expression coincided with that of profilaggrin expression and acquisition of the epidermal barrier. In marked contrast to stratifying keritinized epithelium, matripase expression commenced already in undifferentiated and rapidly proliferating profilaggrin-negative matrix cells and displayed hair growth cycle-dependent expression. Exposure of the epidermis to carcinogens led to the gradual appearance of matriptase in a keratin-5-positive proliferative cell compartment during malignant progression. Combined with previous studies, these data suggest that matriptase has diverging functions in the genesis of stratified keratinized epithelium, hair follicles, and squamous cell carcinoma. PMID:16651618

Delineation of matriptase protein expression by enzymatic gene trapping suggests diverging roles in barrier function, hair formation, and squamous cell carcinogenesis.

PubMed

List, Karin; Szabo, Roman; Molinolo, Alfredo; Nielsen, Boye Schnack; Bugge, Thomas H

2006-05-01

The membrane serine protease matriptase is required for epidermal barrier function, hair formation, and thymocyte development in mice, and dysregulated matriptase expression causes epidermal squamous cell carcinoma. To elucidate the specific functions of matriptase in normal and aberrant epidermal differentiation, we used enzymatic gene trapping combined with immunohistochemical, ultrastructural, and barrier function assays to delineate the spatio-temporal expression and function of matriptase in mouse keratinized tissue development, homeostasis, and malignant transformation. In the interfollicular epidermis, matriptase expression was restricted to postmitotic transitional layer keratinocytes undergoing terminal differentiation. Matriptase was also expressed in keratinizing oral epithelium, where it was required for oral barrier function, and in thymic epithelium. In all three tissues, matriptase colocalized with profilaggrin. In staged embryos, the onset of epidermal matriptase expression coincided with that of profilaggrin expression and acquisition of the epidermal barrier. In marked contrast to stratifying keritinized epithelium, matripase expression commenced already in undifferentiated and rapidly proliferating profilaggrin-negative matrix cells and displayed hair growth cycle-dependent expression. Exposure of the epidermis to carcinogens led to the gradual appearance of matriptase in a keratin-5-positive proliferative cell compartment during malignant progression. Combined with previous studies, these data suggest that matriptase has diverging functions in the genesis of stratified keratinized epithelium, hair follicles, and squamous cell carcinoma.

Grhl3 and Lmo4 play coordinate roles in epidermal migration.

PubMed

Hislop, Nikki R; Caddy, Jacinta; Ting, Stephen B; Auden, Alana; Vasudevan, Sumitha; King, Sarah L; Lindeman, Geoffrey J; Visvader, Jane E; Cunningham, John M; Jane, Stephen M

2008-09-01

In addition to its role in formation of the epidermal barrier, the mammalian transcription factor Grainy head-like 3 (Grhl3) is also essential for neural tube closure and wound repair, processes that are dependent in part on epidermal migration. Here, we demonstrate that the LIM-only domain protein, LMO4 serves as a functional partner of GRHL3 in its established roles, and define a new cooperative role for these factors in another developmental epidermal migration event, eyelid fusion. GRHL3 and LMO4 interact biochemically and genetically, with mutant mice exhibiting fully penetrant exencephaly, thoraco-lumbo-sacral spina bifida, defective skin barrier formation, and a co-incident eyes-open-at-birth (EOB) phenotype, which is not observed in the original individual null lines. The two genes are co-expressed in the surface ectoderm of the migrating eyelid root, and electron microscopy of Grhl3/Lmo4-null eyes reveals a failure in epithelial extension and a lack of peridermal clump formation at the eyelid margins. Accumulation of actin fibers is also absent in the circumference of these eyelids, and ERK1/2 phosphorylation is lost in the epidermis and eyelids of Grhl3(-/-)/Lmo4(-/-) embryos. Keratinocytes from mutant mice fail to "heal" in in vitro scratch assays, consistent with a general epidermal migratory defect that is dependent on ERK activation and actin cable formation.

RNA-seq Analysis of Host and Viral Gene Expression Highlights Interaction between Varicella Zoster Virus and Keratinocyte Differentiation

PubMed Central

Singh, Manuraj; Kanda, Ravinder K.; Yee, Michael B.; Kellam, Paul; Hollinshead, Michael; Kinchington, Paul R.; O'Toole, Edel A.; Breuer, Judith

2014-01-01

Varicella zoster virus (VZV) is the etiological agent of chickenpox and shingles, diseases characterized by epidermal skin blistering. Using a calcium-induced keratinocyte differentiation model we investigated the interaction between epidermal differentiation and VZV infection. RNA-seq analysis showed that VZV infection has a profound effect on differentiating keratinocytes, altering the normal process of epidermal gene expression to generate a signature that resembles patterns of gene expression seen in both heritable and acquired skin-blistering disorders. Further investigation by real-time PCR, protein analysis and electron microscopy revealed that VZV specifically reduced expression of specific suprabasal cytokeratins and desmosomal proteins, leading to disruption of epidermal structure and function. These changes were accompanied by an upregulation of kallikreins and serine proteases. Taken together VZV infection promotes blistering and desquamation of the epidermis, both of which are necessary to the viral spread and pathogenesis. At the same time, analysis of the viral transcriptome provided evidence that VZV gene expression was significantly increased following calcium treatment of keratinocytes. Using reporter viruses and immunohistochemistry we confirmed that VZV gene and protein expression in skin is linked with cellular differentiation. These studies highlight the intimate host-pathogen interaction following VZV infection of skin and provide insight into the mechanisms by which VZV remodels the epidermal environment to promote its own replication and spread. PMID:24497829

Blumeria graminis interactions with barley conditioned by different single R genes demonstrate a temporal and spatial relationship between stomatal dysfunction and cell death.

PubMed

Prats, Elena; Gay, Alan P; Roberts, Peter C; Thomas, Barry J; Sanderson, Ruth; Paveley, Neil; Lyngkjaer, Michael F; Carver, Tim L W; Mur, Luis A J

2010-01-01

Hypersensitive response (HR) against Blumeria graminis f. sp. hordei infection in barley (Hordeum vulgare) was associated with stomata "lock-up" leading to increased leaf water conductance (g(l)). Unique spatio-temporal patterns of HR formation occurred in barley with Mla1, Mla3, or MlLa R genes challenged with B. graminis f. sp. hordei. With Mla1, a rapid HR, limited to epidermal cells, arrested fungal growth before colonies initiated secondary attacks. With Mla3, mesophyll HR preceded that in epidermal cells whose initial survival supported secondary infections. With MlLa, mesophyll survived and not all attacked epidermal cells died immediately, allowing colony growth and secondary infection until arrested. Isolines with Mla1, Mla3, or MlLa genes inoculated with B. graminis f. sp. hordei ranging from 1 to 100 conidia mm(2) showed abnormally high g(l) during dark periods whose timing and extent correlated with those of each HR. Each isoline showed increased dark g(l) with the nonpathogen B. graminis f. sp. avenae which caused a single epidermal cell HR. Guard cell autofluorescence was seen only after drying of epidermal strips and closure of stomata suggesting that locked open stomata were viable. The data link stomatal lock-up to HR associated cell death and has implications for strategies for selecting disease resistant genotypes.

Secreted HoxA3 Promotes Epidermal Proliferation and Angiogenesis in Genetically Modified Three-Dimensional Composite Skin Constructs

PubMed Central

Kuo, Jennifer H.; Cuevas, Ileana; Chen, Amy; Dunn, Ashley; Kuri, Mauricio; Boudreau, Nancy

2014-01-01

Objective: Homeobox (HOX) transcription factors coordinate gene expression in wound repair and angiogenesis. Previous studies have shown that gene transfer of HoxA3 to wounds of diabetic mice accelerates wound healing, increasing angiogenesis and keratinocyte migration. In this study, we examined whether HoxA3 can also improve angiogenesis, epidermal integrity, and viability of composite skin grafts. Approach: To determine the effects of HoxA3 on composite skin grafts, we constructed bilayered composite grafts incorporating fibroblasts engineered to constitutively secrete HoxA3. We then transplanted these composite grafts in vivo. Results: The composite grafts produced a stratified epidermal layer after seventeen days in culture and following transplantation in vivo, these grafts exhibit normal epidermal differentiation and reduced contraction compared to controls. In addition, HoxA3 grafts showed increased angiogenesis. Quantitative polymerase chain reaction (PCR) analyses of HoxA3 graft tissue reveal an increase in the downstream HoxA3 target genes MMP-14 and uPAR expression, as well as a reduction in CCL-2 and CxCl-12. Innovation: Expression of secreted HoxA3 in composite grafts represents a comprehensive approach that targets both keratinocytes and endothelial cells to promote epidermal proliferation and angiogenesis. Conclusion: Secreted HoxA3 improves angiogenesis, reduces expression of inflammatory mediators, and prolongs composite skin graft integrity. PMID:25302136

Outer Solutions for General Linear Turning Point Problems.

DTIC Science & Technology

1977-02-01

i l t e r e n t i a l equat ions near a pole wi th respect to a parameter . For general inves t iga t ions such d i f f e ren t i a l equat...analyt ic funct ions Ar (X) are allowed to have poles at x = 0. This the ory can easily be extended to slightly more involved types of s ingular i t...4) means that the order of the poles of A (x) can grow , at worst , l inearly with r. This restraining inequal i ty is the stronger the larger K i s

Steam conversion of liquefied petroleum gas and methane in microchannel reactor

NASA Astrophysics Data System (ADS)

Dimov, S. V.; Gasenko, O. A.; Fokin, M. I.; Kuznetsov, V. V.

2018-03-01

This study presents experimental results of steam conversion of liquefied petroleum gas and methane in annular catalytic reactor - heat exchanger. The steam reforming was done on the Rh/Al2O3 nanocatalyst with the heat applied through the microchannel gap from the outer wall. Concentrations of the products of chemical reactions in the outlet gas mixture are measured at different temperatures of reactor. The range of channel wall temperatures at which the ratio of hydrogen and carbon oxide in the outlet mixture grows substantially is determined. Data on the composition of liquefied petroleum gas conversion products for the ratio S/C = 5 was received for different GHVS.

Analysis of Sel-Gravitating Planetary Satellites in the Solar System

NASA Astrophysics Data System (ADS)

Yasenev, S. O.

As of today there have been more than 180 planetary satellites discovered in the Solar system, and the number of outer moons found continues to grow. Most of those natural satellites have insufficient mass and are able to retain their shape only due to the strength of the electromagnetic force. The purpose of this paper is to analyze the moons' physical properties. The analysis of planetary satellites as self-gravitating bodies, i.e. celestial bodies which rely on the weight of their own mass and resulting gravitational force to maintain their shape and tend to bring it closer to the hydrostatic equilibrium, was performed.

Subnanosecond-laser-induced periodic surface structures on prescratched silicon substrate

NASA Astrophysics Data System (ADS)

Hongo, Motoharu; Matsuo, Shigeki

2016-06-01

Laser-induced periodic surface structures (LIPSS) were fabricated on a prescratched silicon surface by irradiation with subnanosecond laser pulses. Low-spatial-frequency LIPSS (LSFL) were observed in the central and peripheral regions; both had a period Λ close to the laser wavelength λ, and the wavevector orientation was parallel to the electric field of the laser beam. The LSFL in the peripheral region seemed to be growing, that is, expanding in length with increasing number of pulses, into the outer regions. In addition, high-spatial-frequency LIPSS, Λ ≲ λ /2, were found along the scratches, and their wavevector orientation was parallel to the scratches.

ELECTRON MICROSCOPIC OBSERVATIONS OF AMOEBA PROTEUS IN GROWTH AND INANITION

PubMed Central

Cohen, Adolph I.

1957-01-01

Electron microscopic observations have been made on growing and dividing specimens of Amoeba proteus and also on starving animals. Structures presumably corresponding to the mitochondria, alpha particles, vacuoles, and Golgi material are described. A new entity, designated as a foamy particle, is noted. Descriptions are given of the cytoplasmic and nuclear membranes. During division the inner, thick nuclear membrane component is seen to vanish and the outer membrane persist. Measurements suggest a gradual reappearance of the inner component with growth. Starving animals show a loss of cytoplasmic granularity and an increase in the electron density of mitochondria, presumably due to lipide accumulation. PMID:13481020

Electron microscopic observations of amoeba proteus in growth and inanition.

PubMed

COHEN, A I

1957-11-25

Electron microscopic observations have been made on growing and dividing specimens of Amoeba proteus and also on starving animals. Structures presumably corresponding to the mitochondria, alpha particles, vacuoles, and Golgi material are described. A new entity, designated as a foamy particle, is noted. Descriptions are given of the cytoplasmic and nuclear membranes. During division the inner, thick nuclear membrane component is seen to vanish and the outer membrane persist. Measurements suggest a gradual reappearance of the inner component with growth. Starving animals show a loss of cytoplasmic granularity and an increase in the electron density of mitochondria, presumably due to lipide accumulation.

ETI, SETI and today's public opinion

NASA Astrophysics Data System (ADS)

Pinotti, Roberto

During the last three decades the general public's initial opinions about ETI and SETI changed, turning ignorance, fear and superficiality into a gradual understanding of the importance of these concepts. After a brief analysis of this changing psycho-sociological attitude, the paper provides an "estimate of the situation" about general interest for ETI and SETI, suggesting a growing awareness in today's public opinion. Science fiction movies like Close Encounters of the Third Kind and E.T. the Extra-Terrestrial and popular interest in UFOs as visitors from outer space played a major role in the average man's acceptance of the reality of extra-terrestrial life and its meaning for mankind.

Iron Uptake Mechanisms in the Fish Pathogen Tenacibaculum maritimum

PubMed Central

Avendaño-Herrera, Ruben; Toranzo, Alicia E.; Romalde, Jesús L.; Lemos, Manuel L.; Magariños, Beatriz

2005-01-01

We present here the first evidence of the presence of iron uptake mechanisms in the bacterial fish pathogen Tenacibaculum maritimum. Representative strains of this species, with different serotypes and origins, were examined. All of them were able to grow in the presence of the chelating agent ethylenediamine-di- (o-hydroxyphenyl acetic acid) (EDDHA) and also produced siderophores. Cross-feeding assays suggest that the siderophores produced are closely related. In addition, all T. maritimum strains utilized transferrin, hemin, hemoglobin, and ferric ammonic citrate as iron sources when added to iron-deficient media. Whole cells of all T. maritimum strains, grown under iron-supplemented or iron-restricted conditions, were able to bind hemin, indicating the existence of constitutive binding components located at the T. maritimum cell surface. This was confirmed by the observation that isolated total and outer membrane proteins from all of the strains, regardless of the iron levels of the media, were able to bind hemin, with the outer membranes showing the strongest binding. proteinase K treatment of whole cells did not affect the hemin binding, indicating that, in addition to proteins, some protease-resistant components could also bind hemin. At least three outer membrane proteins were induced in iron-limiting conditions, and all strains, regardless of their serotype, showed a similar pattern of induced proteins. The results of the present study suggest that T. maritimum possesses at least two different systems of iron acquisition: one involving the synthesis of siderophores and another that allows the utilization of heme groups as iron sources by direct binding. PMID:16269729

Iron uptake mechanisms in the fish pathogen Tenacibaculum maritimum.

PubMed

Avendaño-Herrera, Ruben; Toranzo, Alicia E; Romalde, Jesús L; Lemos, Manuel L; Magariños, Beatriz

2005-11-01

We present here the first evidence of the presence of iron uptake mechanisms in the bacterial fish pathogen Tenacibaculum maritimum. Representative strains of this species, with different serotypes and origins, were examined. All of them were able to grow in the presence of the chelating agent ethylenediamine-di-(o-hydroxyphenyl acetic acid) (EDDHA) and also produced siderophores. Cross-feeding assays suggest that the siderophores produced are closely related. In addition, all T. maritimum strains utilized transferrin, hemin, hemoglobin, and ferric ammonic citrate as iron sources when added to iron-deficient media. Whole cells of all T. maritimum strains, grown under iron-supplemented or iron-restricted conditions, were able to bind hemin, indicating the existence of constitutive binding components located at the T. maritimum cell surface. This was confirmed by the observation that isolated total and outer membrane proteins from all of the strains, regardless of the iron levels of the media, were able to bind hemin, with the outer membranes showing the strongest binding. Proteinase K treatment of whole cells did not affect the hemin binding, indicating that, in addition to proteins, some protease-resistant components could also bind hemin. At least three outer membrane proteins were induced in iron-limiting conditions, and all strains, regardless of their serotype, showed a similar pattern of induced proteins. The results of the present study suggest that T. maritimum possesses at least two different systems of iron acquisition: one involving the synthesis of siderophores and another that allows the utilization of heme groups as iron sources by direct binding.

Increased Serum Levels of Epidermal Growth Factor in Children with Autism

ERIC Educational Resources Information Center

Iseri, Elvan; Guney, Esra; Ceylan, Mehmet F.; Yucel, Aysegul; Aral, Arzu; Bodur, Sahin; Sener, Sahnur

2011-01-01

The etiology of autism is unclear, however autism is considered as a multifactorial disorder that is influenced by neurological, environmental, immunological and genetic factors. Growth factors, including epidermal growth factor (EGF), play an important role in the celluler proliferation and the differentiation of the central and peripheral…

Selenoprotein W controls epidermal growth factor receptor surface expression, activation and degradation via receptor ubiquitination

USDA-ARS?s Scientific Manuscript database

Epidermal growth factor (EGF) receptor (EGFR) is the founding member of the ErbB family of growth factor receptors that modulate a complex network of intracellular signaling pathways controlling growth, proliferation and differentiation. Selenoprotein W (SEPW1) is a diet-regulated, highly conserved...

Toxicity Assessment of Six Titanium Dioxide Nanoparticles in Human Epidermal Keratinocytes

EPA Science Inventory

Toxicity Assessment of Six Titanium Dioxide Nanoparticles in Human Epidermal Keratinocytes Nanoparticle uptake in cells may be an important determinant of their potential cytotoxic and inflammatory effects. Six commercial TiO2 NP (A=Alfa Aesar,10nm, A*=Alfa Aesar 32nm, B=P25 27...

CUTIN SYNTHASE 2 Maintains Progressively Developing Cuticular Ridges in Arabidopsis Sepals.

PubMed

Hong, Lilan; Brown, Joel; Segerson, Nicholas A; Rose, Jocelyn K C; Roeder, Adrienne H K

2017-04-03

The cuticle is a crucial barrier on the aerial surfaces of land plants. In many plants, including Arabidopsis, the sepals and petals form distinctive nanoridges in their cuticles. However, little is known about how the formation and maintenance of these nanostructures is coordinated with the growth and development of the underlying cells. Here we report the characterization of the Arabidopsis cutin synthase 2 (cus2) mutant, which causes a great reduction in cuticular ridges on the mature sepal epidermis, but only a moderate effect on petal cone cell ridges. Using scanning electron microscopy and confocal live imaging combined with quantification of cellular growth, we find that cuticular ridge formation progresses down the sepal from tip to base as the sepal grows. pCUS2::GFP-GUS reporter expression coincides with cuticular ridge formation, descending the sepal from tip to base. Ridge formation also coincides with the reduction in growth rate and termination of cell division of the underlying epidermal cells. Surprisingly, cuticular ridges at first form normally in the cus2 mutant, but are lost progressively at later stages of sepal development, indicating that CUS2 is crucial for the maintenance of cuticular ridges after they are formed. Our results reveal the dynamics of both ridge formation and maintenance as the sepal grows. Copyright © 2017 The Author. Published by Elsevier Inc. All rights reserved.

Identification and characterization of a matrix protein (PPP-10) in the periostracum of the pearl oyster, Pinctada fucata.

PubMed

Nakayama, Seiji; Suzuki, Michio; Endo, Hirotoshi; Iimura, Kurin; Kinoshita, Shigeharu; Watabe, Shugo; Kogure, Toshihiro; Nagasawa, Hiromichi

2013-01-01

The periostracum is a layered structure that is formed as a mollusk shell grows. The shell is covered by the periostracum, which consists of organic matrices that prevent decalcification of the shell. In the present study, we discovered the presence of chitin in the periostracum and identified a novel matrix protein, Pinctada fucata periostracum protein named PPP-10. It was purified from the sodium dodecyl sulfate/dithiothreitol-soluble fraction of the periostracum of the Japanese pearl oyster, P. fucata. The deduced amino acid sequence was determined by a combination of amino acid sequence analysis and cDNA cloning. The open reading frame encoded a precursor protein of 112 amino acid residues including a 21-residue signal peptide. The 91 residues following the signal peptide contained abundant Cys and Tyr residues. PPP-10 was expressed on the outer side of the outer fold in the mantle, indicating that PPP-10 was present in the second or third layer of the periostracum. We also determined that the recombinant PPP-10 had chitin-binding activity and could incorporate chitin into the scaffolds of the periostracum. These results shed light on the early steps in mollusk shell formation.

Identification and characterization of a matrix protein (PPP-10) in the periostracum of the pearl oyster, Pinctada fucata☆

PubMed Central

Nakayama, Seiji; Suzuki, Michio; Endo, Hirotoshi; Iimura, Kurin; Kinoshita, Shigeharu; Watabe, Shugo; Kogure, Toshihiro; Nagasawa, Hiromichi

2013-01-01

The periostracum is a layered structure that is formed as a mollusk shell grows. The shell is covered by the periostracum, which consists of organic matrices that prevent decalcification of the shell. In the present study, we discovered the presence of chitin in the periostracum and identified a novel matrix protein, Pinctada fucata periostracum protein named PPP-10. It was purified from the sodium dodecyl sulfate/dithiothreitol-soluble fraction of the periostracum of the Japanese pearl oyster, P. fucata. The deduced amino acid sequence was determined by a combination of amino acid sequence analysis and cDNA cloning. The open reading frame encoded a precursor protein of 112 amino acid residues including a 21-residue signal peptide. The 91 residues following the signal peptide contained abundant Cys and Tyr residues. PPP-10 was expressed on the outer side of the outer fold in the mantle, indicating that PPP-10 was present in the second or third layer of the periostracum. We also determined that the recombinant PPP-10 had chitin-binding activity and could incorporate chitin into the scaffolds of the periostracum. These results shed light on the early steps in mollusk shell formation. PMID:24251105

Hot-start Giant Planets Form with Radiative Interiors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berardo, David; Cumming, Andrew, E-mail: david.berardo@mcgill.ca, E-mail: andrew.cumming@mcgill.ca

In the hot-start core accretion formation model for gas giants, the interior of a planet is usually assumed to be fully convective. By calculating the detailed internal evolution of a planet assuming hot-start outer boundary conditions, we show that such a planet will in fact form with a radially increasing internal entropy profile, so that its interior will be radiative instead of convective. For a hot outer boundary, there is a minimum value for the entropy of the internal adiabat S {sub min} below which the accreting envelope does not match smoothly onto the interior, but instead deposits high entropymore » material onto the growing interior. One implication of this would be to at least temporarily halt the mixing of heavy elements within the planet, which are deposited by planetesimals accreted during formation. The compositional gradient this would impose could subsequently disrupt convection during post-accretion cooling, which would alter the observed cooling curve of the planet. However, even with a homogeneous composition, for which convection develops as the planet cools, the difference in cooling timescale will change the inferred mass of directly imaged gas giants.« less

Towards understanding the biological function of hopanoids (Invited)

NASA Astrophysics Data System (ADS)

Doughty, D. M.; Hunter, R.; Summons, R. E.; Newman, D. K.

2010-12-01

Rhodopseudomonas palustris TIE-1 expresses bacterial hopanoid lipids that are structurally similar and evolutionarily related to eukaryotic sterols. The genome of R. palustris TIE-1 contains two copies of the hpnN gene (hpnN1 and hpnN2) that are orthologs of genes encoding eukaryotic sterol and lipid transporters. Hopanoid localization to the outer membrane was found to be dependent upon hpnN1. Since the cell cycle of R. palustris TIE-1 is obligately bimodal with each cell division resulting in the generation of one mother and one swarmer cell, evidence was obtained that hopanoids where specifically localized to the outer membrane of mother cells. The sequestration of hopanoids to the mother cells was also disrupted by the deletion of the hpnN1 gene. Mutants lacking the hopanoid transporters were able to grow normally at 30 °C but showed decreased growth at 38 °C. The hopanoid transporter mutant formed cellular filaments when grown at elevated temperature. Because sedimentary steranes and hopanes comprise some of the earliest evidence for the emergence of distinct bacteria and eukaryotic phyla, a better appreciation of the function of hopanoids will improve our ability to interpret the evolution of life on Earth.

Histological comparison of long-bone cortex between 11-year-old giant cow with dermal dysplasia and the child cow aged 8.5 years.

PubMed

Mori, Ryoichi; Kodaka, Tetsuo; Naito, Yoshihisa

2012-02-01

Young calves are known to be formed with laminar bone in long-bone cortex during growing periods and the osteon formation begins later. Previously, we reported that an 11-year-old giant Holstein cow with dermal dysplasia showed a delayed osteon formation. An 8.5-year-old cow, born from the giant Holstein cow, also showed some dermal dysplasia and the outer-half layer of the child almost retained laminar bone similar to that of the mother, although the body weight was approximately normal. The mother had formed the inner circumferential lamella and the child was going to form the inner circumferential lamella, but their outer circumferential lamellas were not formed yet in both of them, when compared with a 12-years-old cow as a control of the mother. Therefore, we suggest on long-bone formation pattern that the child resembled the mother rather than the control, and that the child had more or less succeeded to the mother genes of delayed osteon formation as well as dermal dysplasia which seemed to be genetic collagen disorder, although there were mild gene appearances.

Can the Plasmaspheric Plume Significantly Contribute to Magnetosheath Densities?

NASA Technical Reports Server (NTRS)

Gallagher, Dennis; Goldstein, Jerry; Sibeck, David

2010-01-01

Intervals of strong magnetospheric convection electric fields can result in the removal of large portions of the outer plasmasphere and its transport to the vicinity of the magnetopause. Of growing interest is the disposition of that plasma and its possible influence on the processes operating in the regions contributed to by this dense thermal plasma of ionospheric origin. Plasmaspheric plasma may recirculate within the outer magnetosphere through the flanks to become part of the plasmasheet, be entrained on reconnected magnetic field lines drawn anti-sunward over the polar cap, or be lost into the magnetosheath flow and into the solar wind. Of interest here is whether it is reasonable to anticipate that the plume material is sufficient to contribute substantially to magnetosheath densities at the magnetopause where it could influence reconnection between the interplanetary and terrestrial magnetic fields. We present the results of model simulations of plasmaspheric plume and magnetosheath plasmas in the context of several storm-time event periods. Plume and magnetosheath densities are compared as a function of location and storm phase. The short answer is, "yes", but not always and not at all locations. The full answer will be presented.

Nocturnal Accumulation of Malic Acid Occurs in Mesophyll Tissue without Proton Transport to Epidermal Tissue in the Inducible Crassulacean Acid Metabolism Plant Mesembryanthemum crystallinum1

PubMed Central

Winter, Klaus; Edwards, Gerald E.; Holtum, Joseph A. M.

1981-01-01

The inducible Crassulacean acid metabolism plant, Mesembryanthemum crystallinum, accumulates malic acid, i.e. equivalent amounts of malate anions and protons in the mesophyll cells at night. Levels of malate and titratable acidity are low in the epidermal tissue and do not change significantly during the day/night cycle. This result is in contrast to a recent report (Bloom 1979 Plant Physiol 64: 919-923) that the synthesis of malic acid during dark CO2 fixation is associated with an equivalent exchange of inorganic cations from epidermal tissue with protons in the mesophyll cells. PMID:16661916

Ricinus communis-based biopolymer and epidermal growth factor regulations on bone defect repair: A rat tibia model

NASA Astrophysics Data System (ADS)

Mendoza-Barrera, C.; Meléndez-Lira, M.; Altuzar, V.; Tomás, S. A.

2003-01-01

We report the effect of the addition of an epidermal growth factor to a Ricinus communis-based biopolymer in the healing of a rat tibia model. Bone repair and osteointegration after a period of three weeks were evaluated employing photoacoustic spectroscopy and x-ray diffraction. A parallel study was performed at 1, 2, 3, 4, 5, 6, 7, and 8 weeks with energy dispersive x-ray spectroscopy. We conclude that the use of an epidermal growth factor (group EGF) in vivo accelerates the process of bony repair in comparison with other groups, and that the employment of the Ricinus communis-based biopolymer as a bone substitute decreases bone production.

Inhibiting the Epidermal Growth Factor Receptor | Center for Cancer Research

Cancer.gov

The Epidermal Growth Factor Receptor (EGFR) is a widely distributed cell surface receptor that responds to several extracellular signaling molecules through an intracellular tyrosine kinase, which phosphorylates target enzymes to trigger a downstream molecular cascade. Since the discovery that EGFR mutations and amplifications are critical in a number of cancers, efforts have